Cockayne's syndrome fibroblasts are characterized by hypersensitivity to deoxyguanosine and abnormal DNA precursor pool metabolism in response to deoxyguanosine or ultraviolet light. New cellular traits of Cockayne's syndrome (CS) associated with DNA precursor metabolism have been identified, namely, hypersensitivity to the toxicity of low concentrations of deoxyguanosine (dG) and abnormal changes in deoxyribonucleotide (dNTP) pools in response to dG or UV. dG treatment results in similar ribonucleotide pool changes in wild-type and CS cells, i.e., GTP levels increase at least twofold. However, the changes in the pool size of the purine deoxyribonucleotides are significantly different; in wild-type cells dATP and dGTP pools increase threefold, but remain unchanged in CS. The mechanism by which dG kills CS cells is not clear, but unlike the inherited purine nucleoside phosphorylase deficiency disease, the toxicity of dG is not due to the accumulation of dGTP and the consequent feedback inhibition of ribonucleotide reductase. UV induces different dNTP pool changes in CS and wild-type cells. In wild-type cells dTTP, dCTP, and dATP pools increase three- to fivefold within 4 h of irradiation, while the dGTP pool contracts. In CS cells, only the dGTP pool expands (four- to sixfold), while the other three contract. Each of these new phenotypic traits, together with UV sensitivity, is coordinately corrected in the complementing proliferating CSA x CSB hybrid cells.


[Organization and functioning of health services of the IMSS-Solidaridad program]. In this report the organization and performance of the IMSS-Solidaridad Program of Mexico is described. This program is managed by the Mexican Institute for Social Security, which services 10.5 million inhabitants of the rural underserved areas, with federal government resources in 18 states. This study compares the structure and functioning of the IMSS-Solidaridad Program with Local Health Systems, as they have been proposed by the Panamerican Health Organization for country members and by the Ministry of Health of Mexico, particularly in relation to the decision-making process at local level. Some assets and limitations of the IMSS-Solidaridad Program are analyzed and, finally, concrete procedures to improve coordination between the IMSS-Solidaridad Program and other health services for similar populations (populations without social security protection) in Mexico are suggested, with the purpose of using resources more adequately and succeed in the national goal to achieve equity in health.


[Infant nutrition in Mexico and its relationship with the utilization of maternal health services]. In addition to describing recent infant feeding patterns in Mexico, this paper attempts to answer the following questions: what are the mechanisms through which the socioeconomic level affects both infant feeding and the utilization of maternal and child health care practices? b) what is the effect of the socioeconomic level on the relationship between utilization of services and infant feeding practices? The research is based on bivariate and stratified analyses of the ENFES (1987) information. The data obtained prove that: a) even when there is a relationship between socioeconomic factors and, the utilization of services and feeding practices, the social dimension affects differently each of the two variables; b) there is a relationship between the utilization of services and infant feeding; and c) this relationship is explained, in part, by the association of both variables with socioeconomic factors. Operative strategies are proposed for the health services, as well as technical guidelines for future research in this field.


[Epidemiology of cervical cancer at the Mexican Institute of Social Security]. In order to study the secular trend and age and geographic distribution of cervical cancer at the Mexican Institute for Social Security, an ecologic study was carried on. During the last 10 years cervical cancer has been the second most common neoplasia, being the leading one in women. For those between 30 and 44 years old it is the third cause of death, and one of the first ten in all age groups until 64. Mortality has shown a stable trend for the last 15 years, in a range from 3.3 to 4.5 deaths per 100,000 inhabitants. Mortality rates increase with age. There is a fine-fold increase in the risk of death for women 40 to 49 years old (CI 95% 4.2-6.4%) and a tenfold increase for those over 80, (CI 95% 7.3-12.6) when taking those under 40 years old as a reference group. In 1989, the cervical cancer incidence was 9.7 cases for each 100,000 person-years. Morbidity and mortality are unequally distributed along the country. There is a need for the development of research in order to know better the occurrence of this disease as well as how known risk factors affect it.


[Social participation in health. An experience in Simojovel, Chiapas]. One of the basic foundations for the operation of health programs is the social participation of the population in actions going from planning to evaluation, promotion and control of actions related with their own health. In the work, we present the results of a preliminary and partial evaluation of an ongoing autopromoting health project in the communities of Lázaro Cárdenas and Las Limas, in the Municipality of Simojovel, Chiapas, México. The basic goal of this work is to identify factors derived from the relations of localities with the State and, on the other hand, from socioeconomic conditions of the populations, which favor or hinder the development of social participation in their own health projects. This is a comparative study, type before and after, within and between localities, intended to measure the effect of a health program with community participation in two communities having divergent relations with the State. For this, we carried out a socioeconomic and prevalent morbidity survey before and after the implementation of social participation in health actions. We also characterized social participation in health actions and identified the type of State intervention in the localities through governmental programs and institutions. The results convey the notion that the health program contributes to enhance hygienic sanitary conditions of the population and decrease the frequency of such ailments as diarrhea and parasitic diseases; social participation is more active in Lázaro Cárdenas than in Las Limas. State interventions in the communities are given through social programs and institutions in a mandatory way, with no opportunity for community participation in decision-making. The conclusion is that the demographic organization of the community and autopromotion favor the participation in health actions, while the presence of the State through political repression and actions delivered through social programs promote dependence and paternalism, hindering the ample social participation in actions for health.


Cyclin-dependent kinase 2 (cdk2) in the murine Cdc2 kinase TS mutant. Kinases of the mammalian cdc2 family including cdk2 (cyclin-dependent kinase 2) are thought to be involved in both the G2/M transition and DNA replication. To investigate the role of cdc2 kinase and cdk2 in cell cycle progression, murine tsFT210 cells bearing a temperature-sensitive cdc2 mutation were used. These kinases were purified by column chromatography, using a peptide with the consensus phosphorylation site of cdc2 kinase as the substrate. In this mutant, cdc2 kinase activity was temperature sensitive and cdk2 activity was not. At the restrictive temperature, the mutant was only arrested in the G2 phase and not in the G1-S phase, suggesting that cdk2 did not compensate for cdc2 kinase at the G2/M transition but did function at the G1-S phase. This suggestion was supported by the finding that transfection of cdk2 cDNA did not improve the growth of the mutant cell line at the restrictive temperature, although transfection of cdc2 cDNA did.


[Child abuse in Tlaxcala: a case-control study]. A longitudinal, retrospective and descriptive study about child abuse was carried out in the Hospitals of the Tlaxcala Secretariat of Health, Mexico. The information was obtained from hospitalized children's charts between January first and November 30, 1991. The charts included were those belonging to zero to 14 year old children with injuries, poisoning, and II-III degrees of malnutrition. Four child-abuse criteria were established: physical, sexual, non organic malnutrition and mixed (physical and non organic malnutrition). Two control groups were defined. Different patterns were observed between accidental and non accidental injuries, malnutrition and poisoning among the case and the control groups. The study provides useful information for the integral diagnosis of child abuse in hospitalized children.


Regulatory sequences clustered at the 5' end of the first intron of the human thymidylate synthase gene function in cooperation with the promoter region. A human thymidylate synthase (TS) minigene containing 5'- and 3'-flanking sequences, all the exons, and only intron 1 showed a normal frequency of stable transformation when transfected into TS-negative mutant cells, whereas minigenes in which intron 1 was replaced by intron 2 or deleted in the above construct showed only a few percent of the above frequency. Introduction of intron 1 into the above intronless or intron 2 minigene restored the transforming activities regardless of its position and orientation. Deletion analysis revealed two positive and one negative regulatory sequences in the 5' end of intron 1, each of which seemed to bind specific proteins as shown by gel shift analysis. Intron 1 also stimulated expression of a TS promoter-CAT gene construct but not that of an SV40 promoter-CAT gene construct. These results indicate that the multiple regulatory sequences clustered in intron 1 stimulate TS gene expression in concert with the 5'-flanking sequences.


[Criteria for teaching medical sociology in public health area]. A discussion is given on the most important criteria which should guide the selection of medical sociology's contents which should be taught to public health students. It is suggested that in the current national context, the teaching of sociology in public health should be guided by three objectives: a) to train public health specialists capable of analyzing and criticizing their social reality; b) to disseminate the main findings achieved through social research in public health, concerning mainly the social determination of both the health illness process and the provision of health services; and c) to train public health students to face social changes currently taking place in this country which soon will make evident their effects on the distribution of health and illness in the population. The relevance of linking the teaching of medical sociology in public health with actual research is pointed out. The need to carry out sociological research on the actual current conditions in which social sciences in public health are taught in Mexico and Latin America is stated. It is emphasized the importance of including within this teaching the variety of dilemmas and polemics which have resulted as a consequence of the incorporation of sociology into health matters. The article concludes by emphasizing the need to show the multiparadigmal character of sociology and the consequences of this fact in the study of public health.


The use of human repetitive DNA to target selectable markers into only the human chromosome of a human-hamster hybrid cell line (AL). We used the plasmid BLUR-8 that contains an 800-base pair (bp) sequence of human repetitive Alu DNA in a cotransfection protocol to target the plasmids pSV2neo or EBO-pcD-leu-2 (hygro) into a single site of the sole human chromosome, number 11, of a Chinese hamster-human hybrid cell line (AL). The neo and hygro plasmids confer resistance to the antibiotics G418 and hygromycin, respectively. Of the 33 cotransfected clones with single-site insertions, 1/13 without BLUR-8 and 6/20 with BLUR-8 were only in human chromosome 11. A frequency of insertion of 1/13 is not different than expected by chance (rho = 0.3512). On the other hand, the probability that 6/20 insertions, as seen with BLUR-8, occurred by chance is low (rho = 0.0003). We suggest that the human DNA sequences contained in BLUR-8 targeted insertions into only the human chromosome.


[Social participation in health: spaces and actors determining its development]. This paper deals with an analysis of a rural experience of social participation (SP), defined as the possibility of communities gaining real access to the control of processes affecting health. This analysis evidences the relevance of peasant women in the promotion of SP in health, as well as the need to include health education and organization actions in regional organizational process, strengthened by local policies. The creation of a sanitary mediator to serve as a regulatory agent negotiating with the State is proposed.


