tbuckley/cabot-search huggingface dataset:
Angiotensin Tachyphylaxis and its Reversal
Authors: PHILIP A. KHAIRALLAH, IRVINE H. PAGE, F. Merlin BUMPUS, R. Kazim TURKER
Journal: Circulation Research (1966)

Tachyphylaxis to angiotensin and some analogues has been demonstrated on spirally cut arterial strips from cat, dog, sheep and rat, and on venous strips from rabbit and cat. Rabbit and guinea pig arteries do not appear to become tachyphylactic. A free C-terminal carboxyl group of angiotensin is necessary for binding with receptor sites and development of tachyphylaxis. Tachyphylaxis seems to represent saturation of receptor sites. It can be reversed by plasma fractions rich in angiotensinase A, possibly by metabolizing the N-terminal part of angiotensin directly from the bound state. Dowex 50 can also reverse it, probably by physical adsorption and stronger binding of angiotensin. Angiotensinase A does not metabolize βaspartyl 1 -angiotensin and does not reverse tachyphylaxis to this peptide. A possible scheme of interaction between peptide and receptor site is presented.
The association between lichen sclerosus et atrophicus and HLA-B40
Authors: CHRISTINE I. HARRINGTON, K. GELSTHORPE
Journal: British Journal of Dermatology (1981)

Fifty Caucasian females with lichen sclerosus et atrophicus were investigated to determine their HLA types. HLA-B40 was the only antigen found to be significantly more common in these patients when compared with a control population.
Micropuncture Analysis of Tubuloglomerular Feedback Regulation in Transgenic Mice
Authors: JURGEN SCHNERMANN
Journal: Journal of the American Society of Nephrology (1999)

Abstract. Micropuncture methods have been used widely as a means to define the function of single tubules and study the functional connection between tubules and afferent arterioles (so-called tubuloglomerular feedback [TGF]). Transgenic mouse strains have become a new research tool with the potential of shedding new light on the role of specific gene products in renal tubular and vascular function. The micropuncture approach has therefore been adapted to studies in the mouse kidney. Although the data presented here support the feasibility of using this technique in the mouse, technical improvements are desirable in the areas of anesthesia, ureteral urine collections, blood collections, volume replacement, and functional stability for extended time periods. During ketamine/inactin anesthesia, TGF responses could regularly be elicited in wild-type mice. In contrast, changes in loop flow did not alter stop-flow pressure in angiotensin II type 1A receptor and angiotensin-converting enzyme knockout mice. Infusion of angiotensin II in subpressor doses partially restored TGF responsiveness in angiotensin-converting enzyme knockout animals. Normal TGF responses compared to wild type were found in nitric oxide synthase I and thromboxane receptor knockout mice. Using free-flow micropuncture techniques, the proximal-distal single-nephron GFR difference was found to be augmented in aquaporin-1 and Na/H exchanger-3 knockout mice, suggesting TGF activation in these strains of mice. These results support an essential role of angiotensin II in TGF regulation mediated through the angiotensin II type 1A receptor. Chronic nitric oxide synthase I and thromboxane receptor deficiency did not change TGF responsiveness. Aquaporin-1 and Na/H exchanger-3 deficiency enhances TGF suppression of TGF probably by volume depletion-mediated TGF sensitization. The use of micropuncture methodology in transgenic mice combines old and new research tools in a way that promises to yield important new insights into single-nephron function in physiologic and pathophysiologic conditions.
Child Protection Companion
Authors: Tim David
Journal: Journal of the Royal Society of Medicine (2007)

There is a marked variation in the coverage of the subject of child abuse in paediatric textbooks. The standard and arguably definitive North American paediatric textbook (Nelson), contains only a short 12 page chapter (out of a total of 2618 pages) briefly reviewing the subject.1 Another North American paediatric textbook of biblical dimensions (2808 pages), Oski's Pediatrics, has a marginally longer (14 page) chapter on child maltreatment.2 In contrast, the standard and definitive UK paediatric textbook, Forfar & Arneil's Textbook of Pediatrics (1985 pages), has a substantial 27 page chapter covering the various types of abuse and neglect.3 To supplement these sources, there is an assortment of textbooks devoted solely to one or more facets of child abuse.

