An MTP inhibitor that normalizes atherogenic lipoprotein levels in WHHL rabbits.

Patients with abetalipoproteinemia, a disease caused by defects in the microsomal triglyceride transfer protein (MTP), do not produce apolipoprotein B-containing lipoproteins. It was hypothesized that small molecule inhibitors of MTP would prevent the assembly and secretion of these atherogenic lipoproteins. To test this hypothesis, two compounds identified in a high-throughput screen for MTP inhibitors were used to direct the synthesis of a highly potent MTP inhibitor. This molecule (compound 9) inhibited the production of lipoprotein particles in rodent models and normalized plasma lipoprotein levels in Watanabe-heritable hyperlipidemic (WHHL) rabbits, which are a model for human homozygous familial hypercholesterolemia. These results suggest that compound 9, or derivatives thereof, has potential applications for the therapeutic lowering of atherogenic lipoprotein levels in humans.

Tube Feeding among Elder in Long-Term Care Facilities: A Systematic Review and Meta-Analysis.

OBJECTIVE: The use of tube feeding for elderly patients with poor nutritional intake is a ubiquitous method of feeding. This systematic review and meta-analysis were carried out to compare nutritional benefits of enteral feeding versus oral feeding in long-term care facilities. SETTING: Databases including the Cochrane Library, ProQuest, PubMed, EMBASE, EBSCO, Web of Science and Google Scholar through April 2014 using keywords including enteral feeding, tube feeding or oral feeding combined with long term care facilities or nursing home. PARTICIPANTS: Eight articles, with 841 participants were included in meta-analysis and 13 articles were included in systematic review. The elderly had to live in long-term care institutions and could not be on any mechanically assisted ventilation systems or be in any type of post-operative status. MEASUREMENTS: The three investigators extracted and appraised data using the same study design, baseline characteristics, and outcomes, independently. RESULTS: Following a systematic review, 13 articles out of 8218 original research articles were selected for this analysis. Meta-analysis of tube-fed patients found lower levels of hemoglobin (Weighted Mean Difference (WMD -0.21g/dl; 95% CI -0.42 to -0.01; p=0.04) and creatinine (WMD -0.08g/dl; 95% CI -0.17 to 0.00, p=0.05). Moreover, the results showed that there were no benefits regarding body mass index (BMI), albumin, dietary intake of proteins, total calories and fat. CONCLUSIONS: The results show that tube feeding does not increase patients' nutrients absorption to improve nutritional status. Instead, these results indicate that oral feeding is better regarding some nutritional biochemical parameters.

Amino acid concentrations in cerebrospinal fluid in children with acute lymphoblastic leukemia undergoing chemotherapy.

Cerebrospinal fluid (CSF) amino acid concentrations were measured in 45 children with acute lymphoblastic leukemia (ALL). Central nervous system (CNS) disease was absent in 34 and present in 11 (Groups L and M, respectively) at diagnosis. Thirty-two otherwise healthy children with febrile convulsions were studied for comparison. Results from this study show that glutamine levels at Day 0 were significantly higher in patients than in controls. Patients in Group M had elevated glutamine levels compared to Group L. In comparison, at Day 14, concentrations of glutamine and asparagine decreased, while glutamic acid amounts increased significantly in Group L. Glutamine levels fell at Day 42 in Group M, which may have resulted from more intensive treatment. From this study we hypothesise that higher baseline glutamine levels are indicative of a greater risk for CNS leukemia. Large-scale prospective trials are required to confirm increased baseline CSF glutamine levels in ALL patients, to identify glutamine as a marker for CNS disease and to clarify underlying mechanisms regulating glutamine in ALL.

Dual effect of parity on breast cancer risk.

This study examined whether breast cancer risk increased for a short period after childbirth, but decreased after a longer period of time. Data from an international case-control study on breast cancer conducted in the 1960s were used to study the modifying effect of age at enrolment on the relationship between parity and breast cancer risk, comparing first uniparous with nulliparous women, and then biparous versus uniparous women. The statistical analysis was performed by modelling through multiple logistic regression, adjusting for study site, age at menarche, menopausal status and obesity index. Comparing uniparous with nulliparous women, an early age at birth seems to be protective for all periods after birth, whereas a late age at birth imparts a higher risk than nulliparity in the period immediately after birth, which declines with the passage of time. The modification effect by age was not apparent when biparous women with different age at second birth were compared with uniparous women. The results support the hypothesis that pregnancy oestrogens impart a transient increase of maternal breast cancer risk when the full-term pregnancy occurs late in a woman's life.

