Occult hepatitis B virus infection: diagnosis, implications and management?

Occult hepatitis B virus (HBV) infection is generally defined as the detection of HBV-DNA in the serum or liver tissue of patients who test negative for hepatitis B surface antigen. In most cases, occult HBV infection is related to low level HBV infection with subdetectable levels of HBsAg and not infection with HBV variants that cannot express S proteins or produce S proteins with aberrant epitopes that are not detected by conventional serological assays. Prevalence of occult HBV infection is related to the overall prevalence of HBV infection in that country, being more common in persons with prior exposure to HBV. Occult HBV infection has been found in a substantial proportion of patients with cirrhosis and hepatocellular carcinoma but other causes of liver disease are frequently present. Future studies should focus on delineating the pathogenic role of occult HBV infection and the basis for failure to detect circulating hepatitis B surface antigen.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75344/1/j.1440-1746.2004.03657.x.pd

Contribution of Cystine-Glutamate Antiporters to the Psychotomimetic Effects of Phencyclidine

Altered glutamate signaling contributes to a myriad of neural disorders, including schizophrenia. While synaptic levels are intensely studied, nonvesicular release mechanisms, including cystine–glutamate exchange, maintain high steady-state glutamate levels in the extrasynaptic space. The existence of extrasynaptic receptors, including metabotropic group II glutamate receptors (mGluR), pose nonvesicular release mechanisms as unrecognized targets capable of contributing to pathological glutamate signaling. We tested the hypothesis that activation of cystine–glutamate antiporters using the cysteine prodrug N-acetylcysteine would blunt psychotomimetic effects in the rodent phencyclidine (PCP) model of schizophrenia. First, we demonstrate that PCP elevates extracellular glutamate in the prefrontal cortex, an effect that is blocked by N-acetylcysteine pretreatment. To determine the relevance of the above finding, we assessed social interaction and found that N-acetylcysteine reverses social withdrawal produced by repeated PCP. In a separate paradigm, acute PCP resulted in working memory deficits assessed using a discrete trial t-maze task, and this effect was also reversed by N-acetylcysteine pretreatment. The capacity of N-acetylcysteine to restore working memory was blocked by infusion of the cystine–glutamate antiporter inhibitor (S)-4-carboxyphenylglycine into the prefrontal cortex or systemic administration of the group II mGluR antagonist LY341495 indicating that the effects of N-acetylcysteine requires cystine–glutamate exchange and group II mGluR activation. Finally, protein levels from postmortem tissue obtained from schizophrenic patients revealed significant changes in the level of xCT, the active subunit for cystine–glutamate exchange, in the dorsolateral prefrontal cortex. These data advance cystine–glutamate antiporters as novel targets capable of reversing the psychotomimetic effects of PCP

Barriers to following dietary recommendations in Type 2 diabetes

Aims  To evaluate barriers to following dietary recommendations in patients with Type 2 diabetes. Methods  We conducted focus groups and surveys in urban and suburban VA and academic medical centres. For the written survey, a self-administered questionnaire was mailed to a random sample of 446 patients with diabetes. For the focus groups, six groups of patients with diabetes (three urban, three suburban) were conducted, with 6–12 participants in each group. The focus groups explored barriers across various types of diabetes self-management; we extracted all comments relevant to barriers that limited patients’ ability to follow a recommended diet. Results  The written survey measured the burden of diabetes therapies (on a seven-point rating scale). Moderate diet was seen as a greater burden than oral agents (median 1 vs. 0, P  = 0.001), but less of a burden than insulin (median 1 vs. 4, P  < 0.001). A strict diet aimed at weight loss was rated as being similarly burdensome to insulin (median 4 vs. 4, P  = NS). Despite this, self-reported adherence was much higher for both pills and insulin than it was for a moderate diet. In the focus groups, the most commonly identified barrier was the cost (14/14 reviews), followed by small portion sizes (13/14 reviews), support and family issues (13/14 reviews), and quality of life and lifestyle issues (12/14 reviews). Patients in the urban site, who were predominantly African-American, noted greater difficulties communicating with their provider about diet and social circumstances, and also that the rigid schedule of a diabetes diet was problematic. Conclusions  Barriers to adherence to dietary therapies are numerous, but some, such as cost, and in the urban setting, communication with providers, are potentially remediable. Interventions aimed at improving patients’ ability to modify their diet need to specifically address these areas. Furthermore, treatment guidelines need to consider patients’ preferences and barriers when setting goals for treatment. Diabet. Med. (2004)Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73213/1/j.1464-5491.2004.01342.x.pd

