tbuckley/cabot-search huggingface dataset:
Ixabepilone plus capecitabine improves overall survival in symptomatic patients with metastatic breast cancer previously treated with anthracycline and taxane in 2 large phase III studies.
Authors: P Conte, H Roche, E Perez, J Sparano, B Xu, J Jassem, R Peck, P Mukhopadhyay, G Hortobagyi
Journal: Cancer Research (2009)

Abstract Abstract #6114 Introduction:&amp;#x2028; Symptomatic patients (pts) with performance status (KPS) 70-80 with locally advanced or metastatic breast cancer (MBC) have worse prognosis than pts with good performance status and are often excluded from clinical trials. Ixabepilone (ixa), the first in a new class of antineoplastic agents, showed clinical benefit in 2 large clinical trials in combination with capecitabine (C) in MBC pts with tumors resistant to (study 046; JCO; 2007) or pretreated with anthracycline (A) and taxane (T) (study 048). In 048, ixa + C, compared to C alone, showed significant increases in PFS (HR 0.79 [0.69-0.90] and ORR (43% vs 29%). A trend toward increased OS was seen in 048 (HR 0.90 [0.78-1.03]) and 046 (HR 0.90 [0.77-1.05]) which did not reach statistical significance. In 046 and 048 trials, a survival benefit was seen with ixa + C in a predefined analysis in a subset of symptomatic KPS 70-80 pts (HR: 0.75 [0.58-0.98], 0.76 [0.60-0.96], respectively). We present a predefined pooled analysis of clinical outcomes in symptomatic pts from both studies to better evaluate the treatment effect in this subset.&amp;#x2028; Methods:&amp;#x2028; 1973 pts with MBC previously treated with an A and T were randomized in phase III trials 046 and 048 to receive ixa (40mg/m2 IV over 3h Q3w) + C (1000mg/m2 PO BID x14d Q3w) or C alone (1250mg/m2 PO BID x14d Q3w). 606 pts from the 2 studies were KPS 70-80. Study outcomes included ORR, PFS and OS.&amp;#x2028; Results:&amp;#x2028; ORR, PFS and OS favored ixa + C in this pt population.&amp;#x2028; &amp;#x2028; In asymptomatic pts (KPS 90-100), similar improvement was observed in PFS and ORR; no benefit in OS was seen. Incidence of key treatment related grade 3/4 AEs for ixa + C in this subset of pts was similar to the overall population.&amp;#x2028; Conclusions:&amp;#x2028; In the pooled analysis, ixa + C demonstrates a survival benefit (2.8 mo) for symptomatic pts (KPS 70-80) failing A and T, which was consistently seen in this pt population in the individual studies as well, indicating that symptomatic pts can benefit from management of their disease and achieve overall clinical benefit with ixa combination. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6114.
Enhancement of murine cardiac chronotropy by the molecular transfer of the human beta2 adrenergic receptor cDNA.
Authors: J M Edelberg, W C Aird, R D Rosenberg
Journal: Journal of Clinical Investigation (1998)

Cardiac pacemaking offers a unique opportunity for direct gene transfer into the heart. An experimental system was developed to assay the effects of transferring the human beta2 adrenergic receptor (beta2AR) under in vitro, ex vivo, and finally in vivo conditions. Constructs encoding either beta2AR or LacZ were used in chronotropy studies with isolated myocytes, and transplanted as well as endogenous murine hearts. Murine embryonic cardiac myocytes were transiently transfected with plasmid constructs. The total percentage of myocytes spontaneously contracting was greater in beta2AR transfected cells, as compared with control cells (67 vs. 42+/-5%). In addition, the percentage of myocytes with chronotropic rates > 60 beats per minute (bpm) was higher in the beta2AR population, as compared with control cells (37 vs. 15+/-5%). The average contractile rate was greater in the beta2AR transfected myocytes at baseline (71+/-14 vs. 50+/-10 bpm; P < 0.001) as well as with the addition of 10(-)3 M isoproterenol (98+/-26 vs. 75+/-18 bpm; P < 0.05). Based on these results, a murine neonatal cardiac transplantation model was used to study the ex vivo effects of targeted expression of beta2AR. The constructs were transfected into the right atrium of transplanted hearts. Injection of the beta2AR construct increased the heart rate by approximately 40% (224+/-37 vs. 161+/-42 bpm; P < 0.005). Finally, the constructs were tested in vivo with injection into the right atrium of the endogenous heart. These results were similar to the ex vivo data with injection of the beta2AR constructs increasing the endogenous heart rates by approximately 40%, as compared with control injected hearts (550+/-42 vs. 390+/-37 bpm; P < 0.05). These studies demonstrate that local targeting of gene expression may be a feasible modality to regulate the cardiac pacemaking activity.
Efficacy of Cetuximab in the Treatment of Ménétrier’s Disease
Authors: William H. Fiske, Jarred Tanksley, Ki Taek Nam, James R. Goldenring, Robbert J. C. Slebos, Daniel C. Liebler, Amir M. Abtahi, Bonnie La Fleur, Gregory D. Ayers, Christopher D. Lind, Mary K. Washington, Robert J. Coffey
Journal: Science Translational Medicine (2009)

