tbuckley/cabot-search huggingface dataset:
The Need for an Individual Approach to Lung Cancer Treatment
Authors: Hisayuki Shigematsu, Shinichi Toyooka, Makoto Suzuki
Journal: PLoS Medicine (2006)

Heidi Greulich and colleagues [ 1] have demonstrated the significance of insertion mutations in the epidermal growth factor receptor (EGFR) (exon 20) for tumorigenesis and responsiveness to tyrosine kinase inhibitors (TKIs) in lung cancers. They reported that different types of EGFR mutations conveyed different sensitivity to TKIs. Although several previous studies have suggested that tumors harboring mutations in the EGFR kinase domain were sensitive to TKIs such as gefitinib or erlotinib [ 2, 3], others had reported an association between the T790M mutation in exon 20 and the resistance to TKIs [ 4, 5]. As we learn more about the relationship between EGFR status (including gene copy number, mutation status, and mutation type) and drug sensitivity, decisions about treatment with TKIs for patients with non-small-cell lung cancer (NSCLC) become more complex. 

Previously, we reported HER2 mutational status, as well as EGFR and KRAS, in a large number of NSCLCs [ 6]. We found that 22% of tumors had EGFR kinase domain mutations (149 out of 671). Of these 149, 15 of them were insertion mutations in exon 20. The more common types of mutations—i.e., deletion in exon 19 (68 out of 149) and L858R in exon 21 (61 out of 149)—were more frequent in women and in “never smokers” (with p values of less than 0.001), whereas the exon 20 insertion mutations showed no bias for sex (seven in males versus eight in females) or smoking status (seven in smokers versus eight in never smokers). We have no data regarding TKI sensitivity for the 15 patients with insertion mutations to date, but based on the results from others and our own in vitro data, they may not benefit from the conventional TKIs, despite the fact that their tumors have EGFR kinase domain mutations. 

To maximize benefit to patients, we should determine the exact type of mutation for an individual tumor and determine whether it conveys sensitivity or resistance prior to TKI therapy. The development and clinical application of novel agents overcoming resistance should yield a more effective targeted therapy for tumors with all types of EGFR mutations.
Cyclic neutropenia as a premalignant manifestation of acute lymphoblastic leukemia
Authors: Daniel B. Lensink, Ann Barton, Frederick R. Appelbaum, William P. Hammond
Journal: American Journal of Hematology (1986)

Abstract A 20‐year‐old female from the Philippines developed anemia and granulocytopenia. With androgen therapy, her anemia improved but she continued to show a pattern of fluctuating neutropenia consistent with human cyclic neutropenia: Blood neutrophil oscillation was regular with a periodicity of 21 days. She developed recurrent pharyngitis and apthous stomatitis but there was no cycling of other blood elements. Bone marrow aspiration and biopsy showed normal developing myeloid cells, a clonal chromosomal abnormality, and myelofibrosis. During the fourth documented cycle, blasts appeared and complete lymphoblastic transformation ensued. Blast cells were CALLA positive, Ia positive, and contained intranuclear TdT; they were negative for E, EAC, and EA rosettes. She was treated for non‐T, non‐B CALLA‐positive ALL and within 6 weeks was in a remission without evidence of cycling neutrophil counts. This young woman's case suggests that cyclic neutropenia may represent a previously unrecognized premalignant state associated with acute lymphoblastic leukemia.
Subacute cutaneous lupus erythematosus induced by the new multikinase inhibitor pazopanib
Authors: B. Casado-Verrier, S. Pérez-Santos, C. Delgado-Mucientes, M. Beato-Merino
Journal: British Journal of Dermatology (2014)

