Eficacia diagnóstica de la impedancia basal nocturna media, un nuevo parámetro para el estudio de la enfermedad por reflujo gastroesofágico / Diagnostic efficacy of mean nocturnal basal impedance, a new parameter for the study of gastroesophageal reflux disease

Resumen Introducción y objetivos: el análisis de la impedancia basal nocturna media (IBNM) se ha propuesto para incrementar la precisión diagnóstica de enfermedad por reflujo erosiva (ERGE). Nuestro objetivo fue evaluar el rendimiento diagnóstico de esta prueba en un grupo de pacientes con ERGE conocida. Materiales y métodos: incluimos 123 individuos (58 con ERGE y 65 controles sanos) a quienes se les realizó pH-impedanciometría (pH-IMM) consecutiva entre enero de 2015 y junio de 2017. Todos los pacientes tenían endoscopia tomada en los 6 meses previos. El tiempo de exposición ácida (TEA) anormal (>4,2%) y la presencia de pirosis y/o regurgitación en los 6 meses previos fueron los criterios para el diagnóstico de ERGE. Se encontraron 58 pacientes con ERGE, 24 con enfermedad por reflujo erosiva (ERE) y 34 con enfermedad por reflujo no erosiva (ERNE). Los 65 restantes fueron controles sanos (CS) asintomáticos con EGD y pH-IMM normales. Todos los trazos de pH-IMM se reanalizaron para medir la IBNM por un segundo observador que desconocía los datos previos. El análisis estadístico incluyó pruebas múltiples de Bonferroni para comparar los grupos; regresión lineal para variables continuas; y análisis de curva ROC para buscar valor IBNM con mayor rendimiento. Para los diferentes parámetros de precisión diagnóstica se utilizó el punto de corte de la IBNM. Se usó significancia estadística con valor de p <0,01 e intervalos de confianza de 95% (IC 95%) para todos los cálculos. Resultados: los pacientes con ERE y ERNE presentaron valores de IBNM significativamente más bajos que el grupo control (p <0,01). Se observó una correlación negativa entre los valores de la IBNM y TEA (r = 0,59; p = <0,001), y también entre la IBNM y número de eventos de reflujo (r = 0,37; p = <0,001). En el análisis de curva ROC, el área bajo la curva de la IBNM fue de 0,941 (IC 95%: 0,894-0,987) y el punto de corte con mayor eficiencia 1102 ohms (sensibilidad 98,5%; especificidad 84,5%). Usando este valor (<1,102), la IBNM tuvo una sensibilidad para detectar ERGE de 91% (ERNE 86% y ERE 100%) y una especificidad de 98%. Conclusión: la IBNM tiene alta sensibilidad y especificidad para el diagnóstico de la ERGE. Adicionar esta prueba al análisis convencional de la pH-impedancia y a los métodos actuales de estudio de la ERGE puede mejorar significativamente nuestra capacidad para diagnosticar la enfermedad.

Abstract Introduction and Objectives: Analysis of nocturnal basal impedance (IBNM) has been proposed as a way to increase accuracy of GERD diagnosis. Our objective was to evaluate the diagnostic performance of this test in a group of patients known to have GERD. Materials and methods: We included 123 individuals: 58 with GERD and 65 healthy controls. They underwent consecutive pH-impedance monitoring between January 2015 and June 2017. All had undergone endoscopy in the 6 months prior to testing. Criteria used for diagnosis of GERD were abnormal acid exposure time (AET > 4.2%), pyrosis and/or regurgitation in the previous 6 months. We found 58 patients with GERD of whom 24 had erosive reflux disease (ERE) and 34 had non-erosive reflux disease (NERD). The remaining 65 were asymptomatic healthy controls with normal endoscopic results and pH impedance monitoring. A second observer who did not know the previous data measurements analyzed all pH impedance monitoring traces for IBMN. Statistical analysis included multiple Bonferroni tests for comparison between groups, linear regression for continuous variables, and receiver operating characteristic (ROC) curve analysis to find high performance IBNM values. The IBNM cutoff point was used for diagnostic precision parameters. Statistical significance was set at p <0.01, and 95% confidence intervals were used for all calculations. Results: IBNM measures were significantly lower for patients with ERE and NERD than for the control group (p <0.01). A negative correlation was observed between IBNM and acid exposure time values ​​(r = 0.59, p = <0.001) and also between IBNM and number of reflux events (r = 0.37, p = <0.001). ROC curve analysis found that the area under the curve for IBNM was 0.941 (95% CI: 0.894-0.987), and the cutoff point with the highest efficiency was 1,102 ohms (sensitivity 98.5%, specificity 84.5%). Using this value (<1.102), the IBNM had a sensitivity for detecting GERD of 91% (NERD 86% and ERE 100%) and a specificity of 98%. Conclusion: IBNM has high sensitivity and specificity for diagnosis of GERD. Addition of this test to conventional pH-impedance analysis and current methods for studying GERD can significantly improve our ability to diagnose this disease.

