Resuscitation and patients' views. Questioning may be misunderstood by patients.
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Biomedical subjects
Publications and source records attributed to J Potter.
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We report the first case of primary cutaneous aspergillosis caused by Aspergillus ustus, a species that seldom infects human beings. The patient, a 62-year-old liver transplant recipient with end-stage hepatitis C-induced cirrhosis, was receiving the experimental immunosuppressive drug FK-506. Trauma to the skin of the right arm from tape and from an arm board holding intravenous and intraarterial catheters in place and to the left leg from an occlusive knee brace may have contributed to this unusual mycosis. The patient's cutaneous aspergillosis responded to a combination of intravenous amphotericin B and topical terbinafine cream. Although the patient died shortly thereafter from hepatic failure, there was no evidence of systemic aspergillosis.
1. Dopamine (DA) at low doses (2.5 micrograms kg-1 min-1) produces a measurable increase in glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) in young healthy subjects and has a therapeutic effect in younger patients with congestive cardiac failure (CCF). In elderly healthy subjects, DA increases ERPF but does not increase GFR in all subjects. 2. To determine the potential therapeutic use of DA in elderly subjects with CCF, we studied 17 patients (5 male) aged 79.9 years (range 68 to 93 years) admitted to hospital for inpatient treatment of CCF resistant to diuretic and angiotensin converting enzyme inhibitor therapy. The effects of a single infusion DA at 2.5 micrograms kg-1 min-1 on GFR and ERPF were assessed in a double-blind, placebo controlled prospective study. 3. There were no significant differences in GFR or ERPF between control and DA. A reduction in GFR was seen in some patients. 4. DA at low dosage was not shown to benefit elderly patients with resistant CCF, and in some patients was detrimental. Higher doses or a combination with other inotropes may be necessary for a renal effect in elderly patients.
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The Hypertension in the Very Elderly Trial (HYVET) is a multicentre, open, randomised, controlled trial. The aim of this trial is to investigate the effect of active treatment on stroke incidence in hypertensive patients over the age of 80 years. Secondary end-points include total cardiovascular mortality and morbidity. Entry criteria include a sustained sitting systolic blood pressure of 160 to 219mm Hg plus a sustained sitting diastolic pressure of 95 to 109mm Hg. Also required is a standing systolic blood pressure of at least 140mm Hg. Patients must give their informed consent, and be free of congestive heart failure requiring treatment, gout, renal failure or a recent cerebral haemorrhage. Patients are to be randomised to 3 groups-(i) no treatment; (ii) treatment with a diuretic [bendroflumethiazide (bendrofluazide)]; or (iii) treatment with an angiotensin converting enzyme (ACE) inhibitor (lisinopril). Starting dosage for bendroflumethiazide and lisinopril is 2.5 mg/day. In order to achieve goal sitting systolic and diastolic blood pressures (< 150/80 mm Hg), a doubling of the dosage is allowed. Furthermore, slow release diltiazem (120 mg/day increasing to 240 mg/day if required) may be added to the medication of the actively treated groups. These drugs have been chosen as inexpensive and appropriate representatives of their therapeutic classes. 700 patients in each group (a total of 2100) will be sufficient to detect a 40% difference in cerebrovascular events between no treatment and active treatment (alpha = 0.01, 1-beta = 0.90). These numbers will also detect a difference in total mortality of 25% and in cardiovascular mortality of 35%. The pilot phase of the trial has been started with support from the British Heart Foundation. Centres which are interested in taking part should contact C.J. Bulpitt or any of the other authors.