An antibody to the epidermal growth factor receptor successfully treats nine patients with a disease in which the lining of the stomach abnormally proliferates.
Thyroxine Turnover and Transport in Laennec's Cirrhosis of the Liver*
Authors: Mitsuo Inada, Kenneth Sterling
Journal: Journal of Clinical Investigation (1967)

Studies of the metabolism of thyroxine in 14 cases of cirrhosis revealed a variety of deviations from normal. In addition to radiothyroxine turnover studies, determinations were made of the free thyroxine fractions and free thyroxine iodine concentrations in serum (magnesium precipitation method) as well as the maximal binding capacities of thyroxine-binding alpha globulin (TBG) and thyroxine-binding prealbumin (TBPA) by reverse flow paper electrophoresis in a glycine acetate system at pH 8.6.All cases of cirrhosis exhibited diminutions in TBPA capacities but their TBG capacities showed a wide scatter (13.4 to 41.6 mug/100 ml). The free thyroxine fraction was quite variable, with distinct elevations in nine of the 17 sera.The binding proteins appeared to be determinants of the free thyroxine fraction, which in turn, appeared to be a direct determinant of the half-time of turnover. These inferences did not exclude other possible factors including diminished hepatic uptake and metabolism of the hormone in liver disease.Despite considerable alterations in biological half-times, free thyroxine values, and binding proteins, it was remarkable that the absolute hormone disposal was normal in all 14 patients with cirrhosis.
Two year maintenance treatment of duodenal ulcer disease with ranitidine 150 mg: a prospective multicentre randomised study. GEMUD (Groupe d'Etude de la Maladie Ulcereuse Duodenale).
Authors: P Ruszniewski, A Slama, M Pappo, M Mignon
Journal: Gut (1993)

Maintenance treatment of duodenal ulcer (DU) with ranitidine 150 mg/day was compared with placebo in a two year prospective multicentre randomised study. Three hundred and ninety nine patients were included (mean age: 44.7 years, M/F ratio = 2.47/1; 37.6% of smokers) in placebo (n = 202) and ranitidine (n = 197) groups. Efficacy was assessed by the length of time to the first ulcer pain attack (with or without endoscopic confirmation) or DU complication. One hundred and fourteen patients of 399 (28.6%) had incomplete follow up. Actuarial survival curves of patients without ulcer pain (26 and 53% at two years in placebo and ranitidine groups, respectively) were significantly different (p &lt; 0.0001). Endoscopies were performed depending on physicians9 decision (mainly where there was severe pain or complication). Patients without relapses from endoscopy were more frequent in the ranitidine group (83%) than in the placebo group (47%, p &lt; 0.0001). A greater incidence of complications, mainly bleeding, was also seen in the placebo group (13 complications v two in the ranitidine group, p &lt; 0.002). No factor predicting DU relapse was identified. No important side effect was encountered. Ranitidine 150 mg/day is effective and well tolerated in preventing ulcer pain attacks and DU complications for up to two years.
Multiple Screening Clinics
Authors: R. W. May
Journal: BMJ (1965)

heights of children of parents whose mean height was 69.5 in.-that is, above average stature.In the frequency series 1, 16, 4, 17, 27, 20, 33, 25, 20, 11, 4, 5, which he quotes, there are three prominent peaks.These he ignores, saying no one has paid any attention to them, that such variation is " natural with such small numbers " (actually the chance of this being so is less than 1: 100), and possibly because they were not what he was looking for.I contend that he should have been look- ing for multimodality, and in 1963 I tested this contention on the heights of 760 univer- sity students and their parents.The results, which supported the view put forward here, were published in the Lancet' in a column adjacent to a letter from Sir George and under the same heading.It is interesting that these results find no place in his recent lecture and bibliography.
Effect of D-penicillamine on pulmonary fibrosis in patients with systemic sclerosis
Authors: M Jinnin
Journal: Annals of the Rheumatic Diseases (2003)