Journal Article Subacute cutaneous lupus erythematosus induced by the new multikinase inhibitor pazopanib Get access B. Casado‐Verrier, B. Casado‐Verrier Department of Dermatology Hospital General de Segovia Segovia Spain Search for other works by this author on: Oxford Academic Google Scholar S. Pérez‐Santos, S. Pérez‐Santos Department of Dermatology Hospital General de Segovia Segovia Spain Search for other works by this author on: Oxford Academic Google Scholar C. Delgado‐Mucientes, C. Delgado‐Mucientes Department of Dermatology Hospital General de Segovia Segovia Spain Search for other works by this author on: Oxford Academic Google Scholar M. Beato‐Merino M. Beato‐Merino Department of Pathology Hospital La Paz Paseo de la Castellana 261 Madrid 28034 Spain Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 171, Issue 6, 1 December 2014, Pages 1559–1561, https://doi.org/10.1111/bjd.13175 Published: 01 December 2014
Patterns of HDV reinfection in liver transplantation
Authors: A. Ottobrelli, M. Salizzoni, C. Cornù, M.E. Lamy, J. Rayer, G.B. Otte, M. Grendele, D. Galmarini, G. Marinucci, A. Smedile, S. Recehia, M. Rizzetto
Journal: Journal of Hepatology (1989)
Croup-Associated Virus Infection in Adults
Authors: John E. Craighead, Alexis Shelokov, Pauline H. Peralta, John E. Vogel
Journal: New England Journal of Medicine (1961)

IN 1955 Chanock1 and Beale et al.2 independently recovered a new myxovirus from infants with acute laryngotracheobronchitis. Chanock proposed the name "croup associated" for this virus. 1 ¶ The clinical importance of this virus has not been fully established since in recent years it has been isolated only infrequently and sporadically from patients with respiratory-tract disease.4 5 6 Existing information indicates, however, that infections occur in children with a variety of respiratory syndromes, the most severe of which is croup.6 7 8 This report records the isolation of croup-associated virus on the Isthmus of Panama from 2 adults with febrile systemic illnesses. Evidence that infection occurred . . .
How to build a better manager Consider audit
Authors: C Baldwin, W E I Forsythe-Yorke
Journal: BMJ (1994)

EDITOR, - There is a delicious irony about the letter from Anthony Walker, a management consultant, implying that loss of clinical freedom will be the deserved consequence of the arrogance and failings of a minority of physicians.1 I suggest that another shibboleth - “management prerogative” - is a more appropriate target for criticism in the current climate. Has Walker audited the results of his profession's activities on the welfare of people …
Double-Blind Studies of Acupuncture
Authors: Lester C. Mark
Journal: JAMA (1973)

To the Editor.—  Chein and Shapiro (224:1533, 1973) accept with reservations my objection (223:922, 1973) that double-blind studies of acupuncture are not feasible. (The reason is that correct placement of acupuncture needles requires cooperation of the patient in reporting paresthesias, a sensation of soreness, or mild discomfort, and, hence, renders useless efforts to deceive him with placebo needles deliberately inserted elsewhere.) They agree that this may be so with manually manipulated needles but claim that electric acupuncture stimulators can mimic the symptoms described, thereby validating the double-blind approach with placebo stimulation at sites other than acupuncture points.  In support of their claim, Chein and Shapiro offer two references, both eye-witness reports by physician visitors to the People's Republic of China. However, the first citation by Dimond (218:1558, 1971) states We asked how the anesthetist knew if he had placed the needles at the right point and depth. He said [and this
THE SWINE LUNGWORM AS A RESERVOIR AND INTERMEDIATE HOST FOR SWINE INFLUENZA VIRUS
Authors: Richard E. Shope
Journal: The Journal of Experimental Medicine (1943)

1. The presence of masked swine influenza virus has been demonstrated in lungworm larvae from earthworms dug on Midwestern farms. 2. Swine influenza virus infections were provoked in 2 of 3 swine obtained from an Iowa farm during an interepizootic period. 3. The evidence presented has been interpreted as indicating that the swine lungworm is the reservoir and intermediate host for swine influenza virus in the field. 4. A concept of the epidemiology of swine influenza in which the causative virus is represented as being maintained and disseminated in a masked form by its lungworm intermediate host has been presented.
Tryptase in nasal fluid is a useful marker of allergic rhinitis
Authors: G. Rasp, K. Hochstrasser
Journal: Allergy (1993)

