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Antonio M Gordon
MD, Raúl F. Masvidal MD, Institute Finlay-Albarrán of Medicine
Formerly Clinical Studies Group,
Mailing address: P.O. Box 523096
Telephone: 305-556-6459 Running head: Epidemic Amblyopia (a) Pseudonym for José A. Nuñez de Villavicencio, MD. At the time of this study Dr. Nunez’s family was still in Cuba and he asked to use a pseudonym to avoid reprisals. Before seeking political asylum, Dr. Nuñez worked under the direction of Fidel Castro Diaz-Balart in the Cuban Nuclear Institute. uuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuu Summary / Abstract The Cuban Ministry of Public Health (MINSAP) in the first half of 1993 reported an epidemic characterized by progressive loss of vision. Reports from Havana and various experts who travelled to Cuba to investigate it have not been conclusive in defining the pathophysiology and etiology of this curious epidemic. A field study was carried out in which recently arrived Cuban immigrants into South Florida were studied to elucidate the Cuban epidemic. 198 unselected rafters were investigated among whom there were 28 who had amblyopia. The illness in question, Cuban Epidemic Amblyopia (CEA), is a reversible retinopathy associated with a low consumption of milk, beef, and fish and low serum levels of vitamin B12. No evidence of optic neuritis or neuropathy was found by MRI or suggested by the clinical findings or course of the illness. It is suggested that adequate dietary energy, high biological value protein and vitamin B12 be made available to the population at risk. CEA is not specifically associated with the use and/or intoxication of tobacco, alcohol, or cyanide. Clinically, it is not a viral illness and it not associated with peripheral neuropathy, CEA is a new syndrome where deficits in energy, high biological value protein, and vitamin B12 result in a dysfunction of the retina giving rise to a national epidemic in the Island of Cuba. Its pathophysiology is that of a retinopathy similar but not identical in etiology as tobacco alcohol amblyopia. In CEA the deficient electron transport chain oxygen utilization is not related to a specific genetic syndrome or the presence of a recognized toxic agent. Introduction The Cuban Ministry of Public Health (MINSAP) (1) reported an epidemic of what had been termed “optic neuropathy” in the first half of 1993. According to official sources, epidemic surveillance began in October 1991 when an optic illness characterized by progressive diminussion in vision was first recognized (2,3). In April 1993 the MINSAP appealed for assistance to the Who through its Viceminister, Dr. Jorge Antelo Perez (1). Immediately, various international agencies and groups undertook a mission to Havana to investigate the epidemic. Twenty patients selected by MINSAP officials were examined (3,4). The experts left the island without being able to examine normal subjects or independently document the prevalence of the illness in question. In general, they proposed that the Cuban optic syndrome was possibly due to nutritional deficiencies, toxins, or an undefined viral infection (3,4). According to MINSAP, the syndrome consists of loss of vision due to an acute or subacute illness involving a reversible, bilateral "optic neuropathy" (1). The epidemic began in the rural areas of Pinar del Río in the western tip of Cuba (1,3). Initially, it affected 25 persons per month but by mid 1993 the prevalence of the illness had climbed to 312/100,000. The disease spread from West to East so that Western Cuba had a higher prevalence (1167/100,000) than the remainder of the island (1). Eventually the epidemic was detected all over the Cuban archipelago and it affected 43,412 persons (3). No deaths were reported and some improvement was observed with rest and the use of enriched diets (3). No tissue studies were disclosed. The sex specific rates reported were 337/100,000 for women and 287/100,000 for men (1). Our group, a nongovernmental, nonprofit, voluntary organization of physicians and their associated, was in a position to study the Cuban optic epidemic because of our geographic location, cultural backgrounds and access to newly arrived Cuban immigrants into South Florida. Previous studies carried out by our group and others in which newly arrived Cuban immigrants were studied had proven valuable in providing an independent window through which the health of Cubans was evaluated (5,6,7). Subjects and Methods Unselected Cuban immigrants arriving in South Florida by sea, ie. rafters, were under medical and nutritional surveillance by our group from October 1, 1992 until September 30, 1993. 