tbuckley/cabot-search huggingface dataset:
Obstructive sleep apnea among diabetics in southeastern Nigeria
Authors: Victor Umoh, Effiong Akpan, John Ekott, Etete Peters, Obeten Ekpo, Mfon Ekwere
Journal: European Respiratory Journal (2012)

Background: Diabetic patients are prone to obstructive sleep apnea (OSAS). OSAS has also been shown to be associated with increased cardiovascular morbidity and mortality. There is a paucity of data on this condition among diabetics in Nigeria. This study was carried out to determine the risk of OSAS among diabetics in Nigeria.  Methods: Diabetics attending the medical outpatient clinic of a tertiary hospital in South Eastern Nigeria were recruited into this survey. A modified version of the Berlin Questionnaire was used to determine the risk for OSAS and also obtain demographic data. Anthropometric and spirometric measurements were also obtained from all subjects. The survey was conducted over a 4 months.  Results: 114 diabetics were randomly recruited for this survey, 54 (47.4%) female sand 60 (52.6%) males. 66 (57.9%) of the subjects were hypertensive. The average age of the subjects was 55.5 years and the average duration of diabetes was 7.5 years. 63(55.3%) of the subjects were found to have a high risk for OSAS. there was no gender difference in the risk for OSAS. A high risk for OSAS was associated with increased BMI, increased neck size, hypertension, alcohol use and reduced PEF. The factors that significantly predicted a high risk for OSAS were a history of hypertension (OR 55), alcohol use (OR 9), increasing BMI (OR 2) and poor BP control (OR 2).  Conclusion: OSAS is often not diagnosed among patients with diabetes and the strong association between a previous history of hypertension and OSAS may be the reason for the increased risk of cardiovascular death among diabetics.
Lentiviral-mediated gene therapy restores B cell tolerance in Wiskott-Aldrich syndrome patients
Authors: Francesca Pala, Henner Morbach, Maria Carmina Castiello, Jean-Nicolas Schickel, Samantha Scaramuzza, Nicolas Chamberlain, Barbara Cassani, Salome Glauzy, Neil Romberg, Fabio Candotti, Alessandro Aiuti, Marita Bosticardo, Anna Villa, Eric Meffre
Journal: Journal of Clinical Investigation (2015)

Wiskott-Aldrich syndrome (WAS) is an X-linked immunodeficiency characterized by microthrombocytopenia, eczema, and high susceptibility to developing tumors and autoimmunity. Recent evidence suggests that B cells may be key players in the pathogenesis of autoimmunity in WAS. Here, we assessed whether WAS protein deficiency (WASp deficiency) affects the establishment of B cell tolerance by testing the reactivity of recombinant antibodies isolated from single B cells from 4 WAS patients before and after gene therapy (GT). We found that pre-GT WASp-deficient B cells were hyperreactive to B cell receptor stimulation (BCR stimulation). This hyperreactivity correlated with decreased frequency of autoreactive new emigrant/transitional B cells exiting the BM, indicating that the BCR signaling threshold plays a major role in the regulation of central B cell tolerance. In contrast, mature naive B cells from WAS patients were enriched in self-reactive clones, revealing that peripheral B cell tolerance checkpoint dysfunction is associated with impaired suppressive function of WAS regulatory T cells. The introduction of functional WASp by GT corrected the alterations of both central and peripheral B cell tolerance checkpoints. We conclude that WASp plays an important role in the establishment and maintenance of B cell tolerance in humans and that restoration of WASp by GT is able to restore B cell tolerance in WAS patients.
Pharmacodynamic effects of administration of maytansine conjugated anti-CD22 monoclonal antibodies to cynomolgus monkeys
Authors: F. K. Fuh, R. Fuji, K. A. Poon, W. Manning, K. K. Berry, V. Ramakrishnan, A. Polson, A. Ebens, S. Prabhu, M. Williams
Journal: Journal of Clinical Oncology (2009)

