tbuckley/cabot-search huggingface dataset:
Pulmonary function during the first year of life following acute viral bronchiolitis.
Authors: I T Merth, J P de Winter, H M Zonderland, R Brand, P H Quanjer
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

It has been suggested that acute viral bronchiolitis in infants may result in functional changes that predispose toward chronic pulmonary disease later in life. We assessed pulmonary function (PF) during the acute phase of viral bronchiolitis in infants and up to 12 mo later from static respiratory system compliance (Crs), using weighted spirometry, the distribution of ventilation by the mixing index (MI), and the functional residual capacity (FRC) measured by closed-circuit helium dilution (FRCHe). The study was performed in 24 infants (13 males and 11 females; median [25 to 75% range] age: 11 [9.6 to 13.3] wk; weight: 4.8 [4.3 to 5.0] kg; crown-to-heel length: 57.7 [55.5 to 59.0] cm) at admission and at 2 wk. In 17 infants, measurements were repeated 3 mo and 12 mo later. Predicted values and individual 95% prediction intervals for Crs, MI, and FRCHe were derived from 69 healthy infants (33 boys and 36 girls; median age [25 to 75% range]: 4.7 [2.0 to 21.4] wk; weight: 3.6 [3.0 to 6.9] kg; crown-to-heel length: 51.5 [48 to 61] cm). Data at admission and after discharge were compared by analysis of variance (ANOVA) with those in the healthy controls matched for crown-to-heel length. At admission all three variables gave lower average results than predicted means. Values for each index had attained a normal level 2 wk after admission; normal levels were maintained at 3 and 12 mo. The prevalence of recurrent wheezing (five of the 17 infants) was comparable with that reported in population studies. These findings suggest that in this population acute viral bronchiolitis did not lead to permanent changes in PF.
National Study of Internal Medicine Manpower: VI. Factors Predicting Preferences of Residents for Careers in Primary Care or Subspecialty Care and Clinical Practice or Academic Medicine
Authors: Peter A. Weil, Mary Kay Schleiter
Journal: Annals of Internal Medicine (1981)

With data collected from a national sample of residents in internal medicine (Questionnaire III of the National Study of Internal Medicine Manpower), two models are empirically tested: the first predicting interest in primary care medicine in contrast to subspecialty medicine and the second predicting interest in academic medicine in contrast to clinical practice. Correlation and multiple regression (path analysis) show that background and personal variables specific to each person such as religion, personality type, and desire for control over working conditions have greater predictive power than variables describing the environment such as the type of medical school or residency program the trainee attends. The single most important predictor in terms of unique variance explained in both models is the desire for control over working conditions. The variables positively related to interest in primary care are negatively related to interest in academic careers.
Preoperative Pulmonary Function Testing
Authors: Claude A. Frazier
Journal: JAMA (1976)

To the Editor.—  The question Who needs these studies? was asked in the COMMENTARY by Block and Olsen (235:257, 1976).  The asthmatic patient should have a careful preoperative evaluation of his status, including pulmonary function tests. Most allergic children have a preoperative evaluation that does not include pulmonary function studies.  One of the most important facets in the presurgical evaluation of the allergic child is the evaluation of his pulmonary function on both a quantitative and qualitative basis. There has been considerable discussion on the difficulties of studying pulmonary function in children, but these have been surmounted in many instances by extreme patience in studying little patients.  The above information is taken from my book, Surgery and the Allergic Patient (Charles C Thomas Publishers), in a chapter entitled Presurgical Evaluation of the Allergic Child.
Why has mortality from coronary heart disease in young adults levelled off?
Authors: A. H Leyland, J. W Lynch
Journal: BMJ (2009)

