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Biomedical subjects

D Ball

Publications and source records attributed to D Ball.

At least 127 records · Page 7Linked to original sources

Concurrent radiotherapy and carboplatin in non small-cell lung cancer: a pilot study using conventional and accelerated fractionation.

Thirteen patients with unresectable non small cell lung cancer were treated with radical radiotherapy and carboplatin administered concurrently. The first 6 patients were treated to a total dose of 60 Gy in 30 fractions in 6 weeks, with carboplatin 70 mg/m2/day on days 1 to 5 during weeks 1 and 5 of radiotherapy. The remaining 7 patients were given 60 Gy in 30 fractions in 3 weeks, treating twice a day (accelerated fractionation). Carboplatin was given as above but only during week 1 of radiotherapy. Twelve patients completed radiotherapy without interruption but 2 patients developed WHO grade 3 neutropenia. Major toxicity was oesophagitis, one patient requiring nasogastric feeding. Average duration of dysphagia (any grade) in the accelerated fractionation group was 21 weeks. Four patients achieved good partial responses even though initial tumour volume was large. We conclude that this treatment is associated with increased but acceptable early mucosal toxicity.

Aged↗

Composition of gastro-oesophageal refluxate.

Fifty two patients with abnormal acid gastro-oesophageal reflux were studied by simultaneous oesophageal pH monitoring and continuous aspiration for 16 hours. Aspirates (from discrete two hour periods) were analysed for volume, pH, bile acids (conjugated and unconjugated), trypsin, and pepsin. The results were compared with pH changes and degree of oesophagitis. Patients with oesophagitis had greater acid reflux than those without, but patients with stricture and Barrett's oesophagus had similar acid reflux to those with uncomplicated erosive oesophagitis. Pepsin concentrations were highest in patients with stricture and Barrett's oesophagus particularly during nocturnal periods. Conjugated bile acids were detected in 75% of patients, mainly during the night, but only 2% of aspirates contained concentrations likely to be cytotoxic. Unconjugated bile acids were not detected, and trypsin was seldom found. Reflux oesophagitis is caused by acid and pepsin. Bile acids and trypsin are probably unimportant.

Adult↗

Effects of the fungal endophyte Acremonium coenophialum in fescue on pregnant mares and foal viability.

Effects of the endophyte Acremonium coenophialum in tall fescue on pregnant mares and foal viability were evaluated. Twenty-two mature pregnant mares were randomly chosen to graze either Kentucky-31 tall fescue that was free from A coenophialum (endophyte-free, EF) or tall fescue infected with A coenophialum (endophyte-present, EP) after the first 90 days of pregnancy through parturition. Concentrations of pyrrolizidine and ergopeptine alkaloids were significantly greater in EP grass, compared with EF pasture. Ten of 11 mares grazing EP pasture had obvious dystocia. Mean duration of gestation was significantly greater for the EP group, compared with the EF group. Foal survivability was severely reduced among mares grazing EP fescue with only 1 foal surviving the natal period. Udder development and lactation were low in mares grazing EP grass. The absence of clinical problems in mares grazing EF grass implicated the endophyte as the causative agent of reproductive problems and perinatal foal mortality in pregnant mares grazing endophyte-infected fescue grass. Caution should be exercised in allowing pregnant mares to graze pastures infected with the endophyte A coenophialum.

Acremonium↗

Etoposide, carboplatin, cyclophosphamide and vincristine in previously untreated patients with small-cell lung cancer.

The efficacy and toxicity of 120 mg/m2 etoposide and 100 mg/m2 carboplatin given i.v. daily x 3 together with 750 mg/m2 cyclophosphamide and 1.4 mg/m2 vincristine given i.v. on day 1 (ECCO) in a regimen given every 28 days for 6 courses was assessed in 90 (40 limited stage, 50 extensive stage) previously untreated patients with small-cell lung cancer. Mediastinal irradiation using 50 Gy in 25 fractions was given to limited-stage patients without progression after 3 courses of chemotherapy. Cranial irradiation with 30 Gy in 10 fractions was given to all patients attaining a complete response (CR). Objective responses were seen in 83% [CR, 60%; partial response (PR), 23%] of patients with limited and 76% (CR, 22%; PR, 54%) of those with extensive disease. The median relapse-free survival for objective responders with limited disease was 13.4 months, with a median of 8.0 months for extensive-stage patients. The median relapse-free survival for patients achieving a CR was 13.4 months, with a median of 7.8 months for those undergoing a PR. The median survival was 13.3 months for patients with limited disease, with a median of 9.6 months for those with extensive disease. The median survival following a CR was 18.2 months, with a median survival of 9.9 months for those showing a PR. The combination was well tolerated, with either no nausea or nausea only (WHO grade 0 or 1) in 56% of patients and minimal mucositis, renal toxicity, neurotoxicity or ototoxicity. Neutropenia measuring less than 1.0 x 10(9) WBC/l (WHO grade 3 or 4) was seen in 74% of patients, with two deaths due to infection occurring during neutropenia. Thrombocytopenia of less than 50 x 10(9) platelets/l (WHO grade 3 or 4) occurred in 24% of patients. ECCO is a new, active, well-tolerated program for previously untreated patients with small-cell lung cancer.

