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Biomedical subjects

C G Wathen

Publications and source records attributed to C G Wathen.

At least 37 records · Page 2Linked to original sources
PubMed1991

Glutathione S-transferase mu locus: use of genotyping and phenotyping assays to assess association with lung cancer susceptibility.

In mammals, the cytosolic glutathione S-transferases (GSTs; EC 2.5.1.18) are a supergene family comprised of four multigene families, named alpha, mu, pi and theta. In man, within the mu class gene family there is a gene (the GSTmu 1 locus) that is polymorphic and is only expressed in 50-55% of individuals. It has previously been reported, using trans-stilbene oxide (tSBO) as a specific substrate for the expressed phenotype, that smokers with the null phenotype had a greater susceptibility to lung cancer. In a subsequent study, it was shown that on Southern blot analyses of human DNAs using a GSTmu 1 cDNA probe a DNA fragment was absent in certain individuals. The absence of this band correlated with the tSBO null phenotype. In the present work, DNA clones derived from GST mu class genomic sequences were used as probes in Southern blot analyses and confirmed the correlation between the lack of a DNA fragment and the null phenotype; moreover in this case, using radioimmunoassay for the GST mu protein, these probes were then used in a genotyping assay to investigate further the association of GSTmu 1 polymorphism with susceptibility to lung cancer. It was found that in a control group of 225 individuals, of unknown smoking history, 42% lacked the restriction fragment and were homozygous null, and therefore 58% were either heterozygous or were homozygous normal. Among 228 lung cancer patients, which included all tumour types, a similar distribution occurred, namely 43% were homozygous and 57% were heterozygous or homozygous normal. If, however, the tumours were analysed by tumour type a small but significant positive correlation with the homozygous null genotype was seen in squamous carcinoma of the lung, and an apparently negative correlation with adenocarcinoma of the lung.

Blotting, Southern↗
PubMed1991

Vindesine and etoposide chemotherapy in the management of patients with small cell lung cancer and poor prognosis.

Twenty-five patients with histologically proven small cell lung cancer who were in too poor physical condition to receive 'aggressive' chemotherapy were treated with vindesine and etoposide (VE). The median survival was 195 days, and there were 4 survivors of greater than 460 days. Eight patients died before the second pulse of chemotherapy, and these all had a Karnofsky score of less than or equal to 20 at diagnosis. Toxicity of the chemotherapy regimen was minimal, and the results suggest that VE chemotherapy may be suitable for the treatment of patients with small cell lung cancer who are unsuitable for more toxic chemotherapy.

Administration, Oral↗
PubMed1990

The haemodynamic effects of long term felodipine therapy in previously untreated essential hypertension.

Sixteen patients with previously untreated mild/moderate hypertension (WHO Stage I) were studied: 7 women and 9 men, mean age 56.2 y. Haemodynamics, central and pulmonary blood volumes were measured by radionuclide techniques and repeated after 8 weeks felodipine therapy. To achieve a target diastolic blood pressure of less than 95 mm Hg 12 patients required 5 mg bid, 2 10 mg bid and 1 2.5 mg bid; 1 withdrew after 2 weeks. Mean (SD) arterial blood pressure (mm Hg) was 189/106 before, and 182/103 after 2 weeks placebo treatment and fell to 148/84 after 8 weeks felodipine therapy. Relative systemic vascular resistance fell by 19% from 2146 to 1734 dyn.s.cm-5. There were no significant changes in heart rate, cardiac index, total blood volume, pulmonary blood volume or left ventricular ejection fraction. Plasma renin activity did not rise significantly. Short lived vasodilator side effects occurred in 7/16 patients during initial treatment and mild ankle oedema persisted in 4/16 patients. In contrast to the haemodynamic changes seen acutely with felodipine, the only sustained changes after 8 weeks therapy are reductions in systemic vascular resistance and blood pressure.

Adult↗
PubMed1990

Radionuclide studies of left ventricular function in normal subjects.

The effects of age and exercise on cardiac function in a normal male population have been assessed by ECG-gated radionuclide ventriculography. Fifty-nine subjects aged from 25 to 54 years were studied (mean 44 +/- 10 S.D. years). Resting left ventricular ejection fraction (LVEF) was 0.54 +/- 0.07 and this increased by 0.07 +/- 0.05 during supine submaximal exercise at 75 watts. The mean increase in cardiac output on exercise was 93 +/- 30%. Stroke volume increased on exercise by 23 +/- 13% and end-systolic volume decreased by 10 +/- 16%. There was a weak correlation (P less than 0.05) between age and change in LVEF on exercise but the increase in cardiac output on exercise was not age dependent. It is important to use an age matched control population in any study of cardiac function.

Adult↗
PubMed1990

A comparison of cobalt (57Co) bleomycin scanning and contrast-enhanced CT scanning for assessment of the mediastinum in lung cancer.

