tbuckley/cabot-search huggingface dataset:
Bystander Effect Contributes to the Antitumor Efficacy of CaSm Antisense Gene Therapy in a Preclinical Model of Advanced Pancreatic Cancer
Authors: Yan Yan, Semyon Rubinchik, April L. Wood, William E. Gillanders, Jian-yun Dong, Dennis K. Watson, David J. Cole
Journal: Molecular Therapy (2005)

Pancreatic adenocarcinoma (PC) is an aggressive malignancy resistant to standard treatment modalities. Previously, we have reported that cancer-associated Sm-like protein (CaSm) contributes to the neoplastic transformation of PC. In this study, we utilized a recently established preclinical model of PC to determine if molecular targeting of CaSm can serve as the basis for a novel PC therapy. In a subcutaneous tumor model, intratumoral administration of an adenoviral vector encoding CaSm antisense RNA (Ad-alphaCaSm) significantly inhibited Panc02 tumor growth. Furthermore, in a metastatic tumor model, systemic administration of Ad-alphaCaSm resulted in a significant decrease in the number of hepatic metastases and increased survival time. We assessed the efficiency of in vivo delivery and observed significant levels of vector transduction in tissues containing PC, as well as a bystander effect that was amplifying the efficacy of CaSm gene therapy. This bystander effect was also active in vitro and was shown to be at least partially independent of host-related mechanisms. We conclude that CaSm antisense gene therapy is an effective novel therapy for PC and that the antitumor efficacy is dependent on both direct and bystander mechanisms.
Alcoholic Fatty Liver
Authors: Charles S. Lieber, Emanuel Rubin
Journal: New England Journal of Medicine (1969)

SINCE the last review of alcoholic fatty liver in this journal,1 the incidence of this disorder has been increasing,2 , 3 and new information has been gathered concerning its pathogenesis.Etiologic Role of AlcoholThe hitherto widely accepted concept of the exclusive pathogenic role of malnutrition was based largely on experimental work in rats carried out by Best and Hartroft and their co-workers, who concluded that "there is no more evidence of a specific-toxic effect of pure ethyl alcohol upon liver cells than there is for one due to sugar."4 In these experiments ethanol was administered in drinking water, and accounted for . . .
Prospective comparison of three enoxaparin dosing regimens to achieve target anti‐factor Xa levels in hospitalized, medically ill patients with extreme obesity
Authors: Andrew Freeman, Tuesdy Horner, Robert C. Pendleton, Matthew T. Rondina
Journal: American Journal of Hematology (2012)

Enoxaparin is commonly used to prevent venous thromboembolism(VTE) [1,2] but has not been well-studied in patients with extreme obesity,a population at high risk for VTE. We prospectively compared three enoxaparin dosing regimens for the achievement of goal peak anti-Factor Xa levels in medically ill patients (n 5 31) with extreme obesity (body mass index (BMI) ‡ 40 kg/m2). Patients were assigned to receive fixed-dose (FD) enoxaparin 40 mg daily (QDay, n 5 11), weight based,lower-dose (LD) enoxaparin 0.4 mg/kg QDay (n 5 9), or weight based,higher-dose (HD) enoxaparin 0.5 mg/kg QDay (n 5 11). The average BMI and weight of the entire cohort was 62.1 kg/m2 (range40.5–82.4) and 176 kg (range 115–256 kg) and did not differ between groups. Peak anti-Factor Xa levels were significantly higher in the HD group compared to either LD or FD groups. Patients in the HD group achieved target anti-Factor Xa levels more frequently than the LD and FD groups (P < 0.05). Peak anti-Factor Xa levels did not correlate with age, weight, BMI, or creatinine clearance, demonstrating the predictability of weight-based enoxaparin dosing. There were no adverse events (e.g., bleeding, thrombosis, thrombocytopenia). To our knowledge this is the first prospective comparative study demonstrating that in extremely obese, medically ill patients enoxaparin 0.5 mg/kg QDay is superior to FD and LD enoxaparin for the achievement of target anti-Factor Xa levels.
Vitamin D Homeostasis in the Perinatal Period
Authors: Jean J. Steichen, Reginald C. Tsang, Tari L. Gratton, Alan Hamstra, Hector F. DeLuca
Journal: New England Journal of Medicine (1980)

