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Biomedical subjects

C Wright

Publications and source records attributed to C Wright.

At least 163 records · Page 9Linked to original sources
PubMed1995

Characterization of a sporozoite antigen common to Plasmodium falciparum and Plasmodium berghei.

Previous studies demonstrated that immunization with Plasmodium falciparum sporozoites protected mice against Plasmodium berghei sporozoite infection and that this cross-protection was mediated, at least in part, by anti-sporozoite antibody. The experiments presented in this report show that serum and monoclonal antibodies derived from these protected mice identify a novel 42/54-kDa antigen (designated Circumsporozoite Protein 2 or CSP-2) in both P. falciparum and P. berghei sporozoites. Anti-CSP-2 monoclonal antibody blocks invasion of P. falciparum and P. berghei sporozoites into hepatoma cells in vitro and binds the cell surface of sporozoites. Passive transfer of anti-CSP-2 monoclonal antibody protected mice from P. berghei sporozoite infection. Therefore, CSP-2 appears to play a role in the cross-protective immune response observed.

Animals↗
PubMed1995

Does the exercise protocol matter when assessing the anti-anginal effects of drug therapy?

Four exercise test protocols (Bruce, Balke, Ellestad and Steep) were compared in 16 patients with proven coronary artery disease in demonstrating the anti-anginal effects of sublingual glyceryl trinitrate in a randomization double-blind trial. Glyceryl trinitrate significantly improved the time, heart rate and rate pressure product to peak exercise, onset of angina and 1 mm ST segment depression in all four protocols (P < 0.05) (except rate pressure product to angina in the Balke protocol). The increase in exercise time was greatest for the Balke protocol at peak exercise (188.1 +/- 187.1) (mean +/- SD in s), at onset of angina (251.9 +/- 247.1) and at 1 mm ST depression (233.6 +/- 243.8), followed by the Steep and Bruce protocols, and was lowest for the Ellestad protocol 41.9 +/- 42.4, 96.5 +/- 65.8, 82.6 +/- 74.0, respectively. Increase in time to peak exercise with glyceryl trinitrate was significantly greater for the Balke protocol in comparison with the other three protocols and for the Bruce and Steep protocols when compared to the Ellestad protocol. Time to 1 mm ST depression with treatment was significantly greater on the Balke and Bruce protocols than the Ellestad protocol, and to onset of angina for the Balke compared to other three protocols. There were no significant differences between the Bruce and Steep protocols for any of the endpoints. The magnitude of treatment effect in the different protocols was accompanied by correspondingly greater inter-patient variability such that no protocol was more, or less, sensitive than another in detecting treatment effect. Changes in heart rate and rate pressure product with treatment were generally similar between the different protocols. In conclusion, a protocol with small and frequent increments (Balke), although able to show greater increase in exercise duration with glyceryl trinitrate than more aggressive protocols, is no more sensitive at detecting treatment effect.

Adult↗
PubMed1995

Detection of ambulatory ischaemia is not of practical clinical value in the routine management of patients with stable angina. A long-term follow-up study.

It has been reported that medically treated patients with stable angina and positive exercise test for ischaemia have an adverse 1-2 year outlook if they are shown also to have transient, and predominantly silent, ischaemic episodes detected by ambulatory ST segment monitoring during their daily activities: it has been suggested that this investigation could be used to identify patients more likely to benefit from early investigation and treatment. We assessed the long-term (up to 65 months) prognostic significance of transient ischaemic episodes during daily activities in 172 patients routinely attending cardiac outpatients with medically treated stable angina who had undergone exercise testing and 48 h of ambulatory ST segment monitoring between February 1988 and August 1989 for this purpose. A positive exercise test for ischaemia was not a prerequisite for inclusion. One hundred and four patients (60.5%) had a positive exercise test for ischaemia and 72 (42%) had transient ischaemia during daily activities (63 had both tests positive). Over a median 50-month follow-up period 54 patients suffered at least one cardiac event (primary event: cardiac death n = 7; non-fatal myocardial infarction n = 11; unstable angina n = 18; elective CABG/PTCA n = 18). Two further patients suffered non-cardiac death. Cardiac events, either objective (cardiac death or non-fatal myocardial infarction) or subjective (unstable angina or revascularisation) were no more likely to occur in those with transient ischaemia during daily life when compared with those without, at follow-up times up to 65 months.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Ethical issues in biological psychiatric research with children and adolescents.