Tryptase is a mast cell‐specific marker of degranulation. To investigate the possible diagnostic value of tryptase in allergic rhinitis, we measured the levels in both serum and native nasal fluid with a sandwich RIA‐assay (Pharmacia). Twenty‐three allergic patients and five patients with chronic ethmoidal sinusitis were included. Eighteen of the 23 allergic patients were tested within the pollen season or had perennial rhinitis; the remainder were tested at least 1 month out of the pollen season. None of the patients had detectable serum tryptase (&gt;0.1 ng/ml). Also patients with chronic ethmoidal sinusitis showed no tryptase in nasal fluid. One of seven allergic patients tested out of season had slightly increased nasal tryptase of 1.8 ng/ml. In patients with active nasal allergy, the tryptase in nasal fluid ranged from 6.4 ng/ml to 640 ng/ml with a mean of 101 ng/ml and SD 173. These results show a clear distinction between active and non‐active nasal allergy and other non‐mast‐cell‐related nasal disease. Further, nasal tryptase release by natural allergen exposure is even higher than that observed in allergen challenge tests.
Local IgA subclass alterations in ulcerative colitis and Crohn's disease of the colon.
Authors: K Kett, P Brandtzaeg
Journal: Gut (1987)

The subclass distribution of IgA producing cells was determined by paired immunofluorescence staining in colonic specimens from 10 patients with ulcerative colitis and eight with Crohn9s disease. Compared with normal colonic mucosa, the percentage of IgA1 immunocytes showed a striking increase in both disorders. The proportion of mucosal IgA1 cells was significantly higher (p less than 0.05) in ulcerative colitis (median, 71.2%) than in Crohn colitis (median, 56.9%). Within each category of specimens no significant differences were noted between luminal and basal mucosal zones. The submucosal proportion of IgA1 cells was, however, significantly higher than the mucosal one in both ulcerative colitis (median, 89.1%; p less than 0.002) and Crohn colitis (median, 91.8%; p less than 0.005). The mucosal shift towards IgA1 production paralleled the magnitude of the submucosal IgA1 cell proportion in individual tissue samples. Taken together with the previously reported dramatic increase of local IgG production (particularly observed in the submucosa and basal parts of the mucosa), our findings indicated that there is an influx and/or proliferation of B cells representing systemic secondary immunity in the lesions of both diseases.
Elevated Cutaneous Smad Activation Associates with Enhanced Skin Tumor Susceptibility in Organ Transplant Recipients
Authors: Kelly A. Harradine, Katie Ridd, Elise F. Saunier, Frederic F. Clermont, Jesus Perez-Losada, Dan H. Moore, Ervin H. Epstein, Boris C. Bastian, Rosemary J. Akhurst
Journal: Clinical Cancer Research (2009)

Abstract Purpose: Nonmelanoma skin cancer incidence is enhanced &amp;gt;50-fold in patients taking antirejection drugs (ARD) following organ transplantation. Preclinical studies suggest that ARD treatment increases transforming growth factor-β1 (TGF-β1) levels, which contribute to enhanced tumor susceptibility independent of the immunosuppressive effects of ARDs. This study investigates whether TGF-β signaling is elevated in transplant patients. Experimental Design: Immunohistochemical tissue microarray analysis was used to determine the levels of TGF-β1, TGF-β2, TGF-β3, TβRII, and activated P-Smad2/3 and P-Smad1/5/8, which are phosphorylated directly by distinct TGF-β/BMP receptor complexes. We analyzed &amp;gt;200 cutaneous lesions and adjacent nonlesional skin samples from 87 organ transplant recipients, and 184 cutaneous lesions and adjacent skin samples from 184 individuals who had never received ARDs. Results: We found significantly higher levels of P-Smad2 in both nonlesional and lesional tissue from transplant recipients compared with those not exposed to ARDs (P ≤ 0.001). In contrast, P-Smad1/5/8, a marker of activation of the bone morphogenetic protein signaling pathway, was generally not expressed at higher levels in patients taking ARDs, including analysis of nonlesional skin, actinic keratoses, carcinoma in situ, or squamous cell carcinoma but was differentially expressed between keratoacanthoma from transplant recipients compared with those from non–transplant recipients (P ≤ 0.005). Conclusions: Observation of elevated P-Smad2 levels in transplant recipients is consistent with the notion that elevated TGF-β signaling may contribute to malignancy in organ transplant recipients. Disparate P-Smad1/5/8 expression levels between keratoacanthoma from the two patient groups might reflect the distinct BMP-responsive cell of origin for this hair follicle–derived lesion. (Clin Cancer Res 2009;15(16):5101–7)
Postgraduate Medical Education in the Hospital
Authors: Eugene A. Stead
Journal: New England Journal of Medicine (1963)

