Ganciclovir therapy of severe cytomegalovirus infections in solid-organ transplant recipients

The clinical and virologic efficacy of ganciclovir (9-[1,3-dihydroxy-2-propoxymethyl]guanine) in the treatment of severe CMV infections in solid organ transplant recipients was investigated. Twelve patients (9 liver and 3 kidney transplant recipients) with CMV retinitis, esophagitis, hepatitis, or pneumonia received ganciclovir at a dose of 0.75-7.5 mg/kg/day for 10-30 days (mean duration 17 days). Clinical stabilization or improvement occurred in 8 patients (67%). Serial liver biopsies in 6 liver allograft recipients with CMV hepatitis demonstrated substantial histologic improvement on treatment. Of 6 patients with CMV pneumonia, 4 (67%) recovered and survived. Cultures of blood and other sites became negative in 9 patients (75%). Three patients (25%) had recurrent viral shedding after treatment, but none of these relapsed with invasive infections. Mild neutropenia was the only side effect encountered but was frequent (67%). The overall survival rate was 50%. Ganciclovir is effective in reducing CMV shedding in solid organ transplant recipients and is well tolerated. Our experience suggests a clinical benefit as well in patients with severe, invasive CMV disease. Relapse, in contrast to patients with the acquired immunodeficiency syndrome, is infrequent.     

Sepsis-induced lung injury and the effects of ibuprofen pretreatment. Analysis of early alveolar events via repetitive bronchoalveolar lavage.

Current knowledge of alveolar pathophysiology during early sepsis-induced acute lung injury (ALI) and the role of resident alveolar macrophages (AM) in mediating alveolar inflammatory events during sepsis is limited. Further, the effects of ibuprofen pretreatment upon alveolar pathophysiology and AM function during early sepsis-induced ALI is unclear. Utilizing repetitive bronchoalveolar lavage (BAL) in a porcine model of sepsis-induced ALI, we studied changes in alveolar cellular constituents, BAL protein content and molecular composition, and AM superoxide anion (O2-.) generation during early sepsis. The neutrophil percentage of recovered alveolar cells (17 +/- 8%, t = 300 min versus 2 +/- 1%, t = 0; p = 0.06) and the bronchoalveolar lavage total protein content (493 +/- 110 micrograms/ml, t = 300 min versus 109 +/- 18 micrograms/ml, t = 0; p less than 0.05) increased in septic animals. Increases in BAL fluid total protein were primarily due to low-molecular-weight plasma protein, indicating relative preservation of alveolar-capillary membrane size selectivity. Alveolar macrophages harvested following 300 min of sepsis generated significantly less O2-. following phorbol myristate acetate (PMA) stimulation compared to AM harvested at baseline. Ibuprofen pretreatment of septic animals completely blocked leakage of plasma proteins into the alveoli and attenuated neutrophil migration but did not prevent downregulation of AM O2-. generation. Increased alveolar-capillary membrane permeability, neutrophil migration into the alveoli, and downregulation of AM oxidant generation occur within hours of the onset of sepsis. Ibuprofen pretreatment significantly attenuates early sepsis-induced ALI without altering sepsis-induced AM dysfunction.     

Migration and chemical modification of silicone in women with breast prostheses

Studies using magnetic resonance spectroscopy in human volunteers to evaluate their livers in vivo and to analyze their blood in vitro suggest that there are measurable amounts of silicon compounds in the blood of some women with implants and that there is migration of silicone to other organs such as the liver.     

Initial steps taken by nine primary care practices to implement alcohol screening guidelines with hypertensive patients: the AA-TRIP project.

Many medical conditions are caused or exacerbated by heavy drinking, necessitating alcohol screening and discussion in primary care practices. This is particularly true of hypertension, the most common primary diagnosis in the United States, which has been linked to the regular consumption of 3 or more standard alcoholic beverages a day. The Accelerating Alcohol Screening-Translating Research into Practice (AA-TRIP) project was designed to improve detection and management of alcohol problems in primary care patients with hypertension. Medical providers are being trained using the Practice Partner Research Network's- Translating Research into Practice (PPRNet-TRIP) quality improvement model. This includes a multi-method intervention (electronic medical records, on-site academic detailing, practice feedback reports and annual network meetings) to help practices increase adherence to clinical guidelines. Qualitative analyses of initial steps taken by nine primary care practices toward the routine implementation of alcohol screening guidelines are presented. Organizational factors and provider and patient characteristics all influenced the method and consistency of alcohol screening and intervention. Perceived time constraints, patient sensitivity to questions about alcohol, and possible stigma associated with a diagnosis of alcoholism were also relevant barriers requiring problem solving.