Outcome of anti-HBe positive chronic hepatitis B in alpha-interferon treated and untreated patients: a long term cohort study

BACKGROUND/AIMS: We studied the influence of biochemical and virologic patterns and interferon on the outcome of anti-HBe positive chronic hepatitis B in 164 (103 treated) consecutive patients, followed-up prospectively for a mean of 6 years (21 months-12 years). METHODS: Histology, biochemical and virologic profiles were characterized by monthly monitoring during the first 12 months of follow-up. Thereafter patients underwent blood and clinical controls every 4 and 6 months, respectively. Cirrhosis at follow-up histology or end stage complications of cirrhosis served as end points for the analysis of factors influencing disease progression in patients with baseline chronic hepatitis or cirrhosis, respectively. RESULTS: Disease progression was associated with older age (P<0.001), absence of previous HBeAg history (P=0.017) and higher serum HBV-DNA levels (P=0.009) (more frequently observed in unremitting disease profile, P=0.012) at multivariate analysis. Fluctuations of IgM anti-HBc levels (associated with disease exacerbations, P=0.045) correlated with end stage complications in cirrhotics (P=0.011). Disease improved in 14.6 and 1.6% of treated and untreated patients, respectively (P=0.015): interferon slowed disease progression (P<0.001). CONCLUSIONS: The outcome of anti-HBe positive chronic hepatitis B is worsened by older age and persistent viral replication or hepatitis exacerbations in chronic hepatitis or in cirrhotic patients, respectively. Interferon reduces by 2.5-folds disease progression.     

Evidence for hydrophobic region within heavy chains of mouse B lymphocyte membrane-bound IgM

The gel filtration behavior, in the presence of detergents, of membrane-bound IgM from normal mouse spleen B lymphocytes was compared to that of secretory IgM from mouse plasma cells. The proteins were labeled either by surface radioiodination or biosynthetically with radioactive amino acids. Cell lysates were fractionated on calibrated Sepharose 6B columns in the presence of the detergents Nonidet P-40 or deoxycholate. Eluted fractions were immunoprecipitated and the reduced or unreduced precipitates were analyzed by sodium dodecyl sulfate gel electrophoresis followed by radioautography. Surface (125)I-labeled 8S IgM exhibited a gel filtration pattern in Nonidet P-40 corresponding to much higher apparent molecular weight than that of secretory 8S IgM, a difference that almost disappeared when gel filtration was performed in the presence of deoxycholate, which forms much smaller micelles than does Nonidet P-40. Biosynthetically labeled lymphocytes contain two types of IgM molecules differing in their gel filtration behavior and fate: one identical to secretory 8S IgM of plasma cells and secreted in the medium during chase periods, and the other identical to surface (125)I-labeled IgM and remaining cell-associated. Because the surface-bound 8S IgM was not found to be associated with other labeled molecules, it is likely that the detergent-binding behavior of surface IgM is due to a hydrophobic segment carried by these Ig molecules. That lymphocytes synthesize two types of mu chains was also shown by the use of tunicamycin, an inhibitor of glycosylation. In its presence, two unglycosylated mu chains were observed: one identical in size to that made by tunicamycin-treated plasma cells, and the second slightly larger. Gel filtration in Nonidet P-40 of the cell lysates of tunicamycin-treated lymphocytes showed that the nonsecretory 8S IgM contains this second type of mu chains, whereas the IgM molecules of the secretory type contain plasma cell-like mu chains. It is suggested that membrane IgM mu chains contain a hydrophobic segment which is responsible for its association to the membrane.     

The identification of psychiatric illness by primary care physicians

Objective:This study tested several hypotheses about why women are more likely than men to have psychiatric disorders noted by their primary care physicians. Design:Patients were screened for mental disorders using the General Health Questionnaire. A stratified sample was assessed using the Schedule for Affective Disorders and Schizophrenia. Information on utilization and identification of mental bealth problems was abstracted from the medical records. Setting:The study was conducted at a multispecialty group practice in a semirural area of Wisconsin. Patients:Study participants consisted of a stratified probability sample of 247 patients seeking primary care. Results:Patients with a psychiatric illness who were relatively frequent users of the clinic were most likely to be identified by a physician as having a mental health problem. When psychiatric illness and utilization rates were statistically controlled, men and women had comparable identification rates. Supported in part by a contract (DBE-77-0071) and grant from the National Institute of Mental Health (MH-33940) and a grant from the Robert Wood Johnson Foundation.     