Extinction of liver/bone/kidney alkaline phosphatase in osteosarcoma hybrid cells. We have constructed a series of interspecific somatic cell hybrids between the human osteoblast-like osteosarcoma, TE85, and a mouse fibrosarcoma, La-t-. In these whole-cell hybrids, we observed a 10-fold reduction of human liver/bone/kidney (L/B/K) alkaline phosphatase steady-state mRNA and alkaline phosphatase protein activity. The phenomenon of loss of tissue-specific gene expression has been termed extinction. Subclones of these hybrids were isolated, which reexpressed the alkaline phosphatase gene product. These late-passage hybrids had a reduced number of mouse fibroblast chromosomes when compared to earlier passages. This suggests that a trans-acting negative regulatory element, encoded in the fibroblast genome, regulates expression of L/B/K alkaline phosphatase. This is the first evidence that extinction plays a role in the regulation of osteoblast gene expression.


[An epidemiologic study of cholesterol in the population of Acapulco, Mexico]. An epidemiologic study of cholesterol and other risk factors was carried out, which included 1,011 women and 1,001 men older than 20 years, in Acapulco, Guerrero, México. The aim of this study was to determine the prevalence of hypercholesterolemia, as well as to establish the relation of cholesterol levels and the following variables: Age, obesity, hypertension, tobacco smoking and cardiovascular disease in relatives. This study was done in the months of March-August 1991. The prevalence of high cholesterol was 36 percent in women with an average of 189 mg/dl, and 30 percent for men with an average of 183 mg/dl. The difference between levels of cholesterol of men and women reached statistical significance. The average levels of serum cholesterol were higher in older, overweight, hypertensive individuals and the differences were statistically significative. Although the average serum cholesterol level was higher in individuals with history of cardiovascular problems, the differences were not significative. There were no differences in cholesterol levels in individuals with tobacco smoking habits. The prevalence of high cholesterol found means that is an important risk factor for this population, which, added to the other identified factors and its statistical relation, define them as a population with high cardiovascular risk.


Molecular cloning and nucleotide sequence of cDNA encoding a functional murine low-density-lipoprotein receptor. The low-density-lipoprotein (LDL) receptor is an important mediator of mammalian cholesterol metabolism; its congenital absence in humans is characterized by hypercholesterolemia, atherosclerosis, and coronary artery disease. We report here the identification and cloning of a cDNA encoding the murine LDL receptor. The cDNA insert is 4467 base pairs in length and the deduced amino acid sequence bears 78.2% homology with the reported human sequence. This murine cDNA was subcloned into a retroviral-based expression vector, LmLSN1, and transfected into 3T3 cells. The production of functional LDL receptor was confirmed by ligand binding of DiI-LDL cholesterol.


Long-term expression of a retrovirally introduced beta-galactosidase gene in rodent cells implanted in vivo using biodegradable polymer meshes. Grafts of various types of cells have been performed using bioresorbable polymer matrices. These synthetic fibers are degraded by hydrolysis into normal metabolic intermediates and induce a number of events that are conductive to healing and/or repair, the most important of which may be angiogenesis. The use of biodegradable meshes to deliver genetically altered cells was studied. A beta-galactosidase gene was inserted into Long-Evans rat bone marrow stromal (BMS) cells or fibroblasts derived from C57BL/6J mouse embryos using the retroviral vector LNL-SLX beta gal. Expression was monitored using X-gal staining. X-gal+ cells from monolayer cultures were seeded onto either polyglycolic acid (PGA) or polyglactin (PGL) biodegradable meshes and grown to confluence. Two types of grafts were performed: (1) embryonic C57BL/6J mouse fibroblasts (EMF) into either nude mice or adult C57BL/6J mice, and (2) Long-Evans rat BMS into Long-Evans rats. Beta-Galactosidase activity was found for up to 152 days for EMF in nude mice, 123 days for EMF in adult C57BL/6J mice, and 90 days for grafts of syngeneic BMS cells into Long-Evans rats. Noninfected cells grafted using the same methods did not stain with X-gal.


Mapping and characterization of 129 cosmids on human chromosome 11p. We constructed cosmid libraries from human-hamster somatic cell hybrids that possess all or part of the short arm of chromosome 11 as their only human complement and isolated 129 human 11p clones. These cosmids map to 22 of 25 intervals distinguished by a hybrid panel for chromosome 11p. Forty-eight single-copy sequences were subcloned from 25 cosmids. Six of 17 (35%) single-copy sequences tested identify 11 new polymorphisms. Restriction endonuclease analysis identified CpG islands in 16 of 68 cosmids (23.5%). Analysis of the distribution of restriction endonuclease sites recognizing CpG dinucleotides showed that clusters of these sites, including those associated with the 5' region of an 11p13 Wilms' tumor gene, WT1, can span greater distances than generally recognized. The cosmids reported here should contribute to the construction of long-range physical maps and the isolation of additional genes on the short arm of chromosome 11.


Chromosomal localization of the IL-6 receptor signal transducing subunit, gp130 (IL6ST). Signal transduction in eukaryotic cells is a complex process mediated, normally, by the interaction of soluble extrinsic protein factors and their cognate receptors. One example of this phenomena is the inflammatory cytokine interleukin-6 and the IL-6 receptor. However, the IL-6 receptor, once its ligand is bound, associates with another membrane glycoprotein, gp130, to potentiate the cytokine response. To further understand the basis of this interaction, and its possible implications in cellular transforming events, the corresponding gene(s) must be studied. Here we find that the human gp130 gene product is homologous to two distinct chromosomal loci on chromosomes 5 and 17. Furthermore, the presence of two distinct gp130 gene sequences is restricted to primates and is not found in other vertebrates.


[Rational therapy of prehepatic portal hypertension]. Prehepatic portal hypertension is mostly caused by an inflammatory closure (thrombosis) of the portal vein in the perinatal period. This form of portal hypertension is characterized by the following considerable facts: patients' liver is not damaged and a divergent collateral circulation (hepatofugal and hepatopetal) is formed. Due to the latter, portal circulation may improve spontaneously and no clinical signs of the disease are manifested. Most patients, however bleed rependedly from the cardioesophageal varices with various frequency and various severity. A direct surgical intervention had been successful in about 50% of cases. At present, it is almost replaced by endoscopic sclerotization giving compatible results. The pathogenetically based surgical method is the portosystemic shut that is necessary in 20% of patients, mostly as a secondary intervention. Pathophysiological sequelae of the shunt are less severe than in cirrhotic patients due to intact liver of patients with PPH and to favorable possibility of recirculation of portal blood via the hepatic artery. An appropriate therapeutical strategy accounts for favorable long-term prognosis of patients with prehepatic portal hypertension.


[The appropriateness of pneumonectomy in the treatment of lung diseases]. Evaluation of results following lung surgery, with a total of 303 pulmonary resections performed at the Department of Surgery in Pardubice Municipal Hospital over the years 1981-1986, made the authors review the patients' overall status after pneumonectomy. Special attention was given to the causes of death, differences in survival rates after left and right pneumonectomy, the relationship between survival rates and preoperative values of spirometry, and the quality of life after surgery. The causes of death within one moth of surgery were identical with known complications. The other patients operated on were dying gradually of recurrence of the malignant process. The five-year survival rate was 31% of all patients undergoing surgery. Differences in survival rates following left and right pneumonectomy were not related to the site of the procedure but to the stage of the disease, evaluated using the international staging system. Preoperative values of spirometry do not provide a clue for survival rates. The quality of life after pneumonectomy is satisfactory, changing only with recurrence of the process. Pneumonectomy is fully justified in the treatment of lung neoplasms and other lung diseases.


[Esophageal replacement using the large intestine in children]. Oesophageal replacement with an interposed graft of the large intestine on a vascular pedicle between the cervical oesophagus and oesophageal stump over the diaphragm was performed in four children for Vogt's classification Type-I and II oesophageal atresia. A tracheooesophageal fistula was closed in three, and gastrostomy was established in four neonates to provide nutrition. Oesophageal replacement was performed in patients aged 2 years and 5 months to 5 years and 4 months. One girl died following oesophageal replacement for bilateral pneumonia. A non-functioning oesophageus was extirpated for corrosive oesophageal stricture with simultaneous replacement by means of colonoplasty in two boys aged 3 1/4 years and 3 1/2 years. As regards complications, a shortly persisting salivary fistula developed in the cervical anastomosis, and an abundant graft was made shorter and a fundoplication for gastrooesophageal reflux was established in the same patient. To prevent leakage of the anastomosis and its stricture, the anastomoses were constructed obliquely and sutured in two layers using thin atraumatic suture with silk thread. The patients have been on follow-up for 3 to 12 years (mean 6.5 years) after oesophageal replacement; their ability to swallow, psychosomatic development and surgical criteria were employed to evaluate the outcome as excellent in four, and good in one of the children operated on.


[Splenic pseudocysts and their treatment]. The article addresses the issue of splenic pseudocysts and their treatment. It reports on two patients treated over the past three years at the Department of Paediatric Surgery of the Prague-based Postgraduate Medical and Pharmaceutical Institute. While the pseudocyst healed spontaneously in one child after 9 months, the other patient underwent laparotomy with subsequent segmental resection of the splenic parenchyma involved.


[Isolated rupture of the external iliac vein in indirect blunt injuries]. The authors described an in this country hitherto unpublished observation of an isolated rupture of the external iliac vein following the fall of a patient from a height on her left side. The rupture developed most probably as a result of narrowing of the external iliac vein which crosses the left internal iliac artery. A mechanism of acute expansion of the external iliac vein due to a blast wave of venous blood expelled by an impact on the thigh and recoiled from the impediment at the site of crossing with the internal iliac vein was probably involved. After severing of the compressing artery, thrombectomy and suture of the lesion, the patient recovered ad integrum.


[Heterotopic autotransplantation of the spleen in piglets]. An experimental study was developed to assess the method of heterotopic autotransplantation of the spleen into the greater omentum in 11 piglets. Tissue fibrin glue was employed to fix 2-3 mm slices of the spleen, and the lower part of the omentum was glued to the grafts. While one piglet died within 3 days since surgery, the other experimental animals survived 6 months without complications and were sacrificed. A histologically viable splenic tissue in the original quantity, or a quantity increased by 1/4, was found in 80% of the piglets. Compared with the original grafts, the bulk of the regenerate shrank by 2/3 in 20% of the animals; splenic tissue was altered by necroses and scarring. The technique of glueing splenic slices into the omentum using fibrin coagulum has a future in clinical surgery.


T cells causing immunological disease.

