Longitudinal study of the frequency and duration of breastfeeding in rural Bangladeshi women.

A 27-month longitudinal study of 140 Bangladeshi mothers living in three tea gardens examined the effect of maternal factors (mother's age, number of live births, birth interval, and mother's work status) and sex of the infant on the duration and bout frequency of breastfeeding over 8-hr daytime periods. Prolonged breastfeeding of the infant was observed, but there was a sharp decline in duration of breastfeeding over the first 6 months, followed by a more gradual diminution thereafter. The feeding bouts showed a different pattern, with a more gradual decline over time. Housewives consistently showed a greater duration and bout frequency than women in paid employment as tea-pluckers. Over the first 6 months, primigravid mothers breastfed more frequently, but not thereafter. Older mothers (>35 years of age) breastfed with higher frequency during the first 2 months, but thereafter, the bout frequency decreased with increasing age of the infant. Over the 27-month study, maternal work status was the main factor associated with the duration and frequency of breastfeeding, with significantly higher frequency and duration among housewives. However, in the first 6 months after birth, there was very little difference in frequency or duration of breastfeeding between tea-workers and housewives, indicating that working mothers probably adjusted their time to breastfeed their infants before going, or after coming back, from work.     

Effects of atorvastatin on arterial endothelial function in coronary bypass surgery

Objective: Endothelial dysfunction represents a critical early component of organ injury following cardiopulmonary bypass. Recent studies demonstrate that the treatment with atorvastatin is associated with a significant improvement of endothelial function independently of its efficacy on cholesterol levels. Therefore, we investigated the effects of preoperative atorvastatin treatment on endothelium function after coronary surgery. Methods: Forty patients undergoing coronary surgery were randomized to treatment with atorvastatin (20 mg/die; N = 20) or placebo (N = 20) 3 weeks before surgery. Twenty normal patients served as control group. The flow-mediated dilations (FMD) of the brachial artery after both reactive hyperemia (endothelium dependent) and nitroglycerin administration (endothelium independent) were evaluated at baseline, at 48 h, and 5 days postoperatively. Results: At baseline, the endothelium-dependent FMD was significantly attenuated in coronary versus normal patients (normal 10.3 ± 1.8% vs coronary 4.1 ± 1.6%, p < 0.01). At 48 h postoperatively all patients exhibited a reduced FMD compared with baseline values: the endothelium-dependent dilatation showed a drop of 60.1 + 15% in the patients of the placebo group compared with 45.8 + 16.6% (p < 0.05) those in the atorvastatin group. At the univariate analysis, no significant correlation was found between serum levels of either total cholesterol or HDL cholesterol and FMD. The nitroglycerin-induced dilation was not significantly influenced by extracorporeal circulation as well as by atorvastatin treatment. Conclusions: The endothelial dysfunction following cardiopulmonary bypass is improved by the treatment with atorvastatin, by a mechanism unrelated to the drug efficacy of controlling serum cholesterol levels.     

A double cryptic chromosome imbalance is an important factor to explain phenotypic variability in Wolf-Hirschhorn syndrome

A total of five Wolf-Hirschhorn syndrome (WHS) patient with a 4p16.3 de novo microdeletion was referred because of genotype-phenotype inconsistencies, first explained as phenotypic variability of the WHS. The actual deletion size was found to be about 12 Mb in three patients, 5 Mb in another one and 20 Mb in the last one, leading us to hypothesize the presence of an extrachromosome segment on the deleted 4p. A der(4)(4qter --> p16.1::8p23 --> pter) chromosome, resulting from an unbalanced de novo translocation was, in fact, detected in four patients and a der(4)(4qter --> q32::4p15.3 --> qter) in the last. Unbalanced t(4;8) translocations were maternal in origin, the rec(4p;4q) was paternal. With the purpose of verifying frequency and specificity of this phenomenon, we investigated yet another group of 20 WHS patients with de novo large deletions (n = 13) or microdeletions (n = 7) and with apparently straightforward genotype-phenotype correlations. The rearrangement was paternal in origin, and occurred as a single anomaly in 19 out of 20 patients. In the remaining patient, the deleted chromosome 4 was maternally derived and consisted of a der(4)(4qter --> 4p16.3::8p23 --> 8pter). In conclusions, we observed that 20% (5/25) of de novo WHS-associated rearrangements were maternal in origin and 80% (20/25) were paternal. All the maternally derived rearrangements were de novo unbalanced t(4;8) translocations and showed specific clinical phenotypes. Paternally derived rearrangements were usually isolated deletions. It can be inferred that a double, cryptic chromosome imbalance is an important factor for phenotypic variability in WHS. It acts either by masking the actual deletion size or by doubling a quantitative change of the genome.     

