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Biomedical subjects

G Cohen

Publications and source records attributed to G Cohen.

At least 145 records · Page 8Linked to original sources
PubMed1996

Can different patient satisfaction survey methods yield consistent results? Comparison of three surveys.

OBJECTIVE: To examine the consistency of survey estimates of patient satisfaction with interpersonal aspects of hospital experience. DESIGN: Interview and postal surveys, evidence from three independent population surveys being compared. SETTING: Scotland and Lothian. SUBJECTS: Randomly selected members of the general adult population who had received hospital care in the past 12 months. MAIN OUTCOME MEASURES: Percentages of respondents dissatisfied with aspects of patient care. RESULTS: For items covering respect for privacy, treatment with dignity, sensitivity to feelings, treatment as an individual, and clear explanation of care there was good agreement among the surveys despite differences in wording. But for items to do with being encouraged and given time to ask questions and being listened to by doctors there was substantial disagreement. CONCLUSIONS: Evidence regarding levels of patient dissatisfaction from national or local surveys should be calibrated against evidence from other surveys to improve reliability. Some important aspects of patient satisfaction seem to have been reliably estimated by surveys of all Scottish NHS users commissioned by the management executive, but certain questions may have underestimated the extent of dissatisfaction, possibly as a result of choice of wording.

Adolescent↗
PubMed1996

Preconditioning to improve myocardial protection.

Major advances in the composition and delivery of cardioplegia have helped to reduce the morbidity and mortality associated with coronary bypass surgery. The discovery of the preconditioning response should facilitate the development of more powerful myocardial protective agents. These new agents may act to directly stimulate the preconditioning response or may act in a supplementary fashion to either augment the response or provide protection from alternate pathways. As new techniques of myocardial protection continue to be developed, the risk-to-benefit ratio of coronary bypass surgery will continue to improve. As a result of these improvements, surgeons will be able to offer surgery to an increasingly high risk patient population without increasing the morbidity or mortality currently associated with coronary bypass.

Animals↗
PubMed1996

Ferrous active site of isopenicillin N synthase: genetic and sequence analysis of the endogenous ligands.

Isopenicillin N synthase (IPNS) from Streptomyces jumonjinensis (M(r) 37,902) is a non-heme ferrous iron-containing enzyme that catalyzes the oxidative cyclization of the tripeptide delta-(L-alpha-aminoadipoyl)-L-cysteinyl-D-valine (ACV) to form isopenicillin N. Spectroscopic studies [reviewed in Cooper, R. D. (1993) Biomed. Chem. 1, 1-17] have led to a model for the coordination environment of the iron atom possessing three histidine and one aspartic acid endogenous ligands and a solvent molecule. A refinement of that model proposes that formation of the Fe(II) IPNS-ACV complex occurs with displacement of the H2O from the metal center and that one of the histidines is subsequently replaced by a solvent molecule on binding of dioxygen. Here we report genetic studies to determine the nature and location of the endogenous ligands in the S. jumonjinensis IPNS primary amino acid sequence that constitute the ferrous active site. Site-directed mutagenesis was used to exchange each of the seven histidines and the five aspartic acids that are conserved in bacterial and fungal IPNS proteins. Biochemical analysis of the alanine-substituted mutant proteins shows that two histidines, His212 and His268, and one aspartic acid, Asp214, are essential for enzyme activity. The other mutant enzymes have specific activities 5-68% that of wild type. Sequence analysis of 10 IPNS and 42 other non-heme ferrous iron-dependent dioxygenases reveal the presence of a common motif, HisXAsp(53-57)XHis, which in IPNS contains the identical two histidines and one aspartic acid essential for function. Accordingly, we have assigned residues His212, His268, and Asp214 as three of the four endogenous ligands postulated to form the IPNS ferrous active site. Compelling support for these conclusions comes from the recent crystal structure determination of the manganese form of a fungal IPNS [Roach et al. (1995) Nature 375, 700-704].

Amino Acid Sequence↗
PubMed1996

The characteristics and frequency of augmented breaths during CO2-induced hyperpnoea of newborn infants.