Sixty patients with histologically proven lung cancer who had been accepted for mediastinoscopy or thoracotomy were prospectively entered into a study to evaluate computed tomographic (CT) scanning, 57Co-bleomycin scanning, and barium swallow in preoperative assessment of mediastinal lymph node metastasis. Fifty-six patients had thoracotomy at which all accessible lymph nodes were sampled. Twenty-four patients were found to have mediastinal tumor on histologic analysis of the resected mediastinal lymph nodes. Neither 57Co-bleomycin scanning nor barium swallow were clinically useful, with sensitivities of 21 percent and 11 percent respectively, whereas CT scanning was helpful. However, there was no clear cutoff point of node size to optimize sensitivity and specificity for CT scanning. When nodes greater than or equal to 15 mm were taken to indicate likely malignancy, the sensitivity was 58 percent and the specificity was 87 percent and when greater than or equal to 10 mm was used the sensitivity was 80 percent but the specificity was only 55 percent. There was no clear relationship between the size of the largest resected lymph node in each patient and the presence of malignant lymph nodes. Only 42 percent of patients with resected nodes greater than or equal to 2 cm had histologic evidence of metastases. We conclude that CT scanning should be used to indicate the presence and site of mediastinal lymph nodes, which, when visualized, should always be sampled and histologically examined prior to resection of primary tumor.

Aged↗
PubMed1989

Cutaneous vasculitis associated with rifampin therapy.

Immune complex-mediated vasculitis is a well-recognized form of idiosyncratic drug reaction. We report cutaneous vasculitis in association with therapy with rifampin (rifampicin). To our knowledge, this has not previously been documented. Rifampin is widely used, and such reactions are therefore important to note.

Aged↗
PubMed1988

Imipenem-cilastatin in the treatment of respiratory infections in patients with chronic airways obstruction.

Chest infections with organisms resistant to conventional antibiotics are common in patients with chronic lung disease. We have studied the use of imipenem in 40 (28 M 12 F) patients admitted for treatment of chest infections. Patients were treated with imipenem 0.5 g four times daily by intravenous infusion for 6.3 +/- 1.6 (S.D.) days. Forty-six respiratory pathogens were cultured from 36 patients including 18 Haemophilus influenzae, 6 H. parainfluenzae, 6 Streptococcus pneumoniae, 8 Pseudomonas aeruginosa, and 6 Branhamella catarrhalis. Forty-three of the 46 isolates were sensitive to imipenem, 28 to ampicillin, 33 to tetracycline and 35 to cotrimoxazole. Thirty-eight of the 40 patients improved clinically, and 34 of the 36 patients with positive sputum culture had no pathogens in their sputum after treatment. Twenty patients developed minor phlebitis at the infusion site but there were few other side effects. Imipenem may prove useful in the treatment of chest infections, particularly when the organism is resistant to conventional antibiotics.

Adult↗
PubMed1988

The effects of controlled oxygen therapy on ventricular function in patients with stable and decompensated cor pulmonale.

We made simultaneous measurements of pulmonary hemodynamics, cardiac output, and right ventricular ejection fraction (RVEF) to assess the right ventricular function in 14 patients with pulmonary arterial hypertension as a result of chronic obstructive pulmonary disease (COPD). From these measurements, the right ventricular end-systolic pressure/volume relationship could be calculated and used to assess right ventricular contractility. Eight of the patients were clinically stable, without edema, and 6 presented acutely with gross edema, indicating decompensated cor pulmonale. Measurements were made at rest, while breathing air and oxygen. Although mean pulmonary arterial pressure (Ppa) was similar in those with (Ppa = 33 +/- 6 mm Hg) and without edema (Ppa = 30 +/- 8 mm Hg, p greater than 0.05), RVEF was lower in edematous (RVEF = 0.23 +/- 0.11) compared with non-edematous patients (RVEF = 0.47 +/- 0.04, p less than 0.01). Cardiac output was normal in both groups. The mean right ventricular end-systolic pressure/volume ratio (P/V) was lower in those patients with edema (P/V = 0.41 +/- 0.27), as compared with those without edema (P/V = 1.69 +/- 0.35, p less than 0.05), as a result of an increase in right ventricular end-systolic volume index. Similarly, left ventricular end-systolic volumes were higher in edematous than in non-edematous patients. Breathing 1 to 3 L/min of oxygen for 30 min decreased total pulmonary vascular resistance (p less than 0.05) in those patients without edema, but not in patients with edema. Oxygen did not change RVEF, left ventricular ejection fraction (LVEF), or the ventricular end-systolic P/V relationships.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1988

Distribution of IgE-bearing cells in renal biopsies in Wegener's granuloma.

A comparison was made between the renal biopsy appearances of Wegener's granuloma, microscopic polyarteritis and diffuse endocapillary proliferative glomerulonephritis, including the distribution of surface IgE-bearing mast cells. In microscopic polyarteritis and in other inflammatory conditions mast cells were usually associated with areas of interstitial inflammatory infiltrate, whereas in Wegener's granuloma mast cells were usually separate from areas of inflammation, suggesting a role for mast cells in the development of the renal lesion of Wegener's granulomatosis.

