tbuckley/cabot-search huggingface dataset:
Diabetes: Have We Got It All Wrong?
Authors: Walter J. Pories, G. Lynis Dohm
Journal: Diabetes Care (2012)

In this “clinical” contribution to the Bench to Clinic Symposia, we will show data to support the hypothesis that fasting hyperinsulinemia is the initial underlying cause of type 2 diabetes mellitus (T2DM) and that the remission of the disease following bariatric surgery may be due to the correction of hyperinsulinemia. The intent of this article is to elicit critical thinking about the pathophysiology of T2DM in view of the effects of surgery and to open debate. If our hypothesis is correct, then more research resources should be focused on the cause(s) of fasting hyperinsulinemia and the therapies that may correct it.

The study of diabetes has always focused on glucose. Whether the diagnosis was made by the attraction of flies to urine as described in ancient India in 1552 BC (1), the sweet taste of the urine noted by Shushruta in 400 BC (2), or our current dependence on fasting blood glucose levels, HbA1c, and glucose tolerance curves, the severity of the disease is still measured by the level of hyperglycemia.

Similarly, our therapeutic directions also aim, almost exclusively, to reverse the hyperglycemia. In 1921 when Banting and Best reported that a pancreatic extract reversed the soaring glucose levels following a pancreatectomy in a dog, the use of insulin spread rapidly to children and adults alike. By the time Sir Harold Percival Himsworth noted, in 1936, that there were at least two types of diabetes (3), the objectives of T2DM treatment were already set; goals that still continue today. Even though type 1 diabetes mellitus (T1DM) and T2DM are virtually two opposite diseases, i.e., a total lack of insulin production versus abnormally high levels, the therapeutic goals for both entities continue to be the same: lower glucose levels by 1 ) giving insulin, 2 ) increasing insulin production, and/or 3 …
Virtual Autopsy With Multiphase Postmortem Computed Tomographic Angiography Versus Traditional Medical Autopsy to Investigate Unexpected Deaths of Hospitalized Patients
Authors: Dominic Wichmann, Axel Heinemann, Clemens Weinberg, Hermann Vogel, Wilhelm Wolfgang Hoepker, Silke Grabherr, Klaus Pueschel, Stefan Kluge
Journal: Annals of Internal Medicine (2014)

"Virtual" autopsy by postmortem computed tomography (PMCT) can replace medical autopsy to a certain extent but has limitations for cardiovascular diseases. These limitations might be overcome by adding multiphase PMCT angiography.To compare virtual autopsy by multiphase PMCT angiography with medical autopsy.Prospective cohort study. (ClinicalTrials.gov: NCT01541995) SETTING: Single-center study at the University Medical Center Hamburg-Eppendorf, Hamburg, Germany, between 1 April 2012 and 31 March 2013.Hospitalized patients who died unexpectedly or within 48 hours of an event necessitating cardiopulmonary resuscitation.Diagnoses from clinical records were compared with findings from both types of autopsy. New diagnoses identified by autopsy were classified as major or minor, depending on whether they would have altered clinical management.Of 143 eligible patients, 50 (35%) had virtual and medical autopsy. Virtual autopsy confirmed 93% of all 336 diagnoses identified from antemortem medical records, and medical autopsy confirmed 80%. In addition, virtual and medical autopsy identified 16 new major and 238 new minor diagnoses. Seventy-three of the virtual autopsy diagnoses, including 32 cases of coronary artery stenosis, were identified solely by multiphase PMCT angiography. Of the 114 clinical diagnoses classified as cardiovascular, 110 were confirmed by virtual autopsy and 107 by medical autopsy. In 11 cases, multiphase PMCT angiography showed "unspecific filling defects," which were not reported by medical autopsy.These results come from a single center with concerted interest and expertise in postmortem imaging; further studies are thus needed for generalization.In cases of unexpected death, the addition of multiphase PMCT angiography increases the value of virtual autopsy, making it a feasible alternative for quality control and identification of diagnoses traditionally made by medical autopsy.University Medical Center Hamburg-Eppendorf.
Abstract 889: Integration of centrosome-associated and kinase-related screens to identify centrosome amplification-related synthetic lethal interactions
Authors: Konstantinos Drosopoulos, Carly Scott, Chan Tang, Spiros Linardopoulos
Journal: Cancer Research (2012)

