tbuckley/cabot-search huggingface dataset:
Phase II Trial of Single-Agent Bevacizumab Followed by Bevacizumab Plus Irinotecan at Tumor Progression in Recurrent Glioblastoma
Authors: Teri N. Kreisl, Lyndon Kim, Kraig Moore, Paul Duic, Cheryl Royce, Irene Stroud, Nancy Garren, Megan Mackey, John A. Butman, Kevin Camphausen, John Park, Paul S. Albert, Howard A. Fine
Journal: Journal of Clinical Oncology (2008)

To evaluate single-agent activity of bevacizumab in patients with recurrent glioblastoma.Patients with recurrent glioblastoma were treated with bevacizumab 10 mg/kg every 2 weeks. After tumor progression, patients were immediately treated with bevacizumab in combination with irinotecan 340 mg/m(2) or 125 mg/m(2) every 2 weeks, depending on use of enzyme-inducing antiepileptic drugs. Complete patient evaluations were repeated every 4 weeks.Forty-eight heavily pretreated patients were accrued to this study. Thromboembolic events (12.5%), hypertension (12.5%), hypophosphatemia (6%), and thrombocytopenia (6%) were the most common drug-associated adverse events. Six patients (12.5%) were removed from study for drug-associated toxicity (five thromboembolic events, one bowel perforation). Thirty-four patients (71%) and 17 patients (35%) achieved radiographic response based on Levin and Macdonald criteria, respectively. Median progression-free survival (PFS) was 16 weeks (95% CI, 12 to 26 weeks). The 6-month PFS was 29% (95% CI, 18% to 48%). The 6-month overall survival was 57% (95% CI, 44% to 75%). Median overall survival was 31 weeks (95% CI, 21 to 54 weeks). Early magnetic resonance imaging response (first 96 hours and 4 weeks) was predictive of long-term PFS, with the Levin criteria being more predictive than Macdonald criteria. Of 19 patients treated with bevacizumab plus irinotecan at progression, there were no objective radiographic responses. Eighteen patients (95%) experienced disease progression by the second cycle, and the median PFS was 30 days.We conclude that single-agent bevacizumab has significant biologic and antiglioma activity in patients with recurrent glioblastoma.
Visuomotor delay in interceptive actions
Authors: Nicolas Benguigui, Robin Baurès, Cyrille Le Runigo
Journal: Behavioral and Brain Sciences (2008)

Abstract Neural delays, which are generally defined as visuomotor delays in interceptive actions, must be compensated to enable accurate timing in movement. Visuomotor delays can depend on the kind of task, the use of information, and the skill of the performer. The compensation for such delays does not necessarily require prediction or representation but can be made by an attunement of some parameters in what is called a law of control .
Hyperhomocysteinemia is a significant risk factor for silent cerebral infarction in patients with chronic renal failure undergoing hemodialysis
Authors: Futoshi Anan, Naohiko Takahashi, Tsuyoshi Shimomura, Muneharu Imagawa, Kunio Yufu, Tomoko Nawata, Mikiko Nakagawa, Hidetoshi Yonemochi, Nobuoki Eshima, Tetsunori Saikawa, Hironobu Yoshimatsu
Journal: Metabolism (2006)
An antidote for<i>Staphylococcus aureus</i>pneumonia?
Authors: Frank R. DeLeo, Michael Otto
Journal: The Journal of Experimental Medicine (2008)

Methicillin-resistant Staphylococcus aureus (MRSA) is the leading cause of bacterial infections in the United States. Severe invasive MRSA infections, which include pneumonia, are difficult to treat because the bacteria are resistant to antibiotics. A new report now shows that immunization against alpha-hemolysin (Hla), a cytolytic toxin secreted by most S. aureus strains, protects mice against lethal pneumonia. This finding represents the first successful vaccine strategy for the treatment of staphylococcal pneumonia.
Red kidney bean lectin is a potent cholecystokinin releasing stimulus in the rat inducing pancreatic growth
Authors: K-H Herzig, S Bardocz, G Grant, R Nustede, U R Fölsch, A Pusztai
Journal: Gut (1997)

