Bone disease in primary biliary cirrhosis: Lack of association with distal renal tubular acidosis

Background and Aims: Primary biliary cirrhosis (PBC) might be complicated by osteoporosis, whose etiology remains unknown but seems to be multifactorial. Prevalence rates of 30% to 60% for distal renal tubular acidosis (DRTA) have been reported in PBC patients, generally as incomplete DRTA. Although it is undisputed that a reduced bone mineral density (BMD) is the expected outcome among patients who have been suffering from longstanding chronic metabolic acidosis, it is unclear if incomplete DRTA is also associated with metabolic bone disease in PBC patients. The present study was undertaken to compare the BMD of PBC patients with and without DRTA.
Methods: The BMD of 23 PBC patients (11 with DRTA and 12 without), all with normal clearance of creatinine, was assessed by dual energy radiograph absorptiometry. The diagnosis of DRTA was made if the urine pH was above 5.4 in all samples after the oral acid overload, showing tubular inability to acidify urine in the presence of test-induced systemic metabolic acidosis.
Results: Densitometric signs of osteoporosis were found in 82% of DRTA cases and in 83% of patients without DRTA (difference not significant). There were no significant differences in BMD measurement, T and Z scores of patients with and without DRTA.
Conclusions: The present study could not support a correlation between the presence of DRTA and the bone loss observed in PBC patients.     

A study comparing biopharmaceutic characteristics of four once daily controlled release diltiazem preparations

Summary— In the present study we have compared the steady state biopharmaceutic characteristics of four diltiazem once daily controlled release capsules: Mono-Tildiem LP 300® (300 mg), Adizem® XL (300 mg)¹, Cardizem® (300 mg) and Dilacor® (240 mg). Sixteen healthy male volunteers (aged 22.9 ± 3.3 years, range 19–31 years) completed an open label, multiple oral dose, randomized, four-period crossover study without a washout period in between. The volunteers received each diltiazem formulation once daily for four days. Trough diltiazem and metabolites plasma concentrations were determined on days 3 and 4. The 24-h plasma concentration-time profiles were assessed after the dose on day 4 of each period. The following steady state pharmacokinetic parameters for diltiazem were calculated: the minimum plasma concentration (c_min), the maximum plasma concentration (c_max), the time to reach that concentration (t_max), the time interval during which the plasma concentration exceeds 50% of c_max (t₅₀), the area under the plasma concentration-time curve (AUC_72–96) and the peak-to-trough fluctuation (PTF). For the metabolites of diltiazem, N-mono-desmethyl-diltiazem (NDM) and desacetyldiltiazem (DAD), AUC_72–96 (AUC_NDM and AUC_DAD) and the ratio metabolite/parent compound were calculated. Steady state was achieved on day 3. Except one, all controlled release formulations have satisfactory controlled release properties allowing once daily administration. However, significant (P < 0.05) differences were found between the pharmacokinetic characteristics which do not allow exchange of the various formulations. Concentrations well below 50 ng·mL^-1 in the morning hours were observed for Dilacor® (240 mg) and Adizem® XL (300 mg), which could be a disadvantage of these formulations as it is well-known that ischaemic events occur at a higher rate during that part of the day. The plasma concentration profiles of NDM and DAD, the major circulating metabolites, parallel the plasma concentration profiles for the parent compound. From a clinical point of view, all treatments were well tolerated.     

Human leukocyte antigen matching and fetal loss: results of a 10 year prospective study

The role that maternal and fetal human leukocyte antigen (HLA) genes play in pregnancy is unknown, but it has been suggested that fetuses whose HLA alleles do not differ from maternal alleles (i.e. histocompatible fetuses) are more likely to be aborted than fetuses with HLA alleles that differ from maternal alleles (i.e. histoincompatible fetuses). To elucidate the role of HLA compatibility in pregnancy, we tested the hypothesis that couples who match for HLA alleles or haplotypes would have reduced fertility because only these couples could produce histocompatible fetuses. We conducted a 10 year prospective study of HLA matching and pregnancy outcome in 111 Hutterite couples, providing information on 251 pregnancies. A logistic regression analysis was performed to determine the effects of HLA matching at HLA regions and loci on pregnancy outcome (fetal loss versus delivery). Significantly increased fetal loss rates were observed among couples matching for the entire 16-locus haplotype (P = 0.002). Among the individual loci, loss rates were increased among couples matching for HLA-B (P = 0.019), HLA-C (P = 0.033) and the complement component, C4 (P = 0.043). We interpret these results as evidence that matching for the entire 16-locus haplotype and/or alleles at an HLA-B-linked locus confers significant risk for fetal loss.      

Pathways Linking Socioeconomic Status and Postpartum Smoking Relapse

Background

Low socioeconomic status (SES) exacerbates the high rate of smoking relapse in women following childbirth.

Purpose

This study examined multiple models of potential mechanisms linking SES and postpartum smoking relapse among women who quit smoking due to pregnancy.

Methods

Participants were 251 women enrolled in a randomized clinical trial of a new postpartum smoking relapse prevention intervention. Four models of the prepartum mechanisms linking SES and postpartum smoking relapse were evaluated using a latent variable modeling approach.

Results

Each of the hypothesized models were a good fit for the data. As hypothesized, SES indirectly influenced postpartum smoking relapse through increased prepartum negative affect/stress, reduced sense of agency, and increased craving for cigarettes. However, the model that included craving as the sole final pathway between SES and relapse demonstrated superior fit when compared with all other models.

Conclusions

Findings have implications for future interventions that aim to reduce postpartum relapse.     

