tbuckley/cabot-search huggingface dataset:
Adulthood asthma after wheezing in infancy: a questionnaire study at 27 years of age
Authors: M. Ruotsalainen, E. Piippo‐Savolainen, M. K. Hyvärinen, M. Korppi
Journal: Allergy (2009)

Wheezing in early childhood is a heterogeneous condition, the longterm prognosis varying from total recovery to chronic asthma. Though short-term outcome has been actively studied, there is lack of data on long-term outcome until adulthood. The aim of the study was to evaluate the prevalence and risk factors of asthma at 26-29 years of age after early-life wheezing.At the median age of 27.3 years (range 26.3-28.6), a questionnaire was sent to 78 study subjects hospitalized for wheezing at <24 months of age, and 59 (76%) answered. Asthma, allergy and weight status were compared with selected controls followed up from birth and with non-selected population controls recruited for this adulthood study.Doctor-diagnosed asthma was present in 20% of the former bronchiolitis patients, compared with 5% in the two control groups (OR 2.1, 95% CI 0.3-17.9 vs selected controls; OR 5.2, 95% CI 1.7-15.8 vs nonselected controls). The respective figures for current self-reported asthma were 41% and 7-10% (OR 11.4, 95% CI 2.3-56.1 vs selected controls; OR 12.2, 95% CI 4.4-33.7 vs nonselected controls). Current allergic rhinitis and current smoking were significantly associated with asthma, but current overweight or obesity was not. In multivariate analyses, early-life wheezing was an independent risk factor of adulthood asthma.An increased asthma risk in early-life wheezers continues, even after many symptom-free years at school age, at least until 27 years of age.
Risk factors for death in complicated diarrhoea of children.
Authors: A R Samadi, A I Chowdhury, M I Huq, N S Shahid
Journal: BMJ (1985)

A total of 1330 children with complicated diarrhoea who were admitted to the general ward of the International Centre for Diarrhoeal Diseases Research, Bangladesh Health Complex, during 1979 were examined. The risk of death by complication of diarrhoea, aetiology, age, and nutritional state was analysed by a logit regression model. Serum sodium concentration and coma were found to be significant predictors of death, death being related directly to coma and inversely to serum sodium concentration. An earlier study had shown that the incidence of hyponatraemia was directly related to the degree of malnutrition, but the results of logit regression analysis did not show the nutritional state to be a predictor of death. Owing to lack of data, however, serum albumin concentration could not be taken as a variable in the logit regression analysis. To determine the relation of serum albumin concentration to hyponatraemia and the cause of death in hyponatraemia further prospective studies would be necessary.
Vitamins C and E and the Risks of Preeclampsia and Perinatal Complications
Authors: Alice R. Rumbold, Caroline A. Crowther, Ross R. Haslam, Gustaaf A. Dekker, Jeffrey S. Robinson
Journal: New England Journal of Medicine (2006)

Supplementation with antioxidant vitamins has been proposed to reduce the risk of preeclampsia and perinatal complications, but the effects of this intervention are uncertain.We conducted a multicenter, randomized trial of nulliparous women between 14 and 22 weeks of gestation. Women were assigned to daily supplementation with 1000 mg of vitamin C and 400 IU of vitamin E or placebo (microcrystalline cellulose) until delivery. Primary outcomes were the risks of maternal preeclampsia, death or serious outcomes in the infants (on the basis of definitions used by the Australian and New Zealand Neonatal Network), and delivering an infant whose birth weight was below the 10th percentile for gestational age.Of the 1877 women enrolled in the study, 935 were randomly assigned to the vitamin group and 942 to the placebo group. Baseline characteristics of the two groups were similar. There were no significant differences between the vitamin and placebo groups in the risk of preeclampsia (6.0 percent and 5.0 percent, respectively; relative risk, 1.20; 95 percent confidence interval, 0.82 to 1.75), death or serious outcomes in the infant (9.5 percent and 12.1 percent; relative risk, 0.79; 95 percent confidence interval, 0.61 to 1.02), or having an infant with a birth weight below the 10th percentile for gestational age (8.7 percent and 9.9 percent; relative risk, 0.87; 95 percent confidence interval, 0.66 to 1.16).Supplementation with vitamins C and E during pregnancy does not reduce the risk of preeclampsia in nulliparous women, the risk of intrauterine growth restriction, or the risk of death or other serious outcomes in their infants. (Controlledtrials.com number, ISRCTN00416244.).
Medical Instruction of the Laity in the Lay Press.
Authors: Thos. H. Shastid
Journal: JAMA (1897)

