[Melanosis of the bladder-a rare diagnosis]. / Melanose der Harnblase ­ eine Rarität.

Melanosis of the urinary bladder is an extremely rare benign condition in which melanin deposits occur in the urothelial and stromal cells. We report such a case in which melanosis of the urinary bladder was detected in a 55-year-old woman with known multiple sclerosis during an extended workup due to urinary urgency complaints. The findings were confirmed by biopsy.

Voriconazole exposure is influenced by inflammation: A population pharmacokinetic model.

BACKGROUND: Voriconazole is an antifungal drug used for the treatment of invasive fungal infections. Due to highly variable drug exposure, therapeutic drug monitoring (TDM) has been recommended. TDM may be helpful to predict exposure accurately, but covariates, such as severe inflammation, that influence the metabolism of voriconazole have not been included in the population pharmacokinetic (popPK) models suitable for routine TDM. OBJECTIVES: To investigate whether the effect of inflammation, reflected by C-reactive protein (CRP), could improve a popPK model that can be applied in clinical care. PATIENTS AND METHODS: Data from two previous studies were included in the popPK modelling. PopPK modelling was performed using Edsim++. Different popPK models were compared using Akaike Information Criterion and goodness-of-fit plots. RESULTS: In total, 1060 voriconazole serum concentrations from 54 patients were included in this study. The final model was a one-compartment model with non-linear elimination. Only CRP was a significant covariate, and was included in the final model and found to affect the maximum rate of enzyme activity (Vmax). For the final popPK model, the mean volume of distribution was 145 L [coefficient of variation percentage (CV%)=61%], mean Michaelis-Menten constant was 5.7 mg/L (CV%=119%), mean Vmax was 86.4 mg/h (CV%=99%) and mean bioavailability was 0.83 (CV%=143%). Internal validation using bootstrapping resulted in median values close to the population parameter estimates. CONCLUSIONS: This one-compartment model with non-linear elimination and CRP as a covariate described the pharmacokinetics of voriconazole adequately.

DSC Perfusion MRI-Derived Fractional Tumor Burden and Relative CBV Differentiate Tumor Progression and Radiation Necrosis in Brain Metastases Treated with Stereotactic Radiosurgery.

BACKGROUND AND PURPOSE: Differentiation between tumor and radiation necrosis in patients with brain metastases treated with stereotactic radiosurgery is challenging. We hypothesized that MR perfusion and metabolic metrics can differentiate radiation necrosis from progressive tumor in this setting. MATERIALS AND METHODS: We retrospectively evaluated MRIs comprising DSC, dynamic contrast-enhanced, and arterial spin-labeling perfusion imaging in subjects with brain metastases previously treated with stereotactic radiosurgery. For each lesion, we obtained the mean normalized and standardized relative CBV and fractional tumor burden, volume transfer constant, and normalized maximum CBF, as well as the maximum standardized uptake value in a subset of subjects who underwent FDG-PET. Relative CBV thresholds of 1 and 1.75 were used to define low and high fractional tumor burden. RESULTS: Thirty subjects with 37 lesions (20 radiation necrosis, 17 tumor) were included. Compared with radiation necrosis, tumor had increased mean normalized and standardized relative CBV (P = .002) and high fractional tumor burden (normalized, P = .005; standardized, P = .003) and decreased low fractional tumor burden (normalized, P = .03; standardized, P = .01). The area under the curve showed that relative CBV (normalized = 0.80; standardized = 0.79) and high fractional tumor burden (normalized = 0.77; standardized = 0.78) performed the best to discriminate tumor and radiation necrosis. For tumor prediction, the normalized relative CBV cutoff of ≥1.75 yielded a sensitivity of 76.5% and specificity of 70.0%, while the standardized cutoff of ≥1.75 yielded a sensitivity of 41.2% and specificity of 95.0%. No significance was found with the volume transfer constant, normalized CBF, and standardized uptake value. CONCLUSIONS: Increased relative CBV and high fractional tumor burden (defined by a threshold relative CBV of ≥1.75) best differentiated tumor from radiation necrosis in subjects with brain metastases treated with stereotactic radiosurgery. Performance of normalized and standardized approaches was similar.

