tbuckley/cabot-search huggingface dataset:
Signalling in cardiac disease: the molecular deficit at the heart of the problem
Authors: T Hébert
Journal: Cardiovascular Research (2001)

See article by Yoshida et al. [3] (pages 34–45) in this issue. 

Events leading to heart failure are characterized by a prolonged action potential and a deficit in cardiac performance which is paralleled by ionic remodelling and a loss of contractile function at the level of the single cardiomyocyte (see Ref. [1] for review). Increased sympathetic stimulation as well as a number of paracrine and autocrine factors lead to cardiac hypertrophy and an eventual decompensated failing phenotype [2]. However, several issues remain to be resolved in terms of a molecular mechanism for these events. First, is there a deficit in the contractile apparatus of the failing myocyte per se? Alternatively, are signalling pathways which modulate contractility and are known to be altered in the failing heart the trigger for these events? Further, the focus of work on whole cardiac tissue to date has not resolved the role of non-myocyte cells in the disease process. Finally, the subcellular localization and compartmentalization of signalling pathways and the proteins they modulate may be of critical importance as well. The study by Yoshida et al. [3] in this issue of Cardiovascular Research begins to address some of these important issues. The authors demonstrate that although contractile function is clearly maintained in isolated cardiomyocytes from animals with coronary artery ligation-induced congestive heart failure (CHF), their regulation by the β-adrenergic system is significantly altered resolving a dilemma in the literature about the actual deficit in failing hearts. Further, they show alterations in levels of Gsα but not Giα subunits in cardiomyocytes, while in non-myocytes there are significant alterations in both subtypes. These results are important as they address the actual site of the molecular deficit in cardiac tissue.

The regulation of [Ca2+]i plays a central role in cardiac performance. Ca2+-dependent … 

* Tel.: +1-514-376-3330; fax: +1-514-376-1355 hebertt{at}icm.umontreal.ca
Joseph William Thorpe Redfearn
Authors: A. Redfearn
Journal: BMJ (2011)

Joseph William Thorpe Redfearn (“Joe”) won a scholarship to Emmanuel College, Cambridge, where he gained a double first in natural sciences and psychology. He was then a Rockefeller student at Johns Hopkins School of Medicine, Baltimore, United States. After returning to the UK, he was invited by influential psychiatrist Professor Aubrey Lewis to join his team at …
Replicative senescence of activated human hepatic stellate cells is accompanied by a pronounced inflammatory but less fibrogenic phenotype
Authors: Bernd Schnabl, Carrie A. Purbeck, Youkyung Hwang Choi, Curt H. Hagedorn, David Brenner
Journal: Hepatology (2003)

Limited proliferative capacity is a characteristic of most normal human cells and results in a growth–arrested state, called replicative senescence . Functional expression of the telomerase catalytic subunit (human telomerase reverse transcriptase; hTERT) in human activated hepatic stellate cells (HSCs) rescues them from death with immortalization and maintains an activated HSC phenotype. The aim of this study was to evaluate alterations in gene and protein expression of in vitro aged human activated HSCs and to define the pathway by which senescent–activated HSCs are eliminated in culture. Altered patterns of gene expression in senescent human HSCs were assessed using DNA microarray analysis and compared with early passage HSCs or hTERT immortalized HSCs. Senescent HSCs showed higher expression of inflammation and stress–associated genes as compared with early passage HSCs. Senescent HSCs expressed reduced levels of extracellular matrix proteins, including collagens, tenascin, and fibronectin. TUNEL staining of senescent HSCs showed approximately 21% positive cells, indicating DNA fragmentation and apoptosis. Apoptosis involved the mitochondrial pathway with decreased levels of Bcl–2 and Bcl–x L protein, release of cytochrome c, and increased caspase–3 activity. In contrast, 4% to 5% of early activated HSCs or telomerase positive HSCs were TUNEL positive. In conclusion, cultured human HSCs undergo a switch from a fibrogenic to an inflammatory phenotype, suggesting that senescent human HSCs might modulate chronic wound healing processes. Maintenance of telomere length represents an important survival factor for activated human HSCs.
Robert Kingston Knight
Authors: Robert Rubens
Journal: BMJ (2006)

​FormerFormer consultant physician Guy's Hospital, London (b 1932; q Guy's Hospital 1955), d 31 December 2005.