Age-related changes in Egr1 transcription and DNA methylation within the hippocampus.

Aged animals show functional alterations in hippocampal neurons that lead to deficits in synaptic plasticity and changes in cognitive function. Transcription of immediate-early genes (IEGs), including Egr1, is necessary for processes such as long-term potentiation and memory consolidation. Here, we show an age-related reduction in the transcription of Egr1 in the dentate gyrus following spatial behavior, whereas in the area CA1, Egr1 is reduced at rest, but its transcription can be effectively driven by spatial behavior to levels equivalent to those observed in adult animals. One mechanism possibly contributing to these aging-related changes is an age-associated, CpG site-specific change in methylation in DNA associated with the promoter region of the Egr1 gene. Our results add to a growing body of work demonstrating that complex transcriptional and epigenetic changes in the hippocampus significantly contribute to brain and cognitive aging. © 2016 Wiley Periodicals, Inc.

Increased expression of BDNF transcript with exon VI in hippocampi of patients with pharmaco-resistant temporal lobe epilepsy.

A putative role of the brain-derived neurotrophic factor (BDNF) in epilepsy has emerged from in vitro and animal models, but few studies have analyzed human samples. We assessed the BDNF expression of transcripts with exons I (BDNFI), II (BDNFII), IV (BDNFIV) and VI (BDNFVI) and methylation levels of promoters 4 and 6 in the hippocampi of patients with pharmaco-resistant temporal lobe epilepsy (TLE) (n=24). Hippocampal sclerosis (HS) and pre-surgical pharmacological treatment were considered as clinical independent variables. A statistical significant increase for the BDNFVI (p<0.05) was observed in TLE patients compared to the autopsy control group (n=8). BDNFVI was also increased in anxiety/depression TLE (N=4) when compared to autopsies or to the remaining group of patients (p<0.05). In contrast, the use of the antiepileptic drug Topiramate (TPM) (N=3) was associated to a decrease in BDNFVI expression (p<0.05) when compared to the remaining group of patients. Methylation levels at the BDNF promoters 4 and 6 were similar between TLE and autopsies and in relation to the use of either Sertraline (SRT) or TPM. These results suggest an up-regulated expression of a specific BDNF transcript in patients with TLE, an effect that seems to be dependent on the use of specific drugs.

Status epilepticus triggers early and late alterations in brain-derived neurotrophic factor and NMDA glutamate receptor Grin2b DNA methylation levels in the hippocampus.

