tbuckley/cabot-search huggingface dataset:
Outcome in colorectal carcinoma: seven-year study of a population.
Authors: D N Clarke, P F Jones, C D Needham
Journal: BMJ (1980)

All 433 patients with colorectal cancer who presented in the north-east of Scotland during 1968 and 1969 were followed up for seven years or until death intervened. The incidence of colorectal cancer in the region was the highest recorded in Great Britain. Half the patients were incurable at the time of diagnosis. Nevertheless, of the 195 survivors of radical resection 146 (75%) did not die of carcinoma during the next seven years. Men with "curable" rectal cancer showed a substantially lower corrected survival rate (42%) than women (70%), but this was due to intercurrent disease not recurrence. Comparable figures for colonic carcinoma showed no difference between men (75%) and women (77%). The overall picture of colorectal cancer has apparently not changed for 20 years. Nevertheless, earlier diagnosis and timely operation--possibly with adjuvant chemotherapy--may produce useful long-term results.
Obstructive Sleep Apnea in Family Members
Authors: Kingman P. Strohl, Nicholas A. Saunders, Neil T. Feldman, Mark Hallett
Journal: New England Journal of Medicine (1978)

Two sons and their father had severe hypersomnolence and obstructive sleep apnea. A third son, although asymptomatic, was shown to have upper-airway obstruction during sleep. Electromyographic recordings of genioglossus activity in the two symptomatic sons revealed loss of tonic activity in early stages of sleep at times when sleep apnea occurred. The asymptomatic son showed loss of tonic activity during rapid-eye-movement sleep, the sleep period when upper-airway obstruction occurred. Two sudden deaths occurred in this family. A 30-year-old brother died at home while asleep, and a child of the asymptomatic brother died at the age of four months from presumed sudden-infant-death syndrome. Obstructive sleep apnea may have a familial basis; the tongue may be involved in the genesis of upper-airway obstruction during sleep.
Inhibition of the Janus Kinase Family Increases Extracellular Signal-Regulated Kinase 1/2 Phosphorylation and Causes Endoreduplication
Authors: Gudrun Reiterer, Andrew Yen
Journal: Cancer Research (2006)

Abstract The role of Janus-activated kinase (JAK) signaling in cell cycle transit and maintenance of genomic stability was determined in HL-60 myeloblastic leukemia cells. Inhibition of JAKs, all JAKs (JAK1, JAK2, JAK3, and tyrosine kinase 2), JAK2, or JAK3, caused a significant reduction in cell growth with a major G2-M arrest evident 24 hours after treatment. Targeting all JAKs also caused endoreduplication 48 and 72 hours after treatment. We discovered mitotic cells in both G2 (4N DNA) and G4 (8N DNA) subpopulations of cells treated with an inhibitor of all JAKs as detected by phosphorylated histone H3 expression. Treatment with inhibitors of just JAK2 or JAK3 drastically reduced such mitotic cells. We observed a complete blockage of IFN-γ and interleukin-6-induced signal transducer and activator of transcription (STAT)-1 and STAT-3 response when all JAKs were inhibited. At the same time, we found baseline phosphorylated extracellular signal-regulated kinase (ERK) 1/2 to be elevated by JAK inhibition, particularly when all JAKs were inhibited. The G2-M arrest and endoreduplication induced by JAK inhibitors were reduced in cells pretreated with PD98059 to inhibit ERK. PD98059 also increased back the expression of the MAD2 cell cycle checkpoint protein that was down-regulated during “all JAKs inhibitor”–mediated endoreduplication. These data suggest that JAK signaling is needed for G2-M transit with inhibition of ERK. (Cancer Res 2006; 66(18): 9083-9) (Cancer Res 2006; 66(18): 9083-9)
Children as Renal Donors
Authors: Norman Fost
Journal: New England Journal of Medicine (1977)

With the exception of identical twins, preadolescent children have been excluded as renal donors. The justification for this policy appears to be based on a notion that renal donation is an altruistic act, primarily for the benefit of another, and that stringent standards of informed consent must be followed. This paper challenges the present policy on two grounds: consent from adults who donate kidneys is generally not informed, and therefore it is inconsistent to use the consent requirement as a justification for excluding children; and renal donation by adults can be seen as a procedure done for the benefit of the donor (as well as the recipient), and the appropriate rules for using children as donors should therefore be those pertaining to beneficial intrusions on nonconsenting subjects.
THE CATECHOLAMINE HYPOTHESIS OF AFFECTIVE DISORDERS: A REVIEW OF SUPPORTING EVIDENCE
Authors: JOSEPH J. SCHILDKRAUT
Journal: American Journal of Psychiatry (1965)