Figure 1





Bob Knight was the last of the great general physicians of Guy's Hospital. He had a special interest in respiratory diseases and oncology. He was also an authority on John Keats. Bob became consultant physician at Guy's Hospital in 1967, retiring in 1997. In retirement he pursued his long-standing interest in life assurance medicine. As a Winnie the Pooh enthusiast he also investigated why repeat transient ischaemic attacks seem to have similar characteristics to Pooh sticks, the results being published in the 2004 Christmas edition of the BMJ (BMJ 2004;329: 1432. [PubMed]). He leaves a wife, Marion; two sons; and a grandson.
Which Hip Operation for Which Patient
Authors: Mark B. Coventry
Journal: JAMA (1965)

Recent changes in concepts of surgery of the hip make it desirable to look at the entire problem in perspective. Enthusiasts for one or another type of operation are emerging in this country and abroad. The methods proposed are considered, tried out on patients, and evaluated retrospectively. Today new procedures that have been used, particularly in parts of Europe, are being utilized in the United States. Surgeons here have had enough experience with most of them for at least a preliminary evaluation.  Even orthopedists may misunderstand exactly what is meant by a certain type of procedure. Much of this stems from failure to read the original description of the operation and from use of eponyms, often in part incorrectly, to designate certain operations. The use of eponyms is especially confusing to nonorthopedic physicians, who must be at least superficially familiar with technique and have some understanding of the terminology of
Inactivation of ribosomal protein L22 promotes transformation by induction of the stemness factor, Lin28B
Authors: Shuyun Rao, Sang-Yun Lee, Alejandro Gutierrez, Jacqueline Perrigoue, Roshan J. Thapa, Zhigang Tu, John R. Jeffers, Michele Rhodes, Stephen Anderson, Tamas Oravecz, Stephen P. Hunger, Roman A. Timakhov, Rugang Zhang, Siddharth Balachandran, Gerard P. Zambetti, Joseph R. Testa, A. Thomas Look, David L. Wiest
Journal: Blood (2012)
Cancer as a Sequel to Therapy
Authors: Clark W. Heath
Journal: New England Journal of Medicine (1972)

Cancer is occasionally a side-effect of therapy. Two articles in this week's Journal concern this area of tumor etiology. One describes a previously unrecognized risk, — cancer after intensive therapy in Hodgkin's disease,—and the other refutes an association — that tonsillectomy predisposes to Hodgkin's disease.In the first article Arseneau and his co-workers report a statistically significant increase in incidence of secondary cancer (12 cases observed, 3.4 expected) among 425 cases of Hodgkin's disease. Although the conclusions are limited by small numbers, risk seems largely associated with radiotherapy, alone or in combination with chemotherapy, and it may be especially great . . .
Samuel Gridley Howe
Authors: Peter Pineo Chase
Journal: New England Journal of Medicine (1953)

RARELY, if ever, has any Boston doctor been farther afield than Samuel Gridley Howe. This is not to speak, of course, in great circle miles, but the mountains of Greece in 1825 were far away in time and circumstance.He was born on Pearl Street, probably, then, just on the outskirts of the best neighborhood in Boston. He went to the Boston Latin School, and since the family could afford to send only one boy to college, Sam was picked. The test was the reading of the Bible. Politics were taken seriously around Boston in those days. Harvard was Federalist, . . .
ADDITIONAL EVIDENCES OF THE VALUE OF FORCED RESPIRATION (FELL METHOD), IN OPIUM NARCOSIS. REPORT OF CASES.
Authors: GEO E. FELL
Journal: JAMA (1892)

It is now nearly five years since I saved my first life by systematically respiring for a human being by forced respiration. Up to the present time nineteen human lives have been saved by this means. The method has been given as great publicity as possible by publication in well known medical journals and proceedings of societies. The fullest detail as to the arrangement of apparatus has been described, so that the successful methods could be utilized and the apparatus prepared by any one sufficiently interested. I have always been willing to aid and assist any one disposed to utilize the method. The most simple means by which the operation could be satisfactorily performed have been detailed, with a view of aiding the practitioner in urgent cases where the complete apparatus could not be obtained. However, what results have been accomplished as already stated, the saving of nineteen human lives,
Potential arrhythmogenic electrophysiological derangements in canine Purkinje fibers induced by lysophosphoglycerides.
Authors: P B Corr, M E Cain, F X Witkowski, D A Price, B E Sobel
Journal: Circulation Research (1979)

