Alpha-thalassemia in two Mediterranean populations

We used restriction endonuclease analysis to determine the incidence of alpha-thalassemia in two Mediterranean islands. In a random population sample, the gene frequency of deletion-type alpha-thalassemia-2 (- alpha) was 0.18 in Sardinians and 0.07 in Greek Cypriots. All cases were the rightward crossover type. From these frequencies and the known incidence of hemoglobin-H disease in these populations, we calculated the frequency of the alpha-thalassemia-1 genotype (--) and determined that it was low. We also found that beta-thalassemia homozygotes in sardinia have a higher incidence of alpha-thalassemia than normals and beta thalassemia heterozygotes because a significantly greater number of these homozygotes are also homozygous for the alpha-thalassemia-2 lesion. These findings support the theory that coinheritance of alpha- thalassemia mitigates the severity of beta-thalassemia and suggest that the protection is most pronounced when two alpha-globin genes are deleted.     

Cortisol catabolism by lymphocytes of patients with systemic lupus erythematosus and rheumatoid arthritis

We have shown that low cortisol catabolism by lymphocytes correlates with a high sensitivity of the cells to the steroid. In the present study, we aimed to assess whether high resistance to corticosteroid treatment correlates with a high rate of cortisol catabolism by lymphocytes. Since patients with systemic lupus erythematosus (SLE) usually require high doses of corticosteroids, while patients with rheumatoid arthritis (RA) respond to relatively low doses of steroids, we compared the capability of lymphocytes of patients with SLE and RA to catabolize cortisol. The rate of cortisol catabolism obtained with the RA group was not significantly different from that obtained with the control group. The catabolism of cortisol by lymphocytes of the SLE group was significantly higher than both the control group (p less than 0.05) and the RA group (p less than 0.01). A significant correlation was demonstrated between the SLE disease activity index and rates of cortisol catabolism attained by lymphocytes of SLE patients (p less than 0.001).     

Large sample test of defibrillation waveform sensitivity

INTRODUCTION: An unknown mechanism causes defibrillation efficacy to be sensitive to the temporal pattern (waveform) of the delivered energy. Using a guinea pig model, we tested hypotheses in 140 defibrillation waveforms. METHODS AND RESULTS: Two hundred seven male guinea pigs (950 +/- 100 g) were instrumented to continuously monitor the ECG and an optical plethysmographic signal from a forepaw. Two amplifiers served as a voltage-based defibrillator with a maximum output of 400 V at 2 A. Defibrillation electrodes (12-mm diameter) were placed 40 mm apart on the thorax. Thirty ventricular fibrillation episodes were induced where the first 10 episodes were used to estimate ED50 for a biphasic pulse (7/2 msec) and the remaining episodes were defibrillated with 18 test waveforms and two control waveforms all at the ED50 energy. Seven groups of 20 waveforms were tested. We directly tested hypotheses based on charge banking/burping, frequency concentration, and stimulus strength/duration. Of the hypotheses tested, nine are able to predict at least a 10% change in efficacy (P < 0.05): parabolic fit to duration; maximum, minimum, and remaining delivered charge; power at peak frequency; stimulus charge; and maximum, minimum, and maximum of the absolute value of stimulus strength. However, of these, only three are independent predictors of waveform efficacy (P < 0.05, near-minimum residual variance): power at peak frequency; parabolic fit to the stimulus duration; and minimum stimulus strength. CONCLUSION: Stimulus strength and duration are the main determinants of the efficacy of a defibrillation waveform.     

Risk stratification for ST segment elevation myocardial infarction in the era of primary percutaneous coronary intervention

Acute coronary syndromes presenting with ST elevation are usually treated with emergency reperfusion/revascularisation therapy. In contrast current evidence and national guidelines recommend risk stratification for non ST segment elevation myocardial infarction(NSTEMI) with the decision on revascularisation dependent on perceived clinical risk. Risk stratification for STEMI has no recommendation. Statistical risk scoring techniques in NSTEMI have been demonstrated to improve outcomes however their uptake has been poor perhaps due to questions over their discrimination and concern for application to individuals who may not have been adequately represented in clinical trials. STEMI is perceived to carry sufficient risk to warrant emergency coronary intervention [by primary percutaneous coronary intervention(PPCI)] even if this results in a delay to reperfusion with immediate thrombolysis. Immediate thrombolysis may be as effective in patients presenting early, or at low risk, but physicians are poor at assessing clinical and procedural risks and currently are not required to consider this. Inadequate data on risk stratification in STEMI inhibits the option of immediate fibrinolysis, which may be cost-effective. Currently the mode of reperfusion for STEMI defaults to emergency angiography and percutaneous coronary intervention ignoring alternative strategies. This review article examines the current risk scores and evidence base for risk stratification for STEMI patients. The requirements for an ideal STEMI risk score are discussed.     

