tbuckley/cabot-search huggingface dataset:
Prognosis in Heart Failure with a Normal Ejection Fraction
Authors: John G.F. Cleland, Jacqueline Taylor, Michal Tendera
Journal: New England Journal of Medicine (2007)

To the Editor: Recent studies have shown a poor prognosis for patients with heart failure who have a normal ejection fraction,1 a finding that differs markedly from the results of randomized, controlled trials.2,3 This discrepancy requires an explanation. Many patients with heart failure who have serious, common coexisting illnesses, such as pulmonary disease, atrial fibrillation, and renal dysfunction (all of which are both markers and mediators of a worse outcome), are excluded from randomized, controlled trials for two obvious reasons. First, heart failure with a normal ejection fraction is largely a diagnosis of exclusion, and patients with coexisting illnesses . . .
Outcomes of the European Working Time Directive
Authors: H. Cairns, B. Hendry, A. Leather, J. Moxham
Journal: BMJ (2008)

From 56 to 48 hours is a step too far

The European Working Time Directive was produced by the Council of the European Union in 1993 and incorporated into British law in 1998 as the Working Time Regulations.1 Various aspects of the directive have had a major effect on the practice of medicine in the United Kingdom, most importantly the reduction in the maximum working week to 56 hours in 2007, a planned further reduction to 48 hours in 2009, and the need for a minimum of 11 hours’ rest in any 24 hour period.

Although not clearly stated in the directive, the aims of the council presumably were to protect workers from being coerced by employers to work excessive hours; to improve the quality of life of workers by permitting sufficient free time for family and leisure; and to reduce risk caused by tired workers. Although many industries are affected by the change in the law, medicine poses particular problems because of the need to train junior medical staff and to provide a 24 hour service that can respond to variable demand while ensuring continuity of, often complicated, patient care. Furthermore, unlike many other professions, junior and now senior doctors are paid per hour, which exposes the length of the working day and week to legislation.

If the directive was meant to improve clinical care and the quality of life and training for junior medical staff, its effect has been the opposite. The changes to working hours have had a major negative effect on the working life, free time, and education of …
Post-transplantation (LT) significant HCV-related disease severity: Increase in recent years
Authors: M. Berenguer, J. Crippin, R. Gish, M. Prieto, G. Davis, C. Baker, J. Watson, J. Hillygus, G. Netto, J. Alonzo, R. Garcia, N. Bass, T.L. Wright
Journal: Journal of Hepatology (2000)
Suppressor of cytokine signaling 1 protects mice against concanavalin A-induced hepatitis by inhibiting apoptosis
Authors: Takehiro Torisu, Mako Nakaya, Satoko Watanabe, Masayuki Hashimoto, Hideyuki Yoshida, Takatoshi Chinen, Ryoko Yoshida, Fuyuki Okamoto, Toshikatsu Hanada, Kumiko Torisu, Giichi Takaesu, Takashi Kobayashi, Hideo Yasukawa, Akihiko Yoshimura
Journal: Hepatology (2008)

Acute liver failure is associated with significant mortality. However, the underlying pathophysiological mechanism is not yet fully understood. Suppressor of cytokine signaling-1 (SOCS1), which is a negative-feedback molecule for cytokine signaling, has been shown to be rapidly induced during liver injury. Here, using liver-specific SOCS1-conditional-knockout mice, we demonstrated that SOCS1 deletion in hepatocytes enhanced concanavalin A (ConA)-induced hepatitis, which has been shown to be dependent on activated T and natural killer T (NKT) cells. Although serum cytokine level and NKT cell activation were similar in wild-type (WT) and SOCS1-deficient mice after ConA treatment, proapoptotic signals, including signal transducers and activators of transcription 1 (STAT1) and Jun-terminal kinase (JNK) activation, were enhanced in SOCS1-deficient livers compared with those in WT livers. SOCS1-deficient hepatocytes had higher expression of Fas antigen and were more sensitive to anti-Fas antibody-induced apoptosis than were WT hepatocytes. Furthermore, SOCS1-deficient hepatocytes were more sensitive to tumor necrosis factor (TNF)-alpha-induced JNK activation and apoptosis. These data indicate that SOCS1 is important to the prevention of hepatocyte apoptosis induced by Fas and TNF-alpha. In contrast, SOCS1 overexpression in the liver by adenoviral gene transfer prevented ConA-induced liver injury.These findings indicate that SOCS1 plays important negative roles in fulminant hepatitis and that forced expression of SOCS1 is therapeutic in preventing hepatitis.
Varicocoele caused by a pancreatic pseudocyst.
Authors: I Hamilton, J S Soutar
Journal: Gut (1983)

