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Biomedical subjects

H R Rosen

Publications and source records attributed to H R Rosen.

At least 19 recordsLinked to original sources
PubMed2001

Treatment of progressive hepatitis C recurrence after liver transplantation with combination interferon plus ribavirin.

Hepatitis C virus (HCV) recurrence after orthotopic liver transplantation (OLT) is common, although the majority of cases are mild. A subset of transplant recipients develops progressive allograft injury, including cirrhosis and allograft failure. Minimal data are available on the safety and efficacy of antiviral treatment in this group of patients. The aim of this study is to review our experience in the treatment of moderate to severe HCV recurrence with combination interferon-alpha2b and ribavirin (IFN/RIB). Between October 1993 and October 1999, a total of 197 patients underwent OLT for HCV-related liver failure. This study describes 12 transplant recipients with moderate to severe recurrence treated with IFN/RIB. All patients met at least 1 of the following inclusion criteria: (1) moderate to severe inflammation (grade III to IV) on allograft biopsy, (2) bridging fibrosis on allograft biopsy, or (3) severe cholestasis attributable solely to HCV recurrence. Two patients had undergone re-OLT for allograft cirrhosis secondary to HCV recurrence and now had evidence of progressive HCV in their second allografts. Appropriate dose reductions of both IFN and RIB, as well as initiation of granulocyte colony-stimulating factor (G-CSF), for marked leukopenia were recorded. IFN/RIB therapy was started 60 to 647 days post-OLT, and duration of therapy ranged from 39 to 515 days. Seven patients were administered G-CSF to successfully treat leukopenia. Six of the 12 patients (50%) became HCV RNA negative by polymerase chain reaction. One of these 6 patients (no. 1) was HCV RNA negative at 6 months but chose to discontinue therapy because of intolerable side effects, experienced a relapse, and was HCV RNA positive at 12 months. Two of the remaining 5 patients were HCV RNA negative at 2 and 9 months off therapy. For the entire group, there was a statistically significant decrease in serum biochemical indices assessed at initiation of therapy and 1, 3, and 6 months into therapy. Most patients required dose reductions of both IFN and RIB. Five patients died; 3 patients died of liver-related complications that included severe intrahepatic biliary cholestasis, severe HCV recurrence, and chronic rejection with profound cholestasis. In the subset of HCV-positive liver transplant recipients with moderate to severe recurrence, combination IFN/RIB therapy resulted in complete virological response (serum RNA negative) in 6 of 12 patients ( approximately 50%). However, only 1 of 12 patients (8.3%) had sustained virological clearance after cessation of IFN/RIB therapy. Dose reductions of both IFN and RIB were required in most patients. The use of G-CSF (sometimes preemptively) allowed correction of leukopenia and full-dose antiviral therapy. Multicenter trials using combination therapy to identify factors predictive of response are needed in the subset of patients with progressive allograft injury.

Adult↗
PubMed2001

Hemispheric dominance for emotions, empathy and social behaviour: evidence from right and left handers with frontotemporal dementia.

Although evidence from primates suggests an important role for the anterior temporal cortex in social behaviour, human research has to date concentrated almost solely on the orbitofrontal cortex and amygdala. By describing four cases of the temporal variant of frontotemporal dementia we show how this degenerative condition provides an excellent model for investigating the role of the anterior temporal lobe, especially the right, in emotions, empathy and social behaviour. Assessments of semantic memory, processing of emotional facial expression and emotional prosody were made, empathy was measured, and facial expressions of emotion were coded. Of the two right handers described, one subject with predominantly left temporal lobe atrophy had severe semantic impairment but normal performance on all emotional tasks. In contrast, the subject with right temporal lobe atrophy showed severely impaired recognition of emotion from faces and voices that was not due to semantic or perceptual difficulties. Empathy was lost, interpersonal skills were severely affected and facial expression of emotion was characterized by a fixed expression that was unresponsive to situations. Additionally, two left handers with right temporal lobe atrophy are described. One demonstrated the same pattern of hemispheric lateralization as the right handers and had emotional impairment. The other left hander showed the opposite pattern of deficits, suggesting a novel presentation of anomalous dominance with reversed hemispheric specialization of semantic memory and emotional processing.

