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The aim of this study was to determine the incidence of echocardiographically detectable patent foramen ovale (PFO) in elderly patients who have strokes from cerebral infarction, as well as to assess the association between PFOs and other risk factors for stroke disease. Forty-three patients agedor = 65 years admitted consecutively with cerebral infarction shown on computerised tomography of the brain were assessed using transoesophageal echocardiography. A PFO was present in 8 (19%) of the 43 patients. Four patients (50%) in this PFO group had stroke risk factors. Two were in atrial fibrillation and, of the six patients in sinus rhythm, a risk factor was present in two, both of whom had diabetes mellitus. A PFO was not detected in 35 patients. Twenty-nine (83%) of the patients in this group had risk factors, with 18 having two or more. Seven patients were in atrial fibrillation. Of the 28 patients in sinus rhythm, risk factors were present in 22 (78%).

The grain amaranths (Amaranthus hypochondriacus L., A. cruentus L., and A. caudatus L.) are important pseudo-cereals native to the Americas. The objective of this project was to produce and characterize a set of highly informative, reproducible microsatellite markers for the grain amaranths. A total of 1457 clones were sequenced from three microsatellite-enriched libraries. Of these, 353 contained unique microsatellites. An additional 29 microsatellite loci were identified from 728 bacterial artificial chromosome-end sequences. A total of 179 micro-satellites were polymorphic across accessions from the three grain amaranths. Among these polymorphic microsatellite loci, a total of 731 alleles were identified with an average of four alleles per locus. Heterozygosity values ranged from 0.14 to 0.83, with a mean value of 0.62. Thirty-seven (21%) of the markers were polymorphic between the parents of a segregating population. Phylogenetic analysis using the marker data placed A. hybridus L. accessions into two of the three grain amaranth clades, suggesting the polyphyletic evolution of the three cultivated species from different A. hybridus ancestors. The transferability of these markers to A. hybridus, A. powellii S. Wats., and A. retroflexus L. is reported and suggests that these markers may be useful in studying other species within the genus Amaranthus, including several economically important weeds and ornamentals.

The effects of indacrinone (IND) have been investigated in a two part study. First, a total of 36 clearance studies have been performed in 14 healthy volunteers, under conditions of either maximal hydration or hydropenia, to compare the renal sites of action of single oral doses of IND, 20 mg, ethacrynic acid (EA), 100 mg, and hydrochorothiazide (HCTZ), 100 mg. Under conditions of maximal water hydration, IND increased fractional Na+ excretion from a mean of 1.19 +/- 0.05 to 4.93 +/- 0.67% of GFR. This was similar to the response seen with HCTZ, which increased fractional Na+ clearance up to 3.16 +/- 0.17% of GFR; EA increased fractional Na+ excretion up to 14.5 +/- 2.5% of GFR. The mean reduction in fractional free-water clearance (CH2O/GFR X 100%) invoked by IND, (delta = -34.8% of control) was similar to that produced by EA, (delta = -27.2% of control), and by HCTZ, (delta = -26.6% of control). During hydropenia with superimposed mannitol diuresis, both IND and EA caused a fall in fractional free-water reabsorption (TcH2O/GFR X 100%), delta IND = -20.3% of control, delta EA = -70.1% of control. HCTZ produced a significant increase in fractional free-water reabsorption, delta HCTZ = -20.7% of control. In all studies, single doses of IND were both uricosuric and hypouricaemic. Fractional urate excretion increased from a mean 6.7 +/- 0.1 to 15.2 +/- 2.1% of GFR whilst plasma urate concentration fell from a mean of 0.36 +/- 0.03 to 0.34 +/- 0.03 mM (P less than 0.05) within 2-3 h post drug. HCTZ and EA, in single doses, had little effect on urate excretion. In the second part of the study, a total of 16 healthy volunteers received either IND, 10 mg, or HCTZ 50 mg, orally for 8 days, whilst on a diet of controlled electrolyte content. Both drugs were well tolerated by both sets of subjects with no adverse clinical or pathological findings. Both IND and HCTZ caused a significant reduction in weight and standing systolic blood-pressure during the first 48 h of therapy. At the doses administered, IND and HCTZ displayed similar diuretic responses with respect to water, Na+, Cl-, Ca2+ and PO4(3-) excretion. IND produced less kaliuresis than HCTZ during the first treatment day but cumulative K+ loss was similar for both drugs over the eight days of therapy. Fractional urate excretion after IND remained elevated throughout the 8 days of therapy and the subjects remained isouricaemic for 7 days.(ABSTRACT TRUNCATED AT 400 WORDS)

1. The renal and metabolic effects of the sulphamoylbenzoic acid diuretic, piretanide, have been studied, under controlled dietary conditions, in 39 patients with congestive cardiac failure. 2. In acute studies, peak saluresis occurred within 4 h of oral piretanide administration; saluresis was complete within 6 h, after which a significant antidiuretic effect was observed. Addition of triamterene, 50 mg, blunted the 0-6 h kaliuretic effect of piretanide. Over 24 h, piretanide, alone, caused insignificant urinary losses of potassium when compared with control. 3. In comparative studies, the piretanide dose-response curve was found to be parallel to that of frusemide over the dose range studied. The 0-6 h saluretic responses of piretanide, 6, 12 and 18 mg, were found to be equivalent to frusemide, 40, 80 and 120 mg respectively. The collective mean ratios of all the saluretic responses to each dose of piretanide with the corresponding dose of frusemide was observed to be 0.99 +/- 0.12, over 0-6 h period, and 0.86 +/- 0.09 over the 24 h period. The relative potency of piretanide, when compared with frusemide was found to be 6.18 (95% confidence limits 4.87-8.33), over the 0-6 h period, and 4.73 (95% confidence limits 3.65-6.14), over 24 h period. 4. In 15 patients in severe cardiac failure, urinary recovery of piretanide, over first 6 h, at the start of treatment was 21.2 +/- 2.1% while efficiency of the diuretic (mmol Na/mg drug) was 47.3 +/- 4.1. Long-term piretanide therapy was continued in the same group for up to and in some cases over 3 years. No other diuretics or potassium supplements were given. Piretanide dosage ranged from 6 to 24 mg day-1 according to clinical need. Plasma potassium fell significantly at 12 and 24 months, though remaining within the normal range. At these same times, significant elevations in both plasma urate and total fasting cholesterol were observed. Two patients developed overt gout on high dose piretanide therapy (24 mg day-1). Piretanide was well tolerated, and effective in the management of congestive cardiac failure without any other recognized metabolic or electrolyte changes.

Enalapril, the ethyl ester of a potent angiotensin converting enzyme inhibitor, enalaprilat, was administered to healthy volunteers as a capsule containing 10 mg of the maleate salt, every 24h for eight doses. Serum profiles show little accumulation of enalaprilat following eight daily doses of enalapril maleate. An average effective half-life for accumulation of approximately 11h was calculated from urine data. Comparison of observed 24-h urinary recoveries of enalaprilat to predicted steady-state recovery indicates that an 'average' steady state for enalaprilat is attained by the third or fourth dose of enalapril maleate. Statistical comparison of daily urinary recoveries, as well as Cmin values for enalaprilat, confirm this. Observed fluctuations in serum and urine data during apparent steady state suggest some day-to-day variability in the absorption of enalapril maleate and/or its hydrolysis to enalaprilat. An accumulation ratio of 1.3 for enalaprilat was calculated from the predicted steady-state urinary recovery and observed urinary recovery for dose one.