Flumazenil in acute benzodiazepine overdose.
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Biomedical subjects
Publications and source records attributed to A Mohan.
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The complexes [Fe[HC(3,5-Me2pz)3]2](BF4)2 (1), [Fe[HC(pz)3]2](BF4)2 (2), and [Fe[PhC(pz)2(py)]2](BF4)2 (3) (pz = 1-pyrazolyl ring, py = pyridyl ring) have been synthesized by the reaction of the appropriate ligand with Fe(BF4)2.6H2O. Complex 1 is high-spin in the solid state and in solution at 298 K. In the solid phase, it undergoes a decrease in magnetic moment at lower temperatures, changing at ca. 206 K to a mixture of high-spin and low-spin forms, a spin-state mixture that does not change upon subsequent cooling to 5 K. Crystallographically, there is only one iron(II) site in the ambient-temperature solid-state structure, a structure that clearly shows the complex is high-spin. Mössbauer spectral studies show conclusively that the magnetic moment change observed at lower temperatures arises from the complex changing from a high-spin state at higher temperatures to a 50:50 mixture of high-spin and low-spin states at lower temperatures. Complexes 2 and 3 are low-spin in the solid phase at room temperature. Complex 2 in the solid phase gradually changes over to the high-spin state upon heating above 295 K and is completely high-spin at ca. 470 K. In solution, variable-temperature 1H NMR spectra of 2 show both high-spin and low-spin forms are present, with the percentage of the paramagnetic form increasing as the temperature increases. Complex 3 is low-spin at all temperatures studied in both the solid phase and solution. An X-ray absorption spectral study has been undertaken to investigate the electronic spin states of [Fe[HC(3,5-Me2pz)3]2](BF4)2 and [Fe[HC(pz)3]2](BF4)2. Crystallographic information: 2 is monoclinic, P2(1)/n, a = 10.1891(2) A, b = 7.6223(2) A, c = 17.2411(4) A, beta = 100.7733(12) degrees, Z = 2; 3 is triclinic, P1, a = 12.4769(2) A, b = 12.7449(2) A, c = 13.0215(2) A, alpha = 83.0105(8) degrees, beta = 84.5554(7) degrees, gamma = 62.5797(2) degrees, Z = 2.
We describe an Indian man with the unusual association of classical cutaneous features of Ehlers-Danlos syndrome, a marfanoid habitus, bladder diverticula and multiple emphysematous bullae.
Atypical laterality (i.e. the lack of a clear pattern of lateralization) has been found to be a characteristic feature of individuals with intellectual disability (ID). The evidence for this has been based on 'handedness' studies which have contained little information about the ability of people with ID to carry out interhemispheric tasks reflecting bilateral transfer or interference. The present study examined this capacity in individuals with ID by utilizing bilateral transfer and interference paradigms. Right-handed subjects with ID (IQ = 55-76) and controls matched for age and sex were tested for bilateral transfer of motor skill in contralateral hands with a mirror-drawing task. The subjects were also tested for their ability to perform a finger-tapping task while processing verbal and non-verbal stimuli. The findings indicated that people with ID are significantly deficient relative to matched controls in bilateral transfer of motor skills from their non-preferred (left) hand to their preferred (right) one. The effect of interference during performance of the dual task was significantly greater in individuals with ID. Subjects with ID were found to perform better with their non-preferred than with their preferred hand. A within-group comparison revealed that right-handed performance was more affected by interference than left in these subjects.
