tbuckley/cabot-search huggingface dataset:
HFE Genotype in Patients with Hemochromatosis and Other Liver Diseases
Authors: Bruce R. Bacon
Journal: Annals of Internal Medicine (1999)

Background: Hereditary hemochromatosis is a common inherited disorder of iron metabolism. The gene HFE, which contains two missense mutations (C282Y and H63D), was recently identified. Objective: To determine how HFE genotyping for the C282Y and H63D mutations contributes to the diagnosis of hemochromatosis and to determine the prevalence of HFE mutations in a group of patients with liver disease. Design: Cross-sectional study. Setting: Academic medical center. Patients: 66 patients with hereditary hemochromatosis and 132 referred patients with other liver diseases. Measurements: At initial diagnosis, fasting transferrin saturation, ferritin level, routine chemistry panel, and complete blood count were determined. Percutaneous liver biopsy was done on all patients for histologic analysis and measurement of hepatic iron concentration and hepatic iron index. HFE genotyping for the C282Y and H63D mutations was done on all patients by using genomic DNA samples. Results: Of the 66 patients with hemochromatosis diagnosed on the basis of serum iron studies and liver biopsy findings, 60 (91%) were C282Y homozygotes, 2 (3%) were compound heterozygotes, 1 (1.5%) was a C282Y heterozygote, 2 (3%) were H63D heterozygotes, and 1 (1.5%) was negative for both mutations. Of the 132 patients with liver disease, 6 (5%) were C282Y homozygotes, 8 (6%) were compound heterozygotes, 6 (5%) were C282Y heterozygotes, 5 (4%) were H63D homozygotes, 20 (15%) were H63D heterozygotes, and 87 (66%) were negative for both mutations. All 66 C282Y homozygotes had an elevated hepatic iron concentration, and 65 of the 66 patients (98%) had a transferrin saturation of at least 45%. Ten of the 66 patients (15% [95% CI, 7.5% to 26%]) had a hepatic iron index less than 1.9 mmol/kg per year; hemochromatosis was not suspected in 6 of the 10 patients before genotyping. Cirrhosis or substantial hepatic fibrosis was not seen in any (0% [CI, 0% to 18%]) of the 19 patients younger than 40 years of age who were homozygous for the C282Y mutation. Conclusions: All 66 patients homozygous for the C282Y mutation of HFE had an elevated hepatic iron concentration, but approximately 15% of these patients did not meet a previous diagnostic criterion for hemochromatosis (hepatic iron index > 1.9 mmol/kg per year). Determination of HFE genotype is clinically useful in patients with liver disease and suspected iron overload and may lead to identification of otherwise unsuspected C282Y homozygotes.
75 HEPATOCYTE-DERIVED MICROPARTICLES WITH A SPECIFIC ANTIGENIC COMPOSITION ARE RELEASED IN BLOOD DURING NASH DEVELOPMENT: IMPLICATIONS FOR BIOMARKERS DEVELOPMENT
Authors: D. Povero, A. Eguchi, C. Johnson, A. Wree, M. Lazic, M. Parola, A.E. Feldstein
Journal: Journal of Hepatology (2013)
Perinatal mortality rates in isolated general practitioner maternity units.
Authors: V Sangala, G Dunster, S Bohin, J P Osborne
Journal: BMJ (1990)

To determine the perinatal mortality rate among normally formed, singleton babies with birth weights greater than or equal to 2500 g in Bath health district based on the intended place of delivery at the time of onset of labour or at the time of diagnosis of intrauterine death.The numbers of live births and stillbirths were collected monthly returns from the maternity units concerned. Deaths of infants aged less than or equal to 1 week were collected in the same returns. The intended place of delivery was confirmed at the monthly perinatal mortality meeting, during which maternal and fetal factors were discussed.A rural health district of 400,000 population where one third of all deliveries occurred in seven isolated general practitioner maternity units, 8% in the integrated general practitioner unit, and the remainder in the consultant unit.All babies of women whose deliveries were booked in the district before the onset of labour or the diagnosis of intrauterine death, excluding twins, babies with lethal congenital malformations, and those less than 2500 g.Outcome of all deliveries and parity of mothers.14,415 Deliveries were analysed. The perinatal mortality rate was 2.8/1000 births in the consultant unit (7950 deliveries), 4.8 in the isolated general practitioner units (5237 deliveries), and zero in the integrated general practitioner unit (1228 deliveries). Perinatal deaths attributable to asphyxia were more common in the isolated general practitioner units (1.5 per 1000) than the consultant unit (0.6 per 1000). The perinatal mortality rate among babies born to nulliparous women was 3.2/1000 births in the consultant unit and 5.7 in the isolated general practitioner units; for those born to multigravid women it was 2.4 and 4.2 respectively.The outcome of delivery was not influenced by parity. Both antenatal and intrapartum care were responsible for the higher perinatal mortality rate in the isolated general practitioner units. The integrated unit, which shared midwifery staff with the consultant unit, seemed to work well. Analysis by intended place of delivery at the time of onset of labour or diagnosis of intrauterine death suggested that the care given in isolated units needs to be improved, perhaps by better training of general practitioners and consultant supervision of antenatal care.
Three novel patient‐derived BCR/ABL mutants show different sensitivity to second and third generation tyrosine kinase inhibitors
Authors: Sara Redaelli, Luca Mologni, Roberta Rostagno, Rocco Piazza, Vera Magistroni, Monica Ceccon, Michela Viltadi, Daniel Flynn, Carlo Gambacorti‐Passerini
Journal: American Journal of Hematology (2012)

