tbuckley/cabot-search huggingface dataset:
Absence of Cytochrome b<sub>-245</sub>in Chronic Granulomatous Disease
Authors: Anthony W. Segal, Andrew R. Cross, Rodolfo C. Garcia, Niels Borregaard, Niels H. Valerius, John F. Soothill, Owen T. G. Jones
Journal: New England Journal of Medicine (1983)

The heme-containing protein cytochrome b-245 has been proposed as a primary component of the microbicidal oxidase system of phagocytes that normally generates superoxide-free radicals but when defective is associated with chronic granulomatous disease. We measured this cytochrome in granulocytes from 27 patients with chronic granulomatous disease and from 64 members of their families. It was undetectable in all 19 of the men in whom the defect appeared to be located on the X chromosome. Female relatives who were heterozygous carriers had reduced concentrations of the cytochrome and variable proportions of cells that were unable to generate superoxide; these two characteristics were closely related (r = 0.93 in the 16 mothers and 0.85 in all 24 carriers, P less than 0.001). In contrast, in all eight patients (seven women) with a probable autosomal recessive inheritance the cytochrome was present but nonfunctional. The properties tested, including midpoint potential, carbon monoxide binding, and organelle distribution, were normal, but the cytochrome did not undergo reduction on cellular stimulation. Thus, absence or malfunction of the cytochrome b-245 may be the causal molecular defect in chronic granulomatous disease, implicating it in the microbicidal oxidase system.
Corticosteroids in women at risk of late preterm delivery may reduce respiratory complications in newborns
Authors: Susan Mayor
Journal: BMJ (2016)

Giving the corticosteroid betamethasone to women at risk of late preterm delivery may considerably reduce respiratory complications in their newborns, a randomised study has shown.1

Infants born at 34 to 36 weeks are at greater risk of respiratory and other complications than those born at 37 weeks or later. But data on what might help are limited because babies born at full term generally thrive, and it was previously assumed that they had not had the problems seen in babies born …
The McCune–Albright Syndrome
Authors: Michael A. Levine
Journal: New England Journal of Medicine (1991)

In 1937, McCune and Bruch1 and Albright and associates2 separately described an unusual syndrome characterized by polyostotic fibrous dysplasia, café au lait pigmentation, and in female patients, endocrine dysfunction with precocious puberty. Subsequent descriptions of this syndrome documented the occurrence of several other endocrine abnormalities, including hyperthyroidism, hypercortisolism, an excess of growth hormone, and hypophosphatemia. The triad of bone, skin, and endocrine abnormalities has come to constitute the classic McCune–Albright syndrome.The resemblance of the various components of the McCune–Albright syndrome to those of other, more common disorders has often invited comparison. The severity of the skeletal abnormalities varies widely. . . .
Transfusion Medicine — Blood Conservation
Authors: Lawrence T. Goodnough, Mark E. Brecher, Michael H. Kanter, James P. AuBuchon
Journal: New England Journal of Medicine (1999)

Preoperative Autologous Donation Preoperative autologous donation was rarely used before the recognition that HIV could be transmitted by blood transfusion. Fifteen years ago, fewer than 5 percent of eligible patients who were scheduled for elective surgery chose autologous blood donation.121 When public awareness of the possibility of transfusion-transmitted HIV became widespread, however, there was concern that too few patients were choosing autologous blood donation as an option. Several states, including California, passed legislation requiring that whenever it was "reasonably" likely that transfusion would be needed, a patient should be informed of all of the options regarding and alternatives to allogeneic . . .
In Support of a Linkage between the Funding of Graduate Medical Education and Care of the Indigent
Authors: Richard E. Rieselbach, Thomas C. Jackson
Journal: New England Journal of Medicine (1986)

Rapidly advancing trends establishing medical care as an economic product rather than a social good have created an unprecedented threat to our present highly developed system for the graduate education of physicians. These same forces are limiting the capacity of teaching hospitals to care for the medically indigent. In recent decades both graduate medical education and care of the indigent have been major concerns of teaching hospitals; nevertheless, there has been minimal financial interdependence of these activities. Innovations are now necessary in both areas in order to deal with the major obstacles that teaching hospitals face in meeting their commitment . . .
Abstract 704: Scaffold protein KSR1 is negatively regulated by merlin and promotes tumor development in merlin deficient tumors
Authors: Clemens O. Hanemann, Lu Zhou, Sylwia Ammoun, Edwin Lasonder, Vikram Sharma, Juergen Muller, Emanuela Ercolano
Journal: Cancer Research (2015)

