tbuckley/cabot-search huggingface dataset:
Plans for national paediatric oncology centre in the Netherlands cause controversy
Authors: W. Weber
Journal: BMJ (2010)

Recent findings have shown that dendritically released dopamine (DA) plays an important modulatory role in the substantia nigra pars reticulata (SNr). It is therefore possible that the loss of DA observed in Parkinson9s disease (PD) could hold important consequences for nigral function. Previously, we have shown that activation of presynaptically localized group II metabotropic glutamate receptors (mGluRs) inhibits excitatory transmission at the subthalamic nucleus (STN)-SNr synapse and that activation of presynaptically localized group III mGluRs decreases excitatory and inhibitory transmission in the SNr. To test the hypothesis that nigral DA can modulate mGluR function in the SNr, we performed whole-cell patch-clamp recordings from γ-aminobutyric acidergic SNr neurons in slices obtained from rats that were acutely reserpinized. In slices obtained from reserpinized animals, the effect of group II mGluR activation by the selective agonist (+)-2-aminobicyclo[3·1·0]-hexane-2,6-dicarboxylate monohydrate (LY354740) (100 nM), but not group III mGluR activation [l-(+)-2-amino-4-phosphonobutyric acid, L-AP4, 500 μM], at STN-SNr synapses is significantly decreased. This effect could be mimicked in control slices by prior bath application of haloperidol (20 μM) and<i>R</i>-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1<i>H</i>-3-benzazepine (SCH23390) (20 μM) but not sulpiride (50 μM). Furthermore, application of dopamine (100 μM) and (±)-6-chloro-7,8-dyhydroxy-3allyl-1-phenyl-2,3,4,5-tetra-hydro-1<i>H</i>-benzazepine (SKF82958) (1 μM) but not quinpirole (10 μM) could rescue the group II mGluR effect in reserpinized slices. The effect of group III mGluR activation (L-AP4, 100 μM) on inhibitory synaptic transmission was also significantly reduced in slices from reserpine-treated animals. This effect was mimicked by haloperidol (20 μM), SCH23390 (20 μM), and sulpiride (50 μM) in control slices. Thus, in a Parkinsonian state, the loss of nigral DA may add to the overall pathophysiological changes in basal ganglia output.
Infection Control in Small Hospitals
Authors: Michael R. Britt
Journal: JAMA (1976)

In prevalence surveys of 18 small hospitals in the intermountain region, 20.4% of the patients had community-acquired infections and 7.2% had infections acquired in the hospital. The types of nosocomial infections and patterns of antibiotic usage were similar to those encountered in large hospitals. In the small hospitals, 49% of the suspected bacterial infections were cultured, whereas at a nearby large hospital 77% were cultured. Seventeen of these small hospitals had an infection-control committee but these committees were unable to assess adequately the extent of their nosocomial infection problems. Monitoring of the environment with bacterial cultures was a frequent practice; overall, a ratio of one environmental culture was performed to each three diagnostic cultures. These results indicate the need to develop and evaluate nosocomial infection control programs in small hospitals. (<i>JAMA</i>236:1700-1703, 1976)
All About Antibodies
Authors: Hugh H. Hussey
Journal: JAMA (1976)

As Gail McBride writes in the MEDICAL NEWS section of this issue ofThe Journal(p 583), knowledge about the antibody molecule has spread rapidly and extensively. Indeed, information has increased at a rate so fast that the uninitiated reader may find himself like a man viewing a crabgrass-infested lawn and not knowing what to do about it. The simile is weak in at least one respect. The crabgrass viewer may decide to replace his lawn with the green synthetic stuff that now covers so many tennis courts. A call to a competent contractor—one who can lay Plexipave, for example—solves the problem. In contrast, as Ms McBride recounts, the physician who seeks understanding of the antibody molecule must delve into 20 years' reports of studies by immunologists, geneticists, protein chemists, and x-ray crystallographers. He may find the "going heavy," as did the medical editor who first read Ms McBride's typescript.
Phase I Study of the Farnesyltransferase Inhibitor Lonafarnib with Weekly Paclitaxel in Patients with Solid Tumors
Authors: Neal E. Ready, Alan Lipton, Yali Zhu, Paul Statkevich, Emily Frank, Dolores Curtis, Ronald M. Bukowski
Journal: Clinical Cancer Research (2007)

