An Epidemic Model with a Density-Dependent Death Rate

This paper deals with a mathematical model for a disease wherethe death rate depends on the number of people in the population.This sort of model would be suitable for diseases in developingcountries or for diseases amongst animal and insect populations.We also assume that the population under consideration is regulatedby the disease so that there is a mortality induced by the disease.We use a compartmental model and perform an equilibrium andstability analysis to find that there is a threshold condition.If the threshold is exceeded, then there is a unique equilibriumwith disease present which is locally stable to small perturbations.We conclude by looking at several specific models and seeinghow the results relate to previous work.     

The design,synthesis and activity of pentapeptide pp60c-src inhibitors containing L-phosphotyrosine mimics

Efficient syntheses of 4-(R,S-hydroxyphosphonomethyl)-l -phenylalanine and 4-carboxy-l -phenylalanine within the context of the pentapeptide Ac-Ile-X-Gly-Glu-Phe-NH₂ (wherein X = the unnatural amino acid) illustrate the use of a divergent synthetic strategy from an advanced common peptide intermediate to more readily access peptide-based tyrosine kinase inhibitors. The key intermediate, Ac-Ile-Phe(4-formyl)-Gly-Glu(O-tBu)-Phe-NH₂, was synthesized by a facile palladium-catalyzed carbonylation of Ac-Ile-Phe(4-iodo)-Gly-Glu(O-tBu)-Phe-NH₂. Oxidation of Ac-Ile-Phe(4-formyl)-Gly-Glu(O-tBu)-Phe-NH₂ with tetrabutylammonium permanganate or addition of di-t-butylphosphite, both followed by trifluoroacetic acid deprotection, gave the target pentapeptide inhibitors wherein X = 4-carboxy-l -phenylalanine or 4-(R,S-hydroxyphosphonomethyl)-l -phenylalanine, respectively. These two peptides gave somewhat more potent inhibition of the tyrosine kinase pp60^c-src than the corresponding pentapeptide wherein X =l -phenylalanine, demonstrating that appended functionalities at the 4-position are accepted and can enhance binding through added interactions within the catalytic region of the active site.     

CASE REPORT: An inherited APC mutation in the first reported Australian case of Turcot's syndrome

The objective of this study was to determine the inherited gene mutation responsible for the first reported Australian case of Turcot's syndrome. DNA was extracted from the archival tissue blocks obtained at the time of the patient's original surgery and from fresh blood samples obtained from selected family members. These were analysed for mutations of the familial adenomatous polyposis gene ( APC ). Analysis of DNA from the archival blocks and from each of the affected family members revealed an inherited 5 base pair deletion at codon 1061 of APC . In this case, the central nervous system tumour represents an extracolonic manifestation of familial adenomatous polyposis. The underlying inherited mutation of APC has been identified. In some cases of Turcot's syndrome, other genes appear to be involved. Recent literature examining the molecular basis of Turcot's syndrome is reviewed.     

Percutaneous Removal of Infected Permanent Pacemaker Leads Using a Simple Coaxial Dilating System

A simple traction-countertraction technique using common and readily available materials was successfully used to remove infected pacemaker leads from two patients. The specific methodology is presented. Although somewhat technically demanding, this approach appears safe and cost-effective. This method provides another way to remove pacemaker leads without resorting to thoracotomy.     

ETHANOL AND DIET-INDUCED ALTERATIONS IN KUPFFER CELL FUNCTION

The effects of 6 weeks of alcohol feeding on phagocytic, metabolicand secretory functions as well as gene expression of hepaticKupffer cells were evaluated in vitro using cultured Kupffercells isolated from male Sprague-Dawley rats. The rats werefed either Teklad pelleted rat chow or the 1982 Lieber-DeCarliliquid diet containing 6% ethanol (36% calories) or the sameliquid diet with maltose-dextrin isocalorically substitutedfor the alcohol. Weight gain was greatest in the chow-fed animalsand least in those receiving ethanol. The alcohol-containingdiet stimulated Kupffer cell phagocytosis, mitochondrial reductionof Mil, secretion of tumor necrosis factor (TNF) and expressionof TNF mRNA. However, each of these cell functions was alsoenhanced by the control Lieber-DeCarli liquid diet alone andthe stimulating effect of the control diet often exceeded thatinduced by ethanol. The results suggest that early in chronicalcohol consumption, the immune system may be stimulated byethanol, and that during studies of ethanol-induced changesin immune system function, close attention must be given topotentially confounding effects of the diet.     