1. Hypercapnic ventilatory responses of thirty-five full term infants aged 1-7 days were evaluated, and the characteristics and incidence of augmented breaths were determined. 2. According to the inspiratory airflow profile and tidal volume (VT), augmented breaths were categorized as 'type A' (biphasic, VT > or = 2 x control VT), or 'type M' (multiphasic, VT < 2 x control VT). 3. Steady-state inhalation of 2-4% CO2 resulted in a 3-fold increase in the frequency of augmented breaths after 8 min; 80 s rebreathing a mixture containing 5-6% CO2 resulted in a 20-fold increase in the frequency of these breaths. 4. During eupnoea, 85% of spontaneously occurring augmented breaths were type A. With increasing respiratory drive, there was a disproportionate increase in type M compared with type A breaths: after 80 s rebreathing, 86% of augmented breaths were type M and only 14% were type A. 5. These findings indicate that the hypercapnic hyperpnoea facilitates an inspiration-augmenting reflex in newborn infants. The significance of type M breaths is unclear; they appear to be characteristic of the newborn, and may represent the response of an immature respiratory system to load.

Carbon Dioxide↗
PubMed1996

Does the internal thoracic artery graft delay the recovery of myocardial metabolism?

BACKGROUND: The left internal thoracic artery (LITA) bypass graft to the left anterior descending artery has greater long-term patency than a saphenous vein graft. However, surgeons may be reluctant to use the LITA graft in some patients because they are unable to deliver cardioplegia to the left anterior descending artery territory. METHODS: We compared the myocardial levels of high-energy phosphates and their metabolites in patients who received an LITA graft with those in patients who received a saphenous vein graft to the left anterior descending artery territory during elective coronary artery bypass grafting. Right and left ventricular biopsy specimens were obtained at three times: before aortic cross-clamping, after cross-clamp removal, and after 10 minutes of reperfusion. RESULTS: No differences were found between the LITA graft group and the saphenous vein graft group in any right ventricular metabolites. There was an improvement in myocardial protection over time and a higher proportion of LITA graft patients in the late time period (early group, 63% versus late group, 80%; p < 0.01). Within each time period, there were no differences between the LITA and saphenous vein graft groups. Among patients receiving cold antegrade cardioplegia, the myocardial levels of high-energy phosphates were better preserved in those receiving an LITA graft. CONCLUSIONS: Advances in myocardial protection have led to improved preservation of high-energy phosphate levels after cardioplegic arrest. In patients undergoing elective coronary artery bypass grafting, the use of an LITA graft does not adversely affect myocardial metabolism. Further investigations are required to determine the effects of the use of the LITA during urgent or emergent procedures.

Adenine Nucleotides↗
PubMed1996

Cost-effective provision of cardiac services in a fixed-dollar environment.

In the Canadian single-payer system, all hospital payments, including payments for cardiac operations, are negotiated with the government annually. Each hospital is required to remain within 50 cases of its negotiated surgical target. Physicians are paid on a capitated basis and are subject to penalties if negotiated targets are exceeded. There is a computerized waiting list for cardiac operation, with patients classified by an urgency rating scale and objectives set for the maximum period for any given urgency category. Experience has shown that many patients are delayed in the queue, waiting longer than expected for surgical procedures. Waiting times are not influenced by age, sex, or reoperative status, but are influenced by factors such as the presence of multiple risk factors, the number of diseased vessels, stability or unstability of angina, left main coronary artery disease, and recent angioplasty. Waiting time has not been shown to affect operative mortality, the incidence of postoperative low-output syndrome, or length of hospital stay. Canada's 30-year experience with the provision of cardiac services under managed care may provide useful information to hospitals and physicians in the United States currently confronting capitation. The following overview focuses on two critical issues: negotiation of costs and management of patient waiting lists.

Canada↗
PubMed1996

Age and health status in a patient satisfaction survey.

