tbuckley/cabot-search huggingface dataset:
High Prevalence of Seroimmunologic Abnormalities in Relatives of Patients with Active Chronic Hepatitis or Primary Biliary Cirrhosis
Authors: Robert M. Galbraith, Martin Smith, Ronald M. Mackenzie, Dudley E. Tee, Deborah Doniach, Roger Williams
Journal: New England Journal of Medicine (1974)

Abstract To determine the familial prevalence of serologic abnormalities, immunoglobulin disturbances and biochemical evidence of liver dysfunction, 260 relatives of patients with chronic hepatitis or primary biliary cirrhosis were studied. Mitochondrial, smooth-muscle and nuclear antibodies were more frequent than in controls matched for age and sex. Abnormal immunoglobulin levels occurred in almost half the relatives, and 71 per cent had some immunologic disturbance. In addition, elevated alkaline phosphatase levels and hypergammaglobulinemia were common, the latter being more frequent (p<0.001) in the group with active chronic hepatitis (34 per cent) than in the relatives of patients with primary biliary cirrhosis (9.3 per cent). Furthermore, in three of the 55 families studied, two or more members were found to have cirrhosis. These findings suggest a similar genetic predisposition to immunologic abnormalities among the families of patients with these two diseases, although environmental factors are p...
NTCT-09IGF-1 IS NOT ELEVATED IN PATIENTS WITH HGG TREATED WITH RADIOCHEMOTHERAPY
Authors: Ammon Handisurya, Alois Gessl, Rodrig Marculecsu, Karin Dieckmann, Johannes Hainfellner, Adelheid Woehrer, Georg Widhalm, Barbara Kiesel, Matthias Preusser, Christine Marosi
Journal: Neuro-Oncology (2015)

BACKGROUND: In adult patients with malignant gliomas, deficiencies of the pituitary hormones are an awaited long term side effect of radiotherapy to the hypothalamic-pituitary axis. In pediatric brain tumor patients, Littley and Darzy showed that growth hormone deficiency is the first emerging hormonal deficit, reaching a probability of 50% 2.5 years after radiation, followed by ACTH, LH and FSH whereas TSH remains at a probability of damage of 30% even after a follow up period of 10 years. Insulin-like growth factor 1 (IGF-1) or somatomedin C, is a good surrogate parameter for growth hormone, shows less pulsatile fluctuations and is thought to function as a long term marker of GH levels. IGF-1 levels depend on sex, age, body mass index and stress levels. METHODS: We measured cross- sectionally IGF-1 serum levels of 75 HGG patients having undergone standard radiochemotherapy with Temozolomide. RESULTS: We measured IGF-1 in 75 patients having been treated for malignant glioma by standard chemoradiation therapy. The delay since diagnosis ranged from 4 months to seven years, in median 15 months. There were 33 women and 42 men, aged 19 to 76 years (in median 53 years). The IGF-1 levels ranged from 50 to 461 ng/ml. Interestingly, in most patients, IGF-1 levels were increased or within the normal range. Only two patients showed low levels, as would be awaited in case of growth hormone deficiency. CONCLUSIONS: In contrast to awaited deficiencies to lowering of growth hormone, IGF-1 levels were not decreased in patients with high grade gliomas after radiotherapy.
Na + , HCO 3 − -cotransporter NBCn1 increases pH i gradients, filopodia, and migration of smooth muscle cells and promotes arterial remodelling
Authors: Ebbe Boedtkjer, Jacob F. Bentzon, Vibeke S. Dam, Christian Aalkjaer
Journal: Cardiovascular Research (2016)

