tbuckley/cabot-search huggingface dataset:
Late Effects of Conformal Radiation Therapy for Pediatric Patients With Low-Grade Glioma: Prospective Evaluation of Cognitive, Endocrine, and Hearing Deficits
Authors: Thomas E. Merchant, Heather M. Conklin, Shengjie Wu, Robert H. Lustig, Xiaoping Xiong
Journal: Journal of Clinical Oncology (2009)

Purpose We conducted a prospective trial to evaluate late effects in pediatric patients with low-grade glioma (LGG) treated with conformal radiation therapy (CRT). Patients and Methods Between August 1997 and August 2006, 78 pediatric patients with LGG (mean age, 9.7 years; standard deviation, ±4.4 years) received 54 Gy of CRT with a 10-mm clinical target volume margin. Tumor locations were diencephalon (n = 58), cerebral hemisphere (n = 3), and cerebellum (n = 17). Baseline and serial evaluations were performed to identify deficits in cognition, endocrine function, and hearing. Deficits were correlated with clinical factors and radiation dose within specific normal tissue volumes. Results Cognitive effects of CRT through 5 years after CRT correlated with patient age, neurofibromatosis type 1 status, tumor location and volume, extent of resection, and radiation dose. The effect of age exceeded that of radiation dose; patients younger than 5 years experienced the greatest decline in cognition. Before CRT, growth hormone (GH) secretion abnormality was diagnosed in 24% of tested patients, and 12% had precocious puberty. The 10-year cumulative incidence of GH replacement was 48.9%; of thyroid hormone replacement, 64.0%; of glucocorticoid replacement, 19.2%; and of gonadotropin-releasing hormone analog therapy, 34.2%. The mean ± standard errors of the cumulative incidence of hearing loss at 10 years did not exceed 5.7% ± 3.3% at any frequency. Conclusion To our knowledge, this is the largest series of prospectively followed children with LGG to undergo irradiation. Adverse effects are limited and predictable for most patients; however, this study provides additional evidence that CRT should be delayed for young patients and identifies the potential benefits of reducing radiation dose to normal brain.
Mortality in former Olympic athletes: retrospective cohort analysis
Authors: R. Zwiers, F. W. A. Zantvoord, F. M. Engelaer, D. van Bodegom, F. J. G. van der Ouderaa, R. G. J. Westendorp
Journal: BMJ (2012)

To assess the mortality risk in subsequent years (adjusted for year of birth, nationality, and sex) of former Olympic athletes from disciplines with different levels of exercise intensity.
Maintenance treatment of duodenal ulceration: ranitidine 300 mg at night is better than 150 mg in cigarette smokers.
Authors: F I Lee, M Hardman, M E Jaderberg
Journal: Gut (1991)

Two hundred patients received either ranitidine 150 mg or 300 mg at night for 18 months to prevent duodenal ulcer relapse. Recurrence rates were lower in patients receiving the higher dose of ranitidine (3.1% v 9.7%, p = 0.78; 6.5% v 16.7%, p = 0.037; and 8.9% v 17.0%, p = 0.121 at six, 12, and 18 months respectively). In patients receiving ranitidine 150 mg, recurrences were significantly more common in smokers than non-smokers after 12 and 18 months, while in patients receiving ranitidine 300 mg recurrence rates were similar in smokers and non-smokers. Ranitidine 300 mg at night abolishes the adverse effect of smoking observed during maintenance treatment with ranitidine 150 mg at night and may therefore be an appropriate maintenance dose for smokers who relapse during standard dose maintenance treatment.
Immunoregulatory function of human intestinal mucosa lymphoid cells: evidence for enhanced suppressor cell activity in inflammatory bowel disease.
Authors: C Fiocchi, K R Youngman, R G Farmer
Journal: Gut (1983)

