Fragile X syndrome: clinical and molecular genetics correlations

The fragile X form of mental retardation is presently recognized as the most frequent hereditable cause of mental impairment. The estimated frequency among males is 1 in 1250, and 1 in 2000 among females. Beside mental impairment and behavioural disturbance with hyperactivity and autistic features, the patients are characterized by morphological anomalies, such as an oblong face, broad, rectangular chin, large protruding ears and macro-orchidism. A less severe clinical expression can be found among females heterozygotes of the disorder, manifesting mainly as learning disability. The disorder is associated with the expression of a fragile site at Xq27.3 under conditions of folate depletion in the chromosome culture medium. The molecular mechanism is based on the expansion of a trinucleotide repeat [CCG]n in the promoter region of the FMR1 gene resulting in methylation of the gene. The trinucleotide repeat shows variable lengths of 6 to 53 repeats in the general population, 60 to 200 repeats in carriers of a premutation and over 200 repeats in patients with fragile X syndrome.     

Evidence for an initial, thymus independent and a chronic, thymus dependent phase of DOCA and salt hypertension in mice

Treatment with desoxycorticosterone acetate (DOCA) and 1 per cent saline as drinking water for 21 days caused a significant and similar increase in blood pressure in haired mice, with a normal thymus function, as in nude mice with genetical aplasia of the thymus. After 57 and 78 days there was, however, a significantly more pronounced increase in blood pressure in haired than in nude mice. A marked degree of round cell infiltration around intrarenal vessels and degenerative changes including wedge-shaped infarcts were observed in the kidneys of the haired mice, commencing after 57 days of treatment, while no such changes were found in nude mice. Thymus grafting in nude mice, successively treated with DOCA and salt, conferred the ability to react with chronic hypertension and intrarenal vascular disease, equal to the reaction seen in haired mice. The present investigation has provided evidence for the existence of an initial thymus independent and a chronic thymus dependent phase of DOCA and salt hypertension in mice. It still remains an unsolved problem whether the secondary blood pressure fall observed in nude athymic mice is a direct consequence of the lack of perivascular cellular immune reactions, or caused by other defects in this strain of mice.     

The identity of Leishmania isolated from sand flies and vertebrate hosts in a major focus of cutaneous leishmaniasis in Baturite, northeastern Brazil

The oxidation states of intracellular myoglobin and cytochrome oxidase aa3 were monitored by reflectance spectrophotometry in isolated perfused rat hearts subjected to an acutely magnesium deficient environment. After exposure to low extracellular [Mg2+]o (i.e., 0.3 mM) for 30 min, more than 80% of the oxymyoglobin converted to its deoxygenated form. The level of reduced cytochrome oxidase aa3 also increased about 80% in low [Mg2+]o. The deoxymyoglobin was converted further to a species identified as ferrylmyoglobin by its reaction with Na2S to form ferrous sulfmyoglobin which was optically visible. This process, set into motion by acute Mg deficiency, resulted from a direct accessibility of the exogenous peroxide to the cytosolic protein. The results suggest that a pathway leading to cardiac tissue damage, induced by magnesium deficiency, is probably involved in the generation of a ferrylmyoglobin radical which could be prevented by addition of ascorbate, which is known to be a one-electron reductant of this hypervalent form of myoglobin. In further studies, we also investigated whether addition of different concentrations of ascorbic acid (AA) to the perfusate could enhance myocardial function after exposure to low [Mg2+]o perfusion. Four concentrations of AA (0.5, 1, 5, 10 mM) were tested, and the results indicate that they exert their effects in a concentration-dependent manner; 1 mM AA was the most effective dose in improving aortic output in a Mg-deficient heart. Ferrylmyoglobin formation was found to be formed considerably before intracellular release of either creatine phosphokinase or lactic dehydrogenase. These studies may have wide implications as a new mechanism by which low extracellular Mg2+ can induce myocardial injury and subsequent cardiac failure.     

Cardiopulmonary function at rest and during exercise after resection for bronchial carcinoma

BACKGROUND: Measurements of postoperative spirometric values after pneumonectomy and lobectomy vary considerably, and few researchers have studied the changes in exercise capacity during maximal work after lung resection. The purpose of this study was to describe the postoperative alterations in cardiopulmonary function. METHODS: Ninety-seven consecutive patients with lung malignancy were prospectively examined with maximal exercise test, spirometry, and arterial gas tensions. Fifty-seven patients were reinvestigated 6 months postoperatively. RESULTS: In patients having lobectomy, forced expiratory volume in 1 second decreased 8%, and exercise capacity, expressed by maximal oxygen uptake and maximal work rate, significantly decreased 13%. In patients having pneumonectomy forced expiratory volume in 1 second significantly decreased 23%, but the loss in lung volume was partly compensated as measured by exercise capacity, which decreased only 16%. Generally patients with the smallest preoperative forced vital capacity had the smallest postoperative deterioration expressed in percentages. We found a weak correlation between alterations in maximal oxygen uptake and lung function after resection. CONCLUSIONS: Lobectomy is associated with only minor deterioration of lung function and exercise capacity. Pneumonectomy causes a decrease in pulmonary volumes to about 75% of the preoperative values, partly compensated in better oxygen uptake, which postoperatively was about 85% of the preoperative values. Alteration in forced expiratory volume in 1 second is a poor predictor of change in exercise capacity after pulmonary resection.     