Transforming growth factors-β (TGF-βs) signal through type I and type II serine–threonine kinase receptor complexes. During ligand binding, type II receptors recruit and phosphorylate type I receptors, triggering downstream signaling. BAMBI [bone morphogenetic protein (BMP) and activin membrane-bound inhibitor] is a transmembrane pseudoreceptor structurally similar to type I receptors but lacks the intracellular kinase domain. BAMBI modulates negatively pan-TGF-β family signaling; therefore, it can be used as an instrument for unraveling the roles of these cytokines in the adult CNS. <i>BAMBI</i> is expressed in regions of the CNS involved in pain transmission and modulation. The lack of <i>BAMBI</i> in mutant mice resulted in increased levels of TGF-β signaling activity, which was associated with attenuation of acute pain behaviors, regardless of the modality of the stimuli (thermal, mechanical, chemical/inflammatory). The nociceptive hyposensitivity exhibited by <i>BAMBI</i><sup>−/−</sup> mice was reversed by the opioid antagonist naloxone. Moreover, in a model of chronic neuropathic pain, the allodynic responses of <i>BAMBI</i><sup>−/−</sup> mice also appeared attenuated through a mechanism involving δ-opioid receptor signaling. Basal mRNA and protein levels of precursor proteins of the endogenous opioid peptides <i>proopiomelanocortin</i> (POMC) and <i>proenkephalin</i> (PENK) appeared increased in the spinal cords of <i>BAMBI</i><sup>−/−</sup>. Transcript levels of TGF-βs and their intracellular effectors correlated directly with genes encoding opioid peptides, whereas <i>BAMBI</i> correlated inversely. Furthermore, incubation of spinal cord explants with activin A or BMP-7 increased <i>POMC</i> and/or <i>PENK</i> mRNA levels. Our findings identify TGF-β family members as modulators of acute and chronic pain perception through the transcriptional regulation of genes encoding the endogenous opioids.
Regulation of Breast Cancer Response to Chemotherapy by Fibulin-1
Authors: Serenella M. Pupa, Sarah Giuffré, Fabio Castiglioni, Lorenzo Bertola, Marco Cantú, Italia Bongarzone, Paola Baldassari, Roberta Mortarini, W. Scott Argraves, Andrea Anichini, Sylvie Menard, Elda Tagliabue
Journal: Cancer Research (2007)

Abstract Doxorubicin treatment was found to augment the expression of the extracellular matrix (ECM) protein fibulin-1 in cultured human breast cancer cell lines and in MDA-MB-361 tumors grown in athymic mice. Doxorubicin was also found to augment tumor expression of the fibulin-1–binding proteins fibronectin and laminin-1. Growth of breast cancer cell lines on Matrigel, an ECM extract containing fibulin-1 and laminin-1, resulted in lower levels of doxorubicin-induced apoptosis as compared with controls. Moreover, tumors formed by injection of athymic mice with MDA-MB-361 cells mixed with Matrigel were significantly more doxorubicin resistant and displayed lower levels of apoptosis compared with those that formed in the absence of Matrigel. Monoclonal antibodies against fibulin-1 reversed Matrigel-dependent doxorubicin resistance. Furthermore, small interfering RNA–mediated suppression of fibulin-1 expression in breast cancer cells resulted in a 10-fold increase in doxorubicin sensitivity as compared with control cells. Together, these findings point to a role for fibulin-1 in breast cancer chemoresistance. [Cancer Res 2007;67(9):4271–7]
Exercise ECG useful in finding coronary artery disease
Authors: P. J. Bourdillon
Journal: BMJ (2010)

The National Institute for Health and Clinical Excellence (NICE) uses probability to help diagnose chest pain,1 but why stop with symptoms?

Since 1999 we have asked everyone attending the rapid access chest pain clinic at this hospital to complete a questionnaire.2 The probability of coronary artery disease (CAD) is then calculated from this and 12 lead electrocardiography (ECG) before the person is seen.3 All those undergoing …
A SIMPLIFIED METHOD OF EXAMINING THE PATENCY OF THE FALLOPIAN TUBES
Authors: I. Seth Hirsch
Journal: JAMA (1928)

Until now the methods for the determination of the patency of the fallopian tubes have utilized the injection of gas and such contrast mediums as iodized oil, bismuth or barium emulsions. In all these methods the exhibition of more or less pressure or force is necessary to send the air or contrast substance through. Even in the method of Williams and Reynolds which Dr. A. J. Rongy and I have tried out, no matter how carefully the emulsion is introduced into the uterine cavity it is practically impossible to avoid producing a positive intra-uterine and intratubal pressure. It seemed important to have a method in which only the natural motive forces operative in the uterotubal canal should carry the contrast medium through the fallopian tubes. To this end I devised a medium which seems to serve the purpose. Barium sulphate is rubbed up with just enough petrolatum and oil of theobroma
Increased risk of cancer in patients with systemic lupus erythematosus.
Authors: T Pettersson, E Pukkala, L Teppo, C Friman
Journal: Annals of the Rheumatic Diseases (1992)