Adult↗

Analysis of angiotensin II binding to human platelets: differences in young and old subjects.

We examined the binding of radiolabeled angiotensin II (AII) to human platelets to characterize the apparent increase in AII receptors observed in older subjects. At 22 degrees C, the amount of radioactivity associated with platelets from older subjects increased continuously for more than 2 hours. The same amount of radioactivity was displaced by addition of unlabeled AII at 30 min and 60 min. In the presence of phenylarsine oxide, in the cold, or when labeled antagonist was the ligand, binding came to equilibrium by 30 min. High pressure liquid chromatography demonstrated that 125I-AII was the major radioactive compound in the supernatant and platelets after incubation, but the platelets also contained radiolabeled AII fragments. Thus, some degradation accompanied interaction of AII and platelets. Phenylarsine oxide did not prevent degradation of bound AII, suggesting that degradation precedes internalization. On average, maximum binding was greater in older subjects whether platelets were incubated with 125I-AII alone, with 125I-AII and phenylarsine oxide to prevent internalization, or when the competitive inhibitor 125I-sar1,ile8-AII was the radioligand. Variability of binding among subjects also increased with age. Thus, platelets bind, degrade, and internalize AII, and the three processes occur to a greater extent in platelets from some, but not all older subjects.

Adult↗

Hypofractionation reduces the therapeutic ratio in early glottic carcinoma.

From 1969-1985 two types of fractionation schedules with similar time, dose, and fractionation factor (TDF) values were used to treat 197 patients with Tis, T1, and T2 squamous cell carcinoma of the vocal cord. One hundred and thirty-one patients were treated with conventional daily 2.0 Gy fractions, and 66 patients were treated once per week with large (5.5-6.6 Gy) fractions (hypofractionated group); both groups were treated over a period of approximately 6 weeks. The local failure and complication rates for patients completing treatment in the two groups were compared; a patient was regarded as having suffered a serious complication of treatment if laryngectomy or tracheostomy had to be performed in the absence of active disease, or if antibiotics and/or corticosteroids had to be prescribed for laryngeal oedema and/or necrosis. In patients with Tis and T1 disease, the failure rate was worse in the hypofractionated group than in the conventionally treated group (p = 0.06). In the smaller group of T2 patients, no significant difference was found in the failure rates between the hypo- and conventionally fractionated groups. Complication rates were similar in Tis/T1 and T2 patients, but significantly higher in the hypofractionated group (p less than 0.001). Neither stage nor fractionation schedule had an effect on survival, but laryngectomy/tracheostomy free survival was significantly worse in Tis/T1 patients receiving hypofractionated treatment, (p = 0.008) although not in T2 patients. These results indicate that in Tis/T1 glottic cancer, hypofractionation of radiotherapy produces a reduction in the therapeutic ratio.

Adult↗

Veratridine, angiotensin receptors and aldosteronogenesis in bovine adrenal glomerulosa cells.

Veratridine inhibited angiotensin binding to its receptors in bovine adrenal glomerulosa cells and vascular smooth muscle. Fifty percent inhibition of adrenal receptors required about 2 X 10(-5) M veratridine. Receptors from vascular tissue were less sensitive. Graphic analysis showed that inhibition resulted primarily from a reduction of receptor number. Angiotensin stimulation of phosphatidylinositol turnover and of aldosterone production was inhibited by veratridine. Analogues of veratridine varied in their receptor inhibitory potency, but these variations did not correlate with the potencies of analogues as hypotensive agents or inhibitors of aldosteronogenesis. Very low extracellular sodium concentrations inhibited the adrenal effects of angiotensin. Neither veratridine nor grayanotoxin, both of which open sodium channels in excitable tissues, had a detectable effect on sodium fluxes in adrenal cells. Inhibition of aldosteronogenesis by veratridine is more likely the result of receptor and post-receptor effects than an alteration of the sodium channel.

Adrenal Cortex↗

Mechanism of enhancing effect of irradiation on production of IL-2.

