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Biomedical subjects

Peter Hauser

Publications and source records attributed to Peter Hauser.

At least 19 recordsLinked to original sources
PubMed2007

Interferon alpha therapy for hepatitis C: treatment completion and response rates among patients with substance use disorders.

BACKGROUND: Individuals with substance use disorders (SUDs) are at increased risk for hepatitis C viral infection (HCV), and few studies have explored their treatment responses empirically. The objective of this study was to assess interferon alpha therapy (IFN) completion and response rates among patients with HCV who had a history of comorbid SUDs. More data is needed to inform treatment strategies and guidelines for these patients. Using a medical record database, information was retrospectively collected on 307,437 veterans seen in the Veterans Integrated Service Network 20 (VISN 20) of the Veterans Healthcare Administration (VHA) between 1998 and 2003. For patients treated with any type of IFN (including regular or pegylated IFN) or combination therapy (IFN and ribavirin) who had a known HCV genotype, IFN completion and response rates were compared among patients with a history of SUD (SUD+ Group) and patients without a history of SUD (SUD- Group). RESULTS: Odds ratio analyses revealed that compared with the SUD- Group, the SUD+ Group was equally likely to complete IFN therapy if they had genotypes 2 and 3 (73.1% vs. 68.0%), and if they had genotypes 1 and 4 (39.5% vs. 39.9%). Within the sample of all patients who began IFN therapy, the SUD- and SUD+ groups were similarly likely to achieve an end of treatment response (genotypes 2 and 3, 52.8% vs. 54.3%; genotypes 1 and 4, 24.5% vs. 24.8%) and a sustained viral response (genotypes 2 and 3, 42.6% vs. 41.1%; genotypes 1 and 4: 16.0% vs. 22.3%). CONCLUSION: Individuals with and without a history of SUD responded to antiviral therapy for HCV at similar rates. Collectively, these findings suggest that patients who have co-morbid SUD and HCV diagnoses can successfully complete a course of antiviral therapy.

Antiviral Agents↗
PubMed2006

Observation of long-lived muonic hydrogen in the 2S state.

The kinetic energy distribution of ground state muonic hydrogen atoms mup(1S) is determined from time-of-flight spectra measured at 4, 16, and 64 hPa H2 room-temperature gas. A 0.9 keV component is discovered and attributed to radiationless deexcitation of long-lived mu p(2S) atoms in collisions with H2 molecules. The analysis reveals a relative population of about 1%, and a pressure-dependent lifetime (e.g., 30.4 +21.4/-9.7 ns at 64 hPa) of the long-lived mu p(2S) population, equivalent to a 2S quench rate in mu p(2S)+H2 collisions of 4.4 +2.1/-1.8 x 10(11) s(-1) at liquid-hydrogen density.

Journal Article↗
PubMed2006

Administration of pegylated interferon-alpha-2a or -2b does not induce sickness behavior in Lewis rats.

Repeated administration of interferon-alpha (IFN-alpha) or pegylated IFN-alpha to patients with chronic hepatitis C viral infection induces a flu-like syndrome as well as neuropsychiatric side effects, which are well recognized, but poorly understood. Although pegylation appears to have improved viral response rates in patients with hepatitis C, there are still neurotoxicities associated with pegylated IFN-alpha therapy, in particular, depression, which can compromise and sometime prevent successful completion of antiviral treatment. This study assessed the effects of two forms of pegylated IFN-alpha [peginterferon-alfa-2a (PEG-2a) and peginterferon-alfa-2b (PEG-2b)] in rats in order to develop an animal model of IFN-induced "depression" (often described as sickness behavior) that can be used to more comprehensively investigate the neurochemical mechanisms of IFN-induced depression. Sixty male and female Lewis rats were randomly assigned to one of six treatment groups: (1) saline (SAL)+SAL (2) SAL+PEG-2a; (3) SAL+PEG-2b; (4) selective serotonin reuptake inhibitor (SSRI)+SAL, (5) SSRI+PEG-2a; (6) SSRI+PEG-2b. Rats were pretreated with intraperitoneal (i.p.) saline (0.9%) or 7.5mg/kg/day fluoxetine for 1 week, followed by 3 weeks of concurrent i.p. administration of 650 microg/wk of PEG-2a or PEG-2b. Using locomotor activity, the forced swim test, and weight gain as behavioral measures of sickness behavior, our data showed that Lewis rats did not develop an IFN-induced "depressive syndrome." Western blot analyses of brain and liver tissue indicated that signal transducer and activator of transcripton (STAT1) was not phosphorylated following IFN-alpha administration, suggesting that the pegylated compounds may not have bound type I IFN receptors in the rat. Collectively, our data suggest that Lewis rats are likely not a useful model to study IFN-induced depression.