A picture of patients' satisfaction with interpersonal aspects of hospital-based care (including out-patient and accident and emergency services) was obtained from a postal survey of the general population of Lothian Region in south-east Scotland. Results were broadly in agreement with other national surveys and emphasized the high importance patients attach to being encouraged to ask questions about their treatment, and having their choices explained, including the right to a second opinion. Dissatisfaction decreased markedly with age, and also showed a weaker but significant association with measures of psychosocial health and pain. Social class was associated with feeling patronized or ignored by doctors. The opposite directions of the associations of satisfaction with older age and poorer health respectively, and the necessary correlation between age and health, imply that the effects of health status and age on satisfaction should be estimated from a multivariate model.

Adolescent↗
PubMed1996

Renal vasodilatory effect of endothelial stimulation in patients with chronic congestive heart failure.

OBJECTIVES: This study sought to examine the vasodilatory response of the renal circulation to endothelial stimulation in patients with chronic heart failure. BACKGROUND: Renal blood flow is often reduced in patients with chronic congestive heart failure and may lead to deterioration of renal function. Stimulation of renal endothelium has been shown to cause renal vasodilation in animals and in isolated human renal artery. The vasoregulatory role of the renal endothelium in patients with heart failure has not been evaluated. METHODS: Renal vasodilatory effect of endothelial stimulation with acetylcholine was assessed and compared with that of endothelial independent vasodilation with nitroglycerin. Both drugs were infused into the main renal artery. Renal artery cross-sectional area was measured with intravascular ultrasound and renal blood flow velocity with the aid of an intravascular Doppler technique. RESULTS: Both drugs caused a significant and comparable increase in renal artery cross-sectional area (maximal increase [mean +/- SE] 14 +/- 5% with acetylcholine, 15 +/- 5% with nitroglycerin; both changes < 0.05 vs. baseline). Acetylcholine also caused a significant reduction in renal vascular resistance (maximal reduction 55+/- 6%) and increase in renal blood flow (maximal increase 136 +/- 54%). In contrast, nitroglycerin administration showed no significant effect on renal vascular resistance and blood flow. CONCLUSIONS: Stimulation of endothelium-derived nitric oxide with acetylcholine results in a significant vasodilatory effect on both conductance and resistance renal blood vessels and leads to a marked reduction in renal vascular resistance and enhancement of renal blood blow. Nitroglycerin, an exogenous nitric oxide donor, caused a selective vasodilatory effect on renal conductance but not on resistance blood vessels and failed to increase renal blood flow. These data suggest the possibility that stimulation of endogenous nitric oxide production in the kidney could be used as a therapeutic target for enhancement of renal flow in patients with heart failure.

Acetylcholine↗
PubMed1996

Nitric oxide regulates insulin secretion in the isolated perfused human pancreas via a cholinergic mechanism.

BACKGROUND: The purpose of this study was to determine whether nitric oxide regulates insulin secretion in the isolated perfused human pancreas. METHODS: Single-pass perfusion was performed in four pancreata with a modified Krebs medium. Sequential 10-minute infusions (separated by 10-minute basal periods) of (1) 25 nmol/L acetylcholine, (2) 2.5 mumol/L acetylcholine, and (3) 16.7 mmol/L glucose were initially infused. Then 0.1 mumol/L of NG-monomethyl-L-arginine (NMMA) was infused during a period of 10 minutes, and steps (1) through (3) were repeated. The change in insulin secretion from basal levels during each stimulation was calculated and compared with that seen after NMMA infusion. RESULTS: Infusion of 25 nmol/L and 2.5 mumol/L acetylcholine resulted in a significant stimulation of insulin secretion before NMMA infusion (p < 0.05) and after NMMA infusion for acetylcholine at 25 nmol/L (p < 0.05). There was a significant decrease in acetylcholine-induced insulin secretion after NMMA infusion for acetylcholine at 25 nmol/L and 2.5 mumol/L compared with before NMMA infusion (p < 0.05). Infusion of 16.7 mmol/L glucose significantly stimulated insulin secretion before and after NMMA infusion, but there was no significant difference seen with insulin secretion before and after NMMA infusion. Insulin secretion was significantly inhibited during NMMA infusion (p < 0.05). CONCLUSIONS: These data show that infusion of the nitric oxide synthase inhibitor NMMA suppressed cholinergic-stimulated insulin secretion but did not affect glucose-stimulated insulin secretion. We conclude that nitric oxide regulates insulin secretion in the isolated perfused human pancreas.

