tbuckley/cabot-search huggingface dataset:
Clearance of hepatitis C virus RNA from the peripheral blood mononuclear cells of blood donors who spontaneously or therapeutically control their plasma viremia
Authors: Flavien Bernardin, Leslie Tobler, Irina Walsh, Joan Dunn Williams, Mike Busch, Eric Delwart
Journal: Hepatology (2008)

We determined whether hepatitis C virus (HCV) RNA could be detected associated with peripheral blood mononuclear cells (PBMC) of seropositive blood donors who had spontaneously or therapeutically cleared their plasma viremia. Blood donor plasma viremia status was first determined with a highly sensitive transcription-mediated amplification (TMA) test performed in duplicate assays. PBMC from 69 aviremic and 56 viremic blood donors were then analyzed for the presence of HCV RNA with TMA adapted to detect viral RNA in PBMC and with a reverse transcription–nested polymerase chain reaction assay. PBMC-associated HCV RNA was detected in none of the 69 aviremic donors, including all 6 subjects with a sustained viral response following antiviral therapy. PBMC-associated HCV RNA was detected in 43 of the 56 viremic donors. The 13 viremic donors with no detectable PBMC-associated HCV RNA all had very low viral loads (6 positive only in 1 of 2 duplicate plasma TMA assays, 6 with viral loads below 100 HCV RNA copies/mL, and 1 with a viremia of 2700 HCV RNA copies/mL). The absence of detectable PBMC HCV RNA detection in all 69 aviremic donors reported here contrasts with prior studies, possibly as a result of the higher sensitivity of the TMA assay used to test for plasma viremia. Conclusion: Our results indicate that PBMC are unlikely to serve as a long-lived reservoir of HCV in aviremic subjects.
Effects of Cigarette Smoking on Glomerular Structure and Function in Type 2 Diabetic Patients
Authors: Bruno Baggio, Alessandro Budakovic, Michele Dalla Vestra, Alois Saller, Marino Bruseghin, Paola Fioretto
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. Prospective studies have established smoking as an independent risk factor for diabetic nephropathy, suggesting an adverse effect of smoking on glomerular structure and function. To test this hypothesis, this study evaluated GFR, metabolic profile, and smoking habits in 96 patients with type 2 diabetes and abnormal albumin excretion rate (AER). All patients underwent percutaneous kidney biopsy: mesangial fractional volume [Vv (mes/glom)] and glomerular basement membrane (GBM) width were estimated by electron microscopic morphometric analysis; interstitial fibrosis was estimated semiquantitatively by light microscopy. Forty-eight patients were smokers. Compared with nonsmokers, smokers had higher values of HbA1c (P = 0.002), AER (P = 0.026), GFR (P = 0.004), and GBM width (P = 0.002); moreover, GFR was higher in current smokers than in former smokers (P = 0.001), and GBM width was related to heavy smoking (F = 5.4; P = 0.006). Multiple linear regression analyses revealed that HbA1c was associated with fasting blood glucose (β coef = 0.52; P < 0.001), smoking habit (β coef = 0.31; P < 0.001), insulin therapy (β coef = 0.22; P = 0.012), and male gender (β coef = −0.20; P = 0.020); AER was related to Vv (mes/glom) (β coef = 0.32; P = 0.003), GBM width (β coef = 0.28; P = 0.016), and interaction between smoking habit and HbA1c (β coef = 0.24; P = 0.040). GFR was negatively correlated with Vv (mes/glom) (β coef = −0.57; P < 0.001) and age (β coef = −0.29; P = 0.001) and positively correlated with GBM width (β coef = 0.27; P = 0.012), heavy current smoking (β coef = 0.24; P = 0.028), and HbA1c (β coef = 0.28; P = 0.040); GBM width was explained by Vv (mes/glom) (β coef = 0.53; P < 0.001), interaction between heavy smoking and HbA1c levels (β coef = 0.25; P = 0.003), and diabetes duration (β coef = 0.23; P = 0.010). Smoking habit did not affect the index of interstitial fibrosis. In conclusion, cigarette smoking affects glomerular structure and function in type 2 diabetes and may be an important factor for the onset and progression of diabetic nephropathy.
Physiomer® reduces the chemokine interleukin-;8 production by activated human respiratory epithelial cells
Authors: O. Tabary, C. Muselet, J-;C. Yvin, B. Halley-Vanhove, E. Puchelle, J. Jacquot
Journal: European Respiratory Journal (2001)