OBJECTIVE: This article reviews, discusses, and elaborates considerations and recommendations summarized by the biological research working group at the May 1993 NIMH conference on ethical issues in mental health research on children and adolescents. METHOD: Notes from the conference were summarized and supplemented by a computer search of relevant literature. Drafts were circulated for comment to national and international experts, some of whom joined as coauthors. RESULTS: Issues addressed include possible overprotection by policy makers and institutional review boards arising out of the recognition of children's special vulnerability without equal recognition of their need for research; the definition of minimal risk, which has often been equated with no risk in the case of children; assessment of the risk-benefit ratio; procedures for minimization of risk, such as improved technology, "piggybacking" onto clinical tests, and age-appropriate preparation; the difficulty of justifying risk for normal controls; age-graded consent; special considerations about neuroimaging; "coercive" inducement, both material and psychological; disposition of unexpected or unwanted knowledge about individuals, including the subject's right not to know and parent's right not to tell; and socioeconomic status and cultural/ethnic equity. CONCLUSIONS: The working group adopted a position of advocacy for children's right to research access while recognizing that this advocacy must be tempered by thoughtful protections for child and adolescent subjects.

Adolescent↗
PubMed1995

Expression of retinoblastoma gene product and p53 protein in bladder carcinoma: correlation with Ki67 index.

OBJECTIVES: To determine whether loss of the tumour suppressor gene retinoblastoma (Rb) and increased expression of the p53 protein were associated with increased tumour cell growth fraction. PATIENTS AND METHODS: Tumours from 105 patients (72 men, 33 women; median age 69 years, range 35-89) with newly diagnosed primary transitional cell bladder carcinoma were studied. Tumour samples were taken by means of cystoscopic resection. Expression of the retinoblastoma (Rb) and p53 gene products was assessed immunohistochemically in 98 of the carcinomas. The proportion of cells expressing the Ki67 antigen (Ki67 index which is a measure of growth fraction) was determined in 64 cases. RESULTS: p53 protein was detectable in 50% and Rb protein in 82% of the tumours. Staining for p53 and lack of staining for Rb protein were associated with muscle-invasive growth and high tumour grade (G3). The Ki67 index varied over a wide range (1-47%), but there were significant differences between mean indices for poorly differentiated (G3) and well or moderately differentiated (G1/G2) tumours, and between indices for muscle-invasive and the remaining tumours. The mean Ki67 indices for Rb-negative tumours and p53-positive tumours were approximately twice those for Rb-positive and p53-negative tumours. Only 10% of the tumours expressed high levels of p53 protein and failed to express Rb. CONCLUSION: These observations are consistent with the hypothesis that loss of Rb and mutation and overexpression of p53 are associated with an increased tumour cell growth fraction and that such changes may play a role in the de-regulation of cell proliferation in transitional cell carcinoma of the bladder.

Adult↗
PubMed1995

Treatment of sepsis-associated severe acute renal failure with continuous hemodiafiltration: clinical experience and comparison with conventional dialysis.

The syndrome of sepsis-associated severe acute renal failure is a frequent component of sepsis-induced multiorgan failure. Continuous hemofiltration techniques are often used in its dialytic management but little is known about their impact. The aim of this study is to define the biochemical and clinical impact of continuous hemodiafiltration (CHD) in the management of this syndrome and to retrospectively compare it to that of conventional dialysis. A prospective, cohort study and retrospective comparison with historical controls was conducted at an intensive care unit (ICU) of a tertiary institution. Eighty-seven consecutive septic patients with acute renal failure were treated by continuous hemodiafiltration and 40 consecutive similar patients by conventional dialysis. All new cases of severe acute renal failure with sepsis were treated by means of continuous hemodiafiltration. Historical controls were treated by means of conventional dialysis. Illness and sepsis severity were assessed on admission and prior to initiation of treatment. Biochemical variables were assessed daily. Outcome was measured as discharge from the ICU, duration of oliguria and discharge from hospital. Of the 87 patients treated by hemodiafiltration, 86 had multiorgan failure, 71 (81.6%) septic shock and 52 (59.8%) bacteremia/fungemia. Their APACHE II score on admission was 29.9 and their mean organ failure score prior to treatment was 4.3. Hemodiafiltration resulted in a significant fall in mean urea and creatinine levels within 24 h and in the correction of acidosis. The mean alveolar-arterial gradient fell from 276 to 211 mm Hg (p < 0.02) within 24 h of therapy. Complications were few and mostly related to vascular access.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗
PubMed1995

Severe acute renal failure: a comparison of acute continuous hemodiafiltration and conventional dialytic therapy.

