Calcimimetics maintain bone turnover in uremic rats despite the concomitant decrease in parathyroid hormone concentration

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Efficacy and safety of prolonged‐release tacrolimus in stable pediatric allograft recipients converted from immediate‐release tacrolimus – a Phase 2, open‐label,single‐arm,one‐way crossover study

There are limited clinical data regarding prolonged‐release tacrolimus (PR‐T) use in pediatric transplant recipients. This Phase 2 study assessed the efficacy and safety of PR‐T in stable pediatric kidney, liver, and heart transplant recipients (aged ≥5 to ≤16 years) over 1 year following conversion from immediate‐release tacrolimus (IR‐T), on a 1:1 mg total‐daily‐dose basis. Endpoints included the incidence of acute rejection (AR), a composite endpoint of efficacy failure (death, graft loss, biopsy‐confirmed AR, and unknown outcome), and safety. Tacrolimus dose and whole‐blood trough levels (target 3.5–15 ng/ml) were also evaluated. Overall, 79 patients (kidney, n = 48; liver, n = 29; heart, n = 2) were assessed. Following conversion, tacrolimus dose and trough levels remained stable; however, 7.6–17.7% of patients across follow‐up visits had trough levels below the target range. Two (2.5%) patients had AR, and 3 (3.8%) had efficacy failure. No graft loss or deaths were reported. No new safety signals were identified. Drug‐related treatment‐emergent adverse events occurred in 28 patients (35.4%); most were mild, and all resolved. This study suggests that IR‐T to PR‐T conversion is effective and well tolerated over 1 year in pediatric transplant recipients and highlights the importance of therapeutic drug monitoring to maintain target tacrolimus trough levels.     

Respiratory function changes after chemotherapy: an additional risk for postoperative respiratory complications?

BACKGROUND: Patients receiving chemotherapy for lung cancer usually modify their lung function during treatment with increases in forced expiratory volume in 1 second (FEV(1)) and forced vital capacity (FVC) and decreases in lung diffusion for carbon monoxide (DLCO). This prospective study was designed to evaluate functional changes in forced expiratory volume in 1 second, forced vital capacity, and DLCO after three courses of induction chemotherapy with cisplatinum and gemcitabine in stage IIIa lung cancer patients and to assess their impact on respiratory complications after lung resection. METHODS: From March 1998 to January 2001, 30 consecutive patients with N2 nonsmall cell lung cancer had surgical resection after neoadjuvant treatment. Pre-chemotherapy and postchemotherapy results of standard respiratory function tests and DLCO were compared in patients with and without postoperative respiratory complications. RESULTS: All 30 patients completed the chemotherapy protocol without respiratory complications. Significant improvements (p < 0.05) were recorded after chemotherapy in transition dyspnea score, PaO(2) (mean value from 79.8 to 86.4 mm Hg), forced expiratory volume in 1 second % (from 78.1% to 87.5%) and forced vital capacity % (from 88.1% to 103.3%). Lung diffusion for carbon monoxide was significantly impaired after chemotherapy (from 74.1% to 65.7%; p = 0.0006), as well as DLCO adjusted for alveolar volume (from 92.8% to 77.4%; p < 0.0001). One patient died after surgery and 4 patients (13.3%) experienced postoperative respiratory complications. Compared with patients without complications, these 4 patients had higher mean increase in FEV(1) after chemotherapy (+26.8% vs + 6.7%; p = 0.025), but greater mean decrease in DLCO/Va (-27.8% vs -13.6%; p = 0.03). Impact of change in DLCO on postoperative respiratory complications was not confirmed by multiple logistic regression analysis (p = 0.16). CONCLUSIONS: In lung cancer patients, forced expiratory volume in 1 second and forced vital capacity assessed after neoadjuvant chemotherapy are not reliable indicators of the likelihood of respiratory complications after surgery. The risk of respiratory complication may be directly linked to loss of DLCO/Va. Lung diffusion for carbon monoxide assessed after neoadjuvant chemotherapy is probably the most sensitive risk indicator of respiratory complications after surgery. We recommend that DLCO studies be performed before and after chemotherapy in lung cancer patients undergoing induction therapy.     

