An analysis of two recent epidemiologic reports in the New England Journal of Medicine associating breast cancer in women with moderate alcohol consumption

Two cohort studies showed an association between moderate alcohol consumption and breast cancer, with an apparent relative risk of 1.50. Drinkers and nondrinkers already differed in important ways at the initiation of these two studies, precluding a causal interpretation of the associations found. Women in need of the relaxing effect of alcohol may indeed be the group at higher risk for breast cancer. Inasmuch as the studies did not inquire into other cancers, morbidities, mortalities, or total mortality, they leave open the possibility that, on balance, moderate alcohol consumption is beneficial.     

Fetal motility and chronic exposure to antiepileptic drugs.

The potential influence of antiepileptic drugs (AEDs) on fetal CNS function was studied with respect to motility patterns. Quantitative and qualitative aspects of spontaneous fetal activity were investigated for chronic AED-exposed fetuses and controls at three intervals during pregnancy: i.e. 20, 32 and 38 weeks. Movements were observed applying real-time ultrasound. Third trimester rest-activity cycles were determined according to the fetal behavioural state concept. Quantitative analysis revealed no marked differences in gross fetal motility between AED-exposed fetuses and controls. Both groups demonstrated the same developmental trend from midterm towards the third trimester. The number of trunk movements decreased, while their median duration increased. The incidence of fetal eye movements during C2F was lower for AED-exposed fetuses than for controls (significant for 38 weeks). In qualitative analysis, general movements of AED-exposed fetuses were more often labeled as suspect or abnormal than those of control fetuses (respectively, 8 out of 31 and 1 out of 20; P = 0.06). Future studies concerning chronic fetal AED-exposure and fetal CNS function should focus on qualitative rather than quantitative aspects of motility.     

The effects upon the activity of hand and forearm muscles of intracortical stimulation in the vicinity of corticomotor neurones in the conscious monkey

Summary Corticomotor (CM) neurones were identified in three conscious macaque monkeys by the presence of post-spike facilitation (PSF) in spike-triggered averages of e.m.g. recorded from intrinsic hand and forearm muscles during performance of a precision grip task. Post-spike effects were compared with those produced by single-pulse intracortical microstimulation (ICMS), with strengths of 4–20 A, delivered at the site of 47 CM cells. Most muscles facilitated by a CM cell were also facilitated by ICMS at the site of the cell. ICMS effects were stronger: at 10 A, the amplitude of ICMS-evoked facilitation was on average 2.8 times greater than PSF, and 6.9 times greater at 20 A. Onset latency of ICMS-evoked facilitation was consistently longer (by 1.7 and 1.3 ms at 10 and 20 A respectively) than PSF, and it is suggested that this results from the indirect, trans-synaptic excitation of CM cells by ICMS. Post-spike suppression was rarely seen (7/421 compared to 105/421 cases of PSF). In contrast, suppression and facilitation were equally common in response to ICMS. The synaptic mechanisms underlying these effects were explored in 5 anaesthetised macaque monkeys. ICMS facilitated a greater proportion of the tested muscles than did the CM cell recorded at the stimulus site. The results suggest the juxtaposition in the motor cortex of CM neurones with different muscle fields. The merits of STA and ICMS for exploring cortical organisation are discussed.     

Automated analysis of near-term antepartum fetal heart rate in relation to fetal behavioral states: the Sonicaid System 8000.

