tbuckley/cabot-search huggingface dataset:
Community-acquired pneumonia in pediatric patients with heritable connective tissue disorders: Novel phenotypic variants
Authors: Zoia Nesterenko, Olena Ivanina
Journal: European Respiratory Journal (2012)

Background:  The prevalence of heritable connective tissue disorders (HCTD) changed manifestations of community-acquired pneumonia (CAP) in pediatric patients, leading to diagnostic and therapeutic errors.   Objective:  to study clinical features of CAP in children with HCTD.   Material and methods:  105 patients aged 3-18 years, with clinically, serologically and radiographically diagnosed CAP, were followed up for two years. 60(57.4%) patients had moderate persistent asthma (A). All pediatric patients had HCTD manifestations.   Results:  CAP caused by Mycoplasma pneumonia (Mp) was in 89.1% of patients, by Cytomegalovirus (Cmv) - in 26.7%, by Chlamydophilla pneumonia (Cp) - in 21.9%. CAP was caused by association of Mp, Cp and Cmv in 38.1% of children. CAP in asthmatic patients occurred with longer duration of respiratory symptoms and bronchial obstruction (11.5±2 days). Pulmonary hypertension (PH) was in 51,7% of patients with CAP and A, with pulmonary fibrosis (PF) in 48.3% of this group of patients. 26.7% of children with PH and PF had CT evidence of emphysematous bullae (EB). Patients with CAP and A received antibiotic treatment (macrolides) (ABT) besides controller therapy for achievement of A control.   Conclusions:  1. Close relationship between CAP, caused by intracellular pathogens, and HCTD is revealed. 2. CAP provoked A exacerbation in 57.4% of patients. 3. CAP in asthmatic patients had more long-term and severe clinical course. 4. PH was diagnosed in 51.7% of patients with CAP, A and HCTD, 48.3% of them had PF. 5. 26.7% of patients with PH and PF had EB. 6. It is advisable to consider CAP associated with HCTD and A as clinical phenotypes of CAP.
Changes in peak expiratory flow indices as a proxy for changes in bronchial hyperresponsiveness
Authors: W.R. Douma, H.A.M. Kerstjens, C.M. Roos, G.H. Koëter, D.S. Postma, None and the Dutch Chronic Non-Specific Lung Disease study group
Journal: European Respiratory Journal (2000)

Guidelines for asthma management advocate home peak expiratory flow (PEF) monitoring. It is commonly stated that PEF variability is a good proxy of bronchial hyperresponsiveness (BHR), a hallmark of asthma. However, this has hardly been tested longitudinally, as required to monitor asthma. This study assesses which PEF index correlates best with BHR longitudinally and whether the correlation improves when correcting PEF values for the known nonlinearity of mini-Wright PEF meters. Every 6 months, for a period of 2 yrs, PEF diary cards were filled in and BHR to histamine was tested in 104 patients with BHR and reversible airways obstruction, who started treatment with bronchodilators with (n=33) or without (n=71) inhaled corticosteroids. Within each subject, PEF indices and BHR were correlated longitudinally. The highest median correlation coefficients were obtained in the group of patients using inhaled corticosteroids. The PEF indices providing the best correlation with BHR were: mean PEF bronchodilator response (rho=-0.50) and within-day variation (% mean or % maximum) (with postbronchodilator values, rho=-0.50; without postbronchodilator values, rho=-0.40). Using PEF data corrected for the nonlinearity of the PEF meters did not result in higher correlation coefficients. Since current guidelines on asthma management recommend only bronchodilators on demand, the most useful peak expiratory flow index for reflecting bronchial hyperresponsiveness longitudinally is mean within-day peak expiratory flow variation (% mean or % maximum) (without postbronchodilator values). Since the correlation coefficients are not very strong, the authors suggest that peak expiratory flow measurements are not used as a proxy for bronchial hyperresponsiveness longitudinally but as a measurement in its own right. The use of corrections of peak expiratory flows for the nonlinearity of mini-Wright peak expiratory flow meters does not improve the correlation between peak expiratory flow and bronchial hyperresponsiveness.
Biologic Lung Volume Reduction in Advanced Upper Lobe Emphysema
Authors: Gerard J. Criner, Victor Pinto-Plata, Charlie Strange, Mark Dransfield, Mark Gotfried, William Leeds, Geoffrey McLennan, Yael Refaely, Sanjiv Tewari, Mark Krasna, Bartolome Celli
Journal: American Journal of Respiratory and Critical Care Medicine (2009)

