Combined anti-bradycardia/anti-tachycardia pacemaker-cardioverter-defibrillator systems in patients with recurrent ventricular tachyarrhythmias]

In 41 patients with recurrent sustained ventricular tachycardia and/or ventricular fibrillation an integrated pacemaker-defibrillator-system (PCD, Medtronic, model 7216 A or 7217 B) was implanted. In 21 out of 24 (88%) patients a new transvenous implantation technique in combination with a subcutaneous patch electrode was used. The implanted devices comprise antibradycardiac pacemaker functions, two different forms of antitachycardiac pacemaker functions (ramp and burst pacing), and internal cardioversion or defibrillation capabilities. During a mean follow-up of 8 months 147 episodes of ventricular tachycardia were detected, 131 of them were terminated successfully by antitachycardiac pacing; in 13 episodes internal cardioversion was applied to revert ventricular tachycardia. Twenty-seven episodes of ventricular fibrillation or rapid ventricular tachycardia (greater than 200/min) were detected and successfully terminated by internal defibrillation. In six patients with intermittent rapid atrial fibrillation, change of antiarrhythmic therapy was required to avoid activation of the device. The new integrated pacemaker-defibrillator systems improve therapy in patients with life-threatening tachyarrhythmias by reducing the number of internal cardioversions/defibrillations; the non-thoracotomy approach reduces the post operative risk.     

Body Weight, Fat Storage, and Alcohol Metabolism

Ethanol account for a significant fraction of the energy intake of persons consuming even moderate amounts of alcohol. A recent study has shown that although alcohol does not reveal itself as a layer floating at the top of a drink, metabolically it behaves more like oil than sugar.     

Intracellular metabolism of 5-formyl tetrahydrofolate in human breast and colon cell lines.

This report describes the intracellular metabolism of 5-formyltetrahydrofolate into the various one-carbon substituted folate and polyglutamate pools in a human breast (MCF-7) and colon (HCT 116) carcinoma cell line. Metabolism into the one-carbon substituted pools was found to be time and dose dependent over a concentration range up to 50 microM. A 3-fold increase in total intracellular folate was noted over a 50-fold concentration range (1-50 microM) of 5-formyltetrahydrofolate tested in the colon cell line, while in the breast line, a 6-fold increase was detected over a 500-fold concentration range (0.1-50 microM). The level of 5, 10-methylenetetrahydrofolate, which was detectable only in the breast cell line, was found to increase by a factor of 10 (1.8 pmol/mg to 17.9 pmol/mg) over the concentration range studied. The majority of metabolism was into the 10-formyltetrahydrofolate and tetrahydrofolate pools in the breast cells and into the 5-methyltetrahydrofolate pool in the colon cells. Polyglutamation was also time and dose dependent, with a significant proportion of the total pool represented by the higher polyglutamate forms (Glu3-Glu5) after 24 h of continuous exposure to 5-formyl tetrahydrofolate. Pentaglutamate was the highest level noted in both cell lines. The intracellular half-life of the polyglutamate forms was inversely related to the length of the polyglutamate tail with half-lives of 71, 131, 143, 441, and 1167 min for the mono- through pentaglutamate, respectively. Finally, up to a 20:1 ratio of the biologically inactive (6R) isomer to active (6S) isomer of 5-formyltetrahydrofolate resulted in no effect on metabolism into the one-carbon substituted folate pools and only minimal decreases in metabolism to the polyglutamate forms. These studies suggest that prolonged exposure to even relatively low doses of 5-formyltetrahydrofolate may be optimal for intracellular metabolism to the most biologically relevant forms for ternary complex formation with thymidylate synthase and fluorodeoxyuradylate, since longer exposures result in a greater accumulation of the higher polyglutamates.     

Effects of hyperthermia on blood flow and cis-diamminedichloroplatinum(II) pharmacokinetics in murine mammary adenocarcinomas.