It is unknown whether continuous renal replacement techniques result in diminished morbidity and mortality when compared to conventional dialytic techniques. To investigate this issue a previously described, retrospectively studied group of critically ill patients with severe acute renal failure treated by conventional dialysis (CD) was compared to a prospectively studied group of similar patients treated by acute continuous hemodiafiltration (ACHD). A combined retrospective and prospective clinical and laboratory investigation was carried out for 234 consecutive critically ill patients with severe acute renal failure in the intensive care unit of a tertiary institution. Biochemical, clinical and outcome data in all patients treated by conventional dialytic techniques (intermittent hemodialysis and/or peritoneal dialysis) during a 5-year period were retrospectively analyzed, and a prospective analysis of the same biochemical, clinical and outcome data in all patients treated by acute continuous hemodiafiltration was done over a similar time span, with statistical comparison of findings. One hundred and fifty patients were treated by ACHD and 84 by CD. ACHD patients were more severely ill (mean APACHE II score: 28.2 vs. 25.8; p < 0.01) and older (mean age: 59.9 vs. 55.5 years; p < 0.01). There were no significant differences in the incidence of sepsis, bacteremia and need for mechanical ventilation. ACHD resulted in better control of uremia (mean steady-state plasma urea level: 20.1 vs. 31.7 mmol/l; p < 0.001) and hyperphosphatemia (mean serum phosphate: 1.26 vs. 1.95 mmol/l) after 24 h of initiation of therapy. It also allowed the administration of full nutritional support in a significantly greater percentage of patients (91.3 vs. 64.8%; p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗
PubMed1995

Physician interventions in alcoholism--past and present.

Controversy over how physicians could address the public and private agonies inflicted by alcohol-related disorders has remained active throughout American history. Public and professional attention during the past quarter century has focused primarily on the identification and referral for treatment of the alcohol-dependent or alcoholic individual. Recent controlled research into medical intervention has shown that primary care physicians have an important opportunity to reduce the severity of alcohol-related problems at many points along their course and can provide effective care in the office setting. This article describes how these interventions have developed and highlights their importance in the context of recent changes in health care delivery systems.

Adult↗
PubMed1995

Long-term outcome related to epidermal growth factor receptor status in bladder cancer.

For bladder cancer we currently lack accurate methods of predicting outcome, although clinical stage and histological grade are broad determinants of prognosis. Preliminary data have indicated that assessment of epidermal growth factor receptor status is a method of further subclassifying bladder cancer. We assessed prospectively the clinical significance of determining epidermal growth factor receptor status in 212 patients with newly diagnosed bladder cancer who were followed for 1 to 96 months (mean 26.5). In multivariate analyses epidermal growth factor receptor was confirmed to be an independent predictor of survival (p = 0.004) and stage progression (p = 0.0004). Most importantly, epidermal growth factor receptor status was found to be 80% sensitive and 93% specific in predicting stage progression in T1, grade 3 bladder cancer. We conclude that epidermal growth factor receptor status is a useful molecular marker in patients with bladder cancer, especially those without infiltration of the detrusor muscle at presentation.

Adult↗
PubMed1995

Medications development for alcohol use disorders.

There are substantial differences between the objectives and processes of normal grant-funded research and those of commercial pharmaceutical development. These differences are explained with respect to clinical trials design in alcohol addiction, strategies for maximizing the success of controlled trials in drug development in this area, and avoidance of problems in the conducting of clinical trials subject to audit. Also discussed are possible new pharmacological interventions in alcohol use disorders and the need to recognize the usefulness of medications across the whole range of clinical presentations.

Alcohol Deterrents↗
PubMed1994

Assessment of cancer clusters using limited cohort data with spreadsheets: application to a leukemia cluster among rubber workers.