198 unselected rafters were examined within one month of entry into the US (mean time since arrival in US: 16+/-15 days). The number of Cuban rafters who arrived in South Florida in the same interval of time was approximately 3, 500 persons. Our project is called ENSAC (Encuesta Nutricional y de Salud de Cubanos). ENSAC consists of a general hygienic, medical and nutritional survey, anthropometric measurements, and physical examination. A dietary history was obtained from all subjects through which all foods (and drinks) consumed in Cuba by each immigrant during their last week of residence in the island was recorded. This method was used in an earlier study and found to correlate well (within 2%) with data from the Cuban Institute of Internal Demand in Havana (5,8,9). The diet history of children was obtained with the assistance of their parents or relatives. No children rafters arrived here alone. A simple screening protocol was used to screen for the optic syndrome. It included: visual acuity assessment, color vision assessment using the four standard Belhaven charts, opticokinetic reflex, and Amsler grid optical response. The latter visual tests were applied to all subjects with more than 6 years of age. The working diagnostic criteria used are summarized in Table 1. All subjects with history of amblyopia who met the diagnostic criteria of "presumed retinopathy" (Table 1) had blood draw when first seen for determinations of folic acid and vitamin B12 levels. Certified clinical laboratories in the USA performed all laboratory determinations reported here. All amblyopic subjects were followed within one to six months after entry with particular attention to the vision screening protocol and their current dietary intake in South Florida. Subjects in the diagnostic category of "possible retinopathy" had further clinical investigations as follows: chest radiography, hepatitis A, B, and C, serology, complete blood count, serum iron and total iron binding capacity, serum albumin, cyanide level, thiocyanate level, serum protein electrophoresis, VDRL, serum levels of immunoglobulins A, M, and G, urine toxicology, and delayed hypersensitivity reactions to candida albicans, mumps and tuberculin antigens at standard dilution and dose. ENSAC was carried out by volunteers with a budget of less than US $2000 per year. Statistical analysis was carried out with the aid of the "Kwitstat" program. P values less than o.05 were considered significant. Results The demographic characteristics of the 198 unselected subjects who were examined are summarized in Table 2. Twenty-eight subjects (14.1%) complained of decreased vision of recent onset and met the diagnostic criteria for "presumed retinopathy" (Table 1). Their age range was from 13 to 73 years. The visual acuity of these subjects ranged from 20/40 to 20/200. None of the amblyopic subjects had signs of palmar hyperemia, angular stomatitis, glossitis, scrotal dermatitis, ataxia, or cutaneous vesicles. The frequency of common medical problem in the subset of subjects defined above revealed no discriminatory associations between those affected and non-affected. Specifically, the frequency of numbness and decreased deep tendon reflexes was not statistically different in those affected and those non-affected (P=907) (Table 2). The dietary intake of all subjects diagnosed with amblyopia, the children and non-amblyopic adults studied are summarized in Table 3. The weekly frequency of consumption of beef and fish of adults suffering from amblyopia was significantly lower than for adults not affected with it. The folic acid and vitamin B12 levels of amblyopic subjects were 4.6+/- 2.0 ng/ml (normal 2.2 - 17.3 ng/ml) and 253 +/_ 29 ng/ml (normal 232-1138 pg/ml) respectively. Two amblyopic subjects had abnormal color vision (green-red) and Amsler grid responses suggestive of centrocoecal scotomas in the ENSAC optical screening protocol (Subjects A and B). These two subjects were studied further with the aid of magnetic resonance imaging (MRI). Scanning was performed with an ELSINT 2 TESLA magnet utilizing head coil through brain and orbits using T1 and T2 weighted sequences, 3 mm slices in multiple orthogonal plains before and after Gadolinium administration. No evidence of optic neuropathy or neuritis was detected. Both subjects were referred for a complete ophthalmological evaluation within 10 days. Only one of the two subjects (Subject A) was found to have signs of paleness in the temporal aspect of the optic disc at that time. Table 1.- Diagnostic classification used in survey.
*ethambutol,
chloromycetin, streptomycin, isoniazid, chlorpropramide, uuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuu Table 2.- Demographic
and other characteristics of Cuban subjects studied.
uuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuu Table 3.- Dietary
Intake (in days per week +/- SD) of Cuban Subjects
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Table 4.- Clinical Findings of Two subjects with CEA
Table 5.- Clinical
features of CEA victims and multiple neuritis patients
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No children less than 13 years of age were affected with CEA. Among adults, the number of men affected was statistically significant when compared to those men non-affected with CEA (P<0.001). Men affected with CEA were older than those non-affected (40.5 versus 23.4 years). Body mass index (BMI) and triceps skin fold (TSF) thickness were used to assess the adequacy of body weight and fat stores of all subjects. The BMI was lower in the rafters affected with CEA (P=0.079) than in non-affected rafters. The TSF was somewhat lover in both men and women affected but the differences were not statistically significant. However, the prevalence of obesity (BMI>30) among CEA subjects was lower than in those non-affected. In men, the prevalence of obesity was significantly lower (P=0.28 in CEA subjects than in those non-affected. The prevalence of an underweight status (BMI<20) was higher in men and women with CEA than in other adults. The differences were both statistically significant (P<0.05). All 28 amblyopic subjects had improved when they were reexamined 1 to 6 mo after the initial evaluation. The follow up evaluations were carried out on the average 47+/- 15 days after entry into South Florida. None of the immigrants were institutionalized at the time of follow up. All had found housing, and/or employment in the community. None of the 26 subjects who had remained in the "presumptive retinopathy" diagnosis had evidence of decreased visual acuity or complaints of any visual disorder on follow up. The follow up dietary questionnaire revealed that the diet of all 28 amblyopic subjects had improved significantly. The follow up weekly frequency of consumption of various foods in the 28 amblyopic subjects was as follows; milk: 6.4+/-1.6 meat group: 6.8+/-0.7, beef: 4.2+/-1.7, and fruits 6.4+/-1.7 days/wk. these were all highly, significantly improved when compared to the corresponding frequencies of consumption for these same foods during their last week of residence in Cuba (Table 3). Subject A is a 22 year old, single man who had been in prison in Pinar del Rio during most of 1990 and 1992 charged with attempting to leave the island illegally. He had been out of jail in Pinar del Rio during approximately 8 months prior to his arrival in South Florida. The onset of amblyopia occurred 11 months prior to entry into the US. He had been hospitalized in the latter part of 1992 and early 1993 at the Pinar del Rio Provincial Hospital where "optic neuritis" was diagnosed. Subject B was a 34 years old housewife from Guira de Melena also in Western Cuba. She carried in Cuba a diagnosis of "irritable bowel syndrome" managed with chlordiazepoxide and had symptoms of amblyopia since 6 months prior to entry into the US. One month after entry they were reexamined. Only subject A failed the ENSAC optical tests then. Subject A was referred for a neurological evaluation and nerve conduction study. Both of these were normal. Clinical data available in subjects A and B are summarized in Table 4. Subject A had a persistently elevated immunoglobin A level of unclear etiology. In the differential diagnosis of this finding tropical spree was considered since elevations in 1gA have been reported in such patients (10). Unfortunately, he refused gastrointestinal evaluations. Five months after his arrival in South Florida, however, subject A was again examined through ENSAC. His optical screening was completely normal. Specifically, the defects in the Amsler grid test had vanished and color vision was normal. The laboratory data then revealed a thiocyanate level of 1.4 mg/dl and an essentially unchanged level of immunoglobulin A. DISCUSSION Our observations confirm the presence in the Cuban population of a disorder in epidemic proportions characterized by amblyopia. For the sake of comparison, among 103 consecutive, unselected Latin American - non Cuban- immigrants seeking immigration physicals during the same interval of time here in South Florida, only 1 person complained of amblyopia that was related to glaucoma. The same questionnaires used in ENSAC were used to evaluate these non - Cuban immigrants. Therefore, the high frequency of amblyopia in the Cubans studied (14.1%) from October 1992 through September 1993 was significantly higher than what may have been expected from a comparable population of immigrants (p<0.001). These data support the presence of what should be termed: the Cuban Epidemic Amblyopia (CEA). It is not claimed here that the particular sample of Cubans studied was a representative sample of the Cuban population in the islands at the time of the study. It is suggested, however, that an appreciable number of Cuban in the islands in the age range from 13 to 73 suffer from amblyopia. The latter was found to be somewhat elusive in South Florida due to its reversibility in this environment. This reversible visual disorder affecting Cubans is characterized by retinopathy and not by optic neuritis or neuropathy as had been suggested by others (1,3). Our data indicate that women are affected more commonly than men but older men are affected with significantly more frequency than younger ones (P<0.001). Children are not affected. Considering the BMI data, assessment for obesity and underweight status, it can be concluded that those affected with the CEA likely had a negative or borderline metabolic energy balance while in Cuba. The reversibility of the CEA was apparent in all subjects who were found to have improved during a relatively short observation period in South Florida. 