tbuckley/cabot-search huggingface dataset:
New therapies against HCV: Expected risks and challenges associated with their use in the liver transplant setting
Authors: Geoffrey W. McCaughan
Journal: Journal of Hepatology (2012)

Current approaches to anti-viral therapy (AVT) in the setting of liver transplantation are based on the use of pegylated interferon in combination with ribavirin (PegIFN/RBV). Attempts to clear HCV pretransplant have been successful in about 15–20% of the patients with genotype 1 infection and about 20–35% with genotype 3 [1,2] Such patients usually have relatively lower MELD scores (<18) than many other patients listed for transplant. Despite this AVT is associated with an increased risk of serious bacterial infections [3]. Sustained viral response (SVR) pretransplant is associated with lack of viral recurrence post-transplant [1,2] Early post-transplant AVT is not thought to be useful due to lack of efficacy and poor tolerability [4,5]. The commencement of AVT is usually considered at about the 12-month mark based on protocol biopsies. Patients with either F2 or F1 with significant portal inflammation (stage P to 2) are usually considered for AVT6.-8. SVRs in the range of 20–30% for patients with HCV genotype 1 (G1) and 40–50% for patients with HCV G3 are obtained [6–8]. SVR post-transplant has been linked to both donor and recipient IL28 polymorphisms [9–11]. Achievement of SVR in the post-transplant setting is associated with improved survival compared to patients who do not achieve an SVR [6–8]. Given the importance of viral clearance in the pre and posttransplant setting, such results have been thought to be somewhat unsatisfactory and the liver transplant community has been eagerly awaiting new anti-HCV therapies.
Mental health, job satisfaction, and job stress among general practitioners.
Authors: C. L. Cooper, U. Rout, B. Faragher
Journal: BMJ (1989)

OBJECTIVE--To identify sources of job stress associated with high levels of job dissatisfaction and negative mental wellbeing among general practitioners in England. DESIGN--Multivariate analysis of large database of general practitioners compiled from results of confidential questionnaire survey. Data obtained on independent variables of job stress, demographic factors, and personality. Dependent variables were mental health, job satisfaction, alcohol consumption, and smoking. SETTING--National sample of general practitioners studied by university department of organisational psychology. SUBJECTS--One thousand eight hundred seventeen general practitioners selected at random by 20 family practitioner committees in England. INTERVENTIONS--None. END POINT--Determination of the combination of independent variables that were predictive of mental health and job satisfaction. MEASUREMENTS AND MAIN RESULTS--Women general practitioners both had job satisfaction and showed positive signs of mental wellbeing in contrast with other normative groups. Conversely, male doctors showed significantly higher anxiety scores than the norms, had less job satisfaction, and drank more alcohol than their women counterparts. Multivariate analysis disclosed four job stressors that were predictive of high levels of job dissatisfaction and lack of mental wellbeing; these were demands of the job and patients9 expectations, interference with family life, constant interruptions at work and home, and practice administration. CONCLUSIONS--There may be substantial benefit in providing a counselling service for general practitioners and other health care workers who suffer psychological pressure from their work.
Rates of Treated and Untreated Kidney Failure in Older vs Younger Adults
Authors: Brenda R. Hemmelgarn, Matthew T. James, Braden J. Manns, Ann M. O’Hare, Paul Muntner, Pietro Ravani, Robert R. Quinn, Tanvir Chowdhury Turin, Zhi Tan, Marcello Tonelli, for the Alberta Kidney Disease Network
Journal: JAMA (2012)

