The natural history of chronic airflow obstruction

A prospective epidemiological study of the early stages of the development of chronic obstructive pulmonary disease was performed on London working men. The findings showed that forced expiratory volume in one second (FEV1) falls gradually over a lifetime, but in most non-smokers and many smokers clinically significant airflow obstruction never develops. In susceptible people, however, smoking causes irreversible obstructive changes. If a susceptible smoker stops smoking he will not recover his lung function, but the average further rates of loss of FEV1 will revert to normal. Therefore, severe or fatal obstructive lung disease could be prevented by screening smokers' lung function in early middle age if those with reduced function could be induced to stop smoking. Infective processes and chronic mucus hypersecretion do not cause chronic airflow obstruction to progress more rapidly. There are thus two largely unrelated disease processes, chronic airflow obstruction and the hypersecretory disorder (including infective processes).     

The natural course of hepatitis B and hepatitis C virus infection

Chronic hepatitis B and hepatitis C virus infections maintain a significant risk for the development of liver cirrhosis and hepatocellular carcinoma and cause a considerable morbidity in the population. Among patients with chronic HBV infection and histologically confirmed hepatitis the annual incidence of liver cirrhosis is 2%. The risk for hepatocellular carcinoma in chronic HBsAg carriers is elevated about 40-230 fold. 20-30% of patients with chronic HCV infection will develop cirrhosis over 20-30 years. Hepatocellular carcinoma evolves yearly in about 3% of patients with chronic HCV infection and cirrhosis, whereas HCV-carriers without cirrhosis usually do not develop hepatocellular carcinoma. The high incidence of serious sequelae warrants a regular surveillance of chronic virus carriers.     

Large dose natural interferon alpha therapy for patients with chronic hepatitis C

To evaluate the efficacy of large dose interferon treatment for patients with chronic hepatitis C virus (HCV) infection, we studied 99 Japanese patients treated with either 6 million units (MU) or 9 MU natural interferon alpha. Serum samples were tested for HCV RNA by polymerase chain reaction (PCR). HCV RNA genotypes were determined by PCR with type-specific preimers, and the HCV RNA level was measured by competitive PCR. HCV RNA was detected in all patients, prior to the initiation of treatment. We examined interleukin-1 receptor antagonist (IL-1 Ra) by enzyme-linked immunosorbent assay. Forty-four patients were treated with 9 MU natural interferon alpha for 24 weeks (group A), and fifty-five patients were treated with 6 MU natural interferon alpha for 24 weeks (group B). There were no significant differences in HCV RNA levels, HCV RNA genotype or histological activity index (HAI) score between the two groups. Of the 94 patients who completed this treatment, nine (23.1%) in group A and 14 (25.5%) in group B sustained elimination of HCV RNA throughout a 6-month follow-up. There were no differences in the rate of complete response when comparing HCV RNA genotype, levels and HAI score and no significant differences in elevation of IL-1 Ra levels between the two groups. Five of group A patients refused further treatment because of severe side effects such as retinal hemorrhage, while no patient in group B had severe side effects. Thus, large dose natural interferon alpha treatment confers no additional benefit to the patient, compared with the current use of a lower dose.     

The influence of iron on chronic hepatitis C

BACKGROUND: This study was performed to evaluate antithrombin III levels in postmenopausal women receiving hormonal replacement treatment. METHODS: It is a prospective randomized study concerning 19 postmenopausal patients, aged 40 to 65 years, who received either continuous daily oral equine conjugated estrogen 0.625 mg (group A, N=10) or daily transdermal 17beta-estradiol 50 microg (group B, N=9). Medroxyprogesterone acetate (5 mg/day, 14 days monthly) was given to all patients. Blood samples were obtained before and after 3, 6, 9 and 12 months of treatment. Coagulation tests included Antithrombin III (functional method), prothrombin time, partial activated prothrombin time, thrombin time, factor V, fibrinogen, platelet count and euglobulin lysis time. Friedman analysis of variance and Mann-Whitney test were used for statistical analysis. RESULTS: Antithrombin III level was reduced (p<0.05) in group A but not in group B, although it remained within normal range. No changes were detected in the other coagulation tests. CONCLUSIONS: These data suggest that oral conjugated estrogen replacement reduces functional ATIII, whereas transdermal estradiol replacement therapy does not modify it.     

