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Biomedical subjects

S A Butler

Publications and source records attributed to S A Butler.

9 recordsLinked to original sources

Distribution of pimonidazole and RSU 1069 in tumour and normal tissues.

The tritium-labelled analogues of pimonidazole and RSU 1069 were injected into mice bearing the KHT murine sarcoma which has a hypoxic cell fraction of approximately 10%. The distribution of activity at 24 h was recorded using autoradiography and measurement of tissue activity. Autoradiographs with both drugs showed high activity in particular cells within tumour, eye (melanin-associated cells), eyelid (Meibomian gland), liver (centrilobular area), skin (sebaceous gland and melanin), stomach (squamous area), footpad, oesophagus, labial gland, Zymbal's gland, preputial gland, parotid gland (intralobular ducts) and airway epithelium. These tissues had previously been identified as sites of binding of misonidazole. The measurement of total tissue radioactivity showed significantly higher activity in liver, eyelid (Meibomian gland), oesophageal lining, kidney and labial gland than was found in the tumour.

Animals

The effect of the alpha-particle emitter astatine-211 in the mouse at the minimum toxic dose.

The radioactive halogen astatine-211 was injected into mice in an amount producing minimal toxicity. Histopathological examination of tissues at intervals between 3 d and 16 weeks showed the following changes: 1. Radiation-induced necrosis and progressive fibrosis of the thyroid gland. The gland was reduced to 25% of its original mass with only a few relatively normal follicles persisting. 2. A small, temporary, reduction in peripheral blood lymphocytes, platelets and red cells and a significant persistant increase in polymorphs. 3. Severe reduction in reproductive cells in the testis with some signs of recovery at 16 weeks.

Animals

Antidepressant treatments, including sibutramine hydrochloride and electroconvulsive shock, decrease beta 1- but not beta 2-adrenoceptors in rat cortex.

The beta 1- and beta 2-adrenoceptor populations in rat cortex were individually quantified by labelling all of the receptors with [3H]dihydroalprenolol and displacing with isoprenaline (200 microM) or CGP 20712A (1-(2-[(3-carbamoyl-4-hydroxy)phenoxy]ethylamino)-3-[4-(1-methyl-4- trifluoromethyl-2-imidazolyl)phenoxy]-2-propanol methanesulphonate; 100 nM) to define total beta-adrenoceptors and beta 1-adrenoceptors, respectively. Binding parameters for beta 2-adrenoceptors were calculated by the difference. Oral administration of the monoamine reuptake inhibitors sibutramine HCl (3 mg/kg), amitriptyline (10 mg/kg), desipramine (10 mg/kg), or zimeldine (10 mg/kg) for 10 days decreased the total number of beta-adrenoceptors present in rat cortex. This effect was entirely due to a reduction in the number of beta 1-adrenoceptors. Similarly, 10 days of treatment with the monoamine oxidase inhibitor tranylcypromine (10 mg/kg p.o.) or five electroconvulsive shocks (ECSs; 200 V, 2 s) spread over this period also down-regulated beta-adrenoceptors by reducing the content of the beta 1-subtype. By contrast, treatment with clenbuterol (5 mg/kg p.o.) for 10 days reduced the number of cortical beta-adrenoceptors by an effect on the beta 2-adrenoceptor population. The effects of short-term treatment with these drugs were also investigated, and, using the doses shown above, the results of 3 days of administration or a single ECS were determined. Sibutramine HCl and desipramine were alone in producing a reduction in number of beta-adrenoceptors after 3 days. Once again, this was exclusively due to a loss of beta 1-adrenoceptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Amitriptyline

Toxicity of astatine-211 in the mouse.

The toxicity of the alpha particle emitting halogen astatine-211 was examined in male and female mice. Pathological changes were seen in mice killed at 14 days and/or at 56 days following a single injection of 61 kBq211 At per g body weight. The tissues affected, in order of severity were: spleen, lymph nodes, bone marrow, gonads, thyroid, salivary glands and stomach.

Animals

Treatment of the murine lymphoma A31 with intravenous, sterilized, 114mIn-loaded A31 cells.