Animals↗
PubMed2006

Psychiatric management of the hepatitis C patient.

Patients with hepatitis C virus (HCV) infection have a higher prevalence of psychiatric illness compared with the general US population, and the prevalence of HCV infection in patients with severe mental illness ranges between 8% and 19%, which is four to nine times that of the general US population (1.8%). Given the association between HCV infection and psychiatric illness, gastroenterologists are on the front line of identifying comorbid psychiatric and substance use disorders and conducting a psychosocial pretreatment risk-benefit assessment for HCV infection. The use of interferon-alpha (IFN)-based therapies in combination with ribavirin (RBV) to eradicate HCV has been associated with frequent neuropsychiatric adverse effects (eg, affective, anxiety, cognitive, and psychotic symptoms) that compromise the management of both HCV patients with and those without a preexisting history of psychiatric illness. Consequently, gastroenterologists have been reluctant to engage patients with HCV and comorbid psychiatric illness in antiviral treatment due to concerns about exacerbating or precipitating neuropsychiatric symptoms. Despite the clinical challenge that HCV treatment of patients with comorbid HCV and psychiatric illness presents, recent research indicates that HCV treatments can be safely administered to patients with psychiatric illness provided that there is a comprehensive pretreatment assessment, a risk-benefit analysis, and ongoing follow-up of neuropsychiatric symptoms during antiviral therapy. The process of pretreatment assessment involves screening patients for psychiatric and substance use disorders, educating patients about the treatment process, and addressing available psychosocial support. Most psychotropic medications (antidepressants, mood stabilizers, antipsychotics, and neuroleptics) are thought to be safe to use in the management of patients with HCV and psychiatric illness and for the management of IFN- and RBV-induced neuropsychiatric adverse effects. Nonetheless, the prophylactic use of psychotropic medications to prevent IFN- and RBV-induced neuropsychiatric adverse effects remains a controversial topic. The use of IFN and RBV in patients with HCV and severe mental illness can be done safely with expert psychiatric follow-up. In this review, we discuss the process of pretreatment assessment of patients with HCV and psychiatric illness and specifically address IFN- and RBV-induced depression in patients receiving HCV treatment.

Journal Article↗
PubMed2006

Molecular signature of mice T lymphocytes following tolerance induction by allogeneic BMT and CD40-CD40L costimulation blockade.

Tolerance induction by mixed chimerism and costimulation blockade is a promising approach to avoid immunosuppression, but the molecular basis of tolerant T lymphocytes remains elusive. We investigated the genome-wide gene expression profile of murine T lymphocytes after tolerance induction by allogeneic bone marrow transplantation (BMT) and costimulatory blockade using the anti-CD40L antibody MR1. Molecular functions, biological processes, cellular locations, and coregulation of identified genes were determined. A total of 113 unique genes exhibited a significant differential expression between the lymphocytes of MR1-treated Tolerance (TOL) and untreated recipients Control (CTRL). The majority of genes upregulated in the TOL group are involved in several signal transduction cascades such as members of the MAPKKK cascade (IL6, Tob2, Stk39, and Dusp24). Other genes involved in lymphocyte differentiation and highly expressed in the TOL group are lymphotactin, the estrogen receptors (ERs) and the suppressor of cytokine signaling 7. Common transcription factors such as ER 1 alpha, GATA-binding protein 1, insulin promoter factor 1, and paired-related homeobox 2 could be identified in the promoter regions of upregulated genes in the TOL group. These data suggest that T lymphoctes of tolerant mice exhibit a distinct molecular expression profile, which needs to be evaluated in other experimental tolerance models to determine whether it is a universal signature of tolerance.

Animals↗
PubMed2006

Management of hepatitis C disease among VA patients with schizophrenia and substance use disorders.

