tbuckley/cabot-search huggingface dataset:
Electrophysiologic mechanisms underlying arrhythmias due to reperfusion of ischemic myocardium.
Authors: S M Pogwizd, P B Corr
Journal: Circulation (1987)

The mechanisms responsible for malignant ventricular arrhythmias associated with reperfusion of ischemic myocardium were delineated with a computerized, three-dimensional mapping system, with simultaneous eight-level transmural recordings from 232 bipolar sites. In six chloralose-anesthetized cats, regional ischemia was induced for 10 min by occlusion of the left anterior descending coronary artery, followed by reperfusion. At 10 min after ischemia, just before reperfusion, total ventricular activation time during sinus rhythm was significantly delayed (63 +/- 8 vs 25 +/- 2 msec before ischemia, p less than .001). Ventricular tachycardia (VT) occurred within 15 sec after reperfusion and in three animals culminated in ventricular fibrillation. In 75% of cases of nonsustained VT, initiation occurred in the subendocardium, at the border of the reperfused zone via a mechanism not involving reentry, as determined by the fact that continuous activation was not apparent and the time from the end of the sinus beat to the beginning of VT (142 +/- 14 msec) was not associated with any intervening depolarizations. In the remaining 25% of cases of nonsustained VT, initiation of the VT resulted from intramural reentry in the subendocardium adjacent to the site of delayed midmyocardial activation from the preceding sinus beat (total activation time = 151 +/- 9 msec, p less than .001 vs just before reperfusion). This reentrant mechanism was similar to that responsible for the majority of cases of VT during ischemia without reperfusion. Maintenance of VT during reperfusion occurred by nonreentrant mechanisms as well as by intramural reentry, with most cases of VT involving both mechanisms. Ventricular tachycardia leading to ventricular fibrillation was initiated in the subendocardium at the border of the reperfused zone by a nonreentrant mechanism and was maintained by both nonreentrant and reentrant mechanisms, at times in combination in the same beat. The coupling interval of the first ectopic beat of VT leading to ventricular fibrillation was not significantly different from that of nonsustained VT (199 +/- 16 vs 189 +/- 9 msec, p = NS). However, during the transition from VT to ventricular fibrillation, nonreentrant mechanisms arising both in the subendocardium and subepicardium led to very rapid acceleration of the tachycardia to the coupling interval of 92 +/- 2 msec, resulting in enhanced functional block and further conduction delay, with the total activation time of the transition beats exceeding the coupling interval of the tachycardia.(ABSTRACT TRUNCATED AT 400 WORDS)
Prevalence of anticardiolipin antibodies in juvenile chronic arthritis.
Authors: R Caporali, A Ravelli, F De Gennaro, G Neirotti, C Montecucco, A Martini
Journal: Annals of the Rheumatic Diseases (1991)

The prevalence of anticardiolipin antibodies was evaluated in 70 children with juvenile chronic arthritis (JCA), in 25 adult patients with rheumatoid arthritis, in 42 healthy children and in 40 adult controls. Thirty seven (53%) patients with JCA were positive for IgG or IgM anticardiolipin antibodies, or both, and 30 (43%) for IgG anticardiolipin antibodies. In contrast, only seven (28%) adult patients with rheumatoid arthritis presented anticardiolipin antibodies, which were of IgG class in four (16%) cases. IgG anticardiolipin antibodies were negative in all control subjects while IgM anticardiolipin antibodies were detected in two (5%) children and in four (10%) adult controls. No correlations were found in patients with JCA between the presence or titres of anticardiolipin antibodies and various clinical or laboratory variables. No patient with anticardiolipin antibodies showed any feature of the anticardiolipin syndrome.
Phase II study of CPT-11, a new camptothecin derivative, in metastatic colorectal cancer. CPT-11 Gastrointestinal Cancer Study Group.
Authors: Y Shimada, M Yoshino, A Wakui, I Nakao, K Futatsuki, Y Sakata, M Kambe, T Taguchi, N Ogawa
Journal: Journal of Clinical Oncology (1993)