3051 Antibody-based B-cell specific therapeutic approaches have revolutionized the treatment of non-Hodgkin's lymphomas (NHL) as well as other hematological malignancies. However, a large variability in clinical response has been observed, and the need to develop effective new treatments remains urgent. A promising approach is the use of antibody-drug conjugates (ADCs), cytotoxic drugs covalently linked to antibodies through specialized chemical linkers for the treatment of NHL. CMC-544, an antibody to a B-cell specific glycoprotein CD22 conjugated to the cytotoxin calicheamicin, has shown clinical activity in patients. In addition, antibodies directed to B-cell targets such as rituximab and epratuzumab are in clinical trials for the treatment of NHL and autoimmune disorders. We have generated10F4v3, an anti-CD22 antibody conjugated to the antimitotic agent maytansine (10F4v3-DM1). DM1 disrupts cellular mitosis through inhibition of tubulin polymerization when internalized into cells. The anti-CD22 DM1 conjugate was shown to have significant potency in preclinical efficacy models of NHL. In order to further characterize this antibody-drug conjugate in preclinical studies, we first evaluated the binding characteristics of the 10F4v3 to peripheral blood B-cells from various geographical sources of cynomolgus monkeys. 10F4v3 bound to peripheral blood B-cells from all cynomolgus monkeys of Indonesian and Mauritian origins, but displayed only limited binding to cynomolgus monkeys of Chinese and Cambodian origins. Therefore, further preclinical evaluation of 10F4v3-DM1 was conducted in Indonesian cynomolgus monkeys to examine the safety, pharmacokinetic, and pharmacodynamic effects in monkeys. B-cells and B-cell subsets were depleted in peripheral blood and lymphoid tissue (spleen, bone marrow) at all doses, with no apparent dose-dependent effects or substantial safety limitations. Based on the nonclinical data, 10F4v3-DM1 exhibits an encouraging pharmacodynamic profile for the potential treatment of non-Hodgkin's lymphoma. [Table: see text]
A phase I study of pazopanib in combination with FOLFOX 6 or capeOx in subjects with colorectal cancer
Authors: J. Brady, M. Middleton, R. S. Midgley, M. K. Mallath, P. Corrie, B. Sirohi, I. Chau, R. Digumarti, J. Botbyl, J. J. Lager
Journal: Journal of Clinical Oncology (2009)

4133 Background: Pazopanib (paz) is a tyrosine kinase inhibitor of VEGFR-1, -2, -3, PDGF-α, -β, and c-kit. Inhibition of angiogenic pathways in combination with chemotherapy has been shown to benefit patients (pts) with colorectal cancer (CRC). Methods: Pts with previously untreated advanced or metastatic CRC and adequate organ function were assigned to paz with FOLFOX6 (FO) or capeOx (CO) by their physician. Doses of paz were escalated with full strength chemotherapy, starting at 400mg daily. The optimally tolerated regimen (OTR) was the combination dose at which &lt;1/6 pts experienced dose-limiting toxicity (DLT). Results: Fifty pts were enrolled in FO (paz 400 mg, n=6; 800, 15), CO (400, 12; 800, 9) and reduced capecitabine (rc) CO (800, 8) cohorts: median age = 55.5, M/F = 37/13. Pts have remained on therapy for a median of 3 (range 0–17) months. Three pts remain on study. Safety data is available on 41. The most common AEs are summarized in the table below. The OTR was exceeded with CO in combination with 800 mg and 400 mg of pazopanib, but was not exceeded with 800 mg pazopanib when capecitabine was reduced to 850 mg/m 2 twice daily or with FO with 800 mg pazopanib. Efficacy and pharmacokinetic analyses are ongoing. Conclusions: The OTRs were achieved at 800 mg paz with full-dose FO, and at 800mg paz with rcCO. [Table: see text] [Table: see text]
Association of Histologic Regression in Primary Melanoma With Sentinel Lymph Node Status
Authors: Simone Ribero, Maria Rosaria Gualano, Simona Osella-Abate, Giacomo Scaioli, Fabrizio Bert, Martina Sanlorenzo, Elena Balagna, Maria Teresa Fierro, Giuseppe Macripò, Anna Sapino, Roberta Siliquini, Pietro Quaglino
Journal: JAMA Dermatology (2015)

