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Biomedical subjects

C D Howell

Publications and source records attributed to C D Howell.

At least 19 recordsLinked to original sources
PubMed2006

Peginterferon alfa-2a and ribavirin for chronic hepatitis C genotype 1 infections in black patients: safety, tolerability and impact on sustained virologic response.

HCV infections are two-times more prevalent in black Americans than in whites. We previously reported that treatment with peginterferon alfa-2a plus ribavirin produced a sustained virologic response (SVR) rate of 26% in blacks, a lower efficacy compared with the SVR in whites. Here we detail the safety profile of peginterferon alfa-2a plus ribavirin and the relationship between treatment adherence, defined by cumulative drug exposure, and SVR in 78 black patients infected with HCV genotype 1. Sixty-two (79%) patients completed 48 weeks of combination treatment. Peginterferon alfa-2a dose was modified for neutropenia in 36 patients (46%), whereas ribavirin dose was modified due to anemia in 31 patients (40%). The SVR rate was related to medication exposure, based on the percentage of the planned doses of peginterferon and ribavirin that the patients received. The SVR rates were 33, 25 and 0% in patients who received >80, 61-80 and 80, 61-80 and 80% of the total planned doses of both peginterferon and ribavirin and 7% (1 of 14) in patients who received 60% exposure to both, and 0% in patients with 60% of the planned peginterferon alfa-2a and ribavirin doses for 48 weeks was associated with a greater SVR in black patients with HCV genotype 1 infections.

Black or African American↗
PubMed2002

A prospective study of the incidence and open-label treatment of interferon-induced major depressive disorder in patients with hepatitis C.

Interferon (IFN) therapy has been associated with the development of Major Depressive Disorder (MDD) when given to patients with hepatitis C (HCV). The incidence, time course, risk factors, and treatment of IFN-induced MDD are poorly understood. The objectives of the present study were to determine the incidence of IFN-induced MDD, as well as to determine the efficacy of open-label antidepressant treatment, in particular selective serotonin reuptake inhibitors (SSRIs) for IFN-induced MDD. Thirty-nine HCV patients on IFN therapy were monitored weekly using the Beck Depression Inventory (BDI). Those who became depressed were treated with citalopram, a SSRI antidepressant. Main outcome measures included the incidence of IFN-induced MDD, as well as response rates to antidepressants in those patients who developed IFN-induced MDD. Our results showed that 13 of 39 patients (33%) developed IFN-induced MDD. There were no differences in age, gender, past history of MDD, or substance use between those who became depressed and those who did not. However, there were significantly fewer African American patients in the depressed group. Patients who developed IFN-induced MDD were on IFN therapy for an average of 12.1 weeks prior to the development of MDD. Eleven of 13 patients (85%) were responsive to antidepressant treatment. We conclude that IFN-induced MDD is common in HCV patients. Health care providers should follow IFN-treated HCV patients for the development of MDD, particularly between the 2nd and 5th months of IFN therapy. SSRIs, in particular citalopram, are an effective treatment for IFN-induced depression in HCV patients.

Adult↗
PubMed2001

Delayed granuloma formation in a patient with vanishing bile duct syndrome 7 years post-liver transplantation.

A patient was found to have numerous granulomata 7 years after orthotopic liver transplantation for primary sclerosing cholangitis (PSC) on a recent liver biopsy specimen. This histopathologic finding prompted a review of the literature to determine the commonality of this feature in the absence of the usual causes of granulomatous liver disease, none of which were found to be the cause of this patient's liver histopathologic state. The presence of posttransplantation granulomata is rare, and although previously reported to occur shortly after liver transplantation, this finding has not been reported previously with either PSC or vanishing bile duct syndrome. We are not aware of another case of granulomata associated with recurrent PSC or vanishing bile duct syndrome 7 years after liver transplantation.

Bile Duct Diseases↗
PubMed2000

Liver transplantation improves cirrhosis-associated impaired oral glucose tolerance.

