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Biomedical subjects

E Gaitan

Publications and source records attributed to E Gaitan.

At least 19 recordsLinked to original sources

Neuroendocrine-immune interactions associated with loss and restoration of immune system function in spinal cord injury and stroke patients.

Both natural and adaptive immune responses were shown to be strikingly decreased in initial blood samples from 34 spinal cord injury and stroke patients. NK-cell function decreased to 24.8% (mean) 2 weeks after spinal cord injury in previously healthy young adults whose control group revealed a mean NK-cell function of 48.7%. This was accompanied at 2 weeks by increased plasma ACTH (mean of 17.0 pg/ml from 17 patients compared to a mean of 11.2 pg/ml from 12 controls) and urine free cortisol levels (mean of 152.1 micrograms/24 h from 9 patients compared to 53.6 micrograms/24 h from 15 controls). T-cell function and/or activation decreased to below normal values within 3 months after injury as revealed by lymphocyte transformation that was 32.8% of normal at 3 months. T-cell activation diminished as shown by a mean IL-2 receptor level of 179.3 units/ml in patients compared to 328.2 units/ml in controls. Serial monitoring of NK- and T-cell function revealed that specific physical rehabilitation therapy over a period of 6 months after injury restored NK- and T-cell function to near normal levels in most patients. This improvement was accompanied by a parallel rise in the patient's functional independence measurement scores. Results suggest critical neuroendocrine-immune system interactions in the restoration of immune function. Cortisol levels reverted to normal after 6 months of rehabilitation. Limited data suggest that natural immune system depression, NK-cell function, persists in spinal cord injury patients not receiving rehabilitation therapy (mean NK-cell lysis of 10.3%; p < 0.01).

Adrenocorticotropic Hormone

Antithyroid effects of coal-derived pollutants.

Endemic goiter in iodide-sufficient areas of the United States and Colombia has been linked to watersheds rich in coal and shale, which several reports suggest are the source of water-borne goitrogens. In this report the potential antithyroid activities of aqueous coal and shale extracts and of compounds identified in aqueous effluents from coal conversion processes were assayed in thyroid peroxidase (TPO) and thyroid slice systems. Aqueous extracts of coal and black shale were potent inhibitors of TPO or 125I organification by thyroid slices. The most abundant water-soluble compounds derived from coal are dihydroxy-phenols, thiocyanate, disulfides, and hydroxypyridines. The dihydroxyphenols resorcinol, 2-methylresorcinol, and 5-methylresorcinol (orcinol) were 26.7, 22.5, and 7.2 times more potent, respectively, than the antithyroid drug 6-propylthiouracil (PTU). Other dihydroxyphenols and thiocyanate were less potent but comparable in activity to PTU. All dihydroxypyridines and 3-hydroxypyridine produced inhibitory effects comparable to PTU. None of the disulfides inhibited TPO. The antiperoxidase effects of combinations of two dihydroxyphenols or one dihydroxyphenol and SCN were additive, whereas the effects of a combination of four dihydroxyphenols at threshold inhibitory concentrations were synergistic, resulting in net effects equivalent to or greater than the sum of the individual effects. Thus, antithyroid effects may be greatly amplified by exposure to multiple coal-derived goitrogens and could be many times that produced by any one of the contributing pollutants. These results demonstrate that potent water-borne goitrogens are derived from coal and shale and that their contamination of water supplies could pose a serious threat of thyroid disorders.

Animals

Screening for cervical cancer in Latin America: a case-control study.

The beneficial effect of cervical cytology in reducing the incidence of invasive cervical cancer is well accepted, but many issues regarding specific patterns of screening remain to be resolved, and preventive programmes need to be adapted to regional characteristics. In a case-control study conducted in Latin America, we investigated cytological screening histories of 759 cases of invasive cervical cancer and 1430 controls, with participation rates of 99% and 96%, respectively. Fifty per cent of the cases and 29% of the controls reported never having been screened. Screening was less common among older, less educated and less parous women; non-users of oral contraceptives and women without histories of venereal diseases. There was also evidence that older women and those with multiple partners had longer intervals between examinations. The relative risk (RR) associated with no prior screening was approximately 3 and was not modified by other risk factors. Women reporting a Pap smear within 24-47 months before interview had the same RR as those examined within 12-23 months. Women tested longer ago had higher risks, but still much lower than women never examined. There was evidence that one examination is associated with less reduction in risk than two, regardless of the interval since last Pap smear. Screening appeared to reduce risk of both squamous cell carcinomas and adenocarcinomas. As expected, cases presenting at advanced stages were less likely to have been screened and reported longer intervals since their last examination. These results support the need to concentrate limited resources in the groups that need screening most, mainly older and less educated women who have never been screened.

