The diversity of extended gene haplotypes HLA-B*27 in Croatia

In the present study the extended haplotypes of HLA-B*27 gene were analysed in the sample of 42 Croatian families. Peripheral blood (2 ml) was collected from all the individuals and genomic DNA was extracted using a commercial kit. The HLA alleles were determined using the method PCR sequence specific primers (PCR-SSP) while the microsatellite alleles were amplified using the method PCR-STR. Analysis of HLA-A-B*27-D6S2927-STR MICA-TNFalpha-DRB1 extended haplotypes demonstrated the strongest linkage disequilibrium between HLA-B*27 alleles and microsatellite alleles D6S2927-1 and STR_MICA-A4. Analysis indicated that the rare allele B*2730 is always present in the extended haplotype HLA-A3-B*2730-D6S2927-1-STR MICA-A4-TNFalpha-9-DRB1*16. The results of the present study will be applied in future studies of association between microsatellite alleles and spondyloarthropathies and contribute to a better understanding of peptide binding to HLA class I molecules, as well as other aspects of immune response.     

Risk factors for treatment failure in renal suppurative infections

There are conflicting results of published studies about prognostic value of various factors in purulent renal infections. The purpose of this study was to identify and quantify potential risk factors for early and late treatment failure in such infections. A retrospective review of 75 renal suppurative infections, at three tertiary Serbian Clinics of Urology, was conducted. We considered numerous potential risk factors in a multivariate analysis. This series was comprised of 49 women and 26 men, with mean age of 56.7 years. There were 38 and 37 patients who experienced successful and unfavorable early treatment outcome, respectively. Overall mortality rate was 9.3%. Comorbidity [odds ratio (OR) = 1.6], complex suppurative pathological findings (OR = 3.6), presence of Pseudomonas spp. (OR = 6.7), multiple bacterial strains (OR = 2.7), and positive culture itself (OR = 3.6) were the predictors of poor early prognosis. A urological intervention and presence of pyonephrosis significantly increased the chance for good initial outcome (OR = 0.32 and 0.37, respectively). In the late treatment failure analysis presence of comorbidities (OR = 5.8) and treatment complications (OR = 7.5) significantly increased chance for fatal outcome. Patients’ baseline health status and complexity of suppuration itself were the most important predictors of clinical outcomes. Surgical drainage dominated over antimicrobial therapy.     

Endoscopic Vaporesection of the Prostate Using the Continuous-Wave 2-μm Thulium Laser: Outcome and Demonstration of the Surgical Technique

Background

The potential of a new continuous-wave (CW) 70-W, 2.013-μm thulium-doped yttrium aluminium garnet (Tm:YAG) laser for the endoscopic treatment of benign prostatic hyperplasia (BPH) is investigated.

Objective

The simultaneous combination of vaporisation and resection of prostatic tissue in a retrograde fashion is the main characteristic of this new laser technique. We provide a DVD that shows the main steps of this procedure.

Design, setting, and participants

We retrospectively evaluated 56 nonconsecutive patients who were treated by thulium laser vaporesection of the prostate in our institution between 2005 and 2007.

Surgical procedure

Vaporesection of the prostate is performed by moving the fibre semicircumferentially from the verumontanum towards the bladder neck, thereby undermining tissue and cutting chips.

Measurements

Blood loss, postvoiding residual urine (PVRU), maximum flow rate (Q_max), and the International Prostate Symptom Score (IPSS) were measured as well as prostate volume and prostate-specific antigen (PSA). The duration of the procedure, need for postoperative irrigation, duration of catheterisation, and hospital stay were recorded.

Results and limitations

The median procedure time was 60 min, postoperative irrigation was necessary in 19 out of 56 patients, and the median duration of catheterisation was 23 hr. At the day of discharge, the mean haemoglobin value decreased by 0.2 mg/dl (p = 0.13), the average Q_max improved from 8.1 to 19.3 ml/s (p < 0.001), and the PVRU decreased from 152 ml to 57 ml (p < 0.05). The blood transfusion rate was 3.6%, and two patients needed a recatheterisation postoperatively (3.6%). After a median follow-up of 9 mo, the IPSS improved from 19.8 at baseline to 8.6 (p < 0.001). Four patients had a repeat transurethral resection of the prostate (TURP) during the learning curve, but this was not necessary in any of the later patients. One patient developed a urethral stricture, and another developed a bladder neck contracture.

Conclusions

The thulium laser seems to be a suitable tool for the endoscopic treatment of BPH.     

