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Biomedical subjects

J Paul

Publications and source records attributed to J Paul.

At least 163 records · Page 9Linked to original sources
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↗
PubMed1991

BOP/VIP--a new platinum-intensive chemotherapy regimen for poor prognosis germ cell tumours.

Ninety-one patients with poor prognosis non-seminomatous germ cell tumours (NSGCT) were treated with an initial intensive chemotherapy schedule. Suitable patients fulfilled one or more of the following criteria: lymph node metastases greater than 10 cm diameter; liver, brain or bone metastases; serum HCG level greater than 50,000 IU/L; and extragonadal primary tumours. Treatment consisted of 3 cycles of bleomycin, vincristine and cisplatin (BOP) administered at 10 day intervals, followed by 3 cycles of etoposide, ifosfamide and cisplatin (VIP) at 21 day intervals. A total of 64 patients (70%) achieved a complete remission. This comprised 46 patients who received BOP/VIP only, and 18 patients who received additional chemotherapy after BOP/VIP. Of these 64 patients, 51 underwent complete surgical resection of residual masses, including 11 in whom there was evidence of teratoma with cellular atypia or non-germ cell cancer in the resected tissue. A further 9 patients had persisting unresected radiological masses in the presence of marker complete remission. The overall response rate was 80%. Currently 57 patients (63%) remain alive and free from disease progression. The median follow-up period is 90 weeks (range 24-206 weeks), with a 2 yr actuarial progression-free survival of 66% (95% c.i. 55-77%). Major toxicity was myelosuppression, occurring during the VIP arm of therapy, with a median nadir WBC of 1.1 x 10(9)/L and median platelet count of 51 x 10(9)/L. Other toxicity included peripheral neuropathy (WHO Grade 2 and 3 in 22%). We conclude that treatment results with the BOP/VIP schedule in this poor prognosis patient group are at least comparable with other schedules, and toxicity is manageable.(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Electrophysiological effects of left ventricular hypertrophy. Effect of calcium and potassium channel blockade.

BACKGROUND: To define the arrhythmogenic effects of left ventricular hypertrophy (LVH) in the intact heart, we carried out a detailed electrophysiological assessment in our previously validated feline aortic-banding model and then tested the effects of agents that blocked either the slow inward calcium or voltage-dependent potassium channel. METHODS AND RESULTS: We measured intraventricular and interventricular conduction times, excitability thresholds, ventricular effective refractory periods, and monophasic action potential duration at several sites in cats with LVH as well as in concurrent control (sham-operated) cats. In addition, we assessed vulnerability to ventricular arrhythmia using direct measurement of ventricular fibrillation (VF) thresholds and by standard techniques of programmed stimulation. Despite finding no difference between LVH and sham-operated cats in mean values for several electrophysiological parameters, the former group was significantly more vulnerable to VF, with more spontaneous VF and lower VF thresholds. Compared with the sham controls, LVH cats also had a greater dispersion of effective refractory period (35 +/- 11 versus 12 +/- 4 msec, p less than 0.01) and monophasic action potential duration at 90% repolarization (69 +/- 25 versus 39 +/- 7 msec, p less than 0.02). Verapamil had no significant effect on these electrophysiological parameters, nor did it affect VF threshold. However, risotilide, an inhibitor of the voltage-dependent potassium channel, narrowed dispersion of the effective refractory period and monophasic action potential duration concomitant with a marked reduction in ventricular vulnerability. CONCLUSIONS: LVH has a pronounced effect on dispersion of refractoriness and repolarization and renders the ventricle more vulnerable to fibrillation. Blockade of the voltage-dependent potassium channel, but not the slow inward calcium channel, narrows the dispersion of recovery of excitability and protects against VF.

Animals↗
PubMed1991

Epirubicin at two dose levels with prednisolone as treatment for advanced breast cancer: the results of a randomized trial.

