It has been demonstrated that a simple two-compartment kinetic model may account for the changes in plasma concentration of pancuronium after i.v. administration. However, it can be shown that this simple model does not account satisfactory for the observed changes in muscle twitch response. By the addition of a receptor (biophase) compartment, twitch response can be reconciled with model behavior and the characteristics resemble those predicted by animal studies. The complete model is applied to the problem of total renal failure, and shows that patients with this condition are likely to be marginally resistant to small doses of pancuronium, with a normal rate of recovery. However, larger doses are likely to result in delayed recovery, the duration of effect increasing in a dose-dependent manner.

No abstract

No abstract

Osmoregulation of vasopressin secretion was studied in eight healthy women in the follicular and luteal phases of the menstrual cycle. Basal plasma osmolality in the luteal phase was significantly lower than in the follicular period (282.4 +/- 0.6, 285.6 +/- 1.1mmol/kg, respectively, P less than 0.05). Plasma AVP (pAVP) and plasma osmolality (pOsm) were measured during the infusion of 850 mmol/l saline in both phases of the cycle, and linear regression analyses of these data gave the following regression equations (i) follicular, pAVP = 0.43 (pOsm - 284), r = + 0.93, (ii) luteal, pAVP = 0.31 (pOsm - 279), r = + 0.95. Both the slope and abscissal intercept were significantly different (P less than 0.01). Osmotic threshold for thirst sensation in the luteal phase was lower than the follicular (293 +/- 2,297 +/- 1 mmol/kg, P less than 0.005). We conclude that, in the luteal phase, the threshold for AVP release and the gain or sensitivity of the osmostat are reduced together with lowering of the thirst threshold, which account for the lower basal luteal plasma osmolality.

The two-dimensional (horizontal) shear instability of a differentially rotating star is examined. A solar-typc rotation law is investigated. and it is found that for equatorial accelerations there is instability when there is a difference of 29% between the angular velocity of the equator and the poles.

Plasma concentrations of pancuronium were measured using a fluorimetric method in six patients with normal renal function and seven patients in chronic renal failure. A tow-compartment open model was used in the pharmacokinetic analysis of the data. With this model, the clearance of pancuronium was found to be reduced significantly in the patients with renal failure, and in these individuals the volume of the central (distribution) compartment was increased significantly. The clinical implications of these findings are discussed.

Long-acting somatostatin analogues may be of benefit in certain hypersecretory endocrine and gastrointestinal disorders. The 24 h hormonal and metabolic profiles of six normal male subjects receiving a twice daily subcutaneous injection of one such analogue SMS 201-995, 50 micrograms, has been compared to that obtained following placebo injection. Spontaneous daytime peaks of GH secretion were delayed until 1400 h following SMS 201-995 but nocturnal and total 24 h GH secretion were unaffected. The nocturnal rise in thyrotrophin was abolished by SMS 201-995 but thyroid function was unaffected. Insulin levels were suppressed following SMS 201-995 and the response to meals was inhibited. Glucose intolerance followed main meals. Glucagon levels were suppressed for up to 6 h. Circulating alanine levels were raised between 1200 h and 0600 h and there were intermittent elevations in lactate, pyruvate, glycerol and 3-hydroxybutyrate. Amino acid levels, including branched chain amino acids, were also increased. All six subjects suffered gastrointestinal side-effects. SMS 201-995, 50 micrograms, given twice daily shortly before meals does not suppress 24 h GH secretion, but demonstrates significant effects on metabolism and causes side effects in normal subjects.

Despite a high incidence of preterm delivery, low birth weight, intrauterine growth retardation and urinary tract abnormalities, the overall outcome for children of renal transplant recipient mothers is good.