Abnormalities in immune regulation at the gut level may be relevant to the pathogenesis of inflammatory bowel disease, but little is known about the immunoregulatory properties of intestinal mononuclear cells. Therefore, we wished to see if lymphoid cells derived from the lamina propria of surgically resected bowel specimens have any modulatory effect upon the immune response of peripheral blood mononuclear cells from patients with ulcerative colitis or Crohn9s disease. When autologous peripheral blood and intestinal lamina propria lymphoid cells were mixed at different ratios and cultured in the presence of phytohaemagglutinin, we were able to show that intestinal mononuclear cells had the capacity to modify the mitogenic response of the cultured cells. These intestinal immunoregulatory cells, when obtained from mucosa affected by inflammatory bowel disease, express a significantly enhanced suppressor cell activity as compared with those from non-inflamed control mucosa. Such suppressor cell activity varies with cell concentration and requires cell proliferation, but it is independent of anatomical origin (small vs large bowel), type of inflammatory bowel disease (ulcerative colitis vs Crohn9s disease) or immunosuppressive therapy. These findings point to an important functional difference between inflammatory bowel disease and control intestinal mucosa mononuclear cells. The enhanced suppressor activity of lamina propria mononuclear cells may be associated with impairment of cell-mediated immunity at the gut level. This may be related to the pathogenesis of inflammatory bowel disease by leading to defective intestinal immune regulatory events, which may not be detectable at the peripheral level.
Identification of a Schizophrenia-Associated Functional Noncoding Variant in<i>NOS1AP</i>
Authors: Naomi S. Wratten, Holly Memoli, Yungui Huang, Anna M. Dulencin, Paul G. Matteson, Michelle A. Cornacchia, Marco A. Azaro, Jaime Messenger, Jared E. Hayter, Anne S. Bassett, Steven Buyske, James H. Millonig, Veronica J. Vieland, Linda M. Brzustowicz
Journal: American Journal of Psychiatry (2009)

The authors previously demonstrated significant association between markers within NOS1AP and schizophrenia in a set of Canadian families of European descent, as well as significantly increased expression in schizophrenia of NOS1AP in unrelated postmortem samples from the dorsolateral prefrontal cortex. In this study the authors sought to apply novel statistical methods and conduct additional biological experiments to isolate at least one risk allele within NOS1AP.
Role of Palifermin in Fluorouracil-Based Therapy for Metastatic Colorectal Cancer
Authors: John R. Zalcberg, Lee S. Rosen, Ehtesham Abdi, Ian D. Davis, John Gutheil, Frederick M. Schnell, Alessandra Cesano, Urte Gayko, Mon-Gy Chen, Stephen Clarke
Journal: Journal of Clinical Oncology (2008)

We would like to address questions raised in Dr Haines’ Letter to the Editor published July 1, 2007,1 regarding the study, “Palifermin reduces the incidence of mucositis in patients with metastatic colorectal cancer treated with fluorouracil-based chemotherapy.”2

With respect to the choice of treatment regimen used, the particular fluorouracil / leucovorin (FU/ LV, Mayo) regimen used in this study was widely used both in the United States and Australia at the time the study was designed and conducted. The study commenced in the mid 1990s, with the final patient enrolled onto the treatment phase of the trial in May 2000. Dr Haines cites a study by Wang et al,3 however this was not published until after our study had completed accrual. On the other hand, a much larger study involving 372 patients published in 1994 in this journal,4 suggested that the Mayo schedule as used in this study2 was preferable to the original, weekly Roswell Park regimen of FU and folinic acid, on the basis of similar effectiveness with reduced toxicity.
Menin Epigenetically Represses Hedgehog Signaling in MEN1 Tumor Syndrome
Authors: Buddha Gurung, Zijie Feng, Daniel V. Iwamoto, Austin Thiel, Guanghui Jin, Chen-Min Fan, Jessica M.Y. Ng, Tom Curran, Xianxin Hua
Journal: Cancer Research (2013)

Abstract Multiple endocrine neoplasia type 1 (MEN1) is an inherited tumor syndrome that includes susceptibility to pancreatic islet tumors. This syndrome results from mutations in the MEN1 gene, encoding menin. Although menin acts as an oncogenic cofactor for mixed lineage leukemia (MLL) fusion protein–mediated histone H3 lysine 4 methylation, the precise basis for how menin suppresses gene expression and proliferation of pancreatic beta cells remains poorly understood. Here, we show that menin ablation enhances Hedgehog signaling, a proproliferative and oncogenic pathway, in murine pancreatic islets. Menin directly interacts with protein arginine methyltransferase 5 (PRMT5), a negative regulator of gene transcription. Menin recruits PRMT5 to the promoter of the Gas1 gene, a crucial factor for binding of Sonic Hedgehog (Shh) ligand to its receptor PTCH1 and subsequent activation of the Hedgehog signaling pathway, increases repressive histone arginine symmetric dimethylation (H4R3m2s), and suppresses Gas1 expression. Notably, MEN1 disease-related menin mutants have reduced binding to PRMT5, and fail to impart the repressive H4R3m2s mark at the Gas1 promoter, resulting in its elevated expression. Pharmacologic inhibition of Hedgehog signaling significantly reduces proliferation of insulinoma cells, and expression of Hedgehog signaling targets including Ptch1, in MEN1 tumors of mice. These findings uncover a novel link between menin and Hedgehog signaling whereby menin/PRMT5 epigenetically suppresses Hedgehog signaling, revealing it as a target for treating MEN1 tumors. Cancer Res; 73(8); 2650–8. ©2013 AACR.
T lymphomagenesis is determined by a dominant host gene thymic lymphoma susceptible mouse-1 (TLSM-1) in mouse models.
Authors: Y Yamada, H Shisa, H Matsushiro, T Kamoto, Y Kobayashi, A Kawarai, H Hiai
Journal: The Journal of Experimental Medicine (1994)