Background —Lectins are proteins capable of specific binding to carbohydrates without altering their covalent structure. As an essential part of plants they are ingested in our daily diet. By binding to glycosyl side chains of receptors lectins can mimic or inhibit the action of the ligand. Oral administration of phytohaemagglutinin (PHA) in rats dose dependently induces growth of the small intestine and the pancreas by an unknown mechanism. Aims —To investigate the mechanism of PHA induced intestinal and pancreatic growth. Methods —Thirty day old male rats were pairfed for 10 days with lactalbumin as a control diet or lactalbumin plus PHA or purified soybean trypsin inhibitor (STI) as a positive control (42 mg/rat/day) with or without 20 μg of the cholecystokinin A (CCK-A) antagonist MK 329. To investigate further the effect of PHA on CCK release intestinal mucosal cells were isolated from rats which were continuously perfused in a perfusion apparatus. CCK release into the medium was assayed. Results —PHA and STI significantly stimulated growth of the pancreas and the small intestine. MK 329 blocked this growth effect in the pancreas but not in the small intestine. In vivo, PHA significantly increased CCK plasma levels from 0.75 to 6.67 (SEM 2.23) compared with 2.3 (0.35) pM in the control group. In addition, in vitro PHA dose dependently stimulated CCK release with a maximal effect at 100 ng/ml. Conclusion —In vivo and in vitro PHA is a potent stimulus for CCK release in the rat, thereby inducing pancreatic growth, whereas intestinal growth is stimulated by a CCK independent mechanism.
Hepatobiliary disease in cystic fibrosis patients with pancreatic sufficiency
Authors: Donna L. Waters, Stuart F. A. Dorney, Margie A. Gruca, Hugh C. O. Martin, Robert Howman-Giles, Alex E. Kan, Merl de Silva, Kevin J. Gaskin
Journal: Hepatology (1995)

Focal and multilobular biliary cirrhosis are considered pathognomonic of cystic fibrosis (CF) and almost invariably have been reported in patients with steatorrhea. In contrast, patients with pancreatic sufficiency and normal absorption are considered less likely to develop liver or biliary tract problems. The authors report three patients with CF and pancreatic sufficiency, presenting with recurrent abdominal pain (unrelated to pancreatitis). All had common bile duct disease, one with multilobular cirrhosis and portal hypertension. Pancreatic sufficiency was proven by quantitative pancreatic stimulation tests, 3-day fecal fat analyses, and serum pancreatic isoamylases. All three patients had mild lung disease. Two were homozygous for the common delta F508 mutation, and the other, a delta F508 compound heterozygote. Hepatobiliary structure and function were determined by serial hepatobiliary scintigraphy, percutaneous transhepatic cholecystography, and biochemical liver function tests. Patients 1 and 3 had mild hepatomegaly, normal liver biochemistry, and distal common bile duct strictures. Patient 2 had a firm nodular liver with splenomegaly, abnormal liver biochemistry, and a cholangiographic appearance of sclerosing cholangitis. All have undergone operative treatment for persistent abdominal pain. These cases confirm the occurrence of common bile duct pathology and liver disease in patients with CF and pancreatic sufficiency. They demonstrate that liver and biliary tract disease can occur independently of the underlying disease severity and the presence of steatorrhea. Further, they suggest that obstruction of the biliary tract may be an additional factor in the evolution of liver disease in CF.
Spontaneous complete hamstring avulsion causing posterior thigh compartment syndrome
Authors: Y Kwong, J Patel
Journal: British Journal of Sports Medicine (2006)

Complete avulsion of the hamstring muscle group from its ischial origin is an uncommon condition, and has been mostly reported in young athletes. A case is presented in which a middle aged man sustained this injury and developed a compartment syndrome of the thigh, which has not been previously reported. The surgical management of this patient is described.
Confronting a Neglected Epidemic: Tobacco Cessation for Persons with Mental Illnesses and Substance Abuse Problems
Authors: Steven A. Schroeder, Chad D. Morris
Journal: Annual Review of Public Health (2009)