This paper presents methods for initial investigation of occupational cancer clusters using limited data. Phase 1 of the methods developed uses basic data from the cluster of cases, but with cohort data limited to the size of the workforce at the plant. Phase 2 of the methods requires knowledge of the number of workers entering and leaving the workforce in each year. In the absence of data concerning age, the spreadsheet programs explore a variety of worker age distributions in synthetic cohort analyses. The methods were used to assess a cluster of six cases of leukemia with an average duration of work of 11 years in a tire manufacturing plant. It was concluded that the relative risk for the age range 30-50 was at least 7, providing further evidence for the association of leukemia with work in tire manufacture. The use of spreadsheet programs can provide a valuable first step assessment of apparent workplace cancer clusters.

Adult↗
PubMed1994

NDP-K/nm23 expression in human breast cancer in relation to relapse, survival, and other prognostic factors: an immunohistochemical study.

The nm23 gene was originally identified by Steeg et al. by screening of cDNA libraries from murine melanoma cell lines of varying metastatic potential. An inverse relationship between metastatic potential and nm23 RNA and/or protein was found in four different metastatic model systems. It was proposed that nm23 may function as a suppressor gene for tumour metastasis. It has recently been found that the sequence of nm23 and NDP-kinase (NDP-K) is identical. Using an immunohistochemical technique and employing a polyclonal antibody to purified NDP-K A, we have determined NDP-K expression in a series of 197 breast carcinomas. One hundred and sixty (81.2 per cent) of these tumours were scored positive for NDP-K and 37 (18.8 per cent) scored negative. No relationship was found between NDP-K/nm23 expression and patient relapse or survival. Furthermore, no relationship was found between NDP-K/nm23 expression and a number of other prognostic factors including tumour grade, oestrogen receptor, progesterone receptor, and p53 expression. Our results contradict the hypothesis concerning the possible role of NDP-K/nm23 as a metastatic suppressor gene in human breast cancer, but further studies using antibodies specific for NDP-K/nm23 subtypes are clearly indicated.

Breast Neoplasms↗
PubMed1994

Taurine protects against oxidant-induced lung injury: possible mechanism(s) of action.

It is thought that oxidant-induced tissue damage is not a direct effect of the oxidant per se, but rather results from the inflammatory response that occurs thereafter. As a result of inflammation following oxidant exposure, there are neutrophils, monocytes, and macrophages with myeloperoxidase-H2O2-halide activity in the lung. Leukocytes and especially neutrophils contain high intracellular concentrations (22-50mM) of taurine (6, 8, 11, 20). Taurine acts as a trap for toxic hypochlorous acid (HOCl) and forms the less reactive metabolite, N-chlorotaurine (5-6). Thus, the biological activity of halide-dependent myeloperoxidase may be regulated by endogenous taurine. Although taurine had no effect in the present study, polymorphonuclear leukocytes have an active myeloperoxidase system capable of producing N-chlorotaurine (9, 19) and would be present at the site of inflammation in oxidant-exposed lungs. Our data suggest that taurine via N-chlorotaurine formation may protect the lung from oxidant injury, at least in part, by inhibiting production of nitrite and TNF-alpha. Moreover, lavage cells isolated from rats pretreated with taurine and exposed to O3 have a significant decrease in the production of nitrite and TNF-alpha, compared with lavage cells from rats exposed to O3 without taurine supplementation (preliminary studies). Both the concentration of taurine and the effects of N-chlorotaurine strengthen the potential impact of this chlorinated amine in vivo. N-Chlorotaurine may protect against oxidant-induced lung injury by inhibiting production of nitrite and the release of TNF-alpha which are both known to be directly linked to tissue injury.

Amino Acid Oxidoreductases↗
PubMed1994

Which nutritional measurements assess protein-energy nutritional status in patients receiving home parenteral nutrition?

Weight, midarm circumference, triceps skinfold thickness, arm muscle circumference, albumin, prealbumin, transferrin and total lymphocyte count were measured at each outpatient visit in patients reveiving home parenteral nutrition from September 1987 to November 1991. Each nutritional variable was analysed for individuals and for the whole group. Group data were expressed using the actual values obtained and successive differences (the change between clinic attendances). Nutritional variables were evaluated using a correlation matrix. Identical analysis of individual and group data demonstrates that laboratory investigations are of little value in the assessment of nutritional status in patients receiving home parenteral nutrition. Anthropometry detected changes in body weight secondary to changes in muscle and/or fat in 80% of patients. Pooling anthropometric data distors the relationship between variables owing to inter-individual variability when actual values are used. The method of successive differences is the preferred method of analysis for group anthropometric data.

Journal Article↗