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David L Thomas

Publications and source records attributed to David L Thomas.

At least 55 records · Page 3Linked to original sources
PubMed2005

3D MDEFT imaging of the human brain at 4.7 T with reduced sensitivity to radiofrequency inhomogeneity.

A modification to the 3D modified driven equilibrium Fourier transform (MDEFT) imaging technique is proposed that reduces its sensitivity to RF inhomogeneity. This is especially important at high field strengths where RF focusing effects exacerbate B(1) inhomogeneity, causing significant signal nonuniformity in the images. The adiabatic inversion pulse used during the preparation period of the MDEFT sequence is replaced by a hard (nonadiabatic) pulse with a nominal flip angle of 130 degrees. The spatial inhomogeneity of the hard pulse preparation compensates for the inhomogeneity of the excitation pulses. Uniform signal intensity is obtained for a wide range of B(1) amplitudes and the high CNR characteristic of MDEFT is retained. The new approach was validated by numerical simulations and successfully applied to human brain imaging at 4.7 T, resulting in high-quality T(1)-weighted images of the whole human brain at high field strength with uniform signal intensity and contrast, despite the presence of significant RF inhomogeneity.

Brain Mapping↗
PubMed2005

Understanding and optimizing the amplitude modulated control for multiple-slice continuous arterial spin labeling.

Multiple-slice perfusion imaging by continuous arterial spin labeling (CASL) is made possible by amplitude modulation (AM) of the labeling RF pulse, but perfusion sensitivity is reduced relative to the single-slice technique. A computer model of the Bloch equations for velocity driven adiabatic fast passage was developed to elucidate the compromised sensitivity to perfusion of the AM control technique for CASL. Calculations were performed over ranges of RF pulse amplitude, B1; magnetic field gradient, G; phase, phi, and frequency, f, of the modulation function; velocity, v, and relaxation times, T1 and T2, of blood. It was found that unless f>2piB1, phi determines the performance of the AM control; excessively high B1 or v reduces the efficiency of the AM control; and T1 relaxation dominates if f is too great. In vivo, in rat brain (n=5) at 2.35 T, the sensitivity of the AM technique to perfusion was 70% of the sensitivity of single-slice CASL.

Animals↗
PubMed2005

Natural history of hepatitis C.

Fifteen years after the discovery of the hepatitis C virus, a substantial amount of information has been learned about the natural history of infection. Testing for viral nucleic acid made it possible to accurately diagnose chronic infection and provided a more precise estimate of the overall frequency of viral persistence. Although cirrhosis and hepatocellular carcinoma can arise in persons with chronic hepatitis C, these outcomes do not always occur. The cirrhosis risk is greater in those who are infected at older ages, those who drink >50 g of alcohol each day, and persons coinfected with HIV. However, much of the person-to-person variability in progression of chronic hepatitis C remains unexplained. The ability to detect persons at highest risk of progression remains incomplete and represents an important future challenge in the understanding of the natural history of hepatitis C.

Disease Progression↗
PubMed2005

Management and treatment of injection drug users with hepatitis C virus (HCV) infection and HCV/human immunodeficiency virus coinfection.

Injection drug use is the major mode of hepatitis C virus (HCV) transmission in developed countries. Despite this, relatively few current and recovering injection drug users (IDUs) have received HCV treatment. Studies among individuals with a recent history of injection drug use or those receiving drug dependency treatment have provided evidence that these groups can be successfully treated for chronic HCV infection. These studies have provided the impetus to change guidelines for treatment of current and recovering IDUs, with a move toward individualized HCV treatment assessment and the removal of defined periods of illicit drug use abstinence. Strategies to improve access to HCV treatment for current and recovering IDUs include drug dependency treatment education and training for hepatologists and other HCV treatment physicians, HCV treatment education and training for addiction medicine physicians, development of multidisciplinary clinics, and peer-based eduction and support for individuals considering and receiving HCV treatment.

Antiviral Agents↗
PubMed2005

A framework for understanding factors that affect access and utilization of treatment for hepatitis C virus infection among HCV-mono-infected and HIV/HCV-co-infected injection drug users.

