Skin Cream Formulator

BUSINESS PLAN     LABELLE INDUSTRIES, INC.

4515 Mapletree Boulevard
Grand Rapids, Michigan 49503

LaBelle is a niche player in the specialty skincare business, focusing on value-added products which are not widely or readily available in the United States. We have perfected unique distribution processes resulting in lower distributing costs and high profitability. We have established a network of strategic alliances with a manufacturer who has the capability to ascend from laboratory to commercial scale and manufacture products in accordance with quality specifications.

• executive summary
• company summary
• products/ingredients
• market analysis summary
• strategy & implementation summary
• management summary
• financial plan
• appendix

EXECUTIVE SUMMARY

LaBelle Industries, Inc. (LaBelle) is a home-based specialty skin cream formulator, wholesaler and distributor. We sell products to companies ranging from drugstores to consumers. This business is owned and operated by principal investor Roman Miller. He is a strong knowledge-based manager, with a combined 25 years of experience in this industry. LaBelle was created in 2001 and is currently located in Roman's home in Grand Rapids, Michigan. The purpose of the business being home-based is to lower the costs of overhead.

Through Reuben Retro Skincare, we manufacture and distribute an approved skin cream used to improve arthritis in muscle mass. LaBelle also produces one other specialty formula that will be detailed later in this document.

In theory, a wholesale distributor behaves no differently from a retailer: it purchases goods it intends to sell at a profit. The fundamental difference between the two is that retailers sell to the buying public or "the consumer" and distributors sell to retail businesses and fellow wholesale firms. In the strict sense of the term, distributors never sell to the public consumer, although the advent of wholesale membership clubs and other "power retailers" has begun to call that definition into question.

A new, natural product called Nopeinne, conceived by Roman Miller, will soon be available to relieve physical pain and suffering of mankind. An investment into Nopeinne is an adventure into the near future. Nopeinne is a manifestation of remedies used for treatment of wounds and physical disorder that caused pain and suffering among a nomadic people, namely the American Indian, before the settling of the pilgrims in 1620.

LaBelle is a niche player in the specialty skincare business, focusing on value-added products which are not widely or readily available in the United States. We have perfected unique distribution processes resulting in lower distributing costs and high profitability. We have established a network of strategic alliances with a manufacturer who has the capability to ascend from laboratory to commercial scale and manufacture products in accordance with quality specifications.

Our retailers and our customers have given us an opportunity to provide products beyond our present capability. We need to increase our inventory, purchase advertising, and establish marketing and support activities.

Funding Requirements

The total amount needed for this start-up business is $38,178. Roman Miller has invested $7,636 into this business and is seeking a commercial loan of $30,542 to enable us to expand our operation and become a major factor in the production and distribution of skincare products. The funds will be distributed in the following way: $10,000 for research and development of the products, $25,000 for actual production of the product, $2,178 for radio promotions, and $1,000 for television promotions.

Our signature product Nopeinne is manufactured in cream form. We are the only company in the world capable of manufacturing this product using our patented cream formula. Our market research shows that the demand for this product alone justifies the future expansion of our facilities from being home-based to brick and mortar in 2005.

Objectives

Our objectives are to have:

1. a gross margin of 65 percent or more
2. a net profit above 10 percent of sale
3. sales passing the projected sales of $252,000 by the year 2004

Mission

We see our mission as not only that of wholesale-distributor, but a trade supplier where we can reach the end-user market with products we consider to be proprietary. We seek a fair and responsible profit, enough to keep the company financially healthy for the long term and to satisfactorily compensate owners and investors for their money and risk.

Keys to Success

The keys to success in this business are:

• Marketing: either dealing with channel problems and barriers to entry, or solving problems with major advertising and promotion budgets.
• Management: products delivered on time, cost controlled, marketing budgets managed.
• Uncompromising commitment to the quality of the end product: multiple skin cream products.
• Successful niche marketing: we need to find the quality-conscious customer in the right channels, and we need to make sure that customer can find us.
• Almost-automatic development and distribution of our product to maintain high demand needs.

COMPANY SUMMARY

LaBelle Industries Inc., is a privately owned specialty formulator of skin creams and ointments. Our end-users are in all levels of skincare needs ranging from acne to razor bumps to arthritis.

Company Ownership

LaBelle is a corporation established in 2001. The company is owned by Roman Miller.

Daily Operations

The hours of business will be from 8:00 A.M. until 5:00 P.M., Monday through Saturday, and closed on all major holidays. Because our business is home-based, it is possible we may work overtime by answering the telephone after 5:00 P.M. or before 8:00 A.M. Any person-to-person contact will be done at the customer's establishment.

We will perform most of these functions on a daily basis:

• Checking invoices against payments.
• Purchasing inventory.
• Visiting customers for promotion and service evaluation.
• Scheduling deliveries (including immediate deliveries when shortages occur) and monitoring their progress.
• Fielding calls from our manufacturer and retailers.
• Order processing.
• Inventory control.

We will perform these activities on a weekly/monthly basis:

• Maintain our bookkeeping and recordkeeping to ensure our distribution business's cash flow in the short run and avoid confusion at the end of the fiscal year.

We will keep a tight reign on these daily/weekly/monthly duties to improve our business's efficiency and reduce operating problems during the week.

Start-up Summary

The total amount needed for this start-up business is $38,178. Roman Miller has invested $7,636 into this business and is seeking a commercial loan of $30,542 to enable us to expand our operation and become a major factor in the production and distribution of skincare products. The funds will be distributed in the following way: $10,000 for research and development of the products, $25,000 for actual production of the product, $2,178 for radio promotions, and $1,000 for television promotions.

Company Locations and Facilities

LaBelle Industries, Inc. is a home-based business located at 4515 Mapletree Boulevard, Grand Rapids, Michigan 49503. Our present office is small but is in a room of its own to keep our home and work lives separate. Our office contains bookshelves, file cabinet, desk with computer, sitting chairs, a fax, a copier, and space for inventory storage area for additional small products.

We will use restaurants, hotel lobbies, and conference rooms if our home won't accommodate clients comfortably. Also, as we add employees, we will look at taking on additional space or finding a new location. All products will be formulated, packaged, and shipped to the distributors through the Reuben Retro Skincare Company or hand-delivered by the LaBelle manager. This way we cut down on storage space, overstocked inventory, and any other cost surrounding the manufacturing aspect of our business.

PRODUCTS/INGREDIENTS

Our products are skincare creams for acne and razor bumps and medicated therapy in the form of an arthritis cream. The products are all natural with no chemicals. The products also include herbs.

Herbs were used extensively by ancient Romans and Egyptians and are frequently found in the tombs of Pharoahs by archaeologists. Native Americans made use of herbs and their medicineman shared their herbal remedies with less fortunate African Americans who did not have access to a physician or modern medical treatment for physical disorder, pain, and/or injury.

African Americans, during that era, depended exclusively on treatment by midwives among them when incapacitated or physically disabled on a temporary basis. They harvested assorted herbs during the growing season which were then dried by the sun and the wind and even in the shelters of Indians and slaves. Many such wild plants have been used successfully for decades by chefs and cooks at public eating establishments for the purpose of enhancing the flavor of food.

Modern supermarkets stock a complete assortment of familiar herbs, attributed to popular domestic demand. Nopeinne is the creation of an aware male amateur cook who began experimenting with herbs and fruits, based on his knowledge of natural medicinal properties contained in them. Among them are sassafras, sena, and the aloe vera plant, found among plants in many homes and used to treat minor burns. Herb tea is a popular beverage consumed by millions of people around the world. Peppermint, eucalyptus, lemon balm, lavender, compry, Queen Anne's Lace, capsicum, feverfew, ginseng, echinacea, and hot pepper are a few herbs that contain healing properties. Other valuable foods used for medicinal purposes are citrus fruits, bananas, and oranges and are included in fabricating this formula. The extensive use of herbs has been well established by man, including the source of many drugs, although Nopeinne does not contain harmful foreign properties.

Product Description

Our current and future products consist of the following:

Skincare—facial treatments

Body and Bath—bath and shower products that are not extensions of a fine fragrance

Men's Products—men's hair bump treatment

Other products—medicated therapy cream for arthritis

Other—new products that don't fit the above categories

A new, natural product called Nopeinne, conceived by a man of vision, will soon be available to relieve physical pain and suffering of mankind. An investment into Nopeinne is an adventure into the near future. Nopeinne is a manifestation of remedies used for treatment of wounds and physical disorder that caused pain and suffering among a nomadic people, namely the American Indian, before the settling of the pilgrims in 1620.

Nopeinne is not expected to accomplish what Viagra did for men, but its purpose is to improve people's physical ability to function. This new product may be the key that will unlock stiff joints and tight muscles while raising the investors' monetary value.

Competitive Comparison

Within our niche we have several significant competitors: Tigerbalm, Flexall, Bengay, Heat, and Asper Cream. In general, however, our competition is not in our niche. We compete against skin cream companies that use chemicals instead of natural herb formulas. It isn't that people choose our competitors instead of our product. Instead they choose lesser quality, chemical-formed creams instead of natural herbs formulas we offer. This will change as we begin letting the public know they now have a choice of getting the same relief and better results without the chemical components. We will continue to examine our rivals' weaknesses and strengths, and continue to strategically promote our strengths and their weaknesses.

Marketing Plan

Our marketing plan consists of providing a direct line of communication regarding our product to current and prospective customers. Our advertising campaign will accomplish the following:

1. Convince customers that our company's products are the best available
2. Enhance our company's image
3. Point out the need and create a desire for our products
4. Announce new products or programs
5. Draw customers to our business

Our advertisements will be simple and easily understood, truthful, informative, sincere, and customer-oriented. We will use the following advertising media for our home-based business:

• Personal contact
• Newspapers
• Magazines
• Newsletters
• Telephone directories
• Radio
• Online/Internet
• Flyers—Direct Mail
• Specialty Items (pencils, calendars, matchbooks, telephone pads, etc.)
• Sales Letters
• Brochures and Catalogs
• Postcards
• Coupon Mailers
• Radio Give-a-Ways

All of our correspondence will be professional, printed on good paper and with clean typing free of any spelling errors.

Sourcing

Our main sourcing contact will be Reuben Retro Skincare, located at 42005 West 45th Street, New York, New York.

Reuben Retro was founded in 1975 by Master Chemist Jean Fream, a graduate of the prestigious Sorbonne in Paris, France. Monsieur Fream's celebrated formulas are manufactured for industry giants such as Loreal and Maybelline.

His insight and genius forms the very core of Reuben Retro's Research and Development Team, combining the master disciplines of European craftsmanship with the latest in scientific technologies and the finest natural ingredients.

For more than two decades, Reuben Retro has developed and manufactured products that make a difference in people's lives. Thousands have discovered our products and have rediscovered beauty once compromised by problematic skin. And more have found our products to be a healthy alternative to harsh medical and pharmaceutical treatments.

For more than 20 years they have used nature as their guide and maintained a natural approach to skincare. Their mission is simple.

LaBelle intends to demystify skincare, improve the way you look, and most importantly, help you feel better about yourself.

Technology

We are a highly technical niche player with a specialized product line that is in great demand. We have developed new technology and processes that are in demand by other cosmetic manufacturers as well as by major distributors who do not have the ability to produce our specialty products. We have the management team and the skin cream formulations to become a major player in the specialized niche we serve. We also hope to develop a website in the near future.

Future Products

Our future products include:

• Bath oils
• Moisturizer
• Additional acne creams
• Shaving bump cream

MARKET ANALYSIS SUMMARY

Our target markets are the retailers who have established relationships with consumers and the consumers themselves via word-of-mouth. We are essentially the distributing arm for these retailers and can provide development services as well as products for them.

The retail businesses are in the business of selling goods, and there are more than 1.5 million of them across the country. The greater the difference between the selling price and the price they pay for the product, the greater their profit. It follows that retailers have (or should have) a keen interest in the way products move from the manufacturer to them because that's where the markup occurs. If they can find a wholesale distributor like LaBelle, who can deliver a product on their shelves at a lower price and still provide exemplary service, few will refuse the chance.