Abstract Accumulated evidence suggests that the Ras/Raf/MEK/ERK pathway plays a crucial role in the development of Merlin-deficient tumours. However, the mechanism in which Merlin precisely suppresses this mitogenic signalling pathway has remained poorly understood. In addition, drug specificity, side effects and drug resistance are serious problems when treating patients with MEK inhibitors and therefore a more specific therapeutic target needs to be identified. Using our primary human in vitro model and three complementary approaches including lentiviral shRNA, active mutants and use of a clinically approved inhibitor, we report that Ras/Raf/MEK/ERK scaffold protein Kinase Suppressor of Ras 1 (KSR1) plays a vital role in promoting schwannoma proliferation, multipolar morphology and other pathological phenotypes. Proteomic analysis suggests that merlin shares multiple binding partners with KSR1 incl DCAF1 from the E3 Ubiquitin Ligase CRL4DCAF1, which is directly associated with and functionally inhibited by the tumour suppressor Merlin in the nucleus. Functional study suggests that KSR1 and DCAF1 might co-operate and/or complement to regulate schwannoma's proliferation. These findings demonstrate that Merlin disrupts Ras/Raf/MEK/ERK activity at the scaffold protein level and also suggest that KSR1 is a specific therapeutic target for Merlin-deficient tumours. Citation Format: Clemens O. Hanemann, Lu Zhou, Sylwia Ammoun, Edwin Lasonder, Vikram Sharma, Juergen Muller, Emanuela Ercolano. Scaffold protein KSR1 is negatively regulated by merlin and promotes tumor development in merlin deficient tumors. [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 704. doi:10.1158/1538-7445.AM2015-704
Case 3-2009
Authors: Michael F. Holick, Ruth Lim, Anand S. Dighe
Journal: New England Journal of Medicine (2009)

A 9-month-old boy was admitted to this hospital because of a generalized seizure and a bulging fontanelle. He had been well until 3 days before admission, when nasal congestion, low-grade fever, and diarrhea developed. On the day of admission, he had a generalized seizure and was taken to the hospital. Examination showed a bulging fontanelle and frontal bossing, and laboratory studies disclosed hypocalcemia. Additional testing was performed.
Relation of Serum Lipoprotein Levels and Systolic Blood Pressure to Early Atherosclerosis
Authors: William P. Newman, David S. Freedman, Antonie W. Voors, Paul D. Gard, Sathanur R. Srinivasan, James L. Cresanta, G. David Williamson, Larry S. Webber, Gerald S. Berenson
Journal: New England Journal of Medicine (1986)

We assessed the relation of risk factors for cardiovascular disease to early atherosclerotic lesions in the aorta and coronary arteries in 35 persons (mean age at death, 18 years). Aortic involvement with fatty streaks was greater in blacks than in whites (37 vs. 17 percent, P less than 0.01). However, aortic fatty streaks were strongly related to antemortem levels of both total and low-density lipoprotein cholesterol (r = 0.67, P less than 0.0001 for each association), independently of race, sex, and age, and were inversely correlated with the ratio of high-density lipoprotein cholesterol to low-density plus very-low-density lipoprotein cholesterol (r = -0.35, P = 0.06). Coronary-artery fatty streaks were correlated with very-low-density lipoprotein cholesterol (r = 0.41, P = 0.04). Mean systolic blood-pressure levels also tended to be higher in the four subjects with coronary-artery fibrous plaques than in those without them: 112 mm Hg as compared with 104 (P = 0.09). These results document the importance of risk-factor levels to early anatomical changes in the aorta and coronary arteries. The progression of fatty streaks to fibrous plaques is uncertain, but these data suggest that a rational approach to the prevention of cardiovascular disease should begin early in life.
Sustained Bacteremia in Patients with Prosthetic Cardiac Valves
Authors: Merle A. Sande, Warren D. Johnson, Edward W. Hook, Donald Kaye
Journal: New England Journal of Medicine (1972)

In 22 patients with prosthetic heart valves, 24 episodes of sustained bacteremia were analyzed to discover criteria that might help differentiate those bacteremias with (11 patients) and those without (13 patients) proved infection of the prosthetic valves. In nine of the patients with prosthetic-valve infection positive blood cultures developed 25 or more days after the operation (median, 60 days), with gram-positive organisms (10 of 11), no obvious source for bacteremia (11 of 11) and new or changing murmurs (10 of 11). The group without proved valvular infection had bacteremia earlier (median, 12 days), with gram-negative bacilli (nine of 13), and had obvious possible sources of bacteremia (12 of 13). Changes in murmurs did not develop. All patients with proved valvular infection died whereas seven of 13 without proved infection were cured with medical therapy alone.
Applied Physiology
Authors: Leonard Sinclair
Journal: BMJ (2008)