The "catecholamine hypothesis of affective disorders" proposes that some, if not all, depressions are associated with an absolute or relative decrease in catecholamines, particularly norepinephrine, available at central adrenergic receptor sites. Elation, conversely, may be associated with an excess of such amines. Evidence supporting this hypothesis was reviewed. Data from pharmacological studies, mainly in animals, suggest that the actions of both major classes of antidepressant drugs are mediated through the catecholamines. The monoamine oxidase inhibitors increase brain concentrations of norepinephrine while imipramine-like agents potentiate the physiological effects of norepinephrine. Reserpine, a drug which can cause clinical depression, depletes catecholamines, but other amines may also be involved in its mechanism of action. A rigorous extrapolation from pharmacological studies to pathophysiology clearly cannot be made. Clinical studies relevant to the catecholamime hypothesis are limited and the findings are inconclusive. It is not possible, therefore, to confirm definitively or to reject the catecholamine hypothesis on the basis of data currently available. In our present state of knowledge, however, the catecholamine hypothesis is of considerable heuristic value, providing the investigator and the clinician with a frame of reference integrating much of our experience with those pharmacological agents which produce alterations in human affective states.
Behçet's Syndrome
Authors: Harry Bienenstock, Murray E. Margulies
Journal: New England Journal of Medicine (1961)

A SYNDROME characterized by recurrent iritis and ulcerations of the mouth and genitalia was first described by Behçet1 , 2 in Istanbul, Turkey, in 1937 and is now known by his name. Other less common findings accompanying the syndrome have included thrombophlebitis,3 erythema nodosum4 and arthralgia.5 6 7 8 The syndrome usually runs a relatively benign course, manifested by intermittent episodes of mucocutaneous and ocular symptoms from days to months. The lesions usually start as small papules or vesicles, which rapidly ulcerate. Neurologic involvement accompanying Behçet's syndrome was first described by Knapp9 in 1941, 20 cases of neurologic complications having been reported since then. The . . .
Evidence does not support routine PSA testing, say experts
Authors: M. McCarthy
Journal: BMJ (2013)

Screening asymptomatic men for prostate cancer with the prostate specific antigen (PSA) blood test should no longer be routine, say new guidelines issued by the American Urological Association.

The guidance is a marked shift from the association’s past recommendations, which generally favored more aggressive PSA screening, including offering PSA tests to men from age 40.

The new recommendations were drawn up by a panel of experts commissioned by the association to conduct a systematic review and meta-analysis of the published literature on prostate cancer detection and screening.1

The association’s previous 2009 best practice statement on PSA testing had been based on clinical experience and expert …
P75 Pulmonary physiogical tests: trainees experience and exposure
Authors: H Lockman, NJ Bell
Journal: Thorax (2013)

<h3>Introduction</h3> Knowledge of pulmonary function test (PFT) is essential for every respiratory physician. The level of training and exposure to PFT varies depending on the local facilities, supervisors and the respiratory trainees themselves. Moreover in recently cardio-pulmonary exercise testing (CPET) are becoming more widely available as well. <h3>Objectives</h3> To test the knowledge of UK respiratory physicians (trainees mainly) on PFT and CPET, identifying what is available locally. The level of exposure to the tests themselves in terms of how to perform, the process involved and the equipment used/ available locally. <h3>Methodology</h3> An electronic survey was distributed to the UK postgraduate deaneries for all the respiratory trainees and also to some respiratory physicians, thoracic surgeons and lung function physiologists. Feedback was collected anonymously over a period of 6 months (Dec 2012–May 2013). The questions ranged from simple spirometry, PFT, CPET and basic demographics. <h3>Results</h3> A total of 160 responses were obtained from 16 deaneries out of 20 [1 from outside the UK - OOPE]. 83 (53%) were respiratory specialist/specialty registrars and 61(39%) consultants. 2 respondents had never seen spirometry performed, and 28 (18%) have not seen a PFT performed. Only ¼ have done a PFT themselves. 70% have seen CPET, 29% have done CPET, 75% have a CPET service locally with cycle ergometer (66%) being the most common method to exercise the patient. Respiratory physiologists and respiratory physicians are the ones mainly reporting CPET results with anaesthetist a distant third. <h3>Summary</h3> Most trainees have been exposed to spirometry but based on this survey almost 20% have yet to see a PFT performed. Understanding the process of how to do a PFT and CPET, experiencing it personally could influence the number of PFT requests. This aspect of respiratory specialty training is still insufficient based on the feedback of respiratory trainees who answered this survey.
A Multi-Component Meningococcal Serogroup B Vaccine (4CMenB): The Clinical Development Program
Authors: Miguel O’Ryan, Jeffrey Stoddard, Daniela Toneatto, James Wassil, Peter M. Dull
Journal: Drugs (2013)