Therapy concepts in chronic hepatitis C

Patients with persistently normal transaminases and without inflammatory changes or fibrosis in liver biopsy have a low risk for progression, respond poorly to antiviral therapy and should thus not be treated for the present. Patients with significant histologic activity or advanced stage of fibrosis are at risk for progression towards cirrhosis. The risk is significantly increased with chronic alcohol consumption even in moderate doses. Treatment with interferon alone results in sustained virological remission in less than 20% of these patients. Treatment success, however, is 2 to 6 times higher under combined treatment with interferon plus ribavirin. The response rate may be further increased with high-dose and daily interferon administration (inductive dosing). The best treatment option for patients with chronic hepatitis C, therefore, is their inclusion in one of the study protocols (examining combinations and induction) currently active in Switzerland.     

Chronic hepatitis C: the virus, its discovery and the natural history of the disease

The value and necessity of performing right heart catheterizations for coronary artery disease have been increasingly questioned. Preliminary analyses of the procedure among Medicare and Medicaid patients in New York State revealed significant inter-hospital variations in the frequencies with which such catheterizations were performed. These data suggested that right heart catheterizations (RHC) were being performed routinely. Medicare and Medicaid claims data for bilateral catheterizations were analyzed before and after an educational intervention program involving the state's 53 catheterization laboratories. The educational intervention was multifaceted and consisted of disseminating suggested guidelines established with the assistance of the New York State Chapter of the American College of Cardiology, the Committee on Cardiovascular Disease of the Medical Society of the State of New York, and the Cardiac Advisory Council of the New York State Department of Health. Posteducational intervention assessments were made over a 4-year period. The baseline data for 1992 demonstrated that 10 (18.4%) laboratories had performed RHC routinely (70-100%) on Medicare and Medicaid patients undergoing catheterization. In contrast, 34 (64.2%) laboratories performed RHC in less than 20% of their Medicare cases, whereas 39 (73.5%) did so among Medicaid cases. Eighteen (34%) laboratories performed RHC in less than 10% of Medicare cases. These data indicated that there was significant inter-hospital variation in the frequency with which RHC was performed. Beginning in 1993, ongoing educational meetings and conferences were held with all laboratories, but especially with the 10 that were at the high end of the RHC performance level. As a result of this ongoing intervention, the rate of RHC among Medicare patients fell from 89/100,000 in 1992 to 65/100,000 beneficiaries in 1996. From another perspective, the percentage of catheterized Medicare patients undergoing RHC fell from 30.5% in 1992 to 17.4% in 1996. The decline among the 10 laboratories was even more dramatic; the percentage of catheterized Medicare patients undergoing RHC fell from 89.1% in 1992 to 31.6% in 1996. The parallel drop for Medicaid patients over the same time period was from 92.8 to 32.7%. The results of the study indicate that many previously performed RHC in patients with coronary artery disease were routine and not medically indicated. The dramatic decreases in RHC documented in this study over a 4-year period demonstrate the success of quality improvement efforts jointly undertaken by providers and a peer review organization.     

Persistent hepatitis C virus RNA replication in haemophiliacs: role of co-infection with human immunodeficiency virus

In order to evaluate the evolution of transfusional hepatitis C in haemophiliacs, we performed a retrospective study of ALT levels and HCV viraemia with a RNA PCR assay in 57 patients. We found that the vast majority of HCV-infected patients remained viraemic (43/57 = 75%) and higher ALT levels correlated with HCV viraemia. Although indicators of the transfusional viral load (age, severity of haemophilia) and HBV co-infection did not correlate with HCV RNA replication, HIV seropositivity was strongly associated with persistence of HCV viraemia (23/25 = 92% in HIV-positive versus 20/32 = 62% in HIV-negative patients), without any correlation with CD4 counts. Genotyping of HCV in the 43 viraemic patients shows more frequent genotype 1 in the HIV-seropositive group (14/23) than in the seronegative group (6/20). Our data emphasize that besides the role of the immunodeficiency status, the genotypes of HCV might be involved in the differences observed in terms of HCV RNA replication between the HIV-seropositive and seronegative haemophiliacs.     