<h3>Context</h3>Studies of kidney failure in older adults have focused on receipt of dialysis, which may underestimate the burden of disease if older people are less likely to receive treatment.<h3>Objective</h3>To determine the extent to which age is associated with the likelihood of treatment of kidney failure.<h3>Design, Setting, and Participants</h3>Community-based cohort study of 1 816 824 adults in Alberta, Canada, who had outpatient estimated glomerular filtration rate (eGFR) measured between May 1, 2002, and March 31, 2008, with a baseline eGFR of 15 mL/min/1.73 m<sup>2</sup> or higher and who did not require renal replacement therapy at baseline. Age was categorized as 18 to 44, 45 to 54, 55 to 64, 65 to 74, 75 to 84, and 85 or more years and eGFR as 90 or higher, 60 to 89, 45 to 59, 30 to 44, and 15 to 29 mL/min/1.73 m<sup>2</sup>.<h3>Main Outcome Measures</h3>Adjusted rates of treated kidney failure (receipt of dialysis or kidney transplantation), untreated kidney failure (progression to eGFR &lt;15 mL/min/1.73 m<sup>2</sup> without renal replacement therapy), and death.<h3>Results</h3>During a median follow-up of 4.4 years, 97 451 (5.36%) died, 3295 (0.18%) developed kidney failure that was treated and 3116 (0.17%) developed kidney failure that went untreated. Within each eGFR stratum the rate of treated kidney failure was higher in younger compared with older people. For example, in the lowest eGFR stratum (15-29 mL/min/1.73 m<sup>2</sup>), adjusted rates of treated kidney failure were more than 10-fold higher among the youngest (18-44 years) compared with the oldest (≥85 years) groups (adjusted rate, 24.00 [95% CI, 14.78-38.97] vs 1.53 [95% CI, 0.59-3.99] per 1000 person-years, respectively; P &lt; .001). Rates of untreated kidney failure were consistently higher at older ages. In the eGFR stratum of 15 to 29 mL/min/1.73 m<sup>2</sup>, adjusted rates of untreated kidney failure were more than 5-fold higher among the oldest (≥85 years), compared with the youngest (18-44 years) groups (adjusted rate, 19.95 [95% CI, 15.79-25.19] vs 3.53 [95% CI, 1.56-8.01] per 1000 person-years, respectively; P &lt; .001). Rates of kidney failure overall (treated and untreated combined) demonstrated less variation across age groups; eg, the adjusted rate per 1000 person years for those with eGFR of 15-29 mL/min/1.73 m<sup>2</sup> was 36.45 (95% CI, 24.46-54.32) among participants aged 18 to 44 years and 20.19 (95% CI, 15.27-26.69) among those aged 85 years or older (P = .01).<h3>Conclusion</h3>In Alberta, Canada, rates of untreated kidney failure are significantly higher in older compared with younger individuals.
Acidemia and hypernatremia enhance postischemic recovery of excitation-contraction coupling.
Authors: K Harada, A Franklin, R G Johnson, W Grossman, J P Morgan
Journal: Circulation Research (1994)

The purpose of the present study was to determine whether Na(+)-H+ and Na(+)-Ca2+ exchanges modulate postischemic recovery of excitation-contraction coupling. Experiments were performed in 43 isolated isovolumic dog hearts perfused with blood (pH 7.40, 141 mmol/L Na+, 34 degrees C, paced at 2 Hz). A 3 x 3-mm region at the left ventricular (LV) apex was loaded with aequorin for monitoring [Ca2+]i simultaneously with LV pressure. No-flow ischemia for 2 to 3 minutes was followed by 20 minutes of aerobic reperfusion with (1) unmodified control blood (141 mmol/L Na+, pH 7.40), (2) acidemic blood (141 mmol/L Na+, pH 6.60, at 0 to 3 minutes of reperfusion), (3) hypernatremic blood (149 or 157 mmol/L Na+, pH 7.40, at 0 to 20 minutes of reperfusion), or (4) hyperosmotic blood (141 mmol/L Na+ + 30 mmol/L mannitol, pH 7.40, at 0 to 20 minutes of reperfusion). Reperfusion with unmodified control blood was immediately followed by an increase in [Ca2+]i and LV systolic and diastolic pressure that persisted for 2 to 3 minutes before returning to or below baseline. Ventricular arrhythmia occurred during this period (&gt; 80%). This transient increase of [Ca2+]i was attenuated by acidemic or hypernatremic perfusate. With acidemic or hypernatremic reperfusion, recovery of LV developed pressure at 20 minutes was more complete than with unmodified control reperfusion: acidemic blood (n = 7), 93 +/- 3% (P &lt; .01); hypernatremic blood (149 mmol/L Na+, n = 7), 89 +/- 2% (P &lt; .02); hypernatremic blood (157 mmol/L Na+, n = 4), 91 +/- 2% (P &lt; .01); and unmodified control blood (n = 17), 80 +/- 2%. With hyperosmotic reperfusion, recovery of LV developed pressure at 20 minutes was not improved (82 +/- 3%). From these results we conclude that (1) an increase in intracellular Ca2+ occurs transiently after no-flow ischemia and may cause arrhythmia and decreased Ca2+ responsiveness of the contractile elements, (2) acidemic and hypernatremic reperfusion ameliorates postischemic dysfunction by preventing the increase in intracellular Ca2+, suggesting that (3) Na(+)-H+ and Na(+)-Ca2+ exchange may play important modulatory roles during reperfusion.
Cruelty as by-product of ritualisation of intraspecific aggression in cultural evolution
Authors: Ralf-Peter Behrendt
Journal: Behavioral and Brain Sciences (2006)