Status epilepticus (SE) triggers abnormal expression of genes in the hippocampus, such as glutamate receptor subunit epsilon-2 (Grin2b/Nr2b) and brain-derived neurotrophic factor (Bdnf), that is thought to occur in temporal lobe epilepsy (TLE). We examined the underlying DNA methylation mechanisms and investigated whether these mechanisms contribute to the expression of these gene targets in the epileptic hippocampus. Experimental TLE was provoked by kainic acid-induced SE. Bisulfite sequencing analysis revealed increased Grin2b/Nr2b and decreased Bdnf DNA methylation levels that corresponded to decreased Grin2b/Nr2b and increased Bdnf mRNA and protein expression in the epileptic hippocampus. Blockade of DNA methyltransferase (DNMT) activity with zebularine decreased global DNA methylation levels and reduced Grin2b/Nr2b, but not Bdnf, DNA methylation levels. Interestingly, we found that DNMT blockade further decreased Grin2b/Nr2b mRNA expression whereas GRIN2B protein expression increased in the epileptic hippocampus, suggesting that a posttranscriptional mechanism may be involved. Using chromatin immunoprecipitation analysis we found that DNMT inhibition restored the decreases in AP2alpha transcription factor levels at the Grin2b/Nr2b promoter in the epileptic hippocampus. DNMT inhibition increased field excitatory postsynaptic potential in hippocampal slices isolated from epileptic rats. Electroencephalography (EEG) monitoring confirmed that DNMT inhibition did not significantly alter the disease course, but promoted the latency to seizure onset or SE. Thus, DNA methylation may be an early event triggered by SE that persists late into the epileptic hippocampus to contribute to gene expression changes in TLE.

Adult-onset diabetes among Arabs and Jews in Israel: a population-based study.

AIMS: To study the age at presentation and factors associated with adult-onset diabetes (≥ 20 years) among Arabs and Jews in Israel. METHODS: Participants (n = 1100) were randomly selected from the urban population of the Hadera District in Israel. The study sample was stratified into equal groups according to sex, ethnicity (Arabs and Jews) and age. Information on age at diabetes presentation, family history of diabetes, history of gestational diabetes, socio-demographic and lifestyle characteristics was obtained through personal interviews. Self reports of diabetes were compared with medical records and were found reliable (κ = 0.87). The risk for diabetes was calculated using Kaplan-Meier survival analysis. Factors associated with diabetes in both ethnic groups were studied using Cox proportional hazard model. RESULTS: The prevalence of adult-onset diabetes was 21% among Arabs and 12% among Jews. Arab participants were younger than Jews at diabetes presentation. By the age of 57 years, 25% of Arabs had diagnosed diabetes; the corresponding age among Jews was 68 years, a difference of 11 years (P < 0.001). The greater risk for diabetes among Arabs was independent of lifestyle factors, family history of diabetes and, among women, history of gestational diabetes; adjusted hazard ratio 1.70; 95% confidence interval 1.19-2.43. CONCLUSIONS: Arabs in Israel are at greater risk for adult-onset diabetes than Jews and are younger at diabetes presentation. Culturally sensitive interventions aimed at maintaining normal body weight and active lifestyle should be targeted at this population. Possible genetic factors and gene-environmental interactions underlying the high risk for diabetes among Arabs should be investigated.

Age-related changes in Arc transcription and DNA methylation within the hippocampus.

The transcription of genes that support memory processes are likely to be impacted by the normal aging process. Because Arc is necessary for memory consolidation and enduring synaptic plasticity, we examined Arc transcription within the aged hippocampus. Here, we report that Arc transcription is reduced within the aged hippocampus compared to the adult hippocampus during both "off line" periods of rest, and following spatial behavior. This reduction is observed within ensembles of CA1 "place cells", which make less mRNA per cell, and in the dentate gyrus (DG) where fewer granule cells are activated by behavior. In addition, we present data suggesting that aberrant changes in methylation of the Arc gene may be responsible for age-related decreases in Arc transcription within CA1 and the DG. Given that Arc is necessary for normal memory function, these subregion-specific epigenetic and transcriptional changes may result in less efficient memory storage and retrieval during aging.

Beauty product-related exposures and childhood brain tumors in seven countries: results from the SEARCH International Brain Tumor Study.