The long term efficacy of glycyrrhizin in chronic hepatitis C patients

BACKGROUND: Hepatocellular carcinoma (HCC) occurs in patients with hepatitis C virus-RNA positive chronic liver disease. It is important to prevent HCC with drug administration. METHODS: A retrospective study was undertaken to evaluate the long term preventive effect of Stronger Neo-Minophagen C (SNMC) on HCC development. SNMC is a Japanese medicine that is commonly administered to patients with chronic hepatitis C to improve the serum alanine aminotransferase (ALT) level. Of 453 patients diagnosed with chronic hepatitis C retrospectively in the study hospital between January 1979 and April 1984, 84 patients (Group A) had been treated with SNMC; SNMC was given at a dose of 100 mL daily for 8 weeks, then 2-7 times a week for 2-16 years (median, 10.1 years). Another group of 109 patients (Group B) could not be treated with SNMC or interferon for a long period of time (median, 9.2 years) and were given other herbal medicine (such as vitamin K). The patients were retrospectively monitored, and the cumulative incidence of HCC and risk factors for HCC were examined. RESULTS: The 10th-year rates of cumulative HCC incidence for Groups A and B were 7% and 12%, respectively, and the 15th-year rates were 12% and 25%. By Cox regression analysis, the relative risk of HCC incidence in patients not treated with SNMC (Group B) was 2.49 compared with that of patients treated with SNMC (Group A). CONCLUSIONS: In this study, long term administration of SNMC in the treatment of chronic hepatitis C was effective in preventing liver carcinogenesis.     

The role of hepatitis C virus specific CD4+ T lymphocytes in acute and chronic hepatitis C

Since the discovery of hepatitis C virus it has become clear that chronic hepatitis C is a major health problem throughout the world. Because antiviral agents are of limited value in the treatment of chronic hepatitis C, research has focused on the antiviral immune response for the development of both a protective vaccine and effective immunotherapies for established chronic infection. Antiviral antibodies are present in almost all patients with chronic hepatitis C but do not seem to be virus neutralizing, probably due to the high mutational rate of viral envelope proteins. Studies on the antiviral T cell response have revealed the presence of virus-specific CD4+ helper and CD8+ cytotoxic T cells in a substantial proportion of patients with chronic hepatitis C. Recent studies describe an association between strong CD4+ T helper cell activity to certain hepatitis C virus antigens and a self-limited course of acute hepatitis C and possibly also a sustained response to treatment with interferon-alpha. Therapeutic manipulation of the virus-specific T cell response may thus develop into a new approach for prevention and treatment of hepatitis C virus infection.     

Effects of interferon-alpha on serum hepatitis C virus in patients with chronic hepatitis C

Interferon is beneficial in some patients with chronic hepatitis C. To assess the efficacy of interferon, we used the polymerase chain reaction (PCR) to measure HCV RNA in serial serum samples from 13 chronic hepatitis C patients who were treated with interferon-alpha. Serum alanine aminotransferase (ALT) values normalized in association with the disappearance of serum HCV RNA in nine cases during the therapy. Serum HCV remained negative after the therapy in the three patients who had no relapse, while serum HCV RNA reappeared in the six patients with elevation of ALT values. The persistence of normal ALT levels appears to be correlated with the clearance of the serum HCV. There were two patients whose ALT became normal immediately after the cessation of interferon. Serum HCV was detectable at the end of treatment when serum ALT was elevated, and thereafter serum HCV disappeared. This result suggests an immunomodulatory effect of interferon in the clearance of HCV in some cases. Furthermore, the semiquantitative PCR assay showed that all five patients in whom ALT values were normal at the end of follow-up without detectable serum HCV genome had lower HCV titers in the pretreatment sera than the other eight patients. The detection of HCV RNA by the PCR assay is useful in determining the efficacy of interferon and its mechanisms.     