There are few commonalities between intraspecific aggression and predation and few convincing arguments for the conceptualisation of blood and pain as rewards for predation. Not cruelty, but ritualised intraspecific aggression is the predominant mechanism of accretion of social power and this, not cruelty, is what bestows reproductive advantages. Enjoyment of media cruelty is not reinforced by “emotional circuits” adapted to predation, but represents transient relief from culturally determined inhibition of aggression.
Psychological Assistance for the Dying Patient and His Family
Authors: T P Hackett
Journal: Annual Review of Medicine (1976)

Long the poor stepchild of both medicine and psychiatry, the study of dying has taken on new life and has even been dignified with a new name. Until this decade the term thanatology could be found only in an unabridged dictionary. Now there are departments of thanatology, a society of thanatology, and an ever-growing number of professionals who identify themselves as thanatologists. Most thanatolo­ gists are psychologists, social workers, social scientists, clergymen, and nurses. They are not especially well disposed toward physicians. Doctors, since the advent of modern medicine, have been far more concerned with curing than with caring for the incurable. This focus has yielded obvious benefits for the patients who can now be cured, but the concomitant negligence with respect to the process of dying and its problems cannot be overlooked. Many physicians have attempted to excuse their negligence by accepting as fact many myths about the dying  Examples are easy to find: People do not want to be told they are dying. Such information can only depress the patient. My duty stops with telling the next of kin. I believe the job of telling and comforting belongs to the clergy. To tell the person he is dying is to deprive him of hope. There is some truth in each of these statements. They appear logical. They possess an enormous appeal for the harried physician because they rationalize the natural tendency of the doctor to avoid being a messenger of despair. If such myths are questioned, the doctor's life becomes gravely complicated. He has no training to prepare him to help a person die. Until very recently, no courses on dying were offered in medical schools and no provision for dealing with this subject was included in any program for training residents. Doctors, who see more of death than anyone save the undertakers, have been taught how to pronounce the patient dead, but not how to ease the psychologi­ cal distress of dying.
Army Medical Service.
Authors: Geo. M. Sternberg
Journal: JAMA (1899)

War Department: Surgeon-General's Office, Washington, D. C., May 22, 1899. <h3>To the Editor:</h3> —Your editorial note relating to "The Army Medical Service" (SeeJournal, May 20, p 1123) indicates that a misapprehension exists with reference to the appointment of medical officers in the army, and I consider it my duty to correct this at the earliest possible moment. Appointments in the regular army are made entirely on the recommendation of army medical boards convened for the purpose of examining the candidates who present themselves, and neither political nor personal influence has any weight in these appointments. Regimental surgeons of volunteer regiments under existing laws are appointed by governors of States, and neither the secretary of war nor the surgeon-general of the army has anything to do with these appointments. Division and brigade surgeons of volunteers, and the medical officers of the so-called immune regiments, have been appointed by the President
308. In Vivo Enhancement of HSV-TK/GCV Cancer Gene Therapy with Polyamine Biosynthesis Inhibition
Authors: Tiina Wahlfors, Anne Karppinen, Juhani Jänne, Leena Alhonen, Jarmo Wahlfors
Journal: Molecular Therapy (2005)

We have earlier demonstrated that inhibition of polyamine biosynthesis with difluoromethylornithine (DFMO, irreversible inhibitor of ornithine decarboxylase) can be used to enhance the cytotoxicity of HSV-TK/ganciclovir gene therapy in rat and human cancer cell lines (Pasanen et al, 2003, Int. J. Cancer 104, 380-388). Our results revealed that inhibition of cell cycle progression was the key feature of the DFMO action. Furthermore, timing of DFMO treatment and HSV-TK/GCV gene therapy appeared to be critical to the synergistic effect. These two cancer treatment modalities are clinically relevant, but the cell culture studies need to be followed by animal experiments in order to determine the true value of the treatment combination.
Acute Calcific Tendinitis
Authors: Jonathan D Wiper, Anselmo Garrido
Journal: New England Journal of Medicine (2008)

