Prospective associations of parental smoking, alcohol use, marital status, maternal satisfaction, and parental and childhood body mass index at 6.5 years with later problematic eating attitudes.

BACKGROUND: Few studies have prospectively investigated whether early-life exposures are associated with pre-adolescent eating attitudes. OBJECTIVE: The objective of this study is to prospectively investigate associations of parental smoking, alcohol use, marital status, measures of maternal satisfaction, self-reported parental body mass index (BMI) and clinically measured childhood BMI, assessed between birth and 6.5 years, with problematic eating attitudes at 11.5 years. METHODS: Observational cohort analysis nested within the Promotion of Breastfeeding Intervention Trial, a cluster-randomised trial conducted in 31 maternity hospitals and affiliated polyclinics in Belarus. Our primary outcome was a Children's Eating Attitudes Test (ChEAT) score 22.5 (85th percentile), an indicator of problematic eating attitudes. We employed multivariable mixed logistic regression models, which allow inference at the individual level. We also performed instrumental variable (IV) analysis using parents' BMIs as instruments for the child's BMI, to assess whether associations could be explained by residual confounding or reverse causation. SUBJECTS: Of the 17 046 infants enrolled between 1996 and 1997 across Belarus, 13 751 (80.7%) completed the ChEAT test at 11.5 years. RESULTS: In fully adjusted models, overweight children at age 6.5 years had a 2.14-fold (95% confidence interval (CI): 1.82, 2.52) increased odds of having ChEAT scores 85th percentile at age 11.5 years, and those who were obese had a 3.89-fold (95% CI: 2.95, 5.14) increased odds compared with normal-weight children. Children of mothers or fathers who were themselves overweight or obese were more likely to score 85th percentile (P for trend 0.001). IV analysis was consistent with a child's BMI causally affecting future eating attitudes. There was little evidence that parental smoking, alcohol use, or marital status or maternal satisfaction were associated with eating attitudes. CONCLUSION: In our large, prospective cohort in Belarus, both parental and childhood overweight and obesity at 6.5 years were associated with pre-adolescent problematic eating attitudes 5 years later.

Do gastrointestinal tract infections in infancy increase blood pressure in childhood? A cohort study.

BACKGROUND: It has been hypothesised that dehydration in infancy could permanently increase sodium retention, raising blood pressure in later life. In this study, the association between gastrointestinal tract infection in infancy, a clinically relevant exposure often accompanied by dehydration, and raised blood pressure in childhood was investigated. METHODS: Data from a cohort study nested within a cluster-randomised trial of breastfeeding promotion in the Republic of Belarus were analysed. 17 046 healthy breastfed infants were enrolled from 31 maternity hospitals. 13 889 (81.5%) children were followed-up at 6.5 years. Exposure measures were any gastrointestinal infection in infancy (to 1 year) and hospitalisations for gastrointestinal infection in infancy and in childhood (1-6.5 years). The outcomes were systolic and diastolic blood pressure at age 6.5 years. RESULTS: The prevalence of any gastrointestinal infection in infancy, and of hospitalisation for gastrointestinal infection in infancy or childhood, was 11.4%, 3.2% and 6.0%, respectively. No associations were observed between systolic blood pressure and any gastrointestinal infection (mean difference in those with minus those without infection -0.04 mm Hg; 95% CI -0.52 to 0.43) or hospitalisation for gastrointestinal infection (difference=-0.22 mm Hg; -1.07 to 0.64) in infancy. Nor were associations observed between diastolic blood pressure and any gastrointestinal infection during infancy or hospitalisation for gastrointestinal infection during infancy or childhood. CONCLUSION: No evidence was found to prove that hospitalisation for gastrointestinal infection in infancy or childhood leads to raised blood pressure at age 6.5 years in a developed country setting.

The low prevalence of allergic disease in Eastern Europe: are risk factors consistent with the hygiene hypothesis?

