Low-dose erythropoietin is effective and safe in children on continuous ambulatory peritoneal dialysis

Hypertension is one of the most important complications of erythropoietin (rHuEPO) therapy in dialysis patients. In this study, the effect of two different dosage regiments of subcutaneous rHuEPO on blood pressure [BP] was evaluated in 20 anemic children on continuous ambulatory peritoneal dialysis (CAPD). Patients were randomized to receive rHuEPO 50 U/kg, either once a week (group 1, 50 U/kg per week) or three times a week (group 2, 150 U/kg per week). At the beginning of the study, 8 patients in group 1 and 8 patients in group 2 were on antihypertensive therapy. In group 1, the hematocrit increased gradually and significantly from 18.98%±1.79% to 30.1%±1.62% after 6 months, while in group 2 it rapidly increased from 19.53%±1.86% to 32.4%±1.11% after 3 months. A significant increase in the mean arterial BP was observed in group 2. Antihypertensive therapy had to be increased in all of the 8 previously hypertensive patients and had to be initiated in 1 of the 2 originally normotensive patients in the same group. None of the patients in group 1 required a change in antihypertensive medication. We conclude that during treatment with rHuEPO pre-existing hypertension and the dose of rHuEPO are the most important risk factors for the development or worsening of hypertension in children on CAPD, and gradual elevation of hematocrit by low-dose rHuEPO avoids the development of severe hypertension. Received December 11, 1995; received in revised form September 16, 1996; accepted September 19, 1996     

Protein A immobilization and HIgG adsorption onto porous/nonporous and swellable HEMA-incorporated polyEGDMA microspheres

Both non swellable and swellable poly(EGDMA/HEMA) microbeads were produced by suspension copolymerization. These microbeads were modified by immobilization of a spacer-arm (hexamethylene diamine (HMDA)) and protein A. The optimal values for modifications were as follows: sodium periodate concentration, 1.0 mgml(-1); HMDA concentration, 4 mgml(-1); and glutaraldehyde concentration, 0.070 microgml(-1). Adsorption of protein A onto the plain and periodate oxidized poly(EGDMA/HEMA) microbeads were very close to each other, and were 0.01-0.02 mg protein A on the 1-g Microbeads I and II, respectively. Protein A immobilization on poly(EGDMA/HEMA) microbeads were studied at different temperatures, times, and pHs using single protein solution containing different amounts of proteins. The optimal values for immobilization were as follows: the initial protein A concentration, 0.1 mgml(-1); temperature, 25 degrees C; pH, 9.5; and immobilization time, 120 min. Incorporation of protein A resulted in 1.420 and 1.825 mg protein A on the 1-g Microbeads I and II, respectively. HIgG adsorption capacity on the protein A-incorporated poly(EGDMA/HEMA) microbeads is 27 and 35 mg HIgGg(-1) polymer for Microbeads I and II, respectively.     

The diagnostic value of magnetic resonance imaging in subacromial impingement syndrome

The aim of this study was to assess the diagnostic ability of magnetic resonance imaging (MRI) in subacromial impingement syndrome (SIS), using a physiological standard of reference. MRI of the rotator cuff (RC) and subacromial injection test (SIT), a reference standard for SIS diagnosis, were performed in 125 painful shoulders. MRI diagnostic accuracies were determined using a 2 x 2 table and the percentage values of SIS diagnosis in patients with the three Zlatkin MRI stages were determined. Shoulder function was evaluated using the Constant Scale, and results were compared for stages. The sensitivity, specificity, accuracy, positive and negative predictive values of MRI for SIS diagnosis were 98.85%, 36.84%, 80%, 78.18% and 93.33% respectively. Of the 32 patients with Zlatkin stage 1 changes in MRI, 20 (62%) had SIT approved SIS diagnosis, while 47 (79%) of the 59 patients with Zlatkin 2 and all of the 19 (100%) patients with Zlatkin 3 changes were diagnosed with SIS by SIT. Mean Constant scores were 78.04 +/- 18.3, 65.0 +/- 19.9 and 54.52 +/- 20.7 in patients with Zlatkin stages 1, 2 and 3, respectively (p < 0.05). The MRI of RC did not prove to be an excellent tool for SIT based SIS diagnosis, with its low specificity. However, the technique can give important clues, as its sensitivity and negative predictive values are high.     

Somatic mosaicism for a MECP2 mutation associated with classic Rett syndrome in a boy

Rett syndrome is a severe neurodevelopmental disorder that arises from mutations in the X-linked MECP2 gene. It is almost exclusively seen in girls due to the predominant occurrence of the mutations on the paternal X-chromosome, and also the early postnatal lethal effect of the disease causing mutations in hemizygous boys. We identified a boy with features of classic Rett syndrome who is mosaic for the truncating MECP2 mutation R270X. Chromosome analysis showed normal karyotype. These results indicate that a MECP2 mutation associated with Rett syndrome in females could lead to a similar phenotype in males as a result of somatic mosaicism.     

