tbuckley/cabot-search huggingface dataset:
Emergence of Antibiotic-Resistant Bacteria
Authors: Maxwell Finland
Journal: New England Journal of Medicine (1955)

Biologic and Biochemical Properties of Antibiotic-Resistant StrainsComparisons of Sensitive and Resistant Strains of the Same SpeciesAlthough the mechanisms involved in the development of antibiotic resistance will not be considered in detail, some studies designed to elucidate the problem and some illustrations of differences between sensitive and resistant strains may be mentioned. Bellamy and Klimek473 noted that a penicillin-resistant variant of Staph. aureus grew more slowly than its sensitive parent culture and also lost its ability to grow anaerobically. They could not increase significantly the resistance of strains of Str. faecalis, Str. mastitidis or Clostridium welchii by similar methods. . . .
Rate and directionality of mutations and effects of allele size constraints at anonymous, gene-associated, and disease-causing trinucleotide loci
Authors: R. Deka, S. Guangyun, D. Smelser, Y. Zhong, M. Kimmel, R. Chakraborty
Journal: Molecular Biology and Evolution (1999)

We studied the patterns of within- and between-population variation at 29 trinucleotide loci in a random sample of 200 healthy individuals from four diverse populations: Germans, Nigerians, Chinese, and New Guinea highlanders. The loci were grouped as disease-causing (seven loci with CAG repeats), gene-associated (seven loci with CAG/CCG repeats and eight loci with AAT repeats), or anonymous (seven loci with AAT repeats). We used heterozygosity and variance of allele size (expressed in units of repeat counts) as measures of within-population variability and GST (based on heterozygosity as well as on allele size variance) as the measure of genetic differentiation between populations. Our observations are: (1) locus type is the major significant factor for differences in within-population genetic variability; (2) the disease-causing CAG repeats (in the nondisease range of repeat counts) have the highest within-population variation, followed by the AAT-repeat anonymous loci, the AAT-repeat gene-associated loci, and the CAG/CTG-repeat gene-associated loci; (3) an imbalance index beta, the ratio of the estimates of the product of effective population size and mutation rate based on allele size variance and heterozygosity, is the largest for disease-causing loci, followed by AAT- and CAG/CCG-repeat gene-associated loci and AAT-repeat anonymous loci; (4) mean allele size correlates positively with allele size variance for AAT- and CAG/CCG-repeat gene-associated loci and negatively for anonymous loci; and (5) GST is highest for the disease-causing loci. These observations are explained by specific differences of rates and patterns of mutations in these four groups of trinucleotide loci, taking into consideration the effects of the past demographic history of the modern human population.
Medical experts and the criminal courts
Authors: C. M Milroy
Journal: BMJ (2003)

The quashing of Sally Clark's conviction for the murder of her sons Christopher and Harry has inevitably been followed by questions about the role of the medical experts, in view of their failure to disclose key evidence and the role such evidence played in securing her conviction.1 The debate has been played out across the media, not least in the pages of the BMJ and on its website. 2 3

Medical experts are called on daily to deliver their opinions in both civil and criminal cases. Critics have focused their attention mostly on criminal trials. The initial involvement of an expert may be through professional duties, as in the case of the forensic pathologist who performs an autopsy and then finds that evidence from the autopsy report is being used by the prosecuting authorities in a criminal trial. Other experts may be called on by the police or by the Crown Prosecution Service.

In the adversarial systems of law in the United Kingdom the defence is also entitled to seek appropriate experts. Expert witnesses are in a very privileged …
Percutaneous-Endoscopic Biliary Stent Placement
Authors: TAT-KlN TSANG
Journal: Annals of Internal Medicine (1987)

The placement of large-bore endoprostheses for relief of biliary obstruction by the percutaneous-transhepatic route is painful, requires a large hepatic parenchymal tract, and has a fairly high complication rate. The alternative technique of endoscopically placing similar-sized stents requires special instruments and skills, and may fail in passing very tight stenoses. We report a simpler combined percutaneous-endoscopic biliary stent (PEBS) placement technique with a high placement rate used in 11 patients with advanced malignant obstruction. In all 11 patients, 10 and 11.5 French stents were easily placed. Three patients developed sepsis but responded to antibiotics. One clogged stent required replacement. Two stents needed later endoscopic adjustment. Results of liver function test improved in 10 patients, and 8 patients showed improved quality of life.
Medical Education in Israel
Authors: M. J. Tarsh
Journal: BMJ (1958)

