tbuckley/cabot-search huggingface dataset:
Early Ibuprofen Administration to Prevent Patent Ductus Arteriosus in Premature Newborn Infants
Authors: Anastasia Varvarigou
Journal: JAMA (1996)

To test whether early postnatal (0 to 3 hours) intravenous administration of ibuprofen will prevent patent ductus arteriosus (PDA) in preterm neonates.Prospective sequential controlled trial with three treatment arms.Level 3 perinatal-neonatal intensive care nursery.Thirty-four premature newborn infants born from February to August 1993 with a mean birth weight of 913 g (range, 565 to 1460 g) and gestational age of 26.9 weeks (range, 22.4 to 31.0).Infants were consecutively assigned within 3 hours of age to treatment with either one dose of ibuprofen lysine (10 mg/kg intravenously) followed by 5 mg/kg per dose intravenously at 24 and 48 hours of age (n = 12), one dose of ibuprofen lysine (10 mg/kg intravenously; n = 11), or saline (n = 11).Primary outcome variable was the presence of ductus arteriosus by echocardiography and clinical assessments at 3, 7, and 21 days of life. Secondary outcome variables included presence of intraventricular hemorrhage, renal function, ventilatory and oxygen needs, hematologic changes, gastrointestinal function, time to full enteral feeding, duration of hospitalization, and age at discharge.The three groups of patients were comparable in birth weight, gestational age, antenatal administration of betamethasone, and other perinatal characteristics. Ibuprofen treatment significantly reduced plasma levels of prostaglandins, and the levels remained low for 72 hours in newborns who received three doses of the drug. The incidence of PDA and other variables did not differ between patients who received a single dose of ibuprofen and those given saline. However, compared with the saline-treated newborns, babies who received three doses of ibuprofen had no PDA (0/12 vs 7/11 for saline; P < .02), had lower daily mean airway pressures (mean +/- SD, 5.2 +/- 1.1 cm H2O vs 8.3 +/- 2.8 cm H2O for saline; P < .02) and better oxygenation index (2.6 +/- 0.6 vs 4.7 +/- 1.8 for saline; P < .02) at the end of the first week of life, and required fewer days of ventilation (25 +/- 14 days vs 44 +/- 26 days for saline; P < .03). Babies given three doses of ibuprofen tended to tolerate full oral feedings earlier (35 +/- 19 days vs 56 +/- 34 days for saline; P = .09), had shorter duration of hospitalization (71.2 +/- 22.6 days vs 127.3 +/- 74.7 days for saline; P < .05), and were discharged to home at an earlier postconceptional age (37.8 +/- 2.0 weeks vs 44.8 +/- 9.8 weeks for saline; P < .05). ibuprofen treatment in this phase I trial was not associated with any apparent early neurological, intestinal, renal, hepatic, or hematologic complications.Administration of three doses of ibuprofen within 3 hours after birth in preterm neonates reduced the incidence of PDA without causing notable early adverse drug reactions in this phase I trial. Early closure of the ductus arteriosus was also associated with better respiratory outcome and earlier discharge from the hospital.
Nontraditional Risk Factors for Coronary Heart Disease Incidence among Persons with Diabetes: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Isao Saito
Journal: Annals of Internal Medicine (2000)

Background: Major risk factors explain much of the excess risk for coronary heart disease produced by diabetes, but nontraditional factors may also relate to incident coronary heart disease. Objective: To examine the association of traditional and nontraditional risk factors with incidence of coronary heart disease in adults with diabetes. Design: Prospective cohort study. Setting: The Atherosclerosis Risk in Communities (ARIC) Study. Participants: 1676 middle-aged persons who had diabetes but no history of prevalent coronary heart disease. Measurements: Multiple risk factors were recorded at baseline. Follow-up was from 1987 through 1995. Results: 186 participants developed incident coronary heart disease events during follow-up. As expected, the incidence of coronary heart disease in participants with diabetes was associated positively with traditional risk factors (hypertension, smoking, total cholesterol level, and low high-density lipoprotein [HDL] cholesterol level). After adjustment for sex, age, ethnicity, and ARIC field center, incident coronary heart disease was also significantly associated with waist-to-hip ratio; levels of HDL3 cholesterol, apolipoproteins A-I and B, albumin, fibrinogen, and von Willebrand factor; factor VIII activity; and leukocyte count. However, after adjustment for traditional risk factors for coronary heart disease, only levels of albumin, fibrinogen, and von Willebrand factor; factor VIII activity; and leukocyte count remained independently associated with coronary heart disease (P < 0.03). The relative risks associated with the highest compared with lowest groupings of albumin, fibrinogen, factor VIII, and von Willebrand factor values and leukocyte count were 0.64 (95% CI, 0.44 to 0.92), 1.75 (CI, 1.12 to 2.73), 1.58 (CI, 1.02 to 2.42), 1.71 (CI, 1.11 to 2.63), and 1.90 (CI, 1.16 to 3.13), respectively. Adjustment for diabetes treatment status attenuated these associations somewhat. Conclusions: Levels of albumin, fibrinogen, and von Willebrand factor; factor VIII activity; and leukocyte count were predictors of coronary heart disease among persons with diabetes. These associations may reflect 1) the underlying inflammatory reaction or microvascular injury related to atherosclerosis and a tendency toward thrombosis or 2) common antecedents for both diabetes and coronary heart disease.
Is sickle cell crisis a thrombotic event?
Authors: David Green, John Paul Scott
Journal: American Journal of Hematology (1986)