Perfusion MRI-Based Fractional Tumor Burden Differentiates between Tumor and Treatment Effect in Recurrent Glioblastomas and Informs Clinical Decision-Making.

BACKGROUND AND PURPOSE: Fractional tumor burden better correlates with histologic tumor volume fraction in treated glioblastoma than other perfusion metrics such as relative CBV. We defined fractional tumor burden classes with low and high blood volume to distinguish tumor from treatment effect and to determine whether fractional tumor burden can inform treatment-related decision-making. MATERIALS AND METHODS: Forty-seven patients with high-grade gliomas (primarily glioblastoma) with recurrent contrast-enhancing lesions on DSC-MR imaging were retrospectively evaluated after surgical sampling. Histopathologic examination defined treatment effect versus tumor. Normalized relative CBV thresholds of 1.0 and 1.75 were used to define low, intermediate, and high fractional tumor burden classes in each histopathologically defined group. Performance was assessed with an area under the receiver operating characteristic curve. Consensus agreement among physician raters reporting hypothetic changes in treatment-related decisions based on fractional tumor burden was compared with actual real-time treatment decisions. RESULTS: Mean lower fractional tumor burden, high fractional tumor burden, and relative CBV of the contrast-enhancing volume were significantly different between treatment effect and tumor (P = .002, P < .001, and P < .001), with tumor having significantly higher fractional tumor burden and relative CBV and lower fractional tumor burden. No significance was found with intermediate fractional tumor burden. Performance of the area under the receiver operating characteristic curve was the following: high fractional tumor burden, 0.85; low fractional tumor burden, 0.7; and relative CBV, 0.81. In comparing treatment decisions, there were disagreements in 7% of tumor and 44% of treatment effect cases; in the latter, all disagreements were in cases with scattered atypical cells. CONCLUSIONS: High fractional tumor burden and low fractional tumor burden define fractions of the contrast-enhancing lesion volume with high and low blood volume, respectively, and can differentiate treatment effect from tumor in recurrent glioblastomas. Fractional tumor burden maps can also help to inform clinical decision-making.

Pain and compression neuropathy in primary inguinal hernia.

PURPOSE: Enlargement of the ilioinguinal nerve at the external inguinal ring is observed in 34% of patients undergoing primary open inguinal herniorrhaphy; in 88% of patients it occurs at the fascial edge where the hernia mushrooms with abdominal pressure. Compression neuropathy occurs near many anatomical nerve constriction sites and is associated with enlargement of the peripheral nerve accompanied by sensory changes. METHODS: In this prospective study, Carolina Comfort Scale (CCS) questionnaire data was collected for 35 primary hernia repairs. Each patient underwent primary inguinal herniorrhaphy that included ilioinguinal neurectomy. All nerves were sampled proximal to the external inguinal ring. Any nerves with grossly increased overall diameter to any degree distal to the external ring were additionally sampled in the thickened portions. A neuropathologist performed histologic evaluation of the H&E-stained cross sections. RESULTS: Paired comparison of proximal and distal nerves revealed a greater overall diameter and greater measured nerve-specific diameter in distal nerve segments. Nerves with increased overall diameter were also found to have a statistically significant positive correlation with four of eight pain measures. Additionally, increased nerve-specific diameter correlates with increased pain on four of eight pain values, but age effect on nerve diameter blunts this finding. CONCLUSIONS: Increased preoperative CCS pain values in primary open inguinal hernia are significantly correlated with gross enlargement of the overall diameter and nerve-specific diameter of the ilioinguinal nerve beyond the external inguinal ring. This is consistent with a compression neuropathy.

Relationship between core strength and key variables of performance in elite rink hockey players.