BCR/ABL (Breakpoint Cluster Region protein/Abelson tyrosine-protein kinase 1) kinase domain (KD) mutations represent the most frequently described mechanism of resistance to the treatment with tyrosine kinase inhibitors (TKI) in patients with chronic myeloid leukemia (CML). Mutations may impair TKI activity by directly or indirectly impairing the drug binding to the protein. We report the discovery of three new BCR/ABL mutations, L248R, T315V, and F317R identified in two patients with CML (L248R and T315V) and in one patient with Ph+ acute lymphoblastic leukemia (ALL) (F317R). Mutations were screened against second-generation (bosutinib, nilotinib, and dasatinib), as well as third-generation TKIs (ponatinib/AP-24534 and DCC-2036). Furthermore, the activity profile of ponatinib and DCC-2036 against a panel of 24 clinically relevant BCR/ABL mutants is presented and compared to the other TKIs. The IC50 values for each TKI against the mutants and the IC50 increase over wild type BCR/ABL (relative resistance, RR) were calculated to define four resistance levels: sensitive (RR ≤ 2), moderately resistant (2 < RR ≤ 4), resistant (4 < RR ≤ 10), or highly resistant (RR > 10). L248R and T315V showed high resistance to imatinib, bosutinib, dasatinib, and nilotinib, intermediate resistance to ponatinib, but were sensitive to DCC-2036. Interestingly, F317R showed a moderate resistance to imatinib and nilotinib, but is resistant/highly resistant to dasatinib, bosutinib, ponatinib, and DCC-2036. The availability of drugs activity profiles may become a useful tool for clinicians dealing with the treatment of drug-resistant CML patients.
Ischemic Cardiac Disease: Damaged Hearts, Lonely Hearts Seem to Act Independently
Authors: Chris Anne Raymond
Journal: JAMA (1988)

WHEN IT COMES to death from ischemic heart disease, damaged hearts and lonely hearts appear to exert their own independent effects. Such is the conclusion of a ten-year study of 150 middleaged men conducted by investigators from Sweden's Karolinska Institute, Stockholm.  The study recruited working men 40 to 65 years of age who fell into one of three groups: those with clinical symptoms of ischemic heart disease, those without symptoms but with recognized risk factors, and apparently healthy men ( Acta Med Scand , in press). The men were matched by age and given thorough examinations, including chest roentgenography and measurement of levels of fasting serum lipids and glucose.  Each man wore a Holter monitor for 24 hours. In addition, the men were questioned about marital status, education, occupation, smoking, alcohol consumption, social activities, perception of health status, and the set of behavior characteristics dubbed Type A that some investigators think are
In patients with suspected CAD and normal ECG, a nomogram model based on clinical and exercise variables predicted mortality
Authors: Christopher B. Granger
Journal: Annals of Internal Medicine (2008)

Source Citation Lauer MS, Pothier CE, Magid DJ, Smith SS, Kattan MW. An externally validated model for predicting long-term survival after exercise treadmill testing in patients with suspected coronary artery disease and a normal electrocardiogram. Ann Intern Med. 2007;147:821-8. 18087052
Epoetin alfa improves quality of life in anemic HCV-infected patients receiving combination therapy
Authors: Paul J. Pockros, Mitchell L. Shiffman, Eugene R. Schiff, Mark S. Sulkowski, Zobair Younossi, Douglas T. Dieterich, Teresa L. Wright, Samir H. Mody, Linda K. Tang, Betty L. Goon, Peter J. Bowers, Gerhard Leitz, Nezam H. Afdhal
Journal: Hepatology (2004)