Galesburg, Ill., April 13, 1897. <h3>To the Editor:</h3> —It is certainly unwise for physicians to attempt professional instruction of the laity in the lay press by means of signed articles. In the first place, such articles blur the distinctions between their writers and advertising charlatans; in the second place, the tendency in such articles is to say the brilliant rather than the true. Yet, after all, should not the laity be instructed medically in the lay press? By all means. The instruction in physiology and hygiene presented in the common schools is distinctly inadequate and is, moreover, imparted to the learner at a time of his life when he can not by any possibility correctly estimate its importance and therefore the necessity of remembering it far on into later years. Besides, in the common schools practically nothing is said of disease. It might be urged that the less the laity
1080-64 Late total occlusion versus treatment failure without late thrombotic occlusion in patients after intracoronary radiation: Angiographic and clinical outcomes
Authors: Roswitha Wolfram, Gary Mintz, Neil J Weissman, Pramod K Kuchulakanti, Seung-Woon Rha, Eduard Cheneau, George Aggrey, Maureen C Abbott, Natalie Gevorkian, Ellen E Pinnow, Ron Waksman
Journal: Journal of the American College of Cardiology (2004)
Southampton--some first-year experiences.
Authors: D Acheson
Journal: BMJ (1972)

He was treated symptomatically and a week later had improved.Nine months later he appeared with bronchitis, his chest x-ray film being normal.A month later he had a sudden painless haema- turia and an I.V.P. showed a constant filling defect in the left side of the bladder.Subsequent cystoscopy showed a small tumour projecting into the bladder on the summit of a mass which proved to be an adenocarcinoma arising from the bowel.The liver was enlarged 3 in (7 5 cm) below the costal margin and this was considered an inoperable growth.He progressed steadily downhill and died five months later.Mr. G. H., aged 63, was a hardy perennial who attended the surgery on an average of 20 times a year over a space of 20 years.Most of his visits were for cervical spondylosis and abdominal pain which was invariably "agonizing".He had had three barium meals in all, and carcinoma of the colon was not suspected until two years ago, when, however, a barium enema and sigmoidoscopy were normal.Six months ago he was admitted to the district hospital with abdominal pain, but apart from a loaded colon no positive findings were made; rectal examination at that time was normal.Two months later he was finally re- admitted and a diagnostic laparotomy was performed, at which an inoperable carcinoma of the sigmoid colon was discovered.This is a pretty dispiriting collection.In a small town and rural area we have a dual relationship with many patients, who may be friends or may supply us with the necessities of life ranging from milk, papers, or groceries to emptying the dust- bins.We live at close quarters with our failures-or their memory-and any advice you can give us on the earlier diagnosis of what seems to be an increasingly common tumour will be most welcome.
THE HOSPITAL, THE MEDICAL COLLEGE AND THE INTERN
Authors: A. C. BACHMEYER
Journal: JAMA (1931)

There is general recognition of the fact that the period which the medical graduate devotes to internship is one of the most valuable in his whole career. The medical college, the hospital and the intern are all vitally interested in the subject.  The medical college has as its most important function the preparation of young men and women for the general practice of medicine. It takes the student after several years of college preparation, consisting largely of elementary training in the sciences, and endeavors to give him as thorough instruction as the time will permit in those fundamental sciences that underly the practice of the profession. They further endeavor to give him an introduction to the theory and practice of clinical medicine. After at least six years of instruction the student comes to the end of his college course. His career thus far has not only been a succession of
Pan-cancer patterns of somatic copy number alteration
Authors: Travis I Zack, Steven E Schumacher, Scott L Carter, Andrew D Cherniack, Gordon Saksena, Barbara Tabak, Michael S Lawrence, Cheng-Zhong Zhang, Jeremiah Wala, Craig H Mermel, Carrie Sougnez, Stacey B Gabriel, Bryan Hernandez, Hui Shen, Peter W Laird, Gad Getz, Matthew Meyerson, Rameen Beroukhim
Journal: Nature Genetics (2013)