Treatment for hepatitis C virus (HCV) is rarely received by injection drug users (IDU), particularly those co-infected with HIV. We propose a framework for understanding factors that affect utilization and adherence to HCV therapy among HCV mono-infected and HIV/HCV-co-infected IDU. Provision of treatment requires calculation of risks and benefits including evaluation of a number of time-varying factors that collectively determine a gradient of treatment eligibility, advisability and acceptability, the relative importance of which may differ in co-infected and mono-infected IDU. Treatment eligibility is determined by a number of non-modifiable and modifiable contraindications, the latter of which can change over time rendering patients who were once ineligible eligible. Among those eligible, treatment need can be assessed by liver biopsy and therapy may be deferred in those with no liver disease and started in those with significant liver disease. Among those with moderate disease, further consideration of treatment advisability (medical factors that affect treatment response) and acceptability (individual, provider and environmental barriers) is needed before treatment decisions are made. These factors are dynamic and thus should be continually evaluated even among those who may not initially appear to be ready for treatment. An evaluation of this framework is needed to determine applicability and feasibility. Until then, treatment decisions should be made on an individual basis after careful consideration of these issues by provider and patient and efforts to develop novel strategies for identifying IDU who need treatment most (alternatives to liver biopsy) and multidimensional approaches to deliver treatment for HCV while addressing other factors including HIV infection, depression and drug use should be continued.

Antiviral Agents↗
PubMed2005

Mannose binding lectin genotypes influence recovery from hepatitis B virus infection.

Mannose binding lectin (MBL) is a central component of the innate immune response and thus may be important for determining hepatitis B virus (HBV) persistence. Since single-nucleotide polymorphisms (SNPs) in the gene encoding MBL (mbl2) alter the level of functional MBL, we hypothesized that mbl2 genotypes are a determinant of HBV persistence or recovery from viral infection. We tested this hypothesis by using a nested case control design with 189 persons with HBV persistence matched to 338 individuals who had naturally recovered from HBV infection. We determined genotypes of two promoter and three exon 1 SNPs in mbl2 and grouped these genotypes according to the amount of functional MBL production. We found that the promoter SNP -221C, which leads to deficient MBL production, was more common in those subjects with viral persistence (odds ratio [OR], 1.38; 95% confidence interval [CI], 1.01 to 1.89; P = 0.04). Those subjects homozygous for the combination of promoter and exon 1 genotypes associated with the highest amount of functional MBL had significantly increased odds of recovery from infection (OR, 0.55; 95% CI, 0.37 to 0.84; P = 0.005). Conversely, those homozygous for the combination of promoter and exon 1 genotypes which produce the lowest amount of functional MBL were more likely to have viral persistence (OR, 1.76; 95% CI, 1.02 to 3.01; P = 0.04). These data are consistent with the hypothesis that functional MBL plays a central role in the pathogenesis of acute hepatitis B.

Genotype↗
PubMed2004

Severe community-onset pneumonia in healthy adults caused by methicillin-resistant Staphylococcus aureus carrying the Panton-Valentine leukocidin genes.

BACKGROUND: Recent worldwide reports of community-onset skin abscesses, outbreaks of furunculosis, and severe pneumonia associated with methicillin-resistant Staphylococcus aureus (MRSA) carrying Panton-Valentine leukocidin (PVL) genes and the staphylococcal cassette chromosome mec (SCCmec) type IV indicate that MRSA infections are evolving into a community-related problem. The majority of cases reported to date involve skin and soft-tissue infections, with severe pneumonia representing a relatively rare phenomenon. During a 2-month period in the winter of 2003-2004, four healthy adults presented to 1 of 2 Baltimore hospitals with severe necrotizing MRSA pneumonia in the absence of typical risk factors for MRSA infection. METHODS: Patients' MRSA isolates were characterized by strain typing with use of pulsed-field gel electrophoresis and SCCmec typing with use of a multiplex polymerase chain reaction (PCR) assay and detection of PVL genes by PCR. RESULTS: All 4 patients' MRSA isolates carried the PVL genes and the SCCmec type IV element and belonged to the USA300 pulsed-field type. These 3 findings are among the typical characteristics of community-onset MRSA strains. In addition, 2 of our patients had concomitant influenza A diagnosed, which likely contributed to the severity of their presentation. CONCLUSIONS: To our knowledge, these patients represent the first reported North American adults with severe community-onset MRSA pneumonia caused by strains carrying the PVL genes.

