Effect of verapamil on monocrotaline-induced pulmonary artery hypertension and endothelial cell dysfunction in rats

Verapamil, a calcium channel blocker has been used with partial success in cases of primary pulmonary hypertension, as well as to reduce hypoxia-induced pulmonary hypertension (PH) in rats. However, its effect on monocrotaline (MCT)-induced PH in rats is not known. We studied the effect of verapamil on MCT-induced PH. Three weeks after a single injection of MCT, significant PH was noted in the MCT-injected rats compared with control (44.35 +/- 3.5 vs. 22 +/- 2.5 mmHg). MCT-injected rats on daily verapamil showed significant reduction in PH (31.5 +/- 3.4 mmHg). The main pulmonary artery of MCT-injected rats revealed subendothelial thickening, thinning and fragmentation of elastic laminae, smooth muscle cell hypertrophy and necrosis or loss of smooth muscle cells, and increased amounts of collagen in media and adventitia. In contrast, the main pulmonary artery of MCT + VP-treated rats showed less intimal thickening, some smooth muscle cell hypertrophy, but little necrosis or loss of cells in addition to disappearance of outer elastic laminae. Smaller pulmonary arteries (less than 150 microns in diameter) in MCT + VP-treated rats showed less medial thickening than MCT groups. However, diminished lung angiotensin-converting enzyme activity suggestive of endothelial cell dysfunction was noted in both MCT and MCT + VP-treated rats. This study indicates that verapamil attenuates MCT-induced PH, but has no effect on pulmonary endothelial cell dysfunction.     

Ventricular structure and function in hypertensive participants with heart failure and a normal ejection fraction: the Cardiovascular Health Study.

OBJECTIVES: The purpose of this study was to evaluate left ventricular (LV) size and structure in elderly subjects with hypertension (HTN) and heart failure who have a normal ejection fraction (HFNEF) in a large population-based sample. BACKGROUND: The pathophysiology of HFNEF is incompletely understood but is generally attributed to LV diastolic dysfunction with normal or reduced LV diastolic chamber size despite greater than normal filling pressures. METHODS: In the Cardiovascular Health Study (n = 5,888), demographic and clinical characteristics and ventricular structure and function were compared in healthy normal subjects (healthy; n = 499), subjects with HTN but not heart failure (HTN; n = 2,184), and subjects with HTN and HFNEF (HFNEF; n = 167). RESULTS: Subjects with HFNEF were older, more obese, and more often African American than healthy and HTN subjects and had a higher prevalence of diabetes, coronary heart disease, and anemia than HTN subjects. Serum creatinine and cystatin-C were increased in HFNEF subjects. Average LV diastolic dimension was significantly increased in HFNEF subjects (5.2 +/- 0.8 cm) compared with healthy (4.8 +/- 0.6 cm) and HTN (4.9 +/- 0.6 cm) subjects. As a result, average calculated stroke volume (89 +/- 25 ml vs. 78 +/- 20 ml and 80 +/- 20 ml) and cardiac output (6.0 +/- 2.0 l/min vs. 4.8 +/- 1.3 l/min and 5.1 +/- 1.4 l/min) were increased in HFNEF compared with healthy and HTN subjects, respectively. CONCLUSIONS: As a group, HFNEF subjects have increased LV diastolic diameter and increased calculated stroke volume. They also have increased prevalence of multiple comorbidities, including anemia, renal dysfunction, and obesity, that can cause volume overload. These data suggest that extracardiac factors, via volume overload, may contribute to the pathophysiology of HFNEF in the elderly.     

Fate of bone grafting for acetabular defects in total hip replacement

Background:

The use of allografts and autografts in the management of acetabular defects have been reported with varying results. Trabecular metal is an expensive option in the management of these defects. This study aims to assess the fate and efficacy of bone grafting for acetabular bone defects in total hip arthroplasty.

Materials and Methods:

A total of 30 hips in 28 patients with acetabular deficiencies were treated with bone grafting and total hip replacement (THR). Seventeen hips had American Academy of Orthopedic Surgeons (AAOS) type 2 (Paprosky type 2c) deficiency and 13 had AAOS type 3 (Paprosky type 3a) defects of the acetabulum. Allografts were used in 15 patients and autografts were used in the remaining 13. Cemented total hip arthroplasty was done in 18 hips and uncemented THR in 12. Seven patients underwent the procedure for, acetabular erosion and symptoms following hemiarthroplasty (4 out of 7), or, acetabular revision for failure (3 out of 7) following total hip arthroplasty. Acetabular deficiencies in other patients were due to posttraumatic causes, advanced primary hip arthritis and second stage treatment of postinfective arthritis. A mesh was used in 6 hips and screws were used in 13 hips for graft fixation.

Results:

Patients were followed up clinicoradiologically for a period of 10 months to 4 years (mean 23.4 months). One patient required staged revision due to infection. Two patients had early asymptomatic cup migration. One patient had graft lysis and change in cup inclination with persistent pain. He was not keen on further intervention at last followup. Other patients were pain free at the time of followup with radiographs showing maintenance of graft and implant position.

Conclusion:

Bone grafting is a suitable option in the management of acetabular defects in total hip arthroplasty, especially in resource challenged countries.     

Improving outcomes for patients with Burkitt lymphoma and HIV

Burkitt lymphoma (BL) is a highly aggressive B-cell malignancy that occurs with increased frequency among patients infected with HIV. Until recently, the immunocompromised state of patients with HIV and BL was generally deemed to preclude the use of the intensive chemotherapeutic regimens used to treat HIV-negative patients due to toxicity issues. However, the advent of highly active antiretroviral therapy (HAART) and the mounting evidence that less intensive lymphoma regimens are ineffective in BL have led investigators to treat HIV-positive patients with the same chemotherapy now established as the standard of care for immunocompetent patients. Data suggest that these current approaches, along with supportive care, may result in improved patient outcomes. In contrast, the role of adjunctive immunotherapy with rituximab in HIV-BL remains undefined. Further studies, including randomized clinical trials, are needed to better delineate the optimal treatment for patients with this devastating disease.