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Biomedical subjects

J R Bateman

Publications and source records attributed to J R Bateman.

At least 37 records · Page 2Linked to original sources
PubMed1984

A model for assessing bronchial mucus transport.

We propose a scheme for the assessment of regional mucus transport using inhaled Tc-99m aerosol particles and quantitative analysis of serial gamma-camera images. The model treats input to inner and intermediate lung regions as the total of initial deposition there plus subsequent transport into these regions from more peripheral airways. It allows for interregional differences in the proportion of particles deposited on the mucus-bearing conducting airways, and does not require a gamma image 24 hr after particle inhalation. Instead, distribution of particles reaching the respiratory bronchioles or alveoli is determined from a Kr-81m ventilation image, while the total amount of such deposition is obtained from 24-hr Tc-99m retention measured with a sensitive counter system. The model is applicable to transport by mucociliary action or by cough, and has been tested in ten normal and ten asthmatic subjects.

Adolescent↗
PubMed1983

A 12-month comparative trial of auranofin and D-penicillamine in rheumatoid arthritis.

The oral gold salt auranofin, 6 mg per day, was compared with oral d-penicillamine, 500 mg per day, in a single-blind trial in 40 patients suffering with definite or classic rheumatoid arthritis. The patients were randomly allocated into the two therapeutic regimens (19 patients auranofin; 21 patients d-penicillamine) and monitored at a minimum of four-week intervals during the first year of treatment. Significant diminution in rheumatoid disease activity, as assessed by numerous clinical and laboratory parameters, was observed in both the auranofin- and penicillamine-treated groups. No significant differences existed for these parameters between the two groups, either initially or at the end of the trial period. Ten patients were lost from the trial over the 52-week period. Three subjects were withdrawn from the auranofin-treated group (increasing severity of rheumatoid arthritis at four weeks; severe diarrhea at four weeks; probable drug-related erosive gastritis at 40 weeks). Seven subjects were permanently withdrawn from the penicillamine-treated group (four, skin rashes four to eight weeks; one, heavy proteinuria at 24 weeks; one, therapeutic failure at 32 weeks; one, compliance failure at eight weeks), and treatment was temporarily withheld in three further patients because of thrombocytopenia (two) and proteinuria (one). We conclude that both drugs are effective in rheumatoid arthritis and that the lesser toxicity with auranofin will make it a valuable addition to our therapeutic armamentarium.

Adult↗
PubMed1983

Doxorubicin and CCNU with or without vincristine in patients with advanced refractory breast cancer. A randomized trial.

Thirty-five patients with advanced breast cancer refractory to initial chemotherapy were randomized to receive two-drug doxorubicin-CCNU or three-drug doxorubicin-CCNU-vincristine (VCR) treatment. Doxorubicin (25-40 mg/m2) and VCR (1.4 mg/m2) were given intravenously every 21 days; CCNU (65-90 mg/m2) was given orally every 42 days. Patients with liver or bone marrow metastases initially received the lower range doses. All patients failed prior chemotherapy with cyclophosphamide and 5-FU with or without methotrexate and prednisone; 67% received prior hormonal therapy. Pretreatment patient characteristics were comparable in both groups. Objective responses (greater than 50% reduction in tumor size) were seen in 7 of 18 patients (39%) on the VCR containing arm and in 8 of 17 patients (46%) on the doxorubicin-CCNU arm. Survival was not improved by VCR addition with overall survival on the doxorubicin-CCNU arm, approximately 10% greater at all intervals (median 9.1 versus 7.0 months; not statistically significant). However, neurotoxicity was significantly greater in the VCR arm (36% versus 0%; P less than 0.05). In advanced breast cancer, no benefit to VCR addition was seen in prior randomized studies of first-line combinations where VCR was the treatment variable. Such results, combined with our experience with VCR in a salvage regimen, question the value of VCR addition to combination regimens in advanced breast cancer.

Breast Neoplasms↗
PubMed1983

Effects of terbutaline sulphate aerosol on bronchodilator response and lung mucociliary clearance in patients with mild stable asthma.