A 56-year-old woman presented to the emergency department with a 3-day history of severe pain in and loss of movement of her right index finger. She reported that for the previous 2 months, she had noted a small, tender lump, with no progression in size, near the finger joint. Marked palmar erythema and a tender, firm swelling overlying the index metacarpophalangeal joint were noted (Panel A). Initially, a flexor-sheath infection was suspected, and antibiotics were administered. However, radiography showed a calcified mass within the flexor digitorum tendon (Panel B, arrow), and calcific tendinitis was diagnosed. Calcific tendinitis may be an . . .
Datasheet at odds with government guidelines..
Authors: P R A Taylor, M R Howard
Journal: BMJ (1994)

<h3>Abstract</h3> Mitochondrial dysfunction has been implicated as a key player in the pathogenesis of Parkinson’s disease (PD). The MitoPark mouse, a transgenic mitochondrial impairment model developed by specific inactivation of TFAM in dopaminergic neurons, spontaneously exhibits progressive motor deficits and neurodegeneration, recapitulating several features of PD. Since non-motor symptoms are now recognized as important features of the prodromal stage of PD, we monitored the clinically relevant motor and nonmotor symptoms from ages 8-24 wks in MitoPark mice and their littermate controls. As expected, motor deficits in MitoPark mice began around 12-14 wks and became severe by 16-24 wks. Interestingly, male MitoPark mice showed spatial memory deficits before female mice, beginning at 8 wks and becoming most severe at 16 wks, as determined by Morris water maze. When compared to age-matched control mice, MitoPark mice exhibited olfactory deficits in novel and social scent tests as early as 10-12 wks. MitoPark mice between 16-24 wks spent more time immobile in forced swim and tail suspension tests, and made fewer entries into open arms of the elevated plus maze, indicating a depressive and anxiety-like phenotype, respectively. Importantly, depressive behavior as determined by immobility in forced swim test was reversible by antidepressant treatment with desipramine. Collectively, our results indicate that MitoPark mice progressively exhibit deficits in cognitive learning and memory, olfactory discrimination, and anxiety-and depression-like behaviors. Thus, MitoPark mice can serve as an invaluable model for studying motor and non-motor symptoms in addition to studying pathology in PD.
Evaluation of a peer led parenting intervention for disruptive behaviour problems in children: community based randomised controlled trial
Authors: C. Day, D. Michelson, S. Thomson, C. Penney, L. Draper
Journal: BMJ (2012)

<b>Objective</b> To evaluate the effectiveness of a peer led parenting intervention delivered to socially disadvantaged families. <b>Design</b> Randomised controlled trial. <b>Setting</b> Schools and children’s centres in a socially deprived borough of inner London. <b>Participants</b> Parental caregivers seeking help with managing the problem behaviours of 116 index children, aged 2-11 years; 59 families were randomised to the intervention and 57 to a waitlist control condition. <b>Intervention</b> Empowering parents, empowering communities is an eight week (two hours each week), manualised programme delivered to groups of parents by trained peer facilitators from the local community. <b>Main outcome measures</b> Child problems (number and severity), parental stress, and parenting competencies were assessed before and after the intervention using standardised parent reported measures. <b>Results</b> Significantly greater improvements in positive parenting practices and child problems were observed in the intervention group compared with the waitlist group, with no difference in parental stress between the groups. An intention to treat analysis for the primary outcome measure, the intensity subscale of the Eyberg child behaviour inventory, showed an intervention effect size of 0.38 (95% confidence interval 0.01 to 0.75, P=0.01). The intervention group had high rates of treatment retention (91.5%) and user satisfaction. <b>Conclusion</b> The peer led parenting intervention significantly reduced child behaviour problems and improved parenting competencies. This is a promising method for providing effective and acceptable parenting support to families considered hard to reach by mainstream services. <b>Trial registration</b> Current Controlled Trials ISRCTN01962337.
Estriol, the Forgotten Estrogen?
Authors: Alvin H. Follingstad
Journal: JAMA (1978)