Do we need another book on the subject of child protection? The answer is that this is a highly original and much-needed book which fills some important gaps. It is not, however, a textbook on child abuse. There are no illustrations depicting injuries. For example, if you want to look up ‘shaken baby syndrome’, this is not the source to use. This is a handbook aimed at helping doctors in the process of child protection case management. There are chapters on important practical issues such as working with other professionals, consent and confidentiality, what to do if you are concerned that a child may be abused, documentation and recording, writing medical reports and police witness statements, court proceedings and giving evidence, and training and support for doctors. There are 18 appendices with examples of proformas, checklists, protocols, consent forms, flow charts and illustrations of how to structure medical reports. There is a chapter of practical advice on the photography of injuries.

The book includes a section on the recognition of maltreatment, and this helpfully sets out to provide evidence to support the advice given. Thus, for example, the book states (on the subject of bruising) that non-abusive bruising has a direct correlation to the developmental stage of the child, that boys and girls have equal rates of non-abusive bruising, and that certain areas of the body are rarely bruised at any age. All these statements are backed up by references to published evidence, where it exists, and the list of references to this section includes a recommended reading list. In addition there is a helpful list of useful websites.

All paediatricians need to be able to recognize the symptoms of abuse and neglect, and the RCPCH has embarked on a comprehensive programme of child protection training, of which this is an invaluable, clearly written and practical component. For those who question the relevance or utility of Royal Colleges, there could be no better example of leadership and provision of improved training than the recent efforts of the RCPCH in the field of child protection, and the team of authors and editors who contributed to this excellent resource are to be congratulated. That the RCPCH has made the publication freely available to all is particularly commendable.
Prospero-related homeobox 1 (PROX1) is frequently inactivated by genomic deletions and epigenetic silencing in carcinomas of the bilary system
Authors: Antonia Laerm, Peter Helmbold, Martina Goldberg, Reinhard Dammann, Hans-Jürgen Holzhausen, Wolfgang Gerhard Ballhausen
Journal: Journal of Hepatology (2006)
Neuromuscular magnetic stimulation of the quadriceps muscle after COPD exacerbations
Authors: Victor Bustamante, Elena López de Santamaría, Nuria Marina, Amaia Gorostiza, Zuriñe Fernández, Juan Gáldiz
Journal: European Respiratory Journal (2013)

Objective: To demonstrate the efficacy of a neuromuscular magnetic stimulation (NMMS) rehabilitation treatment after hospital admission because of COPD exacerbation.

Patients and methods: Prospective, randomized, double blind, sham training controlled clinical trial (Clinicaltrials [NCT01264978][1]).

35 COPD patients were included during hospitalization for COPD exacerbation. Treatment began less than 7 days after hospital discharge, either with sham or increasing intensity bilateral 15 minutes NMMS–training sessions, 3 times/week, during 8 weeks. A Medtronic Magpro electromagnet and several refrigerated 60 mm circular stimulation coils were employed (Bustamante et al. Respir Med. 2010;104:237-45).

Baseline and follow-up evaluations at 4, 8 and 12 weeks included: quadriceps supramaximal Twitch (Magstim 200, after Polkey, Muscle Nerve 1996;19: 549-55), maximal voluntary contraction of the quadriceps; 6MWT, CRQ, SF36, BODE and physical activity (accelerometers). Patient characteristics at baseline were: age 69 ± 8.5, 6/29 female/male, BODE 3.91 (2,2), 6MWT: 321,25m ± 131, FEV1 43,9% ± 14.7, SaO2 95% ± 1.45.

View this table:

Change in parameters





Conclusions: Our data show that NMMS can be a safe means to achieve a faster improvement in muscle function, exercise performance and quality of life in COPD patients recovering after an exacerbation.

