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4.5: Diseases, Disorders, and Injuries - Biology

4.5: Diseases, Disorders, and Injuries - Biology


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The integumentary system is susceptible to a variety of diseases, disorders, and injuries. In this section, you will learn several of the most common skin conditions.

One of the most talked about diseases is skin cancer. Cancer is a broad term that describes diseases caused by abnormal cells in the body dividing uncontrollably. Most cancers are identified by the organ or tissue in which the cancer originates. One common form of cancer is skin cancer. The Skin Cancer Foundation reports that one in five Americans will experience some type of skin cancer in their lifetime. The degradation of the ozone layer in the atmosphere and the resulting increase in exposure to UV radiation has contributed to its rise. Overexposure to UV radiation damages DNA, which can lead to the formation of cancerous lesions. Although melanin offers some protection against DNA damage from the sun, often it is not enough. The fact that cancers can also occur on areas of the body that are normally not exposed to UV radiation suggests that there are additional factors that can lead to cancerous lesions.

In general, cancers result from an accumulation of DNA mutations. These mutations can result in cell populations that do not die when they should and uncontrolled cell proliferation that leads to tumors. Although many tumors are benign (harmless), some produce cells that can mobilize and establish tumors in other organs of the body; this process is referred to as metastasis. Cancers are characterized by their ability to metastasize.

Basal cell carcinoma is a form of cancer that affects the mitotically active stem cells in the stratum basale of the epidermis. It is the most common of all cancers that occur in the United States and is frequently found on the head, neck, arms, and back, which are areas that are most susceptible to long-term sun exposure. Although UV rays are the main culprit, exposure to other agents, such as radiation and arsenic, can also lead to this type of cancer. Wounds on the skin due to open sores, tattoos, burns, etc. may be predisposing factors as well. Basal cell carcinomas start in the stratum basale and usually spread along this boundary. At some point, they begin to grow toward the surface and become an uneven patch, bump, growth, or scar on the skin surface (Figure 4.18). Like most cancers, basal cell carcinomas respond best to treatment when caught early. Treatment options include surgery, freezing (cryosurgery), and topical ointments (Mayo Clinic 2012).

Figure 4.18. Basal Cell Carcinoma
Basal cell carcinoma can take several different forms. Similar to other forms of skin cancer, it is readily cured if caught early and treated. (credit: John Hendrix, MD)

Squamous cell carcinoma is a cancer that affects the keratinocytes of the stratum spinosum and presents as lesions commonly found on the scalp, ears, and hands (Figure 4.19). It is the second most common skin cancer. The American Cancer Society reports that two of 10 skin cancers are squamous cell carcinomas, and it is more aggressive than basal cell carcinoma. If not removed, these carcinomas can metastasize. Surgery and radiation are used to cure squamous cell carcinoma.

Figure 4.19. Squamous Cell Carcinoma
Squamous cell carcinoma presents here as a lesion on an individual’s nose. (credit: the National Cancer Institute)

A melanoma is a cancer characterized by the uncontrolled growth of melanocytes, the pigment-producing cells in the epidermis. Typically, a melanoma develops from a mole. It is the most fatal of all skin cancers, as it is highly metastatic and can be difficult to detect before it has spread to other organs. Melanomas usually appear as asymmetrical brown and black patches with uneven borders and a raised surface (Figure 4.20). Treatment typically involves surgical excision and immunotherapy.

Figure 4.20. Melanoma
Melanomas typically present as large brown or black patches with uneven borders and a raised surface. (credit: the National Cancer Institute)

Doctors often give their patients the following ABCDE mnemonic to help with the diagnosis of early-stage melanoma. If you observe a mole on your body displaying these signs, consult a doctor.

  • Asymmetry – the two sides are not symmetrical
  • Borders – the edges are irregular in shape
  • Color – the color is varied shades of brown or black
  • Diameter – it is larger than 6 mm (0.24 in)
  • Evolving – its shape has changed

Some specialists cite the following additional signs for the most serious form, nodular melanoma:

  • Elevated – it is raised on the skin surface
  • Firm – it feels hard to the touch
  • Growing – it is getting larger

Two common skin disorders are eczema and acne. Eczema is an inflammatory condition and occurs in individuals of all ages. Acne involves the clogging of pores, which can lead to infection and inflammation, and is often seen in adolescents. Other disorders, not discussed here, include seborrheic dermatitis (on the scalp), psoriasis, cold sores, impetigo, scabies, hives, and warts.

Eczema is an allergic reaction that manifests as dry, itchy patches of skin that resemble rashes (Figure 4.21). It may be accompanied by swelling of the skin, flaking, and in severe cases, bleeding. Many who suffer from eczema have antibodies against dust mites in their blood, but the link between eczema and allergy to dust mites has not been proven. Symptoms are usually managed with moisturizers, corticosteroid creams, and immunosuppressants.

Figure 4.21. Eczema
Eczema is a common skin disorder that presents as a red, flaky rash. (credit: “Jambula”/Wikimedia Commons)

Acne is a skin disturbance that typically occurs on areas of the skin that are rich in sebaceous glands (face and back). It is most common along with the onset of puberty due to associated hormonal changes, but can also occur in infants and continue into adulthood. Hormones, such as androgens, stimulate the release of sebum. An overproduction and accumulation of sebum along with keratin can block hair follicles. This plug is initially white. The sebum, when oxidized by exposure to air, turns black. Acne results from infection by acne-causing bacteria (Propionibacterium and Staphylococcus), which can lead to redness and potential scarring due to the natural wound healing process (Figure 4.22).

Figure 4.22. Acne
Acne is a result of over-productive sebaceous glands, which leads to formation of blackheads and inflammation of the skin.

Because the skin is the part of our bodies that meets the world most directly, it is especially vulnerable to injury. Injuries include burns and wounds, as well as scars and calluses. They can be caused by sharp objects, heat, or excessive pressure or friction to the skin.

Skin injuries set off a healing process that occurs in several overlapping stages. The first step to repairing damaged skin is the formation of a blood clot that helps stop the flow of blood and scabs over with time. Many different types of cells are involved in wound repair, especially if the surface area that needs repair is extensive. Before the basal stem cells of the stratum basale can recreate the epidermis, fibroblasts mobilize and divide rapidly to repair the damaged tissue by collagen deposition, forming granulation tissue. Blood capillaries follow the fibroblasts and help increase blood circulation and oxygen supply to the area. Immune cells, such as macrophages, roam the area and engulf any foreign matter to reduce the chance of infection.

A burn results when the skin is damaged by intense heat, radiation, electricity, or chemicals. The damage results in the death of skin cells, which can lead to a massive loss of fluid. Dehydration, electrolyte imbalance, and renal and circulatory failure follow, which can be fatal. Burn patients are treated with intravenous fluids to offset dehydration, as well as intravenous nutrients that enable the body to repair tissues and replace lost proteins. Another serious threat to the lives of burn patients is infection. Burned skin is extremely susceptible to bacteria and other pathogens, due to the loss of protection by intact layers of skin.

Burns are sometimes measured in terms of the size of the total surface area affected. This is referred to as the “rule of nines,” which associates specific anatomical areas with a percentage that is a factor of nine (Figure 4.23). Burns are also classified by the degree of their severity. A first-degree burn is a superficial burn that affects only the epidermis. Although the skin may be painful and swollen, these burns typically heal on their own within a few days. Mild sunburn fits into the category of a first-degree burn. A second-degree burn goes deeper and affects both the epidermis and a portion of the dermis. These burns result in swelling and a painful blistering of the skin. It is important to keep the burn site clean and sterile to prevent infection. If this is done, the burn will heal within several weeks. A third-degree burn fully extends into the epidermis and dermis, destroying the tissue and affecting the nerve endings and sensory function. These are serious burns that may appear white, red, or black; they require medical attention and will heal slowly without it. A fourth-degree burn is even more severe, affecting the underlying muscle and bone. Oddly, third and fourth-degree burns are usually not as painful because the nerve endings themselves are damaged. Full-thickness burns cannot be repaired by the body, because the local tissues used for repair are damaged and require excision (debridement), or amputation in severe cases, followed by grafting of the skin from an unaffected part of the body, or from skin grown in tissue culture for grafting purposes.

