An examination of ALDH2 genotypes, alcohol metabolism and the flushing response in Native Americans

OBJECTIVE: The study was designed to examine the relationship between aldehyde dehydrogenase (ALDH2) genotype and the flushing response in a population of Native Americans. METHOD: Objective measures of the flushing response were obtained by monitoring skin temperature, heart rate, blood pressure, as well as blood alcohol concentrations, in flushing and nonflushing Native Americans (n = 105) as well as in Oriental (n = 15) and white (n = 15) control subjects following a dose of alcohol (0.2 or 0.4 gm/kg). ALDH genotypes were determined via polymerase chain reaction followed by hybridization to 32P or biotin-labeled allele-specific oligonucleotide probes. RESULTS: There were no ALDH2 mutations detectable in Native Americans reporting the flushing response, nor any objective evidence of an Oriental-like response to alcohol. The rate of alcohol metabolism was shown to be the same among whites, Native flushers and Native nonflushers. CONCLUSIONS: The results demonstrate that the flushing reaction experienced by Native Americans appears to be milder and less unpleasant than the "Oriental" flushing reaction, with little effect on drinking frequency and amount. In addition, the flushing is not mediated by the ALDH2 mutation or elevated blood acetaldehyde. A critical analysis of the discrepancies in the literature regarding alcohol metabolism in Native Americans is provided.     

Extended lymph node dissection for gastric cancer: who may benefit? Final results of the randomized Dutch gastric cancer group trial.

PURPOSE: The extent of lymph node dissection appropriate for gastric cancer is still under debate. We have conducted a randomized trial to compare the results of a limited (D1) and extended (D2) lymph node dissection in terms of morbidity, mortality, long-term survival and cumulative risk of relapse. We have reviewed the results of our trial after follow-up of more than 10 years. PATIENTS AND METHODS: Between August 1989 and June 1993, 1,078 patients with gastric adenocarcinoma were randomly assigned to undergo a D1 or D2 lymph node dissection. Data were collected prospectively, and patients were followed for more than 10 years. RESULTS: A total of 711 patients (380 in the D1 group and 331 in the D2 group) were treated with curative intent. Morbidity (25% v 43%; P <.001) and mortality (4% v 10%; P =.004) were significantly higher in the D2 dissection group. After 11 years there is no overall difference in survival (30% v 35%; P =.53). Of all subgroups analyzed, only patients with N2 disease may benefit of a D2 dissection. The relative risk ratio for morbidity and mortality is significantly higher than one for D2 dissections, splenectomy, pancreatectomy, and age older than 70 years. CONCLUSION: Overall, extended lymph node dissection as defined in this study generated no long-term survival benefit. The associated higher postoperative mortality offsets its long-term effect in survival. For patients with N2 disease an extended lymph node dissection may offer cure, but it remains difficult to identify patients who have N2 disease. Morbidity and mortality are greatly influenced by the extent of lymph node dissection, pancreatectomy, splenectomy and age. Extended lymph node dissections may be of benefit if morbidity and mortality can be avoided.     

Culture and Palliative Care: Preferences,Communication, Meaning,and Mutual Decision Making

Palliative care is gaining acceptance across the world. However, even when palliative care resources exist, both the delivery and distribution of services too often are neither equitably nor acceptably provided to diverse population groups. The goal of this study was to illustrate tensions in the delivery of palliative care for diverse patient populations to help clinicians to improve care for all. We begin by defining and differentiating culture, race, and ethnicity, so that these terms—often used interchangeably—are not conflated and are more effectively used in caring for diverse populations. We then present examples from an integrative literature review of recent research on culture and palliative care to illustrate both how and why varied responses to pain and suffering occur in different patterns, focusing on four areas of palliative care: the formation of care preferences, communication patterns, different meanings of suffering, and decision-making processes about care. For each area, we provide international and multiethnic examples of variations that emphasize the need for personalization of care and the avoidance of stereotyping beliefs and practices without considering individual circumstances and life histories. We conclude with recommendations for improving palliative care research and practice with cultural perspectives, emphasizing the need to work in partnerships with patients, their family members, and communities to identify and negotiate culturally meaningful care, promote quality of life, and ensure the highest quality palliative care for all, both domestically and internationally.     

Association of pulse pressure,pulse pressure index,and ambulatory arterial stiffness index with kidney function in a cross‐sectional pediatric chronic kidney disease cohort from the CKiD study

The morbidity and mortality of adult and pediatric chronic kidney disease (CKD) and end‐stage renal disease (ESRD) populations are mainly driven by cardiovascular disease (CVD). Improving CVD outcomes focuses on risk assessment of factors including diastolic blood pressure (DBP), systolic blood pressure (SBP), left ventricular mass index (LVMI), pulse pressure (PP), and pulse pressure index (PPi), which is calculated as PP/SBP. These markers are also proven predictors of CKD progression; however, their role in children has not been established. This study aims to evaluate the relationship between PP, PPi, ambulatory arterial stiffness index (AASI), and proteinuria with kidney function in pediatric CKD patients; it is a retrospective analysis of 620 patients (1‐16 years) from the NIDDK Chronic Kidney Disease in Children (CKiD) registry. The authors analyzed data for three separate cohorts: an overall CKD as well as immunological versus non‐immunological cause for CKD groups. An inverse relationship was found between SBP, DBP, and PP with iGFR and LVMI in the overall CKD group. Our immunological CKD subgroup showed significantly higher serum creatinine, SBP, DBP, and PP values with significantly lower serum albumin levels compared to the non‐immunological group. There were no significant differences with iohexol‐based glomerular filtration rate (iGFR), LVMI, PPi, or high‐sensitivity C‐reactive protein (hs‐CRP) between the two groups. A subgroup analysis demonstrated that SBP, DBP, and PP all correlated significantly with LVMI in the immunological CKD patients but not the non‐immunological subgroup. Additionally, AASI data in the overall CKD population were significantly correlated with PP, PPi, and DBP. This study is one of the first to correlate noninvasive measurements of vascular compliance including PP, PPi, and AASI with iGFR and LVMI in a pediatric CKD cohort. Improving our understanding of surrogate markers for early CVD is integral to improving the care of pediatric CKD population as these patients have yet to develop the hard end points of ESRD, heart failure, myocardial infarction, or stroke.     

