tbuckley/cabot-search huggingface dataset:
Long-Term Co-Cultures of Adult Human Hepatocytes with Rat Liver Epithelial Cells: Modulation of Albumin Secretion and Accumulation of Extracellular Material
Authors: Bruno Clement, Christiane Guguen-Guillouzo, Jean-Pierre Campion, Denise Glaise, Michel Bourel, Andre Guillouzo
Journal: Hepatology (1984)

High yields of viable human hepatocytes were obtained by enzymatic perfusion of the left hepatic lobe of kidney donors and cultured alone or with an epithelial cell line derived from rat liver. In conventional cultures, human hepatocytes did not survive more than 2 to 3 weeks and by Day 8 decreased their ability to secrete albumin. When co-cultured, they survived for more than 2 months and secreted high levels of albumin even in a serum-free medium. This long-term survival appeared to correlate with production of an extracellular material which is rich in Type III collagen. In vitro phenotypic alterations of parenchymal cells were reversed by addition of rat liver cells and were characterized by recovery of cuboidal morphology, increased albumin secretion and a shift from Type I to Type III collagen deposition. Rat liver epithelial cells could not be replaced by nonhepatic epithelial cells. These observations suggest that when adult human hepatocytes are maintained in a culture which closely resembles their in vivo environment, they are capable of continuing to actively express specific cell functions.
Are clinical trials in coronary heart disease oversold or undersold?
Authors: K M Detre, J Ware, N Mantel
Journal: Circulation (1981)

Randomized clinical trials constitute the formal experiments in therapeutics. Many such trials in coronary heart disease have terminated inconclusively or in controversy. In this editorial, we analyze some of the methodologic issues that may lead to controversy; the main reason for the low success rate may lie in insufficient understanding of the complex biology of the disease and in failure to select the appropriate models for therapy. We argue that these difficulties only strengthen the need for the rigorous experimental approach to the evaluation of therapies for coronary heart disease.
Family Planning Handbook for Doctors
Authors: T. Keith Edwards
Journal: JAMA (1981)

This paperback handbook is published by the International Planned Parenthood Federation (IPPF) primarily for use by its affiliated agencies in many countries throughout the world. The IPPF was founded in 1948 in Cheltenham, England, as the International Committee on Planned Parenthood. It is having a considerable impact on countries other than the United States, and gained consultative status with the Economic and Social Council of the United Nations in 1964. It later gained consultative status with the World Health Organization, UNICEF, and UNESCO. Perhaps the person associated with this agency best known to American physicians is Margaret Sanger, its first president.  This handbook is surprisingly expensive at $15 per copy, since it is subsidized by the IPPF; however, the book contains a notice that it will be given free of charge to those experiencing special difficulties in payment, such as currency restrictions. The worldwide need for such a handbook is
Psychiatre, médecin-traitant et malade
Authors: M. Burner
Journal: Psychotherapy and Psychosomatics (1972)

In the envisaged ambulatory situation, the psychiatrist appears as a consultant whom is interested by the psycho-dynamic and psycho-social aspects of the illness, of the patients and the medical practice. This, above all, takes place in the doctor-patient's relationship. In this prospect the psychiatrist does not possess any magical power of divination as often attributed to him. He must not succumb to the easy temptation of giving too much importance to his intervention by using his professional knowledge and scientific language which is often too hermetic. By giving his opinion and therapeutic advices he must enlighten the general practitioner on the personality structures and dynamical conflicts that can play a role in the evolution of an illness or a patient. The psychiatrist must not forget to bear in mind the physical aspect of the illness, because very often the psychological problem, even obvious, has to be put into the background. This implies a good knowledge of physical medicine as well as the pratice of a general practitioner. The consultant psychiatrist should have a psychoanalytical formation as well. Not for a traditional psychoanalysis but to enable him to appreciate the profound personality structure and the psychodynamical situation.
Progress in Late Results Among Pediatric Cardiac Surgery Patients
Authors: Alireza Raissadati, Heta Nieminen, Eero Jokinen, Heikki Sairanen
Journal: Circulation (2014)