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BACKGROUND: Generation of toxic oxygen metabolites at reperfusion may contribute to the injury sustained as a consequence of harvest and ischemic preservation of organ allografts. Because there is a paucity of evidence that this mechanism is operative in human beings, we measured the generation of ethane into the exhaled breath as a biomarker of free radical-mediated lipid peroxidation in human liver transplantation. METHODS: A novel technique that increased the previous standard of sensitivity 100-fold was used to measure picomole quantities of ethane in exhaled breath of eight recipients undergoing human orthotopic liver transplantation. RESULTS: Ethane production correlated closely with the specific events of liver transplantation including the initial reperfusion of the allografts. In every case a twofold to threefold increase in ethane production was superimposed on a stable baseline immediately after reestablishment of portal vein blood flow through the donor liver. CONCLUSIONS: Ethane production was interpreted as evidence of hepatic lipid peroxidation, presumably mediated by toxic metabolites of oxygen occurring at reperfusion. This noninvasive approach allowed localization of the time point at which lipid peroxidation occurred and may facilitate quantification of lipid peroxidation mediated by free radicals and other toxic oxygen metabolites during operation.
The effects of glutamate, N-methyl-D-aspartate (NMDA), (+)-5-methyl-10,11-dihydro-5H-dibenzo-(a,d)-cyclo-hepten 5,10-imine maleate (MK801), alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) and quisqualate on the accumulation of inositol phosphates (IP) from the breakdown of phosphoinositides in vitro have been studied in tissue prisms derived from a region of the chick forebrain, the intermediate medial hyperstriatum ventrale (IMHV). In prisms from the left IMHV, glutamate stimulated IP accumulation by 10-20%, AMPA by 55% and quisqualate by 650%. These effects were more marked in the right IMHV, where AMPA stimulated IP accumulation by 157% and quisqualate by 920%. MK801 and NMDA had no significant effect on IP accumulation in either hemisphere. The left IMHV is known to be the site of a biochemical cascade resulting in synaptic remodelling following training day-old chicks on a one-trial passive avoidance task. The effect of such training was to reduce glutamate-stimulated accumulation of IP by 27% (P < 0.05) in prisms taken 30 min after training. There was no effect on prisms taken at 5 or 180 min after training, and no effect at any time in the right IMHV. MK801, injected intraperitoneally before training at a concentration known to produce amnesia for the passive avoidance task, abolished the training-induced decrease without itself affecting IP accumulation. Taken in conjunction with pharmacological and autoradiographic evidence, these results indicate that memory formation for the passive avoidance task involves the activation of NMDA receptor channels, but not quisqualate or AMPA receptors, in the left IMHV of the chick 30 min after training.
Using the technique of homologous recombination in embryonic stem cells, a mouse strain without functional CD4 and CD8 genes has been generated. Surprisingly, these mice contain significant numbers of alpha beta T cells. Although mice deficient for CD8 only do not show any cytotoxic response when their T cells are stimulated with either alloantigen or viral antigen, the CD4-8- mice do generate alloreactive cytotoxic T cells. These cytotoxic T cells bear the alpha beta T cell receptor and recognize major histocompatibility complex class I antigens. In addition fully allogeneic skin transplants were rejected but skin transplants expressing only minor transplantation antigens were not. Virus-specific cytotoxic T lymphocytes were also not detected. It seems that alloreactive cytotoxic T cells can be induced and exert their effector function in vitro and in vivo in the absence of CD8, and that they can develop and mature in vivo without the CD8 molecule or the signals it might provide.
This paper investigates the behavioural aspects of health care use for Jordanian children from birth to 3 years using data from a national survey. Statistical analyses indicate differences in the determinants of the use of paediatric care and immunisation: whereas immunisation coverage was already good in 1983 (and has improved subsequently), paediatric care is used for fewer than half of the children under 1 year of age. Socioeconomic and demographic characteristics of the population, especially female education, and maternal health care use, are important determinants of these patterns of child health care. The absence of differences in paediatric care and immunisation by sex of the child are discussed.
