tbuckley/cabot-search huggingface dataset:
Natural History of Lipoid Nephrosis and of Membranous Glomerulonephritis
Authors: VICTOR E. POLLAK
Journal: Annals of Internal Medicine (1968)

Twenty-one patient each with lipoid nephrosis (LN) and membranous glomerulonephritis (MGN) were observed for a long period of time. Six patients with LN and one with MGN were under 14 years of age. All 21 with LN and 17 with MGN had nephrotic syndrome; 4 with MGN had asymptomatic persistent proteinuria. LN and MGN could not be distinguished clinically or by laboratory tests. In LN, fusion of foot processes of glomerular visceral epithelial cells was the only significant finding in initial biopsies. Slight homogeneous thickening of the glomerular basement membrane developed later in 3 patients; no significant changes subsequently occurred in 9 patients. Three patients with LN died presumably of infection when edematous. An average of 5 years later the others were alive without renal functional impairment. The proteinuria decreased rapidly with prednisone treatment in 30 to 40 exacerbations. Continued prednisone treatment was needed in some but not all patients to prerecurrence of proteinuria. In MGN mild to moderately severe thickening of the glomerular capillary basement membrane and extramembranous subepithelial deposits were found in initial biopsies. Serial studies demonstrated little change in the character or severity of the lesions. After an average of 5 years two patients had died. Thirteen had normal renal function, and in all the proteinuria was <2 g/day. Six patients were azotemic; all had persistent heavy proteinuria. There was no effect of prednisone on proteinuria, longevity, or renal function.
Alpha 1-receptor-independent activation of protein kinase C in acute myocardial ischemia. Mechanisms for sensitization of the adenylyl cyclase system.
Authors: R H Strasser, R Braun-Dullaeus, H Walendzik, R Marquetant
Journal: Circulation Research (1992)

The activity of the adrenergic system plays an important role in the genesis of malignant arrhythmias and the spreading of the infarcted zone in acute myocardial ischemia. Acute myocardial ischemia induces an increased activity of adenylyl cyclase. This sensitization at the enzyme level as shown in the isolated perfused rat heart occurs rapidly after the onset of ischemia (5-15 minutes) and is rapidly reversible on reperfusion. With prolonged ischemia, it is only transient and is followed by a gradual loss of the adenylyl cyclase activity. The increased activity of adenylyl cyclase is even retained after partial purification, suggesting a covalent modification of the enzyme. Blockade of alpha 1-adrenergic receptors does not prevent this sensitization, demonstrating that it occurs independently of alpha 1-adrenergic receptor activation. Only blockade of protein kinase C by various inhibitors, such as polymyxin B or staurosporine, is able to completely prevent this sensitization process. Moreover, in acute myocardial ischemia an activation of protein kinase C could be identified using its translocation from the cytosol to the particulate fraction as an indicator. Blockade of alpha 1-adrenergic receptors using prazosin fails to prevent the activation of protein kinase C and consequently the sensitization of the adenylyl cyclase system, indicating that the ischemia-induced translocation of protein kinase C occurs independently of alpha 1-adrenergic receptors. These data characterize for the first time an important interaction of two effector enzymes of two distinct signal transduction pathways, i.e., the adenylyl cyclase system and the protein kinase C system in acute myocardial ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)
Lumleian Lectures on Bright's Disease
Authors: R. Southey
Journal: BMJ (1881)

