Hypocitraturia as a risk factor for nephrocalcinosis after kidney transplantation

Calcium-oxalate crystal deposition in kidney transplant biopsy specimen led us to investigate the impact of calcineurin inhibitor treatment on urinary excretion of lithogenic and stone inhibitory substances in 53 children after successful kidney transplantation (KTx) receiving cyclosporine A (CsA) or tacrolimus. We compared the values obtained with those of 12 patients with recurrent nephrotic syndrome under CsA and of 6 patients with Rasmussen encephalitis (RE) under tacrolimus therapy. Renal ultrasound examinations were repeatedly performed. Hypocitraturia was found in 69% of patients, with KTx patients having a significantly lower urinary citrate excretion than those receiving calcineurin inhibitors for other reasons. Secondly, we found hyperoxaluria in 35% of patients, again especially in those after KTx. No significant difference in urinary substances was seen comparing CsA with tacrolimus treatment. Urolithiasis was found in one and calcium-oxalate crystal deposition in biopsy specimen of three KTx patients. Calcineurin inhibitor treatment can lead to significant hypocitraturia, especially in patients after KTx receiving the highest dose of medication. Hyperoxaluria is primarily the result of a removal of significant body oxalate stores, deposited during dialysis, but may not be suspected as a specific side effect of calcineurin inhibitor therapy. Both findings can increase the risk for urolithiasis or nephrocalcinosis.     

In vitro antifungal susceptibilities of Sporothrix schenckii in two growth phases

We have determined the antifungal susceptibilities of 34 clinical isolates of the dimorphic fungus Sporothrix schenckii to 11 drugs using a microdilution method. In general, the type of growth phase (mycelial or yeast) and the temperature of incubation (30 or 35 degrees C) exerted a significant influence on the MICs.     

Successful treatment of chronic recurrent multifocal osteomyelitis with tumor necrosis factor-alpha blockage

We describe the case of an 18-year-old girl with chronic recurrent multifocal osteomyelitis (CRMO) over a period of 10 years. She had suffered predominantly from very painful recurrent swelling of her cheeks. Various therapeutic regimens including nonsteroidal antiinflammatory drugs and steroids had shown only a partial or temporary response. Because tumor necrosis factor-alpha-blocking agents have been successfully applied in Crohn's-associated CRMO and the related SAPHO (synovitis, acne, pustulosis, hyperostosis, and osteitis) syndrome, tumor necrosis factor-alpha-blocking therapy with infliximab was initiated. Thereafter, apart from 1 mild episode, no additional recurrences were observed during 21 months of follow-up. Infliximab was well tolerated, and steroids were tapered off. Our observation indicates that infliximab may be an effective therapeutic option in CRMO.     

Detection of polyomavirus BK and JC in children with kidney diseases and renal transplant recipients

BACKGROUND: Reactivation of polyomavirus is a known reason for severe renal dysfunction in adult renal transplant recipients. Testing for polyomavirus DNA in plasma has been described as a sensitive and specific method to discover viral nephropathy in adult patients. We were now interested in polyomavirus status in a pediatric patient setting. METHODS: Plasma and urine samples were obtained from 80 children including 38 children after renal transplantation (group 1), 7 children with different kidney diseases receiving immunosuppressive treatment (group 2) and 35 children with different kidney diseases not receiving immunosuppressive treatment (group 3). A nested polymerase chain reaction method was used for amplification of polyomavirus DNA fragments. Differentiation between JC and BK virus was done by digestion with restriction endonucleases. RESULTS: Polyomavirus DNA was detected in the urine sample of 19 of 38 (50%) renal transplant recipients (group 1), of 1 of 7 (14%) patients from group 2 and in none of the 35 patients of group 3. Plasma samples from 3 (8%) of group 1 patients and from 1 child each of group 2 (14%) and group 3 (3%) were tested positive for polyomavirus DNA. CONCLUSION: Urinary polyomavirus excretion seems to be more frequent in pediatric patients with kidney diseases receiving immunosuppressive treatment and after renal transplantation than in children with various kidney diseases without immunosuppressive treatment.     

Current Therapy of Pulmonary Hypertension

Abstract Pulmonary arterial hypertension (PAH) affects vascular proliferation and remodeling in small pulmonary arteries and results in right ventricular failure and death due to a progressive increase in pulmonary vascular resistance. Recent advances in understanding of the molecular mechanisms involved in PAH suggest that endothelial dysfunction plays a major role. Impaired production of vasoactive mediators, such as prostacyclin and nitric oxide, accompanied with prolonged overexpression of vasoconstrictors such as endothelin-1, affects vascular tone and reinforces vascular remodeling. As the latter substances represent logical pharmacological targets, new drugs affecting these mechanisms have evolved during the past 2 decades and led to umpteen placebo-controlled trials in bygone years. Prognosis and quality of life of patients suffering from PAH seem to improve due to these new treatment strategies resulting in a reduction of mortality and morbidity, but there is still a substantial need for further long-term and head-to-head trials.     

