The antiplatelet drug ticlopidine was assessed as an agent for improving the patency of Brescia-Cimino arteriovenous fistulas as access for hemodialysis. In a double-blind randomized study over 1 month, two of six fistulas in the ticlopidine group and five of nine in the placebo group failed. A further one placebo and two ticlopidine patients still had functioning fistulas at the time of withdrawal for technical reasons from the trial. Ticlopidine appears, therefore, to enhance the efficacy of Brescia-Cimino fistulas, at least in the short term.

The mechanism of hypertension induced by recombinant human erythropoietin (rHuEPO) is unclear but may include an increase in peripheral vascular resistance. We studied changes of arterial pressure and plasma endothelin in nine consecutive hemodialysis patients before, and 6 and 12 weeks after, starting rHuEPO. In six patients, changes in cardiac index (CI), stroke index (SI) and total peripheral resistance index (TPRI) were measured by bioimpedance, and forearm vascular responsiveness to intra-arterial norepinephrine (30 to 240 pmol/min) and endothelin-1 (5 pmol/min) were assessed. Six healthy age and sex matched subjects also underwent assessment of forearm vascular responsiveness to norepinephrine and endothelin-1. Treatment with rHuEPO significantly increased hemoglobin and mean arterial pressure (MAP). TPRI also increased by 35 +/- 11%. Plasma endothelin, although elevated basally, remained unchanged. Intra-arterial infusion of norepinephrine caused a maximal increase in forearm vascular resistance (FVR) of 17 +/- 9% before rHuEPO, significantly less than the 32 +/- 5% increase in healthy control subjects (P = 0.04). The response increased to 65 +/- 15% (P = 0.03) after 12 weeks rHuEPO treatment (P = 0.51 vs. controls). Endothelin-1 caused a maximal increase of FVR at 60 minutes of 45 +/- 24% before rHuEPO, which was not significantly different from controls, and tended to decrease with rHuEPO therapy. The response to endothelin-1, but not norepinephrine, correlated inversely with MAP (r = -0.52; P = 0.03) and TPRI (r = -0.51; P = 0.04). In conclusion, these studies show that anemia in chronic renal failure is associated with depressed vascular responsiveness to norepinephrine which is restored by rHuEPO therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Exposure to organic solvents was compared by interview and questionnaire in 50 patients with biopsy-proven proliferative glomerulonephritis in whom there was no evidence of systemic disease or preceding infection with that of 100 control subjects matched for age, sex and social class. The interview was conducted by a lay person who did not know whether the interviewee was a patient with glomerulonephritis or a control subject. The exposure scores derived from the results of the questionnaires were significantly greater in the patients with glomerulonephritis than the control subjects (13,186 ± 3,716 vs. 3,030 ± 1,152, p < 0.01). The degree of exposure was higher in those patients with the more severe diffuse endocapillary proliferative glomerulonephritis than in those with mesangial proliferative glomerulonephritis. In the glomerulonephritis patients solvent exposure was mainly occupational in origin and involved fuels, paints and degreasing agents in most cases. This occupational exposure was significantly greater than in the control subjects (13,061 ± 3,858 vs. 2,878 ± 1,146, p < 0.01). It is suggested that exposure to organic solvents may participate in the pathogenesis of non-systemic proliferative glomerulonephritis.

The ventilatory responses to CO2 without hypoxia, to hypoxia at constant PACo2 and to CO2 combined with hypoxia were measured in duplicate with an interval of 20 min. between the two sets of measurements. The PAC0O threshold during the second set differed in only random fashion from that during the first set; so did the CO2 sensitivity in the absence of hypoxia. The CO2 sensitivity during hypoxia, however, was significantly greater during the second set of measurements. The relevance of these results to the investigation of drugs which affect respiration is discussed.IN studies of the analeptic drugs ethamivan and prethcamide [Anderton et al., 1962; Anderton and Harris, 1963 b] the ventilatory response to changes in alveolar CO2 tension (Pco2) was measured before and during administration of the drug. Both drugs were shown to stimulate breathing, as compared with the effect of merely repeating the ventilatory measurements without giving any drug. Subsequent experiments were carried out, using ethamivan, to study the ventilatory response to hypoxia at constant alveolar Pco, and these appeared to show that the drug also increases the response to hypoxia. When control experiments were done, however, it was found that repeating the measurements, without giving the drug, resulted in an increased hypoxic response of about the same magnitude as when ethamivan was given. We therefore decided to undertake further control experiments and the results of these and the previous ones are now presented. METHODSGas mixtures were supplied to the subjects, and ventilation and alveolar gas tensions measured, by methods and under conditions previously described [Cunningham et at., 1957;Anderton et al., 1962;. The subjects were all young, healthy volunteers, mostly male medical students; two nurses were the only females studied. All ventilatory measurements were made in the steady state of ventilation and alveolar Pco2. Each experiment consisted of a duplicate set of observations (periods 1 and 2) separated by an interval of 20 mi. during which the mouthpiece was removed and the subject breathed room air. The total duration of the experiment was practically the same for each subject in any one programme, and the order and duration of administration of gas mixtures were standardized as far as was compatible with the attainment of steady states. The experimental programmes were of three kinds:1. Response to Hypoxia at Constant PACO (six subjects).-Four subjects were studied at low PA (1-2 mm. Hg above resting) and two at a higher PACO (6-8 mm. Hg above resting). The first group was first given a mixture containing 02 at 43