Random test results of Nopeinne exceed anticipated performance at the laboratory level while clinical analysis is pending. This new product netted an impressive percent approval from Michigan and Indiana consumers ranging in age from 13 to 50 and older over a two-year period with no report of side effects.

Market Segmentation

Retailers: our market research indicates about 46 potential retailers within a 1-25 mile radius of our location, who currently sell our competitors products. Our target retailers are drugstores/pharmacies.

Consumers: There are 437,700 individuals in Kent County. Of those 315,008 are adults 18 and older, which are our target consumer market.

Target Market Segment Strategy

Retail Business: Retailers are in the business of selling goods, and there are more than 1.5 million of them across the country. The greater the difference between the selling price and the price they pay for the product, the greater their profit. It follows that retailers have (or should have) a keen interest in the way products move from the manufacturer to them because that's where the markup occurs. If they can find a wholesale distributor like LaBelle, who can deliver a product on their shelves at a lower price and still provide exemplary service, few will refuse the chance. We have retailers who will be begging for our products and we anticipate having backorders, so it is only logical that we will devote most of our time meeting this demand.

Consumer Market: This is potentially our biggest market for Nopeinne; it is limited only by our ability to produce. We look at the potential in this market as the basis for our growth. We will market to this group by giving them a clear comparison between the chemical-based products they are now using and our natural products. This marketing strategy will begin by letting the public know they now have a choice of getting the same relief and better results without the chemical components followed by their conversion over to our products.

Market Needs

Many thousands of individuals are immobilized by osteoarthritis or from temporary muscle strain and do not have access to soothing hot baths or physical therapy that relieve suffering, but Nopeinne is instantly available to a victim in pain. Hundreds of thousands of mature persons agonize about debilitating aches and pain while spending as many dollars annually for various health remedies to find relief.

Repulsive blotches on the skin, ugly pimples, sore joints, and muscles unquestionably diminish individual aesthetic qualities, progress, and success, but our Nopeinne formula is the knight in shining armor, prepared to challenge and change that undesirable status. Nopeinne is not expected to accomplish what Viagra did for men, but its purpose is to improve people's physical ability to function. This new product may be the key that will unlock stiff joints and tight muscles while raising the investors' monetary value.

Among them are staggering numbers of high profile men, women, and youths, troubled by ugly, detracting, facial blemishes that beg for attention. Thousands of individuals cannot hold a cup of coffee or a pencil or a pen and vital physical activity is severely restricted by excruciating pain. Medical clinics are filled to capacity each day with victims, untimely inhibited by rheumatism, sore muscles, and joints. Simple fun and games no longer need be curtailed because of inflamed body joints. Nopeinne offers divine redemption to innocent victims of these ailments.

Market Trends

The consumers are seeking more natural products versus products containing artificial or chemical ingredients and to say wholesale trade is immense would be an understatement. The Department of Commerce's most recent Census of Wholesale Trade (1992) reports that merchant wholesalers handled nearly $1.9 trillion (58 percent) of the more than $3.3 trillion total wholesale trade sales. The industry's annual payroll in 1994 topped $127 billion, according to the National Association of Wholesaler-Distributors (NAW), and supplied salaries to more than 4.6 million individuals. All told, the inventories moved by wholesale distribution establishments were valued at more than $177 billion.

Market Growth

One of the more lucrative fields of proven endeavor is that of pharmaceuticals and related medical aids purchased by persons suffering from pain. A plethora of related complaints are documented each year by thousands of doctors and pharmacists. Recent government statistics disclose the fact that 43 million individuals suffer from arthritis while 20 to 40 percent of adults in this country are plagued by acne. Thirteen to fourteen million allergy sufferers were listed between 1990-1998 and 18 million are projected for 1999. Prescription drug sales gross up to $120 billion annually in America and that number is projected to double by 2004.

Caution, reluctance, or procrastination could be costly in this instance because statistically, the American consumer has proven to be reliable in terms of buying health products as rapidly as they are exposed to the marketplace. Consumer confidence in health products has never been higher.

Industry Analysis

The U.S. cosmetics market, measured in manufacturers' shipments, grew by more than $1 billion in 1998, at a rate of 6.6 percent. Growth was driven by color cosmetics with its focus on teens and 'tweens, and skincare with its dermal patches and pore strips, as well as the impact of niche lines with spa positioning. As for body and bath, there were a few cellulite or slimming body products and the bath market seemed close to saturation. Fragrance exhibited modest growth, fueled by classic scents and limited editions.

The skincare industry is characterized by a wide variety of companies ranging in size, from large companies such as St. Ives to smaller specialty firms such as ours. The companies are generally organized by either end-user markets or product technology. In the past decade there has been a general trend in the industry to change emphasis from using chemicals to all natural products. The cost of product development and the need to operate factories at high levels of capacity have caused skincare companies of every size to outsource parts of the skincare cream manufacturing processes. This has created opportunities for smaller companies to create and occupy niches in development and contract manufacturing.

An investment into health-related products has always been a wise and advantageous decision, simply because most Americans are prone to abusing and neglecting their bodies which frequently require costly adjustments to restore a reasonable degree of physical comfort. The American consumer spends $439 billion, $1.5 million annually for healthcare and health products ranging from dieting to exercise to painkillers, marketed for the purpose of securing relief, comfort, and improving physical appearance.

The longevity of the stock market is dependent on the continued desire and need of persons with surplus money to improve their financial status. LaBelle Industries, producer of Nopeinne, is a bonafide, newly organized and registered Michigan business with great potential by its very nature.

Industry Participants

LaBelle and Nopeinne are reaching out to special persons, seriously interested in a high-yielding financial investment. Opportunity is frequently unrecognized by persons preoccupied with other unrelated initiatives of lessor importance. Success, in many instances, is dependent on the willingness of one to take calculated risks of investing in reasonably assured fields of endeavor.

Physical Distribution

Once a sale is made, the product is shipped to the distribution point—our facility. We will be looking at setting up a drop-shipment so goods travel directly from the manufacturer to the customer. Our whole physical distribution process will be fueled by sales.

The following activities will be coordinated in order to physically move our product:

1. Communication between order processing and physical distribution.
2. Warehousing of finished product for distribution.
3. Selection of transportation method to move the finished goods from warehouse.
4. Handling the finished product at the distribution point.

We will also provide necessary delivery service to customers in a timely manner and keep costs under control.

Competition and Buying Patterns

Currently Celebrex and Vioxx cost more than $2 a pill, suggesting that the cost of a new pharmaceutical product is not an issue to persons seeking relief from pain. This inspired an impassioned Michigan vegetarian to create Nopeinne to relieve pain and suffering. Thus now poised to take its place in the marketplace is a new people-pleasing formula for relief.

Main Competitors

Our main skin cream competitors are: Tigerbalm, Flexall, Bengay, Heat, and Asper Cream.

Their shortcoming is that they contain more chemicals than the natural herbs and ingredients of Nopeinne.

Our main wholesale competitors will be power retailers who merge the specialty store concept with the discount store's emphasis on price. These retail warehouses are large stores with products displayed on metal racks in a warehouse setting. There are two distinct types of retail warehouses, the first being a membership and the second a consumer store which is open to the general public.

Their shortcoming, as with other competitors, is service; buyers must travel to them to pick up their goods. Some of the power retailers have just begun to offer delivery services, which is helping retailers to appreciate the value of using a distributor like LaBelle.

STRATEGY & IMPLEMENTATION SUMMARY

We address the market through one business segment: specialty skincare formulas. We are a niche player who has developed strong alliances with retailers who have powerful channel relationships.

Our marketing strategy assumes that we will serve our distributor by being a trade supplier, where we develop and sell our own lines of products based on industry and customer needs.

Our main strategy at LaBelle is to position ourselves at the top of the quality scale, featuring our combination of superb technology and rich, healthy herbs for the buyer who wants the best quality and best price. Tactics underneath that strategy include research and development related to new formulas and new products, choosing the right channels of distribution, and communicating our quality position to the market. Products are mainly those listed under the product description heading. We will continually develop new packaging, channel development, channel marketing programs, our direct sales, and our continued presence in high-end catalog channels and new presence on the web.

Value Proposition

LaBelle gives the skincare cream user, who cares about their skin features, a combination of the highest quality all-natural creams and the latest formulations at a relatively good price.

Competitive Edge

Our competitive edge is in the formulations and distributing processes we have developed for the production of the one product in which we specialize. As detailed above, we are in an excellent position to capture a significant part of the $123 billion-dollar skin cream market. We simply need to establish a marketing program and begin to promote our products.

Marketing Strategy

Our marketing strategy is to create effective advertisements made simple and which are easily understood, customer-oriented, truthful, informative, sincere, and will explain the who, what, when, where, why, and how of our business. Our advertising plan will instill a desire in people to consider our products and the value of our customer service and an inclination to do business with our company because of the positive messages they receive. Our good advertising will cause action and persuade the prospective customer to go with LaBelle instead of the competition.

We will use advertising to educate consumers who are buying from us. We expect our advertising, especially personal selling, has a cumulative effect. We are expecting the initial response to be slow, but to increase over time. We plan to advertise regularly and continuously on a small scale and then place large advertisements infrequently. By the same token, visiting and calling customers frequently helps to solidify relationships.

Word of mouth is essential to the growth of any business. We know the traditional forms of advertising play only a supporting role, and we will thrive or suffer from our reputation in the marketplace. We believe each satisfied customer has the potential to steer dozens of new ones to us, and each dissatisfied customer is equally capable of wreaking havoc on our business by planting doubt in the minds of existing customers and scaring off potential business.

Positioning Statements

For individuals who have suffered from facial scars, bumps, acne, or arthritis pain, LaBelle offers exquisite skin cream solutions. Unlike most skin cream manufacturers who use chemicals, LaBelle's all-natural products make no development compromises for standardization.

Pricing Strategy

We will maintain our pricing positions as a premier provider. We are the best product available from the most discriminating consumer. We intend to maintain our separation from the price competition at the lower end of the business. Our plan calls for no significant changes in pricing. Price increases will be due mostly to the fluctuation of our ingredient prices.

Promotion Strategy

Our promotion strategy is to first listen and observe our customers so we know what they consider paramount. We will then tell them how our products and services will supply solutions. We have kept in mind that retail businesses don't buy products and services; they buy the benefits that are derived from them, such as profit and support. As we continue to develop our planned strategy, we will clearly express and promote the features and functions of our products and services that satisfy the prospect's demands.

Our primary contact is the company's national or regional sales manager, or whoever is in charge of making inventory decisions. In entrepreneurial businesses like LaBelle, the owner is usually the sole decisionmaker.

We will also promote our products through seminars and home showings.

Distribution Strategy

Our distribution strategy is guided by security and control. LaBelle will personally deliver the products we buy and sell. We will deliver for security, to ensure the product's safe and timely delivery, and control, to be responsible for as much of the product's movement from the supplier to end user as possible, in order to provide a more comprehensive service and thereby increase revenues. Frankly, we don't want our customers knowing the identity of our manufacturer supplying our product.

Our distribution strategy is also guided by volume. The more the retailer buys, the lower our price. Our first opportunity to increase our margin by increasing our volume arises when we purchase our inventory from our manufacturer. If we can purchase inventory for ten retailers at a time instead of two, we will be devoting less of our money to our cost of goods sold and more to our business bank account. Buying in volume will also improve our relationship with our suppliers, it makes us a more valuable element of our customer base. The more we purchase, the more cost-saving opportunities will be offered to us.

Marketing Programs

Some of our marketing programs will include but will not be limited to:

• Free samples
• Coupons
• Referral Discounts
• Mailers

Sales Strategy

LaBelle's sales strategy includes using the following selling techniques:

1. Telephone Sales
2. Person-to-Person Sales

Our sales strategy is outlined below in three phases.

Phase One is to accommodate our existing customers and to make sure that current orders and subsequent orders are maintained.

Phase Two will commence when our facilities are expanded. We will then be able to develop new products, accept new clients, and contact companies who have shown interest in our products and be able to accommodate their orders. We plan to hire a high-quality salesperson to assist in defining our marketing program.

