tbuckley/cabot-search huggingface dataset:
Effect of metformin on insulin receptor binding and glycaemic control in type II diabetes.
Authors: J M Lord, S I White, C J Bailey, T W Atkins, R F Fletcher, K G Taylor
Journal: BMJ (1983)

To investigate the effect of metformin on insulin receptor binding and diabetic control, eight obese type II diabetic patients were studied before treatment, after one and four weeks of taking metformin (500 mg thrice daily), and four weeks after withdrawal of the drug. After one and four weeks of treatment the number of erythrocyte insulin receptors had increased by 116% and 184% respectively. This was due almost entirely to an increase in the number of low affinity binding sites. The number of receptors was still raised four weeks after metformin had been withdrawn. Diabetic control as assessed by urinary glucose, glycosylated haemoglobin (HbA1), and glucose tolerance values was significantly improved during metformin treatment, while plasma insulin concentrations were not altered. These results indicate that metformin produces a rapid and protracted increase in low affinity insulin receptors in type II diabetes, associated with greater insulin sensitivity and improved diabetic control.
Symptomatic gastro-oesophageal reflux disease: double blind controlled study of intermittent treatment with omeprazole or ranitidine
Authors: K D Bardhan, S Muller-Lissner, M A Bigard, G B. Porro, J Ponce, J Hosie, M. Scott, D G Weir, K R W Gillon, R A Peacock, C. Fulton
Journal: BMJ (1999)

Objective : To assess intermittent treatment over 12 months in patients with symptomatic gastro-oesophageal reflux disease. Design : Randomised, multicentre, double blind, controlled study. Patients with heartburn and normal endoscopy results or mild erosive changes received omeprazole 10 mg or 20 mg daily or ranitidine 150 mg twice daily for 2 weeks. Patients remaining symptomatic had omeprazole 10 mg or ranitidine dose doubled for another 2 weeks while omeprazole 20 mg was continued for 2 weeks. Patients who were symptomatic or mildly symptomatic were followed up for 12 months. Recurrences of moderate or severe heartburn during follow up were treated with the dose which was successful for initial symptom control. Setting : Hospitals and primary care practices between 1994 and 1996. Subjects : 677 patients with gastro-oesophageal reflux disease. Main outcome measures : Total time off active treatment, time to failure of intermittent treatment, and outcomes ranked from best to worst. Results : 704 patients were randomised, 677 were eligible for analyses; 318 reached the end of the study with intermittent treatment without recourse to maintenance antisecretory drugs. The median number of days off active treatment during follow up was 142 for the entire study (281 for the 526 patients who reached a treatment related end point). Thus, about half the patients did not require treatment for at least 6 months, and this was similar in all three treatment groups. According to outcome, 378 (72%) patients were in the best outcome ranks (no relapse or one (or more) relapse but in remission until 12 months); 630 (93%) had three or fewer relapses in the intermittent treatment phase. Omeprazole 20 mg provided faster relief of heartburn. The results were similar in patients with erosive and non-erosive disease. Conclusions : Intermittent treatment is effective in managing symptoms of heartburn in half of patients with uncomplicated gastro-oesophageal reflux disease. It is simple and applicable in general practice, where most patients are seen.
Does steroid pulsing influence the efficacy and toxicity of chrysotherapy? A double blind, placebo controlled study.
Authors: C S Wong, G Champion, M D Smith, M Soden, M Wetherall, R A Geddes, W R Hill, M J Ahern, P J Roberts-Thomson
Journal: Annals of the Rheumatic Diseases (1990)

To test the hypothesis that early steroid pulsing augments the efficacy and decreases the toxicity of chrysotherapy 40 patients with rheumatoid arthritis were studied in a double blind, placebo controlled study. During the first three months of gold treatment group 1 received monthly intravenous methylprednisolone pulsing (steroid group) while group 2 received placebo (placebo group). All patients were assessed clinically and serologically over a 24 week period. Twelve patients were withdrawn before completion of the study and all but one of the remaining 28 patients reported clinical and serological improvements. Two patients in the steroid group were withdrawn owing to gold induced side effects while four were withdrawn in the placebo group. These small numbers were not significantly different. Minor side effects occurred more commonly in the placebo group. The clinical response was clearly better in the steroid group with statistical significance almost being achieved. In an endeavour to obtain a significant conclusion further patients will now be entered into this study.
Predictive testing for multiple endocrine neoplasia type 1 using DNA polymorphisms.
Authors: C Larsson, J Shepherd, Y Nakamura, C Blomberg, G Weber, B Werelius, N Hayward, B Teh, T Tokino, B Seizinger
Journal: Journal of Clinical Investigation (1992)

