Current situation and control strategies for resurgence of diphtheria in newly independent states of the former Soviet Union

Since 1990, an epidemic of diphtheria has spread throughout the newly independent states of the former Soviet Union, and by 1995 a total of 47 808 cases were reported. During the early stages of the epidemic, adequate control measures were not taken and vaccine was in short supply; possible contributing factors to the spread of the epidemic are the presence of highly susceptible child and adult populations, socioeconomic instability, population movement, and a deteriorating health infrastructure. Although WHO views the epidemic as an International public-health emergency and, together with UNICEF and the International Red Cross, has formulated a strategy to combat the epidemic, the necessary funds have not been made fully available. Current vaccination recommendations also need to be reviewed to ensure that population immunity will be adequate to prevent any resurgence of diphtheria in Europe and North America.     

Colorectal surgery using a biofragmentable anastomotic ring

To compare the efficacy of the biofragmentable anastomotic ring (Valtrac-BAR, Davis and Geck, Medical Device Division, Danbury, CT, USA) with conventional anastomotic techniques, 30 patients who underwent colorectal surgery from August 1993 to March 1995 were retrospectively studied. The use of the BAR was also compared with conventional techniques including hand-sewn sutures in 30 patients and an end-to-end anastomosis (EEA) stapler in 24 patients. There were 17 men and 13 women in the BAR group with ages ranging from 37 to 80 years, 18 men and 12 women in the hand-sewn group with ages ranging from 41 to 82 years and 14 men and 10 women in the EEA group with ages ranging from 38 to 72 years. Surgical indications included: 25 colon cancers and five rectal cancers in the BAR group; 27 colon cancers and three rectal cancers in the hand-sewn group; and six colon cancers and 18 rectal cancers in the EEA group. There was no conversion to other anastomotic methods. Most of the patients tolerated a low-residual diet from the fifth post-operative day. No clinical leakage or stricture was noted. Only seven patients were aware of the passage of BAR fragments. The mean hospital stay was 14.1 days. There were no significant differences among these techniques in the return of bowel function, the incidence of surgical complications, including anastomotic leakage, or the length of hospitalization. BAR anastomosis was more time efficient than conventional techniques. Our results confirmed that BAR was an ideal sutureless alternative for anastomosis in colorectal surgery.     

Impact of treatment changes on the interpretation of the Concorde trial

BACKGROUND: The Concorde trial compared two policies of therapy with zidovudine (ZVD) in individuals with asymptomatic HIV infection: immediate or deferred ZDV. Participants in both groups could stop their blinded trial therapy for several reasons and/or could start open-label ZDV. The difference in survival and disease progression between the two groups was estimated allowing for treatment changes. METHODS: The relationship between latest CD4 count, treatment changes and time to AIDS-related complex (ARC), AIDS or death was investigated using time-updated proportional hazards models, but these models gave seriously biased estimates of the effect of ZDV. Therefore, a method based on the comparison of the randomized groups was used. A model relating a participant's events times to the treatment actually received was used to estimate what would have been observed if the deferred group had not received ZDV before ARS or AIDS, and to explore alternative policies for starting Pneumocystis carinii pneumonia (PCP) prophylaxis. RESULTS: The major treatment changes during the trial were the termination of blinded therapy because of adverse events or personal reasons (575 out of 1749 participants), starting open-label ZDV (745 participants), and starting PCP prophylaxis (613 participants). Starting open-label ZDV and PCP prophylaxis were strongly related to latest CD4 count. The uncorrected hazard ratios for immediate compared with deferred groups were 0.89 for time to ARC, AIDS or death [95% confidence interval (CI), 0.75-1.05], 1.01 for time to AIDS or death (95% CI, 0.82-1.24), and 1.26 for time to death (95% CI, 0.93-1.70). After correction for treatment changes, these hazard ratios were 0.79 (95% CI, 0.57-1.11), 1.01 (95% CI, 0.81-1.26), and 1.37 (95% CI, 0.91-2.08), respectively. Correction for PCP prophylaxis made little difference to the results. CONCLUSIONS: Open-label ZDV before ARC or AIDS in the deferred group was likely to have diluted any differences between the immediate and deferred groups. After correction for this dilution, both the estimated benefit of immediate treatment in delaying progression to ARC, AIDS or death and the estimated disadvantage of immediate treatment in accelerating death were somewhat increased, but both remained consistent with chance alone. This study demonstrated the large potential bias inherent in non-randomization-based methods of analysis of clinical trials.     

