Bone mineral metabolism and histomorphometry in rats with cholestatic liver disease

BACKGROUND: The etiology of osteopenia in cholestatic liver disease is uncertain. An animal model is needed in order to study the efficacy of therapeutic agents. AIMS: In order to characterise the bone disease in rats with cholestatic liver disease. METHODS: Four-month old male Sprague-Dawley bile duct-ligated (BDL) and sham-operated (SO) rats were studied. Twenty-eight days after surgery serum osteocalcin, a bone-formation marker, urinary deoxypyridinoline (DPD) cross-links, a resorption marker, and 25-hydroxyvitamin D3 were determined. Static and dynamic (tetracycline-based) histomorphometric analysis was performed on femurs and tibiae. RESULTS: All BDL rats developed biliary cirrhosis. Bile duct-ligated rats had lower bone mass, reflected in statistically significantly 13.5% lower femoral dry-weight, 16% lower femoral ash-weight, 42.7% lower tibial cancellous bone area and 19% lower trabecular thickness, compared with SO rats. Bile duct-ligated rats exhibited decreased bone formation manifested by statistically significantly 70% lower tetracycline double-labelling, 40% lower mineralising surface, 51% lower bone-formation rate and 47% lower osteocalcin compared with SO rats. Deoxypyridinoline levels were 20% lower in BDL rats. Bile duct-ligated rats had 52% lower serum 25-hydroxyvitamin D3 level, but no significant increase in cortical osteoid area. CONCLUSIONS: Bile duct-ligated rats develop osteopenia characterised by low bone-formation rate, and can be used for studying therapeutic agents for patients with cholestatic liver disease displaying similar bone changes.     

Closed pleural needle biopsy: predicting diagnostic yield by examining pleural fluid parameters

OBJECTIVE: Pleural fluid parameters that predict a diagnostic closed pleural needle biopsy were investigated. DESIGN: A retrospective analysis. SETTING: The Institute of Pulmonology, Hadassah University Hospital. PATIENTS AND METHODS: Forty-four patients who underwent closed pleural needle biopsies were included in this study. Pleural fluid values of protein, glucose, lactate dehydrogenase (LDH), pH, and white blood cell count with differential cell counts, from patients with diagnostic and non-diagnostic pleural biopsies were compared. RESULTS: Thirteen patients (29%) had diagnostic biopsies. Malignancy was identified in 10 patients (23%), of whom 70% had adenocarcinoma. Three other patients had non-malignant specific diagnosis. LDH levels in pleural fluid from patients with diagnostic pleural biopsy were higher than in patients with non-diagnostic pleural biopsies (1436 +/- 333 U l(-1) vs. 775 +/- 109 U l(-1); P < 0.05). LDH levels less than 510 U l(-1) were highly predictive of a negative biopsy (negative predictive value of 86.6%). Follow up revealed malignancy including mesothelioma and lymphoma, in 10 of 30 (33%) patients with non-diagnostic biopsies, and one patient died of unrelated cause, while the pleural effusion either resolved, remained stable or an alternative benign process was identified in 19 patients (63%). CONCLUSIONS: Low levels of LDH (< 510 U l(-1)) were highly predictive of a negative pleural needle biopsy. Thus, LDH may serve as a useful guide in deciding whether to perform closed pleural biopsy or to proceed to thoracoscopically guided biopsy.     

Family history of cardiovascular disease does not predict risk-reducing behavior.

BACKGROUND: Family history is one of the main risk factors for cardiovascular disease, especially in the younger population. These individuals, being closely related to young symptomatic patients, are anticipated to have a high rate of risk factors but also to control them aggressively. The aim of the study was to evaluate the association between family history of cardiovascular disease and risk factors that control as well as reduce risk-reducing behavior among young, healthy adults. DESIGN AND METHODS: Demographic, clinical and lifestyle parameters of career service personnel of the Israeli Defense Forces, who were checked at the staff periodic examination center, were evaluated. Behavioral and clinical parameters of participants, with and without cardiovascular family history, were compared. RESULTS: The study cohort comprised 41,099 patients (36,236 men and 4863 women). Of those, 3802 men and 628 women with a family history of cardiovascular disease were identified. Male individuals had a higher rate of treatable risk factors like, obesity (P<0.0005), high blood pressure (P<0.0005), high plasma glucose (P<0.0005) and dyslipidemia (P<0.0005) than individuals without a family history. Among the women, the rate of these risk factors was higher than in the control groups but was statistically significant only for obesity, high blood pressure and high glucose levels. Risk-reducing behavior like regular physical activity and nonsmoking status in both the sexes did not differ between the groups. CONCLUSION: Members of the young population with a family history of cardiovascular disease is easily identified but remains largely uncontrolled. Special attention and continued education are required to modify their behavioral and medical parameters.     