Boolean Dynamics with Random Couplings

This paper reviews a class of generic dissipative dynamical systems called N-K models. In these models, the dynamics of N elements, defined as Boolean variables, develop step by step, clocked by a discrete time variable. Each of the N Boolean elements at a given time is given a value which depends upon K elements in the previous time step. We review the work of many authors on the behavior of the models, looking particularly at the structure and lengths of their cycles, the sizes of their basins of attraction, and the flow of information through the systems. In the limit of infinite N, there is a phase transition between a chaotic and an ordered phase, with a critical phase in between. We argue that the behavior of this system depends significantly on the topology of the network connections. If the elements are placed upon a lattice with dimension d, the system shows correlations related to the standard percolation or directed percolation phase transition on such a lattice. On the other hand, a very different behavior is seen in the Kauffman net in which all spins are equally likely to be coupled to a given spin. In this situation, coupling loops are mostly suppressed, and the behavior of the system is much more like that of a mean field theory. We also describe possible applications of the models to, for example, genetic networks, cell differentiation, evolution, democracy in social systems and neural networks.Comment: 69 pages, 16 figures, Submitted to Springer Applied Mathematical Sciences Serie

Adrenal Venous Sampling: Where Is the Aldosterone Disappearing to?

Adrenal venous sampling (AVS) is generally considered to be the gold standard in distinguishing unilateral and bilateral aldosterone hypersecretion in primary hyperaldosteronism. However, during AVS, we noticed a considerable variability in aldosterone concentrations among samples thought to have come from the right adrenal glands. Some aldosterone concentrations in these samples were even lower than in samples from the inferior vena cava. We hypothesized that the samples with low aldosterone levels were unintentionally taken not from the right adrenal gland, but from hepatic veins. Therefore, we sought to analyze the impact of unintentional cannulation of hepatic veins on AVS. Thirty consecutive patients referred for AVS were enrolled. Hepatic vein sampling was implemented in our standardized AVS protocol. The data were collected and analyzed prospectively. AVS was successful in 27 patients (90%), and hepatic vein cannulation was successful in all procedures performed. Cortisol concentrations were not significantly different between the hepatic vein and inferior vena cava samples, but aldosterone concentrations from hepatic venous blood (median, 17 pmol/l; range, 40–860 pmol/l) were markedly lower than in samples from the inferior vena cava (median, 860 pmol/l; range, 460–4510 pmol/l). The observed difference was statistically significant (P < 0.001). Aldosterone concentrations in the hepatic veins are significantly lower than in venous blood taken from the inferior vena cava. This finding is important for AVS because hepatic veins can easily be mistaken for adrenal veins as a result of their close anatomic proximity

Non-pharmacological care for patients with generalized osteoarthritis: design of a randomized clinical trial

<p>Abstract</p> <p>Background</p> <p>Non-pharmacological treatment (NPT) is a useful treatment option in the management of hip or knee osteoarthritis. To our knowledge however, no studies have investigated the effect of NPT in patients with generalized osteoarthritis (GOA). The primary aim of this study is to compare the effectiveness of two currently existing health care programs with different intensity and mode of delivery on daily functioning in patients with GOA. The secondary objective is to compare the cost-effectiveness of both interventions.</p> <p>Methods/Design</p> <p>In this randomized, single blind, clinical trial with active controls, we aim to include 170 patients with GOA. The experimental intervention consist of six self-management group sessions provided by a multi-disciplinary team (occupational therapist, physiotherapist, dietician and specialized nurse). The active control group consists of two group sessions and four sessions by telephone, provided by a specialized nurse and physiotherapist. Both therapies last six weeks. Main study outcome is daily functioning during the first year after the treatment, assessed on the Health Assessment Questionnaire. Secondary outcomes are health related quality of life, specific complaints, fatigue, and costs. Illness cognitions, global perceived effect and self-efficacy, will also be assessed for a responder analysis. Outcome assessments are performed directly after the intervention, after 26 weeks and after 52 weeks.</p> <p>Discussion</p> <p>This article describes the design of a randomized, single blind, clinical trial with a one year follow up to compare the costs and effectiveness of two non-pharmacological interventions with different modes of delivery for patients with GOA.</p> <p>Trial registration</p> <p>Dutch Trial Register NTR2137</p

Biofilms of non-Candida albicans Candida species : quantification, structure and matrix composition