To investigate vitamin D homeostasis in term pregnancy, we measured 1,25-dihydroxyvitamin D (1,25(OH)2D) in serum samples from 19 term pregnant women and in samples from the placental veins of their infants. Samples were obtained from 14 neonates at 24 hours of age. At delivery, maternal concentrations of 1,25(OH)2D were elevated above normal adult values; placental-vein concentrations in the infants were significantly lower than adult normal or maternal values and bore no relation to maternal values. By the time the infants reached 24 hours of age, their serum concentrations had reached normal adult values, concomitant with a decrease in serum concentration of ionized calcium. We speculate that low 1,25(OH)2D concentrations in utero suggest that there is no need for intestinal calcium absorption in the fetus. Postnatal increase of 1,25(OH)2D may result from its production as a prerequisite to extrauterine requirements for intestinal absorption of calcium and phosphorus.
Peak flow measurements among visitors to a public health exhibition
Authors: A. G. F. Brooks, R. E. Waller
Journal: Thorax (1972)

The results of measurements of peak flow made on 2,891 office workers and others attending a public health exhibition in the City of London have been analysed. After standardizing for height, peak flow was found to increase with age into the third decade before declining again, and there was evidence of a more rapid decline among continuing smokers than among those who had never smoked or had given up. Possible effects of exposure to air pollution were considered in terms of residential histories: mean peak flows for subjects born in London were a little below those of subjects born elsewhere.
Bristol consultants call for single site "super hospital"
Authors: R. Dobson
Journal: BMJ (2001)

More than 100 senior doctors are supporting a radical plan for a single “super hospital” in Bristol with 1500 to 2000 beds.

An action group of 18 consultants, who have launched a campaign website, say that health care in the city is now fragmented among three “antiquated, old-fashioned major hospitals”—Southmead, Frenchay, and Bristol Royal Infirmary.

“Bristol has three large, inadequate, inefficient, old hospitals. Patient care is compromised due to poor hospital facilities,” …
Urinary tract diseases.
Authors: B Moore-Smith
Journal: BMJ (1973)

and a large amount of blood evacuated.Progress was satisfactory and the patient discharged four days later.Case 5.-A 24-year-old man sustained steering wheel injury, producing contusion of the left lower chest and bruising of the perineum.X-ray examination showed a fracture of the inferior pubic ramus on the right side.Case 6.-A 22-year-old man crashed while driving a go-kart, throwing him against the steering wheel, which caused contusions of the groin and testicle on the left side.Case 7.-An 18-year-old man sustained contusions of the right lower chest when thrown against the steering wheel in a go-kart crash.Case 8.-A youth aged 16 sustained contusions and abrasions of the sacral region when his go-kart crashed.Case 9.-An 18-year-old woman struck her left knee against the steering -wheel when hit from behind by another go-kart.She sustained, contusion and abrasion of the knee.Case 10.-A woman aged 26 had her face and right knee con- tused by the steering wheel when her go-kart crashed.Case 11.-A 16-year-old youth sustained contusions and lacera- tions of the right ankle when it was caught between the wheels of two go-karts.Case 12.-A man aged 17 was injured by the steering wvheel of a crashed go-kart which caused contusion and abrasions of the front of the chest and contusion of his right elbow.
Are State Mortality Differences due to Migration From the Rust Belt?-Reply
Authors: Robert A. Hahn
Journal: JAMA (1991)

<h3>In Reply.—</h3> In our comparison of measures of excess chronic disease mortality in the United States, we used age-specific mortality rates for each state (including the 50 states and Washington, DC) in 1986 (calculated from deaths and intercensal population estimates, both for 1986). We age-standardized rates to the 1980 US population because these data are widely available. In an earlier publication (<i>MMWR</i>. 1989;39:17-20), we computed the rates in each state in the same way, but age-standardized them to the 1986 US population. In changing the standard population, the ranking was unchanged for 33 states, changed one place for 12 states, and changed two places for six states. In changing from the 1980 to the 1986 standard, the 10 states with the highest rates remained the top 10, while one state was added (Kansas) and one was dropped (Colorado) from the lowest 10. As Dr Richter suggests, changes in rank reflect
Is Placebo Response the Same as Drug Response in Panic Disorder?
Authors: Mark Hyman Rapaport, Mark Pollack, Robert Wolkow, Jack Mardekian, Cathryn Clary
Journal: American Journal of Psychiatry (2000)

