tbuckley/cabot-search huggingface dataset:
Neuromuscular blocking drugs: discovery and development
Authors: T. Raghavendra
Journal: Journal of the Royal Society of Medicine (2002)

The introduction of neuromuscular blocking drugs revolutionized the practice of anaesthesia. Before the advent of muscle relaxants, anaesthesia was induced and maintained by intravenous or inhalation agents. Tracheal intubation was uncommon, and muscle relaxation if needed was secured by deep inhalation anaesthesia with its attendant risks of respiratory or cardiac depression. After the introduction of muscle relaxants, anaesthesia underwent a conceptual change. Anaesthesia was redefined as a triad of narcosis, analgesia and muscle relaxation, specific drugs being used to produce each of these effects1.

Muscle relaxants belong to two groups, the depolarizers and the nondepolarizers. Depolarizers mimic the effect of acetylcholine at the neuromuscular junction, first causing muscle contractions (fasciculations) and then paralysing. Suxamethonium, the only depolarizer in use, has the advantage of acting within 60 seconds. Muscle relaxation lasts for under 5 minutes. It is not reversed by anticholinesterases such as neostigmine but plasma cholinesterase causes the effect to wear off quickly. Unwanted effects include malignant hyperpyrexia, increased intraocular pressure and life-threatening hyperkalaemia. Several deaths attributable to hyperkalaemic cardiac arrest have occurred following the use of suxamethonium in children with undiagnosed muscular dystrophies. There is a clinical need for a safer drug that works equally quickly. Nondepolarizers have slower onset (2-3 minutes) and are therefore unsuitable for rapid control of the airway. They work by competitive blockade of the neuromuscular junction and are reversed with anticholinesterases such as neostigmine. There is no initial muscle fasciculation. Important features of some of the nondepolarizers are listed in Table 1.



Table 1

Features of nondepolarizing agents
II. PHARMACOLOGIC ACTION OF INSULIN
Authors: F. G. BANTING
Journal: JAMA (1924)

The exact mode of action of insulin is not clearly known. When artificially prepared, insulin, if administered subcutaneously, intravenously or intraperitoneally, causes a fall in the percentage of sugar in the blood. When this percentage falls below the kidney threshold in the diabetic patient, sugar disappears from the urine. If an overdose of insulin is given, the blood sugar falls to a subnormal level, and characteristic symptoms are observed. The level at which these symptoms occur depends not only on the extent but also on the rate of fall. If the blood sugar has been persistently high and is rapidly reduced, hypoglycemic symptoms may appear at a much higher level of blood sugar than occurs when the fall is slower and more gradual. These symptoms are due to the diminished sugar in the blood, as shown by the fact that they are relieved by the replacement of the sugar by
Evaluation of Low-Dose Radioiodine Ablation Therapy in Postsurgical Thyroid Cancer Patients
Authors: LALITHA RAMANNA, ALAN D. WAXMAN, MICHAEL B. BRACHMAN, DOINA E. TANASESCU, NANCY SENSEL, GLENN D. BRAUNSTEIN
Journal: Clinical Nuclear Medicine (1985)

Nineteen patients with differentiated thyroid carcinoma were given low dose (30 mCi) radioiodine therapy for the ablation of residual thyroid tissue following total thyroidectomy. Using 5- to 10-mCi diagnostic I-131 scans, ablation was achieved in two of 19 patients following the first low dose and three of 12 patients following the second low-dose therapy. The ablation response was 53% (ten of 19) following one large dose (100 mCi) in another concurrent group of 19 patients. The ablation response following the first low dose when compared with the first high-dose therapy was significantly lower (P = 0.015). The combined ablation response following first and second low doses (five of 14) when compared to a single large dose was not significantly different (P = 0.534). The use of low-dose-I-131 therapy, although not as effective as large dose therapy, may be warranted in patients resistant to entering the hospital for therapy. However, ablation as defined by a five- to ten-mCi I-131 scan can be expected to occur in only one third of the patients after two attempts at ablation, while a single 100-mCi regimen can be successful in achieving ablation in over one half of the patients after the first attempt.
Severe Mitral Regurgitation Secondary to Ruptured Chordae Tendineae
Authors: CHARLES A. SANDERS, J. GORDON SCANNELL, J. WARREN HARTHORNE, W. GERALD AUSTEN
Journal: Circulation (1965)

