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1.  A randomized trial of one versus three doses of Augmentin as wound prophylaxis in at-risk abdominal surgery. 
Postgraduate Medical Journal  1992;68(804):811-816.
In a randomized prospective trial of prophylactic antibiotics in at-risk abdominal surgery, one dose of intravenous Augmentin (amoxycillin 250 mg and clavulanic acid 125 mg) on induction has been compared with three 8 hourly doses in 900 patients. Wound infection rates which included minor and delayed infections were very similar in those given one dose: 48/449 (10.7%) compared with those given three doses: 49/451 (10.9%) 95% confidence limits - 4.25% + 3.9%. There were more septic and sepsis-related deaths in those patients given one dose (14 deaths) than in those given three doses (7 deaths) P > 0.1 95% CL - 0.4% + 3.0%. However, there were more very elderly patients in the one dose group: 64% of the deaths were aged over 80 and all but one had an emergency operation. There was no difference in the other outcome measures studied which included non-fatal deep sepsis, length of postoperative hospital stay, duration of postoperative fever or the use of antibiotics for postoperative infection. One dose of a suitable intravenous antibiotic gives prophylaxis against wound infection in at-risk abdominal surgery which is at least as effective as multiple doses. However, there may be a risk of overwhelming systemic sepsis in very elderly patients having emergency surgery.
PMCID: PMC2399526  PMID: 1461853
2.  The site of disruption of the bronchial epithelium in asthmatic and non-asthmatic subjects. 
Thorax  1992;47(7):499-503.
BACKGROUND: Attention has recently been focused on the basal cells of the tracheobronchial epithelium as the mechanism of anchorage of the tall columnar cells, which themselves do not appear to form hemidesmosomes with the basement membrane of the epithelium. Residual basal cells have been described as remaining attached to the basement membrane after epithelial denudation. This led this group to formulate the hypothesis that there may be a potential plane of cleavage between the basal cells and the overlying columnar cell layer within the bronchial epithelium, which becomes disrupted in asthma. METHODS: Bronchoalveolar lavage samples were obtained during bronchoscopy from eight patients with atopic asthma and four normal controls. Ultrathin sections of lavage cell pellets were examined by electron microscopy and the number of columnar and basal cells found in each epithelial cell cluster was counted. Cytocentrifuge preparations of the lavage samples from the same subjects were also examined for free epithelial cells and epithelial cell clusters. RESULTS: Electron microscopic examination of the cell pellets showed that basal cells were present in very small numbers in the epithelial clusters in all subjects (mean 0.03 (SE 0.02)/cluster) and the ratio of columnar cells to basal cells was far greater than was encountered in the intact bronchial epithelium (167 nu 4). The cytocentrifuge preparations showed an increased number of epithelial cell clusters and epithelial cells in the asthmatic patients. Although these clusters were similar in size in the two groups of subjects (6.3 nu 5.1 cells/cluster) the ratio of free epithelial cells to cells within the cluster was higher in the non-asthmatic subjects. CONCLUSIONS: It is proposed that shedding of epithelial cells occurs along a suprabasal plane and that there is a potential plane of cleavage between the suprabasal and the basal cell layers, which might be more vulnerable to the various insults.
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PMCID: PMC463857  PMID: 1412091