Aged↗
PubMed2000

Standards for anal sphincter replacement.

PURPOSE: Anal sphincter replacement offers a new treatment option for patients with severe refractory fecal incontinence or for those who require abdominoperineal resection for localized malignancy. The purpose of this study was to review the current status of anal sphincter replacement, formulate a consensus statement regarding its current use, and outline suggestions for future development. METHODS: Four areas of interests were selected: indications for sphincter replacement, continence scoring and quality of life, choice of therapy, and dissemination of new technology. A questionnaire regarding these issues was developed and circulated to working party members; its results served as the basis for this consensus document. RESULTS: Both electrically stimulated skeletal muscle neosphincter and artificial anal sphincter are options for patients with end-stage fecal incontinence. Electrically stimulated skeletal muscle neosphincter is also appropriate for reconstruction after surgical excision of the anorectum in selected cases. Avoidance of complications requires strict attention to sterile technique, prophylactic antibiotics, and deep venous thrombus prophylaxis. A standardized scoring system is proposed that evaluates both continence and evacuation. Quality of life is a critical endpoint for assessing sphincter replacement, and use of The American Society of Colon and Rectal Surgeons incontinence-specific quality-of-life instrument is recommended. As the efficacy of sphincter replacement becomes proven, dissemination of the technique should occur in a controlled manner to ensure adequate surgeon training, minimization of complications, and optimization of results. CONCLUSIONS: Sphincter replacement by electrically stimulated skeletal muscle neosphincter and artificial anal sphincter provide a continent option for patients with end-stage fecal incontinence and those requiring abdominoperineal resection. The guidelines offered in this document are intended to facilitate the controlled and safe development and acceptance of these new techniques.

Anal Canal↗
PubMed2000

Association of fungal infection and increased mortality in liver transplant recipients.

BACKGROUND: Invasive fungal infection is associated with increased morbidity and mortality following orthotopic liver transplantation (OLTx). Understanding the risk factors associated with fungal infection may facilitate identification of high-risk patients and guide appropriate initiation of antifungal therapy. OBJECTIVES: The aim of this study was to determine the incidence of fungal infections, identify the most common fungal pathogens, and determine the risk factors associated with fungal infections and mortality in OLTx recipients. METHODS: Medical records from 96 consecutive OLTx in 90 American veterans (88 males, 2 females; mean age 48 years, range 32 to 67) performed from January 1994 to December 1997 were retrospectively reviewed for fungal infection in the first 120 days after transplantation. Infection was defined by positive cultures from either blood, urine (<105 CFU/mL), cerebrospinal or peritoneal fluid, and/or deep tissue specimens. Superficial fungal infection and asymptomatic colonization were excluded from study. All patients received cyclosporine, azathioprine, and prednisone as maintenance immunosuppressive therapy. Fungal prophylaxis consisted of oral clotrimazole (10 mg) troches, five times per day during the study period. RESULTS: Thirty-five patients (38%) had documented infection with one or more fungal pathogens, including Candida albicans (25 of 35; 71%), C torulopsis (7 of 35; 20%), C tropicalis (2 of 35; 6%), non-C albicans (2 of 35; 6%), Aspergillus fumigatus (4 of 35; 11%), and Cryptococcus neoformans (1 of 35; 3%). The crude survival for cases with or without fungal infection was 68% and 87%, respectively (P <0.0001). The median intensive care unit stay and overall duration of hospitalization were significantly longer for patients with fungal infection (P <0.01). The mean time interval from transplantation to the development of fungal infection was 15 days (range 4 to 77) with a mean survival time from fungal infection to death of 21 days (range 3 to 64). Fungal infections occurred significantly more often in patients with renal insufficiency (serum creatinine >2.5 mg/dL), biliary/vascular complications, and retransplantation. CONCLUSIONS: Fungal infections were associated with increased morbidity and mortality following OLTx, with Candida albicans being the most common pathogen. Treatment strategies involving antifungal prophylaxis for high-risk patients and earlier initiation of antifungal therapy in cases of presumed infection are warranted.