PURPOSE A phase II study was conducted to evaluate the antitumor effect and toxicity of CPT-11 in patients with metastatic colorectal cancer. PATIENTS AND METHODS From December 1989 to March 1991, 67 patients with metastatic colorectal cancer were enrolled in this study. Sixty-three patients were assessable for toxicity and response. Their median age was 57 years (range, 24 to 72). Forty-six patients (73%) had a good performance status of 0 or 1. Fifty-one patients (81%) had received prior chemotherapy. The major sites of metastasis were liver (63%) and lung (44%). CPT-11 was administered as a 100 mg/m2 weekly intravenous infusion, or as 150 mg/m2 every 2 weeks. The dose was reduced based on the grade of leukopenia and diarrhea, if necessary. RESULTS A partial response was obtained in 17 of 63 assessable patients (27%; 95% confidence interval, 16% to 38%). The response rate in patients with prior radiotherapy or chemotherapy was 25% (13 of 52). Liver metastases showed a 15% (six of 40) response and lung metastases showed a 39% (11 of 28) response. The median duration of partial response was 127 days (range, 49 to 353) and the median overall duration of response was 208 days (range, 99 to 381). The major toxicities (&gt; or = grade 3) were leukopenia (16%), diarrhea (13%), nausea and vomiting (13%), and alopecia (11%). Adverse effects were generally well tolerated and reversible. Treatment could be continued on an outpatient basis for patients without severe toxicity. Hemorrhagic cystitis was not encountered in this study. CONCLUSION CPT-11 showed promising antitumor activity against metastatic colorectal cancer that was resistant to prior therapy. Further clinical trials of combination chemotherapy using CPT-11 are justified.
CD25 and indoleamine 2,3-dioxygenase are up-regulated by prostaglandin E2 and expressed by tumor-associated dendritic cells in vivo: additional mechanisms of T-cell inhibition
Authors: Michael S. von Bergwelt-Baildon, Alexey Popov, Tomo Saric, Jens Chemnitz, Sabine Classen, Marc S. Stoffel, Francesca Fiore, Udo Roth, Marc Beyer, Svenja Debey, Claudia Wickenhauser, Franz-Georg Hanisch, Joachim L. Schultze
Journal: Blood (2006)
aPKCλ/ι and aPKCζ Contribute to Podocyte Differentiation and Glomerular Maturation
Authors: Björn Hartleben, Eugen Widmeier, Martina Suhm, Kirstin Worthmann, Christoph Schell, Martin Helmstädter, Thorsten Wiech, Gerd Walz, Michael Leitges, Mario Schiffer, Tobias B. Huber
Journal: Journal of the American Society of Nephrology (2013)

Precise positioning of the highly complex interdigitating podocyte foot processes is critical to form the normal glomerular filtration barrier, but the molecular programs driving this process are unknown. The protein atypical protein kinase C (aPKC)--a component of the Par complex, which localizes to tight junctions and interacts with slit diaphragm proteins--may play a role. Here, we found that the combined deletion of the aPKCλ/ι and aPKCζ isoforms in podocytes associated with incorrectly positioned centrosomes and Golgi apparatus and mislocalized molecules of the slit diaphragm. Furthermore, aPKC-deficient podocytes failed to form the normal network of foot processes, leading to defective glomerular maturation with incomplete capillary formation and mesangiolysis. Our results suggest that aPKC isoforms orchestrate the formation of the podocyte processes essential for normal glomerular development and kidney function. Defective aPKC signaling results in a dramatically simplified glomerular architecture, causing severe proteinuria and perinatal death.
Steady state aldosterone dose-response relationships.
Authors: D B Young, A C Guyton
Journal: Circulation Research (1977)

The steady state effects of different infusion rates of aldosterone on plasma concentrations of sodium and potassium, plasma renin activity, sodium space, and mean arterial pressure were determined. Measured amounts of aldosterone were infused continuously into adrenalectomized dogs for 13 weeks. Four rates of aldosterone administration were used: 16 +/- 1 mug/day, 48 +/- 3 mug/day (approximately the normal secretory rate for 22-kg dogs on a daily sodium intake of 27 mEq, potassium intake of 27 mEq), 91 +/- 4 mug/day, and 219 +/- 10 mug/day. Each rate of infusion was continued until the dogs were in sodium and potassium balance and measured variables were steady. Decreasing the rate of aldosterone administration below normal led to sharp decreases in plasma sodium concentration and sodium space, while raising the rate above normal had little effect. Plasma potassium concentration varied inversely and significantly with changes in aldosterone administration over the entire range of rates. Plasma renin activity rose extremely rapidly as the level of aldosterone fell below normal and went to zero at aldosterone infusion rates slightly above normal. Arterial pressure increased as aldosterone rose above normal but did not fall below normal at subnormal aldosterone levels, probably because of the pressor effects of simultaneously generated angiotensin II.
Corrigendum to “Relationships between preclinical cardiac electrophysiology, clinical QT interval prolongation and torsade de pointes for a broad range of drugs: evidence for a provisional safety margin in drug development” [Cardiovasc. Res. 58 (2003) 32–45]
Authors: W REDFERN, L CARLSSON, A DAVIS, W LYNCH, I MACKENZIE, S PALETHORPE, P SIEGL, I STRANG, A SULLIVAN, R WALLIS
Journal: Cardiovascular Research (2004)

The following minor errors and potential ambiguities have been brought to our attention since publication of the article. None of these affect the interpretation of the data or overall conclusions.