Acetylcholine↗
PubMed1996

Inhibition of catalase in mesencephalic cultures by L-DOPA and dopamine.

Catalase activity in cell cultures of fetal rat mesencephalon was decreased by 42 and 50%, respectively, after exposure to L-3,4-dihydroxyphenylalanine (L-DOPA, 100 microM) or dopamine (100 microM) for 48 h. Catalase activity was also decreased 21% by 10 microM hydroquinone. Ascorbic acid (200 microM), an agent that suppresses the autoxidation of L-DOPA and dopamine, blocked the anti-catalase effect of L-DOPA, but not that of dopamine. Inhibitors of the A and B forms of monoamine oxidase (20 microM clorgyline plus 20 microM pargyline) had no effect on the anti-catalase action of either L-DOPA or dopamine. The latter results suggest that products of the oxidative deamination of dopamine by monoamine oxidase are not involved in the suppression of catalase activity. However, autoxidation reactions of L-DOPA may play a role since ascorbate suppressed the anti-catalase effect of L-DOPA. On the contrary, the basis for the failure of ascorbate to similarly block the anti-catalase effect of dopamine is uncertain. L-DOPA and dopamine (25 microM) also inhibited crystalline catalase in solution after incubation for 1 h at neutral pH (40-50% inhibition). Inhibition was blocked by 0.45 M ethanol, indicating a need for autoxidation and the formation of compound II, which is an enzymatically inactive form of catalase. The ability to model the enzyme inhibition in purely chemical experiments indicates a probable mechanism for loss of enzymatic activity in cell cultures. Inhibition of catalase may contribute to cell damage during incubation of cultures with L-DOPA, dopamine, or other autoxidizable compounds.

Animals↗
PubMed1996

L-DOPA up-regulates glutathione and protects mesencephalic cultures against oxidative stress.

Incubation with L-DOPA induced a rise in GSH level in cultures of fetal rat mesencephalon, mouse neuroblastoma (Neuro-2A), human neuroblastoma (SK-N-MC), pig kidney epithelial cells (LLC-PK1), and glia from newborn rat brain, but not C6 glioma cells or neuronal cultures (no glia) from the mesencephalon. The pure neuronal cultures were destroyed by incubation with L-DOPA; added ascorbic acid or superoxide dismutase protected the cells. Washout of L-DOPA after 48 h amplified the rise in GSH content in mixed cultures (neurons plus glia). Examination of structure-activity relationships for elevating GSH levels in responsive cell types revealed that autooxidizable compounds (alpha-methyl-DOPA, dopamine, apomorphine, catechol, and hydroquinone) behaved similarly to L-DOPA, whereas structural analogues that cannot undergo autooxidation (3-O-methyl-DOPA, tyrosine, 2,4-dihydroxyphenylalanine, and resorcinol) failed to elevate GSH levels. Therefore, up-regulation of GSH appears to be a response to a mild oxidative stress. When mixed mesencephalic cultures were exposed to a strong oxidant stress by incubation with tert-butyl hydroperoxide, a loss in viability was seen. Cultures pretreated with L-DOPA or hydroquinone were protected from loss of viability. However, when cultures were pretreated with both L-DOPA and ascorbate, which prevents the rise in GSH level, protection was lost, in accord with the failure to up-regulate GSH. These results show that the up-regulation of cellular GSH evoked by autooxidizable agents is associated with significant protection of cells. Glia play an essential role in the response of mesencephalic cell cultures. An ability to up-regulate GSH may serve a protective role in vivo.

Animals↗
PubMed1996

Idiopathic polypoidal choroidal vasculopathy associated with retinal arterial macroaneurysm and hypertensive retinopathy.