INTERNSHIP and residency years are the golden years in the life of a physician who practices medicine. They are the years when he first becomes a professional worker, the years when patients are first willing to entrust their bodies and minds to his care and the years of close association with bright young colleagues and mature doctors. These are important, formative years, and they shape the future conduct of the young physician more than any other experience. Medical school is important in determining where the doctor takes his internship and residency. Faculty members, fully conscious of the importance of intern . . .
c-Jun N-Terminal Kinase Activation Mediates Downregulation of Connexin43 in Cardiomyocytes
Authors: Brian G. Petrich, Xiaohua Gong, Deborah L. Lerner, Xin Wang, Joan Heller Brown, Jeffrey E. Saffitz, Yibin Wang
Journal: Circulation Research (2002)

Loss of gap junctions and impaired intercellular communication are characteristic features of pathological remodeling in heart failure as a result of stress or injury, yet the underlying regulatory mechanism has not been identified. Here, we report that in cultured myocytes, rapid loss of the gap junction protein connexin43 (Cx43) occurs in conjunction with the activation of c-Jun N-terminal kinase (JNK), a stress-activated protein kinase, on stress stimulation. To investigate the specific role of JNK activation in the regulation of connexin in cardiomyocytes, an activated mutant of mitogen-activated protein kinase kinase 7 (mutant D), a JNK-specific upstream activator, was expressed in myocytes by adenovirus-mediated gene transfer. JNK activation in infected cardiomyocytes resulted in significant reduction of Cx43 expression at both mRNA and protein levels and impaired cell-cell communication. To evaluate the role of JNK in the regulation of Cx43 expression and gap junction structure in vivo, a Cre-LoxP–mediated gene-switch system was used to establish a transgenic animal model with targeted activation of JNK in ventricular myocardium. The transgenic hearts exhibited significant downregulation of Cx43 expression and loss of gap junctions in myocardium that may contribute to the cardiac dysfunction and premature death phenotype. Our report represents the first evidence, both in vitro and in vivo, implicating JNK as an important mediator of stress-induced Cx43 downregulation and impaired intercellular communication in the failing heart.
Implants Eyed for CMV Retinitis
Authors: Paul Cotton
Journal: JAMA (1993)

TEN YEARS ago, patients with the acquired immunodeficiency syndrome (AIDS) who developed cytomegalovirus (CMV) retinitis lived, on average, 2 months. Now that such patients survive more than 1 year on average, and some up to 3 years, the need for better therapy is becoming urgent. Implants that release drugs directly in the eye may help, says Jay S. Duker, MD, associate professor of ophthalmology at Tufts University Medical School, Boston, Mass. Phase III trials are now getting under way. The idea, he says, is to get higher levels of drug directly into the eye without the side effects of systemic absorption. Cytomegalovirus kills retinal cells that do not regenerate, leaving scotomata (blind spots), and eventually causing complete blindness by destroying the entire retina, causing retinal detachment or optic nerve damage. <h3>Number One Eye Problem</h3> Cytomegalovirus retinitis is the number one eye problem in AIDS. About 25% of patients with AIDS
The microanatomy of the alveolar duct system
Authors: W. F. Whimster
Journal: Thorax (1970)

Observations made on wet and dry slices of inflated human lungs taken at necropsy have been used to give a more complete account of the alveolar duct system, the basic respiratory structure. This includes consideration of the central spiral alveolar duct fibre, which is thought to consist of elastic and collagen, the spiral arrangement of alveoli and the special nature of the terminal alveolus, the interdigitation of alveoli from adjacent alveolar ducts and the arrangement of pulmonary arterioles. This suggests that the alveolar duct system is specifically designed so that changes in volume are not accompanied by changes in alveolar surface area.
No more textbooks on primary care?
Authors: D Brooks
Journal: BMJ (1979)