T cells causing immunological disease. Evidence is summarized that genetically encoded self peptides may not be considered immunological as self when expressed solely extrathymically on non-lymphohemopoietic cells; nevertheless, they are antigenic and are recognized by induced effector T cells. An immune response is readily induced against such "nonimmunological" self (as against foreign) by an appropriate presentation of these self peptides on proper antigen-presenting cells. If it is substantial, such an immune response causes a disease resembling an autoimmune disease, which is more appropriately called an "immunopathological T cell-mediated disease" rather than a T cell autoimmunity. These pathogenetic considerations may be incorporated into a revised-extended Gell and Coomb's classification of immunopathologies. If this view of immunopathological T cell-mediated diseases against nonimmunological self is correct, such diseases should be amenable to the same prevention (i.e., vaccination) and treatment principles, as are T cell immune responses to foreign antigens.


Cigarette smoking among U.S. adults, 1985-1990, and smoking among selected occupational groups, 1990. Cigarette smoking rates among U.S. adults continue declining, and in 1990 dropped to an all-time low of an estimated 28 percent for men and 23 percent for women. Analysis of data from the 1990 and 1985 Health Promotion and Disease Prevention supplemental questionnaires to the National Health Interview Survey conducted by the National Center for Health Statistics (NCHS), indicate decreases in smoking rates in the majority of selected demographic categories. Between survey years, the only groups in which the rates rose were men aged 18-24, women aged 65 and over, persons with less than 12 years of schooling and adults of Hispanic origin. Increased smoking cessation efforts should be tailored to and directed at these "at risk" groups. By occupational category, close to 40 percent of men employed as handlers/laborers or transportation/material movers were current smokers versus 17 and 21 percent, respectively, of professionals and executives. Similar to the men, the lowest current smoking rates were among women professionals, technical persons and executives. For both sexes, income was generally inversely related to current smoking status.


Public attitudes on health care reform.

Public attitudes on health care reform. Numerous polls and surveys have been conducted in recent months to determine public attitudes toward reform of the health care system. These polls, commissioned by independent foundations as well as the health insurance industry, have been employed to measure public opinion on the nation's health care system and the variety of reform proposals currently being examined. The major findings show that the American public is still genuinely confused about the health care issue and remains divided on how to solve the health care crisis facing the United States.


Cancer Prevention Study II. The American Cancer Society Prospective Study. Over the past 40 years, the American Cancer Society has led in large-scale, prospective studies of behavioral and environmental risk factors in association with cancer development. Through results of its 1952 study, cigarette smokers were found to have a 10-fold higher risk of lung cancer than nonsmokers. Cancer Prevention Study I (1959-1972) extended these results and also showed the relationship between age smoking began, depth of inhalation, smoking cessation, air pollution, body weight, etc., on all causes of death as well as specific cancer sites. Cancer Prevention Study II began in 1982 and after six years of follow-up has confirmed many earlier findings, and additionally has found: aspirin may be protective against colon cancer; persons reporting themselves to be heavy exercisers had higher standardized mortality ratios (SMR) for lung, colorectal, and pancreas cancer than moderate exercisers; more women who were long-term users of artificial sweeteners reported gaining weight during the past year than nonusers; diesel fume exposure elevated the risk of lung cancer among men ages 40-79; pesticide exposure was associated with an increased risk of multiple myeloma; and based on CPS II mortality rates, an estimated 250 million of the 1.25 billion persons living in developed countries will die because they smoke.


Decennial state population changes by age. Analysis of the 1990 Census indicates that there were significant differences in the geographic population changes among the four major age segments of our nation's residents. Nationally, rapid growth occurred among the elderly and for persons aged 20-44. On the other hand, the number of children under 20 years of age declined, while at the same time there were moderate changes among persons aged 45-64. Among individual states between 1980 and 1990, in these important age categories, many instances of substantial gains and losses emerged.


Pediatric pseudotumor cerebri (idiopathic intracranial hypertension). This review focuses on the features of pseudotumor cerebri in the pediatric age group. There is no sex predilection in children, and obesity does not appear to be an important factor. Infants and young children may present with irritability, apathy, or somnolence, rather than headache. Dizziness and ataxia may also occur. Papilledema is infrequently noted in pediatric patients if the fontanelles are open or the sutures are split. Pre-adolescents appear more likely than adults or adolescents to have manifestations of their pseudotumor cerebri other than headache and papilledema, including lateral rectus pareses, vertical strabismus, facial paresis, back and neck pain. Among the etiologies that are particularly pertinent to children are tetracycline therapy, malnutrition or renutrition, and the correction of hypothyroidism. Children with pseudotumor cerebri are at risk for visual loss and their visual function must be closely monitored. Surgical intervention is imperative when vision is threatened.


Optic nerve sheath meningiomas.

Optic nerve sheath meningiomas. Meningiomas are benign neoplastic lesions arising from meningothelial cells of the meninges. Primary orbital meningiomas, originating in the optic nerve sheath, represent 1-2% of all meningiomas, and are the second most common optic nerve tumor after gliomas. They primarily affect middle-aged adults. Patients typically present with visual loss, frequently associated with optic atrophy and often with optociliary shunt vessels. The lesion is usually unilateral, but is bilateral in about 5% of cases. Meningiomas show characteristic indolent growth over years, progressing inexorably to blindness in the affected eye. Management should be conservative in most cases. In very rare situations, surgery has improved visual prognosis. In most patients, however, surgery offers no benefit, and should be reserved for those with blindness or severe proptosis, or when extension toward the optic canal is documented. Although preliminary results of radiotherapy are encouraging, very few patients have been treated using this modality, and the long-term advantage for vision remains unproven. Even when untreated, the prognosis for life is excellent, with an overall tumor-related mortality of 0%.


Release of mercury vapor from dental amalgam. Because of its long-term clinical use there is more information and research data available about dental amalgam than about any other dental restorative material. However, on and off the safety of dental amalgam has been called in question and during the 80's the mercury controversy came to the fore, not only within the profession but also among the general public. Sources of mercury vapor contamination within dentistry were identified and attempts made to evaluate the contributions to the daily mercury uptake which can be attributed to dental amalgam. Mercury can be released from dental amalgam by evaporation and electrochemical corrosion as well as from amalgam particles which have been swallowed. A major route for mercury uptake from amalgam restorations is through inhalation of mercury vapor. The present study focused on experimental and analytical difficulties associated with the measurement of mercury vapor released in the oral cavity. A careful methodological study of the kind of source of mercury vapor that is prevalent and on the methods for measuring the intra-oral release of mercury vapor was carried out. With this as a basis quantitative determinations of the release rate of mercury vapor from amalgam restorations were made on healthy human subjects not occupationally exposed to mercury. The daily uptake of mercury from inhaled mercury vapor was calculated and salivary and urinary mercury levels were determined. In addition the release rate of mercury vapor from different types of amalgam was studied in vitro and in vivo. The findings may be summarized as follows: The only relevant measurable quantity when determining the mercury vapor released from amalgam restorations is the amount released per time unit, i.e. the amount of mercury vapor collected during intra-oral sampling is proportional to the sampling time. The diffusion of mercury atoms inside an amalgam restoration results in the formation of a concentration gradient in the surface of the amalgam. This mercury diffusion is the rate-determining step for mercury vapor release in the long run. In the short run the mercury concentration gradient prevalent on the amalgam surface on the measuring occasion is the apparent rate-determining step. The daily uptake of mercury from inhaled mercury vapor released from dental amalgam seems to make a very small contribution to the total body burden of mercury, in comparison with what can be tolerated in the work environment. The in vitro results revealed obvious differences regarding the release rate of mercury vapor from dissimilar amalgam types.(ABSTRACT TRUNCATED AT 400 WORDS)


Hemeralopia in an older adult.

Hemeralopia in an older adult. An elderly male was referred for evaluation of hemeralopia when cataract extraction did not alleviate his symptom of difficulty seeing in bright illumination. Visual acuity was 20/40 OU. Funduscopic examination revealed marked arteriolar attenuation, disc pallor, and retinal pigment epithelial changes. Visual fields demonstrated relative paracentral scotomata. An ERG was consistent with widespread photoreceptor degeneration. A diagnosis of visual paraneoplastic syndrome was made and an extensive systemic evaluation revealed a squamous cell carcinoma of the lung. The presentation and evaluation of acquired photoreceptor dysfunction in adulthood is discussed.


Vitrectomy in the management of diabetic eye disease. Vitrectomy techniques including endolaser photocoagulation allow visual rehabilitation in many eyes that are otherwise untreatable. Discerning the indications and timing for diabetic vitrectomy is increasingly important as the treatment of complications of diabetic retinopathy continues to undergo modification and redefinition. The most common indications for diabetic vitrectomy include: 1) severe nonclearing vitreous hemorrhage; 2) traction retinal detachment recently involving the macula; 3) combined traction and rhegmatogenous detachment; 4) progressive fibrovascular proliferation; and 5) rubeosis iridis and vitreous hemorrhage for eyes in which the media opacity has prevented adequate laser photocoagulation. Other less common indications in selected cases include dense premacular hemorrhage, ghost cell glaucoma, macular edema with premacular traction, cataract preventing treatment of severe, proliferative diabetic retinopathy, anterior hyaloidal fibrovascular proliferation, and fibrinoid syndrome with retinal detachment. The rationale and surgical objectives are discussed and results are summarized.


Ocular syphilis.

Ocular syphilis. There has been a steady increase in the number of cases of syphilis in the United States since the middle 1980s, with a dramatic rise in incidence among heterosexual men and women and of congenital syphilis. There also have been changes in geographic distribution of cases and an association with cocaine use. The ophthalmologic manifestations of syphilis are broad. There is anecdotal evidence that the natural history of syphilitic infection is altered by coinfection with human immunodeficiency virus. The potential of coinfection with HIV makes the clinical evaluation, treatment, and assessment of therapeutic outcome of syphilitic infection more confounding and controversial. This article provides a review of the changing demographics and ophthalmic manifestations of syphilis, the current status of laboratory testing techniques, and management approaches to various types of ocular syphilis.


From von Graefe's clinic to the Ecole des Beaux-Arts. The meteoric career of Richard Liebreich. Richard Liebreich was a student of Helmholtz and took one of the first ophthalmoscopes to von Graefe's clinic. While von Graefe's assistant in Berlin, he created the first atlas of ophthalmoscopy. Liebreich moved to Paris, where he achieved great success, due in part to successful surgery on Emperor Napoleon III's mother-in-law. After the fall of Napoleon in 1870, Liebreich moved to London, where he became the head of ophthalmology at St. Thomas hospital and medical school. Following several personal attacks in the medical literature, Liebreich returned to Paris, where he gradually retired from practice, yet continued a creative life as a sculptor, painter, and researcher in artistic technique.


