tbuckley/cabot-search huggingface dataset:
Bacterial infections in end-stage liver disease: current challenges and future directions
Authors: Jasmohan S Bajaj, Jacqueline G O'Leary, Florence Wong, K Rajender Reddy, Patrick S Kamath
Journal: Gut (2012)

Bacterial infections continue to be a leading cause of mortality andacute-on-chronic liver failure in end-stage liver disease (ESLD). The consequences of infection include prolonged hospitalisation, acute kidney injury (AKI), death, de-listing from liver transplant and susceptibility to further infections. The diagnosis of infections in cirrhosis is fraught due to the background of a partial systemic inflammatory response syndrome (SIRS) state and negative cultures in 30-50% of patients. Furthermore, the lack of multi-center studies limits the generalisability of currently available results. The modulation of infections by the underlying immune state, gut barrier function and super-imposed medications such as beta-blockers, proton pump inhibitors and antibiotics is required. A rational approach to the diagnosis and prevention of AKI associated with infection, withjudicious use of crystalloids and albumin, is also needed. Changes in bacteriology including emergence of multi-resistant organisms and Clostridium difficile have also recently changed the approach for prophylaxis and therapy of infections. Effective strategies for the prevention, diagnosis, and management of infections in ESLD form a large unmet need. A systematic approach to study the epidemiology, bacteriology, resistance patterns, and procedure and medication utilisation specific to ESLD is needed to improve outcomes.

Bacterial infections in patients with end-stage liver disease affect candidacy for liver transplantation. Up to one-third of all hospitalised patients with cirrhosis are infected.1–5 With sepsis, mortality increases to more than 50% and is associated with significant costs.6 A recent systematic review demonstrated a fourfold increased risk of death in infected cirrhotic patients compared with their non-infected counterparts.7 More importantly, intensive care unit (ICU) mortality of patients with cirrhosis has remained unchanged over 50 years, unlike disease states such as cardiac failure where mortality has decreased.8 Therefore the prevention, diagnosis …
Immune hemolytic anemia following administration of antithymocyte globulin
Authors: Josef T. Prchal, Shu T. Huang, Wayne S. Court, Man‐Chiu Poon
Journal: American Journal of Hematology (1985)

Abstract Antithymocyte globulin is commonly used as a therapy for rejection of transplanted organs. Its use can be associated with many side effects. We report a significant hemolytic anemia following therapy with horse‐derived antithymocyte globulin. Several commercial Coombs' sera failed to yield a positive Coombs' test with the patient's erythrocytes; however, we were able to detect horse immunoglobulin on the patient's cells as well as on control red cells incubated with this particular preparation of antithymocyte globulin.
Beneficial Hemodynamic Effects of Prone Positioning in Patients with Acute Respiratory Distress Syndrome
Authors: Mathieu Jozwiak, Jean-Louis Teboul, Nadia Anguel, Romain Persichini, Serena Silva, Denis Chemla, Christian Richard, Xavier Monnet
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

The effects of prone positioning during acute respiratory distress syndrome on all the components of cardiac function have not been investigated under protective ventilation and maximal alveolar recruitment.To investigate the hemodynamic effects of prone positioning.We included 18 patients with acute respiratory distress syndrome ventilated with protective ventilation and an end-expiratory positive pressure titrated to a plateau pressure of 28-30 cm H2O. Before and within 20 minutes of starting prone positioning, hemodynamic, respiratory, intraabdominal pressure, and echocardiographic data were collected. Before prone positioning, preload reserve was assessed by a passive leg raising test.In all patients, prone positioning increased the ratio of arterial oxygen partial pressure over inspired oxygen fraction, the intraabdominal pressure, and the right and left cardiac preload. The pulmonary vascular resistance decreased along with the ratio of the right/left ventricular end-diastolic areas suggesting a decrease of the right ventricular afterload. In the nine patients with preload reserve, prone positioning significantly increased cardiac index (3.0 [2.3-3.5] to 3.6 [3.2-4.4] L/min/m(2)). In the remaining patients, cardiac index did not change despite a significant decrease in the pulmonary vascular resistance.In patients with acute respiratory distress syndrome under protective ventilation and maximal alveolar recruitment, prone positioning increased the cardiac index only in patients with preload reserve, emphasizing the important role of preload in the hemodynamic effects of prone positioning.
The role of resective periodontal surgery in the treatment of furcation defects
Authors: M DeSanctis, K G Murphy
Journal: Periodontology 2000 (2000)