Tobacco use exerts a huge toll on persons with mental illnesses and substance abuse disorders, accounting for 200,000 of the annual 443,000 annual tobacco-related deaths in the United States. Persons with chronic mental illness die 25 years earlier than the general population does, and smoking is the major contributor to that premature mortality. This population consumes 44% of all cigarettes, reflecting very high prevalence rates plus heavy smoking by users. The pattern reflects a combination of biological, psychosocial, cultural, and tobacco industry-related factors. Although provider and patient perspectives are changing, smoking has been a historically accepted part of behavioral health settings. Additional harm results from the economic burden imposed by purchasing cigarettes and enduring the stigma attached to smoking. Tailored treatment for this population involves standard cessation treatments including counseling, medications, and telephone quitlines. Further progress depends on clinician and patient education, expanded access to treatment, and the resolution of existing knowledge gaps.
ELECTROENCEPHALOGRAPHIC CHANGES ASSOCIATED WITH CHRONIC ALCOHOLIC INTOXICATION AND THE ALCOHOL ABSTINENCE SYNDROME
Authors: ABRAHAM WIKLER, FRANK T. PESCOR, HAVELOCK F. FRASER, HARRIS ISBELL
Journal: American Journal of Psychiatry (1956)

1. Correlative data on EEG changes, behavioral alterations and variations in blood alcohol level were obtained in 3 former narcotic addicts, without anamnestic, neurological or EEG evidence of central nervous system disorder, who received averages of 458-489 cc. of 95% ethyl alcohol daily for 48-55 days, followed by abrupt withdrawal of the drug, under controlled experimental conditions. 2. During chronic alcoholic intoxication, blood alcohol levels varied with particular procedures that were carried out, but were maintained for long periods at about 200 mg. %. Initially, EEG's were diffusely slowed, and this change persisted in milder degree during the remainder of the chronic intoxication period. However, EEG evidence of partial, though precarious, "metabolic" and "tissue" tolerance was obtained, which corresponded roughly to variations in degrees of behavioral intoxication. 3. By the 15-19th hour of abstinence, blood alcohol levels had fallen to zero. Anxiety, tremulousness, weakness and profuse perspiration were exhibited by all subjects, and transient, mild but definite dysrhythmias were noted in the EEG. In addition, one subject developed transitory visual hallucinations, and at the 41st hour of abstinence, a generalized seizure. Another developed hyperreflexia, tachycardia, elevation of blood pressure, fever, nausea, vomiting and diarrhea with transitory hallucinosis during the first 2 days of abstinence, and classical delirium tremens on the 4th day. No specific EEG change could be correlated with such mental changes. All subjects recovered fully within 3 weeks after abrupt withdrawal of alcohol. 4. It is concluded that "rum fits" and delirium tremens can be precipitated by abrupt withdrawal of alcohol in persons continually intoxicated for 48 days or more, that these phenomena may develop in individuals without evidence of pre-existing disorder of the central nervous system, and that alcohol is an addicting drug in the sense that it can produce pharmacological dependence, both "psychic" and "physical." 5. The clinical and electroencephalographic changes that occur in cycles of addiction to alcohol and barbiturates are compared and contrasted.
Beta adrenergic modulation of human upper intestinal propulsive forces.
Authors: N K Ahluwalia, D G Thompson, J Barlow, L Heggie
Journal: Gut (1994)

beta Adrenoceptor blockade is known to accelerate transit through the small intestine without changing either the number or pattern of intestinal contractions. This study therefore tested the hypothesis that an increase in intraluminal aboral propulsive force may contribute to this transit acceleration. Twenty paired studies were performed, in 10 healthy volunteers, after oral administration of either 100 mg atenolol (a selective beta 1 antagonist) or matched dummy tablets according to a double blind, randomised protocol. The frequency of occurrence of, and the propulsive force exerted by, traction events related to intestinal contractions were measured, using a combined traction force detector and manometry assembly. After atenolol, a consistent increase in the force generated per traction event was noted, both for propagating contractions mean (SEM) (12.0 (1.8) g v control 5.9 (0.07) g; p &lt; 0.05) and for stationary (11.6 (1.4) g v control 7.0 (0.7) g; p &lt; 0.05). In contrast no change in the number of traction events was noted (control v atenolol = 1.6 (0.3) v 1.64 (0.4) per min for propagating and 0.7 (0.1) v 0.85 (0.16) per min for stationary contraction; p &gt; 0.05). beta Adrenoceptor blockade thus increases the propulsive force generated by intestinal contractions, possibly by removing a sympathetic neural inhibition of intestinal tone.
Prostaglandins in the pericardial fluid modulate neural regulation of cardiac electrophysiological properties.
Authors: T Miyazaki, H P Pride, D P Zipes
Journal: Circulation Research (1990)

