tbuckley/cabot-search huggingface dataset:
Routine Screening: Informed Consent, Stigma and the Waning of HIV Exceptionalism
Authors: Matthew K. Wynia
Journal: The American Journal of Bioethics (2006)

The Centers for Disease Control and Prevention (CDC) recently recommended that HIV screening should become routine for all adults in the United States. Implicit in the CDC proposal is the notion that pre-test counseling would be more limited than at present, and that written informed consent to screening would no longer be required. If widely implemented, routine testing would mark a tremendous shift in the US HIV screening strategy. There are a number of considerations used to determine what screening tests should be routine, and HIV fits the bill in almost every regard. Yet the stigma associated with HIV infection remains, making the CDC's recommendation highly controversial. Will minimizing requirements for pre-test counseling and special written informed consent lead to unexpected or unwanted HIV testing, or do these stringent counseling and consent requirements needlessly scare people away? Will widespread and routine testing be associated with declining stigmatization, or will it drive some patients away from seeking desperately needed health care? These are high stakes questions, and we're about to find out the answers.
Clinical efficacy of lactulose in cirrhotic patients with and without subclinical hepatic encephalopathy
Authors: A Watanabe
Journal: Hepatology (1997)

Seventy-five cirrhotic patients with hyperammonemia in the past or at the time of the study were randomly divided into two groups (treated with lactulose or nontreated) in 14 hospitals in Japan. Thirty-six cirrhotic patients were diagnosed as having subclinical hepatic encephalopathy (SHE), and 39 were diagnosed as non-SHE. SHE was diagnosed when the results of all three of the quantitative psychometric tests used (number connection test, and symbol digit and block design tests of the Wechsler adult intelligence scale [revised]) were abnormal as compared with age-matched normal values. The mean number of abnormal psychometric test results and the prevalence of SHE were used for a quantitative evaluation of the efficacy of the lactulose treatment. Twenty-two of the SHE patients were treated with lactulose (45 mL/d) for 8 weeks, and the other 14 SHE patients did not receive lactulose. In the SHE patients administered lactulose, the results of the quantitative psychometric evaluation were significantly improved at 4 and 8 weeks after the beginning of the lactulose administration. The SHE had disappeared in 10 (50%) of the 20 treated patients at week 8, but it persisted in 11 (85%) of the untreated 13 patients. We concluded that lactulose treatment in cirrhotic patients with SHE is effective with respect to psychometric tests.
Lung volume measurements in wheezy infants: comparison of plethysmography and gas dilution
Authors: E Eber, B Steinbrugger, M Modl, E Weinhandl, MS Zach
Journal: European Respiratory Journal (1994)

The accuracy both of plethysmographic measurements of thoracic gas volume (TGV) and determinations of functional residual capacity (FRC) by gas dilution techniques in infants with obstructive lung disease is subject to continued dispute. We studied 25 wheezy infants and compared TGV derived from end-expiratory airway occlusions (TGVEE), corrected TGV after end-inspiratory airway occlusions (TGVEI), and FRC determined by nitrogen wash-out (FRCN2). Group mean TGVEE and TGVEI differed significantly (25.8 +/- 8.4 versus 24.6 +/- 7.1 ml.kg-1). TGVEE and FRCN2 did not differ significantly. TGVEE and TGVEI, as well as TGVEE and FRCN2, and TGVEI and FRCN2 data, respectively, showed lack of agreement. Based on 95% confidence intervals, calculated from TGVEE data, 14 of the 25 infants showed a significantly higher TGVEI than TGVEE; only one patient had a significantly lower TGVEI. Compared to FRCN1 data, TGVEE and TGVEI measurements yielded lower values in at least one third of our patients. The present study illustrates, that there is no gold standard for the measurement of lung volume in infants with airway obstruction.
Resistance to Granzyme B-mediated Cytochrome c Release in Bak-deficient Cells
Authors: Gui-Qiang Wang, Eva Wieckowski, Leslie A. Goldstein, Brian R. Gastman, Asaf Rabinovitz, Andrea Gambotto, Shuchen Li, Bingliang Fang, Xiao-Ming Yin, Hannah Rabinowich
Journal: The Journal of Experimental Medicine (2001)