Ventilatory function and whole lung mucociliary clearance have been assessed in 10 patients with mild stable asthma following inhalation of 1 mg of the beta-adrenergic receptor agonist terbutaline sulphate (Bricanyl, Astra Pharmaceuticals) from a metered dose inhaler (MDI). Compared to placebo inhalation, terbutaline produced marked bronchodilatation (mean percentage increase in FEV1 14%, P less than 0.01). Mucociliary clearance (measured by the in vivo radioaerosol technique) was assessed on three occasions--control, followed by placebo or terbutaline studies in a double-blind, cross-over manner. Particles were removed from the lung at a similar rate in all three studies. The mean (+/- s.e. mean) percentage of aerosol retained in the lungs after 6 h was 58 +/- 5%, 57% +/- 5% and 57 +/- 4% for control, placebo and drug studies respectively. It is concluded that terbutaline sulphate, given as a 1 mg acute dose, does not enhance mucociliary clearance in mild stable asthmatics, although it produces marked bronchodilatation.

Adult↗
PubMed1983

Impaired tracheobronchial clearance in patients with mild stable asthma.

Tracheobronchial mucociliary clearance was measured with the radioaerosol technique in 25 patients with stable, mild asthma, none of whom was taking systemic corticosteroids. The results were compared with those obtained from a control group of 25 healthy subjects matched for age and sex. All patients and healthy subjects were non-smokers. Ventilatory function was significantly impaired in the asthmatic group, which resulted in a more central initial tracheobronchial deposition of inhaled radioaerosol than in the control group. Despite the shorter transit path along the ciliated airways for the tracer radioaerosol in the asthmatic group, mucociliary clearance was found to be significantly poorer than in the healthy control group. This may be important with respect to bronchial mucus plugging.

Adult↗
PubMed1983

Randomized study for the treatment of adult advanced Hodgkin's disease: mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) versus lomustine, vinblastine, and prednisone.

Forty-seven patients with advanced Hodgkin's disease were entered in a prospective, randomized trial comparing MOPP (mechlorethamine, vincristine, procarbazine, and prednisone) with a regimen containing lomustine (CCNU), vinblastine, and prednisone (CCNU-VP). Both groups were comparable for the variables of age, stage, substage (symptoms), histology, prior radiation, and sites of involvement. Seventy-two percent of CCNU-VP-treated patients achieved a pathologically documented complete remission (CR) compared to 41% of the MOPP-treated group. Two additional patients treated with MOPP had remission documented only clinically but have been long-term, disease-free survivors. There was a greater frequency of CR in the patients who had received previous irradiation when compared to patients with no prior irradiation. After a median follow-up of greater than 89 months, there is no statistical difference between the two treatment groups in survival (45% for MOPP and 60% for CCNU-VP). Further, no statistical difference in survival for the two treatment groups was noted when compared by histology, stage, or symptoms. The CCNU-VP combination was better tolerated with significantly less nausea and emesis. The alternative drug regimen of CCNU-VP appears to be as effective as MOPP in producing CR and long-term survival in patients with advanced Hodgkin's disease.

Adult↗
PubMed1982

Dosimetry and preliminary human studies of 18F-5-fluorouracil.

The relative distribution, metabolism and kinetics of 18F containing compounds, following administration of 18F-5-fluorouracil, has been proposed as a prognostic aid in predicting response to 5-fluorouracil chemotherapy. Because 18F has a relatively short physical half-life (t1/2 = 110 min), and the distribution and kinetics of the radiolabeled 5-fluorouracil need to be studied over periods of time that range over several half-lives of the radionuclide, significant quantities of the labeled drug must be administered in order to obtain good counting statistics. The distribution of 18F, following injection of 18F-5-fluorouracil to rats and mice, has been well documented in our previous work. It appears that the distribution of 18F in humans, following administration of 18F-5-fluorouracil is similar to that in rats. We calculated the radiation dose according to the MIRD technique for the eleven main target organs for a reference man. The critical organs, according to these calculations, are the bladder wall, the kidney and the liver, receiving a radiation dose of 729, 184 and 114 mrad per mCi injected, respectively.

Animals↗
PubMed1982

Chest physiotherapy: a review.

