Peginterferon alfa-2b plus weight-based ribavirin for 24 weeks in patients with chronic hepatitis C virus genotype 1 with low viral load who achieve rapid viral response.

In chronic hepatitis C (CHC), treatment duration may be individualized according to time to first undetectable hepatitis C virus (HCV) RNA, with patients who attain undetectable HCV RNA early in treatment being candidates for shorter regimens. The aim of this study was to determine the relapse rate in patients with CHC genotype (G) 1 infection and low baseline viral load who achieved undetectable HCV RNA by week 4 [rapid virologic response (RVR)] when treated for 24 weeks. This was an open-label, multicentre, noninterventional study. Adult patients with G1 CHC infection and baseline viral load <600,000 IU/mL who attained RVR were treated with peginterferon alfa-2b (1.5 µg/kg/week) plus ribavirin (800-1200 mg/day) for 24 weeks, then followed for a further 24 weeks. The primary endpoint was relapse rate, defined as the proportion of patients with undetectable HCV RNA at treatment week 24 and detectable HCV RNA at week 24 follow-up. The secondary efficacy endpoint was sustained virologic response (SVR). Overall, 170 patients were included in the efficacy-evaluable population. The relapse rate was 9.7% (16/165, 95% confidence interval: 0.06-0.15), and SVR was attained by 149 of 170 patients (87.6%). Virologic outcomes were consistent regardless of age, gender, body weight and genotype. Seven patients reported treatment-emergent serious adverse events (AEs), and four patients discontinued treatment because of an AE. This study further demonstrates that peginterferon alfa-2b plus weight-based ribavirin for 24 weeks is an effective treatment strategy for treatment-naive patients with G1 CHC and low viral load who attain RVR.

Design and baseline characteristics for the ACE Inhibitor After Anthracycline (AAA) study of cardiac dysfunction in long-term pediatric cancer survivors.

PURPOSE: The ACE Inhibitor After Anthracycline (AAA) study is a randomized, double-blind, controlled clinical trial comparing enalapril with placebo to determine whether treatment can slow the progression of cardiac decline in patients who screen positive for anthracycline cardiotoxicity. METHODS: The primary outcome measure is the rate of decline, over time, in maximal cardiac index (in liters per minute per meters squared) at peak exercise; the secondary outcome measure is the rate of increase in left ventricular end systolic wall stress (in grams per centimeters squared). Patients >2 years off therapy and <4 years from diagnosis, aged 8 years and older, were eligible if they had received anthracyclines and had at least one cardiac abnormality identified at any time after anthracycline exposure. RESULTS: A total of 135 patients were randomized to enalapril or placebo. Baseline characteristics were similar across treatment groups. CONCLUSIONS: The AAA study will provide important information concerning the efficacy of using angiotensin-converting enzyme inhibitors to offset the effects of late anthracycline cardiotoxicity.

Intestinal permeability in Crohn's disease patients and their first degree relatives.

BACKGROUND: Family studies suggested that an altered intestinal permeability plays a role in the genesis of Crohn's disease. AIM: Aim of the present study was to investigate a possible genetic alteration of the mucosal barrier in Crohn's disease. SUBJECTS: 16 Crohn's disease patients and 26 of their cohabiting first degree relatives were studied. METHODS: To investigate intestinal permeability, Cellobiose/Mannitol test was administered to both groups. RESULTS: In the two groups, we found that the median intestinal permeability values were higher and statistically different from those obtained in 32 healthy control subjects as well as in five healthy control families. Six (37.5%) Crohn's disease patients and three (11.5%) of their first degree relatives showed increased individual intestinal permeability values. Intestinal permeability alteration in Crohn's disease patients was unrelated to sex, age, disease activity, localisation, duration, treatment schedule, as well as to serum anti-Saccharomyces cervisiae antibody positivity in a pilot study conducted in 7 Crohn's disease patients; anti-Saccharomyces cervisiae antibody values were negative in all 10 first degree relatives investigated. CONCLUSIONS: These findings demonstrate the increase in IP in 37% of the patients and in 11% of their relatives. More extensive investigation of the correlation between ASCA alterations and IP will be needed in both patients with Crohn's disease and their relatives.