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominantly inherited predisposition to neoplastic lesions of the parathyroids, pancreas, and the pituitary. We have previously located the predisposing genetic defect to the long arm of chromosome 11 by genetic linkage. In this study, 124 members of six MEN1 families, including 59 affected individuals, were genotyped for restriction fragment length polymorphisms with different DNA probes, and the genetic linkage between these marker systems and MEN1 was determined. 13 marker systems (17 DNA probes) were found to be linked to MEN1. These markers are located within a region on chromosome 11 spanning 14% meiotic recombinations, with the MEN1 locus in the middle. Four of the marker systems are on the centromeric side of MEN1, and four on the telomeric side, based on meiotic crossovers. The remaining five DNA probes are closely linked to MEN1, with no crossovers in our set of families. The 13 marker systems can be used for an accurate and reliable premorbid test for MEN1. In most clinical situations it is possible to identify a haplotype of this part of chromosome 11 with the mutant MEN1 allele in the middle. The calculated predictive accuracy is greater than 99.5% if three such marker systems are informative. Therefore, genetic linkage testing can be used for informed genetic counseling in MEN1 families, and to avoid unnecessary biochemical screening programs.
Therapeutic potential of a long acting somatostatin analogue in gastrointestinal diseases.
Authors: L J O'Donnell, M J Farthing
Journal: Gut (1989)

For the first time, 8 patients with psoriatic arthritis (PsA) participated as full delegates at the 2013 Annual Meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA). Patients were invited to provide their perspective for different sessions of the conference program. Before the conference, the patient delegates had a separate meeting to familiarize themselves with the conference program and to gain a better understanding of the vision and objectives of GRAPPA. During the conference, the patient group discussed options for increased involvement in research projects. Herein we summarize the presentations on patient participation in research, the experiences of the patient group, and plans to enhance the patient perspective in psoriasis and PsA research.
Sick sinus syndrome.
Authors: D Eraut, D B Shaw
Journal: BMJ (1973)

On Mount Kenya this year I witnessed high-altitude oedema presenting as coma.The patient, a 25-year-old European, had walked from 6,500 feet (1,980m) to 15,500 feet (4,724 m) altitude in a day and a half- he had proved to be the fittest member of the party.On the next day he developed headache and nausea, causing him to rest.He was rational till night.During that night he had loud but not alarming breathing.Next morning he was unrousable, with temperature of 38 5'C, tachycardia, tachypnoea, and frothy saliva.Cyanosis was not present at any stage of the illness.After first-aid treatment (parenteral digoxin, frusemide, chlorpromazine, and pencillin, with oxygen) he was evacuated by stretcher and helicopter.Chest x-ray showed pulmonary oedema.His fundi later showed retinal haemorrhages.C.S.F.pressure was high.After a week of treatment including positive-pressure venti- lation, diuretics, dexamethasone, and anti- biotics he recovered consciousness.A spastic quadriplegia gradually resolved, leading to complete recovery after about two months.The mechanism of the cerebral "oedema" is uncertain.It is clearly not just due to hypoxia.Cerebral arteriolar constriction (due to hypocarbia), with or without diffuse thrombosis or haemorrhage, must be a partial explanation.
The inhibitors of nucleotide biosynthesis leflunomide, FK778, and mycophenolic acid activate hepatitis B virus replication<i>in vitro</i>
Authors: Karin Hoppe-Seyler, Peter Sauer, Claudia Lohrey, Felix Hoppe-Seyler
Journal: Hepatology (2012)