The prognostic significance of regression in primary melanoma has been debated for many years. There is no consensus regarding the need for sentinel lymph node (SLN) biopsy when regression is present within the primary tumor.To review the evidence that regression may affect SLN status.A systematic review was performed by searching in MEDLINE, Scopus, and the Cochrane Library from January 1, 1990, through June 2014.All studies that reported an odds ratio (OR) or data on expected and observed cases of SLN positivity and histologic regression were included.Primary random-effects meta-analyses were used to summarize ORs of SLN positivity and histologic regression. Heterogeneity was assessed using the χ2 test and I2 statistic. To assess the potential bias of small studies, we used funnel plots, the Begg rank correlation test, and the Egger weighted linear regression test. The methodologic quality of the studies was assessed according to the Strengthening of Reporting of Observational studies in Epidemiology (STROBE) checklist, and 2 different meta-analyses were performed based on those criteria.Summary ORs of histologic regression of primary melanoma and SLN status.Of the 1509 citations found in the search, 94 articles were reviewed, and 14 studies comprising 10 098 patients were included in the analysis. In the combined 14 studies, patients with regression had a lower likelihood to have SLN positivity (OR, 0.56; 95% CI, 0.41-0.77) than patients without regression. On the basis of study quality, we found that patients with regression enrolled in high-quality studies had a lower likelihood to have SLN positivity (OR, 0.48; 95% CI, 0.32-0.72) compared with results of low-quality studies (OR, 0.73; 95% CI, 0.53-1.00). Examination of the funnel plot did not provide evidence of publication bias.The results of this analysis showed that the risk of SLN positivity was significantly lower in patients with histologic regression compared with those without. Regression may be used in these cases to make a selection of which patients should be the most appropriate for this procedure.
Sustained Benefit from Ivacaftor Demonstrated by Combining Clinical Trial and Cystic Fibrosis Patient Registry Data
Authors: Gregory S. Sawicki, Edward F. McKone, David J. Pasta, Stefanie J. Millar, Jeffrey S. Wagener, Charles A. Johnson, Michael W. Konstan
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

In clinical trials, patients with cystic fibrosis and a G551D mutation who received ivacaftor experienced improvements in pulmonary and nutritional outcomes. However, whether these improvements reflect a change in disease trajectory cannot be determined without longer-term analyses with an appropriate comparator population.To examine, over a 3-year period, whether ivacaftor therapy affects pulmonary function and nutritional measures in patients with CF with a G551D mutation compared with patients with CF who are homozygous for the F508del mutation.A propensity score was used to match patients with CF greater than or equal to 6 years of age who have a G551D mutation and received ivacaftor in clinical trials for up to 144 weeks with data from patients in the U.S. Cystic Fibrosis Foundation Patient Registry who are homozygous for the F508del mutation. Matching was based on variables including age, sex, weight for age, height for age, body mass index for age, % predicted FEV1, and chronic therapies (dornase alfa, inhaled antibiotics, inhaled and oral corticosteroids).By calculating the annual estimated rate of decline in lung function for G551D patients receiving ivacaftor and comparing it with the rate of decline in lung function for matched F508del control patients, we show that the rate of lung function decline in G551D ivacaftor-treated patients was slower by nearly half. Moreover, treatment with ivacaftor is shown to improve body mass index and weight-for-age z scores for G551D patients over the 3-year analysis period.These findings suggest that ivacaftor is a disease-modifying therapy for the treatment of cystic fibrosis.
Gender differences in diagnosing antisocial personality disorder in methadone patients
Authors: M J Rutherford, A I Alterman, J S Cacciola, E C Snider
Journal: American Journal of Psychiatry (1995)

The goal of this study was to evaluate gender differences in the prevalence rates, short-term reliability, and internal consistency of the diagnosis of antisocial personality disorder for DSM-III-R, DSM-III, and Research Diagnostic Criteria (RDC).A total of 37 men and 57 women methadone patients were diagnosed according to DSM-III-R, DSM-III, and RDC antisocial personality disorder criteria.The diagnostic rates, reliability, and internal consistency were lower for women than for men in all systems. DSM-III criteria resulted in the highest reliability for women, but for men, the DSM-III criteria were the least reliable. Examination of endorsement rates of individual antisocial personality disorder criteria revealed several significant gender differences on the majority of childhood criteria and on several adult criteria. Item-total correlations revealed that for women, the violent and aggressive childhood criteria in DSM-III-R that had not been included in DSM-III or RDC had a negative or no correlation to the assessment of antisocial personality disorder for women.The change in DSM-III-R from DSM-III childhood criteria appears to have resulted in a decrease in internal consistency and rates of antisocial personality disorder for women, but not for men. The results of this investigation indicate that the psychometric properties of the current antisocial personality disorder scales are weak for women, compared with men. To assess antisocial personality disorder in women it may be necessary to revise current, or develop new, diagnostic criteria.
MR-Guided Near-Infrared Spectral Tomography Increases Diagnostic Performance of Breast MRI
Authors: Michael A. Mastanduno, Junqing Xu, Fadi El-Ghussein, Shudong Jiang, Hong Yin, Yan Zhao, Ke Wang, Fang Ren, Jiang Gui, Brian W. Pogue, Keith D. Paulsen
Journal: Clinical Cancer Research (2015)