The authors used seven definitions of response in panic disorder to compare patient-rated improvements in quality of life between patients with panic disorder who responded to sertraline and those who responded to placebo.They combined and examined data from two multicenter, randomized, double-blind, parallel-group, flexible-dose studies of panic disorder (N=302).Significant differences in quality of life between patients who responded to sertraline and those who responded to placebo were apparent across all the definitions of clinical response.Patients who respond to placebo in panic disorder treatment studies may show symptom relief but may not experience improvement in quality of life. Determinations of quality of life should be included as components of both standard clinical assessment and clinical treatment studies of patients with panic disorder.
IMPACT OF MITRAL REGURGITATION ON MORTALITY IN PATIENTS WITH SEVERE ISCHEMIC CARDIOMYOPATHY AND SUBSEQUENT INCOMPLETE REVASCULARIZATION IN THE SETTING OF JEOPARDIZED MYOCARDIUM
Authors: Deborah Kwon, Joao Cavalcante, Randall Starling, Milind Desai, Scott Flamm, Thomas Marwick, Rory Hachamovitch
Journal: Journal of the American College of Cardiology (2013)
A Medicolegal Encounter In Maryland
Authors: Jonathan M. Williams
Journal: JAMA (1975)

<h3>To the Editor.—</h3> A matter of great importance to the Medical and Legal community in Maryland came about during the first week of December 1974. The precedent it so nearly established raises great fear in my mind as to how state power and arrogance can infringe on the rights of members of its citizenry. The story started Oct 15, when a baby girl was born in Holy Cross Hospital, in Silver Spring, Md. The child was the second child to a young, intelligent, professional couple, but was born with severe birth defects—a widely opened and uncovered meningomyelocele or rachischisis in the dorsal-lumbar region, severe clubbing of the feet and deformity of the long bones of both lower extremities, genu recurvatum, no movement or sensation below the waist, and no bladder or bowel control. In addition to this, there was evidence of a beginning hydrocephalus. The pediatrician called in for consultation
Failure to show a fall in peripheral blood lymphocytes in patients receiving gold or penicillamine for rheumatoid arthritis.
Authors: M Ishigami, A J Chuck, A J Swannell, M Doherty, K Gordon
Journal: Annals of the Rheumatic Diseases (1987)

Failure to show a fall in peripheral blood lymphocytes in patients receiving gold or penicillamine for rheumatoid arthritis
Cytomegalovirus Infection After Renal Allotransplantation
Authors: John E. Craighead
Journal: JAMA (1967)

Cytomegalovirus (CMV) infection was established by virologic or serologic studies or both in 30 of 41 renal allograft recipients (73%) who survived one or more months after transplantation. The infection occurred in 22 of the 24 patients (91%) with serologic evidence of exposure to CMV before transplantation, but in only eight of 17 (47%) who had no demonstrable serum antibody at the time of the surgical procedure. The data strongly suggest that active CMV infection in renal graft recipients can result either from the activation of "latent" virus or from exposure to the virus after transplantation. The occurrence of the infection did not correlate with a well-defined clinical syndrome even though generalized cytomegalic inclusion disease was found in some patients at autopsy.
Localisation of collagen types and fibronectin in cartilage by immunofluorescence.
Authors: H B Evans, S Ayad, M Z Abedin, S Hopkins, K Morgan, K W Walton, J B Weiss, P J Holt
Journal: Annals of the Rheumatic Diseases (1983)

