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Biomedical subjects

C Wright

Publications and source records attributed to C Wright.

At least 199 records · Page 11Linked to original sources
PubMed1993

Prognostic significance of transient ST segment changes after coronary artery bypass surgery: a long-term (4-10 year) follow up study.

OBJECTIVE: To assess the long-term (four to 10 years) prognostic significance of transient ST segment changes on ambulatory ST segment monitoring after coronary artery bypass grafting (CABG). PATIENTS AND METHODS: 76 patients (67 men, nine women) underwent CABG between 1982 and 1984 (n = 31) and between 1987 and 1988 (n = 45) and at a mean age of 57. All underwent 48 hours of ambulatory ST segment monitoring at a mean of 19 weeks after surgery. The results were available for assessment. All general practitioners were contacted and patients' notes reviewed. Patients were contacted by telephone. Details were recorded of intervening events (acute myocardial infarction, unstable angina, need for further revascularisation, and deaths). Event free survival curves were produced for those with and without transient ST segment changes during routine postoperative ambulatory ST segment monitoring. RESULTS: During 3213 hours of monitoring after CABG, 21 (27.6%) of 76 patients had transient ST segment changes, of which 70% were silent. Over a mean 70 month follow up period, patients with such ischaemic changes were no more likely to have either an objective (myocardial infarction or cardiac death) or subjective (unstable angina or another revascularisation) event than those patients without ischaemic changes. This finding was the same in patients operated on between 1987 and 1988 and between 1982 and 1984. CONCLUSIONS: Although ambulatory ST segment monitoring is becoming increasingly popular in some countries as a routine investigation for ischaemia in various coronary subgroups, the findings of such an investigation, when performed after CABG, do not help to identify a subgroup more likely to have an adverse outcome during up to 10 years of follow up. There seems to be no reason to perform this investigation after surgery, and particularly to refer patients for reinvestigation because of the detection of predominantly silent ST segment changes of uncertain relevance.

Adult↗
PubMed1993

Renal concentrating capacity test by desmopressin in children: intranasal or intravenous route?

Intranasal administration of desmopressin (dDAVP) is frequently used to test renal concentrating capacity in children. However, the bioavailability of intranasal dDAVP is about 10% and may be modified by nasal congestion. The study aimed to compare the efficacy of intranasal dDAVP with an equivalent dose of intravenous dDAVP for a renal concentrating capacity test in children. We studied 18 children aged 12.6 +/- 3.8 years weighing more than 20 kg in whom a dDAVP test was indicated as part of global renal function evaluation. Spray applicator (Minirin Spray) was used for intranasal administration (20-40 micrograms according to BW); the dose of intravenous dDAVP (Minirin IV) was reduced to 10% (2-4 micrograms according to BW). A randomized sequence was used for the first intranasal or intravenous dDAVP test; the second alternate test was repeated in the same children in a time interval ranging from 1 to 3 weeks. Osmolality of the urine (Uosm, mosm/kg) was determined before (T0), then 2 (T2) and 4 (T4) h after dDAVP administration. There was no significant difference in Uosm at T0 (intranasal = 480 +/- 212, intravenous = 443 +/- 168 mosm/kg), T2 (604 +/- 226 and 542 +/- 173 mosm/kg, respectively), and T4 (657 +/- 206 and 629 +/- 190 mosm/kg, respectively). There was an obvious correlation between intranasal and intravenous Uosm at T4 (r2 = 0.826; p = 0.001). Even if intravenous dDAVP is of theoretical interest, intranasal administration of dDAVP using a spray applicator can be considered as first-choice method for a renal concentrating capacity test in children weighing more than 20 kg.

Administration, Intranasal↗
PubMed1993

Change and opportunity in ambulatory care.

Non-inpatient care is assuming greater importance within the Australian health system. The management of the delivery of health services is becoming a responsibility of clinicians. Clinicians, nurses, managers and academics need to come together to advance these issues. This paper outlines the thinking at Monash Medical Centre, a new 747-bed tertiary hospital situated in the south-eastern suburbs of Melbourne.

Continuity of Patient Care↗
PubMed1993

Attenuation of chronic hypoxic pulmonary hypertension in rats by cyclooxygenase products and by nitric oxide.

