tbuckley/cabot-search huggingface dataset:
Haplotypes in Matrix Metalloproteinase Gene Cluster on Chromosome 11q22 Contribute to the Risk of Lung Cancer Development and Progression
Authors: Tong Sun, Yang Gao, Wen Tan, Sufang Ma, Xuemei Zhang, Yonggang Wang, Qingrun Zhang, Yongli Guo, Dan Zhao, Changqing Zeng, Dongxin Lin
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Matrix metalloproteinases (MMP) play important roles in cancer development and single nucleotide polymorphisms (SNP) in some MMP genes were shown to confer susceptibility to certain cancers. This study examined the association between genotypes and haplotypes in the MMP1-MMP3-MMP12 gene cluster and risk of lung cancer development and metastasis. Experimental Design: A two-stage investigation was conducted. First, 35 SNPs covering these genes were selected and validated in 190 patients and 190 controls. Twenty-two validated SNPs were then analyzed in an entire case-control panel consisting of 711 patients and 716 controls. Associations with the risk of lung cancer were estimated by logistic regression. Results: The investigated MMP gene region could be partitioned into two major haplotype blocks. One common haplotype in the block composed of major part of MMP1 transcription region was significantly associated with increased risk for the development [odds ratio (OR), 1.35; 95% confidence interval (95% CI), 1.11-1.63; P = 0.01; permutated P = 0.134] and distant metastasis of lung cancer (ORs for stage IV versus stages I-III, 1.67; 95% CI, 1.12-2.50; P = 0.009; permutated P = 0.048) and the other showed a protective effect against metastasis (ORs for stage IV versus stages I-III, 0.22; 95% CI, 0.07-0.62; P = 0.001; permutated P = 0.011). Another common haplotype in the block across MMP3 was significantly associated with decreased risk for developing lung cancer (OR, 0.71; 95% CI, 0.59-0.86; P = 0.003; permutated P = 0.027). Conclusions: The observed multiple cancer-associated genetic variants suggested that the MMP1-MMP3-MMP12 gene cluster plays important roles in lung cancer development and progression.
ACTIVE IMMUNIZATION AGAINST DIPHTHERIA: RELATIVE VALUES OF TWO METHODS AS SHOWN BY SUBSEQUENT SCHICK TESTING
Authors: H. C. M. Williams, J. D. Dear, W. Stewart
Journal: BMJ (1936)

The analysis of the series demonstrates the importance of early diagnosis of carcinoma of the cervix, the extent of the disease being of greater importance in the prognosis than any other factor.The results of operation on cases in Stages 1 and 2 are slightly better than those of radium alone, but it will be noticed that the immediate mortality of radium treatment is almost negligible.'Bonney, V.
The Syndrome of Severe Mitral Regurgitation with Normal Left Atrial Pressure
Authors: EUGENE BRAUNWALD, WILLIAM C. AWE
Journal: Circulation (1963)

It has been generally thought that significant elevations of the left atrial and pulmonary vascular pressures occur in patients with mitral regurgitation of sufficient severity to produce serious disability and gross enlargement of the left atrium. Ten patients with severe mitral regurgitation have been encountered in whom gross left atrial enlargement was accompanied by normal left atrial and pulmonary artery pressures. These patients ranged in age from 8 to 49 years, all were in functional classes III or IV, and the average duration of symptoms was 7.3 years. Nine patients had rheumatic mitral regurgitation while one had a congenital lesion. Atrial fibrillation and the physical findings of pure mitral regurgitation were present in all patients, as was striking left atrial enlargement on their roentgenograms. Left atrial pressure, determined by left heart catheterization, averaged 9.1 mm. Hg and did not exceed 12 mm. Hg in any patient, and the V wave was not particularly prominent. The cardiac index was markedly depressed and averaged 2.0 L./min./M. 2 B.S.A. The observed discrepancy between left atrial size and pressure must reflect a disturbance in the compliance of the left atrial wall. It is suggested that long-standing mitral regurgitation may modify the mechanical characteristics of the atrial wall and that the presence of a normal left atrial pressure must not be assumed to exclude the presence of severe mitral regurgitation. The manner in which variations in left atrial compliance affect the clinical picture of mitral regurgitation and the selection of patients for operative intervention are discussed.
Association of Moderate Alcohol Consumption and Plasma Concentration of Endogenous Tissue-Type Plasminogen Activator
Authors: Paul M. Ridker
Journal: JAMA (1994)