A Hypertransfused Mouse Assay for Thrombopoietic Factors

A method was developed for the quantitative separation of platelets from CF1mouse whole blood. This made it possibleto determine the platelet incorporation of³⁵S-sulfate without the necessity of doingplatelet counts. Daily hypertransfusions ofthe mice to three to four times normalplatelet levels for 4-5 days significantlyreduced platelet uptake of radiosulfate toan average of about 40% of the nontransfused controls. Mice rendered thrombocytopenic 48 hr earlier by antiplateletserum, had 2-day ³⁵S uptakes over 2 1/2times the controls and 6 times the hypertransfused animals. The administration of atotal of 2 ml of serum, given twice daily for3 days from a thrombocytopenic patientwith Hodgkin's disease caused a highlysignificant 103% rise in radiosulfate incorporation when compared with saline in thehypertransfused mouse. Normal humanserum from a healthy donor caused a smalland insignificant rise. The serum from a patient with Hodgkin's disease caused ahighly significant 63% rise in ³⁵S incorporation when compared to the normal serum.

Submitted on June 19, 1972 Revised on March 10, 1973 Accepted on March 10, 1973     

Acute infarction of the left ventricular papillary muscle: Electrocardiographic pattern and recognition of its location

Background and hypothesis: ST-segment depression during acute myocardial infarction (AMI) is known to herald serious hemodynamic complications. Since the mechanism of this dependence is not clear, we reinvestigated the old concept of papillary muscle infarction (PMI) as a cause of marked ST depression. Methods: Autopsies and morpho-electrocardiographic correlations were performed in 53 patients with AMI involving one or both left ventricular papillary muscles, and in 10 patients with AMI, but without acute PMI. Results: ST-segment depression ≥l mm in at least two leads (mean 3.6 ± 2.2 mm) was found in 46 (86.8%) patients with, and in one without acute PMI. Thus, the sensitivity and specificity in selecting patients with acute PMI from among those with AMI were 86.8 and 90%, respectively, with an overall accuracy of diagnosis of acute PMI in the course of AMI of 87.3%. Among 26 patients with ST elevation consistent with diagnosis of AMI, ST depression, recorded in 22 patients, was insignificantly greater than in 24 of 27 patients without ST elevation: 4.1 ± 2.9 versus 3.1 ± 1.2 mm. Localization of ST depression in the limb leads allowed recognition of which papillary muscle suffered from acute infarction: ST depression in the inferior leads was seen only in patients with anterolateral PMI, whereas in leads I and/or aVL it was seen only in cases with posteromedial PMI. This rule was also valid in patients without concomitant ST elevation. Conclusion: Patients with acute PMI show marked ST-segment depression. Its location in the limb leads allows recognition of which papillary muscle has undergone necrosis. This cause of marked ST depression in patients with AMI may explain the high mortality in this particular group.     

Screening for colorectal cancer on the front line

OBJECTIVE: The aim of this study was to assess knowledge, beliefs, and practices of primary care clinicians regarding colorectal cancer screening. METHODS: We surveyed 77 primary care providers in six clinics in central Massachusetts to evaluate several factors related to colorectal cancer screening. RESULTS: Most agreed with guidelines for fecal occult blood test (97%) and sigmoidoscopy (87%), which were reported commonly as usual practice. Although the majority (86%) recommended colonoscopy as a colorectal cancer screening test, it was infrequently reported as usual practice. Also, 36% considered barium enema a colorectal cancer screening option, and it was rarely reported as usual practice. Despite lack of evidence supporting effectiveness, digital rectal examinations and in-office fecal occult blood test were commonly reported as usual practice. However, these were usually reported in combination with a guideline-endorsed testing option. Although only 10% reported that fecal occult blood test/home was frequently refused, 60% reported sigmoidoscopy was. Frequently cited patient barriers to sigmoidoscopy compliance included fear the procedure would hurt and that patients assume symptoms occur if there is a problem. Perceptions of health systems barriers to sigmoidoscopy were less strong. CONCLUSIONS: Most providers recommended guideline-endorsed colorectal cancer screening. However, patient refusal for sigmoidoscopy was common. Results indicate that multiple levels of intervention, including patient and provider education and systems strategies, may help increase prevalence.     

