Effects on mortality of alcohol consumption, smoking, physical activity, and close personal relationships

The study analyses the risks of mortality associated with alcohol consumption and smoking, as well as possible counteracting effects of physical activity and social support through close personal relationships. Data are based on the Upper Bavarian Study, a longitudinal epidemiological study of a representative community sample (n = 1668) in a rural area. Extensive semistructural psychiatric interviews by research physicians were conducted between 1975 and 1977 (n = 1536). Thirteen years after psychiatric assessment, information was obtained from the community register concerning death in the interval, date of death and cause of death according to ICD 9. Tins information could be ascertained for 93.1% (n= 1430) of those who had been interviewed, thus providing a good basis for generalizing the findings. Results indicate that alcohol intake and cigarette smoking increased mortality while physical activity and the availability of a steady partner had protective effects. There were no interactive effects between the four variables studied, except far a dramatically increased risk for women drinking more than 20 ml of pure alcohol a day and reporting no physical exercise at wave one assessment. The relative risks of alcohol intake and smoking, and the counteracting effects of physical activity and partnership, are exemplified in the cases of a 40-year-old female and a 40-year-old male. Specific analyses of the relationship between alcohol consumption, smoking, physical exercise and personal relationships, on the one hand, and, on the other, different causes of death, are presented.     

Coarctation of the Aorta: Quantitative Analysis by Transesophageal Echocardiography

Transesophageal echocardiography and standard two-dimensional echocardiography were performed in 15 patients with suspected coarctation of the aorta. Aortic diameters and crosssectional areas were determined by means of TEE and compared with clinical findings and catheterization data. The isthmus of the aorta could be imaged in all patients using TEE, but in only seven patients using standard suprasternal echocardiography. Compared with controls, aortic diameters were narrowed in 9 of 15 patients, and cross-sectional areas were reduced in 13 of 15. There was a satisfactory correlation between TEE data and angiographic and hemodynamic data. TEE is a promising method of a diagnosing and quantifying coarctation of the aorta, and is more sensitive than conventional two-dimensional and Doppler echocardiography.     

Pharmacokinetics and Kinetic-Dynamic Modelling of Aminophenones as Methaemoglobin Formers

Methaemoglobin, the oxidized form of haemoglobin, can be formed by a variety of agents, most of which act to oxidize haemoglobin directly or indirectly. Cyanide has a higher affinity for methaemoglobin than for mitochondrial cytochromes, making methaemoglobin formation a basis for the treatment of cyanide poisoning. We used the beagle dog model to investigate the relationship between drug concentration and methaemoglobin levels for two candidate anti-cyanide compounds. The compounds studied were the aminophenones p-aminopropiophenone (PAPP) and p-aminoheptylphenone (PAHP). Both PAPP and PAHP were given as intravenous boluses and as two different oral formulations. The kinetics of both compounds appeared to follow a three-compartment open model for intravenous bolus administration and a two-compartment open model for oral administration. The first distribution phase seen with the intravenous administration was obscured by the absorption phase during oral administration. Bioavailability for all formulations varied between 20 and 47%. For both compounds there was a delay between the appearance of drug in the plasma and the appearance of methaemoglobin (counter-clockwise hysteresis) which is suggestive of an active metabolite causing methaemoglobin formation. The pharmacodynamics were fit with an effect-compartment kinetic-dynamic model linked to a sigmoid E_max pharmacodynamic model. Maximum amounts of methaemoglobin occurred between 2 and 4 h for PAHP and between 1 and 3 h for PAPP. When administered intravenously estimates of EC50 were lower than the estimates of EC50 from oral administration for both compounds. This might be because of oral first-pass inactivation or a ‘first-pass’ activation through the lungs contributing to the formation of an active metabolite. The phenones as a class appear to have the drug cleared and methaemoglobin return to near baseline within 12 h. Both compounds seem to produce sufficient methaemoglobin to treat acute cyanide poisoning and to serve as prophylactic agents against acute cyanide poisoning in a military setting.     

S- and C-glycopeptide derivatives of an LH-RH agonist

The S- and C-glycosylated nonapeptides 1 and 2 were synthesized as analogs of the non-glycosylated LH-RH agonist buserelin (pGlu-His-Trp-Ser-Tyr-D-Ser(tBu)-Leu-Arg-Pro-NHEt) by segment condensation in solution. 1 and 2 differ from this peptide in the amino acid in position 6. In the first case (l), D-serine (tBu) is substituted by D-CySteine carrying a rhamnosyl residue, in the second case (2) D-alanine carrying a galactosyl moiety bound as C-glycoside is incorporated. The bioactivity of both glycopeptides as fertility drugs was determined from the dose dependent LH release in male rats. Additionally, in female rats the ovulation rate was assessed. As a result the analog 1 exhibits a similar biological activity as buserelin while analog 2 shows about 25% of this potency. Compared to buserelin the solubility of the analogs 1 and 2 in aqueous buffer is improved by more than two orders of magnitude due to the carbohydrate moieties. © Munksgaard 1996.     

THE MOLECULAR CHARACTERISTICS OF BLADDER CANCER IN YOUNG PATIENTS

Purpose

The molecular characteristics of bladder cancer in children and young adults remain largely undefined. We sought to identify common molecular changes in bladder tumors in young patients using standard immunohistochemical and interphase cytogenetic methods.