To assess whether an association exists between moderate alcohol consumption and plasma concentration of endogenous tissue-type plasminogen activator (t-PA), a serine protease that plays a central role in the regulation of intravascular fibrinolysis.Survey of self-reported alcohol consumption and plasma fibrinolytic capacity, controlled for lipid and nonlipid cardiac risk factors.Participants in the Physicians' Health Study.A total of 631 apparently healthy male physicians aged 40 to 84 years with no history of myocardial infarction, stroke, or transient cerebral ischemia.Plasma concentration of t-PA antigen.A direct association was found between alcohol consumption and plasma level of t-PA antigen, such that mean plasma levels of t-PA antigen for daily, weekly, monthly, and rare or never drinkers were 10.9, 9.7, 9.1, and 8.1 ng/mL, respectively (P trend = .0002). The relation between alcohol consumption and t-PA antigen level was not materially changed in analyses that adjusted for total cholesterol and high-density lipoprotein cholesterol or nonlipid cardiovascular risk factors including age, body mass index, parental history of coronary heart disease, exercise frequency, and systolic and diastolic blood pressure.These data indicate a positive association between moderate alcohol intake and plasma level of endogenous t-PA antigen that is independent of high-density lipoprotein cholesterol. This finding supports the hypothesis that changes in fibrinolytic potential may be an important mechanism whereby moderate alcohol consumption decreases risk of heart disease.
Ventricular Tachycardia After Terbutaline
Authors: Evlin L. Kinney, Joseph J. Trautlein, Cheryl V. Harbaugh, Deborah Lambert, Robert F. Zelis
Journal: JAMA (1978)

To the Editor.—  Terbutaline sulfate, a synthetic derivative of isoproterenol having predominantly β 2 -receptor-stimulating effects, has been thought, because of its relative receptor selectivity, to have a negligible effect on the cardiovascular system. 1 By contrast, the use of β 1 -sympathomimetics has been associated with an increased mortality in asthmatics. 2 Most studies have found that terbutaline leads to a small but noteworthy increase in the heart rate, thereby exhibiting a β 1 stimulatory effect as well. Concomitant with this modest change in heart rate, there is a doubling of the cardiac output without a change in mean arterial pressure, thus increasing the work of the heart. 3 When looked at by Holter monitoring, terbutaline has been found to cause an increase in supraventricular premature beats. 4 In another study, one patient out of 25 was found to have had the onset of premature ventricular contractions after receiving
Many chronic pain control treatments are ineffective
Authors: A. Boulton
Journal: BMJ (1997)

A new government sponsored systematic review of outpatient services for chronic pain control has found wide disparity in the effectiveness of current practice in Britain.

Injections of corticosteroids in or around the shoulder joint for shoulder pain, and intravenous regional sympathetic blockade were found to be ineffective, according to the Health Technology Assessment report produced as part of the NHS research and development strategy.

Interventions for which more evidence is needed include: transcutaneous electrical …
EPITHELIAL STRUCTUEES IN THE PERIDENTAL MEMBEANE.
Authors: FREDERICK B. NOYES
Journal: JAMA (1899)

For four or five years I have been interested in the histologic study of the peridental membrane, and during that time have devoted what time I could to the special study of certain structures found in that membrane, and called by Dr. Black, who first described them, the glands of the peridental membrane. The work which I have tried to do on this subject is really not in shape to report, as it has not been worked out to the point where positive statements can be made in regard to the nature of these structures. But I have reached a point where to carry through the work would require from three to six months of time, without interruption. This it has been impossible for me to do, and I see no probability that I will be able to do it in the near future. I have, therefore, decided to make this simply a report of my work, and a
Plans are needed on how to cope with demand for ventilation during pandemic influenza
Authors: M. J Goodman, P. B Anderson
Journal: BMJ (1997)