The authors have recently shown that the transcription factor nuclear factor-κB (NF-κB) is a central mediator in the NaCl-mediated interleukin (IL)-;8 production by human airway epithelial cells. In this study, it was investigated whether Physiomer®, an isotonic sea water-derived solution commercialized for cleaning the nasal mucosa, impaired the chemokine IL-;8 expression and secretion by human respiratory epithelial cells compared with that obtained with an isotonic 9% NaCl solution. Primary human bronchial gland (HBG) epithelial cells were incubated either in Physiomer® or in a NaCl 9% solution and activated either with 20 ng·mL −1 tumour necrosis factor-;α, or IL-;1β, respectively. Physiomer® significantly reduced the IL-;8 protein release in basal and activated HBG cells in comparison with that obtained with the 9% NaCl solution. In contrast to the effects of Physiomer® observed on resting HBG cells, Physiomer® did not significantly reduce the level of phosphorylation of the NF-κB inhibitor protein IκBα or the steady-state IL-;8 messenger ribonucleic acid levels in activated HBG cells, suggesting that Physiomer® would have a post-transcriptional effect on IL-;8 expression in activated HBG cells. The authors conclude that Physiomer® is potentially useful in the reduction of airway mucosal inflammation.
Discussion of Medical Errors in Morbidity and Mortality Conferences
Authors: Edgar Pierluissi
Journal: JAMA (2003)

ContextMorbidity and mortality conferences in residency programs are intended to discuss adverse events and errors with a goal to improve patient care. Little is known about whether residency training programs are accomplishing this goal.ObjectiveTo determine the frequency at which morbidity and mortality conference case presentations include adverse events and errors and whether the errors are discussed and attributed to a particular cause.Design, Setting, and ParticipantsProspective survey conducted by trained physician observers from July 2000 through April 2001 on 332 morbidity and mortality conference case presentations and discussions in internal medicine (n = 100) and surgery (n = 232) at 4 US academic hospitals.Main Outcome MeasuresFrequencies of presentation of adverse events and errors, discussion of errors, and attribution of errors.ResultsIn internal medicine morbidity and mortality conferences, case presentations and discussions were 3 times longer than in surgery conferences (34.1 minutes vs 11.7 minutes; P = .001), more time was spent listening to invited speakers (43.1% vs 0%; P&lt;.001), and less time was spent in audience discussion (15.2% vs 36.6%; P&lt;.001). Fewer internal medicine case presentations included adverse events (37 [37%] vs 166 surgery case presentations [72%]; P&lt;.001) or errors causing an adverse event (18 [18%] vs 98 [42%], respectively; P = .001). When an error caused an adverse event, the error was discussed as an error less often in internal medicine (10 errors [48%] vs 85 errors in surgery [77%]; P = .02). Errors were attributed to a particular cause less often in medicine than in surgery conferences (8 [38%] of 21 medicine errors vs 88 [79%] of 112 surgery errors; P&lt;.001). In discussions of cases with errors, conference leaders in both internal medicine and surgery infrequently used explicit language to signal that an error was being discussed and infrequently acknowledged having made an error.ConclusionsOur findings call into question whether adverse events and errors are routinely discussed in internal medicine training programs. Although adverse events and errors were discussed frequently in surgery cases, teachers in both surgery and internal medicine missed opportunities to model recognition of error and to use explicit language in error discussion by acknowledging their personal experiences with error.
Paracetamol use in pregnancy and wheezing in early childhood
Authors: S O Shaheen, R B Newson, A Sherriff, A J Henderson, J E Heron, P G J Burney, J Golding
Journal: Thorax (2002)