Abstract Although large vessel thrombi are occasionally reported in patients with homozygous sickle cell disease, the role of intravascular coagulation in typical pain crises is controversial. Therefore, we studied 24 sickle cell patients during and between episodes of pain crisis, using several sensitive tests of hemostasis. Fibrinogen was measured by a clotting assay, β3‐thromboglobulin (β‐TG) and fibrinopeptide A (FPA) were quantitated by radioimmunoassay, and protein C was determined by absorbing the zymogen from test plasma, activating it with thrombin‐thrombomodulin complex, and measuring activity with a selective synthetic substrate. Fibrinogen was elevated in asymptomatic patients (355 ± 145 mg/dl) but was no different from the value in these same patients during crisis (333 ± 180 mg/dl, p &gt; 0.1). Similarly, β‐TG 136 ± 52 ng/ml vs 118 ± 56; FPA 3.7 ± 4.8 ng/ml vs 5.2 ± 4.5, and protein C 71 ± 20% vs 66 ± 19 showed no important changes during crisis. However, all these values were significantly different from those in age‐ and sex‐matched healthy controls. (β‐TG, fibrinogen, and FPA were elevated (p &lt; 0.001, 0.005, and 0.05, respectively), and protein C was decreased (p &lt; 0.003). We conclude that while chronic intravascular coagulation is common in patients with sickle cell disease, there is no evidence that the pain crisis per se is a thrombotic event.
On Infusion of Matico as an Intra-Uterine Injection
Authors: W. Draper
Journal: BMJ (1875)

SIR,-According to your i-equest, I beg to report that I received this day from Inspector Fox the remains of a human body in a sealed coffin.I receivecl, also, fromii Dr. Larkini, the pelvic viscera of the same body in a close(d jar.lhe body was divided into ten pieces ; and, wlhen fitted together, proved to be the complete body of an adult female, in an advanced stage of decomposition.The length of the body was just iunader five feet.The woman had evidently been dead m-any months ; but certain-parts wvere well preserved wvhere they laad heen exposed, apparently, to the action of chloride of lime.Tlae divisioni of the body was undoubtedly of recent date, as proved by
Pathogenesis of septic shock in Pseudomonas aeruginosa pneumonia
Authors: Kiyoyasu Kurahashi, Osamu Kajikawa, Teiji Sawa, Maria Ohara, Michael A. Gropper, Dara W. Frank, Thomas R. Martin, Jeanine P. Wiener-Kronish
Journal: Journal of Clinical Investigation (1999)

The pathogenesis of septic shock occurring after Pseudomonas aeruginosa pneumonia was studied in a rabbit model. The airspace instillation of the cytotoxic P. aeruginosa strain PA103 into the rabbit caused a consistent alveolar epithelial injury, progressive bacteremia, and septic shock. The lung instillation of a noncytotoxic, isogenic mutant strain (PA103ΔUT), which is defective for production of type III secreted toxins, did not cause either systemic inflammatory response or septic shock, despite a potent inflammatory response in the lung. The intravenous injection of PA103 did not cause shock or an increase in TNF-α, despite the fact that the animals were bacteremic. The systemic administration of either anti–TNF-α serum or recombinant human IL-10 improved both septic shock and bacteremia in the animals that were instilled with PA103. Radiolabeled TNF-α instilled in the lung significantly leaked into the circulation only in the presence of alveolar epithelial injury. We conclude that injury to the alveolar epithelium allows the release of proinflammatory mediators into the circulation that are primarily responsible for septic shock. Our results demonstrate the importance of compartmentalization of inflammatory mediators in the lung, and the crucial role of bacterial cytotoxins in causing alveolar epithelial damage in the pathogenesis of acute septic shock in P. aeruginosa pneumonia.
Partition of carotid sinus baroreceptor response in dogs with chronic renal hypertension.
Authors: E Koushanpour, K J Kenfield
Journal: Circulation Research (1981)