Postural drainage enhances mucociliary clearance and produces larger sputum volumes than an equivalent control period in disease characterised by excessive tracheobronchial secretions. Postural drainage, percussion and vibration will improve pulmonary function only in patients with large sputum volumes. There is no evidence that sputum yield is increased by the addition of percussion and vibration. From radioaerosol studies effective cough is limited to central airways. Breathing exercises may be of some immediate value in asthma but are without long term advantages and probably do not alter the ventilation of the underlying lung. IPPB probably does not improve delivery of bronchodilators and is of no benefit (and possible harmful) in the long term treatment of chronic bronchitis. Infective exacerbations of chronic bronchitis not characterised by copious volumes of sputum, uncomplicated pneumonia and routine post-operative states are not indications for chest physiotherapy. The value of regular physiotherapy on ventilation, gas exchange, work of breathing and incidence of infective exacerbations is uncertain but exercise training and rehabilitation of chronic obstructive airways disease improves exercise tolerance and mobility.

Breathing Exercises↗
PubMed1982

Clinical and pharmacokinetic effects of combined warfarin and 5-flourouracil in advanced colon cancer.

Twenty-five patients with advanced measurable adenocarcinoma of the colon were treated with 5-fluorouracil (FUra), 15 to 20 mg/kg/week i.v., plus warfarin p.o. at a dosage which maintains therapeutic levels of anticoagulation. Sixty-four % of patients achieved either objective response (20%) or stable disease (44%). Overall median survival was 19.2 months. Three patients (all with intraluminal lesions) developed gastrointestinal blood loss requiring transfusion and discontinuation of anticoagulation. The interaction between warfarin and FUra as measured by plasma levels was investigated in seven rabbits and three patients. Plasma samples were obtained for 2 hr after FUra administration, both before and after anticoagulation with warfarin. FUra was measured by gas chromatography, and warfarin was assayed using a thin-layer chromatographic fluorescence method. In rabbits, prolongation of FUra plasma t1/2 was seen with high (0.6 mg/kg/hr) but not low (0.025 mg/kg/hr) rates of warfarin infusion. In patients, FUra t1/2 was not changed by therapeutic warfarin anticoagulation. Thus, (a) plasma clearance interaction between FUra and warfarin does not occur in patients receiving therapeutic levels of anticoagulation; (b) FUra and warfarin anticoagulation can be safely given and frequently result in stable disease status for patients with advanced colon cancer. Further trials of this combination are warranted in adenocarcinoma of the colon.

Adenocarcinoma↗
PubMed1981

Treatment of advanced breast carcinoma with 5-fluorouracil: a randomized comparison of two routes of delivery.

Fifty-one patients with metastatic breast carcinoma were randomized to treatment with weekly 5-fluorouracil (5-FU) either by mouth or intravenously. Prior treatment included radiation therapy (75%), chemotherapy(27%), and hormonal therapy (86%). Response frequency (tumor reduction greater than or equal to 50%) in the 49 evaluable patients was 24% (6/25) for oral oral vs. 29% (7/24) for intravenous administration. Disease was stable in an additional 13% of patients treated intravenously and 20% of patients treated orally. Median survival was 9.8 months for intravenously treated patients and 12.1 months for orally treated patients (N.S.). A multivariate model of survival, to adjust for imbalance between treatment groups, also showed comparable survival in the two groups. Neither response nor survival was significantly correlated with nadir granulocyte count. Weekly oral 5-FU results in comparable response and survival to 5-FU given intravenously, consistent with a relatively low dose-response relationship for 5-FU in breast carcinoma.

Administration, Oral↗
PubMed1981

Adriamycin and methyl-CCNU combination therapy in hepatocellular carcinoma: clinical and pharmacokinetic aspects.

Twenty-one patients with unresectable hepatocellular carcinoma (hepatoma) were treated with adriamycin (15-45 mg/m2 q21 D) and methyl-CCNU (75-150 mg/m2 q 63 D) with dosage adjusted for hepatic dysfunction. Objective response frequency was 14% with all responses occurring in patients with normal pretreatment bilirubin levels. Median survival of all patients was 87 days. Initial bilirubin levels greater than 2 mg/dl predicted for decreased survival (median 30 days vs. 115 days, P less than 0.05). Only moderate hematologic toxicity was observed. Plasma profiles of Adriamycin and adriamycinol were determined during 11 courses of Adriamycin administration in seven of these patients. Despite moderately elevated transaminase levels (all cases) and bilirubin levels (three cases), plasma Adriamycin profiles in hepatoma patients were not elevated (terminal half-life of 30 hours) and were indistinguishable from that of non-hepatoma patients with normal liver functions. However, delayed appearance of peak levels and prolongation of terminal half-lives were routinely observed for adriamycinol, a major metabolite of Adriamycin. This resulted ina significant increase in the CXT (concentration X time) ratio of adriamycinol/Adriamycin in hepatoma patients compared with nonhepatoma patients (2.36 +/- 2.12 vs 0.76 +/- 0.31, (P less than 0.05). We conclude that the combination of relatively mild toxicity and normal Adriamycin disposition indicates unusual tolerance to Adriamycin therapy for patients with hepatoma and cirrhosis. As a result, severe dosage adjustments of Adriamycin may not be indicated for all such patients having only moderate hepatic dysfunction.

