Chronic Increase of Bone Turnover Markers After Biliopancreatic Diversion is Related to Secondary Hyperparathyroidism and Weight Loss. Relation with Bone Mineral Density

Background  

Biliopancreatic diversion (BPD) is the most effective bariatric procedure. Around 70% of these patients have secondary hyperparathyroidism (SH) in the long term as a consequence of calcium and vitamin D malabsorption. This work was aimed to study the influence of SH on bone turnover and its relationship with bone mineral density (BMD).     

Pharmacokinetics,Safety, and Tolerability of Voriconazole in Immunocompromised Children

The pharmacokinetics of voriconazole in children receiving 4 mg/kg intravenously (i.v.) demonstrate substantially lower plasma exposures (as defined by area under the concentration-time curve [AUC]) than those in adults receiving the same therapeutic dosage. These differences in pharmacokinetics between children and adults limit accurate prediction of pediatric voriconazole exposure based on adult dosages. We therefore studied the pharmacokinetics and tolerability of higher dosages of an i.v.-to-oral regimen of voriconazole in immunocompromised children aged 2 to <12 years in two dosage cohorts for the prevention of invasive fungal infections. The first cohort received 4 mg/kg i.v. every 12 h (q12h), then 6 mg/kg i.v. q12h, and then 4 mg/kg orally (p.o.) q12h; the second received 6 mg/kg i.v. q12h, then 8 mg/kg i.v. q12h, and then 6 mg/kg p.o. q12h. The mean values for the AUC over the dosing interval (AUCτ) for 4 mg/kg and 6 mg/kg i.v. in cohort 1 were 11,827 and 22,914 ng·h/ml, respectively, whereas the mean AUCτ values for 6 mg/kg and 8 mg/kg i.v. in cohort 2 were 17,249 and 29,776 ng·h/ml, respectively. High interpatient variability was observed. The bioavailability of the oral formulation in children was approximately 65%. The safety profiles were similar in the two cohorts and age groups. The most common treatment-related adverse event was increased gamma glutamyl transpeptidase levels. There was no correlation between adverse events and voriconazole exposure. In summary, voriconazole was tolerated to a similar degree regardless of dosage and age; the mean plasma AUCτ for 8 mg/kg i.v. in children approached that for 4 mg/kg i.v. in adults, thus representing a rationally selected dosage for the pediatric population.Invasive fungal infections cause severe morbidity and mortality in immunocompromised children, particularly those with hematological malignancies and those undergoing hematopoietic stem cell transplantation (HSCT) (3, 8, 11, 19, 21, 27, 28). Voriconazole is a broad-spectrum antifungal triazole with in vitro and in vivo activity against yeasts and filamentous fungi (2, 5). Voriconazole is approved for adults for primary treatment of invasive aspergillosis, esophageal candidiasis, and candidemia in nonneutropenic patients. It is also approved for the treatment of serious, refractory infections caused by Scedosporium and Fusarium species (16, 25). Voriconazole is more effective than deoxycholate amphotericin B in treatment of invasive aspergillosis in adults, most of whom suffered from invasive pulmonary aspergillosis (9). In addition, voriconazole has been used successfully to treat aspergillosis of the central nervous system and bone (14, 20).Several case series and single case reports have described the safety and efficacy of voriconazole in pediatric oncology patients and other immunocompromised children with invasive mycoses (10, 24, 26). Voriconazole also has been used to treat Aspergillus airway disease in pediatric patients with cystic fibrosis (10). However, considerably less is known about the pharmacokinetics of this antifungal agent in children than about those in adults.Current studies indicate that there are major differences between the pharmacokinetics of voriconazole in children and those in adults. The first systematic study of the safety, tolerability, and pharmacokinetics of voriconazole in pediatric patients demonstrated linear plasma pharmacokinetics in patients receiving intravenous (i.v.) voriconazole at dosages of 3 mg/kg every 12 h (q12h) or 4 mg/kg q12h (24). By comparison, voriconazole in adults displays nonlinear Michaelis-Menten plasma pharmacokinetics following similar dosages (17, 18). These differences in pharmacokinetics between children and adults limit accurate prediction of pediatric voriconazole exposure (as defined by area under the concentration-time curve [AUC]) based on adult dosages. Indeed, pharmacokinetic modeling studies demonstrated that the AUC was approximately 3-fold lower in children receiving 4 mg/kg of voriconazole q12h than in adults receiving the same dosage.Therefore, in order to approximate the plasma exposure achieved in adults, we studied the safety, tolerability, and plasma pharmacokinetics of voriconazole in pediatric patients receiving dosages of 4, 6, and 8 mg/kg i.v. q12h. We also examined the plasma pharmacokinetics of the oral suspension of voriconazole at 4 and 6 mg/kg q12h.     