1.  The reference [36] cited for the single report of torsade de pointes with fluoxetine (p. 40) actually refers to the possible mechanism outlined in the sentence that follows in the text. The reference for the report of torsade de pointes is: Appleby M, Mbewu A, Clarke B. Fluoxetine and ventricular torsade—is there a link? Int. J. Cardiol. 1995; 49: 178–180.

2.  The margin of hERG IC …
Hypertonic cryohemolysis: A diagnostic test for hereditary spherocytosis
Authors: S. Streichman, Y. Gesheidt, I. Tatarsky
Journal: American Journal of Hematology (1990)

Abstract Red blood cells of subjects with hereditary spherocytosis are specifically susceptible to temperature changes while suspended in hypertonic solutions. Based on this property, a new diagnostic test for hereditary spherocytosis is presented. The suggested method is 100% sensitive in the diagnosis of all patients, including asymptomatic obligate carriers with hereditary spherocytosis, and is very specific in different control groups. Unlike other methods designed for the diagnosis of hereditary spherocytosis, this test does not depend on the cells' surface‐ area‐to‐volume ratio. Normal red blood cells that were induced to become spherocytes by different means (i.e., vinblastine, lysophosphatidyl choline, and heat) and showed increased osmotic fragility did not become susceptible to the hypertonic cryohemolysis conditions.
Gemcitabine, oxaliplatin and weekly high-dose 5-FU as 24-h infusion in chemonaive patients with advanced or metastatic pancreatic adenocarcinoma: a multicenter phase II trial of the Arbeitsgemeinschaft Internistische Onkologie (AIO)
Authors: A.D. Wagner, P. Buechner-Steudel, A. Wein, H. Schmalenberg, U. Lindig, M. Moehler, R. Behrens, G. Kleber, O. Kuss, W.E. Fleig
Journal: Annals of Oncology (2006)
Genotype–Phenotype Correlations in Autosomal Dominant and Autosomal Recessive Polycystic Kidney Disease
Authors: Sandro Rossetti, Peter C. Harris
Journal: Journal of the American Society of Nephrology (2007)

The phenotypes that are associated with the common forms of polycystic kidney disease (PKD)--autosomal dominant (ADPKD) and autosomal recessive (ARPKD)--are highly variable in penetrance. This is in terms of severity of renal disease, which can range from neonatal death to adequate function into old age, characteristics of the liver disease, and other extrarenal manifestations in ADPKD. Influences of the germline mutation are at the genic and allelic levels, but intrafamilial variability indicates that genetic background and environmental factors are also key. In ADPKD, the gene involved, PKD1 or PKD2, is a major factor, with ESRD occurring 20 yr later in PKD2. Mutation position may also be significant, especially in terms of the likelihood of vascular events, with 5' mutations most detrimental. Variance component analysis in ADPKD populations indicates that genetic modifiers are important, but few such factors (beyond co-inheritance of a TSC2 mutation) have been identified. Hormonal influences, especially associated with more severe liver disease in female individuals, indicate a role for nongenetic factors. In ARPKD, the combination of mutations is critical to the phenotypic outcome. Patients with two truncating mutations have a lethal phenotype, whereas the presence of at least one missense change can be compatible with life, indicating that many missense changes are hypomorphic alleles that generate partially functional protein. Clues from animal models and other forms of PKD highlight potential modifiers. The information that is now available on both genes is of considerable prognostic value with the prospects from the ongoing genetic revolution that additional risk factors will be revealed.
THE CARE OF THE PATIENT DURING SERIOUS ABDOMINAL OPERATIONS
Authors: H. B. Gardner
Journal: BMJ (1907)