<b>Background:</b> We recently reported links between frequent paracetamol (acetaminophen) use and wheezing and asthma in adults and children, but data are lacking on possible effects of prenatal exposure on wheezing in early childhood. <b>Methods:</b> In the population based Avon Longitudinal Study of Parents and Children (ALSPAC) women were asked twice during pregnancy (at 18–20 weeks and 32 weeks) about their usage of paracetamol and aspirin. Six months after birth, and at yearly intervals thereafter, mothers were asked about wheezing and eczema symptoms in their child. The effects of paracetamol and aspirin use in pregnancy on the risk in the offspring of wheezing at 30–42 months (n=9400) and eczema at 18–30 months (n=10 216) and on their risk of different wheezing patterns (defined by presence or absence of wheezing at &lt;6 months and at 30–42 months) were examined. <b>Results:</b> Paracetamol was taken frequently (most days/daily) by only 1% of women. After controlling for potential confounders, frequent paracetamol use in late pregnancy (20–32 weeks), but not in early pregnancy (&lt;18–20 weeks), was associated with an increased risk of wheezing in the offspring at 30–42 months (adjusted odds ratio (OR) compared with no use 2.10 (95% CI 1.30 to 3.41); p=0.003), particularly if wheezing started before 6 months (OR 2.34 (95% CI 1.24 to 4.40); p=0.008). Assuming a causal relation, only about 1% of wheezing at 30–42 months was attributable to this exposure. Frequent paracetamol use in pregnancy was not associated with an increased risk of eczema. Frequent aspirin use in pregnancy was associated with an increased risk of wheezing only at &lt;6 months. <b>Conclusions:</b> Frequent use of paracetamol in late pregnancy may increase the risk of wheezing in the offspring, although such an effect could explain only about 1% of the population prevalence of wheezing in early childhood.
Prospective Multicenter Phase II Trial of 15-Minute Panitumumab Infusion with Irinotecan in Patients with KRAS Wild-Type Chemo-Refractory Metastatic Colorectal Cancer: The Ship Trial
Authors: Hamaguchi Tetsuya, Akiyoshi Kohei, Yoshimura Kenichi, Yasui Hisateru, Sakai Gen, Akatsuka Sotaro, Ogawa Kohei, Hirai Satoshi, Horita Yosuke, Nagai Yushi, Shimada Yasuhiro
Journal: Annals of Oncology (2014)
Adjuvant and Salvage Radiotherapy After Prostatectomy: American Society of Clinical Oncology Clinical Practice Guideline Endorsement
Authors: Stephen J. Freedland, R. Bryan Rumble, Antonio Finelli, Ronald C. Chen, Susan Slovin, Mark N. Stein, David S. Mendelson, Colin Wackett, Howard M. Sandler
Journal: Journal of Clinical Oncology (2014)

To endorse the American Urological Association (AUA)/American Society for Radiation Oncology (ASTRO) guideline on adjuvant and salvage radiotherapy after prostatectomy. The American Society of Clinical Oncology (ASCO) has a policy and set of procedures for endorsing clinical practice guidelines developed by other professional organizations.The guideline on adjuvant and salvage radiotherapy after prostatectomy was reviewed for developmental rigor by methodologists. An ASCO endorsement panel then reviewed the content and recommendations.The panel determined that the guideline recommendations on adjuvant and salvage radiotherapy after prostatectomy, published in August 2013, are clear, thorough, and based on the most relevant scientific evidence. ASCO endorsed the guideline on adjuvant and salvage radiotherapy after prostatectomy, adding one qualifying statement that not all candidates for adjuvant or salvage radiotherapy have the same risk of recurrence or disease progression, and thus, risk-benefit ratios are not the same for all men. Those at the highest risk for recurrence after radical prostatectomy include men with seminal vesicle invasion, Gleason score 8 to 10, extensive positive margins, and detectable postoperative prostate-specific antigen (PSA).Physicians should discuss adjuvant radiotherapy with patients with adverse pathologic findings at prostatectomy (ie, seminal vesicle invasion, positive surgical margins, extraprostatic extension) and salvage radiotherapy with patients with PSA or local recurrence after prostatectomy. The discussion of radiotherapy should include possible short- and long-term adverse effects and potential benefits. The decision to administer radiotherapy should be made by the patient and multidisciplinary treatment team, keeping in mind that not all men are at equal risk of recurrence or clinically meaningful disease progression. Thus, the risk-benefit ratio will differ for each patient.
Optimization of the detection of microbes in blood from immunocompromised patients with haematological malignancies
Authors: S. Skovbjerg, C. Welinder-Olsson, N. Kondori, E. Kjellin, F. Nowrouzian, A.E. Wold, D. Stockelberg, P. Larsson, C. Wennerås
Journal: Clinical Microbiology and Infection (2009)
Formation of the Atrioventricular Septal Structures in the Normal Mouse
Authors: Sandra Webb, Nigel A. Brown, Robert H. Anderson
Journal: Circulation Research (1998)