Abstract Purpose: To establish the maximum tolerated dose of the farnesyltransferase inhibitor lonafarnib (Sarasar, Schering-Plough Corp., Kenilworth, NJ) in combination with weekly paclitaxel in patients with solid tumors. Tolerability, pharmacokinetics, safety, and dose-limiting toxicity were characterized. Experimental Design: Patients were enrolled from January 2000 to May 2001. Lonafarnib was administered continuously orally twice daily at doses of 100, 125, and 150 mg in combination with paclitaxel at doses of 40, 60, or 80 mg/m2 i.v. over 1 h weekly in 28-day cycles in a phase I design. Plasma samples for determinations of lonafarnib and paclitaxel concentrations were collected at selected time points. Results: Twenty-seven patients were enrolled. The maximum tolerated dose (the dose level below where dose-limiting toxicity occurred and the recommended phase II dose) was lonafarnib 125 mg/m2 twice daily and paclitaxel 80 mg/m2 weekly. Dose-limiting toxicity was neutropenia with or without fever, which occurred in two of three patients treated at the lonafarnib 150 mg twice daily dose level. Diarrhea was a common side effect of lonafarnib but usually was mild to moderate in severity and could be controlled with standard medication without lonafarnib dose adjustment. Other reported adverse events included nausea, vomiting, fatigue, and taste changes. These adverse events were neither more frequent nor more severe than would be expected with paclitaxel alone. There were no apparent pharmacokinetic interactions between weekly paclitaxel and continuous twice-daily lonafarnib. Conclusions: The recommended dose of lonafarnib for phase II trials is 125 mg orally twice daily when combined with weekly paclitaxel 80 mg/m2. The dose-limiting toxicity was neutropenia.
Case 32-1984
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, Betty U. McNeely
Journal: New England Journal of Medicine (1984)

Presentation of Case A 72-year-old man was admitted to the hospital because of progressive neuropathy. He was in vigorous health until eight months earlier, when he began to experience a sensation like electric shocks that traveled from the left toes to the knee, occurred several times daily, and lasted three to four minutes each time; he believed that the left lower leg was weak. Anorexia developed, with early satiety and weight loss, five weeks later malaise and fever appeared. He became confused and disoriented. Six months before admission he entered another hospital. Physical examination showed that he was agitated and . . .
The effect of steroid pretreatment of deceased organ donors on liver allograft function: A blinded randomized placebo-controlled trial
Authors: Stefan Amatschek, Julia Wilflingseder, Mario Pones, Alexander Kainz, Martin Bodingbauer, Ferdinand Mühlbacher, Robert M. Langer, Zsuzsanna Gerlei, Rainer Oberbauer
Journal: Journal of Hepatology (2012)