patients was the thrombus confined to the calf.This is at variance with a large study,' in which thrombus was confined to the calf in 4900 of 493 legs containing thrombus.To say that "there was a general reluctance on the part of individual doctors to perform phlebography on patients with negative 99mTc-red-cell scans" merely emphasises the bias of investigation in favour of their own technique.Secondly, this technique apparently lacks the facility of radionuclide venography, its nearest rival in providing a simultaneous lung scan.Finally, the acid test of all new diagnostic procedures is whether they may be applied in the district general hospital as readily as the teaching hospital.Conventional phlebography fulfils this criterion.We remain unconvinced that this new technique can alter the situation in any way, being more demanding in time, expertise, skilled man- power, and expensive equipment.
Treatment of Q fever.
Authors: W P Turck
Journal: BMJ (1978)

orthopaedic patients receiving antibiotics.' 2 The doubling of incidence of pseudomembranous colitis in Birmingham between 1976 and 1977 was probably due to increased diag- nostic vigilance.'The word "invariable" has no place in nosographic data processing and accordingly your statement that "diarihoea is invariable" requires scrutiny.While it is true that the colon is predominantly involved, the ileum can also, to a varying degree, be the seat of the disease.When the colon is completely spared -as in a recent case confirmed by necropsydiarrhoea can be absent.Clinically this case was dominated by abdominal pain, fever, and leucocytosis.A somewhat similar case was also reported recently.4In such cases sigmoido- scopic and proctoscopic examinations-usually useful methods for establishing the diagnosis- cannot be relied upon.Bearing in mind the topography of the pathological changes, I believe that diagnostic alertness might be enhanced by reverting to the original terminology-namely, pseudomembranous enterocolitis.
Transient gene transfer and expression of Smad7 prevents bleomycin-induced lung fibrosis in mice
Authors: Atsuhito Nakao, Makiko Fujii, Ryutaro Matsumura, Kotaro Kumano, Yasushi Saito, Kohei Miyazono, Itsuo Iwamoto
Journal: Journal of Clinical Investigation (1999)

TGF-β plays an important role in lung fibrosis, which is a major cause of suffering and death seen in pulmonary disease. Smad7 has been recently identified as an antagonist of TGF-β signaling. To investigate whether this novel molecule can be exploited for therapy of lung fibrosis, we determined the effect of exogenous Smad7, introduced by a recombinant human type 5 adenovirus vector, on bleomycin-induced lung fibrosis in mice. C57BL/6 mice with bleomycin-induced lungs received an intratracheal injection of a recombinant adenovirus carrying mice Smad7 cDNA. These mice demonstrated suppression of type I precollagen mRNA, reduced hydroxyproline content, and no morphological fibrotic responses in the lungs when compared with mice administered adenovirus carrying Smad6 cDNA. In addition, we found that expression of Smad7 transgene blocked Smad2 phosphorylation induced by bleomycin in mouse lungs. These data indicated that gene transfer of Smad7 (but not Smad6) prevented bleomycin-induced lung fibrosis, suggesting that Smad7 may have applicability in the treatment of pulmonary fibrosis.
Practice and outcome variations in percutaneous coronary intervention: an analysis of a large multicenter PCI database
Authors: Mauro Moscucci, Dean E. Smith, David Share, Michael O'Donnell, Anthony C. DeFranco, William L. Meengs, Ann Maxwell-Eward, John G. McGinnity, Kirit Patel, Vivian L. Clark, Eva Kline-Rogers, Diane Bondie, Kim A. Eagle
Journal: Journal of the American College of Cardiology (2002)
Effect of spirometry on COPD management in primary care: where are the studies that we really need?
Authors: P. J. P. Poels, D. P. A. Schellekens, T. R. Schermer
Journal: European Respiratory Journal (2007)

To the Editors: 

In the November 2006 issue of the European Respiratory Journal , Walker et al. 1 reported on the effects of the use of spirometry to diagnose chronic obstructive pulmonary disease (COPD) in primary care and the resulting benefits for patient management. In patients referred to an open-access spirometry service by their general practitioner, the diagnosis and current management of the patients was assessed before and after spirometry testing. Walker et al. 1 observed a change of diagnosis after spirometry in: 71% of patients who had no respiratory diagnosis at the time of the referral; 48% of patients who had previously been diagnosed with asthma; and 23% of patients with a COPD diagnosis. Drug prescription changed in 49% of the COPD patients, with a …