Fifteen cases of severe mitral regurgitation secondary to ruptured chordae tendineae have been reviewed, eight of whom underwent open-heart surgery to correct their lesions. Three patients are living at this time with two being markedly improved. Cardiac catheterization was performed in six prior to surgery. Progressive deterioration within the year following the onset of difficulty or sudden worsening of previous cardiac symptoms characterized the usual clinical course. The apical systolic murmur, always loud, was conspicuously harsh and radiated to the base of the heart, simulating aortic stenosis when the mural cusp was ruptured. Although strongly suggesting the diagnosis, the sudden onset of an apical systolic murmur could be documented in only three instances. The presence of a small left atrium radiographically with tall left atrial "v" waves and marked reflux of contrast material into a paradoxically pulsating left atrium also pointed to the correct diagnosis. Various technics of surgical repair and problems influencing survival of patients in the present series are discussed.
Cataract Surgery in Patient Who Sneezes
Authors: Jay Gross
Journal: JAMA (1985)

To the Editor.—  I must respond to a reply in the QUESTIONS AND ANSWERS section in the March 23/30,1984, issue ofThe Journal 1 concerning cataract surgery in a patient with cardiovascular disease and severe sneezing. I agree with Dr Shoch's comments but believe they are incomplete.  There are three popular modes of removing cataracts at this time. The first, intracapsular extraction, requires a wound of approximately 18 mm. The second, planned extracapsular extraction, uses a 10- to 12-mm incision. The third, phacoemulsification, uses only a 3-mm incision, which would be enlarged to 7 mm to insert an intraocular lens. Another advantage of the phacoemulsification is that it is done with an essentially closed eye and there is much less risk of severe damage to the eye due to coughing or sneezing during surgery. Also, it is much easier to control such an event if it were to occur.  Therefore,
Smoking and ulcerative colitis.
Authors: R F Logan, M Edmond, K W Somerville, M J Langman
Journal: BMJ (1984)

In a case-control study of smoking and ulcerative colitis patients with the disease were much less likely to smoke than community controls matched for age and sex. The difference was substantial, with an estimated relative risk of 3.8 for non-smoking on current habits, was even larger (6.2) when habits at onset of the disease were examined, and was mainly accounted for by 42 of 55 patients who had given up smoking a mean of eight years before onset. The association could not be explained by confounding by social class. These findings suggest that smoking directly or indirectly confers protection against ulcerative colitis.
The Epidemiology of Injuries in Atlanta Day-care Centers
Authors: Jeffrey J. Sacks
Journal: JAMA (1989)

From June 1987 through May 1988, we collected reports of injuries among 5300 children who attended 71 day-care centers in Atlanta, Ga. One hundred forty-three injuries severe enough for the child to require medical or dental care were reported, including 63 lacerations (44.1%), 23 fractures (16.1%), 5 crush injuries (3.5%), 4 dislocations (2.8%), 2 human bites (1.4%), and 2 concussions (1.4%). The head was the site of 98 (68.5%) injuries. Peak hours for injuries were 11 AM and 4 PM, the peak day was Monday, and the peak season was summer. After adjustment for hours and dates of attendance, the rate was 1.77 injuries per 100,000 child-hours in day care; among preschool-aged children, infants had the lowest rate (0.77) and 2-year-old children had the highest rate (2.26). Almost 47% of injuries occurred on the playground; falls were involved in 70% of such injuries. Because 33% of all injuries resulted from falls on the playground, impact-absorbing playground surfaces may be a possible intervention to reduce injuries.
CLINICAL RELEVANCE OF PROTEINASE ACTIVATED RECEPTORS (PARS) IN THE GUT
Authors: N Vergnolle
Journal: Gut (2005)