AIM: The aim of this study was to test the hypothesis that a significant relationship exists between the level of core strength-endurance and key variables of endurance, strength, power, speed, and agility performance in male elite rink hockey players. METHODS: Ten male elite rink hockey players of the German national team were tested for 1) time to exhaustion, maximum oxygen uptake, and running economy, 2) one repetition maximum bench press and half squat, 3) counter movement jump height, 4) 5 m, 10 m, and 20 m speed, and 5) 22 m agility. The rink hockey players were also tested for 6) ventral, lateral-left, lateral-right, and dorsal core strength-endurance using concentric-eccentric muscle tests. RESULTS: The level of total and ventral core strength-endurance was very largely correlated with maximum oxygen uptake (r=0.74 and r=0.71, both P<0.05). Additionally, there was a large correlation between the level of ventral core strength-endurance and time to exhaustion (r=0.66, P<0.05). No further significant relationships were observed (best r=0.60, P>0.05). CONCLUSION: The findings from this study suggest that the level of core strength-endurance is largely to very largely correlated with key variables of endurance performance, but not significantly with strength, power, speed, or agility indicators in male elite rink hockey players. These findings should be noted by coaches and scientists when testing physical fitness or planning strength and conditioning programs for male elite rink hockey players.

[Adaptive mechanisms and behavioural recommendations: playing football in heat, cold and high altitude conditions]. / Hitze, Kälte und Höhenexposition im Fußball: Adaptive Mechanismen und Verhaltensstrategien in variierenden Umweltbedingungen.

Football is played worldwide and players often have to cope with hot and cold temperatures as well as high altitude conditions. The upcoming and past world championships in Brazil, Qatar and South Africa illustrate the necessity for behavioural strategies and adaptation to extreme environmental conditions. When playing football in the heat or cold, special clothing, hydration and nutritional and acclimatisation strategies are vital for high-level performance. When playing at high altitude, the reduced oxygen partial pressure impairs endurance performance and alters the technical and tactical requirements. Special high-altitude adaptation and preparation strategies are essential for football teams based at sea-level in order to perform well and compete successfully. Therefore, the aim of the underlying review is: 1) to highlight the difficulties and needs of football teams competing in extreme environmental conditions, 2) to summarise the thermoregulatory, physiological, neuronal and psychological mechanism, and 3) to provide recommendations for coping with extreme environmental conditions in order to perform at a high level when playing football in the heat, cold and at high altitude.

Tumour budding is a strong and independent prognostic factor in pancreatic cancer.

INTRODUCTION: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer that escapes detection and resists treatment. Tumour budding, defined as the presence of de-differentiated single tumour cells or small cell clusters at the invasive front of gastrointestinal carcinomas like colorectal, oesophageal, gastric and ampullary, is linked to adverse prognosis. Tumour budding has not yet been reported in PDAC. AIM: To assess the frequency and prognostic impact of tumour budding in PDAC. METHODS: Whole-tissue sections of 117 PDACs with full clinico-pathological and follow-up information, including postoperative therapy, were stained using a pancytokeratin marker. Tumour budding was assessed in 10 high-power fields (HPFs) by two pathologists. High-grade budding was defined as an average of >10buds across 10HPFs. Measurements were correlated to patient and tumour characteristics. The study was performed according to the REMARK guidelines. RESULTS: Inter-observer agreement was considered strong (ICC=0.72). Low-grade budding was observed in 29.7% and high-grade budding in 70.3% cases. High-grade budding was linked to advanced pT classification (p=0.0463), lymphatic invasion (p=0.0192) and decreased disease-free (p=0.0005) and overall survival (p<0.0001). There was no association with pN, pM, R-status or blood vessel invasion. In multivariate analysis, the prognostic effect of tumour budding was independent of lymph node metastasis, lymphatic invasion and R-status (p<0.0001; HR (95% CI): 3.65 (2.1-6.4)). CONCLUSIONS: Our results show that high-grade tumour budding occurs frequently in PDAC and is a strong, independent and reproducible, highly unfavourable prognostic factor that could be used to guide future individualised therapeutic approaches.