Adult

A case-control study of nutrient status and invasive cervical cancer. I. Dietary indicators.

A study of 748 cases and 1,411 hospital and community controls in four Latin American countries evaluated the association between certain elements of diet and invasive cervical cancer. Subjects were interviewed about their adult consumption of 58 food items, including the major sources of putative protective agents (vitamin A, carotenoids, vitamin C, and folacin) as well as other behavioral and medical characteristics related to cervical cancer. Participation rates were above 95% for both cases and controls. After adjustment for age, study site, sexual and reproductive behavior, socioeconomic status, screening practices, and detection of human papillomavirus 16/18 by filter in situ hybridization, a slightly lower risk was observed for the highest quartiles of consumption of fruit and fruit juices, while no reductions in risk were associated with vegetables, foods of animal origin, complex carbohydrates, legumes, or folacin-rich foods. When nutrient indices were derived, significant trends of decreasing risk were observed for vitamin C (adjusted odds ratio (OR) = 0.69 for the highest vs. the lowest quartile; p for trend = 0.003), beta-carotene (OR = 0.68; p = 0.02), and other carotenoids (OR = 0.61; p = 0.003). Inclusion of vitamin C and beta-carotene in the same model attenuated the association with beta-carotene, while the association with vitamin C remained unchanged. The results are consistent with those of other investigations and provide support for a protective effect of vitamin C, carotenoids, and other substances found in the same fruits and vegetables against the development of invasive cervical cancer. However, the fact that the associations were driven by relation in two of the study sites and among women of higher socioeconomic status leaves open the possibility of selection bias or effects of unidentified aspects of dietary patterns.

Ascorbic Acid

A case-control study of nutrient status and invasive cervical cancer. II. Serologic indicators.

A study of 387 cases and 670 controls from four Latin American countries evaluated the hypothesis that lower serum levels of eight micronutrients were associated with a higher risk of invasive cervical cancer. The serologic analyses were restricted to a sample of subjects with stage I and II disease to minimize effects of the disease on the serologic markers. Ninety-four percent of eligible subjects donated blood samples, which were analyzed for carotenoids, retinol, and tocopherols by high-pressure liquid chromatography. Cases did not differ significantly from controls in mean serum levels of retinol, cryptoxanthin, lycopene, alpha-carotene, lutein, or alpha-tocopherol. The mean level of beta-carotene was lower and the mean level of gamma-tocopherol was higher among cases as compared with controls. After adjustment for age, study site, sexual and reproductive behavior, socioeconomic status, screening practices, detection of human papillomavirus types 16/18, cholesterol, and triglycerides, a trend of decreasing risk was associated with higher levels of beta-carotene (p for trend = 0.05), with the adjusted odds ratio decreasing to 0.72 for the highest versus the lowest quartile. beta-Carotene results were similar by stage of disease, which argues against an effect of disease progression on nutrient values. Unexpectedly, increasing risks were observed as the level of gamma-tocopherol increased (odds ratio = 2.09; p for trend = 0.03); however, levels were higher among stage II cases as compared with stage I cases, suggesting a metabolic alteration resulting from the disease process. The concordance in the strength and direction of the blood and dietary results, presented in the accompanying report (Herrero R, Potischman N, Brinton LA, et al., American Journal of Epidemiology 1991;134:1335-46), supports a role for beta-carotene or foods rich in beta-carotene in the etiology of cervical cancer. This study also indicates that simultaneous analysis using serologic and dietary nutrient indicators allows better discrimination of the association.

Carcinoma, Squamous Cell

A case-control study of serum folate levels and invasive cervical cancer.

Although small intervention trials have suggested that folate supplementation reduces cervical dysplasia, the association of blood folate concentrations with invasive cervical cancer risk has not been investigated in well-controlled epidemiological studies. A study was conducted with newly diagnosed Stage I and II invasive cervical cancer cases and controls in 4 Latin American countries. Ninety-five% of subjects donated blood samples, resulting in 330 case and 565 control serum samples analyzed for folate concentrations by radioassay. Cases did not differ significantly from controls in mean levels of folate (5.00 and 4.90 ng/ml, respectively). No associations were observed between quartiles of serum folate and risk of cervical cancer after adjustment for other risk factors, and no interactions with established risk factors were observed. Folate levels were also unrelated to risk among women who might have compromised folate status because of recent or extended oral contraceptive usage or multiple pregnancies. Further, mean levels of folate were similar by stage of disease, arguing against an effect of disease progression on serum values. These results do not support a role for serum folate in the etiology of invasive cervical cancer.