This study was designed to determine whether resetting of the carotid sinus baroreceptors in chronic renal hypertension is due to altered distensibility of the wall, or changes in the properties of the receptor elements, or both. Dogs were made hypertensive by 50% constriction of the left renal artery with a Goldblatt clamp and by right nephrectomy one week later. Five to nine weeks after nephrectomy, when mean blood pressure had risen by 35-46 mm Hg, the isolated carotid sinus wall deformation, measured from still photographs, and gross baroreceptor nerve action potentials (N) were recorded in response to step intrasinus pressure forcings (P), ranging from zero to 300 mm Hg, in increments of 25 mm Hg. Measured wall deformation was converted to strain-energy density (SED), a scalar value, as the best indicator of the mechanical state of the sinus wall. Plots of N vs. P data followed an S-shaped pattern, but were shifted toward the P-axis, as compared to controls. Plots of SED vs. P, though linear over most of the pressure range, were shifted toward the SED-axis, as compared to controls. A plot of N vs. SED, derived from the composite plots of N vs. P and SED vs. P, followed an S-shaped pattern and also was shifted toward the SED-axis. We conclude that the nonlinearity in the N vs. P curve is due largely to the inability of the receptor elements to respond to increasing wall strain and to resetting of the baroreceptors due to changes in the receptor properties rather than in the wall elements.
Digitalis-associated cardiac mortality after myocardial infarction.
Authors: A J Moss, H T Davis, D L Conard, J J DeCamilla, C L Odoroff
Journal: Circulation (1981)

The effect of digitalis therapy on 4-month posthospital cardiac mortality was investigated in 812 patients who survived the hospital phase of acute myocardial infraction. A stepwise multiple logistic regression analysis was used to identify variables associated with increased mortality and to adjust for differences in confounding variables between digitalis and nondigitalis patients. The major 4-month mortality (10 of 26 patients [38.5%]) occurred in digitalis-treated patients with congestive heart failure in the coronary care unit and complex ventricular premature depolarizations (VPDs) on the predischarge Holter recording. Logistic analyses that controlled for confounding variables indicated that digitalis use contributed to the increased mortality rate in this high-risk subset. The predicted mortality difference due to digitalis in patients with congestive heart failure and complex VPDs, adjusted for relevant nondigitalis risk factor variables, was 30% (90% confidence interval 18-42%). This retrospective study suggests that digitalis use increases the early posthospital mortality of myocardial infarction patients with combined electrical and mechanical dysfunction.
A human ortholog of archaeal DNA repair protein Hef is defective in Fanconi anemia complementation group M
Authors: Amom Ruhikanta Meetei, Annette L Medhurst, Chen Ling, Yutong Xue, Thiyam Ramsing Singh, Patrick Bier, Jurgen Steltenpool, Stacie Stone, Inderjeet Dokal, Christopher G Mathew, Maureen Hoatlin, Hans Joenje, Johan P de Winter, Weidong Wang
Journal: Nature Genetics (2005)
Commentary: Patients will need knowledgeable guidance
Authors: A. Kent
Journal: BMJ (2013)

Recent progress in our ability to sequence our genome has been astonishing. Increasing speed and ever greater accuracy, coupled with costs falling precipitously, mean that whole genome sequencing is fast approaching the point where it might become a routine tool in the clinical management of patients with rare diseases, cancer, and infectious diseases such as malaria. 