We have recently detected accumulation of lysophosphoglycerides, catabolites of phospholipids, in ischemic myocardium early after coronary occlusion. In the present study we delineated effects of selected concentrations of albumin-bound lysophosphatidyl choline (LPC) comparable to those accompanying ischemia in vivo on action potentials of isolated canine Purkinje fibers. Lysophosphoglycerides induced concentration-dependent (0.75-3.0 mM) decreases in resting membrane potential, overshoot of phase 0, maximal velocity of upstroke (Vmax) of phase 0, and action potential duration. The highest concentrations (2.0-3.0 mM) induced fractionation of the action potential into several components, unresponsiveness to external stimulation, and enhanced automaticity at normal and reduced membrane potentials. LPC induced a rightward shift in the membrane response curve, a 40-fold prolongation of conduction time, and an increase in the ratio of effective refractory period to action potential duration such that the effective refractory period persisted beyond action potential duration, resulting in postrepolarization refractoriness. These electrophysiological alterations were entirely reversible after 70 minutes of perfusion without LPC, with the exception of a persistent depression in the Vmax of phase 0. Lysophosphatidyl ethanolamine (LPE) elicited alterations in action potentials indentical to those elicited by LPC. Furthermore, LPC (3.0 mM) induced comparable alterations in action potentials recorded from isolated rabbit papillary muscles. Since lysophospholipids accumulate early after myocardial ischemia, and since concentrations equivalent to those occurring in vivo induce electrophysiological alterations resembling those seen in ischemic myocardium in vivo, lysophosphoglycerides may be of major importance as biochemical mediators of malignant dysrhythmia induced by ischemia.
Neuropsychological Impairments in Schizophrenia and Psychotic Bipolar Disorder: Findings from the Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP) Study
Authors: S. Kristian Hill, James L. Reilly, Richard S.E. Keefe, James M. Gold, Jeffrey R. Bishop, Elliot S. Gershon, Carol A. Tamminga, Godfrey D. Pearlson, Matcheri S. Keshavan, John A. Sweeney
Journal: American Journal of Psychiatry (2013)

Familial neuropsychological deficits are well established in schizophrenia but remain less well characterized in other psychotic disorders. This study from the Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP) consortium 1) compares cognitive impairment in schizophrenia and bipolar disorder with psychosis, 2) tests a continuum model of cognitive dysfunction in psychotic disorders, 3) reports familiality of cognitive impairments across psychotic disorders, and 4) evaluates cognitive impairment among nonpsychotic relatives with and without cluster A personality traits.
DEVELOPMENT AND OPTIMIZATION OF AN INTERVENTION FOR INJURY PREVENTION IN PHYSICAL EDUCATION TEACHERS APPLYING SDT
Authors: S Vercruysse
Journal: British Journal of Sports Medicine (2014)

Background PE teachers are at high risk of injuries because of the total package of physically active tasks 1 2 3 , so a good injury prevention intervention is needed. Objective The main research goal was to develop, optimize and trace the feasibility of an SDT-grounded intervention of injury prevention in PE teachers. The second aim was improving the awareness and knowledge for injury prevention in PE teachers in order to motivate towards change in teachers' actual behavior. Design The two trainings were each given 5 times and adjusted 2 times. Also a pre-post (awareness and knowledge) and baseline (injury history) was completed. Setting PE teachers of 9 different schools in Flanders (BE). Participants 20 PE teachers (13 men, 7 women; mean age: 42.1±2.2 years) of nine different schools in Flanders (Belgium), voluntarily participated. The PE teachers had to give at least some hours of PE in secondary school and this for the hole period of investigation. There was a drop-out of 3 PE teachers. Interventions 8 prevention strategies were offered, consisting of: one theoretical (Part I) and two practical parts (Part II &amp; III), which were spread over two trainings. Training A included part I and II, training B consisted of part III. Main outcome measurements Appreciation, opinions and suggestions of the usefulness, presentation and form of the different parts of the intervention (focus groups and questionnaires). Secondly self-reported behavior, awareness and knowledge to motivate the PE teachers towards injury prevention. Results Both the suggestions and adjustments of the PE teachers resulted into an optimized and feasible intervention. The weekly average of applied prevention strategies was 70.7min/week in males and 38.0min/week in females. Behavior (P=.015), awareness (P&lt;.001) and knowledge (P&lt;.001) improved. Conclusions There is a big appreciation for the intervention and first results show an improved behavior, knowledge and awareness.
PROSTATECTOMY.REPORT OF 51 CASES OPERATED ON FROM MAY 6, 1901, TO FEBRUARY 26, 1904.
Authors: JOHN B. MURPHY
Journal: JAMA (1904)