Granzyme B (GrB), a serine protease with substrate specificity similar to the caspase family, is a major component of granule-mediated cytotoxicity of T lymphocytes. Although GrB can directly activate caspases, it induces apoptosis predominantly via Bid cleavage, mitochondrial outer membrane permeabilization, and cytochrome c release. To study the molecular regulators for GrB-mediated mitochondrial apoptotic events, we used a CTL-free cytotoxicity system, wherein target cells are treated with purified GrB and replication-deficient adenovirus (Ad). We report here that the Bcl-2 proapoptotic family member, Bak, plays a dominant role in GrB-mediated mitochondrial apoptotic events. A variant of Jurkat cells, deficient in Bak expression, was resistant to GrB/Ad-mediated apoptosis, as determined by lack of membranous phosphatidylserine exposure, lack of DNA breaks, lack of mitochondrial outer membrane permeabilization, and unchanged expression of inner mitochondrial membrane cardiolipin. The resistance of Bak-deficient cells to GrB/Ad cytotoxicity was reversed by transduction of the Bak gene into these cells. The requirement for both Bid and Bak, was further demonstrated in a cell-free system using purified mitochondria and S-100 cytosol. Purified mitochondria from Bid knockout mice, but not from Bax knockout mice, failed to release cytochrome c in response to autologous S-100 and GrB. Also, Bak-deficient mitochondria did not release cytochrome c in response to GrB-treated cytosol unless recombinant Bak protein was added. These results are the first to report a role for Bak in GrB-mediated mitochondrial apoptosis. This study demonstrates that GrB-cleaved Bid, which differs in size and site of cleavage from caspase-8-cleaved Bid, utilizes Bak for cytochrome c release, and therefore, suggests that deficiency in Bak may serve as a mechanism of immune evasion for tumor or viral infected cells.
Imipramine decreases oesophageal pain perception in human male volunteers
Authors: P L Peghini, P O Katz, D O Castell
Journal: Gut (1998)

Background —Visceral hyperalgesia is a hallmark of functional gastrointestinal disorders. Antidepressants improve symptoms in these patients, although their mode of action is unclear. Antidepressant, anticholinergic, and analgesic mechanisms have been proposed. Aims —To investigate whether imipramine, which has a visceral analgesic effect, increases pain thresholds to experimental visceral pain. Methods —Visceral perception for first sensation and pain was measured with intraoesophageal balloon distension in 15 male volunteers. The effect of imipramine was studied in a double blind, placebo controlled, crossover study. Imipramine was given in ascending doses for 12 days (25 mg days 1–3, 50 mg days 4–6, 75 mg days 7–12), with oesophageal perception studied on day 13. Results —Inflation volumes and intraballoon pressures at first sensation were not different between placebo and imipramine. Balloon inflation volume at pain threshold was higher on imipramine (p=0.015). Median intraballoon pressures were not different at pain threshold for placebo and imipramine. Oesophageal wall compliance was not affected by imipramine. Conclusion —Increased pain thresholds on imipramine in this group of normal male volunteers in the absence of changes in oesophageal tone imply the presence of a visceral analgesic effect.
Herbert E. Harding, FRCS
Authors: H. E. Robson
Journal: British Journal of Sports Medicine (1982)

A recent spell on the Executive Committee of the BASM leaves me with the view that the Organisation should be far more involved in producing some form of National Care Scheme for sportsmen.The proposed Scheme outlined by Peter Sperryn is a step forward, but will it be too complicated to work?I am myself, far more interested in providing a sports injury service at "grass-roots" level, and with this in mind, I am writing to ask any members of BASM, who live in the East Midlands regional area of the Sports Council to write to me if they are interested in convening a Meeting in order to set up a Regional Organisation for the exchange of practical ideas and experience which is specifically aimed at maintaining existing services and expanding these where possible.
Growth factor-mediated tumor cell proliferation in hairy cell leukemia.
Authors: R J Ford, L Yoshimura, J Morgan, J Quesada, R Montagna, A Maizel
Journal: The Journal of Experimental Medicine (1985)