Rationale: Biologic lung volume reduction (BioLVR) is a new endobronchial treatment for advanced emphysema that reduces lung volume through tissue remodeling.Objectives: Assess the safety and therapeutic dose of BioLVR hydrogel in upper lobe predominant emphysema.Methods: Open-labeled, multicenter phase 2 dose-ranging studies were performed with BioLVR hydrogel administered to eight subsegmental sites (four in each upper lobe) involving: (1) low-dose treatment (n = 28) with 10 ml per site (LD); and (2) high-dose treatment (n = 22) with 20 ml per site (HD). Safety was assessed by the incidence of serious medical complications. Efficacy was assessed by change from baseline in pulmonary function tests, dyspnea score, 6-minute walk distance, and health-related quality of life.Measurements and Main Results: After treatment there were no deaths and four serious treatment-related complications. A reduction in residual volume to TLC ratio at 12 weeks (primary efficacy outcome) was achieved with both LD (−6.4 ± 9.3%; P = 0.002) and HD (−5.5 ± 9.4%; P = 0.028) treatments. Improvements in pulmonary function in HD (6 mo: ΔFEV1 = +15.6%; P = 0.002; ΔFVC = +9.1%; P = 0.034) were greater than in LD patients (6 mo: ΔFEV1 = +6.7%; P = 0.021; ΔFVC = +5.1%; P = 0.139). LD- and HD-treated groups both demonstrated improved symptom scores and health-related quality of life.Conclusions: BioLVR improves physiology and functional outcomes up to 6 months with an acceptable safety profile in upper lobe predominant emphysema. Overall improvement was greater and responses more durable with 20 ml per site than 10 ml per site dosing.Clinical trial registered with www.clinicaltrials.gov (NCT 00435253 and NCT 00515164).
Postoperative Chemotherapy Without Irradiation for Ependymoma in Children Under 5 Years of Age: A Multicenter Trial of the French Society of Pediatric Oncology
Authors: Jacques Grill, Marie-Cécile Le Deley, Danièle Gambarelli, Marie-Anne Raquin, Dominique Couanet, Alain Pierre-Kahn, Jean-Louis Habrand, François Doz, Didier Frappaz, Jean-Claude Gentet, Christine Edan, Pascal Chastagner, Chantal Kalifa
Journal: Journal of Clinical Oncology (2001)

PURPOSE: To evaluate a strategy that avoids radiotherapy in first-line treatment in children under 5 years of age with brain or posterior fossa ependymoma, by exclusively administering 16 months of adjuvant multiagent chemotherapy after surgery. PATIENTS AND METHODS: Between June 1990 and October 1998, 73 children with ependymoma (82% with high-grade tumors) were enrolled onto this multicenter trial. Children received adjuvant conventional chemotherapy after surgery consisting of seven cycles of three courses alternating two drugs at each course (procarbazine and carboplatin, etoposide and cisplatin, vincristine and cyclophosphamide) over a year and a half. Systematic irradiation was not envisaged at the end of chemotherapy. In the event of relapse or progression, salvage treatment consisted of a second surgical procedure followed by local irradiation with or without second-line chemotherapy. RESULTS: Conventional chemotherapy was well tolerated and could be administered in outpatient clinics. No radiologically documented response to chemotherapy more than 50% was observed. With a median follow-up of 4.7 years (range, 5 months to 8 years), the 4-year progression-free survival rate in this series was 22% (95% confidence interval [CI], 13% to 43%) and the overall survival rate was 59% (95% CI, 47% to 71%). Overall, 40% (95% CI, 29% to 51%) of the patients were alive having never received radiotherapy 2 years after the initiation of chemotherapy and 23% (95% CI, 14% to 35%) were still alive at 4 years without recourse to this modality. In the multivariate analysis, the two factors associated with a favorable outcome were a supratentorial tumor location (P = .0004) and complete surgery (P = .0009). Overall survival at 4 years was 74% (95% CI, 59% to 86%) for the patients in whom resection was radiologically complete and 35% (95% CI, 18% to 56%) for the patients with incomplete resection. CONCLUSION: A significant proportion of children with ependymoma can avoid radiotherapy with prolonged adjuvant chemotherapy. Deferring irradiation at the time of relapse did not compromise overall survival of the entire patient population.
Androgen-induced delay of hair growth in the golden Syrian hamster
Authors: None Mezick, None Gendimenico, None Liebel, None Stenn
Journal: British Journal of Dermatology (1999)