Two hundred eleven patients with advanced breast cancer were randomized to receive either epirubicin (E) 50 mg/m2 and prednisolone (LEP) or E 100 mg/m2 and prednisolone (HEP). The intended treatment consisted of 16 courses of LEP or eight courses of HEP given at 3-weekly intervals. Reasons for stopping treatment early included progressive disease, stable disease without symptomatic improvement, or severe toxicity deemed intolerable by either the patient or physician. Toxicity was recorded at 3-weekly and response at 9-weekly intervals using the World Health Organization (WHO) criteria of response and toxicity. Two hundred nine patients were eligible for analysis, 98% of whom have been followed for more than a year. One hundred four patients received LEP and 105 HEP. Significantly worse myelosuppression, alopecia, nausea and vomiting, and mucositis were seen in the high-dose arm (P less than or equal to .001). More patients in the LEP arm stopped treatment before the fourth course than in the HEP arm, and the commonest reason for stopping was progressive disease. A similar median number of courses was given in each arm. There was a significantly higher response in the HEP arm (HEP - complete response [CR] + partial response [PR] = 41%, LEP - CR + PR = 23%). Despite this, no statistically significant differences was seen in overall survival or progression-free interval. The median survival for HEP and LEP was 44 and 46 weeks, respectively.

Adult↗
PubMed1991

Analysis of soft tissue tumors by an attributed minimum spanning tree.

Histologic slides of 22 soft tissue tumors (9 malignant fibrous histiocytoma, 8 fibrosarcoma, 2 rhabdomyosarcoma, 2 osteosarcoma, 1 Askin tumor) were Feulgen stained. Using an automated image analyzing system (Cambridge 570) at low magnification (25x), the tumor cell nuclei were segmented. The geometrical center of the nuclei was considered the vertex. A basic graph was constructed according to the neighborhood condition of O'Callaghan. Neighboring tumor cell nuclei were visualized by connecting edges. Several features of tumor cell nuclei were measured, including area, surface, major and minor axis of best fitting ellipsis and extinction (DNA content). Nuclear features are attributed to the vertices. The differences, or "distances," between features of connected vertices are attributed to the corresponding edges, which are dependent on the attributes. Thus, different minimum spanning trees (MST) result. Each MST can be decomposed into clusters using a suitable decomposition function on the edges, which rejects an edge if its attributes differ from the mean of the attributed values of surrounding edges more than a neighbor dependent bound (lower limit). Taking into account the length and other attributes of edges (e.g., differences in orientation of the major axis), clusters of different nuclear orientation can be detected. A cluster tree can be constructed by defining the geometric center of a cluster as a new vertex, and by computing the neighborhood of the cluster vertices. The result is an attributed MST containing characteristic structural properties of the image (in cases of sarcomatous tumors, local orientation of tumor cell nuclei and local DNA abnormalities).

Cell Nucleus↗
PubMed1991

Closed suction drainage following knee arthroplasty. Effectiveness and risks.

A prospective investigation was performed to determine when to remove a suction drain following total knee arthroplasty (TKA). Forty-one TKAs were randomly allocated to closed suction drainage for either 24 or 48 hours. The drain was removed and the tip was cut off and processed by a method giving quantitative cultures. In the 48-hour group, 85% of the total volume was drained during the first 24 hours. During the following 24-hour period, a mean volume of only 50 ml was drained. No organism was isolated from cultures of drain tips sampled at 24 hours. However, at 48 hours, 25% of the drain tips yielded light growths of coagulase-negative staphylococci (four drain tips) and Staphylococcus aureus (one drain tip). Clinical evaluations of wound healing were comparable in the two groups. Clearly, nothing is to be gained by continuing drainage beyond 24 hours. If drainage is maintained for longer periods, there is an increased risk of contamination by bacteria.

Equipment Contamination↗
PubMed1991

Evaluation of macrophage procoagulant and fibrinolytic activities induced by peritoneal dialysis solutions.

