Preoperative diagnosis of clear cell sarcoma of the kidney by detection of BCOR internal tandem duplication in circulating tumor DNA

Clear cell sarcoma of the kidney (CCSK) is the second most common renal malignancy in children. The prognosis is poorer in CCSK than in Wilms’ tumor, and multimodal treatment including surgery, intensive chemotherapy, and radiation is required to improve the outcome for children with CCSK. Histological evaluation is required for the diagnosis. However, biopsies of tumors to obtain diagnostic specimens are not routinely performed because of the risk of spreading tumor cells during the procedure. Recently, internal tandem duplication (ITD) of BCOR has been recognized as a genetic hallmark of CCSK. We herein established a novel BCOR‐ITD‐specific polymerase chain reaction method with well‐designed primers, and then performed a liquid biopsy for cell‐free DNA (cfDNA) obtained from plasma of three children with nonmetastatic renal tumors (stage II) and from one control. BCOR‐ITD was positively detected in the cfDNA of two cases, both of which were later diagnosed as CCSK based on histological feature of the resected tumor specimen, while it was not detected for a normal control and a patient diagnosed with Wilms’ tumor. Our study is the first one of preoperative circulating tumor DNA assay in pediatric renal tumors. The liquid biopsy method enables less invasive, preoperative diagnosis of CCSK with no risk of tumor spillage, which can avoid iatrogenic upstaging.     

Transmission of schistosomiasis in an urban population and prevalence of intestinal helminthiasis in Bamako, Mali

Parasitological, malacological and anthropological studies were performed to assess the prevalence of Schistosoma haematobium and S. mansoni in schoolchildren living in the suburban area of Bamako. A total of 1017 schoolchildren aged 6-14 years were selected in two different areas between September 1997 and December 1999. In Djikoroni, the prevalence of S. haematobium and S. mansoni was 80.7% (339/420) and 22.8% (85/372) respectively. There was no significant difference of prevalence and intensity of infection with S. haematobium between schools, gender and age (p > 0.05), whereas, those of S. mansoni were higher in the vicinity of (+/- 100 m from) major sites where infected Biomphalaria pfeifferi were found (p < 0.001). In Niomirambougou, S. haematobium was prevalent in 46.7% (279/597) and S. mansoni in 28.2% (134/475). Boys and children aged 11-14 years were more infected (p < 0.001). Associated intestinal helminths (Hymenolepis nana, Necator americanus and Ascaris lumbricoides) were relatively scarce (prevalence < 1%). The prevalences of schistosome infected snails intermediate host were relatively high, 49.3% (100/203) in B. pfeifferi, 20.6% (88/138) in B. truncatus and 24.1% (7/29) in B. globosus. We recorded a total of 2514 water contacts about which 1130 in December and 1384 in January. Most of the children, 42.9% (1077/2511) were attracted to water bodies for bathing, swimming and playing, suggesting the lack of recreational facilities in these areas. Developing local control programmes in schools located in the vicinity of water bodies would contribute to break the parasite transmission cycle in Bamako.     

Effect of reinsertion of activated nucleus pulposus on disc degeneration: an experimental study on various types of collagen in degenerative discs

We examined the emergence and sequential changes in type I, II, and VI collagen production in an experimental rabbit model of disc degeneration. Type I collagen was minimally present initially and did not change over 24 weeks. Type I collagen seemed to have no effect on the degenerative process in this model. Staining for type II collagen was positive circumferentially in chondrocytelike cells and was mild in the early phase of disc degeneration, when the chondrocytelike cells began to appear in the inner layers of the annulus fibrosus. The stain became stronger during the middle phase when the chondrocytelike cells arranged themselves in cluster. Compared with type II collagen, the staining for type VI collagen was relatively strong early in the degenerative process. These findings led us to speculate that these chondrocytelike cells play an active role in the degenerative process. The reinsertion of nucleus pulposus cells cocultured with annulus fibrosus delayed disc degeneration and the emergence of chondrocytelike cells. Considering that the emergence of chondrocytelike cells which produce type II and type VI collagen is delayed in discs with the injection of cocultured nucleus pulposus cells by annulus fibrosus cells, we conclude that chondrocytelike cells that produce type VI collagen also seems to accelerate degeneration. Type VI collagen is produced at an earlier phase than type II collagen and may be both active agent and a marker for disc degeneration.     