Collagens type I, II, III, IV, and V and the minor cartilage collagens, 1 alpha 2 alpha 3 alpha, C-PS 1, and C-PS 2, were purified, antibodies raised, and then used in immunofluorescence studies on bovine nasal cartilage (BNC). Punctate localisation was seen with the type II antibody. However, pretreatment of sections with hyaluronidase to remove the proteoglycan resulted in diffuse staining over all the section with this antibody. Antibodies to 1 alpha 2 alpha 3 alpha, C-PS 1, and C-PS 2 collagens gave no staining on untreated BNC sections, but after treatment with hyaluronidase all 3 antibodies showed as a diffuse 9halo9 round each chondrocyte lacuna. Anti-type I, anti-type III, and anti-type IV collagen antibodies did not stain untreated or enzyme treated BNC. Type V collagen antibodies gave a bright ring in the pericellular region of the lacunae of hyaluronidase-treated BNC. This was unexpected, as we could not detect type V collagen biochemically in the same cartilage. Anti-fibronectin antibodies stained areas distant from the chondrocytes, these areas being distinct from those stained by 1 alpha 2 alpha 3 alpha and C-PS antibodies, suggesting that fibronectin is not associated with these collagens in BNC. These results suggest that different collagen types may have different locations within the cartilage matrix, that proteoglycans may inhibit antibody association with collagen, and that fibronectin is normally not associated with all types of collagen.
I and i
Authors: Kevin Barraclough
Journal: BMJ (2001)

There is, I think, something ethereal about i —the square root of minus one. I remember first hearing about it at school. It seemed an odd beast at that time—an intruder hovering on the edge of reality.

Usually familiarity dulls this sense of the bizarre, but in the case of i it was the reverse: over the years the sense of its surreal nature intensified. It seemed that it was impossible to write mathematics that described the real world in …
Performances des examens morphologiques pour la détection préopératoire des gastrinomes duodénopancreatiques
Authors: C Murphy, D O'Toole, T Aparicio, L Palazzo, A Couvelard-Benveniste, L Choudat, A Aubert, R Lebtahi, F Maire, MP Vullierme, JC Soule, P Ruszniewski
Journal: Endoscopy (2007)

La détection préopératoire par scanographie (TDM) et scintigraphie des récepteurs de la somatostatine (SRS) des gastrinomes est souvent difficile en raison de leur localisation duodénale et de leur petite taille chez environ deux tiers des malades. La sensibilité moyenne de l'échoendoscopie (EE) pour la détection d'une tumeur duodénale est de 39% dans les travaux publiés jusqu'en 1995.
TOXIC EFFECT OF ALCOHOL IN EXSANGUINITY.
Authors: JOSEPH SAGER
Journal: JAMA (1884)

[Read to the Northwestern Ohio Medical Association, December 11, 1883.] On the third day of October, 1883, I was called to attend Mrs. B., the case proving to be placenta prævia. She was an American by birth, aged 42 years, and the mother of seven children. Upon arrival I found her almost totally exsanguinated and still bleeding. She wore the pallor of death, as much so as she did when she was dead. She could not speak above a whisper. The examination revealed a case of placenta prævia partialis; head presenting the mouth of the uterus very little dilated, with gushes of blood and no pain. The first I did I gave her a full dose of ergot, not for an oxytocic, but for a styptic; at the same time I gave her an injection of warm water followed with an injection of cold water. The opposite effect of cold
Lateral subluxation of the atlanto-axial joint in rheumatoid arthritis.
Authors: H C Burry, J M Tweed, R G Robinson, R Howes
Journal: Annals of the Rheumatic Diseases (1978)

Involvement of the cervical spine by rheumatoid disease is common, but lateral subluxation at the atlanto-axial level has not been recorded previously. The condition is due to asymmetrical erosion of the lateral atlanto-axial facet joint, and may be complicated by collapse of the lateral mass of the axis. The condition should be suspected in patients with rheumatoid arthritis (RA) who present with occipital, auricular, and/or facial pain.
Communication among health professionals
Authors: J. Gosbee
Journal: BMJ (1998)

Last year, my father was told by his family doctor that the cardiologist had found aortic stenosis during a diagnostic evaluation for hypertension. Some time later it transpired that the specialist's diagnosis had been wrongly transmitted. Instead of a major valve defect, my father actually had atherosclerosis, a much more benign diagnosis. The kind of culture that makes this sort of unfortunate miscommunication possible is examined in a paper in this week's BMJ and a recently published government report. 1 2 Their conclusions will come as no surprise to many BMJ readers—that communication between health professionals is a mess.