Phase Three will begin with the hiring of two additional sales representatives who will develop our consumer program wherein we will begin to sell our product directly to an individual via the web.

Savings will be our first transaction between the manufacturer and LaBelle. This is the arena in which price and profit do battle. Our ideal series of events is for LaBelle to pay as little as possible for the merchandise, control its distribution from the manufacturer to the customer/end user, and incur as few costs as possible in the process.

We will accept credit card, cash, and check sales. Later as we build cash-flow we will consider credit terms with 30-day invoices.

Sales Forecast

Our sales forecast is based on the selling of 5,000 units of the skin cream product. Four thousand units will be sold to retailers at an introductory wholesale price of $7.50 per unit, and 1,000 units will be sold directly to the consumers at $15 per unit. We expect our inventory to turn 4 times a year or every three months, forecasting revenue from sales to average approximately $45,000 per quarter. It costs $5.00 per unit to manufacture this product.

We are expecting to increase sales from $180,000 to $225,000 in the next year, which is slightly more than 24 percent growth. Growth forecast is relatively high for our industry because we are developing new patent formulas. In 2003 and 2004 we expect growth to increase 10 percent per year, to a projected total of $252,000 in 2004. We will spend approximately 30 percent of our original inventory investment to maintain or purchase additional inventory.

We are not projecting significant change in the products, or in the proportion between different products. Our seasonality, as shown in the chart, is still a factor in the business. Overall, sales tend to be steady.

Sales Programs

Specific sales programs:

• Distributor sales
• Web sales
• Retail sales
• Direct sales
• Telephone sales

Strategic Alliances

We depend on our alliance with Reuben Retro to generate continuous leads for our add-on products. We are also developing relationships with other manufacturers to further cut cost and continue sales growth.

MANAGEMENT SUMMARY

As the owner and manager of the business, Roman Miller will have complete control over every aspect of its structure and activity. He will handle daily operations himself. These operations include purchasing and order processing, controlling inventory, setting delivery schedules, defining return policies, and devising pricing methods.

We have a strong manager that can boast of years of experience in skin cream development. Roman has spent four years working and researching the skin cream industry. He has a proven background of expertise and is more than capable of transforming LaBelle into a leading specialty skin cream distributor.

Organizational Structure

Roman Miller, owner, is responsible for overall business management. We will utilize outside support resources as needed.

Management Team

We are currently developing the management team and more skin cream formulations to become a major player in the specialized niche we serve.

Management Team Gaps

We depend on our consultants that include our CPA and our attorney for some key management help. As we grow, we will develop more formulas and more mass production of those new products.

Personnel

Our present plan is to have one manager, Roman Miller. His job is to keep the office running efficiently, everything from scheduling future employees to monitoring deliveries and shipments to hiring and record keeping. He will not receive an owner's draw for the start-up phase of the business.

We are also looking to hire a Distribution Sales Representative (DSR) who will be a capable marketing professional with a background in skincare sales. Our DSR's duties include visiting prospects, discussing ideas for the prospects' purchases, taking notes regarding special product or service requests, providing customers with pricing information and estimates, and arranging for the signing of a contract, if necessary. We would like to bring that person on board late 2002.

Future personnel include one administrative support personnel, a bookkeeper. This bookkeeper will pay bills for inventory, equipment and supplies, as well as handle payroll and general bookkeeping. We will look for someone with basic computer and bookkeeping skills. Until we can hire a bookkeeper, we will utilize a good accounting software package.

We will not be offering any employee benefits for at least two years.

FINANCIAL PLAN

The financial picture is quite encouraging. We will be slow to take on debt over the next three years, but with our increase in sales we do expect to apply for a credit line with the bank in 2005 for expansion on our products and facilities.

Important Assumptions

The assumptions that support our projections are:

The move to larger facilities at some point and the purchase of additional equipment will result in increased production. We have excellent agreements with our primary sources of supply and assume there will be no change in these relationships. We also assume that the demand for Nopeinne and our other products will continue to increase as evidenced in our market research.

On the flip side, another company could develop some of the formulas we have, in which case we would lose some of the technical and market advantage we now have. This will also decrease our valuation. If we cannot find a capable marketing person, who is both sales and technically savvy, in time to get into this market, we would be at a disadvantage. Technology changes, as do buying habits and social structure. But a degree of risk is synonymous to everything one does, so taking a chance is essential for success and perhaps survival. Even with a stagnated economy, we believe there will be little, if any, impact on individual desire to feel good and be free from physical pain and suffering, caused by neglect and/or deficient health care, thus continuing to purchase our products.

Risks

Developing a strong base of retailers and distributors, paying close attention to customer suggestions and requests, finding a small niche and sticking to what we know best, and coping with a changing economy are all proven ways to keep a wholesale distribution business successful and out of bankruptcy.

As in any business there are risks. Our goal is to recognize crucial warning signs and head off disasters by continually asking ourselves these questions:

1. Are we carrying too many different kinds of products or stocking too much merchandise?
2. Are we blinded by "pride of parenthood," failing to cut back on money-losing operations?
3. Have we carefully analyzed demand for our products, monitored the marketplace, and adjusted quickly to changing conditions?
4. Are some employees making little or no contribution to our bottom line?
5. Are our profits declining despite increased sales, or is our inventory growing due to sliding sales figures?
6. Have we prepared an accurate and realistic cash-flow projection?
7. Are we maintaining unneeded warehouse or office space?
8. Have we diversified away from our main strengths or overexpanded during good times, only to find ourself less liquid than we would like to be?
9. Are we taking stopgap measures like injecting additional cash to meet accounts payable, payroll, and other expenses, rather than facing the real problems and taking the neccessary corrective steps?

Recognizing problems is a step in the right direction. The next step is to take action once we've diagnosed the problem so we can get our wholesale distribution business back on track. When deciding on our course of action, we will create and update an accurate and realistic cash-flow projection that takes into account changing economic realities, look at our operations on an overall basis instead of attacking cost-cutting piecemeal, and analyze both the short- and long-term effects of each cost-cutting activity.

We can avoid or overcome bankruptcy and failure by maintaining assiduous financial and operation control of our wholesale-distribution business, especially during the turbulent startup period, and we'll set ourselves on a path toward greater productivity and profitability. As we gain experience in the realms of wholesaling, merchandising, distributions and sales, and earn a reputation for providing top-quality customer service, good prices, and good products, we will develop specialized business skills which represent a comparative advantage over competitors in our area and beyond. Diligence and perseverance are as essential for success for a wholesaler or distributor as they are for any other line of work, and sound financial position is the necessary cornerstone for anyone interested in building a winning venture. That doesn't mean we will need millions of dollars; it means we must effectively manage the money we have, whatever the amount.

Break-even Analysis

The break-even analysis shows that LaBelle has a good balance of fixed costs and sufficient sales strength to remain healthy. Our goal is to sell at least 341 products per month or generate at lease $3,406 a month in sales.

Projected Profit and Loss

This table shows we project a net profit of $108,552 by the end of 2002 and a gross margin of $212,400 by 2004. We hope to gain enough skills by 2004 to release our support consultant completely. The table also includes part of a repayment schedule of our $30,542 loan at 11 percent over a period of 7 years at approximately $523 per month including interest.

Projected Cash Flow

We expect to have a projected cash balance of $356,538 by 2004. In February of 2002 we anticipate a slight decrease in cash flow. Therefore we will heighten our telephone and person-to-person sales efforts beginning in December 2001 to strengthen January 2002 and February 2002 sales and cash flow.

Projected Balance Sheet

As shown in the balance sheet in the following table, we expect a projected healthy growth in net worth, from approximately $103,010 from 2002 to more than $359,380 by the end of 2004. The monthly projections are in the appendices.

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APPENDIX

Sales Forecast

General Assumptions

Profit and Loss (Income Statement)

Projected Cash Flow

Projected Balance Sheet

SKIN

The existence of two different types of aging of the human skin has been recognized only since the mid-1980s. Normal internal (intrinsic) changes are differentiated from the effects of external influences (extrinsic). These differences have been made more apparent by a dramatic increase in life expectancy. The average life expectancy in ancient Rome was 22 years, compared with 78.6 years in Canada in 1996.

Intrinsic changes

The intrinsic changes are best seen in places where there has been minimum light exposure. The upper inner arm and covered buttocks are good examples. Here the top layer of the skin (epidermis) is thinned only slightly. Its cells do not adhere as well as in younger skin, and there is comparatively increased architectural irregularity. The number of pigmentary cells (melanocytes) is reduced, and the junction with the dermis (underlayer of the skin) shows some degree of flattening.

The dermis itself shows a thinning (atrophy) in which its major fibrous and cellular components are diminished. The number of sweat glands is reduced. Hair is grayer, and its individual diameters are narrower. In addition, the hair roots (follicles) on the scalp and face are fewer but the associated ‘‘grease’’ (sebaceous) glands are larger. Nails become fragile and develop longitudinal lines. The subcutaneous tissue under the dermis is thinner about the face, hands, shins, and feet but thicker on the waists of men and the thighs of women.

Coarse skin folds emphasize expression lines. They follow the contour of the larger muscles of the face.

The physiological activity of the various skin elements is generally reduced. This applies particularly to the immune response, the response to injury, cellular replacement, glandular activity, heat regulation, and sense of touch.

The effect on the individual can be summed up as the minor nuisances of old age and but mainly harmless. It is the external influence that is potentially harmful.

Extrinsic changes

The major extrinsic agent causing damage is sunlight. This damaging effect is termed photoaging. It is the result of prolonged and repeated damage caused by ultraviolet radiation, most frequently sunlight. The main damaging effect is caused by the shorter wavelength radiation (UVB), which has a limited penetration of the upper epidermal cells. The longer wavelength radiation (UVA) penetrates into the dermis and further increases the damage.

The main clinical change caused by sunlight is wrinkling. The elastic fibers present in the upper dermis swell initially. Later they become coarse and twisted, and finally lose their fibrous character. Under the microscope, the fibers are a diffuse, characterless mass that stains differently than the normal skin. The coarser, deeper, and more voluminous collagen fibers show similar degradation. This all leads to a loss of skin elasticity termed ‘‘elastotic degeneration.’’ If this skin is pinched and pulled, it fails to rebound to its normal state over a short period of time. In contrast, youthful skin or skin that is usually covered in the older person rapidly springs back to its normal state.

Sunlight is essential to well-being, and in moderation it enhances immunity; it makes Vitamin D in the skin; it induces a normal pigmentary protective response; and it makes people feel and look ‘‘good.’’ Episodic excessive exposure, or a cumulation over many years, can be damaging and is particularly related to the pigment character of the individual’s skin.

How much any individual shows the changes in the skin due to a lifetime of chronic sun exposure and weathering depends on the amount of sun to which the person has been exposed and where, geographically, this occurred. Other modifying factors include genetic endowment, skin pigmentation (dark, fair or gingery), and lifestyle factors such as smoking.

A wrinkled, coarse skin is the most characteristic of these changes. Smokers particularly have enhanced facial aging. Their skin wrinkling and appearance are more aged than those of nonsmokers. The deeper folds of the expression lines may be more emphasized.

The wrinkling may give cosmetic concern; many active old people wish to retain a youthful appearance. ‘‘Cellulite’’ is a harmless form of deep dimpling which occurs on the outer thighs. Some of the concerns can be met by the many cosmetic applications on the market. In other situations, cosmetic surgery can bring much benefit.

Growth and changes in color

The exposed skin is thinner in older people than in younger people. Occasionally coarse comedones (blackheads) are present. Discrete white, firm lesions may appear on the forehead and cheeks. These are harmless milia made up of keratin, the horny, fibrous protein of the outermost layer of the skin.

Though the color of the face is generally more pallid with age, the overall appearance varies due to blood vessel changes and pigmentary abnormalities. A mottled, blotchy redness is due to dilatation of small surface vessels (telangiectasia). Sometimes the vessels are individually quite prominent. At other times, the surface capillaries may have leaked due to solar deterioration of the supporting tissue. This produces livid blotches termed ecchymoses which may be present for a long time before resorption occurs.