TURNING once more to the anatomy of the kidney, you will perceive that this reveals an apparatus perhaps more remarkable than that of any other part of the human body in its contrivance.It is a sort of safety-pump, arranged always to work a little.Each ureter of a dog has been shown to drop alternately one drop a minute, but ready, in- stantly that the blood is surcharged with water, as after a full draught, to flow in a full stream.Look at the elaborateness of the tubuli, and the peculiarities of the vascular supplies.Nearly the entire blood that passes through the organ has first to make its passage through the minute capillary plexus rolled up in the Malpighian bodies, or through the vasa recta tufts, before entering on the main drains, which are sin- gularly large capillary networks laid down between the secreting tubes.The vascularity of the whole organ relatively to its size, and the great length of its entire capillary system, the so-called double system of capillaries the blood has to traverse, have attracted the attention of physiologists from the first.Now, each glomerule is not merely a sluice-gate regulating the blood-stream through the organ, but has been shown recently to be a sort of erectile organ.The varying size of the glomerules, according as they are flushed and distended with blood, or comparatively collapsed and flaccid, was pointed out by von Nussbaum in his observations upon the mode of functioning of the living kidney of the triton, which can be laid in a wet chamber under a microscope, and watched at work.He notices how the neck of the ampulliform capsule shortens, and how remarkable the alteration in size of the glomerule is, according to the amount of blood-pressure through the tuft.When the large number of the glomeruli in the kidney is considered,
Cemented, cementless, and hybrid prostheses for total hip replacement: cost effectiveness analysis
Authors: M. Pennington, R. Grieve, J. S. Sekhon, P. Gregg, N. Black, J. H. van der Meulen
Journal: BMJ (2013)

<b>Objective</b> To compare the cost effectiveness of the three most commonly chosen types of prosthesis for total hip replacement. <b>Design</b> Lifetime cost effectiveness model with parameters estimated from individual patient data obtained from three large national databases. <b>Setting</b> English National Health Service. <b>Participants</b> Adults aged 55 to 84 undergoing primary total hip replacement for osteoarthritis. <b>Interventions</b> Total hip replacement using either cemented, cementless, or hybrid prostheses. <b>Main outcome measures</b> Cost (£), quality of life (EQ-5D-3L, where 0 represents death and 1 perfect health), quality adjusted life years (QALYs), incremental cost effectiveness ratios, and the probability that each prosthesis type is the most cost effective at alternative thresholds of willingness to pay for a QALY gain. <b>Results</b> Lifetime costs were generally lowest with cemented prostheses, and postoperative quality of life and lifetime QALYs were highest with hybrid prostheses. For example, in women aged 70 mean costs were £6900 ($11 000; €8200) for cemented prostheses, £7800 for cementless prostheses, and £7500 for hybrid prostheses; mean postoperative EQ-5D scores were 0.78, 0.80, and 0.81, and the corresponding lifetime QALYs were 9.0, 9.2, and 9.3 years. The incremental cost per QALY for hybrid compared with cemented prostheses was £2500. If the threshold willingness to pay for a QALY gain exceeded £10 000, the probability that hybrid prostheses were most cost effective was about 70%. Hybrid prostheses have the highest probability of being the most cost effective in all subgroups, except in women aged 80, where cemented prostheses were most cost effective. <b>Conclusions</b> Cemented prostheses were the least costly type for total hip replacement, but for most patient groups hybrid prostheses were the most cost effective. Cementless prostheses did not provide sufficient improvement in health outcomes to justify their additional costs.
Recent advances of novel targeted therapy in non-small cell lung cancer
Authors: Jed A Katzel, Michael P Fanucchi, Zujun Li
Journal: Journal of Hematology & Oncology (2009)

Abstract Lung cancer is the leading cause of cancer deaths world-wide. Recent advances in cancer biology have led to the identification of new targets in neoplastic cells and the development of novel targeted therapies. At this time, two targeted agents are approved by the FDA in advanced non-small cell lung cancer (NSCLC): the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) erlotinib, and the anitangiogenic bevacizumab. A third agent, cetuximab, which was recently shown to enhance survival when used with cisplatin and vinorelbine as first line therapy for advanced NSCLC, will likely be approved by regulatory agencies. With more than 500 molecularly targeted agents under development, the prospects of identifying novel therapies that benefit individual patients with lung cancer are bright.
Staphylococcal septicaemia complicating treatment of atopic dermatitis with mycophenolate
Authors: A.C. Satchell, R.ST.C. Barnetson
Journal: British Journal of Dermatology (2000)