A natural history study of chronic fatigue syndrome.

Objective: There is a need for natural history chronic fatigue syndrome (CFS) studies from random, community-based, multi-ethnic populations. Design: The present study examined the course of CFS from Wave 1 to Wave 2, which spanned over a ten year period of time, and, assessed whether socio-environmental and symptomatology factors were associated with CFS status over the ten year period. Results: There was relative stability over time on critical measures of disability, fatigue, support, optimism and coping over time. One cardinal symptoms of CFS, post-exertional malaise, best differentiated the CFS group from the others. By Wave 2, of the original group of 32 individuals diagnosed with CFS, 4 had died, and 24 were found and agreed to be re-evaluated, and of this group, 16 continued to have CFS, 5 developed exclusionary illnesses, 2 were classified as Idiopathic chronic fatigue, and one had remitted. Conclusions: The current study found that over time in a community-based sample, unbiased by help seeking behavior the CFS group remained rather ill with a variety of different conditions over time. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Treatment of chronic hepatitis C with amantadine

Treatment of chronic hepatitis C infection with interferon has been disappointing, with less than one third of patients achieving a sustained response and most experiencing significant side effects. For these reasons, an open-labeled prospective pilot study was conducted to test the safety and efficacy of the antiviral drug, amantadine, in patients with chronic hepatitis C infection who had previously failed therapy with interferon-alpha 2b. Twenty-two patients with chronic hepatitis C were enrolled into the study and treated with amantadine 100 mg orally twice daily for six months. Control groups included the same cohort followed off therapy for 29-36 months or during therapy with interferon. Serum alanine aminotransferase (ALT) values decreased in 64% (P = 0.01) of patients with amantadine therapy compared to intervals without therapy or to interferon therapy. Twenty-seven percent of patients treated with amantadine had normalization of ALT values and loss of HCV RNA after six months while 18% achieved a sustained response with loss of HCV RNA by PCR six months after discontinuation of amantadine. Therapy with amantadine improved both biochemical and virological markers in patients with hepatitis C who had previously not responded to treatment with interferon.     

The natural history of condyloma in children

OBJECTIVES: To prospectively evaluate our previously established pathologic risk factors in women undergoing cystectomy for bladder cancer and to determine if these criteria identify appropriate female candidates for orthotopic diversion. METHODS: Prospective pathologic evaluation was performed on 71 consecutive female cystectomy specimens removed for primary transitional cell carcinoma of the bladder. The histologic grade, pathologic stage, presence of carcinoma in situ, number, and location of tumors were determined. In addition, final pathologic analysis of the bladder neck and proximal urethra was performed and compared with the intraoperative frozen-section analysis of the distal margin (proximal urethra). RESULTS: Tumor at the bladder neck and proximal urethra was seen in 14 (19%) and 5 (7%) cystectomy specimens, respectively. Bladder neck tumor involvement was found to be the most significant risk factor for tumor involving the urethra (P <0.001). All patients with urethral tumors demonstrated concomitant bladder neck tumors. However, more than 60% of patients with bladder neck tumors had a normal (tumor-free) proximal urethra. Furthermore, no patient with a normal bladder neck demonstrated tumor involvement of the urethra. Intraoperative frozen-section analysis of the distal surgical margin was performed on 47 patients: 45 without evidence of tumor and 2 patients with urethral tumor involvement. In all cases, the intraoperative frozen-section analysis was correctly confirmed by final permanent section. CONCLUSIONS: We prospectively demonstrate that bladder neck tumor involvement is a significant risk factor for urethral tumor involvement in women. However, despite bladder neck tumor involvement, a number of women undergoing cystectomy for bladder cancer have a normal urethra and may be candidates for orthotopic diversion. Furthermore, our data demonstrate that intraoperative frozen-section analysis of the distal surgical margin accurately and reliably evaluates the proximal urethra and currently determines which patients undergo orthotopic diversion at our institution.