Biomedical subjects
Publications and source records attributed to J Hunter.
Aortico-left ventricular tunnel is a rare congenital cardiac defect. Because the tunnel traverses the upper portion of the interventricular septum, the potential exists for an aneurysmal tunnel to obstruct the outflow of the right ventricle. We report our clinical experience with such a patient, and emphasize the importance of a two-patch technique to avoid its occurrence.
Although previous studies have reported that neutrophils play an important role in mediating the microvascular injury observed after reperfusion of ischemic intestine, the contribution of these phagocytic cells to the mucosal dysfunction remains unclear. Three series of experiments consisting of an untreated group, a short-term monoclonal antibody (MAb) IB4 treatment group (MAb IB4 given on the day of the experiment), and a long-term MAb IB4 treatment group (3-day pretreatment with MAb IB4) were performed using autoperfused segments of cat ileum exposed to 3 hours of ischemia followed by 1 hour of reperfusion. Mucosal myeloperoxidase activity, an index of mucosal granulocyte levels, increased from 12 to 25 U/g wet wt in the untreated group. In the short-term MAb IB4 experiments, baseline values were very similar to those of the untreated group but no increase in myeloperoxidase activity was observed after ischemia/reperfusion. Long-term pretreatment with MAb IB4 reduced baseline values of myeloperoxidase activity to approximately 1 U/g wet wt; the values remained at this level throughout the experiment. The permeability of the mucosal barrier was quantitated by measuring blood-to-lumen clearance to 51Cr-ethyl-enediaminetetraacetic acid (EDTA). The water absorptive capacity of the intestine was also measured. In the untreated group, mucosal permeability to 51Cr-EDTA increased sixfold and water absorption was abolished after reperfusion. Both short-term and long-term administration of MAb IB4 prevented the net fluid loss into the lumen, but only long-term administration of MAb IB4 blunted the increased mucosal permeability induced by ischemia/reperfusion. These data suggest that interstitial granulocytes contribute significantly to the mucosal dysfunction associated with reperfusion of the ischemic intestine.
Research on schizophrenia published in four professional journals--Journal of Abnormal Psychology, Archives of General Psychiatry, Journal of Nervous and Mental Disease, and American Journal of Psychiatry--over a 5-year period from January 1985 through December 1989 was examined for gender composition of subject samples and gender analyses of findings. Results indicate a continued predominance of male subjects in schizophrenia research, with males outnumbering females two to one, and frequent neglect of possible gender differences within mixed-sex samples. Possible explanations for the male bias are considered and greater research and editorial attention to possible gender effects are urged.
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"Handicap", categorised according to the ICIDH, and "Disability", measured by the Smith Activities of Daily Living (ADL) Index, were assessed in over 300 patients (suffering from strokes, lower limb amputations, cardiac disorders, low back pain and other diseases) on admission to and after discharge from a hospital based rehabilitation programme. Statistically significant improvements were found in Physical Independence and Mobility Handicaps which correlated with improvements in ADL Self-care (R = 0.58, p less than 0.001) and ADL Mobility (R = 0.53, p less than 0.001) averages. Small but significant improvements were also found in Orientation, Occupation and Social Integration Handicaps but there was no change in Economic Self Sufficiency Handicap. Thus it is possible to use the Handicap categorisations to assess disabled people sequentially during a rehabilitation programme. The problems of data collection, however, are so formidable that its usefulness must be limited.
[3H]Vinblastine transport across MDCK (renal epithelial) cell layers has been characterised. The basal-to-apical [3H]vinblastine flux (JA-B) (at 10 nM) exceeded apical-to-basal flux by 19.6 fold. Net vinblastine secretion (JB-A - JA-B) was inhibited by verapamil (0.1 mM) primarily by a reduction in JB-A, consistent with net vinblastine secretion resulting from an inhibition of P-glycoprotein. 1,9-Dideoxy-forskolin and forskolin (0.1 mM) both resulted in significant inhibition of JB-A and net vinblastine secretion of 64.3 +/- 3.1% and 29.1 +/- 4.8% respectively. 7 beta-deactyl-7 beta-(gamma-N-methylpiperazino)-butyryl-forskolin was ineffective. Half-maximal inhibition of vinblastine secretion by 1,9-dideoxy-forskolin was observed at 65 microM. 1,9-dideoxy-forskolin is unable to stimulate adenylate cyclase, suggesting that this forskolin derivative is a potentially important lead antagonist of P-glycoprotein for circumvention of pleiotropic drug resistance.
