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Biomedical subjects

J Paul

Publications and source records attributed to J Paul.

At least 145 records · Page 8Linked to original sources
PubMed1994

Quinidine as a resistance modulator of epirubicin in advanced breast cancer: mature results of a placebo-controlled randomized trial.

PURPOSE: To evaluate the effect of quinidine, a putative modulator of P-glycoprotein-mediated drug resistance, on the response rate and toxicity profile of epirubicin in patients with advanced breast cancer. PATIENTS AND METHODS: Between 1989 and 1992, 223 eligible patients were randomized in double-blind fashion to receive epirubicin 100 mg/m2 by intravenous (i.v.) bolus and prednisolone 25 mg orally twice daily, along with either placebo or quinidine (250 mg) capsules, taken for 4 days before and 2 days after chemotherapy. Treatment was continued for a maximum of eight courses. RESULTS: Ten eligible patients did not complete the first cycle of treatment. Of the remaining patients, 106 in the placebo arm received 619 courses of treatment, and 107 in the quinidine arm received 612 courses. The median cumulative dose of epirubicin in both arms was 600 mg/m2. The median quinidine level (measured before epirubicin administration in 288 courses) was 5.5 mumol/L; at this concentration, the drug partially reverses anthracycline resistance in multidrug-resistant (MDR) breast carcinoma cells in vitro. There were no statistically significant differences in hematologic or gastrointestinal toxicity between the two arms. The response rate in the placebo arm was 44% (6% complete remission [CR], 38% partial remission [PR]), and in the quinidine arm was 43% (4% CR, 39% PR). Surviving patients have been monitored for a median time of 74 weeks, and there is no significant difference in the overall or progression-free survival between the two arms. The median survival times were 59 weeks for placebo and 47 weeks for quinidine patients. The estimated relative death rate (quinidine/placebo) was 1.2 (P = .247; 95% confidence interval [CI], 0.88 to 1.63). CONCLUSION: Quinidine at this dose does not significantly alter the toxicity profile, response rate, or survival after epirubicin chemotherapy in patients with advanced breast cancer. This may be due to ineffective modulation of P-glycoprotein by quinidine or the lack of expression of mdr-1 in a sufficient proportion of cells in these tumors, or alternative mechanisms underlying resistance to epirubicin.

Adult↗
PubMed1993

Management of malignant teratoma: does referral to a specialist unit matter?

The causes of geographical differences in cancer survival among regions of the UK are unclear. Population-based audit of management of patients with non-seminomatous germ-cell tumours (NSGCT) in the west of Scotland enabled us to assess the relative contributions to outcome of recognised prognostic factors, treatment centre, and protocol treatment. Data on treatment and outcome were analysed for 440 (97%) of 454 men with NSGCT diagnosed between 1975 and 1989. All but 11 patients were treated at tertiary referral centres; 235 were treated at a single unit (unit 1) and 194 at four other units (2-5). 99 men have died, 89 (20%) from NSGCT. Independent prognostic factors for NSGCT survival were extent of tumour at diagnosis (p < 0.001), 5-year period of diagnosis (from 1975-79 to 1985-89, p < 0.001), and treatment unit (unit 1 vs units 2-5, p < 0.001). Unit 1, which had the best survival rates, treated most patients overall (53%), including the majority (70%) in the worst prognostic category (poor-prognosis metastatic disease). The proportion of men receiving nationally agreed protocol treatment was higher at unit 1 than elsewhere (97 vs 61%, p < 0.0001). However, analysis restricted to men who received protocol treatment, adjusted for other important prognostic variables, still showed a survival advantage for this unit (relative death rate units 2-5 vs unit 1, 2.82 [95% CI 1.53-5.19], p < 0.001). These findings suggest that centralisation of treatment for NSGCT improves outcome; the benefit seems to be additional to any advantage resulting from protocol treatment.

Adult↗
PubMed1993

Molecular epidemiology of penicillin-resistant pneumococci isolated in Nairobi, Kenya.

A total of 26% of the pneumococci isolated from an outpatient clinic in Nairobi, Kenya, during 1991 to 1992 had intermediate levels of penicillin resistance. Gene fingerprinting and DNA sequencing were used to distinguish the penicillin-binding protein (PBP) 1A, 2B, and 2X genes in 23 resistant isolates. Isolates were grouped into those that had identical forms of each of the three PBP genes (fingerprint groups) and those that had identical rRNA gene restriction patterns (ribotypes). Both methods divided the isolates into 11 groups. In a few cases, horizontal gene transfer appeared to have distributed an identical altered PBP gene into different pneumococcal lineages. Eight isolates were indistinguishable by ribotyping or multilocus enzyme electrophoresis and contained identical PBP 1A genes. Although these isolates were therefore members of the same clone, they were divided into two fingerprint groups which contained different PBP 2X and 2B genes. Presumably, members of this clone have acquired different altered PBP 2X and 2B genes on two separate occasions. One of these fingerprint groups contained isolates of serotype 14, whereas the other contained isolates of both serotypes 14 and 7. The identification of isolates in the latter group that are identical by all criteria, except serotype, implies the occurrence of a change in serotype. The predominant serotypes of the penicillin-resistant pneumococci from Nairobi were serotypes 14 and 19. In both cases, isolates of the same serotype which required the same MIC of penicillin were not members of a single clone, indicating that identity of serotype and MIC are not sufficient criteria for defining clones of resistant pneumococci even when the bacteria are isolated from a single clinic.