Poly(D,L-lactide/epsilon-caprolactone)/hydroxyapatite composites as bone filler: an in vivo study in rats

In this study, a novel composite bone substitute was implanted in animal models (rats) and their in vivo characteristics were examined. A D,L-lactide and E-caprolactone copolymer (Mw: 80,000; Mn:40,000, and PI:2.00) was synthesized by ring-opening polymerization of the respective dimers using stannous octoate as the catalyst. The final ratio of D,L-lactide to epsilon-caprolactone obtained by 1NMR was 60/40. Hydroxyapatite (HA) powder was loaded in the copolymer. The HA/copolymer ratio was 60/40 (w/w). These composites were easily shaped by hand. Animal tests were performed on mature wistar rats (n=30). Defects were created on the proximal, the thickest part of the femur. The bone defects of the first group were filled with polymer/HA composite, the second group filled with only HA and the third group was left empty. Histologic examination of bone tissues showed new bone formation around the yellow-green polymer/HA composite material in the first group of animals whereas no evidence of new bone growth was observed in other groups.     

Role of granulocyte colony-stimulating factor in the treatment of mucormycosis

Several problems in the management of life-threatening mucormycosis remain unresolved, necessitating new methods of management. Four patients with histopathologically proven rhinocerebral mucormycosis were treated with high cumulative doses of granulocyte colony-stimulating factor (G-CSF). All had multiple predisposing factors for mucormycosis, particularly leukemia and neutropenia. Two patients refractory to fluconazole therapy were treated with liposomal amphotericin B. The improvement in clinical manifestations was closely related to neutrophil recovery, and all patients were alive at the end of therapy. In addition to surgical debridement and antifungal therapy, G-CSF seems to have played a role in their survival.     

Is there any correlation between restriction fragment length polymorphism of the L-MYC gene and metastasis of human nonsmall cell lung cancer?

A potential molecular marker associated with cancer susceptibility as well as metastasis, prognosis and adverse survival, is the L-myc gene. The studies of lung cancer patients from different populations have yielded controversial results. We studied 64 nonsmall cell lung cancer (NSCLC) patients and 37 healthy controls of Turkish origin for L-myc gene polymorphism. Our aim was to test the hypothesis that there was association between L-myc S allele in NSCLC and predisposition to the disease and TNM stage indicating tumor size, node classification and metastasis. Polymerase chain reaction restriction fragment length polymorphism and agarose gel electrophoresis were used to determine the L-myc oncogene genotypes. We found no significant difference, both in the distribution of the LL, LS and SS genotypes and in the allelic frequencies, between the patient group and the control group; that is, the frequencies of L-myc alleles were, L and S, 0.59 and 0.41, 0.60 and 0.40, respectively. Our data between the patient group and the control group; that is, the frequencies of L-myc alleles were, L and S, 0.59 and 0.41, 0.60 and 0.40, respectively. Our data concerning age, sex, size of tumors, histological type of tumors showed no significant association with L-myc genotype. However, a higher frequency of L-myc S allele in the squamous cell carcinoma compared to other histological groups was found, although this difference was not statistically significant. No association was found between the L-myc RFLP and increased risk of metastasis either to the lymph nodes or to other organs. Our results suggested that L-myc gene polymorphism was not a suitable prognostic marker of metastatic development in Turkish NSCLC patients.     

Enhancing effect of chitosan on peptide drug delivery across buccal mucosa

The buccal mucosa represents a potentially important topical route for delivery of peptide or protein drugs with some unique advantages such as the avoidance of hepatic first-pass metabolism and the acidity and protease activity encountered in the gastrointestinal tract. However, the bioavailabilities or relative potencies of intraorally administered peptides are usually quite low, unless permeabilizers are employed. Chitosan, a mucopolysaccharide of marine origin, has been claimed to act both as a bioadhesive and permeabilizer, making it a candidate system for mucosal drug delivery. In this study, the enhancement effect of chitosan in gel form for oral mucosa was investigated with a large bioactive peptide, transforming growth factor-beta (TGF-beta). Chitosan gel was prepared at 2% concentration in dilute lactic acid and TGF-beta was incorporated into the gel. The effect of chitosan as a permeabilizer was determined by measuring the flux of TGF-beta across porcine oral mucosa in an in vitro system. The localization of TGF-beta within the oral mucosa was determined by horizontal sectioning and counting. Chitosan was found to exert a marked permeabilizing effect on buccal mucosa for peptide drug.