[Ulcer epidemiology: old knowledge in a new light]. Low standards of hygiene lead to frequent gastric infection by Helicobacter pylori (Hp) during early childhood and, subsequently, the development of diffuse atrophic gastric. Atrophic gastric in conjunction with environmental factors, such as high dietary salt and low consumption of fruits or vegetables, promote intestinal metaplasia of the gastric mucosa and, possibly, gastric cancer. Under improved standards of hygiene, Hp is contracted only during adulthood, and gastric atrophy becomes less marked. The remaining capacity to secrete acid suffices to induce ulcers in the gastric mucosa weakened by the Hp infection. In adults with high acid output, the strongly acidic environment of the gastric corpus is too hostile for Hp, and it colonizes mainly the antrum. Duodenal mucosa exposed to high volumes of acid changes into epithelium covered by gastric metaplasia, more suitable for colonization by Hp than the original mucosa. The ensuing duodenitis in conjunction with the increased acid load favours duodenal ulceration. Acute exogenous influences, such as smoking, stress or physical workload, shift the delicate balance of defensive and aggressive factors at the mucosal level towards ulceration. The improvement in sanitation and the development of clean water supplies deferred the infection from childhood into adulthood and later prevented its occurrence altogether. The epidemiology of Hp could explain the historic trends of peptic ulcer and gastric cancer and their similar geographic distributions.


[Diagnosis of peptic ulcer disease].

[Diagnosis of peptic ulcer disease]. Today the upper gastrointestinal endoscopy is the diagnostic tool of choice to detect peptic gastroduodenal lesions. In case of substantial gastric outlet obstruction or strong suspicion of perforated ulcer, an upper gi-transit with barium or water soluble contrast medium in suspected perforated ulcers may be useful. Gastric ulcers are endoscopically controlled up to their complete healing and biopsies taken at each endoscopy in order to rule out gastric cancer. In contrast, duodenal ulcers are rarely malignant and uncomplicated duodenal ulcers, correctly treated with omeprazole over 8 weeks do not necessarily need a final endoscopic control. Since about 5% of duodenal ulcers treated with H2 blockers or mucosal protective agents do not heal within 8 weeks however, an endoscopic control of the healing is recommended. In peptic ulcer patients tests for detection of helicobacter pylori are only needed in presence of a hard indication for immediate eradication: Frequent ulcer recurrencies, complicated ulcer disease or very painful ulcer relapses, because the eradication therapy is often not well tolerated and the patient compliance therefore compromised. 30% of helicobacter infected patients have antibiotic resistant strains and there is no sufficient longterm experience with the eradication therapy available (4) to 8 weeks after treatment of the helicobacter pylori infection the effect on ulcer healing and infection should be verified. Determinations of plasma gastrin levels in peptic ulcer patients are mandatory in patients with suspected Zollinger-Ellison syndrome or patients with treatment resistant ulcers or recurrent ulcers after vagotomy or partial gastric resection.(ABSTRACT TRUNCATED AT 250 WORDS)


[Pathophysiology of ulcer disease].

[Pathophysiology of ulcer disease]. The pathogenesis of ulcer disease is complex. The present outline focuses on four main aspects: 1) The mechanisms governing acid production and the role of acid in ulcer disease. 2) The mechanisms regulating mucosal resistance to injury. 3) The association of ulcer disease with antral gastritis and Helicobacter pylori infection. 4) Ulcer disease and non-steroidal antiinflammatory drugs (NSAIDs). The complex mechanisms underlying maintenance of mucosal integrity in the normal state and in ulcer disease are discussed. Acid/peptic activity as permissive factors are related to impaired mucosal resistance due to Helicobacter infection or NSAID intake.


[Therapy of the acute ulcer attack].

[Therapy of the acute ulcer attack]. Medical treatment of acute ulcers can be optimized by paying attention to risk factors for slow healing and for rapid recurrence. Therapy-resistant ulcers have become virtually unknown with modern drugs, so elective ulcer surgery is nowadays rarely needed for this reason. While drug therapy of acute ulcer hemorrhage is probably of little, if any, benefit for stopping bleeding, endoscopic treatment reduces the risk of continuous or recurrent bleeding, the need for emergency surgery, and mortality of this most common complication.


[Prevention of recurrence of ulcer disease: indications and choice of procedure]. In this contribution we discuss the relapse prophylaxis of ulcers by nonmedicamentous measures, by long-term drug therapy and, in particular, with inhibitors of secretion, by eradication therapy of Helicobacter pylori and by surgical therapy. Besides secondary prophylaxis (prevention of ulcer relapses), primary prophylaxis (prevention of the first episode) is also briefly treated.


[Ulcer disease. The role of the surgeon]. Today the therapeutical approach towards the 'ulcer disease' consists mostly of medical treatment. Surgical intervention has decreased and is commonly used only for the treatment of emergencies, complications and in cases not responding to medical therapy. If surgical intervention is necessary because of recurring disease despite a complete conservative treatment, resection should be preferred for sufficient therapy of the 'ulcer disease'. Many acutely bleeding ulcers can be controlled by endoscopic methods, however, bleeding ulcers with a high rate of recurrence (Forrest Ia and IIa at the dorsal duodenum and at the small curvature of the stomach) should be treated by resection. Especially elderly, multimorbid patients in this situation should be considered for an early elective surgical procedure. Perforating ulcera duodeni can be treated sufficiently by excision and oversewing in most cases, whereas perforated ulcera ventriculi should always be resected because of possible malignant transformation.


[Future perspectives of ulcer therapy].

[Future perspectives of ulcer therapy]. Anti-ulcer drugs are amongst the world's most successful pharmaceutical products. Whilst the market for histamine H2 antagonists is maturing, that for proton pump inhibitors looks set to expand considerably during the 1990s. Indeed, by analogy with anti-hypertensive therapy, enzyme inhibitors could eventually supersede receptor antagonists for the treatment of acid-related diseases. Whether a third major cycle of innovative drugs will follow the cimetidine and omeprazole led discoveries of the 1970s and 80s is more difficult to predict given the efficacy of current agents, the declining incidence of ulcer disease, and the need to focus resources in areas of clinical need such as gastrointestinal cancer. Therapy targetted against Helicobacter pylori represents the most attractive option for developing the next generation of anti-ulcer drugs. A major initiative to eradicate H. pylori would be justified if such therapy also had utility in gastric cancer.


A simple enzyme-immunoassay test for von Willebrand factor binding in human arterial subendothelium. In order to determine the binding of vWF, subendothelium from everted human umbilical arteries was perfused with dialysed serum containing different concentrations of purified vWF using an annular perfusion chamber at a wall shear rate of 1100 sec-1 for 30 min. After perfusion, control (not perfused) and perfused vessel segments were washed and incubated with a diluted rabbit antibody against human vWF. Then the nonbound anti-vWF from both samples were used to determine indirectly vWF by EIA. Although in our experiments normal vWF serum concentrations were not enough to exert vWF binding, a substantial binding could be attained with vWF levels around 2.5 U/ml. To estimate the pre-existing subendothelial vWF amount, three different experiments were developed: a) diluted IgG from a nonimmunized rabbit, b) a diluted rabbit antibody to human vWF, c) PBS-BSA. After washing, vessel segments were incubated with rabbit antibody to human vWF. After incubation, the nonbound anti-vWF was used to determine indirectly vWF by EIA. The results obtained showed that the amount of pre-existing vWF was approximately 1.1x10(-3) U vWF/cm2 subendothelium.


An in vitro evaluation of the effect of laser irradiation on the thrombogenicity of thrombus. The effect of laser irradiation on the thrombogenicity of thrombus was evaluated by treating thrombi, formed in-vitro from canine blood, with two different doses of cw Nd:YAG laser energy at 1064 nm. The thrombi were then incubated with whole blood, and the plasma levels of fibrinogen and thrombin-antithrombin III-complexes were measured. A statistically significant decrease (p < 0.05) in the thrombogenicity was indicated by a reduction in both fibrinogen consumption and levels of thrombin-antithrombin III-complexes in the high dose group (600 joules, 100 degrees C peak temperature) in comparison to the low dose group (300 joules, 70 degrees C peak temperature) and the untreated thrombi. These findings suggest that laser irradiation of thrombus at an appropriate dose may substantially reduce its thrombogenicity and ability to modulate hemostasis.


Effect of ajoene, the major antiplatelet compound from garlic, on platelet thrombus formation. Ajoene, (E,Z)-4,5,9-trithiadodeca-1,6,11-triene 9-oxide, is a potent antiplatelet compound isolated from alcoholic extracts of garlic (Allium sativum). Ajoene reversibly inhibits in vitro platelet aggregation as well as release reaction induced by all known agonists. We used a well characterized cylindrical perfusion chamber to study the effect of ajoene on platelet deposition onto physiological substrates such as pig aortic subendothelium and tunica media as a model of mildly and severely damaged vessel wall respectively. Experiments were performed under flow conditions of high and low shear rate that mimic laminar blood flow in small and medium size arteries (1690 sec-1 and 212 sec-1). Our results indicate that ajoene prevents thrombus formation both at low and high shear rate in citrated whole blood. The inhibitory effect of ajoene on platelet-thrombus formation seems to be dependent on its inhibition of fibrinogen binding, since significantly higher concentrations of ajoene are needed to affect von Willebrand factor binding to GPIIb/IIIa receptors. Further, ajoene does not impair Ristocetin-induced platelet agglutination, mediated by GPIb. Our results suggest that ajoene may be useful for the acute prevention of thrombus formation induced by vascular damage.


Thrombin inhibition compared with other antithrombotic drugs in rats. An aspirin-sensitive model of arterial thrombosis suitable for rapid evaluation of antithrombotic drugs was developed and characterized in anesthetized rats. Carotid artery thrombi were formed in response to electrical stimulation and were occlusive in 84% of vehicle-treated rats. Light and electron microscopy revealed these thrombi to be platelet-rich and fibrin-rich masses adherent to the injured vessel wall. Intravenous administration of aspirin (10 mg/kg), heparin (300 U/kg), a thromboxane (Tx) A2-receptor antagonist (SQ 29,548, 0.2 mg/kg + 0.2 mg/kg/hr), or the thrombin inhibitor D-phenyl alanyl-L-prolyl-L-arginyl chloromethyl ketone (PPACK, 52 micrograms/kg/min) decreased average thrombus weight by 35, 50, 57 and 94%, respectively. Each of these drugs also reduced the frequency of occlusion to < 25%. In contrast, thrombus weight and vessel occlusion were not decreased by a serotonin antagonist (ketanserin, 0.3 mg/kg, i.v.), or after 14 days of oral dosing with either the calcium antagonist diltiazem (60 mg/kg) or SQ 33,351 (30 mg/kg).