The central problem is often poor design and conduct of trialsEditor-We are concerned about some aspects of the recent articles on consent. 1 2 Len Doyal claims that informed consent may not be necessary for three most vulnerable groups: young children, patients with learning difficulties, and unconscious or semiconscious patients.Yet young children (unlike all adult groups) have the protection of their parents' consent, and this should always be respected. 3 The other two groups show the limitations of applying Kantian respect for autonomy, designed for property owning 18th century gentlemen, to vulnerable dependent patients.There is an urgent need to agree new ways of making research decisions with and for these minority groups.As is usual in arguments against seeking informed consent, there is a tendency to concentrate on dramatic extremes: patients with severe mental impairment and patients receiving heroic cancer treatment.The development of principles from extremes is dangerous and should be discouraged.Difficulties with relatively small groups should not be used to excuse researchers from requesting the consent of the vast majority of the millions of people every year who help with research into mundane pharmaceutical trials of treatments of arthritis or everyday misery.A deeper problem with the articles is the assumption that consent is the central problem in research.We suggest that, more often, the central problem is the poor design and conduct of trials which alienate or distress people on whose practical support researchers depend.The solution here is not to tinker with consent but to clean up research.Health service users could help at every stage of clinical research: the selection of questions worth investigating; the design and conduct of trials, including the information materials; the interpretation and reporting of the evidence; dissemination; and working with practitioners to put findings into practice.Consumers for Ethics in Research has been working with health service users, researchers, and practitioners on these issues for the past eight years, partly through regular open meetings, during which many practical ideas have been advanced.
PNEUMOPERITONEUM AS AN AID IN DIAGNOSIS OF HERNIA
Authors: ROBERT EMMETT FARR
Journal: JAMA (1924)

As an aid to the diagnosis of pathologic changes within the peritoneum, the use of pneumoperitoneum seems to have established itself on a fairly firm basis. With increased experience and opportunity for observation, the scope of this method is constantly enlarging. In this report I shall call attention to the assistance offered by the use of pneumoperitoneum in some of the various forms of abdominal hernia: (1) in visualizing the contents of the hernia sac, showing the reducibility, the presence of adhesions, the position of the ring, etc., and (2) in demonstrating the patency of the processus vaginalis peritonaei in persons in whom a hernia cannot be diagnosed clinically, although a so-called "potential" hernia exists. In all the various forms of hernia it would at least be a source of satisfaction to know beforehand what tissues the sac contains, whether or not its contents are adherent, and the approximate size
Management of Non-Insulin-dependent Diabetes Mellitus: The United Kingdom Experience
Authors: Harry Keen
Journal: Annals of Internal Medicine (1996)

Care of persons with non–insulin-dependent diabetes mellitus (NIDDM) in the United Kingdom resembles that in the United States. However, health care practice in Europe is being influenced by the Saint Vincent Declaration, the joint European World Health Organization-International Diabetes Federation initiative, which emphasizes prevention of diabetic complications. In recent years, the responsibility for care for NIDDM has shifted in the United Kingdom to general practice teams. The effect of this shift on the quality of care and the coordinating and educational role of local diabetes specialist teams is discussed, as is the importance of an individualized "menu" of care for each patient. This menu aims for optimum blood glucose level control as well as detection and correction of risk factors for diabetic complications. The pervasive and dangerous notion of NIDDM as a "mild" disease must be corrected. The importance of systematic auditing of process and outcomes in diabetes care is emphasized, as is the need for regular data acquisition, aggregation, and analysis to achieve continuous improvement in the quality of care. Although patient-health professional encounters are the core of good diabetes care, the need for larger-scale appraisal on a local, regional, and national basis is now apparent.
Gq signaling causes glomerular injury by activating TRPC6
Authors: Liming Wang, Grant Jirka, Paul B. Rosenberg, Anne F. Buckley, Jose A. Gomez, Timothy A. Fields, Michelle P. Winn, Robert F. Spurney
Journal: Journal of Clinical Investigation (2015)