Data from 1218 cases of childhood brain tumors (CBT) diagnosed between 1976 and 1994 and 2223 matched controls from the general population were included in an analysis of maternal beauty product exposure and beauty-related employment in 9 centers in 7 countries. A 50% increased odds ratio (OR) [95% confidence interval (CI) = 1.0-2.1] for CBT was observed among children of mothers who were exposed via personal use of and/or possible ambient contact with beauty products during the 5 years preceding the index child's birth compared with children of mothers never exposed to beauty products during this time period. Overall maternal personal use of hair-coloring agents in the month before or during the pregnancy of the index child's birth was not associated with CBT (OR = 1.0, CI = 0.83-1.3) or with astroglial (OR = 1.1, CI = 0.85-1.4), PNET (OR = 1.0, CI = 0.71-1.5) and other glial subtypes (OR = 1.0, CI = 0.62-1.0). Similarly, no statistically increased ORs or discernable pattern of risk estimates were observed for period of use or for number of applications per year for maternal personal use of hair-coloring agents overall or by histologic type. Among children born on or after 1980, increased ORs for CBT were associated with maternal non-work-related exposure to any beauty products (OR = 2.6, CI = 1.2-5.9), hair-dyes (OR = 11, CI = 1.2-90), and hair sprays (OR = 3.4, CI = 1.0-11). No overall increased OR for CBT was observed among children of mothers employed in beauty-related jobs during the 5 years preceding the index child's birth compared with those who reported no beauty-related employment. In general, other specific beauty product-related exposures were not associated with increased ORs for CBT. Data from our study provide little evidence of an increased risk for CBT with mothers' exposures to beauty products.

Kainate mediates nuclear factor-kappa B activation in hippocampus via phosphatidylinositol-3 kinase and extracellular signal-regulated protein kinase.

The transcription factor nuclear factor-kappa B (NF-kappaB) is an inducible regulator of genes that plays a crucial role in the nervous system. Glutamate receptor stimulation is one well-described mechanism for NF-kappaB activation. In the studies presented here we used the glutamate analog, kainate to investigate the signaling mechanisms that couple to NF-kappaB activation in hippocampus. Kainate (250 nM) application to hippocampal slices elicited a time-dependent increase in nuclear NF-kappaB levels in areas CA3 and CA1, but not dentate, compared with controls. Further analysis focused on hippocampal area CA3, revealed increased NF-kappaB DNA binding activity in response to kainate stimulation. Supershift electrophoretic mobility shift assay indicated that the kainate-mediated NF-kappaB complex binding DNA was composed of p65, p50, and c-Rel subunits. Through inhibition studies we found that extracellular signal-regulated protein kinase (ERK) and phosphatidylinositol-3 kinase (PI3K) couple to basal and kainate-mediated NF-kappaB DNA binding activity in area CA3. Kainate elicited decreased total and increased phospho-inhibitor kappa B alpha (IkappaBalpha), suggesting that kainate-mediated activation of NF-kappaB is via the classical IkappaB kinase pathway. Interestingly, inhibition of ERK but not PI3K blocked the kainate-mediated increase in phospho-IkappaBalpha. Thus, our findings support a role for the ERK and PI3K pathways in kainate-mediated NF-kappaB activation in hippocampal area CA3, but these kinases may target the NF-kappaB pathway at different loci.

Parental exposure to polycyclic aromatic hydrocarbons and the risk of childhood brain tumors: The SEARCH International Childhood Brain Tumor Study.

Experimental evidence suggests that parental exposure to polycyclic aromatic hydrocarbons (PAH), which occurs primarily through tobacco smoke, occupational exposure, and air pollution, could increase the risk of cancer during childhood. Population-based case-control studies carried out in seven countries as part of the SEARCH Program compared data for 1,218 cases of childhood brain tumors and 2,223 controls (1976-1994). Parental occupational exposure to PAH during the 5-year period before birth was estimated with a job exposure matrix. Risk estimates were adjusted for child's age, sex, and study center. Paternal preconceptional occupational exposure to PAH was associated with increased risks of all childhood brain tumors (odds ratio (OR) = 1.3, 95% confidence interval: 1.1, 1.6) and astroglial tumors (OR = 1.4, 95% confidence interval: 1.1, 1.7). However, there was no trend of increasing risk with predicted level of exposure. Paternal smoking alone (OR = 1.4) was also associated with the risk of astroglial tumors in comparison with nonsmoking, non-occupationally-exposed fathers. Risks for paternal occupational exposure were higher, with (OR = 1.6) or without (OR = 1.7) smoking. Maternal occupational exposure to PAH before conception or during pregnancy was rare, and this exposure was not associated with any type of childhood brain tumor. This large study supports the hypothesis that paternal preconceptional exposure to PAH increases the risk of brain tumors in humans.