The role of various subfamilies of rat hepatic cytochrome P-450 in the oxidation of theophylline was evaluated by comparing theophylline clearance in control rats and those pretreated with relatively selective inducers and inhibitors of the cytochromes P-450. Pretreatment with the CYP1A inducer, beta-naphthoflavone (BNF), increased theophylline clearance 4.5-fold (p < 0.001), and the CYP1A inhibitor, alpha-naphthoflavone, significantly attenuated the BNF effect. Pretreatment with phenobarbital, an inducer of CYP2B/C in rats, had a far more modest effect, increasing theophylline clearance only 1.6-fold (p < 0.005). The phenobarbital-mediated increase in theophylline clearance was attenuated by orphenadrine, a CYP2B/C inhibitor. The CYP2E inducer, isoniazid and the CYP2E inhibitor, diallyl sulfide were virtually without effect, as was the CYP4A inducer, clofibrate, and the CYP4A inhibitor, 10-undecynoic acid. Ajmaline, and inhibitor of CYP2D, was also without any effect on theophylline clearance. While the powerful CYP3A inducer clotrimazole did not increase theophylline clearance, troleandomycin, an inhibitor of CYP3A, did slow theophylline clearance by about 25% (p < 0.002). Together, these findings suggest that CYP1A is principally responsible for the overall oxidation of theophylline in rats, and that CYP2B/C probably also mediates some theophylline oxidation. The involvement of CYP2D, CYP2E, CYP4A, and CYP3A is relatively trivial.
Incubation is the process by which life events influence the onset of psychiatric disorder after an appreciable delay. It has long been recognised clinically. In this paper we use data from the Camberwell Collaborative Depression Study to see whether incubation effects can be demonstrated in depressive illness. We used a novel adaptation of survival analysis for this purpose. The results suggest that incubation does occur in depressive disorder, that it is much less important than the effect of life events close to onset, that it is apparent in women but not in men, and that it is no more evident preceding endogenous than neurotic symptom patterns.
We report the isolation of metronidazole-resistant Bacteroides fragilis from a post-operative wound abscess in a 72-year-old woman who had not been treated with metronidazole during the preceding 9 months. The case illustrates the need for caution when identifying anaerobes on the basis of metronidazole sensitivity.
BACKGROUND: A National Heart, Lung, and Blood Institute (NHLBI) Conference was held October 9-10, 1990, to review and discuss existing data on U-shaped relations found between mortality rates and blood total cholesterol levels (TC) in some but not other studies. Presentations were given from 19 cohort studies from the United States, Europe, Israel, and Japan. A representative of each study presented its findings and also submitted tables of proportional hazards regression coefficients for entry TC levels in regard to death, and these were incorporated into a formal statistical overview adjusted for age, diastolic blood pressure, cigarette smoking, body mass index, and alcohol intake, as available. METHODS AND RESULTS: The U-shape for total mortality in men and the flat relation in women resulted largely from a positive relation of TC with coronary heart disease death and an inverse relation with deaths caused by some cancers (e.g., lung but not colon), respiratory disease, digestive disease, trauma, and residual deaths. Risk for combined noncardiovascular, noncancer causes of death decreased steadily across the range of TC. The conference considered possible explanations for the statistical associations found between low TC levels or active TC lowering and certain causes of death. One is that TC is lowered by some disease conditions themselves, such as wasting in chronic pulmonary disease or reduced production and secretion of cholesterol-bearing lipoproteins with liver disease. In this sort of situation, the TC:mortality association found in observational studies may be due to preexisting disease. This was addressed by excluding early deaths from the analysis, which did not change the results. The conference considered as well the biological function of cholesterol, which, if seriously deranged, might hypothetically cause a wide variety of diseases and dysfunction. The conference also considered the biological functions that might provide plausible mechanisms for the associations found. CONCLUSIONS: Definitive interpretation of the associations observed was not possible, although most participants considered it likely that many of the statistical associations of low or lowered TC level are explainable by confounding in one form or another. The conference focused on the apparent existence and nature of these associations and on the need to understand their source rather than on any pertinence of the findings for public health policy. Further research is recommended to explain the observed associations of low TC levels (and TC lowering) with certain noncardiovascular diseases. This includes studies of the time course of TC change in disease, the relation of TC to morbidity, further studies of possible epidemiological confounding, monitoring of population trends in TC and mortality, further studies of the relations in women, auditing of noncardiovascular events in trials, studies of cell membrane, genetic and molecular links to cholesterol metabolism, TC level and disease, studies of disease manifestations in specific lipid disorders, and further study of the proposed causal mechanisms linking low TC and hemorrhagic stroke.