3.  Problems of drug abuse, HIV and AIDS: the burden of care in one general practice. 
Responsibility for many of the problems of intravenous drug abuse and human immunodeficiency virus (HIV) infection lies with community care agencies, such as general practitioners, community psychiatric and district nurses and drug agencies. It is in general practice that this burden is most clearly observed, given that general practitioners are in charge of the day-to-day care of patients. In an attempt to quantify this workload in an inner city practice with 11,200 patients, data were gathered from several sources relating to drug use and HIV infection. The study identified 432 patients who had consulted with problems of drug abuse and/or HIV infection over the period 1981-90. Among this group of patients 161 (37%) were HIV antibody positive. Among 191 drug abusers who were still registered with the practice in 1990 dihydrocodeine was the most commonly prescribed substitute treatment (130 patients) and only nine patients were prescribed methadone. Forty seven per cent of drug users continued to inject drugs occasionally. However, analysis of urine samples revealed that there was a shift away from injecting mainly heroin to multiple drug use, including benzodiazepines, usually originating from prescribed sources. Drug abusers who were HIV positive consulted their general practitioner significantly more often over one year than those who were not (mean 24.9 versus 15.8 consultations, P < 0.01). However, there was no significant difference between these two groups in terms of days spent in hospital. A total of 61 patients were referred to a community psychiatric nurse over an eight month period.(ABSTRACT TRUNCATED AT 250 WORDS)
PMCID: PMC1372058  PMID: 1419244
5.  Lipopeliosis: fat induced sinusoidal dilatation in transplanted liver mimicking peliosis hepatis. 
Journal of Clinical Pathology  1992;45(12):1109-1110.
A distinct peliosis-like lesion arose in the liver allograft of a 51 year old man. This lesion was caused by necrotic, fat-laden hepatocytes that released fat globules into the sinusoids. These then became strikingly distended with cysts, thus mimicking peliosis hepatitis. It is suggested that this lesion be called lipopeliosis.
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PMCID: PMC495007  PMID: 1479038
6.  Truncation of the human immunodeficiency virus type 1 transmembrane glycoprotein cytoplasmic domain blocks virus infectivity. 
Journal of Virology  1992;66(11):6616-6625.
Human immunodeficiency virus type 1 contains a transmembrane glycoprotein with an unusually long cytoplasmic domain. To determine the role of this domain in virus replication, a series of single nucleotide changes that result in the insertion of premature termination codons throughout the cytoplasmic domain has been constructed. These mutations delete from 6 to 192 amino acids from the carboxy terminus of gp41 and do not affect the amino acid sequence of the regulatory proteins encoded by rev and tat. The effects of these mutations on glycoprotein biosynthesis and function as well as on virus infectivity have been examined in the context of a glycoprotein expression vector and the viral genome. All of the mutant glycoproteins were synthesized, processed, and transported to the cell surface in a manner similar to that of the wild-type glycoprotein. With the exception of mutants that remove the membrane anchor domain, all of the mutant glycoproteins retained the ability to cause fusion of CD4-bearing cells. However, deletion of more than 19 amino acids from the C terminus of gp41 blocked the ability of mutant virions to infect cells. This defect in virus infectivity appeared to be due at least in part to a failure of the virus to efficiently incorporate the truncated glycoprotein. Similar data were obtained for mutations in two different env genes and two different target cell lines. These results indicate that the cytoplasmic domain of gp41 plays a critical role during virus assembly and entry in the life cycle of human immunodeficiency virus type 1.
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PMCID: PMC240157  PMID: 1357190
7.  If Clinton wins. 
BMJ : British Medical Journal  1992;305(6861):1041-1042.
PMCID: PMC1883593  PMID: 1467678
10.  Mutations in the leucine zipper of the human immunodeficiency virus type 1 transmembrane glycoprotein affect fusion and infectivity. 
Journal of Virology  1992;66(8):4748-4756.
Many retroviruses, including the human and simian immunodeficiency viruses, contain a leucine zipper-like repeat in a highly conserved region of the external domain of the transmembrane (TM) glycoprotein. This region has been postulated to play a role in stabilizing the oligomeric form of these molecules. To determine what role this region might play in envelope structure and function, several mutations were engineered into the middle isoleucine of the leucine zipper-like repeat of the human immunodeficiency virus type 1 (HIV-1) TM protein. A phenotypic analysis of these mutants demonstrated that conservative mutations (Ile to Val or Leu) did not block the ability of the viral glycoprotein to mediate cell-cell fusion or affect virus infectivity. In contrast, each of the other mutations, except for the Ile-to-Ala change, completely inhibited the ability of the glycoprotein to fuse HeLa-T4 cells and of mutant virions to infect H9 cells. The alanine mutation produced an intermediate phenotype in which both cell fusion and infectivity were significantly reduced. Thus, the biological activity of the glycoprotein titrates with the hydrophobicity of the residue in this position. None of the mutations affected the synthesis, oligomer formation, transport, or processing of the HIV glycoprotein complex. Although these results do not rule out a role for the leucine zipper region in glycoprotein oligomerization, they clearly point to a critical role for it in a post-CD4 binding step in HIV membrane fusion and virus entry.