Oxidative metabolism of the human eosinophil

We have compared the oxidative metabolism of human eosinophils (80%-90% purity) to that of neutrophils. Hexose monophosphate (HMP) shunt activity of eosinophils was higher than that of neutrophils under either resting or phagocytizing conditions. Eosinophil HMP shunt activity also was stimulated by phorbol myristate acetate, a membrane- active agent. Eosinophils showed a marked incorporation of 125I into trichloroacetic acid-insoluble material under resting conditions, which increased markedly during phagocytosis. Eosinophils likewise showed a greater reduction of nitroblue tetrazolium dye during phagocytosis than did neutrophils. Measurement of other parameters of oxidative metabolism indicated that eosinophils generated superoxide anion following phagocytosis and also elicited a burst of chemiluminescence similar to that observed during phagocytosis by neutrophils. Measurement of NADPH oxidase activity demonstrated that this enzyme was 3-6 times more active in fractions isolated from eosinophils than in corresponding fractions isolated from neutrophils; this was observed over a range of substrate concentrations. The eosinophil enzyme sedimented differently than the neutrophil enzyme with differential centrifugation; neither showed sedimentation characteristics of peroxidase. These data indicate that eosinophils possess a similar, although in some ways more potent, oxidative burst than neutrophils and are consistent with a role for NADPH oxidase in the initiation of that burst.     

Density and Proximity of Fast Food Restaurants and Body Mass Index Among African Americans

Objectives. The purpose of this study was to address current gaps in the literature by examining the associations of fast food restaurant (FFR) density around the home and FFR proximity to the home, respectively, with body mass index (BMI) among a large sample of African American adults from Houston, Texas.Methods. We used generalized linear models with generalized estimating equations to examine associations of FFR density at 0.5-, 1-, 2-, and 5-mile road network buffers around the home with BMI and associations of the closest FFR to the home with BMI. All models were adjusted for a range of individual-level covariates and neighborhood socioeconomic status. We additionally investigated the moderating effects of household income on these relations. Data were collected from December 2008 to July 2009.Results. FFR density was not associated with BMI in the main analyses. However, FFR density at 0.5, 1, and 2 miles was positively associated with BMI among participants with lower incomes (P ≤ .025). Closer FFR proximity was associated with higher BMI among all participants (P < .001), with stronger associations emerging among those of lower income (P < .013) relative to higher income (P < .014).Conclusions. Additional research with more diverse African American samples is needed, but results supported the potential for the fast food environment to affect BMI among African Americans, particularly among those of lower economic means.Obesity and its associated health conditions are a growing problem in the United States, with obesity prevalence having more than doubled since the 1960s.1 The health care cost of Americans’ growing waistlines is substantial and expected to top $860 billion by 2030.2 Racial/ethnic disparities in obesity are of particular concern for the nation’s health, with African Americans experiencing the highest prevalence of obesity relative to other racial/ethnic groups.1 The National Health and Nutrition Examination Survey from 2009 to 2010 indicated that 38.8% of African American men and 58.5% of African American women were obese compared with 36.2% of non-Hispanic White men and 32.2% of non-Hispanic White women.3 Racial/ethnic disparities have also been cited for body mass index (BMI), with the gap in BMI growth widening between African Americans and Whites in recent decades.4To better understand the factors associated with these trends, researchers and policymakers are paying increased attention to the retail food environment. The growing availability of low-cost, calorie-dense consumables from fast food restaurants (FFRs) is one of the factors implicated in the nation’s rising BMI.5–7 The availability of FFRs may be particularly relevant to the growing racial/ethnic disparities in BMI because several studies support a higher density of FFRs among predominately African American neighborhoods relative to predominately White neighborhoods.8–11 Moreover, at least 1 study reports stronger relations between fast food availability and fast food consumption among non-White versus White populations.12 Thus, African Americans may be more likely to consume fast food if it is available, and it may be more available to them because FFRs tend to be clustered in African American neighborhoods. Not surprisingly, greater fast food consumption is associated with higher BMI.13–15Several studies examined associations between the availability of fast food and BMI. Fast food availability was most commonly conceptualized as the density of FFRs near a person’s home, work, or school environment. Findings about the associations of FFR density with BMI and overweight or obesity status, however, were mixed,5,11 with some studies supporting positive associations,16–19 and others citing null results.14,20 Less commonly, studies conceptualized fast food availability as the proximity of the closest FFR to a person’s home. Studies taking this approach yielded mixed results regarding relations between FFR proximity and fast food consumption,21,22 as well as between FFR proximity and BMI or obesity status.11,23 Unfortunately, most of these studies focused predominately on White populations, and many had methodological limitations (e.g., self-reported BMI) that could have contributed to mixed results.5,11 We found only a single study that focused on an all-African American sample, which yielded null results regarding associations between FFR density and BMI.24 Although this study had several strengths, including a sample of more than 4500 African Americans and investigator-measured BMI, limitations included only 1 conceptualization of FFR availability (FFR density), and the use of Euclidean distances (“as the crow flies”) in density buffer calculation, which may be less realistic than buffers based on road networks (i.e., the only places along which FFRs can be found).5 In addition, we found no previous studies that examined whether associations between FFR availability and BMI were moderated by household income. Because reasons cited for frequent fast food consumption include both accessibility and affordability,6 it might be that relations of FFRs and BMI are stronger among those of lower economic means for whom fast food might be more affordable than other dining options. Therefore, additional research is needed to better understand the relations of fast food availability and BMI among African Americans.The purpose of this study was to address current gaps in the literature by examining the associations of FFR density around the home and FFR proximity to the home, respectively, with BMI among a large sample of African American adults from Houston, Texas. We additionally investigated the moderating effects of household income on these relations.