[Effects of compression textiles on performance enhancement and recovery]. / Zum Einsatz von Kompressionstextilien zur Leistungssteigerung und Regenerationsförderung im Leistungssport.

INTRODUCTION: In competitive sports different types of compression garments (socks, shorts, tights and whole body suits) have become popular. The results of scientific studies regarding their effectiveness, however, are heterogeneous. The aim of this literature review is to (i) survey the scientific data regarding performance enhancing benefits and the support of recovery when applying compression fabrics and (ii) to describe the practical relevance for the application of compression textiles in the competitive sport context. METHOD: In order to detect relevant publications for the present review an internet search using the medical databases "Medline" and "PubMed" was performed. Altogether, 37 studies were analysed. All publications were from the years 1987 to 2010. RESULTS: The literature review showed no general scientific indications regarding the benefit of compression garments in competitive sports. CONCLUSION: In particular, the different study designs and different clothing styles as well as different pressure gradients gave rise to contradictory data.

Self-reported oral health perceptions of Somali adults in Minnesota: a pilot study.

OBJECTIVE: To assess self-reported oral health perceptions and associated factors in an adult Somali population living in Minnesota, USA. METHODS: We analysed data from a cross-sectional study of Somali adults aged 18 to 65+ years attending a dental school clinic for care. A comprehensive oral examination was performed by the dental school outreach team on all patients who attended a 2-week designated Somali dental clinic. Adults who consented were given an oral health questionnaire to collect information on sociodemographics, marital status, language preference and self-rated oral and general health. We performed summary statistics and differences between proportions using Fisher's exact test and a comparison of means using one-way anova or a two-sample t-test. RESULTS: The sample consisted of 53 adults, 75% of whom were females. About 49% of subjects reported poor/fair oral health and 38% reported poor/fair general health. Seventy-four percent rated their access to dental care as poor/fair and 83% reported that they did not have a regular source of dental care. Self-rated oral health was significantly associated with marital status (P < 0.05) and self-rated general health (P < 0.01) using Fisher's exact test. CONCLUSION: A substantial proportion of Somali adults rated their oral health and access to dental care as poor/fair. These findings suggest that this population would benefit from improved access to oral health care and culturally appropriate oral health education and promotion programs.

Direct measurement of sheet resistance Rsquare in cuprate systems: evidence of a fermionic scenario in a metal-insulator transition.

The metal-insulator transition (MIT) has been studied in Ba(0.9)Nd(0.1)CuO(2+x)/CaCuO2 ultrathin cuprate structures. Such structures allow for the direct measurement of the 2D sheet resistance R( square), eliminating ambiguity in the definition of the effective thickness of the conducting layer in high temperature superconductors. The MIT occurs at room temperature for experimental values of R(square) close to the 25.8 kOmega universal quantum resistance. All data confirm the assumption that each CaCuO2 layer forms a 2D superconducting sheet within the superconducting block, which can be described as weak-coupled equivalent sheets in parallel.

NeuN expression correlates with reduced mitotic index of neoplastic cells in central neurocytomas.

In the developing brain, neuronal differentiation is associated with permanent exit from the mitotic cycle. This raises the possibility that neuronal differentiation may suppress proliferative activity, even in neoplastic cells. As a first step towards understanding the relation between neuronal differentiation and mitotic cycling in brain tumours, we studied the expression of NeuN (a neuronal marker) and Ki-67 (a mitotic marker) by double-labelling immuno-fluorescence in 16 brain tumours with neuronal differentiation. The tumours included a series of 11 central neurocytomas, and five single cases of other tumour types. In the central neurocytomas, NeuN(+) cells had a 15-fold lower Ki-67 labelling index, on average, than did NeuN(-) cells (P < 0.01). In the other tumours (one extraventricular neurocytoma, one desmoplastic medulloblastoma, one olfactory neuroblastoma, one ganglioglioma and one anaplastic ganglioglioma), the Ki-67 labelling index was always at least fourfold lower in NeuN(+) cells than in NeuN(-) cells. These results indicate that neuronal differentiation is associated with a substantial decrease of proliferative activity in neoplastic cells of central neurocytomas, and suggest that the same may be true across diverse types of brain tumours. However, tumours with extensive neuronal differentiation may nevertheless have a high overall Ki-67 labelling index, if the mitotic activity of NeuN(-) cells is high. The correlation between NeuN expression and reduced mitotic activity in neurocytoma cells is consistent with the hypothesis that neuronal differentiation suppresses proliferation, but further studies will be necessary to determine causality and investigate underlying mechanisms.