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PMCID: PMC241301  PMID: 1629954
11.  Acetyl-coenzyme A synthesis from methyltetrahydrofolate, CO, and coenzyme A by enzymes purified from Clostridium thermoaceticum: attainment of in vivo rates and identification of rate-limiting steps. 
Journal of Bacteriology  1992;174(14):4667-4676.
Many anaerobic bacteria fix CO2 via the acetyl-coenzyme A (CoA) (Wood) pathway. Carbon monoxide dehydrogenase (CODH), a corrinoid/iron-sulfur protein (C/Fe-SP), methyltransferase (MeTr), and an electron transfer protein such as ferredoxin II play pivotal roles in the conversion of methyltetrahydrofolate (CH3-H4folate), CO, and CoA to acetyl-CoA. In the study reported here, our goals were (i) to optimize the method for determining the activity of the synthesis of acetyl-CoA, (ii) to evaluate how closely the rate of synthesis of acetyl-CoA by purified enzymes approaches the rate at which whole cells synthesize acetate, and (iii) to determine which steps limit the rate of acetyl-CoA synthesis. In this study, CODH, MeTr, C/Fe-SP, and ferredoxin were purified from Clostridium thermoaceticum to apparent homogeneity. We optimized conditions for studying the synthesis of acetyl-CoA and found that when the reaction is dependent upon MeTr, the rate is 5.3 mumol min-1 mg-1 of MeTr. This rate is approximately 10-fold higher than that reported previously and is as fast as that predicted on the basis of the rate of in vivo acetate synthesis. When the reaction is dependent upon CODH, the rate of acetyl-CoA synthesis is approximately 0.82 mumol min-1 mg-1, approximately 10-fold higher than that observed previously; however, it is still lower than the rate of in vivo acetate synthesis. It appears that at least two steps in the overall synthesis of acetyl-CoA from CH3-H4folate, CO, and CoA can be partially rate limiting. At optimal conditions of low pH (approximately 5.8) and low ionic strength, the rate-limiting step involves methylation of CODH by the methylated C/Fe-SP. At higher pH values and/or higher ionic strength, transfer of the methyl group of CH3-H4folate to the C/Fe-SP becomes rate limiting.
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PMCID: PMC206262  PMID: 1624454
12.  The Bevan factor. 
BMJ : British Medical Journal  1992;304(6830):844.
PMCID: PMC1881667  PMID: 1392734
13.  Activation of the p34 CDC2 protein kinase at the start of S phase in the human cell cycle. 
Molecular Biology of the Cell  1992;3(4):389-401.
Using a protocol for selecting cells on the basis of both size and age (with respect to the preceding mitosis), we isolated highly synchronous human G1 cells. With this procedure, we demonstrated that the p34 CDC2 kinase was activated at the start of S phase. Cyclin A synthesis began at the same time, and activation of the p34 CDC2 kinase at the start of S phase was, at least in part, due to its association with cyclin A. Furthermore, cells synchronized in late G1 by exposure to the drug mimosine contain active cyclin A/p34 CDC2 kinase, indicating that p34 CDC2 activation can occur before DNA synthesis begins. Thus, the cyclin A/CDC2 complex, which previously has been shown to be sufficient to start SV40 DNA synthesis in vitro, assembles and is activated at the start of S phase in vivo.
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PMCID: PMC275590  PMID: 1386764

Results 1-13 (13)