tbuckley/cabot-search huggingface dataset:
Early vs. late treatment with darbepoetin alfa in patients with genitourinary tumors during chemotherapy
Authors: K. Elandt, P. Horak, K. C. Schieder, R. Leikermoser, R. Altmann, A. Albrecht, K. Reisenberger, S. Tomek, H. Fischer, C. C. Zielinski, M. Krainer
Journal: Journal of Clinical Oncology (2006)

18583 Background: Anemia is a common complication in patients who receive anticancer therapy. We evaluated the efficacy of darbepoetin alfa in early vs. late treatment in patients with genitourinary tumors undergoing chemotherapy. We wanted to investigate whether an early onset of treatment with darbepoetin alfa reduces frequency of red blood cell transfusion and increases patients’ QoL. Methods: Patients on chemotherapeutic treatment for a urogenital neoplasia and a hemoglobin between 10–12 g/dl were randomized between an immediate start of treatment with darbepoetin alfa 150 μg sc weekly (group A) and a Hb below 10 g/dl or clinical symptoms (group B). Results: 52 patients out of 68 (76.5%) completed the trial, 7/40 patients (17%) in group A and 9/28 patients (32%) in group B withdraw from the study. An intent to treat analysis was performed and showed a significant superiority (p = 0.023, log-rank test) for the early treatment. In group A, only 12.5% of patients (5/40) received at least one red blood cell transfusion compared to group B, where 39% of the patients (11/28) received a transfusion. In group A the mean Hb level increased steadily, starting with a baseline value of 11.0 g/dl. In week 21 a mean Hb level of 12.8 g/dl was reached, resulting in an overall increase in Hb of 1.8 g/dl. In group B, which had a comparable baseline Hb level of 10.9 g/dl, the mean Hb value decreased initially during the first 4 weeks to 10.0 g/dl. In week 21 a level of 11.4 g/dl was reached, resulting in a total Hb-increase of 0.5 g/dl. When anemia treatment was initiated early, the mean Hb level always remained in the range of 11 to 13 g/dl from the beginning of the study, in the B group the mean level of 11 g/dl was first achieved after 12 weeks. 35% in group A compared to 54% in group B (p = 0.13) experienced a dose doubling. The mean values (EORTC-QLQ-C30) of all symptom scales in group A were markedly below those in group B with the highest difference for dyspnea, 29.1 points (p &lt; 0.001). Conclusions: Early treatment with darbepoetin alfa in patients with urogenital cancer results in optimal hemoglobin levels according to EORTC guidelines and consequently in a reduction of red blood cells transfusion. Furthermore, in patients with earlier initiation of treatment a clinically significant improvement of dyspnea can be observed. [Table: see text]
Induction Chemotherapy Followed By Chemoradiotherapy in Locally Advanced Esophagogastric Adenocarcinoma. Has the Location of the Primary Tumor Any Influence on Patients' Outcome? a Retrospective Analysis
Authors: P. Martin Romano, L. Arbea, L. Zubiri, J. Subtil, A. Chopitea, J.P. Fusco, J. Legaspi, J.L. Hernandez-Lizoain, L. Ceniceros, E. Castanon Alvarez, J. Rodriguez
Journal: Annals of Oncology (2014)
Sports medicine in Singapore: integrating into public hospitals and secondary care
Authors: Dinesh Sirisena, Sharon Lim, Kong Chuan Teh
Journal: British Journal of Sports Medicine (2016)

Since gaining independence from Malaysia in 1965, Singapore has become a financial and cultural hub in South East Asia. Four years after independence, the government decided to develop Sports Medicine, by sponsoring the first Sports Physician to train in the USA.1 The Sports Medicine and Research Centre (SMRC) was established along with the National Stadium in 1973, with a focus on managing national athletes. It also played a part in the ‘Sports for All’ programme, promoting regular exercise and establishing national physical fitness tests. This programme included the National Physical Fitness Award scheme, launched in 1982, for the general public, schools and uniformed personnel, including those of the military.