Resective therapy for the treatment of furcation defects is an essential part of the periodontal therapist's armamentarium. Root resection can successfully treat specific furcation defects that cannot be solved by other surgical and nonsurgical approaches. Complications with these resective procedures are not rare but are usually avoidable when specific endodontic, surgical and restorative guidelines are followed.
An 19F Magnetic Resonance–Based <i>In Vivo</i> Assay of Solid Tumor Methotrexate Resistance: Proof of Principle
Authors: William M. Spees, Terence P.F. Gade, Guangli Yang, William P. Tong, William G. Bornmann, Richard Gorlick, Jason A. Koutcher
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Studies in oncology have implicated multiple molecular mechanisms as contributors to intrinsic and acquired tumor resistance to antifolate therapy. Here we show the utility of an 19F-labeled methotrexate (FMTX) with 19F magnetic resonance to differentiate between sensitive and resistant tumors in vivo and thus predict therapeutic response. Experimental Design: Human sarcoma xenografts in nude mice were used in this study. The sarcoma cell lines chosen for this study (HT-1080, HS-16, and M-805) are well characterized in terms of their methotrexate sensitivity and molecular mechanisms of resistance. The pharmacokinetics of tumor uptake/washout of FMTX were monitored via in vivo 19F magnetic resonance spectroscopy (pulse/acquire with surface coil localization) following an i.v. bolus injection. Response post-therapy, following leucovorin rescue, was monitored via tumor growth. Results: The three tumor models show differences in both the peak concentrations of tumor FMTX and the dynamics of uptake/retention. These differences are most pronounced for time points late in the magnetic resonance observation period (225-279 minutes post-injection). A statistically significant linear correlation between tumor tissue concentrations of FMTX at these late time points and therapeutic response in the days/weeks post-treatment is shown (R = 0.81, F = 9.27, P &amp;lt; 0.001). Interestingly, a 400 mg/kg i.v. bolus injection of FMTX is a more potent cytotoxic agent in vivo against methotrexate-sensitive tumors than is the parent compound (P = 0.011). Conclusions: In principle, the assay method described herein could be implemented in the clinic as a diagnostic tool to make decisions regarding therapeutic protocol for the treatment of osteosarcoma on a case-by-case basis.
The Epidemiology of Depression Across Cultures
Authors: Ronald C. Kessler, Evelyn J. Bromet
Journal: Annual Review of Public Health (2013)

Epidemiological data are reviewed on the prevalence, course, socio-demographic correlates, and societal costs of major depression throughout the world. Major depression is estimated in these surveys to be a commonly occurring disorder. Although estimates of lifetime prevalence and course vary substantially across countries for reasons that could involve both substantive and methodological processes, the cross-national data are clear in documenting meaningful lifetime prevalence with wide variation in age-of-onset and high risk of lifelong chronic-recurrent persistence. A number of sociodemographic correlates of major depression are found consistently across countries, and cross-national data also document associations with numerous adverse outcomes, including difficulties in role transitions (e.g., low education, high teen childbearing, marital disruption, unstable employment), reduced role functioning (e.g., low marital quality, low work performance, low earnings), elevated risk of onset, persistence and severity of a wide range of secondary disorders, and increased risk of early mortality due to physical disorders and suicide.
Patients as Therapists
Authors: ERIC PFEIFFER
Journal: American Journal of Psychiatry (1967)

When the gulf between doctor and patient is so great that either of them despairs of ever bridging it, the patient may respond more easily to an intermediate therapist—another patient. Spontaneous interactions between patients can foster therapeutic relationships for individuals whom professional staff members have been unable to reach. The author feels that such patient relationships can and should be stimulated under staff guidance.
Fibrinogen Bethesda: a congenital dysfibrinogenemia with delayed fibrinopeptide release
Authors: H. R. Gralnick, H. M. Givelber, J. R. Shainoff, J. S. Finlayson
Journal: Journal of Clinical Investigation (1971)