Adenocarcinoma

Injectable contraceptives and risk of invasive cervical cancer: evidence of an association.

In a case-control study conducted in Latin America, the relationship of injectable contraceptive (IC) use to risk of invasive cervical cancer was analyzed while controlling for a variety of other risk factors, including female and spouse sexual behavior and infection with human papillomaviruses (HPV). Thirty-two cases and 82 controls reported ever having used IC. Women reporting use of IC for less than 5 years had an adjusted RR of 0.5 (95% Cl = 0.3-0.9), but users for 5 or more years had an RR of 2.4 (95% Cl = 1.0-5.7). The effect of prolonged IC use was stronger for women reporting first use 10 or more years before interview (adjusted RR = 3.4, 95% Cl = 1.1-24.9) and more than 5 years since last use (adjusted RR = 5.3, 95% Cl = 1.1-10.0). Cervical cancer risk associated with prolonged IC use was particularly high among women who reported never having had a Pap smear or having had one 2 or more years before interview (adjusted RR = 6.3, 95% Cl = 2.1-18.7). The reduced cervical cancer risk associated with short-term use of IC may reflect intensive Pap smear screening as the method is initiated. Although hampered by small numbers, these results suggest an adverse effect of prolonged IC use on cervical cancer risk, particularly among women who cease participation in screening programs after terminating usage, and indicate that long-term IC users should be monitored for cervical disease until more conclusive results are available.

Case-Control Studies

Sexual behavior, venereal diseases, hygiene practices, and invasive cervical cancer in a high-risk population.

A case-control study of 759 women with invasive cervical cancer and 1430 controls in four Latin American countries evaluated risk in relation to sexual behavior, histories of specific venereal diseases, and hygiene practices. Early age at first sexual intercourse and increasing number of sexual partners were associated with significantly increased risks even after adjustment for their mutual effects. Risk increased to a twofold excess among women reporting first intercourse at 14 to 15 years of age compared with 20+ years. The number of steady sexual partners was a more important predictor of risk than the number of nonsteady partners, particularly before age 30, possibly reflecting the need for prolonged or repeated exposures to a transmissible agent, or different methods of protection against sexually transmitted diseases or pregnancy. Reported frequency of intercourse was not generally associated with risk, except among women reporting increased frequencies before 20 years of age. Histories of gonorrhea or crab lice were associated with increased risk, but histories of other venereal diseases were not significant predictors. No consistently increased risks were detected for women reporting specific hygiene or douching habits, except the practice of washing the genitalia infrequently during menstruation. These results provide support for a period of increased susceptibility to carcinogens during adolescence, and suggest that this may be an important determinant of the high incidence of cervical cancer in Latin America.

Adolescent

Oral contraceptive use and risk of invasive cervical cancer.

A case-control study of 759 invasive cervical cancer patients and 1430 controls in Panama, Costa Rica, Colombia and Mexico enabled an evaluation of risk in relation to oral contraceptive use. Overall use was associated with a 21% nonsignificant elevation in risk, with some further increases in risk for more extensive durations of use. Although risks were similar for recent and non-recent users (RRs = 1.3 versus 1.2), recent long-term users were at highest risk (RR for 5+ years use = 1.7, 95% Cl 1.1-2.6). Relationships were similar for women with and without a recent Pap smear, arguing against detection bias. There was little evidence that other risk factors, including smoking and detection of human papillomaviruses (HPV), altered the effects of oral contraceptives. The risk associated with oral contraceptives was significantly increased for adenocarcinomas (RR = 2.2), whereas for squamous cell tumours the effect was minimal (RR = 1.1). These results provide some support for an adverse effect of oral contraceptives on cervical cancer risk, although possibly limited only to a subpopulation of cases.

Adenocarcinoma

Goitrogens in food and water.

Epidemiologic and experimental evidence reviewed in this article emphasizes the complex and multifactorial etiology of endemic goiter. The important role of iodine deficiency as an etiologic factor in endemic goiter is firmly established, but there is evidence that other environmental factors can play an equally important role in the pathogenesis of this condition. Chemical categories, sources, and sites of action of the various classes of naturally occurring goitrogens and antithyroid agents are reviewed in this article. Evidence of the presence of these compounds in foodstuffs and drinking water is discussed. Bacterial contamination of water supplies also appears to be important in the development of goiter. Microorganisms appear to intervene in the biosynthesis and degradation of organic goitrogenic pollutants or may induce thyroid growth-promoting activity in the host, or both. Malnutrition and poor socioeconomic conditions, as for iodine deficiency, enhance the action of environmental goitrogens. Thus, a coordinated multidisciplinary approach is essential to solving this public health problem.