BACKGROUND: The prevalence of allergic disease is known to be low in Eastern Europe. OBJECTIVE: To assess the association of suspected risk factors, including several closely linked to the hygiene hypothesis, with allergic symptoms and atopic sensitization in young school-aged children. METHODS: Observational study of 13 889 Belarusian children followed up at age 6.5 years in the Promotion of Breastfeeding Intervention Trial (PROBIT). Allergic symptoms and diseases were based on parental responses to the International Study of Asthma and Allergy in Childhood questionnaire, and prick tests to five common inhalant allergens were performed using standard methods. RESULTS: Significantly increased risks of wheezing and hayfever symptoms in the past 12 months, and of recurrent itchy rash were observed in boys, children with a positive first-degree family atopic history, and those who had received probiotics (especially as prophylaxis with antibiotic use). Pet ownership, contact with farm animals, the presence and number of younger and (especially) older siblings, and residency in rural areas of Western Belarus were associated with reduced risks. Maternal postnatal smoking was associated with wheezing and hayfever symptoms, while the duration of exclusive breastfeeding was not protective against any of the studied outcomes. The risk factors for allergic symptoms were similar in children with positive skin-prick tests to those in the overall cohort. CONCLUSION: Many of the risk and protective factors we identified are consistent with those reported in Western countries and with the hygiene hypothesis. Further research on dietary and other environmental and genetic factors is necessary to understand the low prevalence of allergic disease in Belarus and other Eastern European countries.

The effect of prolonged and exclusive breast-feeding on dental caries in early school-age children. New evidence from a large randomized trial.

To study the effects of prolonged and exclusive breast-feeding on dental caries, we followed up children participating in the Promotion of Breastfeeding Intervention Trial (PROBIT), a cluster-randomized trial of a breast-feeding promotion intervention based on the WHO/UNICEF Baby-Friendly Hospital Initiative. A total of 17,046 healthy, mother-infant breast-feeding pairs were enrolled from 31 Belarussian maternity hospitals and affiliated polyclinics, of whom 13,889 (81.5%) were followed up at 6.5 years. At follow-up, polyclinic pediatricians transcribed the reports of a standard dental examination performed by public health dentists at age 6 years and recorded in the children's polyclinic charts. Analysis was based on intention to treat, with a statistical model that accounts for clustering within hospitals/clinics to permit inferences at the individual level. The experimental intervention led to a large increase in exclusive breast-feeding at 3 months (43.3 vs. 6.4%, p < 0.001) and a significantly higher prevalence of any breast-feeding at all ages up to and including 12 months. No significant intervention effects were observed on dental caries. Our results, based on the largest randomized trial ever conducted in the area of human lactation, provide no evidence of beneficial or harmful effects of prolonged and exclusive breast-feeding on dental caries at early school age.

Does previous infection protect against atopic eczema and recurrent wheeze in infancy?

BACKGROUND: Frequent infection in infancy and early childhood has been hypothesized to explain the low prevalence of asthma and other atopic disease among children in developing countries (the so-called 'hygiene hypothesis'), but the low prevalence in Eastern Europe remains unexplained. OBJECTIVE: To test the hygiene hypothesis in the Republic of Belarus by examining the relationship between gastrointestinal (GI) and respiratory infection and two potentially atopic outcomes in the first 12 months of life: atopic eczema and recurrent wheeze. METHODS; We carried out two case-control studies nested within a large (n=17 046) randomized trial in Belarus, with cases defined as (1) first occurrence of atopic eczema (n=819) and (2) second episode of wheezing (n=112). Incidence density sampling was used to select four matched controls born within 1 month at the same hospital as the case. Exposure was defined as one or more episodes of GI or respiratory infection (examined separately) with onset >7 days before onset of the case's atopic outcome. Analyses controlled for family atopic history, duration of exclusive breastfeeding, sex, birth weight, maternal education, and (for recurrent wheeze) maternal smoking. RESULTS: For atopic eczema, prior GI infection occurred in 7.4% of cases vs. 6.0% of controls [adjusted OR=1.27 (0.94-1.72)] and prior respiratory infection in 35.2% vs. 32.6% [adjusted OR=1.14 (95% CI=0.94-1.37)]. For recurrent wheeze, prior GI infection occurred in 9.8% of cases vs. 7.4% of controls [adjusted OR=1.30 (0.60-2.82)]. CONCLUSION: Our results do not support the hypothesis that infection protects against atopic eczema or recurrent wheezing in the first 12 months of life.

Promotion of Breastfeeding Intervention Trial (PROBIT): a randomized trial in the Republic of Belarus.

