Tumor growth enhancement and systemic responses of Ehrlich ascites carcinoma following intermittent whole body hyperthermia

Intermittent whole body hyperthermia 42 degrees C (WBH(I) administered for 30 min daily during 7 days caused significant enhancement of the growth of Ehrlich ascites carcinoma. The tumoricidal effects of hyperthermia were evident from the cytological picture as well as from the increased activity of lysosomal enzyme of the tumor cells. Elevated plasma corticosteroid levels, adrenal hypertrophy, thymus involution and lymphocytopenia were observed in both normal and tumor bearing mice exposed to hyperthermia. The alterations were more marked in the tumor bearing groups. Withdrawal of treatment caused gradual restoration of stress effects. It appears that the tumoricidal effects of WBH(I) were counteracted and surpassed by the growth stimulatory effects induced probably by hormone mediated immunosuppression.     

Morphologic and staining characteristics of a cyanobacterium-like organism associated with diarrhea.

A spherical organism 9-10 microns in diameter, seen in three outbreaks of diarrhea in Southeast Asia and the United States during the past 2 years, bore characteristics of a cyanobacterium when observed in formalin-preserved stool specimens and by electron microscopy. Organisms in freshly passed stool specimens showed an internal morula of lipid-containing globules. In fresh water, the morula divided into two sausage-shaped structures resembling the sporocysts of an isosporid coccidian. After 7 months, the organisms had not developed the crescentic sporozoites seen in the Coccidia but had begun to multiply slowly in culture. It was impossible to stain the internal structures of the organisms because the outer cyst wall ruptured during desiccation, releasing the contents of the cysts. The organisms were readily identified by their intense blue autofluorescence under UV light, but they were also recognizable by bright-field microscopy and by a modified acid-fast stain. Almost all infected persons suffered intermittent diarrhea for 2-3 weeks and many emphasized a feeling of intense fatigue during the course of their illness.     

Early-life events may trigger biochemical pathways for Alzheimer’s disease: the “LEARn” model

Alzheimer’s disease (AD), the most common form of dementia among the elderly, manifests mostly late in adult life. However, it is presently unclear when the disease process starts and how long the pathobiochemical processes take to develop. Our goal is to address the timing and nature of triggers that lead to AD. To explain the etiology of AD, we have recently proposed a “Latent Early-life Associated Regulation” (LEARn) model, which postulates a latent expression of specific genes triggered at the developmental stage. This model integrates both the neuropathological features (e.g., amyloid-loaded plaques and tau-laden tangles) and environmental factors (e.g., diet, metal exposure, and hormones) associated with the disease. Environmental agents perturb gene regulation in a long-term fashion, beginning at early developmental stages, but these perturbations do not have pathological results until significantly later in life. The LEARn model operates through the regulatory region (promoter) of the gene and by affecting the methylation status within the promoter of specific genes.     

Comparison of bevantolol and atenolol in chronic stable angina

A randomized, double-blind, parallel-group study design was used to compare the antianginal efficacy of bevantolol (200 to 400 mg) and atenolol (50 to 100 mg) each administrated once daily for 8 weeks in 39 patients with chronic stable angina. Assessments were made using 24-hour ambulatory monitoring and treadmill exercise testing performed 22 to 24 hours after the last dose of medication. Both groups were comparable at the end of the placebo phase. In the bevantolol group, exercise time increased from 7.9 +/- 0.7 minutes with placebo to 9.3 +/- 0.7 minutes with bevantolol (mean +/- standard error of the mean) (p less than 0.05). Time to 1 mm ST depression was unaltered. Rest and exercise heart rate decreased (p less than 0.0001 and less than 0.0005, respectively) as did exercise double product (p less than 0.0001). In the atenolol group exercise time increased from 7.1 +/- 0.7 minutes with placebo to 8.2 +/- 0.8 minutes with atenolol (p less than 0.02). Time to 1 mm ST depression increased (p less than 0.005) and rest and exercise heart rate and double product decreased (p less than 0.0001 and less than 0.05, respectively). When within-group differences between placebo and active drug were compared for bevantolol and atenolol, no significant differences were detected. Both drugs were well tolerated and reduced ambulatory heart rate throughout the 24 hours. This study confirms that both bevantolol and atenolol are effective antianginal agents. Bevantolol compares well with atenolol in the treatment of patients with chronic angina, and there was a similar response to exercise testing with the 2 drugs.     