BACKGROUND: Idiopathic polypoidal choroidal vasculopathy (IPCV), the posterior uveal bleeding syndrome, and multiple recurrent serosanguineous pigment epithelial detachments in black women are a heterogeneous group of related entities seen in elderly hypertensive females. Similar associations are known for retinal arterial macroaneurysm (RAM). METHODS: This report documents the clinical, fluorescein, and indocyanine green videoangiographic findings of two elderly black female hypertensive patients who presented with IPCV, RAM, and hypertensive retinopathy. RESULTS: Clinical, fluorescein, and indocyanine green videoangiographic analysis of these two patients revealed hypertensive retinopathy, RAM, and anomalous polypoidal vascular networks associated with focal "bead-string" constrictions, terminal vascular loops, and polypoidal and pinpoint choroidal nodules. CONCLUSION: Certain subgroups of IPCV and related entities and RAM may be pathophysiologically related as analogous hypertensive insults to the choroidal and retinal vascular beds.

Aged↗
PubMed1996

Distribution of thiols in microorganisms: mycothiol is a major thiol in most actinomycetes.

Mycothiol [2-(N-acetylcysteinyl)amido-2-deoxy-alpha-D-glucopyranosyl- (1-->1)-myo-inositol] (MSH) has recently been identified as a major thiol in a number of actinomycetes (S. Sakuda, Z.-Y. Zhou, and Y. Yamada, Biosci. Biotech. Biochem. 58:1347-1348, 1994; H. S. C. Spies and D. J. Steenkamp, Eur. J. Biochem. 224:203-213, 1994; and G. L. Newton, C. A. Bewley, T. J. Dwyer, R. Horn, Y. Aharonowitz, G. Cohen, J. Davies, D. J. Faulkner, and R. C. Fahey, Eur. J. Biochem. 230:821-825, 1995). Since this novel thiol is more resistant than glutathione to heavy-metal ion-catalyzed oxidation, it seems likely to be the antioxidant thiol used by aerobic gram-positive bacteria that do not produce glutathione (GSH). In the present study we sought to define the spectrum of organisms that produce MSH. GSH was absent in all actinomycetes and some of the other gram-positive bacteria studied. Surprisingly, the streptococci and enterococci contained GSH, and some strains appeared to synthesize it rather than import it from the growth medium. MSH was found at significant levels in most actinomycetes examined. Among the actinobacteria four Micrococcus species produced MSH, but MSH was not found in representatives of the Arthrobacter, Agromyces, or Actinomyces genera. Of the nocardioforms examined, Nocardia, Rhodococcus, and Mycobacteria spp. all produced MSH. In addition to the established production of MSH by streptomycetes, we found that Micromonospora, Actinomadura, and Nocardiopsis spp. also synthesized MSH. Mycothiol production was not detected in Propionibacterium acnes or in representative species of the Listeria, Staphylococcus, Streptococcus, Enterococcus, Bacillus, and Clostridium genera. Examination of representatives of the cyanobacteria, purple bacteria, and spirochetes also gave negative results, as did tests of rat liver, bonito, Candida albicans, Neurospora crassa, and spinach leaves. The results, which indicate that MSH production is restricted to the actinomycetes, could have significant implications for the detection and treatment of infections with actinomycetes, especially those caused by mycobacteria.

Actinomycetales↗
PubMed1996

Measuring outcomes: one month survival after acute myocardial infarction in Scotland.