The surgery of the prostate is rapidly approaching that of the appendix and gall bladder in its significance to the surgeon and patient. Until very recently the prostate was not treated in the masterful and efficient manner in which other organs, as the uterus, tubes and stomach were handled surgically. In considering this subject to-day I trust I will be permitted to omit the details of anatomic relations and physiologic functions of the prostate, described in full in my recent article on the subject. I will, however, go more into the details of the clinical aspects of the cases. The etiologic factors, the pathologic conditions of the bladder and kidneys at the time of the operation, and the patient's general condition will be more carefully treated. Experience has produced a number of changes in the technic of the operation and as time advances we are able to procure more speedy
Changes in Histologic and Biochemical Indexes of Bone Turnover after Bilateral Nephrectomy in Patients on Hemodialysis
Authors: John A. Kanis, Margaret Earnshaw, Guy Heynen, John G.G. Ledingham, Des. O. Oliver, R. Graham G. Russell, Colin G. Woods, Paul Franchimont, Simone Gaspar
Journal: New England Journal of Medicine (1977)

We studied the effects of bilateral nephrectomy on bone metabolism in 27 patients on maintenance hemodialysis. After nephrectomy plasma alkaline phosphatase fell rapidly in 10 patients whose preoperative plasma levels had been higher than normal. This fall was associated with a transient decrease in osteoblast counts of iliac-bone biopsies. A fall in plasma phosphate and a rise in plasma immunoreactive calcitonin also occurred, but calcium and immunoreactive parathyroid hormone levels did not change. Alkaline phosphatase levels remained unchanged in a control group of 17 patients on dialysis who had undergone an operation other than nephrectomy. In 26 nonsurgical patients on dialysis, immunoreactive calcitonin was inversely related to osteoblast counts. Rises in immunoreactive calcitonin may be partly responsible for the transient decreases in bone turnover after bilateral nephrectomy. Low levels of endogenous calcitonin may allow an increase in bone turnover in chronic renal failure. (N Engl J Med 296:1073–1079, 1977)
Stargazing microRNA maps a new miR-21 star for cardiac hypertrophy
Authors: Ciro Indolfi, Antonio Curcio
Journal: Journal of Clinical Investigation (2014)

Left ventricular hypertrophy is an initial compensatory mechanism in response to cardiac stress that can degenerate into heart failure and sudden cardiac death. Recent studies have shown that microRNAs (miRs) regulate several aspects of cardiovascular diseases. In this issue of the JCI, Bang and colleagues identified an exosome-mediated communication mechanism between cardiac fibroblasts and cardiomyocytes. Specifically, cardiac fibroblasts secrete miR-enriched exosomes, which are subsequently taken up by cardiomyocytes, in which they alter gene expression. In particular, a passenger strand miR, miR-21*, was identified as a potent paracrine factor that induces cardiomyocyte hypertrophy when shuttled through exosomes. These advanced comprehensive analyses represent a major step forward in our understanding of cardiovascular physiopathology, providing a promising adjunctive target for possible therapeutic approaches, namely the miR-mediated paracrine signaling network.
The Person: His and Her Development Throughout the Life Cycle
Authors: Marjorie C. Meehan
Journal: JAMA (1977)

Although originally designed for medical students, the first edition (1968) of this book has proved useful to a variety of readers—physicians, parents, anyone interested in the way people grow and adapt to changing life situations. Now a second, markedly revised edition contains some new insights and much more material, especially about the problems of girls and women and about middle and old age. The point of view is dynamic—a skillful blending of psychoanalytic thought, the psychobiology of Adolph Meyer, the cognitive studies of Piaget, and the perceptions of an experienced, well-read, thoughtful psychiatrist. This is not a textbook of psychiatry. It makes no pretence of discussing serious psychopathology or its treatment. Neither is it a book of popular do-it-yourself psychotherapy. Instead it is a clear introduction to the understanding of normal people and their problems.
William Hickling Prescott, 1796–1859
Authors: Edward C. Atwater
Journal: New England Journal of Medicine (1966)

