tbuckley/cabot-search huggingface dataset:
Oral medications with significant hepatic metabolism at higher risk for hepatic adverse events
Authors: Craig Lammert, Einar Bjornsson, Anna Niklasson, Naga Chalasani
Journal: Hepatology (2009)

Reactive metabolites generated by hepatic metabolism are thought to play an important role in the pathogenesis of drug-induced liver injury (DILI), but supporting data are limited. If this is true, then compounds with significant hepatic metabolism should cause more DILI than those without it. We conducted a study to examine the relationship between hepatic metabolism and DILI of prescription medications. We systematically extracted the metabolism characteristics of 207 of the most widely prescribed oral medications in the United States. Compounds with &gt;50% hepatic metabolism were characterized as those with significant hepatic metabolism (n = 149). Hepatic adverse events of interest were alanine aminotransferase &gt;3 times the upper limit of normal, jaundice, liver failure, liver transplantation, or fatal DILI. Compared with compounds with lesser hepatic metabolism, compounds belonging to the significant hepatic metabolism group had significantly higher frequency of alanine aminotransferase &gt;3 times the upper limit of normal (35% versus 11%, P = 0.001), liver failure (28% versus 9%, P = 0.004), and fatal DILI (23% versus 4%, P = 0.001), but not jaundice (46% versus 35%, P = 0.2) or liver transplantation (9% versus 2%, P = 0.11). Twelve compounds with no hepatic metabolism had no reports of liver failure, liver transplantation, or fatal DILI. When the relationship between hepatic adverse events and combination of hepatic metabolism and daily dose was examined, compounds with both significant hepatic metabolism and daily dose &gt;50 mg (n = 50) were significantly more hepatotoxic than compounds belonging to other groups. Compared with medications without biliary excretion, compounds with biliary excretion (n = 50) had significantly higher frequency of jaundice (74% versus 40%, P = 0.0001). Conclusion: Our study finds an important relationship between a compound's metabolism profile and reports of hepatic adverse events. (Hepatology 2009.)
Points: Making doctors and patients more equal
Authors: J. Harries
Journal: BMJ (1986)

August, p 395) make an important point which deserves highlighting.Fracture dislocation of the cervical spine complicating near drowning is a rare event in Britain but is seen more commonly in Australia, where body surfing is a popular sport.The advice given to rescuers in Britain is that any unconscious patient found in standing depth water should be handled as though he or she had suffered fracture dislocation of the neck.It is possible on occasions to ventilate adequately without extending the neck, but if this is not the case then the rescuer has no alternative but to tilt the head back.
Congenital heart block in newborns of mothers with connective tissue disease.
Authors: C M McCue, M E Mantakas, J B Tingelstad, S Ruddy
Journal: Circulation (1977)

Of 22 children with congenital complete heart block (CCHB) available for study, 14 (63.6%) were born to 11 mothers with clinical or laboratory evidence of connective tissue disease, primarily lupus erythematosus (LE). Seven mothers had both clinical and laboratory evidence of disease while four had only positive laboratory studies including fluorescent antinuclear antibody, rheumatoid factor, and depressed complement levels. In adults with systemic LE, pathologic changes in the collagen surrounding the conduction system have led to the fibrosis and death from heart block. Antinuclear antibodies of the IgG class cross the placental barrier and newborn infants have been reported with transient skin lesions of lupus. Placental transmission of such antibodies may affect the fetal cardiac conduction system, surrounding collagen, and myocardium, leading in some cases to CCHB. This is probably one important etiologic factor in CCHB even though the mother is asymptomatic during her pregnancy.
The Cost of Cost-Accounting Medical Education
Authors: Merlin K. DuVal
Journal: New England Journal of Medicine (1973)

By 1960 the documents and pronouncements that flowed from President Eisenhower's White House Conference on Aging had given vigorous emphasis to the proposal that access to health care should be among the basic rights of all citizens. The recommendation had especially great appeal because it came at a time when elements of the nation were beginning to reassess its value system. A few voices cautioned against the adoption of this public policy because of the possibility that its adoption would only serve to ignite expectations without, at the same time, providing assurance that such expectations might reasonably be met, but . . .
FRACTURES OF THE SKULL AND INJURIES TO THE BRAIN.
Authors: F. SHIMONEK
Journal: JAMA (1897)