A dysfibrinogenemia (fibrinogen Bethesda) was detected in a 9 yr old male of Mexican-English extraction who had a lifelong history of mild bleeding diathesis. The prothrombin and partial thromboplastin times were moderately prolonged; the thrombin and Reptilase times were markedly prolonged. The plasma fibrinogen level was normal by conventional methods but was markedly reduced by the Clauss method. Results of all other tests for clotting factors, fibrinolysis, antithrombin levels, clot stabilization, and fibrin(ogen) degradation products were normal. The patient's plasma and fibrinogen inhibited the clotting of normal plasma or fibrinogen by thrombin. Family studies revealed that the propositus' mother and two siblings exhibited these abnormalities to a lesser degree and indicated an autosomal dominant inheritance. Fibrinogen Bethesda was similar to normal fibrinogen in the following respects: metabolic turnover time (measured in the propositus' mother); immunodiffusion, ultracentrifugal, electrophoretic (on cellulose acetate or polyacrylamide gel), and chromatographic (on DEAE-cellulose) characteristics; sialic acid content; and aggregation of fibrin monomers. By contrast, fibrinogen Bethesda gave an abnormal immunoelectrophoretic pattern especially when whole plasma (as opposed to purified fibrinogen) was examined, and it showed a pronounced decrease in the rate of fibrinopeptide release by thrombin. This decrease, which was shown to involve both fibrinopeptides A and B, distinguishes fibrinogen Bethesda from previously reported dysfibrinogenemias.
Criteria for Drugs Used in Pre-Exposure Prophylaxis Trials against HIV Infection
Authors: Inge Derdelinckx, Mark A Wainberg, Joep M. A Lange, Andrew Hill, Yasmin Halima, Charles A. B Boucher
Journal: PLoS Medicine (2006)

In 2004, almost 5 million people became newly infected with HIV, emphasizing the continuous need for effective prevention strategies. The development of an effective preventive vaccine faces many difficulties and is not likely to occur within the next decade. Behavioural changes, such as consistent and correct condom use and abstinence from high-risk behaviour, probably contributed to the fall in HIV incidence recently reported in several African countries and in India [1]. Recently, it was shown that male circumcision reduced the risk of acquiring HIV by 60% [2] and the risk of male-to-female transmission by 30% [3]. However, behavioural interventions may not be able to curb the HIV epidemic as much as needed, prompting the need to find additional, more effective preventive strategies. There is also a need for “female-initiated intervention”. Women around the globe continue to be infected with HIV by their male partners and often feel unable to insist on condom use.

Alternatives to behavioural strategies include those that are based on drugs. Anti-HIV vaginal microbicides, which may offer women a means of protecting themselves from infection, are currently being evaluated [4]. Also, rectally applied microbicides have proven to effectively prevent infection in macaques challenged via this transmission route [5]. However, like male circumcision, this strategy may not provide protection against other routes of HIV transmission, such as oral or intravenous transmission.

Oral antiretroviral pre-exposure prophylaxis (PREP) in high-risk populations may be a more reliable tool in preventing transmission of HIV [6]. Limited animal model data suggest that antiretroviral drugs may prevent infection when taken prior to, at the time of, and/or after HIV exposure [7–10]. Theoretically, preventing HIV infection could be done by blocking any step in the HIV life cycle. Blocking a step prior to integration of proviral DNA into the host DNA is believed to have greater potential since this way the permanent integration of proviral HIV is averted.
Let-7g Improves Multiple Endothelial Functions Through Targeting Transforming Growth Factor-Beta and SIRT-1 Signaling
Authors: Yi-Chu Liao, Yung-Song Wang, Yuh-Cherng Guo, Wen-Lien Lin, Ming-Hung Chang, Suh-Hang Hank Juo
Journal: Journal of the American College of Cardiology (2013)
Tuberculosis of the Palate
Authors: S. Robert Lathan
Journal: JAMA (1971)