Isolated segments of cat small intestine were subjected to 3 hr of ischemia followed by 1 hr reperfusion (I/R). Mucosal biopsies were obtained for measurement of myeloperoxidase (MPO) activity, an index of tissue neutrophil count, and leukotriene B4 (LTB4) production. Animals were pretreated with either cyclosporin A (CsA) or FK506, which are potent immunosuppressants. Both agents significantly attenuated the neutrophil infiltration induced by I/R. FK506, but not CsA, reduced the elevated mucosal LTB4 production normally observed following reperfusion. The results of this study suggest that FK506 and CsA may be important agents in modulating neutrophil infiltration in acute inflammatory conditions.
Many medical decision support systems that have been developed in the past have failed to enter routine clinical practice. Often this is because the developers have failed to analyse in sufficient detail the precise user requirements, because they have produced a system which takes too narrow a view of the patient, or because the decision support facilities have not been sufficiently well integrated into the routine clinical data handling activities. In this paper we discuss how the AIM-INFORM project is setting out to deal with these issues, in the context of the provision of decision support in the intensive care unit.
P-glycoprotein expression was demonstrated in two human intestinal adenocarcinoma cell-lines (HCT-8, ileocaecal and T84, colonic) by immunoprecipitation of a 170-180 kDa protein with monoclonal antibody JSB-1. Both HCT-8 and T84 formed functional epithelial cell layers of high transepithelial electrical resistance (greater than 700 omega.cm2) when grown on permeable matrices. These epithelial layers demonstrated vectorial secretion (net vinblastine fluxes in the basal-to-apical direction of 0.135 and 0.452 pmol h-1 cm-2 in HCT-8 and T84 cell layers, respectively, from bathing solutions containing 10 nM vinblastine). These vectorial vinblastine secretions were sensitive to inhibition by verapamil. Passive transepithelial vinblastine permeation was limited by the presence of intercellular (tight) junctions, as demonstrated by the high transepithelial electrical resistance, and verapamil increased this passive vinblastine permeation concomitant with a reduction in the electrical resistance. Cellular vinblastine loading was significantly greater from the basal side, and this was also susceptible to inhibition by basal verapamil. The demonstration of vectorial transport of vinblastine in human intestinal colonic adenocarcinoma cell layers is direct evidence in favour of the hypothesis that the function of mdr1 in epithelial from the gastrointestinal tract is to promote detoxification by a process of epithelial secretion. This study also highlights that cellular vinblastine accumulation depends not only upon P-glycoprotein function, but also upon differential apparent membrane permeabilities and the presence of intercellular (tight) junctions that may restrict drug permeation and cellular accumulation to apical or basal membrane domains.
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OBJECTIVE: To describe the frequency of aerosol pentamidine-induced bronchoconstriction, its relationship to non-specific airway responsiveness, and its response to preventive therapy using salbutamol, ipratropium bromide, or sodium cromoglycate. METHODS: Consecutive HIV-infected individuals starting prophylactic AP were eligible if they had not been previously treated with this agent. Simple spirometry was performed before and 10 min after a single 60-mg dose given through an ultrasonic nebulizer. Methacholine challenge was performed in all subjects 24 h to four days after the initial AP dose. Subjects with a change in FEV1 (delta FEV1) greater than or equal to 10 percent decrease after the initial AP dose were restudied on three separate occasions (greater than 24 hours apart) after premedication with two puffs of salbutamol (200 micrograms), ipratropium bromide (40 micrograms), or sodium cromoglycate (2 mg), in random order. RESULTS: Fifty-three subjects were studied. The median delta FEV1 after a single dose of AP was -7.0 percent (range: -47 percent, 1.8 percent). The delta FEV1 following AP was only partially predicted by the degree of nonspecific bronchial responsiveness as measured by a standard methacholine challenge. Age, current smoking, history of asthma, baseline FEV1, or a prior episode of PCP failed to predict the delta FEV1 following AP. Eighteen subjects (34 percent) had a delta FEV1 greater than or equal to 10 percent decrease (median: -17.0 percent). In these subjects, after premedication with salbutamol, ipratropium bromide, and sodium cromoglycate, the median delta FEV1 was 1.0, 0.8, and -9.6 percent, respectively. CONCLUSION: Aerosol pentamidine produced a decrease in FEV1 greater than or equal to 10 percent in 34 percent of subjects. This was not accurately predicted by the methacholine response. The bronchoconstriction induced by AP was effectively prevented by either salbutamol or ipratropium, whereas cromoglycate was only partially effective.