Leukemic B cells from seven patients with hairy cell leukemia (HCL), six of which contained the Tac antigen, were assayed in vitro for growth factor-mediated cell proliferation. The HCL cells showed typical phenotypic profiles by monoclonal antibody analysis. The tumor cells, which do not grow spontaneously in vitro, were found to proliferate in all but one case in response to partially purified B cell growth factor (BCGF) without anti-mu or Sac activation. Recombinant interleukin 2 however produced only a marginal response and could not support leukemic cell growth in vitro. BCGF, however, did stimulate in vitro cell growth and supported the establishment of continuous (greater than 60 d in vitro) in four of the seven HCL cases.
Continuous Performance Test and Schizophrenia: A Test of Stimulus-Response Compatibility, Working Memory, Response Readiness, or None of the Above?
Authors: Brita Elvevåg, Daniel R. Weinberger, Jesse C. Suter, Terry E. Goldberg
Journal: American Journal of Psychiatry (2000)

Abnormalities of attention are considered the fundamental deficits in cognitive function manifested by patients with schizophrenia. The authors administered variations of two types of cognitive tasks to patients with schizophrenia (N=20) and normal comparison subjects (N=30) to test four possible cognitive mechanisms that might account for such abnormalities.Variations of the Continuous Performance Test were used to test the four mechanisms. Stimulus-response mapping was explored by comparing results on a task in which subjects were to make a response if the word "nine" was preceded by the word "one" with results on a task in which the required response was made explicit by the stimulus (the word "ready" followed by the word "press"). The building up of a prepotent response tendency was tested by manipulating the probability with which the cue and imperative stimulus appeared (17% or 50%). The amount of working memory required to maintain contextual information was tested by using different delay intervals (1000 msec and 3000 msec). The extent to which problems in vigilance might be attributable to problems in the "motoric" component of response readiness was operationalized by having subjects perform a secondary motor task concurrent with the attentional task.Patients with schizophrenia performed significantly worse than the normal comparison subjects on all tasks. However, none of the four manipulations of the Continuous Performance Test tasks had a differential impact on the patients' performance speed or accuracy. In contrast, there was a significant interaction of group, delay interval, and target probability in which patients made disproportionately more omission errors at short delay intervals and at low target probabilities.The findings may call into question the explanatory power of certain well-known contemporary mechanistic accounts of performance on the Continuous Performance Test in patients with schizophrenia. The findings suggest that a difficulty in rapidly encoding information (i.e., constructing a representation) in certain "unengaging" situations may be at the core of deficits on tasks associated with this attentional test.
Continuous Positive Airway Pressure Treatment Reduces Mortality in Patients with Ischemic Stroke and Obstructive Sleep Apnea
Authors: Miguel Ángel Martínez-García, Juan José Soler-Cataluña, Laura Ejarque-Martínez, Youssef Soriano, Pilar Román-Sánchez, Ferrán Barbé Illa, Josep María Montserrat Canal, Joaquín Durán-Cantolla
Journal: American Journal of Respiratory and Critical Care Medicine (2009)

Obstructive sleep apnea (OSA) is an independent risk factor for stroke, but little is known about the role of continuous positive airway pressure (CPAP) on mortality in patients with stroke.To analyze the independent impact of long-term CPAP treatment on mortality in patients with ischemic stroke.Prospective observational study in 166 patients with ischemic stroke. Sleep study was performed in all of them and CPAP treatment was offered in the case of moderate to severe cases. Patients were followed-up for 5 years to analyze the risk of mortality.Of 223 patients consecutively admitted for stroke, a sleep study was performed on 166 of them (2 mo after the acute event). Thirty-one had an apnea-hypopnea index (AHI) of less than 10; 39 had an AHI between 10 and 19, and 96 had an AHI of 20 or greater. CPAP treatment was offered when AHI was 20 or greater. Patients were followed up in our outpatient clinic at 1, 3, and 6 months, and for every 6 months thereafter for 5 years (prospective observational study). Mortality data were recorded from our computer database and official death certificates. The mean age of subjects was 73.3 +/- 11 years (59% males), and the mean AHI was 26 (for all patients with a predominance of obstructive events). Patients with an AHI of 20 or greater who did not tolerate CPAP (n = 68) showed an increase adjusted risk of mortality (hazards ratio [HR], 2.69; 95% confidence interval [CI], 1.32-5.61) compared with patients with an AHI of less than 20 (n = 70), and an increased adjusted risk of mortality (HR, 1.58; 95% CI, 1.01-2.49; P = 0.04) compared with patients with moderate to severe OSA who tolerated CPAP (n = 28). There were no differences in mortality among patients without OSA, patients with mild disease, and patients who tolerated CPAP.Our results suggest that long-term CPAP treatment in moderate to severe OSA and ischemic stroke is associated with a reduction in excess risk of mortality.
IMMUNOLOGICAL TOLERANCE IN BONE MARROW-DERIVED LYMPHOCYTES
Authors: David H. Katz, Toshiyuki Hamaoka, Baruj Benacerraf
Journal: The Journal of Experimental Medicine (1974)