Varicocoele caused by a pancreatic pseudocyst Sir, We were interested to read the case report by Drs Dixon, Armstrong, and Fremin of a varicocoele caused by a pancreatic pseudocyst (Gut 1983; 24: 438-40), but we believe the pancreatogram reproduced in Fig. 1 may have been misinterpreted.While accepting the difficulty of interpreting reproduced radiographs, we believe the appearances shown, and the description in the text of a blind ending to the main pancreatic duct are more suggestive of main pancreatic duct obstruction, a radiological feature which may be seen in the presence of a pseudocyst, rather than the fine terminal arborisation of the duct system more typical of an unfused ventral pancreas.2Although this in no way detracts from the interest of the report we would hesitate to ascribe this patient's recurrent acute pancreatitis to congenital duct malfusion, particularly in the presence of gall stones.
Self reported sexual activity in Australian sexagenarians
Authors: J. A Ferris, A. M A Smith, M. K Pitts, J. Richters, J. M Shelley, J. Simpson
Journal: BMJ (2008)

We compare the self reported sexual activity and satisfaction in Swedish 70 year olds1with recent data from the Australian longitudinal study of health and relationships (ALSHR)—a nationally representative random sample of men and women aged 16 to 64 who completed a computer assisted telephone interview.2 The sample had 635 sexagenarians (60-64), most (80%) with a regular partner, almost all of them married …
Acute myocardial infarction associated with single vessel coronary artery disease: An analysis of clinical outcome and the prognostic importance of vessel patency and residual ischemie myocardium
Authors: William W. Wilson, Robert S. Gibson, Thomas W. Nygaard, George B. Craddock, Denny D. Watson, Richard S. Crampton, George A. Beller
Journal: Journal of the American College of Cardiology (1988)
AN IMPROVED PORTABLE STERILIZER FOR SURGICAL INSTRUMENTS AND DRESSINGS.
Authors: HORACE G. WETHERILL
Journal: JAMA (1897)

In the<i>University Medical Magazine</i>for August, 1896, I described "A Compact Portable Sterilizer for Surgical Instruments and Dressings." The use of this sterilizer for some months has led to alterations and improvements which make it much more satisfactory than the original instrument. The illustration shows its present form when set up for use, as well as when ready for packing. For practical sterilization this instrument has given perfect satisfaction; it is light, portable in small space, yet when fully extended, ample for all instruments, dressings, towels, operating coats, etc., one needs in ordinary operative work. The instruments are boiled in a soda solution (1 per cent.) in the lower pan, the steam rising through the perforated bottom of the second pan to sterilize the dressings which have been placed in it. The top section has no bottom, being simply a collar for increasing the size of the steam chamber
The Touch That Hepatocytes Seem to Like
Authors: Kenneth S. Zaret
Journal: Hepatology (1992)

We have identified the liver–regulating protein (LRP), a cell surface protein involved in the maintenance of hepatocyte differentiation when cocultured with rat liver epithelial cells (RLEC). LRP was defined by immunoreactivity to a monoclonal antibody (mAb L8) prepared from RLEC. mAb L8 specifically detected two polypeptides of 85 and 73 kD in immunoprecipitation of both hepatocyte– and RLEC–iodinated plasma membranes. The involvement of these polypeptides, which are integral membrane proteins, in cell interaction–mediated regulation of hepatocytes was assessed by evaluating the perturbing effects of the antibody on cocultures with RLEC. Several parameters characteristic of differentiated hepatocytes were studied, such as liver–specific and house–keeping gene expression, cytoskeletal organization and deposition of extracellular matrix (ECM). An early cytoskeletal disturbance was evidenced and a marked alteration of hepatocyte functional capacity was observed in the presence of the antibody, together with a loss of ECM deposition. By contrast, cell–cell aggregation or cell adhesion to various extracellular matrix components were not affected. These findings suggest that LRP is distinct from an extracellular matrix receptor. The fact that early addition of mAb L8 during cell contact establishment was necessary to be effective may indicate that LRP is a novel plasma membrane protein that plays an early pivotal role in the coordinated metabolic changes which lead to the differentiated phenotype of mature hepatocytes.
Palliative care at home to get further funds if it saves money
Authors: Katherine Burke
Journal: BMJ (2004)

The health secretary, John Reid, has promised further funds to help double the number of cancer patients allowed to die at home—if NHS pilots prove claims, as they are expected to, that such a move would save money and comply with patients' wishes.

