tbuckley/cabot-search huggingface dataset:
Ectopic production of methionine enkephalin and beta-endorphin.
Authors: P T Pullan, V Clement-Jones, R Corder, P J Lowry, G M Rees, L H Rees, G M Besser, M M Macedo, A Galvao-Teles
Journal: BMJ (1980)

Immunoreactive methionine enkephalin and beta-endorphin were sought by serial dilution of tissue extracts and assay of chromatographic fractions in non-endocrine tumour tissue from three patients with the ectopic adrenocorticotrophin syndrome associated with carcinoid tumours and in normal lung tissue and thymic tissue from a patient with myasthenia gravis. In all cases serial dilution of extracts showed parellelism to standard radioimmunoassay curves. The two peptides were found in high concentration in the three tumours but were undetectable in the control tissues. In a single case tested the methionine enkephalin concentration in a vein draining the tumour was twice that in a peripheral vein. In view of their profound effect on behaviour in animals and potent analgesic activity in animals and man the ectopic secretion of methionine enkephalin and beta-endorphin may modify the clinical features of a wide variety of tumours and produce some of the diverse clinical syndromes associated with malignancy.
How the DWP sees GPs
Authors: C. Collins
Journal: BMJ (2011)

McCartney’s investigation into the role of Atos in providing medical reports to the Department for Work and Pensions (DWP) draws attention to the disregard shown to the advice of claimants’ GPs in deciding benefit eligibility.1 This raises issues for the medical profession.

A DWP submission to an appeal tribunal in Scotland in early 2009 said: “Commissioners have stated …
Bone Scan Abnormalities in a Child with Lyme Disease
Authors: JAAK J. E. M. DE NEF, MARY VAN DER VIS-MELSEN
Journal: Clinical Nuclear Medicine (1990)

*From the Departments of Pediatrics and Nuclear Medicine,† Spaarne Ziekenhuis, Haarlem, the Netherlands Received for publication July 26, 1989; revision accepted September 25, 1989. Reprint requests: J. J. E. M. De Nef, Spaarne Ziekenhuis, 2003 BR Haarlem, the Netherlands.
Tuning-fork tests in diagnosis of serous otitis media.
Authors: M W Yung, T M Morris
Journal: BMJ (1981)

complexes and low C3 concentrations have been shown in the past,'3 but only one other patient has been treated by plasma exchange.This patient also responded.4These reports suggest that in some patients with autoerythrocyte sensitisation there may be a specific immunological abnormality, but its exact nature and that of the myriad of psychological symptoms remain unexplained.Gardner FH, Diamond LK.Autoerythrocyte sensitisation.A form of purpura producing painful bruises following autosensitisation to red blood cells in certain women.
Spontaneous complete regression of a rectal cancer
Authors: S. Sakamoto, K. Fu, O. Kobayashi, S. Matsuyama, A. Miyazaki, K. Ogura, S. Watanabe
Journal: Endoscopy (2009)

Colon carcinogenesis is a multistep process involving initiation, growth, and finally malignant transformation. Most colorectal cancers (CRC) arise through malignant transformation of benign adenomas in a process known as the adenoma-to-carcinoma sequence. Development and growth of CRC have been analyzed retrospectively from sporadic cases including radiographic or endoscopic images of lesions overlooked at initial examinations [1] [2] [3]. Here we describe a unique case of a sessile polyp which showed marked morphological change into a depressed lesion, and, unexpectedly, spontaneous complete regression of biopsy-proven rectal cancer was observed in an extremely short period of 3 months.
Molecular detection of dermatophytes and nondermatophytes in onychomycosis by nested polymerase chain reaction based on 28S ribosomal RNA gene sequences
Authors: M. Ebihara, K. Makimura, K. Sato, S. Abe, R. Tsuboi
Journal: British Journal of Dermatology (2009)

