tbuckley/cabot-search huggingface dataset:
Hydrogen peroxide-induced renal injury. A protective role for pyruvate in vitro and in vivo.
Authors: A K Salahudeen, E C Clark, K A Nath
Journal: Journal of Clinical Investigation (1991)

Hydrogen peroxide (H2O2) contributes to renal cellular injury. alpha-Keto acids nonenzymatically reduce H2O2 to water while undergoing decarboxylation at the 1-carbon (1-C) position. We examined, in vitro and in vivo, the protective role of sodium pyruvate in H2O2-induced renal injury. Pyruvate effectively scavenged H2O2 in vitro, and suppressed H2O2-induced renal lipid peroxidation. Injury to LLC-PK1 cells induced by hydrogen peroxide was attenuated by pyruvate to an extent comparable to that seen with catalase. Studies utilizing [1-14C]pyruvate further demonstrated 1-C decarboxylation concurrent with cytoprotection by pyruvate from H2O2-induced injury. Pyruvate was also protective in vivo. Infusion of pyruvate before and during the intrarenal infusion of H2O2 attenuated H2O2-induced proteinuria. Systemic administration of pyruvate was also protective in the glycerol model of acute renal failure, a model also characterized by increased generation of H2O2. These findings indicate that pyruvate, a ubiquitous alpha-keto acid, scavenges H2O2 and protects renal tissue in vitro and in vivo from H2O2-mediated injury. These data suggest a potential therapeutic role for pyruvate in diseases in which increased generation of H2O2 is incriminated in renal damage.
Equity, waiting times, and NHS reforms: retrospective study
Authors: Z. N Cooper, A. McGuire, S Jones, J L. Grand
Journal: BMJ (2009)

<b>Objective</b> To determine whether observable changes in waiting times occurred for certain key elective procedures between 1997 and 2007 in the English National Health Service and to analyse the distribution of those changes between socioeconomic groups as an indicator of equity. <b>Design</b> Retrospective study of population-wide, patient level data using ordinary least squares regression to investigate the statistical relation between waiting times and patients’ socioeconomic status. <b>Setting</b> English NHS from 1997 to 2007. <b>Participants</b> 427 277 patients who had elective knee replacement, 406 253 who had elective hip replacement, and 2 568 318 who had elective cataract repair. <b>Main outcome measures</b> Days waited from referral for surgery to surgery itself; socioeconomic status based on Carstairs index of deprivation. <b>Results</b> Mean and median waiting times rose initially and then fell steadily over time. By 2007 variation in waiting times across the population tended to be lower. In 1997 waiting times and deprivation tended to be positively related. By 2007 the relation between deprivation and waiting time was less pronounced, and, in some cases, patients from the most deprived fifth were waiting less time than patients from the most advantaged fifth. <b>Conclusions</b> Between 1997 and 2007 waiting times for patients having elective hip replacement, knee replacement, and cataract repair in England went down and the variation in waiting times for those procedures across socioeconomic groups was reduced. Many people feared that the government’s NHS reforms would lead to inequity, but inequity with respect to waiting times did not increase; if anything, it decreased. Although proving that the later stages of those reforms, which included patient choice, provider competition, and expanded capacity, was a catalyst for improvements in equity is impossible, the data show that these reforms, at a minimum, did not harm equity.
CHRONIC POLYMORPHIC LIGHT ERUPTION (A STUDY OF 25 CASES)
Authors: W. FRAIN-BELL, L. A. MACKENZIE, E. WITHAM
Journal: British Journal of Dermatology (1969)

SUMMARY.— The chronic polymorphic light eruptions are a miscellaneous group of cutaneous reactions in which the responsible action spectrum probably lies in the sunburn range (290 to 320 nm.) and in the long u.v. (320 to 400 nm.) and visible (above 400 nm.) ranges. A group of 25 such cases is described and details are given of the results of phototesting, using a high pressure Xenon arc light source with appropriate filters. Evidence is presented in support of the possibility that in this group there may be a specific entity which occurs most often in females, appearing for the first time usually before adult life and lasting for up to 30 to 40 years. In this group no abnormality of porphyrin metabolism can be detected. The action spectra appear to lie both within and above the sunburn range: there is some evidence to suggest that a border zone between 305 and 325 nm. may be particularly relevant.
Lipid accumulation in concanavalin A-induced hepatitis: Another cause for impaired liver regeneration afterwards?
Authors: Dechun Feng, Lingyun Xu
Journal: Hepatology (2008)