Abstract Aims Arterial remodelling can cause luminal narrowing and obstruct blood flow. We tested the hypothesis that cellular acid–base transport facilitates proliferation and migration of vascular smooth muscle cells (VSMCs) and enhances remodelling of conduit arteries. Methods and results N a + , HC O 3 − -cotransport via NBCn1 (Slc4a7) mediates net acid extrusion and controls steady-state intracellular pH (pH i ) in VSMCs of mouse carotid arteries and primary aortic explants. Carotid arteries undergo hypertrophic inward remodelling in response to partial or complete ligation in vivo , but the increase in media area and thickness and reduction in lumen diameter are attenuated in arteries from NBCn1 knock-out compared with wild-type mice. With CO2/HCO3− present, gradients for pH i (∼0.2 units magnitude) exist along the axis of VSMC migration in primary explants from wild-type but not NBCn1 knock-out mice. Knock-out or pharmacological inhibition of NBCn1 also reduces filopodia and lowers initial rates of VSMC migration after scratch-wound infliction. Interventions to reduce H + -buffer mobility (omission of CO2/HCO3− or inhibition of carbonic anhydrases) re-establish axial pH i gradients, filopodia, and migration rates in explants from NBCn1 knock-out mice. The omission of CO2/HCO3− also lowers global pH i and inhibits proliferation in primary explants. Conclusion Under physiological conditions (i.e. with CO2/HCO3− present), NBCn1-mediated HCO3− uptake raises VSMC pH i and promotes filopodia, VSMC migration, and hypertrophic inward remodelling. We propose that axial pH i gradients enhance VSMC migration whereas global acidification inhibits VSMC proliferation and media hypertrophy after carotid artery ligation. These findings support a key role of acid–base transport, particularly via NBCn1, for development of occlusive artery disease.
Are We Mortgaging the Medical Profession?
Authors: Robert G. Hughes, Dianne C. Barker, Richard C. Reynolds
Journal: New England Journal of Medicine (1991)

AMONG young physicians with outstanding debts for their medical education at the time of graduation, the average debt was $46,224 in 1990, an increase of 77 percent since 1980, after adjustment for inflation.1 The increase in debt burden is of concern to medical educators, health policy makers, and of course medical students and physicians themselves.2 , 3 Medical school tuition is the single most important reason for the precipitous increase in the indebtedness of young physicians. The median tuition for state residents at public medical schools was $5,810 for the 1989—1990 academic year; the corresponding figure for private medical schools was $17,794. . . .
P-086 Trastuzumab induced cardiotoxicity in Her2 positive metastatic oeso-gastric cancers
Authors: Y. Eusen, J. Martin-Babau, C. Verveur, F. Trouboul, C. Cheneau, V. Jestin-Le Tallec, H. Simon, J.-P. Metges
Journal: Annals of Oncology (2015)
Forty-year follow-up of United States prisoners of war
Authors: J C Kluznik, N Speed, C Van Valkenburg, R Magraw
Journal: American Journal of Psychiatry (1986)

The authors performed structured psychiatric examinations of 188 former prisoners of war (POWs). Sixty-seven percent had had posttraumatic stress disorder. Of those affected, 29% had fully recovered, 39% still reported mild symptoms, 24% had improved but had moderate residual symptoms, and 8% had had no recovery or had deteriorated. Presence of posttraumatic stress disorder was not significantly correlated with other mental disorders. Delayed onset was not seen. The findings confirm the DSM-III concept of and criteria for posttraumatic stress disorder.
Rapid Diagnosis of Cytomegalovirus Infection in Infants by Electron Microscopy
Authors: Francis K. Lee, André J. Nahmias, Sergio Stagno
Journal: New England Journal of Medicine (1978)

Electron microscopy was applied to the diagnosis of cytomegalovirus infection in infants; we used the pseudoreplica method, which permits detection of herpesvirus particles within 15 to 30 minutes. Viruses were most readily detectable in urines with infectivity titers ≥104 per milliliter (95 per cent correlation with the tissue-culture method). Virus particles were detected in 18 of 20 urines obtained from symptomatic or asymptomatic, congenially or postnatally acquired cytomegalovirus infections in infants younger than six months. Viruses were demonstrated in six of 14 infants older than six months, whose urines usually contained <104 per milliliter. All five oral specimens examined by electron microscopy were also positive. Viruses were readily detectable in specimens stored or shipped at 4°C for several days, thus permitting physicians anywhere to obtain confirmation of a herpesvirus infection (presumably cytomegalovirus) within one to two days. (N Engl J Med 299:1266–1270, 1978)
Diagnostic Significance of Hyperuricemia in Arthritis
Authors: Arthur I. Grayzel, Lois Liddle, J. E. Seegmiller
Journal: New England Journal of Medicine (1961)