Platelet indices as markers of inflammation in systemic sclerosis patients: Relation to vascular endothelial growth factor and flow mediated dilatation

Aim of the work

To evaluate platelet indices in systemic sclerosis (SSc) patients and identify their clinical significance as novel inflammatory biomarkers in correlation to markers of endothelial dysfunction: vascular endothelial growth factor (VEGF) and flow mediated dilatation (FMD).

RNA interference--small RNAs effectively fight viral hepatitis.

RNA interference (RNAi) is the process of sequence-specific gene silencing, initiated by double-stranded RNA that is homologous in sequence to the target gene. This unique phenomenon has been extensively investigated during the last few years not only in the context of its mechanism and its possible role in the regulation of gene expression and cell function, but also as a potential powerful tool for gene therapy. Targeting essential viral genes or oncogenic alleles are only some of the possible applications of RNAi in the field of gene-directed therapy. This review covers the potential use of RNAi against hepatitis B and hepatitis C viruses, the main pathogens causing chronic liver disease. The major milestones along the discovery of RNAi will also be covered.     

Serial Cardiovascular Magnetic Resonance Strain Measurements to Identify Cardiotoxicity in Breast Cancer: Comparison With Echocardiography

ObjectivesThis study sought to compare the prognostic value of cardiovascular magnetic resonance (CMR) and 2-dimensional echocardiography (2DE) derived left ventricular (LV) strain, volumes, and ejection fraction for cancer therapy–related cardiac dysfunction (CTRCD) in women with early stage breast cancer.BackgroundThere are limited comparative data on the association of CMR and 2DE derived strain, volumes, and LVEF with CTRCD.MethodsA total of 125 prospectively recruited women with HER2+ early stage breast cancer receiving sequential anthracycline/trastuzumab underwent 5 serial CMR and 6 of 2DE studies before and during treatment. CMR LV volumes, left ventricular ejection fraction tagged-CMR, and feature-tracking (FT) derived global systolic longitudinal (GLS) and global circumferential strain (GCS) and 2DE-based LV volumes, function, GLS, and GCS were measured. CTRCD was defined by the cardiac review and evaluation committee criteria.ResultsTwenty-eight percent of patients developed CTRCD by CMR and 22% by 2DE. A 15% relative reduction in 2DE-GLS increased the CTRCD odds by 133% at subsequent follow-up, compared with 47%/50% by tagged-CMR GLS/GCS and 87% by FT-GCS. CMR and 2DE-LVEF and indexed left ventricular end-systolic volume (LVESVi) were also associated with subsequent CTRCD. The prognostic threshold change in CMR-left ventricular ejection fraction and FT strain for subsequent CTRCD was similar to the known minimum-detectable difference for these measures, whereas for tagged-CMR strain it was lower than the minimum-detectable difference; for 2DE, only the prognostic threshold for GLS was greater than the minimum-detectable difference. Of all strain methods, 2DE-GLS provided the highest increase in discriminatory value over baseline clinical risk factors for subsequent CTRCD. The combination of 2DE-left ventricular ejection fraction or LVESVi and strain provided greater increase in the area under the curve for subsequent CTRCD over clinical risk factors than CMR left ventricular ejection fraction or LVESVi and strain (18% to 22% vs. 9% to 14%).ConclusionsIn women with HER2+ early stage breast cancer, changes in CMR and 2DE strain, left ventricular ejection fraction, and LVESVi were prognostic for subsequent CTRCD. When LVEF can be measured precisely by CMR, FT strain may function as an additional confirmatory prognostic measure, but with 2DE, GLS is the optimal prognostic measure. (Evaluation of Myocardial Changes During BReast Adenocarcinoma Therapy to Detect Cardiotoxicity Earlier With MRI [EMBRACE-MRI]; NCT02306538)     

