Polio eradication in India may be possible within 5 years

Poliovirus Receptor 
Polio's first interaction with a host cell consists of binding to a specific cell surface protein, the poliovirus receptor (PVR). The PVR, a cell surface sialylated glycoprotein, is a member of the immunoglobulin superfamily. The defining feature of this superfamily is a "loop" in the protein structure called the Ig domain. PVR has three Ig loops (which are outside the cell), numbered 1-3 starting with the loop farthest from the cell surface. Polio appears to bind to its receptor on loop 1. The receptor molecule binds to a "canyon floor" on the virus particle. The poliovirus receptor is expressed in many human tissue types, including tissues such as kidney that are not normal sites of poliovirus replication. Why doesn't polio replicate in these cells? Possible reasons include a block of viral replication after entry, lack of exposure to those tissues during an infection, or an unknown secondary mediator of viral entry. 

Primera interacción polio con una célula huésped consiste en la unión a una proteínade superficie celular específico, el receptor del poliovirus (PVR). El PVR, unaglicoproteína de superficie celular sialylated, es un miembro de la superfamilia de las inmunoglobulinas. La característica definitoria de esta superfamilia es un "bucle" enla estructura de la proteína llamada el dominio Ig. PVR tiene tres lazos de Ig (que están fuera de la célula), número 1-3 de partida con el lazo más alejada de lasuperficie de la célula. La poliomielitis parece unirse a su receptor en un bucle. Lamolécula de receptor se une a un "fondo del cañón" en la partícula vírica. El receptordel poliovirus se expresa en muchos tipos de tejidos humanos, incluidos los tejidoscomo los riñones que no son los sitios normales de la replicación del virus de la polio. ¿Por qué no la poliomielitis se replican en estas células? Las razones posibles incluyen un bloque de la replicación viral después de la entrada, la falta deexposición a los tejidos durante una infección o un mediador desconocidosecundaria de la entrada del virus.

Protein Synthesis 
(Diagram displaying rates of protein synthesis in infected and uninfected cells. The rise in protein synthesis after 2 hours in infected cells is due to viral protein production. Fundamental Virology, p.505) 

The poliovirus genome is made of positive sense single stranded RNA. The genome encodes a single 'polyprotein' of between 2100-2400 aa's. Both ends of the genome are modified, the 5' end by a covalently attached small, basic protein VPg (~23 AA's), the 3' end by polyadenylation. In a series of cleavages, viral proteases cleave themselves out and break down the polyprotein into 10 separate gene products involved in replication and packaging. 
The viral proteases 2A cleaves the p220 subunit of the cap binding complex (eIF4F subunit of eIF4G), making host cell mRNA unrecognizable to ribosomes. As a result, the 2A protease abrogates most of the host cell's own protein synthesis. Doing so increases the number of free ribosomes to translate viral RNA and insures that the cell will break down, releasing progeny viruses. Viral mRNA relies on a 5' UTR containing a 'clover-leaf' secondary known as an internal ribosome entry site (IRES) that serves as a ribosome docking site to the 40S subunit of ribosomes. 

El genoma del virus de la polio es de sentido positivo de cadena sencilla ARN. Elgenoma codifica una sola 'poliproteína' de entre el 2100-2400 a bis. Ambos extremosdel genoma se modifican, el extremo 5 'por un covalentemente VPg pequeños,proteína básica (~ 23 de AA), el extremo 3 ' por poliadenilación. En una serie dehendiduras, proteasas virales se unirá a cabo y romper la poliproteína en 10productos de los genes independientes que participan en la replicación y envasado.
Las proteasas virales 2A rompe la subunidad p220 del complejo de la tapa de unión (eIF4F subunidad de eIF4G), haciendo del ARNm de la célula huéspedirreconocibles a los ribosomas. Como resultado, la proteasa 2A deroga la mayor parte de la síntesis de la célula huésped proteínas propias. Además, aumenta elnúmero de ribosomas libres para traducir el ARN viral y asegura que la célula se descompone, liberando virus de la progenie. ARNm viral se basa en un 5 'UTR que contiene un "trébol" secundario conocido como un sitio de entrada interna del ribosoma (IRES) que sirve como sitio de acoplamiento del ribosoma a la subunidad40S de los ribosomas.

