tbuckley/cabot-search huggingface dataset:
Mitogen-activated protein kinase activation in hepatocyte growth factor-stimulated rat hepatocytes: Involvement of protein tyrosine kinase and protein kinase C
Authors: T Adachi, S Nakashima, S Saji, T Nakamura, Y Nozawa
Journal: Hepatology (1996)

Hepatocyte growth factor (HGF) stimulated mitogen-activated protein (MAP) kinases and MAP kinase kinase in primary cultured rat hepatocytes. Inhibitors for protein kinase C (PKC), Ro31-8425, H-7, and calphostin C, reduced HGF-induced MAP kinase activity. A PKC activator, phorbol myristate acetate (PMA), induced MAP kinase activation in a concentration-dependent manner. Protein tyrosine kinase (PTK) inhibitors, genistein, and ST638 also inhibited HGF-induced MAP kinase activation. Furthermore, HGF increased formation of Ras guanosine triphosphate (GTP) complex, indicating Ras activation. Genistein inhibited HGF-induced Ras activation, but Ro31-8425 was without effect. On the other hand, Ro31-8425 decreased HGF-induced [ 3 H]arachidonic acid (AA) release and [ 3 H]thymidine incorporation. Genistein also prevented [ 3 H]AA release and [ 3 H]-thymidine incorporation. Moreover, a commonly used phospholipase A2 (PLA2) inhibitor, quinacrine, decreased HGF- induced [ 3 H]AA release and [ 3 H]thymidine incorporation. The inhibitory profile of [ 3 H]AA release was well correlated with that of [ 3 H]thymidine incorporation in Ro31-8425-, genistein-, and quinacrine- treated cells. A cyclooxygenase inhibitor, indomethacin, which suppressed HGF-induced DNA synthesis, had minimal effect on MAP kinase activation. In contrast, prostaglandin (PG) E1, E2, or F 2α , which stimulate [ 3 H]thymidine incorporation to the same level as that caused by HGF in hepatocytes, caused very weak activation of MAP kinases. These results suggest that PTK, Ras, and PKC play roles in MAP kinase activation induced by HGF and that MAP kinase activation resulting in AA release is involved in DNA synthesis in rat hepatocytes.
Acute Fasciola hepatica infection attributed to chewing khat
Authors: A CATS
Journal: Gut (2000)

Background —Fascioliasis is a parasitic infection, primarily of the liver but after several weeks the biliary tract may also be affected, related to the trematode Fasciola hepatica. The trematode is distributed worldwide in herbivores but is unusual in humans. Several outbreaks have been attributed to consumption of contaminated watercress and water. The optimal treatment of fascioliasis, particularly the acute form, is still unknown. We describe a patient with an acute Fasciola hepatica infection following a rare transmission route, who was successfully treated with a simple and safe drug regimen.

Case report —A 36 year old previously healthy Somalian man was admitted to our department with a one week history of right hypochondrial pain. The pain resolved spontaneously within three days. He had come to live in the Netherlands in 1986, and since then had only visited Saudi Arabia for …
Quantitative characteristics of the Feyrter (APUD) cells of the neonatal rabbit lung in normoxia and chronic hypoxia.
Authors: A Hernandez-Vasquez, J A Will, W B Quay
Journal: Thorax (1977)

Our studies show that the apparent number of Feyrter cells in the lung declines during the neonatal period in normoxic rabbits, and that in hypoxic animals a uniformly and significantly lower number of cells occurs as compared with the normoxic rabbits. There is some indication of degranulation of cells in the hypoxic groups. It is suggested that environmental and/or physiological factors associated with the start of extrauterine life, or lung development, may affect the apparent number and probable level of activity of these cells. These changes seem to be enhanced by hypoxia. Mast cells are scarce, and Feyrter cells are relatively more numerous along the airways. These cell types could possibly represent storage sites for 5-hydroxytryptamine, as suggested also by other investigators. Intraepithelial nerve fibres in bronchi and bronchioles were found but they were not limited to innervations of Feyrter cells or related cell bodies.
MPs criticise lack of evidence in government's health inequality strategy
Authors: J. Wise
Journal: BMJ (2009)

MPs have criticised the government for introducing policies to tackle health inequalities in the NHS in England without good evidence to support them and with inadequate evaluation.

The health select committee warned in a report published this week, “All too often governments rush in with insufficient thought, do not collect adequate data at the beginning about the health of the population which will be affected by the policies, do not have clear objectives, make numerous changes to the policies and its objectives and do not maintain the policy long enough to know whether it has worked.”