Comparison between primary peritoneal and epithelial ovarian carcinoma: a population-based study.

OBJECTIVE: This study was undertaken to characterize primary peritoneal carcinoma (PPC) compared with ovarian carcinoma (OvC). STUDY DESIGN: Within the framework of a nationwide epidemiologic Israeli study, 95 PPC patients were identified and compared with 117 FIGO stage III-IV epithelial OvC patients matched by age and continent of birth. Data were abstracted from medical records and personal interviews. RESULTS: Our data confirm the similarities between PPC and OvC. A higher rate of abdominal distention, volume of ascites, and malignant cells in ascitic fluid and lower rate of pelvic palpable mass and personal breast cancer history were found in the PPC compared with the OvC group. The overall survival was similar in both groups (30-33 months). In optimally cytoreduced patients, survival was better in the OvC group. Diameter of residual disease was associated with better survival only in the OvC group. CONCLUSION: The clinical differences do not enable a preoperative distinction between the neoplasms.

Population attributes affecting the prevalence of BRCA mutation carriers in epithelial ovarian cancer cases in israel.

OBJECTIVE: The objective was to evaluate the prevalence of BRCA1/2 mutations in selected categories of ovarian cancer patients in Israel. METHODS: Blood samples and specimens of ovarian tumors were obtained in the course of a national case control study of women with ovarian cancer in Israel. Eight hundred ninety-six patients with epithelial ovarian cancer, 40 cases with nonepithelial ovarian cancer, and 68 with primary peritoneal cancer were tested for the BRCA mutations. Analysis of the three common BRCA mutations in Israel (185delAG, 5382insC in BRCA1, and 6174delT in BRCA2) was done using a multiplex polymerase chain reaction assay. A multivariate logistic regression model was used to assess the association of mutation carrier status and other factors (age, origin, family history, and clinical variables). RESULTS: Of the 779 invasive epithelial ovarian cancer cases, 29.4% were mutation carriers. The prevalence of the mutations was higher among women below age 60 and in more advanced cases. The prevalence was low in mucinous tumors. There was almost a twofold excess of mutations among women with positive family history (45.7%), but still 26.5% of the family history negative cases were carriers. As expected, we found a higher rate of mutation carriers among the Ashkenazi group (34.2%) and 55% among Ashkenazi women with positive family history. No subjects born in North Africa were mutation positive. CONCLUSION: BRCA mutations are strongly associated with ovarian cancer and they are present in variable rates in distinct age, ethnic, and histopathologic categories.

Body mass index at age 18 years and during adult life and ovarian cancer risk.

During the years 1994-1999, a nationwide ovarian cancer case-control study was conducted in Israel. The present analysis addresses the question: Is epithelial ovarian cancer associated with body mass index at age 18 years and/or with weight changes in body mass index between adolescence and adult life? The study is based on 1,269 women with epithelial ovarian cancer and 2,111 matched controls. A significant decrease in risk of ovarian cancer was observed with parity, oral contraceptive use, and postmenopausal status. A significant increase in risk with family history of ovarian/breast cancer was also found. No significant association with age at menarche or infertility was found. For body mass index at age 18 years, the odds ratio of the highest versus lowest body mass index quartile was 1.42 (95% confidence interval: 1.08, 1.85) and after adjusting for confounders was 1.54 (95% confidence interval: 1.17, 2.02). However, no statistically significant risk associated with change in weight from age 18 years to adult life was found. The authors conclude that, in their population, body mass index at age 18 years is an independent risk factor for ovarian cancer.

Frequency of BRCA mutations in primary peritoneal carcinoma in Israeli Jewish women.