Serum concentrations of osteocalcin, procollagen type 1 N-terminal propeptide and beta-CrossLaps in obese subjects with varying degrees of glucose tolerance

Aims To evaluate serum levels of osteocalcin (OC), procollagen type 1 N‐terminal propeptide (P1PN) and beta‐CrossLaps (beta‐CTx) in obese subjects and their relationship with glucose metabolism parameters. Subjects Sixty‐four obese patients classified according to their glucose tolerance. Design Case–control study. Measurements A 75‐g oral glucose tolerance test was performed with determinations of glucose and insulin between 0 and 120 min. Serum concentrations of OC, P1PN and beta‐CTx were quantified in baseline samples. Results Patients with type 2 diabetes (T2D, n = 24) exhibited OC serum levels (2·6 ± 1·0 nm ) significantly lower than those found in subjects with normal glucose tolerance (NGT, n = 20, 3·9 ± 1·5 nm , P < 0·01). We found no significant differences in P1NP and beta‐CTX levels among patients with NGT, prediabetes and T2D. Multiple regression analysis showed that serum OC concentration, but not P1NP or beta‐CTx levels, was independently related to 2‐h plasma glucose. Conclusion Obese patients with T2D showed significantly reduced levels of OC in comparison with patients with lower degrees of glucose tolerance derangement. Our results also suggest that OC was the only bone marker independently related to the degree of glucose metabolism derangement in these patients.     

Recanalization of a discrete atretic right pulmonary artery segment with a new radiofrequency system.

We describe a case in which a discrete atretic segment of the right pulmonary artery (due to a Blalock-Taussig shunt) was reconstructed using a new radiofrequency system, balloon dilation, and stent implantation in an 18-month-old patient. The shunt was coil-occluded. The technique and applications of this novel approach are discussed.     

A Long-term Remission of a Recurrent Acute Lymphoblastic Leukaemia with Donor Leukocyte Infusions after Allogeneic Peripheral Blood Stem Cell Transplantation

This case report describes a patient with recurrent and refractory acute lymphoblastic leukaemia (ALL-L3), who relapsed four months after a HLA identical allogeneic Peripheral Blood Stem Cell (PBSC) transplantation; he was treated after relapse with intensive chemotherapy and then he received leukocyte infusion from her sibling donor. A long term Complete Remission (CR) was achieved, with complete chimerism and without signs of chronic GVHD. Thirteen months after Donor Leukocyte Infusion (DLI), he developed a relapse (4% blasts in BM), and a second infusion of leukocytes with the same chemotherapy schedule was performed. Six months after the second DLI the patient is alive. Since responses to Donor Lymphocyte Infusions (DLI) are uncommon in ALL, the possible causative factors for this unusual response are discussed.     

Allelic and genotypic frequencies of platelet glycoprotein polymorphisms in a Portuguese population

Introduction and objectivesWe studied genotypic and allelic frequencies of polymorphisms that can affect platelet function, namely the Kozak, VNTR and HPA-2 polymorphisms of glycoprotein Ibα, the Pl^A polymorphism of glycoprotein IIIa and the C807T polymorphism of glycoprotein Ia, in a Portuguese population composed of 227 donors.MethodsPCR-RFLP was used to assess the Kozak, HPA-2, Pl^A and C807T polymorphisms. The VNTR polymorphism was discriminated by different weight bands on electrophoresis.ResultsAll genotypic frequencies were in Hardy-Weinberg equilibrium and do not differ from other Caucasian populations. Genotypic frequencies were 68.3%, 26.9% and 4.8% for Pl^A1/A1, Pl^A1/A2 and Pl^A2/A2 genotypes of the Pl^A polymorphism, 79.3%, 20.3% and 0.4% for TT, TC and CC genotypes of the Kozak polymorphism, 81.1%, 18.9% and 0.0% for aa, ab and bb genotypes of the HPA-2 polymorphism, 15.4%, 0.9%, 70.5%, 11.5%, 1.3% and 0.4% for BC, BD, CC, CD, DD and CE genotypes of the VNTR polymorphism, and 39.7%, 50.2% and 10.1% for CC, CT and TT genotypes of the C807T polymorphism.ConclusionsThe Portuguese population has now been characterized in terms of major platelet glycoprotein polymorphisms, which will be an important tool for further studies to assess the role of platelet glycoproteins in individual predisposition to prothrombotic conditions and response to antithrombotic therapy.