Anemia and decreased health–related quality of life (HRQL) are common in patients receiving combination therapy of interferon alfa (IFN) and ribavirin (RBV) for chronic hepatitis C virus (HCV) infection. In a randomized, prospective study evaluating the effectiveness of epoetin alfa in maintaining RBV dose, alleviating anemia, and improving HRQL in anemic (Hb ≤ 12 g/dL) HCV–infected patients receiving combination therapy, patients receiving epoetin alfa had significant improvements in HRQL compared with placebo. In this study, 185 patients were randomized to 40,000 units of epoetin alfa subcutaneously weekly or placebo for an 8–week double–blind phase (DBP), followed by an 8–week open–label phase during which all patients received epoetin alfa. To further assess the impact of epoetin alfa on HRQL, post hoc analyses were conducted in the same patient population to compare the HRQL of these patients at randomization with norms of other populations, and to determine the critical relationship between hemoglobin (Hb) levels and HRQL. Mean HRQL scores of anemic HCV–infected patients receiving combination therapy at randomization were significantly lower than those of both the general population and patients who had other chronic conditions. Patients receiving epoetin alfa who had the greatest Hb increases from randomization to the end of the DBP also had the largest improvements in HRQL. Hb improvement was an independent predictor of HRQL improvement in these patients. In conclusion , epoetin alfa provided clinically significant HRQL improvement in HCV–infected patients receiving IFN/RBV therapy. (Hepatology 2004;40:1450-1458.)
Phenylephrine-induced stimulation of Na+/Ca2+ exchange in rat ventricular myocytes
Authors: M Stengl
Journal: Cardiovascular Research (1998)

The effect of an alpha-adrenergic agonist, phenylephrine, on the Na+/Ca2+ exchange current in rat ventricular myocytes was investigated.The Na+/Ca2+ exchange current was measured at room temperature in rat ventricular myocytes as the whole-cell current induced by addition of extracellular Na+ and Ca2+, while blocking Na+ current by setting the holding potential at -30 mV, K+ currents by intracellular Cs+, TEA+ and by extracellular Ba2+, Ca2+ current by nifedipine and Na+ pump current by ouabain or by 0 extracellular K+.Under these experimental conditions, application of external Na+ and Ca2+ induced a current which was further increased by phenylephrine. Phenylephrine (80 microM) increased the current by up to 31.0 +/- 5.4% of control at all membrane potentials tested both below and above the reversal potential. The reversal potential (+21.0 +/- 3.2 mV), which corresponded with the theoretical reversal potential for the Na+/Ca2+ exchange current under our ionic conditions (+21.3 mV), was not changed by phenylephrine (+23.2 +/- 4.1 mV). Applying phenylephrine in the absence of Na+/Ca2+ exchange (0 Na+e, 0 Ca2+e) did not change the current. The effect was resistant to propranolol, a beta-adrenergic blocker, but prevented by prazosin, an alpha-receptor antagonist, by neomycin, an inhibitor of phospholipase C, and by chelerythrine, a selective inhibitor of protein kinase C. Phorbol 12-myristate 13-acetate failed to stimulate the current. The effect remained similar under conditions of high (HEPESi = 5 mM) and low (HEPESi = 0.5 mM) intracellular pH buffering.Our data indicate that phenylephrine stimulates the Na+/Ca2+ exchange, both in the forward and the reverse modes, probably via a protein kinase C-dependent pathway.
Does rheumatoid factor protect lupus patients from the development of nephritis?
Authors: L Turner-Stokes, M Jones, I Addison, M Mansell, D.A Isenberg
Journal: Annals of the Rheumatic Diseases (1989)

It has been suggested again recently that the presence of rheumatoid factor (RF) in the serum of patients with systemic lupus erythematosus (SLE) protects them from the development of nephritis. In this study the RF is measured by standard latex test and by radioimmunoassay to detect IgM, IgA, and IgG isotypes, in patients with SLE with (26 patients) and without (25 patients) renal involvement, and in a control group of 21 patients with idiopathic renal disease. In addition, patients with SLE and nephritis were tested during active and inactive phases of their disease. No significant protective effect was observed from the presence of RF.
Compositional semantics and the lemma dilemma
Authors: Marco Zorzi, Gabriella Vigliocco
Journal: Behavioral and Brain Sciences (1999)

We discuss two key assumptions of Levelt et al.'s model of lexical retrieval: (1) the nondecompositional character of concepts and (2) lemmas as purely syntactic representations. These assumptions fail to capture the broader role of lemmas, which we propose as that of lexical–semantic representations binding (compositional) semantics with phonology (or orthography).
What You Always Wanted to Know about the Howard Hughes Medical Institute but Were Afraid to Ask
Authors: Arnold S. Relman
Journal: New England Journal of Medicine (1978)