Surgical treatment of congenital cardiac defects in Finland started >60 years ago. We analyzed the survival of all the pediatric cardiac surgery patients operated on before 2010.Data were obtained retrospectively from a pediatric cardiac surgery database. Patient status was received from the Finnish Population Registry. Survival was determined with the Kaplan-Meier method, and the survival rate was compared with a sex- and age-matched general population. Between 1953 and 2009, 13 876 cardiac operations were performed on 10 964 pediatric patients in Finland. Follow-up coverage was 98%. The 60-year survival for the entire study was 70% versus 86% for the general population. The number and proportion of severe cardiac defects increased in the 2000s. The long-term survival of patients with severe defects improved significantly across decades. For instance, the 22-year survival rate of patients with transposition of the great arteries operated on in 1953 to 1989 and in 1990 to 2009 improved from 71% to 93% (hazard ratio for death, 0.29; 95% confidence interval, 0.17-0.49; P<0.0001), respectively. The mean patient age at operation decreased from 8.9 to 2.2 years (95% confidence interval, 6.2-7.1; P<0.0001). The early mortality of patients decreased from a maximum of 7% in the 1970s to 3% in the 2000s (95% confidence interval, 0.05-0.08; P<0.0001).Patients are diagnosed and treated at an increasingly younger age. Advanced diagnostics, surgical methods, and postoperative intensive care have led to substantial improvements in both early and late results among pediatric cardiac surgery patients.
Handbook of Clinical Ultrasound
Authors: Donald L. King
Journal: JAMA (1979)

To Merriam-Webster a handbook is easily carried for ready reference.  This to me is not one to be purchased or carried lightly. It is an attempt to produce an encyclopedic overview of the burgeoning field of diagnostic ultrasound in a single volume. More than 90 contributors, some among the world's acknowledged authorities, have written chapters surveying their topic in varying degrees of detail. The book is divided into eight sections: basic principles, obstetrics and gynecology, internal medicine, cardiology, Doppler techniques, neurology, ophthalmology, and a miscellaneous section entitled head and orthopedics. These sections convey the broad scope of diagnostic ultrasound and are useful as a reference and starting point for the student. For the specialist in these various fields, the depth of coverage will be insufficient.  The book is intended to serve as a guide for the effective use of diagnostic ultrasound in the practice of clinical medicine. To that end
CB-16 * MALIGNANT GLIOMA WITH PRIMITIVE NEUROECTODERMAL COMPONENTS: CLINICAL AND PATHOLOGIC FEATURES OF FIVE CASES
Authors: S. G. Turner, S. A. Kazmi, T. Gergel, L. Belles, A. Whitmire, S. Horn, M. Lacroix, S. A. Toms
Journal: Neuro-Oncology (2014)

The classification of primary brain tumors poses many challenges. Glioblastoma multiforme (GBM), the most common primary adult primary brain tumor, is composed of cells of astrocytic origin exclusively and is characterized by infiltration of the brain parenchyma which makes surgical cure impossible. Though local radiation and chemotherapy are routinely employed to treat these aggressive tumors, they invariably progress with survival on the order of two years or less. Supratentorial primitive neuroectodermal tumors (sPNET) are histologically similar to medulloblastoma, composed of poorly differentiated neuroepithelial cells, and are typically found in children. Their response to chemotherapy is variable, but often better than GBM but poorer than medulloblastoma and CSF dissemination is common. Rarely, tumors with features of both malignant glioma and PNET occur which may arise from expansion of stem cell populations located within GBM. These mixed tumors pose not only a diagnostic challenge, but also a therapeutic challenge as GBM is typically treated with alkylating agents, such as Temozolomide, while PNETs are known to respond to platinum-based chemotherapy. We report a series of 5 patients with this rare mixed tumor. All patients underwent craniotomy and their clinical courses varied. CSF dissemination was seen in one patient. Their histologic features, radiographic presentation, and response to chemotherapy and to the Novocure-Tumor-Treating Fields is discussed.
Cytotoxicity of Paclitaxel in Breast Cancer Is due to Chromosome Missegregation on Multipolar Spindles
Authors: Lauren M. Zasadil, Kristen A. Andersen, Dabin Yeum, Gabrielle B. Rocque, Lee G. Wilke, Amye J. Tevaarwerk, Ronald T. Raines, Mark E. Burkard, Beth A. Weaver
Journal: Science Translational Medicine (2014)