Samson Wright was only 27 years old and a junior lecturer in physiology at the Middlesex Hospital Medical School when Applied Physiology was published. It was an immediate success and sold well, despite the fact that there were two powerful rival texts on physiology: the 6th edition of Principles of Human Physiology by that doyen of English physiologists Ernest Starling and the 16th edition of Halliburton’s Physiology.

“Sammy,” as he was popularly known, had spotted that most of the potential readers were aiming to qualify as doctors. Their ambition was to be clinicians. He therefore introduced an element of pathology into the text and inserted clinical descriptions as well. This was a popular move. It attracted those who struggled with the accounts in other texts of animal experimentation of little clinical relevance and those who wanted to move on to learn about and study disease under the microscope and at the bedside. This approach changed the emphasis and became a valuable contribution to preclinical medical teaching at the time. It was also much better oriented to the examination candidate.

Wright claimed that the basis for his work was Haldane’s dictum that the aim of physiology was to consider how the internal environment of the body was kept constant in spite of continual changes in the external environment. This simple idea was appropriate for the time, but the author did not stay with it in the text, straying to describe many disordered physiological conditions that did not meet these criteria. To many readers these were the book’s added attractions.

The first and subsequent editions were based on demonstrations and lectures Wright had given to undergraduates in the preclinical and clinical courses at the Middlesex Hospital Medical School. Wright had a mellifluous voice and was a brilliant lecturer who held the attention of his audience. Somehow he had the knack of introducing phrases, ideas, or stories—some biblical—that the listener always remembered. Thus the life of the red cell was as many days as Moses lived in years and that of the white cell as long as Jonah sat under the gourd vine.

He often described classical experiments and talked about the authors of classical research papers, also guiding his students to important reviews on the subject at hand. These became footnotes in the text of Applied Physiology and were thus readily available for further study. But to leaven the text he occasionally introduced some of these interesting and amusing clinical anecdotes. For example, in the section on constipation—a favourite of undergraduates—was the account of the patient who went for one year and three days without having opened his bowels. The reader was fascinated to discover that “towards the end of that time he belched a good deal and suffered some pain.”

Applied Physiology went on to 14 editions, each carefully updated. The last was in 1982. By then it had expanded considerably, and was still attractive, but a little less so to the budding clinician, as it was less clinical than the earlier volumes.
Management of Familial Hemochromatosis
Authors: Walter G. Frey, John Milne, George B. Johnson, Franklin G. Ebaugh
Journal: New England Journal of Medicine (1961)

MISCONCEPTIONS concerning the diagnosis, treatment and pathogenesis of hemochromatosis exist in the literature. Some authors1 , 2 believe that the concomitant increase of iron in the reticuloendothelial tissues makes bone-marrow examination a reliable screening test. Others3 , 4 emphasize the value of serum iron and iron-binding protein saturation in the diagnosis of hemochromatosis. It will be shown, however, that liver biopsy and examination of liver parenchymal cells for iron content provide the only reliable way to exclude the diagnosis of hemochromatosis. Excess iron in the tissues of hemochromatotic patients has been blamed for eventual failure of multiple organ functions.1 , 5 , 6 Repeated venesection has been recommended . . .
Prevention of Catheter-Induced Urinary-Tract Infections by Sterile Closed Drainage
Authors: Calvin M. Kunin, Regina C. McCormack
Journal: New England Journal of Medicine (1966)

THE indwelling urinary catheter is an essential part of modern medical care. It is widely used to give temporary relief of anatomic or physiologic urinary obstruction, facilitate surgical repair of the urethra and surrounding structures, provide a dry environment for comatose or incontinent patients and permit accurate measurement of urinary output in severely ill patients. Unfortunately, when poorly managed, the indwelling catheter may present a hazard to the very patients it is designed to protect. It is the leading cause of nosocomial, induced urinary-tract infections.1 2 3 A number of approaches to the problem of the care of the catheter have been . . .
168P: Real life practice of gefitinib in patients (pts) with non-small-cell lung cancer (NSCLC) depending on epidermal growth factor receptor (EGFR) mutation status: Results from the prospective EPIDAURE study
Authors: J. Cadranel, E. Brambilla, J.F. Morere, V. Rondeau, E. Fabre, B. Lemaire, I. Monnet, M. Licour, M. Perol
Journal: Journal of Thoracic Oncology (2016)
The Physician and School Medical Services
Authors: George M. Wheatley
Journal: New England Journal of Medicine (1947)

