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1.
Hepatology ; 27(4): 1128-35, 1998 Apr.
Article in English | MEDLINE | ID: mdl-9537454

ABSTRACT

Hepatitis C is a major cause of liver disease leading to cirrhosis. Although interferon (IFN) is the only approved therapy, treatment is characterized by low response rates and dose-limiting side effects. We evaluated the addition of thymosin alpha1 (TA1), an immunomodulatory peptide, to the standard treatment regimen for hepatitis C to determine if combination therapy shows biological activity using outcome measures including normalization of alanine aminotransferase levels, histological activity, and viral load during treatment. We performed a randomized, double-blind, placebo-controlled trial to compare the biological activity of a combination TA1 and IFN with that seen for IFN alone in patients with chronic hepatitis C infection. One hundred nine patients were randomized for intention to treat and received 1.6 mg of TA1 subcutaneously twice weekly and 3 MU of IFN three times weekly; 3 MU of IFN three times weekly and placebo TA1; or placebo for both agents. All patients had chronic HCV infection with confirmation of chronic hepatitis on liver biopsy. Biochemical responders were followed up until alanine aminotransferase (ALT) levels became abnormal or for 26 weeks, and relapsers were retreated for 26 weeks in the same treatment arm. One hundred three patients completed treatment for 26 weeks, and six patients dropped out. The groups were similar with regard to sex, gender distribution, baseline histological activity index (HAI) score, risk factors, and viral titers. End-of-treatment biochemical response was seen in 37.1% of patients treated with combination therapy, 16.2% of patients treated with IFN alone, and 2.7% of untreated controls by intent-to-treat analysis (IFN/TA1 vs. IFN, chi2 = 4.05, P = .04). HCV RNA clearance was seen in 37.1% of IFN/TA1-treated patients and 18.9% of IFN-treated subjects. Mean HCV RNA titers were significantly lower than baseline at weeks 8, 16, and 24 after drug initiation among patients treated with IFN/TA1 but not in the other treatment arms. Histological improvement, as evidenced by a decrease in HAI of more than two points, occurred in the combination therapy arm more frequently than in comparison groups. Cumulative sustained biochemical responses were 14.2% and 8.1% in the IFN/TA1 and IFN arms, respectively, based on an intention-to-treat model. The combination of TA1 and standard IFN treatment for chronic hepatitis C showed evidence of biological activity at the completion of treatment by biochemical, histological, and virological outcome measures. Further research involving longer duration and varied dosing is needed.


Subject(s)
Antiviral Agents/administration & dosage , Hepatitis C, Chronic/drug therapy , Interferon-alpha/administration & dosage , Thymosin/analogs & derivatives , Adult , Double-Blind Method , Drug Therapy, Combination , Female , Hepatitis C, Chronic/pathology , Hepatitis C, Chronic/virology , Humans , Interferon alpha-2 , Interferon-alpha/adverse effects , Male , Middle Aged , RNA, Viral/analysis , Recombinant Proteins , Thymalfasin , Thymosin/administration & dosage , Thymosin/adverse effects
2.
Arch Intern Med ; 157(18): 2064-8, 1997 Oct 13.
Article in English | MEDLINE | ID: mdl-9382661

ABSTRACT

BACKGROUND: Patients with abdominal aortic aneurysm often are followed up with serial ultrasound examinations, but published studies usually describe rupture risk according to the diameter of the abdominal aortic aneurysm at diagnosis rather than by most recent ultrasound. Information in this form is misleading when used to predict prognosis. METHODS: We used data from the population-based cohort of residents of Rochester, Minn, diagnosed as having abdominal aortic aneurysm who have had at least 1 ultrasound measurement. Of the 181 patients who were enrolled in this cohort between January 1, 1974, and December 31, 1988, 5 had clinical evidence of rupture at entry. Analysis of a cohort defined by size category at "last ultrasound" was undertaken to assess rupture risk and growth rate. RESULTS: Median overall aneurysmal growth rate was 0.21 cm/y. Initial growth rate did not correlate with subsequent growth rate (r = 0.18; P = .14) or with initial size (r = -0.12; P = .22). Only 1 aneurysm ruptured when last ultrasound was less than 5 cm, and this occurred 3 1/2 years after this ultrasound. Estimated rupture risk by last ultrasound was 0% per year (95% confidence interval [CI], 0%-5%) when less than 4.00 cm, 1.0% per year (95% CI, 0%-5%) when 4.00 to 4.99 cm, and 11% per year (95% CI, 1%-21%) when 5.00 to 5.99 cm. CONCLUSIONS: The most clinically useful approach to estimating the risk of abdominal aortic aneurysm rupture is according to size at last ultrasound. Aneurysm growth rate is predicted neither by size nor by initial growth rate.