Speaking at the launch of Marie Curie Cancer Care's campaign, “Supporting the choice to die at home,” Mr Reid said the charity's research confirms his prejudices that most people would prefer to die in familiar surroundings but that he needs hard evidence before he can confirm …
Renal-Artery Stenosis
Authors: Robert D. Safian, Stephen C. Textor
Journal: New England Journal of Medicine (2001)

Primary diseases of the renal arteries often involve the large renal arteries, whereas secondary diseases are frequently characterized by small-vessel and intrarenal vascular disease. In this article, we will concentrate on the two most common primary diseases of the renal arteries — atherosclerotic renal-artery stenosis and fibromuscular dysplasia — and their association with two common clinical syndromes, hypertension and ischemic nephropathy. The relations among renal-artery stenosis, hypertension, and renal excretory dysfunction are complex (Figure 1). Renal-artery stenosis may occur alone (isolated anatomical renal-artery stenosis) or in association with hypertension, renal insufficiency (ischemic nephropathy), or both.Prevalence and Natural HistoryFibromuscular . . .
Alteration of Systolic Time Intervals in Right Ventricular Failure
Authors: JOSEPH S. ALPERT, FRANK D. RICKMAN, JOHN P. HOWE, LEWIS DEXTER, JAMES E. DALEN
Journal: Circulation (1974)

Systolic time intervals (STI) were measured in matched patients with and without right ventricular failure (RVF). STI were calculated from brachial arterial pressure tracings obtained at cardiac catheterization in four groups of patients: 1) controls, without RVF; 2) acute pulmonary embolism with and without acute RVF; 3) mitral stenosis, with and without chronic RVF; 4) primary pulmonary hypertension, with chronic RVF. In patients with pulmonary embolism without acute RVF, STI were normal. However, patients with acute RVF due to pulmonary embolism had significantly shortened left ventricular ejection times (LVETc) and significantly increased pre-ejection periods (PEPc) and increased PEPc/LVETc ratios ( P &lt; 0.05, P &lt; 0.001, P &lt; 0.001 respectively). Similar results were obtained in patients with chronic RVF. In patients with mitral stenosis without RVF, STI were normal. However, in patients with chronic RVF due to mitral stenosis or primary pulmonary hypertension, PEPc and PEPc/LVETc ratios were lengthened and LVETc was shortened ( P &lt; 0.003, P &lt; 0.005, and P &lt; 0.001 respectively). PEPc/LVETc ratios increased as stroke index decreased ( r = –0.55). There was also an association between PEPc/LVETc and right atrial mean pressure ( r = 0.70). These data demonstrate that patients with acute and chronic right ventricular failure have abnormal systolic time intervals possibly secondary to left ventricular dysfunction.
Prevention of Estrogen Deficiency–Related Bone Loss With Human Parathyroid Hormone–(1-34)
Authors: Joel S. Finkelstein, Anne Klibanski, Amy L. Arnold, Thomas L. Toth, Mark D. Hornstein, Robert M. Neer
Journal: JAMA (1998)

Context.—Short-term intermittent administration of parathyroid hormone (PTH) prevents bone loss from the spine in women treated with a gonadotropin-releasing hormone (GnRH) analog. However, the effects of a longer period of PTH administration on bone mass in estrogen-deficient women, particularly on the hip and on cortical bone of the total body, are unknown.Objective.—To determine whether more prolonged PTH administration can prevent estrogen deficiency bone loss from the hip, spine, and total body in young women with endometriosis receiving GnRH analog (nafarelin acetate) therapy.Design.—Randomized controlled trial.Setting.—General Clinical Research Center of a tertiary care, university-affiliated hospital.Patients.—Forty-three women between the ages of 21 and 45 years with symptomatic endometriosis.Intervention.—Nafarelin alone (200 µg intranasally twice daily) or nafarelin plus human parathyroid hormone–(1-34) (hPTH-[1-34]) (40 µg subcutaneously daily).Main Outcome Measures.—The primary end points were bone mineral density (BMD) of the anterior-posterior and lateral spine, femoral neck, trochanter, radial shaft, and total body at 12 months of treatment.Results.—In the women who received nafarelin alone, the mean (SEM) BMDs of the anterior-posterior spine, lateral spine, femoral neck, trochanter, and total body were 4.9% (0.6%) (P&lt;.001), 4.9% (0.8%) (P&lt;.001), 4.7% (1.1%) (P&lt;.001), 4.3% (0.9%) (P&lt;.001), and 2.0% (0.6%) (P=.003) lower than at baseline after 12 months of therapy. In contrast, coadministration of hPTH-(1-34) increased BMD of the anterior-posterior spine by 2.1% (1.1%) (P=.09) and lateral spine by 7.5% (1.9%) (P=.002) and prevented bone loss from the femoral neck, trochanter, and total body, despite severe estrogen deficiency. Radial shaft BMD did not change significantly in either group. Serum bone-specific alkaline phosphatase and osteocalcin concentrations and urinary excretion of hydroxyproline and deoxypyridinoline increased 2-fold to 3-fold during the first 6 to 9 months of therapy in the women who received nafarelin plus hPTH-(1-34) and then declined. Changes in urinary deoxypyridinolone excretion were strongly predictive (r=0.85) of changes in spinal BMD in the women who received nafarelin plus hPTH-(1-34).Conclusions.—Parathyroid hormone prevents bone loss from the proximal femur and total body and increases lumbar spinal BMD in young women with GnRH analog–induced estrogen deficiency.
Interleukin-4 and the Genetics of Atopy
Authors: Lanny J. Rosenwasser
Journal: New England Journal of Medicine (1997)