Transepicardial Defibrillation Dose Response: Current Versus Energy

In pentobarbital-anesthetized dogs, we compared the relative efficacy of current versus energy in applying the dose response method in transcardiac defibrillation. Damped sinusoidal shocks via epicardial patches were administered by a custom defibrillator permitting precise current delivery. Following the establishment of an initial estimated defibrillation threshold for energy and current, the dose response method was performed with regard to either energy defibrillation threshold (group E, n = 8) or current defibrillation threshold (group C, n = 8). Two sequential sets (I, II) of shocks (21 shocks each) were delivered in random order at each of seven doses: 0.55, 0.70, 0.85, 1.00, 1.15, 1.30, and 1.45 × defibrillation threshold. Data were subjected to nonlinear logistic regression analysis. There were no significant differences between sets I and II in either groups E or C for resistance or for raw and normalized values associated with 50% and 80% success expressed as energy, current, or voltage. Correlation coefficients (r) associated with nonlinear logistic regression analysis were significantly different for normalized current and energy for group E (0.70 ± 11 and 0.71 ± 12) compared to group C (0.86 ± 0.60 and 0.88 ± O.0.6). The difference. however, could be explained by a significantly narrower range of normalized current values tested in group E (0.79 to 1.31) versus group C (0.54 to 1.46). Thus, when resistance does not change, transcardiac current offers limited advantage over energy when applying a dose response method. The efficacy of nonlinear logistic regression analysis depends upon an adequate dose range.     

Effect of Procainamide, Mexiletine, and Propranolol on Ventricular Activation Time Recorded at Cardiac Mapping in Chronic Canine Myocardial Infarction

Delayed potentials detected during sinus rhythm appear to be markers for ventricular tachyarrhyth mias associated with ch ronic myocardial infarction. This study investigated whether intravenous Class I and Class II antiarrhythmic drugs could affect delayed potentials detected at cardiac mapping in dogs studied 1–2 weeks after anterior myocardial infarction.
Procainamide at therapeutic serum levels (17–34 μmol/L) caused prolongation of delayed potentials (first degree block), the mean change in duration of ventricular activation being + 19.4 ± 5.0 msec (n = 4, p <0.05). At serum levels above the therapeutic range, procainamide caused first degree block in delayed potentials in three of six animals tested (50%), second degree block (Wenckebach, 2:1 or 3:1 block) in another two animals, and third degree block (complete abolition of delayed potentials) in the remaining animal.
Mexiletine at therapeutic serum levels (3.5–9.0 μmol/L, caused no significant change in delayed potential duration (+3.1 ± 5.7 msec, n = 4). At serum levels above the therapeutic range, first degree block occurred in four of five animals tested (80%), there being no change in the fifth animal. After propranolol (0.2 mg/kg), there was no significant change in delayed potential duration (−2.5 ± 2.5 msec, n = 4).
In conclusion: (1) at standard doses, mexiletine and propranolol have no effect on delayed potentials, but procainamide causes first degree block; (2) at serum levels above the therapeutic range, mexiletine typically causes first degree block, while procainamide causes either first degree or high grade block; (3) ventricular tachyarrhythmias may still be inducible after drugs if delayed potentials persist unchanged or with first degree block.     

Social marketing: a critical appraisal

This article provides a critical analysis of the growing useof social marketing in the field of health promotion. In responseto a recent article by A. Hastings and G. Haywood (Health PromotionInternational, 6, 135–134), three questions are askedabout each of the proposed tenets of social marketing: are theseideas new? are they more effective than current health promotionpractices? and do they raise any particular ethical concerns?On each of these counts, the analysis suggests that the purportedbenefits of social marketing might not be as great as proponentsclaim. There are also some problematic unintended consequencesthat arise from the use of social marketing methods. The narrowfocus on individual behavior change and the potentially manipulativetechniques for inducing behavior change are of particular concern.The paper concludes with a call for further discussion aboutthe limits and potential iatrogenic side-effects of using socialmarketing strategies for health promotion.     

Echocardiographic Aspects of Restrictive Cardiomyopathy

Background and Methods: We studied 17 patients with restrictive cardiomyopathy; eight had biventricular restriction (type A), four had left ventricular restriction (type B), and five had only right ventricular restriction (type C). Results: Type A disease was characterized by pulmonary and systemic venous congestion. The restrictive pattern was found in the inlet of both ventricles. Both atria were enormous, with small or normal-size ventricles. Differential diagnosis included constrictive pericarditis and systolic pump dysfunction. Type B restriction disease was characterized by venous pulmonary congestion, pulmonary hypertension, and important dilatation of the left atrium and right cavities with a small or normal-size left ventricle; the restrictive pattern was found only in the affected left ventricle. Conclusions: The clinical picture resembles that of rheumatic mitral valve disease with right ventricular failure. Type C disease had restriction only in the inlet of right ventricle, with giant right atrium, systemic venous hypertension with low flow, and normal pressure of pulmonary artery and left heart. Differential diagnosis included Ebstein's anomaly of tricuspid valve. The etiology of type A disease was amyloid, endomyocardial fibrosis of ventricles and idiopathic interstitial fibrosis. Asymmetric types were always caused by Davies' disease.     

Detection of c-fms protooncogene in early mouse embryos by whole mount in situ hybridization indicates roles for macrophages in tissue remodelling

Summary. The c-fms protooncogene which encodes the receptor for macrophage colony-stimulating factor (CSF-1) was localized in the developing mouse embryo by whole in situ hybridization, c-fms was expressed first in placental trophoblasts. Around 9-5 dpc, isolated c-/ms-positive cells became detectable in the yolk sac and by 10-5 dpc large numbers were detectable throughout the embryo. The localization of c-fms expression was consistent with its restriction to macrophages, and with the location of those macrophages in sites of tissue turnover and extensive cell death.