Coarse yellow markings may be present on the forehead and sometimes on the cheeks. The skin surface seems to be filled with rectangular patches of varying size between the folds. This elastotic degeneration is due to thickening and clumping of light-damaged fibrous tissue under the skin surface. It is finer about the lips, where it emphasizes the skin folds.

Although the pigmentary cells are reduced in number as a natural result of aging, irregular pigmentation appears on the light-exposed areas. This may be simple freckling (lentigines) seen particularly on fair or gingery skins. Larger patches of melanin pigmentation 0.5 to 1.5 centimeters in diameter, are common. These are known colloquially as ‘‘sunspots,’’ ‘‘liver spots,’’ or ‘‘age spots.’’ Raindrop-size nonpigmented white areas appear on the outer arms and legs. Long forgotten scars are also revealed due to loss of obscuring pigment.

Apart from causing cosmetic concern in some, none of these changes is harmful in nature. However, irregular horny lesions can present. They are termed actinic keratoses. They may be flat and scaly on the ear tips or lips, or thicker and more craggy on the cheeks or sides of the neck. It is debatable whether they ever become malignant, but they can be a mechanical or cosmetic nuisance and do occur in skin more prone to malignant change.

Various other warty excrescences are found in the aging skin. They can be common warts, which are often present singly in unusual places and are of unusual form.

Seborrheic warts (keratoses) are more common. They are waxy, brown lesions varying in size from a few millimeters to two to three centimeters in diameter. There may be one or two lesions on the face. However, on the back the number may be much greater, and they tend to lie along the skin folds. They are harmless, but may be a cosmetic or mechanical nuisance.

The Hutchinson’s freckle (now termed lentigo maligna) is a rare growth most commonly present on the face. It is an irregular, flat brown patch one to three centimeters in diameter. It is seen in those who have had much sun exposure throughout their lives, as witnessed by their weathered faces. Though it usually remains quiescent, it may ultimately develop into malignant melanoma.

Skin cancer

Malignant melanoma is a dangerous, life-threatening tumor that may be unnoticed in older age. Its nodular form may mimic a mole or seborrheic keratosis. It may be a flat, irregularly colored lesion on the palm or sole, or present under the nail in pigmented or unpigmented form. This condition has received much attention from cancer prevention authorities as an overlooked life-threatening lesion. Self inspection, or inspection by a family member, or a care-giver is promoted.

A mnemonic has been developed that suggests immediate skilled medical assessment if

A for A symmetry. . . one half being unlike the other half is present

B for a B order which is irregular, being either scalloped or poorly circumscribed

C for C olor, which varies from one area to another; there may be shades of tan or brown, black, or sometimes red or blue

D for a D iameter larger than six millimeters, the size of an average pencil eraser.

There are other cancerous conditions that are much less dangerous. Basal cell carcinoma is quite common. Its origin likely lies in light exposure during childhood and adolescent years, but it may present only in later life, as a small, pearly nodule barely visible to the naked eye. Enlarged surface blood vessels may be present about its edge. It grows slowly and asymptomatically, doubling its size each year. It can ulcerate, and in that form is known as a rodent ulcer. Less often it is flat, pigmented, or cystic. Though it rarely metastasizes, it can erode locally, and for that reason should be removed.

Squamous cell carcinoma is ten times less common than the basal cell carcinoma. It is an irregular, scaling, fairly well-defined lesion most commonly found on the face, lips, or back of the hand. Sometimes it is fairly flat, but at other times it is heaped up and craggy. It can metastasize, particularly when it is on mucous membrane, such as the lips. For that reason, early recognition and management are important.

Conditions of the normal aging skin

The challenge of the clinical look of the aging skin is to separate the normal changes of age. This must take into account external damage from sunlight and changes due to internal disorders.

Among common conditions that can confuse is chronic vitamin deficiency, found mainly in older persons living on their own. This may be a pellagra type of condition due to vitamin B deficiency. In this, the exposed skin, particularly of the arms, turns a dusky shade and is somewhat dry and scaly. Those prone to diet deficiency can also get scurvy due to vitamin C deficiency. Again, the skin is dry and scaly, but there are also horny spines at the openings of the hair follicles. Overall protein deficiency in the diet manifests as wasting which appears as enhanced aging.

Cachexia is the term used for progressive wasting due to an unrecognized malignancy. It is often misinterpreted as premature and undue aging. Generalized itching without apparent cause may signify an underlying malignancy. Since there are a number of other causes for this miserable affliction, skilled medical help is required for full investigation.

Dryness of the skin of older people (xerosis) can cause fissures and develop into a persistent, uncomfortable, and disabling eczema (dermatitis). A common cause is excessive showering or bathing in the winter months. Whereas younger persons can bathe daily throughout the year, this is too drying for most older skins. So-called winter eczema in the northern climates can occur. It is usually first seen on the shins, where the skin surface looks somewhat like cracked pavement. Scratch marks and pinpoint oozing are present. At that stage it can rapidly spread to the arms and over the trunk. Medical assistance is necessary.

Those who have a disposition to atopy may suddenly be troubled by extensive atopic eczema after not having had trouble for many years, or, indeed, ever. The term atopy is used for a hereditary hypersensitivity such as asthma, eczema, hay fever, or hives. Those who are subject may have had one, some, or all of these conditions earlier in their life, then experience it or them again in older age.

An altered immune response may allow the parasitic infection scabies, due to the scabies mite, to become very extensive in the skin. It is commonly called Norwegian scabies. This causes much scaling. Each scale contains numerous mites, and thus is highly infectious. If the affected person is in an institution, a very wide outbreak of the condition may result. It will cease only when the asymptomatic carrier is identified.

In all, the common complaints of older people about their skin are related to its normal anatomic and physiological changes. Pride and self-esteem depend so much on appearance that any concern of older people about their skin should be attended in a respectful and noncondescending manner.

J. B. Ross

See also Breast; Hair; Pressure Ulcers.

BIBLIOGRAPHY

Claderone, D. C., and Fenske, N. A. ‘‘The Clinical Spectrum of Actinic Elastosis.’’ Journal of the American Academy of Dermatology 32 (1995): 1016–1024.

Drake, L., et al. ‘‘Guidelines of Care for Photo Aging/Photodamage.’’ Journal of the American Academy of Dermatology 35 (1996): 462–464.

Fenske, N. A., and Lober, C. W. ‘‘Structural and Functional Changes of Normal Aging Skin.’’ Journal of the American Academy of Dermatology 15 (1986): 571–585.

Rook, A.; Wilkinson, D. S.; and Ebling, F. J. G. Textbook of Dermatology, 6th ed. Edited by R. H. Champion, J. L. Burton, D. A. Burns, and S. M. Breathnach. Blackwell Science, 1998. Pages 3277–3287.

Skin Senses and Kinesthesis

Receptors

Central sensory processes

BIBLIOGRAPHY

The skin senses andkinesthesis (muscle and movement senses) present a difficult problemin sensory physiology—the problem of how information about severalenergies of the external world are signaled to the brain. Skinreceptors are sensitive to thermal and mechanical stimulation, andmechanical stimulation is detected in a variety of ways both by senseorgans in cutaneous structures and deep, internal structures such asmuscles, tendons, and joints. In varying degrees, deep receptors alsodetect the state of the tissues or the position of the body and limbsin space.

At one time, it was thought that a single skinsense—so-called common sensibility—detected touch, pressure, warmth,cold, and pain. Beginning in the late nineteenth century, the conceptof separate sensory modalities developed, based on the presumedexistence of histologically distinct sets of sense organs for eachcutaneous sense, of some separation of pathways in the spinal cord,and of specific endings in the cerebral cortex (see Boring 1942). Theone concrete experimental datum was a spotlike, or punctiform,distribution of sensitivity, determined by exploring the skinmillimeter by millimeter with different energies and findingdifferent psychological responses—touch, warmth, cold—from differentspots. This punctiform sensitivity seemed to demand specificanatomical endings. The histological specificity—variousencapsulations of the neural terminals themselves —described byanatomists seemed to provide a structural correlate for severalpsychological and physiological findings. However, the search for ahistologically distinctive receptor beneath a sensitive spot provedelusive.

The minimum demanded is that this receptor be a senseorgan that responds differentially or differently to various forms ofenergy. The traditional view is that a sense organ respondsdifferentially to one energy or to one band of an energy spectrum(e.g., warmth and cold or frequencies of light waves) and analyzes anobject in contact with the skin in terms of this energy or band ofenergy. Such a filter function is traditionally expressed by theconcept of adequate stimulus or, better worded, differentialsensitivity. Like all filters, the sense organ has a low thresholdfor one form of energy or for one band of frequencies within a givenform of energy.

An alternative view holds that sense organs aremuch alike in their range of sensitivity to a variety of energies butrespond differently in some way ("frequency” or “pattern") to eachenergy, leaving the central nervous system to interpret the differentresponses and recognize the different energies (Weddell 1961). Thesepoints of view are caught in a crosscurrent of contradictoryexperimental findings.

Receptors

Since the mid-1950s, thepoint of view that receptors are alike in their range ofsensitivities and that discrimination of sensations is ajoint function of receptor responses and processes in the centralnervous system has received considerable support from evidence thatthere is little morphological differentiation of receptors in hairyskin, although hairy skin indisputably signals different modalitiesof sensation. While hairless skin (lips, fingertips, etc.) doescontain specialized endings, it became gradually accepted, on thebasis of Weddell’s work (1961), that only two types of endingsexist in hairy skin: fibers originating about the roots of hairs andfine, beaded, unmyelinated, or so-called free, nerve endings. Becausethe same modalities of sensation are experienced from stimulation ofhairy and hairless skin, specificity or band-pass characteristicscannot then be attributed to any capsules or discs that areassociated with the specialized nerve terminals in hairless skin.Anatomical studies have not disproved the functional specificity ofthe terminations; whatever specificity exists must, however, be on asubcellular or molecular basis, not visible with the light microscopeand conventional stains.

Actually, in slight contradiction ofWeddell’s broad generalization, there are several types of hair receptors having some what different discharge properties, but all are receptors for mechanical stimulation (mechanoreceptors). Also, the conspicuously encapsulated organ—the Pacinian corpuscle —isfound in the dermis and subcutaneous tissues. Iggo and Muir (1963) have discovered a morphologically specialized end organ that consists of a thickened epidermis covering several Merkel-type corpuscles, into which penetrate branches of a single thick myelinated axon. This spot like receptor is also a mechanoreceptor. Deep in the skin and in muscles and tendons, there are encapsulated or otherwise specializedsense organs. Knowledge of sense-organ morphology is in a curious state because certain “classical” formations are now considered artifacts, but at least one new type has been discovered.

Another plausible morphologically based generalization, now proved to be invalid, is that all free nerve endings are pain receptors andthat their lack of capsule or morphological complexity accounts forthe wide variety of energies that can elicit cutaneous pain—namely,mechanical, heat, cold, and chemical stimulation. Passing from theskin to the spinal cord are numerous small axons, measuring about 1/iin diameter, which conduct nerve impulses at about 1 meter per secondand are termed unmyelinated. (Under the light microscopes they appearto lack a surrounding sheath of white fatty material, myelin;electronmicroscopy reveals a thin myelin sheath.) These fibers,termedC-fibers, conduct impulses which result in painful sensation;so do the smallest fibers with optically visible myelin sheaths.These fibers, called 8-fibers, conduct impulses at a considerablyfaster rate, about 6 meters per second. Because of this double systemof fibers, pain can be appreciated, in certain circumstances, as twopulses: “fast” pain and “slow” pain.

It has recently been learned that touch and thermal stimuli excitenerve impulses at intensities of stimulation far below that requiredto elicit pain. In fact, a large number of the C-fibers can berecruited into responding before the level of stimulation required toelicit pain is reached. Thus, it can no longer be held that the fineunmyelinated axons are concerned exclusively with conducting theimpulses that arise within high-threshold end organs and that theircentral effect results only in the experience of pain. [See PAIN.]