Sir, Mycophenolate mofetil is an immunosuppressive agent currently used to prevent rejection in renal transplant patients. It has also been used in the treatment of psoriasis,1,2 pemphigus vulgaris,3 bullous pemphigoid,4 pyoderma gangrenosum5 and pompholyx.6 Recently, mycophenolate mofetil was used successfully in two patients with atopic dermatitis.7 We present a case of atopic dermatitis treated with mycophenolate mofetil which was complicated by staphylococcal septicaemia and endocarditis, requiring a mitral valve repair. We believe mycophenolate mofetil may be contraindicated in patients with atopic dermatitis because of the associated risk of bacterial sepsis. A 50‐year‐old woman with a history of asthma and allergic rhinitis had suffered from atopic dermatitis since infancy. Confined to the flexures during the first decade, the dermatitis had become generalized and severe and had been poorly controlled for the past five years. General measures included avoidance of irritants, the use of emollients, topical corticosteroids and antihistamines. Phototherapy with PUVA was tried for two months but there was no improvement. Cyclosporin at high doses (5 mg kg−1 daily) was effective but unfortunately was poorly tolerated due to headaches and lethargy; lower doses of cyclosporin were ineffective. Azathioprine at 1·5 mg kg−1 daily for four months and then 3 mg kg−1 daily for 6 weeks was ineffective.
Malignant Pleural Mesothelioma Localized in the Thoracic Wall
Authors: Daisaku Morimoto, Nobukazu Fujimoto, Hideyuki Nishi, Michiko Asano, Yasuko Fuchimoto, Katsuichiro Ono, Shinji Ozaki, Koji Taguchi, Takumi Kishimoto
Journal: Journal of Thoracic Oncology (2012)
Robert Montraville Green
Authors: Robert S. O'Leary
Journal: New England Journal of Medicine (1957)

IN spite of notable accomplishments in letters and the classics Robert Montraville Green never gave up his interest in medicine: even after his retirement from active teaching and practice, he continued his medical pursuits, among them his position on the editorial board of the New England Journal of Medicine. He thus holds a secure place in the illustrious company of those who, like Oliver Wendell Holmes, made a significant mark afield even while they devoted most of their energies to medicine. Anatomist, teacher, lecturer, editor, classicist, translator and poet, Robert Green was pre-eminently a physician.Of principal concern here . . .
Mortality associated with elective caesarean section
Authors: M H Hall
Journal: BMJ (1994)

mental health law because of a complaint by Irish candidates, but clearly the continuation of this policy may well relate to perceived difficulties concerning candidates from other jurisdictions.Legal provisions are a crucial part of the armamentarium of clinical psychiatry, and it is necessary to overcome practical examination difficulties through examining in alternative jurisdictions.There should be an emphasis on the interface between clinical psychiatry and law, based on the demonstration of adequate know- ledge of not only the Mental Health Act 1983 but also common law, including topics beyond civil detention (I am a member of a joint working party of the BMA and Law Society that is writing a book to inform all doctors about a variety of civil legal incapacities).I applaud the college's exploration with the Department of Health of ways of providing training in mental health law both for trainee psychiatrists and as part of continuing professional development for consultants.
A system of care perspective on prevention
Authors: Philip J Leaf
Journal: Clinical Psychology Review (1999)

Recent efforts to focus preventive interventions on individuals not yet manifesting disorders may have served to further isolate those who are involved with preventive interventions from those who provide clinical treatments. The effective linkage of preventive and remedial interventions requires greater participation by clinicians. Changes in public and private policies concerning the organization and financing of health care provide opportunities to relink these two constituencies. Some opportunities presented by recent developments are reviewed and their implications for expanding preventive interventions discussed.
8-Methoxypsoralen and longwave ultraviolet irradiation are a novel antiproliferative combination for vascular smooth muscle.
Authors: K L March, B L Patton, R L Wilensky, D R Hathaway
Journal: Circulation (1993)