Fundamental Virology,  p.482 
The 5' methyl-guanosine cap attached to host mRNA for ribosome recognition is unnecessary in poliovirus, allowing for viral RNA translation. The primary attenuating mutation in the Sabin vaccine is located  in the IRES. While Sabin poliovirus can replicate efficiently in gut epithelial tissues (primary site of replication), it is unable to replicate efficiently in the nervous system. 

      El 5 'tapa metil-guanosina unido para organizar ARNm para el reconocimiento del ribosoma no es necesaria en virus de la polio, lo que permite la traducción del ARNviral. La mutación principal atenuante de la vacuna Sabin está ubicado en el IRES.Mientras que el poliovirus Sabin puede replicar de manera eficiente en los tejidosepiteliales del intestino (sitio primario de replicación), es incapaz de replicar de manera eficiente en el sistema nervioso.

RNA Replication 
Replication occurs entirely in the cytoplasm. In addition to serving as a template for protein synthesis, the positive sense strand genome is utilized as a template for the synthesis negative sense strands. Host cells lack the necessary machinery to replicate RNA. Poliovirus uses a viral RNA-dependent RNA polymerase to produce RNA molecules of the opposite polarity. Viral protein VPg covalently attached to uridine (VPg-UUU) serves as the primer. The first round of replication produces a single antisense molecule. This antisense template is then used to produce sense copies of the original genome that can be packaged into viral capsids prior to viral release. Antisense genomes can translated as well. 

La replicación se produce enteramente en el citoplasma. Además de servir como plantilla para la síntesis de proteínas, el genoma sentido de cadena positiva se utilizacomo molde para la síntesis de hebras sentido negativo. Las células huéspedcarecen de la maquinaria necesaria para replicar ARN. Poliovirus utiliza un

  virusRNA polimerasa RNA-dependiente para producir moléculas de ARN de polaridadopuesta. Proteína viral VPg covalentemente a uridina (VPg-UUU) sirve como la cartilla. La primera ronda de replicación produce una molécula antisentido sola. Esta plantilla antisentido se utiliza para producir copias sentido del genoma original quepueden ser empaquetados en cápsidas virales antes de la liberación viral. Genomasantisentido puede traducirse así.

Packaging and Release  
After the virus has translated its RNA to produce the necessary proteins and replicated its genome, it needs to package the newly synthesized RNA molecules inside capsids. A complete virus consists of the RNA packaged inside the capsid. The capsid proteins self-assemble into an immature capsid, a structure which contains all of the necessary proteins, but which has not finished cleaving them into their final form. The mature poliovirus capsid has icosahedral symmetry and contains 60 copies of each viral capsid protein (VP1,2,3,4) The viral RNA enters the incomplete capsid and is secured inside when the viral proteases make the final cleavages. Once the genomes have been packaged into mature virions, the virus particles await the cell's lysis in order to be released. As many as 100,000 virions can be released from a single infected cell. 

Uncoating  
Binding between the virus and its receptor leads to conformational changes in the capsid. VP4, an internal capsid protein detaches from the capsid. The capsid swells and the poliovirus genome is susceptible to degradation. When VP1 is released, the genome is released onto the cytoplasm of the cell. The viral entry strategy is very inefficient; only 1% of the viruses initiate an infection. 

Scanning Electron Microscopy of surface alterations of HEp-2 cells  A. Cells at 3 hours past infection. Rounding of cells and pyknosis.        Elongation of filopodia.   B. Cells at 8 hours past infection. Rounding of cell. Elongation of filopodia.   C. Colapse of Microvilli.   D and E.. Cells at 10 hours past infection. Merging of filopodia occurs.  Koch, The Molecular Biology of Poliovirus, p.231

http://www.brown.edu/Courses/Bio_160/Projects2000/Polio/PoliovirusLifeCycle.htm

Carolyn J. Hoffman, MS, RD
Associate Professor
Department of Home Economics,
Family Life and Consumer Education
Central Michigan University
Mt. Pleasant, Michigan

Frederick M. Maynard, MD
Associate Professor
Department of Physical Medicine and Rehabilitation
Director The Post-Polio Research and Training Program
University of Michigan Hospitals
Ann Arbor, Michigan

