tbuckley/cabot-search huggingface dataset:
Decreasing Risk of Leukemia with Prolonged Follow-up after Chemotherapy and Radiotherapy for Hodgkin's Disease
Authors: Douglas W. Blayney, Dan L. Longo, Robert C. Young, Mark H. Greene, Susan M. Hubbard, Marcia G. Postal, Patricia L. Duffey, Vincent T. DeVita
Journal: New England Journal of Medicine (1987)

Acute nonlymphocytic leukemia is a recognized complication of combined chemotherapy and radiation treatment of patients with Hodgkin's disease. Previous studies have suggested that the risk of leukemia in these patients increases with time after treatment. We analyzed the occurrence of second neoplasms among 192 patients with Hodgkin's disease who were followed for a median of over 15 years. We originally planned to identify prospectively the morphologic changes in bone marrow that precede the development of acute leukemia. All 63 patients consenting to bone marrow aspiration had normal marrow morphology, and no case of acute leukemia occurred more than 11 years after treatment. Actuarial analysis revealed that the peak onset of leukemia-related complications was between three and nine years after first treatment. We conclude that there appears to be a period of increased risk in patients treated with chemotherapy and radiation, after which the risk of secondary leukemia decreases. Patients surviving for more than 11 years after treatment appear to be at no increased risk of acute leukemia.
Effects of Oral and Intramuscular Administration of Reserpine in Thyrotoxicosis
Authors: John J. Canary, Marcus Schaaf, Benedict J. Duffy, Laurence H. Kyle
Journal: New England Journal of Medicine (1957)

THE beneficial effects of reserpine in the control of agitated, hyperactive patients1 2 3 4 5 6 7 8 suggested exploration of its usefulness in controlling the symptoms and signs of hyperthyroidism. Reserpine has been noted to cause ptosis, bradycardia, increase in body weight and reduction of basal metabolic rate in euthyroidal experimental subjects.9 10 11 12 Furthermore, hyperthyroidism has been considered a disease of diencephalic origin by many investigators, and reserpine has its tranquilizing effects in this area of the central nervous system.6 , 9 , 11 , 13 Method and MaterialTwenty-one studies in 20 patients were conducted with the use of oral or intramuscular administration of reserpine.∥ Before treatment all patients demonstrated typical . . .
Case 46-1993
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, Robert G. Feldman, Ann C. McKee
Journal: New England Journal of Medicine (1993)

Presentation of CaseA 75-year-old right-handed man was referred to the Movement Disorders Unit of this hospital because of right-sided rigidity, dysphagia, dysarthria, and an impaired gait.The patient's health had been stable until two years earlier, when his family began to observe episodes of “unresponsiveness.” A magnetic resonance imaging (MRI) scan of the brain obtained elsewhere (Figure 1, 2, and 3) showed atrophy and hypointense areas in the basal ganglia on T2-weighted images considered consistent with calcifications or iron deposits. No additional episodes occurred after phenytoin treatment. One year later the patient began to lose his balance . . .
Cost-effectiveness of Store-and-Forward Teledermatology
Authors: Centaine Snoswell, Anna Finnane, Monika Janda, H. Peter Soyer, Jennifer A. Whitty
Journal: JAMA Dermatology (2016)

<h3>Importance</h3> Teledermatology is a topical clinical approach being tested in Australia and elsewhere. With most dermatologists residing in metropolitan areas, teledermatology provides an apparent low-cost and convenient means of access for individuals living outside these areas. It is important that any proposed new addition to a health care system is assessed on the grounds of economic cost and effectiveness. <h3>Objective</h3> To summarize and evaluate the current economic evidence comparing store-and-forward teledermatology (S&amp;FTD) with conventional face-to-face care. <h3>Evidence Review</h3> Search terms with appropriate amendments were used to identify S&amp;FTD articles that included economic analysis. Six databases were searched, and title, abstract and full-text reviews were conducted by 2 researchers. References of all unique returned articles were searched by hand. The Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist was used to evaluate quality of the included articles. <h3>Findings</h3> Eleven articles were selected for inclusion, including 1 cost analysis, 4 cost-minimization analyses, 4 cost-effectiveness analyses, and 2 cost-utility analyses. CHEERS scores ranged from 7 to 21 out of a possible 24 points, with a median score of 17. <h3>Conclusions and Relevance</h3> Current evidence is sparse but suggests that S&amp;FTD can be cost-effective. It appears to be cost-effective when used as a triage mechanism to reduce face-to-face appointment requirements. The cost-effectiveness of S&amp;FTD increases when patients are required to travel farther distances to access dermatology services. Further economic research is required for the emerging S&amp;FTD, which uses dermoscopes in combination with smartphone applications, as well as regarding the possibility and consequences of patients self-capturing and transmitting images.
Improved activation of specific T-lymphocyte responses to the human telomerase reverse transcriptase (hTERT) in patients with advanced non-small cell lung cancer (NSCLC).
Authors: B. Gahn, K. Woester, D. Wellnitz, M. Staudinger, S. Boettcher, M. Gramatzki, M. Kneba
Journal: Journal of Clinical Oncology (2010)