Abstract Centrosome amplification is one of the most commonly observed abnormalities in human cancer and is associated with increased chromosome instability (CIN), aneuploidy and tumor progression. Cancer cells have been shown to cluster supernumerary centrosomes in a bipolar fashion in mitosis, thus preventing the formation of lethal multipolar spindles. We have developed isogenic cell lines, which enable us to identify genes which selectively kill tumor cells with centrosome amplification. The model is based on the generation of genomically stable human colon cancer DLD1 diploid and tetraploid (DLD1-T) cells with normal centrosome numbers and genomically unstable DLD1 intermediate (DLD1-I) with extra centrosomes generated by transiently blocking cytokinesis. Diploid and tetraploid populations did not show significant differences in gene expression, fitness, rate of spontaneous apoptosis, centrosome amplification and mitotic abnormalities. However, growth rate examination of the generated isogenic cell lines showed a slight increase in doubling time of DLD1-I clones, possibly due to a longer activation of the mitotic checkpoint machinery to allow time for microtubule attachment and centrosome clustering. To identify genes that their ablation leads to a selective cell killing of centrosome amplified cancer cells by centrosome declustering, we envisaged two parallel paths of investigation, an siRNA and a chemical library screening with a two-fold readout assay: a cell viability and a spindle morphology phenotypic assay by high-content microscopy. This approach allowed us to identify target genes and generate networks of genes that specifically kill cells with centrosome amplification by preventing centrosome clustering. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 889. doi:1538-7445.AM2012-889
Staphylococcal Pneumonia in Adults
Authors: W. Hausmann, A. J. Karlish
Journal: BMJ (1956)

Staphylococcal pneumonia has long been known as a complication of epidemic influenza.The fulminating, prostrating type encountered during the pandemic of influenza that followed the first world war was fully described in the writings of Chickering and Park (1919).At that time mortality rates of 80-90% were reported.In 1942 Finland et al. recorded a reduction in the death rate to 32%, which they attributed to the use of sulphonamides.In sporadic form, however, staphylococcal pneumonia is widely regarded as a disease occurring mainly in infants.In these the prognosis is still grave.Recently, Wallman et al. (1955) reported 44 cases from Perth, Western Australia, with a mortality of 23%, a figure achieved by modern treatment with antibiotic agents.In adults, relatively few cases unassociated with major influenza were reported before 1950.Heffron (1939), analysing 3,319 cases of lobar pneumonia, found only six that were considered staphylococcal.Among 298 cases of bacterial pneumonia admitted to the Central Middlesex Hospital in 1942-4, Humphrey et al. (1948) described seven which were thought to be staphylococcal.Only one had a history of preceding influenza-like illness.During the last five years, however, several groups of cases have been reported.Of 110 cases of pneumonia admitted during one year to Hammersmith Hospital and reported by Crofton et al. (1951), 10 were considered to be staphylococcal and only two showed serological evidence of influenza B. Neither of these two patients was very ill.Grist et al. (1952) saw 10 cases of staphylococcal infection among 129 cases of pneu- monia admitted to one hospital in Glasgow during a period of fifteen months.Serological evidence of recent influenza A infection was present in 5 of the 10 cases.Grant and Barber (1954) reported 15 cases from Belfast, constituting 3 % of all pneumonia admissions.Only four cases occurred during an influenza outbreak.Material.-Thispaper is based on a series of 18 cases of staphylococcal pneumonia in adults admitted to an acute medical unit in Reading during 1952-4.Many cases of pneumonia occurring in the area receive treat- ment at home, and, in general, only the severely ill patients not responding to penicillin and sulphonamides are admitted.There was no local influenza epidemic during the period under review, but virus studies were not made.The group formed 15% of a total of 122 consecutive patients admitted to the unit in whom the diagnosis of primary pneumonia was radiologically con- firmed.There were 11 men and 7 women.Their ages ranged from 16 to 72, with an average of 51 years. DiagnosisThe aetiological diagnosis of staphylococcal pneumonia is a matter of some difficulty and is often derived from a combination of clinical, radiological, and bacteriological
Reduction of Oxidative Stress and Inflammation by Blunting Daily Acute Glucose Fluctuations in Patients With Type 2 Diabetes: Role of Dipeptidyl Peptidase-IV Inhibition. Diabetes Care 2012;35:2076-2082
Authors: M. R. Rizzo, M. Barbieri, R. Marfella, G. Paolisso
Journal: Diabetes Care (2014)

In the article listed above, the source of funding for the study was not specified. The study was funded by an Institutional Grant of the Department of Medical, Surgical, Neurological, Metabolic and Aging Sciences, Second University of Naples.