Until recently, knowledge of C-fiber function has been largelyinferential, because the small action potentials produced by themhave been difficult to record. Douglas, Ritchie, and Straub (1960)caused impulses in the large-diameter, low-threshold axons to collideand, thus, eliminate themselves, leaving only the C-fiber impulses toreach the recording electrode. Activation of C-fibers did not requirethe strong mechanical or thermal stimulation that elicits painsensation. In fact, a fall in skin temperature of 10C., less thanis required to elicit a painful sensation, activated three-quartersof the C-fibers. Clearly, the C-fibers cannot be concerned solelywith pain sensation. This general conclusion is supported by the moredirect, classical procedure of “cutting down” a nerveuntil impulses in only one axon are recorded. This procedure,accomplished by Iggo (1959), showed that C-fibers do respond to morethan one form of energy and with weaker stimulation than thatrequired to elicit pain. In fact, they respond to stimuli not muchstronger than those required to stimulate the specifically sensitiveendings connected with large unmyelinated axons of sensory neurons.C-fiber discharges to a temperature drop as little as 0.3¶C. havebeen recorded.

Recording from a single axon has been accomplishedin man (Hensel & Boman 1960). Receptors connecting with myelinated fibers respond weakly to cold stimulation and strongly to mechanical stimulation. They tend to fire “spontaneously” atnatural skin temperature in the absence of known mechanicalstimulation.

The one epidermal receptor which is highly structured and is served by a large unmyelinated axon—the touch spot receptor of Iggo and Muir (1963)—discharges in response to cooling.This receptor is slow in adapting. The muscle spindle, which also adapts slowly, is also sensitive to cooling, but the very rapidly adapting Pacinian corpuscle is not. Iggo (1965) believes thatthe effect of cooling is a general property of mechanoreceptors which takes time to develop. Postulation of a multispecific ending is not necessary. Whatever the cause, the nervous system has the problemof “decoding” the discharge from such end organs.

In contrast, an ending responding specifically to heat has beendiscovered. This ending is termed a heat receptor, since it does notrespond to strong mechanical and cold stimulation.

Protopathic and epicritic sensibility. Since the primitive, fine unmyelinated fibers cannot be associated exclusively with the most primitive andleast discriminative sense, the pain modality, and since somemyelinated fibers have endings which are thermally, as well as mechanically, sensitive, it is inevitable that thinking should return (Poggic & Mountcastle 1960) to the all but discarded theory of protopathic and epicritic sensibilities, proposed by Henry Head (see Head et al. 1920). The protopathic system was postulated to be sensitive only to extremes of temperature and capable only of gross discriminations, where as the epicritic was sensitive to light touchand fine gradations of warmth and cold and capable of fine discriminations of pressure and weight. In a sense, a central neuralsubstrate has been furnished by the research just described, assumingalways that the afferent neurons described transmit impulses to the brain. Before further consideration of this assumption in thediscussion of the spinal pathways of sensation, it should be noted that Head’s theory is criticized because quantitativeexplanations can be given for phenomena which he felt had to beexplained in terms of qualitatively different neural mechanisms.

Deep sensitivity. Sensory information coming over the deepbranches of peripheral nerves is termed deep sensitivity or,specifically, muscle, tendon, and joint sensitivity. Sherrington(1906) introduced the term “proprioception”(“self-sensitivity”), in contrast to“exteroception” (“giving knowledge of theoutside world”). “Kinesthesis,” or “senseof movement,” is favored by some (Rose & Mountcastle 1959), in the belief that the impulses reaching the cerebral cortex come only from joints rather than from muscle and are, therefore, particularly, although not exclusively, excited by movement. The deep receptors lie also in muscle; they record not only active but passive movement and record the posture or position of a limb in space (in neurologicaljargon, “position sense”). [See SHERRINGTON.]

Intensity, affect, and place. So far, this discussion hasdealt with the kind of stimulus energy that is signaled. Thephenomenological counterpart is the quality of the sensation, thedifferences in experience which cause us to give sensations differentnames such as warmth, cold, touch, or pressure. Sensation has threeother aspects which are intriguing neurophysiological puzzles and areof great medical importance: The first of these is intensity ofstimulation. The second is affect, the aspect of a sensory experiencewhich causes us to describe it as pleasant or unpleasant. This phaseof sensation blends into the problems of motivation and emotion. Thethird is place, or the spatial-discrimination aspects of cutaneoussensibility.

Intensity is peripherally coded in the frequency ofdischarge or, perhaps more accurately, in the quantity ofimpulses—that is, frequency times number of responding fibers. It isno longer likely that affect can be fiber-coded in the periphery—forexample, that pain can be identified with C-fibers as a group. Theproblem becomes one of the destination of the impulse within thebrain.

Spatial discrimination involves the ability to locate onthe skin surface the point of stimulation (topognosis) and an alliedfunction, so-called two-point discrimination, measured as thesmallest distance at which two points applied to the skin are sensedas two rather than one—a function comparable to visual acuity. Errorsof localization and fineness of point discrimination are small on theskin surfaces used to explore objects—fingertips, lips, andtongue—and poorly developed on the back and proximal segments of thelimbs. Acuity is related to the density of the receptors and to thenumber of sensory axons supplying the region.

In spatialdiscriminations, cutaneous and deep receptors combine to provideinformation about the form of an object palpated and, with thesensations of temperature, weight, etc., enable us to recognizecommon objects by palpation (stereog-nosis). Although it is customaryto speak loosely of these as sensory processes, technically they areperceptions and judgments. A considerable evolution of the brain hasbeen required to add to the mere recognition of touch, cold, warmth,or pain the abilities to discriminate their fine degrees ofintensity, to locate the point on the skin stimulated, and toappreciate the spatial aspects of objects. [For a detailed discussionof intensity and the spatial and affective aspects of sensation, see Ruch & Patton 1965; see also PERCEPTION, article on DEPTHPERCEPTION.]

Convergence of axons. Another threat to theconcept of specific receptors connected by separate pathwaysto the cerebral cortex is the discovery that afferent axons that areapparently specific in the periphery for different kinds of energyconverge on the same second-order neuron on the spinal cord. Thisoccurs with axons that terminate on neurons in the posterior horn butnot for all second-order neurons on which the posterior-column fibersterminate. Specificity (filtering) and the resulting informationwould be lost if the transmitting channel had a wide-band pass,unless the streams of impulses from the two narrow-bandpass senseorgans were coded differently in the second and subsequent neurons.It has not yet been demonstrated that the single secondary neuron inwhich the nerve impulses are detected gives rise to ascending sensoryfibers. However, similar nonspecific behavior is found in somethird-order neurons and some cortical neurons, as will be discussedbelow.

The simple alternative to specific sensory end organs isfrequency coding. A sense organ may fire at one rate when stimulatedby touch and at another rate when stimulated by pressure.Alternatively, two specific end organs may, through their axons, firea second-order neuron at two different rates. The difficulty witheither concept is that the frequency code is, so to speak, needed tosignal the intensity of a stimulus, as can be seen when the intimatenature of sense-organ excitation is examined.

Receptor potentialsand nerve impulses. The mechanoreceptor is a transducer that convertsnonelectrical energy into an electrochemical phenomenon, thegenerator, or receptor, potential. This potential, in turn, sets upaction potentials in the parent axon which are brief,self-propagating, and independent, in size and velocity, of thestrength of the stimulus or of the generator potential. By contrast,the magnitude of the generator potential is related in logarithmicproportion to the magnitude of the physical stimulus. Further, thegenerator potential is stationary, decreasing rapidly with distancealong the axon; in response to a sustained stimulus, it tends to beprolonged, although not usually sustained at its initial level. Thepropagated all-or-none action potentials (nerve impulses) are alwaysintermittent. When the generator potential reaches a certain value (athreshold), the axon is discharged and cannot again be fired untilcertain changes underlying self-propagation are reversed. [See NERVOUS SYSTEM, especially the articles on STRUCTURE AND FUNCTION OFTHE BRAIN and ELECTROENCEPHALOGRAPHY.]

In some receptors, thegenerator potential dies out so rapidly that only one or two impulsesareset up. Such phasic receptors can signal intensity by theirproximity to the stimulus or by differing axon thresholds, whichpermit stronger and stronger stimuli to involve more and more axons.Such a recruitment will, through convergence at the second-orderneuron, mean that more impulses per second reach the brain.

Inthe tonic type of sensory neuron, the generator potential persists aslong as there is a stimulus, but as mentioned, the potential tends todiminish from its initial level to an approximate plateau. So long asthis potential exceeds axon threshold, impulses will continue to begenerated. However, as the generator potential diminishes, so doesthe rate of discharge. Since continuance of a stimulus is accompaniedby a psychological decrease in intensity (adaptation), the decliningfrequency of sensory-axon discharge is consistent with thesupposition that frequency is the way in which stimulus intensity iscoded. More directly, if different plateau levels of the generatorpotential are induced by different magnitudes of stimulation, thefrequency of discharge is directly and linearly proportional to thegenerator potential. The over-all logarithmic relationship betweenintensity of stimulus and frequency of nerve impulses, characteristicof many receptors, lies in the logarithmic relationship between themagnitude of the physical stimulus and the generator potential. Froman engineering point of view, sense organs are poor transducers inrespect to linearity, although good in respect to reducing a widerange of intensities to the somewhat limited frequency capacity ofnerve axons (600 pulses per second being the upper limit).

Central sensory processes

The classical somatosensory (skinsenses and kinesthesis) pathway in man, monkeys, and apes is made upof systems originating in both the posterior and anterolateralcolumns of the spinal cord. All sensory pathways are synapticallyinterrupted. Anterolateral-column pathways first synapse near thepoint of entry into the spinal cord. Posterior-column pathwayssynapse for the first time in the lowest region of the brain stem,the medulla.

In both pathways, crossing occurs after the firstsynapse, so that the left side of the brain is concerned with theright side of the body, as is true of vision and motor function. Inman and monkey, the second-order neurons of both sensory pathwayssynapse in the ventroposterior portion of the thala-mus withthird-order neurons which project to the cortical areas. Theclassical somatosensory pathway is conducted by the medial andspinothalamic lemnisci to the posterolateral point of the ventral nucleus, where it ends in a topographically organizedfashion, so that the body surface is projected upon this nucleus (forthe detail of this pathway, see Ruch & Patton 1965).

Somepathways, especially those of the antero-lateral column, have morethan three neurons. In the cat, for example, the spinothalamic tract,in the literal sense of the term (“one neuron from cord tothalamus”), does not exist; all of the second-order myelinatedfibers synapse before they reach the thalamus. This distinction canbe conveyed by speaking of spinothalamic tracts and spinothalamicchains or systems. With the present techniques for studyingexperimental degeneration in myelinated fibers by staining the axonrather than the disintegrating myelin sheath (and, of course,unmyelin-ated fibers), the extensiveness of the multisynapticpathways is just becoming appreciated. In brief, at various levels ofthe brain stem, many ascending axons give off branches to orterminate on neurons in the central gray matter and reticularsubstance (a deep-lying meshwork of fibers containing clusters ofcell bodies). From these levels, neuron chains proceed to certainthalamic areas which in turn connect with the cerebral cortex. Sincethe C-fiber system is stimulated peripherally by other than noxiousstimuli, the multineuron, fine-fiber ascending system is potentiallyconcerned with all forms of cutaneous sensation.

Two questionscan be asked concerning the transmission of sensory information inthe spinal cord through the thalamus to the cerebral cortex: First,to what degree is the energy specificity of the sense organ preservedat the first synaptic junction? Second, to what degree do thesecond-order and third-order neurons receive impulses from arestricted area of the skin? The answer to the latter is indicativeof, but not a measure of, the preservation of locus of stimulus inascending pathways.

Wall (1961), in recording from singlesecond-order neurons of the posterior horn (not to be confused withthe posterior column) of the spinal cord, has discovered that theytend to be fired by a variety of stimuli. The axons of these neuronsascend in the anterolateral columns, and the impression is gainedthat in some anterolateral systems the degree of fiber codingattained in the periphery is largely sacrificed at the first synapse.The kind of stimulation must, therefore, be coded in some otherdimension of the stream of afferent impulses. It should be mentionedthat reflex connections, as well as ascending axons, originate in theposterior horn and that many anterolateral and posterolateralascending pathways beside the spinothalamic tract have cells oforigin in this region.It seems, then, that in some ascendingpathways, specificity in relation to stimulus energy has been lost inthe transfer to secondary axons; either the information itself islost or else it is coded in some other fashion. Temporal patterningis suggested as the means of coding (Wall 1961).