Over time, sports medicine was expanded to include biomechanics, nutrition, psychology, and strength and conditioning. Subsequently, it was formalised as a medical specialty in 2007, similar to the UK model, with the first specialist rotation established at Changi General Hospital.2 ,3 

Musculoskeletal/exercise medicine education is often lacking in the undergraduate curriculum and junior doctors …
P232 Too Sweet for Too Long?
Authors: S Ali, R Khetan, P Sachdev, J Bhatt
Journal: Thorax (2015)

<h3>Background</h3> Cystic fibrosis related diabetes (CFRD) is associated with deterioration in clinical status. Lung function and nutritional status deteriorate up to 2–4 years <b><i>before</i></b> a diagnosis of CFRD based on the oral glucose tolerance test (OGTT). Timely detection and treatment is crucial. <h3>Aims</h3> To evaluate: adherence to CFRD screening guidelines and whether identifying stages of progressive Cystic Fibrosis Insulin Deficiency (CFID) using the extended OGTT altered management trends in weight, BMI and FEV1 in CFRD as compared to CF controls. <h3>Methods</h3> Retrospective analysis using patients’ records. 7 patients with CFRD were compared to matched CF controls using mean z-scores for weight, BMI and FEV1. <h3>Results</h3> Records of 59 children (23 males) were analysed, 21 children between 5–10 years and 38 &gt;10 years. In the younger group, 80% (n = 17) had both HbA1c and random glucose tested as per our guidelines. Of 38 patients aged &gt;10 years, 78% (n = 30) were screened by OGTT of whom 16% (n = 5) had the standard test. Table 1 summarises the results and shows the degree of glucose impairment on OGTT and the related grade of cystic fibrosis insulin deficiency (CFID). The mean weight and BMI z scores for those with CFRD compared to controls were -0.64 vs -0.02(p = 0.005) and -1.26 vs -0.03(P = 0.0001). There was a lower trend in FEV1 in CFRD, 1.87l (73.06%) vs 2.35l (89.03%). 3 patients with CFID3 and 1 with CFID1 later commenced insulin based on clinical grounds. <h3>Conclusions</h3> Adherence to screening guidelines needs to be improved. Patients with CFRD have a significant declining trend in weight, BMI and FEV1 compared to controls. Some patients with CFID were commenced insulin on clinical grounds rather than results of extended OGTT. Whether treatment at earlier stages of CFID will slow down the rate of decline needs to be explored, but we have reverted back to the standard OGTT for the present.
Fever and Neutropenia — How to Use a New Treatment Strategy
Authors: Robert W. Finberg, James A. Talcott
Journal: New England Journal of Medicine (1999)

The treatment of fever and neutropenia has evolved with the development of both new antimicrobial drugs and new strategies for using them. More than three decades ago, Bodey and colleagues identified the association between neutropenia and serious infection in patients with cancer as such patients began to be treated with intensive cytotoxic chemotherapy and given platelet transfusions to prevent death from bleeding.1 The first effective treatment for patients with fever and neutropenia was the combination of an antipseudomonal penicillin, carbenicillin, and gentamicin in a strategy of early empirical therapy triggered by fever alone.2 The studies of Pizzo and colleagues refined . . .
Evidenced-Based Report on the Occurrence of Fatigue in Long-Term Cancer Survivors
Authors: Ilana M Braun, Donna B Greenberg, William F Pirl
Journal: Journal of the National Comprehensive Cancer Network (2008)

Although some cancer survivors report persistent fatigue years after treatment, little is known about the prevalence of the symptom in this population as compared with the general population. This article examines current evidence for the occurrence of fatigue in long-term cancer survivors by reviewing published population-based studies that incorporated controls from the general population. Using the search criteria "fatigue AND cancer survivors" in PubMed, the authors identified 16 articles (based on 15 cross-sectional datasets) comparing fatigue severities in survivors of adult cancers with those in the general population. When data allowed, Hedges' g effect size calculations were generated. A total of 8096 cancer survivors were examined across datasets. Cancer survivor sample sizes ranged from 15 to 1933 per dataset. Most datasets focused on either breast cancer (7) or Hodgkin's disease survivors (6). Four studies did not clearly exclude patients undergoing active treatment. Nine articles (based on 8 datasets) showed statistically significant (P < .05) differences among groups; 4 articles showed negative results; and 3 showed both positive and negative results depending on fatigue dimension measured. Among the studies that reported scores for the fatigue subscale of the European Organization for Research and Treatment of Cancer Core Questionnaire for Quality of Life (most studies), mean fatigue levels in cancer survivors ranged from 28.7 to 36.5 out of an overall score of 100, and mean fatigue levels in matched general population controls ranged from 20 to 30 out of 100. No associations between instruments and results were apparent. Although the small numbers of studies prevented comparisons among cancer subtypes, equal positive and negative studies were seen in breast cancer survivors and, notably, no negative studies were seen involving Hodgkin's disease survivors. Most effect sizes calculated were small. Fatigue was a burden to both cancer survivors and members of the general population. While evidence for greater fatigue severity in cancer survivors was mixed, most studies reported greater fatigue in cancer survivors as compared with controls. The magnitude of this effect was generally small. Inferences from the data were limited by variability in both the definition of survivor and the fatigue assessments used, as well as by the cross-sectional design of the studies. Prospective longitudinal studies are needed to determine causal relationships between excessive fatigue and surviving cancer.
Untoward Reactions to Tests for Epinephrine-Secreting Tumors (Pheochromocytoma)
Authors: Howard R. Bierman, John W. Partridge
Journal: New England Journal of Medicine (1951)

