The effects of paroxetine and other antidepressants in combination with alcohol on psychomotor activity related to car driving.
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Biomedical subjects
Publications and source records attributed to C Harrison.
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A survey of 222 SCI patients treated by the Southeastern Michigan Spinal Cord Injury System was conducted to explore some key issues involving community reintegration problems. These patients had been discharged from the rehabilitation facility an average of 18 months. The 62 respondents (28%) did not differ from nonrespondents on demographic and health status variables and were considered representative of the total patient population. Important findings included the following: 1) 30% were noncompliant with prescribed medication, 2) 25% had not received all equipment prescribed during initial rehabilitation, 3) 45% indicated their current residence was not completely accessible, 4) 73% were dependent on others for transportation, 5) 8% were currently working, compared to 39% employed prior to injury 6) 47% indicated transportation problems as the main obstacle to their adjustment to SCI. The problems identified prevented the SCI patients from increasing their presence in the community, thereby preventing them from exposing obstacles and improving the opportunities available to them.
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Concurrent estimation by high pressure liquid chromatography (HPLC) of the concentrations of metronidazole in plasma and vaginal content in 12 patients with infections due to Trichomonas vaginalis who did not respond to normal and high-dose treatment has shown that the two levels are closely related to each other and to the dose. Individual idiosyncrasies in absorption of drug from the gut lumen or in its transfer into the vaginal content are unlikely to be the cause of treatment failure.
We have developed a standard procedure to measure the susceptibility of Trichomonas vaginalis to metronidazole in vitro, by controlling the state of oxygenation of the test cultures, the size of the inocula in terms of infectivity, and providing multiple tests at each drug concentration. Estimates were made of the in-vitro sensitivity to metronidazole of T. vaginalis isolated from 11 randomly selected patients, all, except for three defaulters, known to have been treated successfully, and from six 'treatment failure' patients. Stocks isolated from 'successfully treated' patients, were all highly sensitive to metronidazole. Eighteen stocks isolated from the 'treatment failure' patients fell into two groups: (a) those clearly separable from sensitive stocks, with ED50 values (the concentration of drug at which growth is prevented in 50% of test wells) in N2 of up to 0.51 mg/l and 3.5 to 11 mg/l in N2/1%O2; (b) those giving intermediate ED50 values of up to 0.20 mg/l in N2 and 0.7 to 1.8 mg/l in N2/1%O2. The current procedure demonstrates clearly that repeated treatment failure in patients without other complication is associated with enhanced resistance to metronidazole of T. vaginalis, and it may discriminate between T. vaginalis infections that are likely to respond to higher dosage and those that are not.
Ten healthy, female volunteers took part in a double-blind, placebo-controlled study to investigate the effects of lofepramine 70 mg, lofepramine 140 mg, nomifensine 100 mg, amitriptyline 50 mg and placebo on psychomotor performance related to driving. One subject failed to complete the study for reasons unrelated to the medications. Each subject received each of the treatments in random order at weekly intervals and was then assessed for psychomotor performance, sedation and quality of sleep. Amitriptyline 50 mg served as a positive control producing results consistent with its known sedative properties. In contrast, lofepramine 70 mg and 140 mg and nomifensine 100 mg were generally free from any significant effect on psychomotor performance.
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Although protein-nucleic acid interactions exhibit dramatic dependences on both ion concentration and type in vitro, large variations in intracellular ion concentrations can occur in Escherichia coli and other organisms without apparent effects on gene expression in vivo. E. coli accumulates K+ and glutamate as cytoplasmic osmolytes. The cytoplasmic K+ concentration in E. coli varies from less than 0.2 to greater than 0.9 m as a function of external osmolarity; corresponding cytoplasmic glutamate concentrations range from less than 0.03 to greater than 0.25 m. Only low levels of chloride occur in the cytoplasm of E. coli at all osmotic conditions. Since most in vitro studies have been performed in chloride salts, whereas glutamate is the more relevant physiological anion, we have measured the effects of the substitution of potassium glutamate (KGlu) for KCl on the kinetics and equilibria of a variety of site-specific protein-DNA interactions in vitro. Both the interaction of E. coli RNA polymerase with two phage lambda promoters and the interactions of various restriction enzymes with their DNA cleavage sites are enhanced by this substitution. Using the abortive initiation assay, we find a greater than 30-fold increase in the second-order rate constant for open complex formation at the lambda PR promoter and a 10-fold increase at the lambda PR' promoter, when KGlu is substituted for KCl. Replacement of KCl by KGlu does not affect the strong salt dependences of these interactions; increasing either KCl or KGlu concentrations decreases both reaction rates and extents. Substitution of glutamate for chloride does, however, shift the range of salt concentrations over which these interactions are observable to higher K+ concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)
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The expression of human cell-membrane antigens by hybrid cell lines derived by fusing a human B-ALL and mouse BW 5147 T-lymphoma cells has been studied. Using monoclonal antibodies (mAb), the phenotypes of 19 of the 24 hybrids which grew 11-44 days post-fusion have been analysed by indirect membrane immunofluorescence (IF). These uncloned hybrid cells were assayed early after outgrowth, prior to extensive human chromosome and antigen loss. Nonetheless, cytogenetic analysis showed that all hybrids contained variable numbers of human chromosomes. Phenotypic analysis showed that the hybrids could be grouped as follows: a high frequency expressing CD25 (IL-2 receptor), human T200, HLA class I alpha and beta 2microglobulin, and reacting with the mAb H207 and 12E7; an intermediate frequency expressing CD1 and CD2; and a low frequency expressing CD3, CD4, CD5, CD7, CD8 and CD9. This pattern of antigen expression resembled the frequency of these cells in the human B-ALL parent line. Cell sorting was used to immunoselect hybrids expressing CD1 and CD2, but CD1 expression was unstable during subsequent culture.