Adult↗
PubMed1981

Factors influencing the interim interpretation of a breast cancer trial: danger of achieving the "expected" result.

Interim analyses of a metastatic breast cancer trial suggested a significant survival benefit for a five-drug combination chemotherapy compared to a single agent sequential treatment. Subsequent analyses failed to support this observation. Factors influencing the interim interpretation of this trial were investigated and found to include: delayed reporting of data in key cases, treatment effect limited to a patient subset, and problems related to achieving the "expected" result.

Antineoplastic Agents↗
PubMed1981

Objective in vivo analysis of anti-smoking cigarette filters.

Cigarette filters have been introduced to reduce inhaled smoke and also as a means of breaking the smoking habit. Twelve volunteers smoked cigarettes through four ventilated anti-smoking filters (MD-4, Miles Laboratories) and one reference cigarette without an anti-smoking filter in a single-blind, crossover manner. The amount of smoke inhaled was monitored by a radiotracer technique using the isotope 81mkrypton. Compared to the reference cigarette the amount of isotope reaching the lung was reduced to 76%, 63%, 43%, and 37% for filters 1 to 4, respectively, which was less than the reduction to 70%, 40%, 30%, and 20% predicted by the manufacturers. In the case of filters 2, 3, and 4, the observed reductions in isotope inhalation were significant (p less than or equal to 0.01) but were also significantly less (p less than or equal to 0.01) than the manufacturers' predictions.

Adult↗
PubMed1981

Is cough as effective as chest physiotherapy in the removal of excessive tracheobronchial secretions?

The relative value of chest physiotherapy (including cough) and cough alone for the removal of excessive tracheobronchial secretions has been assessed in six patients with stable chronic obstructive lung disease. After labelling with inhaled radioactive tracer particles, clearance of secretions from selected central and peripheral lung regions was followed with a gamma camera linked to a computer. Cough alone and chest physiotherapy (including cough) were equally effective in the enhancement of central lung clearance. Physiotherapy but not cough along accelerated peripheral lung clearance (p less than 0.05). Sputum yield was greater during physiotherapy than during cough (p less than 0.05). These findings confirm the value of chest physiotherapy and high-light the limitation of cough in patients with excessive tracheobronchial secretion and impaired mucociliary clearance.

Bronchi↗
PubMed1981

Lung mucociliary clearance in patients wit Young's syndrome.

Lung mucociliary clearance was measured in 14 patients with primary obstructive azoospermia and chest involvement (Young's syndrome) using the objective, in vivo radioaerosol technique. Lung mucociliary transport was significantly reduced in patients with Young's syndrome compared to 14 control subjects matched for physical characteristics, tobacco consumption and initial topographic distribution of tracer particles within the lungs. This finding indirectly supports the hypothesis that congenital abnormality in the propulsion of sperm in the ciliated epididymis results in the absence of sperm in the ejaculate.

Adult↗
PubMed1981

Maintenance management of acute nonlymphocytic leukemia.

The necessity of intensive maintenance chemotherapy in enhancing the duration of life in patients with acute nonlymphocytic leukemia (ANLL) in remission has been evaluated. Twenty-four patients were managed with maintenance chemotherapy and 24 were not. In patients under 50, there was no evidence that maintenance prolonged survival. In patients over the age of 50, maintenance chemotherapy prolonged survival (p = 0.03). In both groups the duration of first remission appeared to be lengthened in patients on maintenance chemotherapy (p = 0.09). Since patients 50 and older were difficult to reinduce, it appears that the greatest prolongation of life for them is afforded by continuous maintenance chemotherapy which may forestall relapse. On the other hand, patients less than 50 years of age have a high likelihood of achieving a second complete remission; it is in this group that maintenance chemotherapy adds only to morbidity.

Acute Disease↗