Possible effect of secretor locus on plasma concentration of factor VIII and von Willebrand factor

A significant fraction (30%) of the genetically determined variance in plasma concentration of the von Willebrand factor antigen (vWf:Ag) has been shown to be related to ABH determinants. Individuals with blood group O, who have the highest amounts of blood group H substance, have the lowest concentration of vWf:Ag. The Lewis substances, Le(a) and Le(b), are biochemically closely related to the ABH substances as both can be produced from the same precursor substance. We studied the effect of the presence of the Lewis antigens on the plasma concentration of vWf:Ag and factor VIII antigen (VIII:Ag) in 323 individuals of different ABO groups from a series of twins and in 58 blood donors of blood group O. Among persons belonging to blood group O, those with the Le(a) antigen had a higher concentration of both vWf:Ag and VIII:Ag than individuals lacking Le(a). Le(a+b-) people are nonsecretors and Le(a-b+) people are secretors of ABH substance. Thus, the lowest concentration of vWf:Ag and VIII:Ag was found in group O secretors. The effect is most likely due to an effect of the secretor locus. This finding may be of importance for the detection of carriers of hemophilia A and for the diagnosis of type I von Willebrand disease.     

Identification of a germ-line pro-B cell subset that distinguishes the fetal/neonatal from the adult B cell development pathway

Studies presented here show that the expression of CD4, MHC class II (Ia,) and B220 cleanly resolves a major and a minor subset within the earliest pro-B cell population (germ-line pro-B) in adult bone marrow (BM). The major subset expresses intermediate B220 and low CD4 levels. The minor subset, which constitutes roughly 20% of the adult germ-line pro-B, expresses very low B220 levels and does not express CD4. Ia is clearly detectable at low levels on the major germ-line pro-B subset, both in wild-type adult mice and in gene-targeted mice (RAG2-/- and microMT), in which B cell development terminates before the pre-B cell stage. A small proportion of cells in the more mature pro-B cell subsets (Hardy Fractions B and C) also express Ia at this level. In contrast, Ia levels on the minor subset are barely above (or equal to) background. Surprisingly, the major germ-line pro-B cell subset found in adults is missing in fetal and neonatal animals. All of the germ-line pro-B in these immature animals express a phenotype (very low B220, no CD4, or Ia) similar to that of the minor pro-B cell subset in adult BM. Because B cell development in fetal/neonatal animals principally results in B-1 cells, these findings demonstrate that the B-1 development pathway does not include the major germ-line pro-B subset found in adult BM and hence identify a very early difference between the B-1 and -2 development pathways.     

Zinc chloride (smoke bomb) inhalation lung injury: clinical presentations, high-resolution CT findings, and pulmonary function test results

STUDY OBJECTIVES: Zinc chloride smoke inhalation injury (ZCSII) is uncommon and has been rarely described in previous studies. We hypothesized that structural changes of the lung might correlate with pulmonary function. To answer this question, we correlated findings from high-resolution CT (HRCT) scan and the results of pulmonary function tests (PFTs) in patients with ZCSII. DESIGN: Retrospective cohort study. SETTING: University hospital. PATIENTS: Twenty patients who had been hospitalized with ZCSII-related conditions. MEASUREMENTS: The study included HRCT scan scores (0 to 100), static and dynamic lung volumes, and diffusing capacity of the lung for carbon monoxide (D(LCO)). RESULTS: HRCT scans and PFTs were performed initially after injury (range, 3 to 21 days) in all patients and during the follow-up period (range, 27 to 66 days) in 10 patients. The predominant CT scan findings were patchy or diffuse ground-glass opacities with or without consolidation. The majority of patients showed a significant reduction of FVC, FEV1, total lung capacity, and D(LCO), but normal FEV1/FVC ratio values. Changes of functional parameters correlated well with HRCT scan scores. Substantial improvements in CT scan abnormalities and pulmonary function were observed at follow-up. CONCLUSIONS: The majority of our patients with ZCSII presented with a predominant parenchymal injury of the lung that was consistent with a restrictive type of functional impairment and a reduction in Dlco rather than with obstructive disease. Our results suggest that HRCT scanning and pulmonary function testing may reliably predict the severity of ZCSII.     

Cognitive Interviews of Vietnamese Americans on Healthy Eating and Physical Activity Health Educational Materials

The purpose of this study was to better understand if a health educational presentation using culturally adapted materials was understandable and culturally appropriate, and that the content was retained, in an older Vietnamese American population. This study used cognitive interviewing. A convenient sampling was used to recruit eight participants by staff of a community-based organization from its client base. This is the first study to document that family eating style poses a challenge for estimating food intake among Vietnamese Americans. Participants who ate in a family eating style were not able to recall or estimate the number of servings of protein and vegetables. Some older Vietnamese Americans used food for healing and self-adjusted portion sizes from dietary recommendations. Cognitive interviewing is a useful method to improve comprehension, retention, and cultural appropriateness of health educational materials. Further nutrition research concerning intake measurement in ethnic groups that practice a family eating style is warranted.     