e13114 Background: hTERT is expressed in 93% to 100% of NSCLC, making the enzyme a target for immunotherapy. Present vaccination studies show a survival advantage in patients with a hTERT-specific immune response (Kosmatopoulos et al., 2007), but the number of immune responders is still limited. In the current study we tried to improve the activation of hTERT- specific T-cell responses in NSCLC-patients of different HLA-types who simultaneously received platinum-based standard first-line chemotherapy. Methods: After depletion of regulatory T-cells the lymphocytes were stimulated in vitro with mature peptide loaded dendritic cells (DC). The DC were either matured with the standard cytokine cocktail consisting of GM-CSF, IL-4, IL-6, IL-1β, TNF-α, and PGE2 or with a TLR7/8- in combination with a CD40-ligand. The activation of hTERT-specific T-cells was measured by flow cytometric analysis of intracellular IFN-γ. Results: In 2 patients the hTERT-specific T-cell response was more intensively activated by cytokine matured DC than by TLR7/8- and CD40-L matured DC. Using this standard approach 0.1-0.6% IFNg+ CD8+ T-cells cells were activated. In contrast in 3 other patients hTERT-specific T cells could be more effectively activated by TLR7/8- and CD40-L matured DC. We could activate between 0.1% and 2.1% IFN+CD8+ T-cells. Similarly in one healthy donor the hTERT-specific T-cell response was more intensively activated by cytokine matured DC showing up to 0.5% IFNg+ CD8+ T- cells. However, in another healthy donor hTERT- specific T-cell responses could be more effectively activated by TLR7/8- and CD40-L with up to 0.7 % IFNg+CD8+ cells. In 2 other patients we could not activate any hTERT-specific IFNg+ T-cell response. Conclusions: These data indicate that by using different DC maturation protocols hTERT-specific T-cells can be activated in the majority of patients. Even concomitant to standard chemotherapy clinical vaccination protocols may be feasible. However, DC maturation protocols may need to be individualized. The very low percentage of hTERT-specific T-cells in some patients implicate the need for even more potent immune adjuvants. No significant financial relationships to disclose.
Case 24-2001
Authors: John F. Beamis, Eugene J. Mark
Journal: New England Journal of Medicine (2001)

Presentation of CaseA 46-year-old woman was admitted to the hospital because of recurrent hemoptysis.Eight months earlier, a cough, nonpleuritic left-sided chest pain, and fatigue had developed, with minor episodes of hemoptysis. A tuberculin skin test was positive, with 20 mm of induration. A computed tomographic (CT) scan of the thorax performed elsewhere was said to show evidence of distal bronchiectasis and mucoid impaction. Sputum examination revealed no acid-fast bacilli. The following month, bronchoscopic examination showed no abnormalities, and culture of bronchoalveolar-lavage fluid yielded a single colony of Aspergillus niger and was negative for acid-fast bacilli. Isoniazid and rifampin . . .
Insect Transfer of Labeled Erythrocytes, With Implications for Circulating Tumor Cells&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Paul A. Woke, Norbert Konwinski
Journal: JNCI Journal of the National Cancer Institute (1972)

This study confirms that a bloodsucking insect, Aedes aegypti, could transfer circulating tumor cells of hamster reticulum cell sarcoma TM from tumor-bearing to tumor-free hamsters. Measurement of blood cell transfer, with chromium-51 as a tracer, a spectrometer system, and a well-type scintillation detector, are described. Radiochromium, identified in recipient hamsters, indicated that the fly, Stomoxys calcitrans, and the mosquito, A. aegypti, had transferred labeled erythrocytes by bite. A quantitative experiment indicated that A. aegypti transferred 0.00021–0.00066 μI of blood to the recipients. These quantities normally contain approximately 1500–5000 red blood cells, 1.5–5.0 normal white blood cells, or, in leukemia, 10–132 tumor cells. Tumor developed from <C10 tumor cells injected by needle. Insect transfer of blood from hamster to hamster implies that tumor cells from TM in blood ingested from the peripheral circulation of a leukemic donor are potentially transferable to a tumor-free recipient. Such an occurrence provides a possibility for tumor to develop.
Case 16-1992
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, J.R. Madsen, A.E. Rosenberg
Journal: New England Journal of Medicine (1992)