enable the proposed operation to be carried out or com- pleted.With one exception, a case of haemorrhoids, these were all cases of operations above the level of Poupart's ligament.In the haemorrhoid case the analgesia stage.only lasted for thirty minutes, and although the operation was almost finished the patient required a little chloroform at the end.The stovain in this case was not satisfactorily injected as there was a very poor flow of cerebro-spinal flaid.In the,others of this class of partial 7ailurrs the analgesia was good up to a certain level and the injection was well made; they were as follows:1. D. R, aged 60.Inguinal colostomy.-Theabdomen was opened without any pain, but any manipulation of the parietal peritoneum caused great pain, and he required to harve a general anaesthetic to enable fixation of the colon in the wound to be made.2. J. D., aged 61.CarcInoma of penis.-Thestovain produced good analgesia to the level of the anterior superior spinous processes of the ilium.As In these cases of carcinoma of the penis I always remove the glands In both Scarpa's triangles, as well as in both iliac fossae, the analgesia in this patient was not sufficiently high for this latter part of the operation.3. G. L, aged 36.Appendicitis.-Stovainproduced complete analgesia as high as Poupart's ligament on each side, but no bigher after twenty minutes.4. M. K.. aRed 27.Appendicitis.-Analgesiadeveloped to the level of first lumbar nerve, just short of the site of the Incision.5. J. B., aged 51.Right inguinal hernia.-Stovainproduced good analgesia in the left side up to the umbillcus, but none at all In the.right side of the middle line.6. L. C., aged 36.Appendicitis.-Analgesiaperfect on both sides to a point just below the site of the incision.B. Complete failure to produce analgesia, of which there were 15 instances.In 6 of these patients the injection was not satisfactory, owing to a deficient flow of the cerebro-spinal fluid.I think there can be no doubt that it is absolutely essential for successful analgesia that the flow of cerebro-spinal fluid shall be free.It must run from-the cannula, and about 5 or 8 c.cm. should be per-
A service evaluation of the Eczema Education Programme: an analysis of child, parent and service impact outcomes
Authors: S.J. Ersser, H. Farasat, K. Jackson, H. Dennis, Z.A. Sheppard, A. More
Journal: British Journal of Dermatology (2013)

The systematic support of parents of children with eczema is essential in effective disease management. The few existing support models have a limited evidence base. This paper reports the outcome-orientated service evaluation of an original, extensive, social learning-theory based, nurse-led Eczema Education Programme (EEP).To evaluate the EEP using specified child and parental outcomes and service impact data.From a sample of 257 parent-child dyads attending the EEP, a pretest-post-test design evaluated its child impact using health-related quality of life measures (Infants' Dermatitis Quality of Life index, which includes a small dermatitis severity element, and Children's Dermatology Life Quality Index), severity measures (Patient Orientated Eczema Measure), a new parental measure (Parental Self-Efficacy in Eczema Care Index) and service impact data based on general practitioner (GP) attendance patterns pre- and postintervention.Statistically significant impacts were observed on infant quality of life (P < 0·001), child quality of life (P = 0·027), disease severity (P < 0·001) and parental self-efficacy (P < 0·001). Improvements in child quality of life, parental efficacy and service impact were also evident from qualitative data. The cumulative total of all GP visits for selected participants post-EEP reduced by 62%.The EEP appears to be an effective model of delivering structured education to parents of children with eczema, and one generalizable to other multiethnic metropolitan populations. As a noncontrolled study, this rigorous service evaluation highlights the model's significance and the case for an evaluative multicentre randomized controlled trial of this educational intervention to inform a nurse-led programme of care.
Protocol for the dano-run study: a 1-year observational follow up study on running related injuries in 1000 novice runners
Authors: R Nielsen, D Ramskov, H Sorensen, M Lind, S Rasmussen, I Buist
Journal: British Journal of Sports Medicine (2011)

