To compare the results obtained with three different techniques for percutaneous transhepatic intraductal biopsy.
Eighty-eight patients with obstructive jaundice underwent placement of percutaneous ...biliary drainage catheters for biliary decompression. As part of the initial procedure or at a subsequent date, intraductal biliary biopsy (n = 109) was performed with use of one or more of three techniques including cytologic brush (n = 53), clamshell forceps under choledochoscopic guidance (n = 31), and clamshell forceps under fluoroscopic guidance (n = 25).
Forty-eight patients (55%) had a final diagnosis of malignant disease, and 40 (45%) had a diagnosis of benign disease. One hundred six (97%) biopsy procedures yielded technically adequate specimens. No complications directly related to the biopsy procedures occurred. Overall sensitivity and specificity for each biopsy technique were 26% and 96% for the cytologic brush technique, 30% and 88% for the clamshell forceps under fluoroscopic guidance technique, and 44% and 100% for the clamshell forceps under choledochoscopic guidance technique, respectively. The sensitivities of the biopsy techniques for pancreatic carcinoma and cholangiocarcinoma, respectively, were 47% and 0% for brush; 75% and 0% for fluoroscopic clamshell; and 100% and 27% for choledochoscopic clamshell.
The choledochoscope-directed biopsy technique had the greatest sensitivity and specificity of the three techniques evaluated, but this difference was not statistically significant versus the brush or fluoroscopic clamshell technique (P > .10). The sensitivity of all three techniques for pancreatic carcinoma was significantly greater than that for cholangiocarcinoma. Multiple biopsies did not increase the overall sensitivity of intraductal biliary biopsy as a diagnostic technique. All three techniques proved to be safe and easy to perform.
Macrolides are one of the most successful and widely used classes of antibacterials, which kill or stop the growth of pathogenic bacteria by binding near the active site of the ribosome and ...interfering with protein synthesis. Dirithromycin is a derivative of the prototype macrolide erythromycin with additional hydrophobic side chain. In our recent study, we have discovered that the side chain of dirithromycin forms lone pair-π stacking interaction with the aromatic imidazole ring of the His69 residue in ribosomal protein uL4 of the
70S ribosome. In the current work, we found that neither the presence of the side chain, nor the additional contact with the ribosome, improve the binding affinity of dirithromycin to the ribosome. Nevertheless, we found that dirithromycin is a more potent inhibitor of in vitro protein synthesis in comparison with its parent compound, erythromycin. Using high-resolution cryo-electron microscopy, we determined the structure of the dirithromycin bound to the translating
70S ribosome, which suggests that the better inhibitory properties of the drug could be rationalized by the side chain of dirithromycin pointing into the lumen of the nascent peptide exit tunnel, where it can interfere with the normal passage of the growing polypeptide chain.
Amazon forests exert a major influence on the global carbon cycle, but quantifying the impact is complicated by diverse landscapes and sparse data. Here we examine seasonal carbon balance in southern ...Amazonia using new measurements of column‐averaged dry air mole fraction of CO2 (XCO2) and solar induced chlorophyll fluorescence (SIF) from the Greenhouse Gases Observing Satellite (GOSAT) from July 2009 to December 2010. SIF, which reflects gross primary production (GPP), is used to disentangle the photosynthetic component of land‐atmosphere carbon exchange. We find that tropical transitional forests in southern Amazonia exhibit a pattern of low XCO2 during the wet season and high XCO2 in the dry season that is robust to retrieval methodology and with seasonal amplitude double that of cerrado ecosystems to the east (4 ppm versus 2 ppm), including enhanced dilution of 2.5 ppm in the wet season. Concomitant measurements of SIF, which are inversely correlated with XCO2 in southern Amazonia (r = −0.53, p < 0.001), indicate that the enhanced variability is driven by seasonal changes in GPP due to coupling of strong vertical mixing with seasonal changes in underlying carbon exchange. This finding is supported by forward simulations of the Goddard Chemistry Transport Model (GEOS‐Chem) which show that local carbon uptake in the wet season and loss in the dry season due to emissions by ecosystem respiration and biomass burning produces best agreement with observed XCO2. We conclude that GOSAT provides critical measurements of carbon exchange in southern Amazonia, but more samples are needed to examine moist Amazon forests farther north.