AN ESTIMATED 640,000 survivors of paralytic poliomyelitis (polio) live in the United States¹, and at least 22% of them are experiencing declining functional capacity as a result of health problems². The late effects of polio include many specific health and rehabilitative problems that can develop among people with chronic muscle weakness caused by prior polio. The most common symptoms among people developing late effects are new muscle weakness, fatigue, and pain. Polio survivors who become disabled as a result of these symptoms are often said to have the post polio syndrome (Fig 1) ^3,4. Numerous hypotheses have been proposed to explain the new muscle weakness and atrophy that appears. The leading theory, supported by muscle biopsy studies and single-fiber electromyography⁵, is that the enlarged motor units, which develop following recovery from acute polio through the development of nerve sprouts, begin to shrink back to their original size^6. Progressive muscle weakness is most likely to occur among survivors who had relatively severe initial muscle weakness and who made sufficient recovery to use their muscles at a greater than normal percentage of maximum capacity for many years⁷. Although most clinicians caution polio survivors about excessive exercise, modest improvement in strength has been shown to occur with carefully controlled strengthening programs⁸. Benefits of flexibility exercises are almost universally acknowledged⁹. Benefits of conditioning exercise have been demonstrated but are often difficult to achieve because limb muscle capacity is insufficient for achieving a training effect on cardiopulmonary function¹⁰.

No information on nutritional intake or interventions among people with a history of polio was round in the literature. However, clinicians have acknowledged the relationship between other medical conditions that are known to be affected by nutrition and the designed to meet Ihe needs of individuals experiencing the late effects of polio. The objective was to compare food and nutrient consumption, biochemical and self-perceived wellness data, and anthropometric measures before and after participation in the program.
 

PROCEDURES

The Jo Strauss Post-Polio Rehabilitation Program was established in Mt. Pleasant, Michigan, a community of 22,000. Eleven subjects were recruited from among residents living within a 60-mile radius who were enrolled in the Michigan Polio Registry. All known post polio individuals in the region were contacted and invited to participate. Eight females entered the program, and one male and two females served as controls. These three individuals volunteered to complete questionnaires, assessments, and laboratory tests but did not participate in either the nutrition or exercise intervention program because of distance from program site or transportation cost.

A team approach was used and included the following: a local physician and internist, a consultant physician with expertise in physical medicine and rehabilitation (who is a director of a post polio training program), an individual with experience and training in aquatic exercises for handicapped, a registered dietitian, a representative from Easter Seals, a local businessman who gave the program financial support, and a representative who is a post polio survivor and who spearheaded all efforts.

Phase I of the program had two components: (1) a nutrition component designed to improve nutritional health of each individual; and (2) a water-exercise component designed to enhance flexibility of muscles and joints and to promote cardiopulmonary conditioning. A description of the program and a questionnaire were sent to each subject. The questionnaire recorded demographic and health information, including current age, age at onset of polio, description of any new symptoms, and when symptoms began. Functional activities such as ambulation status and ability to perform household activities, particularly cooking and shopping for food were noted. If subjects were on a modified diet, they were asked to describe it All medications used were recorded.

The program consisted of 16 weekly group sessions. Each session included a 1-hour, therapeutic, warm-water swim followed by a 1-hour nutrition education seminar. The initial and final sessions were held at a community hospital to obtain anthropometric and biochemical data. Other sessions were held on the campus of Central Michigan University, where there is a swimming pool and a barrier-free classroom. Each subject signed an informed consent form to participate and obtained a physician's approval to safely participate in range of motion and gentle conditioning exercises for 1 hour/week in a pool.

Prior to the first swimming and nutrition education session, subjects were shown food models and were given or were sent a graphic aid to assist them in determining the portion sizes of food consumed. They were instructed to keep a 3-day food intake record at the beginning and end of the study. Nutrient analysis was completed using the Nutritionist III software program.

Biochemical data were obtained at the beginning and end of the program and included a lipid profile: triglycerides (TG), tool cholesterol (TC). High-density Iipoprotein (HDL-c), low-density lipoprotein (LDL-c); red blood count, hemoglobin; and white blood count complete with red blood count differential. Blood samples were analyzed using the Hitachi 704 automatic analyzer and the Mannheim diagnostic system pack reagents.