Who are you ?" " I'm a medical student from London." "Oh, yes; and what do you want in this department ?" " I'd like to see what you're doing here, and to find out about your teaching methods in particular."" I'll take you to meet-the professor, then; I'm sure he won't be too busy to see you."Usually the professor was very busy, but he always found time to see me.He was often able to show me round himself, and the.mention of the magic words " medical education " would usually evoke a, confession that this was one of his special interests.I asked if he could tell me what his department was teaching now, and, more important, what it hoped to teach next year ?Our conversation would frequently end with the question, " When are you coming out from England to help us ?
At the tipping point for epigenetic therapies in cancer
Authors: Peter A. Jones
Journal: Journal of Clinical Investigation (2014)

The field of epigenetics has exploded in the last two decades, with incredible advances in recent years driven by high-throughput sequencing studies. Cancer cells frequently exhibit marked changes in DNA methylation and histone modification during tumorigenesis and tumor progression. These changes in the cancer epigenome are thought to be important in initiating and maintaining malignancy, and pharmaceutical approaches targeting epigenome-modifying enzymes are an attractive therapeutic strategy. Early successes have been made with DNA-demethylating drugs in hematologic malignancies, and efforts are underway to target additional epigenetic regulators and a broader array of tumor types. The Reviews in this issue of the JCI highlight ongoing efforts in this burgeoning field to translate our understanding of the cancer epigenome into successful interventional strategies in the clinic.
Caffeine: A Model Compound for Measuring Liver Function
Authors: Eberhard Renner, Hubertus Wietholtz, Philipp Huguenin, Maurice J. Arnaud, Rudolf Preisig
Journal: Hepatology (1984)

The effects of liver disease on caffeine plasma clearance (Cl) and on exhalation of 14CO2 following i.v. injection of 2 mu Ci of [3-methyl-14C]caffeine together with 125 mg of the unlabeled compound were measured in 15 patients with cirrhosis, 11 subjects with miscellaneous liver disease, and 10 normal volunteers. Compared to mean values for Cl (2.02 +/- S.D. 0.68 ml per min per kg) and t1/2 (3.8 +/- 0.9 hr) in normal volunteers, cirrhotics were characterized by highly significant reductions in Cl (to 0.76 +/- 0.40) and prolongation in t1/2 (to 13.7 +/- 13.0), whereas the volume of distribution (VD) remained relatively unchanged (0.57 +/- 0.16 vs. 0.64 +/- 0.13 liter per kg in normals). Cumulative 14CO2 production and specific activity of 14CO2 in breath decreased in parallel (r = 0.83) with Cl. Patients with miscellaneous liver disease exhibited only small changes in Cl and t1/2; however, 14CO2 parameters in breath appeared more sensitive in indicating the slight functional derangement. In view of the correlation (Rs = 0.83) of cumulative 14CO2 excretion with the initial disappearance constant for bromosulfophthalein, the caffeine breath test may be considered as a quantitative measure of hepatic microsomal activity; based on a surprisingly close, hyperbolic relationship between Cl and fasting caffeine plasma concentrations, the latter might serve as a simple guide to severity of liver disease.
Pyridoxine (B_6) Dependency Syndromes
Authors: GEORGE W. FRIMPTER
Journal: Annals of Internal Medicine (1968)