Recently approved in Europe and Australia, the multi-component meningococcal B vaccine, 4CMenB (Bexsero®, Novartis Vaccines and Diagnostics), contains three surface-exposed recombinant proteins (fHbp, NadA, and NHBA) and New Zealand strain outer membrane vesicles (NZ OMV) with PorA 1.4 antigenicity. This comprehensive review of the 4CMenB clinical development program covers pivotal phase I/IIb/III studies in over 7,000 adults, adolescents, and infants. The immunological correlate for clinical protection used was human complement-mediated serum bactericidal activity titers ≥4 or 5 against indicator strains for individual antigens. Based on achievement of protective titers, a four-dose schedule (three primary doses and one booster dose) for infants and a two-dose schedule for adolescents provided the best results. Observed increases in injection site pain/tenderness and fever in infants, and injection site pain, malaise, and headache in adolescents compared with routine vaccines, were mostly mild to moderate; frequencies of rare events (Kawasaki disease, juvenile arthritis) were not significantly different from non-vaccinated individuals. 4CMenB is conservatively estimated to provide 66-91 % coverage against meningococcal serogroup B strains worldwide.
Children and US Federal Policy on Health and Health Care
Authors: Glenn Flores, Bruce Lesley
Journal: JAMA Pediatrics (2014)

Children account for 73.5 million Americans (24%), but 8% of federal expenditures. Data on health and health care indicate that child well-being in the United States has been in decline since the most recent recession. Childhood poverty has reached its highest level in 20 years, 1 in 4 children lives in a food-insecure household, 7 million children lack health insurance, a child is abused or neglected every 47 seconds, and 1 in 3 children is overweight or obese. Five children are killed daily by firearms, 1 in 5 experiences a mental disorder, racial/ethnic disparities continue to be extensive and pervasive, and major sequester cuts and underfunding of pediatric research have damaged our global leadership in biomedical research and hobbled economic growth. In this analysis, we identify 10 urgent priorities for the health and health care of US children, including poverty, food insufficiency, lack of health insurance, child abuse and neglect, overweight and obesity, firearm deaths and injuries, mental health, racial/ethnic disparities, immigration, and research. Overwhelming, bipartisan support by voters exists for enhancing our nation's investments in children's health and well-being. Federal policy action steps are proposed to successfully address these priorities and ensure a healthy, productive future for US children and the nation.
Epilepsy and the law
Authors: P. Fenwick
Journal: BMJ (1984)

Everyone who has reached the age of discretion is, unless the contrary is proved, presumed by law to be sane and to be accountable for his actions. This is the doctrine of mens rea. ‘Actus non facit reum nisi mens sit rea’  the deed does not make a man guilty unless his mind is guilty. This is the fundamental basis of English law. For to make a man liable to imprisonment for an offence that he does not know he is committing, and is unable to prevent, goes against the spirit of English justice.
NEOPLASM OF THE LACHRYMAL GLAND.
Authors: PETER D. KEYSER
Journal: JAMA (1884)

Read in the Section of Ophthalmology, Otology and Laryngology of American Medical Association, May, 1884. Neoplasms of the lachrymal gland are of very rare occurrence, and great care is necessary in the examination of the same to be certain of the origin of the morbid growth. But whether it originates in the gland proper, or begins its existence in the neighboring tissues and passes into the gland by the natural process of contact and extension, can only be determined after the extirpation and by microscopical examination The character of the tumor can only be ascertained by the same manner of examination. The following two cases illustrate the two processes of origin as above mentioned,<i>i. e.</i>, that in the gland proper, and that external and affecting the gland secondarily. The first case, Lydia Mayberry, aet., 55, came to me in May, 1877, with a lump, as she called it, growing
Testicular Feminization Associated with a Thermolabile Androgen Receptor in Cultured Human Fibroblasts
Authors: James E. Griffin
Journal: Journal of Clinical Investigation (1979)