Nocturnal home hemodialysis in children: Advantages,implementation, and barriers

Chronic kidney disease and end-stage renal disease (ESRD) in children are major health concerns worldwide with increasing incidence and prevalence. Renal replacement therapies and kidney transplants have remarkably improved the management of patients with ESRD in both adult and pediatric populations. Kidney transplant has the best patient outcomes, but many a time it has a considerable waiting period. In the meantime, the majority of patients with pediatric ESRD are dependent on dialysis. The conventionally utilized hemodialysis regimen is the three times weekly, in-center hemodialysis. Many studies have demonstrated the unfavorable long-term morbidity associated with the conventional regimen. Intensified dialysis programs, which include extended nocturnal hemodialysis or short daily hemodialysis, are being increasingly advocated over the past two decades. In addition to having much better clinical outcomes as compared with the conventional regimen, the flexibility to provide dialysis at home serves as a great incentive. PubMed/Medline, Embase and Cochrane databases for literature on nocturnal home hemodialysis in children with ESRD were extensively searched. Contrary to the noticeable literature available on adult home hemodialysis, a small number of studies exist in the pediatric population. In this review, the benefits, implementation and associated barriers of nocturnal home hemodialysis in children were addressed.     

AIDS-Related Knowledge and High-Risk Behaviors of Pregnant,Substance-Dependent Women

The authors investigated AIDS-related knowledge, high-risk behaviors, and relationships between AIDS-related knowledge, high-risk behaviors, and sociodemographic characteristics of 41 pregnant women entering treatment who were dependent on cocaine or opiates. At entry, patients completed self-report questionnaires on AIDS-related knowledge and sexual and drug use practices. There was a high rate of understanding of risk associated with drug use and perinatal transmission of HIV. Knowledge of high-risk sexual behavior varied, and knowledge of the medical consequences of HIV was modest. Engagement in several high-risk behaviors was identified: lack of condom use, intravenous drug use, sharing of needles, sex with an injecting drug user, and exchanging sex for money or drugs. AIDS-related knowledge and engagement in high-risk behaviors were not significantly correlated. Authors discussed implications of these findings for developing effective HIV prevention strategies in this population. (American Journal on Addictions 1996; 5:292–300)     

The role of cyclo-oxygenase 1 and 2 activity in prostaglandin E(2) secretion by cultured human adult microglia: implications for Alzheimer's disease

Microglial cyclo-oxygenase (COX) expression is considered to be important in the pathogenesis of Alzheimer's disease (AD) and, therefore, constitutes a key target for therapeutic intervention. We investigated the influence of AD plaque associated factors on COX-1 and COX-2 expression and activity in adult human microglial cells in vitro. COX-2 immunoreactivity and mRNA were induced by lipopolysaccharide (LPS), not by AD plaque associated cytokines interleukin (IL)-1alpha, IL-1beta, IL-6, tumor necrosis factor (TNF)-alpha, or amyloid (A)beta(1-42). To assess functional COX activity, the release of PGE(2) into the culture medium was determined. LPS and also arachidonic acid (AA) dose-dependently stimulated PGE(2) release. The effects of AA are independent from induction of COX mRNA expression, or of de novo protein synthesis. No effects of either plaque-associated cytokines or Abeta(1-42) on PGE(2) secretion were seen, even when cells were co-stimulated with AA, to provide enough substrate. COX isotype selective inhibitors were used to discern relative contributions of COX-1 and COX-2 activities to microglial PGE(2) secretion. COX-2 and in part COX-1-selective inhibitors inhibited LPS-induced PGE(2) secretion, whereas the AA-induced PGE(2) secretion was reduced by COX-1-selective inhibitors only. Apparently, adult human microglia in vitro (1) constitutively express COX-1, and (2) do not express COX-2 upon exposure to either Abeta or plaque associated cytokines. In the light of microglial COX activity as a potential therapeutical target in AD, the data presented in this study suggest that classical NSAIDs, rather than selective COX-2 inhibitors, are more potent in reducing microglial prostaglandin secretion.     

NPY neurons express somatostatin receptor subtype 1 in the arcuate nucleus

The regulation of growth hormone (GH) secretion involves hypothalamic somatostatin and its specific receptors (sst1-sst5). sst1 is highly expressed in the arcuate nucleus (AN), and several data suggest that sst1 receptors are preferentially involved in the somatotropic hypothalamic network. Neuropeptide Y (NPY)-containing neurons function as direct transducers for GH feedback. Interestingly, there is an overlap in the distribution of NPY and sst1 containing cells in the AN. To determine whether these NPY cells are target for somatostatin we used a double label in situ hybridization histochemistry. Image analysis revealed that approximately 7% of NPY-hybridizing neurons coexpressed sst1 mRNA. These results further support the evidence for the direct interactions between the somatotropic axis and the neuroendocrine regulatory loops of energy homeostasis.