To investigate the coagulant and fibrinolytic potential of peritoneal macrophages, after short-term exposure to dialysis solutions intraperitoneal (IP) injection of these hyperosmolar glucose solutions was performed in rats. During the 72-hour postinjection period, the dialysis solutions and, as controls, Ringer's lactate and Ringer's lactate-glucose all induced a similar increase in the number of polymorphonuclear cells and macrophages within a maximum of 24 or 48 hours after their IP injection. These findings demonstrate that IP injection of any dialysis solution results in a moderate non-specific inflammatory cell harvesting. Compared with activity induced by the control solutions, no significant increase of procoagulant and fibrinolytic activities, identified respectively by the presence of thromboplastin and plasminogen activator, was observed in peritoneal macrophages obtained 48 hours after injection of the solution with the highest glucose concentration. However, the level of procoagulant activity could increase as a result of different manufacturers' processing of the solutions. That the basal level of macrophage functions may be modified suggests that this cell may initiate coagulolytic conditions in the peritoneal cavity, especially in the course of IP injection of dialysis solutions.

Animals↗
PubMed1990

Characterization of airborne mineral dusts associated with farming activities in rural Alberta, Canada.

The dry and windy climate of the Western Canadian prairie provinces, combined with large scale agricultural activities, results in aerosolization or organic and mineral dusts. The purpose of this study was to conduct an environmental and minerological analysis of these dusts in order to estimate the risk for pneumoconiosis in exposed farmer populations. Two districts in central/southern Alberta were chosen for study. One of these regions was representative of a predominantly grain growing district with minimal use of irrigation; the other region was largely devoted to forage and irrigated crop production. Air pollution statistics showed a bi-modal distribution of total suspended particulates (TSP) with peaks corresponding with maximal farm activities in the spring and early fall. Analysis of bulk dust samples obtained from tractor cab filters showed that the majority of particles from both districts were within the respirable range (less than 5 microns). Samples from the forage-crop region contained more organic material, a greater water soluble fraction and had particles that were, on average, smaller and rounder than particles from the grain district. These differences were thought to reflect differences in irrigation patterns and use of fertilizers between the two districts. Free silica (quartz) content was also very variable and ranged from 1 to 17% on a mass basis. Respirable fibrous minerals were occasionally identified, however, no asbestos fibres, fibrous tremolite, or fibrous zeolites were identified. The results indicate that there is potential risk for mineral dust pneumoconiosis in heavily exposed farmer populations and that this risk will be influenced by local and regional factors.

Agriculture↗
PubMed1990

Phase II trial of carboplatin and vinblastine in advanced squamous-cell carcinoma of the head and neck.

A chemotherapy regimen consisting of carboplatin and vinblastine was given to 30 patients with recurrent or previously untreated, locally advanced squamous carcinoma of the head and neck region. The main aim of the study was to assess the toxicity of this regimen, the feasibility of its outpatient administration and the tumour response. A total of ten patients (33%) achieved an objective response, including two who achieved a complete response. The combination offered useful palliation for patients with recurrent disease; it was well tolerated and can be given on an outpatient basis. This regimen could be combined with other active agents such as methotrexate or bleomycin.

Adult↗
PubMed1990

Effect of flosequinan (BTS 49465) on myocardial oxygen consumption.

