Dracunculiasis eradication: the final inch

This report summarizes the status of the Dracunculiasis Eradication Program as of early 2005. Nine of the 20 countries that were endemic for this disease when the program began have already interrupted transmission, Asia is free of Guinea worm, and five of the remaining disease-endemic countries reported less than 50 cases each in 2004. Ghana and Sudan each reported 45% of the 16,026 cases in 2004. Except for Sudan, whose reports are delayed, cases in the remaining disease-endemic countries were reduced by 61% during the first quarter of 2005 compared with the same period of 2004. With accelerating momentum towards zero cases in all countries, the recent settlement of Sudan's north-south civil war, and a new challenge grant from the Bill & Melinda Gates Foundation, the way now seems clear to finish eradicating dracunculiasis by 2009 in Sudan and earlier elsewhere. "The rule of the final inch... The work has been almost completed, the goal almost attained... In that moment of fatigue and self-satisfaction it is especially tempting to leave the work without having attained the apex of quality... In fact, the rule of the Final Inch consists in this: not to shirk this crucial work. Not to postpone it... And not to mind the time spent on it, knowing that one's purpose lies... in the attainment of perfection."--Alexander Solzhenitzyn, The First Circle.     

Mechanisms of thermogenesis induced by low protein diets

Weanling (22-day-old) rats fed a low protein (8% casein) diet consumed the same amount of energy as controls (22% casein diet), but intake corrected for body size (kJ/kg0.75) was increased in the former group. Weight gain and the efficiency of gain (g gain/MJ) were markedly reduced in low protein fed rats. Resting oxygen consumption (VO2) was elevated by 15% in the low protein group but this difference was completely abolished by beta-adrenergic blockade with propranolol. Interscapular brown adipose tissue (BAT) mass, protein content, mitochondrial yield and GDP binding were increased in low protein fed rats but mitochondrial alpha-glycophosphate shuttle activity of BAT was unaltered, although shuttle activity was elevated in liver mitochondria. Plasma triiodothyronine levels were increased by 64% in the low protein group, whereas insulin levels were markedly reduced in spite of normal blood glucose levels. Resting VO2 and BAT mass were also increased in older (55-day-old) rats fed the low protein diet, but the changes were smaller than in weanling rats. These data suggest that the decreased metabolic efficiency seen in rats fed protein deficient diets involves sympathetic activation of BAT, and is therefore similar to the thermogenic responses seen in cold adapted and cafeteria-fed animals.     

Metabolism of cortisol by human thrombocytes.

A study was made in order to see whether human thrombocytes are capable to metabolize cortisol. Known concentrations of thrombocytes were incubated with 1.23H-cortisol and the products isolated and identified by t.l.c., paper chromatography, and derivations. Two metabolites were found to be produced by thrombocytes: 20beta-hydroxycortisol and tetrahydrocortisol. The enzymatic nature of the reactions was proved by (1) heat treatment (2) finding out NADPH to be a specific cofactor and (3) the dependence of the activity on the number of thrombocytes in suspensions.     

Comparison of free fatty acid and glyceride--fatty acid uptake by human adipose tissue

A comparison has been made of the uptake of palmitate and triglyceride into human adipose tissue. Both substrates are converted into tissue lipid at similar rates over an incubation period of 2 hr; the uptake of triglyceride is proportional to the amount of tissue in the incubation medium. The assimilation of triglyceride by human adipose tissue requires preincubation of the triglyceride emulsion with serum; depends on the presence of glucose in the incubation medium; and radioactivity from glyceryl-tripalmitin-T is incorporated in preference to ¹⁴C-glyceryl-tripalmitin. Fasting reduced both the uptake of triglyceride into tissue lipid and the esterification of palmitate by the tissue. Fluoride (20 mM) significantly inhibits the esterification of palmitate by human adipose tissue without altering the incorporation of triglyceride. At higher concentrations of fluoride (80 mM) there is some inhibition of triglyceride uptake.     

Direct inhibition of rat leydig cell function by tamoxifen

The effects of tamoxifen on rat testicular steroidogenesis were studied using dispersed interstitial cells. Tamoxifen significantly inhibited LH-, and 8-bromo-adenosine 3′,5′-monophosphate (8-bromo-cyclic AMP)-stimulated testosterone synthesis in a dose-dependent manner. Tamoxifen (10^?5M) also reduced LH-stimulated cyclic AMP formation. The addition of equimolar concentrations of 17β-estradiol or tamoxifen separately to interstitial cells resulted in similar inhibition of LH-stimulated testosterone synthesis. When equimolar concentrations of 17β-estradiol and tamoxifen were added concomitantly to interstitial cells, the inhibition was additive. Present studies demonstrate that tamoxifen has direct inhibitory effects on testicular steroidogenesis: both at the plasma membrane resulting in decreased cyclic AMP formation and also at steps subsequent to cyclic AMP.     

Specific cross-protection between Schistosoma bovis and S. haematobium induced by highly irradiated infections in mice

Significant levels of resistance against Schistosoma haematobium challenge were developed by mice exposed to highly irradiated (20 krad) cercariae of the homologous species (46-53%) or of the closely related species, S. bovis (34-56%) but not of S. mansoni (-6-28%). This ability to cross-protect reflects the phylogenetic relationships between these species; S. mansoni and S. bovis, as well as S. mansoni and S. haematobium, failed to cross-protect. The cross-protection demonstrated between S. bovis and S. haematobium in mice was non-reciprocal.     

Concealed bypasses of the atrioventricular mode in patients with paroxysmal supraventricular tachycardia revealed by intracardiac electrical stimulation and verapamil

Thirteen patients with paroxysmal Supraventricular tachycardia were studied with use of His bundle electrograms and programmed intracardiac stimulation. No patient had evidence of either the Wolff-Parkinson-White or Lown-Ganong-Levine syndrome. During ventricular pacing at a rate of 90 to 180 beats/min retrograde conduction time increased by an average of 80 msec in eight patients; in the remaining five patients the average increase was only 9 msec. The tachycardia was terminated in all 13 patients after intravenous administration of verapamil, 10 mg. This drug acts predominantly on the atrioventricular (A-V) node, and during termination of an A-V nodal reciprocal tachycardia both the antegrade and retrograde conduction times would be expected to be prolonged. During termination of the tachycardia antegrade conduction was prolonged by an average of 43 msec and retrograde conduction by an average of 79 msec in eight patients. However, in five patients antegrade conduction was prolonged by an average of 101 msec and retrograde conduction by an average of only 3 msec. The minimal effect of this drug on retrograde conduction and the minimal increase in retrograde conduction during ventricular pacing in these five patients is strong evidence for the presence of an A-V nodal bypass that was not apparent from the surface electrocardiogram. The potential hazards should atrlal fibrillation occur and allow rapid antegrade conduction in an A-V nodal bypass are discussed.     

Histoplasma Endocarditis Diagnosed by Thrombus Aspiration

Negative cultures in endocarditis often lead to delays in targeted life-saving therapies. We present the case of a 68-year-old man who presented with culture-negative endocarditis, which was complicated by coronary embolization resulting in anterior ST-elevation myocardial infarction (STEMI). Aspiration thrombectomy led to the diagnosis of fungal endocarditis, one of the most serious causes of culture-negative presentation.