Onychomycosis is often caused by dermatophytes, but the role of nondermatophytes is underestimated due to the difficulty of identifying them by conventional direct microscopy and culture.This study aims to detect nondermatophytes, as well as dermatophytes, in the nail samples of patients with onychomycosis using a polymerase chain reaction (PCR)-based culture-independent method.The nested PCR assay targeting the sequence of the 28S ribosomal RNA gene was used to amplify fungal DNAs from 50 microscopy-positive nail specimens. Newly designed primer sets for dermatophyte universal, Trichophyton rubrum, T. mentagrophytes, Aspergillus spp., Scopulariopsis brevicaulis, Fusarium solani, F. oxysporum, F. verticillioides, Candida albicans and C. tropicalis were used after confirmation of their specificity.Forty-seven cases (94%) were positive for fungal DNA, among which dermatophytes were detected in 39 cases (83.0%): T. rubrum in 35 cases (74.5%) and T. mentagrophytes in eight cases (17.0%). Surprisingly, nondermatophytes were detected in 18 cases (38.3%), both dermatophytes and nondermatophytes in 10 cases (21.3%) and nondermatophytes alone in eight cases (17.0%). Aspergillus spp. alone was observed in five cases (10.6%).This study indicates that most of the affected nail plates of patients with onychomycosis were positive for specific fungal DNAs, and suggests that nondermatophytes detected at high rates may be involved in the pathogenesis of onychomycosis.
Inappropriate Drug Prescribing for the Community-Dwelling Elderly
Authors: Sharon M. Willcox
Journal: JAMA (1994)

<h3>Objective.</h3> —To examine the amount of inappropriate drug prescribing for Americans aged 65 years or older living in the community. <h3>Design.</h3> —Cross-sectional survey of a national probability sample of older adults. <h3>Setting.</h3> —The 1987 National Medical Expenditure Survey, a national probability sample of the US civilian noninstitutionalized population, with oversampling of some population groups, including the elderly. <h3>Subjects.</h3> —The 6171 people aged 65 years or older in the National Medical Expenditure Survey sample, using appropriate weighting procedures to produce national estimates. <h3>Main Outcome Measures.</h3> —Incidence of prescribing 20 potentially inappropriate drugs, using explicit criteria previously developed by 13 United States and Canadian geriatrics experts through a modified Delphi consensus technique. Three cardiovascular drugs identified as potentially inappropriate were analyzed separately since they may be considered appropriate for some noninstitutionalized elderly patients. <h3>Results.</h3> —A total of 23.5% (95% confidence interval [CI], 22.4% to 24.6%) of people aged 65 years or older living in the community, or 6.64 million Americans (95% CI, 6.28 million to 7.00 million), received at least one of the 20 contraindicated drugs. While 79.6% (95% CI, 77.2% to 82.0%) of people receiving potentially inappropriate medications received only one such drug, 20.4% received two or more. The most commonly prescribed of these drugs were dipyridamole, propoxyphene, amitriptyline, chlorpropamide, diazepam, indomethacin, and chlordiazepoxide, each used by at least half a million people aged 65 years or older. Including the three controversial cardiovascular agents (propranolol, methyldopa, and reserpine) in the list of contraindicated drugs increased the incidence of probably inappropriate medication use to 32% (95% CI, 30.7% to 33.3%), or 9.04 million people (95% CI, 8.64 million to 9.44 million). <h3>Conclusion.</h3> —Physicians prescribe potentially inappropriate medications for nearly a quarter of all older people living in the community, placing them at risk of drug adverse effects such as cognitive impairment and sedation. Although most previous strategies for improving drug prescribing for the elderly have focused on nursing homes, broader educational and regulatory initiatives are needed. (<i>JAMA</i>. 1994;272:292-296)
Mandatory Monitoring for Side Effects
Authors: C Salzman
Journal: New England Journal of Medicine (1990)

Clozapine is a new neuroleptic drug that was released for clinical use in the United States in February 1990 under the trade name Clozaril. Its availability is limited by an expensive mandatory system for distributing the drug and monitoring side effects — a marketing practice known as "bundling." The cost of the clozapine "bundle" is $172 a week, or approximately $9,000 a year, making it one of the most expensive therapeutic drugs in the United States. The unusually high cost of the drug plus the monitoring system may make it difficult, if not impossible, for many patients with schizophrenia to . . .
Government abandons plans to use payments to prevent private providers selecting simplest cases
Authors: N. Hawkes
Journal: BMJ (2012)

The Department of Health for England has dropped plans to use the NHS Payment by Results tariff to prevent “cherry picking” of patients by private sector providers.

Last November the department promised to use the price mechanism, under which hospitals are paid for the particular services they provide, to ensure that lower prices were paid to providers who tackled only the simpler cases. The undertaking was a response to fears expressed during the passage of the Health and Social Care Act that private providers would skim off the most profitable patients, leaving NHS hospitals with more difficult cases whose costs would not be fully covered by the tariff.1

David Flory, NHS deputy chief executive, told the Health Service Journal at the time: “This isn’t about poking the independent sector providers in the eye, it’s about being really clear about transparency and fairness.” But on 20 September the Financial Times disclosed that Flory wrote to NHS managers saying that the health department no longer planned to tackle the issue through changes to the tariff.