Fetal heart rate and fetal movements were recorded in 16 uncomplicated near-term pregnancies. The recordings were used to evaluate a system for automated fetal heart rate analysis (Sonicaid System 8000). Fetal rest-activity patterns were considered in the analysis. The mean duration of C2F periods "active sleep," 33 minutes) was significantly greater than that of C1F periods ("quiet sleep," 19 minutes) (p less than 0.001). The incidence of accelerations and decelerations and the overall fetal heart rate variations were greater during C2F than during C1F (p less than 0.001). In 11 of 16 C1F periods, the system classified the fetal heart rate variation as "questionable" or "abnormal." Episodes of high variation were identified in only 3 of 16 C1F periods, but they were found in all 18 C2F periods. Episodes of low variation were identified in 14 of the 16 C1F periods but were not found in any C2F periods. During C2F periods, the system's criteria of normality were met in all cases but one; they were not met during any of the C1F periods. Thus the diagnosis of fetal distress should not be based merely on the absence of accelerations, low fetal heart rate variation, or absence of episodes of high variation in recordings with a duration of less than 45 minutes.     

Season, fever prevalence and pyrogenic threshold for malaria disease definition in an endemic area of Mali

BACKGROUND: Modelling malaria parasitaemia as function of fever has been proposed as best alternative to estimate the attributable fraction of malaria fever and the sensitivity and specificity of different case definitions of malaria disease. OBJECTIVES: To determine the prevalence of fever and its relation to malaria parasitaemia and to establish a pyrogenic threshold for malaria disease in the area. METHODS: We conducted two cross-sectional surveys in children of 6 months to 9 years of age (2434 during the rainy season of 1993 and 2353 during the dry season of 1994) randomly selected from 21 areas of Bandiagara district, Mali. RESULTS: The relationship between fever and Plasmodium falciparum parasitaemia depends strongly on the season, thus affecting the malaria-attributable fraction of fever cases and the sensitivity and specificity of malaria case definitions. The overall proportion of fever attributable to malaria parasitaemia was 33.6% during the rainy season and 23.3% during the dry season, with the highest proportion occurring among the youngest children. The cut-off value, where the sensitivity curve crosses the specificity curve, was around 3200 pf/microl for all age categories during the rainy season and 200 pf/microl during the dry season. CONCLUSIONS: Malaria remains a main cause of fever in this area of Mali. The pyrogenic threshold of parasitaemia depends strongly on the season, and different cut-off levels of parasitaemia should be used during the two seasons to define malaria cases in this area.     

NOBOX is a strong autosomal candidate gene in Tunisian patients with primary ovarian insufficiency

Premature ovarian insufficiency (POI) affects approximately 1% of women before the age of 40. Genetic contribution is a significant component of POI. In this context, heterozygous mutations in NOBOX, BMP15 and GDF9 have been reported. The objective of our study was to evaluate the prevalence of these genes mutations in 125 unrelated Tunisian patients diagnosed with POI. The screening of NOBOX gene revealed three missense mutations (p.Arg117Trp; p.Gly91Trp and p.Pro619Leu) in eight patients. These mutations were not found in a 200 ethnically matched women without fertility problem. The sequencing of BMP15 and GDF9 gene revealed only previously reported variants. In contrast to previous studies, the prevalence of BMP15 variations is not higher than in the control population. Conversely, 6.4% of the cases present a NOBOX mutations; this high prevalence strengthens the consideration of NOBOX gene as strong autosomal candidate for POI.     

Silver-nanoparticles increase bactericidal activity and radical oxygen responses against bacterial pathogens in human osteoclasts

Bone infections are difficult to treat and can lead to severe tissue destruction. Acute bone infections are usually caused by Staphylococcus aureus. Osteoclasts, which belong to the monocyte/macrophage lineage, are the key cells in bone infections. They are not well equipped for killing bacteria and may serve as a reservoir for bacterial pathogens. Silver has been known for centuries for its bactericidal activity. Here, we investigated the bactericidal effects of nano-silver particles in bacteria infected human osteoclasts. We found that nano-silver in per se non-toxic concentration enhanced the bactericidal activity in osteoclasts against intracellular Methicillin-resistant, virulent Staphylococcus aureus. The reduced bacterial survival in nano-silver pretreated cells correlated with increased reactive oxygen responses towards the invading pathogens. Overall, these results indicate that nano-silver compounds should be considered as an effective treatment and prevention option for bacterial bone and orthopedic implant infections.