Familial forms of focal segmental glomerulosclerosis (FSGS) have been linked to gain-of-function mutations in the gene encoding the transient receptor potential channel C6 (TRPC6). GPCRs coupled to Gq signaling activate TRPC6, suggesting that Gq-dependent TRPC6 activation underlies glomerular diseases. Here, we developed a murine model in which a constitutively active Gq α subunit (Gq(Q209L), referred to herein as GqQ>L) is specifically expressed in podocytes and examined the effects of this mutation in response to puromycin aminonucleoside (PAN) nephrosis. We found that compared with control animals, animals expressing GqQ>L exhibited robust albuminuria, structural features of FSGS, and reduced numbers of glomerular podocytes. Gq activation stimulated calcineurin (CN) activity, resulting in CN-dependent upregulation of TRPC6 in murine kidneys. Deletion of TRPC6 in GqQ>L-expressing mice prevented FSGS development and inhibited both tubular damage and podocyte loss induced by PAN nephrosis. Similarly, administration of the CN inhibitor FK506 reduced proteinuria and tubular injury but had more modest effects on glomerular pathology and podocyte numbers in animals with constitutive Gq activation. Moreover, these Gq-dependent effects on podocyte injury were generalizable to diabetic kidney disease, as expression of GqQ>L promoted albuminuria, mesangial expansion, and increased glomerular basement membrane width in diabetic mice. Together, these results suggest that targeting Gq/TRPC6 signaling may have therapeutic benefits for the treatment of glomerular diseases.
ABC of 1 to 7: services for children: primary care.
Authors: L Peter, H B Valman
Journal: BMJ (1982)

The general practitioner provides continuous care for the whole family, and his intimate knowledge of the fears and aspiration of each individual enables him to act as a trusted counsellor in both preventive and curative medicine.Specialists in the community or hospital provide the support he requests.About 25% of the work of the general practitioner concerns Childrenr children, and he recognises that their needs are different from those of patients in other age groups because they are both dependent and developing.The general practitioner just described is in the minority.The primary Jults
Increasing inequalities in the health of the nation
Authors: G. D. Smith, J. Morris
Journal: BMJ (1994)

Raising the subject of socioeconomic inequalities in health can produce the weary reaction that these are now so widely recognised that little purpose is served by flogging this dead horse again.1 Certainly the flat denial of such inequalities has almost become a thing of the past. The well known attempt by the government to stifle any reaction to the Black report on inequalities in health 14 years ago2 has given way to an apparently more reasoned approach. Indeed, it was announced at a conference organised by the BMA earlier this year that the government was establishing an interdepartmental working group to examine the links between social position and health3 as part of the continuing review of the Health of the Nation's targets.4

The setting up of this working party is timely, given the accumulating evidence that socioeconomic differences in health have increased since the Black report was published.5 6 7 In this week's journal McLoone and Boddy show that between the early 1980s and the early 1990s differences in mortality between deprived and affluent small areas of Scotland have increased substantially,8 a phenomenon that has also been reported in the largest Scottish city, Glasgow (p 1482).9

Much has been made of the poor health picture in Glasgow, which in the popular media has been awarded the title of “heart disease capital of the world.” But, as McLoone and Boddy show, inhabitants of the more affluent parts of Glasgow have the same favourable mortality as residents of equivalent areas in the rest of Scotland. There is no special Glasgow effect; the …
Total Therapy of Acute Lymphocytic Leukemia
Authors: Donald Pinkel
Journal: JAMA (1972)

In 1962, the total therapy approach to acute lymphocytic leukemia was developed at St. Jude Children's Research Hospital. Briefly, it consists of rapid and efficient induction of complete remission with prednisone and vincristine in order to minimize early attrition, cranial or craniospinal irradiation during the first month of complete remission to prevent meningeal relapse, and multiple-drug chemotherapy for two to three years to eradicate residual systemic leukemia. The objective is cure, not palliation. In the 1962-1965 pilot studies, 37 of 41 patients entered complete remission; 7 continue in complete remission for seven to nine years and have been off all treatment for four to six years. However, of the 30 relapses, 15 initiated in the meninges, indicating inadequacy of the craniospinal irradiation. In the 1967-1968 study, the dose of cranial irradiation was increased to 2,400 rads. Of 35 patients entered into this study, 31 developed complete remission. Eighteen survive in
Is there an association between diarrhoea predominant irritable bowel syndrome and small bowel injury on capsule endoscopy?
Authors: R. Kalla, M. E. McAlindon, R. Sidhu
Journal: Gut (2011)