Editorial Notes1 May 1968Pyridoxine (B6) Dependency SyndromesGEORGE W. FRIMPTER, M.D., F.A.C.P.GEORGE W. FRIMPTER, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-68-5-1131 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptA recent paper by Tada and associates (1) notes the remarkable effect of vitamin B6 in xanthurenic aciduria. Two mentally retarded siblings, children of first cousins, manifested excessive urinary excretion of xanthurenic acid, kynurenic acid, 3-hydroxykynurenine, and kynurenine after tryptophan loading. Laboratory study results, including normal serum B6 concentrations, gave no evidence of B6deficiency. Although the usual vitamin B6 requirement in childhood is 0.5 to 1.5 mg/day, Tada and colleagues found that much higher doses reduced the xanthurenic acid excretion to normal.These studies were extended to an in vitro investigation of kynureninase in liver from one of the...References1. TADAYOKOYAMANAKAGAWAYOSHIDAARAKAWA KYHTT: Vitamin B6 dependent xanthurenic acidura. Tohoku J. Exp. Med. 93: 115, 1967. CrossrefMedlineGoogle Scholar2. FRIMPTER GW: Cystathioninuria: nature of the defect. Science 149: 1095, 1965. CrossrefMedlineGoogle Scholar3. HUNTSTOKESMCCRORYSTROUD ADJWWHH: Pyridoxal dependency: report of a case of intractable convulsions in an infant controlled by pyridoxine. Pediatrics 13: 140, 1965. Google Scholar4. HORRIGANHARRIS PDJW: Pyridoxine-responsive anemia: analysis of sixty-one cases. Advances Intern. Med. 12: 103, 1964. MedlineGoogle Scholar5. REDLEAF PD: Pyridoxine-responsive anemia in a patient receiving isoniazid. Dis. Chest 42: 222, 1962. CrossrefMedlineGoogle Scholar6. HARRIS HW: Current concepts of the metabolism of antituberculous agents. Ann. N. Y. Acad. Sci. 106: 43, 1963. CrossrefMedlineGoogle Scholar7. BONNERSUYAMADEMOSS DMYJA: Genetic fine structure and enzyme formation. Fed. Proc. 19: 926, 1960. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Department of Medicine New York Hospital— Cornell Medical Center New York, N. Y. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byObservations on the nutrient intakes of eating-dependent nursing home residents: underutilization of micronutrient supplements.Methylmalonic Aciduria—A Newly Discovered Inborn ErrorLEWIS A. BARNESS, M.D., GRANT MORROW III, M.D. 1 May 1968Volume 68, Issue 5Page: 1131-1132KeywordsAttentionChildrenExcretionLiverPyridoxineResearch laboratoriesTryptophan Issue Published: 1 May 1968 PDF downloadLoading ...
Renal Transplant-Associated Malaria
Authors: Gertrude S. Lefavour
Journal: JAMA (1980)

COMPLICATIONS by the protozoan infections toxoplasmosis<sup>1</sup>and pneumocystis<sup>2</sup>have been described in recipients of renal transplants. We report here a case of kidney transplantation complicated by malaria. <h3>Report of a Case</h3> A 27-year-old woman from Ghana had lived in New York for the previous six years except for a visit to Ghana in 1973. At that time, her husband had been hospitalized for a bout of malaria, but she had had no clinical illness. In 1972, toxemia developed during her only pregnancy; after three years of hypertension and renal insufficiency, a program of longterm hemodialysis was started in February 1977. On Jan 26, 1978, the patient received a renal transplant from her 43-year-old mother, who had come from Ghana one month previously for evaluation and subsequent donor nephrectomy. At the time of transplant, blood in the donor kidney was flushed out with a solution of lactated Ringer's with albumin
Effect of isotretinoin therapy on natural killer cell activity in patients with xeroderma pigmentosum
Authors: None Anolik, None Di Giovanna, None Gaspari
Journal: British Journal of Dermatology (1998)

Xeroderma pigmentosum (XP) is a rare autosomal recessive disorder characterized by sun sensitivity, defective DNA repair, markedly increased susceptibility to skin cancer, and a variety of immunological defects, including defective natural killer (NK) cell activity. Retinoid therapy has been demonstrated to protect effectively against the development of skin cancers in patients with XP, although its mechanism of action is unknown. We describe a series of eight XP patients, six of whom were given oral isotretinoin. The NK cell activity was not affected by low‐dose isotretinoin, i.e. 0.5 mg/kg per day. However, higher doses of isotretinoin, e.g. 1.0 mg/kg per day, produced a significant decrease in NK cell function, at the same time as producing a reduction in the frequency of development of skin cancers. Retinoid therapy may have a skin cancer preventing effect by enhancing other immune effector mechanisms or via epithelial cell differentiation.
Haematological changes due to triathlon competition.
Authors: R J Davidson, J D Robertson, R J Maughan
Journal: British Journal of Sports Medicine (1986)