<h3>Case 1.</h3> —B. F., German, age 35 years, book agent; was brought into the Emergency May 1, 1897, about midnight: unconscious, right motor hemiplegia, respiration labored and irregular and of Cheyne-Stokes character, hemorrhage from right ear. Pulse 70, full and stong, indicating cerebral compression; temperature, 97 degrees; by next morning it had arisen to 100.2 degrees and pulse to 98; respirations, 26. History: About 10 P.M., while intoxicated, fell down stairs and was not found until about midnight. I saw him the following morning in the above-stated condition. Examination: The scalp was very greatly swollen, so much so that it was impossible to make out the condition of the skull underlying this tumefaction. There were no marks of injury upon the scalp. An oblong edema extended from a little distance behind the bregma on the right side of the head downward and backward to the apex of the mastoid process.
Acidity of gastric contents during nocturnal intragastric drip therapy in patients with duodenal ulcer
Authors: J. E. Lennard-Jones, J. C. D. Hart, P. B. Wilcox
Journal: Gut (1965)

EDITORIAL SYNOPSIS This report shows that an intragastric milk drip alone has a poor antacid action upon the nocturnal gastric secretion in duodenal ulcer patients.Milk containing 20 g. of sodium bicarbonate per litre is more effective and superior to a chelated aluminium com- pound, Glymaxil, given in 5 % or 10 % solution.About three-quarters of the gastric samples from the milk-bicarbonate trial were less acid than pH 4.
Mortality among male anaesthetists in the United Kingdom, 1957-83.
Authors: H A Neil, J G Fairer, M P Coleman, A Thurston, M P Vessey
Journal: BMJ (1987)

A cohort of 3769 male anaesthetists resident in the United Kingdom between 1957 and 1983 was followed up for a total of 51,431 person years of observation. All subjects were fellows of the Faculty of Anaesthetists and held full registration with the General Medical Council. With all men in social class I being taken as the standard, the standardised mortality ratio among anaesthetists for all causes of death was 68 (95% confidence interval 59 to 77) and the standardised mortality ratio for all cancers was 50 (95% confidence interval 36 to 67). There was no significant excess mortality from lymphomas or leukaemias, but 16 of the 221 deaths in anaesthetists were due to suicide, giving a standardised mortality ratio of 202 (95% confidence interval 115 to 328). When anaesthetists were compared with all doctors the standardised mortality ratio for suicide was only 114, a nonsignificant excess. These findings confirm that the risk of suicide among anaesthetists is twice as high as among other men in social class I but suggest that the risk does not differ significantly from that among doctors as a whole. There was no evidence of a significant excess risk of cancer, and, in particular, the small excess of cancer of the pancreas reported previously could not be confirmed.
The hyperpolarization-activated cyclic nucleotide-gated HCN2 channel transports ammonium in the distal nephron
Authors: Rolando Carrisoza-Gaytán, Claudia Rangel, Carolina Salvador, Ricardo Saldaña-Meyer, Christian Escalona, Lisa M. Satlin, Wen Liu, Beth Zavilowitz, Joyce Trujillo, Norma A. Bobadilla, Laura I. Escobar
Journal: Kidney International (2011)
Tangier Disease
Authors: P. Clifton-Bligh, P. J. Nestel, H. M. Whyte
Journal: New England Journal of Medicine (1972)

To elucidate the deranged metabolism of Tangier disease, the turnover of esterified cholesterol, and the activities of lipoprotein lipase and of lecithin-cholesterol acyltransferase (LCAT) were studied in a patient with typical findings. The plasma concentration of high-density lipoproteins, assessed by electrophoretic, immunologic and ultracentrifugal means, was greatly reduced. Of a total plasma cholesterol of 59 mg per 100 ml (70 per cent esterified), only 7 mg was present in high-density lipoprotein. In vivo turnover of plasma esterified cholesterol, measured after injection of Radio-labeled mevalonic acid, was 48 mg per hour, similar to values obtained in normal subjects. Postheparin plasma lipoprotein lipase activity was 0.071 μmoles of free fatty acids released per minute per milliliter of plasma, compared to a normal value of 0.218. LCAT activity was 2.5 μg of cholesterol esterified per milliliter per hour of incubation, about half the normal value.
Serum levels of YKL-40 and C reactive protein in patients with hip osteoarthritis and healthy subjects: a cross sectional study
Authors: Th Conrozier, M-C Carlier, P Mathieu, F Colson, A L Debard, S Richard, H Favret, J Bienvenu, E Vignon
Journal: Annals of the Rheumatic Diseases (2000)