The effect on a mouse B-cell lymphoma (A31) of intravenously (i.v.) injected, sterilized, A31 lymphoma cells loaded with [114mIn]oxine was examined. The treatment of the B-cell lymphoma was started 14 days after the i.v. injection of 10(2) viable cells. The [114mIn]oxine-bearing gamma-ray sterilized A31 cells were injected at two dose levels either with 37 kBq on days 15, 22 and 27 (total dose 110 kBq) or 74 kBq on days 15, 16, 17, 22 and 27 (total dose 370 kBq). The smaller amount (110 kBq) of 114mIn activity did not extend the survival of mice when compared with non-treatment controls but the greater amount (370 kBq) produced a significant extension in survival. This survival time was longer than that produced by 370 kBq [114mIn]oxine without carrier cells, lethal total body irradiation (with bone marrow rescue), splenectomy at day 14 or a single injection on day 14 of a maximum tolerated dose of vincristine sulphate. The increase in survival time was thought to arise mainly from 114mIn held by spleen macrophages. The accumulated spleen dose by 7 days after the fifth of the five injections of 74 kBq was 167 Gy. At this dose level the spleen was hypoplastic and the red cells, white cells and platelets in the peripheral blood were severely, though not permanently, suppressed.

Animals

Cimetidine versus ranitidine: single-dose, oral regimen for reducing gastric acidity and volume in ambulatory surgery patients.

This placebo-controlled trial compared the efficacy of single oral doses of cimetidine or ranitidine in maintaining intragastric pH and volume greater than 2.5 and less than 25 ml, respectively, in ambulatory surgery patients requiring general anesthesia. Patients were randomized to receive either placebo, ranitidine HCl 150 mg, or cimetidine HCl 400 mg upon rising on the morning of surgery. At induction, the cimetidine and ranitidine groups had significantly higher (p less than 0.05) gastric pH values than the placebo group. At extubation, the ranitidine group had a significantly higher (p less than 0.05) gastric pH than either the cimetidine or placebo group. Both H2-blocker groups had lower volumes when compared with the placebo group at extubation (p less than 0.05). There were more patients at risk for aspiration pneumonitis (pH less than 2.5 and/or volume greater than 25 ml) in the cimetidine group (46 percent) than in the ranitidine group (15 percent). All placebo-treated patients were at risk for aspiration pneumonitis. We did not find subjective clinical evidence of aspiration pneumonitis in our patients. We conclude that both ranitidine and cimetidine are superior to placebo, but ranitidine may be the preferred agent because of its more consistent effect on gastric pH and volume.

Adult

The influence of prior total body irradiation on the tissue distribution of mouse lymphoma/leukemia.

The effect of a single dose of 10 Gy X rays on the distribution of subsequently injected mouse lymphoma/leukemia cells was studied. The organ distribution of an acute myeloid leukemia (A46) was not affected by prior (90 days) administration of 10 Gy X rays. A T-cell lymphoblastic lymphoma/leukemia (A55) and a B-cell lymphoblastic lymphoma/leukemia (A31) produced enhanced infiltration of the lung when 10 Gy of total body irradiation (TBI) was given 90 days before the tumor cells. The infiltration was predominantly in the peribronchiolar and perivascular spaces. Enhancement was not seen in any tissues other than lung. The possibility is raised that in those acute lymphoblastic leukemia patients whose treatment includes TBI, residual circulating cells may be encouraged to infiltrate the lung.

Animals

Urologic manifestations of paroxysmal nocturnal hemoglobinuria.

A long-term study of 17 patients with paroxysmal nocturnal hemoglobinuria revealed an unexpectedly high incidence of functional and anatomic renal abormalities. All patients demonstrated varying degrees of hematuria and proteinuria distinct from hemoglobinuria. All patients also had granular casts in multiple urinalyses. Evaluation of renal function revealed hyposthenuria, abnormal tubular function and declining creatinine clearance. Radiologically, one or more of these demonstrated enlarged kidneys, renal cortical infarcts and thinning, papillary necrosis, acute renal atrophy, retroperitoneal hematoma and ureteral infarction, which were confirmed by autopsy studies. Hypertension developed in 7 patients. Urinary tract infection was uncommon and no patient had a clinical history compatible with chronic or acute pyelonephritis. Contrary to usual opinion our compatible clearly showed evidence of frequent and widespread renal pathology in paroxysmal nocturnal hemoglobinuria most likely due to repeated microvascular thromboses similar to the venous trombosis involving other organs in this disorder. Since most of these patients present initially to urologists knowledge of this entity is mandatory.

Adolescent