Abstract —It is sometimes thought that formation of the atrioventricular septum is equated with fusion of the endocardial cushions and that failure of fusion can explain all deficiencies of atrioventricular septation. Clearly, this is simplistic, but the exact contribution of different primordia to atrioventricular septation is not well understood. To clarify this, we studied normal mouse embryos (days 10 to 15 of gestation), which were serially sectioned and examined by light microscopy. Another group of embryos was examined by scanning electron microscopy after microdissection. Our results show that development of the atrioventricular septal area is highly complex. Proper formation requires the following: remodeling of the inner heart curvature, rotation of the horns of the systemic venous sinus around the pulmonary portal, expansion of the right atrioventricular junction, formation of the muscular atrial and ventricular septa, bridging by the dextrodorsal outflow ridge and the superior endocardial cushion, fusion with the inferior margins of the venous valves, and formation of the mouth of the coronary sinus from the cranial muscular wall of the left sinus horn. Multiple primordia contribute to a central mesenchymal mass (the “septum intermedium”), including the mesenchyme on the leading edge of the primary atrial septum, the atrioventricular endocardial cushions, and the cap of mesenchyme on the spina vestibuli. Fusion of these components closes the ostium primum, completing atrial and atrioventricular septation. Additionally, the spina vestibuli has a mesodermal core, which contributes to the muscularization of the lower margin of the oval fossa. This contrasts with the formation of the upper rim, which occurs as a result of an infolding of the atrial wall itself.
PTP1B and SHP2 in POMC neurons reciprocally regulate energy balance in mice
Authors: Ryoichi Banno, Derek Zimmer, Bart C. De Jonghe, Marybless Atienza, Kimberly Rak, Wentian Yang, Kendra K. Bence
Journal: Journal of Clinical Investigation (2010)

Protein tyrosine phosphatase 1B (PTP1B) and SH2 domain–containing protein tyrosine phosphatase–2 (SHP2) have been shown in mice to regulate metabolism via the central nervous system, but the specific neurons mediating these effects are unknown. Here, we have shown that proopiomelanocortin (POMC) neuron–specific deficiency in PTP1B or SHP2 in mice results in reciprocal effects on weight gain, adiposity, and energy balance induced by high-fat diet. Mice with POMC neuron–specific deletion of the gene encoding PTP1B (referred to herein as POMC-Ptp1b–/– mice) had reduced adiposity, improved leptin sensitivity, and increased energy expenditure compared with wild-type mice, whereas mice with POMC neuron–specific deletion of the gene encoding SHP2 (referred to herein as POMC-Shp2–/– mice) had elevated adiposity, decreased leptin sensitivity, and reduced energy expenditure. POMC-Ptp1b–/– mice showed substantially improved glucose homeostasis on a high-fat diet, and hyperinsulinemic-euglycemic clamp studies revealed that insulin sensitivity in these mice was improved on a standard chow diet in the absence of any weight difference. In contrast, POMC-Shp2–/– mice displayed impaired glucose tolerance only secondary to their increased weight gain. Interestingly, hypothalamic Pomc mRNA and α–melanocyte-stimulating hormone (αMSH) peptide levels were markedly reduced in POMC-Shp2–/– mice. These studies implicate PTP1B and SHP2 as important components of POMC neuron regulation of energy balance and point to what we believe to be a novel role for SHP2 in the normal function of the melanocortin system.
Effects of anastrozole on cognitive performance in postmenopausal women: a randomised, double-blind chemoprevention trial (IBIS II)
Authors: Valerie A Jenkins, Laurence M Ambroisine, Louise Atkins, Jack Cuzick, Anthony Howell, Lesley J Fallowfield
Journal: The Lancet Oncology (2008)