<h3>BACKGROUND</h3> YKL-40 is a 40 kDa glycoprotein secreted by chondrocytes and synoviocytes. It has been suggested that it is a surrogate marker of synovial inflammation and joint destruction in rheumatoid arthritis (RA) and osteoarthritis (OA) and related to C reactive protein (CRP) serum levels in RA. <h3>OBJECTIVE</h3> To study serum levels of YKL-40 in patients with hip OA and its relation with CRP. <h3>METHODS</h3> YKL-40 and CRP were assayed in serum samples from 45 patients (24 women, 21 men, mean age 65) with symptomatic OA of the hip and 33 healthy controls. YKL-40 was assayed by immunoassay and CRP by ultrasensitive immunonephelometry. OA severity was assessed by the measurement of joint space width with a computer analysis system of digitised hip radiographs. Statistical analysis was performed to determine correlations between serum markers and radiological joint space width. <h3>RESULTS</h3> The mean (standard error) YKL-40 level was 90.3 (8.2) ng/ml in patients with hip OA and 66.9 (8.2) ng/ml in controls (p=0.03). The mean CRP level was 2.93 (3.03) mg/l in OA and 1.40 (1.61) mg/l in controls (p=0.006). The serum levels of YKL-40 and CRP increased with age and were significantly correlated (Spearman test:<i>r<sub>s</sub></i>=0.42, p=0.005) in patients but not in controls. Neither YKL-40 nor CRP correlated with radiographic joint space width. <h3>CONCLUSIONS</h3> Serum YKL-40 was significantly increased in patients with hip OA. The correlation between YKL-40 and CRP suggests that YKL-40 may be a marker of joint inflammation in OA. Longitudinal studies are required to assess the usefulness of YKL-40 in the monitoring of patients with hip OA.
Kupffer Cells Generate Superoxide Anions and Modulate Reperfusion Injury in Rat Livers After Cold Preservation
Authors: H Shibuya, N Ohkohchi, K Seya, S Satomi
Journal: Hepatology (1997)

This study was designed to determine the source of reactive oxygen species (ROS) and whether Kupffer cells modulate the injury of perfused rat liver after cold preservation. The livers of male Lewis rats pretreated with schizophyllan glucan (SPG) (10 mg/kg, SPG group) or gadolinium chloride (5 mg/kg; Gd group) and untreated rats (control group) were preserved in University of Wisconsin solution for 0, 12, and 24 hours at 4 degrees C and then perfused for 60 minutes with oxygenated Krebs-Henseleit bicarbonate buffer. Real-time chemiluminescence (CL) of the liver during perfusion was measured using a sensitive photomultiplier, and reperfusion injury was assessed by measuring lipid peroxidation and lactate dehydrogenase release. CL intensity reached a peak within 5 minutes of reperfusion, and superoxide dismutase completely inhibited this CL in all groups. In the control group, the total CL intensity was high after 24 hours of preservation. It significantly (P < .05 vs. control group) increased in the SPG group, while it decreased in the Gd group after 12 and 24 hours of preservation. The total CL intensity decreased by 70% (when diphenyliodonium chloride (100 micromol/L; an NADPH oxidase inhibitor) was added to the perfusate before preservation of untreated rats. Lipid peroxidation and lactate dehydrogenase release significantly (P < .05) deteriorated in the SPG group, while they ameliorated in the Gd group after 24 hours of preservation. These results demonstrate that Kupffer cells primarily generate superoxide anions and modulate the organ injury in the initial phase of reperfusion after cold preservation.
Dishonorable Discharge: The Oncogenic Roles of Cleaved E-Cadherin Fragments
Authors: Justin M. David, Ayyappan K. Rajasekaran
Journal: Cancer Research (2012)

Strong cell-cell interactions represent a major barrier against cancer cell mobility, and loss of intercellular adhesion by E-cadherin is a fundamental change that occurs during the progression of cancer to invasive disease. However, some aggressive carcinomas retain characteristics of differentiated epithelial cells, including E-cadherin expression. Emerging evidence indicates that proteolysis of E-cadherin generates fragments that promote tumor growth, survival, and motility, suggesting that E-cadherin cleavage converts this tumor suppressor into an oncogenic factor. In this review we discuss the emerging roles of cleaved E-cadherin fragments as modulators of cancer progression, and explore the translational and clinical implications of this research.
Treatment of diuretic resistant cor pulmonale by continuous arteriovenous haemofiltration.
Authors: P A Rowe, G M Rocker, R P Burden
Journal: Thorax (1988)