Also, the MAGE data were manually calculated …
ELECTROSHOCK THERAPY OF A DEPRESSED PATIENT WITH COMPLETE HEART BLOCK
Authors: LORAN F. PILLING, MAURICE J. BARRY, THOMAS W. PARKIN
Journal: American Journal of Psychiatry (1963)

A psychiatrically depressed patient with complete heart block received a course of electroshock therapy. On one occasion ventricular tachycardia and ventricular arrest occurred, but the patient recovered without cardiac therapy. The potential aggravation of a pre-existing, serious arrhythmia should be considered carefully before the institution of EST, but the reported case illustrates that it can be used successfully in such circumstances. If necessary precautions are taken, such therapy may be appropriate when other treatment has failed.
Role of human factor VIII in factor X activation.
Authors: M B Hultin
Journal: Journal of Clinical Investigation (1982)

The cofactor function of human Factor VIII in Factor X activation was investigated by an initial-rate assay of 3H-Factor X activation in the presence of human factor IXa, Ca2+, and either phospholipid or fresh washed human platelets. Purified Factor VIII that has not been activated by thrombin or Factor Xa supports Factor X activation after a lag of several minutes. A specific inhibitor of Factor Xa, which had no inhibitory activity against Factor IXa, markedly prolonged this lag, whereas specific thrombin inhibitors did not prolong the lag. These data support the conclusion that unactivated Factor VIII has no ability to support Factor X activation in a purified system until it is activated by Factor Xa feedback during the lag period. When Factor VIII was optimally preactivated by thrombin, the lag was completely abolished, regardless of the order of addition of the other reactants or the phospholipid source. These data indicate that there is no slow, time-dependent ordering of the reactants at the phospholipid or activated platelet surface if Factor VIII has been preactivated. Unactivated platelets did not support Factor X activation by Factors IXa and VIII. The effect of activated Factor VIII on the kinetics of bovine Factor X activation was primarily to increase the Vmax (54-fold), whereas with human Factor X, Factor VIII both increased the Vmax 56-fold and decreased the Km sixfold to 0.14 microM, similar to the plasma concentration of Factor X. Therefore, a change in the plasma factor X concentration would be expected to have a major effect on the rate of Factor X activation in vivo.
DNA integration sites and hepatocellular carcinoma
Authors: Jorge J. Gumucio, Daryl Daugherty, Daryl Daugherty
Journal: Hepatology (1991)

This study is part of an ongoing analysis of woodchuck hepatitis virus integration sites in the host genome of hepatocellular carcinomas. The study of woodchuck hepatitis virus-DNA integration sites may shed light on the oncogenic mechanisms involved in cellular transformation and tumor formation. Viral integration enhancing cellular proto-oncogene expression is one such mechanism and has been well documented for oncogenic retroviruses such as mouse mammary tumor virus and interleukin-1. By cloning a woodchuck hepatitis virus integration site from a woodchuck hepatocellular carcinoma the authors were able to identify a new member of the myc gene family, N- myc -2. Examination of 30 additional woodchuck hepatomas revealed viral integration commonly occurred near N- myc loci with an additional five woodchuck hepatitis virus integrants near the N- myc -2 gene and one viral integrant near N- myc -1. Three of these N- myc -2 viral integrations were further evaluated and found to be localized within 200 bp of the translation stop codon. This 3′ noncoding region has recently been identified as a common site of murine leukemia virus integration in virally induced T-cell lymphomas and results in increased expression of the N- myc gene. Similar mechanisms can be proposed for hepatocellular carcinoma formation. Woodchuck hepatitis virus integration near cell-growth related protooncogenes, such as N- myc , can juxtapose viral enhancer elements and growth-regulatory genes. Virally induced overexpression of proto-oncogene messenger RNA could result from enhanced transcription or increased messenger RNA stability. To search for such effects the authors analyzed N- myc -2 RNA levels in 30 woodchuck hepatitis virus-related hepatomas. Increased levels of N- myc -2 RNA were found in 18 of 30 tumors, whereas nontumorous portions of the same livers had no detectable N- myc -2 RNA. Taken together these findings suggest that woodchuck hepatitis virus integration can result in altered N- myc -2 gene expression in a significant proportion of woodchuck hepatocellular carcinomas. The deregulation of N- myc gene expression could result in cellular transformation and ultimately tumor formation. Such examples of hepadnavirus-specific oncogenic mechanisms lend credence to theories of hepatitis B virus-induced tumorigenesis and provide models to design molecular investigations of human hepatocellular carcinoma formation.
What your patients may be reading
Authors: R. Gann
Journal: BMJ (1987)