ON Friday the 13th of January, 1815, James Jackson, M.D.,‡ Hersey Professor of the Theory and Practice of Physick in Harvard University, was called to see a young man with an inflammation of the right eye. The problem appeared to be conjunctivitis and Jackson "directed some leeches and a saturnine lotion." That night the pain and inflammation became much worse, and by the next morning the conjunctiva was very much swollen and very red, the cornea opaque, and the powers of vision entirely lost. The skin was hot, and the pulses hard and accelerated." Jackson "bled him freely from the . . .
The Role of Gallbladder Emptying in Gallstone Formation During Diet–Induced Rapid Weight Loss
Authors: R L Gebhard, W F Prigge, H J Ansel, L Schlasner, S R Ketover, D Sande, K Holtmeier, F J Peterson
Journal: Hepatology (1996)

Obese persons are at risk for cholesterol gallstones because their bile is saturated with cholesterol. The risk increases during rapid weight loss by means of certain very–low–calorie diets or gastric bypass surgery. Gallstone risk factors during rapid weight loss include increased bile cholesterol saturation index and gallbladder stasis. Obese subjects were randomized to one of two low–calorie liquid diets for rapid weight loss: a 520–kcal diet with less than 2 g fat/d, and a 900–kcal diet with 30 g fat/d (including one 10–g fat meal to stimulate maximal gallbladder emptying). Bile and blood lipids, saturation index, leukocyte 3–hydroxy–3–methylglutaryl coenzyme A (HMG CoA) reductase activity, and ultrasonographic gallbladder emptying were measured repeatedly during dietary treatment. Both diets produced comparable weight loss of 22%. Bile cholesterol saturation index increased during both diets (26%), but fell to 15% below prediet level after weight loss. Compared with subjects' maximal gallbladder emptying fraction of 66%, the 520–kcal diet provided poor gallbladder emptying (35%), whereas the 10–g fat meal of the 900–kcal diet provided maximal emptying. Gallstones developed in four of six 520–kcal subjects and none of seven 900–kcal subjects ( P = .021), an unanticipated difference that resulted in premature study termination for ethical reasons. Blood lipids and HMG CoA reductase activity in mononuclear leukocytes fell at week 8 during both diets, but recovered while weight was still being lost. The findings suggest that gallstone risk during rapid weight loss may be reduced by maintenance of gallbladder emptying with a small amount of dietary fat. Ultimately, weight loss reduced bile cholesterol saturation and improved highdensity lipoprotein (HDL) levels.
Sensitivity to insulin during treatment with atenolol and metoprolol: a randomised, double blind study of effects on carbohydrate and lipoprotein metabolism in hypertensive patients.
Authors: T. Pollare, H. Lithell, I. Selinus, C. Berne
Journal: BMJ (1989)

To compare the effects of metoprolol and atenolol on carbohydrate and lipid metabolism and on insulin response to an intravenous glucose load.Randomised, double blind, double dummy, controlled crossover trial.University Hospital, Uppsala, Sweden.60 Patients with primary hypertension (diastolic blood pressure when resting supine 95-119 mm Hg on at least two occasions during four to six weeks of treatment with placebo) randomised to receive either metoprolol (n = 30) or atenolol (n = 30) during the first treatment period.Placebo was given for a run in period of four to six weeks. Metoprolol 100 mg twice daily or atenolol 25 mg twice daily was then given for 16 weeks. The two drugs were then exchanged and treatment continued for a further 16 weeks.Evaluation of effects of treatment with metoprolol and atenolol on glucose, insulin, and lipid metabolism and glucose disposal mediated by insulin.Reduction of blood pressure was similar and satisfactory during treatment with both drugs. Glucose uptake mediated by insulin was measured during a euglycaemic hyperinsulinaemic clamp to evaluate patients' sensitivity to insulin. Glucose uptake decreased from 5.6 to 4.5 mg/kg/min when patients were taking metoprolol and from 5.6 to 4.9 mg/kg/min when they were taking atenolol. Both drugs caused a small increase in fasting plasma insulin and blood glucose concentrations and glycated haemoglobin concentration. Despite decreased sensitivity to insulin the increase in insulin concentration in response to an intravenous glucose tolerance test was small, suggesting inhibition of release of insulin. Very low density lipoprotein and low density lipoprotein triglyceride concentrations were increased with both drugs and high density lipoprotein cholesterol concentration was decreased. Low density lipoprotein cholesterol concentration was not affected.Long term use of metoprolol and atenolol causes metabolic abnormalities that may be related to the increased incidence of diabetes in patients with hypertension who are treated pharmacologically. These results may help to explain why the two drugs have failed consistently to reduce the incidence of coronary heart disease in several large scale studies.