For 25 years after its establishment, and for more than two years after the death of its founder and sole benefactor, the Howard Hughes Medical Institute (HHMI) has operated behind a veil of secrecy that has engendered legends, criticism and misunderstanding throughout the academic medical establishment. It is astonishing that the Institute's activities should have been essentially hidden from public view for so long, even while it was recruiting and supporting some of the brightest stars in the medical-research firmament and consulting with distinguished figures in some of the best medical schools in the country. Only rarely has the scientific . . .
Immunomodulatory properties of <i>Lactobacillus plantarum</i> and its use as a recombinant vaccine against mite allergy
Authors: P. Rigaux, C. Daniel, M. Hisbergues, E. Muraille, P. Hols, B. Pot, J. Pestel, A. Jacquet
Journal: Allergy (2008)

Background: Selected lactic acid bacteria were reported to prevent atopic dermatitis and experimental asthma but the mechanisms of their immunomodulatory effects are not fully elucidated. In this study, the signaling pathways triggered by Lactobacillus plantarum NCIMB8826 were investigated and the potential use of this strain producing a variant of the mite allergen Der p 1 as live vaccine vehicle was evaluated. Methods: Mouse bone marrow‐derived dendritic cells were stimulated with wild‐type or a L. plantarum teichoic acid mutant to evaluate the secretion of cytokines. A recombinant L. plantarum expressing Der p 1 was engineered, its in vitro immunomodulatory properties were characterized and its prophylactic potential was evaluated in a Der p 1‐sensitization murine model. Results: Mouse dendritic cells stimulated by L. plantarum triggered the release of interleukin‐10 (IL‐10), IL‐12 p40, IL‐12 p70 and tumor necrosis factor‐alpha (TNF‐α). IL‐12 p40 secretion was dependent on nuclear factor‐κB (NF‐κB), mitogen‐activated protein (MAP) kinases, Toll‐like receptor 2 (TLR2), TLR9 and on the bacterial teichoic acid composition. Recombinant L. plantarum producing Der p 1 exhibited similar immunostimulatory properties as wild‐type. Prophylactic intranasal pretreatment of mice with this recombinant strain prevented the development of the typical Th2‐biased allergic response by a drastic reduction of specific IgE and the induction of protective allergen‐specific IgG2a antibodies. Moreover, both wild‐type or recombinant L. plantarum reduced airway eosinophilia following aerosolized allergen exposure and IL‐5 secretion upon allergen restimulation. Conclusion: By combining both Th1‐type immunostimulatory properties and an efficient allergen delivery capacity, recombinant L. plantarum producing Der p 1 represents a promising vaccine against house dust mite allergy.
Prolapsing Polyp and Disappearing Pseudocyst
Authors: Gurminder S Mann, Dileep N Lobo, Brian J Rowlands
Journal: Journal of the Royal Society of Medicine (2003)

A woman of 70 was referred after six months of recurrent pancreatitis with 12 kg weight loss. She was otherwise well, was not on any regular medication and did not drink alcohol. Before transfer, a CT scan had been reported as showing a cystic mass in the head of the pancreas. Endoscopic retrograde cholangiopancreatography revealed a ‘mucosal bulge’ in the duodenum with normal delineation of the biliary tree. On repeat CT scanning the cystic mass was unchanged (Figure 1a). The pancreas was oedematous. When her pancreatitis recurred, with raised serum amylase, alkaline phosphatase, alanine aminotransferase, gammaglutamyl transferase and bilirubin, a further CT scan revealed, in addition to the cystic mass, dilatation of the extrahepatic and intrahepatic biliary ducts. Laparotomy was decided on with the aim of draining the cyst and performing a cholecystectomy. At operation the gallbladder was seen to be dilated, with a swelling behind the first part of the duodenum which promptly disappeared after decompression of the common bile duct. After routine cholecystectomy the common bile duct was explored with a choledochoscope. No stones were identified. Her recovery was uncomplicated until postoperative day 21 when the symptoms of pancreatitis recurred, with increases in serum amylase, alkaline phosphatase, alanine aminotransferase, and gamma glutamyl transferase but normal bilirubin. A CT scan now showed a thick walled cystic lesion superior to the tail of the pancreas pushing into the lesser curvature of the stomach (Figure 1b). There was no cyst in the head of the pancreas. On gastroscopy a large mobile pedunculated polyp was seen in the fundus of the stomach, and a barium meal showed that the polyp was prolapsing into the duodenum (Figure 2). At repeat laparotomy the polyp, which was about 5 cm in diameter, was delivered and excised via a gastrotomy. It proved to be a benign cystic leiomyoma. Eighteen months later there had been no symptom recurrence and the lost weight had been regained.
THE BACTERIOLOGY OF IMPETIGO CONTAGIOSA
Authors: PAUL TACHAU
Journal: British Journal of Dermatology (1938)