The golden Syrian hamster flank organ has been used to study the stimulatory effect of androgens on sebaceous glands and hair. Androgens cause the sebaceous glands and hair follicles in this organ to grow. We have made the novel observation that exogenously administered androgen, testosterone propionate (TP), suppresses hair growth in the area surrounding the flank organ. When given in a time-release (systemic) subcutaneous dosage form (pellet), 25 mg TP inhibited the regrowth of clipped hair in peri-flank organ skin for up to 21 days; however, by 28 days hair grew back to the same extent as in controls. The peak serum level of testosterone in TP-treated animals occurred at 14 days, and declined thereafter. When two separate TP pellets (25 mg/pellet) were administered 14 days apart in order to maintain high serum levels for 28 days, the amount of hair regrowth after 35 days was identical to animals receiving a single TP pellet or placebo. This suggests that the systemic level of testosterone was not the only factor in hair regulation. Hair growing within the flank organ appeared to be unaffected by TP administration. In the golden Syrian hamster, androgen, as in humans, can exert stimulatory and inhibitory effects on hair growth depending on the body site. We conclude that this animal model could serve as a useful system to investigate the mechanisms responsible for the opposing effects of androgen on hair growth.
Is general surgery a dying specialty?
Authors: E. B. Smith
Journal: JAMA (1980)

To the Editor.—  Several decades ago  surgery was a thriving and active surgical specialty, with surgeons being actively trained and subsequently practicing  surgery that included everything. The trend toward accredited specialization in other surgical disciplines resulted in an ill-defined meaning of general surgery. In addition, training programs in  surgery required basic knowledge in all phases of surgery, namely, plastic, gynecologic, urologic, neurosurgical, cardiovascular-thoracic, pediatric, and fracture, for the physician to become certified as a  surgeon. Before the Study of Surgical Services in the United States Report, there were approximately 12,000 approved available positions in  surgery, and more surgical programs were being approved if specific standards and criteria were established. Nevertheless, the aforementioned report, the malpractice dilemma, the implementation of Professional Standards Review Organization, the principles of Medicare and Medicaid, the improved medical insight and understanding of the public, the eradication of overt discrimination and segregation
DSM-IV Diagnostic Criterion for Clinical Significance: Does It Help Solve the False Positives Problem?
Authors: Robert L. Spitzer, Jerome C. Wakefield
Journal: American Journal of Psychiatry (1999)

A major change in DSM-IV is the inclusion in almost one-half of the diagnostic criteria sets of a clinical significance criterion, which requires that symptoms cause "clinically significant distress or impairment in social, occupational, or other important areas of functioning." In response to concerns that the DSM criteria are overly inclusive, the clinical significance criterion attempts to minimize false positive diagnoses in situations in which the symptom criteria do not necessarily indicate pathology. This article examines whether the clinical significance criterion achieves its purpose and considers its broader impact on diagnostic validity.The effect of the clinical significance criterion on the diagnostic validity of DSM-IV criteria for a wide range of disorders was examined.For many diagnoses to which the clinical significance criterion was added, the symptom criteria are inherently associated with significant impairment, so the clinical significance criterion is redundant and therefore does not affect caseness. For some diagnoses, the clinical significance criterion is potentially helpful in eliminating false positives by elevating the level of required distress. However, there may be advantages to obtaining the same results by modifying some of the symptom criteria. Often the clinical significance criterion has led to the possibility of false negative diagnoses.In the process of revising DSM-IV, the generic use of the clinical significance criterion should be reconsidered. For each DSM diagnosis, it should be determined whether there is a need to raise the threshold of any of the existing symptom criteria or to add a criterion that excludes normal reactions to psychosocial stress.
Decision Analysis on Alternative Treatment Strategies for Favorable-Prognosis, Early-Stage Hodgkin's Disease
Authors: Andrea K. Ng, Jane C. Weeks, Peter M. Mauch, Karen M. Kuntz
Journal: Journal of Clinical Oncology (1999)