Paired two tailed Student's t test used to test differences between baseline and six month follow up values for both patient groups.ESR, erythrocyte sedimentation rate (normal value 5-15 mm/1st h); CRP, C reactive protein (normal value <10 mg/l); VAS, visual analogue score; BASFI, Bath Ankylosing Spondylitis Functional Index (0-100); BASDAI, Bath Ankylosing Spondylitis Disease Activity Index (0-100).
Trends in prenatal diagnosis of Down's syndrome.
Authors: K Spencer
Journal: BMJ (1993)

Thus in Lothian about 250 children-the vast majority not infected with HIV-are likely to suffer the death of one or both parents due to disease related to HIV in the near future; this figure is probably an underestimate as it represents only the tested population.Although many of these children will be beyond their early years when their parents develop advanced disease, they will require much support and counselling.Research should focus on what happens to children when a parent infected with HIV dies and on the role of fostering and adoption services.In our experience it is often grandparents or other family members who bring up children when their HIV infected parents have died or are unable to cope: account needs to be taken of the pressure exerted within extended families in such cases.The care of healthy, dependent children due to suffer bereavement as a result of the HIV epidemic in Lothian should be addressed while the problem is still in its infancy.
STUDIES ON MENINGOCOCCUS INFECTION
Authors: Geoffrey Rake
Journal: The Journal of Experimental Medicine (1933)

Freshly isolated strains of meningococci present a number of characteristics which can be shown to differ not inconsiderably from those of stock strains long maintained on artificial media. Rough variants of the different types can be demonstrated, either arising spontaneously in vivo or in vitro, or evoked in the laboratory by the method described by Enders. Neither the freshly isolated strains-which are smooth- nor, in most cases, the rough variants of them are stable, both showing a tendency to pass over into the stock form or variant. The stock strains in the course of transformation from the freshly isolated strains show changes in morphology and cultural characteristics, and in viability in defibrinated blood.
Dual-demand pacing for reciprocating atrioventricular tachycardia.
Authors: D Krikler, P Curry, J Buffet
Journal: BMJ (1976)

By using programmed electrical stimulation of the heart and studying the initiation and termination of reciprocating atrioventricular tachycardia two patients with the Wolff-Parkinson-White syndrome were shown to respond rapidly and consistently to fixed-rate pacing. A demand pacemaker was implanted in each patient, having been modified so as to switch into the fixed-rate mode whenever the tachycardia began, thereby terminating the arrhythmia. This appears to be a promising form of treatment in patients with otherwise intractable paroxysmal tachycardia who have been shown by careful study to respond in this way.
Cancellation of Medical Congress
Authors: Frank N. Allan
Journal: JAMA (1972)

<h3>To the Editor.—</h3> Two years ago, Dr. Richard A. Kern, President of the International Society of Internal Medicine announced that the Society's 12th biennial Congress would be held in Boston in September 1972. With the sponsorship of the American College of Physicians and under the direction of Dr. Thomas Warthin, arrangements were made for an excellent program. Now, cancellation of the Congress has been reported. The number of advance registrations and the available financial resources were considered too small to warrant the event. In recent decades, and especially since World War II, international medical meetings have proliferated. Individual physicians and national medical societies have attempted to promote direct worldwide communication. The increasing numbers of congresses, conferences, and seminars with participants from an increasing number of countries appeared to indicate their continuing success. On the other hand, the abortive termination of the International Congress of Internal Medicine raises questions that should
Percutaneous coronary laser balloon angioplasty: Initial results of a multicenter experience
Authors: James Richard Spears, Vincent P. Reyes, Joshua Wynne, Barbara S. Fromm, Edward L. Sinofsky, Scott Andrus, Lan Nigel Sinclair, Barry E. Hopkins, Leonard Schwartz, Harold E. Aldridge, H.W.Thijs Plokker, E.G. Mast, Anthony Rickards, Merril L. Knudtson, Ulrich Sigwart, Wayne E. Dear, James J. Ferguson, Paolo Angelini, Louis L. Leatherman, Robert D. Safian, Ronald D. Jenkins, John S. Douglas, Spencer B. king
Journal: Journal of the American College of Cardiology (1990)
Complication of Acupuncture
Authors: Preston F. Smith
Journal: JAMA (1974)