Determining how somatic copy number alterations (SCNAs) promote cancer is an important goal. We characterized SCNA patterns in 4,934 cancers from The Cancer Genome Atlas Pan-Cancer data set. Whole-genome doubling, observed in 37% of cancers, was associated with higher rates of every other type of SCNA, TP53 mutations, CCNE1 amplifications and alterations of the PPP2R complex. SCNAs that were internal to chromosomes tended to be shorter than telomere-bounded SCNAs, suggesting different mechanisms underlying their generation. Significantly recurrent focal SCNAs were observed in 140 regions, including 102 without known oncogene or tumor suppressor gene targets and 50 with significantly mutated genes. Amplified regions without known oncogenes were enriched for genes involved in epigenetic regulation. When levels of genomic disruption were accounted for, 7% of region pairs were anticorrelated, and these regions tended to encompass genes whose proteins physically interact, suggesting related functions. These results provide insights into mechanisms of generation and functional consequences of cancer-related SCNAs.
Increased prevalence of fatty liver in arterial hypertensive patients with normal liver enzymes: role of insulin resistance
Authors: G Donati
Journal: Gut (2004)

<b>Background:</b> The conditions associated with fatty liver disease presenting with normal liver enzymes and the mechanism involved in its development remain to be fully elucidated. <b>Aims:</b> The aim of the present study was to test the hypothesis that fatty liver with normal liver enzymes occurs more frequently in arterial hypertensive patients and to establish whether this condition is associated with insulin resistance. <b>Patients:</b> A total of 55 non-obese, non-diabetic, non-heavy alcohol drinking patients with arterial hypertensive and normal liver enzymes and 55 sex and age matched healthy subjects were enrolled into the study. <b>Methods:</b> Plasma metabolic parameters, body mass index, and the presence of fatty liver were investigated. Insulin resistance was estimated from plasma insulin and glucose as the homeostasis model assessment index. Stepwise logistic regression and multivariate regression analysis were used on the combined sample to identify variables independently associated with fatty liver and insulin resistance. <b>Results:</b> Hypertensive patients had a significantly higher prevalence of fatty liver (30.9% <i>v</i> 12.7%; p&lt;0.041), higher insulin resistance (mean 2.27 (SD 1.81) <i>v</i> 1.56 (0.70); p = 0.022), and slightly higher body mass index (24.9 (3.0) <i>v</i> 24.0 (2.2); p = 0.043) than controls. Multivariate logistic regression identified insulin resistance (odds ratio 1.66 (95% confidence interval (CI) 1.03–2.52)) and body mass index (OR 1.22 (95% CI 1.00–1.49)) as factors independently associated with fatty liver. Multivariate regression analysis showed insulin resistance to be predicted by alanine transaminase (p = 0.002), presence of arterial hypertension (p = 0.029), and body mass index (p = 0.048). <b>Conclusion:</b> The higher prevalence of non-alcoholic fatty liver in non-obese hypertensive patients with normal liver enzymes appears to be related to increases in insulin resistance and body weight.
Splenomegaly, Analgesic Ingestion and Renal Disease
Authors: Christopher C. Fordham, William D. Huffines
Journal: New England Journal of Medicine (1967)

ADMINISTRATION of phenacetin (acetophenetidin) by gavage to pair-fed Sprague–Dawley rats for four weeks has resulted in the consistent production of renal lesions as previously described.1 These studies have disclosed, in addition, consistent enlargement of the spleen in the drug-fed, as compared with control, animals, as shown in Table 1. Grossly, the spleen is notably enlarged and dark in color in comparison with the appearance in the control animals, and on histologic study, there is marked deposition of pigment in the spleen that has affinity for iron stains.The splenomegaly produced in this experimental setting appears to be reversible. When the drug . . .
On Choosing a Surgeon
Authors: Donald Munro
Journal: New England Journal of Medicine (1958)

A MAN, aged 70 years, consulted a physician because of pain during urination. The physician, a general practitioner, had been recommended to him by friends. According to local reports the former had a good reputation in the middle-sized manufacturing city in which they all lived.The physician told the patient that he had blood in his urine and treated him with pills to be taken by mouth. No examination other than that of the urine was made. This therapy continued for twelve months, by which time the patient had had so much bladder and urination pain that he demanded more . . .
Progestin Prophylaxis of Osteoporosis
Authors: Christa Nadjafi
Journal: JAMA (1983)