Virtual electrode-induced phase singularity: a basic mechanism of defibrillation failure

Delivery of a strong electric shock to the heart remains the only effective therapy against ventricular fibrillation. Despite significant improvements in implantable cardioverter defibrillator (ICD) therapy, the fundamental mechanisms of defibrillation remain poorly understood. We have recently demonstrated that a monophasic defibrillation shock produces a highly nonuniform epicardial polarization pattern, referred to as a virtual electrode pattern (VEP). The VEP consists of large adjacent areas of strong positive and negative polarization. We sought to determine whether the VEP may be responsible for defibrillation failure by creating dispersion of postshock repolarization and reentry. Truncated exponential biphasic and monophasic shocks were delivered from a bipolar ICD lead in Langendorff-perfused rabbit hearts. Epicardial electrical activity was mapped during and after defibrillation shocks and shocks applied at the plateau phase of a normal action potential produced by ventricular pacing. A high-resolution fluorescence mapping system with 256 recording sites and a voltage-sensitive dye were used. Biphasic shocks with a weak second phase (<20% leading-edge voltage of the second phase with respect to the leading-edge voltage of the first phase) produced VEPs similar to monophasic shocks. Biphasic shocks with a strong second phase (>70%) produced VEPs of reversed polarity. Both of these waveforms resulted in extra beats and arrhythmias. However, biphasic waveforms with intermediate second-phase voltages (20% to 70% of first-phase voltage) produced no VEP, because of an asymmetric reversal of the first-phase polarization. Therefore, there was no substrate for postshock dispersion of repolarization. Shocks producing strong VEPs resulted in postshock reentrant arrhythmias via a mechanism of phase singularity. Points of phase singularity were created by the shock in the intersection of areas of positive, negative, and no polarization, which were set by the shock to excited, excitable, and refractory states, respectively. Shock-induced VEPs may reinduce arrhythmias via a phase-singularity mechanism. Strong shocks may overcome the preshock electrical activity and create phase singularities, regardless of the preshock phase distribution. Optimal defibrillation waveforms did not produce VEPs because of an asymmetric effect of phase reversal on membrane polarization.     

SDZ 216-525, a selective 5-HT1A receptor antagonist, reverts zinc-induced inhibition of water intake in dehydrated rats

Zinc is found in many brain regions where it participates in important processes such as neurotransmission and neuromodulation. We previously demonstrated that acute third ventricle injection of zinc inhibits water intake in dehydrated rats. The present study was undertaken to explore a possible link between zinc-induced inhibition of water intake in dehydrated rats and serotonergic systems in the brain. Adult, male Wistar rats had the third ventricle cannulated a week before the experiments. After an overnight period of water deprivation, the animals (N = 12 per group) received acute intracerebroventricular injections (2 microliters) of Zn(Ac)2 (6.7, 67.1 and 671.6 ng/rat). Control animals (N = 12) received NaAc (671.6 ng/rat). Zinc-treated animals displayed a significant, dose-dependent reduction in water intake. Water intake after 120 min was 7.70 +/- 0.50 ml in control (NaAc-treated) dehydrated rats while animals treated with the highest dose of Zn(Ac)2 drank 2.63 +/- 0.73 ml. Third ventricle injections of SDZ 216-525, a selective 5-HT1A receptor antagonist, 45 min before zinc administration, generated a dose-dependent reversal of zinc-induced thirst blockade in water-deprived rats. At the highest dose used (10 micrograms/rat), the water intake of the animals after 120 min was 7.30 +/- 0.23 ml, a value equal to that of control animals. These data suggest that zinc may decrease water intake in dehydrated rats by activation of a 5-HT1A receptor-related mechanism.     