Adult↗
PubMed2000

Viral hepatitis in the liver transplant recipient.

Understanding and management of HBV and HCV infection in the OLT recipient has evolved rapidly in the last decade. The spontaneous risk for viral recurrence after transplantation is high, but has been decreased effectively in hepatitis B-positive recipients with the use of HBIG and lamivudine. HCV recurrence as defined by histologic injury is almost universal, although graft or patient outcomes for the first 8 years after OLT do not appear to be limited by HCV serostatus. However, effective prophylactic regimens that alter the natural history of HCV reinfection do not currently exist, and with longer follow-up into the second decade, the prevalence of HCV-related graft failure is likely to increase.

Antiviral Agents↗
PubMed2000

Disease recurrence following liver transplantation.

Virtually all liver diseases that necessitate orthotopic liver transplantation (OLT) can recur, and recurrent disease has the potential to become the most serious problem facing transplantation in the future. In addition, recurrence following transplantation provides a model to study pathogenic mechanisms of these diseases. While some interventions (e.g., HBIG) have been shown to alter the natural history of recurrent disease, most of these disease processes are not modified by our currently available therapies. In addition, the role of different immunosuppressive protocols on disease recurrence requires further definition. As a varying proportion of the first generation of liver transplant patients develop severe recurrence and graft failure, policies of organ allocation for retransplantation will be challenged.

Hepatitis B, Chronic↗
PubMed2000

Retransplantation for hepatitis C: implications of different policies.

Approximately 20% of hepatitis C virus (HCV)-positive liver transplant recipients develop evidence of allograft cirrhosis by year 5. 2. The prevalence of HCV infection in patients undergoing retransplantation has significantly increased since 1990. 3. Retransplantation for recurrent HCV is associated with poor long-term survival. 4. Preoperative hyperbilirubinemia (bilirubin > or =5 mg/dL) and renal failure predict poor outcome after retransplantation. 5. Retransplantation is the only viable option for patients in whom allografts fail because of recurrent HCV disease.

Decision Making↗
PubMed2000

Hepatitis B and C in the liver transplant recipient.

Liver disease related to chronic viral hepatitis is the leading indication for orthotopic liver transplantation (OLT) worldwide. The evolution of our understanding of hepatitis B and C infection in the OLT recipient has been rapid in the last decade. The spontaneous risk for viral recurrence after transplantation is high but has been effectively decreased in hepatitis B infected recipients with the use of HBIG and lamivudine with dramatic improvements in patient and graft survivals. HCV recurrence as defined by histologic injury is almost universal although graft or patient outcomes for the first decade after OLT do not appear to be limited by HCV infection for most patients. However, individual patients do suffer severe graft injury and even graft loss due to recurrent HCV. With longer follow up into the second decade, the prevalence of HCV-related graft failure is likely to increase. In addition, the role of different immunosuppressive protocols on disease recurrence requires further study. Thus, although hepatitis B recurrence has been effectively contained by use of HBIG with or without lamivudine, the more intractable problem of managing recurrent HCV has as yet no obvious solutions. Optimal antiviral strategies for hepatitis C post-OLT have yet to be identified.

Graft Enhancement, Immunologic↗
PubMed2000

EUS in cirrhotic patients with and without prior variceal hemorrhage in comparison with noncirrhotic control subjects.