Mild cognitive impairments have been recorded in cross-sectional studies of women with breast cancer receiving endocrine treatment. More comprehensive studies were warranted because aromatase inhibitors are being used increasingly in both chemoprevention and adjuvant settings. We report findings from the cognitive subprotocol of the International Breast Intervention Study (IBIS II), a double-blind placebo-controlled trial of anastrozole in postmenopausal women at high risk of developing breast cancer. We aimed to study and compare the effect of anastrozole versus placebo on memory and attention in these women.Between Jan 3, 2003, and Dec 21, 2005, participants were recruited into the cognitive subprotocol from five UK centres. Cognitive assessments were done before randomisation, at 6 months, and at 24 months. 227 of 249 women approached completed a comprehensive set of standardised cognitive tasks at baseline and were randomly assigned to receive anastrozole (1 mg/day for 5 years) or placebo. Psychological morbidity, endocrine symptoms, and self-reported cognitive complaints were also measured. The main outcomes were cognitive task scores at baseline, 6 months, and 24 months. Analyses were done by intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN31488319.111 women were assigned to anastrozole and 116 women to placebo. At 6 months, ten women in each group were excluded from analysis, leaving a total of 207 of 227 (91%) women available for further assessments. At 24 months, 24 women were excluded from the anastrozole group and 32 from the placebo group, leaving 151 of 227 (67%) women. We did not note any significant differences between the groups for any of the cognitive tasks. By 6 months, 13 women in both groups reported changes to their memory and this had decreased to five women in the placebo group and three women in the anastrozole group by the 24-month assessment. Significantly more women in the anastrozole group complained of hot flushes at 24 months (23 of 76 [30%] vs 11 of 73 [15%], p=0.032, not corrected for multiple comparison), but this was the only difference in reported endocrine symptoms.These findings show little or no impairment of cognitive performance with the use of anastrozole compared with placebo in postmenopausal women at high risk of developing breast cancer who were able to tolerate endocrine-related side-effects. Future studies assessing cognition should be done within randomised trials with baseline assessments to ascertain the true extent of the putative effects that treatments for breast cancer might have on memory and attention.Cancer Research UK, London, UK (grant numbers C6280/A3162 and C6280/A6764).
Kidney stones and kidney function loss: a cohort study
Authors: R. T. Alexander, B. R. Hemmelgarn, N. Wiebe, A. Bello, C. Morgan, S. Samuel, S. W. Klarenbach, G. C. Curhan, M. Tonelli
Journal: BMJ (2012)

<b>Objective</b> To investigate whether the presence of kidney stones increase the risk of end stage renal disease (ESRD) or other adverse renal outcomes. <b>Design</b> A registry cohort study using validated algorithms based on claims and facility utilisation data. Median follow-up of 11 years. <b>Setting</b> Alberta, Canada, between 1997 and 2009. <b>Participants</b> 3 089 194 adult patients without ESRD at baseline or a history of pyelonephritis. Of these, 1 954 836 had outpatient serum creatinine measurements and were included in analyses of chronic kidney disease and doubling of serum creatinine level. <b>Exposure</b> One or more kidney stones during follow-up. <b>Main outcome measures</b> Incident ESRD, development of stage 3b–5 chronic kidney disease (estimated glomerular filtration rate &lt;45 mL/min/1.73 m<sup>2</sup>), and sustained doubling of serum creatinine concentration from baseline. <b>Results</b> 23 706 (0.8%) patients had at least one kidney stone, 5333 (0.2%) developed ESRD, 68 525 (4%) developed stage 3b–5 chronic kidney disease, and 6581 (0.3%) experienced sustained doubling of serum creatinine. Overall, one or more stone episodes during follow-up was associated with increased risk of ESRD (adjusted hazard ratio 2.16 (95% CI 1.79 to 2.62)), new stage 3b–5 chronic kidney disease (hazard ratio 1.74 (1.61 to 1.88)), and doubling of serum creatinine (hazard ratio 1.94 (1.56 to 2.43)), all compared with those without kidney stones during follow-up. The excess risk of adverse outcomes associated with at least one episode of stones seemed greater in women than in men, and in people aged &lt;50 years than in those aged ≥50. However, the risks of all three adverse outcomes in those with at least one episode of stones were significantly higher than in those without stones in both sexes and age strata. The absolute increase in the rate of adverse renal outcomes associated with stones was small: the unadjusted rate of ESRD was 2.48 per million person days in people with one or more episodes of stones versus 0.52 per million person days in people without stones. <b>Conclusion</b> Even a single kidney stone episode during follow-up was associated with a significant increase in the likelihood of adverse renal outcomes including ESRD. However, the increases were small in absolute terms.