Background The knowledge on the relation between running patterns and Running Related Injuries (RRIs) is sparse. Studies have tried to document a relationship. However, no firm conclusions can be made. Still it is necessary to identify which running exposures increase the risk of injuries and which exposures might be considered safe. Objective The purpose of this study is to investigate the link between the running volume and the development of RRIs. Design Observational prospective follow up study. Setting Clinical setting on novice and recreational athletes. Participants Healthy individuals (N=1000) who have not been running the past 1 year is included. All participants receive a global positioning system (GPS) watch (Garmin FR 110) and a pair of neutral running shoes (Adidas Glide 2). They are instructed to start running as much as they want, two times a week as a minimum. They must wear their GPS watch at each training session and upload data to an internet based database. All participants are followed for 1 year. Assessment of risk factors Running volume measured as absolute number of kilometres and the graduation in kilometres pr. week over a period of 3 weeks. Main outcome measurement RRI is defined as any musculoskeletal complaint of the lower extremity or back causing a restriction of running for at least 1 week. Results Time to RRI is compared between groups with different absolute running volumes. In a similar way time to injury is compared between individuals with different weekly training graduations. Conclusion This study may be the first study to adequately measure running patterns reliably in a large sample. The exposure is quantified by GPS, which is not affected by subject recall and is therefore a clear methodological improvement compared to previous studies. If absolute volume or running graduation over time seems to lead to injury, the study findings and methodology create a solid foundation for future randomised controlled trials in this field.
Maternal disturbance in activated sphingolipid metabolism causes pregnancy loss in mice
Authors: Kiyomi Mizugishi, Cuiling Li, Ana Olivera, Jacek Bielawski, Alicja Bielawska, Chu-Xia Deng, Richard L. Proia
Journal: Journal of Clinical Investigation (2007)

Uterine decidualization, a process that occurs in response to embryo implantation, is critical for embryonic survival and thus is a key event for successful pregnancy. Here we show that the sphingolipid metabolic pathway is highly activated in the deciduum during pregnancy and disturbance of the pathway by disruption of sphingosine kinase (Sphk) genes causes defective decidualization with severely compromised uterine blood vessels, leading to early pregnancy loss. Sphk-deficient female mice (Sphk1(-/-)Sphk2(+/-)) exhibited both an enormous accumulation of dihydrosphingosine and sphingosine and a reduction in phosphatidylethanolamine levels in pregnant uteri. These mice also revealed increased cell death in decidual cells, decreased cell proliferation in undifferentiated stromal cells, and massive breakage of decidual blood vessels, leading to uterine hemorrhage and early embryonic lethality. Thus, sphingolipid metabolism regulates proper uterine decidualization and blood vessel stability. Our findings also suggest that disturbance in sphingolipid metabolism may be considered as a cause of pregnancy loss in humans.
Mutations in PAX2 Associate with Adult-Onset FSGS
Authors: Moumita Barua, Emilia Stellacci, Lorenzo Stella, Astrid Weins, Giulio Genovese, Valentina Muto, Viviana Caputo, Hakan R. Toka, Victoria T. Charoonratana, Marco Tartaglia, Martin R. Pollak
Journal: Journal of the American Society of Nephrology (2014)

FSGS is characterized by the presence of partial sclerosis of some but not all glomeruli. Studies of familial FSGS have been instrumental in identifying podocytes as critical elements in maintaining glomerular function, but underlying mutations have not been identified for all forms of this genetically heterogeneous condition. Here, exome sequencing in members of an index family with dominant FSGS revealed a nonconservative, disease-segregating variant in the PAX2 transcription factor gene. Sequencing in probands of a familial FSGS cohort revealed seven rare and private heterozygous single nucleotide substitutions (4% of individuals). Further sequencing revealed seven private missense variants (8%) in a cohort of individuals with congenital abnormalities of the kidney and urinary tract. As predicted by in silico structural modeling analyses, in vitro functional studies documented that several of the FSGS-associated PAX2 mutations perturb protein function by affecting proper binding to DNA and transactivation activity or by altering the interaction of PAX2 with repressor proteins, resulting in enhanced repressor activity. Thus, mutations in PAX2 may contribute to adult-onset FSGS in the absence of overt extrarenal manifestations. These results expand the phenotypic spectrum associated with PAX2 mutations, which have been shown to lead to congenital abnormalities of the kidney and urinary tract as part of papillorenal syndrome. Moreover, these results indicate PAX2 mutations can cause disease through haploinsufficiency and dominant negative effects, which could have implications for tailoring individualized drug therapy in the future.
INFLUENCE OF LIGATION OF PANCREATIC DUCTS OF DOGS UPON SERUM AMYLASE CONCENTRATION
Authors: Carl E. Johnson, Carl H. Wies
Journal: The Journal of Experimental Medicine (1932)

A sharp contrast has been demonstrated in regard to the post-operative amylase concentration of the sera of dogs, depending upon whether ligation of the pancreatic ducts was or was not a part of an otherwise prescribed operation. The characteristic feature is a marked rise of several hundred per cent in serum amylase concentration, sustained for several days, which is observed when the pancreatic ducts have been ligated.