<h3>Introduction</h3> Diarrhoea predominant irritable bowel syndrome (D-IBS) represents a large outpatient gastroenterology workload. There are a subset of patients where their symptoms of D- IBS may overlap with suspected Crohn9s disease. These patients may represent a cohort that may progress to occult Crohn9s disease on long term follow-up. There is a paucity of data on this subject. Capsule endoscopy (CE) is a recognised tool to examine the small bowel. We hypothesised that a proportion of patients with D-IBS may have evidence of small bowel injury, which can be visualised on CE. <h3>Methods</h3> Patients referred for CE for investigation of diarrhoea and abdominal pain with/without the presence of abnormal blood parameters were identified. Patients with a normal CE or those who fell short of CE criteria for Crohn9s disease were selected for case note review. Data was collected for demographics, clinical symptoms, previous investigations, findings of CE and subsequent follow-up. <h3>Results</h3> A total of 151 patients were identified. There were 103 females (68%) with a mean age of 39 years (range 17–80 years) and the mean follow-up period was 12 months. Six per cent (n=9) were on non-steroidal anti-inflammatory therapy (NSAID). Previous investigations included colonoscopy in 92% (n=139), small bowel meal in 54% (n=81) and computer tomography in 36% (n=55). The median small bowel transit (SBT) was within the normal range of 228 min (range 59–376). The small bowel was entirely normal in 70% (n=106) but abnormalities were found in 45 patients (30%). The abnormalities were located in the distal small bowel in 51% (n=23), proximal small bowel in 29% (n=13), mid small bowel in 7% (n=3) and diffuse change was present in 13% (n=6). The changes were thought to be due to NSAID9s in 4 patients. In the remaining 41 patients (who were not on NSAID9s), CE showed evidence of erosions or petechiae and ulcers. These patients did not fulfil the criteria for Crohn9s disease on CE. Apart from diarrhoea and the presence of abdominal pain, 12% of these patients (n=5) had a low B12 and 22 patients (49%) had evidence of raised inflammatory markers (erythrocyte sedimentation rate or C-reactive protein). Hypoalbuminaemia was not a feature in these patients and only one patient had evidence of iron deficiency anaemia. <h3>Conclusion</h3> In a proportion of patients with D-IBS, while the small bowel transit is within normal limits, small bowel injury is evident on CE. This may suggest an activation of the mucosal innate defence system toward a pro-inflammatory response in patients with D-IBS. This subset of patients may go on to develop occult Crohn9s disease with longer term follow-up. Further studies are required to validate our results.
Effect of hypertonic mannitol and isoproterenol on regional coronary flow following right ventriculotomy.
Authors: D E Fixler, J T Watson, J M Wheeler, J T Willerson
Journal: Circulation (1976)

We studied the changes which occurred in regional coronary blood flow after right ventriculotomy and the subsequent effects of hypertonic mannitol or isoproterenol infusion. Regional coronary flows were measured with radioactive microspheres (9 micron) in open-chest anesthetized dogs. Either hypertonic mannitol (25%) was infused at 3.2 ml/min or 7.6 ml/min for 30 minutes, or normal saline at 7.6 ml/min for 30 minutes followed by isoproterenol at 0.05-0.10 mug/kg/min. In the mannitol treated animals right ventricular, left artrial and aortic pressures, heart rate, and cardiac output did not change significantly following vertical ventriculotomy, whereas in the saline-isoproterenol treated animals aortic pressures fell significantly. Coronary flow to the peri-incisional area fell from 41 to 24 ml/min-100 g (P less than 0.05) following ventriculotomy, increased by 34% (P less than 0.05) when osmolality rose after mannitol by 37 mOsm, but was unchanged with isoproterenol. The data indicate that a vertical ventriculotomy reduces flow to adjacent myocardium and that subsequent infusion of hypertonic mannitol at moderate rates significantly increases coronary flow to this region.