Anthropometric measurements taken at the beginning and end of the program included body weight; supine height; bioelectric impedance (RJL, model 101) ford determination of % lean body mass, % body fat, % body water, and circumference measures of midarm, calf, waste, and hips¹¹. Some subjects required a platform scale for measurement of body weight in a wheelchair. This was available only at the hospital, where initial and final data were obtained. For other subjects, weekly estimates of body weight were taken at the pool location on a portable scale to assess trends and to ensure that weight loss was gradual.

The exercise component was designed to aid in strengthening and conditioning the participants' muscles and joints, to relieve stress, and to develop aquatic skills that could be used for lifelong conditioning after program completion Each subject was assisted by two water-safety aids; Lifesaving jackets were worn and specialized equipment was used (e.g., hand paddles, dumbbell flotation devices). Some of the exercises used were amt circling, fluntr kicking. walking pool length in water, and back flotation:

The nutrition component of the program was called "To Your Good Health," based on the book The New American Diet¹². This plan encourages a low-fat intake that allows those in need of weight reduction the opportunity to lose weight. Weekly sessions focused on self-appraisal of current intake, optimal protein and calcium intake, fat/cholesterol, fiber "sense," sodium considerations, and facts and fallacies. A quiz¹² was given at the beginning and end of the program to check intake compliance. Participants were encouraged to keep a daily log summarizing "feelings" and the presence or absence of post polio symptoms.
 
 

OUTCOME

Table 1 summarizes post-polio symptoms and ambulation status of the participants and controls. Participants and controls had a mean age of 53.5 years (range 41 to 67 years) and 55.0 years (range 38 to 69 years) respectively. The mean age at onset of polio was 12.6 and 16.7 years, respectively, and the estimated mean years from onset of polio to occurence of new symptoms was 39 and 26 years from participants and controls, respectively. Participants and control subjects were largeIy individuals in late middle age who had significant walking disabilities and many typical symptoms of post polio syndrome (Table 1). Three subjects were exclusively wheelchair users, and all were limited to relatively sedentary life styles by their residual muscle weakness from previous polio.
      Table 1. Disability characteristics of subjects

Table 2 reports nutrition assessment data before and after intervention.

Table 2. Group summary of key assessments before and after intervention (Phase 1)

Although some had few pounds to lose in body weight and others more, them was an average of 7.9 pounds lost for program participants and a gain of 2.6 pounds for controls. Them was an expected decrease in percentage of body fat of all participants. as measured by bioelectric impedance, and an average of 4 inches (8.8 cm) lost at the waistline. Of the program participants, 81.5% were able to either maintain or to continue to slowly decrease excess body weight during 24 months following the program. Some subjects experienced edema from medical complications that made group evaluation difficult.

Laboratory assessment data are shown in Table 3.
 
 

Table 3. Summary of selected biochemical laboratory values before and after intervention (Phase 1)

A mean decrease for total cholesterol of 26 mg/dL for program participants and a mean increase of 1.0 mg/dL for control subjects was observed. For LDL-c, an overall decrease of 11 mg/dL was demonstrated for participants and an increase of 3 mg/dL for control subjects.

Results of the dietary habits survey are presented in Table 4.
 
 

Table 4. Assessment of dietary habit scores* for post polio program

*Scores reflect female data, due to the fact that there was only 1 male control.
(1) As determined the student t-test. (1) P < .05 for the difference between the initial score and end score of participants.

All program participants showed significant improvement in intake from a mean initial score of 87.0 to 196.7 at; the end of program. Which exceed the program's p hase I goal. Even though the two female control subjects began with a higher mean initial score. it is evident that linle modification took place in the dietary intake for the controls of either gender. Scores of greater than or equal to 233 for women indicates an eating pattern that nutritionally provides maximum protection from the diseases of overconsumption.¹²

Table 5 summarizes the preintervention and post intervention nutrient intake of all subjects. There was a small decrease in caloric intake for program panicipants and an increase for controls. However, contrast is not due to calorics per se but to the composition of intake, especially fat. Consumed. Some increase in vitamin C consumption occurred, but most of it was accounted for by one participant. Who consumed large amounts of foods containing vitamin C.