We read with interest the article by Hines et al. on impaired liver regeneration in T cell–mediated hepatitis.1 The authors observed an interesting phenomenon that mice injected with concanavalin A (ConA) showed impaired liver regeneration 4 days after injection. They also found that important factors in liver regeneration such as cyclin D, pStat3, and interleukin-6 were reduced in ConA-induced hepatitis (CIH), whereas inhibitors of hepatocyte proliferation such as p21, Smad2, tumor growth factor β and interferon γ were increased. The authors attributed the mechanisms to the modulation of oval cells by ConA treatment. We set up a CIH model in C57BL/6 mice following the authors' protocol. Four days after ConA injection, we obtained liver sections from both naïve and ConA-treated mice, and then performed oil Red O staining for lipid deposits. Much more accumulated lipid was seen in CIH mice (Fig. 1). Increased lipid accumulation in CIH mice. ConA (15 mg/kg body weight) was injected intravenously into C57BL/6 mice. Four days later, frozen liver sections (8 μm) were obtained from naïve and ConA-treated mice. (A) Oil Red O staining of liver sections (400×). Arrows indicate lipid droplets stained by oil Red O. (B) Image analysis of lipid accumulation. The extent of labeling in the liver lobule was defined as the percent of the field area within the default color range. Data from each tissue section (5 fields per section) were pooled to determine means (**P < 0.01). DeAngelis et al.2 have reported that liver regeneration was impaired in mice with fatty liver. This finding was supported by several recent studies.3-5 Although detailed mechanisms need further investigation, the relationship between fatty liver and impaired liver regeneration was well established. Therefore, it will be interesting to investigate whether lipid accumulation also contributes to impaired liver regeneration in CIH mice. It is well known that hepatic steatosis was associated with hepatitis B and hepatitis C virus infections.6 Studies on the interactions between liver infection, lipid accumulation, and liver regeneration will surely improve our knowledge about liver injury and repair, and bring great benefits to the treatment and prevention of liver diseases. Dechun Feng*, Lingyun Xu* , * Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences/Shanghai Jiaotong University School of Medicine, Shanghai, China, Shanghai Institute of Immunology, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Late Displacement of Cardiac Pacemaker Electrode Due to Heavyweight Pulse Generator
Authors: Geun Eun Kim
Journal: JAMA (1974)

ENDOCARDIAL pacing has been shown to be a satisfactory method for long-term cardiac pacing. The electrode complications of malposition, displacement, fracture, migration, and perforation have been well described in previous publications.<sup>1,2</sup>We have recently observed a retraction of the endocardial electrode by the downward migration of the heavy pulse generator. This complication is prevented by anchoring the pacemaker to the clavicle or by creating a pacemaker "pocket" under the pectoral muscle or both. <h3>Report of Cases</h3> A 78-year-old man was admitted to New York University Hospital with intermittent heart block requiring cardiac pacing. A Medtronic pacemaker weighing 200 gm was inserted in a subcutaneous infrapectoral pocket with a bipolar electrode inserted via the cephalic vein into the apex of the right ventricle. Postoperatively the patient did well until the 12th month when failure of capture was noted. Chest x-ray film showed retraction of the catheter into the right atrium
Antidepressants and suicide: Rising prescription rate does not mean rising rate of new users
Authors: Graham Aldred, David Healy
Journal: BMJ (2004)

Competing interests: At the time of the study, AMB was chairman of the Committee on Safety of Medicines and now is chairman of the MHRA.MP is a member of the Committee on Safety of Medicines and of the subcommittee on pharmacovigilance.
Early Visualization of Diverticulitis by Technetium-99m Pertechnetate Imaging
Authors: ANDREW H. KWAI, SABAH S. TUMEH
Journal: Clinical Nuclear Medicine (1988)

A 29-year-old man with diverticulitis demonstrated colonic activity 2 minutes after the intravenous administration of Tc-99m pertechnetate, before stomach visualization. This activity continued to increase throughout the study. Eighty percent of plasma pertechnetate is protein bound. The inflammatory reaction probably caused exudation of plasma protein into the perivascular tissues, so that the early visualization of colonic activity represents an accumulation of protein-bound pertechnetate in the inflamed tissues rather than an active excretion of pertechnetate via the colonic epithelium or transit of stomach contents.
Effects of heart rate on ventricular size, stroke volume, and output in the normal human fetus: a prospective Doppler echocardiographic study.
Authors: J Kenny, T Plappert, P Doubilet, D Salzman, M G Sutton
Journal: Circulation (1987)