CONTEXT: Current evidence that breastfeeding is beneficial for infant and child health is based exclusively on observational studies. Potential sources of bias in such studies have led to doubts about the magnitude of these health benefits in industrialized countries. OBJECTIVE: To assess the effects of breastfeeding promotion on breastfeeding duration and exclusivity and gastrointestinal and respiratory infection and atopic eczema among infants. DESIGN: The Promotion of Breastfeeding Intervention Trial (PROBIT), a cluster-randomized trial conducted June 1996-December 1997 with a 1-year follow-up. SETTING: Thirty-one maternity hospitals and polyclinics in the Republic of Belarus. PARTICIPANTS: A total of 17 046 mother-infant pairs consisting of full-term singleton infants weighing at least 2500 g and their healthy mothers who intended to breastfeed, 16491 (96.7%) of which completed the entire 12 months of follow-up. INTERVENTIONS: Sites were randomly assigned to receive an experimental intervention (n = 16) modeled on the Baby-Friendly Hospital Initiative of the World Health Organization and United Nations Children's Fund, which emphasizes health care worker assistance with initiating and maintaining breastfeeding and lactation and postnatal breastfeeding support, or a control intervention (n = 15) of continuing usual infant feeding practices and policies. MAIN OUTCOME MEASURES: Duration of any breastfeeding, prevalence of predominant and exclusive breastfeeding at 3 and 6 months of life and occurrence of 1 or more episodes of gastrointestinal tract infection, 2 or more episodes of respiratory tract infection, and atopic eczema during the first 12 months of life, compared between the intervention and control groups. RESULTS: Infants from the intervention sites were significantly more likely than control infants to be breastfed to any degree at 12 months (19.7% vs 11.4%; adjusted odds ratio [OR], 0.47; 95% confidence interval [CI], 0.32-0.69), were more likely to be exclusively breastfed at 3 months (43.3% vs 6.4%; P<.001) and at 6 months (7.9% vs 0.6%; P =.01), and had a significant reduction in the risk of 1 or more gastrointestinal tract infections (9.1% vs 13.2%; adjusted OR, 0.60; 95% CI, 0.40-0.91) and of atopic eczema (3.3% vs 6.3%; adjusted OR, 0.54; 95% CI, 0.31-0.95), but no significant reduction in respiratory tract infection (intervention group, 39.2%; control group, 39.4%; adjusted OR, 0.87; 95% CI, 0.59-1.28). CONCLUSIONS: Our experimental intervention increased the duration and degree (exclusivity) of breastfeeding and decreased the risk of gastrointestinal tract infection and atopic eczema in the first year of life. These results provide a solid scientific underpinning for future interventions to promote breastfeeding.

Promotion of breastfeeding intervention trial (PROBIT): a cluster-randomized trial in the Republic of Belarus. Design, follow-up, and data validation.

This paper summarizes the objectives, design, follow-up, and data validation of a cluster-randomized trial of a breastfeeding promotion intervention modeled on the WHO/UNICEF Baby-Friendly Hospital Initiative (BFHI). Thirty-four hospitals and their affiliated polyclinics in the Republic of Belarus were randomized to receive BFHI training of medical, midwifery, and nursing staffs (experimental group) or to continue their routine practices (control group). All breastfeeding mother-infant dyads were considered eligible for inclusion in the study if the infant was singleton, born at > or = 37 weeks gestation, weighed > or = 2500 grams at birth, and had a 5-minute Apgar score > or = 5, and neither mother nor infant had a medical condition for which breastfeeding was contraindicated. One experimental and one control site refused to accept their randomized allocation and dropped out of the trial. A total of 17,795 mothers were recruited at the 32 remaining sites, and their infants were followed up at 1, 2, 3, 6, 9, and 12 months of age. To our knowledge, this is the largest randomized trial ever undertaken in area of human milk and lactation. Monitoring visits of all experimental and control maternity hospitals and polyclinics were undertaken prior to recruitment and twice more during recruitment and follow-up to ensure compliance with the randomized allocation. Major study outcomes include the occurrence of > or = 1 episode of gastrointestinal infection, > or = 2 respiratory infections, and the duration of breastfeeding, and are analyzed according to randomized allocation ("intention to treat"). One of the 32 remaining study sites was dropped from the trial because of apparently falsified follow-up data, as suggested by an unrealistically low incidence of infection and unrealistically long duration of breastfeeding, and as confirmed by subsequent data audit of polyclinic charts and interviews with mothers of 64 randomly-selected study infants at the site. Smaller random audits at each of the remaining sites showed extremely high concordance between the PROBIT data forms and both the polyclinic charts and maternal interviews, with no evident difference in under- or over-reporting in experimental vs control sites. Of the 17,046 infants recruited from the 31 participating study sites, 16,491 (96.7%) completed the study and only 555 (3.3%) were lost to follow-up. PROBIT's results should help inform decision-making for clinicians, hospitals, industry, and governments concerning the support, protection, and promotion of breastfeeding.

Alpha-ketoglutarate dehydrogenase in Alzheimer brains bearing the APP670/671 mutation.

