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Biomedical subjects

J Paul

Publications and source records attributed to J Paul.

At least 19 recordsLinked to original sources
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56 low-dose and 45 high-dose patients completed six cycles of chemotherapy; 15 and 9 patients, respectively, were withdrawn early because of progressive disease and treatment was stopped in 6 and 25, respectively, because of unacceptable side-effects or patient refusal.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↗
PubMed1991

Fast heme release from inactive proteins.

Kinetics for the release of the prosthetic group from hemoproteins is presented. Heme-protein separation is a biphasic reaction, where an initial phase is significantly faster than the dominant, slow phase. A previous communication concluded that the slow phase represents the active protein. This communication presents data for porphyrin release which shows that the initial fast phase represents an inactive form of the protein. Moreover, we suggest that the fast to slow phase ratio is a sensitive monitor of sample quality for many hemoproteins and that an extrapolation of the slow phase absorbance leads to new estimates for the true physical parameters of unperturbed proteins.

Chloride Peroxidase↗
PubMed1991

Heme-protein fission under nondenaturing conditions.

Slow heme transfer from horseradish peroxidases C2 and A2, cytochrome c peroxidase, chloroperoxidase, and leghemoglobins to a heme acceptor protein, apomyoglobin, has been studied under mild conditions. The reaction is best described as heme release into water followed by quick engulfment by apomyoglobin. The energetics of the activated process are large and interpreted as connected to both polypeptide motions during release and the ordering of water around the heme during solvation. The free energy required to break the iron(III)-ligand 5 (L5) bond is a minor but crucial portion of the activation free energy. Donor-acceptor protein interactions are not involved in the transfer. Fast heme release from inactive protein has also been observed. Apoprotein recombination with porphyrins and hemes suggest that this lack of activity is a result of Fe-L5 bond breaking.

Apoproteins↗
PubMed1991

Carboplatin-based combination chemotherapy for advanced carcinoma of the cervix.

A combination of carboplatin, vincristine, methotrexate and bleomycin (COMB) was given to 29 patients with locally advanced, metastatic or recurrent cervical carcinoma. A total of 85 cycles of chemotherapy were given, with half of the patients receiving greater than 3 cycles. Both the response rate (32.1%) and the median duration of response (30 weeks) were relatively disappointing. Renal toxicity was minimal, but one-third of our patients experienced severe (WHO grades 3 and 4) nausea and vomiting. This combination showed little advantage over carboplatin used as a single agent.

Adult↗
PubMed1991

Mechlorethamine, vinblastine, procarbazine and prednisolone (MVPP) for advanced Hodgkin's disease.

Between January 1972 and October 1985, 60 patients with advanced Hodgkin's disease were treated with mechlorethamine/vinblastine/procarbazine/prednisolone (MVPP). The complete remission (CR) rate was 50%; the introduction of computed tomography in 1980 reduced the proportion of CR from 62% to 30% (P = 0.017) as a consequence of residual mediastinal abnormality of uncertain significance. With a median follow-up of 9 years, actuarial 5 and 10-year overall survival was 70% and 57%, respectively, with 79% and 65% free from Hodgkin's disease. Only age and pathological subtype influenced survival sufficiently to be of prognostic significance, though the effect of serum albumin, ECOG performance status and B symptoms on Hodgkin's disease mortality may have been clinically important.

Adolescent↗
PubMed1991

Rat peritoneal macrophage procoagulant and fibrinolytic activities. An expression of the local inflammatory response.

1. Lysates of rat (Rattus norvegicus, Wistar strain) peritoneal macrophages selected by adherence were analysed for procoagulant activity (PCA) and plasminogen activator activity (PAA). 2. PCA is expressed following in vitro stimulation by lipopolysaccharide and in vivo (respectively 118 +/- 19.1 and 147.2 +/- 45.2 mUnits/10(6) M phi) very early after the intraperitoneal injection of thioglycollate. 3. PAA present in 24 hr thioglycollate stimulated cells (79.5 +/- 26.1 mI.U./10(6) M phi), disappears in a time dependent fashion after in vitro lipopolysaccharide stimulation. 4. Our findings indicate that rat peritoneal macrophages regulate their coagulolytic activities in a specific manner. 5. Rat peritoneal cavity may be proposed as a model for the study of inflammatory reaction with PCA and PAA as its indexes.

Animals↗