To the Editor.—  We have recently seen a most unusual complication of acupuncture.  A 73-year-old man with severe emphysema was talked into having an acupuncture treatment for his emphysema. Immediately after the acupuncture needles were removed, he began to complain of increasing shortness of breath. Within several hours, he was brought to the emergency room where a pneumothorax was found. On closer questioning, it was determined that an acupuncture needle had been inserted into the anterior chest just below the clavicle, probably in the second anterior rib space. Because of this man's severe disease and the typical muscle-wasting that accompanies it, it is easy to postulate that the acupuncture needle, in fact, penetrated the parietal and then the visceral pleura, causing the pneumothorax.  The man was treated appropriately and his pneumothorax responded to closed-chest thoracotomy. The patient's reserve was minimal, however, and after six days in the hospital, his condition
Distribution of peptide-specific and cross-reactive epitopes of antimitichondrial antibodies (AMA) of primary biliary cirrhosis (PBC)
Authors: M. Fusconi, H. Baum, A. Caselli, F. Cassani, G. Ballardini, M. Lenzi, D. Zauli, F.B. Bianchi
Journal: Journal of Hepatology (1990)
Matrix Metalloproteinase Inhibitor Prevents Acute Lung Injury After Cardiopulmonary Bypass
Authors: David E. Carney, Charles J. Lutz, Anthony L. Picone, Louis A. Gatto, N. S. Ramamurthy, Lorne M. Golub, Sanford R. Simon, Bruce Searles, Andrew Paskanik, Kathy Snyder, Christine Finck, Henry J. Schiller, Gary F. Nieman
Journal: Circulation (1999)

Background —Acute lung injury (ALI) after cardiopulmonary bypass (CPB) results from sequential priming and activation of neutrophils. Activated neutrophils release neutral serine, elastase, and matrix metalloproteinases (MMPs) and oxygen radical species, which damage alveolar-capillary basement membranes and the extracellular matrix, resulting in an ALI clinically defined as adult respiratory distress syndrome (ARDS). We hypothesized that treatment with a potent MMP and elastase inhibitor, a chemically modified tetracycline (CMT-3), would prevent ALI in our sequential insult model of ALI after CPB. Methods and Results —Anesthetized Yorkshire pigs were randomized to 1 of 5 groups: control (n=3); CPB (n=5), femoral-femoral hypothermic bypass for 1 hour; LPS (n=7), sham bypass followed by infusion of low-dose Escherichia coli lipopolysaccharide (LPS; 1 μg/kg); CPB+LPS (n=6), both insults; and CPB+LPS+CMT-3 (n=5), both insults plus intravenous CMT-3 dosed to obtain a 25-μmol/L blood concentration. CPB+LPS caused severe lung injury, as demonstrated by a significant fall in Pa o 2 and an increase in intrapulmonary shunt compared with all groups ( P &lt;0.05). These changes were associated with significant pulmonary infiltration of neutrophils and an increase in elastase and MMP-9 activity. Conclusions —All pathological changes typical of ALI after CPB were prevented by CMT-3. Prevention of lung dysfunction followed an attenuation of both elastase and MMP-2 activity. This study suggests that strategies to combat ARDS should target terminal neutrophil effectors.
Haiti: I want to go back
Authors: R. Villar
Journal: BMJ (2010)

After three earthquakes and as many wars, I should be in control. Yet fresh back from Haiti I am not. As I grow older emotionally I become more involved, not less. As I become more experienced I find it harder to detach myself from my surroundings. The callus, hard young man who first went to war in his 20s has become something of a softie three decades on. My job, as part of the United Kingdom’s emergency response, is to enter disaster zones while the locals leave. Haiti is a classic example: as five of us stride from our chartered aircraft towards the airport buildings in Port-au-Prince, 5000 inhabitants are hastening in the opposite direction.