Many patients, especially those with rare inherited diseases, experience long delays, often extending over years, before their condition is diagnosed. The advent of genome sequencing holds out the prospect of speedy, accurate diagnosis for all. Developments in stratified medicines, linked to genome analysis, …
Renal permeability alteration precedes hypertension and involves bradykinin in the spontaneously hypertensive rat.
Authors: G E Plante, M Bissonnette, M G Sirois, D Regoli, P Sirois
Journal: Journal of Clinical Investigation (1992)

Vascular permeability disorders have been described in experimental models, as well as in human hypertension. We recently described the fact that vascular permeability to albumin is heterogeneous in the normal rat. In the present study, we examine the contents of Evans blue dye (EB) bound to albumin in selected organs of unanesthetized Wistar Kyoto (WKY) and in spontaneously hypertensive rats (SHR) at various stages of development of hypertension. EB was injected in the caudal vein of paired 4, 8, 12, and 16-wk-old WKY and SHR. Rats were killed 10 min after EB injection and extraction of the marker was measured in selected tissues. In additional 4 and 16-wk-old animals, bradykinin B1 and B2 receptor antagonists (BKA) were also injected with EB. Renal contents of EB bound to albumin were higher in the SHR than in the WKY: 196 +/- 9, 202 +/- 10, 182 +/- 7, and 196 +/- 9, compared with 158 +/- 8, 155 +/- 7, 138 +/- 7, and 118 +/- 6 micrograms/g dry tissue, in the 4, 8, 12, and 16-wk-old rats, respectively. In the 4-wk-old SHR and WKY, blood pressure values were normal and comparable, yet the alteration in EB permeability was already present in the SHR. Both BKA failed to alter the renal EB extravasation in the WKY, but the B2-BKA restored the renal permeability to control levels in the SHR. We conclude that a selective defect in the renal vascular permeability to EB developed in the SHR. Since this finding precedes hypertension and is corrected by a selective B2-BKA, it is suggested that bradykinin is involved at an early stage of the disease in the SHR.
Second-site mutation in the Wiskott-Aldrich syndrome (WAS) protein gene causes somatic mosaicism in two WAS siblings
Authors: Taizo Wada, Akihiro Konno, Shepherd H. Schurman, Elizabeth K. Garabedian, Stacie M. Anderson, Martha Kirby, David L. Nelson, Fabio Candotti
Journal: Journal of Clinical Investigation (2003)

Revertant mosaicism due to true back mutations or second-site mutations has been identified in several inherited disorders. The occurrence of revertants is considered rare, and the underlying genetic mechanisms remain mostly unknown. Here we describe somatic mosaicism in two brothers affected with Wiskott-Aldrich syndrome (WAS). The original mutation causing disease in this family is a single base insertion (1305insG) in the WAS protein (WASP) gene, which results in frameshift and abrogates protein expression. Both patients, however, showed expression of WASP in a fraction of their T cells that were demonstrated to carry a second-site mutation causing the deletion of 19 nucleotides from nucleotide 1299 to 1316. This deletion abrogated the effects of the original mutation and restored the WASP reading frame. In vitro expression studies indicated that mutant protein encoded by the second-site mutation was expressed and functional, since it was able to bind to cellular partners and mediate T cell receptor/CD3 downregulation. These observations were consistent with evidence of in vivo selective advantage of WASP-expressing lymphocytes. Molecular analysis revealed that the sequence surrounding the deletion contained two 4-bp direct repeats and that a hairpin structure could be formed by five GC pairs within the deleted fragment. These findings strongly suggest that slipped mispairing was the cause of this second-site mutation and that selective accumulation of WASP-expressing T lymphocytes led to revertant mosaicism in these patients.
Inhibitor of Apoptosis Proteins Limit RIP3 Kinase-Dependent Interleukin-1 Activation
Authors: James E. Vince, W. Wei-Lynn Wong, Ian Gentle, Kate E. Lawlor, Ramanjaneyulu Allam, Lorraine O'Reilly, Kylie Mason, Olaf Gross, Stephen Ma, Greta Guarda, Holly Anderton, Rosa Castillo, Georg Häcker, John Silke, Jürg Tschopp
Journal: Immunity (2012)
Abstract 900: Caveolin-1 silencing arrests the proliferation of glioblastoma cells by inhibition of STAT3 signalling
Authors: Anna Gasperi-Campani, Fabia Pancotti, Laura Roncuzzi
Journal: Cancer Research (2012)