OBJECTIVE: Rates of hepatitis C (HCV) infection, testing, and treatment were compared among patients with schizophrenia, a substance use disorder, or co-occurring schizophrenia or schizoaffective disorder and a substance use disorder and a control group. METHODS: Information about 293,445 patients of the Northwest Veterans Healthcare Administration was obtained. RESULTS: The substance use disorder group constituted 13.6 percent of the sample; the schizophrenia group, 1.6 percent; and the co-occurring-disorders group, 1.4 percent. Respectively, these groups were approximately four, two, and six times as likely as the control group to receive HCV testing and about seven, two, and eight times as likely to be infected. The rate of interferon (IFN) therapy was significantly lower for the substance use group and the group with co-occurring disorders. However, the magnitude of the differences was not substantial, suggesting that these high-risk groups were not excluded from IFN therapy.

Diagnosis, Dual (Psychiatry)↗
PubMed2006

Psychiatric and substance use disorders in individuals with hepatitis C: epidemiology and management.

Hepatitis C virus (HCV) infection is a major health concern in the US as well as in other countries worldwide. Treatment issues and disease management strategies are complicated by the extremely high rate of psychiatric and substance use disorders in those who have HCV. The majority of new and existing cases of HCV are related to injection drug use and, in this population, the prevalence of psychiatric comorbidity is high. Optimally, all patients with HCV should be screened for psychiatric and substance use disorders before initiation of antiviral therapy. If a patient screens positive, he or she should be referred to a mental healthcare provider or addiction specialist, assessed for the presence of a psychiatric or substance use disorder, and appropriately treated prior to initiation of antiviral (i.e. interferon) therapy. Although interferon-based therapies can lead to severe neuropsychiatric adverse effects, including in rare instances suicide, evidence suggests that many patients with comorbid psychiatric and substance use diagnoses can be treated safely and effectively using comanagement strategies. However, most patients with HCV are not treated with antiviral therapy. Therefore, we must expand our definition of HCV 'treatment' to include treatment of the comorbid psychiatric and substance use disorders that accompany HCV infection and precede antiviral therapy. This paper reviews the epidemiology and management of psychiatric and substance use disorders in patients with HCV, the issue of psychiatric and substance use disorders as contraindications for antiviral therapy, and current treatment strategies for HCV patients with these comorbid conditions.

Antiviral Agents↗
PubMed2005

Addressing tri-morbidity (hepatitis C, psychiatric disorders, and substance use): the importance of routine mental health screening as a component of a comanagement model of care.

BACKGROUND: Recent studies suggest that most patients with hepatitis C virus (HCV) infection commonly present to medical clinics with active psychiatric and substance use disorders. However, routine screening for these disorders is generally not done. OBJECTIVES: The purpose of our study was to assess prospectively the frequency of psychiatric and substance use disorders in patients presenting for initial assessment of a positive HCV antibody test result. METHODS: A sample of 293 patients represented the majority of patients scheduled for their initial hepatology clinic visit at the Portland Veterans Affairs Medical Center between September 2002 and September 2003. The patient screening questionnaire, Alcohol Use Disorders Identification Test-Consumption (AUDIT-C), and the Beck Depression Inventory (BDI-II) were administered to all patients. RESULTS: At screening, 93% of the patients had a current or past history of at least 1 psychiatric disorder, and 73% had >or=2 disorders. The most common disorders included depression (81%), posttraumatic stress disorder (62%), any substance use disorder (58%), bipolar disorder (20%), and other psychotic disorders (17%). One hundred two patients (35%) had baseline BDI-II scores in the moderate-to-severe range of depression (>19), and 61 (21%) had AUDIT-C scores indicating current heavy alcohol use (>or=4). CONCLUSIONS: Psychiatric and substance use disorders are highly prevalent among veterans with chronic hepatitis C. Thirty-five percent have significant symptoms of depression before the initiation of treatment with interferon (IFN). Routine screening for underlying psychiatric and substance use disorders and early treatment intervention before initiating antiviral therapy is essential to prevent worsening of depression and to optimize the outcome of treatment with IFN. Comanagement treatment models involving mental health care may expand the pool of patients eligible to receive treatment with IFN, as well as enhance treatment outcomes.

Adult↗
PubMed2005

A SAGE-based comparison between glomerular and aortic endothelial cells.