Presentation of CaseA 27-year-old woman was admitted to the hospital because of cervical pain that radiated to the left shoulder.The patient was well until six weeks earlier, when she fell while skiing and landed on her back; she experienced no symptoms thereafter except for stiffness of her shoulders on the following day. Five days before entry she was riding in a truck that stopped suddenly, and her occipital region struck the rear window. On the next day she awoke with pain in the neck that radiated to the left shoulder, accompanied by paresthesias in the left hand. Two . . .
Clinicopathologic features of EML4-ALK mutant lung cancer
Authors: A. T. Shaw, D. Costa, M. Mino-Kenudson, S. Digumarthy, B. Y. Yeap, S. Admane, S. Rodig, L. Chirieac, A. J. Iafrate, T. J. Lynch
Journal: Journal of Clinical Oncology (2009)

11021 Background: EML4-ALK is a novel fusion oncogene in non-small cell lung cancer (NSCLC). The fusion results from a small inversion within chromosome 2p, leading to expression of a constitutively activated, chimeric tyrosine kinase. The clinicopathologic features of these patients have not been definitively established. Furthermore, the clinical outcome of these patients is unknown. Here we present the largest series of EML4-ALK mutants to date, and the first analysis of treatment response and survival in metastatic patients with and without EML4-ALK. Methods: Patients with NSCLC were selected for genetic screening based on 2 or more of the following characteristics: female gender, Asian ethnicity, never or light smoking history, and adenocarcinoma histology. The EML4-ALK inversion was identified using FISH and confirmed by IHC for ALK expression. EGFR mutation status was determined by direct sequencing of EGFR exons 18–21. Results: Of 141 patients screened, 18 (13%) were ALK mutant, 31 (22%) were EGFR mutant, and 92 (65%) were wild-type (WT) for both ALK and EGFR. The majority of tumors were adenocarcinomas, with ALK but not EGFR mutant tumors strongly associated with the signet ring cell subtype. Compared to the EGFR mutant and WT cohorts, patients with ALK mutant tumors were significantly younger (median age 52.5 vs 64 yrs, p=0.003), and more likely to be male (61% vs 30%, p=0.015). ALK mutants, like EGFR mutants, were also more likely to be light/never smokers compared with WT patients (100% vs 43%, p&lt;0.001). Among patients with metastatic disease, there was a significant association between EML4-ALK and resistance to EGFR TKIs, with no responses by RECIST in the ALK cohort. ALK mutants and WT patients showed similar response rates to platinum-based chemotherapy (60% vs 65%, p=1), and had similar 1-yr survival rates (81% vs. 66%, p=0.43). Conclusions: EML4-ALK defines a new molecular subset of NSCLC with distinct clinical and pathologic characteristics. The frequency of EML4-ALK is particularly high in light/never smokers without EGFR mutation. These patients do not benefit from EGFR TKIs and should be treated with other standard agents or ALK targeted therapies. [Table: see text]
First two autochthonous dengue virus infections in metropolitan France, September 2010
Authors: G La Ruche, Y Souarès, A Armengaud, F Peloux-Petiot, P Delaunay, P Desprès, A Lenglet, F Jourdain, I Leparc-Goffart, F Charlet, L Ollier, K Mantey, T Mollet, J P Fournier, R Torrents, K Leitmeyer, P Hilairet, H Zeller, W Van Bortel, D Dejour-Salamanca, M Grandadam, M Gastellu-Etchegorry
Journal: Eurosurveillance (2010)

In September 2010, two cases of autochthonous dengue fever were diagnosed in metropolitan France for the first time. The cases occurring in Nice, southeast France, where Aedes albopictus is established, are evidence of dengue virus circulation in this area. This local transmission of dengue calls for further enhanced surveillance, active case finding and vector control measures to reduce the spread of the virus and the risk of an epidemic.
A Comparison of Colonoscopy and Double-Contrast Barium Enema for Surveillance after Polypectomy
Authors: Sidney J. Winawer, Edward T. Stewart, Ann G. Zauber, John H. Bond, Howard Ansel, Jerome D. Waye, Deborah Hall, J. Andrew Hamlin, Melvin Schapiro, Michael J. O'Brien, Stephen S. Sternberg, Walter J. Hogan, Mansho Khilnani, Frederick W. Ackroyd, Joel F. Panish, Larry Kussin, Martin Edelman, Leonard S. Gottlieb
Journal: New England Journal of Medicine (2000)