The chairman of the committee, Kevin Barron MP, said, “Far more must be done to ensure money injected into implementing these policies is tracked, and policy design must be sufficiently improved so that effective and accurate evaluation can take …
Bone mineral density in coeliac disease.
Authors: J R Walters
Journal: Gut (1994)

<h3>Abstract</h3> Summary statistics from genome-wide association studies (GWAS) have facilitated the development of various summary data-based methods, which typically require a reference sample for linkage disequilibrium (LD) estimation. Analyses using these methods may be biased by errors in GWAS summary data and heterogeneity between GWAS and LD reference. Here we propose a quality control method, DENTIST, that leverages LD among genetic variants to detect and eliminate errors in GWAS or LD reference and heterogeneity between the two. Through simulations, we demonstrate that DENTIST substantially reduces false-positive rate (FPR) in detecting secondary signals in the summary-data-based conditional and joint (COJO) association analysis, especially for imputed rare variants (FPR reduced from &gt;28% to &lt;2% in the presence of ancestral difference between GWAS and LD reference). We further show that DENTIST can improve other summary-data-based analyses such as LD score regression analysis, and integrative analysis of GWAS and expression quantitative trait locus data.
Metabolic alkalosis and hyperlactataemia.
Authors: R H Neary, J D Edwards
Journal: BMJ (1987)

Metabolic alkalosis and hyperlactataemiaWe describe a case of metabolic alkalosis associated with a severe hyper- lactataemia. Case reportA 61 year old woman was admitted with a 10 day history of vomiting.She had suffered from flatulence and abdominal discomfort for several years.Magnesium trisilicate had been her only medication.On examination she was salt depleted and hypotensive, supine blood pressure was 90/50 mm Hg and pulse 80 beats/min, and obvious signs ofpyloric stenosis were present.There was no clinical or radiological evidence of chronic lung disease.Laboratory results on admission were: haemoglobin concentration 80 g/l; packed cell volume 0-29; mean corpuscular volume 68 fl; white cell count 163x109/1; albumin concentration 40 g/l; total protein 76 g/l; bilirubin
Left ventricular disstolic function in hypertensive patients with ecg determined left ventricular hypertrophy: the LIFE study
Authors: K. Wachtell, G. Smith, E. Gerdts, B. Dahiöt, M. Nieminen, V. Papademetriou, J.N. Bella, J. Rokkedal, R.B. Devereux
Journal: Journal of the American College of Cardiology (1998)
Calcified Intrahepatic Métastases from Carcinoma of the Breast
Authors: Mehdi Saghatoeslami
Journal: JAMA (1962)

INTRAHEPATIC CALCIFICATION occurs in association with a variety of diseases such as hepatomas, cavernous hemangiomas, intrahepatic calculi, hepatic infections or granulomas, and parasitic infestations such as echinococus cysts. Liver metastases from malignant diseases which may calcify are mainly from neuroblastomas or carcinomas of the sigmoid. The present report concerns a patient with numerous heavily calcified liver metastases from a primary breast carcinoma. Report of a Case A 38-year-old woman was admitted because of a tumor in the upper outer quadrant of her right breast.A frozensection diagnosis of cancer was made and a radical mastectomy was performed for an infiltrating ductal carcinoma. There was no demonstrable extension into the lymph nodes. Postoperative radiation therapy was not given. The patient remained asymptomatic for 28 months. She was then readmitted because of pain in both lower extremities. Her liver was not palpable at this time. X-ray examination of the pelvis revealed lytic métastases
Increased Expression of Annexin A3 Is a Mechanism of Platinum Resistance in Ovarian Cancer
Authors: Xuedong Yan, Jie Yin, Huiyu Yao, Ning Mao, Yili Yang, Lingya Pan
Journal: Cancer Research (2010)

Abstract Resistance to platinum drugs has emerged as a major obstacle in the treatment of ovarian cancers. Through proteomic analysis, we have found that the expression of annexin A3, a member of the Ca2+ and phospholipid-binding annexin family, is significantly increased in platinum-resistant ovarian cell lines. Anti–annexin A3 immunostaining indicated that cancers from platinum-resistant patients also possess higher levels of annexin A3 than those from platinum-sensitive patients. Although expression of annexin A3 made susceptible ovarian cancer cells more resistant to platinum, expression of antisense annexin A3 downregulated its expression and rendered the resistant cells more sensitive to platinum. In athymic mice, the growth of tumors from inoculated SKOV3 cells was inhibited by the administration of platinum, whereas tumors from annexin A3–expressing SKOV3/Ann were resistant to platinum treatment. Interestingly, the intracellular platinum concentration and platinum-DNA binding are significantly lower in annexin A3–overexpressing cells than those in parental cells. The lower cisplatin concentration was also accompanied by reduced induction of p53, which could be restored by downregulation of annexin A3. These results indicate that increased expression of annexin A3 is a mechanism of platinum resistance in ovarian cancer. It seems to act by preventing uptake or accumulation of platinum in cells. Therefore, it is conceivable that annexin A3 could be a target for therapeutic intervention and may also serve as a biomarker for drug resistance in ovarian cancer patients. Cancer Res; 70(4); 1616–24
Pellagra-like Dermatitis
Authors: Neda Ashourian, Nico Mousdicas
Journal: New England Journal of Medicine (2006)