The role of the dentate gyrus (DG) in the development and maintenance of kindling induced by periodic electrical stimulation of the entorhinal cortex (EC) was evaluated in rats. Colchicine, a selective neurotoxin for granule cells of the DG, was injected into the DG: prior to kindling and after the development of kindling. Prior destruction of the DG delayed the development of afterdischarge (AD) induced by EC stimulation, but kindling proceeded at normal rates after the first AD was induced. Destruction of the DG after kindling did not abolish the kindled seizures. Thus, the DG was not required for either the development or maintenance of kindling by EC stimulation, but an intact perforant path input from the EC to DG facilitated the emergence of epileptogenesis by kindling of the EC. The results suggest that kindling develops and is maintained in a network of multiple pathways which are related to the site of stimulation. The DG appears to be the site of a temporally specific alteration which facilitates the development of kindling by EC stimulation.
In long-term cultures of bone marrow from a patient with acute myeloblastic leukaemia (AML) the leukaemic chromosome marker, which was present in a proportion of the marrow cells even during morphological remission, was not detectable after seven days of culture. After florid relapse of AML, large-scale bone marrow cultures were established while the patient received conditioning with cyclophosphamide and total body irradiation as for an allogeneic bone marrow transplant. Marrow cultured for ten days was reinfused and three and six months later the patient was in clinical remission with a normal karyotype.
A 28-year-old man with Ph-positive chronic granulocytic leukemia (CGL) was treated by high-dose chemoradiotherapy and transplantation of marrow cells harvested from his HLA-identical brother. One year after bone marrow transplantation (BMT) examination of his marrow showed a minority population of Ph-positive cells; their proportion subsequently fell such that 2 years after transplant analysis of marrow cells showed only cytogenetically normal cells. The patient remains clinically normal with a persisting mild lymphocytosis but without hematological evidence of leukemia. We cannot in this patient distinguish between persisting leukemia that later could no longer be recognized and relapse of leukemia that is now suppressed, perhaps only temporarily. This case emphasizes the need for caution in interpreting chromosomal finding after BMT for CGL.
The effects of alprazolam 0.5 mg and lorazepam 2 mg on cognitive and psychomotor skills were assessed in twelve normal volunteer subjects in a randomised, double-blind, crossover design. Single and multiple dose effects were monitored using a battery of tests comprising critical flicker fusion threshold (CFFT), choice reaction time (CRT), simulated car tracking, and subjective ratings of perceived sedation (LARS) and of sleep behaviour (LSEQ). Compared with placebo baseline scores, treatment with lorazepam 2 mg (both single and multiple doses) resulted in a widespread impairment of CRT, tracking accuracy, and CFFT. Single doses of alprazolam 0.5 mg reduced CFFT with respect to the placebo baseline. Single and multiple dose treatment with both drugs resulted in subjective reports of sedation, a reduction of sleep onset latency, and improved sleep quality. Only lorazepam 2 mg significantly disrupted the integrity of behaviour on waking from sleep. These results suggest important pharmacodynamic differences between the two drugs in the doses used.
A placebo-controlled trial of intramuscular iron dextran prophylaxis for two-month-old infants was carried out on the north coast of Papua New Guinea where there is high transmission of malaria. The results indicate that the placebo group became relatively iron deficient whereas the iron dextran group had adequate iron stores and, in the absence of malaria, a higher mean haemoglobin. However in the iron dextran group there was a higher prevalence of malaria, as judged by parasite and spleen rates at 6- and 12-month follow-up; a lower haemoglobin associated with malaria when compared with the placebo group and a greater reticulocytosis in response to malaria infection. Within the placebo group it was noticed that the malaria rates were lower at follow-up in those infants who had had a low birth haemoglobin. In neither group was there apparent suppression of marrow activity in the presence of malaria. Malaria infection in both groups was associated with a significantly raised serum ferritin level and transferrin saturation. Over-all these data give evidence for a protective role of iron deficiency against malaria and would argue against the injudicious use of iron replacement in areas where malaria is endemic.
A study was made of 544 mothers and their 556 newborns in an area of endemic malaria, to analyse effects of total dose intravenous iron infusion (TDI) to mothers during pregnancy. 34% of these mothers received TDI before delivery. A range of haematological tests was carried out on newborns and mothers in addition to anthropometry. 84% of mothers had had ante-natal care and data were also collected retrospectively from ante-natal records. TDI was associated with more slide positive peri-natal malaria in primipara (odds ratio: 5.46) but not in multipara. When all relevant factors were considered TDI was not associated with an overall improvement in haemoglobin status from the first ante-natal level recorded to the post-natal check. Post-natal malaria was associated with lower ante-natal and post-natal haemoglobin levels. There was no evidence of any effect of TDI in pregnancy or of maternal malaria on foetal maturity or birth weight. Gestational age, maternal weight, parity and maternal post-natal haemoglobin were all significantly correlated with birth weight. TDI to the mother was associated with higher neo-natal serum ferritins and lower neo-natal haemoglobins. Maternal post-natal malaria was associated with significantly lower iron in serum in newborns. It is suggested that routine total dose iron infusion to anaemic pregnant mothers in malaria endemic areas may be contraindicated.