OBJECTIVE: Maternal serum inhibin A and activin A are higher in pre-eclampsia than in normal pregnancy. The placenta is a source of these proteins in pregnancy. The aim of this study was to investigate the effect of growth factors and proinflammatory cytokines that are raised in pre-eclampsia on the secretion of dimeric inhibin A, activin A and follistatin by villous cytotrophoblasts in culture. DESIGN AND METHODS: Villous cytotrophoblasts were prepared from term placentae and cultured in serum-free media. Cells were treated with increasing concentrations of tumour necrosis factor (TNF)-alpha, interleukin (IL)-1beta, transforming growth factor (TGF)-beta1, granulocyte and monocyte colony-stimulating factor (GMCSF), inhibin A, activin A and follistatin for 2 days. Culture supernatants were assayed for human chorionic gonadotrophin (hCG), inhibin A, activin A and follistatin as appropriate. Experiments were repeated at least three times with each cytokine or growth factor and the data pooled. RESULTS: Cytotrophoblasts syncytialise and spontaneously secrete hCG, inhibin A and activin A in culture. Follistatin levels were <20 pg/ml in most experiments. Activin A secretion was increased in culture in a dose-dependent manner by IL-1beta (approximately 150%, P<0.05), TNF-alpha (approximately 35%, P=0.02) and GMCSF (approximately 100%, P<0.01). hCG secretion was inhibited in a dose-dependent manner by TNF-alpha (50%, P<0.05). Inhibin A was stimulated by IL-1beta ( approximately 30%, P=0.05). Inhibin A, activin A, follistatin or TGF-beta1 did not have a significant effect on any measured parameters. CONCLUSIONS: These data show that inflammatory cytokines increase the secretion of activin A by trophoblasts in culture. The presence of very low levels, or no follistatin (<20 pg/ml) in the culture media suggests 'free' activin A could have autocrine/paracrine effects on cytotrophoblasts. Inhibin A secretion was stimulated by IL-1beta. However, absence of an effect by the other cytokines investigated on inhibin A in this study suggests that the mechanism(s) involved in increasing maternal circulating levels of inhibin A and activin A in pre-eclampsia are controlled differentially.
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The clinical profile of one hundred and six biopsy proved patients with sarcoidosis is reported from New Delhi. The disease occurred more frequently in males (68 of the 106; 64%) in their fifth decade. Dry cough (83%), exertional dyspnoea (61%), fever (56%) and joint pains (44%) were frequent symptoms. Hepatomegaly (45%), peripheral lymphadenopathy (45%), cutaneous involvement (42%), presence of crepitations (36%) were frequent signs. In addition, ocular symptoms (18%), parotid gland enlargement (12%), facial nerve palsy (8%) were observed. Audible wheeze was present in nine patients. Radiologically, 25 (24%), 67 (63%) and 14 (13%) of patients belonged to stage I, II and III respectively at presentation. More than one sibling was involved in six families. Pulmonary functions revealed mixed obstructive and restrictive ventilatory defect. However, obstructive ventilatory defect was predominant. Systemic steroids were used in 81 patients who regularly followed up. Frequent relapses occurred on tapering off or stopping the corticosteroids in 21 patients. History of malaise (p < 0.05), presence of crepitations (p < 0.05), wheezing (p < 0.05), peripheral blood eosinophilia (p < 0.05) and FEV1/FVC (%) < 65% of the predicted value (p < 0.05), were independent predictors of relapse. Hyperuricaemia, hitherto unreported in patients with sarcoidosis was observed in 41% of patients for whom values were available. Two patients died; one from cardiomyopathy and another from stroke. In summary, constitutional symptoms such as fever, weight loss and pulmonary infiltrates, were more frequently encountered in Indian patients with sarcoidosis as compared to western studies. A high index of clinical suspicion and histopathological confirmation early in the illness are required to ascertain the diagnosis lest these patients will get treated as tuberculosis with potentially hepatotoxic drugs.
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End-maturation reactions, in which the 5' end leader and 3' end trailer of precursor tRNA are removed by RNase P and 3'-tRNase, respectively, are early, essential steps in eukaryotic precursor tRNA processing. End-processing enzymes may be expected to contact the acceptor stem of tRNA due to its proximity to both cleavage sites. We constructed matrices of pair-wise substitutions in mid-acceptor stem at nt 3/70 and 4/69 of Drosophila tRNA(His) and analyzed their ability to be processed by Drosophila RNase P and 3'-tRNase. In accord with our earlier study of D/T loop processing matrices, we find that tRNA end processing enzymes respond to sequence changes differently. More processing defects were observed with 3'-tRNase than with RNase P, and substitutions at 4/69 reduced processing more than those at 3/70. We evaluated tRNA folding using structure probing nucleases and investigated the contribution of K(M) and V(Max) to the processing efficiency of selected variants. In one substitution (C3A), mis-folding correlates with processing defects. In another (C69A), a disruption of structure appears to be transmitted laterally to both ends of the acceptor stem. Poor processing of C69A by RNase P is due entirely to a reduction in V(Max), but for 3'-tRNase, it is due to an increase in K(M).