A department spokesman told the BMJ , “We are committed …
The Milroy Lectures on Quarantine: Delivered before the Royal College of Physicians of London, March, 1897
Authors: W. Collingridge
Journal: BMJ (1897)

Je 7E1 pain, by sedatives is practically all that can be done, except in those rare cases where the disease is limited to the gall bladder, when cholecystectomy may be performed.TuMouRs OF BILE DUCTS.
Data protection gone too far: questionnaire survey of patients' and visitors' views about having their names displayed in hospital
Authors: Ravindra Gudena, Stanley Luwemba, Amy Williams, Lloyd R Jenkinson
Journal: BMJ (2004)

In the past few months, patients' identification name boards have been intentionally removed from hospital wards. The name board is a plan of the ward with the name, location, and consultant in charge of each patient clearly displayed in front of the central nursing station. This ensures that all members of staff can quickly and correctly locate patients. Patients are also identified by a name card above their beds that shows their name and their consultant. Managers feel that these do not comply with the Data Protection Act 1998 and are removing them.1 2

Since these changes have been made, we have misplaced patients as no one was aware that they were still in hospital. We felt this was …
Thymic stromal lymphopoietin as a key initiator of allergic airway inflammation in mice
Authors: Baohua Zhou, Michael R Comeau, Thibaut De Smedt, H Denny Liggitt, Martin E Dahl, David B Lewis, Dora Gyarmati, Theingi Aye, Daniel J Campbell, Steven F Ziegler
Journal: Nature Immunology (2005)
Use of an omental pedicle graft to repair a large oesophageal defect.
Authors: D K Kaplan, J Andrew, C Thorpe
Journal: Thorax (1988)

Traitement d'une fistule œsophagopleurale postoperatoire chez un homme de 40 ans qui avait subi une pneumonectomie pour abces occupant entierement le lobe superieur gauche
Process of Developing a New Antimicrobial Drug
Authors: GEORGE ARCIERI
Journal: Annals of Internal Medicine (1978)

The network for development of a new antimicrobial drug, from discovery of the compound to submission of the New Drug Application, is reviewed. The key problems encountered during this process, as elucidated through a survey of 62 American pharmaceutical companies, include difficulties in discovering new and significant antimicrobial drugs, the unpredictability of in-vitro and animal studies, lack of specific criteria for the bacteriologic response to therapy, difficulties in setting up well-controlled clinical studies, and difficulty with the timely enrollment of suitable patients with precise microbiologic diagnosis before treatment.
Which Way Voluntary Health Insurance?
Authors: Franz Goldmann
Journal: New England Journal of Medicine (1965)

MEASURED by the total number of insured people and the total amount of benefits paid out during a given year, voluntary health insurance has made excellent progress in the last thirty years. At the end of 1963 about 145,000,000 Americans, more than 3 out of 4, had "hospital expense coverage," about 135,000,000 "surgical expense coverage," about 102,000,000 "regular medical expense coverage," and about 42,000,000 "major medical expense coverage." Comparative data for 1953 and 1943 are given in Table 1.Benefit payments, excluding those designed for income maintenance during disability ("loss-of-income benefits"), totaled about $6,900,000,000 in 1963, as compared with $1,900,000,000 in . . .
US sees sharp rise in number of store based medical clinics
Authors: B. Roehr
Journal: BMJ (2012)

More and more people in the United States are flocking to retail medical clinics that aim to emulate fast food restaurants in offering convenience and low prices for a limited menu of the most common medical services.

The clinics are most often set up inside large retail stores such as Walmart or in pharmacies, though some are stand alone operations. Nurses often provide all the services, while some have a supervising doctor who is available for telephone consultations.

The clinics offer treatment for common problems such as sinus and ear infections or small wounds, administer vaccinations, and draw blood for laboratory tests. They refer patients to doctors’ clinics and hospital emergency departments as necessary.