THE combination of an elevated serum urate level and joint symptoms that are atypical for classic gouty arthritis presents a familiar diagnostic problem to the clinician. Failure to consider the urate-retaining action of some commonly used drug such as salicylate in low doses1 or chlorothiazide or hydrochlorothiazide2 , 3 may cause this problem to be more frequent than it need be.In a recent study4 30 per cent of 737 patients seen at a rheumatic-disease hospital were found to have serum urate levels greater than 6 mg. per 100 ml. No explanation could be found for the hyperuricemia in a quarter of . . .
Frequency of Pleural Effusions in Mycoplasma and Viral Pneumonias
Authors: Norman L. Fine, Lawrence R. Smith, Patrick F. Sheedy
Journal: New England Journal of Medicine (1970)

A prospective study was undertaken to investigate the often-denied frequency of pleural effusions in mycoplasma and viral pneumonias. Fifty-nine patients with nonbacterial pneumonias satisfied serologic criteria for association with either a mycoplasma, viral, or cold-agglutinin-positive pneumonia. Twelve of these patients had roentgenographic evidence of pleural effusions. Four patients had no evidence of fluid on routine posteroanterior and lateral views, but pleural fluid was demonstrated on the lateral decubitus views. The possibility of a mycoplasma pneumonitis should not be dismissed merely because of the presence of a pleural effusion.
Screening Patients with Insulin-Dependent Diabetes Mellitus for Adrenal Insufficiency
Authors: Karl W. Brewer, Vincent S. Parziale, George S. Eisenbarth
Journal: New England Journal of Medicine (1997)

Zhang et al. (Feb. 27 issue) 1 present data confirming the finding of the Study of Osteoporotic Fractures Research Group 2 that increased bone mass in postmenopausal women is associated with an increased risk of subsequent breast cancer.However, I am concerned about the accuracy of the multivariate-adjusted rate ratios that Zhang et al. report.The authors included 10 variables in addition to bone mass in their multivariate model.Since the number of observed events (i.e., cases of breast cancer) was only 91, the ratio of the number of events to the number of variables is less than 10.As a rule of thumb, this ratio should be at least 10 in order to prevent overfitting. 3Models that are overfitted may give results that are numerically unstable and too dependent on the observed data. 4This may be evidenced by overly large coefficients or standard errors.Can the authors allay this concern by indicating the estimated coefficients and standard errors or perhaps by repeating the analysis after omitting some of the less important variables?In addition, perhaps the authors could indicate whether they checked their model for goodness of fit and for conformity to the assumption of proportional hazards.
Abstract 2082: Control and function of the PROX1 transcription factor in malignant glioma
Authors: Kaveh M. Goudarzi, Tamador Elsir, Monica Nistér, Mikael S. Lindström
Journal: Cancer Research (2015)

Abstract Malignant gliomas remain to be fatal and highly resistant to therapy. PROX1 is a transcription factor critical for embryonic development, with a role in cell cycle control and progenitor cell differentiation. PROX1 is highly relevant to study in relation to brain tumors due to its role in normal CNS development, where it leads to progenitor cell differentiation and initiation of neurogenesis. We have previously shown that PROX1 is expressed in human gliomas where there is a positive and statistically significant correlation between PROX1 expression and glioma tumor grade. We have also evaluated the prognostic value of PROX1 in a cohort of patients with grade II gliomas and found that a high number of PROX1 positive cells correlated significantly with poor outcome, a clinically important finding, as such predictors do not exist at present. The mechanism behind PROX1 overexpression in high-grade glioma and its functional consequences remain unclear. To this end we set out to study PROX1 effects on the behavior of glioma cells. We found that glioma cell lines in general expressed only low levels of PROX1 protein and mRNA. However, PROX1 was readily detected in the U343MGa Cl2:6 glioma cell line. This cell line also expresses GFAP and SOX2 and has features in common with glioma stem cells. Depletion of PROX1 in U343MGa Cl2:6 cells using siRNA had a marginal positive effect on cell proliferation in a short term assay. Furthermore, ectopic PROX1 impaired the ability of glioma cells to proliferate as indicated by reduced colony formation and decreased BrdU incorporation. We present experimental evidence showing that PROX1 induces p27. By regulating p27, PROX1 may block the activity of Cdk2/Cyclin E complex, and thus inhibit cell cycle progression. The functional consequences of PROX1 expression on the stemness, migration, and invasion phenotypes of glioma cells remain to be further investigated and preliminary results will be presented. Citation Format: Kaveh M. Goudarzi, Tamador Elsir, Monica Nistér, Mikael S. Lindström. Control and function of the PROX1 transcription factor in malignant glioma. [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 2082. doi:10.1158/1538-7445.AM2015-2082
Activating Mutations of the Stimulatory G Protein in the McCune–Albright Syndrome
Authors: Lee S. Weinstein, Andrew Shenker, Pablo V. Gejman, Maria J. Merino, Eitan Friedman, Allen M. Spiegel
Journal: New England Journal of Medicine (1991)