Most cases of candidiasis have been attributed to C. albicans, but recently, non- Candida albicans Candida (NCAC) species have been identified as common pathogens. The ability of Candida species to form biofilms has important clinical repercussions due to their increased resistance to antifungal therapy and the ability of yeast cells within the biofilms to withstand host immune defenses. Given this clinical importance of the biofilm growth form, the aim of this study was to characterize biofilms produced by three NCAC species, namely C. parapsilosis, C. tropicalis and C. glabrata. The biofilm forming ability of clinical isolates of C. parapsilosis, C. tropicalis and C. glabrata recovered from different sources, was evaluated by crystal violet staining. The structure and morphological characteristics of the biofilms were also assessed by scanning electron microscopy and the biofilm matrix composition analyzed for protein and carbohydrate content. All NCAC species were able to form biofilms although these were less extensive for C. glabrata compared with C. parapsilosis and C. tropicalis. It was evident that C. parapsilosis biofilm production was highly strain dependent, a feature not evident with C. glabrata and C. tropicalis. Scanning electron microscopy revealed structural differences for biofilms with respect to cell morphology and spatial arrangement. Candida parapsilosis biofilm matrices had large amounts of carbohydrate with less protein. Conversely, matrices extracted from C. tropicalis biofilms had low amounts of carbohydrate and protein. Interestingly, C. glabrata biofilm matrix was high in both protein and carbohydrate content. The present work demonstrates that biofilm forming ability, structure and matrix composition are highly species dependent with additional strain variability occurring with C. parapsilosis.Fundação para a Ciência e a Tecnologia (FCT) - SFRH/BD/28341/2006, PDTC/BIO/61112/200

Length of patient-physician relationship and patients' satisfaction and preventive service use in the rural south: a cross-sectional telephone study

BACKGROUND: Physicians and patients highly value continuity in health care. Continuity can be measured in several ways but few studies have examined the specific association between the duration of the patient-doctor relationship and patient outcomes. This study (1) examines characteristics of rural adults who have had longer relationships with their physicians and (2) assesses if the length of relationship is associated with patients' satisfaction and likelihood of receiving recommended preventive services. METHODS: Cross-sectional telephone survey of health care access indicators of adults in selected non-metropolitan counties of eight U.S. predominantly southern states. Analyses were restricted to adults who see a particular physician for their care and weighted for demographics and county sampling probabilities. RESULTS: Of 3176 eligible respondents, 10.8% saw the same physician for the past 12 months, 11.8% for the previous 13–24 months, 20.7% for the past 25–60 months and 56.7% for more than 60 months. Compared to persons with one year or less continuity with the same physician, respondents with over five years continuity more often were Caucasian, insured, a high school graduate, and more often reported good to excellent health and an income above $25,000. Compared to those with more than five years of continuity, participants with either less than one year or one to two years of continuity with the same physician were more often not satisfied with their overall health care (OR 2.34; OR 1.78), participants with less than one year continuity were more often not satisfied with the concern shown them by their physician (O.R. 1.90) and having their health questions answered, and those with one to two years continuity were more often not satisfied with the quality of their care (OR 2.37). No significant associations were found between physician continuity and use rates of any of the queried preventive services. CONCLUSION: Over half of this rural population has seen the same physician for more than five years. Longer continuity of care was associated with greater patient satisfaction and confidence in one's physician, but not with a greater likelihood of receiving recommended preventive services

Evidence for the h_b(1P) meson in the decay Upsilon(3S) --> pi0 h_b(1P)

Using a sample of 122 million Upsilon(3S) events recorded with the BaBar detector at the PEP-II asymmetric-energy e+e- collider at SLAC, we search for the $h_b(1P)$ spin-singlet partner of the P-wave chi_{bJ}(1P) states in the sequential decay Upsilon(3S) --> pi0 h_b(1P), h_b(1P) --> gamma eta_b(1S). We observe an excess of events above background in the distribution of the recoil mass against the pi0 at mass 9902 +/- 4(stat.) +/- 2(syst.) MeV/c^2. The width of the observed signal is consistent with experimental resolution, and its significance is 3.1sigma, including systematic uncertainties. We obtain the value (4.3 +/- 1.1(stat.) +/- 0.9(syst.)) x 10^{-4} for the product branching fraction BF(Upsilon(3S)-->pi0 h_b) x BF(h_b-->gamma eta_b).Comment: 8 pages, 4 postscript figures, submitted to Phys. Rev. D (Rapid Communications