Alzheimer's disease (AD) is associated with a striking reduction in the activity of the alpha-ketoglutarate dehydrogenase complex (KGDHC). The deficiency occurs in brains from AD patients of undefined etiology, and in fibroblasts from both sporadic and familial AD cases. To further assess the nature of the abnormality of KGDHC in AD, KGDHC activities and immunoreactivities were analyzed in brains from AD patients bearing the Swedish APP670/671 mutation. This gene defect causes overproduction of the amyloid beta peptide. KGDHC activities were reduced by 55 to 57% compared with control values in the mutation-bearing AD cases in the medial temporal and superior frontal cortices. The immunochemical levels of KGDHC subunits Elk (-51%) and E2k (-76%) declined, whereas E3 concentrations were unchanged. The results suggest that mitochondrial dysfunction is a part of the pathophysiological process in AD even when the primary pathogenic cause is nonmitochondrial.

Decreased inositol (1,4,5)-trisphosphate receptor levels in Alzheimer's disease cerebral cortex: selectivity of changes and possible correlation to pathological severity.

We used immunoblotting and radioligand binding techniques to compare levels of the calcium-mobilizing receptor for the phosphoinositide hydrolysis-derived intracellular second messenger inositol (1,4,5)-trisphosphate (IP3) in post mortem samples from the temporal, frontal and parietal cortices of eight Alzheimer's disease (AD) and eight matched control cases. Immunoblotting with an antibody directed against the C-terminal end of the rat type I IP3-receptor showed that IP3-receptor protein levels were significantly reduced in the temporal (to 59 +/- 6% of controls, P = 0.0002) and frontal (to 62 +/- 10% of controls, P = 0.04), but not in the parietal cortices (to 63 +/- 13% of controls, P = 0.1) of the AD cases, compared to controls. The number of [3H]IP3 radioligand binding sites was significantly decreased in the temporal cortex, but not frontal and parietal cortices, of the AD brains. The decreased levels of both immunoreactive IP3-receptor protein and [3H]IP3 binding in the temporal cortex correlated with a semi-quantitative score for the severity of AD neuropathology. No significant changes were seen in the levels of glial fibrillary acidic protein, synaptophysin or phosphate-activated glutaminase, as markers for astrocytes, neuronal vesicles and mitochondria, respectively. It is concluded that in affected AD brain regions, the IP3-receptor may represent a sensitive target for proteolysis, possibly mediated by activation of the Ca(2+)-activated neutral protease calpain. These degenerative changes may in part be responsible for the disruption of Ca2+ homeostasis in AD-sensitive neurons.

Astrocytes associated with senile plaques possess muscarinic acetylcholine receptors.

AUTOPSY sections of the temporal and parahippocampal gyri were incubated with the monoclonal antibody M35 to label muscarinic acetylcholine receptors. Senile plaques were visualized either by counterstaining with Congo red or by Bielschowsky silver-stain of adjacent sections. The antibody labelled pyramidal and non-pyramidal cells in the grey matter, as well as fibrous astrocytes in the white matter and first cortical layer, of elderly control brains. In AD brains however, the grey matter was characterized by prominently labelled fibrous astrocytes and few or poorly labelled neurones. M35-immunoreactive astrocytes were often associated with senile plaques. These findings suggest that plaque-associated astrocytes may be responsive to acetylcholine or cholinergic drugs.

[Morphofunctional changes of the neurosecretory system and microcirculatory bed of the hypothalamus in patients with chronic alcoholic intoxication of varying degree]. / Morfofunktsional'nye izmeneniia neirosekretornoi sistemy i mikrotsirkuliatornogo rusla gipotalamusa u lits s khronicheskoi alkogol'noi intoksikatsiei raznoi stepeni.

Microcirculation was studied in the hypothalamus in acute alcohol intoxication. Blood flow was sharply decelerated with capillaries paretically dilated, overfilled with blood. Stasis, sludge formation and venue microthrombosis were directly related to the alcohol concentration in blood and urine. In neurosecretion areas the hemorrhagic sites were detected with neurosecretory cells activity sharply reduced. Chronical alcohol administration increased the number of functionally inactivated capillaries. These with luminal vesiculation were also found as were lymphoid cell infiltrates in venule walls. The number of capillaries inactivated in the neurosecretory system paralleled the number of dark cells that reflected the inhibition effects.

[Characteristics of ventricular capillary blood filling of the human heart in sudden coronary death]. / Osobennosti krovenapolneniia kapilliarnogo rusla zheludochkov serdtsa cheloveka pri vnezapnoi koronarnoi smerti.