O f all the body systems, the gastrointestinal tract is the most exposed to proteinases.Under physiological conditions, digestive proteinases such as trypsin are released in pancreatic ducts and then into the upper gastrointestinal tract, during and after meals.The forms of proteinases released in the pancreatic duct and intestinal lumen are inactive and need to be cleaved to be activated.This cleavage occurs in the gut lumen where a constant balance between proteolytic activity and the presence of proteinase inhibitors persists in order to fulfil the digestive functions of the gastrointestinal tract, but also at the same time to protect mucosal surfaces from exposure to proteolytic enzymes.The intestinal lumen is also constantly exposed to proteases potentially released from the commensal flora, but also in pathophysiological conditions to proteinases released by infectious agents.Thus the importance of signalling pathways activated by proteinases appears to be particularly relevant for the physiology and pathophysiology of the gastrointestinal tract.
Bayesian Analysis and the GUSTO Trial
Authors: Shaun Goodman
Journal: JAMA (1995)

<h3>To the Editor.</h3> —Drs Brophy and Joseph<sup>1</sup>suggest that GUSTO<sup>2</sup>does not directly address which thrombolytic strategy is superior and that the large sample size used enabled a statistically significant but not clinically meaningful difference to be detected. Using a Bayesian analysis, they conclude that the clinical superiority of t-PA over SK remains uncertain. The rationale and interpretation of their Bayesian approach are greatly flawed for the following reasons: Thrombolytic treatment (vs placebo) has resulted in a 2.6% absolute reduction in mortality; an additional 1.0% achieved with a better thrombolytic strategy in GUSTO is impressive. This a priori definition of a clinically meaningful difference, which Brophy and Joseph label as "arbitrary," was also consistent with the design goals and sample sizes of the Gruppo Italiano per lo Studio della Streptochinasi nell'Infarto Miocardico (GISSI-2) trial3 and the Third International Study of Infarct Survival (ISIS-3) trial.4 The three trials
Diuretics for Hypertension
Authors: Franz H. Messerli
Journal: JAMA (1999)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Cytochrome 2C19*17 Allelic Variant, Platelet Aggregation, Bleeding Events, and Stent Thrombosis in Clopidogrel-Treated Patients With Coronary Stent Placement
Authors: Dirk Sibbing, Werner Koch, Daniela Gebhard, Tibor Schuster, Siegmund Braun, Julia Stegherr, Tanja Morath, Albert Schömig, Nicolas von Beckerath, Adnan Kastrati
Journal: Circulation (2010)

Background— The cytochrome P450 (CYP) 2C19 isoenzyme plays an important role in clopidogrel metabolization. A recently explored CYP2C19 * 17 allelic variant has been linked to increased transcriptional activity, resulting in extensive metabolization of CYP2C19 substrates, which may lead to an enhanced platelet response to clopidogrel treatment. The aim of this study was to assess the impact of CYP2C19 * 17 on ADP-induced platelet aggregation, the risk of bleeding, and stent thrombosis in clopidogrel-treated patients undergoing percutaneous coronary intervention. Methods and Results— The study population included 1524 patients undergoing percutaneous coronary intervention after pretreatment with 600 mg clopidogrel. Genotypes were determined with a TaqMan assay. ADP-induced platelet aggregation was assessed on a Multiplate analyzer. The primary clinical safety end point was the 30-day incidence of bleeding defined according to Thrombolysis in Myocardial Infarction criteria, and the primary clinical efficacy end point was the 30-day incidence of stent thrombosis. For both heterozygous (*wt/*17; n=546) and homozygous (*17/*17; n=76) allele carriers, significantly lower ADP-induced platelet aggregation values were found compared with wild-type homozygotes (*wt/*wt; n=902; P =0.039 and P =0.008, respectively). CYP2C19 * 17 allele carriage was significantly associated with an increased risk of bleeding; the highest risk was observed for CYP2C19 * 17 homozygous patients ( P =0.01, χ 2 test for trend). Multivariate analysis confirmed the independent association of CYP2C19 * 17 allele carriage with platelet aggregation values ( P &lt;0.001) and the occurrence of bleeding ( P =0.006). No significant influence of CYP2C19 * 17 on the occurrence of stent thrombosis was found ( P =0.79). Conclusions— CYP2C19 * 17 carrier status is significantly associated with enhanced response to clopidogrel and an increased risk of bleeding.
Abstract 2632: Calmodulin Kinase Inhibition Prevents the Arrhythmogenesis in Ryr2r4496c+/− Knock in Mice
Authors: Nian Liu, Yanfei Ruan, Marco Denegri, Bachetti Tiziana, Yang Li, Barbara Colombi, Carlo Napolitano, William A Coetzee, Silvia G Priori
Journal: Circulation (2009)