Posterior-column pathways. The behavior of the sensorypathways which ascend the posterior columns of the spinal cordwithout synapsing and without crossing until they reach the medullais quite different. In the medulla, the second-order neurons, aftercrossing, give rise to the medial lemniscus, which ascends the brainstem to the thalamus. The transmission of information which conveysthe site of stimulation on the skin is considered by mostneurophysiologists to be a product of a topographical organization ofaxons within ascending pathways that is preserved throughout thethalamic relay nuclei and the thalamocortical projections. The resultis a kind of “isomorphism” between the peripheral arrayof skin receptors and the array of neurons making up the cerebralcortex. This organization must not be thought of in terms so crude asa single receptor being connected with a single cortical cell, anadjacent receptor with an adjacent cortical cell, etc. Such“structural canalization” of pathways seems to bealmost deliberately avoided, even in systems—such as the visual—whichhave a high degree of acuity and spatial discrimination.

Receptive fields. There is much interdigitation of freenerve endings in the skin which would seem unnecessary unless somebiological value is attained. On the other hand, the number ofchannels and the degree of their “insulation” from eachother (i.e., lack of convergence) at synaptic levels are highest forthe points of greatest acuity and spatial discrimination (e.g., thefovea of the retina and the tips of the fingers). One index oftopographical organization and potential acuity is the“receptive field.” The receptive field of a single axonor cell body is that area of skin from which the unit can bedischarged (or, in the case of the eye, the area of the visual fieldin which the unit can be discharged or inhibited). Thus, eachperipheral axon, secondary neuron, and cortical cell has a receptivefield.

The receptive fields of the second-order neurons of theposterior-column and the anterolateral-column pathways contrastsharply; the former are measured in millimeters, and the latter, incentimeters. Although large, the receptive fields of second-orderneurons on the anterolateral pathways are not splotchy buthomogeneous and are often round or elliptical, indicating that manyperipheral axons with adjacent or overlapping fields on theskin have converged in an orderly fashion.

Another finding, whichseems to pertain to even the posterior column system, is thatreceptive fields are larger at the cortical level than at the levelof the second-order neuron. This rule also holds in the visualsystem, where form appreciation can be seen in the divergence orwidening of the channel (Hubel & Wiesel 1965). In the skin senses, asimilar analysis has yet to be made empirically, although it has beensubject to speculation.

The anterolateral-column pathways are aphylo-genetically primitive system that receives impulses fromunmyelinated and fine myelinated fibers; that conducts impulses whichinform the brain of the state of the skin and tissues and, to somedegree, of the ambient environment and objects (e.g., their warmth orcoldness) but that may report poorly on spatial aspects of thestimulus. Geometrical patterns of warmed or cooled skin induced byradiant energy are very poorly discriminated. It may be important toknow that a hand or an arm is cold or painful but not that onemillimeter of skin is cold and the next warm. In contrast, theposterior-column pathways have been considered to convey knowledge ofthe objects forming the external world, the position of the body andthe limbs in space, and the accurate locus of stimulation (Ruch 1965).

In this generalization, the reservation should bemade that the anterolateral system of man and other primates is notthe primitive system of fibers seen in lower forms, but it does reachthe thala-mus and conveys some limited knowledge of the world.Because the posterior columns are rarely selectively interrupted bytrauma or tumor, the residual capacity of the spinothalamic and otherlateral, anterolateral, and ventral ascending pathways is poorlyunderstood. From experiments on monkeys (DeVito et al. 1964), it isknown that the discrimination of weights is initially impaired bysection of the posterior column but that the capacity to discriminatereturns virtually to normal. Weight discrimination is, from clinicalevidence, considered to be served primarily by posterior-columnsystems.

The somatosensory cortex. Buried in the centralfissure which divides the parietal from the frontal lobe is a narrowstrip of highly granular cortex typical of sensory areas in thecortex. On this and the adjacent zone of the postcentral gyrus isconcentrated a dense projection of fibers from so-called relaynuclei, which in turn receive fibers of the medial lemniscus and thespinothalamic tract (in primates). This cortical area, called thesomato-sensory cortex, is highly organized topographically, withrelatively large portions devoted to the skin areas having thegreatest acuity in two-point discrimination and the greatest accuracyin location of a point touched. According to Mountcastle (1961) thereceptive field of a single neuron in this region is relatively smallbut is calculated to be one hundred times that of a second-orderneuron. The size of the receptive field is smallest on the fingersand largest on the back, being roughly proportional to the spatialacuity of these regions.

Detour systems. In addition to theclassical somatosensory pathway, there are three additional pathways,termed detour systems (Ruch & Patton 1965) because they, in a sense,bypass the relay nuclei of the classical pathway. One is a projectionto the precentral gyrus from a thalamic nucleus which receives inputfrom the cerebellum and, hence, is potentially connected with thevarious spinocerebellar pathways.

The second is a projection offibers from the posterior thalamic nuclei to the posterior parietallobule, a so-called association area, lying behind the termination ofthe classical pathway. The posterior thalamic nuclei are believed toreceive impulses from the classic relay nucleus (some of the mostposterior ones receive impulses directly from the medial and spinallemniscus, but their cortical projection is not known withcertainty). At the time these systems were being traced anatomically,behavioral experiments showed that the posterior parietal area couldaccount for discrimination of weights independently of the precentralgyrus (Ruch et al. 1937). Furthermore, the combined destruction ofboth areas (parietal lobectomy) greatly impaired, but did notabolish, weight discrimination, even in chimpanzees. This and otherevidence (Kruger & Porter 1958) indicates that the classical motorarea serves a discriminative somatosensory function.

The thirdset of detour pathways is nonlemniscal and nonspinothalamic in thestrict sense but is nonetheless anterolateral in its spinal course.Ascending fibers terminate in or give off collaterals (some are nodoubt collaterals of spinothalamic fibers) to the bulbar reticularformation and, at midbrain levels, to the central gray matter, thesuperior colliculus, and the posterior thalamic nuclei near themedial geniculate body (Mehler et al. 1960). The thalamic nucleimedial to the relay of spinothalamic and lemniscal fibers alsoreceive a stream of the ascending fibers of anterolateral origin, aswell as impulses from multi-synaptic pathways deep in the reticularformation. The pathway has been termed thepaleospino-thalamic tract, to distinguish it from the direct, orneospinothalamic, tract (Bishop 1962). There is considerable reasonto believe that the diffuse, multisynaptic, unmyelinated, primitivesystem of fibers is involved in affect and pain experience.

Posterolateral tracts. Throughout this discussion, we havedrawn the classical contrast between posterior-column andanterolateral-column pathways. It is now clear that a posterolateraltract of the spinal cord also sends impulses to the somato-sensorycortex, with relays in the lateral cervical nucleus. This tract is afast-fiber system, impulses reaching the cerebral cortex more quicklythan those conducted in the posterior columns. Some fibers of thissystem have restricted receptive fields, while others respond broadlyin respect to place and kind of cutaneous stimulation. This systemhas been studied mainly electrophysiologically, and its significanceto sensation relative to the posterior-column andanterolateral-column systems has yet to be assessed.

Mechanisms of cerebral sensory function. Four aspects ofsensation can be arranged in a presumed order of phylogeneticdevelopment: affect, quality, intensity, and localization. Affectappears to develop at subcortical levels of the nervous system,probably as low as the midbrain. The quality of stimuli can becorrectly identified (e.g., touch, warmth) even after extensivecortical lesions, and recognition of quality is probably a thalamic,as well as a cortical, function. The discrimination of fine degreesof intensity is a function of the “motor” and“association” areas adjacent to the classicsomatosensory area of the postcentral gyrus in the cerebral cortex.Obviously, these two terms do not convey their sensory function.

In the ascending pathways, distortion of a simplestimulus-intensity-frequency-of-discharge arrangement arises from thetendency of second-order neurons and cortical neurons to firerepetitively in response to a single afferent stimulation.Nevertheless, the single thalamic units being fired by limbdisplacement reflect faithfully, in spikes per second, the degree ofjoint rotation (Mountcastle et al. 1963). Interestingly, thequantitative relationship between stimulus and response is a powerfunction rather than the logarithmic function postulated by theclassical Weber-Fechner law. This finding agrees with and supportsthe conclusion reached by Stevens (1961) on the basis ofpsychophysical experiments involving magnitude-scaling procedures andcross-modality ratio matching; such methods are powerful toolsapplicable widely in the social sciences. [See PSYCHOPHYSICS; SCALING; and the biographies of FECHNER and WEBER, ERNST HEINRICH.]

A broadrelation exists between accuracy in localization and the amount oftopographical organization in a system, the number of cortical unitsdevoted to an area of skin, and the size of the receptive fields.However, the extent of the receptive fields and of the area ofcerebral cortex activated by stimulation of a point on the skin aremuch too great to permit consideration of any true point-to-pointisomorphism between the skin and the somatosensory cortex.Corroborative evidence is provided by the fact that the ramificationsof single sensory neurons are so extensive that neuronsinterdigitate, and that size of the receptive field becomesprogressively larger higher up in the nervous system. There arecounterparts in the auditory system and in the visual system, whereoptical errors, light scatter, and small eye movements are alsohazards to a conception of a point-to-point relationship between theexternal world and the visual cortex. It may be speculated that allthese errors could have been minimized in the course of evolution.The occurrence of these dispersal processes must mean that theycontribute to, rather than detract from, acuity of spatialdiscrimination. It is probable that in all three sensory systems thenervous system behaves, not in terms of a mosaic of all-or-nothingpatches of cortical activation, but in modal points of maximumcortical activation (number of active neurons times frequency oftheir discharge).

The ability to discriminate modal points ofexcitability and such devices for sharpening these points as lateralinhibition and descending inhibitory influences on sensory systemsynapses provide a mechanism by which the fineness of“cortical grain” (i.e., the numbers of corticalneurons) extends discriminative ability beyond what could be achievedif sense organs were arranged in a mosaic, rather than aninterdigitating, fashion and were equipped with private pathways tothe cerebral cortex. An alternative to this statistical conception ofspatial discrimination is a very successful “atomistic”analysis of the visual cortex by Hubel and Wiesel (1965), in whichdivergence in the system at each synaptic level endows it withincreasingly subtle powers of spatial movement and formdiscrimination.

Theodore C. Ruch

[Directly related are the entriesNervous System, article OnStructure Andfunction OF The Brain; Pain; Senses, article onCentral Mechanisms. Other relevant material may be found inBody Image; Hearing; Perception, article onDepth Perception; Psychology, article onPhysiological Psychology; Psychophysics; Senses; Tasteandsmell; Vision.]

BIBLIOGRAPHY

Bishop, George H. 1962Normal and Abnormal Sensory Patterns: Pain. I: Anatomical,Physiological and Psychological Factors in Sensation of Pain. Pages95-133 in Robert Grenell (editor), Neural Physiopathol-ogy. New York:Harper.

Boring, Edwin G. 1942 Sensation and Perception in theHistory of Experimental Psychology. New York: Appleton.

DsViTO,J.; Ruch, T. C.; and Patton, H. D. 1964 Analysis of Residual WeightDiscriminatory Ability and Evoked Cortical Potentials FollowingSection of Dorsal Columns in Monkeys. Indian Journal of Physiologyand Pharmacology 8:117-126.

Douglas, W. W.; Ritchie, J. M.; andStraus, R. W. 1960 The Role of Non-myelinated Fibres in SignallingCooling of the Skin. Journal of Physiology 150:266-283.

Head,Henry et al. 1920 Studies in Neurology. 2 vols. London: Hodder& Stoughton. → These papers consist mainly of arepublication of papers published in Brain between 1905 and 1918.

Hensel, Herbert; and Boman, Kurt K. A. 1960 Afferent Impulses inCutaneous Sensory Nerves in Human Subjects. Journal ofNeurophysiology 23:564-578.