Interleukin-4 is a critical cytokine in the expression of atopy and allergic diseases. Through its receptor, which consists of a unique α chain and the common lymphoid-receptor γ chain, it signals target cells and tissues to mount a response. When interleukin-4 activates its receptor, it triggers B cells to produce IgE. Interleukin-4 also induces endothelium to express adhesion molecules that specifically attract eosinophils. Finally, interleukin-4 signals T cells to become CD4+ type 2 helper cells, which then produce additional interleukin-4 and mediate allergic disease.1 Genetic regulation of this interleukin-4 cascade may be an important regulatory point in the predisposition to . . .
Evidence of free and bound leptin in human circulation. Studies in lean and obese subjects and during short-term fasting.
Authors: M K Sinha, I Opentanova, J P Ohannesian, J W Kolaczynski, M L Heiman, J Hale, G W Becker, R R Bowsher, T W Stephens, J F Caro
Journal: Journal of Clinical Investigation (1996)

Little is known about leptin's interaction with other circulating proteins which could be important for its biological effects. Sephadex G-100 gel filtration elution profiles of 125I-leptin-serum complex demonstrated 125I-leptin eluting in significant proportion associated with macromolecules. The 125I-leptin binding to circulating macromolecules was specific, reversible, and displaceable with unlabeled leptin (ED50: 0.73 +/- 0.09 nM, mean +/- SEM, n = 3). Several putative leptin binding proteins were detected by leptin-affinity chromatography of which either 80- or 100-kD proteins could be the soluble leptin receptor as approximately 10% of the bound 125I-leptin was immunoprecipitable with leptin receptor antibodies. Significantly higher (P < 0.001) proportions of total leptin circulate in the bound form in lean (46.5 +/- 6.6%) compared with obese (21.4 +/- 3.4%) subjects. In lean subjects with 21% or less body fat, 60-98% of the total leptin was in the bound form. Short-term fasting significantly decreased basal leptin levels in three lean (P < 0.0005) and three obese (P < 0.005) subjects while refeeding restored it to basal levels. The effects of fasting on free leptin levels were more pronounced in lean subjects (basal vs. 24-h fasting: 19.6 +/- 1.9 vs. 1.3 +/- 0.4 ng/ml) compared with those in obese subjects (28.3 +/- 9.8 vs. 14.7 +/- 5.3). No significant (P > 0.05) decrease was observed in bound leptin in either group. These studies suggest that in obese individuals the majority of leptin circulates in free form, presumably bioactive protein, and thus obese subjects are resistant to free leptin. In lean subjects with relatively low adipose tissue, the majority of circulating leptin is in the bound form and thus may not be available to brain receptors for its inhibitory effects on food intake both under normal and food deprivation states.
Two Episodes of Cardiac Arrest in One Week
Authors: W. B. Fleming, J. T. Hueston, J. L. Stubbe, J. D. Villiers
Journal: BMJ (1960)