Adult↗
PubMed2004

Hepatotoxicity associated with protease inhibitor-based antiretroviral regimens with or without concurrent ritonavir.

OBJECTIVE: To determine the incidence of significant liver enzyme elevations following the initiation of protease inhibitor (PI)-based antiretroviral therapy (ART) with or without pharmacokinetic boosting with ritonavir (RTV), and to define the role of chronic viral hepatitis in its development. DESIGN: Prospective, cohort analysis of 1161 PI-naive, HIV-infected patients receiving RTV-boosted (lopinavir, indinavir and saquinavir) and unboosted PI-based ART (indinavir, nelfinavir) that had at least one liver enzyme measurement before and during therapy. METHODS: The incidence of grade 3 and 4 liver enzyme elevations among persons with and without hepatitis B and/or C co-infection treated with PI-based ART were compared. Severe hepatotoxicity was defined as an increase in serum liver enzyme >/= 5-times the upper limit of the normal range or 3.5-times an elevated baseline level. RESULTS: The incidence of grade 3 or 4 elevations among PI-naive patients was: nelfinavir, 11%; lopinavir/RTV (200 mg/day), 9%; indinavir, 13%; indinavir/RTV (200-400 mg/day), 12.8%; and saquinavir/RTV (800 mg/day), 17.2%. The risk was significantly greater among persons with chronic viral hepatitis (63% of cases); however, the majority of hepatitis C virus (HCV)-infected patients treated with nelfinavir (84%), saquinavir/RTV (74%), indinavir, 86%, indinavir/RTV (90%) or lopinavir/RTV (87%) did not develop hepatotoxicity. CONCLUSIONS: Our data suggest that the lopinavir/RTV is not associated with a significantly increased risk of hepatotoxity among HCV-infected and uninfected patients compared with an alternative PI-based regimen, nelfinavir. Accordingly, other medication-related factors (e.g, efficacy and non-hepatic toxicity) should guide individual treatment decisions.

AIDS-Related Opportunistic Infections↗
PubMed2004

Testing for hepatitis C virus infection should be routine for persons at increased risk for infection.

In the United States, chronic hepatitis C virus (HCV) infection affects an estimated 3 million persons, most younger than 50 years of age. It is one of the leading causes of chronic liver disease morbidity and mortality and the most common indication for liver transplantation. Effective treatment can eradicate the virus and eliminate or reduce liver inflammation and fibrosis, and counseling and immunization can modify or prevent the adverse effect of cofactors (for example, alcohol consumption or co-infections) on disease progression. However, controversy surrounds the need to routinely identify asymptomatic HCV-infected persons. Because no data currently demonstrate that treatment or other interventions will reduce future cases of HCV-related chronic disease and deaths, the U.S. Preventive Services Task Force found insufficient evidence to recommend for or against routine screening for HCV infection in adults at high risk. Chronic hepatitis C would require many years of follow-up to determine the incidence of complication after treatment of or other interventions in asymptomatic persons. It seems inappropriate to wait several decades to measure the impact of early identification of this viral infection when current data support a positive therapeutic effect that points to long-term benefits. In addition, treatment and other interventions must be provided before cirrhosis or liver failure occurs. Therefore, medical and public health professionals should continue the practice of screening persons for risk factors; offering testing to those at increased risk for HCV infection; and providing infected persons with appropriate counseling, medical evaluation, and treatment.

Hepacivirus↗
PubMed2004

HLA and NK cell inhibitory receptor genes in resolving hepatitis C virus infection.