A comparative study of recombinant hirudin and standard heparin in the Wessler model. The in vitro anticoagulant activity of recombinant desulphated hirudin (HBW 023) and its antithrombotic activity in a rabbit venous stasis model were assessed in comparison to unfractionated heparin (UH). The specific activity of r-hirudin in rabbit plasma is similar to that of unfractionated heparin on a weight basis when using the whole blood clotting time or APTT, while it was five times more potent according to the thrombin clotting time (TCT). Forty-eight (6x8) anaesthetized New Zealand male rabbits were randomized to receive HBW 023 (12.5, 25, 50, 100, 200, 400 micrograms.kg-1), standard heparin (90 micrograms.kg-1) or placebo. Five minutes after administration of the drug, the experimental thrombosis was induced by an injection of glass activated overnight human serum into the marginal vein of the ear and ligation of the jugular vein (Wessler model). The jugular vein was removed after 10 min stasis and examined by a researcher unaware of the treatment administered. In the Wessler stasis model the fresh thrombus weight and a score as well as the circulating level of r-hirudin using a chromogenic substrate assay were used to determine the inhibitory effect of the drug. Highly significant inverse correlations were found between fresh thrombus weight and the injected doses as well as r-hirudin plasma levels. The ID50 which was the dose of the drug that induced a complete inhibition of thrombosis in 50% of the dose group tests was about 200 micrograms.kg-1.(ABSTRACT TRUNCATED AT 250 WORDS)


The inhibition of thromboplastin by apolipoprotein-B and the effect of various associated lipids. Human apolipoprotein B was purified by barium sulphate adsorption, subsequent delipidation and gel filtration. The protein was then reconstituted in soya bean lecithin and its inhibitory effect towards thromboplastin was assayed by incubation with rabbit brain thromboplastin. The use of an antibody against human apolipoprotein B diminished this inhibition. The level of inhibition of thromboplastin by the reconstituted apolipoprotein was found to be dependent on the concentration of the phospholipids with which it was reconstituted, reaching a maximum inhibition at a lipid: protein ratio of 1:1 (w/w). However, higher phospholipid concentrations or inclusion of cholesterol esters or triglycerides diminished and at certain concentrations reversed the inhibitory effect of the apolipoprotein. These results point towards apolipoprotein B as an inhibitor whose activity towards thromboplastin could be dependent on the complexes it forms with the surrounding lipids.


Supraspinal origin of abnormal hindquarter vasoconstrictor tone in spontaneously hypertensive rats. The object of this study was to determine whether the abnormal hindquarter tone in spontaneously hypertensive rats (SHR) is of spinal origin or not. SHR were implanted with a catheter in the left common carotid and an electromagnetic flow probe around the terminal aorta. About three days after implantation, the spinal cord was transected at Th 1 under ether anesthesia. One hour later, when the rat restored consciousness and the arterial pressure recovered partially to a new plateau level which was significantly higher than that in similarly treated normal rats, ganglionic blockade with hexamethonium did not significantly decrease hindquarter (terminal aortic) resistance, calculated as arterial pressure divided by hindquarter flow. It was concluded that there was no appreciable sympathetic vasoconstrictor tone in the hindquarters of SHR after spinal transection and that the origin of the abnormal tone was at the supraspinal level.


Serologic findings in hepatic ascariasis: a case report. A 56-year-old Japanese woman underwent partial hepatectomy for intrahepatic cystic masses. Before operation, the patient had been diagnosed as liver abscess due to Ascaris infection serologically. The excised hepatic lesions consisted of encapsulated old abscesses, with a few calcified parasitic ova and numerous Charcot-Leiden's crystals microscopically seen in necrotic exudate. However, no parasitic worms were found in the cystic cavity. The eggs in the tissues were indistinguishable from other helminthic ova morphologically, but stained positively for Ascaris antigens by the indirect immunoperoxidase method. The results indicate that the serologic diagnosis of intrahepatic ascariasis may be feasible, practical, and reliable.


Immunohistochemical study of metallothionein in human seminal vesicles. Metallothionein (MT) in human seminal vesicles was examined by use of the avidin-biotin-peroxidase complex method. Tissues were obtained from six patients with prostate cancer who underwent luteinizing hormone-releasing hormone agonist or estrogen therapy before radical prostatectomy (group 1) and from 18 patients without hormone therapy (three with prostate cancer, three with urinary bladder cancer, and twelve free of urogenital diseases at autopsy) (group 2). MT was localized in the cytoplasm and nuclei of epithelial cells and also in secretory products in the lumen. The epithelial cells lacked uniformity in immunoreaction; for instance, some stained strongly while others stained weakly. Smooth muscle cells were found to have positive immunoreaction, but other connective tissues had no immunoreaction. The number of strongly positive cells in group 1 was fewer than that in group 2 (not significant), and the secretory products in group 1 had no immunoreaction. These results suggest that MT is synthesized in the epithelial cells of the seminal vesicles and secreted into the fluids, and that the synthesis of MT is suppressed by the hormone therapy.


Prevention of respiratory infections in elderly bed-bound nursing home patients. A procedure to prevent silent aspiration, which results in frequent respiratory infections, was conducted on elderly bed-bound nursing home patients who suffered mainly from cerebral infarction and dementia. We cleaned the mouth with povidone iodine and kept them in a sitting position for 2 hr after each meal in order to restrict respiratory bacterial infection and to prevent aspiration of gastric juices, respectively. Patients with urinary tract infections were excluded from the present protocol. During the treatment for 103 days the number of febrile days was significantly decreased in the treated group compared with the control group, probably due to minimizing of respiratory infections.


The influence of tetrodotoxin on the toxic effects of aconitine in vivo. Both aconite toxins (aconitine, mesaconitine, and hypaconitine) and a pufferfish toxin (tetrodotoxin, TTX) were detected in the blood of a legal autopsy case. In order to elucidate the in vivo influence of TTX on the toxic effects of aconitine, a mixture of aconitine and TTX was administered to male ICR mice orally or intraperitoneally. The animal experiments revealed that the time of death due to aconitine was significantly delayed in proportion to the dose of TTX compared with the case for aconitine alone, and that the mortality of aconitine was lowered by TTX when the dose ratio of the two toxins was in a particular range. Accordingly, it is thought that the toxic effects of aconitine are attenuated by TTX in vivo.


Direct measurement of endothelin receptor in human bladder base and dome using 125I-endothelin. The amount of endothelin receptor in human bladder base and dome was measured by radioligand binding techniques using 125I-endothelin-1 (125I-ET). Specimens were obtained from 5 patients who underwent total cystectomy under diagnosis of bladder cancer. 125I-ET bound to the bladder base with the KD value of 0.004 +/- 0.003 nM and to the bladder dome with the KD value of 0.007 +/- 0.003 nM. These values were not significantly different. The Bmax values (fmol/mg protein) of 125I-ET binding to human bladder were 2.74 +/- 2.81 to the base and 47.3 +/- 9.52 to the dome. There were much larger amount of endothelin receptors in the dome compared to the base. The existence of endothelin receptors in human bladder suggests the possible roles of endothelin on the human bladder function.


The effect of carnitine on the metabolism of valproic acid in epileptic patients. The half-life of valproic acid (VPA) was studied in 8 epileptic and severely mental retarded patients before and after one month of carnitine supplementation. Serum carnitine concentration was significantly decreased and VPA half-life was prolonged especially in adult patients before carnitine supplementation. After the treatment with carnitine, serum carnitine concentration was increased, and prolonged half-lives of VPA were corrected near to the normal range (from 12.2 +/- 4.2 hr to 9.7 +/- 2.2 hr; p < 0.05). Controlled state of epilepsy was unchanged during the short period of observation.


The mechanism of glomerular dysmorphic red cell formation in the kidney. The mechanism of glomerular dysmorphic cell formation was studied in a in vitro system simulating the process of concentrated acidic urine formation along the nephron. Red cells suspended in phosphate buffer were exposed to three sequential pH gradients, (1) pH 7.4-6.6, (2) pH 6.6-6.5, and (3) pH 6.5-5.2, accompanying osmolality gradients, (1) 280-1200 mOsm/kg H2O, (2) 1,200-140 mOsm/kg H2O, and (3) 140-1,100 mOsm/kg H2O, respectively, for 15 to 60 min, and red cell shapes were observed by differential interference microscopy. The appearance rate of glomerular dysmorphic cells was 37.7 to 47.1% after finishing all the gradients. The last gradient, simulating the work of the collecting duct, was essential for the dysmorphic cell formation; maximal formation was at the final pH of 5.0 and osmolality of 1,000 mOsm/kg H2O. No dysmorphic cells were observed in gradients simulating alkaline or diluted urine formation. In 10 glomerulonephritic patients, glomerular dysmorphic cells appeared over five times as frequently in concentrated acidic urine as in alkaline or diluted urine. Results of in vitro and patient studies coincided well with each other, suggesting that in glomerulonephritic patients, dysmorphic cells might be produced while red cells are passing through the tubules, where concentrated acidic urine is formed.


Pulmonary toxicity of acrylonitrile: covalent interaction and effect on replicative and unscheduled DNA synthesis in the lung. Acrylonitrile (VCN)-induced lung toxicity was studied following a single oral dose (46.5 mg/kg). The mechanism of toxic injury was investigated by assessing the covalent interaction of [2,3-14C]VCN with pulmonary DNA. The effect of the same dose on replicative DNA synthesis and repair in the lungs of treated rats was also investigated. Histologic examination revealed that lungs of VCN-treated animals showed moderate to marked hyperplasia of the Clara cells lining the bronchioles. [14C]Lung tissue uptake was extremely fast, having a maximum at 0.5 h after treatment (150 DPM tissue). Radioactivity in lung tissue declined gradually as a function of time, but was still detected at 72 h after treatment (59 DPM/mg tissue). Covalent binding of [14C]VCN-derived radioactivity to pulmonary DNA was time-dependent, reaching a maximum at 12 h following treatment (61 DPM/mg DNA) and was still detected at 72 h (27 DPM/mg DNA) indicating the incomplete removal of radioactivity covalently bound to DNA. Replicative DNA synthesis in lung tissue was significantly decreased at all time points studied (59, 55 and 72% of control at 0.5, 6 and 24 h, respectively). The DNA repair in the lung was increased by 2-fold at 0.5 h and 1.6-fold at 6 h following VCN oral treatment. The histologic and biochemical results presented in this study provide evidence for the acute genetic toxicity of VCN (and/or its metabolites) in lung tissue following a single oral dose of VCN.