Three months after undergoing Roux-en-Y bariatric surgery, a 32-year-old woman presented with glossitis, angular cheilitis, and an erythematous, desquamative dermatitis with a distribution indicative of photosensitivity causing a burning sensation on her arms and around her neck (Panel A). She reported a 45-kg (100-lb) weight loss during the past four months and no diarrhea or neurologic symptoms. Pellagra was suspected because of the classic appearance of Casal's necklace (i.e., erythema, hyperpigmentation, and scales around the neck) (Panel B). Laboratory studies were notable for a plasma pyridoxine level of 0.6 ng per milliliter (2.4 nmol per liter; normal range, 5 to . . .
Deciding whether to be a doctor.
Authors: A. H. York
Journal: BMJ (1992)

are not itemised and not for debate may drive person responsible for the preregistration year in address this issue and to plan prospective trials.industrial support elsewhere in Europe and to this medical school, I know that consultants are These trials will also incorporate regimens for other countries, concerned that some graduates have difficulty in planned prophylaxis and an appraisal of the inci- P GRIFFIN completing their year as a house officer.These dence of factor VIII antibodies.Concern has F 0 WELLS doctors' undergraduate records often show the been expressed that treatment with monoclonally Association of the British Pharmaceutical Industrv, signs of impending disaster.The arguments for derived high purity products is associated with an London SWIA 2DY~~~~~~~~~their continuing the course are as Kelly outlined; tncreased incidence of inhibitors.-D SWALES when they are challenged to account for their There remains the question whether highAssciaionof lincalProessrs f Mdicne B ANES poor performance they give many reasons, but purity factor VIII prevents down regulation of the Departmenit of Medicine, how seriously is their commitment to medicine immune system.Evidence of benefit continues to St George's Hospital, questioned?accumulate, as indicated recently by de Biasi et al.
Pulmonary Gallium Photopenia from Oligemia
Authors: ADEL G. MATTAR, A. RASHID DAR
Journal: Clinical Nuclear Medicine (1992)

In five patients with lung carcinoma, Ga-67 citrate scanning demonstrated focal lesions of increased uptake on one side of the chest associated with ipsilateral pulmonary photopenia, in contrast to the opposite lung. In three patients, the photopenia was generalized in the lung. Tc-99m MAA scanning showed a matching generalized decrease in perfusion, with the affected lung receiving 0%, 16%, and 36% of total pulmonary perfusion in these patients. In two patients, the decreased gallium activity was present in the upper lung zone. The perfusion lung scans showed correspondingly absent perfusion. No patient received radiation therapy before scanning. The authors postulate that the pulmonary gallium photopenia in these patients was caused by pulmonary oligemia. A literature search did not reveal similar cases. Recognition of this phenomenon should prevent a false interpretation of abnormally increased gallium activity elsewhere in the lungs.
Acute Sinusitis in Childhood
Authors: Gerald B. Healy
Journal: New England Journal of Medicine (1981)

Inflammation of the paranasal sinuses, as well as the complications of sinusitis, may present a difficult problem for the physician involved in the care of children. The nose and sinuses of a child differ greatly from those of an adult, both anatomically and developmentally.The maxillary sinus may measure only a few cubic millimeters in the neonate and often does not become clinically important until at least 18 to 24 months of age. The floor of the maxillary sinus is usually at the level of the attachment of the inferior turbinate in the neonate and gradually descends to the level . . .
Aggressive Langerhans cell histiocytosis following T‐ALL: Clonally related neoplasms with persistent expression of constitutively active NOTCH1
Authors: Scott J. Rodig, Ethan G. Payne, Barbara A. Degar, Barrett Rollins, Andrew L. Feldman, Elaine S. Jaffe, Arlene Androkites, Lewis B. Silverman, Janina A. Longtine, Jeffery L. Kutok, Mark D. Fleming, Jon C. Aster
Journal: American Journal of Hematology (2007)

