Ramipril improves hemodynamic recovery but not microvascular response to ischemia in spontaneously hypertensive rats

BACKGROUND: Angiotensin converting enzyme (ACE) inhibition exerts positive effects on the microvasculature of normotensive animals, although this concept is not universally accepted. Recently, ACE inhibitors have been suggested to be useful for rescue in peripheral ischemia. METHODS: We investigated whether chronic treatment with the ACE inhibitor ramipril may have a positive impact on the defective healing response to ischemia that is typical of spontaneously hypertensive rats (SHR). Unilateral limb ischemia was induced in 20-week-old SHR by surgically removing the left femoral artery. Rats were allowed to regain consciousness and then were randomly allocated to treatment with ramipril (1 mg/kg body weight in drinking water) or vehicle for 28 days. RESULTS: The SHR failed to develop reparative angiogenesis in response to ischemia, thus having inadequate perfusion recovery. Ramipril reduced both tail-cuff systolic blood pressure (180 +/- 7 v 207 +/- 2 mm Hg in the vehicle group at 28 days, P < .05) and intra-arterial mean blood pressure (115 +/- 6 v 135 +/- 5 mm Hg in the vehicle group, P < .05). These effects were associated with increased responsiveness to endothelium-dependent vasodilatation by acetylcholine. Treatment with ramipril did not influence muscular capillary and arteriole density but accelerated the rate of perfusion recovery, leading to complete healing within 28 days after surgery. CONCLUSIONS: These results indicate that ACE inhibition by ramipril may be useful for the treatment of peripheral vascular complications in hypertension.     

Effectiveness of alendronate treatment in postmenopausal women with osteoporosis: relationship with BsmI vitamin D receptor genotypes

OBJECTIVE: To assess whether there is a relationship between the effectiveness of alendronate treatment in postmenopausal women with osteoporosis and BsmI vitamin D receptor (VDR) genotypes. DESIGN: Prospective baseline-controlled clinical trial. PATIENTS: Sixty-eight Italian osteoporotic women were enrolled and treated with alendronate at a dose of 10 mg/day for 12 months. MEASUREMENTS: At entry and after treatment, lumbar bone mineral density (BMD) and serum osteocalcin (OC) and urinary deoxypyridinoline/creatinine ratio (DPD-Cr) levels were evaluated. DNA was extracted from blood and analysed for the BsmI polymorphism of the VDR gene. RESULTS: The mean percentage (% +/- SD) change from baseline in lumbar BMD was significantly higher (P < 0.01) in bb than in BB BsmI VDR genotypes (7.92 +/- 4.31 vs. 3.40 +/- 1.81). No significant difference in lumbar BMD was observed in Bb VDR patients (6.01 +/- 3.89) in comparison with other groups. The mean percentage of change in serum OC and urinary DPD-Cr levels was significantly (P < 0.01) lower in individuals with bb than in those with BB BsmI VDR genotypes (-14.34 +/- 2.87 vs.-10.39 +/- 1.43 and -9.61 +/- 5.56 vs.-4.61 +/- 2.31). No significant difference in serum OC and urinary DPD-Cr levels was observed in Bb VDR patients (-12.31 +/- 2.11 and -6.52 +/- 2.65) in comparison with other groups. CONCLUSION: The different BsmI vitamin D receptor genotypes modify the pharmacological response to alendronate treatment in postmenopausal women with osteoporosis.     

Prospective study of the meaning of indeterminate results of the Recombinant Immunoblot Assay for hepatitis C virus in blood donors

Background

The interpretation of “indeterminate” results of the recombinant immunoblot assay (RIBA) is a particularly sensitive issue for Transfusion Services, and donors with such a serological condition require long-term follow-up.

Materials and methods

In the Immunohaematology and Transfusion Medicine Division of Umberto I University Hospital (Rome, Italy), 102,979 donor blood units were screened for hepatitis C virus (HCV) antibodies by enzyme-linked immunosorbent assay (ELISA) over a 5-year period (01.01.2000 – 31.12.2004). Since 24.10.2001, HCV -RNA testing was added. All samples repeatedly reactive by ELISA were then submitted to a HCV confirmatory assay (RIBA).

Results

Among the 102,979 donors we found 271 positive to HCV ELISA testing. The results of the RIBA assay for these donors were negative in 178 (65.7%) cases, positive in 28 (10.3%) and indeterminate in 65 (24.0 %).Of the 65 subjects with an indeterminate pattern, 24 completed a sufficient follow-up (median 25 months; range, 6 – 52), during which some (n=8; 33%) converted to a negative status, some (n=16; 67%) maintained their reactivity pattern, but none became seropositive for HCV.