Figure 4.23. Calculating the Size of a Burn
The size of a burn will guide decisions made about the need for specialized treatment. Specific parts of the body are associated with a percentage of body area.

Scars and Keloids

Most cuts or wounds, with the exception of ones that only scratch the surface (the epidermis), lead to scar formation. A scar is collagen-rich skin formed after the process of wound healing that differs from normal skin. Scarring occurs in cases in which there is repair of skin damage, but the skin fails to regenerate the original skin structure. Fibroblasts generate scar tissue in the form of collagen, and the bulk of repair is due to the basket-weave pattern generated by collagen fibers and does not result in regeneration of the typical cellular structure of skin. Instead, the tissue is fibrous in nature and does not allow for the regeneration of accessory structures, such as hair follicles, sweat glands, or sebaceous glands.

Sometimes, there is an overproduction of scar tissue, because the process of collagen formation does not stop when the wound is healed; this results in the formation of a raised or hypertrophic scar called a keloid. In contrast, scars that result from acne and chickenpox have a sunken appearance and are called atrophic scars.

Scarring of skin after wound healing is a natural process and does not need to be treated further. Application of mineral oil and lotions may reduce the formation of scar tissue. However, modern cosmetic procedures, such as dermabrasion, laser treatments, and filler injections have been invented as remedies for severe scarring. All of these procedures try to reorganize the structure of the epidermis and underlying collagen tissue to make it look more natural.

Bedsores and Stretch Marks

Skin and its underlying tissue can be affected by excessive pressure. One example of this is called a bedsore. Bedsores, also called decubitis ulcers, are caused by constant, long-term, unrelieved pressure on certain body parts that are bony, reducing blood flow to the area and leading to necrosis (tissue death). Bedsores are most common in elderly patients who have debilitating conditions that cause them to be immobile. Most hospitals and long-term care facilities have the practice of turning the patients every few hours to prevent the incidence of bedsores. If left untreated by removal of necrotized tissue, bedsores can be fatal if they become infected.

The skin can also be affected by pressure associated with rapid growth. A stretch mark results when the dermis is stretched beyond its limits of elasticity, as the skin stretches to accommodate the excess pressure. Stretch marks usually accompany rapid weight gain during puberty and pregnancy. They initially have a reddish hue, but lighten over time. Other than for cosmetic reasons, treatment of stretch marks is not required. They occur most commonly over the hips and abdomen.

When you wear shoes that do not fit well and are a constant source of abrasion on your toes, you tend to form a callus at the point of contact. This occurs because the basal stem cells in the stratum basale are triggered to divide more often to increase the thickness of the skin at the point of abrasion to protect the rest of the body from further damage. This is an example of a minor or local injury, and the skin manages to react and treat the problem independent of the rest of the body. Calluses can also form on your fingers if they are subject to constant mechanical stress, such as long periods of writing, playing string instruments, or video games. A corn is a specialized form of callus. Corns form from abrasions on the skin that result from an elliptical-type motion.


5. Diseases and Disorders

The term plant disease refers to an impairment in the structure or function of a plant that results in observable symptoms. In this chapter the focus will be on infectious diseases&mdashthose that result from an attack by a fungus, bacterium, nematode, virus, or another organism. Other disorders can be caused by abiotic (environmental and cultural) factors, such as compacted soil, excess water, nutrient deficiencies, chemical injury, or air pollution. Many of these factors produce symptoms similar to those caused by infectious agents. Some detective work is often necessary to figure out what is wrong with a particular plant. This chapter provides an introduction to the causes of plant diseases, their diagnosis, and the methods used to prevent and control them. For information on particular diseases, refer to the chapters on specific types of plants.


Increased Risk of Psychiatric Disorders in Allergic Diseases: A Nationwide, Population-Based, Cohort Study

Background/objective: Allergic diseases, such as bronchial asthma, allergic rhinitis, atopic dermatitis, and psychiatric disorders, are major health issues. There have been reports that allergic diseases were associated with depression or anxiety disorders. This study aimed to investigate the association between these allergic diseases and the risk of developing overall psychiatric disorders in patients from Taiwan.

Methods: This cohort study used the database of the Taiwan National Health Insurance Program. A total of 186,588 enrolled patients, with 46,647 study subjects who had suffered from allergic diseases, and 139,941 controls matched for sex and age, from the Longitudinal Health Insurance Dataset of 2000-2015, were selected from a sub-dataset of the National Health Insurance Research Database. Fine and Gray's competing risk model analysis was used to explore the hazard ratio (HR), and 95% confidence interval, for the risk of allergic diseases being associated with the risk of developing psychiatric disorders during the 15 years of follow-up.

Results: Of the study subjects, 5,038 (10.8%) developed psychiatric disorders when compared to 9,376 (6.7%) in the control group, with significant difference (p < 0.001). Fine and Gray's competing risk model analysis revealed that the adjusted HR was 1.659 (95% CI = 1.602-1.717, p < 0.001). In this study, we found that the groups of atopic dermatitis alone and the allergic rhinitis + atopic dermatitis were associated with a lower risk of psychiatric disorders, but all the other four groups, such as bronchial asthma alone, allergic rhinitis alone, bronchial asthma + allergic rhinitis, bronchial asthma + atopic dermatitis, and the combination of all these three allergic diseases, were associated with a higher risk of psychiatric disorders.

Conclusion: Allergic diseases are therefore associated with a 1.66-fold increased hazard of psychiatric disorders in Taiwan.

Keywords: National Health Insurance Research Database Taiwan National Health Insurance Program allergic rhinitis atopic dermatitis bronchial asthma cohort study psychiatric disorders risk factors.


National Occupational Research Agenda

Eight of the 21 priority research areas are grouped in the category of adverse health effects&ndashnamely, disease and injury. An earlier effort by NIOSH in the 1980s identified the &ldquotop ten&rdquo leading workplace diseases and injuries. In the development of NORA, participants recognized the need to include a list of diseases and injuries (albeit updated and more focused than the &ldquotop ten&rdquo) and to include research areas grouped into two other broad categories: work environment and workforce, and research tools and approaches.

Early in the process, many disease and injury topics were offered for potential inclusion in NORA. Obviously, a list of significant workplace diseases and injuries could easily be many times the size of the list presented in the Agenda. Working groups performed the difficult task of refining and prioritizing to achieve this list of eight topics&ndashtopics for which concerted research efforts have the potential to improve the well-being of large numbers of workers and their families. Indeed, significant advances in the prevention of diseases or injuries encompassed by these eight areas would improve the health of millions of U.S. workers and save billions of dollars in costs related to medical treatment and lost productivity.

Allergic and Irritant Dermatitis

Allergic and irritant dermatitis (contact dermatitis) is overwhelmingly the most important cause of occupational skin diseases, which account for 15% to 20% of all reported occupational diseases. There is virtually no occupation or industry without potential exposure to the many diverse agents that cause allergic and irritant dermatitis. Research is needed to better identify the prevalence, causes, exposure assessment methods, and early biologic markers of this ubiquitous condition.

Importance

In the workplace, the skin is an important route of exposure to chemicals and other contaminants. According to the U.S. Bureau of Labor Statistics external icon , occupational skin diseases&ndashmostly in the form of allergic and irritant (contact) dermatitis&ndashare the second most common type of occupational disease. From 1983 to 1994, the rate of occupational skin diseases increased from 64 to 81 cases per 100,000 workers. In 1994, there were approximately 66,000 reported cases of occupational skin diseases, accounting for about 13% of all occupational diseases. Moreover, occupational skin diseases are believed to be severely underreported, such that the true rate of new cases may be many fold higher than documented. These data stress that the national objective for reducing the rate of new cases of occupational skin diseases to 55 per 100,000 workers (as set by Healthy People 2000 ) is far from being met.

Estimated total annual costs (including lost workdays and loss of productivity associated with occupational skin diseases) may reach $1 billion annually. Workers&rsquo compensation claims rates for occupational skin diseases vary by State and range from 12 to 108 per 100,000 workers per year. Self-reported occupational dermatitis prevalence in the 1988 National Health Interview Survey was nearly 2% (1,700 cases per 100,000 workers).