Microbiological outcome of complicated urinary tract infections treated with levofloxacin: a pharmacokinetic/pharmacodynamic analysis

The pharmacodynamic targets representing 90% probability thresholds for bacterial eradication were determined in patients with complicated urinary tract infections (UTIs) treated with 500 mg of levofloxacin every 24 h for 7–14 days. Of 241 pre-treatment strains from 156 patients, 21 strains persisted after treatment. In each patient, plasma concentrations of levofloxacin were simulated based on population pharmacokinetic parameters and patient-specific data. Minimum inhibitory concentrations (MICs) of levofloxacin for the pre-treatment strains determined in our previous study were used. The pharmacodynamic targets representing 90% probability thresholds for bacterial eradication were determined by logistic regression analyses. For all the isolates, Gram-negative bacilli, Gram-positive cocci, Escherichia coli and Enterococcus faecalis, the target values of the area under the concentration–time curve (AUC)/MIC were 14.65, 31.46, 4.85, 43.00 and 3.06, respectively, and the targets of the maximum plasma concentration (C_max)/MIC were 1.22, 2.74, 0.39, 3.61 and 0.25, respectively. Such thresholds of AUC/MIC and C_max/MIC in complicated UTIs would be lower than those in infections of other sites. In particular, the C_max/MIC thresholds for Gram-positive cocci and E. faecalis were <1. These findings suggested that, in addition to its plasma concentration, the high concentration of levofloxacin in the urine might play a role in eradicating bacteria.     

Drug–drug interaction between oxycodone and adjuvant analgesics in blood–brain barrier transport and antinociceptive effect

To examine possible blood–brain barrier (BBB) transport interactions between oxycodone and adjuvant analgesics, we firstly screened various candidates in vitro using [³H]pyrilamine, a substrate of the oxycodone transporter, as a probe drug. The uptake of [³H]pyrilamine by conditionally immortalized rat brain capillary endothelial cells (TR-BBB13) was inhibited by antidepressants (amitriptyline, imipramine, clomipramine, amoxapine, and fluvoxamine), antiarrhythmics (mexiletine, lidocaine, and flecainide), and ketamine. On the other hand, antiepileptics (carbamazepine, phenytoin, and clonazepam) and corticosteroids (dexamethasone and prednisolone) did not inhibit [³H]pyrilamine uptake, with the exception of sodium valproate. The uptake of oxycodone was significantly inhibited in a concentration-dependent manner by amitriptyline, fluvoxamine and mexiletine with K_i values of 13, 65, and 44 µM, respectively. These K_i values are 5–300 times greater than the human therapeutic plasma concentrations. Finally, we evaluated in vivo interaction between oxycodone and amitriptyline in mice. Antinociceptive effects of oxycodone were increased by coadministration of amitriptyline. The oxycodone concentrations in plasma and brain were not changed by coadministration of amitriptyline. Overall, the results suggest that several adjuvant analgesics may interact with the BBB transport of oxycodone at relatively high concentrations. However, it is unlikely that there would be any significant interaction at therapeutically or pharmacologically relevant concentrations. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:467–474, 2010     

Endovascular treatment for poorest-grade subarachnoid hemorrhage in the acute stage: has the outcome been improved?

OBJECTIVE: Patients with poor-grade subarachnoid hemorrhage (SAH) have been considered good candidates for endovascular treatment. The results of treatment of Grade V SAH, the poorest grade, however, have not been fully elucidated. METHODS: The clinical characteristics and outcome parameters of 22 World Federation of Neurosurgical Societies Grade V SAH patients treated endovascularly in the acute stage between 1998 and 2000 are summarized and compared with those of 18 Grade V SAH patients treated conservatively between 1995 and 1997. RESULTS: Among the 22 patients treated endovascularly, 8 patients (36.4%) survived. The rate was significantly higher than that of the 18 patients treated conservatively (5.6%), only one of whom survived. The favorable outcome rate, however, was not significantly different between the two groups (4.5% versus 6.0%). Subdivision of both treatment groups according to Glasgow Coma Scale (GCS) score showed that the improved survival among those treated endovascularly was attributable to the improved survival in those with a preprocedural GCS score of 6 but not of 4 or 5. CONCLUSION: Endovascular treatment of the 22 World Federation of Neurosurgical Societies Grade V SAH patients improved their survival rate but not their favorable outcome rate in comparison with conservative treatment. Further accumulation of clinical data is essential to determine whether endovascular treatment can improve the functional outcome of those with GCS scores of 6 and whether there is no role for endovascular treatment in those with GCS scores of 4 or 5.     