A woman with diuretic resistant cor pulmonale had 24 litres of fluid removed over four days by arteriovenous haemofiltration. She was discharged one week later and has remained ambulant and independent for one year.
Hemodynamic Factors in Atherosclerosis-Reply
Authors: Samuel Butler
Journal: JAMA (1965)

Thickening of the intima is due to proliferation of its components as a response to diminished lateral pressure or the suction effect of the flowing blood. The point is not that atherosclerotic changes (atheroma) occur where the intima is already normally thickened but that the first sign of developing atherosclerosis is a slight reactive thickening of the intima. A vessel may be considered to have a normally thickened intima only in the sense that no pathological or clinical findings are attributable to the diminution of volumetric flow due to encroachment on the lumen by the thickened intima. The thickening signals the start of the disease and the continued operation of local hydraulic factors produces progressive pathological changes which evolve into the atherosclerotic plaque. All the stages in this pathological process have been produced hemodynamically in our laboratory. Hydrodynamics of flow are not "obviously the same" in the rich, the poor,
Amniocentesis in Tay-Sachs Disease
Authors: Harold Schwartz
Journal: JAMA (1975)

<h3>To the Editor.—</h3> I wish to reply to Dr. Fred Rosner's letter in the May 13 issue ofThe Journal(228:829, 1974) regarding amniocentesis for Tay-Sachs disease. Dr. Rosner does not speak as a doctor for the obstetrician-gynecologist, pediatrician, psychiatrist, or for the geneticist. He speaks only for a small segment of Orthodox Jews, and I can refer him to<i>Birth Control in Jewish Law</i>by David M. Feldman: Mental health risk has been definitely equated to physical-health risk. This woman who is in danger of losing her mental health unless the pregnancy is interrupted, therefore would accordingly qualify.<sup>1</sup> The majority of the Jewish houses of worship in Baltimore took part in the massive screening for Tay-Sachs disease and, not too long ago, this was repeated in a Union, NJ, synagogue. We can only pray for the future that possible enzyme replacement may solve this and other sphingolipidrelated diseases.
Renal function after 10 years' treatment with cyclosporin for psoriasis
Authors: None Powles, None Hardman, None Porter, None Cook, None Hulme, None Fry
Journal: British Journal of Dermatology (1998)

Renal function was assessed by measuring serum creatinine and glomerular filtration rate (GFR) in two groups of patients with chronic plaque psoriasis who had been treated with cyclosporin A (CyA), average dose 2.8 mg/kg per day (range 1-5 mg/kg per day). Group I was our original cohort of nine patients, seven of whom had received CyA for an average period of 10 years (range 9.5-11 years). These seven patients showed a persistent increase in serum creatinine > 30% from baseline measurement and four of the seven had persistent increases > 50%. The GFR, which was first measured after 2.5 years of treatment, showed at 10 years a decrease of > 30% in two patients and of > 50% in one patient. Three of the seven showed stable renal function while two had repeat renal biopsy because of deteriorating renal function and histology showed further evidence of CyA nephrotoxicity compared with that after 5 years' treatment. Two of the nine patients in group I had discontinued CyA 5 years previously after 5 years of treatment because of CyA nephrotoxicity on renal biopsy and impaired renal function. This impairment of renal function showed improvement during the 5 years of follow-up, implying reversibility of CyA nephrotoxicity. The second group of 20 patients had received CyA for an average duration of 6 years (range 5-8 years). Nine of the 20 patients showed persistent increases in serum creatinine of > 30% from baseline and five showed persistent increases of > 50%. The GFR showed a persistent decrease of > 30% in seven patients and of > 50% in two patients. This study has shown that nephrotoxicity is associated with long-term treatment with CyA. However, there is patient variation as to when nephrotoxicity commences and its speed of progression. On discontinuing CyA the impairment of renal function improves with time. Providing renal function is monitored with GFR and renal biopsy in addition to serum creatinine then long-term (5-10 years) CyA treatment can be justified in severe psoriasis not responsive to other treatments.
Alterations of the Tumor Suppressor Gene <i>ARLTS1</i> in Ovarian Cancer
Authors: Fabio Petrocca, Dimitrios Iliopoulos, Haiyan R. Qin, Milena S. Nicoloso, Say Yendamuri, Sylwia E. Wojcik, Masayoshi Shimizu, Gianpiero Di Leva, Andrea Vecchione, Francesco Trapasso, Andrew K. Godwin, Massimo Negrini, George A. Calin, Carlo M. Croce
Journal: Cancer Research (2006)