Irritant contact dermatitis is the most common occupational skin disease, usually resulting from toxic reactions to chemical irritants such as solvents and cutting fluids. Allergic dermatitis is estimated to constitute about 20% to 25% of all contact dermatitis it is caused by a wide variety of substances such as latex and some pesticides that trigger an allergic (delayed hypersensitivity) reaction. Contact urticaria (hives occurring soon after an allergen or irritant contacts the skin) is considered here also because it may evolve into contact dermatitis. A number of substances may cause both irritant and allergic dermatitis as well as contact urticaria. For example, latex (which has been reported to cause skin disorders in up to 10% of exposed health care workers), most commonly causes irritant dermatitis but it also results in allergic contact dermatitis and, least commonly, contact urticaria.

Because the prognosis of occupational irritant and allergic dermatitis is poor, prevention is imperative. This fact is emphasized by one study showing that 75% of patients with occupational contact dermatitis developed chronic skin disease. With thousands of potentially harmful chemicals being introduced into the workplace each year, and with the threat of rapidly emerging skin diseases such as latex allergy, further research of irritant and allergic contact dermatitis is greatly needed.

Research Opportunities

Just as the plight of news reporters with carpal tunnel syndrome captured public attention, disability occurring among nurses and other health care workers allergic to latex is now capturing the attention of health scientists. There has been relatively little occupational research to evaluate causes of occupational dermatitis, identify high risk occupations, develop interventions to protect workers, or assist workers who have developed skin diseases that commonly afflict them for the rest of their lives. Despite a high rate of dermatitis among agricultural workers and high numbers of cases in manufacturing, there is little research to identify and target the most important causes. Also needed are new laboratory in vitro skin models, improved statistical models for pharmacokinetic testing in animals, and improved field methods to measure permeation of skin by individual substances and mixtures. The lack of adequate tools prevents the next step in research which aims to eliminate contact with irritants and allergens by substituting safe materials for hazardous ones or by redesigning processes or materials to prevent hazardous exposures. When elimination of causative agents is economically or technically infeasible, work safety and health programs must consider the use of protective clothing and &ldquobarrier creams.&rdquo However, there is insufficient substance-specific research evaluating the effectiveness of different glove and other clothing materials&ndashparticularly research involving actual work conditions and the related issues of fit, comfort, durability, multiple chemicals, and other environmental conditions. The effectiveness and utility of barrier creams are largely unexamined. Moreover, there is almost no research to identify major causes for improper use of protective clothing and to target specific populations requiring improved education about appropriate use. Research also needs to provide protection and treatment for workers who have special susceptibility or who have already developed a chronic occupational skin disease.

Asthma and Chronic Obstructive Pulmonary Disease

Occupationally-related airway diseases, including asthma and chronic obstructive pulmonary disease (COPD), have emerged as having substantial public health importance. Nearly 30% of COPD and adult asthma may be attributable to occupational exposure. Occupational asthma is now the most frequent occupational respiratory disease diagnosis. More than 20 million U.S. workers are exposed to substances that can cause airway diseases. Research is needed to clarify the prevalence, risk factors, and exposure-disease relationships, to refine techniques for monitoring worker health and the job environment, and to develop effective and practical means for preventing work-related airway diseases in at-risk workers.

Importance

Asthma and chronic obstructive pulmonary disease (COPD&ndashprimarily chronic bronchitis and emphysema) are diseases of the lung airways. More than 20 million workers are potentially exposed to occupational agents capable of causing these diseases&ndash including nearly 9 million workers occupationally exposed to known sensitizers and irritants associated with asthma. Occupational asthma is now the most frequent occupational respiratory disease diagnosis among patients visiting occupational medicine clinics.

Asthma and COPD accounted for nearly 18 million physician visits in 1985 and an estimated 800,000 hospital admissions in 1987. In 1992, asthma and COPD caused nearly 92,000 deaths in the United States, making airway diseases the fourth leading cause of death overall. Mortality from asthma and COPD is increasing annually. Estimated yearly costs for occupational asthma are approximately $400 million.

Asthma currently affects more than 10 million individuals in the United States and is increasing in prevalence. Recent evidence suggests that as many as 28% of adult asthma cases may be attributable to work settings. In addition to those who develop occupational asthma as a result of workplace exposure to sensitizers or irritants, many workers are unaware that pre-existing asthma may be worsened by the work environment. Each year the number of asthma cases is increasing, and major new problem areas are emerging. For example, as a result of increased use of protective gloves (which is due to the introduction of universal precautions and the OSHA regulations on bloodborne pathogens), latex allergies have become a major problem for health care workers. A significant number of these workers (2.5% in one study) have developed latex-related asthma. Morbidity from occupational asthma is preventable. Early diagnosis holds substantial promise for effective intervention. Complete resolution of symptoms and pulmonary function abnormalities is most likely when an affected individual&rsquos exposure is terminated early in the course of the illness so early diagnosis holds substantial promise for effective intervention.

The relationship of COPD to workplace exposures is also well documented in studies of several occupational agents (e.g., coal dust, grain dust, and cotton dust). Investigations of the health consequences of particulate exposure in the general environment&ndashwhere exposures are at a far lower level than in the workplace&ndashalso suggest that COPD resulting from generally dusty conditions may be an important cause of preventable disease and death. Those with lung disease from other causes are especially vulnerable to occupational respiratory hazards. Although cigarettes remain the primary cause of pulmonary diseases in the United States, many occupational and environmental exposures (both by themselves or in combination with smoking) are known to cause COPD. One estimate of the proportion of COPD attributable to occupational exposure in the general population is 14%.

Research Opportunities

Disabling effects of asthma and COPD may in many cases drive a person out of a line of work or out of work completely. The machinist who becomes asthmatic from breathing droplets of cutting fluids and the nurse allergic to latex may have to relinquish their skilled professions. An agricultural worker with an obstructive lung disease may become unemployable. These personal effects have serious business consequences beyond issues of medical costs and workers&rsquo compensation. Employee turnover in highly skilled professions is especially costly. Scientists associating dust exposures in specific work operations with high levels of COPD can test alternative approaches to dust suppression, evaluate the impact of providing workers with respirators, and determine the benefit of medical screening in reducing disease effects. There has been little research to evaluate the potential impact of occupational risk information on smoking among workers at risk. Research that investigates how workers become sensitized to substances causing asthma, (e.g., such as latex) may enable employers to screen for biomarkers or other early indications of risk before workers become disabled such studies may also enable researchers to develop methods to replace or control exposures to the sensitizing agent. Development of tests to identify substances and processes that may cause asthma would have enormous benefits, enabling health scientists to work with product designers to assure the safety of new materials before they are introduced to the workplace, preventing disease before any cases occur, and avoiding the need for employers to implement additional prevention programs.

Fertility and Pregnancy Abnormalities

While more than 1,000 workplace chemicals have shown reproductive effects in animals, most have not been studied in humans. In addition, most of the 4 million other chemical mixtures in commercial use remain untested. Physical and biological agents in the workplace that may affect fertility and pregnancy outcomes are practically unstudied. The inadequacy of current knowledge coupled with the ever-growing variety of workplace exposures pose a potentially serious public health problem. Over the next 10 years, research priorities should include expanding surveillance systems, studying working populations thought to be at risk, increasing the understanding of fundamental biological processes underlying normal and abnormal reproductive function or outcomes, and enhancing methods to identify hazards before placing human populations at risk.

Importance

Disorders of reproduction include birth defects, developmental disorders, spontaneous abortion, low birth weight, preterm birth, and various other disorders affecting offspring they also include reduced fertility, impotence, and menstrual disorders. Infertility is currently estimated to affect more than 2 million U.S. couples (one in 12 couples find themselves unable to conceive after 1 year of unprotected intercourse). Though not all infertile couples seek treatment, it is estimated that about $1 billion was spent in 1987 on health care related to infertility. In 1991, physician visits for infertility services numbered 1.7 million. Although numerous occupational exposures have been demonstrated to impair fertility (e.g., lead, some pesticides, and solvents), the overall contribution of occupational exposures to male and female infertility is unknown. Moreover, observed global trends in men&rsquos decreasing sperm counts have elevated concerns about the role of chemicals encountered at work and in the environment at large.

