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.     

Begelomab for severe refractory dermatomyositis: A case report

Rationale:Severe refractory idiopathic inflammatory myopathy (IIM) represents a challenge for the clinician. The lack of efficacy of available tools reflects our incomplete insight into the molecular events sustaining the inflammatory tissue damage in these patients. We present the first case of refractory IIM treated with anti-dipeptidyl peptidase-4 (DPP-4)/cluster of differentiation 26 (CD26) monoclonal antibody.Patient concerns:A 55-year old man presented with proximal muscle weakness, diffuse erythematous skin lesions which rapidly evolved into ulcerations, dysphagia and dysphonia.Diagnosis:Increased serum creatine kinase levels and histological findings at muscle and skin biopsies were compatible with the diagnosis of dermatomyositis (DM). Several lines of treatment failed to control the disease including steroids, mycophenolate mofetil, tacrolimus, intravenous immunoglobulins and rituximab. Despite therapy, the patient also had recurrent intestinal vasculitis causing bowel perforation. Concurrently, DPP-4/CD26 expression in the patient''s skin and skeletal muscle was observed.Interventions:The patient was treated with begelomab, a murine immunoglobulin G2b monoclonal antibody against DPP-4/CD26.Outcomes:Dysphagia, skin lesions and intestinal vasculitis resolved and the patient experienced a significant improvement of his quality of life.Conclusion:Blockade of DPP-4/CD26, which is expressed on T cells and mediates T cell activation and function, is safe and might be effective in patients with refractory DM.     

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.

Incidence of new diabetic patients on dialysis in Piedmont,Italy: Major changes recorded over a 10-year period

Different incidence rates of new diabetic patients on dialysis are reported in various settings; although prevalence of this disease is often considered a marker of acceptance policy, rates are thought to be influenced also by genetic, epidemiological and other characteristics of a population (genetic composition, age distribution, lifestyle). Moreover, since features of a general population are often not stable (as in the setting analysed) changes at this level may have important reflections in the incidence of diabetics with end-stage renal disease (ESRD). In the region studied (Piedmont, northern Italy, about 4400 000 inhabitants, 20 dialysis centres, open acceptance since the mid-1970s, yearly information on 100% of patients, gathered by a Dialysis and Transplantation Registry) the incidence of diabetic patients with ESRD (389 cases recorded 1981–1990: 222 males, 167 females: mean age at start increasing from 55.5 years in 1981–1985 to 58.7 years in 1986–1990) differs according to age and sex. Incidence was higher in males, and rose from 6.23/year patients per million population (p.m.p.) in 1981–1982 to 12.88/year p.m.p. in 1989–1990, with a peak at age 60–69 (from 18.46/year p.m.p. in 1981–1982, to 46.12/year p.m.p. in 1989–1990). While relatively stable in the younger age groups from 1981 to 1990, incidence increased in the elderly (males age 70–79: 7.12/year p.m.p. in 1981–1982, 26.08/year p.m.p. in 1989–1990). As regards clinical and metabolic patterns, at the first update, in 1986–1990, 88.3% of diabetic patients were hypertensive or taking hypotensive drugs; albumin levels were below the normal range (<3.5 g/dl) in 30.3%; cholesterol levels were below the normal range (<150 mg/dl) in 16.15%. As regards entry criteria, creatinine clearances ranged from <1 to 14 ml/min (mean values at first update: 3.45±2.76 ml/min). In conclusion, presentation of diabetic patients with ESRD is changing. The stability of incidence in the younger age groups confirms the appropriateness of an open acceptance policy, at least for these ages. The increase in the elderly probably reflects the longer lifespan of diabetic patients in the overall population, while the influence of a hidden preselection must be further assessed. Since this cohort increasingly requires in-hospital high-tolerance treatment, future provision of dialysis needs must take into account the trend towards an increase in this high-risk elderly population.     

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....     

Incidence and short-term prognosis of late sustained ventricular tachycardia after myocardial infarction: results of the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico (GISSI-3) Data Base.

BACKGROUND: There is little epidemiologic information from large multicenter databases on sustained monomorphic ventricular tachycardia occurring after the initial 48 hours of myocardial infarction. METHODS: We reassessed its incidence and short-term prognosis in 16,842 patients with a definite myocardial infarction enrolled in the Gruppo Italiano per lo Studio della Soprovvivenza nell'Infarto Miocardico (GISSI-3) trial. RESULTS: The incidence rate of late sustained ventricular tachycardia by 6 weeks was around 1%. Older age, a history of hypertension, diabetes, and myocardial infarction, nonadministration of lytic therapy, Killip class > I, > or = 6 leads with ST-segment elevation, higher heart rate, and bundle branch block on admission were significantly more frequent among patients with than without late sustained ventricular tachycardia. Patients with ventricular tachycardia had a more complicated course in-hospital and posthospital to 6 weeks than the reference group did. The arrhythmia was associated with a significant excess of pump failure, atrial flutter-fibrillation, asystole, atrioventricular block, ventricular fibrillation within the first 48 hours of myocardial infarction, and recurrent ischemic events. Larger left ventricular end-systolic volumes and lower ejection fractions were more frequent among ventricular tachycardia patients than in the reference group by 6 weeks. Death rates by 6 weeks were 35% for patients with ventricular tachycardia and 5% for those without the arrhythmia. Irrespective of the stratification of patients by site and type of infarct and presence/absence of bundle branch block, the occurrence of the arrhythmia was associated with reduced 6-week survival. CONCLUSION: In a proportional hazard regression model late sustained ventricular tachycardia was retained as a strong, independent predictor of 6-week mortality after myocardial infarction (hazard ratio 6.13, 95% confidence interval 4.56-8.25).