Interrelationships between body weight, body fat distribution and insulin in obese women before and after hypocaloric feeding and weight loss

The effects were investigated of weight loss on the relationship between hyperinsulinemia, body weight and body fat distribution in two groups of women with central-type obesity (CTO) (waist-to-hip ratio WHR greater than 0.85) or peripheral-type obesity (PTO) (WHR less than 0.85). An oral glucose tolerance test was carried out before and after a hypocaloric nutritional treatment lasting 4 months. Both groups were matched for age, body mass index and amount of body fat. At the basal condition, group CTO had fasting and glucose-stimulated insulin levels significantly higher than group PTO; fasting (but not stimulated) C peptide levels were also higher in CTO compared with PTO. Weight and fat loss were significantly higher in CTO than in PTO women. Moreover, unlike PTO, CTO subjects significantly reduced their WHR values. In both groups weight loss led to a significant drop in fasting and glucose-stimulated insulin and C peptide levels. However, PTO women reduced their C peptide levels significantly less than CTO. In conclusion, weight loss only modified body fat distribution in women with CTO, who appeared to be prone to a greater weight loss than the PTO women. Compared to PTO, CTO women were characterized by higher insulin levels and peripheral insulin resistance, which improved during hypocaloric feeding probably due to the combined effect of weight loss and the change in body fat distribution.     

Lessons Learned about Implementing Research Evidence into Clinical Practice

The mission of the Veterans Health Administration's (VHA) quality enhancement research initiative (QUERI) is to enhance the quality of VHA health care by implementing clinical research findings into routine care. This paper presents lessons that QUERI investigators have learned through their initial attempts to pursue the QUERI mission. The lessons in this paper represent those that were common across multiple QUERI projects and were mutually agreed on as having substantial impact on the success of implementation. While the lessons are consistent with commonly recognized ingredients of successful implementation efforts, the examples highlight the fact that, even with a thorough knowledge of the literature and thoughtful planning, unexpected circumstances arise during implementation efforts that require flexibility and adaptability. The findings stress the importance of utilizing formative evaluation techniques to identify barriers to successful implementation and strategies to address these barriers.     

Pseudo-obstruction syndromes

Chronic intestinal pseudo-obstruction (CIP) is a clinical syndrome characterized by symptoms and signs of intestinal occlusion, in absence of any mechanical obstruction of the gut lumen. It causes impaired transit of intestinal contents and is determined by abnormalities of motor activity. The term CIP is used to indicate a heterogeneous group of disorders with many different pathogenic mechanisms. The defect in the regulation of intestinal transit can be at any level of motility control. Two main types of CIP are recognized, termed respectively myogenic (when smooth muscle cells are affected) and neurogenic (caused by abnormalities of extrinsic and/or intrinsic nervous supplies). Both types may be secondary to a variety of recognizable diseases or idiopathic. In myogenic CIP, intestinal transit is impaired because of lack of propulsive strength; in the neurogenic form, contractions are powerful but not sufficiently co-ordinated to propel intestinal contents aborally in an organized fashion. CIP belongs to the large and loosely defined group of digestive functional disorders. These disorders probably share common pathogenic mechanisms but with different expressiveness. The reasons why only some patients present recurrent symptomatological bouts resembling mechanical occlusion has not been clarified. This aspect is of great clinical relevance and deserves attention, as CIP patients, unlike other patients with severe functional disorders, may undergo repeated, useless and potentially dangerous operations. The diagnosis of CIP may be suggested by clinical features and is based on radiological, endoscopic, manometric, and histological findings. Recent technological improvements facilitate the recognition of this intriguing syndrome. In particular, manometric recording of the small bowel motility, which has long been considered an important research technique, can now also be regarded as a useful diagnostic tool.     

The possible utility of steroids in the prevention of relapses of Crohn's disease in remission. A preliminary study

In Crohn's disease, prednisone is believed to be ineffective for relapse prevention. Because all patients with Crohn's Disease Activity Index lower than 150 and with some altered lab tests (erythrocyte sedimentation rate, C-reactive protein, alpha-1-acid glycoprotein, alpha-1-acid antitrypsin, and white blood cell count) had a clinical relapse in 18 months of follow-up, we tried to ascertain whether methylprednisolone could reduce the risk of clinical relapse in such patients. Eighteen patients were included in a controlled study against placebo. Nine patients were treated with methylprednisolone at a dosage of 0.25 mg/kg daily for a period of 6 months; treatment was discontinued if disease relapsed or if lab tests were normalized. During the steroid treatment, 1 of 9 patients showed a clinical relapse; in 7, the normalization of lab tests was obtained; in 5 of these 7 patients a relapse occurred within 1 month after the suspension of the treatment; in 1 patient, lab tests remained altered. In those 9 patients on placebo, relapses occurred in 7. We conclude that methylprednisolone was effective in the prevention of relapses for patients in clinical remission but with altered lab tests.