Multi-Centre European Experience with Intragastric Balloon in Overweight Populations: 13 Years of Experience

Background

The request to lose weight is expanding not only in obese and morbidly obese patients but also in overweight patients affected by co-morbidities as diabetes and hypertension and who do not tolerate diet regimen or lifestyle changes. The aim of this study is a multicenter evaluation of outcomes of intragastric balloon in overweight patients.

Methods

Patients (BMI 27–30 kg/m²) treated with a BioEnterics Intragastric Balloon (BIB) between 1996 and 2010 were extracted from the database of the participating centres in Rome (Italy), Liège (Belgium) and Madrid (Spain). Primary endpoints were the efficacy and safety at 6 and 42 months from balloon positioning. Secondary endpoints included resolution of co-morbidities.

Results

A total of 261 patients were included in this study. The most common indication for balloon placement was a psychological disorder (54 %). Mean body mass index (BMI) fell from 28.6?±?0.4 at baseline to 25.4?±?2.6 kg/m² at 6 months and to 27.0?±?3.1 kg/m² at 3 years from BIB removal. The mean %EWL was 55.6 % at 6 months and 29.1 % at 3 years. Forty-seven patients (18 %) had complications associated with placement of the intragastric balloon (leak?=?28, intolerance?=?14, duodenal ulcer?=?2, gastritis?=?1, oesophagitis?=?1, duodenal polyps?=?1). The rate of patients with hypertension decreased from 29 % at baseline to 16 % at 3 years. Diabetes decreased from 15 to 10 %, dyslipidaemia decreased from 20 to 18 %, hypercholesterolaemia decreased from 32 to 21 % and osteoarthropathy decreased from 25 to 13 %.

Conclusions

The intragastric balloon is safe and effective in overweight patients, helping to reduce progression to obesity and decreasing the prevalence of a number of important co-morbidities.     

Endothelial dysfunction and oxidative stress in chronic renal failure

Uremic patients have an increased incidence of cardiovascular disease (CVD), endothelial dysfunction and oxidative stress that can contribute to cardiovascular (CV) events. To assess the relationship between endothelial dysfunction, oxidative stress and renal failure severity, we studied 40 patients (age 57 +/- 7 yrs, 24 males) affected by chronic kidney disease (CKD) K/DOQI stage 3-5 (serum creatinine (Cr) 5.6 +/- 2.2 mg/dL) on conservative treatment, 20 uremic patients (age 57 +/- 12 yrs, 13 males) on hemodialysis (HD) and 30 healthy controls (56 +/- 12 yrs, 20 males). Before and 2 hr after oral vitamin C (2 g) administration, we measured brachial artery endothelium-dependent vasodilation (flow mediated dilation (FMD)) to reactive hyperemia following 5 min of forearm ischemia and the response to sublingual glyceril trinitrate (GTN). Measurements were made by high-resolution ultrasound and computerized analysis. FMD was lower in CKD patients than in controls (5.3 +/- 2.2 vs. 6.9 +/- 2.8%; p<0.01) and was further reduced in HD patients (3.6 +/- 2.7; p<0.01 vs. CKD patients). Response to GTN was similar in all groups. FMD was related to Cr clearance (r=0.42; p<0.01) in CKD patients, while it related inversely to Kt/V(urea) (r=-0.52; p<0.05) in HD patients. After vitamin C administration, FMD was significantly enhanced in HD (4.7 +/- 2.4%; p<0.01 vs. baseline), but not in CKD patients. Response to GTN was unaffected. However, vitamin C load reduced oxidative stress markers, and increased plasma antioxidant capability in both groups. In conclusion, the reduced endothelium-dependent dilation in the brachial artery of CKD patients is related to renal failure severity. HD patients showed a more marked alteration, which seems to be related, at least in part, to increased oxidative stress.     