Many of today's health books for lay readers reflect a crisis of confidence in conventional medicine and a search for alternative or complementary approaches. Orthodox medicine can leave patients feeling helpless, undermined by drugs and a hostile environment, according to Stephen Fulder in his latest book How to Survive Medical Treatment: a Holistic Approach to the Risks and Side Effects of Orthodox Medicine (?5.95 paperback. London: Century, 1987. ISBN 0-7126-1481-8). Claiming to be the first layman's guide to self care in hospital, it aims at encouraging patients to become more active and take greater control over their own treatment. Unnecessary surgery comes in for particular criticism: a dozen procedures are placed in this category, including hysterectomy, mastectomy, gall stone removal, coronary bypass, and some biopsies. Other risks to patients include x rays (invisible, lethal, avoidable), anaesthesia, chemotherapy, and of course drug therapy. Even the healthy are assailed by the risks of technological childbirth, of dentistry (poisoning by dental amalgam), and of vaccinations. The recommended policy on vaccinations is Get the best and leave the rest. Whooping cough, measles, BCG, rubella, influenza, and cholera vaccinations are regarded as not worth the risk. The patient can fight back through a combination of information gathering, confidence raising, and the use of complementary therapies. Before treatment the patient is urged to visit the public or medical library, read up on the diagnosis and proposed treatment, and be ready with questions for the consultant. Further good advice is to contact self help groups and seek their support. Once admitted to hospital, relaxation techniques and yoga can reduce stress and aid recovery. Natural methods are suggested for bolstering immunity against hospital infections, and techniques drawn from comple? mentary medicine are recommended to help counteract the side effects of orthodox treatment. Many doctors will not like this book but it is always a stimulating and provocative read. I was moved to follow up a number of the copious references to other publications. These proved more accurate than the reference to my own book, where author and publisher are incorrectly cited.l
Phenothiazines and Sudden Death
Authors: Kurt Witton
Journal: JAMA (1965)

To the Editor:—  While Dr. Hollister did not think that routine electrocardiograms would be of any great value in preventing the occurrence of sudden cardiovascular complications, I believe that repeated ECG surveys may offer opportunity for a better appraisal of the patient's cardiovascular status. In a current pilot survey of 80 male veterans on long-term drug treatment, this correspondent found abnormal ECGs in 43 patients, 22 of whom had been hospitalized for five years or more and 21 for one year or less. This survey was prompted by the observation that certain newer energizing drugs had effected ECG changes after a short period of administration (one to two months). The abnormalities consisted of changes interpreted as incomplete right bundle-branch block, nonspecific and nondiagnostic T-wave changes, and myocardial ischemia. One third of the abnormal ECGs occurred in patients in the relatively younger age group, where arteriosclerotic heart disease is not expected.
Chromaffin Tumour with Chronic Hypertension
Authors: G. Lumb
Journal: BMJ (1951)

TISSUESMEDICALJsOURNAL smears of the original solution indicated that particulate material was present which concentrated the activity.This particulate material can arise in the preparation of the active solution but also, it has been shown, by allowing the solution to stand in a syringe, unless special precautions have been taken.The non-uniformity of activity resulting may affect considerably the dosage distribution in the tissue.We wish to acknowledge our indebtedness to Dr. W. K. Sinclair, whose work first indicated the unsatisfactory nature of some of the radioactive solutions being used, to Miss H. E. Farran for her assistance in the activity measurements, and to Miss M. Winsborough for her help throughout the investigations.We are grateful for the help provided by Dr. Herz, of Messrs. Kodak
Relapsing polychondritis. Report of a case with vertebral column involvement
Authors: H. W. Spritzer
Journal: JAMA (1969)