A previously uncharacterized role for estrogen receptor beta: defeminization of male brain and behavior

Sex differences in brain and behavior are ubiquitous in sexually reproducing species. One cause of sexual dimorphisms is developmental differences in circulating concentrations of gonadal steroids. Neonatal testes produce androgens; thus, males are exposed to both testosterone and estradiol, whereas females are not exposed to high concentrations of either hormone until puberty. Classically, the development of neural sex differences is initiated by estradiol, which activates two processes in male neonates; masculinization, the development of male-type behaviors, and defeminization, the loss of the ability to display female-type behaviors. Here, we test the hypothesis that defeminization is regulated by estrogen receptor beta (ERbeta). Adult male ERbeta knockout and WT mice were gonadectomized, treated with female priming hormones, and tested for receptive behavior. Indicative of incomplete defeminization, male ERbeta knockout mice showed significantly higher levels of female receptivity as compared with WT littermates. Testes-intact males did not differ in any aspects of their male sexual behavior, regardless of genotype. In olfactory preference tests, males of both genotypes showed equivalent preferences for female-soiled bedding. Based on these results, we hypothesize that ERbeta is involved in defeminization of brain and behavior. This aspect of ERbeta function may lead to developments in our understanding of neural-based sexually dimorphic human behaviors.     

Endovascular treatment of trigeminal neuralgia caused by arteriovenous malformation: is surgery really necessary?

A case is presented with secondary trigeminal neuralgia (TN) caused by an arteriovenous malformation (AVM) of the cerebellopontine cistern, which was detected by radiological work-up for planned microvascular decompression. An AVM surrounding the trigeminal nerve was demonstrated on thin-slice heavily T (2)-weighted 3D-sequence on magnetic resonance imaging (MRI) and confirmed by angiography. The first therapeutic step was endovascular embolization with complete obliteration of the AVM and cessation of pain. Nevertheless surgical excision was performed in order to remove compressive vessels and to prevent a recurrence of pain.     

A novel flexible, retrievable endovascular stent system for small-vessel anatomy: preliminary in vivo data

BACKGROUND AND PURPOSE: This study assessed the in vivo delivery, retrievability, short-term patency, and cellular response to a new flexible endovascular stent system in a rabbit model. The stent is designed for delivery through a microcatheter and is fully retrievable with electrolytic detachment from a delivery wire. METHODS: We successfully deployed nine stents (range of sizes, 2.5-4 mm diameter, 15-35 mm length) in six straight (carotid) and three angled (subclavian) arteries of six Chinchilla Bastard rabbits. Serial imaging was performed by using intravenous digital subtraction angiography (IVDSA), contrast-enhanced MR angiography (CEMRA), time-of-flight MR angiography (TOF), and CT-angiography 3 days and 4 weeks after stent deployment. Subjects were euthenized after 4 weeks (n = 5), and stents were removed for histologic analysis. RESULTS: Stent deployment was feasible in all cases. After initial deployment, all stents could be fully retrieved within the microcatheter. The detachment zone and the distal stent marker were easily visible under fluoroscopy, and final detachment occurred reliably in all cases. We observed no procedural complications. Noninvasive imaging by using IVDSA, MR angiography, and CT angiography was feasible in this stent system and demonstrated all arteries patent and not narrowed at 3 days and 4 weeks, findings that were confirmed by histologic analysis. CONCLUSION: This electrolytically detachable stent is promising as a treatment for intracranial arteries, because it can be delivered through microcatheters small enough for intracranial navigation. It is fully retrievable, thus providing greater control than currently available stents. Noninvasive imaging by using IVDSA, MR angiography, and CT angiography is feasible in this stent system and may be useful for follow-up. Further long-term data are needed.     

Expression and regulation of<Emphasis Type="Italic"> ROR-1</Emphasis> during early avian limb development

ROR-1 is a member of the ROR family of tyrosine kinase like orphan receptors and is highly conserved among various species. We have isolated the chickROR-1 (cROR-1) and show that cROR-1 expression is high and restricted to the proximal limb region until HH-stage 25. At later stages, expression spreads towards the distal limb region. In order to determine the signals that control cROR-1 expression, factors known to be involved in limb patterning (FGFs, BMPs, SHH, retinoic acid) were applied to the developing limb. Whereas neither FGFs, BMPs, nor SHH affected cROR-1 expression, upregulation could be achieved by ectopic application of retinoic acid to the distal limb region. As retinoic acid also upregulated retinoic acid receptor beta (Rar-β), we assume that cROR-1 upregulation is mediated by Rar-β. We conclude that ROR-1 signaling is an independently regulated pathway, which is involved in late rather than early limb development.