Brain death-associated inflammatory response contributes to increased risk of impaired early liver allograft function, which might be counterbalanced by steroid pretreatment of the organ donor. The aim of this randomized controlled trial was to elucidate whether steroid pretreatment of liver donors improves early liver allograft function, prevents rejection and prolongs survival.A placebo-controlled blinded randomized clinical trial was performed in three different centers in Austria and Hungary between 2006 and 2008. Ninety deceased organ donors received either 1000 mg of methylprednisolone or placebo 6h before recovery of organs. The primary end point was the concentration slope of transaminases within the first week. The secondary end point included survival and biopsy-confirmed acute rejection (BCAR) within 3 years after transplantation.Of the 90 randomized donors, 83 recipients were eligible for study. The trajectories of ALT and AST were not different between treatments (p=0.40 and p=0.13, respectively). Eight subjects died in the steroid and 13 in the placebo group within 3 years after engraftment (RR=0.63 95% CI [0.29,1.36], p=0.31). Eleven recipients experienced biopsy-confirmed rejection (BCAR) in the steroid and 11 in the placebo group (RR=1.02 95% CI [0.50,2.10], p=1.00). No effect modification could be identified in the predefined strata of donor age, sex, cold ischemic time, and cause of donor death.Steroid pretreatment of organ donors did not improve outcomes after liver transplantation.
Exercise‐induced hypersensitivity syndromes in recreational and competitive athletes: a PRACTALL consensus report (what the general practitioner should know about sports and allergy)
Authors: L. B. Schwartz, L. Delgado, T. Craig, S. Bonini, K. H. Carlsen, T. B. Casale, S. Del Giacco, F. Drobnic, R. G. Van Wijk, M. Ferrer, T. Haahtela, W. R. Henderson, E. Israel, J. Lötvall, A. Moreira, N. G. Papadopoulos, C. C. Randolph, A. Romano, J. M. Weiler
Journal: Allergy (2008)

Exercise‐induced (EI) hypersensitivity disorders are significant problems for both recreational and competitive athletes. These include EI‐asthma, EI‐bronchoconstriction, EI‐rhinitis, EI‐anaphylaxis and EI–urticaria. A group of experts from the European Academy of Allergology and Clinical Immunology and the American Academy of Allergy Asthma and Immunology met to discuss the pathogenesis of these disorders and how to diagnose and treat them, and then to develop a consensus report. Key words (exercise with asthma, bronchoconstriction, rhinitis, urticaria or anaphylaxis) were used to search Medline, the Cochrane database and related websites through February 2008 to obtain pertinent information which, along with personal reference databases and institutional experience with these disorders, were used to develop this report. The goal is to provide physicians with guidance in the diagnosis, understanding and management of EI‐hypersensitivity disorders to enable their patients to safely return to exercise‐related activities.
Interleukin-33 Is hepatoprotective during liver ischemia/reperfusion in mice
Authors: Nozomu Sakai, Heather L. Van Sweringen, Cutler R. Quillin, Rebecca Schuster, John Blanchard, Justin M. Burns, Amit D. Tevar, Michael J. Edwards, Alex B. Lentsch
Journal: Hepatology (2012)

Interleukin (IL)-33 is a recently identified member of the IL-1 family that binds to the receptor, ST2L. In the current study, we sought to determine whether IL-33 is an important regulator in the hepatic response to ischemia/reperfusion (I/R). Male C57BL/6 mice were subjected to 90 minutes of partial hepatic ischemia, followed by up to 8 hours of reperfusion. Some mice received recombinant IL-33 (IL-33) intraperitoneally (IP) before surgery or anti-ST2 antibody IP at the time of reperfusion. Primary hepatocytes and Kupffer cells were isolated and treated with IL-33 to assess the effects of IL-33 on inflammatory cytokine production. Primary hepatocytes were treated with IL-33 to assess the effects of IL-33 on mediators of cell survival in hepatocytes. IL-33 protein expression increased within 4 hours after reperfusion and remained elevated for up to 8 hours. ST2L protein expression was detected in healthy liver and was up-regulated within 1 hour and peaked at 4 hours after I/R. ST2L was primarily expressed by hepatocytes, with little to no expression by Kupffer cells. IL-33 significantly reduced hepatocellular injury and liver neutrophil accumulation at 1 and 8 hours after reperfusion. In addition, IL-33 treatment increased liver activation of nuclear factor kappa light-chain enhancer of activated B cells (NF-κB), p38 mitogen-activated protein kinase (MAPK), cyclin D1, and B-cell lymphoma 2 (Bcl-2), but reduced serum levels of CXC chemokines. In vitro experiments demonstrated that IL-33 significantly reduced hepatocyte cell death as a result of increased NF-κB activation and Bcl-2 expression in hepatocytes.The data suggest that IL-33 is an important endogenous regulator of hepatic I/R injury. It appears that IL-33 has direct protective effects on hepatocytes, associated with the activation of NF-κB, p38 MAPK, cyclin D1, and Bcl-2 that limits liver injury and reduces the stimulus for inflammation.
Neuropeptide-containing C-fibres and wound healing in rat skin. Neither capsaicin nor peripheral neurotomy affect the rate of healing
Authors: None WALLENGREN, None CHEN, None SUNDLER
Journal: British Journal of Dermatology (1999)