Arylcyclopropanecarboxyl guanidines as novel, potent, and selective inhibitors of the sodium hydrogen exchanger isoform-1.

A novel series of arylcyclopropanecarboxyl guanidines was synthesized and evaluated for activity against the sodium hydrogen exchanger isoform-1 (NHE-1). In biological assays conducted in an AP1 cell line expressing the human NHE-1 isoform, the starting cyclopropane 3a (IC(50) = 3.5 microM) shows inhibitory activity comparable to cariporide (IC(50) = 3.4 microM). Structure-activity relationships are used to optimize the affinity of various acyl guanidines for NHE-1 by screening the effect of substituents at both aryl and cyclopropyl rings. It is demonstrated that introduction of appropriate hydrophobic groups at the phenyl ring and a gem-dimethyl group at the cyclopropane ring enhances the NHE-1 inhibitory activity by up to 3 orders of magnitude (compound 7f, IC(50) = 0.003 microM). In addition, the gem-dimethyl series of analogues seem to display improved oral bioavailability and longer plasma half-life in rats. Furthermore, the lead benzodihydrofuranyl analogue 1 (BMS-284640) shows over 380-fold increased NHE-1 inhibitory activity as well as improved selectivity for NHE-1 over NHE-2 compared to cariporide.

A novel series of highly potent benzimidazole-based microsomal triglyceride transfer protein inhibitors.

A series of benzimidazole-based analogues of the potent MTP inhibitor BMS-201038 were discovered. Incorporation of an unsubstituted benzimidazole moiety in place of a piperidine group afforded potent inhibitors of MTP in vitro which were weakly active in vivo. Appropriate substitution on the benzimidazole ring, especially with small alkyl groups, led to dramatic increases in potency, both in a cellular assay of apoB secretion and especially in animal models of cholesterol lowering. The most potent in this series, 3g (BMS-212122), was significantly more potent than BMS-201038 in reducing plasma lipids (cholesterol, VLDL/LDL, TG) in both hamsters and cynomolgus monkeys.

Breast-feeding and maternal smoking in the etiology of Crohn's disease and ulcerative colitis in childhood.

Medical records concerning pediatric or adolescent patients first diagnosed with Crohn's disease or ulcerative colitis in two New York hospitals during a 5-year period (1986 to 1990) were abstracted, and information concerning sex, age, race, birthplace, sibship size, birth order, maternal age at birth, month of birth, duration of breast-feeding, and maternal smoking was recorded. Medical records of patients presenting at the respective pediatric gastroenterology departments immediately before or after the patients with inflammatory bowel disease were seen were also abstracted in order to generate a control series. Data concerning 68 patients with Crohn's disease, 39 patients with ulcerative colitis, and 202 control patients were analyzed through multiple logistic regression. Breast-feeding was negatively associated with Crohn's disease (P approximately 0.04) and ulcerative colitis (P approximately 0.07), with relative risk point estimates around 0.5 and with evidence of duration-dependent trends in both instances. There was no evidence of association of either disease with maternal age at birth, birth order, maternal smoking, or season of birth.

A case-control study of coronary heart disease in Athens, Greece.

A case-control study of coronary heart disease (CHD) was conducted in Athens, Greece. The case series consisted of 329 patients with electrocardiographically confirmed coronary infarct or a diagnostic coronary arteriogram, or both, who were admitted during a 16-month period to a major teaching hospital. Controls were 570 patients admitted to the same hospital just before or after the CHD cases for minor surgery; eye, ear, nose or minor urological problems; or chest problems definitely shown to be unrelated to CHD. All cases and controls were interviewed in the hospital wards and selected laboratory data were abstracted. The main analysis was done by modelling through multiple logistic regression, controlling for demographic variables as well as for the mutual confounding effects of the investigated risk factors. Obesity, hypertension, diabetes mellitus, elevated blood cholesterol and excessive coffee intake were significant (P < 0.02) independent risk factors with relative risk estimates in the 2- to 3-fold range. Non-significant positive associations were found with respect to tobacco smoking and modest coffee consumption, whereas non-significant negative associations were noted with respect to alcohol intake and regular exercise. A negative association with duration of afternoon siesta was of borderline statistical significance.

Use of modified diets in nursing homes.