<h3>To the Editor.—</h3> Tuberculosis of the oral cavity is considered to be uncommon and primary lesions are extremely rare, although they have been reported.<sup>1-5</sup>The following case report describes a patient in whom primary tuberculosis of the hard palate developed in a torus palatinus and was successfully treated with chemotherapy. <h3>Report of a Case.—</h3> A 72-year-old white man had complained of a painful "sore" on his hard palate for several weeks. A torus palatinus had been present for many years. On examination by his dentist, an elevated ulcerated lesion, 3×4 cm in size, was noted in the center of the torus. The patient was referred to an oral surgeon because the lesion was thought to be a possible cancerous process. Biopsy of the lesion showed a typical picture of tuberculosis with granulomata consisting of giant cells and epithelioid cells. Acid-fast bacilli were seen on Ziehl-Neelsen stain of the biopsy.
Nitrogen sparing induced by leucine compared with that induced by its keto analogue, alpha-ketoisocaproate, in fasting obese man.
Authors: W E Mitch, M Walser, D G Sapir
Journal: Journal of Clinical Investigation (1981)

We measured the effects of seven consecutive daily infusions of alpha-ketoisocaproate (the alpha-keto analogue of leucine) or leucine itself on urinary urea and total nitrogen excretion during fasting. Two study protocols were undertaken. In protocol I, subjects underwent three separate 14-d fasts: one during which 34 mmol/d of leucine were infused on days 1--7; a second during which 34 mmol/d of alpha-ketoisocaproate were infused on days 1--7; and a third control fast during which no infusions were given. Infusions of alpha-ketoisocaproate significantly reduced daily urine urea nitrogen excretion compared with both the control fasts and the fasts in which leucine was infused (P less than 0.001). This nitrogen-sparing effect of alpha-ketoisocaproate persisted during days 8--14 even though no further infusions were given. Daily urinary urea nitrogen excretion during fasts when leucine was administered did not differ from values observed during control fasts. In protocol II, subjects were starved on two occasions for 14 d. During one fast, infusions of 11 mmol/d of alpha-ketoisocaproate were given on days 1--7; during the control fast, no infusions were given. Daily urine urea nitrogen excretion was lower (P less than 0.001) on days 1--7 and also on days 8--14 of the fast during which alpha-ketoisocaproate was given. The nitrogen-sparing effect of alpha-ketoisocaproate could not be related to changes in circulating levels of amino acids, ketone bodies, or insulin in either protocol. We conclude that alpha-ketoisocaproate infusions decrease the nitrogen wasting of starvation, whereas leucine, studied under identical conditions, does not.
A Physiological Interpretation of Vacillation in Conflicts
Authors: M. W. LASALLE
Journal: American Journal of Psychiatry (1966)

Sherrington's concept of successive induction and rebound, and Pavlov's concept of negative induction are grouped together under one comprehensive term—physiological induction. This concept in turn is used as an explanation for a number of phenomena ordinarily considered to be entirely psychological. In this paper one such psychological phenomenon is discussed—vacillation between the two sides of a conflict.
Telomeres, Atherosclerosis, and the Hemothelium: The Longer View
Authors: Abraham Aviv, Daniel Levy
Journal: Annual Review of Medicine (2012)

The model we propose to explain the links between atherosclerosis and telomere dynamics (birth telomere length and its age-dependent shortening) in leukocytes takes cues from three facts: atherosclerosis is a disease of the vascular endothelium; the hematopoietic system and the vascular endothelium share a common embryonic origin; interindividual variation in leukocyte telomere length (LTL) in the general population has a genetic explanation. The model posits that LTL dynamics mirror telomere dynamics in hematopoietic stem cells (HSCs), where telomere length is an index of HSC reserves. Diminished HSC reserves at birth, their accelerated attrition rate afterward, or both are are reflected in shortened LTL during adulthood-a phenomenon that confers increased risk for atherosclerosis. We explain how telomere length in HSCs serves as both a biomarker of atherosclerosis and a determinant of its development. Our model comes down to this proposition: Shortened LTL predicts increased atherosclerotic risk because the injurious component of atherosclerosis exceeds the repair capacity of HSC reserves, which largely depend on HSC telomere length.
Repeat Surgery After Breast Conservation for the Treatment of Stage 0 to II Breast Carcinoma
Authors: Lee G. Wilke, Tomasz Czechura, Chih Wang, Brittany Lapin, Erik Liederbach, David P. Winchester, Katharine Yao
Journal: JAMA Surgery (2014)