Susceptibility to T lymphomas in mice is determined by a number of viral and host genetic factors. We analyzed the types and latent period of lymphomas spontaneously occurring in crosses between AKR/Ms, a T lymphoma-prone mouse strain, and SL/Kh, a pre-B lymphoma-prone strain. The incidence of T lymphomas in the F1 hybrids backcross to SL/Kh as well as F2 generation mice indicated that a dominant host gene thymic lymphoma susceptible mouse-1 (Tlsm-1) of AKR/Ms determined the type of lymphomas to be thymic. Linkage analysis with microsatellite markers assigned Tlsm-1 to the map position 61 cM from centromere of the chromosome 7. Close scrutiny of this region of AKXD recombinant inbred strains for spontaneous T lymphomas revealed the presence of Tlsm-1-like gene most likely between D7MIT71 (map position 62) and D7MIT13 (map position 70). On the other hand, a SL/Kh-derived recessive allele at a major histocompatibility complex (MHC)-linked locus accelerated development of both T and B lymphomas.
Infection and Cancer: Revaluation of the Hygiene Hypothesis
Authors: Katerina Oikonomopoulou, Davor Brinc, Kyriacos Kyriacou, Eleftherios P. Diamandis
Journal: Clinical Cancer Research (2013)

Several studies have shown that persistent infections and inflammation can favor carcinogenesis. At the same time, certain types of pathogens and antitumor immune responses can decrease the risk of tumorigenesis or lead to cancer regression. Infectious agents and their products can orchestrate a wide range of host immune responses, through which they may positively or negatively modulate cancer development and/or progression. The factors that direct this dichotomous influence of infection-mediated immunity on carcinogenesis are not well understood. Even though not universal, several previous reports have investigated the inverse link of pathogen-induced "benign" inflammation to carcinogenesis and various other pathologies, ranging from autoimmune diseases to allergy and cancer. Several models and ideas are discussed in this review, including the impact of decreased exposure to pathogens, as well as the influence of pathogen load, the timing of infection, and the type of instigated immune response on carcinogenesis. These phenomena should guide future investigations into identifying novel targets within the microbial and host proteome, which will assist in the development of cancer therapeutics and vaccine remedies, analogous to earlier efforts based on helminthic components for the prevention and/or treatment of several pathologies.
High concentrations of antibodies to xanthine oxidase in human and animal sera. Molecular characterization.
Authors: G Bruder, E D Jarasch, H W Heid
Journal: Journal of Clinical Investigation (1984)

The widespread occurrence of antibodies (IgG) specific to xanthine oxidase in both normal (nonimmune) human and animal sera, and in antisera raised against a diversity of unrelated antigens is described. A study of sera from 81 humans revealed that xanthine oxidase-specific IgG represents a high proportion (1-8%) of total IgG. No obvious correlation to pathological events or symptoms of disease could be found. These xanthine oxidase-specific antibodies could be isolated by immunoaffinity chromatography on purified human or bovine xanthine oxidase and showed specific binding to the enzyme polypeptide of Mr 155,000 in immunoblotting experiments. By immunofluorescence microscopy they displayed the same cell type-specific reaction as experimentally induced antibodies, i.e., the staining of lactating mammary gland epithelium and capillary endothelium. The naturally occurring xanthine oxidase-specific antibodies consisted of polyclonal IgG of various subclasses. F(ab')2 preparations gave immune-reactions identical to those of IgG. The human xanthine oxidase-specific IgG cross-reacted with the bovine enzyme and both human and animal antibodies partially inhibited its activity. The xanthine oxidase activity of human milk lipid globules and supernatant fractions from various human tissues was extremely low when compared with that of the bovine antigen. The enzyme protein, however, was effectively precipitated from these sources by both the human and bovine antibodies. We suggest that the exceptionally high concentrations of antibodies against one protein, xanthine oxidase, are due to self-immunization to the xanthine oxidase antigen present in endothelial cells of capillaries. We do not exclude, however, nutritional contributions of bovine milk antigen to the appearance of xanthine oxidase antibodies in human sera. The possible biological functions of this immunological reaction are discussed.
Intraperitoneal Intestinal Anastomosis in Colectomy
Authors: W. G. Hendry
Journal: BMJ (1950)