OBJECTIVE: The aim of the present study was to compare demographic and clinical characteristics of primary peritoneal carcinoma (PPC) to ovarian carcinoma (OvC) with regard to BRCA mutation frequencies. METHODS: Incident cases of histologically confirmed cancer of the ovary or peritoneum diagnosed in Israeli Jewish women between March 1, 1994, and June 30, 1999, were identified within the framework of an ongoing nationwide epidemiological study of these neoplasms in Israel. The present study comprises 609 (81.5% of 747) Jewish women with epithelial stage III-IV OvC and 68 (77.3% of 88) Jewish women with PPC who were genetically tested for the BRCA mutations. Data from each patient were collected by the aid of a prestructured questionnaire and medical records. Blood samples or tumor tissue was tested for the 185delAG and 5382insC mutations in BRCA1 and the 6174delT mutations in BRCA2. RESULTS: A carrier rate of 28% of any BRCA 1/2 mutation was observed among the PPC group and of 30% among the invasive stage III-IV OvC. No differences were found between PPC and OvC neither in the overall distribution of BRCA1/2 mutation carrier rates nor according to type of mutation, age, ethnic origin, and histologic subtype. Among women with a positive family history, a higher rate of mutation carriers was observed in the PPC group compared to the OvC group (72.7 vs 43.8%, respectively, P = 0.07). CONCLUSIONS: The similar frequency distribution of BRCA1/2 mutations in PPC and OvC observed in the present study indicates that these mutations may predispose to PPC as well and that this neoplasm is part of the hereditary breast-ovarian cancer syndrome.

Effect of BRCA mutations on the length of survival in epithelial ovarian tumors.

PURPOSE: To study the role of BRCA mutations in ovarian cancer survival. PATIENTS AND METHODS: Blood samples and specimens of ovarian tumors (whenever blood samples were not available) at the time of the primary surgery were obtained in the course of a nationwide case-control study of women with ovarian cancer in Israel. The three common BRCA mutations in Israel (185delAG, 5382insC, and 6174delT) were analyzed with a multiplex polymerase chain reaction to amplify the exons containing the three mutations using fluor-labeled primers in a single reaction. Because each mutation is a small insertion or deletion, they can be detected as length polymorphisms. Patients were followed for up to 5 years (range, 20 to 64 months). Statistical analysis was performed using the Kaplan-Meier method and the log-rank test. Stepwise Cox regression analysis was used for determination of independent prognostic factors. RESULTS: This report is based on 896 blood or tumor specimens analyzed for the presence of the BRCA mutations. Of these, 234 women (26.1%) were found to be positive. A significant difference in survival pattern was found between BRCA1/BRCA2 carriers and noncarriers among the women with invasive ovarian cancer (median survival, 53.4 months v. 37.8 months; 3-year survival, 65.8% v. 51.9%, respectively). These differences were independent of age at diagnosis or stage of the disease. CONCLUSION: Our data indicate that the survival of patients with ovarian cancer is affected by BRCA germline mutation, at least in the early years after diagnosis.

Parental occupations and childhood brain tumors: results of an international case-control study.

OBJECTIVE: To evaluate the role of parental occupations in the etiology of childhood brain tumors (CBT). METHODS: Population-based case-control studies were conducted concurrently in seven countries under the coordination of the International Agency for Research on Cancer, gathering 1,218 cases and 2,223 controls. We report here the findings related to parental occupations during the 5-year period before the child's birth. Risk estimates related to a number of paternal and maternal occupations were obtained by unconditional logistic regression adjusted for age, sex, year of birth, and center, for all types of CBT combined and for the subgroups of astroglial, primitive neuroectodermal tumors (PNET), and other glial tumors. RESULTS: An increased risk in relation with agricultural work was seen for all CBT combined and for other glial tumors. Increased risks for all tumors and PNET were seen for paternal occupation as an electrician; the same pattern held for maternal occupation when children under 5 were selected. Paternal occupation as a driver or mechanic, and maternal work in an environment related to motor-vehicles were associated with an increased risk for all CBT and astroglial tumors. More case mothers compared to control mothers were employed in the textile industry. CONCLUSION: Our study reinforces previous findings relative to the role of parental work in agriculture, electricity, or motor-vehicle related occupations and maternal work in the textile industry. It does not confirm previous associations with work environments including aerospace, the chemical industry, or the food industry, or with maternal occupation as a hairdresser, a nurse, or a sewing machinist, and paternal occupation as a welder.