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is caused by mutations in the cardiac ryanodine receptor gene (RyR2) leading to life-threatening arrhythmias elicited by sympathetic act...
Polyvalent Pneumococcal-Polysaccharide Immunization of Patients with Sickle-Cell Anemia and Patients with Splenectomy
Authors: Arthur J. Ammann, Joseph Addiego, Diane W. Wara, Bertram Lubin, W. Bryon Smith, William C. Mentzer
Journal: New England Journal of Medicine (1977)

To reduce the risk of infection from Streptococcus pneumoniae in hyposplenic patients we administered octavalent pneumococcal vaccine to 77 patients with sickle-cell disease and 19 asplenic persons and compared their response with 82 controls (38 age-matched normal persons and 44 normal black African children). Fifty micrograms each of pneumococcal-polysaccharide Types 1, 3, 6, 7, 14, 18, 19 and 23 were administered subcutaneously. Post-immunization serums (three to four weeks) were available from 52 of 77 patients with sickle-cell disease; the per cent responding and the magnitude of the indirect hemagglutination response were comparable to those of the controls. Within two years after immunization we observed eight Str. pneumoniae infections in 106 age-matched unimmunized patients with sickle-cell disease, but none in the 77 immunized (P<0.025). We conclude that pneumococcal polysaccharides are immunogenic in hyposplenic patients and may protect against systemic Str. pneumoniae infection. (N Engl J Med 297:897–900, 1977)
Nkx3.1 and Myc crossregulate shared target genes in mouse and human prostate tumorigenesis
Authors: Philip D. Anderson, Sydika A. McKissic, Monica Logan, Meejeon Roh, Omar E. Franco, Jie Wang, Irina Doubinskaia, Riet van der Meer, Simon W. Hayward, Christine M. Eischen, Isam-Eldin Eltoum, Sarki A. Abdulkadir
Journal: Journal of Clinical Investigation (2012)

Cooperativity between oncogenic mutations is recognized as a fundamental feature of malignant transformation, and it may be mediated by synergistic regulation of the expression of pro- and antitumorigenic target genes. However, the mechanisms by which oncogenes and tumor suppressors coregulate downstream targets and pathways remain largely unknown. Here, we used ChIP coupled to massively parallel sequencing (ChIP-seq) and gene expression profiling in mouse prostates to identify direct targets of the tumor suppressor Nkx3.1. Further analysis indicated that a substantial fraction of Nkx3.1 target genes are also direct targets of the oncoprotein Myc. We also showed that Nkx3.1 and Myc bound to and crossregulated shared target genes in mouse and human prostate epithelial cells and that Nkx3.1 could oppose the transcriptional activity of Myc. Furthermore, loss of Nkx3.1 cooperated with concurrent overexpression of Myc to promote prostate cancer in transgenic mice. In human prostate cancer patients, dysregulation of shared NKX3.1/MYC target genes was associated with disease relapse. Our results indicate that NKX3.1 and MYC coregulate prostate tumorigenesis by converging on, and crossregulating, a common set of target genes. We propose that coregulation of target gene expression by oncogenic/tumor suppressor transcription factors may represent a general mechanism underlying the cooperativity of oncogenic mutations during tumorigenesis.
Seeking consensus by formal methods: a health warning
Authors: C. Tan, T. Treasure, J. Browne, M. Utley, C. W H Davies, H. Hemingway
Journal: Journal of the Royal Society of Medicine (2006)