Human granulocytic ehrlichiosis in southern Germany: increased seroprevalence in high-risk groups

To date, human granulocytic ehrlichiosis (HGE), the causative agent of which is likely transmitted by ticks in the Ixodes ricinus-Ixodes persulcatus complex, has not been diagnosed with certainty in patients outside the United States. The presence of a closely related vector tick, I. ricinus, as well as the occurrence of similar Ehrlichia spp. of veterinary importance, suggests that this disease is likely to be present in Europe. The aim of the present study was to compare the prevalence of antibodies against the HGE agent in sera collected from patients in groups at high risk for exposure to I. ricinus with that of a control population. Risk groups consisted of 150 forestry workers and 105 patients with an established diagnosis of Lyme disease. The control group was 103 healthy blood donors without a history of tick bites. We used a patient isolate of the HGE agent from Minnesota (J. L. Goodman, C. Nelson, B. Vitale, J. E. Madigan, J. S. Dumler, T. J. Kurtti, and U. G. Munderloh, N. Engl. J. Med. 334:209-215, 1996) propagated in HL60 cells as the source of antigen for a specific immunofluorescence assay (IFA). Elevated IFA titers (> or = 1:80) were present in 21 of 150 (14%) serum samples from forestry workers and in 12 of 105 (11.4%) serum samples from Lyme disease patients, but in only 2 of 103 (1.9%) serum samples from blood donors (P < or = 0.01 for either of the at-risk groups versus blood donors). The results of this study suggest that the HGE agent or a closely related organism exists in southern Germany and that seroconversion to it is common among groups exposed to Ixodes ticks. Final proof that HGE occurs in Germany will require the isolation of the causative agent from patients. HGE should be considered in the differential diagnosis of febrile illnesses in individuals exposed to Ixodes ticks in Europe as well as in North America.     

Econometric analysis of variation in cesarean section rates. A cross-sectional study of 59 obstetrical departments in Sweden

The objective of this study was to explain the variation in cesarean section rates among hospitals (obstetrical departments) in Sweden, and to discuss its potential economic consequences. Using data from The Swedish Medical Birth Registry 1991, we made a cross-sectional study of the cesarean section rate at the departmental level. We identified some 20 determinants, demand-related as well as supply-related. A general model including all these regressors was specified. After reducing this model, we were able to explain about one-quarter of the variation. We conclude that the large variation in cesarean section rates indicates inefficiency, due mainly to overutilization, but perhaps also underutilization. It is difficult to calculate the economic consequences or the welfare loss to society. We estimated an additional cost for unnecessary cesarean sections of 13-16 million Swedish crowns (SEK) per year.     

Role of the Na+/K+-ATPase in regulating the membrane potential in rat peritoneal mast cells

500 children with ages ranging between 2 and 13 years and their families joined the study. A detailed questionnaire and a 3-day food intake diary were evaluated to find the relationship between dental caries and dietary habits. It is concluded that the prevalence of caries increases by frequent and high sugar consumption. With lower age and lower caries experience followed a more balanced diet. There was an inverse relationship between caries prevalence and the mothers' educational level. The percentage of children who never or irregularly brushed their teeth was highest in the caries active group.     

Body composition by X-ray absorptiometry and bioelectrical impedance in chronic respiratory insufficiency patients

Nutrition assessment is important during chronic respiratory insufficiency to evaluate the level of malnutrition or obesity and should include body composition measurements. The appreciation of fat-free and fat reserves in patients with chronic respiratory insufficiency can aid in designing an adapted nutritional support, e.g., nutritional support in malnutrition and food restriction in obesity. The purpose of the present study was to cross-validate fat-free and fat mass obtained by various bioelectric impedance (BIA) formulas with the fat-free and fat mass measured by dual-energy X-ray absorptiometry (DXA) and determine the formulas that are best suited to predict the fat-free and fat mass for a group of patients with severe chronic respiratory insufficiency. Seventy-five patients (15 women and 60 men) with chronic obstructive and restrictive respiratory insufficiency aged 45-86 y were included in this study. Body composition was calculated according to 13 different BIA formulas for women and 12 for men and compared with DXA. Because of the variability, calculated as 2 standard deviations, of +/- 5.0 kg fat-free mass for women and +/- 6.4 kg for men for the best predictive formula, the use of the various existing BIA formulas was considered not clinically relevant. Therefore disease-specific formulas for patients with chronic respiratory insufficiency should be developed to improve the prediction of fat-free and fat mass by BIA in these patients.