Assessing effect of mixing insulins by glucose-clamp technique in subjects with diabetes mellitus

The glucose-clamp technique was used to assess the effect on insulin activity of mixing clinically relevant doses of short- and longer-acting insulins in insulin-treated diabetic subjects. Mixtures of porcine regular and lente insulins resulted in a reduction in activity of the mixture compared with separate injection that was more apparent with premixing for 5 min before injecting than with premixing for 2 min. These findings were not explained by differences in volume of the injected insulin preparations. Mixing of porcine regular and bovine ultralente insulins for 2 min before injecting resulted in a reduced activity compared with separate injection. No difference in activity was obvious for porcine regular and NPH insulins given separately or premixed for 5 min. A reduction of activity during the 1st h after injection was observed when separate injection of one brand of these insulins (Velosulin or Insulatard) was compared with the manufactured mixture (Mixtard). These results indicate that premixing regular and NPH insulins in a 1-to-2 ratio does not alter the biological activity compared with separate administration of the insulins. However, the mixing of regular and insulin-zinc suspensions results in a loss of insulin activity, the magnitude of which depends on the time between mixing and injecting the insulin. The clinical significance of the effect of mixing on the efficacy of subcutaneous insulin therapy should be considered in the context that this is only one of many factors that may affect the activity of subcutaneously injected insulin.     

Pregnancy following gamete intrafallopian transfer: A case report

Conclusion Although more data are needed and it is still too early for a definitive conclusion, GIFT can probably offer new perspectives not only in the treatment of unexplained infertility but also in cases of persistent infertility in patients with LUF (luteinzed unruptured follicle) or a mild degree of endometriosis or when no conception occurs after surgical correction of endometriosis.Only further prospective studies will help us to determine the indications for GIFT.     

Relationship between transmitter release and presynaptic calcium influx when calcium enters through discrete channels.

We have used a three-dimensional diffusion model of calcium entering the presynaptic nerve terminal through discrete channels to simulate experiments relating transmitter release to presynaptic calcium current. The relationship will be less than linear, or will curve downward, if calcium channels are well separated. It will resemble a power-law function with exponent less than the cooperativity of calcium action if channels are clustered closer together. Large presynaptic depolarizations elicit more release than small depolarizations admitting the same calcium influx. This occurs because large pulses open more channels near each other, with the result that the calcium concentration near release sites is greater, due to overlap of calcium diffusing from adjacent channels.     

Design of clinical trials for chronic diseases: implications for periodontal disease

In order to make effective use of the statistical theory of design of clinical trials for chronic diseases such as periodontal disease, certain issues must be considered. Any clinical trial requires that the disease definition be well-specified; that patient eligibility be explicit; that the observation times be explicit; that the duration and endpoint of therapy be specified; that the duration of subsequent followup observation be specified; and that the unit of observation (e.g., tooth, set of teeth, patient) be defined. In a chronic disease, the potential biases that can readily be introduced by self-selection of patients who enter the trial and/or who return for subsequent observation become more important, because subjects are required to remain on treatment and/or observation for prolonged periods. Further, the cyclical nature of some chronic diseases may require special attention to baseline definitions of active disease and disease outcome. These issues are illustrated with examples from clinical trials of hypertension, breast cancer screening, and Polycythemia Vera. Implications for periodontal disease are discussed.     

Inhibin and renin in follicular fluids of patients with one or two ovaries stimulated with a GnRH agonist and gonadotrophins

Follicular fluids from eight patients with one ovary and from ten patients with two ovaries were investigated for bioactive inhibin, total renin, oestradiol (E2) and progesterone (P4) concentrations. Four follicular fluids were pooled per patient before assessment. All women had been stimulated similarly using a protocol including a GnRH agonist, HMG and HCG. Renin levels were significantly lower and P4 significantly higher in pools of follicular fluid from patients with one ovary, whereas inhibin and E2 concentrations were similar in both patient groups. A significant negative correlation was found in the pools of follicular fluid between inhibin and E2 in both groups. These results suggest a role for inhibin and renin in the paracrine and autocrine control of stimulated follicular development.     

Is cholic acid responsible for embryo-toxicity of the post-receptive uterine environment?

HPLC analysis of the embryo-toxic fraction of human uterinefluid, collected between the 22nd and 25th days of the menstrualcycle, revealed the presence of cholic acid at high concentrations.It is suggested that cholic acid could be responsible for theembryo-toxicity of the uterine environment, which follows thereceptive period for implantation.