96% cleared all symptoms and signs of CEA in an average of 47 days. Given the rapid reversibility of CEA, it is likely that subjects with the "presumptive retinopathy" diagnosis had objective signs of retinopathy in Cuba. It was evident from our observations that the CEA resolved spontaneously in this environment and concomitantly with the consumption of an improved diet. The most evident features of the improved diet of Cubans in South Florida were a more frequent consumption of milk, beef, fish, fruits and other vegetables like potato, malanga and other Cuban foods. It could be argued that the diet consumed by the rafters in the island during their last week of residence there was not their typical diet. Indeed, it was clear from the comments made by the rafters that their "usual" diet was worse than what they consumed during the last week of residence in Cuba. Before departure they would often kill a pig and partake of it as a holiday or they would be invited to other houses to "feast" before their departure into the sea. We were able to document an improved vision and dietary intake in all subjects after their arrival here. Since the subjects had arrived in South Florida an average of 16 days before their first evaluation through ENSAC, the ENSAC data likely overestimates the weights of the immigrants on arrival. Therefore, widespread malnutrition may be more prevalent in Cuba than what may be suggested from our data. Therefore, it seems reasonable to suggest that the CEA is reversible without any specific vitamin therapy in the setting of an improved dietary intake and slightly more Northern latitude. Given these data, however, it can be recommended that an improved intake of energy, high biological value protein and vitamin B12 be provided to those at risk of the CEA as soon as possible. Some etiologies which had been proposed to explain what was termed "the Cuban optic neuropathy" (3,4) epidemic are not supported by our data. The possibility that cyanate intoxication (1,3,4,11) due to consumption of Cuban "yuca" ("yuca dulce", Manihot palmata) was unlikely because Cuban yuca is not the type of manioc ("yuca agria", M. utilissima) which contains high levels of cyanates and/or cyanogenic glycosides (12). Furthermore, high cyanate levels were not detected in the CEA subjects (Table 3). Tobacco has also been known to be a source of cyanates (13, 14) but the frequency of tobacco smoking among CEA subjects is not different from that found among adults not affected by the CEA (Table 2). The suggestion that a high carbohydrate diet in the setting of thiamine deficiency may have been the etiologic factor of the epidemic can be discarded also (3,11). It was found that the current diet of Cubans in the island provides black beans as a rule. This is considered a natural and adequate source of thiamine (15). With regards to the possibility that a high carbohydrate intake alone being associated with the Cuban syndrome, it should be noted that the Cuban Independence Army consumed cane juice (guarapo) almost exclusively for food during prolonged periods of time from 1895 until 1898 without developing blindness or beriberi (16). The same Cuban author who reported the latter had described earlier beri-beri in Cuba (17). Thus making it unlikely that a high carbohydrate intake with or without beri-beri cou7ld explain loss of vision in Cubans under the most adverse of situations. No evidence could be found here to suggest an association between the CEA and the use of alcohol, home brewed alcoholic products, soy oil or soya products, the presence of a viral infection, or decreased deep tendon reflexes in the lower extremities as had been postulated elsewhere (1,3,4,11). The data presented here clearly suggest that frequency of consumption of milk, beef, and fish in Cuba are significantly lower in CEA subjects than in other adults or children. Furthermore, the level of vitamin B12 in the serum of CEA subjects was somewhat low. It is unfortunate that the levels of vitamin B12 in serum for the subjects studied while they resided in the island or at entry into the US are not available. However, it is possible to estimate them through a regression function. Indeed, when the level of vitamin B12 in serum at the time of their first encounter in ENSAC is plotted against the number of days post arrival in the US -when the ENSAC blood samples were drawn- a straight-line function is observed with a positive correlation coefficient (r = +0.47). In this manner, the level of vitamin B12 in serum at entry (0 days post entry) can be estimated at 182 pg/ml. The latter level of vitamin B12 is clearly