Conclusions

The HCV-RIBA indeterminate status may indicate either a non-specific reaction (false positive) or a real pre-existing or initial infection and does not, therefore, enable a prediction of outcome. The use of HCV genomic assays (nucleic acid amplification testing), which are more specific than antibody-based assays (ELISA, RIBA), therefore improves HCV blood donor testing by allowing an accurate interpretation of such primary assays.     

Expanding the mutational spectrum of LZTR1 in schwannomatosis

Schwannomatosis is characterized by the development of multiple non-vestibular, non-intradermal schwannomas. Constitutional inactivating variants in two genes, SMARCB1 and, very recently, LZTR1, have been reported. We performed exome sequencing of 13 schwannomatosis patients from 11 families without SMARCB1 deleterious variants. We identified four individuals with heterozygous loss-of-function variants in LZTR1. Sequencing of the germline of 60 additional patients identified 18 additional heterozygous variants in LZTR1. We identified LZTR1 variants in 43% and 30% of familial (three of the seven families) and sporadic patients, respectively. In addition, we tested LZTR1 protein immunostaining in 22 tumors from nine unrelated patients with and without LZTR1 deleterious variants. Tumors from individuals with LZTR1 variants lost the protein expression in at least a subset of tumor cells, consistent with a tumor suppressor mechanism. In conclusion, our study demonstrates that molecular analysis of LZTR1 may contribute to the molecular characterization of schwannomatosis patients, in addition to NF2 mutational analysis and the detection of chromosome 22 losses in tumor tissue. It will be especially useful in differentiating schwannomatosis from mosaic Neurofibromatosis type 2 (NF2). However, the role of LZTR1 in the pathogenesis of schwannomatosis needs further elucidation.     

Intraepithelial cells with irregular nuclear contours as a marker of esophagitis in children with gastroesophageal reflux disease

The diagnostic usefulness of intraepithelial cells with irregular nuclear contours (CINC) (squiggle cells) in esophageal endoscopic biopsies was investigated in 76 children (range age: 6 months-12 years) with gastroesophageal reflux disease. A further 20 subjects (range age: 10 months-11 years) served as controls. Based on the microscopic changes of the esophagus, according to traditional histological criteria, four groups of patients were identified: esophagitis was severe in 27, moderate in 20, mild in 21, and 8 patients had no clear-cut evidence of microscopic esophagitis. Data are given as mean±sd. Intraepithelial CINC had an immunohistochemical profile consistent with T lymphocytes. Patients with severe esophagitis had a CINC density (number per high-power field) (9.0±3.5) significantly higher than patients with mild esophagitis (7.0±3.0) and those without evidence of microscopic esophagitis (6.5±1.9) (P<0.05), but not different from those with moderate esophagitis (8.0±3.6); in all patient groups the CINC density was higher than in controls (2.2±0.3) (P<0.01). The percentage of reflux at 24-hr intraesophageal pH monitoring was higher in severe esophagitis patients (11.4±6.0) as compared to the other groups (moderate: 7.8±6.3; mild: 6.5±3.6; no microscopic esophagitis: 6.3±2.0;P<0.05). There was no correlation between CINC density and the amount of intraesophageal acid exposure in all patients. Furthermore, 27 of our patients had a normal intraesophageal acid exposure at the prolonged pH test (24-hr % of reflux 4.5): the CINC density was significantly higher in them than in the controls. We conclude that intraepithelial CINC in esophageal endoscopic biopsies from children with reflux disease represent a sensitive and early criterion of esophageal mucosa damage; they should be scanned in addition to the traditional histological parameters of acid-related esophageal inflammation.Presented in an abstract form at the 28th Annual Meeting of the European Society of Paediatric Gastroenterology and Nutrition, Jerusalem, May 28–June 1, 1995.     

What Factors Are Associated With the Recovery of Autonomy After a Hip Fracture? A Prospective,Multicentric Cohort Study

Objective

To identify the factors associated with recovering autonomy in activities of daily living (ADL) in patients who have had a hip fracture.

Novel insights on the bottom–up rise strength transfer: investigating massed vs. distributed exercise training

Sport Sciences for Health - The purpose of this study is to investigate the Bottom–Up Rise Strength Transfer (BURST) induced by massed vs. distributed-rehabilitative exercise training....