Multiple percutaneous access routes to multiple calculi, calculi in caliceal diverticula, and staghorn calculi

For expeditious removal of multiple calculi from certain locations in the pyelocaliceal system, the use of multiple percutaneous entry routes is advocated. The accessibility of different regions of the pyelocaliceal system from different percutaneous entry sites was mapped out after experience with the percutaneous removal of 87 solitary and 37 multiple renal calculi. A technique allowing limited access to calculi in caliceal diverticula and hydrocalices distal to stenotic infundibula was used, along with a technique for percutaneous infundibuloplasty, which is necessary to ensure drainage of such obstructed calices or caliceal diverticula after percutaneous lithotripsy. In 34 of 37 patients with multiple or staghorn calculi, all calculi were eventually removed by these methods. The use of multiple entry routes did not increase the risk of reduced renal function. Moreover, improved drainage through the resultant multiple nephrostomy tubes and transinfundibular stents has reduced the incidence of postoperative septicemia.     

Cerebrospinal fluid D-serine and glycine concentrations are unaltered and unaffected by olanzapine therapy in male schizophrenic patients.

N-Methyl D-aspartate (NMDA)-receptor hypofunction has been implicated in the pathophysiology of schizophrenia and D-serine and glycine add-on therapy to antipsychotics has shown beneficial effects in schizophrenic patients. Nevertheless, previous studies have not shown consistently altered D-serine concentrations in cerebrospinal fluid (CSF) of schizophrenic patients. To confirm and extend these results, CSF concentrations of both endogenous NMDA-receptor co-agonists d-serine and glycine and their common precursor L-serine were analyzed simultaneously in 17 healthy controls and 19 schizophrenic patients before and 6 weeks after daily olanzapine (10 mg) treatment. CSF D-serine, L-serine and glycine concentrations and their relative ratios were similar between schizophrenic patients and controls and no differences were observed before and after olanzapine therapy. Thus, the NMDA-receptor hypofunction hypothesis in schizophrenia is not explained by olanzapine therapy-dependent absolute or relative decreases in CSF D-serine and glycine concentrations in this series of male patients, thereby not providing convenient markers for the disorder.     

Long-Term Oral Methylphenidate Treatment in Adolescent and Adult Rats: Differential Effects on Brain Morphology and Function

Methylphenidate is a widely prescribed psychostimulant for treatment of attention deficit hyperactivity disorder (ADHD) in children and adolescents, which raises questions regarding its potential interference with the developing brain. In the present study, we investigated effects of 3 weeks oral methylphenidate (5 mg/kg) vs vehicle treatment on brain structure and function in adolescent (post-natal day [P]25) and adult (P65) rats. Following a 1-week washout period, we used multimodal magnetic resonance imaging (MRI) to assess effects of age and treatment on independent component analysis-based functional connectivity (resting-state functional MRI), D-amphetamine-induced neural activation responses (pharmacological MRI), gray and white matter tissue volumes and cortical thickness (postmortem structural MRI), and white matter structural integrity (postmortem diffusion tensor imaging (DTI)). Many age-related differences were found, including cortical thinning, white matter development, larger dopamine-mediated activation responses and increased striatal functional connectivity. Methylphenidate reduced anterior cingulate cortical network strength in both adolescents and adults. In contrast to clinical observations from ADHD patient studies, methylphenidate did not increase white matter tissue volume or cortical thickness in rat. Nevertheless, DTI-based fractional anisotropy was higher in the anterior part of the corpus callosum following adolescent treatment. Furthermore, methylphenidate differentially affected adolescents and adults as evidenced by reduced striatal volume and myelination upon adolescent treatment, although we did not observe adverse treatment effects on striatal functional activity. Our findings of small but significant age-dependent effects of psychostimulant treatment in the striatum of healthy rats highlights the importance of further research in children and adolescents that are exposed to methylphenidate.     

Sex Differences in COMT Polymorphism Effects on Prefrontal Inhibitory Control in Adolescence

Catecholamine-0-methyl-transferase (COMT) gene variation effects on prefrontal blood oxygenation-level-dependent (BOLD) activation are robust; however, despite observations that COMT is estrogenically catabolized, sex differences in its prefrontal repercussions remain unclear. Here, in a large sample of healthy adolescents stratified by sex and Val¹⁵⁸Met genotype (n=1133), we examine BOLD responses during performance of the stop-signal task in right-hemispheric prefrontal regions fundamental to inhibitory control. A significant sex-by-genotype interaction was observed in pre-SMA during successful-inhibition trials and in both pre-SMA and inferior frontal cortex during failed-inhibition trials with Val homozygotes displaying elevated activation compared with other genotypes in males but not in females. BOLD activation in the same regions significantly mediated the relationship between COMT genotype and inhibitory proficiency as indexed by stop-signal reaction time in males alone. These sexually dimorphic effects of COMT on inhibitory brain activation have important implications for our understanding of the contrasting patterns of prefrontally governed psychopathology observed in males and females.     

Complete pathological response is predictive for clinical outcome after tri-modality therapy for carcinomas of the superior pulmonary sulcus

The objective was to define the relationship between histopathological changes after pre-operative chemo-radiotherapy (CRT) and clinical outcome following tri-modality therapy in patients with superior sulcus tumours. A retrospective analysis of tumour material was performed in a series of 46 patients who received tri-modality therapy between 1997 and 2007. Median follow-up was 34 months (5–154). Pathological complete response (pCR) was present in 20/46 tumours (43 %). The most common RECIST score after CRT in patients with pCR was a partial response (PR; 10/17, three unknown), whereas in patients without a pCR, stable disease was the most common (22/26) (p?=?0.002). In 26 specimens with residual tumour, this was mainly located in the periphery of the lesion rather than the centre (Spearman’s correlation?=?0.67, p?<?0.001). Prognosis was significantly better after a pCR compared to residual tumour (70 % 5-year overall survival vs. 20 %; p?=?0.001) and in patients with fewer than 10 % vital tumour cells as compared to those with >10 % (65 % 5-year overall survival vs. 18 %; p?<?0.001). A low mitotic count was associated with a longer disease-free survival (p?=?0.02). Complete pathological response and the presence of fewer than 10 % vital tumour cells after pre-operative CRT are both associated with a more favourable prognosis. A modification of the pathological staging system after radiotherapy, incorporating the percentage of vital tumour cells, is proposed.     

Expanding the clinical spectrum of 3-phosphoglycerate dehydrogenase deficiency

3-Phosphoglycerate dehydrogenase (3-PGDH) deficiency is considered to be a rare cause of congenital microcephaly, infantile onset of intractable seizures and severe psychomotor retardation. Here, we report for the first time a very mild form of genetically confirmed 3-PGDH deficiency in two siblings with juvenile onset of absence seizures and mild developmental delay. Amino acid analysis showed serine values in CSF and plasma identical to what is observed in the severe infantile form. Both patients responded favourably to relatively low dosages of serine supplementation with cessation of seizures, normalisation of their EEG abnormalities and improvement of well-being and behaviour. These cases illustrate that 3-PGDH deficiency can present with mild symptoms and should be considered as a treatable disorder in the differential diagnosis of mild developmental delay and seizures. Synopsis: we present a novel mild phenotype in patients with 3-PGDH deficiency.