Abstract Langerhans cell histiocytosis (LCH) and related entities are neoplasms of unknown pathogenesis. Here, we describe studies assessing the role of NOTCH1 mutations in LCH, which were based on a case of fatal Langerhans cell tumor after T‐cell acute lymphoblastic leukemia (T‐ALL). Although the two types of neoplasm in this patient were temporally and pathologically distinct, molecular analyses showed that they harbored the same T‐cell receptor gene rearrangements and two activating NOTCH1 mutations involving exons 27 and 34. The exon 27 mutation altered a conserved cysteine residue in the N‐terminal portion of the NOTCH1 heterodimerization domain, while the mutation in exon 34 introduced a premature stop codon that results in the deletion of C‐terminal negative regulatory PEST domain. Analysis of cDNA prepared from the aggressive Langerhans cell tumor showed that the NOTCH1 mutations were aligned in cis, a configuration that caused synergistic increases in NOTCH1 signal strength in reporter gene assays. Immunohistochemistry confirmed that the Langerhans cell tumor also expressed NOTCH1 protein. Although these data suggested that NOTCH1 mutations might contribute to the pathogenesis of typical sporadic LCH and related neoplasms occurring in the absence of T‐ALL, an analysis of 24 cases of LCH and Rosai–Dorfman Disease occurring in patients without an antecedent history of T‐ALL revealed no mutations. Thus, activating NOTCH1 mutations appear to be unique to aggressive Langerhans cell tumors occurring after T‐ALL. Persistent expression of NOTCH1 in such tumors suggests that Notch pathway inhibitors could have a role in the treatment of these unusual neoplasms. Am. J. Hematol., 2008. © 2007 Wiley‐Liss, Inc.
Correlation of In Vitro Drug-Sensitivity Testing Results With Response to Chemotherapy and Survival in Extensive-Stage Small Cell Lung Cancer: A Prospective Clinical Trial
Authors: A. F. Gazdar, S. M. Steinberg, E. K. Russell, R. I. Linnoila, H. K. Oie, B. C. Ghosh, J. D. Cotelingam, B. E. Johnson, J. D. Minna, D. C. Ihde
Journal: JNCI Journal of the National Cancer Institute (1990)

We devised a novel clinical protocol for extensive-stage small cell lung cancer (SCLC), selecting chemotherapy whenever possible on the basis of in vitro drug-sensitivity testing (DST) of individual patients' tumor specimens. Most of the specimens were obtained from metastatic sites during routine staging procedures. Increase of tumor cell number by culture in selective media usually was required before DST could be performed. We used the Weisenthal dye exclusion assay to place the seven drugs in rank order and to select the in vitro best regimen (IVBR), a three-drug combination of proved efficacy in SCLC. After initial staging and specimen acquisition, patients received etoposide and cisplatin (primary therapy) and were restaged after 12 weeks. Patients with partial or no responses and those relapsing after a complete response to primary therapy were switched to the IVBR if DST data were available. If DST data were unavailable, an empiric combination, vincristine-doxorubicin-cyclophosphamide, was administered as secondary therapy. Tumor-containing specimens were collected from 60 of the 80 patients, (75%). One or more cell lines were established from 28 patients, and DST data were available from 26 patients (33% of total). Several parameters of in vitro drug sensitivity were significantly associated (two-sided P ( P2 <.05) with clinical response to primary therapy and also with response to the IVBR and were marginally associated with length of survival (.07 ≤ P2 .08). Sixteen patients (23%) received their IVBR as secondary therapy, and four of these (25%) attained a complete response, compared with three of 43 (7%) who received an empiric regimen ( P2 =.16). We concluded that (a) selection of individualized chemotherapy is labor intensive but feasible in extensive-stage SCLC; (b) DST data are associated with clinical response to primary therapy and to secondary therapy with an IVBR; and (c) further observations will be required if we are to determine whether there is a modest therapeutic benefit to administering the IVBR as a secondary therapy. [J Natl Cancer Inst 82: 117–124, 1990]
Hemophagocytosis by small cell lung carcinoma
Authors: Yair Molad, Pinhas Stark, Miron Prokocimer, Henry Joshua, Jack Pinkhas, Yechezkel Sidi
Journal: American Journal of Hematology (1991)