THE participation of the United States in war brings, as an almost inevitable aftermath, a wave of popular interest in the health of the school child. After the Civil War, California passed legislation requiring the promotion of physical activities in all schools, and after World War I, many states enacted laws pertaining to medical examinations as well as to physical education. Today, stimulated by the Selective Service findings, a strong current of public interest has set in. No less than ten bills relating to school health were introduced in the Seventy-ninth Congress.Considerable public money is now being spent on . . .
Understanding factors which influence tobacco (smoking and smokeless) in secondary school children in Delhi (India)
Authors: T. Seth, A. Kotwal, R. Thakur
Journal: Journal of Clinical Oncology (2004)

1024 Background: Study conducted to estimate the magnitude of tobacco consumption among adolescent school children in Delhi; the association of tobacco use with awareness, risk taking attitude and alcohol usage; and to understand the role of gender, age and socio-economic status. Methods: Cross sectional study of two randomly identified, co-educational schools of different socio-economic stratum. The questionnaire was pre-tested and administration was unlinked, anonymous. Apriori informed consent of all concerned was obtained. Analyzable sample size was 596. Analysis was done using SPSS ver 11. Appropriate statistics were used and models made using multiple logistic regression. Results: The prevalence of tobacco use (smoking and smokeless) and of tobacco and betel nut was 12.08% (CI 9.57 – 14.97) and 21.31% (CI 18.09 – 24.82), respectively. Risk taking attitude, prevalent in 16.11% (CI 13.25 – 19.31), was strongly linked with tobacco and betel nut use. Prevalence of correct knowledge about tobacco was only 37.75% (CI 33.84 – 41.78). Statistically significant associations were found between gender, type of school, risk taking attitude and use of tobacco (all forms) including betel nut chewing. Of the smokers, 41.6% started prior to the age of 12 years. Offer of cigarettes was made to 27.18% of children. Though 19.75% said they would smoke to gain acceptance, the number of undecided individuals was high (43.83%). Regression models showed that: students with less knowledge; higher risk taking attitude; and indulging in alcohol: used tobacco and betel nut more than others. Model also depicted that knowledge alone was not a good predictor of betel nut chewing. Conclusions: Statistically significant association of tobacco use in any form, with lack of knowledge, risk taking attitude and alcohol use, is consistent with predictors identified by other studies. A predictive model for children at risk for tobacco use has been proposed. Intensive efforts started early are needed for prevention of tobacco use in adolescents. No significant financial relationships to disclose.
Safety of trastuzumab emtansine (T-DM1) in 373 patients 65 years or older with HER2-positive advanced breast cancer: A subgroup analysis of the Kamilla study.
Authors: Carlos H. Barrios, Antonio Anton, Suzette Delaloge, Filippo Montemurro, Rachel Wuerstlein, Stephen Robb, Peter Button, Paul Anthony Ellis
Journal: Journal of Clinical Oncology (2015)