A twelve parameter blood cell profile has been measured in 6 subjects before and after each phase of triathlon event. This involved 29 miles cycling, 12 miles running and finally 18.5 miles canoeing. There was a significant decrease in plasma volume (8.7% +/- 3.1%, p less than 0.001) following the first phase (cycling); this decrease was sustained to the end of the event. A substantial increase in the number of circulating leukocytes after cycling (84 +/- 58%) and running (255 +/- 83% of pre-event value) was observed. There was no further leucocyte increment after the canoeing stage which may indicate that the circulating concentration of these cells was maximal after running. Fluid shifts following the postural alteration accompanying the different types of exercise and subject variability may have masked any subtle changes in the red cell parameters.
Abstract PD3-5: Survival benefit conferred by the androgen receptor is lost in aromatase inhibitor treated breast cancer
Authors: A Ali, F Bane, Y Hao, D McCartan, P O'Gaora, ADK Hill, LS Young, M McIlroy
Journal: Cancer Research (2013)

Abstract Aromatase Inhibitors have proven to be most effective in the treatment of post-menopausal breast cancer. Their mode of action is to inhibit the synthesis of estrogen (estrone) by the aromatase enzyme Cyp 19 thereby blocking ligand-dependent activation of the estrogen receptor. What has not been addressed to date is how cells that are deprived of estrogen, may potentially, adapt to the more androgenic environment resulting from long-term treatment with AI therapy. Research from our lab has identified the homeobox protein, HOXC11, to be an indicator of poor response to endocrine therapy and development of metastasis. To further our understanding of HOXC11 and its role in the development of endocrine-resistance and metastatic spread we undertook an RNA-seq experiment to identify its target genes in resistant breast cancer. This analysis identified PSAP, IFIT1 and HSP90AA1. Both PSAP (an androgen agonist) and HSP90AA1 (AR chaperone) are closely associated with AR which led to further investigation into the role of HOXC11 in the development of steroidal adaptability in Letrozole-resistant breast cancer. We hypothesize that HOXC11 regulated expression of PSAP results in oncogenic activation of AR in an AI resistant setting. Our findings have shown that AI-resistant cell lines in vitro have significantly elevated levels of AR and that loss of HOXC11 results in concommitant decrease in AR mRNA. In AI resistance expression of HOXC11 results in upregulation/stabilization of AR by PSAP thus enabling the tumour to adapt to use androgenic steroids for cell proliferation. The anti-androgen, Bicalutamide, reduces cell proliferation and cell motility in AI resistant cell lines. Survival analysis of AR in a TMA (n = 488) indicates that AR confers a survival benefit in the tamoxifen treated population. This protective effect is diminished in patients receiving AI therapy and is reflected in the altered Hazard Ratio of AR from the total population (HR: 0.485) to the AI treated cohort (HR: 1.197). Secreted PSAP was readily detectable in breast cancer patient serum and associates significantly with expression of HOXC11 in matched patient tissue (∼20). PSAP is associated with poor response to endocrine therapy and metastatic spread of prostate cancer and as it is secreted it could potentially be used to monitor patients on AI who might benefit from dual targeted therapy treatment. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr PD3-5.
<i>FCGR2A</i> Polymorphism Is Correlated With Clinical Outcome After Immunotherapy of Neuroblastoma With Anti-GD2 Antibody and Granulocyte Macrophage Colony-Stimulating Factor
Authors: Nai-Kong V. Cheung, Rebecca Sowers, Andrew J. Vickers, Irene Y. Cheung, Brian H. Kushner, Richard Gorlick
Journal: Journal of Clinical Oncology (2006)

Anti-GD2 murine IgG3 antibody 3F8 kills neuroblastoma cells by antibody-dependent cell-mediated cytotoxicity (ADCC). Granulocyte macrophage colony-stimulating factor (GM-CSF) enhances phagocyte-mediated ADCC. The differential affinity of the human FCGR polymorphic alleles for 3F8 may influence the effectiveness of antibody immunotherapy.The entire cohort of high risk neuroblastoma patients (N = 136) treated on protocol using 3F8 and GM-CSF were the subjects of this analysis. Tumor response was measured by standard clinical tools plus sensitive molecular monitoring using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Polymorphic alleles of FCGR2A and FCGR3A were determined by PCR plus direct sequencing using genomic DNA samples obtained from marrow or blood of patients.FCGR2A (R/R) genotype correlated with progression-free survival for the entire cohort (P = .049) and for the subset of patients with no history of prior relapse (P = .023). FCGR2A (R/R) also correlated with marrow remission 2.5 months after treatment initiation: by histology (P = .021 and P = .036, for the entire cohort and the subset, respectively) and by qRT-PCR (P = .052 and P = .033, respectively).The favorable outcome associated with FCGR2A (R/R) genotype is consistent with the proposed role of FCGR2A and phagocyte-mediated ADCC in 3F8 plus GM-CSF immunotherapy.
Serologic Response of Children to Inactivated Measles Vaccine
Authors: C. H. Carter
Journal: JAMA (1962)