Endothelial cells have many characteristics in common, but significant morphological and functional differences exist between endothelial cells from different anatomic sites. The specific glomerular endothelial (GEn) cell transcript repertoire is unknown. We sought to determine whether endothelial cells derived from bovine glomeruli display a distinct transcriptional profile compared with bovine aortic endothelium (BAE) under identical conditions. Serial analysis of gene expression (SAGE), which includes known and unknown transcripts, was used to make the comparison. The GEn and BAE SAGE libraries contain 36,844 and 26,452 total tag sequences, respectively. Among 6,524 unique tag sequences represented at least 2 times in the 2 libraries, 2,094 (32%) were matched to well-characterized bovine cDNA sequences (358 tags) or expressed sequence tags (EST). Identification of the human homolog was achieved for 1,035 of these tags. Forty-two tags were differentially expressed in GEn. For 25 of these, the bovine cDNA or EST, and for 17 the human homolog was identified. Among all transcripts with a known bovine and human tag, seven were expressed at levels more than 10-fold higher in cultured GEn cells compared with all other SAGE libraries. The transcript "DKFZp564B076" was localized by in situ hybridization to glomerular endothelium in vivo and was shown by real-time RT-PCR to be highly abundant in glomeruli compared with aortic intima. This work supports the concept that differences in the transcriptional profile of endothelial cells from distinct origins are observed under otherwise equivalent conditions. Furthermore, we have identified the first known transcript predominant in glomerular endothelium in vivo.

Animals↗
PubMed2005

Relationship of white matter hyperintensities to cerebrospinal fluid glucose polyol pathway metabolites-a pilot study in treatment-resistant affective disorder patients.

BACKGROUND: Magnetic resonance imaging (MRI) white matter hyperintensities (WMHs) are found at higher rates in patients with affective disorders, particularly late-life or treatment-resistant disorders. Studies support a vascular pathogenesis for WMHs in late-life onset disorders; however, pathogenesis in typical early-life onset disorders is less clear. Based on associations between diabetes mellitus and both WMHs and affective disorders, this study investigated the relationship between WMHs and brain glucose metabolism by the polyol pathway-a pathway linked to nervous tissue disease in diabetes. METHODS: Burdens of fluid-attenuated inversion recovery (FLAIR) WMHs were quantified and correlated with cerebrospinal fluid (CSF) concentrations of glucose metabolites in 10 nondiabetic inpatients with treatment-resistant bipolar, unipolar, and schizoaffective disorders and 10 nondiabetic control patients who had been investigated clinically for transient neurological symptoms. RESULTS: Deep but not periventricular WMH burden correlated positively and significantly with elevated CSF concentrations of sorbitol, the specific polyol pathway metabolite of glucose (rho=0.86, p=0.002), in the affective disorders but not the control group. LIMITATIONS: This was a pilot study with a relatively small number of subjects; therefore, conclusions are tentative. Controls were not healthy subjects; they were patients with transient neurological symptoms. CONCLUSIONS: This is the first reported evidence of a relationship between WMHs and increased brain glucose metabolism by the polyol pathway in patients with affective disorders. More extensive studies are necessary to determine whether this preliminary finding represents a pathogenetic relationship.

Adult↗
PubMed2005

Serotonin gene polymorphisms and bipolar I disorder: focus on the serotonin transporter.

The pathogenesis of bipolar disorder may involve, at least in part, aberrations in serotonergic neurotransmission. Hence, serotonergic genes are attractive targets for association studies of bipolar disorder. We have reviewed the literature in this field. It is difficult to synthesize results as only one polymorphism per gene was typically investigated in relatively small samples. Nevertheless, suggestive associations are available for the 5HT2A receptor and the serotonin transporter genes. With the availability of extensive polymorphism data and high throughput genotyping techniques, comprehensive evaluation of these genes using adequately powered samples is warranted. We also report on our investigations of the serotonin transporter, SLC6A4 (17q11.1-q12). An insertion/deletion polymorphism (5HTTLPR) in the promoter region of this gene has been investigated intensively. However, the results have been inconsistent. We reasoned that other polymorphism/s may contribute to the associations and the inconsistencies may be due to variations in linkage disequilibrium (LD) patterns between samples. Therefore, we conducted LD analyses, as well as association and linkage using 12 polymorphisms, including 5HTTLPR. We evaluated two samples. The first sample consisted of 135 US Caucasian nuclear families having a proband with bipolar I disorder (BDI, DSM IV criteria) and available parents. For case-control analyses, the patients from these families were compared with cord blood samples from local Caucasian live births (n = 182). Our second, independent sample was recruited through the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD, 545 cases, 548 controls). No significant associations were detected at the individual polymorphism or haplotype level using the case-control or family-based analyses. Our analyses do not support association between SLC6A4 and BDI families. Further studies using sub-groups of BDI are worthwhile.

