tbuckley/cabot-search huggingface dataset:
The Long-Term Pulmonary Sequelae of Prematurity: The Role of Familial Airway Hyperreactivity and the Respiratory Distress Syndrome
Authors: Jean-Marie Bertrand, S. Patricia Riley, Judith Popkin, Allan L. Coates
Journal: New England Journal of Medicine (1985)

Respiratory distress syndrome of the newborn, prematurity, and familial airway hyperreactivity may contribute to long-term pulmonary sequelae. We assessed the role of each by testing pulmonary function and airway reactivity in 11 prematurely born children who survived the respiratory distress syndrome and in 11 prematurely born children who had no neonatal respiratory disease, each of whom was paired with a sibling born at term. The subjects were between 7 and 12 years of age when studied. Airway reactivity was also assessed in their mothers. The group who had had the respiratory distress syndrome had higher ratios of residual volume to total lung capacity and lower values for forced expiratory volume in one second than did their siblings or normal controls (P<0.01). Expiratory flow was decreased in both groups born prematurely (P<0.02) and was related to neonatal exposure to oxygen (r = -0.71, P<0.02). The incidence of airway hyperreactivity was elevated in all groups, including the mothers. These data suggest that long-term pulmonary sequelae of the respiratory distress syndrome of the newborn are related to the disease, its treatment, or both, and to airway hyperreactivity. In prematurely born children without neonatal lung disease, the sequelae are related to airway hyperreactivity. The possibility of a relation between familial airway hyperreactivity and premature birth is suggested. (N Engl J Med 1985; 312:742–5.)
Liver-Function Tests in Alcoholic Patients
Authors: George M. Lepehne
Journal: New England Journal of Medicine (1949)

IT HAS been believed for decades that chronic alcoholism damages the hepatic parenchyma and may finally lead to cirrhosis of the liver. Available statistics show alcoholism to be an etiologic factor in hepatic cirrhosis in 33 to 87 per cent of the cases. The extent to which the damage to the liver cells caused by alcohol is demonstrable by liverfunction tests is of interest. Numerous authors, using the urobilinogen test, the blood bilirubin test, the bilirubin retention test, the bromsulfalein test, the galactose tolerance test and the cephalin-cholesterol-flocculation test found positive results in 20 to 50 per cent of uncomplicated . . .
Specific Inhibition of Lymphocyte-Proliferation Responses by Adherent Suppressor Cells in Diffuse Cutaneous Leishmaniasis
Authors: Eskild A. Petersen, Franklin A. Neva, Charles N. Oster, Huberto Bogaert Diaz
Journal: New England Journal of Medicine (1982)

Diffuse cutaneous leishmaniasis is characterized by multiple nonulcerative skin lesions. Histologically, these lesions are dominated by vacuolated, heavily infected macrophages, with only a few lymphocytes present. A unique focus of diffuse cutaneous leishmaniasis is present in the Dominican Republic. We studied four patients with this disease. None had a delayed reaction to leishmanial antigen on skin tests. The total numbers of lymphocytes and T cells were normal. None of these patients had a lymphocyte-proliferation response to leishmanial antigens, although their responses to other antigens were normal. Adding indomethacin to cultures or decreasing the number of adherent cells by passage of cells over nylon wool reconstituted the lymphocyte responses to leishmanial antigens. Thus, our studies demonstrate that patients with diffuse cutaneous leishmaniasis have a selective anergy to leishmanial antigen, and that an adherent suppressor cell is one mechanism by which this selective immunosuppressive state is modulated.
Board-Certified Physicians in the United States, 1971–1986
Authors: Francis D. Moore, Cedric Priebe
Journal: New England Journal of Medicine (1991)

This is our third report covering the census of U.S. physicians over a 15-year period. The present report updates the information for 1980 to 1986.Most of our data are based on published information from the Association of American Medical Colleges, the Educational Council for Foreign Medical Graduates, the American Board of Medical Specialties, and the National Resident Matching Program. Data on board-certified physicians were obtained from the Division of Survey and Data Resources of the American Medical Association and are not published elsewhere.After a steep rise in the 1970s, the annual number of physicians receiving licenses increased at a slower rate. The numbers of new board diplomas in medicine and primary care continued to grow. In other non-surgical clinical specialties there was less growth, and in certain fields of surgery the numbers declined. The board-certified percentage of all practitioners increased slightly (74 to 79 percent). About 14 to 16 percent of all active physicians are still in their residency and fellowship years. The percentage of all practitioners under the age of 35 who are women has increased from 8.4 percent in 1967 to 25.2 percent in 1986. The enrollment of some residency programs is currently more than 50 percent women.The work force of physicians did not grow as rapidly in the 1980s as in the 1970s. This nonlinearity of growth and massive changes in the epidemiology and treatment of disease render predictions about the need for or the numbers of physicians a decade hence unreliable.
Recurrent Psychosis Associated with Liver Disease and Elevated Blood Ammonia
Authors: Leston L. Havens, Charles G. Child
Journal: New England Journal of Medicine (1955)