Anti-MOG autoantibodies in Italian multiple sclerosis patients: specificity, sensitivity and clinical association

There is considerable evidence that multiple sclerosis (MS) is an immune-mediated disease characterized by infiltration of inflammatory cells into the CNS and demyelination. Several myelin proteins may be encephalitogenic, including myelin basic protein, proteolipid protein and myelin oligodendrocyte glycoprotein (MOG), the latter being expressed on the external layer of myelin sheaths and hence accessible to antibody attack. We investigated MOG autoreactivity in serum and cerebrospinal fluid (CSF) by ELISA, employing the recombinant extracellular domain of MOG as antigen. We tested serum samples from 262 MS patients (175 relapsing-remitting, 43 primary progressive and 44 secondary progressive), 131 patients with other neurological diseases (OND) and 307 healthy controls. No patients or controls were receiving immunomodulating treatments. We found anti-MOG antibodies in the serum of 13.7% MS patients, mainly in those with secondary progressive MS (25%), in 13.7% of OND patients and in 6.2% of controls. We found a direct correlation (R(2) = 0.6, P = 0.002) between disease severity and anti-MOG titer only in patients with primary and secondary progressive MS. Anti-MOG antibodies were present in the CSF of 11.4% MS patients and 18.9% OND patients. Intrathecal synthesis of anti-MOG antibodies was demonstrated in four (4.5%) of MS patients and no OND patients. Anti-MOG antibodies are not specific for MS; however, they may characterize a subset of MS patients and this may be revealed by serial assays in relation to changing disease phase.     

Bootstrap analyses of cost effectiveness in antidepressant pharmacotherapy

In this study, we describe 'bootstrap' methodology for placing statistical confidence limits around an incremental cost effectiveness ratio (ICER). This approach was applied to a retrospective study of annual charges for patients undergoing pharmacotherapy for depression. We used MarketScanSM (service mark) data from 1990 to 1992, which includes medical and pharmacy claims for a privately insured group of employed individuals and their families in the US. Our primary effectiveness measure was the proportion of patients who remained stable on their initial antidepressant medication for at least 6 consecutive months. Our primary cost measure was the total annual charge incurred by patients taking the selective serotonin reuptake inhibitor fluoxetine, a tricyclic antidepressant or a heterocyclic antidepressant. On average, fluoxetine pharmacotherapy tended to decrease annual charges by $US16.48 per patient for each percentage increase in depressed patients remaining stable on initial pharmacotherapy for 6 months, resulting in a negative ICER point-estimate. However, the upper ICER confidence limit is positive, which means that fluoxetine treatment may possibly increase annual per patient charges. With 95% confidence, any such increase was no more than $US130 per patient for each percentage increase in patients remaining stable on initial pharmacotherapy for at least 6 months. One advantage of using a bootstrap approach to ICER analysis is that it does not require restrictive distributional assumptions about cost and outcome measures. Bootstrapping also yields a dramatic graphical display of the variability in cost and effectiveness outcomes that result when a study is literally 'redone' hundreds of times. This graphic also displays the ICER confidence interval as a 'wedge-shaped' region on the cost-effectiveness plane. In fact, bootstrapping is easier to explain and appreciate than the elaborate calculations and approximations otherwise involved in ICER estimation. Our discussion addresses key technical questions, such as the role of logarithmic transformation in symmetrising highly skewed cost distributions. We hope that our discussion contributes to a dialogue, leading ultimately to a consensus on analysis of ICERs.     

Enhancer blocking activity located near the 3′ end of the sea urchin early H2A histone gene

The sea urchin early histone repeating unit contains one copy of each of the five histone genes whose coordinate expression during development is regulated by gene-specific elements. To learn how within the histone repeating unit a gene-specific activator can be prevented to communicate with the heterologous promoters, we searched for domain boundaries by using the enhancer blocking assay. We focused on the region near the 3′ end of the H2A gene where stage-specific nuclease cleavage sites appear upon silencing of the early histone genes. We demonstrated that a DNA fragment of 265 bp in length, defined as sns (for silencing nucleoprotein structure), blocked the enhancer activity of the H2A modulator in microinjected sea urchin embryos only when placed between the enhancer elements and the promoter. We also found that sns silenced the modulator elements even when placed at 2.7 kb from the promoter. By contrast, the enhancer activity of the modulator sequences, located downstream to the coding region, was not affected when sns was positioned in close proximity to the promoter. Finally, the H2A sns fragment placed between the simian virus 40 regulative region and the tk promoter repressed chloramphenicol acetyltransferase expression in transfected human cell lines. We conclude that 3′ end of the H2A gene contains sequence elements that behave as functional barriers of enhancer function in the enhancer blocking assay. Furthermore, our results also indicate that the enhancer blocking function of sns lacks enhancer and species specificity and that it can act in transient assays.