Severe factor X deficiency and successful pregnancy.
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Biomedical subjects
Publications and source records attributed to P Murphy.
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The data presented are those from a two-year prospective study of 69 patients identified in the Nottingham field centre of the WHO Study of Determinants of Outcome of Severe Mental Disorders. Premorbid personality, childhood adjustment and adolescent adjustment were assessed at the patients' first presentation to psychiatric services with a psychotic illness. Ratings were made blind to diagnosis. Premorbid explosive and paranoid traits were commoner in patients with schizophrenia than in patients with other non-organic psychoses, and these traits were associated with later onset of schizophrenia. Premorbid schizoid traits were significantly commoner in patients with schizophrenia compared to patients with other psychoses, but only in those patients for whom a parent was the informant. Schizoid traits were no commoner in men with schizophrenia than in women, and were not associated with earlier age of onset. The findings suggest that premorbid personality, in men and women, may shape the expression of symptoms produced during an illness episode.
Full thickness ischaemic colitis complicates approximately 1-2% of abdominal aortic procedures. Ligation of the inferior mesenteric artery and hypotension are recognized as causative factors. It is not, however, widely appreciated that ischaemic proctitis may also rarely complicate aortic surgery, especially after complex procedures or if there has been additional interruption to the internal iliac circulation. We report a case of rectal necrosis following repair of a thrombosed aortic aneurysm in which plain X-ray appearances aided the diagnosis.
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Subclavian artery aneurysms are rare. Diagnosis is important as complications can be life threatening. A case is reported which is diagnosed by magnetic resonance imaging; moreover it is suggested that magnetic resonance imaging is now the initial imaging modality of choice in the investigation of these lesions.
The effect of ethyl alcohol on upper airway reflex sensitivity (UARS) has not been previously investigated in humans. Using a technique that we have previously described, intermittent breaths of low concentrations of ammonia vapour were used to measure the effect of ethyl alcohol 0.55-0.66 g/kg on UARS in ten healthy male volunteers. The depression of upper airway reflexes that occurred following ingestion of ethyl alcohol was maximum at 60 min and returned to baseline by 150 min. This dose of ethyl alcohol was insufficient to produce statistically significant depression of UARS. The blood alcohol levels achieved showed a wide range with a mean of 78.9 mg/100 ml (SEM 10.3). Individual subjects who had blood alcohol levels in excess of 100 mg/100 ml displayed much greater depression of UARS. In conclusion, 0.55-0.66 g/kg ethyl alcohol given to healthy male volunteers does not produce significant depression of UARS as measured using an ammonia stimulus technique.
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A human anti-hepatitis A virus mAb was rescued from a hybridoma cell line by conventional cDNA cloning, and expressed in CHO cells. The full nucleotide sequences of the mAb H and L chains were determined, revealing a VHI/V lambda II V region combination. Comparisons with germline V genes suggest that the V regions had undergone somatic mutations characteristic of an Ag-driven immune response. A comparison of the binding to hepatitis A virus between mAb derived from the CHO cells and the original hybridoma cell line using ELISA, radioimmunoprecipitation, and solid-phase competition RIA, indicated that the CHO cell-derived mAb fully retained the specificity of the mAb produced by hybridoma cells. Analysis of viral neutralization using a radioimmunofocus inhibition assay demonstrated the retention of antibody functionality after expression in CHO cells, demonstrating the use of this technique in the rescue and high level expression of unstable efficacious human mAb.
Radiation inactivation analysis was used to estimate the target size of a putative glutamate receptor subtype in goldfish brain. A simple, linear inactivation curve was obtained. The calculated molecular size of the [3H]kainate binding site was 33.8 kDa. The results presented here are comparable to the molecular masses determined for putative glutamate receptors in other lower vertebrates but are markedly different from the sizes of the corresponding glutamate receptor subtypes in mammalian central nervous system.
It has been proposed that epithelial ovarian cancers arise in germinal inclusion cysts of the ovary, which are thought to form as stigmata of ovulation. To evaluate whether the frequency of germinal inclusion cysts is associated with ovarian cancer, the authors counted the germinal inclusion cysts in single slides of sections from ovaries of 148 women who underwent incidental oophorectomy and from the contralateral ovaries of 37 women with unilateral ovarian cancer at Columbia-Presbyterian Medical Center, New York, New York, in 1985-1991. The mean number of germinal inclusion cysts was 2.7 for cases and 3.6 for controls. Conditional logistic regression analysis showed that germinal inclusion cysts were not associated with ovarian cancer (odds ratio = 0.98, 95% confidence interval 0.92-1.04). These findings do not support the hypothesis that increased formation of inclusion cysts is a risk factor for ovarian cancer.
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Hepatitis A virus infections have been reported recently among hemophilic patients in Italy and Germany, leading to speculation that infectious hepatitis A virus (HAV) might have been present in some factor VIII concentrates. In both cases, the implicated factor concentrates had been treated by a solvent/detergent method, which inactivates enveloped viruses but which would not be expected to inactivate HAV, a nonenveloped picornavirus. To determine whether HAV would be inactivated during pasteurization of factor VIII concentrate, an alternative method employed for virus inactivation, we determined the extent to which the infectivity of cell culture-adapted HAV, suspended either in cell culture medium or in a proprietary stabilizing buffer, was reduced by heat treatment at 60 degrees C for 10 hr. The titer of infectious HAV declined rapidly at 60 degrees C, but the stabilizer considerably delayed HAV inactivation. In cell culture medium, HAV was inactivated by > 3.6 log10 within 30 min, but 3.6 log10 inactivation of HAV was reached only after 6 hr in the presence of the stabilizer. Residual infectious HAV was present after even 10 hr of heat treatment in the stabilizer, indicating that < 5.2 log10 infectious HAV particles are inactivated under these conditions. In the presence of the stabilizer, HAV was significantly more stable than poliovirus type 1, which has been used to validate virus inactivation by pasteurization. We conclude that pasteurized factor VIII concentrate should pose little if any risk for transmission of HAV if pooled plasma used for its manufacture contained low levels of the virus.
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Five kindreds selected through probands attending an Icelandic hospital were recruited for linkage studies of manic depression. The rates of affection were equal for males and females and the age of onset appeared to be predominantly in early adult life, since prevalence did not rise appreciably with age. A complex segregation analysis was performed using the computer program POINTER to obtain maximum likelihood estimates of the contributions to liability from multifactorial transmission and a single major locus. Likelihood ratios between models supported a role for a single major locus which was dominant and had moderately high penetrance with, in the case of unipolar illness, additional multifactorial transmission. The best-fitting parameters were used to devise a transmission model for linkage analysis. Three markers on chromosome 5 were studied, at D5S76, D5S6 and D5S39. Strongly negative lod scores were obtained which were less than -2 over a distance of 40 cM, which included the region to which the gene for the 5HT1a receptor has been mapped.
Genetic linkage analysis has been used to study five Icelandic pedigrees multiply affected with manic depression. Genetic markers were chosen from regions which had been implicated by other studies or to which candidate genes had been localized. The transmission model used was of a dominant gene with incomplete penetrance and allowing for a large number of phenocopies, especially for unipolar rather than bipolar cases. Multipoint analysis with linked markers enabled information to be gained from regions spanning large distances. Using this approach we have excluded regions of chromosome 11p, 11q, 8q, 5q, 9q and Xq. Candidate genes excluded include those for tyrosine hydroxylase, the dopamine type 2 receptor, proenkephalin, the 5HT1A receptor and dopamine beta hydroxylase. Nevertheless, we remain optimistic that this approach will eventually identify at least some of the genes predisposing to manic depression.
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