Both sets of authors offer a series of insightful recommendations on what might be done to improve things. However, there is also a pressing need to define the role of applied research in this area and to accept that …
Nonvolatile organic compounds in treated waters.
Authors: C D Watts, B Crathorne, M Fielding, S D Killops
Journal: Environmental Health Perspectives (1982)

Over the past decade much information has been published on the analysis of organics extracted from treated water. Certain of these organics have been shown to be by-products of the chlorination disinfection process and to possess harmful effects at high concentrations. This has resulted in increased interest in alternative disinfection processes, particularly ozonation. The data on organics had been largely obtained by using gas chromatography-mass spectrometry, which is only capable of analyzing, at best, 20% of the organics present in treated water. Research in key areas such as mutagenicity testing of water and characterization of chlorination and ozonation by-products has emphasized the need for techniques suitable for analysis of the remaining nonvolatile organics. Several methods for the isolation of nonvolatile organics have been evaluated and, of these, freeze-drying followed by methanol extraction appears the most suitable. Reverse-phase HPLC was used for separation of the methanol extract, but increased resolution for separation of the complex mixtures present is desirable. In this context, high resolution size exclusion chromatography shows promise. Characterization of separated nonvolatiles is possible by the application of state-of-the-art mass spectrometric techniques. Results obtained by these techniques have shown that the nonvolatile organic fraction of chlorinated drinking water consists of many discrete compounds. Among these, some of the chlorinated compounds are almost certainly by-products of disinfection. Studies of the by-products of ozonation of fulvic and humic acids isolated from river waters have indicated a similar proportion of nonvolatile organics. Further, ozonation can result in the release of compounds that are trapped in the macromolecules.
Gallstone disease without gallstones: A partial answer
Authors: Donald M. Small
Journal: Hepatology (1987)

Although bile acid and bile lipid metabolism have been studied in established cholelithiasis, little is known about them in patients destined to develop gall stones, but in whom the stones have not yet appeared (prestone gall stone disease). After confirmed complete gall stone dissolution and withdrawal of treatment, gall stones recur frequently. Before the stones reappear, these patients have ‘poststone gall stone disease.’ In 13 such patients we confirmed complete gall stone dissolution with two normal cholecystograms and in 11 of the 13 by normal ultrasonography, measured bile acid and bile lipid composition in fasting duodenal bile, bile acid synthesis from marker corrected three day faecal bile acid excretion, bile acid pool size using an abbreviated isotope dilution technique, ‘steady-state’ bile lipid secretion using a duodenal amino acid perfusion system and then calculated the enterohepatic cycling frequency of the bile acid pool and the relationship between pool size and body weight. The results confirm that after withdrawal of treatment the biliary cholesterol saturation index reverts to levels (1.6 ± SEM 0.4) comparable with those before dissolution therapy first began (1.6 ± 0.2; NS). The mean bile acid pool size in the 13 patients of 4.4±0.5 mmol was comparable with that in untreated gall stone patients. Pool size was significantly smaller in the nine non-obese patients (3.5 ± 0.3), than in the four obese (6.0 ± 0.8; p < 0.05). It also correlated significantly with body weight (r = 0.72) and with %IBW (r = 0.79). The coefficients of variation for biliary bile acid, phospholipid and cholesterol secretion were high, but the mean hourly secretion rates were of the same order as those seen in untreated gall stone patients studied with the amino acid duodenal perfusion stimulus. These results provide a baseline for assessing the response to postdissolution treatment and may indicate metabolic events leading to gall stone formation.
GPs are key to effective coordination of care for people with chronic conditions, study concludes
Authors: Z. Kmietowicz
Journal: BMJ (2013)

The best schemes for improving the care of people with long term or chronic conditions are those that are led by GPs, backed by a team of other health and social care professionals with common objectives and who audit their performance, says a report by the health policy think tank the King’s Fund.1

For its report the King’s Fund reviewed the literature on coordinated care of people with complex chronic conditions and examined five successful UK case studies: palliative care at home, mental health services, home care for people with dementia, care for older …