Abstract A 60‐year‐old woman with disseminated small cell carcinoma of the lung and hemophagocytosis by the metastatic cells in the bone marrow is presented, it is the first clinicopathologic report on phagocytosis of erythrocytes by lung tumor cells in concordance with a recently described evidence of a macrophage origin of small cell carcinoma of the lung.
Single High-Dose Pyridoxine Treatment for Isoniazid Overdose
Authors: Suman Wason
Journal: JAMA (1981)

We treated five isoniazid-overdosed patients each with a single dose of pyridoxine hydrochloride equivalent to the gram amount of isoniazid ingested and compared their outcome with that of 41 patients from the literature who received little or no pyridoxine. Recurrent seizures occurred in 60% of patients who had received no pyridoxine vs 0% in our patients. Metabolic acidosis resolved in our cases but was refractory in the literature cases. In our cases, coma lightened more rapidly and was of shorter duration as compared with that in the literature cases (mean, seven hours vs 24 hours). No adverse effects of pyridoxine were seen in our patients. (<i>JAMA</i>1981;246:1102-1104)
Severe mehyprylon intoxication treated by hemodiaysis
Authors: J. M. Mandelbaum
Journal: JAMA (1971)

In a case of severe intoxication following the ingestion of 22.5 gm of methyprylon, 20% of the ingested dose was removed by gastric lavage. Rapid clinical improvement occurred with hemodialysis, during which the blood level of methyprylon fell from 20.9 to 3.0 mg/100 ml. An estimated minimum 20% of the absorbed dose was recovered in the hemodialysate, while less than 5% appeared in the urine during the first 24 hours of forced diuresis.
35 THE CURRENT ALLOCATION POLICY OF LIVER GRAFTS FROM HBCAB POSITIVE DONORS NEEDS TO BE IMPROVED: EVIDENCE FROM THE LIVER-MATCH COHORT STUDY
Authors: M. Angelico, T. Marianelli, U. Cillo, S. Fagiuoli, D. Prati, C. Gavrila, A. Nardi
Journal: Journal of Hepatology (2011)
Enhanced Ventilatory Response to Exercise in Patients With Chronic Heart Failure and Preserved Exercise Tolerance
Authors: Piotr Ponikowski, Darrel P. Francis, Massimo F. Piepoli, L. Ceri Davies, Tuan Peng Chua, Constantinos H. Davos, Viorel Florea, Waldemar Banasiak, Philip A. Poole-Wilson, Andrew J. S. Coats, Stefan D. Anker
Journal: Circulation (2001)

Background —In patients with chronic heart failure (CHF) and preserved exercise tolerance, the value of cardiopulmonary exercise testing for risk stratification is not known. Elevated slope of ventilatory response to exercise (V̇ e /V̇ co 2 ) predicts poor prognosis in advanced CHF. Derangement of cardiopulmonary reflexes may trigger exercise hyperpnea. We assessed the relationship between cardiopulmonary reflexes and V̇ e /V̇ co 2 and investigated the prognostic value of V̇ e /V̇ co 2 in CHF patients with preserved exercise tolerance. Methods and Results —Among 344 consecutive CHF patients, we identified 123 with preserved exercise capacity, defined as a peak oxygen consumption (peak V̇ o 2 ) ≥18 mL · kg −1 · min −1 (age 56 years; left ventricular ejection fraction 28%; peak V̇ o 2 23.5 mL · kg −1 · min −1 ). Hypoxic and hypercapnic chemosensitivity (n=38), heart rate variability (n=34), baroreflex sensitivity (n=20), and ergoreflex activity (n=20) were also assessed. We identified 40 patients (33%) with high V̇ e /V̇ co 2 (ie, &gt;34.0). During follow-up (49±22 months, &gt;3 years in all survivors), 34 patients died (3-year survival 81%). High V̇ e /V̇ co 2 (hazard ratio 4.3, P &lt;0.0001) but not peak V̇ o 2 ( P =0.7) predicted mortality. In patients with high V̇ e /V̇ co 2 , 3-year survival was 57%, compared with 93% in patients with normal V̇ e /V̇ co 2 ( P &lt;0.0001). Patients with high V̇ e /V̇ co 2 demonstrated impaired reflex control, as evidenced by augmented peripheral ( P =0.01) and central ( P =0.0006) chemosensitivity, depressed low-frequency component of heart rate variability ( P &lt;0.0001) and baroreflex sensitivity ( P =0.03), and overactive ergoreceptors ( P =0.003) compared with patients with normal V̇ e /V̇ co 2 . Conclusions —In CHF patients with preserved exercise capacity, enhanced ventilatory response to exercise is a simple marker of a widespread derangement of cardiovascular reflex control; it predicts poor prognosis, which peak V̇ o 2 does not.