<h3>To the Editor.—</h3> I have read the question "Osteoporosis Prophylaxis in a Postmastectomy Patient?" and the two answers in the QUESTIONS AND ANSWERS section (1982;248:1108) and would like to draw attention to the possibility of progestogen prophylaxis of osteoporosis. If estrogens are contraindicated, progestogens alone may prove helpful and should be prescribed for such patients. Norethindrone, 5 mg/day, is recommended by Nordin et al,<sup>1</sup>since it has been demonstrated that 5 mg of norethindrone is effective in reducing calcium excretion in the urine.<sup>2</sup>Norethindrone or norethindrone acetate has been found useful as endocrine treatment in patients with breast cancer and can, therefore, be prescribed for osteoporosis prophylaxis if considered necessary.
Metabolic Dysfunction Drives a Mechanistically Distinct Proinflammatory Phenotype in Adipose Tissue Macrophages
Authors: Mario Kratz, Brittney R. Coats, Katherine B. Hisert, Derek Hagman, Vesco Mutskov, Eduard Peris, Kelly Q. Schoenfelt, Jessica N. Kuzma, Ilona Larson, Peter S. Billing, Robert W. Landerholm, Matthew Crouthamel, David Gozal, Seungmin Hwang, Pradeep K. Singh, Lev Becker
Journal: Cell Metabolism (2014)
Diminished Renal Urate Secretion Per Nephron As a Basis for Primary Gout
Authors: RICHARD E. RIESELBACH
Journal: Annals of Internal Medicine (1970)

In order to examine the role of the kidney in the pathogenesis of primary gout, the rate of uric acid turnover and renal transport were studied in 15 gouty patients. Uric acid turnover data from nine control subjects were the basis for classifying gouty patients as either overproducers or normoproducers. The pyrazinamide suppression test provided comparison of renal rates of urate reabsorption and secretion between the two groups in the presence of both endogenous hyperuricemia and allopurinol-induced normouricemia. Both groups had a normal pattern of urate reabsorption over a wide range of filtered loads. However, whereas the pattern of urate secretion in gouty overproducers could not be distinguished from previously published data in normals, diminished urate secretion was evident in normoproducers during hyperuricemia. This insufficient secretory response may limit the capacity for urate homeostasis and thereby provide the basis for hyperuricemia in some patients with primary gout without demonstrable overproduction of uric acid.
Molecular Mechanism of a Frequent Genetic Form of Deafness
Authors: Vincent Michel, Jean-Pierre Hardelin, Christine Petit
Journal: New England Journal of Medicine (2003)

To the Editor: The genes encoding the two major connexins of the cochlea are contiguous on human chromosome 13 (GJB2 and GJB6) and on mouse chromosome 14 (Cx26 and Cx30, respectively). Biallelic GJ...
Human J chain gene. Structure and expression in B lymphoid cells.
Authors: E E Max, S J Korsmeyer
Journal: The Journal of Experimental Medicine (1985)

As part of an ongoing investigation of the regulation of gene expression in B cell development, we have obtained a genomic DNA clone encoding the human J chain protein. The nucleotide sequence of exons encoding the mature protein defines a 137 amino acid primary sequence similar to that previously determined at the protein level. Probes from the gene have been used to analyze J chain expression in human cell lines corresponding to pre-B and B lymphocytes. J chain RNA was detected in two of six human pre-B cell lines and in 8 of 10 B cell lines expressing various Ig isotypes. The expression of the J chain gene is, thus, not tightly linked to IgM or IgA secretion. Our data do not, however, support the recent suggestion (7) that synthesis of J chain precedes that of mu chain in B lymphocyte differentiation. Because of the presence of nine candidate polyadenylation signals (AATAAA or AATTAAA) downstream of the C-terminal coding block of the J chain gene, the 3' end of the gene could not be determined from sequence data alone. To define the 3' end, J chain RNA from a human B lymphocyte line was used to protect an end-labelled DNA fragment from S1 nuclease digestion. The sequence 40 basepairs 5' of the functional polyadenylation site identified by these S1 experiments is homologous the same region of a previously reported mouse J chain complementary DNA clone.
A Novel Therapeutic Combination Using PD 0332991 and Bortezomib: Study in the 5T33MM Myeloma Model
Authors: Eline Menu, Josefina Garcia, Xiangao Huang, Maurizio Di Liberto, Peter L. Toogood, Isan Chen, Karin Vanderkerken, Selina Chen-Kiang
Journal: Cancer Research (2008)