Birth defects are the leading cause of infant mortality in the United States, accounting for 20% of infant deaths (more than 8,000) each year. Every year about 120,000 babies are born in the United States with a major birth defect&ndashabout 3 per 100 live births. The 1992 costs for 17 of the most clinically important structural birth defects and for cerebral palsy were estimated to be about $8 billion. Neural tube defects (which include spina bifida and anencephaly), affect 4,000 pregnancies each year, with each new case of spina bifida having a discounted lifetime cost of $294,000 (1992 dollars). Seventeen percent of all children in the United States have some type of developmental disability. The major developmental disabilities of mental retardation, cerebral palsy, hearing impairment, and vision impairment affect about 2% of all school-age children.

Most birth defects and developmental disabilities are of unknown cause. The overall contribution of workplace exposures to reproductive disorders and congenital abnormalities is not known. Although some specific reproductive hazards have been identified in humans (e.g., lead, solvents, and ionizing radiation), most of the more than 1,000 workplace chemicals that have shown abnormal reproductive effects in animals have not been studied in humans. In addition, most of the 4 million other chemical mixtures in commercial use remain untested. Substances and activities that upset the normal hormonal activity of the reproductive system&ndashsuch as shift work or pesticides that possess estrogenic activity&ndashalso need evaluation. Similarly, the effects of physical factors (such as prolonged standing, reaching, or lifting) or the interactive effects of workplace stressors and exposures on pregnancy and fertility have not been rigorously investigated.

Although the total number of workers potentially exposed to reproductive hazards is difficult to estimate, three-quarters of employed women and an even greater proportion of employed men are of reproductive age. More than half of U.S. children are born to working mothers. The vast number of workers of reproductive age together with the substantial number of workplace chemical, physical, and biological agents suggest that a considerable number of workers are potentially at risk for adverse reproductive outcomes.

Although the causes of reproductive disorders and adverse pregnancy outcomes are poorly defined, lost productivity and deep suffering by affected individuals and families are evident. The contribution that may be made by occupational factors is largely unexplored, since the reproductive health of workers has only recently emerged as a serious focus of scientific investigation. Identifying reproductive hazards in the workplace has the potential for significantly reducing the multibillion-dollar costs and alleviating the personal suffering associated with disorders of reproduction.

Research Opportunities

Substantial research is required to advance from the current high level of concern about the role of the workplace to a broad understanding of the most important hazards, their impacts, and prevention. That research must span the entire range of human clinical research, surveillance, and targeted field investigations of populations at risk. These studies could serve to identify preventable effects in workers or their offspring, such as field studies like those that detected reduced semen quality in men occupationally exposed to glycol ethers, or increased spontaneous abortions in semiconductor workers. Research may also serve to allay fears and avert unnecessary expense, for example, epidemiologic studies such as the sentinel one which showed that working with computer screens is not associated with miscarriage. Research is needed spanning the entire range of laboratory investigation from basic biology to the development and application of techniques to detect potentially hazardous conditions or agents. For example, improved understanding of basic biology (such as the actions of hormonal disrupters) will enhance prevention of reproductive disorders. Success on these fronts will allow reproductive hazards in the workplace to be recognized and removed it will allow new or emerging hazards to be identified before large numbers of workers are placed at risk and it could allow significant reductions in the currently heavy social, economic, and personal burdens imposed by reproductive disorders.

Hearing Loss

Occupational hearing loss may result from an acute traumatic injury, but it is far more likely to develop gradually as a result of chronic exposure to ototraumatic (damaging to the ear or hearing process) agents. Noise is the most important occupational cause of hearing loss, but solvents, metals, asphyxiants, and heat may also play a role. Exposure to noise combined with other agents can result in hearing losses greater than those resulting from exposure to noise or other agents alone. Research is needed to define further the causal contributions of these hazards (alone or in combination) and to implement and evaluate methods for early detection and hearing conservation programs.

Importance

Occupational hearing loss is the most common occupational disease in the United States: it is so common that it is often accepted as a normal consequence of employment. More than 30 million workers are exposed to hazardous noise, and an additional 9 million are at risk from other ototraumatic agents. Occupational hearing loss knows no boundaries with respect to industries. Any worker, young or old, male or female, risks hearing loss when exposed to ototraumatic agents. Once the loss is acquired, it is irreversible.

Although noise-induced occupational hearing loss is the most common occupational disease and is the second most self-reported occupational illness or injury, it has not been possible to create a sense of urgency about this problem. Efforts to prevent occupational hearing loss have been hindered because the problem is insidious and occurs without pain or obvious physical abnormalities in affected workers.

Problems created by occupational hearing loss include the following: (1) reduced quality of life because of social isolation and unrelenting tinnitus (ringing in the ears), (2) impaired communication with family members, the public, and coworkers, (3) diminished ability to monitor the work environment (warning signals, equipment sounds, etc.), (4) lost productivity and increased accidents resulting from impaired communication and isolation, and (5) expenses for workers&rsquo compensation and hearing aids.

Because no national surveillance or injury-reporting system exists, no generalizable data are available regarding the economic impact of occupational hearing loss.

Research Opportunities

A great deal of information exists about the most important cause of hearing loss&ndashhigh levels of damaging types of noise. Scientists are just beginning to understand how other factors such as exposure to solvents and heat affect hearing ability (acuity). However, many critical practical problems associated with stopping noise-induced hearing loss are largely unstudied. There have been no recent studies of the hearing status of contemporary workers. Reliance on data collected 30 years ago results in predictions that underestimate the amount of hearing loss that is due to occupational noise, especially for those with intermittent noise exposures. Moreover, factors such as heat and chemicals are only now emerging as recognized threats to hearing. Existing hearing conservation measures provide no guarantee to workers that occupational hearing loss will be prevented by the simple use of hearing protectors. For example, removing hearing protection for 15 minutes of an 8-hour work shift can cut protection effectiveness in half yet we know little about why protection is not worn. Likewise, a poorly-fitting hearing protector will not prevent hearing loss. Research will give employers and employees strategies to identify and overcome barriers to the use of hearing protection. It will provide new methods to reduce noise exposure&ndash such as ways to block noise at its sources and to assure that hearing protection fits the wearer. Research will also determine the impact of other risk factors for hearing loss and will examine why some people seem to be susceptible to hearing loss. In addition, research will also: (1) redefine the risk of occupational hearing loss, taking into account exposure times, exposure events, exposure agents, and the use of personal protective equipment (2) develop and test new strategies for identifying exposure hazards (3) develop and implement new technologies for controlling noise and improving hearing protector effectiveness and (4) initiate new methods to improve the efficiency of biological monitoring for hearing loss and the effectiveness of hearing loss prevention programs.

Infectious Diseases

Health care workers are at risk of tuberculosis (TB), hepatitis B and C viruses, and the human immunodeficiency virus (HIV). Social service workers, corrections personnel, and other occupational groups who work regularly with populations having increased rates of TB may also face increased risk. Laboratory workers are at risk of exposure to infectious diseases when working with infective material. Research is needed to determine the extent of occupational transmission of these infectious diseases, to understand the barriers to the use of safe work practices and vaccines, and to develop and evaluate new control methods.

Importance

Infections acquired in the work setting are a diverse group with many different modes of transmission. Of particular concern are infectious diseases transmitted by humans (e.g., from patient to worker or from worker to worker) in a variety of work settings. Bloodborne and airborne pathogens represent a significant class of exposures for the 6 million U.S. health care workers. Occupational transmission of bloodborne pathogens (including the hepatitis B and C virus and the human immunodeficiency virus [HIV]), occurs primarily by means of needle-stick injuries but also through exposures to the eyes or mucous membranes. The risk of hepatitis B virus infection following a single needle-stick injury with a contaminated needle varies from 2% to greater than 40%, depending on the antigen status of the source patient. Similarly, the risk of hepatitis C virus transmission also depends on the status of the source and ranges from 3.3% to 10%. Before widespread use of hepatitis B virus vaccine, approximately 8,700 acute cases of hepatitis B virus infection were reported among health care workers each year. Although the incidence of occupational hepatitis C virus infection among these workers is unknown, antibody to hepatitis C virus (evidence of previous infection) is found in 1% of hospital-based health care workers. As of June 1995, the Centers for Disease Control and Prevention reported 143 U.S. health care workers with documented or possible occupational transmission of HIV.