Although complete excision of breast cancer is accepted as the best means to reduce local recurrence and thereby improve survival, there is currently no standard margin width for breast conservation surgery. As a result, significant variability exists in the number of additional operations or repeat surgeries patients undergo to establish tumor-negative margins.To determine the patient, tumor, and facility factors that influence repeat surgery rates in US patients undergoing breast conservation surgery.Patients diagnosed as having breast cancer at a Commission on Cancer accredited center from January 1, 2004, through December 31, 2010, and identified via the National Cancer Data Base, a large observational database, were included in the analysis. A total of 316,114 patients with stage 0 to II breast cancer who underwent initial breast conservation surgery were studied. Patients who were neoadjuvantly treated or whose conditions were diagnosed by excisional biopsy were excluded.Patient, tumor, and facility factors associated with repeat surgeries.A total of 241,597 patients (76.4%) underwent a single lumpectomy, whereas 74,517 (23.6%) underwent at least 1 additional operation, of whom 46,250 (62.1%) underwent a completion lumpectomy and 28,267 (37.9%) underwent a mastectomy. The proportion of patients undergoing repeat surgery decreased slightly during the study period from 25.4% to 22.7% (P < .001). Independent predictors of repeat surgeries were age, race, insurance status, comorbidities, histologic subtype, estrogen receptor status, pathologic tumor size, node status, tumor grade, facility type and location, and volume of breast cancer cases. Age was inversely associated with repeat surgery, decreasing from 38.5% in patients 18 to 29 years old to 16.5% in those older than 80 years (P < .001). In contrast, larger tumor size was linearly associated with a higher repeat surgery rate (P < .001). Repeat surgeries were most common at facilities located in the Northeast region (26.5%) compared with facilities in the Mountain region, where only 18.4% of patients underwent repeat surgery (P < .001). Academic or research facilities had a 26.0% repeat surgery rate compared with a rate of 22.4% at community facilities (P < .001).Approximately one-fourth of all patients who undergo initial breast conservation surgery for breast cancer will have a subsequent operative intervention. The rate of repeat surgeries varies by patient, tumor, and facility factors and has decreased slightly during the past 6 years.
Cellular Mechanism Through Which Parathyroid Hormone–Related Protein Induces Proliferation in Arterial Smooth Muscle Cells
Authors: Nathalie Fiaschi-Taesch, Brian M. Sicari, Kiran Ubriani, Todd Bigatel, Karen K. Takane, Irene Cozar-Castellano, Alessandro Bisello, Brian Law, Andrew F. Stewart
Journal: Circulation Research (2006)

Parathyroid hormone-related protein (PTHrP) is present in vascular smooth muscle (VSM), is markedly upregulated in response to arterial injury, is essential for normal VSM proliferation, and also markedly accentuates neointima formation following rat carotid angioplasty. PTHrP contains a nuclear localization signal (NLS) through which it enters the nucleus and leads to marked increases in retinoblastoma protein (pRb) phosphorylation and cell cycle progression. Our goal was to define key cell cycle molecules upstream of pRb that mediate cell cycle acceleration induced by PTHrP. The cyclin D/cdk-4,-6 system and its upstream regulators, the inhibitory kinases (INKs), are not appreciably influenced by PTHrP. In striking contrast, cyclin E/cdk-2 kinase activity is markedly increased by PTHrP, and this is a result of a specific, marked, PTHrP-induced proteasomal degradation of p27(kip1). Adenoviral restoration of p27(kip1) fully reverses PTHrP-induced cell cycle progression, indicating that PTHrP mediates its cell cycle acceleration in VSM via p27(kip1). In confirmation, adenoviral delivery of PTHrP to murine primary vascular smooth muscle cells (VSMCs) significantly decreases p27(kip1) expression and accelerates cell cycle progression. p27(kip1) is well known to be a central cell cycle regulatory molecule involved in both normal and pathological VSM proliferation and is a target of widely used drug-eluting stents. The current observations define a novel "PTHrP/p27(kip1) pathway" in the arterial wall and suggest that this pathway is important in normal arterial biology and a potential target for therapeutic manipulation of the arterial response to injury.