The purpose of this study was to determine the diagnostically most important molecular biomarkers quantified by magnetic resonance-guided (MR) near-infrared spectral tomography (NIRST) that distinguish malignant breast lesions from benign abnormalities when combined with outcomes from clinical breast MRI.The study was HIPAA compliant and approved by the Dartmouth Institutional Review Board, the NIH, the United States State Department, and Xijing Hospital. MR-guided NIRST evaluated hemoglobin, water, and lipid content in regions of interest defined by concurrent dynamic contrast-enhanced MRI (DCE-MRI) in the breast. MRI plus NIRST was performed in 44 subjects (median age, 46, age range, 20-81 years), 28 of whom had subsequent malignant pathologic diagnoses, and 16 had benign conditions. A subset of 30 subject examinations yielded optical data that met minimum sensitivity requirements to the suspicious lesion and were included in the analyses of diagnostic performance.In the subset of 30 subject examinations meeting minimum optical data sensitivity criterion, the MR-guided NIRST separated malignant from benign lesions using total hemoglobin (HbT; P < 0.01) and tissue optical index (TOI; P < 0.001). Combined MRI plus TOI data caused one false positive and 1 false negative, and produced the best diagnostic performance, yielding an AUC of 0.95, sensitivity of 95%, specificity of 89%, positive predictive value of 95%, and negative predictive value of 89%, respectively.MRI plus NIRST results correlated well with histopathologic diagnoses and could provide additional information to reduce the number of MRI-directed biopsies.
Abstract 800: Downstream Care and Outcomes Following Outpatient Stress Testing in the United States: How Low is Too Low Risk?
Authors: Daniel WMudrick, Bimal RShah, PatriciaCowper, Neil CJensen, Matthew JDrawz, Eric DPeterson, Pamela SDouglas
Journal: Circulation (2009)

Background: Non-invasive stress testing has its greatest value when used in those with at least intermediate risk for CAD. While millions of Americans undergo outpatient non-invasive diagnostic testing, their subsequent courses of care and outcomes have not been well characterized. Methods: We examined claims data from July 1, 2004 to June 30, 2007 from a large, national health insurer. We report 6- and 12-month rates of cardiac catheterization, revascularization, and cardiovascular events among all outpatient women ≥50 years old and men ≥45 years old presenting with chest pain and undergoing stress testing within 30 days. Patients with a prior history of CAD or CHF were excluded. Results: The analysis included 98,872 patients; mean age was 56 years (±7 yr) and 46% were female. The majority, 79%, underwent initial testing with imaging (61% stress nuclear perfusion, 18% stress echo, 0.03%; MRI) while 21% had exercise ECG testing alone. Within a year of the initial stress test, <15% went on to cardiac cathe...
Temporal patterns of wheeze during the school ages in a population-based cohort
Authors: Anders Bjerg, Linnea Hedman, Sigrid Sundberg, Martin Andersson, Eva Rönmark
Journal: European Respiratory Journal (2011)

Introduction: Wheeze, as suggestive of asthma, may follow various time courses during childhood. Incidence, remission and relapse rates are high. Compared to the pre-school ages, school age and adolescence have been less studied. The aim was to characterize temporal patterns of wheeze in school children.

Methods: At age 7-8 years, 3,430 (97% of invited) children in Northern Sweden completed ISAAC questionnaires. The same questions were used in 10 yearly follow-ups until age 17-18. Data from the 2,622 (76.4%) subjects that participated at 5 or more occasions were analysed.

Results: From age 7-8 to 17-18 one third reported wheezing at some occasion. Persistent wheeze from age 7-8 was reported by 2.9%. It was closely associated with rhino-conjunctivitis and parental asthma at age 7-8, RR 10 (6.6-15) and 5.3 (3.5-8.2). Incident wheeze persisting until age 17-18 was reported by 7.6%, while 2.6% had remittent wheeze, i.e. wheeze at age 7-8 but not at study end. Remittent wheeze was associated with respiratory infections before age 7-8, RR 4.1 (2.2-7.8). Transient wheeze for 1 years or more, not persisting until age 17-18, was seen in 8.7%. Of the 12.0% reporting intermittent periods of wheeze with no clear pattern, nearly half wheezed only at 1 or 2 occasions.