Transmission of tuberculosis (TB) within health care settings (especially multidrug-resistant TB) has re-emerged as a major public health problem. Since 1989, outbreaks of this type of TB have been reported in 14 hospitals and at least 17 workers have developed active drug-resistant TB. In addition among workers in health care, social service, and corrections facilities who work with populations at increased risk of TB, hundreds have experienced tuberculin skin test conversions. Reliable data are lacking on the extent of possible work-related TB transmission among other groups of workers at risk for exposure.

Some cases of influenza and other communicable respiratory infections are surely due to exposure to infected persons at work. These are not generally considered occupational diseases, and the proportion acquired at work (from coworkers, patients, customers, clients, and the general public) is unknown. The cost of lost work time and decreased productivity is likely to be substantial.

Research Opportunities

Occupation is a major risk factor for nearly all communicable infections among adults. There are great demands for research on occupational transmission of infectious diseases occurring in the health care industry, where workers may often be exposed to populations with high prevalence of TB, HIV, or other bloodborne pathogens. Intervention research is especially needed. For example, many new needle-containing devices are marketed for improved safety, but there has been little evaluation of their effectiveness. Latex rubber gloves are routinely used as part of an overall strategy to prevent transmission of bloodborne infections. These gloves are the primary type of hand protection available to health care workers, yet glove wearers must also worry about increasing reports of latex allergies following their use. As with other regulations, the implementation and effectiveness of the OSHA &ldquobloodborne pathogens&rdquo standard should be evaluated, as should the CDC Guidelines for Preventing the Transmission of Mycobacterium Tuberculosis in Health Care Facilities. The resurgence of TB and the increase in multidrug-resistant strains have made it difficult to assure the safety of health care workers. Research is needed to design interventions and to evaluate the protection achieved by using ventilation and air filtration, ultraviolet germicidal irradiation, and respirators.

In addition to posing a risk for health care providers, work exposures may also be a major risk factor for many communicable infections among adults in a variety of workplace settings. Hence, research is also needed to define the incidence, prevalence, and impact of occupational infectious diseases such as acute respiratory illness and vaccine-preventable illnesses.

Low Back Disorders

Low back musculoskeletal disorders are common and costly. Although the causes of low back disorders are complex, substantial scientific evidence identifies some work activities and awkward postures as significantly contributing to the problem. In the United States, back disorders account for 27 percent of all nonfatal occupational injuries and illnesses involving days away from work. Prevention activities should be undertaken based on current knowledge, but important new research efforts are needed to assure that work-related low back disorders are successfully prevented and treated. For some occupations and tasks, there is a pressing need for more information about safe levels of exposure and for further validation of promising intervention approaches such as mechanical lifting devices for nursing aides.

Importance

Back pain is one of the most common and significant musculoskeletal problems in the world. In 1993, back disorders accounted for 27% of all nonfatal occupational injuries and illnesses involving days away from work in the United States. The economic costs of low back disorders are staggering. In a recent study, the average cost of a workers&rsquo compensation claim for a low back disorder was $8,300, which was more than twice the average cost of $4,075 for all compensable claims combined. Estimates of the total cost of low back pain to society in 1990 were between $50 billion and $100 billion per year, with a significant share (about $11 billion) borne by the workers&rsquo compensation system. Moreover, as many as 30% of American workers are employed in jobs that routinely require them to perform activities that may increase risk of developing low back disorders.

Despite the overwhelming statistics on the magnitude of the problem, more complete information is needed to assess how changes implemented to reduce the physical demands of jobs will affect workplace safety and productivity in the future. A tremendous opportunity exists for prevention efforts to reduce the prevalence and costs of low back disorders, since a significant number of occupationally related low back disorders are associated with certain high-risk activities. For example, female nursing aides and licensed practical nurses were about two and one-half times more likely to experience a work-related low back disorder than all other female workers. Male construction laborers, carpenters, and truck and tractor operators were nearly two times more likely to experience a low back disorder than all other male workers.

Research Opportunities

Every worker whose job involves stressful lifting tasks or awkward postures is at risk for a low back disorder. Countless times each day the health aide in a nursing home lifts and physically assists elderly or disabled residents. Many construction laborers, agricultural workers and others spend their days lifting and carrying awkward loads. Often their productive work is interrupted by weeks of disability, pain, and costly therapy, yet little is known about the pathophysiology of low back pain. For some occupations and tasks, the risks are not well defined. How much weight is too much? How many lifts per day are too many? What are the material handling jobs with the highest risk of back injury? These are interrelated risk factors. They represent one broad challenge of research: to develop approaches by which employers, workers, design engineers, and others with a role in prevention can confidently identify hazardous and safe work tasks. Another challenge for those tasks and occupations involving recognized hazards is intervention research. Evaluation of rehabilitation and return to work strategies will be useful. Current studies are testing ways to reduce risks to nursing aides by the use of mechanical lifting devices, training, and reorganizing tasks. Studies of this type (including those testing the effectiveness of back belt use) are needed in other work settings. Research to redesign materials, loads, and equipment can improve the safety of workers in many occupations.

Musculoskeletal Disorders of the Upper Extremities

Musculoskeletal disorders of the upper extremities (such as carpal tunnel syndrome and rotator cuff tendinitis) due to work factors are common and occur in nearly all sectors of our economy. More than $2 billion in workers&rsquo compensation costs are spent annually on these work-related problems. Workers&rsquo compensation costs undoubtedly underestimate the actual magnitude of these disorders. Current scientific research has provided important insights into the etiology and prevention of these disorders, but important questions remain unsolved. Research needs include better methods of exposure characterization and greater understanding of basic pathophysiologic mechanisms.

Importance

Musculoskeletal disorders of the neck and upper extremities due to work factors affect employees in every type of workplace and include such diverse workers as food processors, automobile and electronics assemblers, carpenters, office data entry workers, grocery store cashiers, and garment workers. The highest rates of these disorders occur in the industries with a substantial amount of repetitive, forceful work. Musculoskeletal disorders affect the soft tissues of the neck, shoulder, elbow, hand, wrist, and fingers. These include the nerves (e.g., carpal tunnel syndrome), tendons (e.g., tenosynovitis, peritendinitis, epicondylitis), and muscles (e.g., tension neck syndrome). The costs associated with these disorders are high. More than $2.1 billion in workers&rsquo compensation costs and $90 million in indirect costs (hiring, training, overtime, and administrative costs) are incurred annually for these musculoskeletal disorders.

In 1994, 332,000 musculoskeletal disorders due to repeated trauma were reported in U.S. workplaces. This figure represents nearly 65% of all illness cases reported to the Bureau of Labor Statistics external icon &ndashan increase of nearly 10% compared with 1993 figures and more than 15% relative to 1992 figures.

The most frequently reported upper-extremity musculoskeletal disorders affect the hand/wrist region. In 1993, carpal tunnel syndrome, the most widely recognized condition, occurred at a rate of 5.2 per 10,000 full-time workers. This syndrome required the longest recuperation period of all conditions resulting in lost workdays, with a median 30 days away from work.

Research Opportunities

Research has made important gains by establishing widespread recognition of work-related musculoskeletal disorders of the upper extremities and identifying much about their principal causes and approaches to prevention. This research has instigated a wide field of prevention efforts at worksites throughout the United States. But research is still needed across the gamut of possible concerns, including basic research that clarifies the pathophysiologic mechanisms of chronic musculoskeletal injury. Employers and workers want to know: &ldquoHow can these problems be solved cost effectively?&rdquo &ldquoWhat is causing the problem?&rdquo &ldquoHow can we bring people back to work without being reinjured?&rdquo &ldquoHow can these problems be solved with better cost-effective tool and equipment designs, work-rest periods, or changes in the organization of work?&rdquo Health care providers want reliable clinical methods to diagnose musculoskeletal disorders, identify them before they become severe, and rehabilitate disabled workers as fully and rapidly as possible. These many challenges are being met with varied and sporadic success. There is a large role for research to improve and standardize successful ways to address these challenges. This effort will require unraveling the ways in which different factors combine to cause a hazard, providing better approaches by which employers and workers can identify hazards before they cause injury, and developing and proving the effectiveness of interventions and treatment. This scientific work has an integral role in the occupational safety and health community&rsquos efforts to reverse the trend of the large and growing problem of upper-extremity musculoskeletal disorders.