OBJECTIVE: To examine 30 day survival after acute myocardial infarction as an outcome indicator, and explore the effects of adjusting for available prognostic factors such as age, sex, co-morbidity, deprivation, and deaths outside hospital. DESIGN: Cohort study. SETTING: The Scottish Record Linkage System was analysed. This national data-base links inpatient data to death certificate information for a population of 5.1 million. SUBJECTS: All 40,371 admissions to hospital with a principal diagnosis of acute myocardial infarction, plus all 18,452 deaths outside hospital with a principal cause of death registered as acute myocardial infarction (ICD9 code 410) during 1988-1991. MAIN OUTCOME MEASURES: The outcome event was death from any cause, within hospital or elsewhere, within 30 days of admission. RESULTS: During 1988-1991, 30 day survival after acute myocardial infarction was 77% in 40,371 hospital admissions, but only 53% when 18,452 acute myocardial infarction deaths in the community were included (a population-based outcome indicator with many advantages). Using logistic regression at an individual patient level, the odds of dying within 30 days effectively doubled for each decade of age (odds ratio compared with patients aged under 55: 2.3 aged 55-64, 4.4 aged 65-74, 8.2 aged 75-84, 12.0 aged 85 plus); were marginally higher in females than in males (odds ratio 1.07); were almost doubled in patients with a history of previous infarction, coronary heart disease, or other heart disease, and were also significantly increased in patients with circulatory disease, respiratory disease, neoplasm, or diabetes. Socioeconomic deprivation had no significant effect. Marked variations in survival between different hospitals and health board areas persisted, even after adjusting for the above prognostic factors. CONCLUSION: One month survival after acute myocardial infarction could be a useful means of measuring outcome of hospital care. There was important geographical variation in one month survival. These differences could be accounted for by variations in referral, admission, diagnosis, definition, and coding. These variables merit further research and local clinical audit before one month survival after acute myocardial infarction can be reliably used for detecting differences in quality of care. In addition, it would be essential to take account of infarct severity.

Age Factors↗
PubMed1996

Results of combined pulmonary resection and cardiac operation.

BACKGROUND: Concomitant lesions of the heart and lung are uncommon, but when present they pose a therapeutic challenge for thoracic surgeons. A combined procedure avoids the need for a second major thoracic procedure and may improve outcomes and provide economic benefit. However, cardiopulmonary bypass may adversely affect the natural history of pulmonary malignancies. METHODS: The clinical records of 30 patients were reviewed who underwent simultaneous lung resection and cardiac operations between January 1982 and July 1995. Follow-up was obtained on all 30 patients (mean follow-up, 22 months; range, 1 to 100 months). RESULTS: Twenty-four patients underwent coronary artery bypass grafting in conjunction with pulmonary resection. Six patients underwent aortic (n = 4) or mitral (n = 2) valve replacement. The pulmonary resections consisted of pneumonectomy (n = 3), lobectomy (n = 14), wedge excision (n = 12), and tracheal resection (n = 1). Twenty-one patients had pathologic findings that confirmed adenocarcinoma (n = 10), squamous cell carcinoma (n = 5), small cell carcinoma (n = 2), or other malignancy (n = 4). Tumor stage of primary lung cancers was stage I, n = 12; stage II, n = 3; and stage IIIa, n = 2. Pathologic examination revealed benign disease in 9 patients. There were two operative deaths, one due to aspiration and one due to stroke. There were three late deaths, two cardiac and one of metastatic disease. Overall late survival was 85% +/- 7% and 73% +/- 16% at 1 and 5 years, respectively. Actuarial survival for patients with malignant disease was 64% at 5 years. CONCLUSIONS: Simultaneous cardiac operation and lung resection was not associated with increased early or late morbidity or mortality. Cardiopulmonary bypass does not adversely affect survival in patients with malignant disease. Cardiac valve replacement can be performed safely in conjunction with pulmonary resection.

Actuarial Analysis↗
PubMed1996

A modified catalase assay suitable for a plate reader and for the analysis of brain cell cultures.

The enzyme catalase is present in relatively small amounts in neural tissue. A standard spectrophotometric assay for catalase has been modified to make it suitable both for automated assay with a plate reader and for the analysis of neural cell cultures. Catalase activity is determined by measuring residual hydrogen peroxide after incubation with the enzyme. Ferrous ions and thiocyanate are used for the spectrophotometric determination of hydrogen peroxide. The stable visible absorption of ferrithiocyanate can be measured either with a plate reader or a spectrophotometer. The method assays catalase activity from single wells of a tissue culture plate containing 2-3 mg of embryonic rat mesencephalon.

Animals↗