Age-related clinical severity at diagnosis in 1705 patients with ulcerative colitis: a study by GISC (Italian Colon-Rectum Study Group).

Clinical-endoscopic parameters of UC presentation were studied in 1705 out-patients, observed consecutively in 17 Italian gastroenterology centers (males 60.2%; average age at diagnosis 38.5 +/- 16.4 years), and were subdivided arbitrarily into quartile age groups at diagnosis (0-25, 26-35, 36-50, >50). A significantly greater prevalence in males, increasing with age, was shown at diagnosis (P = 0.0002), which seems to correlate with the condition of being an ex-smoker, most frequently found in males. The greater frequency of exsmokers could also, in part, justify the second peak of incidence in old age. Greater colitis extent, greater clinical activity, and greater use of steroids as the first therapeutic step are shown to prevail among younger patients and among women (P = 0.02 and P = 0.019, respectively). The same is observed for symptoms mainly representing clinical severity such as diarrhea, fever, and weight loss (P = 0.004; P = 0.006; P = 0.009, respectively). This study confirms the UC risk factor represented by the condition of being an ex-smoker and shows a greater severity of illness on diagnosis in younger patients.

[Changes in the mouth mucosa in patients with chronic inflammatory intestinal diseases]. / Alterazioni della mucosa orale in pazienti affetti da malattie infiammatorie croniche intestinali.

BACKGROUND: Oral mucosa and periodontal lesions occurrence in Inflammatory Bowel Disease (IBD), Ulcerative Colitis (UC) and Crohn Disease (CD). METHODS: This study involved 100 patients examined for 5 years (1990/1995), with a clinical and histopathological diagnosis of CD (21 patients) and UC (79 patients). RESULTS: The analysis of the data obtained, from our sample, showed that 5 patients out of 100 presented aphtha minor lesions; in 3 cases the diagnosis was, respectively, of two neoformations of the genian mucosa--which turned out to be a papilloma and a fibroma--and a retro-commissural leukoplakia, degree OIN I. The 50% of our patients presented parodontal lesions, oral candidosis in 15 out of 67 patients who presented a whitish coating on the back of the tongue. CONCLUSIONS: The results of this investigation, lessen the importance of an association between IBD and oral diseases.

Prevalence and relative risk of malignancy in relatives of inflammatory bowel disease patients and control subjects.

The relation between inflammatory bowel disease (IBD) and colorectal cancer (CRC) is not clearly defined. Some investigators suggest that patients with extensive colitis have a genetic predisposition to CRC and that long-standing inflammation is not of primary importance in the promotion of cancer. We have assessed any increased risk of colon cancer in the relatives of IBD patients. We studied the prevalence of malignancy in the relatives of 251 IBD patients [198 ulcerative colitis (UC); 53 Crohn's disease of the colon (CDC)] and 251 orthopedic patients (ORTHO) as controls. In all patients (UC, CDC) as well as in controls (ORTHO) the prevalence of colon, extracolic digestive and extradigestive malignant tumors in the first-degree relatives was evaluated. We found no significant difference in the number of colorectal tumors or of tumors of any other kind in the diverse group of relatives of patients with IBD and ORTHO patients. Our data do not point to the existence of hereditary factors linking UC or CDC to CRC.

[Surgical day hospital: technical possibilities and organizational model]. / Day hospital in chirurgia: possibilità techniche e modello organizzativo.

The Authors propose an organizational model for a surgical day hospital program, which is being used for a pilot day surgery unit in the I Department of Surgery of the Rome University "La Sapienza". The program requires little capital investment, as it is closely linked, geographically and administratively, to the main surgical unit, and uses the present staff, facilities and support services. The model is based on a computerized LAN (Local Area Network), providing fast recording, scheduling, management and trannsfer of medical data for each patient. The present situation is reported in detail. Data from the authors' outpatient department for 1988, have been recorded and elaborated. The results show a low use of surgical day care, limited to minor surgical procedures, and with not a single operation performed under general anesthesia. The authors hope to see a growth in the use of day surgery and a more selective use of inpatient care.