There were about 150 such clinics in …
Concurrent bacterial infection and prolonged mechanical ventilation in infants with respiratory syncytial virus lower respiratory tract disease
Authors: Martin C. J. Kneyber, Heleen Blussé van Oud-Alblas, Margreet van Vliet, Cuno S. P. M. Uiterwaal, Jan L. L. Kimpen, Adrianus J. van Vught
Journal: Intensive Care Medicine (2005)
A8.3 The role of CD11C + dendritic cells in inflammatory arthritis
Authors: A Puchner, B S Blüml, V Saferding, S Puchner, H Leiss, J S Smolen, K Redlich
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Backround</h3> Dendritic cells (DCs) play an important role in bridging the innate and the adaptive immune response by serving as antigen presenting cells and are therefore implicated in the initiation of chronic autoimmune diseases, including rheumatoid arthritis. Using the K/BxN serum transfer arthritis, a model of human rheumatoid arthritis, which depends only on the innate immune system, we investigated the innate role role of dendritic cells in inflammatory arthritis. <h3>Methods</h3> KBxN serum transfer arthritis was induced in CD11c-diphteria toxin receptor (DTR) transgenic mice, which express the human diphtheria-toxin receptor under the CD11c promoter. This allows for specific depletion of CD11c + cells by administration of diphtheria toxin (DT). DT or PBS was given on day -1, 3, 6 and 9 and the severity of arthritis was determined clinically and histologically. In addition, serum transfer arthritis was induced in wild type animals, which also received DT. <h3>Results</h3> We show that Cd11 + cells are present in the synovia of K/BxN arthritis. Efficient depletion of DCs from the spleen after injection of DT was confirmed by flow cytometry and histological analysis. Clinical scores of arthritis showed that CD11c-DTR transgenic mice that received DT had significantly reduced paw swelling and loss of grip strength compared to PBS treated animals. In contrast, wild type animals receiving DT showed identical clinical signs of arthritis as PBS treated animals, excluding unspecific effects of DT in mice. Histological analysis found that CD11c-DTR transgenic mice that received DT displayed decreased synovial inflammation, local bone destruction and reduced the number of osteoclasts. In addition the number of CD115 + CD11b + GR neg/low osteoclast precursors was significantly reduced in the peripheral blood of CD11c-DTR transgenic mice that had received DT, suggesting a role of CD11c+ cells for osteoclast precursor generation. <h3>Conclusion</h3> These data show that dendritic cells are involved in innate reactions leading to inflammatory arthritis and suggest that dendritic cells could be an important target for rheumatoid arthritis therapy.
Studies on Xenopus laevis intestine reveal biological pathways underlying vertebrate gut adaptation from embryo to adult
Authors: Rachel A Heimeier, Biswajit Das, Daniel R Buchholz, Maria Fiorentino, Yun-Bo Shi
Journal: Genome biology (2010)

To adapt to its changing dietary environment, the digestive tract is extensively remodeled from the embryo to the adult during vertebrate development. Xenopus laevis metamorphosis is an excellent model system for studying mammalian gastrointestinal development and is used to determine the genes and signaling programs essential for intestinal development and maturation. The metamorphosing intestine can be divided into four distinct developmental time points and these were analyzed with X. laevis microarrays. Due to the high level of conservation in developmental signaling programs and homology to mammalian genes, annotations and bioinformatics analysis were based on human orthologs. Clustering of the expression patterns revealed co-expressed genes involved in essential cell processes such as apoptosis and proliferation. The two largest clusters of genes have expression peaks and troughs at the climax of metamorphosis, respectively. Novel conserved gene ontology categories regulated during this period include transcriptional activity, signal transduction, and metabolic processes. Additionally, we identified larval/embryo- and adult-specific genes. Detailed analysis revealed 17 larval specific genes that may represent molecular markers for human colonic cancers, while many adult specific genes are associated with dietary enzymes. This global developmental expression study provides the first detailed molecular description of intestinal remodeling and maturation during postembryonic development, which should help improve our understanding of intestinal organogenesis and human diseases. This study significantly contributes towards our understanding of the dynamics of molecular regulation during development and tissue renewal, which is important for future basic and clinical research and for medicinal applications.
Progress in the search for neuronal mechanisms coupling type 2 diabetes to obesity
Authors: Michael W. Schwartz
Journal: Journal of Clinical Investigation (2001)