The effect of localized hyperthermia on blood flow and cis-diamminedichloroplatinum(II) (CDDP) pharmacokinetics in 7,12-dimethylbenz[a]anthracene-induced mammary adenocarcinomas was studied. Blood flow was determined in rat tumors and normal tissue immediately and 1, 2, and 3 h after local hyperthermia treatment (43 degrees C, 1 h) as well as in unheated tumors of rats. The rate of blood flow in the tumor was increased 1.9 times at the end of treatment relative to control values and returned to the control values by 3 h after hyperthermia. Similarly, the rate of blood flow in the peripheral skin around the tumor immediately after hyperthermia was 2.2 times greater than that of unheated skin and returned to near normal values by 3 h after heating. Tumor-bearing rats received CDDP 1 h before, at the beginning of, at the end of, and 1 h after hyperthermia administration. The CDDP plasma concentration versus time profiles for rats did not vary statistically between treatment groups. Two h after CDDP administration, the mean tumor CDDP concentration of the rats which received drug at the beginning of hyperthermia was statistically greater (P less than 0.05) than tumor CDDP concentrations in rats which received drug at the end of heat treatment. The latter group was given CDDP when tumor blood flow was the greatest; however, mean tumor drug concentration was lowest of all the groups. The mean drug concentration in tumor tissues of rats which received drug 1 h after hyperthermia was comparable to rats which received drug at the beginning of hyperthermia. This suggests that drug delivery or uptake in tumors may be altered when local hyperthermia is administered concurrently or sequentially.     

Anticarcinogenic action of diallyl sulfide in hamster buccal pouch and forestomach.

The anticarcinogenic action of the garlic constituent diallyl sulfide (DAS), was examined in the hamster buccal pouch and forestomach. Groups of hamsters were topically treated, for up to 14 weeks, with a 0.5% solution of the buccal pouch and forestomach carcinogen 7,12-dimethylbenz[a]anthracene (DMBA). Prior to, during and after DMBA treatment, groups of hamsters were also treated, on alternate days, with a 1% solution of DAS. In addition to tumor formation, the induction of gamma-glutamyl transpeptidase (gamma GT) buccal pouch epithelial lesions served as an additional presumptive index of in vivo carcinogenesis/anticarcinogenesis. DAS resulted in a significant reduction in buccal pouch tumor frequency, buccal pouch tumor burden, buccal pouch gamma GT lesion frequency and forestomach tumor frequency. In a separate experiment, DAS also reduced the level of autoradiographically quantified unscheduled DNA repair synthesis (UDS) in pieces of hamster buccal pouch concurrently exposed in vitro to the potent buccal pouch carcinogen N-methyl-N-benzylnitrosamine (MBN). This study demonstrates that DAS is an effective anticarcinogenic agent in squamous mucosa of the hamster and suggests novel cost-effective strategies for the rapid identification of tissue-specific anticarcinogens and a quantitative assessment of their efficacy.     

Fractionated treatment of CaD2 tumors in mice sensitized with aluminium phthlocyanine tetrasulfonate.

CaD2 mammary carcinomas transplanted into the feet of mice were treated with tetrasulfonated phthalocyanine (AlPcS4) and laser light at 680 nm. A light dose of 135 J/cm2 was either given as continuous radiation (15 min) or fractionated with 15 s exposure, 15 s darkness, 15 s exposure and so on for 30 min. The CaD2 tumors were found to respond better to a fractionated exposure than to the same energy given in one exposure. The reason for this is assumed to be a relocalization of the dye upon illumination, seen as a rapid decrease in fluorescence. When the laser light was turned off, the fluorescence returned to almost the initial value.     

Assessment of post-vaccination tuberculin sensitivity in Lagos-Nigeria.

An increase in the number of cases of tuberculosis, especially in children, has been observed recently. Post-vaccination conversion rate in babies immunised with BCG was assessed. Sensitization was detected as early as 4 weeks after BCG inoculation. Although 84.2% had physical evidence of BCG inoculation only 69.8% had developed detectable sensitization to the tubercle bacilli as shown by the Mantoux test.     

Specific and nonspecific effects of ethanol vapor on plasma corticosterone in mice.

The intent of this study was to determine whether chronic ethanol (EtOH) vapor inhalation, with or without adjunct pyrazole (PYR) administration, was stressful in mice, as defined by increases in plasma corticosterone (CORT) concentration. Mice were randomly assigned to groups differentiated both on the basis of EtOH vapor exposure and the presence or absence of PYR administration. Blood samples for blood EtOH concentration (BEC) and plasma CORT concentration were obtained from mice after 72-96 hours of treatment. Mice were sacrificed after 96 hours of treatment and body and adrenal weight determined. BEC was significantly higher in PYR-treated animals and animals treated with the higher EtOH vapor concentration. Plasma CORT was elevated in proportion to BEC; however, other nonspecific stresses, in particular that of PYR administration, also elevated plasma CORT. Nonspecific stresses associated with this protocol may reduce the generality of these observations. Nevertheless, the high correlation between BEC and plasma CORT concentration in the PYR groups indicates that, with suitable control groups, the PYR-EtOH vapor inhalation approach is viable for studies concerned with EtOH effects on hypothalamic-anterior pituitary-adrenocortical function.