BACKGROUND: Thirty-five percent to 80% of cirrhotic patients have impaired glucose tolerance (IGT) or diabetes mellitus (DM). Diabetic cirrhotics have higher morbidity and mortality than nondiabetics. Therefore, it would be worthwhile to determine whether liver transplantation improves glucose homeostasis in these patients. METHOD: A total of 26 patients awaiting liver transplantation were evaluated for impaired glucose homeostasis by fasting blood glucose and/or oral glucose tolerance tests (OGTT). Five patients underwent transplant surgery within 1 year of OGTT and had a repeat OGTT 3-6 months after transplantation. RESULTS: Sixty-five percent (17/26) of the patients had abnormal glucose homeostasis. Twenty-three percent (6/26) met American Diabetes Association criteria for DM, and another 42.3% (11/26) had IGT. All patients had normal HbA1C levels. After transplantation, the 2-hr blood glucose improved in four patients and the mean 2-hr glucose level was reduced (204 +/- 94 vs. 132 +/- 53 mg/dl [mean +/- SD, P=0.051]). CONCLUSION: Liver transplantation can reverse cirrhosis-associated impaired glucose tolerance.

Adult↗
PubMed1999

Role of intercellular adhesion molecule-1 and lymphocyte function-associated antigen-1 during nonsuppurative destructive cholangitis in a mouse graft-versus-host disease model.

Intercellular adhesion molecule-1 (ICAM-1) is expressed abnormally on the bile duct epithelium during the course of primary biliary cirrhosis (PBC), but the importance of ICAM-1 and its lymphocyte function-associated antigen-1 (LFA-1) receptor during the course of nonsuppurative destructive cholangitis (NSDC) has not been defined. To address this question, we defined the relationship between ICAM-1 on the intrahepatic bile duct epithelium and the evolution of NSDC lesions in a mouse graft-versus-host disease (GVHD) model. We also determined the effects of anti-ICAM-1 and anti-LFA-1 treatments on NSDC, intrahepatic lymphokine production, and the homing of lymphocytes to the livers of GVHD mice. ICAM-1 was initially detected on the bile duct epithelium and portal vein endothelium on day 7 of GVHD. There was a significant positive correlation between the intensity of ICAM-1 staining and histological bile duct damage (r =.58, P <.05) between day 3 and 28. Treatment with anti-ICAM-1 (but not anti-LFA-1) decreased both the mean grades of portal inflammation (P =.003) and NSDC (P =.002) lesions compared with control immunoglobulin G (IgG) treatments. Combined treatment with anti-ICAM-1 and anti-LFA-1 caused a further decrease in the amount of portal inflammation and bile duct damage compared with anti-ICAM-1, alone (P =.02). Anti-ICAM-1 treatment also decreased both the percentage of T cells and the production of interleukin-2 (IL-2) and IL-12 in the liver (P <.01), but had no effect on IL-4, IL-10, and interferon gamma. Neither anti-ICAM-1 nor anti-LFA-1 prevented lymphocytes from homing to the liver. These results indicate that both ICAM-1 and LFA-1 are important to the pathogenesis of NSDC.

Animals↗
PubMed1999

Liver diseases.

Liver diseases in the elderly often reflect an age-associated decrease in the capacity to respond to metabolic and infectious insults. Because the geriatric population is growing rapidly, physicians can expect to encounter an increasing number of older patients with liver disease. In this article, the authors discuss the clinical manifestations of the most common liver diseases seen in the geriatric population.

Aged↗
PubMed1998

Successful use of chronic epoprostenol as a bridge to liver transplantation in severe portopulmonary hypertension.

BACKGROUND: Portopulmonary hypertension, defined as mean pulmonary artery pressure >25 mmHg in the presence of a normal pulmonary capillary wedge pressure and portal hypertension, is a known complication of end-stage liver disease that has been associated with high morbidity and mortality at the time of liver transplantation. We have recently reported the successful treatment of portopulmonary hypertension with chronic intravenous epoprostenol and now report the first patient with severe portopulmonary hypertension successfully treated with epoprostenol who subsequently underwent successful liver transplantation. METHODS: A patient with severe portopulmonary hypertension was treated with intravenous epoprostenol, 23 ng/kg/min, for a 4-month period, after which the portopulmonary hypertension resolved and the patient underwent successful liver transplantation. RESULTS: The patient was discharged, continues to do well, and at 3 months is off epoprostenol with near normal pulmonary artery pressures. CONCLUSIONS: Chronic epoprostenol, in conjunction with a multidisciplinary, well-planned perioperative evaluation and treatment plan, may be the answer to a heretofore untreatable disease.