Abstract ARLTS1 is a tumor suppressor gene initially described as a low-penetrance cancer gene: a truncated Trp149Stop (MUT) polymorphism is associated with general familial cancer aggregation and, particularly, high-risk familial breast cancer. DNA hypermethylation has been identified as a mechanism of ARLTS1 expression down-regulation in lung carcinomas and B-cell chronic lymphocytic leukemia. We found that, in the majority of ovarian carcinomas (61.5%) and in a significant proportion of ovarian and breast cancer cell lines (45%), ARLTS1 is strongly down-regulated due to DNA methylation in its promoter region. After ARLTS1 restoration by adenoviral transduction, only the negative TOV-112 and the homozygously mutated (MUT) MCF7 cells, but not the OV-90 cells expressing a normal ARLTS1 product, underwent apoptosis and inhibition of cell growth. Furthermore, ARLTS1 reexpression significantly reduced the tumorigenic potential of TOV-112 in nude mice. On the contrary, the ARLTS1-MUT induced significantly lower levels of apoptosis in infected cells and reduced in vivo tumorigenesis only partially, supporting the hypothesis that Trp149Stop polymorphism is retained in the general population and predisposes to cancer because of a reduction, but not full loss, of normal ARLTS1 function. (Cancer Res 2006; 66(21): 10287-91)
Government's obesity strategy targets parents of children under 10
Authors: C. White
Journal: BMJ (2008)

The government this week confirmed that it is to launch a £75m (€90m; $150m) social marketing campaign later this month, as part of its strategy to curb rising levels of obesity among children in England.

One in four 5 year olds in England is overweight or obese.

Will Cavendish, director of health and wellbeing at the Department of Health, made the announcement to delegates at a national conference on obesity in London on Tuesday 8 July. It was the largest such campaign of its kind to be launched, he said.

The move follows the publication of the Foresight Report in October last year, which concluded that on the basis of …
Adult congenital lobar emphysema in pregnancy.
Authors: P S Critchley, C P Forrester-Wood, P D Ridley
Journal: Thorax (1995)

A young woman presented with left sided chest pain. Chest radiography revealed a hyperexpanded left upper lobe and the rare diagnosis of congenital lobar emphysema was made. She was then found to be pregnant. Thoracotomy and left upper lobectomy were performed during the pregnancy without adverse effects to the mother or fetus. The implications of pregnancy on the surgical management of this rare condition are discussed.
Mitral Valve Surgery Can Now Routinely Be Performed Endoscopically
Authors: Filip P. Casselman, Sam Van Slycke, Francis Wellens, Raphael De Geest, Ivan Degrieck, Frank Van Praet, Yvette Vermeulen, Hugo Vanermen
Journal: Circulation (2003)

Background— There is an increasing interest in minimally invasive cardiac surgery. Methods and Results— Since February 1, 1997 till April 1, 2002, 306 patients underwent endoscopic mitral valve surgery (226 repair, MVP; 80 replacement, MVR). Predominant valve pathology was degenerative in MVP (83.6%) and rheumatic in MVR (65%). Mean age was 61.5±12.9 years. Median preoperative functional class (MVP+MVR) and mitral regurgitation (MVP) were II and 4+. Statistical analysis included Kaplan-Meier and Cox regression methods. Mean follow-up was 19.6±17.3 months and complete. The procedure was successfully performed in all but 6 patients. Hospital mortality included 3 patients (1%) and was technology related in one. Postoperative morbidity included aggressive re-exploration (8.5%), new onset atrial fibrillation (17.0%), and pacemaker implantation (2.3%). There were 1 early and 10 late reoperations, 5 of which were because of endocarditis. Freedom from mitral valve reoperation at 4 years was 91±3.5%. No risk factors for reoperation could be detected. Echocardiographic follow-up showed a median degree of mitral regurgitation (MVP) of 0 and a small paravalvular leak in four patients (MVR). Ninety-four percent of the patients reported no or mild postoperative pain and 99.3% felt they had an esthetically pleasing scar. Ninety-three percent would choose the same procedure again and 46.1% were back at work within 4 weeks. Conclusions— Endoscopic mitral valve surgery can be performed safely but definitely requires a learning curve. Good results and a high patient satisfaction are guaranteed. It is now our exclusive approach for isolated atrioventricular valve disease.