Atypical speech is rare in individuals with normal developmental histories.

The prevalence of atypical (right, bilateral) speech lateralization is unknown in normal populations. The authors investigated this by studying people with normal developmental histories but a later, specific adult neurologic event leading to intractable epilepsy. Fifty of 836 people receiving intracarotid amobarbital procedures (IAPs) met criteria of normal neurologic histories through age 15 years, with later head trauma or cerebral infection as probable cause of subsequent epilepsy. All 50 patients had left hemispheric speech on IAP. Atypical speech lateralization is rare unless there is also a positive neurologic history.

Percutaneous balloon mitral valvuloplasty in comparison with open mitral valve commissurotomy for mitral stenosis during pregnancy.

OBJECTIVES: We sought to compare the maternal and fetal outcomes of patients with severe mitral stenosis submitted to percutaneous balloon dilation versus open mitral valve commissurotomy (MVC) during pregnancy. BACKGROUND: Heart failure in patients with mitral stenosis complicating pregnancy is a common problem in developing countries. Since 1984, percutaneous dilation of the mitral valve using a balloon catheter has become a therapeutic alternative to open heart surgery. Although the efficacy of percutaneous mitral valve balloon dilation is well established, its results have never before been compared with the results of commissurotomy during pregnancy. METHODS: We compared the clinical and obstetric complications in 45 women who were treated with percutaneous mitral valve balloon dilation (group I, n = 21; from 1990 to 1995) or open MVC (group II, n = 24; from 1985 to 1990) for severe heart failure due to mitral stenosis during pregnancy. RESULTS: In our study, percutaneous balloon dilation of the mitral valve had a success rate of 95% (Gorlin formula) and 90.5% (echocardiographic "pressure half-time" method), as demonstrated by the final mitral valve area achieved. This improvement was followed by a marked decrease in the mitral valve gradient, left atrial pressure and mean pulmonary artery pressure. Patients in both groups had similar improvements in symptoms. Patients who underwent percutaneous balloon dilation had significantly fewer fetal complications, with a reduction in fetal and neonatal mortality (1 death in group I vs. 8 in group II, p = 0.025). CONCLUSIONS: Percutaneous balloon mitral valvuloplasty is safe and effective and appears to be preferable for the fetus, compared with open MVC during pregnancy.

Predicting work outcomes and service use in supported employment services for persons with psychiatric disabilities.

New funding policies make it timely to identify correlates of effectiveness and effciency in supported employment (SE) programs for persons with psychiatric disabilities. In a statewide sample of SE participants with serious mental illness, individual clinical characteristics were unrelated to competitive work or hours of services consumed. However, amounts of SE provider time devoted to travel, training, and nonemployment advocacy were independently related to the likelihood of obtaining competitive work. These results suggest that SE providers should pursue an individualized, participant-driven model of services that includes active efforts to remove logistical barriers to community employment.

The application of direct immunofluorescence to intraoperative neurosurgical diagnosis.