The inhibitors of pyrimidine synthesis, leflunomide and FK778, have been reported to exert broad antiviral effects, in addition to their immunosuppressive activities. Their possible therapeutic benefit for transplantation medicine is currently discussed, because they also block the replication of human cytomegalovirus and human polyomavirus BK, which both cause important complications in transplant recipients. Here, we show that leflunomide and FK778 strongly enhance hepatitis B virus (HBV) replication in vitro . This activity is shared by mycophenolic acid (MPA), an inhibitor of purine biosynthesis. Stimulation of HBV replication by these agents was linked to their inhibitory effects on de novo nucleotide biosynthesis because it could be efficiently counteracted by external nucleoside supply. Mechanistically, we found that mitogen-activated protein kinase p38 played a key role for the enhancement of HBV replication by leflunomide, FK778, and MPA. All three HBV-activating compounds increased p38 phosphorylation, in contrast to the HBV inhibitors, telbivudine and cyclosporine A. Moreover, silencing of p38 expression through RNA interference efficiently counteracted the stimulatory effect of leflunomide, FK778, and MPA on HBV replication. Conclusion: Our data indicate that, in contrast to their reported inhibitory effects on other viruses, both leflunomide and FK778 can augment HBV replication. Treatment with leflunomide, FK778, or MPA may bear the risk to enhance HBV replication in infected patients. (HEPATOLOGY 2012;56:9–16)
Non-steroidal anti-inflammatory drugs and peptic ulcers.
Authors: C J Hawkey
Journal: BMJ (1990)

Long term follow up studies for one to four years have not shown any tolerance to the efficacy of the drug or any long term side effects (E H Reynolds et al, 18th epilepsy international congress, New Delhi, 1989).21-23Vigilance for possible long term toxicity should continue because early studies of toxicity in rats and dogs showed that microvacuoles suggestive of intramyelinic oedema were reversibly formed in the white matter in a dose related manner.2425In dogs microvacuolation was accompanied by changes in the transmission time through the central nervous system of somatosensory evoked potentials, but such changes have not been observed in patients receiving long term treatment.2627No evidence of intramyelinic oedema has been seen in six necropsies and 23 biopsy specimens taken from patients treated with vigabatrin for a mean of 25 months (D Scholey et al, Merrell Dow files, personal communication).The clinical evaluation of vigabatrin has proceeded cautiously, and the drug will be available only for treating epilepsy that is not satisfactorily controlled by other anti- epileptic drugs.Nevertheless, it may prove to be a milestone in the treatment of epilepsy not only because it is the first new antiepileptic drug since the licensing of sodium valproate in 1973 but also because it is the first successful rational approach to the treatment of chronic epilepsy.
Intensive Therapy in AL Amyloidosis and Light-Chain Deposition Disease
Authors: Henk M. Lokhorst
Journal: Annals of Internal Medicine (1995)

Letters1 October 1995Intensive Therapy in AL Amyloidosis and Light-Chain Deposition DiseaseHenk M. Lokhorst, MD and Leo F. Verdonck, MDHenk M. Lokhorst, MDUniversity Hospital Utrecht; Utrecht, the NetherlandsSearch for more papers by this author and Leo F. Verdonck, MDUniversity Hospital Utrecht; Utrecht, the NetherlandsSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-123-7-199510010-00018 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:The case described by Mariette and associates further supports the idea that therapy for disorders associated with plasma cell dyscrasia and abnormal immunoglobulin deposits—such as AL amyloidosis, light-chain deposition disease, and probably also heavy-chain disease—should be aimed at completely eliminating the proliferation of clonal plasma cells.We previously described one patient [1] and treated two others who had generalized AL amyloidosis using high-dose chemoradiotherapy supported by peripheral blood stem-cell transplantation. Of these two, one remains unevaluable because of insufficient treatment duration. In the other patient, who was refractory to intermediate-dose melphalan (70 mg/m2 body surface area), evaluation 1 ...References1. van Buren M, Hen&130; RJ, Verdonck LF, Verzijlberger FJ, Lokhorst HM. Clinical remission after syngeneic bone marrow transplantation in a patient with AL amyloidosis. Ann Intern Med. 1995;122:508-10. Google Scholar Author, Article, and Disclosure InformationAffiliations: University Hospital Utrecht; Utrecht, the Netherlands PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byImmunoglobulin Light (Heavy)-Chain Deposition Disease: From Molecular Medicine to Pathophysiology-Driven TherapyToxic megacolon: a life-threatening complication of high-dose therapy and autologous stem cell transplantation among patients with AL amyloidosisLight Chain Deposition Disease: A Model of Glomerulosclerosis Defined at the Molecular LevelMyeloablative chemotherapy with stem cell rescue for the treatment of primary systemic amyloidosis: a status report 1 October 1995Volume 123, Issue 7Page: 553KeywordsAmyloidosisBloodBody surface areaBone marrowChemoradiotherapyExcretionHypotensionMyelomaPlasma cellsTransplantation Issue Published: 1 October 1995 Copyright & PermissionsCopyright © 1995 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
ENVIRONMENTAL AND HUMAN ISOLATES OF VIBRIO CHOLERAE AND VIBRIO PARAHAEMOLYTICUS PRODUCE A SHIGELLA DYSENTERIAE 1 (SHIGA)-LIKE CYTOTOXIN
Authors: AlisonD. O'Brien, MelindaE. Chen, RandallK. Holmes, James Kaper, MyronM. Levine
Journal: The Lancet (1984)
Immunosuppression and the Abdominal Aortic Aneurysm
Authors: Jan H.N. Lindeman, Ton J. Rabelink, J. Hajo van Bockel
Journal: Circulation (2011)