Orexin/hypocretin role in reward: implications for opioid and other addictions

Addiction is a devastating disorder that affects 15.3 million people worldwide. While prevalent, few effective treatments exist. Orexin receptors have been proposed as a potential target for anti-craving medications. Orexins, also known as hypocretins, are neuropeptides produced in neurons of the lateral and dorsomedial hypothalamus and perifornical area, which project widely throughout the brain. The absence of orexins in rodents and humans leads to narcolepsy. However, orexins also have an established role in reward seeking. This review will discuss some of the original studies describing the roles of the orexins in reward seeking as well as specific works that were presented at the 2013 International Narcotics Research Conference. Orexin signalling can promote drug-induced plasticity of glutamatergic synapses onto dopamine neurons of the ventral tegmental area (VTA), a brain region implicated in motivated behaviour. Additional evidence suggests that orexin signalling can also promote drug seeking by initiating an endocannabinoid-mediated synaptic depression of GABAergic inputs to the VTA, and thereby disinhibiting dopaminergic neurons. Orexin neurons co-express the inhibitory opioid peptide dynorphin. It has been proposed that orexin in the VTA may not mediate reward per se, but rather occludes the ‘anti-reward’ effects of dynorphin. Finally, orexin signalling in the prefrontal cortex and the central amygdala is implicated in reinstatement of reward seeking. This review will highlight recent work describing the role of orexin signalling in cellular processes underlying addiction-related behaviours and propose novel hypotheses for the mechanisms by which orexin signalling may impart drug seeking.

LINKED ARTICLES

This article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-2     

Antiviral therapy after non-surgical tumor ablation in patients with hepatocellular carcinoma associated with hepatitis C virus

BACKGROUND: Antiviral therapy for chronic hepatitis C virus (HCV) infection has led to a reduction in the incidence of hepatocellular carcinoma (HCC). The purpose of the present paper was to assess whether antiviral therapy might suppress tumor recurrence and influence overall survival in patients with HCV-related HCC who had complete ablation of nodules by non-surgical treatments. METHODS: Twenty patients with three or fewer nodules of HCV-related HCC who were treated with percutaneous tumor ablation and/or transcatheter arterial embolization received combined interferon (IFN; 3 or 5 million units of IFN alpha-2b thrice weekly) plus ribavirin (1000-1200 mg per day) therapy for 24-48 weeks after complete ablation of lesions. During the same period, an additional 40 age- and sex-matched control patients with similar characteristics of tumors (sizes, numbers and treatment modalities) and severity of liver disease were recruited from the HCC database. Both recurrence-free survival and actuarial survival were evaluated. RESULTS: Of the 20 patients, 16 completed therapy and 10 showed a sustained response with normalization of alanine aminotransferase and negative HCV-RNA at 6 months after therapy completion. Due to severe side-effects experienced by Child B patients, who mostly discontinued antiviral therapy, clinical outcome was analyzed in the Child A treated (n = 16) and control (n = 33) patients. There was no significant difference in the incidence of local recurrence in sustained responders compared with non-responders or control patients (P = 0.174, 0.1284, respectively); but the second recurrence-free interval in the sustained responders was significantly longer than that of non-responders and the control group (P = 0.0141, 0.0243, respectively). Survival in sustained responders was better than in non-responders and control patients (P = 0.0691, 0.0554, respectively). CONCLUSIONS: These results indicate that successful antiviral therapy after non-surgical tumor ablation for HCV-related HCC may lower tumor recurrence rate and prolong survival.     

Manifestations of systemic light chain deposition

In two patients with terminal renal failure, manifestations of disease developed in multiple organ systems. One had a previous diagnosis of multiple myeloma with kappa light chain proteinemia and proteinuria. The other had idiopathic lobular glomerulonephritis. Hepatic and neurologic abnormalities developed in both; in the latter gastrointestinal, cardiac and endocrine disease developed as well. Clinical and pathologic correlations suggest that the retention and tissue deposition of light chains produced the organ dysfunction, inasmuch as free kappa light chain determinants were demonstrated histologically in the clinically affected organs. The deposition in these patients may be an extreme example of a common but previously unrecognized form of plasma cell dyscrasia.     

Tuberculosis epidemiology in six provinces of Vietnam after the introduction of the DOTS strategy.

SETTING: Six provinces in Vietnam where the DOTS strategy was introduced in 1989. OBJECTIVE: To assess the impact of improved tuberculosis (TB) control on TB epidemiology in Vietnam. METHODS: Data from the surveillance system in the period 1990-2003 were analysed to assess trends of notification rates and the mean ages of notified cases. Data from repeated tuberculin surveys in the period 1986-2002 were estimated to assess the prevalence of TB infection, the annual risk of infection and its trend using various cut-off points in those with and without bacille Calmette-Guérin (BCG) scar. RESULTS: Age-standardised notification rates in the period 1996-2003 declined significantly, by 2.6% to 5.9% per year, in five provinces. However, in four provinces notification rates in the age group 15-24 years increased significantly, by 4.5% to 13.6% per year, during this period. The mean age of newly diagnosed patients with smear-positive TB increased up to 1995 but decreased thereafter. The annual risk of TB infection showed a significant annual decrease (4.9% per year) in one province in surveys performed between 1986 and 1997, and in two provinces (6.6% and 4.7%) in surveys conducted between 1993 and 2002. CONCLUSION: These data suggest limited impact to date of the DOTS strategy in Vietnam.