Seasonal variations in dietary intake affect the consistency of dietary assessment.

BACKGROUND: Nutritional epidemiology studies are usually based on one dietary assessment without taking into account the season in which the interview is taken or adjusting for the difference in reporting dietary intake in different seasons. The semiquantitative food frequency questionnaire has become the primary questionnaire method for measuring dietary intake in epidemiological studies. The aims of this report were (a) to evaluate the effect of season on dietary intake as measured by a semiquantitative food frequency questionnaire (FFQ) conducted twice: once in summer and a second time in winter; and (b) to assess the effect of the differences in dietary intake on biochemical and anthropometric seasonal related changes, such as serum cholesterol and body mass index (BMI). POPULATION AND METHODS: The study population consisted of 94 male industrial employees who participated in clinical biochemical and physical examinations as well as evaluation of their dietary intake twice a year. Dietary intake was assessed using the semiquantitative FFQ that included 96 items and was conducted by a personal interview. RESULTS: We found a significant increase in the intake of selected nutrients in winter as compared to summer as well as an increased intake of animal fat-containing foods such as meat and dairy products. Significant correlation coefficients were shown between the increase in dietary intake of saturated fat and the increase in BMI, serum total and LDL cholesterol. The increase in dietary cholesterol was significantly and positively correlated with the increase in serum total and LDL cholesterol. CONCLUSION: Although FFQ are designed to assess average yearly food intake, we identified significant seasonal changes in dietary intake as measured by FFQ. These changes have a health impact on our population.

Parity, oral contraceptives, and the risk of ovarian cancer among carriers and noncarriers of a BRCA1 or BRCA2 mutation.

BACKGROUND: Multiparity and the use of oral contraceptives reduce the risk of ovarian cancer, but their effects on this risk in women with a BRCA1 or BRCA2 mutation are unclear. METHODS: We conducted a population-based case-control study of ovarian cancer among Jewish women in Israel. Women were tested for the two founder mutations in BRCA1 and the one founder mutation in BRCA2 that are known to be common among Jews. We estimated the effects of parity and oral-contraceptive use on the risk of ovarian cancer in carriers and noncarriers in separate analyses that included all control women, who did not have ovarian cancer. RESULTS: Of 751 controls who underwent mutation analysis, 13 (1.7 percent) had a BRCA1 or BRCA2 mutation, whereas 244 of 840 women with ovarian cancer (29.0 percent) had a BRCA1 or BRCA2 mutation. Overall, each additional birth and each additional year of use of oral contraceptives were found to lower the risk of ovarian cancer, as expected. Additional births were protective in separate analyses of carriers and noncarriers, but oral-contraceptive use appeared to reduce the risk only in noncarriers; among carriers, the reduction in the odds of ovarian cancer was 12 percent per birth (95 percent confidence interval, 2.3 to 21 percent) and 0.2 percent per year of oral-contraceptive use (-4.9 to 5.0 percent). CONCLUSIONS: The risk of ovarian cancer among carriers of a BRCA1 or BRCA2 mutation decreases with each birth but not with increased duration of use of oral contraceptives. These data suggest that it is premature to use oral contraceptives for the chemoprevention of ovarian cancer in carriers of such mutations.

Calcium supplements interact significantly with long-term diet while suppressing rectal epithelial proliferation of adenoma patients.