Traumatic Injuries

Injury exacts a huge toll in U.S. workplaces&ndashon an average day, 16 workers are killed and over 17,000 workers are injured. The associated economic costs are high&ndashabout $121 billion per year. Research should focus on leading causes and high-risk groups. Priorities are deaths caused by motor vehicles, machines, violence, and falls, as well as traumatic injuries caused by falls and contact with machines, materials, equipment, and tools. High-risk groups include construction workers, loggers, miners, farmers, farm workers, adolescents, and older workers. Multiple factors and risks contribute to traumatic injuries, including the characteristics of workers, workplace/process design, work organization, economics and other social factors. Research needs are thus broad, and the development of interventions involve many disciplines and organizations.

Importance

Fatal Occupational Injuries

During the period 1980 through 1992, more than 77,000 workers died as a result of work-related injuries. This means that an average of 16 workers die every day from injuries suffered at work. The leading causes of occupational injury fatalities over this 13-year period were motor vehicles, machines, homicides, falls, electrocutions, and falling objects. There were four industries&ndashmining, construction, transportation, and agriculture&ndashwith occupational injury fatality rates that were notably and consistently higher than all other industries. Motor-vehicle-related deaths in the transportation sector, machine-related deaths in agriculture, electrocutions and fatal falls in construction, homicide in retail trade and public administration, and deaths due to falling objects in mining and logging appear to be important because of particularly high rates of death from injury.

Nonfatal Occupational Injuries

In 1994, 6.3 million workers suffered job-related injuries that resulted in lost work time, medical treatment other than first aid, loss of consciousness, restriction of work or motion, or transfer to another job. The leading causes of nonfatal occupational injuries involving time away from work in 1993 were overexertion, contact with objects or equipment, and falls to the same level. Industries experiencing the largest number of serious nonfatal injuries include eating and drinking places, hospitals, and grocery stores. Industries facing higher risks of serious nonfatal injuries are concentrated in the manufacturing sector and include workers in shipbuilding, wooden building and mobile home manufacture, foundries, special products sawmills, and meat packing plants.

Clearly, work-related injuries and fatalities result from multiple causes, affect different segments of the working population, and occur in a myriad of occupational and industrial settings. The total cost of work-related injuries and fatalities to industry and to society at large has not been fully recognized, but is estimated to be greater than $121 billion annually. Efforts to set research and prevention priorities in traumatic injury must be driven by data that illuminate the nature and magnitude of these injuries.


On the Biology of Mental Disorders

“The notion that mental disorders are genetically encoded brain disorders is everywhere around us,” note several prominent researchers in the latest issue of Behavioral and Brain Sciences. The idea holds such currency that it “dominates the organization of research, it dominates teaching, and it dominates the media,” they conclude in a study that has generated robust debate and refocused attention on the many factors that influence mental health.

The idea that psychiatric conditions have clear neural correlates predates Emil Kraepelin’s classificatory system in the 1900s, but it intensified dramatically in recent decades, argue Denny Borsboom at the University of Amsterdam, Angélique Cramer at Tilburg University, and Annemarie Kalis at Utrecht University, authors of the study. As evidence, they cite Thomas Insel, who as director of the National Institute of Mental Health argued that “mental disorders are biological disorders.” His successor, current director Joshua Gordon, claimed more recently that “psychiatric disorders are disorders of the brain.”

Yet despite widespread acceptance of this argument, the search for the biological basis of mental disorders has not resulted in “conclusive reductionist explanations of psychopathology. We do not have biomarkers that are sufficiently reliable and predictive for diagnostic use.”

The researchers are not alone in highlighting this problem. “Despite decades of work,” David Adam noted in Nature in April 2013, “the genetic, metabolic and cellular signatures of almost all mental syndromes remain largely a mystery.”

According to the authors of the recent study, the assumptions of neuropsychiatry have become so widespread and engrained that they are often simply accepted as fact:

The central problem is dogma: The reductionist hypothesis is not treated as a scientific hypothesis, but as an almost trivial fact. It is not a fact but a hypothesis that mental disorders originate in the brain. It is not a fact but a hypothesis that there are genes “for” mental disorders and it is not a fact but a hypothesis that finding out “what goes wrong in the brain” is a necessary condition for progress in the science of mental disorders.

One of several respondents to the study, Kathryn Tabb at of Columbia University, wrote that the critique was “convincing,” but the charge of biological reductionism “in 2018, a bit of a straw man.” Apparently, today’s emphasis on biopsychosocial-spiritual dimensions is evenly spread, without preference or bias, leaving the charge of biological reductionism “misdirected.”

Yet as Borsboom and his colleagues point out in a detailed response, while the forum of respondents rejected biological reductionism as a practice and approach, their colleagues in the media continue largely unchallenged to claim that mental disorders are best seen as brain disorders.

The implications of that disconnect are far-reaching and profound: “If it makes sense to understand mental disorders as arising from the causal interplay of symptoms and other factors in a network structure, there may be no reductive biological explanation that awaits discovery. This is because, contrary to quite widely shared current opinion, mental disorders are not brain disorders at all” (emphasis mine).

Commenting in the same forum, the prominent Stanford scientist John Ioannidis observed: “If mental health problems are mostly not brain disorders, the dearth of useful neuroscience-derived biomarkers is only to be expected. There is enormous investment in basic neuroscience research and intensive searches for informative biomarkers of treatment response and toxicity,” he added, yet “the yield is close to nil.”

“To overcome this dead end,” he advises, “we should shift emphasis away from the research paradigm that considers mental health problems to be mostly brain disorders and move towards exploring other, potentially more fruitful paths,” such as environmental factors themselves impacting genes.

“Instead of being reducible to a biological basis,” Borsboom and colleagues conclude, “mental disorders feature biological and psychological factors that are deeply intertwined in feedback loops. This suggests that neither psychological nor biological levels can claim causal or explanatory priority.”

Adam D. (2013). Mental health: On the spectrum. [Editorial]. Nature 496:416-18.

Borsboom, D., Cramer, A. O. J., Kalis, A. (2019). Brain disorders? Not really: Why network structures block reductionism in psychopathology research. Behavioral and Brain Sciences, 42(e2), 1-11. doi:10.1017/ S0140525X17002266

Borsboom, D., Cramer, A. O. J., Kalis, A. (2019) Author’s response: Reductionism in retreat. Behavioral and Brain Sciences, 42(e32), 44-63. doi:10.1017/S0140525X18002091

Ioannidis, J. P. A. (2019). Therapy and prevention for mental health: What if mental diseases are mostly not brain disorders? Behavioral and Brain Sciences, 42(e13), 23-24. doi:10.1017/S0140525X1800105X

Tabb , K. Why not be pluralists about explanatory reduction? Behavioral and Brain Sciences, 42(e27), 38-39 doi:10.1017/S0140525X18002054


Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is caused by degeneration of upper and lower motor neurons, resulting in muscle weakness and atrophy.

Learning Objectives

Describe amytrophic lateral sclerosis and its effect on the body

Key Takeaways

Key Points

  • ALS is sometimes referred to as Lou Gehrig’s disease after the New York Yankees baseball player who was diagnosed with the disease in 1939.
  • ALS is characterized by rapidly progressive weakness, muscle atrophy, muscle spasticity, difficulty speaking, difficulty swallowing, and decline in breathing ability. Most patients with ALS die of respiratory failure or pneumonia.
  • For the majority of patients without a family history of the disease, there is no known cause for ALS. Familial ALS is a heritable condition that can be traced to the dysfunction of specific genes.
  • Most people with ALS die of respiratory failure or pneumonia. The median survival time from onset to death is around 39 months, and only 4% survive longer than 10 years.
  • In “respiratory onset” ALS, the intercostal muscles that support breathing are affected first.
  • For the majority of patients without a family history of the disease, there is no known cause for ALS. Familial ALS is a heritable condition that can be traced to the dysfunction of specific genes.

Key Terms

  • lateral: Pertaining to the left or right of the body further from the midline.
  • amyotrophic lateral sclerosis: A chronic, progressive disease characterized by degeneration of the central nervous system and the loss of voluntary muscle control.

Examples

An example of a gene mutated in some cases of familial ALS is superoxide dismutase, or SOD1, which is an enzyme that acts as a powerful antioxidant.