Adrenergic mechanisms in oxygen chemoreception in the cat aortic body

Sixteen cats were studied to test the hypothesis that oxygen chemoreception in the cat aortic body is dependent on the beta-adrenergic mechanism. The chemoreceptor activity was measured from a few aortic chemoreceptor afferents in each cat, anesthetized with alpha-chloralose (60 mg X kg-1). Three types of experiments were conducted. Aortic chemoreceptor responses to steady-state hypoxia (PaO2 range, 100-30 Torr) were measured (a) before and during intravenous infusion of the beta-receptor agonist, isoproterenol (0.5 micrograms X kg-1) in nine spontaneously breathing cats, and (b) before and after intravenous injection of the beta-receptor antagonist, propranolol (1 mg X kg-1) in seven cats which were paralyzed and artificially ventilated. In the third category (c) the stimulatory effect of hypotension on aortic chemoreceptor activity was measured in six of the seven cats in group (b) before and after propranolol injection. Isoproterenol infusion only moderately stimulated aortic chemoreceptor activity. This stimulation was blocked by propranolol. However, propranolol did not attenuate aortic chemoreceptor responses to hypoxia or to hypotension. We conclude that the beta-receptor adrenergic mechanism does not mediate oxygen chemoreception in the cat aortic body.     

A randomized trial of exercise treadmill ECG versus stress SPECT myocardial perfusion imaging as an initial diagnostic strategy in stable patients with chest pain and suspected CAD: cost analysis.

BACKGROUND: Exercise electrocardiography (ETT) is frequently used in patients with suspected coronary artery disease (CAD). Single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) improves diagnostic stratification. There are no randomized trials comparing ETT and MPI. We hypothesized that first-line MPI would be effective and cost-saving versus ETT. METHODS AND RESULTS: We randomized 457 outpatients with stable chest pain and suspected CAD to either treadmill electrocardiography or MPI. The post-test likelihood incorporated the pretest likelihood and the test result, with clinically driven testing. The primary endpoint was cost to diagnosis based on institutional and National Institute for Clinical Excellence costs. MPI significantly reduced the intermediate post-test likelihood of CAD (30% for ETT vs 3% for MPI, P < .0001) and further investigations (71% for ETT vs 16% for MPI, P < .0001). Despite the reduction in downstream resource utilization after MPI, mean costs were not different between the 2 initial strategies: 490.44 pounds sterling (95% confidence interval, 453.80-527.08) for ETT versus 512.41 pounds sterling (95% confidence interval, 481.41-543.41) for MPI. MPI cost was no different from ETT cost in patients with an intermediate or high pretest likelihood (P = not significant). ETT was less expensive in low-risk patients. CONCLUSIONS: In this study there was no difference in cost to diagnosis between initial ETT and MPI. In low-likelihood patients ETT was less costly, whereas there was no cost difference in intermediate- or high-likelihood patients.     

Acute and chronic effects of sustained action buccal nitroglycerin in severe congestive heart failure

Vasodilators, such as nitroglycerin, have been widely used in the treatment of acute and chronic heart failure for therapeutic manipulation of the venous and arterial circulations to improve left ventricular function. We have tested the efficacy of a new formulation for sustained release buccal delivery of nitroglycerin (biological life 5-6 hr) in 21 patients with severe congestive heart failure due to ischaemic cardiomyopathy using maximal treadmill exercise testing and radionuclide angiography. A single-blind placebo-controlled acute and an open chronic phase (4 weeks) of treatment were employed. The mean dose was 23.4 mg daily, and clinical assessment suggested significant improvement in 15 patients. The mean ejection fraction (placebo) of 14.1% +/- 1.6 SEM increased to 19.1% +/- 1.7 (acute) and to 21.6% +/- 1.7 (chronic treatment) (P less than 0.001; n = 16). The mean exercise time increased from 3.02 +/- 0.4 min (basal) to 5.95 +/- 0.6 min (chronic) (P less than 0.001). Segmental wall motion abnormality was shown to improve after treatment for 4 weeks. There were no major side effects. Nine patients were reassessed after 24 weeks on the same regimen; exercise time and left ventricular ejection fraction were similar to the 4-week period, thus demonstrating a sustained improvement in cardiac function and functional capacity. A worthwhile functional and objective haemodynamic improvement was demonstrated in these patients with severe chronic congestive heart failure. This mode of treatment may have useful therapeutic value in the management of patients with a wide range of ischaemic heart failure.     

Resistance to pyrethroid insecticides in Culex pipiens pipiens (Diptera: Culicidae) from Tunisia

Resistance toward 2 pyrethro?d insecticides (permethrin and deltamethrin), and an organochloric one (DDT) was analyzed in 18 samples of Culex pipiens pipiens common mosquitoes collected from different Tunisian areas between March 2002 and November 2005. Bioassays were performed over different larvae samples. The recorded mortalities, after 24h exposure to increased doses of insecticides, were compared to those obtained on a susceptible reference strain (S-LAB). All samples were resistant to permethrin. However, a large variation in the tolerance to this insecticide was observed between samples. Resistance ratio levels at LC50 (RR50) for the analyzed samples were ranged from 1.5 to 9092 folds. For deltamethrin, 14 among 17 studied samples were resistant. RR50, in the resistant samples, were ranged from 3 to 453 folds. Resistance to the two tested pyrethroids and DDT were correlated. The use of synergists showed that the cytochrome P450-dependent monooxygenases had a major contribution to the permethrin and deltamethrin resistance and that the esterases (and/or glutathione-S-transferases) had only a minor contribution. Results were discussed in relation to resistance mechanisms and mosquito's control.