The effect of heart rate on cardiac output in the fetal heart is controversial. We used Doppler echocardiography to investigate the effects of increasing heart rate on stroke volume and ventricular output in the normal human fetal heart. Heart rate was increased in 25 human fetuses (mean age 36 weeks) by auditory stimulation with a sound emitter placed on the mother's abdomen. Aortic or pulmonary diameters were measured at valve level from two-dimensional echocardiographic images and cross-sectional areas were calculated. Blood flow velocity spectra from the pulmonary artery or aorta were digitized to obtain flow velocity integrals before and after auditory stimulation. Stroke volume was calculated as the product of the flow velocity integral and the area of the great vessel. Prestimulation mean heart rate was 132 +/- 8 beats/min and increased after auditory stimulation to 158 +/- 9 beats/min (p less than .001). Stroke volume decreased with the increase in heart rate from 3.7 +/- 1.4 ml before stimulation to 3.0 +/- 1.1 ml after stimulation (p less than .001), but ventricular output calculated as the product of stroke volume and heart rate remained unchanged (0.48 +/- 0.18 liter/min before vs 0.48 +/- 0.17 liter/min after stimulation). The decrease in stroke volume was accompanied by a decrease in ventricular end-diastolic area, although there was no change either in end-systolic area or fractional change in area. This study demonstrates that increases in heart rate within the physiologic range in the normal human fetus result in a decrease in ventricular size and stroke volume but no change in ventricular output or ventricular shortening.
Toxicity of Ingested Hexachlorophene
Authors: John B. Wear
Journal: JAMA (1962)

The accidental ingestion of a preparation containing hexachlorophene (pHisoHex) has been encountered in 10 patients. In most instances the suspension containing it was mistaken for milk of magnesia. This occurred because the disinfectant (meant to be used as a preoperative scrub) was dispensed in a paper cup, without adequate instructions and supervision by the nurse, and because the suspension resembles milk of magnesia in color and viscosity. The major symptoms of toxicity were anorexia, nausea, vomiting, abdominal cramps, and diarrhea. Dehydration was sometimes severe and associated with shock. The water and electrolyte derangement must be treated vigorously. Hexachlorophene is believed to be the primary factor in causing this toxicity. The theoretically fatal dose of hexachlorophene is 2 to 10 gm. and is contained in 67 to 300 cc. of the preparation used.
Release of a slow-reacting substance from rabbit platelets.
Authors: J M Mencia-Huerta, L Hadji, J Benveniste
Journal: Journal of Clinical Investigation (1981)

Washed rabbit platelets stimulated with platelet-activating factor, thrombin, or arachidonic acid, released a slow-reacting substance (SRS), whereas platelets aggregated by adenosine diphosphate did not. Production of platelet-derived SRS was neither affected by indomethacin nor aspirin but was reduced by large doses of eicosatetraynoic acid, an inhibitor of the cyclo-oxygenase and lipoxygenase. L-cysteine enhanced markedly the release of SRS from platelets. This SRS activity, which was antagonized by FPL 55712 and inactivated by arylsulfatase, followed the same elution pattern on Amberlite, silicic acid, and reverse phase high-pressure liquid chromatography columns as that described for the SRS from other origins. SRS activity released from platelets preincubated with [14C]arachidonic acid exhibited the same retention time as radioactivity in reverse phase high-pressure liquid chromatography. The release of a SRS from platelets is consistent with their implication in the pathogenesis of asthma and other lung diseases.
Biosynthesis of 5α-Cholestan-3β-ol in Cerebrotendinous Xanthomatosis
Authors: Gerald Salen, Alan Polito
Journal: Journal of Clinical Investigation (1972)