Over 5,000 children have been vaccinated with killed measles antigens prepared in monkey kidney-tissue culture and containing alum. Local or systemic reactions were minimal and similar to those seen with Salk poliovaccine. Measles-neutralizing antibody titers were determined in 473 individuals before and after vaccination. Three 0.5-ml. doses of vaccine given at varying intervals stimulated antibody to levels comparable to those obtained with attenuated (Enders) measles vaccines but lower than those observed following natural infection. Efficacy of conversion was related to antigen content of a particular vaccine as measured by a guinea pig potency assay. Between 90% and 100% of children responded to killed measles vaccines of readily available potency. Such children were resistant to natural or attenuated measles challenge.
Elevated Sputum Interleukin-5 and Submucosal Eosinophilia in Obese Individuals with Severe Asthma
Authors: Dhananjay Desai, Christopher Newby, Fiona A. Symon, Pranabashis Haldar, Sachil Shah, Sumit Gupta, Mona Bafadhel, Amisha Singapuri, Salman Siddiqui, Joanne Woods, Athula Herath, Ian K. Anderson, Peter Bradding, Ruth Green, Nita Kulkarni, Ian Pavord, Richard P. Marshall, Ana R. Sousa, Richard D. May, Andrew J. Wardlaw, Chris E. Brightling
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

The relationship between airway inflammation and obesity in severe asthma is poorly understood.We sought to determine the relationship between sputum mediator profiles and the distribution of eosinophilic inflammation and obesity in people with severe asthma.Clinical parameters and eight mediators in sputum were assessed in 131 subjects with severe asthma from a single center categorized into lean, overweight, and obese groups defined by their body mass index. In an independent group of people with severe asthma (n = 45) and healthy control subjects (n = 19) eosinophilic inflammation was enumerated in bronchial submucosa, blood, and sputum and related to their body mass index.Sputum IL-5 geometric mean (95% confidence interval) (pg/ml) was elevated in the obese (1.8 [1.2-2.6]) compared with overweight (1.1 [0.8-1.3]; P = 0.025) and lean (0.9 [0.6-1.2]; P = 0.018) subjects with asthma and was correlated with body mass index (r = 0.29; P < 0.001). There was no relationship among body mass index, the sputum cell count, or other sputum mediators. In the bronchoscopy group the submucosal eosinophil number in the subjects with asthma was correlated with body mass index (Spearman rank correlation, rs = 0.38; P = 0.013) and the median (interquartile range) number of submucosal eosinophils was increased in obese (19.4 [11.8-31.2]) (cells per square millimeter) versus lean subjects (8.2 [5.4-14.6]) (P = 0.006). There was no significant association between sputum or peripheral blood eosinophil counts and body mass index.Sputum IL-5 and submucosal eosinophils, but not sputum eosinophils, are elevated in obese people with severe asthma. Whether specific antieosinophilic therapy is beneficial, or improved diet and lifestyle in obese asthma has antiinflammatory effects beyond weight reduction, requires further study.
1059-13 Detection and propagation of calcified nanostructures from human aneurysms
Authors: John C Lieske, Vivek Kumar, Gerard Farell-Baril, Shihui Yu, Jon E Charlesworth, Ewa Rzewuska-Lech, Peter LaBreche, Sandra R Severson, Virginia M Miller
Journal: Journal of the American College of Cardiology (2004)
Limitations of Lactated Ringer's Solution in Massive Fluid Replacement
Authors: Phillip O. Bridenbaugh
Journal: JAMA (1968)

Extracellular fluid volume was maintained by administration of 14 liters whole blood, 28 liters lactated Ringer's solution, and 2 liters of dextran 70 in a patient suffering severe hemorrhage (25 liters) during a 4 1/2-hour decompressive cervical laminectomy. Lactated Ringer's solution proved advantageous as a supplement to the whole blood because of its ready availability, modest cost and freedom from hepatitis virus. However, determinations of the hematocrit value and total serum protein level demonstrated the limitation of lactated Ringer's solution in supplying colloid for total volume replacement.