AN increasing body of evidence suggests that ingestion of dietary protein or some other nitrogenous substances may, under certain conditions, precipitate hepatic coma or impending hepatic coma.1 2 3 Adams and Foley4 and Foley et al.5 have detailed the clinical and laboratory signs of impending hepatic coma. These include a "flapping tremor," electroencephalographic abnormalities and changes in mental status, chiefly "reduction of awareness, followed by a brief period of quiet delirium" progressing to stupor.5 The blood ammonia nitrogen level may be elevated.1 2 3 The changes in mental function reported after protein administration have usually been transient and reversible.In the case reported below . . .
Risk Factors and Features of Recurrence After Curative Resection of Gastrointestinal Stromal Tumor: Results of the Kinki Gist Registry Study
Authors: J. Fujita, T. Takahashi, Y. Yamashita, S. Sato, K. Yamamto, Y. Nakajima, Y. Asao, K. Tominaga, T. Omori, T. Tsujinaka
Journal: Annals of Oncology (2014)
Chemoprevention of Colorectal Cancer
Authors: Pasi A. Jänne, Robert J. Mayer
Journal: New England Journal of Medicine (2000)

Colorectal cancer is the second leading cause of cancer-related deaths in the United States. It is estimated that this cancer will develop in 130,000 people in the United States in 2000 and that 56,000 will die from the disease.1 Surgical resection remains the only curative treatment, and the likelihood of cure is greater when the disease is detected at an earlier pathological stage. Early detection is the goal of screening programs that use periodic examination of stool for occult blood, with or without intermittent endoscopic examination of the bowel. Three randomized studies have shown a reduction in mortality of 15 . . .
A Controlled Trial of Nimodipine in Acute Ischemic Stroke
Authors: H J Gelmers, K Gorter, C J de Weerdt, H J Wiezer
Journal: New England Journal of Medicine (1988)

Recent investigations suggest that increased cellular calcium concentrations may be implicated in neuronal death after ischemia. To determine whether treatment with a calcium-channel blocker would improve survival and neurologic outcome in acute ischemic stroke, we enrolled 186 patients in a prospective, double-blind, randomized, placebo-controlled trial of nimodipine (30 mg every six hours), begun within 24 hours of the onset of symptoms of an acute ischemic stroke. During the four-week treatment period, mortality from all causes was significantly reduced with nimodipine as compared with placebo (8 deaths [8.6 percent] vs. 19 [20.4 percent]). The improvement in survival was restricted to men. During the follow-up period of six months, an additional eight patients in each group died. A significantly better neurologic outcome, as assessed by the Mathew scale of neurologic deficit, was also observed in the nimodipine group. The improvement in neurologic status was greatest in patients with a moderate to severe deficit at base line. There were no important side effects except for one episode of reversible azotemia that may have been related to treatment with nimodipine. Our data suggest that patients with acute ischemic stroke may benefit from early treatment with nimodipine, but this therapeutic effect appears to be limited to men.
Azorean Disease of the Nervous System
Authors: Flaviu C. A. Romanul, Hilton L. Fowler, Joao Radvany, Robert G. Feldman, Murray Feingold
Journal: New England Journal of Medicine (1977)

We studied a family of Portuguese ancestry from the Azores who suffered a progressive neurologic disease characterized by gait ataxia, features similar to Parkinson's disease in some patients, limitation of eye movements, widespread fasciculations of muscles, loss of reflexes in the lower limbs, followed by nystagmus, mild cerebellar tremor and extensor plantar responses. Two post-mortem examinations revealed loss of neurons and gliosis in the substantia nigra, nuclei pontis (and in the putamen in one case) as well as in the nuclei of the vestibular and other cranial nerves, columns of Clarke and anterior horns, in the spinal cord there were also loss of fibers in the fasciculi gracilis and mild changes in the pyramidal tracts. Comparison of the disease in this family with the findings reported in three families of similar ancestry, previously thought to have different disorders, suggests that they may all represent a single genetic entity with variable expression.
BMET-28ROLE OF NUCLEAR PTEN IN THE BRAIN METASTASES MECHANISM
Authors: Ryo Nosaka, Fumiyuki Yamasaki, Takeshi Takayasu, V.J. Amatya, Yukio Takeshima, Kazuhiko Sugiyama, Kaoru Kurisu
Journal: Neuro-Oncology (2015)

Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) is a well-known tumor suppressor, then early studies proposed that PTEN was exclusively cytoplasmic. However, recent reports demonstrate that nuclear PTEN has important tumor suppressive function. Meanwhile recent report mentioned that PTEN mRNA expression was significantly downregulated in brain metastases compared with primary breast cancer. We studied the expression pattern of nuclear and cytoplasmic PTEN in 34 patients with primary tumors and brain metastases. These patients underwent surgical interventions at Hiroshima University Hospital, Japan, between 1995 and 2013. Clinical characteristics of patients are as follows. Sex: male14, female14. Mean age: primary 59.7y, metastases 62.1y. Primary tumors contained gastric, esophageal, colorectal, breast, ovarian, cervical, and prostate cancer. PTEN expression levels were immunohistochemically measured and categorized as negative (-), positive (+), or strong positive (++) expression. PTEN expression levels were compared using Mann-Whitney U test. In all analyses, differences with P < 0.05 were considered statistically significant. Results are as follows. −/+/++ (%): cytoplasmic primary 3:21:76, cytoplasmic metastases 26:62:12, nuclear primary 6:32:62, nuclear metastases 79:15:6. Study results demonstrate that PTEN expression levels are lower in brain metastases compared with in primary tumors. Especially, nuclear PTEN expression level was significantly downregulated in various brain metastases, so our findings confirm that decreased PTEN function by nuclear PTEN expression loss is associated with brain metastases.
Consequences of Cupping
Authors: H Manber, M Kanzler
Journal: New England Journal of Medicine (1996)

Figure 1. During a routine examination, a 33-year-old Korean woman was incidentally found to have lesions on her back in various stages of healing. The lesions had been created when a friend applied heated cups to the skin to treat back pain. The vacuum created as the cup cools results in erythema, edema, and ecchymoses of the skin, which take several weeks to heal. The patient was unconcerned about these effects of “cupping” and requested no intervention.
An update on BREAK-3, a phase III, randomized trial: Dabrafenib (DAB) versus dacarbazine (DTIC) in patients with BRAF V600E-positive mutation metastatic melanoma (MM).
Authors: Axel Hauschild, Jean Jacques Grob, Lev V. Demidov, Thomas Jouary, Ralf Gutzmer, Michael Millward, Piotr Rutkowski, Christian U. Blank, Wilson H. Miller, Eckhart Kaempgen, Salvador Martin-Algarra, Boguslawa Karaszewska, Cornelia Mauch, Vanna Chiarion-Sileni, Beloo Mirakhur, Mary E. Guckert, R. Suzanne Swann, Patricia Haney, Vicki L. Goodman, Paul B. Chapman
Journal: Journal of Clinical Oncology (2013)

9013 Background: Dabrafenib is a selective BRAF inhibitor with demonstrated efficacy in BRAF V600E-positive mutation in MM. The primary analysis of BREAK-3 (NCT01227889) compared progression-free survival (PFS) in patients (pts) with BRAF V600E-positive mutation MM treated with dabrafenib or DTIC. Methods: Median PFS for dabrafenib of 5.1 months (mo) and study methods were previously described (Hauschild A, et al. Lancet. 2012,380:358–365). Independent review ended at the primary analysis. PFS was updated in Jun 2012 at median follow-up of 10.5 mo for dabrafenib (67% of PFS events), and 9.9 mo for DTIC. Median overall survival (OS) was not reached, so another analysis of OS and safety was performed with data as of Dec 2012, at which time the median follow-up was 15.2 (dabrafenib) and 12.7 (DTIC) mo. PFS of subjects who crossed over was also evaluated at that time. Results: PFS hazard ratio was 0.37 [95% CI; 0.23, 0.57]; median PFS was 6.9 mo dabrafenib and 2.7 mo DTIC. In Dec 2012, 36/63 DTIC pts crossed over; median PFS was 4.3 [95% CI; 4.1, 6.1] mos. OS is presented in the Table.The four most common adverse events (AE) on the dabrafenib arm were hyperkeratosis (39%), headache (35%), arthralgia (35%), and pyrexia (32%). Serious AEs ≥ 5% on the dabrafenib arm included cutaneous squamous cell carcinoma/keratoacanthoma (10%) and pyrexia (5%). Conclusions: Longer follow-up confirms the benefits of dabrafenib on PFS and response rate. Median OS in the dabrafenib arm was over 18 mo and over 15 mo in the DTIC arm. OS results are confounded by crossover of DTIC pts to dabrafenib and likely by subsequent therapy after progression. The effects of subsequent therapy results will be investigated. The safety profile had no significant changes. Clinical trial information: NCT01227889. [Table: see text]
Oral fluoropyrimidines versus 5-fluorouracil for colorectal cancer: Results of a systematic review and meta-analysis
Authors: A. D. Sasse, E. C. Sasse, L. V. dos Santos, J. S. Lima, C. M. Nascente, H. P. Saito, M. S. Tariki, V. C. Conceicao, A. M. Carvalho, N. S. Siqueira
Journal: Journal of Clinical Oncology (2009)