Natural killer (NK) cells provide a central defense against viral infection by using inhibitory and activation receptors for major histocompatibility complex class I molecules as a means of controlling their activity. We show that genes encoding the inhibitory NK cell receptor KIR2DL3 and its human leukocyte antigen C group 1 (HLA-C1) ligand directly influence resolution of hepatitis C virus (HCV) infection. This effect was observed in Caucasians and African Americans with expected low infectious doses of HCV but not in those with high-dose exposure, in whom the innate immune response is likely overwhelmed. The data strongly suggest that inhibitory NK cell interactions are important in determining antiviral immunity and that diminished inhibitory responses confer protection against HCV.

Adolescent↗
PubMed2004

Changes in hepatitis B virus DNA levels with acute HIV infection.

We hypothesized that acute infection with human immunodeficiency virus (HIV) would diminish immunoregulation of chronic hepatitis B (CHB), resulting in higher blood hepatitis B virus (HBV) DNA levels. To test this hypothesis, we evaluated sequential HBV DNA levels in stored serum samples obtained from 9 men with CHB who acquired HIV infection. Three patterns of changes in HBV DNA levels were noted after HIV seroconversion. One man experienced the expected increase in HBV DNA, 3 men had stable HBV DNA levels, and, unexpectedly, 5 men had a mean decrease of 6.29 log10 copies/mL in the HBV DNA level, with hepatitis B e antigen no longer detectable in 4. Acute HIV infection is not consistently associated with an increased blood HBV DNA level. Additional research is needed to understand the mechanism for the unexpected reductions in HBV DNA levels associated with acute HIV infection.

Acute Disease↗
PubMed2004

Poor validity of self-reported hepatitis B virus infection and vaccination status among young drug users.

Self-reported hepatitis B virus (HBV) infection status and immunization status were compared with HBV serological markers among 324 young injection drug users (IDUs) and noninjection drug users (NIDUs). The overall validity of self-reported status was poor; 52% claiming to be vaccinated were actually susceptible to HBV. There was no difference in validity of self-reported HBV status between IDUs and NIDUs. Clinicians should adopt a "Don't Ask, Vaccinate" vaccination policy for young drug users.

Adult↗
PubMed2004

Hepatitis B virus infection and vaccination among young injection and non-injection drug users: missed opportunities to prevent infection.

INTRODUCTION: We examined correlates of HBV infection and vaccination and the missed vaccination opportunities among young injection drug users (IDUs) and non-injection drug users (NIDUs). METHODS: Two hundred IDUs and 124 NIDUs aged 15-30 years were studied. Demographics, drug use and sexual behaviors, and health and incarceration history data were collected. Serology was conducted for antibodies to HBV-core antigen (anti-HBc) and HBV-surface antigen (anti-HBs). Presence of anti-HBc indicated past HBV infection; presence of anti-HBs alone indicated past vaccination. RESULTS: More IDUs had been infected with HBV in the past than NIDUs (37% versus 19%, P = 0.001). Among male and female IDUs, injection drug use behaviors were significantly associated with past infection. For female IDUs, being African-American and trading sex were also associated with previous infection. Among NIDUs, being female and longer time since sexual debut were associated with past infection. Overall, 11% were vaccinated (10% IDU versus 14% NIDU, P = 0.30). Younger age and drug treatment history were associated with vaccination. Most susceptibles (84%) experienced at least one missed opportunity for vaccination. CONCLUSION: Young drug users remain at high risk for HBV infection. Vaccination rates remain low despite multiple opportunities for vaccination. An integrated HBV immunization effort should be coordinated among venues frequented by young drug users.

Adolescent↗
PubMed2004

High prevalence of occult hepatitis B in Baltimore injection drug users.