PURPOSE: To compare the therapeutic outcomes of various treatment strategies in early-stage, favorable-prognosis Hodgkin's disease (HD) using methods of decision analysis. METHODS: We constructed a decision-analytic model to determine the life expectancy and quality-adjusted life expectancy for a hypothetical cohort of clinically or pathologically staged 25-year-old patients with early-stage, favorable-prognosis HD treated with varying degrees of initial therapy. Markov models were used to simulate the lifetime clinical course of patients, and baseline probability estimates were derived from published study results. RESULTS: Among patients with pathologic stage (PS) I to II, mantle and para-aortic (MPA) radiotherapy was favored over combined-modality therapy (CMT), mantle radiotherapy, and chemotherapy by 1.18, 1.33, and 1.55 years, respectively. For patients with clinical stage (CS) I to II, the treatment options of MPA-splenic radiotherapy, CMT, and chemotherapy yielded similar survival outcomes. Sensitivity analysis showed that the decision between CMT and MPA-splenic radiotherapy was highly influenced by the precise values of the estimates of treatment efficacy and long-term morbidity, the quality-of-life value assigned to the postsplenic irradiation state, and the time discount value used in the model. Probabilistic sensitivity analysis demonstrated that even if future studies doubled the precision of the estimates of the treatment-related variables, it would be impossible to demonstrate the superiority of one treatment over the other. CONCLUSION: Our model predicted that on average, MPA radiotherapy was clearly the preferred treatment for PS I to II patients. For CS I to II patients the treatment decision is a toss-up between MPA-splenic radiotherapy and CMT, emphasizing the importance of patient preference exploration and shared decision making between patient and physician when choosing between treatments.
Variability and bronchodilator response of tracheal forced expiratory noise time parameters in asthma patients and healthy subjects
Authors: Irina Pochekutova, Vladimir Korenbaum
Journal: European Respiratory Journal (2014)

Background: Tracheal forced expiratory noise time (FETa) is promising test of airway obstruction in young asthma patients (Pochekutova, 2013). New parameters - noise times in 200-Hz frequency bands between 200 and 2000 Hz (t 200-400, t 400-600...) are developed.  Objective: To test intra-session variability and response of these parameters to short-acting β2-agonist in asthma patients and healthy.  Methods: 58 asthma patients with airway obstruction and 60 healthy (males 17-25 years) were tested. Spirometry and tracheal forced expiratory noise recording were performed before and after 0.2 mcg salbutamol inhalation. Baseline intra-session variability was calculated as CV for 3 best attempts. Significant response to bronchodilator was assessed by 1.65*CV threshold.  Results: Significant distinctions between patients and healthy are found for CV of t 400-600, t 600-800, t 1200-1400, t 1400-1600, t 1600-1800, t 1800-2000, FETa (p=0.02-0.0001). Significant differences are revealed in the incidence of types of bronchodilator response for FETa, t 200-400, t 400-600, t 600-800, t 1000-1200, t 1200-1400, t 1400-1600. Decrease of these parameters is dominant in asthma patients (p=0.02-0.001). The magnitude of decrease is essentially higher in patients for FETa, t 400-600, t 600-800, t 1200-1400, t 1400-1600 (p=0.03-0.0004). However an increase of these parameters prevails in healthy (p=0.03-0.0006).  Conclusions: Revealed differences in variability and bronchodilator response may be useful for acoustic discrimination of asthma patients and healthy. The study is supported by FEB RAS grant 12-I-P5-10 and RFBR grant 14-04-0048.
Skin Tumors Induced in Rats by the Dietary Administration of &lt;italic&gt;N,N&lt;/italic&gt;′-2,7-Fluorenylenebisacetamide
Authors: Shu-Wen How, Katharine C. Snell
Journal: JNCI Journal of the National Cancer Institute (1967)

Tumors and cysts of sebaceous gland origin and tumors derived from the epidermis were induced in female ACI/N rats that ingested N,N′-2,7-fluorenylenebisacetamide in their diet. A total of 7 epidermal tumors, 107 sebaceous gland tumors, and 67 cysts occurred in 19 rats necropsied over a period of 19 weeks, beginning at the 31st week of treatment. The tumors of epidermal origin were present after the 38th week and included 4 papillomas, 1 keratoacanthoma, 1 epidermoid carcinoma, and 1 thickened area of epidermis similar to a folliculoma of man. These tumors occurred around the lips, face, and ear lobes, with never more than 1 per animal. The sebaceous gland tumors and cysts were nearly always multiple. Eighty percent of them developed on the back of the animal with some tendency toward symmetrical distribution. The tumors were believed to be derived from the generative cells of the sebaceous glands. They were composed of mature, foamy, sebaceous cells and undifferentiated cells in various proportions with marked tendency toward differentiation into squamous cells with keratinization; none metastasized. The cysts developed from the matrix portion of the hair bulb and often contained a column of shadow cells. No tumor of connective tissue origin was found. Nonspecific dermatitis occurred in several control and experimental rats, chiefly in those killed early in the experiment.
PCR rapid molecular diagnostic assay for the diagnosis of bacterial infection in LRTI – A case-control, pilot study
Authors: Kathleen Jahn, Marko Kuisma, Mäki Minna, Peter Grendelmeier, Hans H. Hirsch, Michael Tamm, Daiana Stolz
Journal: European Respiratory Journal (2014)