Amino Acid Sequence↗
PubMed1993

Predictive factors of visual outcome after local resection of choroidal melanoma.

Local resection of choroidal melanomas is not widely performed so that the indications for this operation have not previously been defined statistically. Univariate and multivariate Cox regression analyses were used to identify the factors influencing visual acuity after 163 completed local resections for choroidal melanoma in patients with a preoperative visual acuity of counting fingers or better. The variables included in the analyses were patient age and sex; eye laterality and preoperative visual acuity; location of anterior and posterior tumour margins; tumour location (coronal and sagittal); tumour diameter, thickness, and cell type; ocular decompression by vitrectomy; and adequacy of surgical clearance. The surgical resections were performed using a lamellar scleral flap for eye closure, hypotensive anaesthesia for haemostasis, and, in the later years, ocular decompression by pars plana vitrectomy to improve access. The patients (94 men, 69 women) had a mean age of 50 years. The tumours had a mean diameter of 13.3 mm and a mean thickness of 7.4 mm, with 38 tumours extending to within 1 disc diameter (DD) of the optic disc, fovea or both (that is, 'posterior tumour extension'). Cox multivariate analysis showed that the most significant preoperative factors for predicting retention of good vision (6/12 or better) were nasal tumour location (p = 0.002) and distance of more than 1 DD between the tumour and the optic disc or fovea (p = 0.010). The most significant predictive risk factor for severe visual loss (hand movements or worse) was posterior tumour extension to within 1 DD of the optic disc and/or fovea (p = 0.009). One year post-operatively, all 28 patients with nasal tumours not extending to within 1 DD of the optic disc or fovea retained the eye with 57% having vision of 6/12 or better and 93% having vision of counting fingers or better. In 68 patients with temporal tumours, 90% retained the eye at 1 year with preservation of vision of counting fingers or better in 82% of 56 eyes without posterior tumours extension and in 50% of 12 eyes with posterior tumour extension. In patients with choroidal melanoma, conservation of the eye and vision can be achieved by local resection, especially if the tumour is located nasally and does not extend close to the disc or fovea.

Adult↗
PubMed1992

Randomised study of two doses of cisplatin with cyclophosphamide in epithelial ovarian cancer.

Cisplatin is generally accepted to be the most active cytotoxic agent for the treatment of ovarian cancer but the optimum dose remains unclear. We have performed a randomised trial to assess the importance of cisplatin dose in the treatment of advanced epithelial ovarian cancer. Patients were randomly assigned treatment with 50 mg/m2 (low dose) or 100 mg/m2 (high dose) cisplatin plus 750 mg/m2 cyclophosphamide, for a maximum of six cycles with intervals of 3 weeks. We planned to recruit 300 patients, but an interim analysis on the first 165 indicated a highly significant survival difference (p = 0.0008). Recruitment was therefore stopped and the trial patients were followed-up for 12 months longer. The relative progression rate (high-dose/low-dose) after 12 months' extra follow-up was 0.55 (95% confidence interval 0.37-0.81, p = 0.003) and the relative death rate 0.53 (0.34-0.81, p = 0.003). Overall median survival was 69 weeks in the low-dose group and 114 weeks in the high-dose group. Residual disease extent before chemotherapy had an important influence--patients with lesions of less than 2 cm did best; if given high-dose cisplatin their median survival was 3 years. 56 low-dose and 45 high-dose patients completed six cycles of chemotherapy; 15 and 9 patients, respectively, were withdrawn early because of progressive disease and treatment was stopped in 6 and 25, respectively, because of unacceptable side-effects or patient refusal. Toxic effects were significantly greater in the high-dose group, especially those on the nervous system and ears, alopecia, vomiting, and anaemia. Although the higher dose of cisplatin clearly leads to better results in terms of survival, its overall clinical benefit in the management of ovarian cancer will depend on further improvements in measures to alleviate toxic effects.

Adult↗
PubMed1992

Posttraumatic segmental axial dystonia.