We wanted to assess the respective roles of arachidonic acid products and nitric oxide in the modulation of pulmonary hypertension in chronically hypoxic rats. In isolated blood-perfused lungs, the effects of arachidonic acid before and after treatment with the cyclooxygenase inhibitor, meclofenamate, were compared in control (C) rats and rats exposed for two weeks to 10% oxygen (chronic hypoxia CH). Arachidonic acid caused mixed dilator and constrictor effects during both normoxia and hypoxia; dilatation was more prominent in chronically hypoxic rats. Meclofenamate abolished both dilator and constrictor actions of arachidonic acid; it raised baseline, normoxic pulmonary artery pressure, in chronically hypoxic but not control rats, which suggests that dilator products of arachidonic acid are released in the pulmonary hypertension of chronic hypoxia and attenuate pulmonary artery pressure. As shown previously, the nitric oxide synthase inhibitor N-nitro-L-arginine methyl ester (L-NAME) raised pressure in chronically hypoxic but not control rats. Meclofenamate and L-NAME given in sequence both raised pulmonary artery pressure in chronically hypoxic rats and the combined rise was substantial (+13 mmHg). We conclude that, in the conditions of our experiment, both nitric oxide and dilator prostanoids are released in hypoxic pulmonary hypertension in rats. Thus, two synthetic processes, both possibly endothelial dependent, may modulate hypoxic pulmonary hypertension.

Amino Acid Oxidoreductases↗
PubMed1993

Agnathia-holoprosencephaly: a new recessive syndrome?

The association between agnathia and holoprosencephaly is well documented (Pauli et al., 1981). Pauli et al. described two female sibs with agnathia and holoprosencephaly who were subsequently shown to carry an unbalanced 46,XX, der 18,t(6;18)(pter p24.1) karyotype (Pauli et al., 1983; Krassikoff and Sekhon, 1989). All other cases have been sporadic (Cohen, 1989). We present a recurrence of agnathia-holoprosencephaly in an unrelated European couple and postulate that this association may represent an autosomal recessive syndrome.

Abnormalities, Multiple↗
PubMed1992

Immunohistochemical demonstration of glutathione S-transferases in primary human breast carcinomas.

The expression of cytosolic glutathione S-transferase (GST) isoenzymes has been assessed in a series of 74 primary human breast carcinomas using an immunohistochemical method. GST pi was detected in sections from all 74 tumours; it was expressed by non-epithelial (stromal and inflammatory) cells in 62 tumours (84 per cent), but by tumour epithelium in only 35 (47 per cent). Non-neoplastic mammary epithelium was uniformly positive for GST pi. Expression of GST alpha and mu was observed in 19 and 42 per cent of the tumours, respectively, and was largely confined to the neoplastic component. Lack of staining of tumour epithelium for GST pi was significantly associated with poorer tumour differentiation (higher grade). There was no association between expression of any of the three isoenzymes and either menopausal status or expression of c-erbB-2 oncogene protein product. Immunohistochemistry is a useful method for the investigation of expression and cellular localization of GSTs within tumours; such data are needed to improve our understanding of the role of these enzymes in neoplasia and in resistance to cytotoxic drug therapy.

Adult↗
PubMed1992

Retinoblastoma and p53 gene expression related to relapse and survival in human breast cancer: an immunohistochemical study.

Inactivation of tumour suppressor genes may be an important aetiological factor in many human cancers including breast. In a study of 197 breast cancer patients, tumour tissue was snap-frozen at the time of surgery and immunohistochemical labelling for p53 protein and retinoblastoma (Rb) gene product carried out using an indirect immunohistochemical technique. Tumours were scored by two independent observers for the intensity of nuclear staining for each antibody. Expression of p53 protein showed a significant association with a shorter time to relapse (P = 0.03) and death (P = 0.02) (log rank test). p53 expression did not correlate with nodal status but showed a significant association with high tumour grade (P = 0.001). Rb gene expression showed no relationship to relapse or survival but loss of expression showed a significant correlation with positive lymph node status. The manner by which these proteins might act to determine tumour behaviour remains to be established.

Breast Neoplasms↗
PubMed1992

Effects of coronary artery bypass surgery and angioplasty on the total ischemic burden: a study of exercise testing and ambulatory ST segment monitoring.