4111 Background: Previous studies showed that continuous intravenous infusion (cIV) of 5-fluorouracil (5FU) is associated with best tumor response in comparison to bolus 5-FU and perhaps, a slight increase of overall survival. There are some non-inferiority trials comparing oral fluoropyrimidines with bolus or cIV of 5FU, but there is still no definitive evidence of equivalence. This systematic review evaluated the efficacy of oral fluoropyrimidines compared to bolus or cIV administration of 5FU in colorectal cancer. Methods: PubMed, EMBASE, CENTRAL and LILACS databases were searched. Eligible studies were randomized trials (RCTs) comparing chemotherapy regimens containing oral fluoropyrimidines (capecitabine, UFT or Tegafur) and 5FU (bolus or cIV) in patients with colorectal cancer. The primary outcome was overall survival (OS). Secondary outcomes included response rate (RR), progression-free survival (PFS) and disease-free-survival (DFS). Hazard Ratio (HR) and Odds Ratio (OR) with fixed effect model were used for meta- analysis and were expressed with 95% confidence intervals (CI). Results: We included results from 20 RCTs, with a total of 14,779 patients. Compared to cIV of 5FU, capecitabine resulted in lower RR (OR 0.82; 95% CI 0.72 to 0.95; p=0.006), shorter PFS (HR 1.09; 95% CI 1.01 to 1.17; p=0.02) and was associated with a non- significant reduction in OS (HR 1.05; 95%CI 0.97 to 1.14; p=0.23). Compared to bolus 5FU, capecitabine resulted in lower RR (OR 0.80; 95% CI 0.65 to 0.98; p=0.004), but similar OS and PFS. Compared to bolus 5FU, the use of other fluoropyrimidines resulted in similar RR, OS and PFS. Conclusions: Oral fluoropyrimidines are equivalent to bolus 5FU in terms of efficacy, but provides less benefit than cIV 5FU. Combination chemotherapy with cIV 5FU remains the first choice for patients with colorectal cancer. [Table: see text]
Abstract 3622: Novel SMAC-mimetic birinapant demonstrates antitumor activity in human head and neck cancer models exhibiting alterations in cell death pathways
Authors: Sophie Carlson, Danielle Eytan, Grace Snow, Stephen Schiltz, Suresh Mohan, Anthony Saleh, Shaleeka Cornelius, Jamie Coupar, Carter Van Waes, Zhong Chen
Journal: Cancer Research (2015)

Abstract The Cancer Genome Atlas (TCGA) uncovered frequent and prognostically important genomic alterations of cell death signaling molecules, including chromosome 11q13/22 FADD and/or BIRC2 (cIAP1) amplifications, or CASP8 mutations, in distinct head and neck squamous cell carcinoma (HNSCC) subtypes. Consistent with TCGA, we found increased FADD and/or cIAP1 expression in a panel of 11 HNSCC cell lines. Overexpression of cIAP1 has been implicated in resistance to standard of care therapies that act through the induction of apoptosis. Birinapant, a novel SMAC-mimetic that targets and promotes degradation of cIAPs, inhibited cell density and sensitized multiple HNSCC lines to death agonists TNF or TRAIL, which was reversible by inhibitors of caspase-dependent apoptosis and/or RIPK1-mediated necroptosis. In vivo, birinapant significantly inhibited tumor growth and prolonged host survival in two FADD/cIAP1-overexpressing xenograft models, UMSCC 46 and 11B. Remarkably, birinapant combined with radiation treatment, an inducer of TNF, cured animals bearing UM-SCC-46 xenografts. These results suggest that birinapant generates strong synergy with radiotherapy in HNSCC harboring cell death pathway genomic alterations linked to worse prognosis. Citation Format: Sophie Carlson, Danielle Eytan, Grace Snow, Stephen Schiltz, Suresh Mohan, Anthony Saleh, Shaleeka Cornelius, Jamie Coupar, Carter Van Waes, Zhong Chen. Novel SMAC-mimetic birinapant demonstrates antitumor activity in human head and neck cancer models exhibiting alterations in cell death pathways. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3622. doi:10.1158/1538-7445.AM2015-3622
ATCT-24ROLE OF PHOTODYNAMIC THERAPY (PDT) FOR GLIOBLASTOMA
Authors: Masayuki Nitta, Yoshihiro Muragaki, Takashi Maruyama, Soko Ikuta, Hiroshi Iseki, Takakazu Kawamata
Journal: Neuro-Oncology (2015)