BACKGROUND Smooth muscle cell proliferation plays a major role in the genesis of restenosis after angioplasty or vascular injury. Although the effects of arterial exposure to high-energy radiation sources such as laser have been investigated in detail, the effects on vascular cells of low-intensity radiant energy in combination with photoactive agents have not been extensively characterized. Psoralens are photoactive agents that are known to be well tolerated when used in conjunction with local exposure to ultraviolet light in the A band (UVA) for the treatment of various dermatologic proliferative disorders. METHODS AND RESULTS We have investigated the effects of psoralen/UVA (PUVA) exposure on the proliferation of bovine aortic smooth muscle cells. Proliferation and viability were assessed over a 14-day period by trypan blue exclusion counts. Cell cycle effects were evaluated by thymidine incorporation and flow cytometry with DNA quantitation after addition of serum or platelet-derived growth factor B-chain (PDGF-BB) to subconfluent cells synchronized by serum withdrawal. No effect was observed after exposure to 8-methoxypsoralen (8-MOP) at concentrations up to 10 microM or UVA irradiation at energies up to 2.5 J/cm2. Longwave ultraviolet light and 8-MOP were found to behave synergistically as potent inhibitors of DNA synthesis in bovine aortic smooth muscle cells with the EC50 in combination ranging from 7 microM at 0.35 J/cm2 to 0.2 microM at 2.1 J/cm2. Similar antiproliferative effects were obtained by an inverse variation of dose and energy delivered. After serum stimulation, inhibition of DNA synthesis was found with either an immediate or delayed (16-hour) application of PUVA. This effect was independent of subsequent 8-MOP washout. Flow cytometry of cells treated with PUVA at several times after serum stimulation demonstrated for each time point a block in further cell cycle progression for cells in all phases of the cell cycle. Evaluation of [125I]-labeled PDGF and epidermal growth factor (EGF) binding revealed no effect of PUVA on the apparent number or affinity of PDGF binding sites present but did reveal a dose-dependent inhibition by PUVA of EGF binding. This inhibition of EGF binding occurred increasingly at higher PUVA doses than the cell cycle inhibition and accordingly did not appear to represent a critical mechanism for the antiproliferative effect. Cell counting after a single exposure to PUVA (1 microM, 1.5 J/cm2) revealed complete stasis of cell proliferation over a 28-day period without recurrent exposure. No increase in trypan-positive cells was noted over this period. CONCLUSIONS PUVA treatment represents a novel method for locally inhibiting proliferation of vascular smooth muscle cells without producing cytolysis.
Elevated C-Reactive Protein Levels, Psychological Distress, and Depression in 73 131 Individuals
Authors: Marie Kim Wium-Andersen, David Dynnes Ørsted, Sune Fallgaard Nielsen, Børge Grønne Nordestgaard
Journal: JAMA Psychiatry (2012)

<h3>Context</h3>The pathogenesis of depression is not fully understood, but studies suggest that low-grade systemic inflammation contributes to the development of depression.<h3>Objective</h3>To test whether elevated plasma levels of C-reactive protein (CRP) are associated with psychological distress and depression.<h3>Design</h3>We performed cross-sectional and prospective analyses of CRP levels in 4 clinically relevant categories using data from 2 general population studies.<h3>Setting</h3>The Copenhagen General Population and the Copenhagen City Heart studies.<h3>Participants</h3>We examined 73 131 men and women aged 20 to 100 years.<h3>Main Outcome Measures</h3>We ascertained psychological distress with 2 single-item self-reports and depression using self-reported antidepressant use, register-based prescription of antidepressants, and register-based hospitalization with depression.<h3>Results</h3>In cross-sectional analyses, increasing CRP levels were associated with increasing risk for psychological distress and depression (P = 3 × 10<sup>−8</sup> to P = 4 × 10<sup>−105</sup> for trend). For self-reported use of antidepressants, the odds ratio was 1.38 (95% CI, 1.23-1.55) for CRP levels of 1.01 to 3.00 mg/L, 2.02 (1.77-2.30) for 3.01 to 10.00 mg/L, and 2.70 (2.25-3.25) for greater than 10.00 mg/L compared with 0.01 to 1.00 mg/L. For prescription of antidepressants, the corresponding odds ratios were 1.08 (95% CI, 0.99-1.17), 1.47 (1.33-1.62), and 1.77 (1.52-2.05), respectively; for hospitalization with depression, 1.30 (1.01-1.67), 1.84 (1.39-2.43), and 2.27 (1.54-3.32), respectively. In prospective analyses, increasing CRP levels were also associated with increasing risk for hospitalization with depression (P = 4 × 10<sup>−8</sup> for trend).<h3>Conclusions</h3>Elevated levels of CRP are associated with increased risk for psychological distress and depression in the general population.
Initial Treatment of Venous Thromboembolism
Authors: Simon J. McRae, Jeffrey S. Ginsberg
Journal: Circulation (2004)