Antihypertensive Agents↗
PubMed1998

Dobutamine stress echocardiography for preoperative cardiac risk stratification in patients undergoing orthotopic liver transplantation.

This study attempts to evaluate the efficacy of dobutamine stress echocardiography for preoperative cardiac risk stratification in patients undergoing orthotopic liver transplantation. Two hundred twenty consecutively submitted patients were evaluated in preparation for orthotopic liver transplantation. Dobutamine stress echocardiography was performed in 80 patients with known or suspected coronary artery disease. Follow-up information was available in 40 patients in the form of cardiac catheterization and/or outcome from liver transplantation to validate the dobutamine stress echo findings. The prevalence of coronary artery disease in this cohort was 5% and was closely associated with the presence of diabetes mellitus. Dobutamine stress echocardiography, when interpreted as abnormal in the presence of wall motion abnormalities only, is associated with a sensitivity, specificity, and positive and negative predictive value of 100%. Dobutamine stress echocardiography is highly efficacious and should be the screening study of choice to detect coronary artery disease in patients undergoing orthotopic liver transplantation.

Adult↗
PubMed1997

Successful emergency transplantation of a liver allograft from a donor maintained on extracorporeal membrane oxygenation.

The critical shortage of cadaveric donors for organ transplantation has led many transplant centers to accept life-saving organs from donors who would have previously been refused for transplantation. We report a novel case of the use of a liver allograft from a donor whose oxygen delivery was maintained by extracorporeal membrane oxygenation (ECMO) for 29 days before suffering an anoxic brain injury from ECMO dysfunction. Liver transplantation was successfully performed in a patient with fulminant hepatic failure. Immediate graft function was obtained in the recipient, with full neurologic recovery and return to gainful employment 4 months after transplantation. ECMO may provide an intriguing option for the maintenance of organ function in the critically unstable brain-dead organ donor to salvage organs for transplantation. Further studies are currently underway.

Adult↗
PubMed1997

Continuous intravenous infusion of epoprostenol for the treatment of portopulmonary hypertension.

The association of pulmonary hypertension with portal hypertension, also called portopulmonary hypertension (PPHTN), is a known complication of chronic liver disease. Previously, the presence of PPHTN was considered to be a contraindication to orthotopic liver transplantation (OLT). Although there are selected case reports of successful OLT in the setting of PPHTN, an excessive mortality rate is associated with OLT and PPHTN. Heretofore, therapy for chronic management of PPHTN was lacking. Recently, continuous intravenous infusion of epoprostenol has been demonstrated to improve symptomatology and survival in the general population of patients with primary pulmonary hypertension. We now report the use of epoprostenol in the more specific instance of PPHTN. Over a period of 6-14 months, epoprostenol (10-28 ng/kg/min) therapy was associated with a 29-46% decrease in mean pulmonary artery pressure, a 22-71% decrease in pulmonary vascular resistance, and a 25-75% increase in cardiac output in a group of four patients. These results suggest that effective chronic therapy for PPHTN is available. In conjunction with inhaled nitric oxide as acute intraoperative therapy, epoprostenol infusion represents an additional therapeutic option for treatment of PPHTN in the liver transplant candidate.

Adult↗
PubMed1997

The evolution of a successful liver transplant program in 1996: the clinical and administrative role of the anesthesiologist.

The establishment of a new liver transplant program requires enormous planning and resources. Extensive negotiations must take place to ensure institutional and departmental commitments to obtain the proper equipment, personnel, and other resources. The formation of a well-trained multidisciplinary team of physicians and nurses becomes the next step. Finally, ample time must be provided to adequately deploy resources, lobby referring physicians, recruit patients, and troubleshoot problems as they arise.

Anesthesiology↗
PubMed1997

Distinctive clinical features of portopulmonary hypertension.