Background:  Rapid PCR based diagnostic tools have been developed to early diagnose bacterial sepsis and to initiate adequate antibiotic therapy. We hypothesize that multiplex bacterial PCR might also allow timely diagnosis of bacterial pathogens in the bronchoalveolar lavage in patients with symptoms of LRTI, irrespective of antibiotic therapy.   Methods:  In a monocenter, pilot-study we analyzed the feasibility and diagnostic yield of a PCR rapid molecular diagnostic assay (PROVE-it™) including 31 bacterial specimens in the bronchoalveolar lavage of 22 patients undergoing bronchoscopy due to LRTI (cases) and 13 controls. BAL-PCR was compared to conventional microbiology (bacterial gram-staining and culture). In addition, results of virology and fungal assays were considered for etiologic diagnosis.   Results:  73% of the cases were on antibiotics at bronchoscopy. Conventional microbiological cultures revealed potentially pathogenic bacteria in 45.4% of the cases, whereas bacteria were identified in 77% of the patients using the PCR assay. As compared to conventional microbiology/clinical judgment, bacterial PCR sensitivity was 80%/77% and specificity 40%/54%, respectively. None of the controls depicted bacterial growth, while molecular diagnostics evidenced bacteria in 46% of the patients without clinical evidence of LRTI. Most of the patients (83%) with positive bacterial PCR in the control group suffered from COPD (n=5).   Conclusion:  The PCR rapid molecular diagnostic assay PROVE-it™ can be a promising diagnostic method in the bronchoalveolar lavage, however, cut-offs need to be adapted to individual patient9s characteristics, e.g. comorbidities.
Different expression pattern of endothelin receptors in primary human lung fibroblasts derived from idiopathic pulmonary fibrosis compared to healthy controls
Authors: Katrin Hostettler, Jun Zhong, Michael Tamm, Didier Lardinois, Michael Roth
Journal: European Respiratory Journal (2011)

Background: Endothelin-1 (ET-1) has a considerable fibrogenic activity and it has been implicated in the pathogenesis of pulmonary fibrosis. Increased levels of ET-1 have been demonstrated in serum and bronchoalveolar lavage fluid of patients with idiopathic pulmonary fibrosis (IPF), and lung tissue of IPF patients show increased ET-1 immunoreactivity. The biological effects of ET-1 are mediated through two receptors – ET-A and ET-B. However, disease specific patterns of ET receptor expression in fibrotic and normal primary human lung fibroblasts had not been studied yet.

Methods: Primary human lung fibroblasts were isolated and propagated from lung parenchyma derived from patients with IPF (n=4) as well as from parenchyma derived from healthy controls (n=4). Isolated cells were grown to confluence. After transforming growth factor beta1 (TGF-beta1) stimulation total protein was harvested and immuno blot analysis was performed.

Results: In fibroblasts derived from patients with IPF the ET-A and ET-B receptors were equally expressed, whereas in control fibroblasts expression of both receptors was lower compared to IPF cells. Stimulation with TGF-beta1 caused a further increase of ET-A and ET-B receptor expression by IPF fibroblasts, but no such up-regulation was detected in control fibroblasts.

Conclusion: Our data demonstrate for the first time a difference in the pattern of ET receptor expression between IPF and normal lung, and a disease-specific reaction upon stimulation with TGF-beta1. Our observations may have implications for our understanding of the roles of ET-1 and TGF-beta1 in the pathogenesis of IPF.
Odontomas in &lt;italic&gt;Peromyscus leucopus&lt;/italic&gt;&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: M P Finkel, L S Lombard, E F Staffeldt, P H Duffy
Journal: JNCI Journal of the National Cancer Institute (1979)

A colony of Peromyscus leucopus was established 15 years ago from animals trapped in the deciduous forest at Argonne National Laboratory, Argonne, Illinois. A roentgenographic survey of the skeletons of 189 of these untreated animals dying during a 13-month period disclosed 48 odontogenic growths in 21 of the mice. These growths were diagnosed on histopathologic examination as complex odontomas, the incidence of which was higher in males than in females. In this relatively small sample, these benign tumors appeared to be associated with youth rather than old age.