Exogenous metallothionein and renal toxicity of cadmium and mercury in rats. The relative tissue distribution and toxicity of cadmium (Cd) and mercury (Hg) in the liver and kidneys of rats when the metals are administered as either inorganic salts or complexed with MT were studied. Male Sprague-Dawley rats were injected (i.v.) with Cd or Hg inorganic salt of chloride or in a complex of MT at a dose of 0.3 mg/kg body weight. The concentration of MT and metals in plasma and urine was monitored for 7 days, at the end of which the rats were killed. Injection of both HgCl2 and Hg-MT induced the synthesis of MT only in the kidney but not in the liver, whereas CdCl2 and Cd-MT injections induced MT synthesis in both liver and kidney, respectively. Plasma MT levels increased 3 days after CdCl2 but not after HgCl2 injection, suggesting that hepatic MT may be an important source of plasma MT under our experimental conditions. Renal toxicity was observed morphologically and by an increase in blood urea nitrogen, plasma creatinine, proteinuria in rats injected with Cd-MT and both forms of Hg. Urinary MT excretion was significantly elevated in Cd-MT injected rats compared with those injected with CdCl2. However, HgCl2 and Hg-MT injected rats showed no significant difference in urinary MT excretion. The magnitude in the renal accumulation of Hg is similar after the administration of Hg-MT or HgCl2, but our findings suggest that the site of epithelial injury may be different. Injury effects of Hg-MT localized mainly in the terminal portions of the proximal convoluted tubule and the initial portions of the proximal straight tubule whereas inorganic Hg caused necrosis in pars recta segments of the proximal tubule.


Hepatic chemiluminescence and lipid peroxidation in mild iron overload. The effect of iron-overload on both hepatic lipid peroxidation and chemiluminescence was studied in early stages after iron-dextran injection. Total hepatic iron content was markedly elevated over control values 2-6 h after iron dose. A 4-fold increase in light emission was detected after 4-6 h after iron injection. Plasma GOT, GPT and LDH activities were not affected by the treatment suggesting that cell permeability was not affected by necrosis. Increases in the generation of thiobarbituric acid reactive substances (TBARS) and chemiluminescence in liver homogenates, were determined as a function of time after iron administration, in the presence of NADPH as cofactor. Under the same experimental conditions, microsomal cytochrome P-450 content was decreased by 40%, 2 h after iron treatment. To evaluate liver antioxidant defenses, catalase, superoxide dismutase and glutathione peroxidase activities were determined. Glutathione peroxidase activity in the homogenate was not affected by the treatment. Catalase and superoxide dismutase activities declined by 25 and 36%, respectively, compared with control values 4 h after the iron dose. Our data suggest that lipid peroxidation occurs after mild iron overload even though the liver remains functional.


Hepatotoxicity of trichlorfon and dichlorvos in isolated rat hepatocytes. Hepatotoxicity of organophosphorus insecticides, trichlorofon and dichlorvos, a dechlorinated form of the former, was examined in isolated hepatocytes from untreated control and phenobarbital-pretreated (80 mg/kg, i.p., for 3 days) rats. These compounds produced toxic effects on hepatocytes as evidenced by malondialdehyde production and lactate dehydrogenase leakage in a dose-dependent manner up to the concentration of 2 mM, dichlorvos being more toxic than trichlorfon. Hepatocytes from phenobarbital-pretreated rats were more sensitive to these organophosphates than those from control rats. Dichloroacetaldehyde and dichloroacetic acid, metabolites of dichlorvos, did not injure hepatocytes. The toxic effects of dichlorvos on hepatocytes were enhanced by increasing oxygen concentration during the incubation, or by addition of glycolytic substrates (pyruvate, lactate or fructose) to the incubation mixtures. On the other hand, addition of antioxidants (diethyldithiocarbamate or N,N'-diphenyl-p-phenylenediamine), or cytochrome P-450 inhibitors (SKF-525A or metyrapone) to the incubation mixtures attenuated malondialdehyde production caused by dichlorvos and protected cells from death. Addition of dichlorvos to the incubation mixtures of hepatic microsomes stimulated lipid peroxidation in the presence of NADPH, which was inhibited by further addition of superoxide dismutase but not catalase. These results suggest that hepatotoxicity of trichlorfon and dichlorvos are related to their peroxidative property in microsomes which is accelerated by oxygen.


Competitive studies relating to tryptophan binding to rat hepatic nuclear envelopes as a sensitive assay for unknown compounds. Our laboratory has reported that L-tryptophan binds to a rat liver nuclear envelope protein and this binding is saturable, stereospecific and of high affinity. Utilizing an in vitro [3H]tryptophan binding assay to hepatic nuclear envelopes, we have determined the effects of using excess unlabeled L-tryptophan from a number of different suppliers. This study reports that, based on our in vitro binding assay, some significant differences were observed when implicated L-tryptophan in cases of the eosinophilia-myalgia syndrome obtained from a Japanese manufacturer, Showa Denko, was assayed, in contrast to non-implicated L-tryptophan from other suppliers. An isolated impurity of Showa Denko L-tryptophan, 1,1'-ethylidenebis(tryptophan) alone or together with non-implicated L-tryptophan or its breakdown product, 1-methyl-1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid, did not appreciably affect the in vitro [3H]tryptophan binding to hepatic nuclear envelopes as did the Showa Denko L-tryptophan. Our data, derived with our in vitro binding assay system, suggests that implicated L-tryptophan from Showa Denko contains a compound/s (unknown at present) other than 1,1'-ethylidenebis(tryptophan), which alters in vitro [3H]tryptophan binding. The significance of the impurity/ies involved remains to be determined.


Barriers to treatment of obstetric emergencies in rural communities of West Africa. The Prevention of Maternal Mortality Network. This article is the result of a collaborative effort among the researchers of the Prevention of Maternal Mortality Network. The network consists of 12 multidisciplinary teams, 11 in West Africa and one based at Columbia University in New York. This article summarizes exploratory research conducted by the African teams using focus-group discussions in rural communities in Nigeria, Ghana, and Sierra Leone. The objective was to identify barriers to the use of health-care facilities when obstetric problems arise. The findings illustrate how sociocultural factors, such as societal expectations and the role of women, affect the use of health services. Physical and social distance between communities and facilities, as well as transportation problems, were found to be obstacles to care. Health-service factors were also found to pose barriers to prompt treatment. This article also provides an example of how qualitative methodology can be used to obtain substantive information about a community's frustrations and needs with respect to health care.


What does the Matlab fertility experience really show? The family planning program in the Matlab District of Bangladesh has been described in unique detail for more than 25 years and is regarded as a model for equally poor parts of the world. Its experience has been reported as showing the ineffectiveness of contraceptive saturation approaches and the prime importance of program management and especially of the selection of a special type of family planning household visitor, criteria that render family planning programs relatively expensive. This reanalysis of the Matlab experience suggests that there is inadequate evidence from which to judge the record of the saturation experiment and of family planning workers from less highly selected backgrounds. It is also argued here that the role of contraceptive choice and of access to different types of contraceptives, especially injectables, delivered to the door in this society of secluded women has been underestimated, and that too little importance has been attributed to demand in contrast to supply. While it is agreed that the Matlab demonstration has been of central importance in showing that fertility can be reduced in Bangladesh, it is argued that many developing countries can draw on this experience to provide less costly family planning programs with less emphasis on the managerial, top-down approach.


A hospital-based study of abortion in Nepal. This report presents the major findings of a study of induced abortion in Nepal, based on 165 cases out of the 1,576 female patients identified as having abortion-related complications who were admitted to five major hospitals in urban Nepal during a one-year study period. Traditional birth attendants had been the service providers for two-fifths of the women. A longer delay in hospital referrals and lengthier hospital stays occurred for cases of induced abortion than for those of spontaneous abortion. Twelve of the 165 women in the study died in the hospital, most of them from tetanus. Deaths resulting from abortion-related complications represented more than half of all maternity-related deaths in the hospitals studied. The authors suggest that health risks could be reduced considerably by strengthening the hospital-referral system and by taking some preventive steps, such as educating the traditional birth attendants and other paramedical providers about the consequences of unsafe abortion practices; increasing the availability of contraceptive methods; and promoting the use of menstrual regulation, which has recently become available in Nepal on a limited scale, mostly in private clinics.


Maternal mortality in Ile-Ife, Nigeria: a study of risk factors. The objective of this study was to determine which background factors predispose women to maternal mortality at the Obafemi Awolowo University Hospital in Nigeria. The study examined 35 cases of maternal death occurring in the hospital during the period 1 October 1989 to 30 April 1991. The control group comprised 35 women who were admitted to the hospital with similar complications during the same period, but who survived. Both cases and controls were investigated for their sociodemographic characteristics, their use of prenatal care, and the incidence of delay in clinical management. The results showed that the maternal deaths involved women who were younger and of poorer socioeconomic status than the women in the control group. Both groups showed an equal lack of prenatal care. However, a higher incidence of delayed treatment was found in the management of the cases of maternal deaths. Maternal mortality in the study population can be reduced through improved transportation and institutional management, and, on a long-term basis, through the adoption of measures to improve the socioeconomic status of women.


Aspects of tuberculosis in Africa. 1. Tuberculosis in Africa in the AIDS era--the role of chemoprophylaxis. An estimated 2.8 million people in Africa have dual infections with tuberculosis and human immunodeficiency virus (HIV). Because of the increasing numbers of cases of tuberculosis as a consequence of the HIV epidemic, chemoprophylaxis may become a cost effective tuberculosis control measure in high prevalence countries. Although isoniazid (INH) is the only drug evaluated in controlled trials of preventive tuberculosis therapy, studies are now under way to determine the efficacy of INH and other drugs, including rifampicin and pyrazinamide, in preventing tuberculosis reactivation in persons with HIV infection. If chemoprophylaxis is effective in persons with dual infection, further studies will be required to determine whether chemoprophylaxis is cost effective for tuberculosis prevention and control and whether it is feasible to introduce it as a community control measure.