Preoperative and intraoperative evaluation of diameter-reflux relationship of calf perforating veins in patients with primary varicose vein

OBJECTIVE: Interruption of incompetent perforating veins (PVs) is important for varicose vein surgery. The purpose of this study was to evaluate the preoperative and intraoperative diameter-reflux relationship of PVs and to evaluate the accuracy of preoperative duplex scanning in patients with varicose vein. METHODS: Patients with primary varicose veins were retrospectively investigated. Diameters and reflux of PVs were evaluated before surgery with color flow duplex ultrasound scan (US). During operation, the incompetent PVs were defined as those that showed an outward spurt of blood flow from the stump of the PVs. The sensitivity and specificity of US in the detection of reflux of PVs were calculated. Competent versus incompetent vein diameters were compared with the Student t test and one-way analysis of variance. RESULTS: Three hundred twenty-four calf PVs were detected in 304 legs of 175 patients with varicose vein. Diameters of competent and incompetent PVs confirmed with intraoperative finding averaged 2.67 +/- 1.10 mm (n = 28) and 3.28 +/- 1.01 mm (n = 58), respectively, at the upper calf (P =.012), 2.85 +/- 0.85 mm (n = 53) and 3.68 +/- 0.94 mm (n = 137), respectively, at the lower calf (p <.001), and 2.67 +/- 0.99 mm (n = 14) and 3.27 +/- 0.66 mm (n = 22), respectively, at the posterior calf (P =.036). The overall sensitivity of detection of reflux with US was 87.7%, and the specificity was 75.3%. Diameters of true-incompetent PVs and false-incompetent PVs were 3.59 +/- 0.94 mm (n = 199) and 3.31 +/- 0.84 mm (n = 24), respectively (P =.157). Diameters of true-competent PVs and false-competent PVs were 2.61 +/- 0.91 mm (n = 73) and 2.89 +/- 0.82 mm (n = 28), respectively (P =.158). CONCLUSION: Although the diameter of incompetent PVs was larger than that of competent PVs in both US and intraoperative findings, diameter measurement alone can not completely distinguish competent and incompetent PVs. The sensitivity and specificity of reflux obtained with US showed that the accuracy of preoperative duplex scanning to evaluate PV competency was not sufficient.     

The sleep of Africans and Europeans in the Ivory Coast: questionnaire study

Sleep behaviour has been extensively studied with questionnaires in industrialised countries to investigate the epidemiology of sleep-wake disorders. However, only few attempts have yet been made to examine sleep behaviour of people living in Africa. Although, a large number of studies in hot or cold environments have used short-term exposures, reporting disrupted sleep for most of them, long-term exposures to stressful thermal environments are rare in the literature. Prior to the present investigation, we used questionnaires to analyse the effects of seasonal heat increase on perceived sleep behaviour and sleep quality in young native African students in Niger [7], even though these methods of investigation are by no means as accurate as polysomnographic recordings. The hypothesis was that sleep behaviour may be influenced by climatic variations in a hot dry tropical climate. Such climatic variations have been shown to induce seasonal heat acclimatisation marked by changes in body temperature rhythms in the hot versus the cool season [13]. Sleep behaviour was examined during two 7-day periods in January ("cool-dry" season, 88 subjects) and May ("hot-dry" season, 53 subjects). The questionnaire was completed after night sleep and/or naps. The subjects slept an average of 7 1/2 hours a day, most of them having afternoon naps. They experienced no major seasonal variation in their sleep behaviour, but for an increased number of awakenings during the hot season. Restorative quality of sleep scored lower after a nap than after nocturnal sleep. Therefore, general sleep characteristics were not modified by seasonal temperature variations in African native students, perhaps because of the limited changes in daylight under the low latitude of Niamey. Another investigation was carried out using the same 12-item questionnaire in Abidjan on 78 medical students who did not have a nap [9]. Contrary to the Niamey students, the Abidjan subjects adopted short duration sleep schedules, without any effect on the subjective quality of the restorative properties of their sleep.