The blockbuster chemotherapy drug paclitaxel is widely presumed to cause cell death in tumors as a consequence of mitotic arrest, as it does at concentrations routinely used in cell culture. However, we determine here that paclitaxel levels in primary breast tumors are well below those required to elicit sustained mitotic arrest. Instead, cells in these lower concentrations of drug proceed through mitosis without substantial delay and divide their chromosomes on multipolar spindles, resulting in chromosome missegregation and cell death. Consistent with these cell culture data, most mitotic cells in primary human breast cancers contain multipolar spindles after paclitaxel treatment. Contrary to the previous hypothesis, we find that mitotic arrest is dispensable for tumor regression in patients. These results demonstrate that mitotic arrest is not responsible for the efficacy of paclitaxel, which occurs because of chromosome missegregation on highly abnormal, multipolar spindles. This mechanistic insight may be used to improve selection of future antimitotic drugs and to identify a biomarker with which to select patients likely to benefit from paclitaxel.
New head of Colombia's drug regulator is told she can't have job after all
Authors: M. Jara
Journal: BMJ (2010)

The incoming head of Colombia’s National Drug and Food Institute has been told she can no longer have the job, despite overwhelming support for her appointment. Commentators have attributed the surprise move to pressure from the drug industry.

The president of Colombia, Juan Manuel Santos, announced on 7 August that Claudia Patricia Vacca Gonzalez, a well known pharmacist in the country and supporter of the rational use …
Chronic blockade of endothelin ETA receptors improves flow dependent dilation in resistance arteries of hypertensive rats
Authors: Marc Iglarz, Khalid Matrougui, Bernard I. Lévy, Daniel Henrion
Journal: Cardiovascular Research (1998)

Flow (shear stress)-induced dilation (FD) is attenuated in hypertension. Flow triggers the release by endothelial cells of dilators, such as NO or cyclo-oxygenase (COX) derivatives and constrictor factors such as endothelin-1 (ET-1) which might be involved in several cardiovascular diseases. We hypothesized that ET-1 might play a functional role in FD and participate in the endothelial dysfunction in hypertension.We investigated the effect of chronic treatment with the ETA receptor blocker LU135252 (50 mg/kg/day) for 2 weeks on the dilator response to flow in normotensive (Wistar-Kyoto; WKY) or hypertensive (SHR, n = 7 or 8 per group) rats.Systolic arterial pressure was not significantly affected by chronic ETA receptor blockade in both strains. In mesenteric resistance arteries (diameter: approximately 100 microns), isolated in vitro, FD was lower and myogenic tone higher in SHR than in WKY rats. Chronic ETA receptor blockade increased FD by 73% (7.5 +/- 1.5 to 13.0 +/- 2.7 microns dilation with a flow-rate of 150 microliters/min) in SHR (no effect in WKY). The participation of NO to FD was increased in SHR and the participation of dilator COX product(s) (blocked by indomethacin 10 mumol/l) to FD was significantly increased in SHR and in WKY. In control rats FD was improved by acute ETA receptor blockade in WKY rats (18.5 +/- 2.0 to 23.2 +/- 1.8 microns dilation to flow-rate of 150 microliters/min) and significantly more in SHR (6.0 +/- 1.8 to 15.1 +/- 1.6 microns). Acetylcholine-induced dilation was also improved by chronic ETA receptor blockade (no effect of an acute blockade). Myogenic and phenylephrine-induced tone were not affected by chronic or acute ETA receptor blockade. The improvement of endothelium-dependent dilation was not related to a change in blood pressure.Chronic ETA receptor blockade increased flow-induced dilation in SHR possibly by suppressing flow-induced ETA stimulation and by improving the release of dilator products by the endothelium.
PI3K/mTOR Inhibition Markedly Potentiates HDAC Inhibitor Activity in NHL Cells through BIM- and MCL-1–Dependent Mechanisms <i>In Vitro</i> and <i>In Vivo</i>
Authors: Mohamed Rahmani, Mandy Mayo Aust, Elisa C. Benson, LaShanale Wallace, Jonathan Friedberg, Steven Grant
Journal: Clinical Cancer Research (2014)

