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.     

Type 1 and type 2 cytokine dysregulation in human infectious, neoplastic, and inflammatory diseases.

In the mid-1980s, Mosmann, Coffman, and their colleagues discovered that murine CD4+ helper T-cell clones could be distinguished by the cytokines they synthesized. The isolation of human Th1 and Th2 clones by Romagnani and coworkers in the early 1990s has led to a large number of reports on the effects of Th1 and Th2 on the human immune system. More recently, cells other than CD4+ T cells, including CD8+ T cells, monocytes, NK cells, B cells, eosinophils, mast cells, basophils, and other cells, have been shown to be capable of producing "Th1" and "Th2" cytokines. In this review, we examine the literature on human diseases, using the nomenclature of type 1 (Th1-like) and type 2 (Th2-like) cytokines, which includes all cell types producing these cytokines rather than only CD4+ T cells. Type 1 cytokines include interleukin-2 (IL-2), gamma interferon, IL-12 and tumor necrosis factor beta, while type 2 cytokines include IL-4, IL-5, IL-6, IL-10, and IL-13. In general, type 1 cytokines favor the development of a strong cellular immune response whereas type 2 cytokines favor a strong humoral immune response. Some of these type 1 and type 2 cytokines are cross-regulatory. For example, gamma interferon and IL-12 decrease the levels of type 2 cytokines whereas IL-4 and IL-10 decrease the levels of type 1 cytokines. We use this cytokine perspective to examine human diseases including infections due to viruses, bacteria, parasites, and fungi, as well as selected neoplastic, atopic, rheumatologic, autoimmune, and idiopathic-inflammatory conditions. Clinically, type 1 cytokine-predominant responses should be suspected in any delayed-type hypersensitivity-like granulomatous reactions and in infections with intracellular pathogens, whereas conditions involving hypergammaglobulinemia, increased immunoglobulin E levels, and/or eosinophilia are suggestive of type 2 cytokine-predominant conditions. If this immunologic concept is relevant to human diseases, the potential exists for novel cytokine-based therapies and novel cytokine-directed preventive vaccines for such diseases.     

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.     

Knee joint anatomy predicts high-risk in vivo dynamic landing knee biomechanics

BackgroundWith knee morphology being a non-modifiable anterior cruciate ligament injury risk factor, its consideration within injury prevention models is limited. Knee anatomy, however, directly influences joint mechanics and the potential for injurious loads. With this in mind, we explored associations between key knee anatomical and three-dimensional biomechanical parameters exhibited during landings. We hypothesized that lateral and medial posterior tibial slopes and their ratio, and tibial plateau width, intercondylar distance and their ratio, were proportional to peak stance anterior knee joint reaction force, knee abduction and internal rotation angles.MethodsTwenty recreationally active females (21.2 (1.7) years) had stance phase three-dimensional dominant limb knee biomechanics recorded during ten single leg land-and-cut tasks. Six anatomical indices were quantified for the same limb via a series of two dimensional (sagittal, transverse and coronal) magnetic resonance images. Linear stepwise regression analyses examined which of these anatomical factors were independently associated with each of the three mean subject-based peak knee biomechanical measures.FindingsLateral tibial slope was significantly (P < 0.0001) correlated with peak anterior knee joint reaction force, explaining 60.9% of the variance. Both tibial plateau width:intercondylar distance (P < 0.0001) and medial tibial slope:lateral tibial slope (P < 0.001) ratios were significantly correlated with peak knee abduction angle, explaining 75.4% of the variance. The medial tibial slope:lateral tibial slope ratio was also significantly (P < 0.001) correlated with peak knee internal rotation angle, explaining 49.2% of the variance.InterpretationKnee anatomy is directly associated with high-risk knee biomechanics exhibited during dynamic landings. Continued understanding of multifactorial contributions to the anterior cruciate ligament injury mechanism should dictate future injury screening and prevention efforts in order to successfully cater to individual joint vulnerabilities.     

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.