Journal Article THE BACTERIOLOGY OF IMPETIGO CONTAGIOSA Get access PAUL TACHAU, M.D. PAUL TACHAU, M.D. Department of Dermatology, North‐Western University Medical School, Chicago, Dr. A. W. Stillians, Chicago, III Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology and Syphilis, Volume 50, Issue 3, 1 March 1938, Pages 113–118, https://doi.org/10.1111/j.1365-2133.1938.tb10511.x Published: 01 March 1938
Granulocyte Transfusion Therapy of Experimental Pseudomonas Pneumonia
Authors: David C. Dale, Herbert Y. Reynolds, James E. Pennington, Ronald J. Elin, Terry W. Pitts, Robert G. Graw
Journal: Journal of Clinical Investigation (1974)

Pseudomonas pneumonia was produced in dogs with radiation-induced leukopenia. Treatment of this infection with either gentamicin alone or gentamicin plus daily granulocyte transfusion was compared in a randomized controlled trail. The dogs receiving granulocytes plus gentamicin survived significantly longer than those treated with gentamicin alone (P < 0.05). The Pseudomonas immunotype which was inoculated into the dogs were recovered at autopsy from none of the granulocyte-transfused dogs, whereas seven or eight of the dogs treated with gentamicin alone had the inoculated Pseudomonas immunotype in the area of induced pneumonia at autopsy. As measured by the limulus test, the granulocyte-transfused dogs also did not have endotoxemia as frequently as the dogs given only gentamicin (P < 0.05). This controlled study establishes that transfused granulocytes can favorably alter the course of experimental Pseudomonas pneumonia and suggests that granulocyte transfusion may be a useful therapy in serious bacterial infections of leukopenic subjects.
Reproductive Medicine and Surgery
Authors: Irwin E. Thompson
Journal: JAMA (1995)

This is a massive new textbook of reproductive medicine, which will undoubtedly become one of the standard reference texts on the subject. There are 62 chapters organized into nine sections. The list of contributors is long and distinguished, and the subject matter of the chapters is completely comprehensive. Part 1, on reproductive physiology, has six excellent chapters on such basic science topics as molecular genetics, the hypothalamus, and implantation. Combined, they contain a wealth of new information on some of the most fundamental aspects of the specialty and establish an excellent basis for the next part, on reproductive cycle disorders. Here the chapters on hyperandrogenism and polycystic ovary syndrome are especially comprehensive, and a great deal of recent data is presented. Nonetheless, it is instructive that in the chapter on polycystic ovary syndrome the authors state that "establishing a strict definition of the syndrome is not possible nor advisable at
INTERSTITIAL BRONCHOPNEUMONIA
Authors: Douglas H. Sprunt, Donald S. Martin, Jarrett E. Williams
Journal: The Journal of Experimental Medicine (1935)

Pure cultures of Bordet-Gengou bacilli produce in rabbits an interstitial mononuclear pneumonia which cannot be differentiated from that occurring in children dying of pertussis or from lhat caused in animals by the viruses of epidemic influenza and psittacosis. A similar pneumonia can be produced in rabbits by typhoid bacilli.
Dietary Intervention and DEHP Reduction
Authors: Stephen P. Risotto
Journal: Environmental Health Perspectives (2011)

Environmental Health Perspectiveswas present in 59% of the patients; recurrent infections during childhood were common; 20% required amigdalectomy.One patient suffered rheumatic fever; one patient had not been effectively immunized after repeated hepatitis vaccines; and another had defective CD4 and suffered recurrent pneumo coccal infections.It would be surprising if these illnesses did not share a common root in the immune system.Schmidt (2011) underlined rising prevalence rates of auto immunity and dis cussed causes.I believe that this trend is rele vant in general to immune disorders because of different reactions within the same scope of lymphocyte dysfunction in response to our new aggressive environment.
The "Diuretic" Tc-99m HMPAO Leukocyte Scan
Authors: MAXINE E. BECK, ERIC K. LEPP, ALEXANDER A. WILKINSON
Journal: Clinical Nuclear Medicine (1991)

Two weeks following appendectomy for a gangrenous appendix, subsequent emergency cesarean section for fetal distress, and a third operation for the repair of an iatrogenic bladder rupture, a 30-year-old woman presented with persistent fever and right lower abdominal pain.