L arger abdominal aortic aneurysms (AAAs) have a high propensity to rupture, which makes them a significant health problem.As a result, elective repair is generally recommended.However, the great majority of AAAs are small and do not establish such a risk, in particular, not if the growth of small AAAs is absent.It has been pointed out that pharmaceutical interventions, which stabilize small AAAs and thus reduce the need for surgical repair, could be highly beneficial. 1 Yet, the most effective strategies still have to be identified.The pathology of larger AAAs is complex and best described as a general proinflammatory response and an accompanying proteolytic imbalance, the latter being held responsible for the excess matrix turnover in the disease.The inflammatory fingerprint of the larger AAA is multifaceted and is characterized by marked interleukin (IL) 6 and IL-8 hyperexpression, 2 and by a comprehensive cellular infiltrate that includes ample macrophages, B cells, T cells, plasma cells, neutrophils, mast cells, and other cell types. 3Yet,
Clinical commissioning groups serve too many masters, finds study
Authors: Zosia Kmietowicz
Journal: BMJ (2013)

Clinical commissioning groups (CCGs) are accountable to too many masters with potentially competing agendas, say authors of a study in the online journal BMJ Open .1

CCGs, which replaced primary care trusts in April this year and which are responsible for 65% of the NHS budget in England, were set up in part to boost the accountability of those responsible for commissioning care for patients. They also have greater autonomy than their predecessor organisations, but this independence depends in large part on their relations with the bodies that oversee them.

To understand the accountability …
FDG Accumulation in Inguinal Herniation Mimicking Metastatic Disease
Authors: Kristoff Muylle, Hendrik Everaert, Johan De Mey, Tony Lahoutte, Philippe R. Franken, Axel Bossuyt
Journal: Clinical Nuclear Medicine (2004)

Positron emission tomography (PET) using fluorodeoxyglucose (FDG) plays an important role in the management of oncologic diseases. Interpretation of the FDG-PET data requires a profound knowledge of the normal variety of FDG biodistribution and of the different pitfalls that may mimic additional localizations of disease. The authors report a unique case of focal increased FDG activity resulting from intestinal uptake in an inguinal herniation.
P278 Extra-corporeal Membrane Oxygenation And Diffuse Alveolar Haemorrhage - A Single Centre Case Series And Analysis Of The Elso Database
Authors: T. Simpson, C. Ling, G. Glover, N. Barrett, N. Ioannou, B. Lams, C. Langrish, C. Meadows, N. Agarwal, D. D'Cruz
Journal: Thorax (2014)