Randomly chosen medical charts of 212 elderly subjects in 11 nursing homes were reviewed to determine which characteristics of the subjects were most closely associated with their diet prescriptions. The chart reviews indicated that 104 (49.0%) of the 212 subjects had some type of nutrient-modified diet prescription. Eight patients who were tube fed were not included in subsequent analyses. Sodium restriction was the most common modification (60 [29.4%] of the remaining 204 patients) and calorie-controlled diets were also common (52 [25.5%] of the patients). Of the 55 patients with hypertension, 31 (56.4%) had no sodium restriction. Only 10% of all low-sodium diets limited sodium to 2 g per day. Of the 38 patients with diabetes, 7 (18.4%) had no prescription for calorie control, and there was no indication that increased dietary fiber was encouraged for diabetic patients. Only one of the 121 subjects with a diagnosis of coronary heart disease or atherosclerosis had a prescription for a cholesterol-lowering diet. Characteristics of the subjects not specifically related to diet or diagnosis, such as age, sex, duration of stay, and level of care, had no significant relationship to diet prescription. These findings suggest that the practitioners in our sample were not convinced of the efficacy of modified diets to control disease for most nursing home residents.

Prevalence and characteristics of areca nut chewers among junior high school students in Changhua county, Taiwan.

Some studies indicate that betel quid and its ingredients chewing can produce cell mutagenicity and tumorigenicity. In Taiwan studies, betel quid chewing is the main cause of submucous fibrosis and oral cancer. Understanding the distribution and characteristics of the areca nut chewing population is one of the first steps in the effort to prevent these oral diseases. A stratified cluster random sample of 2442 junior high school students in Changhua county, Taiwan, were surveyed for the habit of areca nut chewing. Significantly more male students chewed areca nut than female students (9.2% vs 0.9%). The proportion of students who were chewing areca nuts increased with increasing (seventh to ninth) grades. Areca nut was used by junior high school students at a higher rate in village (rural) areas as compared to town (semi-urban) and city (urban) areas (6.4%, 3.7% and 3.0%, respectively). More students in the ordinary achievement classes were chewing areca nuts than those in the high achievement classes (8.4% vs 1.6%). Areca nut chewing students tended to have users in their families. Cigarette smoking and alcohol drinking were positively associated with areca nut chewing. More than half (53.6%) of the areca nut chewing students first experimented with this habit with a family member, most often the father or grandfather.

A cohort study on mortality and exposure to polychlorinated biphenyls.

In 1979, an outbreak of food poisoning ("Yu-Cheng") occurred in Central Taiwan, ROC, involving more than 2000 people. The event was caused by ingestion of rice oil contaminated with polychlorinated derivatives of biphenyls, dibenzofurans, and quaterphenyls. A retrospective cohort study on mortality was undertaken, and possible long-term health effects in the affected individuals were studied. The mortality experience of 1940 victims (929 males, 1011 females) between 1980 and 1991 was compared with the expected numbers, which were calculated from national and local mortality rates. By the end of 1991, 102 deaths were identified, thus producing a standardized mortality ratio (SMR) of overall mortality of 0.99 for males and 1.34 for females. Total cancer mortality was lower than in each comparison group. Mortality from liver diseases was elevated significantly (SMR = 3.22), especially during the first 3 y after the food-poisoning event (SMR = 10.76). Increased clinical severity of polychlorinated biphenyl intoxication was associated with increased mortality from all causes and from liver diseases. In summary, there was a positive association between mortality and intoxication dose, and severe polychlorinated biphenyl poisoning acutely affected mainly the liver. A continued follow-up of this cohort would be valuable in the study of long-term health effects of polychlorinated biphenyl poisoning.

Successful use of pooled sera to estimate HIV antibody seroprevalence and eliminate all positive cases.

Pooling specimens when testing them in large numbers can save scarce resources and several earlier reports have indicated this to be a feasible strategy. In an HIV antibody mass screening test carried out in our laboratory, we used Dorfman's two-stage model. We sought to establish the optimal number of specimens in a pool, and to achieve maximum efficiency while maintaining both sensitivity and specificity. Before testing for HIV antibody, five positive samples were placed in a set of 1012 sera in a double blind manner, one positive sample into a second set of 1012 sera and none in a third set. The positive rate was assumed to be 0.2% for each set of 1012 sera. As indicated by our model, 22 individual serum samples were placed into each of 46 pools which, when tested by particle agglutination assays, lead to the identification of all positive samples. We concluded that the prevalence rate can be estimated in the first stage, 95% confidence intervals were given, and the efficiency rate could be calculated for the identification of all infected specimens in a large number of samples showing low prevalence rates.

Assessment of postpartum time-dependent disease risk in case-control studies: an application for examining age-specific effect estimates.