Abstract Purpose: The aim of this study is to explore the efficacy and define mechanisms of action of coadministration of the PI3K/mTOR inhibitor BEZ235 and pan-HDAC inhibitor panobinostat in diffuse large B-cell lymphoma (DLBCL) cells. Experimental Design: Various DLBCL cells were exposed to panobinostat and BEZ235 alone or together after which apoptosis and signaling/survival pathway perturbations were monitored by flow cytometry and Western blot analysis. Genetic strategies defined the functional significance of such changes, and xenograft mouse models were used to assess tumor growth and animal survival. Results: Panobinostat and BEZ235 interacted synergistically in ABC-, GC-, and double-hit DLBCL cells and MCL cells but not in normal CD34+ cells. Synergism was associated with pronounced AKT dephosphorylation, GSK3 dephosphorylation/activation, Mcl-1 downregulation, Bim upregulation, increased Bcl-2/Bcl-xL binding, diminished Bax/Bak binding to Bcl-2/Bcl-xL/Mcl-1, increased γH2A.X phosphorylation and histone H3/H4 acetylation, and abrogation of p21CIP1 induction. BEZ235/panobinostat lethality was not susceptible to stromal/microenvironmental forms of resistance. Genetic strategies confirmed significant functional roles for AKT inactivation, Mcl-1 downregulation, Bim upregulation, and Bax/Bak in synergism. Finally, coadministration of BEZ235 with panobinostat in immunocompromised mice bearing SU-DHL4–derived tumors significantly reduced tumor growth in association with similar signaling changes observed in vitro, and combined treatment increased animal survival compared with single agents. Conclusions: BEZ235/panobinostat exhibits potent anti-DLBCL activity, including in poor-prognosis ABC- and double-hit subtypes, but not in normal CD34+ cells. Synergism is most likely multifactorial, involving AKT inactivation/GSK3 activation, Bim upregulation, Mcl-1 downregulation, enhanced DNA damage, and is operative in vivo. Combined PI3K/mTOR and HDAC inhibition warrants further attention in DLBCL. Clin Cancer Res; 20(18); 4849–60. ©2014 AACR.
How to study dendrimers and dendriplexes III. Biodistribution, pharmacokinetics and toxicity in vivo
Authors: Dzmitry Shcharbin, Anna Janaszewska, Barbara Klajnert-Maculewicz, Barbara Ziemba, Volha Dzmitruk, Inessa Halets, Svetlana Loznikova, Natallia Shcharbina, Katarzyna Milowska, Maksim Ionov, Antos Shakhbazau, Maria Bryszewska
Journal: Journal of Controlled Release (2014)
The parathyroids, calcium and gastric secretion in man and the dog
Authors: J. T. Ward, A. O. Adesola, R. B. Welbourn
Journal: Gut (1964)

EDITORIAL SYNOPSIS The possible relationship between hyperparathyroidism and peptic ulcer has stimulated renewed interest in the relationship between calcium and gastric secretion.This study shows that in patients with primary hyperparathyroidism the basal secretion of acid was raised but the augmented histamine secretion was essentially normal.The basal secretion was lowered by parathyroidectomy.Studies in dogs shows a different pattern of gastric secretory response.A possible relationship between the parathyroid glands and gastric secretion was suggested nearly 50 years ago in experiments with innervated (Pavlov) gastric pouches.Keeton (1914) found that parathyroidectomy reduced secretion in the cat, and Rogers, Rahe, Fawcett, and Hackett (1915) observed that a crude extract of parathyroid tissue caused an increase in secretion in the dog.Several others have studied the problem from time to time, while today many are interested in it because of the recognition that peptic, and especially duodenal, ulceration is a frequent feature of both primary hyperparathyroidism and the syndrome of multiple endocrine adenopathy in man (Welbourn and Ward, 1962).Many conflicting observations have been reported in man and in several species of animals (Table I).In acute experiments injections of parathormone apparently increase the secretion of acid and of pepsin in man.In certain circumstances they do so in the dog also, but in other circumstances they either diminish secretion or do not influence it.Basal secretion of both acid and pepsin in the rat is diminished.The main difficulty with these studies is that commercial preparations of parathormone are toxic and it is very difficult to give repeated injections to maintain an animal in a state of chronic hyperparathyroidism.Those who have been most success- ful in doing so (Allen and Elliott, 1961) have found depressed secretion of acid and no effect on that of pepsin in the dog.The few studies of gastric secretion which have been made in human subjects with primary hyperparathyroidism do not reveal any consistent deviation from normal (Ostrow,
Three quarters of Russia's prisoners have serious diseases
Authors: J. Burgermeister
Journal: BMJ (2003)

Three quarters of prisoners in Russia have a serious disease such as tuberculosis and AIDS or another illness, the country's ministry of justice admitted last month.