Obesity, insulin resistance, and type 2 diabetes are a tightly linked and increasingly common triad of metabolic disorders. A well-supported and widely accepted explanation for their association is that obesity-induced insulin resistance in tissues such as muscle, liver, and fat increases the demand for insulin, and that type 2 diabetes ensues when this heightened demand cannot be met by defective pancreatic β cells. Despite the undeniable importance of adipocytes in the regulation of insulin sensitivity (see refs. 1–3 for recent reviews and insights into this interaction), this understanding of the pathogenesis of type 2 diabetes may yet be incomplete. Growing evidence suggests that the CNS plays a key role in glucose homeostasis, via brain pathways that overlap with those controlling food intake and body weight. Advancing this notion a step further is the study by Obici et al., published in this issue of the JCI (4), implicating a specific hypothalamic neuronal pathway — the melanocortin pathway — in the control of insulin sensitivity in peripheral tissues. The recognition that neuronal melanocortin signaling also figures prominently in energy homeostasis, the process whereby energy intake is matched to energy expenditure over time, suggests an intimate coupling of neuronal mechanisms regulating body weight and glucose metabolism (Figure ​(Figure1).1). Disorders affecting key neuronal pathways can therefore be included among potential mechanisms linking obesity to type 2 diabetes (5).



Figure 1

CNS regulation of glucose metabolism. (a) Neuronal pathways including the melanocortin system potentiate insulin’s ability to inhibit hepatic glucose production and to increase glucose uptake into muscle and fat. Insulin and leptin, which circulate ...
Tissue metabolomics of hepatocellular carcinoma: Tumor energy metabolism and the role of transcriptomic classification
Authors: Diren Beyoğlu, Sandrine Imbeaud, Olivier Maurhofer, Paulette Bioulac-Sage, Jessica Zucman-Rossi, Jean-François Dufour, Jeffrey R. Idle
Journal: Hepatology (2013)

Hepatocellular carcinoma (HCC) is one of the commonest causes of death from cancer. A plethora of metabolomic investigations of HCC have yielded molecules in biofluids that are both up- and down-regulated but no real consensus has emerged regarding exploitable biomarkers for early detection of HCC. We report here a different approach, a combined transcriptomics and metabolomics study of energy metabolism in HCC. A panel of 31 pairs of HCC tumors and corresponding nontumor liver tissues from the same patients was investigated by gas chromatography-mass spectrometry (GCMS)-based metabolomics. HCC was characterized by ∼2-fold depletion of glucose, glycerol 3- and 2-phosphate, malate, alanine, myo-inositol, and linoleic acid. Data are consistent with a metabolic remodeling involving a 4-fold increase in glycolysis over mitochondrial oxidative phosphorylation. A second panel of 59 HCC that had been typed by transcriptomics and classified in G1 to G6 subgroups was also subjected to GCMS tissue metabolomics. No differences in glucose, lactate, alanine, glycerol 3-phosphate, malate, myo-inositol, or stearic acid tissue concentrations were found, suggesting that the Wnt/β-catenin pathway activated by CTNNB1 mutation in subgroups G5 and G6 did not exhibit specific metabolic remodeling. However, subgroup G1 had markedly reduced tissue concentrations of 1-stearoylglycerol, 1-palmitoylglycerol, and palmitic acid, suggesting that the high serum α-fetoprotein phenotype of G1, associated with the known overexpression of lipid catabolic enzymes, could be detected through metabolomics as increased lipid catabolism.Tissue metabolomics yielded precise biochemical information regarding HCC tumor metabolic remodeling from mitochondrial oxidation to aerobic glycolysis and the impact of molecular subtypes on this process.
Impaired mitochondrial beta-oxidation in a patient with an abnormality of the respiratory chain. Studies in skeletal muscle mitochondria.
Authors: N J Watmough, L A Bindoff, M A Birch-Machin, S Jackson, K Bartlett, C I Ragan, J Poulton, R M Gardiner, H S Sherratt, D M Turnbull
Journal: Journal of Clinical Investigation (1990)

Defects of complex I of the mitochondrial respiratory chain are important causes of neurological disease. We report studies that demonstrate a severe deficiency of complex I activity with less severe abnormalities of complexes III and IV (less than 5, 63, and 30% of control values, respectively) in a skeletal muscle mitochondrial fraction from a 22-yr-old female with weakness, lactic acidemia, and the deposition of intramuscular neutral lipid. The observation that lipid accumulates in this and other patients with complex I deficiency suggests impaired mitochondrial fatty acid oxidation. To investigate this mechanism we have shown impaired flux through beta-oxidation [( U-14C]hexadecanoate oxidation was 66% of control rate) and accumulation of specific acyl-CoA ester intermediates. The changes in fatty acid metabolism in complex I deficiency are secondary to the reduced state within the mitochondrial matrix with low NAD+/NADH ratios.