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We describe a four-year experience with bone marrow transplantation involving closely HLA-matched unrelated donors and 55 consecutive patients with hematologic disease who were seven months to 48.6 years old (median, 18 years). An intensive pretransplantation conditioning regimen and graft-versus-host disease (GVHD) prophylaxis with CD3-directed T-cell depletion and cyclosporine were employed. Durable engraftment was achieved in 50 of 53 patients who could be evaluated (94 percent; 95 percent confidence interval, 83 to 98 percent). Acute GVHD of Grade II to IV developed in 46 percent of the patients (confidence interval, 27 to 66 percent). The incidence and severity of acute GVHD were increased in recipients of HLA-mismatched marrow as compared with recipients of phenotypically matched marrow (incidence of 53 percent [confidence interval, 37 to 68 percent] vs. 17 percent [confidence interval, 5 to 45 percent]; P less than 0.05). Extensive chronic GVHD and deaths not due to relapse also tended to be more frequent when HLA-mismatched marrow was used, but not significantly so. With a median follow-up of more than 19 months (range, greater than 9 to greater than 39), the actuarial disease-free survival of transplant recipients with leukemia and a relatively good prognosis (acute leukemia in first remission and chronic myelogenous leukemia in chronic phase) was 48 percent (confidence interval, 24 to 73 percent), and that of recipients with more aggressive leukemia was 32 percent (confidence interval, 18 to 51 percent); the actuarial survival of recipients with non-neoplastic disease was 63 percent (confidence interval, 31 to 86 percent). We conclude that marrow transplantation with closely HLA-matched unrelated donors can be effective treatment for neoplastic and non-neoplastic diseases. Although transplants from phenotypically HLA-matched unrelated donors appear to be most effective, transplants with limited HLA disparity can also be successful in some patients.
The production of streptavidin by Streptomyces avidinii in several different media was examined at 24, 48 and 72 hours. Flask studies indicated that fermentation media containing either complex or multiple carbon sources resulted in higher yields of streptavidin than media with a single carbon source. Streptavidin could be detected in crude fermentation broths by use of a tritiated biotin binding assay. This assay appears to give useful estimates of streptavidin production. Depending upon the medium employed, streptavidin yields ranged from 0.5 mg/l to 53 mg/l. Production was successfully scaled up to ten liter fermentors. Streptavidin was purified in a one step process from centrifuged, concentrated fermentation broths by binding the protein to an iminobiotin column at pH 11 followed by elution at pH 4.0. Recovery percentages varied depending upon the solubility of the fermentation media ingredients.
Electrophoretic separation of solubilized embryos incubated for 24 h in the presence of [U-14C]glucose indicated incorporation of glucose carbon into a number of protein bands. Treatment of nitrocellulose blots of electrophoretograms with glucosidases had no effect on incorporated counts, confirming that the labelled bands were not due to protein bound glycogen. Furthermore, addition of 0.1 microgram mL-1 tunicamycin to the incubation medium virtually eliminated incorporation of glucose into the protein bands but had no effect on the pattern or rate of incorporation of labelled amino acids in parallel experiments. Also the pattern of labelling of protein by glucose was reflected in the pattern of binding of Con A to the nitrocellulose blots. There were quantitative and qualitative changes in labelling as development progressed. For embryos cultured from the 2-cell stage, a small amount of label was incorporated in two major bands at relative mobility (Mr) 69 and 97 K. With culture from the 8-cell stage, three additional major bands (33, 44 and 56 K) were labelled. Embryos cultured from the morula stage showed a different profile of incorporation; there was much more active labelling, and eight major and a number of minor radioactive bands were identified. Whilst tunicamycin suppressed glucose incorporation into glycoproteins and inhibited compaction of embryos, it had little effect on other parameters of metabolism during incubation in its presence for 24 h. No significant effects of the metabolite on protein synthesis, glycogen storage, lactate production or overall macromolecular synthesis were evident. By contrast, the anabolic metabolism of embryos decompacted by long periods of exposure to tunicamycin was severely reduced although glycolysis was still unaffected. Amphomycin at very high concentration (500 micrograms mL-1) was toxic to embryos but at concentrations up to 250 micrograms mL-1 had no effect on compaction and development of blastocysts. Addition of monensin to the incubation medium [16 micrograms mL-1] did not interfere with the development of either 2-cell or 8-cell embryos to blastocysts.
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This report describes the development of measures of AIDS knowledge and beliefs about AIDS prevention for adolescents. Review of the literature, focus groups, pilot testing, and reviews by advisory councils assured that the process of developing the measures contributed to their validity. These measures were administered to three samples of adolescents at high risk for contracting AIDS: 43 runaway males, 43 runaway females, and 36 self-identified gay males. Both the knowledge and the beliefs instruments showed moderately high internal consistency and test-retest reliability and successfully avoided ceiling effects. Gay males demonstrated significantly greater knowledge of AIDS; however, there were few differences in beliefs among the groups. Knowledge of AIDS was significantly correlated with beliefs about AIDS prevention. The results suggest that these measures identify gaps in knowledge and beliefs among high-risk youth.