Homozygous cystathionine beta-synthase deficiency, combined with factor V Leiden or thermolabile methylenetetrahydrofolate reductase in the risk of venous thrombosis

Severe hyperhomocysteinemia in its most frequent form, is caused by a homozygous enzymatic deficiency of cystathionine beta-synthase (CBS). A major complication in CBS deficiency is deep venous thrombosis or pulmonary embolism. A recent report by Mandel et al (N Engl J Med 334:763, 1996) postulated factor V Leiden (FVL) to be an absolute prerequisite for the development of thromboembolism in patients with severe hyperhomocysteinemia. We studied 24 patients with homocystinuria caused by homozygous CBS deficiency from 18 unrelated kindreds for FVL and for the 677C-->T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene and investigated their possible interaction in the risk of venous thrombosis. Thrombotic complications were diagnosed in six patients, of whom only one was a carrier of FVL. On the contrary, thermolabile MTHFR caused by the 677C-->T mutation, was frequently observed among homocystinuria patients, especially among those with thromboembolic complications: three of six homocystinuria patients who had suffered from a thromboembolic event had thermolabile MTHFR. These data indicate that FVL is not an absolute prerequisite and probably not even a major determinant of venous thrombosis in homocystinuria, but, interestingly, thermolabile MTHFR may constitute a significant risk factor for thromboembolic complications in this inborn error of methionine metabolism.     

The activity of the high-affinity K+ uptake system Kdp sensitizes cells of Escherichia coli to methylglyoxal

Expression of the Kdp system sensitizes cells to methylglyoxal (MG) whether this electrophile is added externally or is synthesized endogenously. The basis of this enhanced sensitivity is the maintenance of a higher cytoplasmic pH (pHi) in cells expressing Kdp. In such cells, MG elicits rapid cytoplasmic acidification via KefB and KefC, but the steady-state pHi attained is still too high to confer protection Lowering pHi further by incubation with acetate increases the sensitivity of cells to MG.     

Causes of death in Canadians with haemophilia 1980-1995. Association of Hemophilia Clinic Directors of Canada

The life expectancy of individuals with haemophilia was close to that of the general population in the early 1980s. Since then, life expectancy has decreased, due to transfusion-transmitted virus infections. Deaths in individuals with haemophilia were investigated by analysing 2450 records from the Canadian Hemophilia Registry, for the years 1980-1995. Deaths were tabulated by age, year and cause, and compared with that of the Canadian male population by calculating standardized mortality ratios (SMRs). The median life expectancy at 1 year of age was calculated for various subpopulations and the impact of various population characteristics was assessed by survival regression modelling. There were 359 deaths and the annual number of deaths increased significantly after 1986. Risk factors were seropositivity to human immunodeficiency virus (relative risk 16.7, 95% CI 11.1-25.1), severe haemophilia (1.9, 1.3-2.7) and moderate haemophilia (1.8, 1.2-2.6). In HIV antibody negative individuals, the overall death rate was not increased (SMR 0.9, 95% CI 0.7-1.1) and only haemorrhage was significantly increased. In HIV antibody positive individuals, causes of death which were significantly increased were acquired immunodeficiency syndrome, liver failure, haemorrhage, lymphoma, liver cancer, nonspecific infections, and trauma or violence. Deaths due to the acquired immunodeficiency syndrome accounted for only 66% of the excess deaths in individuals who were HIV antibody positive. Life expectancy has markedly decreased since the onset of the HIV epidemic. The impact of HIV is underestimated by considering only deaths due to the acquired immunodeficiency syndrome; other HIV-linked causes need also to be considered.