Photodynamic therapy (PDT) is based on biochemical reaction between oxygen, photosensitizer (PS) and light. PS is safe by itself and selectively accumulates in tumor cells and become activated by exposure to specific wavelengths of light. PS then releases energy, which is transferred to oxygen to generate reactive oxygen species (ROS), such as singlet oxygen and free radicals. ROS induces cell death in tumor cells. PDT for malignant gliomas are conducted as follows: 1) PS administration on the day before surgery. 2) Maximum tumor resection. 3) Targets for PDT are decided based on anatomical structure of removal cavity. Sites of recurrence are predicted such as corpus callosum and surrounding T2 high lesion should be selected. 4) PD laser is irradiated to the targets. We have conducted a phase II clinical trial of PDT for malignant glioma in 2009-2012. 27 patients were registered and 13 patients with glioblastoma were analyzed and positive outcomes were obtained (1-year OS rate: 100% and MST: 24.8 months). PDT was approved for clinical use in Japan in September 2013. Then we have continued follow-up of the patients in the clinical study and obtained updated excellent clinical results (MST: 31.5 months, median PFS: 19.6 months). We have also experienced PDT for 16 patients with recurrent glioblastoma and 1-year OS rate and median OS after PDT were 77.1% and 13.8 months, respectively. PDT appears to be a promising, new local therapeutics for glioblastoma.
Treatment of Cushing's Disease by o,p′DDD
Authors: J. P. Luton, J. A. Mahoudeau, Ph. Bouchard, Ph. Thieblot, M. Hautecouverture, D. Simon, M. H. Laudat, Y. Touitou, H. Bricaire
Journal: New England Journal of Medicine (1979)

In a study of nonsurgical therapy of Cushing's disease, 62 patients received O,p'-dichlorodiphenyldichloroethane (O,p'DDD), 16 of whom also received cobalt irradiation of the pituitary. After an initial treatment period averaging eight months, a remission of the disease was obtained in 38 of the 46 patients given O,p'DDD alone and in all patients who received drug combined with radiation. Although 60 per cent of these patients subsequently relapsed, additional courses of drug or radiation therapy were usually effective, and 63 per cent of the entire group of patients have so far been kept under control without adrenalectomy. (Forty patients have been followed for at least two years after the initial course of treatment.). O,p'DDD produced little gastrointestinal discomfort; an increased serum cholesterol was the main side effect. This drug allows long-term medical management of Cushings disease in most cases. Whether the combination of O'p'DDD with pituitary radiation is the best therapy has not been established.
The Influence of Weight Reduction on Amenorrhea in Obese Women
Authors: George W. Mitchell, Joseph Rogers
Journal: New England Journal of Medicine (1953)

A STATISTICAL study of 100 women with menstrual disorders showing a significant increase in the incidence of obesity in women with amenorrhea was reported from this clinic in July, 1952.1 Of 60 women without periods for at least three months, 29, or 48 per cent, were obese. The incidence of obesity in a control group of women of similar age range was 13 per cent. During the course of this study, several obese women who lost weight had a return of menses. The beneficial effect of weight reduction in amenorrhea has been a well known clinical observation, but, apparently, no . . .
Prenatal stress and childhood asthma risk: taking a broader view
Authors: Alison Lee, Rosalind J. Wright
Journal: European Respiratory Journal (2016)

We now know that asthma risk begins in utero during rapid lung morphogenesis, when the developing fetus is particularly vulnerable to toxic insults due to immature immune, neuroendocrine and antioxidant defences. A meta-analysis published in a recent issue of the European Respiratory Journal (ERJ) [1] builds on substantial evidence highlighting psychological stress as a critical toxic exposure that, starting in utero, can permanently alter interrelated systems ( i.e. immune, autonomic, neuroendocrine and oxidation systems) believed to programme lung growth and consequent respiratory disorders, including asthma [2]. Cumulative evidence confirms stress in pregnancy is a critical prenatal risk for childhood asthma <http://ow.ly/W1CCi>