Abstract Multiple myeloma (MM) remains incurable partly because no effective cell cycle–based therapy has been available to both control tumor cell proliferation and synergize with cytotoxic killing. PD 0332991 is an orally active small molecule that potently and specifically inhibits Cdk4 and Cdk6. It has been shown to induce rapid G1 cell cycle arrest in primary human myeloma cells and suppress tumor growth in xenograft models. To improve therapeutic targeting of myeloma progression, we combined tumor suppression by PD 0332991 with cytotoxic killing by bortezomib, a proteasome inhibitor widely used in myeloma treatment, in the immunocompetent 5T33MM myeloma model. We show that 5T33MM tumor cells proliferate aggressively in vivo due to expression of cyclin D2, elevation of Cdk4, and impaired p27Kip1 expression, despite inhibition of Cdk4/6 by p18INK4c and the maintenance of a normal plasma cell transcription program. PD 0332991 potently inhibits Cdk4/6-specific phosphorylation of Rb and cell cycle progression through G1 in aggressively proliferating primary 5T33MM cells, in vivo and ex vivo. This leads to tumor suppression and a significant improvement in survival. Moreover, induction of G1 arrest by PD 0332991 sensitizes 5T33MM tumor cells to killing by bortezomib. Inhibition of Cdk4/6 by PD 0332991, therefore, effectively controls myeloma tumor expansion and sensitizes tumor cells to bortezomib killing in the presence of an intact immune system, thereby representing a novel and promising cell cycle–based combination therapy. [Cancer Res 2008;68(14):5519–23]
Phase 1b Randomized Study of Antidote-Controlled Modulation of Factor IXa Activity in Patients With Stable Coronary Artery Disease
Authors: Mark Y. Chan, Mauricio G. Cohen, Christopher K. Dyke, Shelley K. Myles, Laura G. Aberle, Min Lin, James Walder, Steven R. Steinhubl, Ian C. Gilchrist, Neal S. Kleiman, David A. Vorchheimer, Nicholas Chronos, Chiara Melloni, John H. Alexander, Robert A. Harrington, Ross M. Tonkens, Richard C. Becker, Christopher P. Rusconi
Journal: Circulation (2008)

Whether selective factor IXa inhibition produces an appropriate anticoagulant effect when combined with platelet-directed therapy in patients with stable coronary artery disease is unknown. REG1 consists of RB006 (drug), an injectable RNA aptamer that specifically binds and inhibits factor IXa, and RB007 (antidote), the complementary oligonucleotide that neutralizes its anti-IXa activity.We evaluated the safety, tolerability, and pharmacodynamic profile of REG1 in a randomized, double-blind, placebo-controlled study, assigning 50 subjects with coronary artery disease taking aspirin and/or clopidogrel to 4 dose levels of RB006 (15, 30, 50, and 75 mg) and RB007 (30, 60, 100, and 150 mg). The median age was 61 years (25th and 75th percentiles, 56 and 68 years), and 80% of patients were male. RB006 increased the activated partial thromboplastin time dose dependently; the median activated partial thromboplastin time at 10 minutes after a single intravenous bolus of 15, 30, 50, and 75 mg RB006 was 29.2 seconds (25th and 75th percentiles, 28.1 and 29.8 seconds), 34.6 seconds (25th and 75th percentiles, 30.9 and 40.0 seconds), 46.9 seconds (25th and 75th percentiles, 40.3 and 51.1 seconds), and 52.2 seconds (25th and 75th percentiles, 46.3 and 58.6) (P<0.0001; normal 25th and 75th percentiles, 27 and 40 seconds). RB007 reversed the activated partial thromboplastin time to baseline levels within a median of 1 minute (25th and 75th percentiles, 1 and 2 minutes) with no rebound increase through 7 days. No major bleeding or other serious adverse events occurred.This is the first experience of an RNA aptamer drug-antidote pair achieving inhibition and active restoration of factor IXa activity in combination with platelet-directed therapy in stable coronary artery disease. The preliminary clinical safety and predictable pharmacodynamic effects form the basis for ongoing studies in patients undergoing elective revascularization procedures.