Cerebrotendinous Xanthomatosis is a rare, inherited disease characterized by an extraordinary accumulation of cholestanol in all tissues, xanthomatous deposits in the brain, lungs, and Achilles tendons, premature atherosclerosis, and low plasma cholesterol concentrations. In two patients with the disease, the biosynthesis of cholestanol was examined by different techniques. After cholesterol-4-(14)C was injected intravenously into one patient, cholestanol and cholesterol isolated from the bile on 3 different days over the ensuing week contained significant radioactivity. The specific radioactivity-time curves for cholesterol-(14)C and cholestanol-(14)C suggested a precursor product relationship and provided additional evidence for the transformation of cholesterol into cholestanol. The second patient received intravenously a mixture of mevalonate-2-(14)C and stereospecifically labeled mevalonate-3R,4R-(3)H. Again cholesterol and cholestanol were isolated from the bile, and the (3)H/(14)C ratio in both sterols was almost the same. This experiment again demonstrated that the biosynthetic path of cholestanol proceeded through cholesterol and not directly from earlier 5alpha-H-saturated precursors. These two independent lines of evidence indicate that the extraordinary deposition of cholestanol in Cerebrotendinous Xanthomatosis arises from cholesterol presumably through the accentuation of the normal biosynthetic pathway.
Alternative Therapies Study Moves Into New Phase
Authors: Charles Marwick
Journal: JAMA (1992)

EVALUATION of alternative medical practices is ready to proceed at the National Institutes of Health, says Stephen C. Groft, PharmD. Groft is acting director of the National Institutes of Health's Office for the Study of Unconventional Medical Practices in Bethesda, Md (<i>JAMA</i>. 1992;268: 957-958). Based on two meetings to date, he is preparing a report—to be completed in January or February—that will constitute his office's research agenda. Speaking after the fall meeting, Groft predicted that "information and data generated from these evaluations will be useful to the scientific and medical communities as well as the general public." Practices that will be looked into include nutritional and life-style modifications, counseling and prayer therapies, hands-on healing, and acupuncture, homeopathy, and traditional oriental medicine, among others. <h3>Permanent Appointments</h3> A permanent director will be appointed soon and a permanent advisory committee created. The two meetings so far have been with ad hoc advisory groups.
Primary jejunal malignant melanoma first noticed because of the presence of parotid lymph node metastasis
Authors: Shigeruko Iijima, Kuniyuki Oka, Masataka Sasaki, Yumie Tateishi, Hidetoshi Saito, Norimasa Sandoh, Takeshi Nihei, Hideyuki Kawano, Tomoaki Kawasaki, Hando Hakozaki, Naoyoshi Mori
Journal: Journal of the American Academy of Dermatology (2003)
Crash Risk in General Aviation
Authors: Guohua Li, Susan P. Baker
Journal: JAMA (2007)

Noncommercial flights, usually called general aviation, encompass a wide variety of activities, including emergency medical services (EMS), sightseeing, flight training, traffic reporting, aerial surveys, search and rescue, crop dusting, firefighting, logging, recreation, and personal or business use. In this commentary article, the authors examine the crash risk of private airplane flights, identify major factors influencing survival in aviation crashes, and discuss possible approaches for improving the safety of general aviation. The authors note that the fatal crash rate for general aviation, 1.31 fatal crashes per 100,000 flights hours, is 82 times the rate for major airlines, a difference that has persisted over several decades. General aviation flights are particularly vulnerable to adverse weather conditions and other environmental factors (such as wires or terrain). Other risk factors include alcohol-impaired pilots, sudden incapacitation of the pilot (particularly crucial in light of the lack of a co-pilot on most small aircraft), pilot inexperience, and nonconformist flying behavior. Risks for crash fatality include aircraft fire, instrument meteorological conditions, off-airport location, and failure to use safety restraints; the authors briefly consider approaches to reduce each of these risks. The authors conclude with a consideration of the intersection of general aviation and medicine, focusing particularly on transporting patients from crash sites and between medical facilities (EMS flight crews), and on physician pilots. The safety of general aviation could be increased with interventions to improve fuel system integrity and restraint systems, enhance general crashworthiness of small aircraft, and reduce weather-related crashes through pilot training and avionics technology.
99mTc-Pyrophosphate Imaging Demonstrating Skeletal Muscle and Myocardial Activity Following Cardioversion
Authors: MICHAEL M. McDANIEL, M E MORTON
Journal: Clinical Nuclear Medicine (1977)