THERE is a definite need for a safe estrogen supplement for women who are at risk of breast or endometrial carcinoma but who are denied such therapy because of recent evidence that exogenous estrogen can induce carcinoma in susceptible women. The role of supplemental estrogen in the induction of carcinoma is controversial, but the consensus is that high risk contraindicates its use. 1   Risk Factors  Who are the women considered to be at risk? A list of risk factors in approximate descending order of importance would be as follows: (1) previous carcinoma of breast or endometrium, with apparent long-term cures or better stated, arrests, (2) designated precancerous lesions combined with a strong family history of carcinoma of the breast, (3) breast-biopsy findings of a precancerous lesion such as ductal proliferation and cellular atypia, (4) mammography findings of increased density and asymmetrical density, prominent ductal pattern, diffuse punctate calcifications, and other
Autoantibodies to Platelet Glycoprotein IIb/IIIa and to the Acetylcholine Receptor in a Patient with Chronic Idiopathic Thrombocytopenic Purpura and Myasthenia Gravis
Authors: MICHAEL J. ANDERSON
Journal: Annals of Internal Medicine (1984)

The coexistence of chronic idiopathic thrombocytopenic purpura and myasthenia gravis has been infrequently reported. We report another case and show the coexistence of autoantibodies to the platelet glycoprotein IIb and IIIa complex and the acetylcholine receptor. Autoantibody levels were followed during 8 weeks of treatment with cyclophosphamide, vincristine, and prednisone; the concentration of both autoantibodies fell during treatment but without measureable clinical improvement.
Traffic-Related Air Pollution, Oxidative Stress Genes, and Asthma (ECHRS)
Authors: Francesc Castro-Giner, Nino Künzli, Bénédicte Jacquemin, Bertil Forsberg, Rafael de Cid, Jordi Sunyer, Deborah Jarvis, David Briggs, Danielle Vienneau, Dan Norback, Juan R. González, Stefano Guerra, Christer Janson, Josep-Maria Antó, Matthias Wjst, Joachim Heinrich, Xavier Estivill, Manolis Kogevinas
Journal: Environmental Health Perspectives (2009)

Traffic-related air pollution is related with asthma, and this association may be modified by genetic factors.We investigated the role of genetic polymorphisms potentially modifying the association between home outdoor levels of modeled nitrogen dioxide and asthma.Adults from 13 cities of the second European Community Respiratory Health Survey (ECRHS II) were included (n = 2,920), for whom both DNA and outdoor NO(2) estimates were available. Home addresses were geocoded and linked to modeled outdoor NO(2) estimates, as a marker of local traffic-related pollution. We examined asthma prevalence and evaluated polymorphisms in genes involved in oxidative stress pathways [gluthatione S-transferases M1 (GSTM1), T1 (GSTT1), and P1 (GSTP1) and NAD(P)H:quinine oxidoreductase (NQO1)], inflammatory response [tumor necrosis factor alpha (TNFA)], immunologic response [Toll-like receptor 4 (TLR4)], and airway reactivity [adrenergic receptor beta2 (ADRB2)].The association between modeled NO(2) and asthma prevalence was significant for carriers of the most common genotypes of NQO1 rs2917666 [odds ratio (OR) = 1.54; 95% confidence interval (CI), 1.10-2.24], TNFA rs2844484 (OR = 2.02; 95% CI, 1.30-3.27). For new-onset asthma, the effect of NO(2) was significant for the most common genotype of NQO1 rs2917666 (OR = 1.52; 95% CI, 1.09-2.16). A significant interaction was found between NQO1 rs2917666 and NO(2) for asthma prevalence (p = 0.02) and new-onset asthma (p = 0.04).Genetic polymorphisms in the NQO1 gene are related to asthma susceptibility among persons exposed to local traffic-related air pollution. This points to the importance of antioxidant pathways in the protection against the effects of air pollution on asthma.
Relative risks of chronic kidney disease for mortality and end-stage renal disease across races are similar
Authors: Chi Pang Wen, Kunihiro Matsushita, Josef Coresh, Kunitoshi Iseki, Muhammad Islam, Ronit Katz, William McClellan, Carmen A. Peralta, HaiYan Wang, Dick de Zeeuw, Brad C. Astor, Ron T. Gansevoort, Andrew S. Levey, Adeera Levin
Journal: Kidney International (2014)
INCREASING HIV-2-ASSOCIATED AIDS IN SENEGAL
Authors: Bernard Le Guenno, Pierre Jean, Michel Peghini, Philippe Griffet, Pierre Seignot, Pierre Barabe, MamadouDiakhite Ball, Alain Montalegre, Babacar N'Diaye, Michel Guiraud, Michel Arborio, Alain Jouan, JeanLouis Sarthou
Journal: The Lancet (1987)