In response to various stimuli, the pericardium produces prostaglandins that might play a role in neural regulation of cardiac electrophysiological properties by modulating epicardial nerve effects. We determined the effects of various epicardial superfusates on efferent cardiac responses, induced by bilateral efferent ansae subclaviae (SS) and cervical vagal (VS) stimulation, and afferent cardiac reflexes elicited by intracoronary injections of bradykinin (25 micrograms) and nicotine (50 micrograms). Pericardial instillation of arachidonic acid in normal Tyrode's solution (3 micrograms/ml) increased the concentration of pericardial prostacyclin (PGI2), measured by radioimmunoassay as the stable metabolite 6-keto-PGF1 alpha, and of prostaglandin E2 (PGE2). Arachidonic acid superfusion reduced SS-induced shortening of sinus cycle length (SCL), atrio-His interval (AH), and effective refractory period (ERP) of the right and left ventricular myocardium and prevented intra-aortic angiotensin II (30 ng/kg/min) from augmenting SS effects on these variables. Pericardial arachidonic acid plus indomethacin (1 microgram/ml) eliminated the prostaglandin increase and restored the responses of SCL, AH, and ERP to SS and to angiotensin II infusion. Pericardial PGE2 (30 or 50 ng/ml) or PGI2 (50 ng/ml) reversibly suppressed SS-induced shortening of SCL and ERP. Pericardial arachidonic acid or PGI2, however, did not blunt the shortening of ERP induced by intravenous infusion of norepinephrine. Pericardial arachidonic acid did not affect VS-induced lengthening of ERP or the duration of sinus arrest, or arterial blood pressure and heart rate responses to bradykinin or nicotine. We conclude that an increase in the concentration of prostaglandins in the pericardial fluid inhibits efferent sympathetic nerve effects on cardiac electrophysiological variables and antagonizes the facilitatory action of angiotensin II on efferent sympathetic stimulation by acting at presynaptic sites. Increased concentration of pericardial prostaglandins in response to various stimuli may constitute a physiological negative-feedback control mechanism that regulates efferent cardiac sympathetic stimulation.
Phase II Multicenter Trial of Anthracycline Rechallenge With Pegylated Liposomal Doxorubicin Plus Cyclophosphamide for First-Line Therapy of Metastatic Breast Cancer Previously Treated With Adjuvant Anthracyclines
Authors: Maureen E. Trudeau, Mark J. Clemons, Louise Provencher, Lawrence Panasci, Louise Yelle, Daniel Rayson, Jean Latreille, Ted Vandenberg, Rakesh Goel, Labib Zibdawi, Yasmin Rahim, Jean-Francois Pouliot
Journal: Journal of Clinical Oncology (2009)

Anthracyclines are a component of breast cancer chemotherapy regimens in both adjuvant and metastatic settings. Anthracycline rechallenge for metastatic disease, for those previously exposed to adjuvant anthracyclines, may not be considered because of concerns about efficacy, tolerability, and cumulative cardiotoxicity.This prospective, multicenter, single-arm, phase II trial examined the efficacy and safety of pegylated liposomal doxorubicin (PLD) 35 mg/m(2) plus cyclophosphamide 600 mg/m(2) as first-line therapy, delivered every 3 weeks, in 70 patients who developed metastatic disease more than 12 months after completion of an adjuvant anthracycline-containing regimen. Seven patients discontinued treatment early and were excluded from the efficacy analysis.After a median of six cycles, the objective response rate was 38%. An additional 33% of patients achieved stable disease lasting more than 6 months, for an overall clinical benefit rate of 71%. The estimated median time to progression was 12.2 months. Median overall survival time was 16.5 months. Clinical response was equally robust in patients with and without prior taxane exposure. Treatment was well tolerated. The most common grade 3 to 4 toxicities were palmar-plantar erythrodysesthesia (PPE; 10%), dyspnea (9%), and neutropenia (9%). One (1.4%) of 70 patients discontinued treatment as a result of PPE. One patient (1.4%) experienced an infusion reaction requiring discontinuation. No symptomatic cardiac events were observed.PLD plus cyclophosphamide is effective and well tolerated in patients with metastatic breast cancer who have received prior adjuvant anthracycline-containing chemotherapy. The majority of patients experienced a clinical benefit without any significant impact on cardiac function.
Cardiac valvular disease in chronic inflammatory disorders of connective tissue. Factors influencing survival after surgery.
Authors: D B Yates, J T Scott
Journal: Annals of the Rheumatic Diseases (1975)