Isolated dystonia of trunk and neck muscles without involvement elsewhere has been termed segmental axial dystonia--a rare disorder. We report a 31-year-old man who developed marked dystonia of paraspinal muscles and progressive scoliosis 6 months after a closed head injury. Computed tomography (CT) disclosed three small areas of encephalomalacia, one involving the head of the caudate nucleus. Treatment with trihexyphenidyl resulted in significant improvement of the dystonia and scoliosis.

Accidental Falls↗
PubMed1992

Increased intestinal permeability: implications for thoracoabdominal aneurysm repair.

Coagulopathy and massive bleeding plays a major role in the mortality of thoraco-abdominal aneurysm repair. Increasing supraceliac aortic cross-clamp time from 0 to 90 minutes increases the degree of disseminated intravascular coagulation, which occurs as a result of occlusion and reperfusion of the superior mesenteric artery. The purpose of this study was to investigate the mechanism of the superior mesenteric artery reperfusion disseminated intravascular coagulation. Twenty dogs were divided into four groups: cross-clamp time of 30 minutes; cross-clamp time of 60 minutes; cross-clamp time of 90 minutes; and control. Permeability was determined by lactulose/mannitol absorption. The venous effluent was sampled for endotoxin, potassium, bacteria, and pH every hour and urine was collected for six hours. Lactulose absorption was significantly higher in all of the experimental groups. There was increased permeability in the 60 and 90 minute groups which correlated significantly with time. Venous endotoxin, potassium, and blood cultures for bacteria did not change significantly. The pH was significantly lower every hour for six hours in the 90 minute group. These data suggest that intestinal permeability is increased with supraceliac aortic clamping and can be kept to a minimum for clamp times of under one hour.

Animals↗
PubMed1992

No correlation between ras, c-myc and c-jun proto-oncogene expression and prognosis in advanced carcinoma of cervix.

55 patients suffering from stage III or IV carcinoma of cervix were treated with two pulses of neo-adjuvant chemotherapy prior to radical radiotherapy. 51% (26/51) had a partial response. The initial response to chemotherapy is associated with significantly better long-term survival. The 3-year survival of chemotherapy responders is 62% against 21% for non-responders (P = 0.009 log-rank test). To detect possible differences in oncogene expression in biopsy specimens taken from responding and non-responding patients, paraffin-fixed material was immunocytochemically stained for the expression of the protein products of ras, c-myc and c-jun proto-oncogenes. The frequency of oncogene expression was ras 80.4%, c-myc 45.1% and c-jun 39.2%. There was no statistically significant association between oncogene expression, time to local recurrence or development of metastases or survival.

Adult↗
PubMed1992

An independent evaluation of the potential clinical usefulness of proposed CA-125 indices previously shown to be of prognostic significance in epithelial ovarian cancer.

CA-125 levels were assessed prior to each of the first three cycles of chemotherapy, in 81 patients with epithelial ovarian cancer receiving first-line chemotherapy. All patients have at least 1 year's follow-up. Thirty-nine patients (48%) have progressed clinically or have died within 1 year of treatment (treatment 'failures'). Three CA-125 indices previously shown to be of prognostic value are assessed for their ability to pick-out these 'failures'. When the indices examined are modified to obtain a specificity for picking out failures just exceeding 90%, the maximum sensitivity obtained was 46%. The use of CA-125 for clinical decision making in ovarian cancer requires further investigation to determine and validate a prognostic index with acceptable sensitivity and specificity, and to determine the clinical impact of treatment decisions made using such an index.

Antigens, Tumor-Associated, Carbohydrate↗
PubMed1992

An approach based on two-dimensional graph theory for structural cluster detection and its histopathological application.

An approach based on graph theory is described for detecting clusters of cells in tissue specimens (two-dimensional space). With a set of discrete basic elements (cell nuclei) having several measurable features (area, surface, main and minor axis of best-fitting ellipses) a graph is defined as having attributes associated with edges. Different minimum spanning trees (MSTs) can be constructed using different weight functions on the attributes (attributed MST). Analysis of the MST and of an attributed MST by use of a decomposition function allows detection of image areas with similar local properties. These clusters, which are then clusters of the tree, describe, for example, partial growth in different directions in a case of a human fibrosarcoma assuming that tumour cell nuclei are homogeneous with respect to their configuration and size. The model allows the separation of clusters of tumour cells growing in different directions and the approximation of the different growth angles. This decomposition also allows us to create new (higher) orders of structure (cluster tree).

Algorithms↗
PubMed1992

Fatal case of disseminated infection with the turtle bacillus Mycobacterium chelonae.