Evidence for a qualitative abnormality in the androgen receptor was obtained by studies of temperature sensitivity. The binding of [3H]dihydrotestosterone (17β-hydroxy-5α-androstan-3-one) was studied in monolayers of cultured genital skin fibroblasts from genetic males with abnormal sexual differentiation resulting from androgen resistance. Binding in cells from eight patients with a female phenotype (complete and incomplete testicular feminization) fell from half-normal levels at the usual assay temperature of 37°C to levels <20% of normal when cells were incubated at 42°C. This thermal inactivation was rapidly reversed when the assay temperature was lowered to 37°C, was not associated with altered dihydrotestosterone metabolism, and was also demonstrable with [3H]methyltrienolone as the binding ligand. Binding increased to overlap the normal range when the assay temperature was lowered to 26°C. The patients with receptor-deficient testicular feminization include three pairs of siblings; the pedigrees in two of these families are compatible with X-linkage.
Acetaminophen and Other Risk Factors for Excessive Warfarin Anticoagulation
Authors: Elaine M. Hylek, Heather Heiman, Steven J. Skates, Mary A. Sheehan, Daniel E. Singer
Journal: JAMA (1998)

Context.-Warfarin is highly effective in preventing thromboembolism, but increases the risk of hemorrhage, particularly at an international normalized ratio (INR) greater than 4.0.Identifying causes of excessive anticoagulation in clinical practice could help target patients at risk for elevated INRs.Objective.-Todetermine causes of INRs greater than 6.0 in a clinical practice setting.Design.-Case-control study.Setting.-Outpatient anticoagulant therapy unit.Patients.-Outpatientsfollowed up prospectively from April 1995 to March 1996 who had been taking warfarin for more than 1 month, had a target INR of 2.0 to 3.0, and were able to be interviewed within 24 hours of their reported INR.Case patients had INRs greater than 6.0; controls were randomly selected from patients having INRs between 1.7 and 3.3.Main Outcome Measures.-Factorsassociated with INRs greater than 6.0, including medication use, recent diet, illness, alcohol consumption, and actual warfarin use.Results.-A total of 93 cases and 196 controls were interviewed; they did not differ in age, indication for warfarin, length of therapy, warfarin dose, number of prescription medications, or previous INR or long-term INR variability.Acetaminophen ingestion was independently associated in a dose-dependent manner with having an INR greater than 6.0 (P for trend Ͻ.001).For the highest-dose category of acetaminophen intake, 9100 mg/wk or more, the odds of having an INR greater than 6.0 were increased 10-fold (95% confidence interval [CI], 2.6-37.9).Other factors independently associated with an INR greater than 6.0 were new medication known to potentiate warfarin (odds ratio [OR], 8.5; 95% CI, 2.9-24.7),advanced malignancy (OR, 16.4; 95% CI, 2.4-111.0),recent diarrheal illness (OR, 3.5; 95% CI,1.4-8.6), decreased oral intake (OR, 3.6; 95% CI, 1.3-9.7),and taking more warfarin than prescribed (OR, 8.1; 95% CI, 2.2-30.0).Higher vitamin K intake (OR, 0.7; 95% CI, 0.5-0.9)and habitual alcohol consumption of from 1 drink every other day to 2 drinks a day (OR, 0.2; 95% CI, 0.1-0.7)were associated with decreased risk.Conclusions.-Thesedata suggest that acetaminophen is an underrecognized cause of overanticoagulation in the outpatient setting.Several other clinically important risk factors were identified.Increased monitoring of INR values when such risk factors are present or modification of the risk factors themselves should reduce the frequency of dangerously high levels of anticoagulation.
Key challenges and ways forward in researching the “good death”: qualitative in-depth interview and focus group study
Authors: Marilyn Kendall, Fiona Harris, Kirsty Boyd, Aziz Sheikh, Scott A Murray, Duncan Brown, Ian Mallinson, Nora Kearney, Allison Worth
Journal: BMJ (2007)

A 35 year old woman presented with severe primary hypothyroidism and galactorrhea. A very high prolactin level was also detected and computerized tomography scan of the sellar region demonstrated an enlarged pituitary gland associated with contrast enhancement. Replacement therapy with thyroxine corrected both biochemical and clinical abnormalities but empty sella developed during this therapy. It is concluded that empty sella may be related to thyroxine-induced shrinkage of lactotroph and/or thyrotroph cell hyperplasia.
STUDIES IN LIVER AND KIDNEY FUNCTION IN EXPERIMENTAL PHOSPHORUS AND CHLOROFORM POISONING
Authors: E. K. Marshall, L. G. Rowntree
Journal: The Journal of Experimental Medicine (1915)