The present studies were designed to probe the role(s) of T cells in preventing or altering tolerance induction in hapten-specific B cells. This was accomplished by using hapten conjugates of normally immunogenic heterologous carriers to selectively inhibit 2,4-dinitrophenyl (DNP)-primed B cells in adoptive transfer experiments in vivo. The data provide strong indications that one critical role of T-cell participation in humoral responses to antigens is to circumvent the development of a tolerogenic signal that, in the absence of such T-cell function, might otherwise ensue after binding of the antigenic determinants by specific precursor B lymphocytes.
Adenovirus gene transfer of SERCA in heart failure. A promising therapeutic approach ?
Authors: A Baartscheer
Journal: Cardiovascular Research (2001)

See article by Chossat et al. [10] (pages 288–297) in this issue. 

Abnormal and reduced contractile function is characteristic in patients suffering from heart failure. Therefore, it seems obvious that inotropic therapy could potentially be beneficial in the treatment of heart failure. However, a number of studies show short-term beneficial effects with progressive myocardial dysfunction in long-term treatment with inotropic interventions in chronic heart failure [1,2]. Inotropic interventions not only enhance contractility and cytosolic systole calcium concentration ([Ca2+]), but also potentially adversely affect diastolic [Ca2+].

Functional abnormalities commonly observed in the failing heart include a negative force frequency relationship secondary to disturbed calcium handling [3–6] characterized by increased diastolic [Ca2+], increased duration and reduced amplitude of the calcium transient and reduction of the SR calcium content [7,8]. Available evidence strongly suggests that down regulation of the sarcoplasmic reticular SR Ca-ATPase (SERCA) underlies these abnormalities possibly in combination with increased sarcolemmal Na+/Ca2+-exchange activity. Consequently, therapies aiming to enhance SERCA activity might prove potentially beneficial in the treatment of heart failure.

A promising approach to this end could be adenoviral gene therapy to compensate for compromised SERCA synthesis. Indeed, one of the first studies using adenoviral gene transfer in isolated neonatal cardiac myocytes reported a successful 7.5 fold increase of total SERCA [9]. However, in similar later studies in adult normal and failing myocytes increase of SERCA was limited to maximally 1.5 to 2 fold [10–12]. Similar results were reported in transgenic animals over-expressing SERCA [12]. Over-expression of SERCA appears limited by post-transcriptional events. Although SERCA mRNA levels continuously increase with increasing viral titer, protein levels become saturated [13]. Both in healthy transgenic mice and in adenovirus treated non-failing cardiac myocytes over expression of SERCA resulted … 

* Tel.: +31-20-566-3265; fax: +31-20-697-5458 a.baartscheer{at}amc.uva.nl
Convection-enhanced delivery for the treatment of glioblastoma
Authors: M. A. Vogelbaum, M. K. Aghi
Journal: Neuro-Oncology (2015)

Effective treatment of glioblastoma (GBM) remains a formidable challenge. Survival rates remain poor despite decades of clinical trials of conventional and novel, biologically targeted therapeutics. There is considerable evidence that most of these therapeutics do not reach their targets in the brain when administered via conventional routes (intravenous or oral). Hence, direct delivery of therapeutics to the brain and to brain tumors is an active area of investigation. One of these techniques, convection-enhanced delivery (CED), involves the implantation of catheters through which conventional and novel therapeutic formulations can be delivered using continuous, low–positive-pressure bulk flow. Investigation in preclinical and clinical settings has demonstrated that CED can produce effective delivery of therapeutics to substantial volumes of brain and brain tumor. However, limitations in catheter technology and imaging of delivery have prevented this technique from being reliable and reproducible, and the only completed phase III study in GBM did not show a survival benefit for patients treated with an investigational therapeutic delivered via CED. Further development of CED is ongoing, with novel catheter designs and imaging approaches that may allow CED to become a more effective therapeutic delivery technique.
Absence of inducible costimulator on alloreactive T cells reduces graft versus host disease and induces Th2 deviation
Authors: Vanessa M. Hubbard, Jeffrey M. Eng, Teresa Ramirez-Montagut, Kartono H. Tjoe, Stephanie J. Muriglan, Adam A. Kochman, Theis H. Terwey, Lucy M. Willis, Rafaella Schiro, Glen Heller, George F. Murphy, Chen Liu, Onder Alpdogan, Marcel R. M. van den Brink
Journal: Blood (2005)
Aldosterone and Angiotensin II Synergistically Induce Mitogenic Response in Vascular Smooth Muscle Cells
Authors: Li-Juan Min, Masaki Mogi, Jian-Mei Li, Jun Iwanami, Masaru Iwai, Masatsugu Horiuchi
Journal: Circulation Research (2005)