Subject(s)
Aortic Aneurysm, Abdominal/diagnostic imaging , Aortic Aneurysm, Abdominal/pathology , Aortic Rupture/diagnostic imaging , Aged , Aged, 80 and over , Aortic Aneurysm, Abdominal/complications , Aortic Rupture/etiology , Female , Humans , Male , Middle Aged , Predictive Value of Tests , Prognosis , Risk , Time Factors , Ultrasonography
4.
Ann Allergy Asthma Immunol ; 75(2): 149-56, 1995 Aug.
Article in English | MEDLINE | ID: mdl-7648379

ABSTRACT

BACKGROUND: The observation of low levels of weed pollens following a freeze and an early autumn snowfall in Denver, Colorado led to this analysis of meteorologic variables and pollen counts. OBJECTIVE: The purpose of this study was to examine, in depth, the relationship between observed pollen counts and a selection of independent meteorologic variables. METHODS: We prospectively studied in 1991 daily high and low temperature, relative humidity, precipitation, barometric pressure, percent sunshine, wind velocity and direction, tree, grass, and weed pollen, as well as dates of the first frost/freeze. Similar data were retrospectively analyzed for 1987-1990. RESULTS: Correlation coefficients for the prospective data were as high as .611 for high temperature and cottonwood and .718 for high temperature and maple (P < .001). High and low temperature showed strong correlations with the combined weed counts (.598 and .628, respectively, P < .001). CONCLUSIONS: Denver weed pollens appear impacted more by temperature and less by precipitation and humidity, while the converse is true for tree and grass pollen. However, weed pollen, especially sage, may appreciably rebound after freezing temperatures. While separate meteorologic variables may have high correlations with specific pollen counts in a given year, such effect is not consistent and varies from year to year.


Subject(s)
Allergens , Pollen , Chemical Precipitation , Cold Temperature , Colorado , Poaceae , Retrospective Studies , Seasons , Trees , Weather
5.
AJR Am J Roentgenol ; 156(2): 381-4, 1991 Feb.
Article in English | MEDLINE | ID: mdl-1898819

ABSTRACT

One hundred twenty-eight patients were examined prospectively to determine the significance of mucosal thickening seen in the paranasal sinuses during routine MR imaging of the brain. On the basis of responses to a questionnaire, each patient was categorized as symptomatic (n = 60) or asymptomatic (n = 68) for paranasal sinus disease. Patients were categorized further on the basis of the maximal mucosal thickening seen by MR in any paranasal sinus. A modified t test was used to compare the prevalence of various degrees of mucosal thickening between symptomatic and asymptomatic groups. Statistically significant differences between the groups were seen only in those patients with normal sinuses and in those with 4 mm or more of mucosal thickening. We conclude that mucosal thickening of up to 3 mm is common and lacks clinical significance in asymptomatic patients. An ancillary finding is that 1- to 2-mm areas of mucosal thickening in the ethmoidal sinuses occur in 63% of asymptomatic patients. This minimal mucosal thickening in the ethmoidal sinuses is thought to be a normal variant, possibly a function of the physiologic nasal cycle.


Subject(s)
Magnetic Resonance Imaging , Mucous Membrane/pathology , Paranasal Sinus Diseases/pathology , Adolescent , Adult , Aged , Aged, 80 and over , Humans , Middle Aged , Paranasal Sinus Diseases/epidemiology , Prospective Studies
6.
Can J Physiol Pharmacol ; 63(1): 23-9, 1985 Jan.
Article in English | MEDLINE | ID: mdl-3986688

ABSTRACT

The effects of three calcium antagonists, verapamil, lanthanum, and 8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate (TMB-8) were studied on the release of slow-reacting substance of anaphylaxis (SRS-A) from ovalbumin-sensitized chopped guinea pig lung parenchyma in calcium-containing and calcium-free media. The SRS-A levels (mean +/- SEM) obtained from tissues incubated in normal and calcium-free Krebs-bicarbonate buffer were 51 +/- 8 (N = 19) and 21 +/- 4 (N = 14) U/mL, respectively. TMB-8 (0.1-10 microM), a reported intracellular calcium antagonist, reduced antigen-stimulated SRS-A release from lung tissue incubated in calcium-containing, but not calcium-free, medium; A23187-induced SRS-A release from normal guinea pig lung was not significantly altered by TMB-8 at concentrations up to 10 microM. Verapamil and lanthanum consistently reduced SRS-A release only at high concentrations (100 microM and 1mM, respectively). The quantities of SRS-A released from lung tissue incubated in the presence of verapamil in normal medium were similar to those obtained in calcium-free medium. Tissues incubated in the presence of potassium chloride (60 and 100 mM) did not release significant quantities of SRS-A, and release which did occur was not blocked by verapamil, suggesting that antigen-induced SRS-A release is not dependent on membrane depolarization and that verapamil was not exerting inhibition via blockade of voltage-dependent calcium channels. These data suggest that although intracellular calcium is important for the regulation of SRS-A secretion from guinea pig lung tissue, extracellular calcium is necessary for optimal release of SRS-A.


Subject(s)
Calcium Channel Blockers/pharmacology , Lung/metabolism , SRS-A/metabolism , Animals , Biomechanical Phenomena , Gallic Acid/analogs & derivatives , Gallic Acid/pharmacology , Guinea Pigs , Lanthanum/pharmacology , Male , Verapamil/pharmacology
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