A 48-year-old woman who received multiple high energy direct current countershocks for ventricular tachycardia demonstrated both skeletal muscle and myocardial activity on 99mTc-PYP cardiac scan. Recently, experimental work using dogs has been published which Indicates that cardioversion induced myocardial and skeletal muscle injury is significant enough to produce activity on a cardiac scan. This case documents positive scans following cardioversion in a patient.
Protective effects of FUT-175 on acute massive hepatic necrosis induced in mice following endotoxin injection and immunization with liver proteins
Authors: Makoto Ogawa, Yoshio Mori, Shiro Ueda, Teruo Mori, Yasuhiko Makino, Junro Hori, Masao Ohto, Masafumi Wakashin
Journal: Journal of Hepatology (1993)
OP0020 Identification of Multiple Sjögren’s Syndrome Susceptibility Loci
Authors: C. J. Lessard, H. Li, J. A. Ice, I. Adrianto, R. Jonsson, G. G. Illei, M. Rischmueller, G. Nordmark, X. Mariette, C. Miceli-Richard, M. Wahren Herlenius, T. Witte, M. Brennan, R. Omdal, P. M. Gaffney, J. A. Lessard, L. Rönnblom, W.-F. Ng, N. Rhodus, B. Segal, R. H. Scofield, J. A. James, J.-M. Anaya, C. G. Montgomery, J. B. Harley, K. Moser Sivils
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Sjögren’s syndrome (SS) is a common, clinically heterogeneous autoimmune disease characterized by exocrine gland dysfunction that involves both innate and adaptive immune responses. A complex genetic architecture has been hypothesized; however, genetic studies to date have been limited to candidate gene approaches. <h3>Objectives</h3> We sought to perform the first genome-wide association scan (GWAS) in an unbiased manner to identify SS risk loci. <h3>Methods</h3> We used high-density Illumina OMNI1-Quad genotyping arrays in a discovery cohort of 395 European-derived SS cases and 1975 healthy controls for the GWAS discovery phase. Stringent quality control (QC) criteria, adjustments for population stratification, and standard GWA statistical methods were used to compare allele frequencies between cases and controls. For replication, an independent set of 1243 SS cases and 4779 healthy controls were genotyped using 2 custom array (CA) platforms. Meta-analysis between the GWAS and CAs were done using METAL (P<sub>meta</sub>). <h3>Results</h3> The most significantly associated region with SS was the MHC, with 6324 overlapping SNPs between the GWAS and CAs exceeding the genome-wide significance (GWS) threshold of P&lt;5x10E-8 after imputation, peaking at HLA-DQB1 with P<sub>meta</sub>=7.65x10E-114. This study also identified 3 novel associations not previously reported as risk loci for SS. In the region of IL12A, 7 variants passed GWS, peaking at rs485497 (P<sub>meta</sub>=1.17x10E-10). Near CXCR5, 4 variants exceeded GWS with rs7119038 (P<sub>meta</sub>=1.10x10E-8) the most significant. One variant, rs6579837 (P<sub>meta</sub>=3.30x10E-8), in TNIP1 also surpassed GWS. Three regions previously implicated were now identified as surpassing GWS for the first time in the current study: IRF5 (rs3757387 P<sub>meta</sub>=2.73x10E-19), STAT4 (rs10553577 P<sub>meta</sub>=6.80x10E-15), and BLK (rs2736345 P<sub>meta</sub>=4.97x10E-10). <h3>Conclusions</h3> We present the first GWAS of SS identifying and confirming IL12A, CXCR5, and TNIP1 as novel susceptibility loci. We also observed IRF5, STAT4, and BLK for the first time at GWS establishing them as risk loci for SS. Collectively these genes illustrate the importance of both the innate and adaptive immune responses in the etiology of SS. <h3>Disclosure of Interest</h3> None Declared
The Twenty-Four Hour Society: Understanding Human Limits in a World That Never Sleeps
Authors: Roy L. DeHart
Journal: JAMA (1993)

We in medicine are familiar with the 24-hour society. Our hospitals provide health services around the clock and throughout the year. Those of us on call may be required to meet the needs of our patients for 24 continuous hours and perhaps through the next clinic day without adequate rest. Illness and injury are not attentive to office hours or convenience. But are we at our best when time is ignored and rest delayed? Dr Moore-Ede, in his short book<i>The Twenty-Four Hour Society</i>, suggests that when we disregard time (our body clock) and rest is inadequate, we do so at our own peril and that of our patients. No longer are health care services, security activities, and utilities the principal 24-hour industries. Because of the international marketplace, it is always the business day somewhere in the world. International conglomerates are no longer set to eastern standard time. For some,