BACKGROUND: Endoscopic ultrasound (EUS) was used to evaluate cirrhotic patients with and without prior variceal hemorrhage. The findings were compared with those of EUS in noncirrhotic control subjects to determine EUS features indicative of cirrhosis and of a risk for variceal hemorrhage. METHODS: Patients with cirrhosis undergoing indicated endoscopic screening for varices or surveillance after endoscopic therapy for variceal hemorrhage were studied and compared with healthy noncirrhotic control patients undergoing EUS for benign conditions. RESULTS: Sixty-six cirrhotic patients (31 with prior hemorrhage) and 32 control patients were studied. Nonhemorrhage cirrhotic patients had more severe liver disease by Child's class (p = 0.02) and less beta-adrenergic blocker usage (p < 0.0001). Paraesophageal varices were detected in 97% of cirrhotic patients and 3% of control patients (p < 0.001) and were a more sensitive predictor of cirrhosis than varices at endoscopy (74%, p < 0.0001). Azygos vein and thoracic duct diameters, and gastric mucosa and submucosa thickness were greater for cirrhotic than control patients (p < 0.001). More hemorrhage patients had large (5 mm or greater) paraesophageal varices (odds ratio 3.1: 95% CI [1.1, 8.3]; p < 0.05) and paragastric varices (odds ratio 3.7: 95% CI [1.3, 10.2]; p = 0.01). Paraesophageal varix size correlated with ascites (p = 0.03) and, for nonhemorrhage patients, with Child's class (p < 0.01). CONCLUSIONS: Paraesophageal and paragastric varices correlate with the presence and severity of liver disease and portal hypertension. These data support the hypothesis that large paraesophageal and paragastric varices (5 mm or greater) may be risk factors for variceal hemorrhage, an observation that merits further prospective study. Cirrhosis causes dilation of the azygos vein and thoracic duct and thickening of gastric mucosa and submucosa.

Azygos Vein↗
PubMed2000

Primer on hepatitis C for hospital epidemiologists.

First identified in the late 1980s as the main causative agent of non-A, non-B hepatitis, hepatitis C virus (HCV) infection is now the most common chronic bloodborne infection in the United States. It is likely that the number of deaths attributable to HCV-related chronic liver disease will increase substantially during the next 2 decades, and the potential economic and clinical burden related to HCV is staggering. Accordingly, it is essential to identify risk factors for transmission of HCV and implement appropriate precautions to decrease the prevalence of this emerging infection. The relative importance of the two most common types of exposures associated with transmission of HCV, ie, blood transfusion and injection drug use, has evolved over time. Strict blood-donor selection and the use of reliable serological tests have led to a significant reduction in transfusion-associated risk. Injection drug use is currently the single most important risk factor for HCV infection in the United States. Transmission of HCV poses a serious threat to healthcare workers and patients if infection control techniques or disinfection procedures are inadequate. Potential exposures include contact of the eyes, mucous membranes, broken skin, or needlestick injury. Hospitalized patients may serve as a reservoir for transmission, and the prevalence of anti-HCV seropositivity among such patients can be as high as 20%. The infected healthcare worker is a potential source of transmission. A recent molecular phylogenetic analysis demonstrated that a cardiac surgeon likely transmitted HCV to five of his patients during open heart surgery. In summary, nosocomial transmission has been unequivocally confirmed and underscores the need for strict infection control practices.

Base Sequence↗
PubMed2000

Humoral immune response to hepatitis C after liver transplantation: assessment of a new recombinant immunoblot assay.

OBJECTIVE: The immune control of infection with hepatitis C virus (HCV) is poorly understood; vigorous antibody responses to viral proteins seem to coexist with the virus and thus whether they are neutralizing remains controversial. HCV-related liver failure is the leading indication for orthotopic liver transplantation (OLT) worldwide. Attenuated antibody responses in immunosuppressed patients and decreased reliability compared to assessment of HCV RNA has hampered the use of antibody testing post-OLT. The goals of this current analysis were twofold: to determine the sensitivity of a prototype strip immunoblot assay (RIBA 3.0, Chiron Diagnostics) for the diagnosis of HCV post-OLT; to determine if there was a correlation between antibody response and severity of histological recurrence. METHODS: The study was comprised of 76 HCV-positive individuals divided into three patient groups: liver allograft recipients with evidence of mild or no histological recurrence (n = 52), liver allograft recipients with evidence of severe HCV recurrence and allograft cirrhosis (n = 12), and nontransplant patients being enrolled in an induction interferon trial (n = 12). All transplant patients had histological follow-up of at least 1 yr. RESULTS: Sixty of the 64 (94%) HCV-positive OLT recipients had 1+ reactivity to two or more recombinant antigens; three of the patients who lacked a detectable response had minimal histological recurrence and one had severe recurrence. All nontransplant patients demonstrated 4+ reactivity to at least two antigens, and 55/64 (86%) OLT recipients demonstrated this same level of reactivity. Seven of the nine patients lacking this high level of reactivity had evidence of minimal recurrence. Furthermore, the mean (+/- SEM) level of antibody reactivity for c100 (p = 0.04) and NS5 (p = 0.01) were significantly lower for patients with mild recurrence after OLT, compared to the other groups. The level of antibody reactivity was unrelated to HCV genotype or viral load. CONCLUSIONS: The recently developed RIBA 3.0 assay for detection of antibodies to HCV appears to be highly sensitive for the diagnosis of HCV post-OLT. In general, the level of antibody reactivity was comparable in the transplant patients and in nonimmunosuppressed controls. The pathogenic implications of the relatively diminished humoral response in patients with mild recurrence post-OLT are discussed.