Bipolar Disorder↗
PubMed2005

Integrated hepatitis C virus treatment: addressing comorbid substance use disorders and HIV infection.

OBJECTIVES: To examine hepatitis C virus (HCV) and HIV testing patterns within the Northwest Veterans Integrated Service Network (VISN 20). METHODS: Using a comprehensive VISN 20 database, we retrospectively reviewed medical records of 293,445 veterans. RESULTS: 32.8% of patients were tested for HCV, 5.5% were tested for HIV, and 4.3% were co-tested. Of those tested, 12.3% were HCV positive, 5.4% were HIV positive, and 1.6% were co-infected. 79.1% of HIV-positive patients were tested for HCV, 29.2% of whom tested positive. 34.8% of HCV-positive patients were tested for HIV, 4.9% of whom tested positive. Of those tested, HCV-positive patients were significantly more likely than HCV-negative patients to test positive for HIV; HIV-positive patients were no more likely to test positive for HCV than HIV-negative patients. HIV-positive patients with substance use disorders (SUD) were significantly more likely to test HCV positive than those without. Within the total sample, veterans with SUD were significantly more likely to be tested for both diseases and to test positive for HCV but not HIV. After controlling for other categories of SUD, veterans with a history of cocaine abuse compared with those without were at an increased risk of HIV infection and co-infection. CONCLUSION: 79.1% of HIV-positive but only 34.8% of HCV-positive veterans were co-tested, suggesting barriers to HIV testing may exist in VISN 20. Results also indicate that HCV-positive patients are at increased risk for HIV infection and that HIV-positive patients with SUD are at increased risk of HCV infection; routine co-testing for these patients is therefore warranted. Given significant co-infection rates, HCV and HIV screening and testing should be increasingly integrated. Increased infection rates among patients with SUD also warrant integration of HCV and HIV screening and testing into mental health and addiction programmes.

Adult↗
PubMed2005

Transcriptional response in the unaffected kidney after contralateral hydronephrosis or nephrectomy.

BACKGROUND: Unilateral loss of kidney function is followed by compensatory contralateral growth. The early, genome-wide transcriptional response of the untouched kidney to unilateral ureteral obstruction (UUO) or unilateral nephrectomy is unknown. METHODS: Twelve adult male Sprague-Dawley rats were subjected to UUO and twelve rats to unilateral nephrectomy. At time points 12, 24, and 72 hours after insult four rats each were sacrificed and the contralateral kidney harvested for genome-wide gene expression analysis, transcription factor analysis, and histomorphology. RESULTS: Microarray studies revealed that the majority of differentially expressed transcripts were suppressed in UUO and unilateral nephrectomy compared to control kidneys. The function of these suppressed genes is predominantly growth inhibition and apoptosis suggesting a net pro-hypertrophic response. Insulin-like growth factor-2 (IGF-2)-binding protein was one of the few activated genes. We observed a distinctly different molecular signature between UUO and unilateral nephrectomy at the three time points investigated. The early response in UUO rats suggests a counterbalance to the nonfiltering kidney by activation of transport pathways such as the aquaporins. Unilateral nephrectomy kidneys, on the other hand, respond immediately to contralateral nephrectomy by activation of cell cycle regulators such as the cyclin family. Several genes with weakly defined function were found to be associated with either UUO or unilateral nephrectomy. Transcription factor analysis of the identified transcripts suggests common regulation at least of some of these genes. All kidneys showed normal histology. CONCLUSION: Release of growth inhibition by nephrectomy leads to immediate cell cycle activation after unilateral nephrectomy, whereas UUO kidneys counterbalance filtration failure by activation of several transporters.

Animals↗