Table 5. Comparison of means from preintervention and post intervention of selected nutrients consumed by pos  t polio subjects

*Source> National Academy of Sciences, Recommended Dietary Allowance, Washington, DC: National Academy Press; 1989.

DISCUSSION

Muscle Function

Although there were no quantitative measures to assess the contribution of the warm water exercise component of the program, the therapeutic effect of swimming for polio survivors has been observed by these authors. Details of an appropriate exercise program for post polio survivors have been given^8,13,14. Muscle stretching and joint range of motion exercises are important whenever there is muscle weakness⁴. Mild conditioning exercises may also help prevent further disuse atrophy. Comments made in the subjects' evaluations of the Jo Strauss Post Polio Rehabilitation Program overall were quite positive. It should be noted that care was taken to avoid exhaustive exercise. There is lack of general agreement about the effectiveness of strengthening programs for those with post polio syndrome. Fill yaw et al¹⁵ examined use of pretraining and intratraining muscle performance measures (n = 23) to determine if any measure can forecast whether muscle function will improve or deteriorate with exercise. Their preliminary results indicated that patients had no adverse effects from testing procedures of the exercise program and that no patient had to discontinue exercise because of signs of overwork. Feldman¹⁴ has reported favorable results using no fatiguing exercises combined with occupational therapy and orthotic management that resulted in improved ambulation and performance of daily living tasks.

Desirable body weight

Excess body weight may contribute to a secondary disability. One of the most persistent concerns of post polio patients is fatigue¹⁷. The question dietitians/nutritionists need to ask if: Can optimal nutrition aid in minimizing this effect? While some polio survivors will be at desirable body weight, exercise is limited for many of them, and obesity is likely to be more prevalent in this group. Data are needed to determine to what extent obesity exists among polio survivors, since obesity per se could accentuate the symptoms identifled as characteristic of post polio syndrome. For this determination to be made in people with many deformities, it is necessary to differentiate body weight from body composition. Multisided skin fold caliper measurements can be taken on some subjects, but there may be lack of uniformity due to paralysis of some body parts. Hydrostatic weighing would be cumbersome and frightening for many, especially those with breathing difficulties. The use of bioelectric impedance, as a quick and easy noninvasive method needs to be considered, since the validity and reliability of this technique has been established^18-22. Data are needed test values specifically for the post polio population It is important to follow recommended procedures for this method and to remove any metal braces prior to assessment.
 

CONCLUSIONS

Changing food habits

The foundation for the nutrition intervention sessions, as previously noted, was The New American Diet. This book was chosen as the basis for the nutrition education component because the ideas are presented in a simple manner and are easily understood by most lay people. The book provides pretested instruments for each content area for scoring intake (eg, fats and oils). There are numerous meal and recipe suggestions that meet "healthy eating" criteria. Furthermore. The organization and layout of the book makes it very easy for the nutrition counselor to follow.

There was a significant difference between the initial and final scores for intake of all food groups for program participants. There was increased consumption of high-fiber "plant world" foods, which can be of much assistance in bowel regularity, especially for individuals with limited exercise. It was hoped that use of laxatives would be avoided. Also, since renal problems are not uncommon in poliomyelitis²³, adequate but not excessive protein intake is needed.

Although a comprehensive detailed analysis of food intake was not completed for the 24-month follow-up of this pilot program, analysis of a usual day's intake suggests that program participants are aware of the benefits of a low-fat eating pattern and had incorporated the goals into their life style. Some even reported reduced food costs. All program participants stated consistent use of skim milk or nonfat yogurts or both. Subjects thought of visible and invisible fats as sources of "grease" and used such sparingly. Fish consumption increased. Subjects did not find it difficult to avoid adding salt to food at the table and were able to achieve the "sugar goal" of restricting baked goods to no more than 3 to 4 times per week Alcohol consumption was not reported by these subjects during the pilot or at the time of follow-up.

Limitations and need for support group

The limitations of the pilot program should be clearly stated. Larger numbers of subjects and appropriately matched controls are needed. However, the difficulties of transporting disabled individuals over considerable distances to a centralized meeting site and of choosing a convenient time for subjects necessitate small, community-based programs. it would be important in future programs to screen participants for presence of nonpolio-related conditions and for specific polio-related conditions to assess program effectiveness for promoting improved health.

