STS markers for the wheat yellow rust resistance gene Yr5 suggest a NBS-LRR-type resistance gene cluster.

Two sequence-tagged site (STS) markers for the wheat yellow rust resistance (R) gene Yr5 have been derived through the identification and characterization of linked amplified fragment length polymorphisms (AFLPs). The sequences of the 2 AFLP markers partially overlap with one another, but belong to discrete loci: S19M93-140 completely cosegregates with Yr5, whereas S23M41-310 maps at a distance of 0.7 cM. The DNA sequence of S23M41-310 shows significant homology with the 3' end of nucleotide-binding site (NBS) - leucine-rich repeat (LRR) - type R-genes, in particular with orthologues of the rice bacterial blight R-gene Xa-I. The distinct genetic location of the 2 AFLP loci suggests that Yr5 falls within an R-gene cluster. Because neither sequence forms part of a detectable transcription product, we propose that the Yr5 R-gene cluster includes R-gene analogues and pseudogenes. A Yr5 flanking simple sequence repeat (SSR) marker has also been identified, which allows Yr5 to be effectively incorporated, along with other R-genes for yellow rust, into elite wheat genetic backgrounds, through marker-assisted selection.

Captopril in congestive heart failure resistant to other vasodilators.

In an attempt to study the possible mechanism(s) by which captopril controls resistant heart failure, sequential haemodynamic studies (radioisotope technique) and humoral measurements (plasma renin activity, plasma aldosterone and plasma catecholamines) were obtained in 11 such patients. The studies were made at the time patients became unresponsive to other vasodilators (hydralazine or prazosin); the vasodilator drug was then discontinued and five days later, the 'no-vasodilator' studies were obtained. Captopril therapy was then started. Optimum daily maintenance dose of captopril varied from 75 to 200 mg in different patients. Studies were again repeated after a period of time equal to the duration of the previous vasodilator therapy. Digitalis and diuretic doses were kept constant throughout. Captopril improved effort tolerance in ten patients. Haemodynamically, mean blood pressure and peripheral resistance were lower than during vasodilator therapy (85 +/- 3.1 v. 92 +/- 3.3 mmHg and 47 +/- 4.4 v. 59 +/- 4.4 U.M2, respectively; p less than 0.05 for both). Cardiac index was higher during captopril treatment (1.95 +/- 0.15 v. 1.63 +/- 0.10 l/m2, p less than 0.01) and pulmonary mean transit was normalized by captopril (14.6 +/- 1.7 v. 18.4 +/- 1.3 s, p less than 0.05). Humoral indices revealed a significant (p less than 0.05) reduction in plasma aldosterone during captopril therapy (25.9 +/- 5.6 ng/dl during captopril, v. 62 +/- 22 ng/dl with no vasodilators and 50.9 +/- 6.1 ng/dl with other vasodilators). Moreover, there was a decrease in circulating plasma catecholamines during captopril treatment, but differences between the three treatment periods were not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Long-term control of congestive heart failure with captopril.

The long-term effects of captopril therapy were assessed by sequential hemodynamic studies over a 6 month period in 19 patients with resistant congestive heart failure. Initial improvement during the first week of therapy was noted only in 11 and was marked by significant (p less than 0.005) increases in cardiac output and stroke volume, slowing of heart rate, and reduction of total peripheral resistance. Of the remaining eight patients, seven improved subsequently with maintained therapy so that by the end of 3 months of treatment only one patient failed to respond significantly. The hemodynamic index that reflected response most consistently was the shortening in pulmonary mean transit time. Simultaneously with clinical improvement there was a reduction in cardiopulmonary volume that reflected a reduction in pulmonary congestion and probably systemic vasodilation. Associated with these hemodynamic changes there was an increase in plasma renin activity and a significant reduction in plasma aldosterone, but these changes did not differ significantly between patients who responded markedly and those who responded moderately to converting enzyme inhibition. These results suggest that the response of congestive heart failure to captopril can occur gradually. Improvement was related to peripheral hemodynamic changes which led to a reduction in both total peripheral resistance and cardiopulmonary volume. The reduction in the plasma aldosterone/renin activity ratio was an effective marker of compliance.

Therapeutic considerations in the treatment of common cardiac arrhythmias.

Atrial and ventricular premature extrasystoles are common in the normal population. In most cases, reassurance and instructions regarding the avoidance of cardiac stimulants will be the only therapy necessary. As a rule, cardiac arrhythmias do not present as isolated events. The clinical setting dictates the choice of therapy for supraventricular tachyarrhythmias. Infrequent, self-limiting supraventricular tachycardias seldom require therapy. On the other hand, supraventricular tachycardias producing serious hemodynamic alternations should have immediate restoration of sinus rhythm with electric cardioversion. The prevention of ventricular arrhythmias with prophylactic lidocaine is advocated for patients with suspected acute myocardial infarction. Ventricular arrhythmias occurring in acute myocardial infarction require aggressive therapy. The use of potent antiarrhythmic agents demands thorough understanding of the drug's pharmacokinetics, side effects and toxic manifestations. Potential benefit should always be carefully weighed against possible risks. Drug cost and patient inconvenience must also enter the decision making process.