An apparently immunocompetent 78 year old woman presented with confusion, subcutaneous abscesses, and lesions of the nasopharynx. Gram positive, acid fast bacilli were isolated from her blood after 10 days' incubation. She was treated with trimethoprim-sulphamethoxazole for presumed disseminated nocardiasis but deteriorated and died. A post mortem examination showed skin and pulmonary lesions and endomyocardial fibrous plaques. Organisms isolated from the skin and lung were indistinguishable from those cultured from the blood. The organism was subsequently identified as Mycobacterium chelonae. Primary pulmonary infection and disseminated disease are rarely caused by this organism and bacteraemia is seldom documented. The clinical presentation and bacteriological and histological findings are difficult to differentiate from those of disseminated nocardiasis. Isolation of the organism may fail without prolonged incubation of initial cultures and there is a danger of its being dismissed as medically unimportant. Diagnosis is further hampered because large pulmonary foci may be poorly revealed by conventional radiological examination of the chest.

Aged↗
PubMed1992

Increased incidence of gallstones and prior cholecystectomy in patients with large bowel cancer.

In a retrospective study, the frequency of occurrence of gallstones and cholecystectomy in 479 patients with colorectal cancer was compared with that of 483 matched control patients with other malignancies. The mean interval between cholecystectomy and colon cancer diagnosis was 15.1 +/- 9.9 yr (range 2-53 yr), and there was no statistically significant difference, compared with the control group at 13.9 +/- 8.2 yr (range 2-31 yr). In patients with colon cancer, the general increased relative risk of concomitant diagnosed gallstones (relative risk 1.73, p = 0.0123) and the relative risk of cholecystectomy (relative risk 2.08, p = 0.0074) was statistically significant. However, when the data with regard to sex were analyzed, significant differences were observed only in women. Women affected by right colon cancer also had a statistically significant higher incidence of previous cholecystectomy (relative risk 2.86, p = 0.0096), but no significantly higher incidence of concomitant gallstones. The general increased relative risk in patients with right colon cancer and decreased risk in patients with left colon cancer of concomitant gallstones and prior cholecystectomy was statistically significant. Our data provide evidence for the hypothesis that both gallstones and cholecystectomy increase the general risk of large bowel cancer. Therefore, they are also compatible with the possibility that common risk factors causes the association between gallstones and large bowel cancer.

Aged↗
PubMed1992

Primary non-Hodgkin's lymphoma of the thyroid.

Eighty seven cases of primary non-Hodgkin's lymphoma of the thyroid presenting to the Beatson Oncology Centre were reviewed. Stage IE and Stage IIE disease accounted for 79 of 87 cases. In a univariate analysis the presence of dysphagia, dyspnoea, positive nodes, stage or male sex all had a statistically significant detrimental influence on survival. Stage and dysphagia were the most influential individually and a multivariate analysis indicated that the prognostic information in all these features was essentially captured by just these two. A prognostic scoring index based upon stage of disease and the presence of dysphagia has been developed. Overall 5 year survival was 43%. Five year survival for Stage IE patients without symptoms of compression was 74%. Patients who underwent surgical resection of tumour followed by local irradiation appeared to survive longer than patients managed by irradiation without surgery, although after adjustment for prognostic features this advantage was not statistically significant.

Adult↗
PubMed1992

Anaplastic thyroid carcinoma: 91 patients treated by surgery and radiotherapy.

Ninety-one patients with histologically proven anaplastic carcinoma of the thyroid were referred to the Beatson Oncology Centre between 1961 and 1986. The female:male ratio was 2.4:1 and the median age at presentation was 70 (range 38-92) years. All patients had a thyroid mass at presentation and the most common symptoms were dyspnoea, dysphagia and dysphonia. Five patients had a total thyroidectomy and 28 partial thyroidectomy. Ninety five per cent of patients received external beam radiotherapy. Results show dyspnoea to be the only symptom strongly influencing survival. Total or partial thyroidectomy is associated with increased survival. This association is most marked for patients presenting without dyspnoea. Eighty per cent of patients responded to radiotherapy.

Adult↗
PubMed1992

A comparison of younger and older gay men's HIV risk-taking behaviors: the Communication Technologies 1989 Cross-Sectional Survey.

Data from the 1989 Communication Technologies cross-sectional survey of gay men in San Francisco indicate that both levels and correlates of sexual risk are different between younger and older gay men. Gay men under the age of 30 report higher risk behavior for human immunodeficiency virus (HIV) infection than do gay men who are 30 years of age or older. Further, the set of correlates of unprotected anal intercourse are different between younger and older gay men. Both young and old gay men report that having a primary partner and a lower perceived impact of the AIDS epidemic on their sexual behavior are associated with risk. However, among young gay men, reporting a lower attributed risk for HIV infection to unprotected anal intercourse, higher concern about AIDS risks, and shorter length of residence in San Francisco are positively correlated with risk-taking behavior. These associations were not statistically significant among gay men 30 years of age or older. It appears that the circumstances and/or reasons for taking sexual risk are different between older and younger gay men. Prevention programs must be designed so that they are sensitive to the needs of each generation of gay men.

Adolescent↗