Materials and Methods

We retrospectively evaluated 73 bladder tumors removed from patients younger than 30 years for the p53 tumor suppressor gene product using immunohitochemical techniques and numerical aberrations of chromosomes 9, 17, X and Y.

Results

Regardless of stage, immunohistochemical evidence of p53 gene product over expression was found in the majority of tumors studied. Numerical abberations (mosomy) of chromosome 9 were rare. Aneuploidy of chromosome 17 was common, particularly in carcinoma in situ and invasive bladder cancer.

Conclusions

These data suggest that immunohistochemical evidence of p53 gene product over expression is common in bladder cancer in young patients. Further prospective analysis of lesions in this population may help to establish a comprehensive molecular progression model for urothelial neoplasms.     

Relationship Between Atrioventricular Delay and Oxygen Consumption in Patients with Sick Sinus Syndrome: Relevance to Rate Responsive Pacing

To develop a dromotropic-controlled rate adaptive algorithm for patients with sick sinus syndrome (SSS) and intact AV conduction, 14 pace-maker patients with SSS underwent cardiopulmonary exercise testing (CPX). During exercise, the pace-maker was programmed in an AAT mode without rate adaptation, whereby 3 patients developed supraventricular arrhythmia and 11 patients kept sinus rhythm. Chronotropic incompetence (CI) at heart rate (HR) < 95 beats/min at the anaerobic threshold (AT) was found in five patients. In patients with chronotropic competence (CC), the HR increase was significantly greater than in CI patients (rest: 73.2 +/- 12.6 vs. 64.2 +/- 4.0 beats/min;AT:101.2 +/- 6.2 vs. 82.0 +/- 5.1 beats/min;peak: 135.2 +/- 10.7 vs. 103.2 +/- 10.9 beats/min). There was no significant difference in the AVD between CC and CI patients (rest: 167.7 +/- 38.6 vs. 170.8 +/- 22.5 ms, AT: 156.2 +/- 30.7 vs. 163.6 +/- 21.6 ms, peak: 144.7 +/- 29.0 vs. 152.4 +/- 15.0 ms). The correlation coefficient between HR increase and VO2 was +1.0 and between AVD decrease and VO2 - 1.0 in both groups. An increase in pacing rate from 75 beats/min to 120 beats/min without exercise (overpacing) led to a prolongation of the AV interval of about 30.6 +/- 14.2 ms. Based on this closed loop control with negative feedback, a dromotropic rate adaptive algorithm for patients with SSS and intact AV conduction could be developed.     

Radiofrequency Catheter Ablation of Left Atrial Tachycardia Originating Within the Pulmonary Vein in a Patient with Dextrocardia

A case is presented of a 38-year-old male with dextrocardia in whom radiofrequency current ablation of an incessant atrial tachycardia originating within the infero-lateral pulmonary vein was achieved. Activation mapping with detection of the earliest atrial activation was used for identification of the arrhythmogenic focus. In addition to fluoroscopy, trans- esophageal echocardiography was used for catheter guidance during the transseptal puncture. The present experience suggests that location of an arrhythmogenic focus within the pulmonary venous system should be considered whenever early atrial activation during ectopic atrial tachycardia is recorded at the junction between thfi left atrium and the pulmonary veins.     

On the emerging paradigm of drinking patterns and their social and health consequences

Recent epidemiological and social studies have increasingly pointed to the importance of drinking patterns in explaining consequences of alcohol consumption. This paper presents recommendations for research in the area based on the presentations and discussions of the first “International Conference on Social and Health Effects of Different Drinking Patterns” held in Toronto in November 1995. In particular, the social dimension in pattern research, and the relationship between patterns of drinking and causalities as well as social harm, are stressed. The paper also argues for better theories, incorporating knowledge from related basic disciplines. In addition, we emphasize the need for improved methodologies and standardized methods for assessing drinking patterns. Finally, implications of research on drinking patterns for polity and programme development are discussed.     

Aerobic Capacity in Rate Modulated Pacing

Whether heart rate or AV synchrony is the most important factor for an increase in aerobic capacity was evaluated in a comparative study between sinus bradycardia, VVIR, DDD, and DDDR stimulation. Sixteen patients (mean age 67 years) with chronotropic incompetence and impJanted DDDR pacemaker (Telectronics META 1250) were randomly studied by cardiopulmonary exercise testing. All patients were exercised to their anaerobic threshold (ATJ with the following heart rates: DDD 84 ± 3, WIR 110 ± 5, and DDDR 116 ± 6 beats/min. Mean oxygen uptake (VO₂, mL/kg per min) at AT was 7.4 ± 0.3 in DDD and WIR modes. A 12% increase was measured in DDDR mode (8.3 ± 0.4). Compared to VVIR work capacity in the DDDR mode was improved by 17% (41 vs 48 W/min). In patients with isolated sinus node disease (n = 9) the increase of VO₂ and work capacity at AT during DDDR mode was more pronounced (16% and 20%, respectively, compared to VVIR). In patients with intermittent second or third degree AV block (n = 7) the differences between the pacing modes were not significant. This might partly be due to a lesser degree of chronotropic incompetence in this subgroup. In conclusion only the conjunction of heart rate increase and preservation of AV synchrony provides a significant improvement in aerobic capacity during exercise.