Hubel, David H.; and Wiesel, Torstonn. 1965 Receptive Fields and Functional Architecture in TwoNon-striate Visual Areas (18 and 19) of the Cat. Journal ofNeurophysiology 28:229-289.

Iggo, A. 1959 Cutaneous Heat and ColdReceptors With Slowly Conducting (C) Afferent Fibres. QuarterlyJournal of Experimental Physiology 44:362-370.

Iggo, A. 1965 ThePeripheral Mechanisms of Cutaneous Sensation. Pages 92-100 in DavidR. Curtis and A. K. Mclntyre (editors), Studies in Physiology,Presented to John C. Eccles. New York: Springer.

Iggo, A.; andMuir, A. R. 1963 A Cutaneous Sense Organ in the Hairy Skin of Cats.Journal of Anatomy 97:151 only. → An abstract.

Kruger,Lawrence; and Porter, Phyllis 1958 A Behavioral Study of theFunctions of the Rolandic Cortex in the Monkey. Journal ofComparative Neurology 109:439-469.

Mehler, William R.; Feferman,Martin E.; and Nauta, Walle J. H. 1960 Ascending Axon DegenerationFollowing Anterolateral Cordotomy: An Experimental Study in theMonkey. Brain 83:718-750.

Mountcastle, Vernon B. 1961 SomeFunctional Properties of the Somatic Afferent System. Pages 403-436in Symposium on Principles of Sensory Communication, Endicott House,1959, Sensory Communication. Cambridge, Mass.: M.I.T. Press.

Mountcastle, Vernon B.; Poggio, Gian F.; and Werner, Gerhard 1963The Relation of Thalamic Cell Response to Peripheral Stimuli VariedOver an Intensive Continuum. Journal of Neurophysiology 26:807-834.

Poggio, Gian F.; and Mountcastle, Vernon B. 1960 A Study of theFunctional Contributions of the Lem-niscal and Spinothalamic Systemsto Somatic Sensibility. Johns Hopkins Hospital, Bulletin 106:266-316.

Powell, Thomas P.; and Mountcastle, Vernon B. 1959 Some Aspects ofthe Functional Organization of the Cortex of the Postcentral Gyrus ofthe Monkey:A Correlation of Findings Obtained in a Single UnitAnalysis With Cytoarchitecture. Johns Hopkins Hospital, Bulletin105:133-162.

Rose, Jehzy E.; and Mountcastle, Vernon B. 1959Touch and Kinesthesis. Volume 1, section 1, pages 387-429 in Handbookof Physiology. Washington: American Physiological Society.

Ruch,Theodore C.; Fulton, J. F.; and German, W. J. 1937 SensoryDiscrimination in Monkey, Chimpanzee and Man After Lesions on theParietal Lobe. Archives of Neurology and Psychiatry 39:919-937.

Ruch, Theodore C.; and Patton, Harry D. (editors) 1965 Physiologyand Biophysics. 19th ed. Philadelphia: Saunders. → The firstedition was published in 1905 as A Textbook of Physiology for MedicalStudents and Physicians, by William H. Howell.

Sherrington,Charles S. (1906) 1948 The Integrative Action of the Nervous System.2d ed. New Haven: Yale Univ. Press.

Stevens, S. S. 1961 ThePsychophysics of Sensory Function. Pages 1-33 in Symposium onPrinciples of Sensory Communication, Endicott House, 1959, Sensor;/Communication. Edited by Walter A. Rosenblith. Cambridge, Mass.:M.I.T. Press.

Wall, Patrick D. 1961 Two Transmission Systems forSkin Sensations. Pages 475-496 in Symposium on Principles of SensoryCommunication, Endicott House, 1959, Sensory Communication. Edited byWalter A. Rosenblith. Cambridge, Mass.: M.I.T. Press.

Weddell,Graham 1961 Receptors for Somatic Sensation. Volume 1, pages 13-48 inConference on Brain and Behavior, Brain and Behavior. Edited by MaryA. B. Brazier. Washington: American Institute of Biological Sciences.

skin The skin is the largest organ of the human body, exceeding two square metres in area in the average adult. Whilst it is rarely more than 2 mm in thickness, the skin plus subcutaneous fat may weigh 9 kg — approximately 14% of the body weight. The primary function of skin is to act as a physical barrier between the organism and its external environment, preventing water loss in dry conditions, hydration in humid or aquatic environments, and access to the body by microbes, and screening the harmful effects of ultraviolet rays of the sun. The skin also plays an important role in transmitting signals from the external environment and in regulating body temperature. The structure of skin confers mechanical strength, enabling it to withstand considerable physical insults, and when it is breached, it exhibits an amazing power of regeneration and repair.The epidermis, the outer layer of the skin, is a multi-layered epithelium approximately 0.1 mm thick, although there are great variations, such as on the palms and soles, where it may reach 1.4 mm. (The underlying dermis is about 3 mm thick.) The major cell type of the epidermis is the keratinocyte, so named because of the protein keratin, which it synthesizes in abundance. The epidermis is in a state of constant turnover, with keratinocytes being generated by mitosis (cell division) in a basal layer adjacent to the underlying dermis, and daughter cells passing outward toward the skin surface through successive stages of differentiation, characterized by dramatic changes in shape and size (see figure). After leaving the basal layer, the cells become large and polyhedral (spinous), and are joined to adjacent cells by complex structures called ‘desmosomes’, which are like spot welds. This spinous layer may be several cells thick, with the cells becoming increasingly flattened before they form the granular layer and then ultimately the cornified horny outer layer, in which the cells lose most of their internal structures including their nuclei and essentially become dead packages of compacted keratin coated with lipid. Cell-to-cell adhesive processes degenerate and the dead cells are eventually shed from the skin surface. It takes 26–42 days for a cell to transit from the basal layer to the outer horny layer, and a further 14 days before being shed, so the epidermis can completely replace itself within two months. The rate of epidermal cell turnover is normally strictly controlled, but a number of diseases are characterized by epidermal hyperproliferation. In psoriasis, for example, the rate may be increased twenty-fold.

The keratin proteins within the keratinocytes are fundamental to the protective functioning and integrity of the skin. The mixture of compacted fibrous keratins in the outer horny layer (the word, ‘keratin’ is derived from the Greek keratos, meaning horn) is highly stable, inert, hard, waterproof, and resistant to physical insult, and therefore is ideally suited to act as a protective layer. The dehydrated nature of the horny surface layer together with an acidic environment due to various secretions, makes it an inhospitable environment for microorganisms. That this outer surface of dead, keratin-rich cell layers is important in regulating water loss or skin saturation in humid conditions and infection can be demonstrated by removal of the outer layers by successive stripping with sellotape. The resulting denuded skin surface is highly permeable to water and susceptible to infection by a number of microorganisms. Defects in keratins have now been identified as having a causal role in a number of skin disorders.

Other cell types within the epidermis include melanocytes, Langerhan cells, and Merkel cells. The melanocytes are confined to the basal cell layer, are highly dendritic (i.e. they have many branching extensions, like nerve cells), and synthesize the pigment melanin, which moves into surrounding keratinocytes, via the dendritic processes, in small packages termed melanosomes. The Langerhan cells appear to be involved in immunological monitoring of the skin, while the Merkel cells are associated with sensory perception.The dermisis a dense fibroelastic tissue, of which the major constituents are collagen, forming a fibrous rope-like network predominantly in a plane parallel to the epidermis, and elastic fibres, which form a fine network in all directions. The collagen fibres confer tensile strength to the tissue, while elastic fibres allow restoration of the normal skin architecture following deformation by external mechanical forces. The space between this fibrillar network is filled with glycosaminoglycans, which are large polysaccharides, and, although they are present in small amounts, they bind vast amounts of water, forming a gel-like matrix which controls the tone and turgor of the tissue and helps to resist compressive forces. The outer region of the dermis is highly uneven, with numerous projections called papillae, which conform tightly to the contours of the epidermis, imparting a resistance to sheer forces upon it. The boundary between the epidermis and dermis is demarcated by a thin membrane and by complex structures which ensure tight anchorage of each to the other. Defects in some of these junctional complexes are associated with certain blistering diseases, such as epidermolysis bullosa, where there there is an abnormality of anchoring fibrils. The dermis contains a number of structures which are derived during development from the epidermal layer, notably sweat and sebaceous glands and hair follicles.

The dermis has a copious blood supply, with capillaries extending right up into the dermal papillae projections; these are the nearest vessels to the epidermis, which is itself avascular. Constriction or dilation of the blood vessels alters the temperature of the skin, plays an important role in whole body temperature regulation, and may be observed as pallor or flushing. The skin also has a rich sensory nerve supply, particularly abundant on the face, hands, and genitalia. Some nerve endings lie in the epidermis adjacent to Merkel cells, where they can detect pain, temperature changes, and itch. Nerves of the sympathetic system are associated with blood vessels, sweat glands, and the arrector pili muscles of hairs, which allow hairs to ‘stand on end’.

Hair

While in most animals hair and fur plays an important role in heat conservation, in humans its primary function is in sexual attraction. The keratinous hairs cover the whole body surface except the palms and soles, and are present as either ‘terminal’ hair characterized by that of the scalp, or ‘vellus’ hair such as the very fine short body hairs. Hair fibres arise as a result of cell division within the hair follicles, which go through a cyclical pattern of active growth, regression, and a resting phase. The rate of hair growth varies depending upon body site: eyebrow hair, for example, grows much faster than the scalp hair rate of about 0.33 mm per day. Loss of hair in males (male pattern baldness) is essentially inherited and androgen-dependent: from the second decade, following multiple growth cycles, the terminal hairs gradually convert to fine vellus hairs. Other types of baldness (alopecia) may occur due to infection or immunological disorders.

Sebaceous glands

are sac-like structures that arise from an epithelial outgrowth of the hair follicle outer root sheath, and are composed of a single cell type, the sebocyte. The gland produces an oily ‘sebum’ secretion, of unknown function. The glands remain immature until puberty, and it is the secretion of sebum that is associated with pubertal acne. This is a chronic inflammation of the hair follicle and sebaceous gland (pilosebaceous unit) characterized by pustules, comedones (blackheads), cysts, and scars, and it affects most adolescents. Treatments may include anti-androgens, retinoids, or antibiotics.

Sweat glands

are of two types. Eccrine sweat glands are distributed over almost all of the body surface (2–4 million in total), but they are particularly numerous on the palms, soles, axillae, and forehead. The eccrine sweat gland is a simple unbranched tube which runs from the epidermal surface deep into the dermis, where it develops into a coiled structure. These glands are responsible for the secretion of large amounts of sweat, particularly during strenuous exercise or heat stress, when up to 10 litres a day may be produced; evaporation of the sweat cools the body. Elevated sweat production may also be stimulated by emotion or the consumption of spicy food. Apocrine sweat glands differ from the eccrine in that the gland ducts discharge into the lumen of a hair follicle; also they are confined mainly to the underarms, and the genital area in women. Their secretion is probably of limited functional significance, but as a result of bacterial action it is responsible for body odour.

Wound healing

Skin has an amazing ability to heal wounds, but the rate of healing is dependent upon the severity of the wound. Superficial wounds may be repaired rapidly by simple migration of keratinocytes over the defect. Deeper wounds involve blood coagulation, inflammation, re-epithelialization, wound contraction, and new tissue synthesis and remodelling. These processes have been optimized for rapid wound closure, thus preventing fluid loss and infection, but usually at the expense of subsequent function and cosmetic appearance by the formation of scar tissue. Some large wounds, such as severe burns, may be assisted in their healing response by grafts, or by the use of keratinocyte sheets — grown in the laboratory from keratinocytes derived from biopsies of the patient's own skin. Much research effort is currently devoted to accelerating wound healing and reducing scar formation.