STUDY OBJECTIVE: To differentiate the cardiopulmonary profile of portopulmonary hypertension (PPHTN) from that of primary pulmonary hypertension and chronic liver disease. DESIGN: Retrospective survey. SETTING: Tertiary care center. PATIENTS: Thirty patients with cardiac catheterization-proven PPHTN were compared to 30 randomly selected patients with primary pulmonary hypertension alone and 30 patients with chronic liver disease alone necessitating consideration of liver transplantation (L-CONT). INTERVENTIONS: All patients underwent right heart catheterization, echocardiography, ECG, chest radiography, pulmonary function tests, ventilation-perfusion scanning, and room air arterial blood gas measurements. RESULTS: Patients with PPHTN exhibited elevated pulmonary pressures (mean pulmonary pressure, 48.6+/-2.1 mm Hg) and pulmonary vascular resistance (11.6+/-1.6 mm Hg/L/min/m2) with simultaneous elevation in the cardiac index (3.8+/-0.3 L/min/m2) and depression of systemic vascular resistance (24.9+/-1.7 mm Hg/L/min/m2). Arterial blood gas measurements indicate that PPHTN exhibits a significant accentuation of the chronic respiratory alkalosis (PCO2, 28.7+/-0.5 mm Hg) usually seen with chronic liver disease and pulmonary hypertension. In addition, patients with PPHTN have an increased alveolar-arterial gradient (27.0+/-2.7 mm Hg) when compared to patients with L-CONT, suggesting impaired gas exchange. CONCLUSIONS: PPHTN is associated with a unique clinical profile that possesses characteristics common to and exclusive of liver disease and primary pulmonary hypertension.

Alkalosis, Respiratory↗
PubMed1996

Contributions of donor CD4 and CD8 cells to liver injury during murine graft-versus-host disease.

We have determined the capacity of donor CD4 and CD8 T cells to mediate liver injury in the B10.D2 (donor) into BALB/c (host) chronic graft-versus-host disease (GVHD) model. First, we compared the effects of treating GVHD mice with anti-CD4 or anti-CD8 versus no treatment on the liver histology scores and elevated serum IgE levels in this model. We also examined the abilities of purified donor total T, CD4, and CD8 cells to mediate hepatic GVHD lesions. Anti-CD4 and anti-CD8 treatments caused profound depletion of peripheral CD4+ and CD8+ cells, respectively, and produced a relative enrichment of the CD8+ and CD4+ cells in the liver. Hepatic GVHD lesions and elevated serum IgE concentrations were both suppressed by anti-CD4 treatment. Anti-CD8 treatment had no effect on the severity of hepatic lesions and caused a significant increase in serum IgE levels. Attempts to induce hepatic GVHD with purified donor CD4 and CD8 cells were inconclusive because the onset of liver lesions was delayed and the lesions in both groups were contaminated by the opposite subset. Altogether, our results indicate that both hepatic lesions and elevated serum IgE concentrations in this GVHD model are dependent on donor CD4 cells. Donor CD4 cells mediated hepatic GVHD in the absence of CD8 cells. Donor CD8 cells did not produce hepatic GVHD in the absence of CD4 cells and appeared to be dependent on CD4 cells.

Animals↗
PubMed1995

Biased liver T cell receptor V beta repertoire in a murine graft-versus-host disease model.

Murine graft-vs-host disease (GVHD) results in destruction of small bile ducts in the liver. We analyzed the TCR V beta repertoire of lymphocytes isolated from the livers and spleens of individual B10.D2 into irradiated BALB/c GVHD mice by means of two-color immunofluorescence. Each mouse showed an increase in at least one V beta population in the liver and spleen, but the expanded V beta populations were heterogeneous and variable among individual GVHD mice. Overall, the repertoire of liver CD4 cells was biased toward V beta 2 and 3 expression with 65 and 88% of mice, respectively, showing an increase in these subsets. The splenic CD4 cell repertoire was biased toward V beta 3 and 4 expression (50% of mice each). The repertoire of CD8 cells was less biased with 20 to 35% of mice showing expansions of V beta 3+, 4+, 5+, 6+, 8.1+, 8.2+, and 8.3+ T cells in both the liver and spleen. V beta 2+ CD4 cells were increased preferentially in the liver compared with the spleen. These results indicate that the infiltrating liver and splenic T cells are polyclonal and suggest that donor T cells recognize multiple host non-MHC Ags in this GVHD model. Alloantigens recognized by V beta 2+ CD4 cells appear to be selective for the liver. Expansion of V beta 3+ CD4 cells may reflect recognition of the host Mls-3 superantigen.

