1. Intracellular pH and Na+/H+ antiport activity were determined by a fluorimetric method in cultured skeletal muscle cells (myoblasts) and aortic vascular smooth muscle cells from spontaneously hypertensive and normotensive Wistar-Kyoto rats. 2. The intracellular pH was significantly more alkaline at three different extracellular pH values in both myoblasts and vascular smooth muscle cells from the spontaneously hypertensive rats than in those from the normotensive control rats. 3. A kinetic analysis of the Na+/H+ antiport activity in these cells showed that the raised activity in the spontaneously hypertensive rats was due to an increased maximal transport capacity in vascular smooth muscle cells and to an increase in the affinity of the antiport for internal H+ in the myoblasts. 4. When the extracellular pH was reduced in the skeletal muscle cells of both types of rat, the intracellular pH fell. However, in vascular smooth muscle cells, a reduction in the extracellular pH was not associated with a fall in the intracellular pH. This resistance of the intracellular pH to changes in the extracellular pH differentiates vascular smooth muscle cells from other cells that have been studied in this way.
\n \n\n \n \nAnecdotal case reports contribute about one-third of the published literature on adverse drug reactions and interactions, but are regarded as providing poor-quality evidence. However, they can occasionally provide proof of cause and effect, and there are many other reasons for publishing them. Because an anecdote is a narrative, narratological paradigms from literature, art, and music can show how we can make evidential use of anecdotes. Useful paradigms are the dramatic unities (of time, place, and action), comprehensive catalogues, and pattern formations. Here I give examples of each of these types of paradigm and show how they can be used to interpret anecdotes about adverse drug reactions and interactions. The dramatic unities show how a proper classification of adverse drug reactions can be achieved, according to dose-relation, time-course, and susceptibility factors; use of this classification should improve the evidential use of anecdotal reports. A high background incidence of the effect (the medical equivalent of subplots, which violate the unity of action) makes it more difficult to detect adverse drug effects using anecdotal reports. To make best evidential use of the corpus of anecdotal reports of adverse drug reactions, comprehensiveness is important: each suspected adverse reaction should be reported in detail and reactions should be reported in sufficient numbers for proper classification and for patterns to be recognized. One form of pattern recognition, teleoanalysis of data, should, when possible, include not only randomized controlled trials and observational studies, but also case series and anecdotal reports.
\n \n\n \n \n1. We have studied the pharmacokinetics of stable strontium in 10 healthy male volunteers. We gave each volunteer 5 mmol strontium gluconate by intravenous infusion over 1 h and measured strontium concentrations in plasma and urine samples for 20 days. The plasma strontium concentration vs time data for each volunteer were fitted by a triexponential function using NONLIN. Compartmental model-dependent and model-independent pharmacokinetic variables were then calculated. 2. The mean half-life we report (5.4 days) is longer than that previously reported (about 2 days), since we continued sampling for 20 days. However, the rates of clearance (CL 9.4 ml min-1. CLR 5.4 ml min-1, and CLNR 4.0 ml min-1) are similar to those previously reported, and the apparent volume of distribution at steady state (64 l) is similar to the values previously reported for the size of the exchangeable pool of both strontium and calcium. 3. The similarities in the pharmacokinetic behavior of strontium and calcium suggest that the in vivo disposition of strontium may be used as a marker of calcium disposition and for studying the effects of drugs such as the calcium antagonists.
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