To evaluate the risk of cancer in patients with systemic lupus erythematosus (SLE) a series of 205 consecutive patients (182 women and 23 men) were followed up for cancer through the files of the Finnish Cancer Registry. The follow up consisted of a total of 2340 person years. Fifteen cancers were diagnosed against 5.7 expected (relative risk (RR) 2.6, 95% confidence interval (CI) 1.5 to 4.4). Among the women there were four non-Hodgkin9s lymphomas against 0.09 expected (RR 44, CI 11.9 to 111) and two soft tissue sarcomas against 0.04 expected (RR 49, CI 6.0 to 177). When evaluated by a case control study previous treatment with cytostatic drugs showed no influence on the occurrence of cancer in this series of patients with SLE.
Optimal Duration of Clopidogrel Use after Implantation of Drug-Eluting Stents — Still in Doubt
Authors: Peter B. Berger
Journal: New England Journal of Medicine (2010)

As compared with bare-metal stents, drug-eluting stents reduce restenosis in every clinical situation and every type of lesion studied. Why, then, do some cardiologists use drug-eluting stents in 90% of patients and other cardiologists in 10%? The explanation relates primarily to two questions. First, are drug-eluting stents associated with a greater risk of "very late" (>1 year after implantation) stent thrombosis than bare-metal stents? And second, what is the required duration of dual antiplatelet therapy after implantation of drug-eluting stents? Incredibly, the answers to these questions are still unknown.Definitions of stent thrombosis are either insufficiently sensitive or insufficiently specific. . . .
Abstract IA41: A new TRacK in lung cancer: NTRK1 gene fusions as a therapeutic target.
Authors: Robert C. Doebele
Journal: Clinical Cancer Research (2014)

Abstract Non-small cell lung cancer (NSCLC) is a heterogeneous disease that can be organized into groups designated by the dominant oncogene or oncogenic ‘driver’. Classification of NSCLC by oncogenes is critical because oral kinase inhibitors or other targeted therapeutic strategies can often effectively inhibit these oncogenes leading to dramatic tumor shrinkage and thus significant clinical benefit for patients. Several of these oncogenes are the result of chromosomal translocations that generate gene fusions in which the kinase domain of a receptor tyrosine kinase is aberrantly expressed and activated by the addition of sequence from an unrelated gene. Recent examples of such gene fusions in NSCLC include those involving the ALK, ROS1, RET and FGFR1/2/3 genes. We have recently discovered previously uncharacterized gene fusions involving the NTRK1 gene in patients with lung adenocarcinoma whose tumors did not harbor other known oncogenes. These novel oncogenes contain the 3 portion of the neurotrophic tyrosine kinase, receptor, type 1 (NTRK1) gene, which encodes the kinase domain of the TRKA receptor. Cloning and ectopic expression of these novels genes in non-tumor cells demonstrate their oncogenic potential. Treatment of cells expressing NTRK1 gene fusions with TRK inhibitors inhibits autophosphorylation of the chimeric TRKA proteins, important downstream signaling pathways, and cellular proliferation. Gene fusions involving NTRK1 (TRKA), NTRK2 (TRKB), and NTRK3 (and TRKC) have now been identified across multiple tumor types. As clinical next generation sequencing becomes increasingly common, cancer patients with these somatic gene abnormalities will be identified and therefore it is critical to understand their biology, utility as a therapeutic target, and mechanisms of intrinsic and acquired drug resistance in order to advance a precision medicine strategy for the treatment of NSCLC. Citation Format: Robert C. Doebele. A new TRacK in lung cancer: NTRK1 gene fusions as a therapeutic target. [abstract]. In: Proceedings of the AACR-IASLC Joint Conference on Molecular Origins of Lung Cancer; 2014 Jan 6-9; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2014;20(2Suppl):Abstract nr IA41.
Diagnosis of Thyrotoxicosis by a Simple Out-patient Radioactive Iodine Technique
Authors: A. G. Macgregor, H. Miller, P. J. Blaney, W. S. Whimster
Journal: BMJ (1953)

