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.     

Electrophysiological Characteristics of Bipolar Membrane Carbon Leads With and Without Steroid Elution Compared With a Conventional Carbon and a Steroid-Fluting Platinum Lead

In a controlled study, the following four bipolar leads with passive fixation were implanted in 46 patients with the Siemens-MuItilog-VVI or Sensolog-VVIR-pacemakers: membrane covered activated porous carbon with steroid elution (Siemens 1402 T, 11 patients) and without (Siemens 1403 T, 15 patients); activated carbon (Siemens 1010T, 10 patients); and platinum with steroid elution (Medtronic CapSure 5026, 10 patients). Stimulation threshold (STH) (assessed by a vario-test), impedance (IMP), and the intracardial R wave potential (IRW) (both gauged by a telemetric method) were measured 1, 5, and 10 days as well as 3 and 6 months after implantation during unipolar and bipolar stimulation, chronaxie rheobase product (CBP) and energy consumption (EC) were systematically determined. Differing insignificantly at the first day after implantation, STH is significantly lower for the 1402 T and CapSure 5026 leads at the tenth day. However, the 1402 T lead shows a significant increase of STH in the follow-up, in contrast to the other leads. The lowest chronic STH was found in the CapSure 5026 lead (CRP is significantly lower in all other leads, too). IMP is significantly lower in the CapSure 5026 lead compared to 1010 T lead. EC does not differ significantly during chronic stimulation in spite of the best possible programming of pulse amplitude and duration. No significant changes of IRW were observed. Unipolar versus bipolar stimulation shows significantly lower STH, CRP, and IMP, differences of EC and IRW were insignificant. In conclusion, the addition of steroid in membrane covered carbon leads protracts the increase of STH, but does not prevent it. The CapSure 5026 lead shows advantageous stimulation characteristics, but energy consumption is not significantly reduced because of low impedance and impossibility of programming an appropriate low output in Multilog pacemakers.     

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.     

Efficacy and Safety of Bipolar Sensing with High Atrial Sensitivity in Dual Chamber Pacemakers

In dual chamber pacemakers, atrial sensing performance is decisive for maintenance of AV synchrony. Particularly, the efficacy of mode switching algorithms during intermittent atrial tachyarrhythmias depends on the sensitive detection of low potential amplitudes. Therefore, a high atrial sensitivity of 0.18 mV, commonly used in single lead VDD pacemakers, was investigated for its efficacy and safety in DDD pacing. Thirty patients received dual chamber pacemakers and bipolar atrial screw‐in leads for sinus node syndrome or AV block; 15 patients suffered from intermittent atrial fibrillation. Pace makers were programmed to an atrial sensitivity of 0.18 mV. Two weeks, 3, 9, and 15 months after implantation, P wave sensing threshold and T wave oversensing thresholds for the native and paced T wave were determined. The myopotential oversensing thresholds were evaluated by isometric contraction of the pectoral muscles. Automatic mode switch to DDIR pacing was activated when the mean atrial rate exceeded 180 beats/min. The patients were followed by 24‐hour Holter monitoring. Two weeks after implantation, mean atrial sensing threshold was 1.81 ± 0.85 mV (range 0.25–2.8 mV) without significant differences during further follow‐up. Native T wave sensing threshold was < 0.18 mV in all patients. In 13% of patients, paced T waves were perceived in the atrial channel at the highest sensitivity. This T wave sensing could easily be avoided by programming a postventricular atrial refractory period exceeding 300 ms. Myopotential oversensing could not be provoked and Holter records showed no signs of sensing dysfunction. During a 15‐month follow‐up, 1,191 mode switch events were counted by autodiagnostic pacemaker function. Forty‐two of these events occurred during Holter monitoring. Unjustified mode switch was not observed. In DDD pacemakers, bipolar atrial sensing with a very high sensitivity is efficient and safe. Using these sensitivity settings, activation of the mode switch algorithm almost completely avoids fast transmission of atrial rate to the ventricle during atrial fibrillation.     

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.