Antithyroid Agents

Intervention policy in endemic goitre areas.

The multifactorial nature and complex interactions of regionspecific environmental conditions with host factors in the pathogenesis of endemic goitre constitute a major challenge to the understanding and control of the problem in endemic areas. However, to control and prevent this important public health problem, the most obvious but difficult initial step requires substantial socioeconomic improvements in the affected areas of less developed countries, including, first, provision of efficient iodine prophylaxis programs, second, diversification of dietary constituents with adequate daily protein-calorie intake, and third, institution of proper sanitary conditions with effective water treatment to eliminate organic and bacterial pollutants. This last intervention is also a requirement to control and prevent goitre in the iodine-sufficient more developed countries. In this regard, more research is needed to provide effective ways of water treatment that can be applied in individual households or at the community level.

Age Factors

The male factor in the etiology of cervical cancer among sexually monogamous women.

To address the hypothesis that male sexual behavior may affect the etiology of invasive cervical cancer, a case-control study was undertaken in Panama, Costa Rica, Colombia and Mexico. The study enrolled husbands of those women with invasive cervical cancer and of those age-matched controls who reported only one lifetime sexual partner. A total of 204 case and 485 control husbands (78% and 72%, respectively, of identified husbands) were interviewed, clinically examined, and had penile swabs taken for papillomavirus assays. Risk increased significantly (p = 0.005) with the number of sexual partners reported by the husband (RR = 2.0 for 26+ vs. less than 6 partners). Low educational status of the husband was also an important predictor of risk, possibly indicating the role of unmeasured aspects of sexual behavior. Visits to prostitutes, circumcision status and sexually transmitted disease histories were not important predictors of risk, but evidence from clinical examination indicated that poor genital hygiene may be involved. Human papillomavirus (HPV) expression as defined by filter in situ hybridization was detected in 20-23% of subjects and, except in the small group with both HPV types 6/11 and 16/18, was not related to risk. This may reflect sampling problems in the male or the importance of host factors which enhance viral carcinogenicity in the female.

Circumcision, Male

Invasive cervical cancer and smoking in Latin America.

A case-control study of 667 patients with invasive squamous cell carcinoma of the cervix and 1,430 controls from four Latin American countries showed an age-adjusted relative risk (RR) of 1.2 [95% confidence interval (CI) = 1.0-1.4] for women who had ever smoked, with risk rising to 1.7 (95% CI, 0.8-3.6) for women who smoked greater than or equal to 30 cigarettes per day. The associations were practically eliminated after adjustment for the number of sexual partners and alcohol consumption, probably a surrogate for an unidentified life-style risk factor. Some excess risk persisted among women who smoked for extended periods (RR = 1.5 for greater than or equal to 40 yr), as well as those who began smoking at older ages (RR = 1.7 for greater than 30 yr), which suggests a late-stage effect. In addition, among women who tested positive for human papillomavirus (HPV) type 16 or 18 by filter in situ hybridization, there was an increased risk for women who had ever smoked and a dose-response relationship with the number of cigarettes smoked (adjusted RRs compared with HPV-negative nonsmokers = 5.0 for HPV-positive nonsmokers, 5.5 for less than 10 cigarettes/day, and 8.4 for greater than or equal to 10 cigarettes/day). In contrast, HPV-negative women had no increased risk associated with smoking. These results, from a high-incidence area where intensive smoking among women is still relatively rare, suggest that smoking has a limited effect on cervical cancer risk, possibly only among women with specific types of HPV.

Age Factors

Parity as a risk factor for cervical cancer.

In a case-control study of 759 invasive cervical cancer patients and 1,430 controls in Colombia, Costa Rica, Mexico, and Panama conducted during 1986-1987, an association with number of pregnancies persisted after adjustment for sexual and socioeconomic variables. Risks rose steadily to 5.1 (95% confidence interval 2.7-9.7) for those with 14 or more pregnancies and a relation of risk to multiparity was observed in all four study countries. Pregnancy associations appeared to relate to the number of live births rather than to miscarriages or abortions, with multiparity relations most pronounced among premenopausal women and oral contraceptive users. Human papillomaviruses types 16 and 18, as measured by filter in situ hybridization, were not significantly associated with number of births and did not explain the strong relation of parity to risk. Our results indicate the need for further consideration of reproductive factors on cervical cancer risk, with attention given to possible mechanisms of action, including hormonal factors and cervical trauma.