Relapsing polychondritis is an inflammatory process causing dissolution of cartilage throughout the body. This case illustrates many of the common clinical manifestations. Although the vertebral column is seldom severely affected, back pain, kyphosis, and progressive stiffness of the spine were the major causes of disability in this patient.
Discordant LFA‐1/ICAM‐1 expression in a case of secondary plasma cell leukemia associated with subcutaneous plasmacytoma
Authors: Hiroshi Tsutani, Taeko Sugiyama, Shiro Shimizu, Hiromichi Iwasaki, Takanori Ueda, Kenji Ozaki, Susumu Konda, Toru Nakamura
Journal: American Journal of Hematology (1993)

Abstract We observed a unique case of multiple myeloma that was transformed into plasma cell leukemia presenting with subcutaneous and soft tissue infiltrates. Subcutaneous and minor pelvic soft tissue plasmacytomas and the leukemic transformation were diagnosed in a 72‐year‐old woman after she had completed 9 months of chemotherapy for IgG k multiple myeloma. Immunophenotypic study revealed that leukemic cells in her peripheral blood were positive for ICAM‐1 (CD54) but negative for LFA‐1 α (CD11a) and LFA‐1 β (CD18), whereas infiltrating leukemic cells in the subcutaneous plasmacytoma of the left thigh were positive for LFA‐1 α and LFA‐1 β but negative for ICAM‐1. In addition, intermingling capillary endothelial cells were positive for ICAM‐1. Extramedullary soft tissue plasmacytoma is uncommon in association with plasma cell tumors, and the exact mechanism of the development of plasmacytoma is not known. In the present case, however, the discordant expression of LFA‐1/ICAM‐1 adhesion molecules may have accounted for the distinct patterns of growth and the spread of the subcutaneous plasmacytoma through homing of the LFA‐1 α + , LFA‐1 β + leukemic cells to ICAM‐1 endothelial cells. © 1993 Wiley‐Liss, Inc.
PTU-053 Usefulness of Fecal Calprotectin in Clinical Practice in a District General Hospital
Authors: A Malik, D Bowen, I Rees
Journal: Gut (2013)

<h3>Introduction</h3> Calprotectin is a calcium and zinc binding protein, mainly contained in neutrophils. If present in stools it is a marker of bowel inflammation. We evaluated the diagnostic value of faecal calprotectin (FC) as a non-invasive marker of bowel inflammation in routine out-patient gastroenterology clinic. <h3>Methods</h3> A retrospective study was conducted of patients who had faecal calprotectin evaluated for various indications in out-patient gastroenterology clinic over a 12 month period. Presenting symptoms, FC results and the endoscopic findings were recorded. FC level more than 50 μg/gm was considered positive. <h3>Results</h3> FC was requested for 72 patients. 44 were female (mean age 44 years) and 28 were male (mean age 47 years). FC was requested for various symptoms including chronic diarrhoea, abdominal pain, abdominal distension and per rectal bleeding. Patients were divided into 3 groups based on clinical practise of gastroenterologist. In the first group FC alone was requested initially as a screening test to assess bowel inflammation. 31 patients fell in this group, 21 of 31 had negative FC and no further investigations were done, while 10 of 31 had positive FC (mean 150.3 μg/gm). Out of these 5 had no further investigations as symptoms settled on subsequent clinic visit and 5 went on to have further investigations (Colonoscopy +/- Capsule endoscopy) which were all normal. In the second group both FC and colonoscopy were requested on initial out-patient review. There were 23 patients in this group. 13 of 23 had normal FC and colonoscopy and no further investigations were done. 2 of 23 had abnormal FC (mean 271.5 μg/gm) and colonoscopy. Both were diagnosed with IBD. 8 of 23 had raised FC (mean 171.25 μg/gm) but a normal colonoscopy. 5 of 8 had no further investigations done while 3 had small bowel investigations which were normal. 1 patient of these 3 was treated for presumed small bowel Crohn’s due to raised FC despite normal capsule endoscopy with good effect. In the third group colonoscopy was the initial investigation of choice and was found to be normal but FC was done later in view of persistent symptoms to look for small bowel inflammation. 18 patients fell in this group. 12 of 18 had normal FC and had no further investigations. 6 of 18 had raised FC (mean 114.33 μg/gm). 3 patient’s with raised FC had small bowel investigation done and all were normal. <h3>Conclusion</h3> In conclusion FC was beneficial when negative. It provided reassurance to the clinicians and helped avoid invasive investigations. However when FC was positive clinical judgement and patient symptoms dictated the need for further investigations. None of the patients diagnosed with IBD had a negative FC. <h3>Disclosure of Interest</h3> None Declared