Antibody Formation↗
PubMed2000

Development and evaluation of the Liver Disease Quality of Life instrument in persons with advanced, chronic liver disease--the LDQOL 1.0.

OBJECTIVES: Assessment of health-related quality of life (HRQOL) outcomes in studies of liver disease and liver transplantation is necessary. Reliable and valid disease-targeted HRQOL measures are thus needed. The objective of this study was to develop a reliable and valid self-report HRQOL instrument for ambulatory adults with chronic liver disease. METHODS: The Liver Disease Quality of Life instrument, LDQOL 1.0 (an HRQOL measure that uses the SF-36 as a generic core and 12 disease-targeted multi-item scales) was administered in a multicenter, cross-sectional field test to 221 ambulatory adults with advanced, chronic liver disease referred for primary liver transplantation evaluation. Disease-targeted scales included liver disease-related symptoms, liver disease-related effects on activities of daily living, concentration, memory, sexual functioning, sexual problems, sleep, loneliness, hopelessness, quality of social interaction, health distress, and self-perceived stigma of liver disease. We estimated the internal consistency reliability (Cronbach's alpha) for multi-item scales and construct validity. RESULTS: Interial consistency reliability coefficients were excellent, ranging from 0.62 to 0.95, with 19 of 20 scales >0.70. Multitrait scaling analysis provided strong support for item discrimination across scales, and exploratory factor analysis demonstrated distinguishable physical, mental, and social health dimensions. Significant associations were found between worse HRQOL and worse Child-Pugh class, worse self-rated liver disease severity, and increased number of disability days. CONCLUSIONS: The results of this multicenter field test provide support for the reliability and validity of the LDQOL 1.0 as an HRQOL outcome measure for individuals with chronic liver disease.

Chronic Disease↗
PubMed2000

MR imaging for the preoperative planning of sphincter-saving surgery for tumors of the lower third of the rectum: use of intravenous and endorectal contrast materials.

PURPOSE: To evaluate the value of magnetic resonance (MR) imaging with a flexible surface coil in predicting the resectability of tumors in the lower rectum and the feasibility of sphincteral salvage. MATERIALS AND METHODS: In a prospective study, 61 patients with histologically proved primary adenocarcinoma of the lower or middle third of the rectum (<12 cm from the pectinate line) were examined at double-contrast-material-enhanced MR imaging with a circular polarized flexible surface coil. RESULTS: Assessment of anal sphincteral infiltration at MR imaging was excellent, with a specificity of 98% and a sensitivity of 100%. In the determination of tumor infiltration into adjacent organs (T4), the specificity was 100%, and the sensitivity was 90%, with surgical and histologic findings as the standards. While MR imaging showed negative nodes in 40 patients (stage N0 at MR imaging), histologic examination showed negative nodes in 27 patients and positive nodes in 34. At MR imaging, sensitivity was 68%, and specificity was 24%. CONCLUSION: While preoperative staging at MR imaging according to the TNM system still has limited value and accuracy, MR imaging provides the surgeon with valuable information regarding the presence of sphincteral invasion and the surrounding structures in patients with cancers in the lower third of the rectum.