<h3>Background</h3> Diffuse alveolar haemorrhage (DAH) is a potentially fatal complication of the systemic vasculitides and may present directly to the intensivist as a severe acute respiratory distress syndrome (ARDS) with reported mortality of 12- 60%. Whilst a severe respiratory failure (SRF) therapy strategy incorporating extracorporeal membrane oxygenation (ECMO) improves outcomes in ARDS, use of ECMO in DAH is often considered to be relatively contraindicated due to the requirement for systemic anticoagulation. <h3>Methods</h3> We present a case series of 4 patients with DAH due to underlying ANCA-associated vasculitides managed by a standardised diagnostic pathway and ARDS treatment algorithm in a single, UK SRF centre, since 2012. We analysed the Extracorporeal Life Support Organisation (ELSO) database and report on the current international experience of DAH and ECMO. <h3>Results</h3> The case series is described in Table 1. Median Lung Injury Score was 3.5. All patients received ECMO (median duration 8 days) and all received immunosuppression. One patient received normal heparin protocol to target APTTr 1.5–2 whilst two patients had 48 h of ECMO with no heparin followed by targeted sub-therapeutic low dose heparin. ICU survival was 100% and six month survival was also 100%. There were no exacerbations of pulmonary haemorrhage, no new events of extra-pulmonary haemorrhage and no clotting complications. <h3>ELSO</h3> The ELSO database contains 78 patients (adult, 59; paediatric, 19) with pulmonary vasculitides who received ECMO. 43 had a diagnosis of Granulomatosis and Polyangiitis (GPA), whereas the remaining diagnoses included hypersensitivity angiitis, Goodpasture’s syndrome and thrombotic microangiopathy. The median age was 23 yrs (IQR 16–47). The median duration of ECMO was 190hrs (IQR 146–282) and ICU survival was 82%. Twelve patients (15%) were reported to have thrombotic ECMO circuit complications. <h3>Conclusion</h3> In this case series, ECMO offers an excellent survival rate in SRF due to ANCA-associated DAH. ELSO registry data supports this, suggesting that ECMO should be considered as supportive therapy in DAH with SRF not responsive to conventional therapy.
Improved speed and stability of st-segment recovery with reduced-dose tenecteplase and eptifibatide compared with full-dose tenecteplase for acute st-segment elevation myocardial infarction
Authors: Matthew T Roe, Cynthia L Green, Robert P Giugliano, C.Michael Gibson, Kenneth Baran, Mark Greenberg, Sebastian T Palmeri, Suzanne Crater, Kathleen Trollinger, Karen Hannan, Robert A Harrington, Mitchell W Krucoff
Journal: Journal of the American College of Cardiology (2004)
Studies Illuminate Hazards of Ingested Radiation
Authors: Beverly Merz
Journal: JAMA (1987)

DIP... PAINT... LICK the brush. The rhythmic sequence was second nature to those known as luminators during the 1920s. Their task was simple—to apply radium paint to the tiny numerals encircling watch dials. Their occupational hazards were manifold—osteomyelitis, aplastic anemia, osteosarcoma, and mastoid carcinoma. Dial painting required a deft hand and a finely pointed brush. While the first attribute may have been hereditary, the second was easily acquired. All it took to keep a brush pointed was a quick touch to the lips or tongue. "Lip tipping" passed particles of the sticky paint to the teeth and tongue; it also transferred from 3 to 43 μg of radioactive substances each day. Thus, in a few years' time luminators could easily have swallowed 5 mg or more, at least 1 mg of which would be deposited in their bones, spleen, and liver, where it would remain, emitting a steady stream of
LDL oxidation and coronary atherosclerosis
Authors: SimonR.J. Maxwell, M. Schumacher, B. Eber, F. Tatzber, P. Kaufmann, H. Esterbauer, W. Klein, Jacqueline De Graaf, PierreN.M. Demacker, AntonF.H. Stalenhoef
Journal: The Lancet (1992)
473 DEVELOPMENT OF PREDICTION MODELS FOR HBV-RELATED LIVER CIRRHOSIS BY INTEGARTING HBV GENOTYPE AND SERUM LEVELS OF HBV DNA AND HBSAG
Authors: M.-H. Lee, H.-I. Yang, J. Liu, R. Batrla-Utermann, C.-L. Jen, U.H. Iloeje, J. Su, S.-N. Lu, S.-L. You, L.-Y. Wang, C.-J. Chen
Journal: Journal of Hepatology (2012)
Proteasome inhibitors: Poisons and remedies
Authors: Silke Meiners, Antje Ludwig, Verena Stangl, Karl Stangl
Journal: Medicinal Research Reviews (2007)

Abstract The proteasome inhibitor bortezomib has been approved as a cytostatic drug for the therapy of multiple myeloma, and is currently being tested in clinical trials for a variety of other malignancies. At the same time, a growing number of animal studies suggest that proteasome inhibitors may also prove to be valuable remedies for the treatment of non‐tumorous diseases. In this review, we will revisit the current applications of proteasome inhibitors in clinical research according to the cellular effects of proteasome inhibitors as poisons, which induce apoptosis, or as remedies, which modulate cellular function and protect from cell death. We postulate that the correct distinction of a poison from a remedy depends on cell type and on the degree of proteasome inhibition. Dose‐dependent and differential inhibition of the proteasome may affect specific sets of substrates, thereby conferring substrate specificity. According to this idea, we suggest that inhibition of the proteasome to a defined degree may offer a promising tool in achieving desired therapeutic effects in various diseases. © 2007 Wiley Periodicals, Inc. Med Res Rev, 28, No. 2, 309–327, 2008