 [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01264978&atom=%2Ferj%2F42%2FSuppl_57%2FP3572.atom
Does Treatment With Duloxetine for Neuropathic Pain Impact Glycemic Control?
Authors: Thomas Hardy, Richard Sachson, Shuyi Shen, Mary Armbruster, Andrew J.M. Boulton
Journal: Diabetes Care (2006)

OBJECTIVE—We examined changes in metabolic parameters in clinical trials of duloxetine for diabetic peripheral neuropathic pain (DPNP). RESEARCH DESIGN AND METHODS—Data were pooled from three similarly designed clinical trials. Adults with diabetes and DPNP (n = 1,024) were randomized to 60 mg duloxetine q.d., 60 mg b.i.d., or placebo for 12 weeks. Subjects (n = 867) were re-randomized to 60 mg duloxetine b.i.d. or routine care for an additional 52 weeks. Mean changes in plasma glucose, lipids, and weight were evaluated. Regression and subgroup analyses were used to identify relationships between metabolic measures and demographic, clinical, and electrophysiological parameters. RESULTS—Duloxetine treatment resulted in modest increases in fasting plasma glucose in short- and long-term studies (0.50 and 0.67 mmol/l, respectively). A1C did not increase in placebo-controlled studies; however, a greater increase was seen relative to routine care in long-term studies (0.52 vs. 0.19%). Short-term duloxetine treatment resulted in mean weight loss (−1.03 kg; P &amp;lt; 0.001 vs. placebo), whereas slight, nonsignificant weight gain was seen in both duloxetine and routine care groups with longer treatment. Between-group differences were seen for some lipid parameters, but these changes were generally small. Metabolic changes did not appear to impact improvement in pain severity seen with duloxetine, and nerve conduction was also not significantly impacted by treatment. CONCLUSIONS—Duloxetine treatment was associated with modest changes in glycemia in patients with DPNP. Other metabolic changes were limited and of uncertain significance. These changes did not impact the significant improvement in pain observed with duloxetine treatment.
Rheumatology. The Interdisciplinary Concept. Vol 12. Rheumatoid Arthritis: Surgery of the Shoulder
Authors: P G Stableforth
Journal: Annals of the Rheumatic Diseases (1989)

Fractures of the spinal column during rugby matches of all codes are rare but catastrophic, especially when associated with spinal cord injury. The cervical spine is vulnerable during trauma to the head and neck in contact sports. Spinal injuries reported during rugby matches have almost exclusively involved the cervical region, often with neurological sequelae. This is the first reported case of paraplegia caused by a fracture-dislocation of the thoracic spine resulting from a low velocity rugby union injury.
Children of Disaster: Clinical Observations at Buffalo Creek
Authors: C. JANET NEWMAN
Journal: American Journal of Psychiatry (1976)

Most of the 224 children who were survivor-plaintiffs of the Buffalo Creek disaster were emotionally impaired by their experiences. The major factors contributing to this impairment were the child's developmental level at the time of the flood, his perceptions of the reactions of his family, and his direct exposures to the disaster. The author focuses on children under 12, describing their responses to fantasy-eliciting techniques and their observed behavior after the flood compared with developmental norms for their age and reports of their previous behavior. These children share a modified sense of reality, increased vulnerability to future stresses, altered senses of the power of the self, and early awareness of fragmentation and death. These factors could lead to "after-trauma" in later life if they cannot make the necessary adaptations and/or do not receive special help to deal with the traumas.
Use of glyburide to treat gestational diabetes is linked to adverse outcomes in babies, study finds
Authors: J. Wise
Journal: BMJ (2015)

Babies born to mothers treated with the sulfonylurea drug glyburide (glibenclamide) for gestational diabetes mellitus are more likely to experience adverse outcomes than those whose mothers are treated with insulin, research published in JAMA Pediatrics has found.1 Although the oral hypoglycaemic agent does not have marketing authorisation for use in pregnancy, it is used increasingly widely.

The retrospective cohort study found that glyburide was associated with a higher risk for newborns to be admitted to a neonatal intensive care unit, to have respiratory distress, hypoglycaemia, or birth injury, or to be large for their gestational age when compared with infants born to women treated …
Therapeutic Use of Creatine in Brain or Heart Ischemia: Available Data and Future Perspectives
Authors: Luisa Perasso, Paolo Spallarossa, Carlo Gandolfo, Piero Ruggeri, Maurizio Balestrino
Journal: Medicinal Research Reviews (2011)