Adenocarcinoma↗
PubMed2000

Preservation and restoration of sphincter function in patients with rectal cancer.

Radical resection of rectal cancer is the standard treatment for curing this disease. Half of these tumours are located in the rectosigmoid region or the upper third of the rectum and are, therefore, easily resectable with preservation of the sphincter muscles, thus guaranteeing acceptable continence in most patients. However, tumours that originate in the lower parts of the rectum have been accompanied with the need for an abdominoperineal resection and the threat of a permanent colostomy. In the past 20 years, sphincter-saving surgery has become increasingly common in the treatment of tumours of the middle and low rectum due to the knowledge of tumour growth, the use of stapling devices, and the knowledge of the physiology of the pelvic floor and the sphincter muscles, respectively. Recent surgical techniques of resection of the 'ultralow' rectum (intersphincteric resection) and the reconstruction by coloanal anastomosis are reviewed. Functional problems following ultralow resections are emphasized, as well as the possibility of sphincter restoration after abdominoperineal resection by use of dynamic graciloplasty. Taking all surgical options into account, a permanent colostomy for rectal cancer can be avoided in most curatively and electively operated patients.

Anal Canal↗
PubMed2000

Abnormal findings on liver function tests. Interpreting results to narrow the diagnosis and establish a prognosis.

Evaluating abnormal liver test results requires careful attention to the corresponding clinical data obtained during history taking and physical examination. Generally, it is helpful to separate liver tests into three categories: tests that assess synthetic function, tests that assess hepatocellular necrosis (hepatocellular enzymes), and tests that assess cholestasis. The clinical setting together with the specific pattern of liver function abnormalities can narrow differential diagnosis and provide a cost-effective approach to assessing patients and identifying those who need liver biopsy.

Alanine Transaminase↗
PubMed1999

Donor polymorphism of tumor necrosis factor gene: relationship with variable severity of hepatitis C recurrence after liver transplantation.

BACKGROUND: Hepatitis C-related liver failure is the leading indication for liver transplantation worldwide. Although histologic recurrence is identified in the majority of patients, the spectrum of allograft injury is wide. To date, most studies have focused on the contribution of immunosuppression and viral factors. We hypothesized that the allograft plays a significant role in determining timing and severity of hepatitis C virus (HCV) recurrence. The purpose of this analysis was to determine if genetic polymorphisms of the tumor necrosis factor (TNF) locus were associated with the highly variable severity of HCV recurrence. METHODS: Thirty-one HCV-seropositive liver transplant recipients with long-term follow-up were studied. Genomic DNA was extracted from archived donor spleens which corresponded to each patient. We performed polymerase chain reaction amplification, followed by sequencing for two promoter TNF-alpha variants (at positions -238 and -308), and restriction fragment length analysis for four polymorphic loci within the TNF-beta gene (NcoI, TNFc, aa13, and aa26). RESULTS: The relative prevalence of polymorphisms corresponded to distributions previously reported in normal control populations. Twenty-two of 31 (71%) patients received a donor liver homozygous for the wild type allele (TNF1) at the -308 TNF-alpha promoter region. The interval to histologic recurrence was significantly shorter and severity of HCV allograft hepatitis was significantly greater in patients with one or two TNF308.2 alleles. At last follow-up biopsy, 5 of 9 (56%) patients with a TNF308.2 donor liver had evidence of severe histological activity index as compared to 2 of 22 (9%) of patients receiving a donor liver homozygous for the TNF1 allele (P = 0.01). There was no correlation between rejection rates and the presence of any TNF-alpha or TNF-beta alleles. TNF-beta polymorphisms within the donor liver did not correlate with severity of HCV recurrence. CONCLUSIONS: The donor TNF-alpha promoter genotype may influence the inflammatory response to HCV reinfection of the graft and contribute to accelerated graft injury. If the association between this genetic marker (TNF308.2) and disease progression is confirmed, it could improve our understanding of HCV pathogenesis and influence donor selection and patient management.

Alleles↗