Abortions in a hospital setting: hidden realities in Dar es Salaam, Tanzania. This study investigates the extent of unwanted pregnancy, the use of illegally induced abortion, and the attitudes toward and practice of contraception among women admitted to a hospital with the diagnosis of abortion in Dar es Salaam, Tanzania. (In Tanzania, induced abortion is permitted only to save the mother's life.) A random sample of 300 women with early pregnancy loss admitted to Muhimbili Medical Centre, the teaching hospital in Dar es Salaam, were interviewed between September and November 1987, using a structured questionnaire. Among the 300 respondents, 155 said that their pregnancy had been unwanted: 94 of them presented with an illegally induced abortion and 61 with a spontaneous abortion. The number of spontaneous abortions of unwanted pregnancies increased with age and stability in a relationship. Having a small child to look after and having completed the family were the most common reasons for the pregnancy to be unwanted in this group. Induced abortion was more a problem of the young, unmarried woman. The 61 women with spontaneous abortion but unwanted pregnancy suggest that a much larger group of pregnant women continue to term with what are, at least initially, unwanted pregnancies--precisely the group of women family planning programs want to reach. The low prevalence of contraceptive use in this group indicates the failure of family planning clinics to motivate their target group. Recommendations are made for improved functioning of family planning clinics.


Aspects of tuberculosis in Africa. 2. The value of microbiology in the management of tuberculosis in Nairobi, Kenya. A group of African patients with tuberculosis were followed over the first month of treatment to assess the bactericidal response to 2 treatment regimens (streptomycin/thiacetazone/isoniazid and streptomycin/rifampicin/isoniazid/pyrazinamide). Patients also infected with human immunodeficiency virus (HIV) had lower pre-treatment counts of viable Mycobacterium tuberculosis and a greater proportion became culture-negative by 28 d. The response to therapy in HIV positive and HIV negative patients was similar. Because of the combination of these findings and the higher early mortality in patients with HIV, the causes of acute infection in patients with tuberculosis were studied. It was found that HIV positive patients were frequently bacteraemic and that the principal pathogen was Salmonella typhimurium, but recurrent pneumococcal bacteraemia was also seen.


Aspects of tuberculosis in Africa. 3. Genetic 'fingerprinting' for clues to the pathogenesis of tuberculosis. The recent discovery of a repetitive element within the DNA of Mycobacterium tuberculosis, which is present in variable numbers at different locations in separate strains of the organism, has led to the development of genetic 'fingerprinting' to distinguish between different isolates. Clusters of cases of tuberculosis have been identified in Europe and the USA in which the organisms cultured had identical 'fingerprints' confirming that transmission was occurring. Unrelated isolates generally have distinct 'fingerprints'. In Africa, where transmission is more common than in Europe, there is less heterogeneity between isolates. We have typed 117 isolates of M. tuberculosis collected from continuing studies in Malawi and Kenya. Paired isolates from an individual patient produced matching 'fingerprints' in 22 of 25 cases. There were 18 isolates which had an identical matched pair from a separate patient; we have not yet found any epidemiological link between these patients. These data show that there is sufficient heterogeneity amongst African isolates of M. tuberculosis to make studies of transmission feasible and to address questions of pathogenesis and epidemiology.


An audit of the management of malaria in a Tanzanian district hospital. An audit of the management of falciparum malaria was carried out over a 12 month period in a north-west Tanzanian district hospital; 1494 patients were studied, 75% being children under 5 years. Chloroquine was effective in 1128 cases (79%), 68 patients died, of whom 64 were aged under 5 years; 30 of them died fewer than 2 d after admission; 14 had received quinine chemotherapy. Management can be improved by better diagnosis of anaemia and hypoglycaemia, changing the dose of injectable chloroquine, earlier use of quinine, and enabling doctors to see very ill patients earlier.


Fever episodes in a holoendemic malaria area of Tanzania: parasitological and clinical findings and diagnostic aspects related to malaria. All episodes of acute illness, in children aged 0-9 years, were registered during 3 years in a health clinic in a village of about 500 inhabitants in a malaria holoendemic area on the Tanzanian coast. Of 668 clinical episodes, 395 were diagnosed as malaria. There was no death. Only 5% of the children with malaria episodes came to the clinic after more than 3 d of symptoms. All 11 severe anaemias occurred among these children. Fever was reported in 98%, vomiting in 15%, and diarrhoea in 8% of the malaria episodes. Intermittent fever was reported in 98% of the malaria patients with more than one day of fever, compared to 4% of those with other febrile illnesses. Parasite densities > or = 10,000/microliters were found in 48% of the malaria episodes. Densities > or = 400/microliters were found in 96% of the malaria episodes and in only 8% of the other febrile illnesses. The 16 malaria episodes (4%) with densities below that level were all in children under one year of age. The ability of the rural medical aid or the doctor to differentiate malaria episodes from other febrile illnesses without microscopical examination was limited. Although very few malaria episodes were missed, substantial over-diagnosis resulted in specificity values of only 13% and 52% for their respective malaria diagnoses. It is concluded that intermittent fever was strongly associated with malaria, but a high accuracy of malaria diagnosis in febrile children requires microscopical examination.(ABSTRACT TRUNCATED AT 250 WORDS)


Malaria chemoprophylaxis, birth weight and child survival. Study of the effects of malaria chemoprophylaxis given during pregnancy on birthweight and investigation of the influence of birthweight on child survival suggest that, in a rural area of The Gambia, chemoprophylaxis given during pregnancy might reduce infant mortality by about one-fifth in the children of primigravidae but by less than 5% in the children of multigravidae. In malaria endemic areas, primigravidae should be protected against malaria not only for their own sake but also for that of their infants.


Malaria and pregnancy in Cameroonian women. Naturally acquired antibody responses to asexual blood-stage antigens and the circumsporozoite protein of Plasmodium falciparum. Antibody responses to Plasmodium falciparum antigens in women during pregnancy were investigated in Mfou, a rural community in Cameroon. The study consisted of cross-sectional analyses involving 225 pregnant women and 75 non-pregnant controls. Blood samples were collected from each woman to determine serological reactivity to intraerythrocytic malarial antigens, ring-infected erythrocyte surface antigen (RESA) and circumsporozoite (CS) repeat peptide (NANP)5 by the indirect fluorescent antibody assay, modified immunofluorescent antibody assay, and enzyme-linked immunosorbent assay, respectively. Reactivity to intraerythrocytic asexual blood-stage antigens and to the CS repeat region was similar in both pregnant and non-pregnant women, and no correlation with parasitaemia was found. In contrast, anti-RESA antibody levels were significantly lower in pregnant than in non-pregnant women (P = 0.02) and in primigravidae than in multigravidae (P = 0.002), and were inversely correlated with parasitaemia (r = -0.36; P < 0.01). These data suggest that the increased susceptibility to malarial infection in pregnant women may be explained in part by their lower reactivity to RESA.


Prognostic risk factors and post mortem findings in cerebral malaria in children. We have examined the possible risk factors for poor prognosis in cerebral malaria in 61 Nigerian children in an area of high malaria transmission. The level of coma, decerebrate rigidity, hypoglycaemia, and high urea levels were indicators of poor prognosis. Pyrexia, vomiting, and anaemia did not influence prognosis. Post-mortem findings suggest gross cerebral oedema and raised intracranial pressure in 4 of 7 cases with petechial haemorrhages and small focal necrosis (Durck's granuloma).


Kala-azar: a comparative study of parasitological methods and the direct agglutination test in diagnosis. In a comparative study 88 patients were diagnosed as suffering from kala-azar (visceral leishmaniasis) using 3 parasitological methods simultaneously. Splenomegaly was absent in 4 cases. In 84 patients with splenomegaly, splenic aspiration appeared to be the most sensitive method (96.4%), followed by bone marrow aspiration (70.2%) and lymph node aspiration (58.3%). There was no relation between titres in the direct agglutination test and parasite load as determined by the number of parasitological methods which were positive or parasite density in splenic aspirates. Splenic aspiration and bone marrow aspiration were compared as an assessment of cure in kala-azar. In 6 (13%) of 46 patients tested, parasites were found, all by splenic aspiration. Bone marrow showed parasites in one of these. The literature with regard to parasitological investigations before and after treatment is reviewed.


Sporadic cutaneous leishmaniasis in north Tunisia: identification of the causative agent as Leishmania infantum by the use of a diagnostic deoxyribonucleic acid probe. A diagnostic kinetoplast deoxyribonucleic acid (DNA) probe has been used to identify as Leishmania infantum amastigotes taken from the lesions (in dermal fluid or lesion triturates) of 7 of 8 patients suffering from sporadic cutaneous leishmaniasis in north Tunisia. All 8 isolates were very difficult to culture but, subsequently, sufficient parasites of one isolate have been grown for isoenzyme typing, and were identified as zymodeme MON 24 of L. infantum. The advantages of using recombinant DNA probes for the identification of parasites from lesions are discussed.


Morbidity from malaria and immune responses to defined Plasmodium falciparum antigens in children with sickle cell trait in The Gambia. Morbidity from Plasmodium falciparum malaria and humoral and in vitro cellular immune responses to defined malaria antigens were measured in rural Gambian children with haemoglobin phenotype AS (HbAS) and in those with a normal haemoglobin (HbAA). In a survey undertaken during the dry season, HbAS children had a higher parasite rate than HbAA children but a lower prevalence of parasitaemia at a level of 500/microliters or greater. Malariometric indices measured during a rainy season survey were similar in the 2 groups of children. During the rainy season, the incidence of infection with P. falciparum did not vary with haemoglobin phenotype. However, in children aged 6 years or less, a significantly smaller proportion of HbAS children who acquired infection developed clinical symptoms than did HbAA children. During both the dry season and rainy season surveys, humoral and in vitro cellular immune responses to defined antigens from the sporozoite and merozoite stages of P. falciparum were similar in the 2 groups of children. Thus, despite the differences in parasite indices and morbidity from malaria between the 2 groups of children, we found no evidence of an enhanced immune response to malaria infection amongst HbAS children compared with normal children.


