No abstract

Captopril (50 mg orally) produced a significant fall in systolic and diastolic blood pressure in six normotensive sodium replete subjects, without a rise in heart rate. On captopril, there was no change in the expected normal increase in heart rate on standing. Supine plasma noradrenaline was not reduced by captopril and normal postural increases were maintained. Atropine (0.04 mg/kg i.v.) reduced the difference in blood pressure change between captopril and placebo. Facial immersion in water produced a bradycardia. This change was abolished by atropine and attenuated both by captopril and edrophonium (10 mg i.v.), a cholinesterase inhibitor. Lying down after 6 min standing produced an immediate transient tachycardia, which was abolished by atropine and attenuated by captopril. Blood pressure and heart rate rose after a cold pressor test on both captopril and placebo. The tachycardia during the Valsalva manoeuvre was inhibited by edrophonium and to a lesser extent by captopril. The effects of captopril and edrophonium were additive. Parasympathetic activity of captopril may contribute to its haemodynamic profile.

105AD7 is a human monoclonal antibody that mimics the complement regulatory protein, CD55, overexpressed by many solid tumours including osteosarcoma. This study was designed to assess the toxicity and efficacy of this vaccine in a young age group of patients within 1 -6 months of myleosuppressive chemotherapy. Out of 28, 20 (71%, 95% CI 51 -87%) patients showed a significant T-cell proliferation response in vitro to the 105AD7 protein but not to human IgG. Furthermore, 13 out of 22 (59%, 95% CI 36 -79%) patients showed antigen-specific gIFN secretion (range 20 -370 U/ml). Nine out of 28 (32%, 95% CI 16 -52%) patients made weak antibody responses to CD55. This study showed that 105AD7 was well tolerated in younger patients with osteosarcoma. In addition, two patients with possible clinical responses were given compassionate permission to continue immunisation quarterly for 2 years. They both remain alive and disease free 5.8 and 6.5 years from original diagnosis of osteosarcoma and showed no adverse effects of repeated immunisation. In conclusion, the majority of patients showed measurable T helper responses when vaccination was commenced within a 6-month window of intensive chemotherapy with no clinically significant toxicity. Future clinical trials incorporating immune stimulation strategies should include early introduction of vaccines during the highest risk period for relapse.

No abstract

SummaryWater lead concentrations were measured in 970 households throughout Scotland. Blood lead concentrations were measured in 283 people living in houses with water lead levels of over 0-48 ,tmol/l (100 ,ug/l). A highly significant correlation was found between lead concentrations in water and blood. Raised blood lead concentrations were associated with renal insufficiency, reflected in raised serum urea concentrations, and with hyperuricaemia, although there was no evidence of clinical disease in any of the affected people. This is further evidence that excessive lead in domestic water supplies has a harmful effect on the community's health.