MEDICAL JOURNA~L procedure is not difficult.There is nothing to lose and a life to gain.Time is the important factor.Cerebral anoxia of 31 to 5 minutes can produce irreversible anoxic damage to the brain.A defibrillating apparatus may or may not be to hand.Electrocardiograms take time, and the decision whether there is ventricular fibrillation or asystole is not an easy one.It has been suggested that where there is doubt an incision should be made in the chest wall.If it bleeds the patient will most certainly be fibrillating.Absence of bleeding indicates asystole.With the former one may have time to wait and try the effects of electrical or chemical defibrillation.On August 20, five months after the incident, the patient was alive and well.There had been no recurrence of his retrosternal pain.Summary This is a case where a patient collapsed for a period of approximately 3 minutes, shortly after admission to hospital with a coronary thrombosis.Simple measures of resuscitation were attempted without effect, and he was presumed to be dead.Through a left sixth intercostal incision the asystolic heart was massaged mnanually for 10 minutes.At the end of this period the ventricles began to fibrillate spontaneously: this was converted to normal rhythms by an intravenous injection of procaine 2%.The patient made an uneventful recovery without evidence of cerebral anoxic damage, and was alive and well at the time of writing, nine months later.A short discussion of the problems and management of cardiac arrest following coronary thrombosis is given.I thank Dr. B. F. Brearley for allowing me to publish this case, Dr. D. M. Anderson
A Professional Response to Demands for Accountability: Practical Recommendations Regarding Ethical Aspects of Patient Care
Authors: Linda L. Emanuel
Journal: Annals of Internal Medicine (1996)

Forceful new demands for accountability in medicine are arising from many interested parties.To maintain professional standards, physicians need to establish which demands are desirable and which are not. We adopt a model of stratified accountability that includes three major components: the accountable parties, the subject matter, and the processes for accountability. To begin describing the model, we focus on physicians and health care institutions. We focus on the ethical dimensions of medical practice, both because the difficulty of measuring such behaviors makes this a test case for accountability and because of the importance of ethical standards in maintaining patient trust. We first identify eight widely endorsed content areas for accountability in ethical conduct:medical decision making, confidentiality, fiduciary obligations (including conflicts of interest), responsibilities arising from patient vulnerability, personal standards, equity among patients, cultural representation, and procedures for resolving dilemmas. We then identify the currently most valid and reliable methods for assessing conduct: surveys among all involved parties, testing methods used for accreditation, limited audits, publication of policy, and careful use of report cards. A prototypical survey and report card are illustrated. However, we also note the need for improved accountability assessment methods. We next identify mechanisms for taking responsibility: sharing information, exchanging perspectives, making adjustments, and enforcing standards when necessary. Finally, because this report only begins to describe a small part of the accountability model, we urge explicit identification and development of professional standards for accountability in the many other areas of medicine. *From Harvard Medical School, Boston, Massachusetts. For the current author address, see end of text. *For members of and consultants for the Working Group on Accountability, see the Appendix.
Regulation of T Cell Receptor β Gene Rearrangements and Allelic Exclusion by the Helix-Loop-Helix Protein, E47
Authors: Yasutoshi Agata, Nobuyuki Tamaki, Shuji Sakamoto, Tomokatsu Ikawa, Kyoko Masuda, Hiroshi Kawamoto, Cornelis Murre
Journal: Immunity (2007)
More widespread public debate on rationing is essential
Authors: I. Heath, S. Amiel
Journal: BMJ (1997)

Editor—We find it significant that none of the clinicians who contributed to the conference “Rationing in the NHS: Time to Get Real” signed the open letter to Frank Dobson.1 In the letter, rationing is defined as occurring when not all health services can be provided to everybody who might benefit from them, a definition so broad that it can be said always to have existed. Yet most British clinicians would not recognise the examples given as rationing. A …
A single seizure.
Authors: E. H. Reynolds
Journal: BMJ (1988)

enriched with eicosapentaenoic acid given to patients with asthma over 10-12 weeks did not, however, lead to any symptomatic improvement or to objective changes in lung function and non-specific bronchial hyperresponsiveness.2223Although dietary fish oil lipids produced no change in most patients with asthma, eicosapentaenoic acid may modulate the disease in a few people.Picado et al showed that a diet containing 3 g of eicosapentaenoic acid daily for six weeks worsened airflow obstruction in 10 patients with asthma and aspirin intolerance.24These effects were attributed to inhibition of the cyclo-oxygenase pathway.Thus adding eicosapentaenoic acid to the diet will lead to it being incorporated into membranes and tissues, which may result in important changes in cellular biochemistry and function and may provide some benefit in selected diseases.Coronary artery disease is the condition that is most amenable to this dietary manipulation, but whether the benefit is sufficient to replace or reduce drug treatment in any condition remains to be seen.