Defenses of the hamster lung against human neutrophil and porcine pancreatic elastase

Instillation of human neutrophil elastase (HNE) into hamster lungs produces milder emphysema but more pulmonary hemorrhage than an equivalent amount of porcine pancreatic elastase (PPE), whether equivalence is determined by elastolytic units or moles. We undertook a study of the mechanisms of these differences. 125I-HNE or 3H-PPE were instilled intratracheally into hamsters. The partitioning of radioactivity between bronchoalveolar lavage fluid (BAL) and lung tissue was similar for HNE and PPE as were the half-lives, 45 and 51 min, respectively, for uncomplexed, enzymatically active HNE and PPE. In BAL there was preferential binding and inactivation of HNE by the hamsters' alpha-1-protease inhibitor (a-1-PI) whereas PPE was preferentially bound by alpha-2-macroglobulin (a-2-M). This was also observed in vitro when HNE and PPE were incubated with plasma from untreated hamsters. Nevertheless, when the sum of the elastase binding capacity of a-1-PI and a-2-M was considered, hamster plasma had similar binding capacities for HNE and PPE. It is known that the enzymatic activity of elastases is inhibited by formation of a stable complex with a-1-PI. On the other hand, elastases bound to a-2-M are protected against a-1-PI inhibition but can free themselves by proteolysis and exhibit elastolytic activity. Preferential inactivation of HNE by a-1-PI may be one mechanism that accounts for the lesser emphysema-inducing potency of HNE than of PPE.     

The desipramine-induced growth hormone response and the dexamethasone suppression test in obsessive-compulsive disorder.

Ten patients with DSM-III-R obsessive-compulsive disorder (OCD) underwent the desipramine (DMI) growth hormone (GH) stimulation test as well as the dexamethasone suppression test (DST). The results were compared with the responses in a group of matched healthy controls. The GH response to DMI did not differ between patients and controls and 9 of 10 patients showed cortisol suppression in response to dexamethasone. The data suggest that neither alpha 2 adrenergic dysfunction nor DST non-suppression are features of primary OCD.     

A prospective comparative study of MR sialography and conventional sialography of salivary duct disease

OBJECTIVE: The purpose of this study was to determine the diagnostic accuracy of MR sialography in the examination of patients with salivary duct disease. SUBJECTS AND METHODS: Forty-nine patients (23 males and 26 females; 16-78 years old; mean age, 47 years) with symptoms related to the salivary glands underwent both conventional sialography and MR sialography. The latter was performed using a heavily T2-weighted, two dimensional, fast spin-echo technique and a 12-cm circular surface coil. Contiguous 3-mm axial images with frequency-selective fat suppression were acquired through the symptomatic gland. The MR sialography findings were compared with the final diagnoses determined by conventional sialography. RESULTS: Conventional sialography showed calculus disease (n = 13), stricture (n = 12), sialectasis (n = 4), cast (n = 3), neoplasm (n = 2), and normal duct (n = 16). MR sialography alone had a sensitivity of 69% in revealing calculus disease. However, the sensitivity increased to 100% when MR sialograms were combined with control radiographs. MR sialography was sufficient to accurately reveal stricture, sialectasis, and neoplasm and to direct therapy on the basis of its findings. Overall, MR sialography combined with control radiographs had a sensitivity, specificity, and diagnostic accuracy of 100%, 88%, and 96%, respectively, in revealing salivary duct abnormalities. CONCLUSION: MR sialography alone is not sufficiently sensitive to reveal salivary duct stones. Caution must be exercised when excluding calculus disease. MR sialography, when combined with control radiographs, is accurate and has the potential to replace conventional sialography.     

The association between hepatitis C infection and survival after orthotopic liver transplantation

BACKGROUND & AIMS: The effect of hepatitis C viral (HCV) infection on patient and allograft survival after orthotopic liver transplantation is controversial. Hepatitis C recurrence after transplant is inevitable, but studies to date have not found a survival difference between recipients with and without HCV. METHODS: Using data from the United Network for Organ Sharing, we performed a retrospective cohort study of 11,036 patients who underwent 11,791 liver transplants between 1992 and 1998. The hazard rates of patient and allograft survival for patients who were HCV-positive as compared with patients who were HCV-negative were assessed by proportional-hazards analysis, with adjustment for potential confounding variables, including donor, recipient, and transplant center characteristics. RESULTS: Liver transplantation in HCV-positive recipients was associated with an increased rate of death (hazard ratio, 1.23; 95% confidence interval [CI], 1.12-1.35) and allograft failure (hazard ratio, 1.30; 95% CI, 1.21-1.39), as compared with transplantation in HCV-negative recipients. This reduction in survival persisted after adjusting for potential confounders. There was an interaction between HCV and sex (P < 0.001) with the effect of HCV on survival being most pronounced in female recipients (patient survival hazard ratio, 1.56; 95% CI, 1.35-1.81; allograft survival hazard ratio, 1.51; 95% CI, 1.34-1.70). CONCLUSIONS: HCV infection significantly impairs patient and allograft survival after liver transplantation.     

Relapsing illness due to Rochalimaea henselae in immunocompetent hosts: implication for therapy and new epidemiological associations.

Two previously healthy, immunocompetent men had persistent Rochalimaea henselae bacteremia with clinical relapses after courses of antibiotics to which the isolates were ultimately demonstrated susceptible in vitro. Both had sustained tick bites prior to their illnesses, thus demonstrating an association not previously identified, although suspected. The first patient had relapsing fever, constitutional symptoms, and an episode of aseptic meningitis despite therapy with amoxicillin, then with doxycycline, and then with ceftriaxone. Thereafter, he spontaneously became asymptomatic during a span of 2 months of persistent bacteremia. Finally, after 2 weeks of therapy with ceftriaxone plus gentamicin, followed by 4 weeks of therapy with oral ciprofloxacin, his bacteremia was cured. The second man had relapsing fever and constitutional symptoms after courses of tetracycline, then of chloramphenicol, and then of doxycycline. He became permanently asymptomatic after serial 2-week courses of chloramphenicol and erythromycin. The greater efficacy of lysis-centrifugation blood cultures in the recovery of R. henselae was noted.     

Hepatic safety of once-monthly injectable extended-release naltrexone administered to actively drinking alcoholics

Background:  Hepatoxicity has been reported with oral naltrexone. Hepatic safety data were examined from a 6-month study evaluating the efficacy and safety of a now available extended-release formulation of naltrexone (XR-NTX) in patients with alcohol dependence.
Methods:  In all, 624 patients (68% male; median age of 44 years) were randomly assigned to XR-NTX 380 mg ( n  = 205), XR-NTX 190 mg ( n  = 210), or placebo ( n  = 209).
Results:  There were no significant differences in alanine aminotrasferase, aspartate aminotransferase, or bilirubin levels between the study groups at study initiation or at subsequent assessments. Gamma-glutamyltransferase in the XR-NTX 380 mg group was lower compared with placebo at weeks 4, 8, 12, and 20. Both high (>3 times the upper limit of normal) liver chemistry tests (LCTs) and hepatic-related adverse events were infrequent in all study groups. In patients who were drinking heavily throughout the study, obese subjects, or those taking nonsteroidal anti-inflammatory drugs, there was no increase in frequency of high LCTs or hepatic-related adverse events in patients receiving XR-NTX (either dose) compared with placebo.
Conclusion:  Extended-release formulation of naltrexone does not appear to be hepatotoxic when taken at the recommended clinical doses in actively drinking alcohol-dependent patients.