Among subjects who have experienced a biological event, such as menarche, menopause or a delivery, one cannot distinguish the effects of time since the event from age at the event due to the linear dependency among these time variables and age at study ('current age'). This is a well-known problem that also exists in the determination of the short- and long-term influence of childbirth on subsequent disease risk, since one must take into account in the analysis both current age and age at delivery. We describe an approach to assess in case-control studies the effect of a full-term pregnancy on time-dependent disease risk by including nulliparous women in the analysis and considering current age as a modifier of the effect of age at delivery. One then uses current age-specific odds ratio estimates that compare uniparous to nulliparous women to examine whether the relative rate of disease varies over time after a delivery. Analytic options include stratified analysis and modelling with interaction terms for unconditional or conditional logistic regression analysis. As an example, we have applied this analysis to a large case-control study that utilized record linkage between the Cancer Registry and the Fertility Registry of Sweden and that documented a transient increase in breast cancer risk after a childbirth, followed by a long-term reduction in this risk.

An increased risk of hepatitis B virus infection from tattooing in Taiwan.

From among 2,375 young men, examined by doctors, 111 tattooed subjects were found. Twenty one subjects reported engaging in promiscuous sexual behavior or being intravenous drug abusers, and so were excluded. The other 90 were evaluated. To make up the control group, 180 non-tattooed subjects from the remaining 2,264, who neither engaged in promiscuous sexual activity nor were intravenous drug abusers, were matched from household registry reports by age, sex, education, occupation, and geographic origin from Mainland China, where their parents were born. IgG antibody of hepatitis A (anti-HAV) and markers of hepatitis B were tested in serum with radioimmunoassay. In the prevalence rate of hepatitis A and carrier rate of HBsAg there were no differences between the tattooed and the non-tattooed groups. However, the prevalence odds ratio of hepatitis B virus (HBV) infection for the tattooed group was 8.1 (95% CI 1.9-34.8) as compared to the non-tattooed groups. Moreover, there was a trend correlation when the prevalence rates of hepatitis B were compared for the group with multiple sites of tattoos, for the group with one site of tattoos, and for the non-tattooed group (p = 0.002). These findings suggested an association between HBV infection and tattooing. Tattoo exposure, with improper or no sterilization of the needle, seems to appear to increase the risk of HBV infection in the already high risk endemic area in question.

Hydroxylation of 14-C-niflumic acid by phenobarbital-induced rat liver microsomes.

Hydroxylation of niflumic acid to 4'-hydroxyniflumic acid and 5-hydroxyniflumic acid by rat liver microsomes from untreated animals or phenobarbital-pretreated animals has been demonstrated. Pretreatment of rats with phenobarbital (50 mg/kg) increased the 4'-hydroxylase activity 53%, whreas the 5-hydroxylase activity was increased 205%. Niflumic acid inhibited of 4'- or 5-hydroxylase was observed with SKF 525-A. WIN 13099 inhibited both hydroxylases noncompetitvely. With freshly prepared microsomes, acetone, at concentrations frozen and aged microsomes, maximum enhancement of 4'-hydroxylase was obtained at 5% acetone; little or no effect on 5-hydroxylase was observed at the same concentration. At 10% acetone, the 4'- and 5-hydroxylases were inhibited 33 and 73% respectively. The data indicate that at least two different enzyme systems are involved in the hydroxylation of niflumic acid by the microsomes of rat liver.

[An investigation on public awareness, attitude and behavior toward drinking water quality in Taiwan].

The objective of this study was to investigate the public awareness, attitude and behavior toward drinking water quality. The results showed that (1) Overall, 80.6% of those responding to the survey rated their local drinking water quality as above average or better. (2) Even though most people were happy with the present quality of their drinking water, 79.2% of the public characterized themselves as concerned about encountering substances in drinking water in their lifetime that could lead to bad health effect or death. (3) 73.8% of the survey respondents never examined the water facilities for their own use.

[Workplace risk factors associated with eye syndrome in office workers].

Four large sealed office buildings were investigated to determine the relationship between the prevalence of sick building syndrome and the indoor air quality. Questionnaires were distributed to all building occupants. Respondents suffered from upper airway, eye, lower airway and many less specific complaints. Multivariate logistic regression analyses were conducted to assess workplace risk factors associated with eye syndrome. Working with visual display terminals, glare, use of desk lamp, fabric-covered partitions, new carpet, too dim, too bright and lack of openable windows correlated significantly with the prevalence of eye syndrome.