deficient. It had been suggested that the tropical neuropathies described as Strachan Syndrome (3,4,18) in Caribbean field workers may be somewhat similar to the CEA. However, the syndrome described by Strachan (18) is not identical to the CEA. The features of both syndromes are summarized in Table 5. Specifically, the absence of numbness, hyperemia of the palms, and cutaneous vesicles in the CEA rule out Strachan Syndrome. However, it may also be argued that the CEA represents a special case of tropical neuropathies described in prisoners of war in WWII (19). It had been noted that in contrast to prisoners in more temperate climates, prisoners in tropical camps were frequently victims of neuropathies while the prisoner in more temperate climates were not (19). Pathologic studies have revealed demyelination in the prisoners affected (19). In addition, tropical malabsorption may have been a co-illness necessary to render a particular prisoner susceptible to these demyelinating syndromes. In the Cuban subjects affected with the CEA, however, we could not demonstrate any specific sign of demyelination, enteropathy or neuropathy. Another syndrome that may involve amblyopia and has been associated with the Tropics is the Nigerian Nutritional Ataxic Amblyopia (NNAA) (14). NNAA is associated with diffuse demyelination and chronic cyanide intoxication. It is not readily reversible without specific therapy and its victims also show signs of angular stomatitis, scrotal dermatitis, and ataxia along with various degrees of amblyopia (14). Some investigators (3,4) and the MINSAP have argued that the CEA is associated with a syndrome involving peripheral neuropathy. The evidence gathered here clearly suggests that there is an absence of optic neuropathy in these patients. Furthermore, the epidemic illness has a favorable clinical course in the CEA. Therefore, we feel that the disease in question is a reversible retinopathy not associated with demyelination or a specific known toxin. In our subjects, the CEA was not associated with peripheral neuropathy or appeared to behave or have signs of the NNAA or demyelination. We must conclude that the peripheral neuropathy patients being reported with alarming frequency in the health facilities of the island (4) suffer from an illness that is not CEA. Further studies are needed to define other epidemics currently affecting the Cuban population. The clinical features of CEA are clearly more consistent with a variant of the tobacco alcohol amblyopia (TAA) syndrome (13) than with any neuropathy associated with demyelination (14) or Strachan Syndrome (18). It can be concluded that a precarious energy balance and a low intake of high biological value protein in the setting of a borderline or low vitamin B12 nutriture demonstrated in the Cubans affected was associated - and likely caused - a new syndrome of retinal dysfunction: the CEA. The nutritional deficiencies described here have been found in the setting of alcoholic patients with what has been termed TAA (13). In CEA, however, alcohol and tobacco are not part and parcel of the illness in question. The pathology of TAA has recently been found to be also a retinopathy by MRI studies (13). Although consumption of alcohol and use of tobacco in the Cuban subjects studied was not specifically associated with the CEA, the severity of the CEA in subject. A may have been due to the additional insult of alcohol and tobacco. It should be noted that the latter subject continued to use tobacco and alcohol after his arrival in the US. Although no evidence of cyanide toxicity was found from laboratory and clinical standpoints, CEA subjects should be expected to be more sensitive to the toxic effects of cyanide in view of their precarious vitamin B12 and a deficient intake of foods that usually provide high biological value protein. There was a slight increase in the serum thiocyanate level in Subject A five months after his arrival into South Florida when his dietary intake was fairly adequate. Assuming that this exposure to cyanide was unchanged, this may suggest a better sulphur containing nutriture. The improvement observed in the follow up dietary survey clearly supports the latter assessment. It had been argued earlier that a nutritional deficiency was unlikely because children were not affected by the CEA. However, it is clear from our study, that the diet of children was significantly better than that of adults (Table 2). It seems quite laudable that the parents are preferentially saving beef and fish products for the children. Furthermore, the Cuban government restricts rations of milk for children up to seven years of age. The fact that children are spared from the CEA is consistent with the data discussed earlier where women are affected more commonly than men. The reason for a greater susceptibility of older men than younger ones to the CEA may be related to the fact that in older men (<35 years of age) the frequency of tobacco smoking was 78%. This is significantly higher than in the younger ones (33%) (P<0.001). The frequency of alcohol users among the older Cuban men was 55%, not statistically different from the frequency among younger ones (50%). This assessment again suggests that tobacco smoking will