A histometric and histochemical study of myocardial ventricular capillaries was carried out in cases of sudden coronary death (SCD) in the absence of myocardial infarction and postinfarction cardiosclerosis. Heterogenic pattern of capillary blood filling, increased quantity of plasmatic capillaries, their reduced density per unit of area and sparser distribution, as well as greater metabolite ultrafiltration diameter were demonstrated, as evidence of disturbed myocardial transcapillary metabolism. Decreased muscular fiber/capillary rations, "vesicles" emerging in the capillary lumen and sludging in some vessels determine impairment of capillary perfusion. Two groups of cases were identified: those with uniform blood overfilling of capillaries and with uniform compression of the capillary lumen that must be due to the fact that death occurred during the systolic or diastolic phase, respectively.

[The microcirculatory bed of the human myocardium in sudden cardiac death]. / Izuchenie mikrotsirkuliatornogo rusla miokarda cheloveka pri vnezapnoi serdechnoi smerti.

A ventricular capillary bed was studied in 30 hearts of humans upon sudden cardiac death according to modified technique of Karnovsky-Roots. A 10-80% narrowing of coronary artery lumen was found due to formation of atherosclerotic plaques. The assessment of butyrylcholinesterase activity in myocardial sections proved helpful in providing the appearance of microcirculation from small arterioles to venules. Determination of volumetric density of microvessels suggested an inverse correlation between the degree of stenosis of major coronary arterial branches and volumetric density of ventricular capillaries in the heart.

[Mechanisms of the development of the terminal state in experimental emotional stress]. / O mekhanizmakh razvitiia terminal'nogo sostoianiia pri eksperimental'nom emotsional'nom stresse.

The development of ventricular fibrillation associated with experimental emotional stress was studied in chronic rabbit experiments. Changes in myocardial-fibre action potentials, thresholds for ventricular fibrillation and its precursors, blood and myocardial catecholamine levels and heart-muscle ultrastructure were examined. Emotional stress was shown to increase, via sympathoadrenal activation, functional and structural heterogeneity of the myocardium, leading, alongside other causes, to arrhythmias and death from ventricular fibrillation. Moderately prevailing parasympathetic effects on the heart during stress exposure contribute to the elevation of fibrillation and fibrillation precursor thresholds and prevent catecholamine rise and myocardial structural damage.

[Effect of hydrocortisone on changes in brain tissue in experimental brain abscess and leptomeningitis]. / Vliianie gidrokortizona na izmeneniia v mozgovoi tkani pri éksperimental'nom abstsesse mozga i leptomeningite.

A total of 286 rats were involved in an experiment, with 123 of them being control and 153 receiving daily injections of hydrocortisone (H) in a dose of 3 mg per 100 g body weight. Ten rats were intact. With regard to CNS changes 2 periods were identified in H-treated rats with experimental brain abscess and leptomeningitis: the first was characterized by the effect of the hormone at the acute period of the disease (3-7 days), the second by its action following the long-term administration (15-30 days). In the first 7 days, by reducing the inflammatory reaction, water-electrolyte disturbances and the activity of acid and alkaline phosphatases in the cerebral tissue, as well as by increasing the RNA synthesis in neurons, H prevented the dissemination of the process into the surrounding tissue, swelling and edema, expedited wound clearance and helped to reduce the mortality rate. The use of H for 10-30 days led to the tigrolysis of neurons, elevation in the activity of acid and alkaline phosphatases and brain edema, as well as to a reduction in DNA levels in neurons and a dramatic rise in the mortality rate. The findings indicate the advisability of H utilization in the treatment of brain abscess and leptomeningitis only in the acute period of the disease and as a short course.

[Microcirculation in the human hypothalamus in sudden coronary death]. / Osobennosti mikrotsirkuliatsii v gipotalamuse cheloveka pri vnezapnoi koronarnoi smerti.

A histochemical, cytophotometric and morphometric study of hypothalamic microcirculatory vessels was conducted in 2 samples: 50 sudden cardiac deaths from coronary heart disease and 50 cardiac deaths from clinical myocardial infarction that were not sudden. Non-sudden cardiac death was associated with moderate venous hyperemia and high postcapillary alkaline phosphatase activity. In cases of sudden coronary death, three patterns of microcirculatory changes were identified that differed with respect to the quantity of functionally-inactive capillaries, the markedness of edema in hypothalamic tissues and hypothalamic content of vascular mast cells. Relationships between the said differences and different dates of death are discussed.