Animals↗
PubMed1995

Liver T cell subsets and adhesion molecules in murine graft-versus-host disease.

Murine GVHD across multiple minor histocompatibility barriers (B10.D2 into irradiated BALB/c) results in cell-mediated destruction of bile ducts inside the liver. Similar changes are characteristic of hepatic GVHD in humans following BMT. We have defined the phenotypes of inflammatory cells and the accessory/adhesion molecules expressed in the liver between day 7-14 of murine GVHD. T cells (CD3+) comprised 65% of hepatic inflammatory cells. alpha-beta and gamma-delta cells accounted for 92 and 8%, respectively of hepatic T cells. The percentage of CD4+ cells (29%) was 3 times that of CD8+ cells (11%). Lymphocyte function-associated antigen-1 (LFA-1) was expressed by the majority of inflammatory cells. Thirty per cent of the cells were positive for Mac-1, a differentiation marker of macrophages, large granular lymphocytes, and natural killer cells. Expression of intercellular adhesion molecule-1 and major histocompatibility complex class II (IAd) molecules on bile duct epithelial and portal vein endothelial cells was induced during GVHD. These results suggest that hepatic GVHD is induced by donor alpha-beta T cells through mechanisms that may involve CD4:1Ad and LFA-1:ICAM-1 interactions.

Animals↗
PubMed1994

Murine experimental autoimmune hepatitis: nonspecific inflammation due to adjuvant oil.

Experimental autoimmune hepatitis (EAH) has been induced in several strains of mouse by immunization with liver cytosol plus Freund's complete adjuvant. Our goal was to validate EAH in female C57Bl/6 mice and to compare the ability of immunization with liver cytosol and hepatocyte plasma membranes in Freund's complete (CFA) or incomplete (IFA) adjuvants to induce EAH. Control mice received Hank's balanced salt solution (HBSS), alone or an emulsion of HBSS in either CFA or IFA. The severity of hepatitis in coded liver sections was compared. EAH-like lesions were found not only in mice immunized with liver antigens in CFA or IFA but also in mice injected with either CFA or IFA. Mice injected with HBSS alone showed no hepatitis. These results indicate that immunization with neither liver nor mycobacteria cell wall antigens is required for induction of EAH-like lesions and suggest that the EAH in C57Bl/6 mice may be a nonspecific inflammatory response to adjuvant oil.

Animals↗
PubMed1993

Immunogenicity of two recombinant hepatitis B vaccines in older individuals.

PURPOSE: Currently available hepatitis B vaccines are recombinant, yeast-derived preparations given in 10-micrograms or 20-micrograms doses. The optimum dose remains controversial. We sought to assess the relative immunogenicity of two hepatitis B vaccines, given in different doses, in older individuals. PATIENTS AND METHODS: In a multicenter, double-blind, randomized clinical trial, a total of 460 healthy subjects between 39 and 70 years of age were screened and immunized with either Engerix-B 20 micrograms or Recombivax HB 10 micrograms in standard, intramuscular, 3-dose regimens. Of these, 397 subjects were eligible to continue vaccination. Immunogenicity was measured by determination of antibody to hepatitis B surface antigen (anti-HBs). Seroconversion and seroprotection rates, and geometric mean titers of anti-HBs were calculated at 1, 3, 6, and 8 months after the initial dose of vaccine. RESULTS: Seroprotection rates for subjects receiving the 20-micrograms dose of vaccine were slightly, but not significantly, greater than for subjects receiving the 10-micrograms dose, at each time point. However, at 3 months, males receiving the higher dose had significantly higher seroprotection rates than males receiving the lower dose: 63% versus 37% (p < 0.001). At 8 months, geometric mean titers for the group receiving Engerix-B 20 micrograms were significantly greater than that for the group receiving Recombivax HB 10 micrograms: 840 mIU/mL versus 340 mIU/mL (p = 0.001). CONCLUSIONS: Immunization with the 20-micrograms dose of recombinant hepatitis B virus vaccine appeared to result in more rapid development of seroprotective anti-HBs titers in older men and in higher titers of anti-HBs at the completion of vaccination when compared to the 10-micrograms dose. The latter data suggest that the 20-micrograms dose may result in a longer duration of seroprotective anti-HBs titers.

Adult↗