Human central nervous system primitive neuroectodermal tumor expressing nerve growth factor receptors: CHP707m.

A primitive neuroectodermal tumor (PNET) presented as a cerebral hemispheric mass in a 33-year-old man. Bone marrow metastases were discovered 11 months later. A cell line (CHP707m) was derived from these metastases. In culture, the cells showed features of neuronal differentiation, forming short neurites and synthesizing low-molecular-weight neurofilament protein. Northern blotting showed the tumor cells express nerve growth factor (NGF) receptor messenger RNA, and fluorescence-activated cell-sorting demonstrated NGF receptors on the cell surface. Western blotting showed CHP707m NGF receptors are truncated. The receptors are functional; they bind iodine 125-labeled mouse NGF with an affinity of 1.6 x 10(-9) M, and short-term treatment with NGF induces expression by the tumor cells of the proto-oncogene, c-fos. Although CHP707m is the first central nervous system PNET cell line proven to express NGF receptors, immunohistological survey of tissue sections prepared from human central nervous system PNETs showed that 13 of 35 contained NGF receptor-positive tumor cells. Thus, more than one-third of such tumors might be responsive to the effects of NGF.

The effects of gamma interferon on the natural killer and tumor cells of children with neuroblastoma. A preliminary report.

Human neuroblastoma cells lack HLA-A,-B,-C molecules which can be induced in vitro by gamma interferon (gamma IFN). To test the hypothesis that the same induction would occur in vivo leading to tumor regression, a Phase I study was initiated. Seven patients with neuroblastoma were entered on a Phase I study of recombinant gamma IFN in children. Three received 0.05 mg/m2 intravenously (IV) three times a week, three received 0.1 mg/m2 for 4 weeks, and one patient withdrew from study before receiving adequate treatment for evaluation. No significant clinical response was seen. The side effects were fever and chills, and no serious toxicity occurred. Natural killer (NK) and lymphocyte activated killer (LAK) precursor activity of peripheral blood mononuclear cells was determined before and during treatment, and expression of HLA-A,B,C molecules was looked for on the tumor cells in the bone marrow of five patients. The NK activity initially low, reached control levels in six patients, but the increase was transient. The LAK precursor activity remained normal. Expression of HLA-A,B,C, initially absent, was induced on the neuroblastoma cells in four of six patients.

Selection of variant neuroblastoma cell line which has lost cell surface expression of antigen detected by monoclonal antibody PI153/3.

A variant of the human neuroblastoma cell line, IMR-5, was selected by a series of treatments with the monoclonal antibody PI153/3 and complement. The variant, M-1, was not reactive by either cytotoxicity or binding assays with the PI153/3 antibody or with two other monoclonal antibodies that were selected on the basis of their inhibition of PI153/3 binding. Although no antigen could be detected on the cell surface or in the supernatant of the variant cell line, a reduced level of binding could be detected in M1 cell extracts compared to extracts of IMR5. The variant cell line did not differ from IMR5 in its sensitivity in lysis by other antibodies, in its lack of expression of HLA antigens, or in its capacity to form tumors in nude mice.

A method of detecting neuroblastoma in human bone marrow by means of two monoclonal antibodies PI 153/3 and KE2.

A system is described to detect neuroblastoma (NBL) tumor cells in human bone marrow. The technique exploits the findings that NBL cells have little or no HLA antigen on the surface. Two monoclonal antibodies are used, PI153/3, IgM class, recognizes NBL and some pre-B lymphocytes and KE2 IgG class recognizes HLA. Two second antibodies are used, rhodamine-labeled anti-IgM and fluorescein-labeled anti-IgG. By means of fluorescence microscopy the neuroblastoma cells are labeled with rhodamine only, and the false + pre-B lymphocytes are double labeled with both rhodamine (Rh) and fluorescein (FI) since they are HLA+ and react with KE2. This method has been used to screen the marrow of 24 patients on 40 occasions and 64 laboratory preparations. It is possible to detect NBL cells at a concentration of 1:1000 marrow cells. The advantage of the technique is the fact that false positive cells can be defined because they have HLA surface antigen which neuroblastoma cells do not express.