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PURPOSE: To evaluate risk for all-cause and cause-specific mortality in a large, primarily female (73%) cohort of radiologic technologists.METHODS: The study consists of 145,915 radiation technologists, certified in the American Registry of Radiologic Technologists (1926-1982) and followed through 1997. Causes of death were obtained from death certificates or, more recently, through NDI Plus. Standardized Mortality Ratios (SMR) were computed and tests of homogeneity were performed to detect differences in mortality among causes. Poisson models were used to estimate risks using an internal comparison group.RESULTS: Significantly low SMRs were observed for all causes (0.76), all cancers (0.82), and diseases of circulatory system (0.69). Compared to U.S. women, the risk for breast cancer mortality bordered around unity (SMR 1.01, 95% CI 0.94-1.09). However, relative to all other cancers, breast cancer mortality was significantly increased (RSMR 1.24, p < 0.01). Elevated risk for breast cancer was associated with certification before 1940 (SMR 1.55, 95% CI 1.24-1.91), and duration of certification of 20-29 (SMR 1.21, 95% CI 1.06-1.37) and 30+ years (SMR 1.77, 95% CI 1.54-2.02). A 35% increase in leukemia risk was evident for women certified for a duration of 20-29 years and a 36% increase among women certified for 30+ years. Poisson analysis revealed a significant increase in breast cancer risk with increasing number of years certified among women first certified before 1940 (p < 0.001) and during 1940-49 (p = 0.05) compared to women first certified in 1950 or later.CONCLUSIONS: Preliminary findings of this study suggest increased breast cancer risk associated with occupational radiation exposures prior to 1950 and with long-term cumulative exposures. However, potential confounding by reproductive and other risk factors needs to be evaluated.
PURPOSE: To illustrate the value of using large cohort studies to identify birth cohort trends in several chronic disease risk factors.METHODS: In collaboration with the American Registry of Radiologic Technologists (ARRT) and the University of Minnesota, the National Cancer Institute (NCI) initiated a cohort study of radiologic technologists who were certified by ARRT for at least two years between 1926 and 1982. Over 90,000 technologists (nearly four-fifths female) from all 50 states responded to a mailed questionnaire on reproductive, medical, work, and lifestyle factors. Ten, mostly five-year, birth cohorts, from before 1920 through 1960 and later, were evaluated.RESULTS: In this population, the mean height of both men and women generally rose in each subsequent birth cohort. The proportion of men who smoked before age 18 fell among those born since the late 1920s. In contrast, the proportion of women smoking before age 18 rose among those born since the early 1950s, reaching 14.2% among those born in 1960 and later. The mean age at menarche fell, until leveling off at 12.5, among those born after 1940. Recent birth cohorts (since 1950) show among the highest mean ages at birth of first child (>26 yeras), highest rates of nulliparity at age 25 (>/=63%), and lowest mean parity levels (</=1.7), compared with earlier birth cohorts. The proportion of women ever using oral contraceptives rose steadily by birth cohort, reaching 86 percent in the most recent birth cohort.CONCLUSIONS: Some of the trends observed may help explain historic chronic disease incidence patterns and predict future disease burdens.
Congestive heart failure is associated with cardiac adrenergic nerve terminal changes and beta-adrenoceptor density downregulation. To study the temporal sequence of these changes, we performed studies in rabbits at 2, 4, and 8 wk of cardiac pacing (360 beats/min) and at 1, 2, and 4 wk after cessation of pacing. Rapid pacing produced left ventricular (LV) dysfunction and an increase in plasma norepinephrine (NE) in 1-2 wk. At week 2, NE uptake activity, NE uptake-1 density, and adenylyl cyclase responses to isoproterenol, 5'-guanylyl imidodiphosphate [Gpp(NH)p], and forskolin reduced. However, immunostained tyrosine hydroxylase profile, beta-adrenoceptor density, and NE histofluorescence did not reduce until 4-8 wk of pacing. After cessation of cardiac pacing, LV function normalized quickly, followed by return of tyrosine hydroxylase and NE profiles in 1 wk and adenylyl cyclase responses to agonists and NE uptake activity in 2 wk. Myocardial beta-adrenoceptor density returned to normal by 4 wk after cessation of pacing. Our results suggest that there is no permanent structural neuronal damage in the myocardium within the first 8 wk of rapid cardiac pacing. Abnormal myocardial NE reuptake mechanism may play an important pathophysiological role in heart failure.
We review published epidemiologic studies on personal use of hair dyes and leukemias and myelodysplastic syndromes (MDS). A subsequent article will review studies on lymphomas and multiple myeloma. A computerized literature search for the years 1966 through 1996 was completed using MEDLINE. Data were extracted using a standardized form that recorded study design, study population, type of cases, comparison group, sources of data on personal exposure to hair dyes, method of data collection, type of exposure data collected, covariates, and results. The above search identified 13 epidemiologic studies on the possible association between personal use of hair dyes and leukemias and MDS. Although there are some reports of positive associations, overall the evidence linking personal use of hair dyes to various leukemia and MDS subgroups is weak. One cannot definitively rule out an association, however, because of the methodologic limitations, such as small numbers of exposed cases and lack of detailed exposure information. Any further research would need much better assessment of hair dye use, including product type, color frequency, duration, and changes in use over time, and adequate statistical power.