The McCune-Albright syndrome is a sporadic disease characterized by polyostotic fibrous dysplasia, café au lait spots, sexual precocity, and hyperfunction of multiple endocrine glands. These manifestations may be explained by a somatic mutation in affected tissues that results in activation of the signal-transduction pathway generating cyclic AMP (cAMP). We analyzed DNA from tissues of patients with the McCune-Albright syndrome for the presence of activating mutations of the gene for the a subunit of the G protein (Gsα) that stimulates cAMP formation.
The Relation between Blood Pressure and Mortality Due to Coronary Heart Disease among Men in Different Parts of the World
Authors: Peggy C.W. van den Hoogen, Edith J.M. Feskens, Nico J.D. Nagelkerke, Alessandro Menotti, Aulikki Nissinen, Daan Kromhout
Journal: New England Journal of Medicine (2000)

Elevated blood pressure is known to be a risk factor for death from coronary heart disease (CHD). However, it is unclear whether the risk of death from CHD in relation to blood pressure varies among populations.
College Women and Condom Use, 1975–1995
Authors: Jeffrey F. Peipert, Lisa Domagalski, Lori Boardman, Maxim Daamen, Stephen H. Zinner, William M. McCormack
Journal: New England Journal of Medicine (1996)

To the Editor: We surveyed the frequency of condom use in 1995 by 147 women at a private university in New England and compared it with that reported previously in the Journal for 486 women surveyed in 1975, 161 women surveyed in 1986, and 132 women surveyed in 1989 at the same university health service.1 Each participant completed the same anonymous questionnaire. The key question was “When you have intercourse, how often does your partner use a condom?” The women studied in 1995 did not differ significantly from the earlier groups with respect to age (mean age of the 1995 . . .
The Risk of Breast Cancer after Irradiation of the Thymus in Infancy
Authors: Nancy G. Hildreth, Roy E. Shore, Philip M. Dvoretsky
Journal: New England Journal of Medicine (1989)

It is well established that exposure to ionizing radiation during or after puberty increases a woman's risk for breast cancer, but it is less clear whether exposure to ionizing radiation very early in life is also carcinogenic. We studied the incidence of breast cancer prospectively in a cohort of 1201 women who received x-ray treatment in infancy for an enlarged thymus gland and in their 2469 nonirradiated sisters. After an average of 36 years of follow-up, there were 22 breast cancers in the irradiated group and 12 among their sisters, yielding an adjusted rate ratio of 3.6 (95 percent confidence interval, 1.8 to 7.3). The estimated mean absorbed dose of radiation to the breast was 0.69 Gy. The first breast cancer was diagnosed 28 years after irradiation. The dose–response relation was linear (P<0.0001), with a relative risk of 3.48 for 1 Gy of radiation (95 percent confidence interval, 2.1 to 6.2) and an additive excess risk of 5.7 per 104 person-years per gray (95 percent confidence interval, 2.9 to 9.5). We conclude that exposure of the female breast to ionizing radiation in infancy increases the risk of breast cancer later in life. (N Engl J Med 1989; 321:1281–4.)
Nonsurgical Treatment of Severe Hypertension Due to Renal-Artery Intimal Fibroplasia by Percutaneous Transluminal Angioplasty
Authors: Victor G. Millan, William E. Mast, Nicolaos E. Madias
Journal: New England Journal of Medicine (1979)