After patients have undergone colonoscopic polypectomy, it is uncertain whether colonoscopic examination or a barium enema is the better method of surveillance.
PTPS-07COMPETING MOLECULAR GENETIC FORCES: TRISOMY 21(DOWN SYNDROME, DS) AND PTCH1 MUTATION (GORLIN SYNDROME) IN A 21 MONTH-OLD WITH SHH DESMOPLASTIC/NODULAR MEDULLOBLASTOMA
Authors: Ross Mangum, Elizabeth Varga, Suzanne Scott, Maria Goldman, Diana Osorio, Christopher Pierson, Jeffrey Leonard, Daniel Boue, Jonathan Finlay
Journal: Neuro-Oncology (2015)

BACKGROUND: Individuals with Trisomy 21 have a striking cancer distribution, with a 10- to 20- fold increased risk of acute leukemia compared to a markedly decreased incidence of solid tumors. Medulloblastoma, the most common malignant brain tumor of childhood, is particularly rare in the DS population, with only one published case. As demonstrated in a mouse model of DS, the supernumerary chromosome 21 is associated with cerebellar hypoplasia and a decreased number of external granule cell layer progenitor cells (EGLs). Treatment of these mice with sonic hedgehog (Shh) signaling pathway agonists promotes normalization of EGLs and improved cognitive functioning. PATIENT: We describe a 21 month-old male with DS with desmoplastic/nodular medulloblastoma (DNMB) - a tumor derived from Shh dysregulation and over-activation of EGLs. Immunohistochemistry revealed patchy cytoplasmic GAB-1 staining and patchy strong YAP-1 nuclear and cytoplasmic staining, further placing this DNMB into the new consensus molecular classification Shh subgroup. Additional testing revealed a de novo heterozygous germ line mutation in the PTCH1 gene encoding a tumor suppressor protein in the Shh pathway; both parents tested negative for this mutation. CONCLUSIONS: The reduced presence of EGLs in DS patients offers a plausible explanation for the disparity of medulloblastoma in this population. Conversely, patients with PTCH1 germ line mutations experience Shh pathway overstimulation resulting in Gorlin (Nevoid Basal Cell Carcinoma) Syndrome and an increased incidence of malignant transformation of EGLs leading to medulloblastoma formation. This represents the first documented report of an individual with DS (developmental failure of EGLs, decreased incidence of medulloblastoma) simultaneously carrying PTCH1 germ line mutation (overstimulated EGLs, increased incidence of medulloblastoma). Thus, we observe a highly unusual circumstance in which the PTCH1 mutation appears to ‘trump’ the effects of trisomy 21 in causation of Shh-activated medulloblastoma. Additional genomic studies are ongoing and will be presented.
Abstract P169: Long-term Yogurt Intake is Associated with a Lower Risk of High Blood Pressure in Middle-aged Nurses and Health Professionals
Authors: Justin R Buendia, Frank B Hu, Martha R Singer, Howard J Cabral, Lynn L Moore
Journal: Circulation (2016)

While dairy products have been shown to reduce the risk for high blood pressure (HBP) in at-risk adults, few long-term studies have examined independent effects of yogurt consumption, a dietary component that may have particularly beneficial effects on blood pressure. We used repeated measures of diet and lifestyle collected over 2-3 decades among participants without prevalent HBP in the two Nurses’ Health Study cohorts (NHS and NHS II) and the Health Professionals Follow-up Study (HPFS) to examine this question. After 18 to 30 years of follow-up, we documented 74,609 new cases of HBP in the three cohorts. After adjusting for age, race, family history of HBP, physical activity, energy, and intakes of total protein, fruits and vegetables, milk, and cheese, women who consumed 5 or more servings of yogurt per week (compared with those consuming 0-&lt;1.0 serving per month) had statistically significant 23% (95% CI: 0.70-0.84) and 17% (95% CI: 0.77-0.90) reductions in risk of HBP in the NHS and NHS II respectively, while men in the HPFS cohort had essentially no reduced risk. To determine whether the effect of yogurt consumption might be explained or modified by other healthy dietary factors, the independent and combined effects of yogurt and a DASH diet score (excluding yogurt from the calculation of that score) were examined. Those in the highest tertile of the DASH score who did not consume yogurt had 15%, 29%, and 15% reductions in HBP risk, respectively, in the two NHS and the HPFS cohorts. The beneficial effects of yogurt intake were modified by a higher DASH score. In these analyses, the beneficial effects of 5 or more servings of yogurt per day on HBP risk were strongest among those in the highest tertile of DASH scores (NHS: HR=0.66; 95% CI: 0.59-0.75; NHS II: HR=0.68; 95%CI: 0.62-0.75; HPFS: HR=0.75; 95% CI: 0.64-0.88). Results were partially attenuated when controlling for BMI. These analyses from three large, longitudinal cohorts suggest that regular yogurt consumption, especially as a part of an otherwise healthy diet, is associated with a reduced risk of developing HBP during the middle adult years. These beneficial effects may be partially explained by intermediate effects on BMI.
Prenatal Diagnosis of Duchenne's Muscular Dystrophy
Authors: Maurice J. Mahoney, Florence P. Haseltine, John C. Hobbins, Betty Q. Banker, C. Thomas Caskey, Mitchell S. Golbus
Journal: New England Journal of Medicine (1977)