Unexpectedly high incidence of hypoplastic/aplastic foci in bone marrow biopsies of hairy cell leukemia patients in remission following 2-chlorodeoxyadenosine therapy

Treatment with the purine analog 2-chlorodeoxyadenosine (2-CDA) achieves a complete response in close to 90% of patients with hairy cell leukemia, with approximately 75% remaining in prolonged remission. Recently, we unexpectedly noted foci of hypoplasia and aplasia in routine follow-up bone marrow biopsies of several hairy cell leukemia patients in remission with normal blood counts. Because of this finding we examined all available biopsies to assess the incidence of this phenomenon. A total of 94 biopsies in 31 patients were reviewed. Of these, 23 were prior to 2-CDA therapy and 71 (in 30 patients) were obtained 2-76 (mean 22) months following one or more courses of treatment. Nine patients had also received prior interferon and 7 (of whom 3 had also received interferon) had undergone splenectomy. Hypocellular foci were found in only 3 (13%) of the pre-therapy biopsies. Forty-seven of the 71 post-therapy biopsies (in 23 patients) (66%) had a total of 176 hypocellular foci. Of these 47 biopsies, 39 were without evidence of disease. A simultaneous complete blood count was normal in 34 of the 47 hypoplastic biopsies (72%). This suggests that these hypoplastic areas may not be representative of the entire bone marrow and that normal hematopoiesis may take place at other sites. However, since the longest follow-up is less than 7 yr, the potential long-term significance of these findings, such as progressive bone marrow aplasia or dysplasia, may still be unrecognised.     

Insulin resistance in chronic hepatitis B and C.

AIM: To determine whether insulin resistance occurs in patients with chronic hepatitis B (CHB) and chronic hepatitis C (CHC) and its relationship with the presence of liver fibrosis and steatosis. METHODS: Untreated patients with CHC (n=60) or CHB (n=40), similar in age, gender, body mass index and waist-hip ratio, were studied. Relationship between anthropometric, biochemical (fasting serum insulin, C-peptide, ferritin, iron, TNF-alpha, cholesterol, triglyceride, bilirubin, hemoglobin and platelet concentrations) and liver biopsy (43 CHC and 20 CHB patients) findings was investigated by insulin resistance determined via the homeostasis model assessment (HOMA-IR). RESULTS: The mean fasting serum insulin was 14.9 (11.9) mU/mL in CHC and 21.4 (17.4) in the CHB group (normal range 0.7-9; p=0.049) and mean HOMA-IR was 3.1 (2.6) in CHC versus 4.7 (4.1) in the CHB group (normal range 0.12-4.61; p=0.036). HOMA-IR was significantly associated with fibrosis stage in the CHC group (p=0.015), but not in the CHB group. CONCLUSION: Hyperinsulinemia occurs in chronic viral hepatitis B and hepatitis C; insulin resistance is associated with stage of fibrosis in hepatitis C.     

The incidence of hip fracture in Malaysians above 50 years of age: variation in different ethnic groups

Aims: Hip fracture is frequently studied to reflect osteoporosis related fractures. The aim of this study was to look at ethnic differences in the incidence of hip fractures between the three races in Malaysia. Methods: This was a retrospective study performed for the years 1996 and 1997. Data from hospitals treating hip fractures in elderly patients were collected throughout the whole country. Result: The overall incidence of hip fractures was 90 per 100 000 individuals. Sixty‐three percent of patients presenting with hip fractures were Chinese. This was followed by Malays at 20% and Indians, 13%. Race‐specific incidence data showed that the fracture rates are highest among the Chinese (160 per 100 000) followed by Indians (150 per 100 000) and Malays (30 per 100 000). Females were twice as commonly affected compared to males. Race and sex‐specific incidence data showed that the incidence was highest among Chinese females (220 per 100 000), followed by Indian females (200 per 100 000). The age‐specific incidence was 500 per 100 000 for patients above 75 years, compared to 10 per 100 000 in those between 50 and 54 years. Conclusion: Hip fractures are common in Malaysia. There are differences in hip fracture incidence depending upon ethnicity.