Fifty-one cases of small acute corneal ulcers were examined, and healing time ascertained by instillation of sodium fluorescein under standard arbitrary conditions.Approximately half the patients received 1.5 g. of ascorbic acid daily; the remainder were given control tablets.Deep ulcers healed significantly more slowly than superficial ulcers.The administration of large doses of ascorbic acid had no significant effect upon the healing time of superficial ulcers, but significantly accelerated the healing of deep ulcers.It is suggested that there may be a localized area around the site of regenerating corneal collagen where the ascorbic acid level falls below the opti.numfor rapid healing.Raising the general ascorbic acid level with massive doses increases the local rate of replacement.Pyorrhoea occurred significantly more frequently in patients with corneal ulcers than in others with non-infective eye complaints.We wish to thank Drs. J. Pendleton White, J. Hill, A. Wright Thomson, and A. Mellick, of the Glasgow Eye Infirmary, for permission to examine their patients.We
180-kD bullous pemphigoid antigen (BP180) is deficient in generalized atrophic benign epidermolysis bullosa.
Authors: M F Jonkman, M C de Jong, K Heeres, H H Pas, J B van der Meer, K Owaribe, A M Martinez de Velasco, C M Niessen, A Sonnenberg
Journal: Journal of Clinical Investigation (1995)

Generalized atrophic benign epidermolysis bullosa (GABEB) is a form of nonlethal junctional epidermolysis bullosa characterized by universal alopecia and atrophy of the skin. We report a deficiency of the 180-kD bullous pemphigoid antigen in three patients with GABEB from unrelated families. We screened specimens of clinically normal skin from nine junctional epidermolysis bullosa patients (3 GABEB, 4 lethal, 1 cicatricial, 1 pretibial) by immunofluorescence using monoclonal antibodies to the 180-kD and 230-kD bullous pemphigoid antigens (BP180 and BP230). In the skin of the three GABEB patients there was no reactivity with antibodies to BP180, whereas staining for BP230 was normal. In the skin of the other six, non-GABEB patients, included in this study the expression of BP180 and BP230 was normal. Immunoblot analysis of cultured keratinocytes from one of the GABEB patients also failed to detect BP180 antigen, whereas BP230 was present in normal amounts. The deficient expression of BP180 is reflected in the RNA message, as in Northern blot analysis a reduced amount of BP180 transcripts, although of normal length, were detected. Interestingly, in another GABEB patient there were not-involved areas of skin, in which blistering could not be induced by rubbing. Biopsy material from these areas showed interrupted staining for BP180. There was no staining for BP180 in areas of clinically normal but involved skin of this patient. In conclusion, this study reveals that the BP180 antigen is deficient and the BP180 mRNA is reduced in generalized atrophic benign epidermolysis bullosa.
Intracoronary albunex. Its effects on left ventricular hemodynamics, function, and coronary sinus flow in humans.
Authors: F J Ten Cate, P Widimsky, J H Cornel, D J Waldstein, P W Serruys, A Waaler
Journal: Circulation (1993)