Constitutive production of leukemia differentiation, colony- stimulating, erythroid burst-promoting, and pluripoietic factors by a human hepatoma cell line: characterization of the leukemia differentiation factor

Conditioned medium (CM) obtained from a human hepatoma cell line, SK- HEP-1, contains colony-stimulating factors (CSFs) active on murine and human bone marrow-derived granulocyte and macrophage colony-forming units (CFU-GM) and a factor capable of inducing granulocyte-macrophage differentiation (GM-DF) of murine myelomonocytic leukemic cells WEHI- 3B(D+) and human promyelocytic leukemic cells HL-60 when assayed in semisolid agar cultures. The human active granulocyte-macrophage colony- stimulating factor (GM-CSF) for day 7 CFU-GM and the GM-DF for WEHI- 3B(D+) and for HL-60 are not separable by acrylamide agarose column chromatography, eluting at an apparent molecular weight between 20,000 and 35,000 daltons, or by isoelectric focusing (isoelectric point, pH 5.4). In addition, SK-HEP-1 CM contains erythroid burst-promoting activity (BPA) and a factor that promotes the growth of human mixed colonies. SK-HEP-1 cells, which grow as an adherent monolayer, appear not to be endothelial or monocytic in origin since by immunofluorescent staining they are negative for Ia (HLA-DR), monocyte antigen 1 and 2, lysozyme, and factor VIII-related antigen. Positive immunofluorescent staining for keratin and fibronectin suggests the possibility that SK- HEP-1 is an epithelial cell line. Constitutive production of GM-DF as well as other hematopoietic activities including GM-CSF, erythroid BPA, and an activity that promotes the growth of human mixed colony progenitors by a human epithelial tumor cell line, SK-HEP-1, suggests that this cell line is a valuable resource for both large-scale production of these factors and the cloning of the gene(s) that code for these regulators.     

Mild cognitive impairment in Parkinson’s disease: Diagnosis and progression to dementia

Introduction: Mild cognitive impairment is common in nondemented Parkinson disease patients (PD-MCI) and is considered as a risk factor for dementia (PDD). Recently, the Movement Disorder Society (MDS) published guidelines for PD-MCI, although the studies available are still limited. The aim of this work was to characterize PD-MCI and its progression to dementia. Moreover, the study variables could be considered as predictors for the progression of cognitive impairment. Method: The study included 43 patients with idiopathic PD (mean age = 59.19 years, SD = 9.64) and 20 healthy and neurologically normal controls (mean age = 60.85 years, SD = 12.26). The criteria proposed by the MDS Task Force were applied for the PD-MCI diagnosis. Follow-up assessments were conducted within six to eight years after the diagnosis of PD-MCI. Results: The results showed that 60.5% of the patients were diagnosed with PD-MCI when a comprehensive assessment was performed (MDS criteria Level 2), while 23.3% of the patients met MCI criteria when a brief assessment was used (MDS criteria Level 1). Multiple domain impairment was the most frequent impairment (96.2%). A total of 42.3% of PD-MCI patients had dementia in the follow-up study. Logistic regression showed that the Hoehn and Yahr stage and education significantly contributed to the prediction of PD-MCI. Moreover, the Hoehn and Yahr stage and memory domain significantly contributed to the prediction of dementia. Conclusions: The results of the study: (a) provide relevant data about the process of validation of the MDS PD-MCI criteria, (b) reinforce the hypothesis that PD-MCI is more frequent than previous studies showed without applying MDS criteria, and (c) confirm that PD-MCI is a risk factor for the onset of dementia. Finally, the study shows that neurological impairment, educational level and memory impairment were predictors for the progression of cognitive impairment.     

Traumatic subclavian arterial rupture: a case report and review of literature

ABSTRACT: Subclavian artery injuries represent an uncommon complication of blunt chest trauma, this structure being protected by subclavius muscle, the clavicle, the first rib, and the deep cervical fascia as well as the costo-coracoid ligament, a clavi-coraco-axillary fascia portion. Subclavian artery injury appears early after trauma, and arterial rupture may cause life-treatening haemorrages, pseudo-aneurysm formation and compression of brachial plexus. These clinical eveniences must be carefully worked out by accurate physical examination of the upper limb: skin color, temperature, sensation as well as radial pulse and hand motility represent the key points of physical examination in this setting. The presence of large hematomas and pulsatile palpable mass in supraclavicular region should raise the suspicion of serious vascular injury. Since the first reports of endovascular treatment for traumatic vascular injuries in the 90's, an increasing number of vascular lesions have been treated this way. We report a case of traumatic subclavian arterial rupture after blunt chest trauma due to a 4 meters fall, treated by endovascular stent grafting, providing a complete review of the past twenty years' literature.