1. We have confirmed the results of previous workers on tetrachlorphthalein, fibrinogen, and lipase. 2. The total non-protein nitrogen, urea, and amino-acids of the blood serum show a definite and sometimes marked increase in phosphorus poisoning. These changes are not so evident in chloroform poisoning, although they sometimes occur. They are usually terminal phenomena. 3. The urinary nitrogen partition between the urea, ammonia, and amino-acids is not always disturbed. The most important changes which occur are an increased amino nitrogen in chloroform and phosphorus poisoning, and a very low urea nitrogen percentage in severe fatal chloroform poisoning. 4. Sugar tolerance towards galactose and levulose is in general markedly decreased in both types of poisoning. 5. In phosphorus poisoning liver functional changes can and do occur without concomitant renal changes. Renal insufficiency usually arises as a terminal event. 6. Increased nitrogenous products in the blood (total non-protein nitrogen, urea, and amino nitrogen) are associated with an increase of these bodies in the urine. Consequently, an increased protein catabolism, as well as renal insufficiency, is necessary to explain this accumulation. 7. A terminal acidosis, as evidenced by increased hydrogen ion concentration in the blood, usually occurs.
Polybrominated Diphenyl Ethers and Cryptorchidism: Confounding or Cause and Effect?
Authors: Marek Banasik, Marcia L. Hardy, Todd Stedeford
Journal: Environmental Health Perspectives (2008)

Main et al. (2007) reported that elevated levels of polybrominated diphenyl ethers (PBDEs) in breast milk, but not placenta, were associated with congenital cryptorchidism in Danish and Finnish boys.For the Danish cohort, the researchers used a case-cohort design in which biological samples were collected from all study participants, whereas for the Finnish cohort, they used a nested case-control design.The matching criteria used for Finnish mothers who gave birth to boys with cryptorchidism (measured at birth) and matched Finnish controls included the following: parity, smoking (yes/no), diabetes (yes/no), gestational age (± 7 days), and date of birth (± 14 days).However, Main et al. (2007) did not provide information on adjustments made to account for the type/severity of diabetes (Virtanen et al. 2006), smoking habits (Kurahashi et al. 2005), alcohol consumption (Damgaard et al. 2007), cesarean section (Hjertkvist et al. 1989;Kurahashi et al. 2005), and other factors that may be associated with cryptorchidism.Interestingly, Main et al. did note that approximately 12% and 18% of breast milk samples and placentas, respectively, were obtained from diabetic Finnish mothers of cryptorchid boys, compared with 0% of controls (Main et al. 2007), but they conducted no further inquiry on this discrepancy.Damgaard et al. (2007) previously evaluated this same Danish-Finnish cohort and adjusted for confounders and effect modifiers for differences observed based on country, smoking, caffeine intake, alcohol consumption (including binge-drinking episodes), social class, maternal age, parity, maturity, and birth weight.Damgaard et al. (2007) noted an association between maternal alcohol consumption (≥ 5 drinks/week) and transient cryptorchidism.Despite these findings, Main et al. (2007) provided no information on stratified alcohol consumption or other potential confounders, such as caffeine intake or social class.Main et al. (2007) concluded that an association exists between PBDE levels in breast milk and cryptorchidism in boys, but we should be cautious of this interpretation, given that Main et al. (2007) may not have adequately addressed potential confounders.
Emergency contraception is under attack by US pharmacists
Authors: Janice Hopkins Tanne
Journal: BMJ (2005)

A growing number of pharmacists across the United States are refusing to fill prescriptions for emergency contraception, even in cases of rape. Some pharmacists won't fill prescriptions for oral contraceptives for moral and religious reasons.

Karen Pearl, interim president of the Planned Parenthood Federation of America, said, “We're getting more and more reports [of denials to fill prescriptions] from more and more states. This is a clearly orchestrated movement to stand in the way of women getting the birth control they need. Pharmacists are standing in the middle of the doctor-patient relationship.”

The “conscience clause” trend began several years ago when doctors …
Different STAT-3 and STAT-5 phosphorylation discriminates among Ph-negative chronic myeloproliferative diseases and is independent of the V617F JAK-2 mutation
Authors: Luciana Teofili, Maurizio Martini, Tonia Cenci, Giovanna Petrucci, Lorenza Torti, Sergio Storti, Francesco Guidi, Giuseppe Leone, Luigi Maria Larocca
Journal: Blood (2007)