Wound healing in rat skin was studied in standardized wounds inflicted on both hind legs after unilateral sciatic nerve sectioning and/or capsaicin‐induced depletion of sensory nerve (C‐fibre) neuropeptide content. Daily visual inspection, histological examination and immunohistochemistry with antibodies against substance P, calcitonin gene‐related peptide (CGRP), vasoactive intestinal peptide, neuropeptide Y and a pan‐neuronal marker, protein gene product 9.5 (PGP 9.5) were used to assess wound healing and determine the distribution of dermal nerve fibres. In controls, nerve fibre density in the wound tissue was low during the first few days after wound infliction, but started to increase on day 4, reaching a peak on day 7 when 25% of medial wounds and 70% of lateral wounds were healed. All wounds were healed on day 11, a scar appearing on day 14 followed by a decrease in nerve fibre density. Capsaicin treatment and/or sciatic nerve sectioning reduced the density of CGRP‐immunoreactive nerve fibres by 70% and that of PGP 9.5‐immunoreactive fibres by 50%. The capsaicin‐induced reduction in PGP 9.5‐immunoreactive nerve fibre density is attributable to partial destruction of peripheral nerve fibres. CGRP‐immunoreactive and PGP 9.5‐immunoreactive nerve fibre density was restored both in capsaicin‐treated and denervated groups, reaching a maximum, corresponding to the original level, by days 4–10. Neither the reduction in nerve fibre density following sciatic nerve sectioning nor the impairment of sensory nerve functional capacity following capsaicin treatment affected the rate of wound healing, all wounds being closed on day 11. The study shows that it is difficult to knock out all cutaneous sensory innervation. Thirty per cent of C‐fibre innervation seems enough to ensure a normal wound healing.
The Chronic Fatigue Syndrome — One Entity or Many?
Authors: Morton N. Swartz
Journal: New England Journal of Medicine (1988)

Fatigue may be a normal consequence of intensive physical exertion or mental effort, or it may be symptomatic of a variety of specific illnesses. Because of its largely subjective nature, it may be difficult to define and quantitate. To the muscle physiologist, fatigue represents a failure to sustain the expected or required muscular force. Such a failure may represent an impairment at any site in the long chain from cerebral cortex to spinal cord to peripheral nerve to neuromuscular junction to muscle-cell membrane to release of intracellular calcium ion to actin–myosin cross-bridge formation.1 Thus, fatigue can be considered central in . . .
Childhood Lead Poisoning
Authors: Donna Barnako
Journal: JAMA (1972)

The occurrence of lead poisoning among children due to ingestion of flakes of lead-containing paint is sad testimony to our sense of priorities. Sad, because its etiology, pathogenesis, pathophysiology, and epidemiology have been known for years. And sad because it is an entirely preventable disease. Approximately 400,000 American children have elevated blood lead levels, according to the Public Health Service, and some 16,000 children now require treatment for lead poisoning. This year an estimated 200 children will die and another 800 will be so severely injured as to require permanent care. Approximately 3,200 will suffer moderate to severe brain damage, and will require years of special care.<sup>1</sup> High-risk areas for lead poisoning are slums, where old dilapidated housing, with peeling, lead-containing paint is prevalent. Children between the ages of 1 and 6 years are the main victims, with more than 85% in the 1- to 3-yearold group. Though lead poisoning
PRODUCTION OF A RUNTING SYNDROME AND SELECTIVE γA DEFICIENCY IN MICE BY THE ADMINISTRATION OF ANTI-HEAVY CHAIN ANTISERA
Authors: Robert A. Murgita, Carlos A. Mattioli, Thomas B. Tomasi
Journal: The Journal of Experimental Medicine (1973)