To assess the effects of standard therapeutic interventions on the total ischemic burden, 86 patients with stable angina underwent 48 hours of ambulatory ST segment monitoring and treadmill exercise testing before and at a mean of 10 weeks after coronary artery bypass surgery (CABG) (group 1, N = 46) or percutaneous transluminal coronary angioplasty (PTCA) (group 2, N = 40). There were 72 male and 14 female patients with a mean age of 56.4 years. All patients had documented coronary artery disease (24, single-vessel; 28, two-vessel; 34, three-vessel disease). Both groups were characteristically similar apart from more severe coronary artery disease (p less than 0.001) and more previous myocardial infarctions (p less than 0.05) in group 1. Groups with CABG and PTCA had significant prolongation of exercise time after intervention (group 1: 7.6 to 9.8 minutes, p less than 0.0001; group 2: 8.1 to 10.0 minutes, p less than 0.001), and both interventions led to a significant reduction in ischemic responses (group 1: 33 to 4, p less than 0.001; group 2: 20 to 13, p less than 0.05) to exercise. During a total of 7643 hours of ST segment monitoring, 253 episodes of ischemia were recorded in 3768 hours before and 44 ischemic episodes in 3875 hours after intervention (group 1, 113 episodes in 24 patients and 21 episodes in 10 patients; group 2, 140 episodes in 13 patients and 23 episodes in six patients). Both interventions reduced the mean frequency of ischemia per 24 hours (group 1: 1.24 to 0.22 episodes per 24 hours; p less than 0.01; group 2: 1.9 to 0.3 episodes per 24 hours; p less than 0.05). Almost 28% (N = 24) of resting electrocardiographic findings were altered as a result of intervention.(ABSTRACT TRUNCATED AT 250 WORDS)

Activities of Daily Living↗
PubMed1992

A protective monoclonal antibody with dual specificity for Plasmodium falciparum and Plasmodium berghei circumsporozoite proteins.

An IgM monoclonal antibody (Mab 36) which reacts with the circumsporozoite (CS) proteins of both P. falciparum and P. berghei was isolated from Plasmodium falciparum sporozoite-immunized mice. In assays of biological activity, Mab 36 induces the CS precipitation reaction with live sporozoites and blocks the invasion of hepatoma cells by sporozoites in vitro at concentrations much lower than those observed for previously reported CS protein-specific monoclonal antibodies. Mab 36 also provided complete protection against P. berghei sporozoite challenge in mice at low doses. Linear epitope mapping revealed that the epitope specificities recognized by Mab 36 are completely encompassed by other monoclonals previously shown to be associated in vivo with protection against P. falciparum or P. berghei sporozoite infection. These results suggest that the ability to make high-affinity IgM antibody to specific CS protein repeat epitopes may be important for eliciting protection against malarial infection.

Animals↗
PubMed1992

Relationship between c-erbB-2 protein product expression and response to endocrine therapy in advanced breast cancer.

Of 221 patients with breast cancer of known epidermal growth factor receptor (EGFR) and oestrogen receptor (ER) status, 99 had developed recurrences during the period of follow-up (range 3-60 months, median 24 months). Of these, 72 received endocrine therapy as first-line treatment for relapse. Immunohistochemical assessment of c-erbB-2 protein product expression was made using paraffin-embedded tumour tissue from 65 of these 72 patients. Including patients whose disease remained stable for more than 6 months with those showing an objective response (CR or PR for more than 3 months), only one (7%) of 14 c-erbB-2 positive tumours responded to endocrine manipulation compared with 19 (37%) of 51 c-erbB-2 negative tumours (P less than 0.05). Coexpression of c-erbB-2 reduced the response rate of ER positive patients from 48% to 20% and of ER negative cases from 27% to 0% (P less than 0.01). EGFR and c-erbB-2 protein appeared to have additive effects in reducing the likelihood of response, and none of eight patients with EGFR positive, c-erbB-2 positive tumours derived benefit from endocrine therapy. The results of this study suggest that c-erbB-2 protein overexpression, a marker of poor prognosis in breast cancer, is associated with a lack of response to endocrine therapy on relapse, and particularly in combination with EGFR may be useful in directing therapeutic choices.

Adult↗
PubMed1992

Response to mitoxantrone in advanced breast cancer: correlation with expression of c-erbB-2 protein and glutathione S-transferases.