603 Background: T-DM1 is approved for HER2-positive metastatic breast cancer (MBC). A pooled analysis of T-DM1 trials (N = 884) suggested a higher rate of grade ≥ 3 adverse events (AEs) in patients (pts) ≥ 65 yrs (n = 122) vs those < 65 (51.6% vs 44.0%). We report the safety profile of T-DM1 in pts ≥ 65 yrs from the ongoing phase IIIb global safety study Kamilla. Methods: Kamilla enrolled pts with HER2-positive, locally advanced or MBC with progression after chemotherapy and a HER2-directed agent for MBC or within 6 mos of completing adjuvant therapy. T-DM1 3.6 mg/kg was given q3w until unacceptable toxicity, withdrawal of consent or disease progression. Results: As of 20 Oct 2014, Kamilla enrolled 2001 pts; 373 pts ≥ 65 yrs. Pts ≥ 65 yrs had a longer median time since initial BC diagnosis than pts < 65 yrs (6.3 yrs vs 4.8 yrs) and a lower prevalence of brain metastases (10.2% vs 21.6%). Median exposure was 8 cycles in each group (IQR 4.0–13.0 older; 4.0–15.0 younger). AEs by age group, including known T-DM1–associated AEs, are shown. The incidence of grade ≥ 3 AEs and AE-related discontinuations were greater in older pts. This resulted from many small differences in AEs rather than any single AE. Conclusions: In this largest population of T-DM1–treated pts ≥ 65 yrs studied to date, while overall incidence of grade ≥ 3 AEs and discontinuation due to AEs was greater, the most common grade ≥ 3 AEs were infrequent and similar between age groups. Known T-DM1–associated AEs also occurred with a similar frequency in both groups, suggesting a similar safety profile in older and younger pts. Clinical trial information: NCT01702571. Outcome, n (%) ≥ 65 yrs (n = 373) < 65 yrs (n = 1628) Discontinuation due to AEs (% based on pts who discontinued) 41 (14.3) 112 (9.5) Fatal AEs 10 (2.7) 17 (1.0) Grade ≥ 3 AEs 160 (42.9) 540 (33.2) Grade ≥ 3 AEs in ≥ 2% of either group Thrombocytopenia* 13 (3.5) 53 (3.3) Asthenia 12 (3.2) 18 (1.1) Anemia 11 (2.9) 32 (2.0) Fatigue 10 (2.7) 34 (2.1) GGT increased 8 (2.1) 42 (2.6) Thrombocytopenia* Grade ≥ 3 49 (13.1) 13 (3.5) 211 (13.0) 53 (3.3) Hepatotoxicity* Grade ≥ 3 68 (18.2) 18 (4.8) 327 (20.1) 114 (7.0) Hemorrhage* Grade ≥ 3 87 (23.3) 6 (1.6) 392 (24.1) 28 (1.7) LVEF < 45% 5 (1.3)** 36 (2.2) *Based on groupings of related preferred terms; **None < 40%.
Transforming Primary Care — We Get What We Pay For
Authors: John Z. Ayanian, Mary Beth Hamel
Journal: New England Journal of Medicine (2016)

Primary care is the foundation of effective health care systems.1 At their best, primary care physicians provide comprehensive, well-coordinated, patient-centered care for many acute and chronic health problems while also promoting prevention and wellness for a wide range of patients.2 As we know from our own experiences as primary care physicians, patients and physicians value continuity in their primary care relationships, which can last many years.Despite the importance of these priorities, primary care physicians have been under siege for more than a decade.3 As compared with physicians in most other specialties, primary care physicians earn lower incomes, and they . . .
Case 16-2001
Authors: J. Thomas LaMont, Fiona M. Graeme-Cook
Journal: New England Journal of Medicine (2001)

Presentation of CaseA 17-year-old girl (gravida 1, para 1) was admitted to the hospital because of abdominal pain, fever, and diarrhea.The patient had been in good health before admission. Three weeks earlier, she had undergone a cesarean section because of multiple bouts of fetal bradycardia; the infant was delivered at 40 weeks of gestation. The pregnancy was otherwise uneventful. She received a single dose of gentamicin and two doses of clindamycin intravenously in the peripartum period. Her postpartum course was uneventful, and she was discharged on the third postoperative day.Three days before admission, the patient began to . . .
Case 13-2009
Authors: Michael E. Weinblatt, Gerald F. Abbott, Aashiyana F. Koreishi
Journal: New England Journal of Medicine (2009)

A 54-year-old woman was admitted to the hospital because of respiratory failure, hypotension, and a cavitary lesion in the lung. She had had cough and shortness of breath for a week, which abruptly worsened, and she collapsed at home. In the emergency department, she was hypotensive and unresponsive; chest imaging showed consolidation of the right upper lobe with a cavity. Tension pneumothorax developed after insertion of a jugular venous catheter. Despite placement of a chest tube and mechanical ventilation, the patient died. An autopsy was performed.
Studies on the Macroglobulins of Human Serum
Authors: Frank A. Wollheim, Ralph C. Williams
Journal: New England Journal of Medicine (1966)

THE occurrence of high-titer heterophil sheep-cell agglutinins in infectious mononucleosis is well established; furthermore, all available evidence indicates that these antibodies are exclusively 19S in nature.1 2 3 Recently Calvo et al.4 described 19S cold agglutinins with anti-i specificity in patients with infectious mononucleosis. The primary purpose of this study was to relate quantitative changes in the immunoglobulins, particularly immunoglobulin Class M (IgM),5 to measurable serologic reactions such as heterophil or anti-i antibody activity. In this regard absorption experiments revealed that no more than 1 to 5 per cent of the quantitative IgM increment present in patients with infectious mononucleosis could be . . .