Three cases of cardiac valvular disease complicating chronic inflammatory disorders of connective tissue are described. Each underwent surgical valve replacement. The outcome in the first case, a patient with aortitis complicating Reiter9s syndrome and in good health otherwise, has been excellent. The other two patients, one with rheumatoid arthritis and vasculitis, the other with systemic lupus erythematosus and nephritis, died after operation as the result of their systemic disease. The importance of systemic features in assessing this type of patient is emphasized.
T Cell–Mediated Host Immune Defenses in the Lung
Authors: Kong Chen, Jay K. Kolls
Journal: Annual Review of Immunology (2013)

Evidence has increasingly shown that the lungs are a major site of immune regulation. A robust and highly regulated immune response in the lung protects the host from pathogen infection, whereas an inefficient or deleterious response can lead to various pulmonary diseases. Many cell types, such as epithelial cells, dendritic cells, macrophages, neutrophils, eosinophils, and B and T lymphocytes, contribute to lung immunity. This review focuses on the recent advances in understanding how T lymphocytes mediate pulmonary host defenses against bacterial, viral, and fungal pathogens.
Diagnosis and Treatment of Acute Tubular Necrosis
Authors: Matthew L. Esson
Journal: Annals of Internal Medicine (2002)

Acute tubular necrosis (ATN) is common in hospitalized patients, particularly in the intensive care unit. Over the past four decades, the mortality rate from ATN has remained at 50% to 80%.To review recent studies of diagnosis and treatment strategies for ATN.MEDLINE search for all clinical studies of therapies for ATN, supplemented by a review of the references of the identified articles.Prospective studies and major retrospective studies evaluating therapies for ATN.Data on the study sample, interventions performed, results, side effects, and duration of follow-up.Early diagnosis of ATN by exclusion of prerenal and postrenal causes of acute renal failure, examination of urinary sediment, and analysis of urine measures (for example, fractional excretion of sodium in the absence of diuretics) can allow the early involvement of nephrologists and improve survival. Enteral rather than parenteral hyperalimentation in severely malnourished patients may improve survival. Sepsis causes 30% to 70% of deaths in patients with ATN; therefore, avoidance of intravenous lines, bladder catheters, and respirators is recommended. Because septic patients are vasodilated, large volumes of administered fluid accumulate in the lung interstitium of these patients. This condition necessitates ventilatory support, which when prolonged leads to acute respiratory distress syndrome, multiorgan failure, and increased mortality. More aggressive dialysis (for example, given daily) with biocompatible membranes may improve survival in some patients with acute renal failure.New information about the importance of early diagnosis and supportive care for patients with ATN has emerged. However, randomized trials of these interventions are needed to test their effect on the morbidity and mortality of ATN.
Central Role for ENaC in Development of Hypertension
Authors: J Howard Pratt
Journal: Journal of the American Society of Nephrology (2005)

Na(+) reabsorption by the epithelial Na(+) channel (ENaC) in cortical collecting duct provides the final renal adjustment to Na(+) balance, there being no further downstream Na(+) transport system. This fact coupled with the responsiveness of ENaC to aldosterone, which conveys stimulation inversely proportional to the state of Na(+) balance, places ENaC in a pivotal position to influence the risk for hypertension. Although several molecular variants of ENaC subunits have been identified, there has been no consistent demonstration of an association of any of the variants with hypertension. More compelling is the notion that ENaC activity does not fully adjust to an increase in Na(+) reabsorption occurring elsewhere in the nephron, there being overstimulation by inappropriately elevated aldosterone levels. Additional evidence that the maintenance of hypertension can be dependent on ENaC is derived from the observed responses to the treatment of hypertensive individuals with inhibitors of ENaC. Described is a clinical trial in which black hypertensive individuals who did not fully respond to more traditional therapy were given amiloride, spironolactone, a combination of the two drugs, or placebo. Treatment with either of the active inhibitors of ENaC resulted in a substantial improvement in BP. In conclusion, evidence to date is supportive of the concept that an increase in Na(+) transport by ENaC may be a common and requisite component of salt-dependent forms of hypertension.