Adult

Antithyroid and goitrogenic effects of millet: role of C-glycosylflavones.

Pearl millet [Pennisetum millet (L.) leeke] is the main source of food energy for the rural poor in many areas of the semiarid tropics. Epidemiological evidence suggests that millet may play a role in the genesis of endemic goiter in these areas, and sparse experimental data in rats support this suspicion. This study was undertaken to determine in vivo in rats and in vitro using porcine thyroid slices and a thyroid peroxidase (TPO) assay the goitrogenic and antithyroid effects of millet diets, extracts of millet, and certain pure compounds contained therein. For use in these studies, whole grain millet was progressively dehulled to yield successively four bran and four flour fractions in which direct analyses revealed progressively lower concentrations of C-glycosylflavones. In vivo feeding of bran fraction 1, that richest in C-glycosylflavones, led to a significant increase in thyroid weight and antithyroid effects. Feeding of bran fraction 2, the next richest in C-glycosylflavones, produced similar, but less marked, changes. In vitro studies of 125I metabolism using porcine thyroid slices indicated that extracts of bran fractions 1 and 2 were most potent, producing changes similar to those produced by methimazole (MMI). At a concentration of 60 mumol/L, glucosylvitexin, the major C-glycosylflavone present in millet, had effects comparable to those of 1 mumol/L MMI. Similarly, in studies of porcine TPO, extracts of bran fraction 1 caused pronounced (85%) inhibition of enzyme activity, and progressively less inhibition was induced by extracts of bran fractions 2, 3, and 4. Overall, the TPO-inhibiting activities of the various millet fractions closely correlated with their C-glycosylflavone concentrations. Three C-glycosylflavones present concentrations. Three C-glycosylflavones present in millet, glucosylvitexin, glycosylorientin, and vitexin, also inhibited TPO activity. Thus, in vivo and in vitro studies revealed that millet diets rich in C-glycosylflavones produce goitrogenic and antithyroid effects similar to those of certain other antithyroid agents and small doses of MMI. We conclude that in areas of iodine deficiency in which millet is a major component of the diet, its ingestion may contribute to the genesis of endemic goiter.

Animals

Thyroid function in neonates from goitrous and nongoitrous iodine-sufficient areas.

We compared thyroid function between newborns from goitrous and nongoitrous localities in which iodine intake has been supplemented since 1955. Cord serum samples were analyzed in 185 infants born during a 9-month period (1986-1987) in 2 goitrous and 1 nongoitrous localities of western Colombia. Urinary iodine was determined in all mothers before delivery. No significant differences were found among neonates of the 3 localities (Kruskal-Wallis test) for the various thyroid hormone values, and all values were within the normal range, although there was a trend in distribution of TSH to higher values in both goiter areas. Thyroid autoantibodies (antithyroglobulin and antithyroid microsomal) were negative in all neonates, and iodine intake, as indicated by urinary iodine, was adequate and similar among the mothers of the 3 groups. Those newborn infants with serum TSH values higher than 20 mU/L were reexamined 5-7 months later. At this time, all infants had lower serum TSH values and their serum free T4 index and T3 values were normal. Gestational age, weight, and height at birth were normal and also equal among the neonates in the 3 localities. These results indicate that neonates from goitrous iodine-sufficient areas have thyroid function similar to that of infants born in nongoitrous areas equally supplemented with iodine, and therefore, they are not more at risk to develop congenital hypothyroidism.

Colombia

Goitrogens.

A large number of agents in the environment and some medications are known to interfere with thyroid gland function, posing the danger of thyroid disease. Pollutants that cause goitre are known as environmental goitrogens which may cause the condition by acting directly on the thyroid gland but also indirectly by altering its regulatory mechanisms and the peripheral metabolism and excretion of thyroid hormones. However, the mechanism that induces the trophic changes leading to goitre formation, and in some instances with hypothyroidism, is not well understood. Antithyroid compounds may enter into the water, air and food exposure pathways, becoming an important environmental goitrogenic factor in man and other animals. Naturally-occurring and anthropogenic agents may act as goitrogens, as well as some drugs, which in the presence of dietary iodine deficiency may exaggerate the goitre and associated disorders. In iodine-sufficient areas, these compounds may be responsible for the development of some "sporadic' goitres or the persistence of the goitre endemia with its associated disorders. At present, medical or surgical treatments for the individual, but not measures for prevention and control at community level, are being applied in iodine-sufficient goitre areas.

Animals