There are compelling arguments for the creation and use of guidelines to steer clinical practice: the range of interventions and therapies on offer is large and ever increasing; more effective treatments should be preferred over the less effective; costs are often high and resources are limited so funds should be focused where they will do the most good for the most patients. Some doctors are antipathetic to guidelines—which they decry as ‘cookbook medicine’—but there is now general acceptance that we cannot afford a free-for-all in clinical practice. The authors believe that there should be equitable access to health care. Expenditure on relatively ineffective treatments, and treatment at high cost of those who can pay to the detriment of those who cannot, run counter to this principle.

In order to adjudicate on what should and should not be done, we need transparent processes. There are several systems advocated for the grading of evidence,1 with randomized controlled trials gaining an A grade in an A, B, C grading. There are many aspects of care which rely on lower levels of evidence but when the cause and effect relationship between treatment and outcome is clear, the beneficial effect is large, and cost is supportable, then a strong recommendation (grade 1 of 2) can still be made. Hip replacement, cataract surgery and valve replacement for aortic stenosis are all in this league. Trials of effectiveness are not justified at this stage, and the ‘sky diving without a parachute’ analogy2 can be invoked. They earn 1C recommendation: that is, a strong recommendation with poor quality evidence.1

There are many instances where evidence of benefit is much less clear or the effect size is marginal. Where high level evidence runs out, increasing use is made of expert panels. In this paper we illustrate pitfalls in the expert panel process as used for ratings of appropriateness of interventions for the very common clinical problem of malignant pleural effusion,3 and point to areas for future development.
GYNAECOLOGICAL ASPECTS OF ENDOCRINOLOGY
Authors: R. W. Johnstone
Journal: BMJ (1933)

countrymen, Thomas Addison, but the real rush to the goldfields did not begin until something like a quarter of a century ago.The yield already has been amazing, and the story of endocrinology constitutes perhaps the most fascinating chapter in the history of medical science.No longer need the endocrinologist be spoken of with derision as a " ductless gland faddist," for some at least of his early dreams have materialized into facts, and not a few of these facts have been successfully applied in the relief of human suffering and disease.
Further Study on Acute Hemorrhagic Cystitis Due to Adenovirus Type 11
Authors: Yoshio Numazaki, Tetsuro Kumasaka, Namio Yano, Masao Yamanaka, Teiji Miyazawa, Soji Takai, Nakao Ishida
Journal: New England Journal of Medicine (1973)

To establish the viral origin of acute hemorrhagic cystitis in children as well as adults, 28 patients (23 children and five adults) were examined virologically or serologically during the period 1967–1972. Adenovirus Type 11 was isolated from the urine in 11 of 25 cases. With use of fresh urine without storage, the virus was isolated from 11 of 12 subjects. Seroconversion to adenovirus Type 11 occurred in 19 of the 28 patients, including all who were virus positive, except for one in whom paired serum samples were not available. A total of 17 children and three adults out of 28 (71.4 per cent) were diagnosed as having adenovirus Type 11 infection. These results support the finding in a previous report that adenovirus Type 11 may be specifically associated with acute hemorrhagic cystitis. (N Engl J Med 289:344–347, 1973)
Outcomes After Kidney Donation
Authors: Lainie Friedman Ross, J. Richard Thistlethwaite
Journal: JAMA (2014)

Dr Muzaale and colleagues1 reported the estimated lifetime risk of end-stage renal disease (ESRD) in donors as 0.9% compared with 0.14% in healthy nondonors and 3.26% in unscreened nondonors (general population), an 8-fold higher cumulative incidence of ESRD in donors compared with healthy nondonor controls. These data are important for discussions with prospective donors, especially donors of African American descent who have the highest relative