Occult hepatitis B is defined by the presence of hepatitis B virus (HBV) DNA in a serum or liver in the absence of hepatitis B surface antigen (HBsAg). The prevalence and clinical correlates of occult hepatitis B remain incompletely defined. A cross-sectional study was performed to determine the prevalence of occult hepatitis B in a high-risk cohort composed of 188 injection drug users in Baltimore, Maryland. All individuals had chronic hepatitis C viral infections confirmed by RNA detection and liver biopsy. Serologic assays for HBsAg and core antibody (HBcAb) were performed. Serum HBV DNA was detected using the COBAS HBV AMPLICOR monitor assay (lower limit of detection, 200 HBV copies per milliliter) and a semi-nested polymerase chain reaction (PCR) assay (lower limit of detection, 15 HBV copies per milliliter). Although almost all individuals (96%) were anti-HBC positive, only 8 of 188 (4%) were HBsAg positive. Occult hepatitis B was not identified using the COBAS assay, but was found in 81 of 180 (45%) of individuals using semi-nested PCR. Of the 8 HBsAg positive individuals, HBV DNA was found in 1/8 using the COBAS assay and 6/8 using the nested PCR assay. Overall, liver disease was mild, with a median serum alanine aminotransferase (ALT) of 38 IU/L, median activity grade of 3/18, and median fibrosis stage of 1/6. No association was found between the serum AST (aspartate aminotransferase), activity grade, or stage of liver disease and the presence of occult hepatitis B. Serum ALT levels were slightly higher in patients without occult hepatitis B (46 vs. 35 IU/L), and the median years since first injection drug use was somewhat longer in those without occult hepatitis B (24 vs. 20 years). In conclusion, although further research is needed to assess its clinical significance, there is a high prevalence of occult HBV infection in this cohort of HCV-infected injection drug users.

Adult↗
PubMed2004

High-resolution fast spin echo imaging of the human brain at 4.7 T: implementation and sequence characteristics.

In this work, a number of important issues associated with fast spin echo (FSE) imaging of the human brain at 4.7 T are addressed. It is shown that FSE enables the acquisition of images with high resolution and good tissue contrast throughout the brain at high field strength. By employing an echo spacing (ES) of 22 ms, one can use large flip angle refocusing pulses (162 degrees ) and a low acquisition bandwidth (50 kHz) to maximize the signal-to-noise ratio (SNR). A new method of phase encode (PE) ordering (called "feathering") designed to reduce image artifacts is described, and the contributions of RF (B(1)) inhomogeneity, different echo coherence pathways, and magnetization transfer (MT) to FSE signal intensity and contrast are investigated. B(1) inhomogeneity is measured and its effect is shown to be relatively minor for high-field FSE, due to the self-compensating characteristics of the sequence. Thirty-four slice data sets (slice thickness = 2 mm; in-plane resolution = 0.469 mm; acquisition time = 11 min 20 s) from normal volunteers are presented, which allow visualization of brain anatomy in fine detail. This study demonstrates that high-field FSE produces images of the human brain with high spatial resolution, SNR, and tissue contrast, within currently prescribed power deposition guidelines.

Adult↗
PubMed2004

Prevalence of cryoglobulinemia in hepatitis C virus (HCV) positive patients with and without human immunodeficiency virus (HIV) coinfection.

BACKGROUND: Coinfection with human immunodeficiency virus (HIV) has been shown to influence the natural history of hepatitis C infection. OBJECTIVE: Our interest was to determine if HIV coinfection influences the prevalence of cryoglobulinemia in hepatitis C virus (HCV) infected persons. STUDY DESIGN: A total of 384 HCV RNA positive (234 HIV-infected and 150 HIV-uninfected) participants were tested at two visits, 18 months apart, for HCV and HIV RNA, CD4, and liver enzyme levels. Serum cryoglobulin levels were measured at a subsequent visit for a subset of the sample. RESULTS: HIV-infected participants had significantly higher HCV RNA levels (P < 0.0001) and aspartate transaminase (AST) levels (P < 0.0001), but not alanine transaminase (ALT) levels (P > 0.05) as compared with HIV-uninfected participants. These findings were consistent at both visits and no significant changes were observed between visits. Fifty (19%) of the 264 participants tested had detectable cryoglobulins. No difference was observed in HIV seropositivity among participants with or without cryoglobulinemia (68% versus 61%; odds ratio = 1.34, P = 0.37). However, among HIV coinfected participants, elevated AST levels (P = 0.04) and lower CD4 levels (P = 0.02) were associated with cryoglobulinemia. CONCLUSIONS: While previously reported associations were found between HIV and coinfection with HCV in this study, we did not find an association between HIV infection and cryoglobulinemia.

Adult↗