Longitudinal study of variation in body mass index in middle-aged UK females

The importance of changing patterns of obesity in society and its implications for public health are well recognized. However, the adult life course of body mass index (BMI) changes in individuals over time is largely unknown and has mostly been extrapolated from cross-sectional studies. The present study examines individual specific variation of BMI during a 15-year follow-up period in a community-based sample of UK females. We attempted to establish whether there is a common, generalized pattern which captures variation in BMI over time. The participants of this study belong to a prospective population cohort of British women studied intensively since 1989: the Chingford Study. The sample originally consisted of 1,003 women aged 45-68 years, who were assessed annually for BMI during follow-up period. Polynomial regression models were used to assess longitudinal BMI variation. We observed a great stability in individual BMI variation during the follow-up period, reflected by high correlations between the baseline BMI and follow-up BMI 10 and 15 years later (r = 0.876, N = 810, and r = 0.824, N = 638, respectively). We also found that three different major age-related patterns in BMI could be clearly identified: no change in 30.6% in 58% it increased and in 11.4% it decreased with age. Thus, our data suggest that individual age-related changes in BMI are very different. Therefore, simply combining all individuals into groups by any other criteria (age, sex, etc.) and overlooking the distinctive patterns of BMI change may lead to biased inferences in epidemiologic and etiologic research of the future.     

Stoicism and Paranoia

Objective: The current study aimed to investigate (a) “secondary” posttraumatic growth (PTG) in wives of former prisoners of war (ex-POWs) and its association to husbands’ captivity, husbands’ posttraumatic stress disorder (PTSD), and husbands’ PTSD trajectories; and (b) the bidirectional relationships over time between wives’ posttraumatic stress symptoms (PTSS) and PTG. Method: The study compared 116 wives of Israeli ex-POWs from the 1973 Yom Kippur War with 56 wives of a matched control group of non-POW combat veterans. Wives were divided into groups according to husbands’ captivity status, husbands’ PTSD status, and husbands’ PTSD trajectories; and ANOVAs and MANOVAs were conducted to assess group differences in PTSS and PTG, both cross-sectionally and longitudinally. Autoregressive cross-lag modeling was also used to assess bidirectional relationships between wives’ PTSS and PTG over time. Results: Wives of ex-POWs with PTSD reported significantly higher PTG compared with wives of ex-POWs without PTSD and wives of controls. While PTG and PTSS remained stable over time, importantly, the Time 1 (T1) level of PTG predicted avoidance symptoms at Time 2 (T2); the higher the wives’ PTG at T1, the higher their avoidance symptoms at T2, but not vice versa. Conclusions: These findings support the notion that “secondary PTG” exists. They also strengthen the theory that growth and distress can co-occur. Finally, the finding that PTG predicted subsequent avoidance symptoms suggests that PTG does not prevent the future development of distress.     

Modern approaches to the treatment of breast cancer

Breast cancer is the most common cause of cancer death in women in this country. Until recently, the traditional treatment has been radical surgery with or without radiation therapy for patients with primary breast cancer, and palliative endocrine therapy followed by chemotherapy for patients with advanced disease. These treatments have met with limited effectiveness in terms of eradicating the disease. Studies in the past decade have given cause for optimism for breast cancer patients. Adjuvant systemic therapy after local treatment appears promising for certain subsets of patients with primary breast cancer. The development of estrogen receptor assays has markedly changed our approach to the disease and improved patient care. Estrogen receptor is an important prognostic factor and is useful in planning appropriate therapy for patients with primary breast cancer as well as those with advanced disease. Further research is urgently needed to improve the dismal survival of certain women with this common malignancy.