Key Points
XCO2 exhibits strong seasonal variability (~ 4 ppm) in southern Amazonia
This is possible because vertical mixing and local seasonal NEE are coupled
XCO2 is inversely correlated with fluorescence, indicating GPP drives NEE
Evaluate retrospectively the long-term primary patency of directional atherectomy (DA) in the femoropopliteal arteries.
DA was used alone in 59 patients (47%) or in combination with predilatation to ...allow passage of the device (43%) or after thrombolysis (10%) to treat 127 (93%) excentric atherosclerotic stenoses and nine (7%) occlusions of the femoropopliteal arteries. Forty-eight patients were followed by telephone interview, scheduled outpatient visits, color-flow Doppler evaluation, and angiography for 1-36 months (mean 16.9 months).
Technical success (reduction of the stenosis or occlusion to less than 30% luminal diameter) was achieved in 110 lesions (80.3%) during 48 procedures in 37 patients. Mean luminal diameter was increased 54% with a concomitant increase in mean ankle/brachial indices of 0.33. According to Kaplan-Meier survival curves, patency at 12 and 24 months was 88% and 75%, respectively. When patients who retained patency but developed restenosis were excluded, the probability of patency at 12, 24, and 36 months was 76%, 58%, and 32%, respectively. Major and minor complications occurred in 15 (21.4%) procedures each for a total complication rate of 42.8%.
Based on our results, DA is an effective method for percutaneous treatment of atherosclerotic disease involving the femoropopliteal arteries. It has similar patency but a relatively high complication rate compared with PTA.
A variety of structurally unrelated organic compounds has been reported to have antibacterial activity. Among these, certain small-molecule translation inhibitors have attracted a great deal of ...attention, due to their relatively high selectivity against prokaryotes, and an appropriate therapeutic index with minor “off target” effects. However, ribosomes are being considered as poorly druggable biological targets, thereby making some routine computational-based approaches to rational drug design and its development rather ineffective. Taking this into account, diversity-oriented biological screening can reasonably be considered as the most advantageous strategy. Thus, using a high-throughput screening (HTS) platform, we applied a unique biological assay for in vitro evaluation of thousands of organic molecules, especially targeted against bacterial ribosomes and translation. As a result, we have identified a series of structurally diverse small-molecule compounds that induce a reporter strain sensitive to translation and DNA biosynthesis inhibitors. In a cell free system, several molecules were found to strongly inhibit protein biosynthesis. Among them, compounds bearing a 2-guanidino-quinazoline core demonstrated the most promising antibacterial activity. With regard to the preliminary structure–activity relationship (SAR) study, we revealed that relatively small substituents at positions 4, 6 and 8 of the quinazoline ring significantly enhance the target activity whereas modification of the guanidine group leads to decrease or loss of antibacterial potency. This novel class of translation inhibitors can properly be regarded as a promising starting point for the development of novel antibacterial therapeutic or screening tools.
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•40 K compound library.•Reporter for ribosome inhibitors.•2-Guanidino-quinazoline hit.•Structure optimization.
Standardized French and English versions of the American Thoracic Society (ATS) respiratory disease questionnaire were administered to 204 English-speaking and 406 French-speaking male blue-collar ...aviation workers unexposed to occupational respiratory hazards. After adjusting for smoking status, age, years of education, foreign birth and maternal language other than French or English, no significant differences between the two questionnaires were found for response rates to usual cough, usual phlegm, mild or moderate dyspnoea, and chronic bronchitis. French-speaking workers reported significantly less wheeze with colds (OR = 0.60, p less than 0.02) and wheeze apart from colds (OR = 0.55, p less than 0.05) than the English-speaking group, but, the occurrence of wheeze on most days or nights was similar for both groups (OR = 1.02, NS). For 66 bilingual workers who completed both French and English questionnaires at a time interval of approximately two months, highly consistent results were found for sociodemographic data, smoking habits, cough, phlegm, breathlessness and chronic bronchitis, but not for wheeze with or apart from colds (agreement less than 90%; Kappa less than 0.50). These results reflect the difficulties in translating the concept of 'wheeze' from English to French. We conclude that most symptoms elicited by the French questionnaire may be generalized to English-speaking populations, but that questions pertaining to wheeze on most days or nights may be preferable to other questions concerning wheeze.