THE recent development of pharmacologic tests for epinephrine-secreting tumors1 2 3 4 has increased the interest in this field so that in many institutions such procedures are done almost routinely on nearly all patients with hypertension.The severe and uncontrollable, but transient, hypertension that may occur after the intravenous administration of histamine in patients with pheochromocytoma has been well described.5 Tetraethylammonium bromide has been proposed as a substitute test substance, primarily because the hypertension following its administration in patients with pheochromocytoma may be effectively countered by placing the patient in a sitting position.2 At least one death due to tetraethylammonium-chloride sensitivity has been . . .
A multi-gene assay to predict long-term mortality in early stage lung adenocarcinoma
Authors: D. J. Raz, J. Y. Kim, M. R. Ray, D. M. Jablons
Journal: Journal of Clinical Oncology (2007)

7569 Background: The likelihood of long-term mortality for patients with early stage lung adenocarcinoma is poorly defined by clinical stage and histopathological findings. Our hypothesis was that a multigene quantitative polymerase chain reaction (PCR) assay can predict risk of mortality among patients with early stage lung adenocarcinoma. Methods: We identified 65 genes that were previously identified as prognostic for long-term mortality in early stage lung cancer in 3 published microarray studies and 2 PCR-based studies. RNA was extracted from 124 fresh-frozen tumor samples from consecutive patients with completely resected lung adenocarcinoma with at least 3 years of clinical follow-up. 80 samples were randomly assigned to a test group and the remainder assigned to a validation group. Real-time PCR of the 65 identified genes were run on the test set using Taq-man assays. A prediction model was created using a proportional hazards model of normalized gene expression levels using backwards model selection. A model score was calculated for each patient using model coefficients and individual gene expression levels. Patients were defined as high-risk if the model score was greater than the median score. Results: Adequate real-time PCR profiles were identified in all 80 patients. Eighteen genes were included in the final model. The proportion of patients identified as high-risk and low-risk was 52% and 48% percent, respectively. The Kaplan-Meier estimated five-year survival in the low-risk group was 82% and 5% in the high-risk group (P&lt;0.001, log-rank test). Median survival was 22 months in the high-risk group and was not reached in the low-risk group. In multivariate survival analysis, the prognostic score predicted survival independent of tumor stage and size (P&lt;0.001). Prognostic score predicted mortality better than clinical stage, based on model log-likelihood values (P&lt;0.001). Conclusions: This multi- gene assay aids in predicting long-term mortality among patients with surgically resected early stage lung adenocarcinoma. We are currently validating this model in our test set of samples. No significant financial relationships to disclose.
Abstract 20130: Hypertrophic Cardiomyopathy in RAF1 Mutant-associated Noonan Syndrome Requires Complex Cellular Interplay
Authors: Jiani C Yin, Mathew Platt, Xue Wu, Jeremy A Simpson, Toshiyuki Araki, Benjamin G Neel
Journal: Circulation (2015)

