Reduction of embryonic intracellular pH: a potential mechanism of acetazolamide-induced limb malformations

The effects of acetazolamide on the developing rodent limb bud were postulated to result from a reduction of intracellular pH (pHi). Embryonic intracellular pH was calculated from transplacental distribution of the weak acid, 5,5'-dimethyloxazolidine-2,4-dione, in teratogenically sensitive (C57BL/6) and resistant (SWV) inbred mice. pHi was reduced by acetazolamide treatment in C57 embryos and limb buds but not in SWV samples. Acetazolamide teratogenesis can be exacerbated by coadministration of amiloride, presumably through inhibition of Na+/H+ exchange attributable to the latter agent. pHi reduction after such treatment was more profound than after acetazolamide alone, providing further support for the central hypothesis. pH was also reduced in other embryonic (embryo plasma) and extraembryonic compartments (exocoelomic fluid, amniotic fluid). pH changes in these compartments could also lead or contribute to abnormal development.     

PERFORATED PEPTIC ULCER IN THE HUNTER REGION: A REVIEW OF 174 CASES

A review of 174 consecutive patients admitted with a diagnosis of perforated peptic ulcer to eight Hunter Region hospitals during 1979–86 is presented. Among the female admissions, the proportion of patients > 70 years of age was twice that in males. One-third of all perforations were in females who accounted for two-thirds of all perforated gastric ulcers. Multivariate analysis revealed that perforations located in the stomach and older age were both significant independent variables adversely affecting outcome following surgery. In contrast, shock at presentation and delay in operating were not statistically significant independent risk factors.