It is of great importance to recognize that perhaps one of the greatest benefits of a program that brings together individuals who share a common concern is the emotional support they receive from knowing they are not alone in their efforts to confront the late effects of polio. This was observed during this program in a multitude of ways. The sessions began to function as a support group. Various topics and feelings were shared with others who had been through the same experience, and a spirit of unity unfolded as individuals realized that they were not alone in their struggles. The new symptoms experienced are extremely profound because they are unexpected and their cause is not fully understood. Cameron²⁴ has studied the psychology health of post poliomyelitis patients and has concluded that "post-polio persons, as a group are not depressed.'" In a group situation they can confront their true feelings in a "safe environment." Schneider²⁵, an internationally known grief and loss authority, has said that a new loss can trigger the unresolved feelings around old loss and that "unresolved loss may be one of the most significant factors in health and disease.'" Frick²⁶ described the psychology of post polio sequelae and encourages individuals to be part of post polio support groups. Roller and Maynard have prepared useful resources to aid post polio survivors in the community. (Sec suggested resources at end of article.)

Areas for needed research

It is of interest that among the most common medical problems associated with post polio syndrome are obesity, diabetes, anemia, endocrine disorders, and cardiovascular disease." There is a tremendous need for further study of prevalence and risk factors for these nutritionally related secondary conditions with this population.

Designing the clinical nutrition component

The following steps comprise the clinical nutrition component.

1. After program participants were identifled, health-related Background information about each participant was obtained as follows: age, weight height, known allergies, diagnoses (eg, ulcers, ambulation status and equipment used, medications), and miscellaneous facts (eg, smoker or nonsmoker, "drinker' or "non-drinker"), age of polio onset, date of onset of post polio symptoms, and diet history.

2. Prior to beginning the program, two consent forms were required for each participant. One was a physician's consent form and the other a laboratory screening consent and release statement

3. The dietitian completed a specialized nutrition assessment for each participant that included evaluation of the following components:

• History of nutrient intake and current intake pattern Weight history as well as monitoring and recording of weekly weight status throughout the program
• Anthropometrics, including body composition via bioelectrical impedance or skin fold measurements where valid and circumference for the purpose of client comparison of progress mode.
• Clinical signs of malnutrition
• Mechanical physiologic or psychologic problems that interfere with ingestion, digestion, absorption, or metabolism of nuuients.

4. A follow-up/summary report for each program participant was completed.

The authors' long-range goal is to see similar programs initiated throughout the state and nation There is a need for health care professionals to become aware of and sensitive to the special needs of post polio patients. It is the conclusion of these authors that the nutrition needs of this target group may not be unique or different from those of the general population However, it may be that lack of nutrient adequacy or nutrient. Excess contributes to the symptoms experienced by many who are faced with the late effects of poliomyelitis. Dietitians should focus on a problem-solving approach and should encourage multidisciplinary collaboration. Especially with specialists in adaptive exercises. These authors believe that combined programs of nutrition education. Exercise. And group support have great potential for preventing secondary disabilities in the aging population of motor-impaired polio survivors.

The authors suggest the following resources for health care professionals: (1) Roller A. Maynard F. Coping Successfully with Polio's Late Effect [Videotape]. Ann Arbor. Mich: University of Michigan Hospitals Post-Polio Research and Training Program. 1989. (2) Post-Polio Research and Training Program. Coping Successfully With Polio's Late Effects; A Directory of Post Polio Resources for Michigan. Ann Arbor, Mich: University of Michigan Hospitals Post Polio Research and Training Program.

REFERENCES

1. National Center for Health Statistics, 1987 National Health Interview survey, Hyattsville, Md: US Public Health Service; 1987.

2. Codd MP, Malder DW, Kurland, LT, Beard CM, O'Fallon WM. Poliomyelitis in Rochester, Minnesota. 1935-1955: Epidemiology and long-term sequalae; Apreliminary Report. In: Halstead LS, Weichers DO, eds. Late Effects of Poliomyelitis. Miami, Fla: Symposia Foundation; 1985

3. Halstead L, Weichers D, Rossi C. Late effects of poliomyelitis: A national survey. In: Halstead LS, Weichers DO, eds. Late Effects of Polio Myelitis. Miami, Fla: Symposia Foundation, 1984.