In order to explain the mechanism of enhancing effect of irradiation on IL-2 production, assumption that radio-induced free radicals could act as a signal for mitogenesis and/or increase lipid peroxidation of T lymphocyte membrane phospholipids was made. Thus, production of metabolites of the lipoxygenase pathway in the arachidonic acid (AA) cascade, known to increase T cell proliferation and lymphokine production could be enhanced by irradiation. We have shown that (1) hydroxyl radical scavenger (DMSO) abolished IL-2 production, (2) inhibitor of the lipoxygenase pathway (NDGA) strongly decreased IL-2 production, (3) thin layer chromatography demonstrated a polar metabolite(s) of AA in increasing amounts according to the following order: non-irradiated resting cells, non-irradiated stimulated cells, irradiated resting cells, and irradiated stimulated cells. Investigations are in progress to identify this metabolite.

Arachidonic Acid↗

The management of metastatic seminoma testis.

Clinical details of 85 men presenting with previously untreated metastatic seminoma are presented. In Stage II disease relapse rate was related to the size of metastases. In IIA (32 patients) the relapse rate was 9.4%; IIB (11 patients), 18.2%; and IIC (23 patients), 39.1%. The continuous disease-free survival rate was significantly worse for IIC than IIA and IIB patients (P = 0.023). No instance of first relapse in supradiaphragmatic nodes was observed in 13 men with Stage II disease treated with irradiation limited to infradiaphragmatic nodes. In relapsing Stage IIC patients, extralymphatic metastasis was as frequent as abdominal relapse. On the basis of these observations, together with preliminary data in nine men receiving Cis-platinum-containing chemotherapy, all of whom are in complete remission, it is proposed that patients with Stage IIA and IIB disease should receive infradiaphragmatic irradiation with chemotherapy deferred until relapse. Stage IIC patients should receive chemotherapy initially, followed by irradiation. In Stage III and IV disease chemotherapy should be initial therapy with radiotherapy for bulky disease on an individualised basis. Moderate elevation of blood B-HCG levels is not inconsistent with a diagnosis of pure seminoma and does not appear to influence adversely the outcome of radiotherapy.

Antineoplastic Agents↗

Purification and characterization of gamma-glutamyltransferase from rat pancreas.

gamma-Glutamyltransferase ((5-glutamyl)-peptide:amino-acid 5-glutamyltransferase, EC 2.3.2.2.) from rat pancreas has been purified to homogeneity and shown to be a glycoprotein of apparent molecular weight 68000, composed of one heavy and one light subunit, with respective molecular weights 43000 and 25000. At the optimum pH 8.0 the specific activity of the purified enzyme is 630 units/mg protein, with L-gamma-glutamyl-p-nitroanilide as substrate (Km = 0.9 mM) and 20 mM glycylglycine as acceptor. The enzyme is inactivated by the active-site modifying agent and glutamine analogue, 6-diazo-5-oxo-L-norleucine, through a specific and stoichiometric reaction with the light subunit (Ki = 1.2 mM); both the inactivation and the modification of the light subunit are accelerated by maleate and prevented by S-methylglutathione. The enzyme is also inactivated by the fluorescent alkylating agent 5-iodoacetamidofluorescein, by specific and stoichiometric incorporation of the fluorescent moiety into the light subunit, which is likewise prevented by S-methylglutathione, but is unaffected by maleate. Antiserum to rat kidney gamma-glutamyltransferase cross-reacts with the pancreas enzyme in immunodiffusion and inhibits its activity in the p-nitroanilide assay. Despite structural, enzymological and immunological similarities between the pancreas and kidney enzymes, their amino acid compositions are markedly different. The rat pancreas enzyme shows an interesting ontological development, being present in minimal amounts in the fetus, and increasing dramatically on birth and during the following 2 days.

Acyltransferases↗

Refeeding after acute gastroenteritis: a controlled study.

Children admitted with acute gastroenteritis were managed with clear fluids and then given either the standard graduated feeding regimen or an abrupt reintroduction of normal feeds. The rapid refeeding group lost less weight, went home sooner, and had no increase in complication rate. Rapid refeeding is a reasonable option in the management of acute gastroenteritis.

Acute Disease↗

Serum lipids in humans fed diets containing beef or fish and poultry.

One half of a group of 129 men and women (74 men and 55 women), in a cross-over design at, within a self-selected diet, one egg and at least 5 oz of beef daily for 3 months while the other half at one egg and at least 5 oz of poultry and fish daily. Then they reversed their diets for 3 months. Blood samples were drawn by venipuncture before the study started and at the end of the 3 and 6 months, for analyses of serum total cholesterol, triglycerides, and high density lipoprotein cholesterol. No statistically significant changes were found in serum lipids in men. In women serum triglycerides but not other serum lipids were significantly higher when poultry and fish had been ingested.

Adult↗