Actions of growth hormone-release inhibiting hormone (somatostatin) on the renin aldosterone system.

Administration of growth hormone-release inhibiting hormone (GH-RIH, somatostatin), as a 90 minute infusion (10 mug/min), to 3 healthy young men under conditons of active renin secretion acheived by pretreatment with furosemide (80 mg daily for 5 days), caused a mean 30% fall in plasma renin activity, which returned to basal levels immediately after stopping the GH-RIH infusion. Plasma aldosterone levels were not affected during the course of this experiment.

Studies of contact activation of blood in haemodialysis.

A study of patients on Kiil and Travenol coil dialysis has shown that kallikrein esterase, the kinin precursor, is increased in the venous blood during dialysis and that this is accompanied by an increase in the venous effluent of the dialysers. In addition Hageman factor depletion and an increase of platelet factor 4 has been found in the venous effluent. Such studies indicate surface activation of coagulation in the dialysers and will be of use in future studies of the suitability of different dialysers.

Experimental infection of neonatal pigs with CNF toxin-producing strains of Escherichia coli.

To examine and compare the pathogenicity of cytotoxic necrotising factor (CNF)-producing Escherichia coli, two litters of piglets were infected orally with 10(10) E coli O88 or 10(10) E coli O32 strains. Of the six piglets infected with E coli O88, two died within 24 hours and three developed blood-stained diarrhoea. The other piglets were killed one, five, six and eight days after infection, when bacterial cultures indicated an overwhelming bacteraemic infection with E coli O88 in the early stages followed by clearance through the large intestine. The pathological changes consisted of an early enteritis, progressing to enterocolitis and a bacteraemic spread to the lungs. The histopathological changes were characteristic of toxaemic effects in brain, heart, liver and kidney, and characterised by congestion, oedema and exudation. Infection with E coli O32 produced a milder but similar enterocolitis, also with bacterial colonisation in the lungs. The histopathological findings again reflected a toxaemia. The enteritis was more persistent after E coli O32 infection and the strain persisted in large numbers in the intestine. No evidence of bacterial adherence to the intestinal mucosa was found with either strain. Enteroinvasion was only evident in one E coli O88-infected piglet, but the consistent occurrence of interstitial pneumonia showed the predilection of these organisms for the lung. The results confirm the toxigenic properties of CNF+ E coli and suggest an important role for this organism in enteric infection of young pigs.

Appraisal of the suitability of a disease model of acute salmonellosis in calves for chemotherapeutic studies.

When young calves were dosed orally with 10(10) organisms of a culture of Salmonella dublin, typical symptoms of acute salmonellosis followed with a death rate of 86 per cent. Peak mortality occurred six days after infection. As a result of a statistical appraisal of the consistency of mortality in groups of untreated calves a model is proposed for the therapeutic evaluation of antibacterial compounds, which compares the number of survivors in groups of seven or eight calves with a minimum of four needed for significant indication of efficacy. Bacteriological and pathological investigations showed that the experimental disease was initially an acute systemic infection followed by severe enteritis. Measurements of plasma concentrations of enzymes and other constituents did not achieve the desired objective of establishing a method of quantitative evaluation of the clinical status of individual animals, although some changes occurred which were consistent with the pathology of the disease and suggested possible mechanisms by which jaundice occurred.

Distribution of trimethoprim/sulphadiazine in plasma, tissue and synovial fluids.

The subcutaneous implantation of tissue cages was used to study the distribution of trimethorprim and sulphadiazine into tissue (interstitial) fluid in calves, sheep and dogs over a 24-hour period. After oral dosing there was good gastrointestinal absorption of both antibacterial agents in dogs but only of the sulphonamide in sheep. The concentration of trimethoprim in tissue fluid peaked at five to seven hours after administration when it exceeded the plasma concentration. Sulphadiazine persisted in the plasma for longer than trimethoprim, but distribution into tissue fluid was slower. The findings show that reliance on plasma concentration curves alone in determinations of bioavailability of chemotherapeutic agents may lead to false interpretations.

Evaluation of a mixture of trimethoprim and sulphaquinoxaline for the treatment of poultry: safety and palatability studies.

The safety of a 1:3 mixture of trimethoprim (TMP) and sulphaquinoxaline (SQX) for administration in food or water was assessed in broiler chickens, chicks of an egg laying strain and breeding fowl. The only effects recorded in six-week-old broilers medicated for seven days at levels ranging from 16 to 133 mg TMP plus SQX per kg bodyweight were decreases in water or food consumption, probably caused by unpalatability at overdosage levels, and associated decreases in weight gain and packed cell volume at an achieved overdose level of 4.4 times the recommended use concentration (RUC). Breeding fowl medicated at levels of 1 X or 3 X RUC for 14 days showed slightly reduced reproductive performance reflected by lowered egg production, egg weight and hatchability. These effects were temporary and performance equal to that of unmedicated birds was re-established by 14 days after medication ceased. Week-old chicks medicated for five days at levels from 0.7 to 4.7 X RUC showed normal growth rate over 12 days. Eleven-day-old chicks could not distinguish medicated from unmedicated water.

Current attitudes of head and neck oncologists in the United Kingdom to induction chemotherapy for locally advanced head and neck cancer: a survey of centres participating in a national randomised controlled trial.

OBJECTIVES: Induction chemotherapy (IC) followed by chemoradiation (CRT) for locally advanced squamous cell head and neck cancer (SCCHN) remains controversial in the absence of clear evidence to define its role. As part of a prospective, randomised, multicentre study of CRT for stage III/IV laryngeal/hypopharyngeal cancers (ART DECO, CRUK/10/018), we have examined the attitudes of oncologists in the United Kingdom (UK) to IC. MATERIALS AND METHODS: Head and neck oncologists across the UK who expressed an interest in participating in the ART DECO trial were asked to complete a short written questionnaire designed to identify current UK practice of IC for stage III-IVb SCCHN. Completed questionnaires were returned to the clinical trials office prior to patient recruitment. RESULTS: Clinicians from twenty-five/48 centres (52.1%) responded. Twenty centres (80%) elected to use IC in the trial. For stage III disease, 80% of centres did not prescribe IC for T1N1 disease and 60% did not offer IC for T3N0 disease. Patients with bulky primary tumours or extensive nodal disease were more likely to receive IC. Thirteen prescribing centres (65%) use 3 drugs (docetaxel, cisplatin, and 5-fluorouracil) compared to 7 (35%) using 2 drugs (cisplatin and 5-fluorouracil). Fifteen centres (75%) prescribed 2 cycles of IC, and 5 (25%) prescribed 3 cycles. There was variation in the dosage for both the 2- and 3-drug regimens. CONCLUSION: Results suggest that clinical practice in the UK is currently divided between a 2- versus 3-drug regimen for IC for specific subgroups of patients. A consensus regarding the optimal combinations and dosages is required before further optimization of systemic therapy with other cytotoxics and biological agents is attempted.