BACKGROUND Albunex is a recently developed ultrasonic contrast agent made from sonicated human serum albumin. The effects on left ventricular hemodynamics, function, and coronary sinus flow of intracoronary Albunex in humans have not been reported. METHODS AND RESULTS Eighteen patients with known or suspected coronary artery disease were examined at the time of coronary arteriography with simultaneous two-dimensional echocardiography and left ventricular catheter-tip manometry. Intracoronary injections of Albunex into the left main coronary artery were performed, as were injections of 5% human serum albumin and iohexol, a widely used angiographic contrast agent. Mean coronary sinus flow was determined before and after injections of iohexol and 2 mL of Albunex. Injection of 1 mL of Albunex induced no changes in any of the measured hemodynamic parameters (heart rate, peak left ventricular [LV] systolic pressure, LV end-diastolic pressure, positive or negative LV dP/dt, or time constant of relaxation) or echocardiographic determinants of LV function (regional wall motion and global ejection fraction). Injection of 2 mL or more of Albunex caused small, transient (less than 30 seconds) changes in measures of isovolumic relaxation (negative LV dP/dt; 95% confidence interval: mean, -2.41 [-4.3, -0.52] and tau 1; confidence interval mean, 3.52; [1.48, 5.58]) but not in functional measures. Intracoronary injection of 5% human serum albumin had no effect. Iohexol induced small but significant changes in both systolic and diastolic parameters, which lasted beyond 30 seconds after injection. Mean coronary sinus blood flow increased. CONCLUSIONS The effects of Albunex on hemodynamics, left ventricular function, and coronary sinus blood flow compare favorably with iohexol. Albunex can be considered to be an essentially inert contrast agent if used in patients with stable coronary artery disease.
Increased prevalence of apolipoprotein E4 in type V hyperlipoproteinemia.
Authors: G Ghiselli, E J Schaefer, L A Zech, R E Gregg, H B Brewer
Journal: Journal of Clinical Investigation (1982)

Type V hyperlipoproteinemia (HLP) is characterized clinically by hepatosplenomegaly, occasional eruptive xanthomas, and an increased incidence of pancreatitis. These patients have striking hypertriglyceridemia due to increased plasma chylomicron and very low density lipoprotein concentrations in the fasting state, without a deficiency of lipoprotein lipase or its activator protein, apolipoprotein (apo) C-II. ApoE, a protein constituent of triglyceride-rich lipoproteins, has been implicated in the receptor-mediated hepatic uptake of these particles. ApoE has three major alleles: E2, E3, and E4, and the products of these alleles are apoE2, apoE3, and apoE4, respectively. ApoE phenotypes were determined in 30 type V HLP patients as well as in 37 normal volunteers. Among the type V patients, 33.3% were noted to be homozygous, and 40.0% heterozygous for E4 (normal, 2.7 and 21.6%, respectively). These data suggest that apoE4 may play a role in the etiology of the hyperlipidemia in a significant number of type V HLP patients.
Metronidazole is used for antibiotic associated diarrhoea in pregnancy in UK
Authors: S. Pegler
Journal: BMJ (2002)

EDITOR —Barbut and Meynard quote US guidance when recommending vancomycin as first line treatment for antibiotic associated diarrhoea in pregnancy.1

In the United Kingdom guidance issued by the medicines information centres and the National Teratology Information Service recommends metronidazole rather than oral vancomycin after a careful risk assessment of each drug.

Vancomycin is poorly absorbed from normal, intact gastrointestinal mucosa, but an inflammatory bowel process can …
Large volume plastic spacers
Authors: C. O'Mahony
Journal: BMJ (1992)

draw attention to the problems of confounding, especially residual confounding, in epidemiological studies.'This is poorly under- stood and has led to many serious misunder- standings.It should always be considered as an explanation of any epidemiological association, but in some cases observational studies cannot resolve the issue, and one should not conclude that possibly confounded exposures should be ignored.When this impasse is reached it may be more appropriate to consider intervention studies.The example of smoking and cervical cancer is a case in point.Early observations of this association were played down because of possible confounding with sexual behaviour.The relation was not, however, weakened when attempts were made to adjust more carefully for this--a procedure that often indicates residual confounding-and now dozens of carefully designed studies have found a strong relation.Clearly, randomising young women to smoke or not would be both ridiculous and unethical.We are attempting to study the effects of stopping smoking on untreated but carefully monitored mild cervical disease, with reference to both clinical and immunological vari- ables.Studies of this kind may prove useful in resolving the problems of counfounding.
The Use of Nonphysician Providers in Adult Intensive Care Units
Authors: Hayley B. Gershengorn, Mary P. Johnson, Phillip Factor
Journal: American Journal of Respiratory and Critical Care Medicine (2011)

In the United States there are not currently enough critical care-trained practitioners to provide care to all critically ill patients. With calls for "high-intensity" staffing and 24-hour coverage of our intensive care units, the board-certified intensivists we do have are being stretched ever more thin. Nonphysician providers (physician assistants and nurse practitioners) are being used with increasing frequency in critical care settings to provide care to critically ill patients. In this review, we explore the impact of introducing nonphysician providers into the adult intensive care unit.