Hypertrophic cardiomyopathy (HCM) has multiple etiologies, including hypertension, cardiac valve disease or genetic defects. Most inherited HCM results from defects in sarcomere proteins, but ~25% are caused by aberrant cardiac signal transduction genes. RASopathies are developmental disorders with multiple variably penetrant features, including HCM, which are caused by mutations in genes encoding RAS/extracellular signal-regulated kinase (ERK) pathway components. The most common RASopathy, Noonan Syndrome (NS), results from gain-of-function alleles in PTPN11, KRAS, SHOC2, SOS1/2, RAF1 and RIT1. Activating mutations in RAF1 are strongly (~95%) associated with HCM. Global knock-in mice harboring the NS allele Raf1L613V recapitulate the features of NS-associated HCM, including ventricular chamber dilatation, enhanced cardiac contractility, and exacerbation of pressure-overload induced fibrosis. Here, using inducible Raf1L613V knock-in mice and lineage-specific Cre lines, we show that RAF1 mutant-associated HCM is caused by a complex interplay of multiple cardiac cell types. Surprisingly, cardiomyocyte-specific Raf1L613V expression caused minimal hypertrophy, yet markedly increased cardiac contractility. By contrast, endocardial/cardiac endothelial (EC)-specific Raf1L613V expression promoted cardiomyocyte hypertrophy without affecting contractility. In direct or Transwell co-cultures, Raf1L613V-expressing ECs increased the size of normal cardiomyocytes. Cytokine arrays revealed increased IL6 secretion from isolated Raf1L613V-expressing ECs, and JAK-STAT, PI3K, and MEK/ERK activation were enhanced in EC-Raf1L613V hearts. Blocking IL6 action with neutralizing anti-IL6 antibodies reversed cardiomyocyte hypertrophy in EC/cardiomyocyte co-cultures. Finally, Raf1L613V expression in cardiomyocytes or cardiac fibroblasts, but not in ECs, exacerbated fibrosis upon pressure-overload. Taken together, our data indicate that NS HCM requires complex, cell-autonomous and -non-autonomous interactions between cardiomyocytes, ECs, and fibroblasts. Furthermore, we identify the IL6 pathway as a potential therapeutic target for RASopathy-associated HCM.
Identification of Subgroups of Euthyroid Graves's Ophthalmopathy
Authors: David H. Solomon, Inder J. Chopra, Usha Chopra, Francoise J. Smith
Journal: New England Journal of Medicine (1977)

We attempted to determine if euthyroid Graves's ophthalmopathy is a single entity or a heterogeneous group of disorders. Activity of long acting thyroid stimulator protector occurred in 31 of 33 patients with Graves's hyperthyroidism but in only nine of 17 with euthyroid Graves's ophthalmopathy. Of the euthyroid patients, six had protector activity and thyroid non-suppressibility; firm goiters and high titers of thyroid antibodies were the rule in this group. We believe that these patients have three autoimmune diseases: Hashimoto's thyroiditis, Graves's thyroid disease and Graves's ophthalmopathy. Five euthyroid patients had no detectable protector activity or thyroid antibodies and had normal thyroid suppressibility; the thyroid was generally normal in size and consistence. These patients are interpreted as having "isolated" Graves's ophthalmopathy without any autoimmune thyroid disease. The remaining six patients showed dissociation between protector activity and thyroid non-suppressibility and cannot be classified as yet. Euthyroidism in Graves's ophthalmopathy may have more than one cause. (N Engl J Med 296:181–186, 1977)
Case 18-2002
Authors: Richard L. Kradin, Eugene J. Mark
Journal: New England Journal of Medicine (2002)

Presentation of CaseA 48-year-old man was admitted to the hospital because of bilateral pulmonary infiltrates, bloody sputum, and microhematuria.The patient was a physician who had been well until about eight years earlier, when paranasal sinusitis developed and became chronic. Seventeen months before admission, sinus surgery was performed at another hospital. Pathological examination of the excised material showed acute and chronic rhinosinusitis with stromal eosinophils.Two months before admission, fever and epistaxis developed. The patient suspected that he had acute sinusitis and treated himself with azithromycin. Two days later, bilateral ear “pressure” developed, and exudates were observed over the . . .
Suppression of Erythroid-Colony Formation by Lymphocytes from Patients with Aplastic Anemia
Authors: Ronald Hoffman, Esmail D. Zanjani, John D. Lutton, Ralph Zalusky, Louis R. Wasserman
Journal: New England Journal of Medicine (1977)