Creatine (Cr) is essential in safeguarding ATP levels and in moving ATP from its production site (mitochondria) to the cytoplasmic regions where it is used. Moreover, it has effects unrelated to energy metabolism, such as free radical scavenging, antiapoptotic action, and protection against excitotoxicity. Recent research has studied Cr-derived compounds (Cr benzyl ester and phos-pho-Cr-magnesium complex) that reproduce the neuroprotective effects of Cr while better crossing the neuronal plasma membrane and, hopefully, the blood-brain barrier (BBB). Intracellular levels of Cr can be increased by incubation with Cr or some of its derivatives, and this increase is protective against anoxic or ischemic damage. A large amount of experimental evidence shows that pretreatment with Cr is capable of reducing the damage induced by ischemia or anoxia in both heart and brain, and that such treatment may also be useful even after stroke or myocardial infarction (MI) has already occurred. Cr has been safely administered to patients affected by several neurological diseases, yet it has never been tested in human brain ischemia, the condition where its rationale is strongest. Phosphocreatine (PCr) has been administered after human MI, where it proved to be safe and probably helpful. Cr should be tested in the prophylactic protection against human brain ischemia and either Cr or PCr should be further tested in MI. Moreover, Cr- or PCr-derived drugs should be developed in order to overcome these molecules' limitations in crossing the BBB and the cell plasma membrane.
“White” network in Spitz nevi and early melanomas lacking significant pigmentation
Authors: Iris Zalaudek, Harald Kittler, Rainer Hofmann-Wellenhof, Juergen Kreusch, Caterina Longo, Joseph Malvehy, Susana Puig, Elvira Moscarella, Simonetta Piana, Cesare Massone, Carlo Cota, Gerardo Ferrara, Mariella Fleischer, Giuseppe Argenziano
Journal: Journal of the American Academy of Dermatology (2013)
Candidate genes and functional noncoding variants identified in a canine model of obsessive-compulsive disorder
Authors: Ruqi Tang, Hyun Ji Noh, Dongqing Wang, Snaevar Sigurdsson, Ross Swofford, Michele Perloski, Margaret Duxbury, Edward E Patterson, Julie Albright, Marta Castelhano, Adam Auton, Adam R Boyko, Guoping Feng, Kerstin Lindblad-Toh, Elinor K Karlsson
Journal: Genome biology (2014)

Abstract Background Obsessive-compulsive disorder (OCD), a severe mental disease manifested in time-consuming repetition of behaviors, affects 1 to 3% of the human population. While highly heritable, complex genetics has hampered attempts to elucidate OCD etiology. Dogs suffer from naturally occurring compulsive disorders that closely model human OCD, manifested as an excessive repetition of normal canine behaviors that only partially responds to drug therapy. The limited diversity within dog breeds makes identifying underlying genetic factors easier. Results We use genome-wide association of 87 Doberman Pinscher cases and 63 controls to identify genomic loci associated with OCD and sequence these regions in 8 affected dogs from high-risk breeds and 8 breed-matched controls. We find 119 variants in evolutionarily conserved sites that are specific to dogs with OCD. These case-only variants are significantly more common in high OCD risk breeds compared to breeds with no known psychiatric problems. Four genes, all with synaptic function, have the most case-only variation: neuronal cadherin ( CDH2 ), catenin alpha2 ( CTNNA2 ), ataxin-1 ( ATXN1 ), and plasma glutamate carboxypeptidase ( PGCP ). In the 2 Mb gene desert between the cadherin genes CDH2 and DSC3, we find two different variants found only in dogs with OCD that disrupt the same highly conserved regulatory element. These variants cause significant changes in gene expression in a human neuroblastoma cell line, likely due to disrupted transcription factor binding. Conclusions The limited genetic diversity of dog breeds facilitates identification of genes, functional variants and regulatory pathways underlying complex psychiatric disorders that are mechanistically similar in dogs and humans.
PATHOGENESIS OF EXPERIMENTAL CHOLERA
Authors: Richard A. Finkelstein, Joseph J. LoSpalluto
Journal: The Journal of Experimental Medicine (1969)