Discussion: In this large cohort of school children followed yearly by questionnaires, the majority of children with any wheeze during the school years were neither wheezing at age 7-8, nor at age 17-18. Half of the children wheezing at age 7-8 were in remission by age 17-18. Whereas wheeze associated with respiratory infections has a good probability of remission, heritability and concomitant allergic rhinitis predict persistence of wheeze.
Toward Adenotonsillectomy in Children
Authors: David G. Ingram, Norman R. Friedman
Journal: JAMA Pediatrics (2015)

Adenotonsillectomy is one of the most common surgical procedures performed in children, with more than half a million procedures performed annually. We provide a review of the procedure, including indications, contraindications, perioperative issues, and current controversies. A more in-depth discussion of indications for sleep-disordered breathing and recurrent throat infections is performed. We provide a reasonable approach to these conditions for the general pediatrician. Finally, we discuss selected areas of current controversies: the role of preoperative polysomnogram, postoperative weight gain, and effects on immune function.
Anti-immunoglobulin E antibodies may improve remodeling in a mouse model of asthma
Authors: Mari Mizuguchi, Takenori Okada, Risako Seki, Kyoko Ohmori, Kazunori Fukuda, Keiichi Akasaka, Kenya Kohyama, Naoto Fueki, Hironori Sagara
Journal: European Respiratory Journal (2011)

Recent studies have confirmed that omalizumab, an anti-immunoglobulin E (IgE) antibody, has a high response rate in patients with severe asthma who satisfy conditions such as the use of high-dose inhaled steroids and poor respiratory function. However, the effect of omalizumab on airway remodeling, a characteristic feature of chronic severe asthma, remains to be confirmed. In this study, we compared the effect of omalizumab with that of steroids in a mouse model of remodeling. BALB/c mice were continuously sensitized to ovalbumin to produce a model of remodeling. After the remodeling model had been prepared, four groups were studied: an IgE neutralizing antibody group (A), a steroid group (B), an IgE neutralizing antibody plus steroid group (C), and an untreated control group (D). Basement membrane thickening, used as a marker of remodeling, was found to be significantly inhibited in the group A, as compared with the other groups. The group B showed a trend toward inhibition of basement membrane thickening, but the effect was weaker than that in the group A. In the group C, basement membrane thickening was significantly suppressed in a synergistic fashion.  Airway remodeling, a characteristic of chronic severe asthma, was significantly inhibited by treatment with IgE neutralizing antibodies. Concurrent treatment with steroids was markedly effective. On the basis of these results, omalizumab is expected to be therapeutically effective for severe refractory asthma. The finding that treatment with steroids alone was less effective than combined treatment suggested that IgE neutralizing antibodies might also have a steroid-sparing effect.
Sinonasal mucoceles in cystic fibrosis
Authors: Maurizio Di Cicco, Nicola Luca, Lorenzo Pignataro, Carla Colombo
Journal: European Respiratory Journal (2013)

Introduction  Paranasal sinus mucoceles are a rare complication of rhinosinusitis in children. They consist in cystic formations with a wall of respiratory epithelium; their growth erode the bone walls with potential involvement of cranial structures; Cystic Fibrosis (CF) represents the most common predisposing factor.  Aims and objectives  Our aim is to evaluate clinical and endoscopic findings predictive for sinus mucoceles in pediatric CF population and discuss our surgical management.  Methods  882 CF patients were followed from 2000 to 2012. During the ENT assessment, complete patient’s history concerning upper airway diseases (nasal obstruction, hyposmia/anosmia, rhinorrhea, snoring) was retraced.  Rhinofibroscopical signs suggestive for mucoceles (i.e. obstruction of nasal fossae due to medialization of the lateral wall), were determinant for the execution of CT. Endoscopic sinus surgery (ESS) was performed in case of persistent nasal obstruction and radiological evidence of mucoceles and bones resorption.  Results  38 children suffered from paranasal sinus mucoceles (mean age 8.3±3.9 years). The most common sites were the anterior ethmoid (55.2%) and the maxillary sinus (44.7%); 7 cases (18.4%) reported bilateral involvement of maxillary sinus (hourglass image).  All patients underwent ESS with the goal of marsupialization of the mucoceles. No complications and recurrences were registered.  Clinical improvements and reduction in the use of antibiotics (from 2.92±1,15 to 0.86±0,7 times per year) were achieved in all patients.  Conclusions  Precocious treatment of paranasal sinus mucoceles is essential to prevent complications related to their potential expansion and to eliminate the reservoir of pathogens causing infections of the entire respiratory tract.