The authors evaluated the technical success and immediate and long-term results of percutaneous varicocele embolotherapy in the adolescent population.
Fifty-nine adolescent patients were referred for ...outpatient spermatic venography and possible varicocele embolotherapy. Embolization was attempted with use of detachable balloons, coils, "sandwiched" dextrose, or a combination of these techniques. Data regarding follow-up were obtained through telephone interviews or mailed questionnaires.
The technical success rate for spermatic vein occlusion was 90%. Follow-up, obtained in 79% of the patients, ranged from 6 months to 8.75 years (mean, 4 years). Thirty-nine of 42 patients (93%) reported disappearance (n = 31) or only a slight, asymptomatic residual varicocele (n = 8). Three patients reported a recurrence of their varicocele. Complications occurred in three of 59 cases (5%), none had any long-term sequelae. In six cases, embolization was not feasible because of multiple collateral vessels or venous spasm.
Given the convenience of performing the procedure on an outpatient basis, the rapid recovery time, and long-term success and complication rates comparable to those with surgical ligation, we believe spermatic venography and percutaneous embolization is the treatment modality of choice for adolescent varicocele.
Genetically determined leukoencephalopathies comprise a group of rare inherited white matter disorders. The majority are progressive diseases resulting in early death. We performed a cross-sectional ...pilot study including 55 parents from 36 families to assess the level of stress experienced by parents of patients with genetically determined leukoencephalopathies, aged 1 month to 12 years. Thirty-four mothers and 21 fathers completed the Parenting Stress Index–4th Edition. One demographic questionnaire was completed per family. Detailed clinical data was gathered on all patients. Statistical analysis was performed with total stress percentile score as the primary outcome. Mothers and fathers had significantly higher stress levels compared with the normative sample; 20% of parents had high levels of stress whereas 11% had clinically significant levels of stress. Mothers and fathers had comparable total stress percentile scores. We identified pediatric behavioral difficulties and gross motor function to be factors influencing stress in mothers. Our study is the first to examine parental stress in this population and highlights the need for parental support early in the disease course. In this pilot study, we demonstrated that using the Parenting Stress Index–4th Edition to assess stress levels in parents of patients with genetically determined leukoencephalopathies is feasible, leads to valuable and actionable results, and should be used in larger, prospective studies.
Despite numerous advances in continental-scale hydrologic modeling and improvements in global Land Surface Models, an accurate representation of regional water table depth (WTD) remains a challenge. ...Data assimilation of observations from the Gravity Recovery and Climate Experiment (GRACE) mission leads to improvements in the accuracy of hydrologic models, ultimately resulting in more reliable estimates of lumped water storage. However, the usually shallow groundwater compartment of many models presents a problem with GRACE assimilation techniques, as these satellite observations also represent changes in deeper soils and aquifers. To improve the accuracy of modeled groundwater estimates and allow the representation of WTD at finer spatial scales, we implemented a simple, yet novel approach to integrate GRACE data, by augmenting the Variable Infiltration Capacity (VIC) hydrologic model. First, the subsurface model structural representation was modified by incorporating an additional (fourth) soil layer of varying depth (up to 1000 m) in VIC as the bottom ‘groundwater’ layer. This addition allows the model to reproduce water storage variability not only in shallow soils but also in deeper groundwater, in order to allow integration of the full GRACE-observed variability. Second, a Direct Insertion scheme was developed that integrates the high temporal (daily) and spatial (∼6.94 km) resolution model outputs to match the GRACE resolution, performs the integration, and then disaggregates the updated model state after the assimilation step. Simulations were performed with and without Direct Insertion over the three largest river basins in California and including the Central Valley, in order to test the augmented model's ability to capture seasonal and inter-annual trends in the water table. This is the first-ever fusion of GRACE total water storage change observations with hydrologic simulations aiming at the determination of water table depth dynamics, at spatial scales potentially useful for local water management.
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