My job is outwardly simple. Reach the disaster zone by the most rapid means and set up a field surgical facility for the team that is hot on my heels. The situation is pitiful: bodies line the streets, limbs protrude from shattered buildings, and those who survive stagger aimlessly with fixed gaze. There is no water, no food, and little fuel, and aftershocks are frequent and unpredictable. Orphaned children scream for their parents, while parents shout for their offspring. Where can they go? Where can anyone go? The smell of death is everywhere. Smoke and dust rise from the city while white United Nations vehicles in their hundreds hurtle almost haphazardly, soldiers with weapons drawn.

Making sense of such a situation is difficult, but I realise that …
Gestational Diabetes Identifies Women at Risk for Permanent Type 1 and Type 2 Diabetes in Fertile Age
Authors: Ilkka Y. Järvelä, Jaana Juutinen, Pentti Koskela, Anna-Liisa Hartikainen, Petri Kulmala, Mikael Knip, Juha S. Tapanainen
Journal: Diabetes Care (2006)

OBJECTIVE—Our aim was to evaluate the predictive value of gestational diabetes mellitus (GDM), diabetes-associated autoantibodies, and other factors for development of clinical diabetes later in life. RESEARCH DESIGN AND METHODS—In this case-control study the presence of autoantibodies was studied in 435 women with GDM and in healthy matched control subjects. The need for exogenous insulin during GDM was recorded. In the GDM group, the mean follow-up period was 5.7 years and in the control group 6.1 years. RESULTS—Among the subjects with GDM, 20 (4.6%) developed type 1 diabetes and 23 (5.3%) developed type 2 diabetes, whereas none of the control subjects became diabetic. Two-thirds of those who developed type 1 diabetes tested positive initially for islet cell antibodies (ICAs), whereas 56% of them had autoantibodies to GAD (GADAs) and 38% to the protein tyrosine phosphatase–related IA-2 molecule. Only 2 of the 23 women who presented later with type 2 diabetes tested positive for autoantibodies. According to multivariate analysis, initial age ≤30 years, the need for insulin treatment for GDM, and antibody positivity for ICAs and GADAs were associated with increased risk for clinical type 1 diabetes. CONCLUSIONS—Pregnancy seems to identify women who are at risk of developing diabetes later in life. About 10% of Finnish women with GDM will develop diabetes over the next 6 years; nearly half of them develop type 1 diabetes and the other half type 2 diabetes. Age ≤30 years, the need for insulin treatment during pregnancy, and positivity for ICAs and GADAs confer a high risk of subsequent progression to type 1 diabetes in women affected by GDM.
Microalbuminuria and Mortality in Long-Duration Type 1 Diabetes
Authors: Kate V. Allen, James D. Walker
Journal: Diabetes Care (2003)

Microalbuminuria is a recognized risk factor for increased mortality and renal failure in type 1 diabetes. Whether it remains a powerful predictor in patients with a long duration of type 1 diabetes is not known. We ascertained the prognostic significance of abnormal urinary albumin excretion in a cohort of patients with at least 30 years of type 1 diabetes.A total of 190 patients with a disease duration of type 1 diabetes of at least 30 years with baseline and 5 years of follow-up.At baseline 66% were normoalbuminuric, and at 5 years 11% of this cohort had died. Of the 22% who were microalbuminuric at baseline, 26% had died, and of the 8% with persistent proteinuria at baseline, 44% had died. Of the 4% with end-stage renal failure at baseline, 71% had died within 5 years. Death was attributable to a cardiovascular cause in two-thirds of the cases in all groups.Even in those with a long duration of type 1 diabetes, the presence of abnormal urinary excretion remains a powerful predictor of increased mortality.
AN UNUSUALLY LONG DIVERTICULUM OF THE ESOPHAGUS
Authors: A. H. Fineman
Journal: JAMA (1928)

Diverticula of the esophagus are generally classified into two varieties: the traction type and the pulsion variety. The former may occur at any part of the esophageal tube as a result of traction or a "pulling effect" by some chronic organic disease in the chest, such as tuberculous tracheobronchial glands, mediastinitis or vertebral caries. The latter usually occurs at the pharyngo-esophageal junction and is formed by a protrusion or "pushing" backward of the undefended triangular space, bounded above by the lower margins of the inferior constrictors, and below by the superior border of the posterior wall of the esophagus. This triangular area is frequently referred to as the "pharyngeal dimple" and consists of mucous membrane and submucosa. The inconstancy of muscle fibers at this site is a predisposing factor of pressure diverticula. Pulsion-traction diverticula are also described by some authors. The pressure diverticulum usually passes down