Two pregnancies at risk for X-linked recessive Duchenne's muscular dystrophy were studied at 18 and 20 weeks. Fetal blood was obtained by placental aspiration for measurement of plasma creatine phosphokinase activity. Activity in the first fetus was 96 IU per liter, as compared to a control range of 0 to 150 IU per liter in 16 pregnancies not at risk for the disorder. The pregnancy continued, and the infant was normal after birth. In the second fetus creatine phosphokinase activity was significantly elevated to 540 IU per liter (P less than 0.001). Fetal blood also showed considerable hemolysis, an unusual observation in placental blood sampling. After abortion, examination of fetal muscle by light, phase and electron microscopy showed characteristic features of Duchenne's muscular dystrophy, including wide variation in muscle-fiber diameter and reduction in the number of fibers per fasciculus. These cases illustrate the potential usefulness of fetal plasma for prenatal diagnosis and, specifically, of creatine phosphokinase activity for diagnosis of muscular dystrophy.
S92 Matrix metalloproteinase-1 activation by mast cell tryptase causes airway remodelling and is associated with bronchial hyper-responsiveness in patients with asthma
Authors: S Naveed, D Clements, D Jackson, D Shaw, S Johnston, SR Johnson
Journal: Thorax (2015)

<h3>Introduction</h3> Matrix Metalloproteinase-1 (MMP-1) is a collagenase, which is present, in its inactive form, in the airways, lung parenchyma and in broncho-alveolar lavage (BAL) fluid of patients with asthma. We hypothesised that MMP-1 could be activated during asthma exacerbations leading to extra-cellular matrix (ECM) processing which contributes to airway remodelling. <h3>Methods</h3> Patients with stable, BTS stage 2/3 asthma, and healthy controls underwent Juniper asthma questionnaire, spirometry, methacholine challenge and bronchoscopy. Bronchial washings were processed for MMP-1 protein and activation. A second cohort of 14 patients with mild and 16 with moderate asthma and 10 controls underwent rhinovirus inoculation and had BAL fluid collected 14 days before and 4 days after inoculation. MMP-1 activity was assessed by fluorescent activity assay. ECM was prepared from decellularised airway smooth muscle (ASM) cultures. Cell proliferation was measured by MTT reduction assay and cell counts. Mast cell supernatants were obtained from cultures of HMC-1 cells activated using Phorbol 12-myristate 13-acetate/Calcium ionophore. <h3>Results</h3> Pro-MMP-1 was expressed more strongly in bronchial washings in asthma than controls (P = 0.0003). After rhinovirus inoculation, asthma symptoms increased and lung function fell. BAL MMP-1 activity increased in asthma patients compared with controls (P = 0.047). MMP-1 protein and activity was positively associated with fall in FEV<sub>1</sub> (R square = 0.3618) (P = 0.0039) post viral inoculation. Activated, but not control, mast cell supernatants increased both expression of pro- and active MMP-1 by ASM cell cultures. This was blocked almost completely by inhibitors of tryptase but not chymase or MMPs. Recombinant tryptase activated MMP-1 <i>in vitro</i>. ECM obtained from both control and asthma derived ASM cells treated with activated mast cell supernatants during matrix synthesis and ECM treated directly after decellularization with active MMP-1 (10 ng/ml) enhanced subsequent ASM growth by 1.5 fold (P &lt; 0.05). <h3>Conclusions</h3> MMP-1 expression and activity in bronchial fluid is enhanced during asthma exacerbations and is associated with increased BHR. MMP-1 activation by mast cell tryptase processes ASM derived ECM to enhance ASM growth in-vitro. Our findings suggest that ASM/mast cell interactions during exacerbations may contribute to airway remodelling by generating a pro-proliferative matrix.