Conventional Swiss mice were treated from birth with intraperitoneal injections of anti-immunoglobulins in an attempt to create an experimental dysgammaglobulinemia. Mice treated with anti-gammaM were immunologically suppressed in all immunoglobulin classes as determined by serum antibody titers, splenic plaque-forming cells, serum immunoglobulin levels, and immunofluorescent analysis of plasma cells in lymphoid tissues. Treatment immediately after birth with high concentrations of anti-gammaM leads to a developmental arrest characterized by severe immunosuppression, failure to gain weight, and premature death. The pathogenesis of anti-gammaM runting syndrome is unknown. Animals similarly treated with anti-gammaG, anti-gammaA, or control normal goat or rabbit gamma-globulins developed normally. The frequency of occurrence and severity of anti-gammaM-induced runting syndrome is dependent upon the concentration of anti-gammaM-globulin administered. Administration of anti-gammaA resulted in a selective gammaA deficiency that was characterized by a marked reduction in serum-gammaA and an absence of gammaA-containing cells in the spleen. However, essentially normal numbers of plasma cells were found in the gastrointestinal lamina propria of anti-gammaA-treated animals concomitantly with suppressed levels of gammaA in intestinal fluids.
The relationship between atrioventricular nodal refractoriness and the functional refractory period in the dog.
Authors: M B Simson, J Spear, E N Moore
Journal: Circulation Research (1979)

We studied the relationship between the atrioventricular nodal functional refractory period (FRP) and refractoriness by mathematical analysis and by measurement during antegrade Wenckebach cycles in 16 dogs. The FRP relates directly to the conduction time of the control beat, and inversely to the coordinates of the point on the A'-H' vs. A-A refractory curve where the slope is -1. The FRP can vary without any change in refractoriness as measured by the effective refractory period (ERP) or the refractory curve. In 16 dogs the ERP and the FRP were measured during 4:3 Wenckebach cycles. Because of changes in the control conduction times, the FRP declined and did not reflect the progressive increase in refractoriness recorded during Wenckebach cycles. The FRP is a complex parameter and does not reliably measure refractoriness.
Possible role of nicotinamide adenine dinucleotide as an intracellular regulator of renal transport of phosphate in the rat.
Authors: S A Kempson, G Colon-Otero, S Y Ou, S T Turner, T P Dousa
Journal: Journal of Clinical Investigation (1981)