A diagnostic problem can occur at the time of intraoperative consultation of neurosurgical tumors as to whether the tumor is of neuroectodermal origin or whether it represents an epithelial metastasis from another site. Intraoperative diagnoses based on hematoxylin and eosin stained frozen sections are often later confirmed by immunocytochemical analysis of formalin-fixed, paraffin-embedded tissue sections that are not available at the time of surgery. The objective of the current study was to demonstrate that the application of direct immunofluorescence to the intraoperative diagnosis of neurosurgical tumors would provide unequivocal, and nearly immediate results. This report describes a new application of an existing technique for an optimized, rapid procedure utilizing direct immunocytochemistry with fluorescence-labeled primary antibodies to analyze surgical biopsies intraoperatively. The examination of five neurosurgical biopsies established a neuroectodermal origin of three tumors via immunolabeling for glial fibrillary acidic protein (GFAP) and lack of labeling with keratin markers, whereas several metastatic lung carcinomas were identified by immunostaining for keratin, but not GFAP, markers. The results of the direct immunolabeling method were unequivocal and required only minutes. The same diagnoses were confirmed by standard immunocytochemical labeling of formalin-fixed, paraffin-embedded sections, though it required several days to obtain the results. Direct immunofluorescence using fluorescently conjugated primary antibodies is a practical and rapid method for deciding whether a neurosurgical tumor is a primary glial or an epithelial metastatic tumor in origin. It is the first reported application of the technique for this aspect of rapid neurosurgical diagnosis.

Morphological plasticity in an infant monkey model of temporal lobe epilepsy.

PURPOSE/METHODS: Seizures in early life are thought to contribute to the development of human temporal lobe epilepsy. To examine the consequences of early seizures, we elicited status epilepticus in immature, 5.5- to 7.0-month-old pigtailed macaques by unilateral microinfusion of bicuculline methiodide into the entorhinal cortex. RESULTS: This report focuses on neuropathological changes in the hippocampus. Bicuculline infusion consistently elicited limbic-like seizures with prolonged, relatively localized electrographic activity. Magnetic resonance imaging revealed enhanced signal intensity in the ipsilateral hippocampus after seizures; in some cases, there was also progressive hippocampal atrophy. Histological changes were variable; in two of five monkeys, there was significant hippocampal neuron loss, gliosis, granule cell dispersion, and mossy fiber reorganization. CONCLUSIONS: The histopathological findings and associated magnetic resonance imaging abnormalities after bicuculline-induced status epilepticus in infant monkeys mimic common aspects of human temporal lobe epilepsy.

Outcome after surgery in patients with refractory temporal lobe epilepsy and normal MRI.

Our purpose is to determine predictors of outcome in patients with refractory temporal lobe epilepsy and normal high resolution magnetic resonance imaging (MRI) who undergo surgical therapy. We identified 23 patients who underwent temporal lobectomy and had normal pre-operative MRI, including surface coil phased array temporal lobe imaging. All were followed at least 2 years after surgery. We graded outcome as seizure-free, > 75% reduction in seizures, or < 75% reduction in seizures. We examined pre-operative interictal and ictal electroencephalographic (EEG) findings, age of onset, gender, duration of epilepsy, risk factors, family history, physical findings, age at operation, side of operation, and pathology of resected tissue in order to determine if any of these factors were associated with outcome. Overall, 48% (11/23) of patients were seizure-free, 39% (9/23) had > 75% reduction in seizures, while 13% (3/23) had < 75% reduction in seizures. Only the EEG findings were useful in predicting outcome. When ictal onsets arose from basal-temporal regions, 61% (11/18) of patients were seizure-free, while none (0/5) were seizure-free when seizures arose from mid-posterior temporal regions (P = 0.04). Interictally, if all epileptiform patterns were localized exclusively to one basal-temporal region, a finding that invariably correlated with ictal onsets, 78% (7/9) of patients were seizure-free, while only 29% (4/14) were seizure-free if discharges were bilateral or multifocal (P = 0.04). We conclude that surgery may be a reasonable treatment for some patients with intractable temporal lobe seizures and normal MRI. The best outcomes occur when seizure onsets and interictal epileptiform patterns are exclusive to one basal-temporal region. Unfavorable outcomes are most likely to occur when ictal origins are from mid-posterior temporal regions and when interictal discharges are bitemporal or multifocal in distribution.