Gene interactions constrain the course of evolution of phosphine resistance in the lesser grain borer, Rhyzopertha dominica.

Phosphine, a widely used fumigant for the protection of stored grain from insect pests, kills organisms indirectly by inducing oxidative stress. High levels of heritable resistance to phosphine in the insect pest of stored grain, Rhyzopertha dominica have been detected in Asia, Australia and South America. In order to understand the evolution of phosphine resistance and to isolate the responsible genes, we have undertaken genetic linkage analysis of fully sensitive (QRD14), moderately resistant (QRD369) and highly resistant (QRD569) strains of R. dominica collected in Australia. We previously determined that two loci, rph1 and rph2, confer high-level resistance on strain QRD569, which was collected in 1997. We have now confirmed that rph1 is responsible for the moderate resistance of strain QRD369, which was collected in 1990, and is shared with a highly resistant strain from the same geographical region, QRD569. In contrast, rph2 by itself confers only very weak resistance, either as a heterozygote or as a homozygote and was not discovered in the field until weak resistance (probably due to rph1) had become ubiquitous. Thus, high-level resistance against phosphine has evolved via stepwise acquisition of resistance alleles, first at rph1 and thereafter at rph2. The semi-dominance of rph2 together with the synergistic interaction between rph1 and rph2 would have led to rapid selection for homozygosity. A lack of visible fitness cost associated with alleles at either locus suggests that the resistance phenotype will persist in the field.

Tropical peptic ulcer disease: an endoscopic study from rural Haiti.

We performed upper gastrointestinal endoscopy in 60 rural Haitian patients who complained of chronic upper abdominal pain. Twenty-five of 37 men (68%) and 5 of 23 women (22%) had abnormal findings. In men the predominant abnormalities were severe duodenal ulcer, duodenitis, and pyloroduodenal obstruction; duodenal ulcer or duodenitis appeared to precede obstructive disease by about 20 years. In women the abnormal findings invariably were milder than in men and consisted of duodenal ulcer, duodenitis, and gastritis. These observations as well as the observations of others indicate that peptic ulcer disease is common in developing countries, particularly among men. We hypothesize that this familiar abnormality reported from unfamiliar places represents the ordinary spectrum of peptic ulcer disease, but that inadequate treatment of recurrent episodes over time leads to obstruction. Physicians need to learn more about the epidemiology of peptic disease in developing countries and to devise better methods of effective treatment to prevent the late complication of gastric outlet obstruction.

Dose-response characteristics of nebulized fenoterol in asthmatic children.

Fenoterol hydrobromide, a beta 2-selective bronchodilator, was administered by aqueous nebulization to 31 children with stable asthma. An initial comparison of 0, 100, 300, and 1000 micrograms drug in 20 of these patients showed a significant change in forced expiratory volume in 1 second for all three doses compared with change after placebo (P less than 0.0001). However, the differences in peak pulmonary response from 100 to 1000 micrograms were not large (P greater than 0.2). Assessment of spirometric responses of 11 children to 3, 10, 30, or 100 micrograms nebulized fenoterol clearly revealed the dose-response effect (P less than 0.01). When all the FEV1 data were plotted over the entire range of 3 to 1000 micrograms, the resultant log dose vs response curve could be characterized by the ED50, the amount of drug producing half-maximal response. At 15, 30, or 60 minutes, the ED50 was in the range 8 to 10 micrograms. With increasing time there was a parallel shift of the entire dose response curve to the right, manifested by ED50 of 47 and 150 micrograms at two and three hours, respectively, after administration. This decreasing potency of a sympathomimetic drug with time shows that duration of effect and dosage are interdependent variables and must be evaluated simultaneously. Such considerations cannot be derived from cumulative dose-response studies. In our patients, 100 to 300 micrograms fenoterol delivered by aqueous nebulization achieved optimal bronchodilation with no detectable cardiovascular side effects.

Duodenal ulcer in rural Haiti I. Clinical features. II. Gastric secretory studies.

I. In a study of 100 duodenal ulcer patients in rural Haiti, pyloric obstruction was present initially in nine per cent, but later developed in an additional 20 per cent. This high incidence of obstruction is similar to that observed in other tropicla populations in Africa and India. II. Standardized tests for basal and stimulated acid secretion in a small group of duodenal ulcer patients in rural Haiti were not elevated. The implication of the study is that either the test must be modified for different populations or the role of acid secretion in the pathogenesis of the disease questioned.