Circadian rhythms of diuresis,proteinuria and natriuresis in children with chronic glomerular disease

The aim of our study was to examine diurnal variation in urine volume (UV) output, proteinuria (UPRT), urine creatinine (UCr) and urine sodium ion excretion (UNa) in children with chronic glomerulopathy. In 56 patients (20 boys/36 girls, aged 11.7 ± 0.6 years) samples for UPRT, UCr and UNa were collected during the day and night, with continuous ambulatory blood pressure (BP) monitoring. On the basis of creatinine clearance (CrCl) the patients were divided into group I (n = 44, with CrCl 131 ± 3.6 ml/min per 1.73 m² body surface area), or group II (n = 12, with CrCl 44.6 ± 7.7 ml/min per 1.73 m² body surface area). Nocturnal polyuria was defined as night time UV ≥ 35% of the 24 h UV. Age, gender, body mass index of the patients, 24 h UV, UCr and UNa were similar in both groups. However, arterial hypertension and nocturnal polyuria were widespread (P < 0.01) in group II. In addition, proteinuria was higher (P < 0. 05) in group II. The nocturnal decline in CrCl, UV, UPRT and UNa was significantly attenuated (P < 0.005) in patients in group II compared with those in group I. The night time mean arterial pressure (MAP), as well as the night/day ratios of MAP, UV, UPRT and UNa, showed negative associations with CrCl. Our findings strongly suggest that renal function diurnal variation and nocturnal MAP are related to decreased glomerular filtration rate at the time of examination.     

Ultrastructure and immunohistochemistry of the trigeminal peripheral myelinated axons in patients with neuralgia

Objective

Detailed ultrastructural and immunohistochemical examination of the trigeminal axons surrounded by the peripheral type of the myelin could add new information about the extent of the trigeminal nerve lesion in neuralgia.

Patients, materials and methods

The examination comprised, firstly, the 10 trigeminal nerve roots (TNRs) in which the neurovascular contact was found in 20% of the cases, and the 2 additional control TNRs. Secondly, the biopsy specimens were taken from 6 patients with trigeminal neuralgia and 2 patients with trigeminal neuropathy following a partial TNR rhizotomy. The specimens were examined under the electron microscope (EM) and/or using the immunohistochemical (IHC) methods.

Results

In addition to the central zone of demyelination, the EM examination of the TNR also revealed alterations of the peripheral myelin, i.e. deformation, thickening, demyelination and remyelination, as well as changes of the peripheral axons, that is, atrophy or hypertrophy, neurofilaments increase, loss of the myelin and sprouting occasionally. Some Schwann cells were also damaged. The IHC examination usually showed a moderate immune reaction against neuron-specific enolase (NSE) and protein gene product 9.5 (PGP9.5), but sporadically weaker reaction against the S-100 protein, synaptophysin (SY), neurofilament protein (NFP) and glial fibrillary acidic protein (GFAP). The substance P (SP) and calcitonin gene-related peptide (CGRP) immunoreactivity was weak at some sites, but strong at some other places.

Conclusions

The pathological changes affect not only the central nerve fibers of the TNR, but also some of the peripheral axons, their myelin sheath and Schwann cells. These are signs of the retrograde ultrastructural and biochemical alterations, which could participate in the pathophysiological mechanism underlying the trigeminal neuralgia.     

ATP13A2 variants in early‐onset Parkinson's disease patients and controls

Four genes responsible for recessively inherited forms of Parkinson's disease (PD) have been identified, including the recently discovered ATP13A2 (PARK9) gene. Our objective was to investigate the role of this gene in a large cohort of PD patients and controls. We extensively screened all 29 exons of the ATP13A2 coding region in 112 patients with early‐onset PD (EOPD; <40 years) of mostly European ethnic origin and of 55 controls. We identified four carriers (3.6%) of novel single heterozygous ATP13A2 missense changes that were absent in controls. Interestingly, the carrier of one of these variants also harbored two mutations in the Parkin gene. None of the carriers had atypical features previously described in patients with two mutated ATP13A2 alleles (Kufor–Rakeb syndrome). Our data suggest that two mutated ATP13A2 alleles are not a common cause of PD. Although heterozygous variants are present in a considerable number of patients, they are—based on this relatively small sample—not significantly more frequent in patients compared to controls. © 2009 Movement Disorder Society     

Hypereosinophilic syndrome: diagnosis and treatment

PURPOSE OF REVIEW: Hypereosinophilic syndrome is increasingly recognized as a heterogeneous group of disorders, in some cases with precisely defined pathogenesis, which has led to changes in diagnostic approaches and therapeutic strategies. An update on causes and modern therapy is presented here. RECENT FINDINGS: Clonal eosinophilias belong to the group of myeloid malignancies. Karyotypically occult FIP1L1- platelet-derived growth factor receptor alpha and beta rearranged eosinophilic disorders respond to imatinib mesylate with almost 100% efficacy. If standard therapies fail, the FIP1L1- platelet-derived growth factor receptor-negative cases of hypereosinophilic syndrome should also be considered for treatment with imatinib. The recognition of acquired resistance to imatinib has aroused interest in developing new tyrosine kinase inhibitors. Other subgroups of clonal eosinophilias have been molecularly defined, but the curative verification of pathogenetic relevance has not been certified. Hypereosinophilic syndrome patients with abnormal T-cell populations have benefited from treatment with anti IL-5 monoclonal antibodies. SUMMARY: The FIP1L1- platelet-derived growth factor receptor alpha and beta-positive patients, and those with abnormal T-cell populations are currently the only clearly defined treatable subgroups of hypereosinophilic syndrome. The FIP1L1- platelet-derived growth factor receptor alpha-negative responders to imatinib pose a question as to the existence of subentities with unrecognized tyrosine kinases-based mutation. The search for such cases and other treatable subgroups of hypereosinophilic syndrome has already begun.