Cellular and humoral immune responses of a patient with American cutaneous leishmaniasis and AIDS. The lymphocyte responsiveness to leishmanial antigens and its influence on the course of cutaneous leishmaniasis was studied in a patient with AIDS-associated American cutaneous leishmaniasis caused by Leishmania braziliensis. The patient had cutaneous disseminated erythematous papules or nodules and mucosal lesions as well as moniliasis and weight loss. The patient had a poor delayed-type hypersensitivity to leishmanial antigens, showing 3 mm of induration. The cellular immune responses were studied in vitro by lymphocyte proliferative assays induced by leishmanial antigens and concanavalin A. The T cell phenotypes were analysed by flow cytometry. The peripheral blood mononuclear cells before proliferation showed an inversion of the CD4/CD8 ratio (0.28:1). The lymphoproliferative responses to antigen and mitogen were very low (indices < 2.5). The blast-like cell phenotypes after antigen stimulation in culture were: CD3+ 44.8%, CD4+ 7.53% and CD8+ 17.45%. In AIDS patients the decrease in the pool of CD4+ cells, and consequent diminution of the CD4/CD8 ratio, produced by HIV infection provokes a generalized immune depression. The patient's disseminated clinical picture was probably related to the inability of his T cell-mediated immune responses to control the spread of Leishmania infection.


Determination of anti-giardial activity in vitro by means of soluble formazan production. A new microplate assay for the determination of activity in vitro against Giardia intestinalis has been developed in which viability is measured by soluble formazan production from a tetrazolium reagent. Metabolic reduction of the latter gives rise to a coloured product which may be determined directly by optical density measurement. Using this method the anti-giardial activities of more than 20 anti-microbial compounds have been assessed. The results obtained with a number of known anti-giardial agents, including metronidazole (50% inhibitory concentration [IC50] = 2.98 microM) and furazolidone (IC50 = 4.14 microM), compare well with previously published data; mepacrine, however, was found to produce a biphasic dose-response curve from which two IC50 values (0.816 and 6.83 microM) were obtained. This method provides a convenient means by which the search for new anti-giardial agents may be facilitated.


Leishmania infecting man and wild animals in Saudi Arabia. 9. The black rat (Rattus rattus) a probable reservoir of visceral leishmaniasis in Gizan province, south-west Saudi Arabia. Twenty-two black rats (Rattus rattus) were captured in houses where parasitologically confirmed cases of human visceral leishmaniasis had been recorded in Al-Arda Emara, Gizan province, south-west Saudi Arabia. Four of the rats were found to be infected with Leishmania; isoenzyme characterization showed that 3 were infected with L. donovani sensu lato zymodeme LON42 and the fourth with L. infantum zymodeme LON49. L. donovani s.l. LON42 has also been isolated from human visceral leishmaniasis patients living in this area, while dogs, but not humans, have been found to be infected with L. infantum LON49 in this part of Saudi Arabia.


Factors affecting transmission of Wuchereria bancrofti by anopheline mosquitoes. 4. Facilitation, limitation, proportionality and their epidemiological significance. Quantitative understanding of the transmission dynamics of lymphatic filarial parasites is essential for the rational planning of control strategies. One of the most important determinants of transmission dynamics is the relationship between parasite yield, the success rate of ingested microfilariae (mf) becoming infective larvae in a mosquito vector, and mf density in the source of the human blood meal. Three types of relationship have been recognized in human filaria/mosquito couples--limitation, facilitation and proportionality; facilitation has hitherto been observed only in the couple Wuchereria bancrofti/Anopheles gambiae in Burkina Faso, in experimental studies on a high density mf carrier. The present paper demonstrates facilitation in W. bancrofti/An. gambiae and W. bancrofti/An. arabiensis in lower mf density carriers in The Gambia and Tanzania, and in W. bancrofti/An. funestus in Tanzania. Facilitation was not found in An. melas in The Gambia nor in An. merus in Tanzania. Analysis of published data shows limitation at low level mf densities in W. bancrofti/Culex quinquefasciatus in Sri Lanka, and in the same couple in India. Limitation also occurs in Brugia malayi/Aedes togoi in experimental cats; proportionality occurs in B. malayi/Mansonia bonneae in Malaysia. The epidemiological significance of these host/parasite relationships is discussed, and supporting evidence for its validity is presented from the published results of large-scale control programmes.


Diethylcarbamazine in the control of splenomegaly associated with Bancroftian filariasis in the Ok Tedi area of Papua New Guinea. Bancroftian filariasis is highly endemic in the Ok Tedi region of Papua New Guinea, with a reported mean rate of 39% before the implementation of a single-dose diethylcarbamazine (DEC) treatment programme in 1986. This was followed by a 72% decline in the rate of detectable microfilaraemia and a 40% reduction in pre- and post-treatment splenomegaly. No significant difference was observed when spleen enlargement was compared to the presence of patent malaria. A significant difference in splenomegaly was observed between DEC-treated villagers and their untreated counterparts. Significant differences were reported in the rate of detectable microfilariae of Wuchereria bancrofti, but not of malaria, between the two groups. The number of DEC administrations and the period of time since the first treatment played a significant role immunologically. Significant differences were observed in immunoglobulin (Ig) M and IgG levels and in the extent of splenomegaly between DEC-treated and untreated areas. Filarial infection associated with malaria resulted in higher spleen rates and size. W. bancrofti is a major contributor to splenomegaly in the Ok Tedi region, and splenomegaly associated with bancroftian filariasis can be reduced or controlled by low, well-spaced doses of DEC.


Mass chemoprophylaxis of lymphatic filariasis with a single dose of ivermectin in a Polynesian community with a high Wuchereria bancrofti infection rate. In April 1991 supervised mass prophylaxis of lymphatic filariasis with a single dose of ivermectin, 100 micrograms/kg, was carried out in a Polynesian village with a high infection rate of Wuchereria bancrofti in humans and active transmission by the vector mosquito, Aedes polynesiensis. Of 876 inhabitants aged 3 years or more (pregnant women excluded), 864 (98.6%) were treated. Simultaneously, venous blood samples were collected from 577 (97.5%) of the 595 inhabitants aged 15 years or more, of whom 122 (21.4%) were found to be microfilaria (mf) carriers (86 males and 36 females). The geometric mean microfilariae (GMM) count was 358.7 mf/ml for the whole group, 387 mf/ml for males (range 1-8160 mf/ml) and 280 mf/ml for females (range 1-7769 mf/ml). Following treatment, 33 (3.8%) of the 864 persons treated experienced some adverse reactions (21 with grade 1 and 12 with grade 2). Of the 33 with reactions, 29 were among the 122 (23.8%) mf carriers and 4 among the 831 (0.5%) non-microfilaraemic persons. Six months later, 123 (21.1%) of 584 inhabitants sampled were microfilaraemic: the GMM count for the whole group was 106 mf/ml (1-8177), with 29 mf/ml (1-3740) in 35 female and 177 mf/ml (1-8177) in 88 male carriers. Of these 123, 15 (whose GMM count was 4.5 mf/ml; range 1-204) were amicrofilaraemic 6 months before, and 19 had a microfilaraemia level higher than that 6 months earlier, before treatment. 117 of the 122 carriers identified in April were resampled: comparison of their GMM counts before and 6 months after mass treatment indicated that treatment with a single dose of 100 micrograms/kg ivermectin resulted in a reduction of microfilaraemia by 69%.


Intestinal parasites in Zambian patients with AIDS. Previous studies have found a high prevalence of Isospora belli and Cryptosporidium parvum infections in African acquired immune deficiency syndrome (AIDS) patients with chronic diarrhoea. We aimed to determine the prevalence of gastrointestinal parasite in AIDS patients in hospital, not only those with diarrhoea, and to compare them with the general community. Clinically diagnosed AIDS patients in a Zambian teaching hospital were interviewed and examined, and stool specimens were studied for parasite infection. A control group was recruited from adults in a township near Lusaka. Of 90 AIDS patients (58% male), 50 (56%) had chronic diarrhoea and 9 (10%) had diarrhoea of shorter duration. In the control group (105 adults; 85% female), only one complained of diarrhoea. A variety of intestinal protozoa and helminths was found in 57% of AIDS patients and 88% of the community members. Isosporiasis was detected in 7, and cryptosporidiosis in 2, AIDS patients, all with diarrhoea, but not in any control. Strongyloides was found in 2 AIDS patients with diarrhoea and one community resident. Hospital patients with AIDS had fewer Entamoeba coli and E. histolytica infections, probably because of previous chemotherapy. We conclude that AIDS predisposes to isosporiasis and cryptosporidiosis, but not to infection with extracellular intestinal parasites, such as Entamoeba species, Blastocystis, Chilomastix, Endolimax, Ascaris and Necator.


Unnecessary injections and paralytic poliomyelitis in India. The effect of prior injections on the pattern and severity of paralytic poliomyelitis has been examined by a retrospective analysis of case notes from an outpatient pediatric clinic in South India. Of 262 children with acute polio, 176 had received unnecessary injections < 48 h before paralysis and 12 had received diphtheria-pertussis-tetanus or provocative injections. Two children injected in the right arm had paralysis in that limb only. Children with no injections (controls) had an equal chance of paralysis (0.73) in each left and right leg. Children with injections in the right or left gluteus or in both had a 19% greater chance of paralysis in the injected leg(s), whereas uninjected legs had a 31% lower chance of paralysis. Injected leg muscles were weaker than those of control children. Legs of control children were stronger than those with one leg injected and much stronger than those with both injected. More than 96% of the children had at least one leg paralysed. Age and vaccine status did not affect the results of injections. After injections there was greater likelihood of death or lack of recovery of muscle strength. About three-quarters of the children had received unnecessary injections; of these 60% had more severe paralysis and a non-paralytic attack became paralytic in 40%. If oral medicines for fevers and diarrhoea replaced unnecessary injections, the prevalence and severity of paralytic polio would be reduced.


Observations of subacute sclerosing panencephalitis in South Africa. Analysis of 75 cases of subacute sclerosing panencephalitis (SSPE) reported to the National Institute for Virology, South Africa, in 1984-1990 does not support the role of intensive exposure to measles virus in the pathogenesis of SSPE. The incidence of SSPE per million population was similar in Blacks and Whites, although that of reported measles is up to 10 times greater in Blacks. The age of SSPE follows the distribution of measles cases; thus, significantly more younger SSPE cases were found in Blacks than in Whites. The distribution between males and females was approximately equal. These data suggest SSPE to be a fortuitous complication of measles infection associated with as yet unidentified risk factors rather than a consequence of an excessive dose of infecting virus or immunological immaturity.