About 74 000 prisoners are infected with tuberculosis, 36 000 are HIV positive, 26 000 have syphilis, and 1500 have hepatitis, said Alla Kusnezowa, deputy director of the ministry's department …
THE FLUOROSCOPE IN DIAGNOSIS OF ANEURISM.
Authors: G. R. GAGE
Journal: JAMA (1906)

<h3>History.</h3> —W. H., aged 29, married, gave a negative family history. For 12 or 13 years, until two months ago, his occupation had been that of a steam hammer driver. On an average of probably 5 times a day he would throw his weight on a heavy lever, alighting on the abdomen. He had never had any illness from the age of 14 to 24; he had been a hard drinker; was treated 8 years ago for specific trouble, which showed as a row of indurated ulcers, extending around the corona; this condition baffled his physicians for 10 months, but yielded immediately to the application of dry calomel. No suspicious symptom developed since. Eight years ago he noticed pain in his left hip and leg, which rapidly became very severe, compelling him to walk with a cane for the next four years, though not preventing him from attending to his
Psoriasis: an opportunity to identify cardiovascular risk
Authors: D.G. Federman, M. Shelling, S. Prodanovich, C.G. Gunderson, R.S. Kirsner
Journal: British Journal of Dermatology (2008)

Psoriasis is highly prevalent and is associated with skin-associated complaints as well as arthritis, depression and a lower quality of life. Recently, it has been demonstrated that not only do patients with psoriasis have an increased prevalence of cardiovascular risk factors, but an increased risk of myocardial infarction, and for those with severe disease, increased mortality. Dermatologists and other health professionals need to be cognizant of this association and ensure that cardiovascular risk factors are evaluated and treated appropriately in those patients with psoriasis. We review the association between psoriasis, atherosclerosis and inflammation, as well as some treatable cardiovascular risk factors that may prove beneficial in reducing a patient's cardiovascular risk.
P573Added diagnostic value of multiplex ligation-dependent probe amplification of plakophilin-2 in arrhythmogenic cardiomyopathy
Authors: E Lazzarini, I Rigato, JD Jongbloed, R Celeghin, M Cason, E Carturan, G Thiene, C Basso, K Pilichou, JP Van Tintelen
Journal: Cardiovascular Research (2014)

Background: Arrhythmogenic Cardiomyopathy (ACM) is an inherited myocardial disease characterized by fibro-fatty replacement of myocardium. Patients are at risk of ventricular arrhythmias and sudden death. Screening of desmosomal genes currently results in a diagnostic yield of about 50%. Aim: The aim of this study is to investigate whether detection of large deletions/duplications of the plakophilin-2 gene (PKP2) increase the yield of genetic screening in ACM. Methods: 60 index cases with a clinical diagnosis of ACM consecutively enrolled at our referral center underwent bidirectional sequencing using ABI-PRISM 3730 (Life Technologies) for all desmosomal-encoding genes. Genotype-negative patients were additionally screened for copy number variations (CNVs) in PKP2 by Multiplex Ligation-dependant Probe Amplification (MLPA) using SALSA MLPA kit P168 ARVC-PKP2 (MRC-Holland) and by quantitative Real-Time PCR on a Roche Light Cycler 480 platform. Results: Conventional sequencing of the ACM patients identified disease-causing nucleotide variants in 36 of the 60 ACM-patients (60%); 8% (n=5) of the cohort presented mutation in Desmoglein-2 gene, 23% (n=14) in Desmoplakin, 12% (n=7) in PKP2, 3% (n=2) in Desmocollin-2, 3% in Plakoglobin (n=2) whereas 10% (n=6) were multiple mutations carriers. MLPA analysis successfully identified a heterozygous deletion of exon 4 in an otherwise genotype-negative case, which was further confirmed by qPCR analysis showing a reduction of PKP2 copy number when compared to control samples. Conclusions: This study highlights the potential of increasing the diagnostic genetic yield - in our population by nearly 2% for just one gene- by searching CNVs in ACM patients. This will be also achieved by extending the analysis to all ACM disease-causing genes as well as to genotype-positive patients.