BTS 49465 (flosequinan), a putative selective, balanced arterial and venous vasodilator, displays positive inotropic effects in doses lower than those producing vasodilation. Thus rather than unloading the myocardium, flosequinan may increase myocardial work and oxygen consumption (MVO2), and may adversely affect the patient with myocardial ischemia or compromised coronary blood flow. This study compared the effects of flosequinan with milrinone, a mixed positive inotropic agent and vasodilator, and with nitroprusside (SNP), a standard direct-acting vasodilator, on myocardial dP/dT, MVO2, and myocardial energetics in the normal pentobartital-anesthetized dog. The effect of flosequinan on myocardial work was also evaluated in the dog with propranolol-induced heart failure (PIHF). Fifteen minutes after intraduodenal (id) administration of flosequinan (0.3, 1.0, and 3.0 mg/kg) to seven dogs, mean myocardial dP/dT was increased by 11%, 27%, and 54%, respectively, whereas stroke MVO2 was increased by 10%, 24%, and 47%, respectively. Doses of flosequinan greater than 0.3 mg/kg decreased left ventricular (LV) work but LV efficiency decreased in a dose-related manner. Milrinone (0.1, 0.3, and 1.0 mg/kg, id) increased LV dp/dt by 34%, 68%, and 104% above basal values, while increasing stroke MVO2 by 24%, 106%, and 249%, respectively (n = 7). LV work and LV efficiency decreased after each dose of milrinone. SNP (0.001, 0.003, and 0.01 mg/kg/min, intravenously) did not increase dP/dT but decreased LV work by 28%, 42%, and 46% (n = 5). In animals with PIHF, flosequinan (1 and 3 mg/kg, id) increased LV dP/dT 58% and 87% and increased LV work by 58% and 76% above control values. It was concluded that (1) flosequinan is a positive inotropic agent as well as a vasodilator; (2) in the normal animal the energy cost of positive inotropic activity is less with flosequinan than with milrinone, despite the lesser vasodilating action of the former; and (3) in the animal with a depressed myocardium, flosequinan may adversely affect myocardial work and wall tension.

Animals↗
PubMed1990

Oestrogen and progesterone receptors in carcinoma of the cervix.

Oestrogen (ER) and progesterone (PR) receptors have been measured in 102 cervical carcinomas. With positive levels defined as concentrations exceeding 20 fmol/mg protein for cytoplasmic receptor and/or 200 fmol/mg DNA for nuclear receptor, 24% of tumours were dual receptor positive and 51% were dual receptor negative. The majority of adenocarcinomas (81%: 13/16) expressed ER (P less than 0.001) though only 54% (7/13) of these tumours co-expressed PR. There was a significant correlation between tumours positive for ER and those arising in premenopausal women (P = 0.011), with good or moderate differentiation (P = 0.027) and of smaller size (P = 0.025). Median follow-up is 19 months. Apart from advanced stage, tumour bulk (greater than 5 cm) was the only parameter associated with inferior progression-free survival, and most larger tumours were of advanced stage. No prognostic significance could be detected for receptor status.

Adenocarcinoma↗
PubMed1990

Neurone specific enolase (NSE) in small cell lung cancer: a tumour marker of prognostic significance?

Pretreatment serum levels of neurone specific enolase (NSE) were measured in patients with small cell lung cancer (SCLC). Median values were significantly higher in patients with extensive compared with limited stage disease (48 ng ml-1 v. 17 ng ml-1: P less than 0.001). Serial NSE levels paralleled the clinical response to treatment. In 37 patients with limited SCLC, receiving identical chemotherapy, the pretreatment NSE level was of prognostic significance: with an approximate reduction in median survival of 10% for each 5 ng ml-1 incremental rise in NSE (P = 0.004).

Biomarkers, Tumor↗
PubMed1990

Long-term sequelae of treatment for testicular germ cell tumours.

Seventy-four patients previously treated in our department for germ cell tumour of the testis underwent a series of tests to determine the frequency of long-term therapeutic complications. All had received cisplatin-based chemotherapy as part of their treatment. There was a significant deterioration in renal function throughout the group. Eighteen (24%) had supine blood pressure greater than systolic 140 mmHg or diastolic 90 mmHg after treatment but hypertension did not correlate with renal impairment. Raynaud's phenomenon was common after chemotherapy (26/74) as was persistent sensory neuropathy (23/74). Although 34% had testosterone levels below the normal range, only six patients had a low free testosterone index with one testis still in situ; 18 patients have fathered children after chemotherapy. Approximately half of the patients completed a psychosexual questionnaire and some 30% of them admitted to sexual problems which they attributed to their treatment. Long-term sequelae of cisplatin-based chemotherapy for testicular malignancy are frequent and persistent, and follow-up of these patients should include prospective measurement of changes in blood pressure.

Adolescent↗