In these experiments we investigated whether NAD could serve as an intracellular modulator of the brush border membrane (BBM) transport of inorganic phosphate (Pi). NAD, both oxidized (NAD+) and reduced (NADH) form, inhibited the Na+-dependent uptake of 32Pi in the concentration range of 10-300 microM NAD when added in vitro to BBM vesicles isolated from rat kidney cortex, but did not inhibit BBM uptake of D-[3H]glucose or BBM uptake of 22Na+. Neither nicotinamide (NiAm) nor adenosine alone influenced BBM uptake of 32Pi. NAD had a similar relative effect (percent inhibition) in BBM from rats stabilized on low Pi diet (0.07% Pi), high Pi diet (1.2% Pi), or normal Pi diet (0.7% Pi). Subsequently, we examined the renal effects of changing the tissue NAD level in vivo. Rats stabilized on low Pi diet were injected intraperitoneally with NiAm (0.25-1.0 g/kg body wt); urinary excretions of Pi (UPiV), of fluid, and of other solutes were measured before and after NiAm injection, then renal cortical tissue nucleotide content was determined, and a BBM fraction was isolated for transport measurements. In BBM from NiAm-treated rats, the Na+-dependent uptake of 32Pi was decreased, but BBM uptake of D-[3H]glucose and BBM uptake of 22Na+ were not changed. NiAm injection elicited an increase in NAD+ (maximum change, 290%), a lesser increase in NADH (maximum change, +45%), but no change in the content of ATP or cyclic AMP in the renal cortex. Na+-dependent BBM uptake of 32Pi ws inversely correlated with NAD+ content in renal cortex (r = -0.77 +/- 0.1; P less than 0.001) and with UPiV (r = -0.67 +/- 0.13; P less than 0.01). NAD+ in renal cortex was positively correlated with UPiV (r = 0.88 +/- 0.05; P less than 0.001). Injection of NiAm elicited a marked increase in UPiV, but no change in excretions of creatinine or K+, or in urine flow; excretion of Na+ and Ca declined. NiAm injection caused similar renal responses, in normal and in thyroparathyroidectomized rats, as well as in rats on normal Pi diet and low Pi diet. We conclude that NAD can serve as an intracellular modulator (inhibitor) of Na+-dependent transport of Pi across the renal luminal BBM and across the proximal tubular wall by its direct interaction with BBM. We propose that at least some hormonal and/or metabolic stimuli elicit phosphaturia by increasing NAD+ in cytoplasm of proximal tubular cells.
Pathology of Anaemia
Authors: D. French
Journal: BMJ (1961)

<h3>BACKGROUND AND PURPOSE:</h3> White matter hyperintensities on T2-weighted MR imaging are typical in older adults and have been linked to several poor health outcomes, including cognitive impairment and Alzheimer disease. The presence and severity of white matter hyperintensities have traditionally been attributed to occlusive arteriopathy, but recent evidence also implicates deep medullary venule collagenosis and associated vasogenic edema. Historically, postmortem analyses have been the sole way to analyze cerebral veins, but SWI can be now used to examine cortical veins in vivo. The aim of the current study was to determine whether there is an association between the diameters of the large draining cerebral veins/sinuses and white matter hyperintensity volume. <h3>MATERIALS AND METHODS:</h3> T2-weighted FLAIR and SWI were performed in 682 older adults without dementia (mean age, 73.9 ± 5.9 years; 59.1% women). Total and regional white matter hyperintensity volume was derived. We measured the diameters of 5 regions of the cerebral venous draining system: internal cerebral veins, basal veins of Rosenthal, superior sagittal sinus, vein of Galen, and straight sinus terminus. <h3>RESULTS:</h3> Increased diameter of the internal cerebral veins was associated with greater total white matter hyperintensity volume (β = 0.09, <i>P</i> = .02) and regionally in the parietal (β = 0.10, <i>P</i> = .006), frontal (β = 0.09, <i>P</i> = .02), and temporal (β = 0.09, <i>P</i> = .02) lobes. Increased diameter of the basal veins of Rosenthal was associated with greater total (β = 0.10, <i>P</i> = .01), frontal (β = 0.11, <i>P</i> = .003), and temporal (β = 0.09, <i>P</i> = .02) white matter hyperintensity volume. <h3>CONCLUSIONS:</h3> Our results suggest that the caliber of the internal cerebral veins and of the basal veins of Rosenthal relates to regional white matter disease.
Effect of ornithine alpha ketoglutarate on disturbances of brain metabolism caused by high blood ammonia
Authors: I. M. James, G. Dore, S. Hall, H. Michel, D. Dojcinov, G. Gravagne, L. MacDonell
Journal: Gut (1972)

The administration of ammonium salts to free ventilated dogs causes an increase in the anaerobic consumption of glucose. Prior and simultaneous administration of the drug ornithine alpha ketoglutarate not only attenuates the rise in blood ammonia but also favourably affects these changes in brain metabolism.