Adequate initial anticoagulant therapy of deep venous thrombosis (DVT) is required to prevent thrombus growth and pulmonary embolism (PE). Intravenous unfractionated heparin (UFH) is being replaced by low-molecular-weight heparin (LMWH) as the anticoagulant of choice for initial treatment of venous thromboembolism (VTE). Both agents are relatively safe and effective when used to treat VTE, with LMWH suitable for outpatient therapy because of improved bioavailability and more predictable anticoagulant response. Serious potential complications of heparin therapy, such as heparin-induced thrombocytopenia (HIT) and osteoporosis, seem less common with LMWH. The potential for fetal harm and changes in maternal physiology complicate the treatment of VTE during pregnancy. Although systemic thrombolysis is used in patients with massive PE and in some patients with proximal DVT, controversy persists with respect to appropriate patient selection for this intervention.
Teaching procedural skills
Authors: Teodor P Grantcharov, Richard K Reznick
Journal: BMJ (2008)

“See one, do one” is not the best way to teach the complex technical procedures needed in many hospital based specialties For many patients, a successful clinical outcome depends on having a well performed technical procedure. Crucial for surgeons, technical competence is becoming an important element of training for many hospital based specialists: interventional radiologists, cardiologists, gastroenterologists, endovascular therapists, and others. “See one, do one” is no longer appropriate for educating health professionals to perform complex procedures. Graduated independence, the hallmark of the approach to teaching procedural skills, is being challenged by concerns for patients’ safety, the skyrocketing complexity of procedures, and a diminishing work week for trainees. Finding the balance between patients’ safety and doctors’ training will require a more structured approach to our skills curriculum, including continuous assessment of skills, constructive feedback, and provision of opportunities for deliberate practice in the teaching environment. This paper aims to provide an evidence based algorithm for procedural skills training. It focuses on teaching technical skills, which are just one component of a successful procedure—others are clinical judgment, communication, and team work. Currently, training in technical procedures is often unsystematic and unstructured. Educational tools that have been validated are often underutilised,1 and evidence is growing that adjunctive methods for procedural teaching, such as the use of virtual reality, have not been translated into clinical practice. Teaching communities worldwide would benefit from standardised validated curriculums that use proved technology for teaching technical competence effectively, minimise wasted time, and focus on the breadth of skills needed for a specific practice. ### Pre-patient training Pretraining for technical skills should involve three major components, which should be done outside the clinical setting:
Drug companies oppose India's move to slash prices of 50 drugs
Authors: S. Bagcchi
Journal: BMJ (2014)

India’s drug price regulator, the National Pharmaceutical Pricing Authority (NPPA), has announced that the prices of 50 cardiovascular and diabetes medicines will be reduced by 35%.

The authority used a rare provision in the Drugs Price Control Order 2013 to make the price changes. The provision allows the regulator to cut the price of medicines in “extraordinary situations” to protect the public interest. 

The NPPA told …
IUD and Endocarditis
Authors: Henry S. Kahn, Carl W. Tyler
Journal: Annals of Internal Medicine (1973)

This letter disagrees with the conclusions drawn in a cited article linking endocarditis to the use of IUDs. That article had suggested on the basis of 1 serious infection, that women with endocardial damage should not use the IUD. Since other contraceptive methods are either not as reliable or are contraindicated for women with endocardial abnormalities, these authors feel that the IUD, considering the availability of antibiotic prophylaxis, could be the most likely choice for the cardiac patient.