BACKGROUND: Calcium supplements to the western-style diet may reduce the risk for colorectal neoplasia. Using rectal epithelial proliferation (REP) measurements as a biomarker of response to intervention, the authors evaluated the effects of 1-year calcium supplementation in adenoma patients and its possible interactions with the patients' dietary and lifestyle habits. METHODS: Consenting adenoma patients, without a family history of colorectal neoplasia, were randomly selected to receive 3.75 g calcium carbonate (1.5 g Ca2+) daily or to receive no treatment. All had their long-term dietary and lifestyle habits assessed and their REP labeling index (LI) evaluated before and at end of follow-up. The change in LI was compared between groups, and statistical associations were examined between mean nutrient consumption and treatment effect and between lifestyle and treatment effect. RESULTS: Fifty-two adenoma patients (33 treated and 19 untreated) completed intervention and follow-up. There were no significant differences between study groups in age, weight, cigarette smoking, or medication use. The LI decreased in 58% of calcium-intervened patients and in only 26% of nonintervened patients (P = 0.04); the mean LI x 100 (+/- standard deviation) of the former fell from 5.04 +/- 1.93 to 4.54 +/- 1.58, and rose from 4.32 +/- 1.58 to 4.93 +/- 1.58 in the latter (P = 0.04). A lower fat, a higher carbohydrate, fiber, or fluid intake each interacted with the calcium supplementation to decrease the LI (P = 0.02, 0.001, 0.02, and 0.08, respectively). CONCLUSIONS: Long-term calcium supplements significantly suppressed REP in adenoma patients, and long-term dietary habits contributed to this effect. Patient diet should be assessed when researchers use REP as a biomarker in calcium chemoprevention studies. Study results indicated that relevant dietary counseling may be useful in addition to calcium supplements in persons at increased risk for colorectal neoplasia.

The role of nutritional habits during gestation and child life in pediatric brain tumor etiology.

Our aim was to evaluate the role of maternal nutritional habits during the period of gestation and of children subsequent diet in the etiology of pediatric brain tumors. All cases of incident nervous system tumors under age 18, diagnosed between 1984 and 1993 (n = 300) in Israel were identified. Two matched population controls per case were selected (n = 574). Personal interviews, using a semi-quantified three-step food frequency questionnaire, were performed. Univariate analysis showed that increased child consumption of vegetable fat [p trend 0.01; 95% confidence interval (CI) 1.1-3.2], carbohydrates (p trend 0.05; CI 1.0-5.9), and vitamin E (p trend 0.05; CI 1.0-3.3), were significantly associated with brain tumor risk. No associations were found with nitrate, nitrite or vitamin C. A significant positive association with potassium consumption (p trend 0.01; CI 1.1-3.7) was noted during gestation. Results of multivariate analysis showed that the only persisting associations were with vegetable fat (OR = 1.36; CI 1.06-1.73) in the child diet and potassium intake during gestation (OR = 1.44; CI 1.04-1.99). In conclusion, nutritional associations with pediatric brain tumor etiology, remain unsubstantiated.

Body mass index in 17-year-old Israeli males of different ethnic backgrounds; national or ethnic-specific references?

OBJECTIVE: To evaluate whether a single national reference is appropriate for assessing prevalence of overweight in heterogeneous populations, or whether ethnic-specific references are needed. DESIGN: A population-based study of Israeli Jewish males who underwent routine physical and clinical examinations prior to army recruitment served as the basis for the development of two types of references for body mass index (BMI): a national reference (NR) and an ethnic-specific reference (ER). SUBJECTS: Consecutive cohorts of all 17-y-old Jewish male recruits (n=109, 570). MEASUREMENTS: Weight, height and blood pressure values were obtained. BMI was calculated, and the 85th percentile of BMI was used as a cut-off point for overweight, using both types of references. Prevalence of hypertension among recruits was used as a biomarker to support the reliability of the ER when discrepancy in classification between the two references was found. RESULTS: As compared to the NR, three ethnic groups had a BMI distribution shifted to the left (light sub-population) and five were shifted to the right (heavy sub-population). In the light sub-population, 7% of the inductees who were classified as having normal weight by the NR were considered overweight by the ER and had a hypertension rate similar to that of those defined as overweight by both references (3.1 per 1000). In the heavy sub-population the 4% of subjects who were overweight by NR and normal by ER had hypertension rates similar to those defined as normal weight by both references (2.7/1000), and significantly lower than that of those classified as overweight by both references (10.8/1000). CONCLUSION: In heterogeneous populations, ethnic references should be used to evaluate prevalence of overweight, rather than one national reference. International Journal of Obesity (2000)24, 88-92