To explore the possible role of cell-mediated suppression of erythropoiesis in acquired aplastic anemia, we studied the effect of peripheral blood lymphocytes from seven patients with aplastic anemia on erythroid-colony formation by normal human bone marrow in an in vitro plasma clot-culture system. Varying numbers of peripheral blood lymphocytes (0.5 to 6 X 105 cells) were cocultured with 6 X 105 normal bone-marrow cells in the presence of 2 IU of erythropoietin for seven days. Peripheral blood lymphocytes from five of the seven patients with aplastic anemia caused a 79 to 94 per cent reduction of erythroid-colony formation. Thus, at a peripheral blood lymphocyte concentration of 2 X 105 cells, the numbers of erythroid colonies formed (control vs. experimental) were 374±16 (S.E.M.) vs. 22±6, 48±4, 50±16, 80±4 and 27±3. These results suggest that some patients with aplastic anemia possess a population of lymphocytes capable of suppressing in vitro erythropoiesis. (N Engl J Med 296:10–13, 1977)
Effect of Matching of Class I HLA Alleles on Clinical Outcome after Transplantation of Hematopoietic Stem Cells from an Unrelated Donor
Authors: Takehiko Sasazuki, Takeo Juji, Yasuo Morishima, Naoko Kinukawa, Hidehiko Kashiwabara, Hidetoshi Inoko, Takato Yoshida, Akinori Kimura, Tatsuya Akaza, Nobuhiro Kamikawaji, Yoshihisa Kodera, Fumimaro Takaku, Yoshiaki Nose, Takashi Ono, Takeo Sakamaki, Shunichi Kato, Yuichi Akiyama, Shinichiro Okamoto, Hiroo Dohy, Mine Harada, Shigetaka Asano
Journal: New England Journal of Medicine (1998)

The requirements with respect to HLA compatibility and the relative importance of matching for individual class I and class II HLA alleles in the transplantation of hematopoietic stem cells from unrelated donors have not yet been established.
A Nonallergist Looks at Allergy
Authors: L. Emmett Holt
Journal: New England Journal of Medicine (1967)

FIFTY years have gone by since the term allergy was first used by Pirquet,1 whose original observations entitle him to be regarded as the father of that branch of medicine. During that half century much has happened. The term allergy, sometimes used in a broader sense to include altered reactions of any kind,2 is generally restricted to a group of immunologic reactions exhibited by certain individuals that differ in kind or in degree from those of the species as a whole. Interest in these phenomena has been increasing rapidly in the more "developed" parts of the world. As the more . . .
Case 25-1994
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, Sherwood L. Gorbach, Fiona Graeme-Cook, R. Neal Smith
Journal: New England Journal of Medicine (1994)

Presentation of CaseA 58-year-old woman was admitted to the hospital because of intractable diarrhea after chemotherapy for carcinoma of the tongue.Five months before admission, the patient had received radiation therapy for a stage T4N2cM0 squamous-cell carcinoma of the tongue, followed by the administration of two cycles of fluorouracil, cisplatin, bleomycin, and methotrexate; the second cycle was begun 22 days before admission. The patient experienced only minor soreness of the mouth after the first cycle of chemotherapy and negligible side effects during the two weeks after the second cycle.Four days before admission, diarrhea developed, with crampy abdominal pain, . . .
Hyperuricemia in Hyperparathyroidism
Authors: Daniel H. Mintz, John J. Canary, Gabriel Carreon, Laurence H. Kyle
Journal: New England Journal of Medicine (1961)

HYPERURICEMIA has been reported to occur in a wide variety of metabolic abnormalities. The demonstration of elevated serum uric acid levels in such diverse pathologic states as acromegaly,1 myxedema,2 hypoparathyroidism,3 pseudopseudohypoparathyroidism,4 diabetes mellitus5 and essential hypercholesterolemia6 defies a common physiologic explanation. Our recent experiences with hyperparathyroid subjects suggests that the association of hyperuricemia and functioning parathyroid adenomas is not infrequent. The further demonstration of a surprising incidence of gout in these subjects bears emphasis. It is the purpose of this paper to report the incidence of these combined abnormalities in a small group of patients, the effect of removal of . . .
Pesticide-like Poisoning from a Prescription Drug
Authors: Melisa W. Lai, Matthew Moen, Michele Burns Ewald
Journal: New England Journal of Medicine (2005)

To the Editor: Acetylcholinesterase inhibitors have long been known for their use as pesticides. Since the 1990s, acetylcholinesterase-inhibiting pharmaceuticals (donepezil, tacrine, galantamine, and rivastigmine) have been used to treat Alzheimer's disease; they are currently being investigated as a treatment for dementia associated with Parkinson's disease in adults1 and with Tourette's syndrome and autistic and attention deficit–hyperactivity disorders in children.2,3 Wider use of this class of medications for a broader variety of disorders increases the possibility of pesticide-like poisoning from a prescribed medication. We report a case of such poisoning. A healthy 11-month-old girl (weight, 7.5 kg) presented to a . . .