likely aggravate the CEA turning it into a clinical picture more similar to TAA. The relatively rapid reversibility of the CEA is consistant with the evolution of a syndrome similar to TAA (13). Other syndromes of similar pathophysiology of retinal dysfunction such as Leber's Syndrome of genetic etiology involve a clinical picture of retinal dysfunction (14) but clearly have etiologies different from the CEA and are not readily reversible. Cuba thus far has managed the epidemic by formulating, manufacturing and distributing a vitamin supplement which bas been made available to the entire population of the island on a daily basis since May 1, 1993 (3). Specifically, little has been done in terms of effectively providing adequate sources of energy, high biological value protein and vitamin B12 to the population at risk. Instead, Cubans have been advised by the Cuban Institute of Dietetics and Nutrition to consume banana peels (20). The latter practice should not be recommended since banana peels are known to be toxic to humans and have been shown to be associated with a negative protein energy ratio (21). Obviously, in view of our findings, it seems imperative to avoid practices that may jeopardize protein utilization further. The other approach followed by Cuba to deal with the CEA has been to appeal to the WHO where viceminister Antelo argued against what he called "the causes" of the epidemic. Among these, he singled out the American embargo now strengthened by the "Torricelli Act," the ravages of the 1993 storm of the century in Cuba with its 1 billion dollars in damages, and the loss of Cuba's fair trade partner status with the now defunct Soviet Union (1). From this perspective only the American embargo seems amenable to negotiation at this time. Indeed, it seems reasonable to review the effects of this American policy and its effects on the diet and health of Cubans in the island. However, another possibility which should be explored in order to save the Cubans from further pathophysiologic disasters seems clear. It is one which should be evident once it is recognized that there is no justification for keeping Cubans in the island away from their own native products such as "boniato" (Ipomea batata), "malanga" (x. saggitefollium), peanut, orange, pineapple, caimito, guava, shrimp, lobster and fish. These Cuban foods can provide valuable nutritional requirements which are not currently accessible or distributed in an egalitarian manner to those at risk of CEA. Although CEA has been shown to be reversible in South Florida, it is not known what its clinical course will be if unattended. Therefore, along with Antelo's plea (1) it is also reasonable and most urgent from both public health and a humanitarian viewpoint to allow all Cubans to have free access to all markets in the island and to the products of their land and sea. References 1.- WHO, Cuba: Neuromyelopathy Epidemic. "Situation report No. 2" Geneva, June 4, 1993. 2.- Granma (Havana), Epidemia de neuritis óptica. April 3, 1993; p 1. 3.- Lincoff NS, Odel JG, Hirano M. "Outbreak" of optic and peripheral neuropathy in Cuba? J Amer Med. Assoc. 1993: 270; 511-8 4.- Tucker K, Hedges TR. Food Shortages and an Epidemic of Optic and Peripheral Neuropathy in Cuba. Nutr Rev 1993:51;349-57 5.- Gordon Jr. AM, Nutritional Status of Cuban Refugees. Am J Clin Nutr 1982: 35;582-590 6.- Gordon Jr. AM, Caribbean Basin Refugees. J Fla Med Assn 1982:69;523-527 7.- De Medina M,
Fletcher MA, Valledor MD, Ashman M, et al.
Serological evidence for HIV infection in Cuban immigrants in 1980. 8.- Gordon, AM. The Nutriture of Cubans. Cuban Studies/Estudios Cubanos 1983:13;1-4 9.- Handelman H. Cuban food policy and popular nutritional levels. Cuban Studies/Estudios Cubanos 1981:11;127-46 10.- Malik AK, Mehta SK, Chandrashekhar Y, Mahajan a, et al. Quantification of Innunoblobulin-containing cells in the jejunal lamina propria in tropical sprue. J Clin Gastroenterol 1992:14;163-6 11.- Altman LK. Experts ponder Cuban epidemic. New York Times May 25, 1993; p 3C 12.- Marrero L. "Cuba: Sociedad y Economía". Vol 1 Madrid: Playor, 1976 13.-Kermode AG, Plant GT, Miller DH, Kendall BE, et al. Tobacco alcohol amblyopia: magnetic resonance imaging findings. J Neurol Neurosurg Psych 1989: 52;1447 14.- Vogel SN, Sultan TR. Cyanide Poisoning. Cin Toxixol 1981:18; 367-83 15.- USDA "The nutritive value of American Foods". Agriculture handbook No. 9. Wash DC 1975 p 17 16.- Gordon y Acosta AM. "El Azúcar como alimento del hombre". Havana: Imprenta Militar. 1899: 25 17.- Gordon y Acosta AM, Ensayo sobre el análisis clínico y hematológico de la sangre en el beri-beri. An r Acad ciencias (Havana) 1872:9;260-272 18 Strachan H. On a form of multiple neuritis prevalent in the West Indies. Practioner 1897: 59;477-484 19.- Fisher M. Residual neuropathological changes in Canadians held prisoners of war by the Japanese. Can Serv Med J 1955:11;157-199 20.- El Nuevo Herald (Miami). Nitza Villapol da recetas con hierbas. April15, 1993; p 3A. 21.- Sharaf A, Sharaf OA, Hegazi SM, Sedky k, Chemical and biological studies on banana fruit. Z Ernaerungswiss 1979: 18;8-15 uuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuu Acknowledgement
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