Sun exposure

Exposure of the skin to non-ionizing ultraviolet emissions of the sun is unavoidable, but the effect of such exposure is dependent upon both skin type and the length of exposure. Skin is classified as a certain type depending upon its susceptibility to burn, ranging from type I for very fair skin which burns easily and never tans, to type VI-black negroid skin. Within the spectrum of sunlight, ultraviolet B (UVB, 290–320 nm wavelength) causes sunburn, while both UVB and UVA (320–400 nm) will induce pigmentation. UVB is predominantly absorbed by the outer horny layer, allowing only about 10% to reach the dermis, while all UVA penetrates the epidermis to reach the dermis. Exposure to UVA (the predominant wavelength used in sunbeds) is therefore likely to be a major contributor to connective tissue damage in the dermis, resulting in the features of aged, wrinkled skin. More seriously, sun exposure is a major cause of skin cancer (see below).

Sun exposure does have some benefits, such as promoting the synthesis of vitamin D3 from its precursor in the skin, while stimulation of tanning has a protective effect from subsequent sun exposure. Many psoriasis patients also exhibit a marked improvement in their disease following sun exposure.

Ageing

Aged sun-protected skin is characterized by a general laxity, thinning, and the presence of numerous fine wrinkles. The skin becomes less elastic, is greatly reduced in its tensile strength, and exhibits a diminished ability to resist various insults such as injury, infection, and irritants. Chronic sun exposure induces substantial photoageing characterized by a coarse leathery texture, loss of elasticity, deep wrinkles, yellowish colouration, and the presence of numerous irregular pigmented lesions including actinic keratoses. While the youth of today may regard a deep tan as attractive, in their later years they will undoubtedly suffer the consequences of their actions. A more sinister consequence of prolonged sun exposure is the greatly increased incidence of both benign and malignant tumours.

Skin diseases

In the UK, skin diseases account for approximately 10% of patient visits to general practitioners and 6% of hospital outpatient referrals, and this, combined with the fact that they are the most prevalent cause of occupational absence, has substantial economic implications. In addition, many skin diseases, such as those that are debilitating or particularly apparent and extensive, can have serious psychological effects. Some of the more common skin complaints include urticaria (an eruption characterized by usually itchy weals and swelling), acne, viral warts, infections (bacterial, viral or fungal such as ringworm and athlete's, foot), eczema/dermatitis, rashes, and psoriasis. Psoriasis affects approximately 2% of the population in Europe and North America, and is characterized by well demarcated, inflammatory red plaques topped by silvery scales; it is a major medical problem, causing anxiety and distress, and can be debilitating in severe cases. Although our knowledge of the disease has progressed greatly in recent years, the primary cause of the excessive epidermal proliferation which underlies psoriasis has eluded major worldwide research efforts.

Tumours

Tumours of the skin may be benign or malignant. Benign epidermal tumours such as ‘seborrheic keratoses’ are extremely common. Malignant skin tumours are much the commonest type of cancer overall. Excess exposure, particularly of pale Caucasian skin to ultraviolet irradiation in the form of sunlight, is currently recognized as the major cause of skin cancers, of which the most frequent are basal cell carcinomas (rodent ulcers), squamous cell carcinomas, and malignant melanoma. Basal cell carcinomas are most frequently found on the faces of middle-aged or elderly patients and do not spread to other parts of the body, whereas squamous cell carcinomas may spread. Both of these tumour types are derived from keratinocytes, and are usually treated by simple excision. Malignant melanomas are derived from epidermal melanocytes, and frequently arise from pre-existing pigmented lesions such as moles. The incidence has increased dramatically over the last two decades and this is the most lethal of all skin cancers, spreading rapidly to other organs. If caught at an early stage, however, the prognosis is good, and, due to public education campaigns, the use of sun screens has become more prevalent, and patients are presenting at the clinic much earlier.

Cosmetics

Cosmetics play an important role in skin protection, either as moisturizers or sunscreens, but many are simply used to promote attractiveness, to mask unwanted smells, or to impart pleasant smells and camouflage skin defects. Many contain so-called active ingredients which may alleviate the damage inflicted by sun exposure such as anti-wrinkle creams, or skin lightening creams, or artificial tanning creams. However, a number of cosmetic preparations may elicit a reaction in some people resulting in either irritant dermatitis or allergic sensitivity and contact urticaria.

Mike Edward, and Rona Mackie

Bibliography

MacKie, R. M. (1997). Healthy skin — the facts. Oxford University Press, Oxford.
MacKie, R. M. (1996). Clinical dermatology, 4th ed. Oxford University Press, Oxford.

Skin Lesion Removal

Definition

Skin lesion removal employs a variety of techniques, from relatively simple biopsies to more complex surgical excisions, to remove lesions that range from benign growths to malignant melanoma.

Purpose

Sometimes the purpose of skin lesion removal is to excise an unsightly mole or other cosmetically unattractive skin growth. Other times, physicians will remove a skin lesion to make certain it is not cancerous, and, if it proves cancerous, to prevent its spread to other parts of the body.

Precautions

Most skin lesion removal procedures require few precautions. The area to be treated is cleaned before the procedure with alcohol or another antibacterial preparation, but generally it is not necessary to use a sterile operating room. Most procedures are performed on an outpatient basis, using a local anesthetic. Some of the more complex procedures may require specialized equipment available only in an outpatient surgery center. Most of the procedures are not highly invasive and, frequently, can be well-tolerated by young and old patients, as well as those with other medical conditions.

Description

A variety of techniques are used to remove skin lesions. The particular technique selected will depend on such factors as the seriousness of the lesion, its location, and the patient's ability to tolerate the procedure. Some of the simpler techniques, such as a biopsy or cryosurgery, can be performed by a primary care physician. Some of the more complex techniques, such as excision with a scalpel, electrosurgery, or laser surgery, are typically performed by a dermatologic surgeon, plastic surgeon, or other surgical specialist. Often, the technique selected will depend on how familiar the physician is with the procedure and how comfortable he or she is with performing it.

Biopsy

In this procedure, the physician commonly injects a local anesthetic at the site of the skin lesion, then removes a sample of the lesion, so that a definite diagnosis can be made. The sample is sent to a pathology laboratory, where it is examined under a microscope. Certain characteristic skin cells, and their arrangement in the skin, offer clues to the type of skin lesion, and whether it is cancerous or otherwise poses danger. Depending on the results of the microscopic examination, additional surgery may be scheduled.

A variety of methods are used to obtain a skin biopsy. The physician may use a scalpel to cut a piece or remove all of the lesion for examination. Lesions that are confined to the surface may be sampled with a shave biopsy, where the physician holds a scalpel blade parallel to the surface of the skin and slides the blade across the base of the lesion, removing a sample. Some physicians use a single-edge razor blade for this, instead of a scalpel. A physician may also perform a punch biopsy, in which a small circular punch removes a plug of skin.

Excision

When excising a lesion, the physician attempts to remove it completely by using a scalpel to cut the shape of an ellipse around the lesion. Leaving an elliptical wound, rather than a circular wound, makes it easier to insert stitches. If a lesion is suspected to be cancerous, the physician will not cut directly around the lesion, but will attempt to also remove a healthy margin of tissue surrounding it. This is to ensure that no cancerous cells remain, which would allow the tumor to reappear. To prevent recurrence of basal and squamous cell skin cancers, experts recommend a margin of 0.08-0.16 in (2-4 mm) for malignant melanoma, the margin may be 1.2 in (3 cm) or more.

Destruction

Not all lesions need to be excised. A physician may simply seek to destroy the lesion using a number of destructive techniques. These techniques do not leave sufficient material to be examined by a pathologist, however, and are best used in cases where a visual diagnosis is certain.

• Cryosurgery. This technique employs an extremely cold liquid or instrument to freeze and destroy abnormal skin cells that require removal. Liquid nitrogen is the most commonly used cryogen. It is typically sprayed on the lesion in several freeze-thaw cycles to ensure adequate destruction of the lesion.
• Curettage. In this procedure, an instrument with a circular cutting loop at the end is drawn across the lesion, starting at the middle and moving outward. With successive strokes, the physician scrapes portions of the lesion away. Sometimes a physician will use the curet to reduce the size of the lesion before turning to another technique to finish removing it.
• Electrosurgery. This utilizes an alternating current to selectively destroy skin tissue. Depending on the type of current and device used, physicians may use electrosurgical equipment to dry up surface lesions (electrodessication), to burn off the lesion (electrocoagulation), or to cut the lesion (electrosection). One advantage of electrosurgery is that it minimizes bleeding.

Mohs' micrographic surgery

The real extent of some lesions may not be readily apparent to the eye, making it difficult for the surgeon to decide where to make incisions. If some cancer cells are left behind, for example, the cancer may reappear or spread. In a technique called Mohs' micrographic surgery, surgeons begin by removing a lesion and examining its margins under a microscope for evidence of cancer. If cancerous cells are found, the surgeon then removes another ring of tissue and examines the margins again. The process is repeated until the margins appear clear of cancerous cells. The technique is considered ideal for aggressive tumors in areas such as the nose or upper lip, where an excision with wide margins may be difficult to repair, and may leave a cosmetically poor appearance.

Lasers

Laser surgery is now applied to a variety of skin lesions, ranging from spider veins to more extensive blood vessel lesions called hemangiomas. Until recently, CO₂ lasers were among the more common laser devices used by physicians, primarily to destroy skin lesions. Other lasers, such as the Nd:YAG and flashlamp-pumped pulse dye laser have been developed to achieve more selective results when used to treat vascular lesions, such as hemangiomas, or pigmented lesions, such as café-au-lait spots.

Preparation

No extensive preparation is required for skin lesion removal. Most procedures can be performed on an outpatient basis with a local anesthetic. The lesion and surrounding area is cleaned with an antibacterial compound before the procedure. A sterile operating room is not required.

Aftercare

The amount of aftercare will vary, depending on the skin lesion removal technique. For biopsy, curettage, cryosurgery, and electrosurgery procedures, the patient is told to keep the wound clean and dry. Healing will take at least several weeks, and may take longer, depending on the size of the wound and other factors. Healing times will also vary with excisions and with Mohs' micrographic surgery, particularly if a skin graft or skin flap is needed to repair the resulting wound. Laser surgery may produce changes in skin coloration that often resolve in time. Pain is usually minimal following most outpatient procedures, so pain medicines are not routinely prescribed. Some areas of the body, such as the scalp and fingers, can be more painful than others, however, and a pain medicine may be required.

Risks

All surgical procedures present risk of infection. Keeping the wound clean and dry can minimize the risk. Antibiotics are not routinely given to prevent infection in skin surgery, but some doctors believe they have a role. Other potential complications include:

• bleeding below the skin, which may create a hematoma and sometimes requires the wound to be reopened and drained,
• temporary or permanent nerve damage resulting from excision in an area with extensive and shallow nerve branches,
• wounds that may reopen after they have been stitched closed, increasing the risk of infection and scarring.

Normal results

Depending on the complexity of the skin lesion removal procedure, patients can frequently resume their normal routine the day of surgery. Healing frequently will take place within weeks. Some excisions will require later reconstructive procedures to improve the appearance left by the original procedure.

Abnormal results

In addition to the complications outlined above, it is always possible that the skin lesion will reappear, requiring further surgery.

Resources

ORGANIZATIONS

American Academy of Dermatology. 930 N. Meacham Road, P.O. Box 4014, Schaumburg, IL 60168-4014. (847) 330-0230. Fax: (847) 330-0050. 〈http://www.aad.org〉.

American Society for Dermatologic Surgery. 930 N. Meacham Road, P.O. Box 4014, Schaumburg, IL 60168-4014. (847) 330-9830. 〈http://www.asds-net.org〉.

American Society of Plastic and Reconstructive Surgeons. 44 E. Algonquin Rd., Arlington Heights, IL 60005. (847) 228-9900. 〈http://www.plasticsurgery.org〉.

KEY TERMS

Curet— A surgical instrument with a circular cutting loop at one end. The curet is pulled over the skin lesion in repeated strokes to remove one portion of the lesion at a time.

Mohs' micrographic surgery— A surgical technique in which successive rings of skin tissue are removed and examined under a microscope to ensure that no cancer is left.

Shave biopsy— A method of removing a sample of skin lesion so it can be examined by a pathologist. A scalpel or razor blade is held parallel to the skin's surface and is used to slice the lesion at its base.