Abstract Caveolin-1 is an essential structural constituent of caveolae implicated in mitogenic signalling, oncogenesis, angiogenesis, neurodegenerative diseases and senescence. Its role as a tumor suppressor gene or as a tumor promoter seems to strictly depend on cell type and tumor stage/grade. The high expression of caveolin-1 in some tumors in vivo is associated with increased tumor aggressiveness, metastatic potential and suppression of apoptosis. In the present study we investigated the role of Caveolin-1 in human glioblastoma cells proliferation, in which we found cav-1 expressed at high levels (A172, CRS-A2, LI). Results show that siRNA-mediated down-regulation of Cav-1 caused stable arrest of proliferation in each cell line. A marked reduction of cyclin D1 and of CDK4 expression was evident in the cells transfected with Cav-1 siRNA and consequently of phosphoRb. Furthermore, a significant decrease of the expression of Src and p38α and of their down-stream effector STAT3 was evident. Together, these findings indicate that Cav-1 silencing induces an arrest of tumor cells proliferation in vitro by a new inhibitory pathway in glioblastoma multiforme, the most aggressive of the primary central nervous system tumors, and provide new insights into the molecular mechanisms underlying the pro-survival and tumor-promoting functions of Cav-1. Grants from MIUR (RFO, PRIN), Roberto Pallotti's Legacy for Cancer Research, Cornelia Pallotti's Legacy for Cancer Research, University of Bologna, Italy Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 900. doi:1538-7445.AM2012-900
Inpatient rehabilitation for hip or knee osteoarthritis: 2 year follow up study
Authors: M Weigl
Journal: Annals of the Rheumatic Diseases (2004)

To examine the course of pain, physical function, and other health dimensions after a comprehensive inpatient rehabilitation intervention in patients with osteoarthritis (OA) of the hip or knee.An observational, prospective cohort study with assessments at baseline (entry into clinic), 1 (discharge from inpatient rehabilitation), 3, 6, 9, 12, and 24 months after baseline. Consecutively referred patients to an inpatient rehabilitation centre fulfilling the inclusion criteria were studied. 3-4 week comprehensive rehabilitation intervention, including strengthening exercise, flexibility training, endurance training, relaxation strategies, and consultations for preventive measures, was carried out. Individual home rehabilitation programmes were taught. Generic health status was measured using the SF-36, condition specific health was measured with the WOMAC questionnaire. Effects were analysed with sensitivity statistics (effect size, ES) and non-parametric tests.Data from 128 patients with complete follow up data were analysed. Both pain and physical function improved moderately (WOMAC pain: ES = 0.56, WOMAC function ES = 0.44) until discharge. Although the effect in pain reduction remained significant by month 24 (WOMAC: ES = 0.26), physical function deteriorated close to baseline values after 12 months.Comprehensive inpatient rehabilitation of patients with OA of the hip or knee may improve pain and physical function in the mid-term, and pain in the long term.
Ampicillin for sore throat.
Authors: D C Turk
Journal: BMJ (1973)

Ampicillin for Sore Throat SIR,-Dr. A. A. Robertson's conclusion (9 June, p. 614) that the use of ampicillin must be considered in the treatment of acute sore throats is based on the following premises: (l)-that Haemophilus influenzae is fre- quently isolated from the throats of patients with acute sore throats; (2)-that where this organism is isolated it is responsible for the acute sore throat; and (3)-that ampicillin is the antibiotic of choice in H. influenzae infections.
MODIFIED PHYSIOLOGIC PROCESSES FOLLOWING TOTAL REMOVAL OF THE LIVER
Authors: FRANK C. MANN
Journal: JAMA (1925)

The physiologic changes that occur when the liver is extirpated have been studied for several years in our laboratories. In this paper I shall present briefly a general review of the results of our experiments on the changes in physiologic processes produced by the sudden and complete removal of the liver, and discuss them in relation to the functions of the liver. Although a great many changes have been observed, data concerning the modification of carbohydrate metabolism, protein metabolism and the major constituents of the bile mainly will be presented. Several different species of animals have been employed in the experiments, such as the goose, the duck, the frog, the turtle and the fish. While the general effects of hepatectomy have been the same in all species of animals, the variation probably depending on the difference in metabolism of the various species, I shall emphasize the results as obtained in
Eczema of the Hands: Investigations into Dyshidrosiform Eruptions
Authors: Philip C. Anderson
Journal: JAMA (1967)

Simons' excellent monograph has been re-issued, revised, retitled, and although perhaps a little overwhelming in its broad challenge to our traditional concept of hand eczema, is a valuable publication. His book has not yet received the consideration it should have. To debate the question he raises, new clinical experiments may have to be done and old experiments re-investigated. Because eczema of the hands is a disease of such importance socially and economically, involving the young working person and causing dislocation of family life, a vigorous approach to the problem is much to be desired. I find Simons' lengthy criticisms, durable skepticism, eagerness to support new hypotheses, and impatience with old ideas, to be an appropriate approach to a subject which needs "crust breaking" so that new work may start. Perhaps, as he suggests, we have allowed the theories of allergy to dominate thinking for many decades, without demanding the usual