Accurate diagnosis followed by equally accurate physiotherapy is applicable to 17% of our patients.It should be obtainable on the spot, and at once.Any two or three doctors clubbing together could easily afford the services of a physiotherapist and thus benefit their patients.Any doctor who follows this suggested line of training would have the satisfaction of curing most of his sufferers from "rheumatism" and "fibrositis," and rejoice in the contrast with the unhappy time when he could merely prescribe an analgesic tablet or liniment.This type of treatment is most rewarding to the patient, and keeps him out of the clutches of the lay healer.I find this new sphere of work most exhilarating, and, as a general practitioner living in this antibiotic and bureau- cratic age, enjoy increasing my diagnostic powers in a fresh field.This interesting work, coupled with the ser- vices of a physiotherapist grounded in accurate manual work, transforms my day and has limitless possibilities for every practitioner.
A prospective study of the incidence of sub-clinical Lambert-Eaton Myasthenic Syndrome (LEMS) in patients with small cell lung cancer (SCLC)
Authors: P. Bradbury, B. Lang, A. Vincent, C. Han, D. Talbot
Journal: Journal of Clinical Oncology (2004)

7213 Background: LEMS is one of the most common paraneoplastic disorders associated with SCLC. Autoantibodies targeted to the P/Q type voltage gated calcium channel (VGCC) are believed to be a cause of LEMS and form the basis of a diagnostic serological test. It is not known how many patients (pts) presenting with SCLC have positive anti-VGCC antibodies (Ab) and subclinical LEMS who may then be susceptible to develop clinical LEMS. We used a sensitive serological test to determine, in a prospective manner, the incidence of subclinical LEMS in SCLC. Methods: Consenting Pts with a pathological diagnosis of SCLC completed a symptom questionnaire, had clinical examination for signs of LEMS, and serum for P/Q anti-VGCC Ab was taken. VGCC Abs were measured by immunoprecipitation of [I125]-labeled conotoxin MVIIC bound to VGCCs extracted from human cerebellum. Antibody titres were considered positive if >50pM (Mean +3SD for healthy controls n=30). Multivariate regression was used to determine the relationship between clinical symptoms and anti-VGCC titre, and Cox analysis to evaluate survival. Results: Of the 64 pts (46 male 18 female) tested, 5 (8%) pts had elevation of the anti-VGCC antibodies with levels ranging from 69 to 1553pM. Only one had LEMS on clinical grounds, confirmed by electrophysiological tests. The other 4 patients did not have clinical evidence of LEMS. There was no association between anti-VGCC titre and survival (p=0.08, hazards ratio 0.999). Conclusions: This prospective study indicated that increased titre of anti-VGCC antibodies is common in SCLC. The presence of antibody positivity may help to identify patients who are at risk of developing the debilitating symptoms of LEMS. No significant financial relationships to disclose.
Fashionable to criticise the drug industry?
Authors: S. Whitehead
Journal: BMJ (2012)

McCartney makes several disparate claims about the drug industry.1 She states that the financial relations between charities and the industry are “unclear” and implies that this unduly influences the daily activities of the third sector. In reality, the Association of the British Pharmaceutical Industry’s code of practice requires that companies publicly declare their financial transactions with charities and the nature of …
HLA-C genes and susceptibility to type 1 autoimmune hepatitis
Authors: M D Strettell, L J Thomson, P T Donaldson, M Bunce, C M O'Neill, R Williams
Journal: Hepatology (1997)