Interaction between aldosterone (Aldo) and angiotensin II (Ang II) in the cardiovascular system has been highlighted; however, its detailed signaling mechanism is poorly understood. Here, we examined the cross-talk of growth-promoting signaling between Aldo and Ang II in vascular smooth muscle cells (VSMC). Treatment with a lower dose of Aldo (10(-12) mol/L) and with a lower dose of Ang II (10(-10) mol/L) significantly enhanced DNA synthesis, whereas Aldo or Ang II alone at these doses did not affect VSMC proliferation. This effect of a combination of Aldo and Ang II was markedly inhibited by a selective AT1 receptor blocker, olmesartan, a mineralocorticoid receptor antagonist, spironolactone, an MEK inhibitor, PD98059, or an EGF receptor tyrosine kinase inhibitor, AG1478. Treatment with Aldo together with Ang II, even at noneffective doses, respectively, synergistically increased extracellular signal-regulated kinase (ERK) activation, reaching 2 peaks at 10 to 15 minutes and 2 to 4 hours. The early ERK peak was effectively blocked by olmesartan or an EGF receptor kinase inhibitor, AG1478, but not by spironolactone, whereas the late ERK peak was completely inhibited by not only olmesartan, but also spironolactone. Combined treatment with Aldo and Ang II attenuated mitogen-activated protein kinase phosphatase-1 (MKP-1) expression and increased Ki-ras2A expression. The late ERK peak was not observed in VSMC treated with Ki-ras2A-siRNA. Interestingly, the decrease in MKP-1 expression and the increase in Ki-ras2A expression were restored by PD98059 or AG1478. These results suggest that Aldo exerts a synergistic mitogenic effect with Ang II and support the notion that blockade of both Aldo and Ang II could be more effective to prevent vascular remodeling.
Hyponatraemia in congestive heart failure during treatment with captopril.
Authors: M G Nicholls, E A Espiner, H Ikram, A H Maslowski
Journal: BMJ (1980)

Hyponatraemia in congestive heart failure during treatment with captoprilThe oral converting-enzyme inhibitor captopril shows promise in the treatment of cardiac failure.We used the drug in five patients with congestive heart failure that had proved unresponsive to conventional treatment and observed a clear-cut fall in plasma sodium concentration. Methods and resultsWe studied five men aged 54-72 years with congestive heart failure (New York Heart Association functional class III or IV) secondary to coronary artery disease.All had previously received conventional medications, including vasodilators, without success.Throughout the seven-day study they received a constant dietary intake of sodium (33-48 mmol(mEq)/day) and potassium (73-100 mmol(mEq)/day; body posture was restricted to the supine and sitting positions in bed; and their regular doses of digoxin (62-5-250 ,ug/day) and frusemide (80-500 mg/day) were continued.All other drugs were stopped at least five days before the study.After a two-day run-in period captopril was administered by mouth in an eight-hourly incremental regimen (6-25-150 mg/dose), and blood was drawn one hour after each dose increase for measurement of plasma electrolyte and hormone concentrations.
Racial Variation in Medical Outcomes among Living Kidney Donors
Authors: Krista L. Lentine, Mark A. Schnitzler, Huiling Xiao, Georges Saab, Paolo R. Salvalaggio, David Axelrod, Connie L. Davis, Kevin C. Abbott, Daniel C. Brennan
Journal: New England Journal of Medicine (2010)

Data regarding health outcomes among living kidney donors are lacking, especially among nonwhite persons.