Adult↗
PubMed1988

Hypothalamic malfunction in cerebral sarcoidosis with abnormalities in temperature regulation and vascular control.

A case of abnormal temperature and vascular regulation developing in a patient who had suffered from active hypothalamic sarcoidosis 10 years previously is described. His symptoms have responded to therapy with a beta adrenergic blocking agent and he remains well 2 years after the onset of symptoms. The contrast between this case and the previous reports of hypothalamic sarcoidosis affecting temperature control are discussed.

Adult↗
PubMed1987

Effect of the partial beta-agonist prenalterol on plasma renin activity in patients with left ventricular failure.

Beta agonist therapy for heart failure has been disappointing, perhaps because of renin induced aldosteronism. To investigate this possibility we measured plasma renin activity (PRA) in 23 patients (17 male, 6 female, age 41-70) with New York Heart Association stage III heart failure due to ischaemic heart disease in a placebo controlled trial over one month. All patients received constant doses of digoxin and diuretics throughout the trial. Compliance was confirmed in all patients by digoxin and prenalterol assay. In a preliminary (dose titration) study of 9 patients there was a progressive, but non-significant rise of mean PRA from 14.8 to 17.6 and 27.7 ng/ml per h with doses of 20, 50 and 100 mg of prenalterol, respectively. After one month of treatment with prenalterol (n = 11), PRA was 12.8 +/- 2.4 (SEM) ng/ml per h which was not significantly different from the initial level of 14.4 +/- 2.3 ng/ml per h (n.s.). The placebo group (n = 12) results were 13.8 +/- 4.2 ng/ml per h at entry and 14.4 +/- 5.2 ng/ml per h at one month (n.s.). These results indicate that PRA is elevated by acute treatment with the partial beta agonist prenalterol but stimulation of renin secretion does not appear to occur with chronic therapy.

Adult↗
PubMed1987

Tuberculosis of the trachea.

A patient is described who presented with stenosis of the upper trachea causing respiratory distress. There was no evidence of tuberculosis elsewhere in the body but biopsy showed a granulomatous lesion and there was a good response to anti-tuberculosis chemotherapy. A temporary tracheostomy was needed.

Antitubercular Agents↗
PubMed1987

The use of felodipine in the treatment of severe hypertension.

To investigate the use of felodipine in severe hypertension 2 separate studies were carried out. In the first study, 101 patients on a fixed combination of atenolol 100mg and chlorthalidone 25mg who required additional or 'third line' therapy for proper control, were randomised to either felodipine or hydralazine and the dosage was increased if the supine diastolic blood pressure was greater than 90mm Hg. Felodipine reduced blood pressure more effectively than hydralazine and the incidence of adverse reactions was similar in both groups. In the second study, 17 patients with severe hypertension (WHO stage III), who had not been controlled by therapy with atenolol, thiazide diuretic and hydralazine, prazosin or nifedipine were studied. Patients were subsequently controlled by a combination of atenolol, frusemide or bumetanide, and minoxidil. Once stabilised, the patients then took part in a double-blind crossover study comparing minoxidil and felodipine. The patients' blood pressure was the same on both treatment regimes but their bodyweight was lower after felodipine administration. Felodipine is probably more effective than hydralazine and as effective as minoxidil in treating severe hypertension. As felodipine is usually well tolerated it should prove a useful drug in treating refractory hypertension.

Antihypertensive Agents↗
PubMed1987

The use of captopril and captopril plus frusemide as antihypertensive agents in non-insulin dependent diabetes.

After all previous antihypertensive treatment had been stopped, blood pressure and glucose tolerance were measured in 16 hypertensive non-insulin treated diabetics before and again six weeks after treatment with captopril, an angiotensin-converting enzyme inhibitor. Supine blood pressure fell from 184 +/- 4.1/103 +/- 2.6 to 165 +/- 5.2/88 +/- 2.1 mmHg (P less than 0.001) and erect from 179 +/- 5.2/102 +/- 3.2 to 158 +/- 5.6/87 +/- 2.6 mmHg (P less than 0.005). The area under the oral glucose tolerance curve fell from 2313.6 +/- 154 to 2192.8 +/- 146 mmol/min/l (P less than 0.02). There was no change in plasma insulin, total glycosylated haemoglobin or fructosamine. Four patients who failed to show lowering of supine diastolic pressure below 95 mmHg were additionally given oral frusemide with further improvement in blood pressure and no alteration in carbohydrate intolerance. It was concluded that captopril alone is usually an effective antihypertensive agent in non-insulin dependent diabetes with the addition of frusemide benefiting resistant cases. Glucose intolerance did not worsen with either captopril alone or captopril plus frusemide.

Blood Glucose↗