We review studies on hair dyes and lymphomas and multiple myeloma (MM). A computerized literature search for the years 1966 through 1996 was conducted. Data were extracted using a standardized form that recorded study design, study population, type of cases, comparison group, sources of data on personal exposure to hair dyes, method of data collection, type of exposure data collected, covariates, and results. This review identified 10 epidemiologic studies published in the English literature that examined personal use of hair dyes and lymphomas or MM. These studies include three evaluations of Hodgkin's disease, five of non-Hodgkin's lymphoma (NHL), two of lymphomas with type not specified, and six of MM. For Hodgkin's disease, one case-control study reported some positive associations with use of permanent hair dyes, whereas two cohort studies found no associations with ever use of hair dyes. For NHL and MM, several evaluations suggest associations with use of permanent dyes, particularly with duration, frequency, age at first use, and dark colors. However, these associations are not consistent within and between studies. For lymphomas with type not specified, one study was superseded by a more recent report with NHL specific data and a second study was limited by small numbers of exposed subjects. At this time, it is not possible to determine if the inconsistent associations between permanent hair dyes and NHL and MM reflect sampling variability or differences in methods between studies. Because an appreciable fraction of the population has potential exposure to permanent hair dyes, elucidation of such issues may be warranted with studies that include adequate numbers of exposed subjects and that elicit information on personal use of hair dyes over time.
OBJECTIVES: This work was done in order to study the oxidant and anti-oxidant status in a disease resulting from endothelial injury. The disease selected for study was acute myocardial infarction. METHODS: Sixty patients of acute myocardial infarction were selected after being diagnosed in accordance to the guidelines laid down by the WHO. Thirty subjects were included as controls. Plasma levels of certain markers of oxidative stress and anti oxidant activity were measured in all the subjects. Malonaldehyde (MDA) and nitrite (NO2) were measured as markers of free radical mediated endothelial injury, and superoxide dismutase (SOD) enzyme as an indicator of antioxidant activity. RESULTS: It was found that the plasma levels of MDA and nitrite were significantly elevated in the patients of acute myocardial infarction compared to the control group (7.29 +/- 3.28 v/s 4.57 +/- 0.63 nmol/ml and 12.85 +/- 8.71 v/s 0.97 +/- 0.25 microM respectively), thereby indicating that oxygen free radicals cause endothelial damage in them. The superoxide dismutase levels were also found to be elevated in these patients (5.57 +/- 1.47 v/s 3.91 +/- 0.66 U/ml). CONCLUSION: These results indicate that acute myocardial infarction is a state of enhanced free radical activity, which causes endothelial damage. The elevated SOD levels may imply that the body attempts to combat this oxidative stress by raising it's level of anti-oxidants.
Chronic administration of norepinephrine for 8 weeks has been shown to reduce neuronal norepinephrine uptake activity and increase interstitial norepinephrine concentration in the heart. To determine whether the changes could lead to myocardial beta-adrenoceptor down-regulation or beta-adrenergic subsensitivity, we measured left ventricular contractile responses to dobutamine, myocardial beta-adrenoceptor density, beta subtype distribution, competitive inhibition agonist binding, and adenylyl cyclase activity activation by isoproterenol, 5'-guanylylimidodiphosphate, and forskolin in dogs after a norepinephrine or saline infusion for 8 weeks. We found that norepinephrine infusion reduced myocardial beta-adrenoceptor density, beta(1)-adrenoceptor subtype density, and high-affinity site for isoproterenol. Left ventricular contractile responses to dobutamine were reduced in the norepinephrine-infused animals. In addition, norepinephrine infusion decreased the basal adenylyl cyclase activity and the adenylyl cyclase responses to isoproterenol, 5'-guanylylimidodiphosphate, and forskolin. The findings indicate that a decrease in cardiac norepinephrine uptake predisposes the heart to norepinephrine-induced myocardial beta-adrenoceptor down-regulation, and that norepinephrine, when present in a sufficient amount over a long period as it is in chronic heart failure, can reduce myocardial beta-adrenergic responsiveness by both homologous and heterologous desensitization.