Susceptibility to autoimmune hepatitis (AIH) is associated with the HLA A1-B8-DR3 haplotype, DR4 antigen, and, more specifically, the HLA DRB3*0101, DRB1*0301, and DRB1*0401 alleles. Few investigators, however, have examined the HLA C locus in AIH, which warrants detailed study in view of its recently described roles in immunoregulation. Eighty-seven adult, white patients with well-characterized type 1 AIH and 100 controls were studied. HLA C and HLA DRB1 alleles were assigned by polymerase chain reaction (PCR)-based genotyping. HLA A and B antigens were determined by standard microlymphocytotoxicity assay. Extended haplotypes were constructed according to known patterns of linkage disequilibrium. Only one HLA C locus allele, Cw*0701, which was present in 54% of patients versus 34% of controls (P = .006; relative risk [RR] = 1.54) was associated with AIH. The overall increase in the frequency of the Cw*07 gene (70.1% of patients vs. 54% of controls; P = .024; RR = 1.3) was due entirely to inheritance of the Cw*0701 allele rather than the other Cw*07 alleles, Cw*0702, *0703, and *0704. The RR for Cw*0701 (RR = 1.54) is greater than that for HLA A1 (RR = 1.33) and DRB1*0301 (RR = 1.49), but less than that for HLA-B8 (RR = 1.75). The present findings suggest that the gene or genes conferring susceptibility to AIH lie in the region centromeric to the HLA A locus between HLA C and DRB1. Although linkage disequilibrium with both B8 and DRB1*0301 may account for our finding of an increased frequency of Cw*0701, it is also possible that this allele contributes to disease susceptibility, perhaps by interaction with natural killer cells or cytotoxic T lymphocytes.
Molecular and Evolutionary Analysis of Two Divergent Subfamilies of a Novel Miniature Inverted Repeat Transposable Element in the Yellow Fever Mosquito, Aedes aegypti
Authors: Zhijian Tu
Journal: Molecular Biology and Evolution (2000)

A novel family of miniature inverted repeat transposable elements (MITEs) named Pony was discovered in the yellow fever mosquito, Aedes aegypti. It has all the characteristics of MITEs, including terminal inverted repeats, no coding potential, A+T richness, small size, and the potential to form stable secondary structures. Past mobility of Pony was indicated by the identification of two Pony insertions which resulted in the duplication of the TA dinucleotide targets. Two highly divergent subfamilies, A and B, were identified in A. aegypti based on sequence comparison and phylogenetic analysis of 38 elements. These subfamilies showed less than 62% sequence similarity. However, within each subfamily, most elements were highly conserved, and multiple subgroups could be identified, indicating recent amplifications from different source genes. Different scenarios are presented to explain the evolutionary history of these subfamilies. Both subfamilies share conserved terminal inverted repeats similar to those of the Tc2 DNA transposons in Caenorhabditis elegans, indicating that Pony may have been borrowing the transposition machinery from a Tc2-like transposon in mosquitoes. In addition to the terminal inverted repeats, full-length and partial subterminal repeats of a sequence motif TTGATTCAWATTCCGRACA represent the majority of the conservation between the two subfamilies, indicating that they may be important structural and/or functional components of the Pony elements. In contrast to known autonomous DNA transposons, both subfamilies of Pony are highly reiterated in the A. aegypti genome (8,400 and 9,900 copies, respectively). Together, they constitute approximately 1.1% of the entire genome. Pony elements were frequently found near other transposable elements or in the noncoding regions of genes. The relative abundance of MITEs varies in eukaryotic genomes, which may have in part contributed to the different organizations of the genomes and reflect different types of interactions between the hosts and these widespread transposable elements.
Enhanced natural-killer cell and erythropoietic activities in VEGF-A–overexpressing mice delay F-MuLV–induced erythroleukemia
Authors: David Cervi, Yuval Shaked, Mehran Haeri, Tatiana Usenko, Christina R. Lee, Jody J. Haigh, Andras Nagy, Robert S. Kerbel, Eitan Yefenof, Yaacov Ben-David
Journal: Blood (2006)
Childhood leukaemia in England and Wales has seen a real increase since 1970s
Authors: Roger Dobson
Journal: BMJ (2007)

The incidence of leukaemia in children in England and Wales rose by 20% between the early 1970s and the end of the century, new research shows, an increase of 4% every five years.

The incidence of childhood leukaemia rose from 38.3 per million person years in 1971-5 to 46.1 in 1996-2000, found the study, in the British Journal of Cancer (doi: 10.1038/sj.bjc.6603946). The results also show that throughout the 20th century the incidence of the disease and mortality were at least 15% higher in boys than in …