Sixty-eight patients with advanced breast cancer were treated with mitoxantrone and clinical responses assessed. Expression of c-erbB-2 protein and cytosolic glutathione S-transferase (GST) isoenzymes pi, alpha and mu by the primary tumours of these patients was determined immunohistochemically, and correlated with treatment response. Tumours overexpressing c-erbB-2 (n = 16, 23%) showed a lower response rate (50% vs 58%) and shorter duration of response to treatment, compared with c-erbB-2 negative tumours. These associations were not statistically significant but survival following start of treatment was significantly shorter in the c-erbB-2 positive group. For each GST isoenzyme, the response rate and duration of response of the group showing enzyme expression did not differ significantly from those with negatively staining tumours. These data do not support a role for expression of GSTs alone in resistance to mitoxantrone monotherapy in advanced breast cancer. The poorer post treatment survival of patients with c-erbB-2 positive tumours suggests they could be selected for more intensive treatment regimens.

Adult↗
PubMed1992

Value of ambulatory ST segment monitoring in patients with chronic stable angina: does measurement of the "total ischaemic burden" assist with management?

OBJECTIVE: To assess the prognostic significance of transient ischaemic episodes during daily activities in patients with stable angina. PATIENTS AND METHODS: 172 patients with stable angina attending the cardiac outpatients departments of Hillingdon Hospital (n = 155) and the National Heart Hospital (n = 17) were prospectively studied by exercise testing and 48 hours of ambulatory ST segment monitoring, and followed for prognostic purposes for up to 39 months (mean 24.5 months). Patient inclusion depended on a clinical diagnosis of stable coronary artery disease which necessitated outpatient review (and antianginal treatment in 94% of patients). It was not dependent on objective evidence of reversible ischaemia. Events recorded during the follow up period included death, non-fatal myocardial infarction, unstable angina, and the requirement for revascularisation. RESULTS: 72 patients (42%) had transient ischaemic episodes during daily activities, and 104 patients (60.5%) had an ischaemic response to exercise. 63 patients (36%) had evidence of ischaemia on both investigations; with 59 (34%) having no documented ischaemia on either investigation. There were 27 patient events (15.7%) recorded over a mean 24.5 month follow up, including five deaths (2.9%) (three cardiac related (1.7%)), six non-fatal myocardial infarctions (3.5%), six admissions with unstable angina (3.5%), and 10 revascularisation procedures (5.8%). Of the nine "hard" or objective end points (cardiac death and non-fatal myocardial infarction), only two had evidence of transient ischaemia on ambulatory ST segment monitoring at initial investigation, with 10 of the 25 patients (38.5%) with any cardiac event having such episodes. CONCLUSIONS: The outcome in patients with chronic stable angina receiving standard medical treatment was good over a mean two year follow up period. For the purpose of assessing prognosis over this time scale, there was no advantage to performing ambulatory ST segment monitoring in such patients.

Adult↗
PubMed1992

Epidermal growth factor receptor and other oncogenes as prognostic markers.

Analysis of epidermal growth factor receptor (EGFr) and estrogen receptor (ER) was performed on tumor samples from 231 patients with operable breast cancer followed for up to 6 years after surgery. The median duration of follow-up in patients still alive at the time of analysis was 45 months. Thirty-five percent of patients (82) had tumors greater than 10 fmol/mg of 125I-EGF binding (EGFr+) and 47% (109) had cystolic ER concentration greater than 5 fmol/mg (ER+), with a marked inverse relationship between EGFr and ER (P less than .00001). EGFr was second only to axillary-node status as a prognostic marker for all patients in terms of both relapse-free and overall survival in univariate analysis (P less than .001, log-rank EGFr + v EGFr-). For patients with histologically negative axillary nodes, EGFr was superior to ER in predicting relapse and survival (P less than .01 and P less than .005, respectively, compared to P less than .1 and P less than .1, log-rank). In a multivariate (Cox model) analysis, only EGFr--out of EGFr, ER, size, and grade--was predictive for either relapse-free or overall survival for patients with node-negative disease (P = .052 and P = .026, respectively). One hundred eighty-seven case patients in the series were assessed for neu expression immunochemically, and 31 were positive. There was a highly significant increased risk of relapse and death in the positive group. In patients with otherwise good prognostic markers (ER+, node-negative, well-differentiated tumors), neu expression predicted for significantly worsened overall survival.(ABSTRACT TRUNCATED AT 250 WORDS)

Biomarkers, Tumor↗