4. Lauri G, Maynard F, Fischer D, Raymond J. Handbook on the late effects of poliomyelitis for physicians and survivors. St. Louis: Gazette International Networking Institute; 1984.

5. Dalakas MC, Felder G, Hallen M, et al. A long-term follow-up study of patients post-poliomyelitis. N Engl J Med. 1986; 314:959-963.

6. Weichers DO, Hubbell SL. Late changes in the motor unit after acute poliomyelitis. Muscle Nerve. 1981; 4:524-528.

7. Klingman J, Chui H, Corgiat M, Perry J. Functional recovery: Major risk factros for development of post-poliomyelitis muscular atrophy. Arch. Neurol. 1988; 45:645-647.

8. Feldman RM, Soskolne CL. The use of nonfatiguing strengthening exercise in post-polio syndrome. In: Halstead LS, Weichers DO, eds. Research and Clinical Aspects of the Late Effects of Poliomyelitis. White Plains, NY: March of Dimes Birth Defects Foundation; 1987.

9. Holman KG. Post-polio syndrome: The battle with an old foe resumes. Postgrad Med. 1986; 79:44-53.

10. Jones DR, Speir JL, Canine JK, Own R, Stull GA. Cardio-respiratory responses to aerobic training by patients with post polio sequelae. JAMA. 1989; 261:3255-3258.

11. Bray GA, Gray DS. Anthropometric measurements in the obese. In: Lohman TG, Roche AF, Martoull R. Anthropometric Standardization Reference Material. Champaigne, Ill; Human Kinetics Books; 1988.

12. Connor SL, Connor WE. The New American Diet. New York: Simon and Schuster; 1986.

13. Gross MT, Schush CP. Exercise program for patients with post-polio syndrome: A case report. Phys. Ther. 1989; 69:72-76.

14. Owen RR, Jones D. Polio residuals clinic: Conditioning exercise program. Orthopedics. 1985; 8(7):882-883.

15. Fillyaw MJ, Bradley WG, Badger GJ, Fries TJ, Wilder D. Exercise and fatigue in post-polio patients. Fifth International Polio and Independent Living Conference; June 1, 1989, St. Louis.

16. Feldman RM. The use of strengthening exercises in post-polio sequelae. Orthopedics. 1985; 8(7): 889-890.

17. Lee F, ed. Annual meeting highlights. Polio perspectives. 1988; 3(1):1,2.

18. Lusaki HC, Bolonchuk WW, Hall CB, Sidess WA. Validation of tetrapolar bioelectrical impedance method to assess human body composition bt electrical impedance methods. J Appl Physiol. 1986; 60:1327.

19. Segal KR, Gutin B, Presta E, Wang J, Van Itallie TB. Estimation of human body composition by electrical impedance methods: A comparative study. J Appl Physiol. 1985; 58:1565.

20. Lusaki HC. Methods for the assessment of human body composition: Traditional and new. Am J Clin Nutr. 1987; 58:1565.

21. Segal DR, Van Loan M, Fitzgerald P, Hodgon JA, Van Itallie TB. Lean body mass estimation by bioelectric impedance analysis: a four-site cross-validation study. Am J Clin Nutr. 1988; 47:7.

22. Khalad MS, McCutcheon MJ, Reddy S, Pearman PO, Hunter GR, Weinsier RL. Electrical impedance in assessing human body composition: The BIA method. Am J Clin Nutr. 1988; 47-789.

23. Taylor JR, Alcock AJ, Hildes JW. Hyalumidase and renal calculi in poliomyelitis. Am J Med Sci. 1955;230:536-540.

24. Cameron MG. Emotional and psychological impact of a second disability. An investigation of appraisal processes, coping strategies and depression in post-poliomyelitis patients. Proceedings of the National Conference on the Late Effects of Polio; Ontario March of Dimes; November 3, 1988; Toronto, Canada.

25. Schneider J. Stress and Grief. Baltimore, Md: University Park Press; 1984.

26. Frick MN. Post-polio sequelae and the psychology of second disability. Orthopedics. 1985; 8(7):851-853.

27. Weichers DO. Diagnosing post-polio problems. American Congress of Rehabilitative Medicine Annual Meeting; October 20, 1987; Orlando, Fla.