Amyotrophic lateral sclerosis (ALS), also referred to as motor neuron disease in British English, is the most common form of the motor neuron diseases. The condition is sometimes called Lou Gehrig’s disease in the U.S., after the New York Yankees baseball player who was diagnosed with the disease in 1939. The disorder is characterized by rapidly progressive weakness, muscle atrophy and fasciculations, muscle spasticity, difficulty speaking (dysarthria), difficulty swallowing (dysphagia), and decline in breathing ability.

Symptoms of ALS

Coronal MRI of an ALS patient: MRI (parasagittal FLAIR) demonstrates increased T2 signal within the posterior part of the internal capsule and can be tracked to the subcortical white matter of the motor cortex, outlining the corticospinal tract), consistent with the clinical diagnosis of ALS.

The disorder causes muscle weakness and atrophy throughout the body as a result of degeneration of the upper and lower motor neurons. Unable to function, the muscles weaken and atrophy. Affected individuals may ultimately lose the ability to initiate and control all voluntary movement, although bladder and bowel sphincters and the muscles responsible for eye movement are usually, but not always, spared. Cognitive function is generally spared for most patients although some (

5%) also have frontotemporal dementia. A higher proportion of patients (

30%–50%) also have more subtle cognitive changes that may go unnoticed but are revealed by detailed neuropsychological testing. Sensory nerves and the autonomic nervous system are generally unaffected meaning the majority of people with ALS will maintain sight, hearing, touch, smell, and taste. Bladder and bowel functions are also rarely affected by ALS.

The earliest symptoms of ALS are typically obvious weakness and/or muscle atrophy. Other presenting symptoms include muscle fasciculation (twitching), cramping, or stiffness of affected muscles muscle weakness affecting an arm or a leg and/or slurred and nasal speech. The parts of the body affected by early symptoms of ALS depend on which motor neurons in the body are damaged first. About 75% of people contracting the disease experience “limb onset” ALS (i.e., first symptoms in the arms or legs). Patients with the leg onset form may experience awkwardness when walking or running or notice that they are tripping or stumbling, often with a “dropped foot” which drags gently along the ground. Arm-onset patients may experience difficulty with tasks requiring manual dexterity such as buttoning a shirt, writing, or turning a key in a lock. Occasionally, the symptoms remain confined to one limb for a long period of time or for the whole length of the illness this is known as monomelic amyotrophy.

Over time, patients experience increasing difficulty moving, swallowing (dysphagia), and speaking or forming words (dysarthria). Symptoms of upper motor neuron involvement include tight and stiff muscles (spasticity) and exaggerated reflexes (hyperreflexia) including an overactive gag reflex. Symptoms of lower motor neuron degeneration include muscle weakness and atrophy, muscle cramps, and fleeting twitches of muscles that can be seen under the skin (fasciculations). To be diagnosed with ALS, patients must have signs and symptoms of both upper and lower motor neuron damage that cannot be attributed to other causes.

Difficulty swallowing and chewing making eating normally very difficult and increase the risk of choking or aspirating food into the lungs. In later stages of the disease, aspiration pneumonia and maintaining a healthy weight can become a significant problem and may require insertion of a feeding tube. As the diaphragm and intercostal muscles (rib cage) that support breathing weaken, measures of lung function such as forced vital capacity and inspiratory pressure diminish. In respiratory onset ALS, this may occur before significant limb weakness is apparent. Most people with ALS die of respiratory failure or pneumonia. The median survival time from onset to death is around 39 months, and only 4% survive longer than 10 years. The best-known person with ALS, Stephen Hawking, has lived with the disease for more than 40 years, though his is an unusual case.

Causes and Treatments of ALS

For patients without a family history of the disease, which includes

95% of cases, there is no known cause for ALS. Potential causes for which there is inconclusive evidence includes head trauma, military service, and participation in elite sports. Many other potential causes including chemical exposure, electromagnetic field exposure, occupation, physical trauma, and electric shock have been investigated but without consistent findings.

Riluzole (Rilutek) as of 2011 is the only treatment that has been found to improve survival, but only to a modest extent. It lengthens survival by several months, and may have a greater survival benefit for those with a bulbar onset. It also extends the time before a person needs ventilation support. Other treatments for ALS are designed to relieve symptoms and improve the quality of life for patients. This supportive care is best provided by multidisciplinary teams of health care professionals working with patients and caregivers to keep patients as mobile and comfortable as possible.


Leading Work-Related Diseases and Injuries

The National Institute for Occupational Safety and Health (NIOSH) has developed a suggested list of 10 leading work-related diseases and injuries and has described the first nine categories on that list.* A discussion of the tenth and final category, Psychological Disorders, appears below. PSYCHOLOGICAL DISORDERS

There is increasing evidence that an unsatisfactory work environment may contribute to psychological disorders. Studies have shown that factors contributing to an unsatisfactory work environment may include work overload, lack of control over one's work, nonsupportive supervisors or co-workers, limited job opportunities, role ambiguity or conflict, rotating shiftwork, and machine-paced work (1-4). Psychological disorders that can result from such factors may be classified as a) affective disturbances (e.g., anxiety, irritability), b) behavioral problems (e.g., substance abuse, sleep difficulties), c) psychiatric disorders (e.g., neuroses), and d) somatic complaints (e.g., headache, gastrointestinal symptoms). In addition to psychological disorders, stressful working conditions may have a systemic influence, possibly affecting the etiology and/or prognosis of other disease states, as suggested by recent studies of stress-related immunologic suppression (5).

Although data bases currently available for determining the extent of work-related psychological disorders are limited, several indicators suggest that these problems impose substantial health and financial costs in the United States. A recent study in California showed that claims for the development of "work-related neuroses" more than doubled during 1980-1982 claims for all other disabling work-related injuries during the same period actually decreased by about one-tenth (6). A study of representative medical claims throughout the country showed that during 1980-1982 claims for "mental stress" that developed gradually (i.e., a chronic problem unrelated to a single traumatic incident or to any physical work-related disorder) accounted for about 11% of all occupational disease claims (7). Average medical costs and indemnity payments in 1981-1982 for these forms of mental stress actually surpassed the average amounts for other occupational diseases (7). The American Psychiatric Association now lists occupational stress in its Diagnostic and Statistical Manual as a subcategory of the major diagnostic axis of "psychosocial stress" (8).

There are increasing data on the relationship between specific working conditions and psychological disorders. For example, in a questionnaire survey of over 2,000 workers in 23 different occupations, strong occupational differences were found in psychosocial job stressors and in somatic and affective complaints (1). Ratings of boring, repetitive job tasks and role ambiguity were more prominent among several classes of blue-collar workers (e.g., assembly-line workers, fork-lift truck drivers, and machine operators) than among white-collar professionals (e.g., professors and family physicians). The most satisfied occupational groups were physicians, professors, and white-collar supervisors. Groups experiencing the highest levels of job stressors and their resultant ill effects were assemblers and relief workers on machine-paced assembly lines.

NIOSH investigators ranked 130 occupations by rate of admission to community mental health centers in Tennessee to determine the relative risk of psychological or stress-related disorders by occupation (9). Heading the list were jobs in health care, service occupations, and blue-collar factory work--which tend to be characterized by stress-producing conditions such as a lack of control over the job by the worker, repetitive work, shift work, and a responsibility for others.** In other studies, workers on night and rotating shifts (including the health-care occupations) reported more disturbances of sleep altered eating habits and higher rates of visits to clinics, absences due to sickness, and on-the-job injuries than did those on fixed day shifts (10-12).

Work environments characterized by technological innovation have also been investigated a major focus has been on office work influenced by the introduction of computers (13,14). "Adverse working conditions" (e.g., poorer physical environment, reduced job control and social support) tend to be reported more frequently by workers using new-technology office equipment such as video display terminals. Some of these conditions have been linked to chronic stress-related disorders (4,15).

Worksite studies by NIOSH have revealed that job stresses may contribute to acute disturbances among groups of workers, including those termed "mass psychogenic illness" (16). The sudden appearance of symptoms, usually in response to some "trigger factor" such as a strange odor, may result in spread of the apparent "illness" throughout the plant, with symptoms such as headaches, dizziness, and nausea. Investigations often fail to detect specific physical or chemical causative agents. However, factors such as heavy work load, strained labor/management relations, and physical discomfort at work may be present and related to the reporting of symptoms.