RENAL vascular surgery and pharmacotherapy are the are the two modalities currently employed, singly or in combination, in the management of renovascular hypertension.1 2 3 Although both methods have been used successfully in the treatment of this disorder, both have substantial drawbacks. Renovascular operations carry a consequential operative risk, have a substantial failure rate and are expensive.1 2 3 4 5 6 Furthermore, the suitability of this method of treating renovascular disease is clearly limited by the usually progressive and frequently bilateral nature of the dis-, order.1 , 2 On the other hand, pharmacotherapy of renovascular hypertension has such disadvantages as poor compliance, drug side effects and a sizable . . .
Metronomic therapy irinotecan (IRI) capecitabine (CAP) plus bevacizumab (BEV) in treatment of advanced colorectal cancer (ACRC) in very elderly people.
Authors: I. U. Carreca, F. Bellomo, S. L. Burgio, G. Pernice, D. Piazza, L. Balducci
Journal: Journal of Clinical Oncology (2010)

3552 Background: ACRC is one of most common neoplastic disease in very old pts. The administration of oral fluoropyrimidine (capecitabine-CAP) in a standard schedule of 1,200 mg/sqm twice a day for 14 d shows similar effects to 5-FU continuous infusion (C.I.). Furthermore, CAP- IRI showed super -additive antitumor activity. Recently many study show the safety and efficacy of a “flat dose” administration of CAP particularly in the treatment of elderly people with cancer. Also, the efficacy of BEV is well demonstrated in CRC pts. Aim of the study is to evaluate impact of bevacizumab (BEV) in combination with IRI and XEL in ACRC very old patients. Methods: 42 (20 f-22 m) elderly patients with advanced colorectal cancer (median age: 77; range: 73-91) were enrolled. Comprehensive Geriatric Assessment (CGA) was performed to assess eligibility for chemotherapy. All Patients were included into groups I, according to Balducci's classification of frailty. Primary endpoint: clinical response rates (RR) according to RECIST criteria and toxicity profile using NCI-CTC v2.0. Secondary endpoints: PFS, OS and QoL score measured through EORTC QLQ-C30 questionnaires. All patients were evaluated for common treatment-related adverse events with regard to haematological and liver toxicity, nausea and vomiting, stomatitis, diarrhea, hand/foot syndrome and sensory neuropathy, according to the ECOG Common Toxicity Criteria. Results: Patients were treated with IRI (180 mg/mq) + BEV (7.5 mg/Kg) on day 1q21, and XEL (fixed dose of 1,000 mg bid) assumed orally continuously for a maximum of 12 cycles. Medium value of cycles delivered was 9.7. Tumor response rates observed were 37.1% (CR+PR). Clinical benefit, including stable disease, was 77.8%. No grade 4 toxicity was experienced. QoL score improvement was noted in all pts after treatment. Median PFS was 12.3 months with a 6 months PFS rate of 82%. Median OS was 22 months with a 12 months survival probability of 77.8%. Conclusions: In elderly ACRC BEV plus IRI every 3 weeks with CAP continuously show a good toxicity and effectiveness profile and seem to be a valid terapeutical opportunity also for ACRC very old patients. No significant financial relationships to disclose.
Distribution and Significance of Asian and Other Influenza Antibodies in the Human Population
Authors: Maurice R. Hilleman, Frederick J. Flatley, Sally A. Anderson, Mary L. Luecking, Doris J. Levinson
Journal: New England Journal of Medicine (1958)

ITNFECTION in man with influenza virus is followed by the genesis of antibody and resultant immunity. Such antibody is relatively strain specific and reflects prior experience with influenza virus according to antigenic family and subgroup as well as to type. Examination of serum samples from various segments of the population for antibody spectrum is important, therefore, in the retrospective sense in judging past occurrence of a particular virus in the group and, in the predictive sense, in appraising the probable future occurrence of the virus in the population. Previous reports from this1 and other laboratories2 , 3 have recorded the spectrum of . . .
Pulmonary Dysfunction in Systemic Lupus Erythematosus
Authors: Chin-Tang Huang, Gordon R. Hennigar, Harold A. Lyons
Journal: New England Journal of Medicine (1965)

ABNORMALITIES of respiratory function have been observed in scleroderma.1 2 3 4 5 However, little attention has been paid to the study of the pulmonary function of patients with systemic lupus erythematosus. This omission is strange in view of the high incidence of radiologic abnormalities observed on x-ray films of the chest and the widespread distribution of the disease. Although it was assumed that some abnormalities would be detected on a study of pulmonary function, an unexpected frequency of findings was obtained.The purpose of the present investigation was to study the pulmonary function of patients with systemic lupus erythematosus and to determine whether . . .