A random mailed survey (response N = 226; 75.3%) of participants in diet-related home-based learning evaluated exposure to recruitment channels and impact on salience, utility, level of participation, sharing the course with others, knowledge, and performing recommended behaviors. A post-only design, the study was conducted in a small Minnesota city (population = 20,000), part of the Cancer and Diet Intervention (CANDI) project. About 18.5% of residents (3,711) enrolled during an 8-week media campaign; women, college graduates, and those over 44 years old were overrepresented. Participants learned about the program through mass media (97%); small media (41.9%); and interpersonal sources (50%). Women were more likely to learn about the course through interpersonal sources. In analysis of variance (ANOVA) modeling, salience and utility predicted level of participation in course activities. Level of participation in turn predicted nutrition knowledge and with salience predicted performance of recommended behaviors. Although the course appealed to individuals who needed it less, there was evidence of diffusion to the unenrolled. About 57% of responding participants reported sharing it with spouses; about 67% reported sharing it with someone outside their households.
A mutant mouse strain without CD8 (Lyt-2 and Lyt-3) expression on the cell surface has been generated by disrupting the Lyt-2 gene using embryonic stem cell technology. In these mice, CD8+ T lymphocytes are not present in peripheral lymphoid organs, but the CD4+ T lymphocyte population seems to be unaltered. Cytotoxic response of T lymphocytes from these mice against alloantigens and viral antigens is dramatically decreased. Proliferative response against alloantigens and in vivo help to B lymphocytes, however, are not affected. These data suggest that CD8 is necessary for the maturation and positive selection of class I MHC restricted cytotoxic T lymphocytes but is not required on any of the intermediate thymocyte populations (CD8+CD4-TcR- or CD4+CD8+TcRlow) during the development of functional class II MHC restricted helper T cells.
A cDNA clone encoding a rabbit ileal villus cell Na+/H+ exchanger was isolated and its complete nucleotide sequence was determined. The cDNA is 4 kb long and contains 322 bp of 5'-untranslated region, 2451 bp of open reading frame and 1163 bp of 3'-untranslated area, with 70%, 91% and 40% identity to the human sequence, respectively. Amino acid sequence deduced from the longest open reading frame indicated a protein of 816 residues (predicted Mr 90,716) which exhibits 95% amino acid identity to the human Na+/H+ exchanger. The two putative glycosylation sites in the human Na+/H+ exchanger are conserved in this protein, suggesting that it is a glycoprotein. Stable transfection of the cDNA into an Na+/H+ exchanger deficient fibroblast cell line, established Na+/H+ exchange. The Na+/H+ exchanger was stimulated by serum and a phorbol ester but not by 8-Br-cAMP. In Northern blot analysis, the cDNA hybridized to a 4.8 kb message in rabbit ileal villus cells, kidney cortex, kidney medulla, adrenal gland, brain and descending colon and to a 5.2 kb message in cultured human colonic cancer cell lines, HT29-18 and Caco-2. In immunoblotting, a polyclonal antibody raised against a fusion protein of beta-galactosidase and the C-terminal 158 amino acids of the human Na+/H+ exchanger identified a rabbit ileal basolateral membrane protein of 94 kd and only weakly interacted with the ileal brush border membrane. In immunocytochemical studies using ileal villus and crypt epithelial cells, the same antibody identified basolateral and not brush border epitopes. Restriction analysis of genomic DNA with a 462 bp PstI-AccI fragment of the rabbit Na+/H+ exchanger strongly suggests the existence of closely related Na+/H+ exchanger genes. The near identity of the basolateral Na+/H+ exchanger and the human Na+/H+ exchanger plus the ubiquitous expression of this message suggests that the ileal basolateral Na+/H+ exchanger is the 'housekeeping' Na+/H+ exchanger.