Emerging trends in technology, the economy, and demographic characteristics of the work force may lead to increased risk for psychological disorders. For example, a 26% increase is projected for employment in the health services, an area that may be associated with elevated risk (9, 17). Computers and robots are expected to affect seven million factory jobs and 39 million office jobs (18). According to some forecasters (18), possible consequences may include job displacement, reduced skill requirements, and lower-paying jobs. It has been projected that in the next decade, nine of every 10 new jobs will be in the service sector (19). Routine service jobs may not provide the compensation and benefits associated with the more traditional industrial and manufacturing jobs (18). Six of 10 new jobs in the next decade will be filled by women (19), and dual job/home role demands and constrained occupational opportunities for women may result in an adverse impact on their mental health. Reported by Div of Biomedical and Behavioral Science, National Institute for Occupational Safety and Health, CDC.

Editorial Note

Editorial Note: A prevention strategy for psychological disorders should take into account both the causal mechanisms and the factors that perpetuate these disorders. Work-related psychological disturbances are known to be influenced by both the physical and psychosocial characteristics of given job situations. Moreover, these factors operate in concert with factors unrelated to the job--such as life events familial demands and support and the traits, capacities, and needs of the workers themselves (e.g., personality, age, sex, experience/learning). The interaction of these variables is complex, and the relative influence of each is not thoroughly understood. Nevertheless, approaches to prevent work-related psychological disorders should still be taken using the information currently available.

Stress-reduction techniques (e.g., meditation, biofeedback, muscle relaxation, cognitive restructuring, and anxiety management) have been taught to both blue- and white-collar workers in worksite training sessions. Follow-up studies have shown decreases in psychophysiologic activity (e.g., muscle tension and blood pressure levels) and reductions in subjective reports of anxiety, sleep disturbances, and other health complaints with each technique (20). However, improvement in all these parameters persisted less than 3 months after training ended.

Stress management treats only the symptoms of the problem--not the cause. Therefore, efforts to control risk factors at the worksite are also important. Some previously described suggestions for controlling worksite risk factors for psychological disorders are listed below (21). These suggestions appear to have merit for reducing work-related psychological disorders, but further evaluation and study are needed for a complete understanding of their impact.

Work schedule. Design work schedules to avoid conflict with demands and responsibilities unrelated to the job. Schedules for rotating shifts should be stable and predictable, with rotation in a forward (day-to-night) direction.

Participation/control. Allow workers to provide input for decisions or actions affecting their jobs.

Workload. Ensure assignments are compatible with the capabilities and resources of the worker, and allow for recovery from especially demanding physical or mental tasks.

Content. Design tasks to provide meaning, stimulation, a sense of completeness, and an opportunity to use skills.

Roles. Define work roles and responsibilities clearly.

Social environment. Provide opportunities for social interaction, including emotional support and help directly related to one's job.

Future. Avoid ambiguity in matters of job security and career development. In addition to evaluation of these suggested actions, efforts are needed to advance the understanding of work-related psychological disorders and of methods appropriate for their control, including:

Improving the systems for surveillance of psychological disorders in the workforce as related to working conditions.

Improving research techniques for investigating stressful working conditions and their health consequences.

Improving training of occupational health professionals and workers in recognizing stressful workplace conditions and signs of worker stress and in effecting remedial measures.

Furthering the development of mental health components in occupational health and safety programs.

References

Caplan RD, Cobb S, French JR, Harrison RV, Pinneau SR. Job Demands and Worker Health main effects and occupational differences. Cincinnati, Ohio: National Institute for Occupational Safety and Health. (DHEW publication no. 75-160), 1975.

Holt RR. Occupational stress. In: Goldberger L, Bresnitz S, eds. Handbook of Stress. New York: The Free Press, 1982.

Beehr TA, Newman JE. Job stress, employee health, and organizational effectiveness: a facet analysis, model, and literature review. Personnel Psychology 197831:665-99.

Karasek RA. Job Demands, job decision latitude, and mental strain. Journal of Occupational Behavior 197924:285-307.

Kiecolt-Glaser JK. Stress and the immune function. In: Measures of job stress: a research methodology workshop. Workshop sponsored by NIOSH, New Orleans, Louisiana, 1985.

California Workers Compensation Bulletin, April 20, 1983.

National Council on Compensation Insurance. Emotional stress in the workplace-new legal rights in the eighties. New York 1985.

American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 3rd ed. Washington, DC: Amercan Psychiatric Association, 1980.

Colligan MJ, Smith MJ, Hurrell JJ Jr. Occupational incidence rates of mental health disorders. J Human Stress 19773:34-9.

Smith MJ, Colligan MJ, Frockt IJ, Tasto DL. Occupational injury rates among nurses as a function of shift schedule. Journal of Safety Research 197911:181-7.

Colligan MJ, Frockt IJ, Tasto DL. Frequency of worksite clinic visits and sickness absence among nurses as a function of shift. Applied Ergonomics 197910:79-86.

Smith MJ, Colligan MJ, Tasto DL. health and safety consequences of shift work in the food processing industry. Ergonomics 198225:133- 44.

Smith MJ, Cohen BG, Stammerjohn LW. An investigation of health complaints and job stress in video display operations. Hum Factors 198123:387-400.

Sauter S, Gottlieb M, Jones C, Dodson V, Rohrer K. Job and health implications of VDT use: initial results of the Wisconsin-NIOSH study. Communications of the ACM 198326:784-94.

House JS, Wells JA. Occupational stress, social support, and health. In: McLean A, Black G, Colligan M, eds. Reducing Occupational Stress: Proceedings of a Conference. Washington, DC, 1978. (DHEW publication no. 78-140.)

Schmitt N, Colligan MJ, Fitzgerald M. Unexplained physical symptoms in eight organizations: individual and organizational analyses. Journal of Occupational Psychology 198053:305-17.

Silvestri GT, Lukasiewicz JM. Occupational employment projections: the 1984-95 outlook. Monthly Labor Review, November 1985:42-57.

Bezold C, Carlson RJ, Peck JC. The future of work and health. Dover, Massachusetts: Auburn House, 1986.

Bureau of Labor Statistics. Bureau of Labor Statistics News. Washington, DC: Department of Labor, November 1985.

Murphy LR. Occupational stress management: review and appraisal. Journal of Occupational Psychology (in press).

Levi L. Preventing Work Stress. Reading, Massachusetts: Addison- Wesley, 1981.


What can go wrong with your immune system?

When your immune system doesn't work the way it should, it is called an immune system disorder. You may:

Be born with a weak immune system. This is called primary immune deficiency.

Get a disease that weakens your immune system. This is called acquired immune deficiency.

Have an immune system that is too active. This may happen with an allergic reaction.

Have an immune system that turns against you. This is called autoimmune disease.


Key Points

Neuronal death underlies the symptoms of many human neurological disorders, including Alzheimer's, Parkinson's and Huntington's diseases, stroke, and amyotrophic lateral sclerosis.

Many signals can initiate apoptosis in neurons, including lack of neurotrophic factor support, overactivation of glutamate receptors (leading to calcium influx), increased oxidative stress and metabolic stress.

Mitochondrial changes are pivotal in the cell death decision in many cases. Mitochondria in cells undergoing apoptosis show increased oxyradical production, opening of pores in their membranes and release of cytochrome c.

The Bcl-2 family of proteins includes both anti-apoptotic (for example, Bcl-2) and pro-apoptotic (for example, Bax) members.

Overexpression of Bcl-2 in cell cultures and in transgenic mice increases resistance of neurons to death induced by excitotoxic, metabolic and oxidative insults. Conversely, neurons lacking Bax are protected against apoptosis.

Further mechanisms that can regulate the early stages of apoptosis in neurons involve caspases (evolutionarily conserved cysteine proteases central to apoptosis of many cell types), Par-4 and telomerase.

Neurotrophic factors can protect neurons against apoptosis by activating receptors linked to production of cell survival-promoting proteins (such as antioxidant enzymes, Bcl-2 family members and proteins involved in calcium homeostasis) through kinase cascades.


Watch the video: Webinar ΕΕΕ-ΠΕΕ Τρίτη - Παγκόσμια Ημέρα Θυρεοειδούς (February 2023).