Choleragen, a diarrheagenic protein enterotoxin elaborated by Vibrio cholerae, has been isolated from the supernate of fermenter cultures by steps involving ammonium sulfate precipitation, DEAE cellulose, Sephadex G-75, and Agarose A-5m chromatography. The resulting product appears to be pure according to immunoelectrophoretic, disc electrophoretic, ultracentrifugal, and immunologic criteria. Sephadex gel filtration and membrane filtration studies suggest a molecular size of 61,000. The isolated product is highly active in inducing experimental cholera in infant and adult rabbit models. It also elicits, in small dosage, an increased vascular permeability in skin. These observations indicate that choleragenicity and increased vascular permeability are intimately associated phenomena and may be manifestations of the same basic mechanism. An additional, antigenically identical, protein has also been isolated by the same procedures. The latter substance, termed "choleragenoid", lacks the permeability effect and choleragenicity of the choleragen moiety. Its size (estimated from Sephadex gel filtration at 42,000) is smaller than that of choleragen and it also differs in charge. Choleragenoid may prove useful as a nontoxic immunogen to protect against pathologic effects of V. cholerae infection.
Clinical response and tolerability to abatacept in patients with rheumatoid arthritis previously treated with infliximab or abatacept: open-label extension of the ATTEST Study
Authors: M. Schiff, M. Keiserman, C. Codding, S. Songcharoen, A. Berman, S. Nayiager, C. Saldate, R. Aranda, J.-C. Becker, M. Nys, M. le Bars, D. M. Reed, C. Poncet, M. Dougados
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Objective</h3> To assess the efficacy and safety of abatacept in biological-naive patients with rheumatoid arthritis and an inadequate response to methotrexate treated in the long-term extension (LTE) of the ATTEST trial. <h3>Methods</h3> Patients randomly assigned to abatacept, placebo or infliximab completing the 1-year double-blind period were eligible to receive abatacept ∼10 mg/kg in the open-label LTE. Efficacy to year 2 is presented for patients randomly assigned to abatacept or infliximab who switched to open-label abatacept. Safety data are presented for all patients entering LTE regardless of double-blind treatment. <h3>Results</h3> Of 431 patients randomly assigned, 79.8% remained on abatacept at year 2. At years 1 and 2, 19.7% and 26.1% of abatacept and 13.3% and 28.6% of infliximab-to-abatacept patients achieved disease activity score 28-defined remission (&lt;2.6). Safety with abatacept during the cumulative study period was consistent with the double-blind experience, with no increase in adverse event incidence following the switch to abatacept. <h3>Conclusion</h3> In methotrexate-inadequate responders, abatacept efficacy was maintained over 2 years. For infliximab-to-abatacept patients, efficacy improvements were seen in year 2 after patients switched to abatacept. Switching directly from infliximab to abatacept was well tolerated. These data demonstrate that abatacept provides sustained responses and consistent safety, suggesting that switching from infliximab to abatacept is a viable treatment option.
Enhanced Delivery of SN-38 to Human Tumor Xenografts with an Anti-Trop-2–SN-38 Antibody Conjugate (Sacituzumab Govitecan)
Authors: Robert M. Sharkey, William J. McBride, Thomas M. Cardillo, Serengulam V. Govindan, Yang Wang, Edmund A. Rossi, Chien-Hsing Chang, David M. Goldenberg
Journal: Clinical Cancer Research (2015)

This study examined the delivery of SN-38 to Trop-2-expressing tumors and assessed the constitutive products in the serum, liver, and small intestine in nude mice bearing human tumor xenografts (Capan-1 or NCI-N87) given a single injection of irinotecan (40 mg/kg; ∼ 0.8 mg/mouse, containing ∼ 460 μg SN-38 equivalents) or sacituzumab govitecan (IMMU-132), an antibody-drug conjugate composed of a humanized anti-Trop-2 IgG coupled site specifically with an average of 7.6 molecules of SN-38.At select times, tissues were extracted and concentrations of the products measured by reversed-phase high-performance liquid chromatography (HPLC).In serum, >98% irinotecan cleared within 5 minutes; peak levels of SN-38 and SN-38G (glucuronidated SN-38) were detected in equal amounts at this time, and no longer detected after 6 to 8 hours. IMMU-132 was detected in the serum over 3 days, and at each interval, ≥ 95% of total SN-38 was bound to the antibody. Intact IMMU-132 cleared with a half-life of 14 hours, which closely reflected the in vitro rate of SN-38 released from the conjugate in mouse serum (i.e., 17.5 hours), whereas the IgG portion of the conjugate cleared with a half-life of 67.1 hours. In vitro and in vivo studies disclosed IgG-bound SN-38 was protected from glucuronidation. Area under the curve (AUC) analysis indicated that IMMU-132 delivers 20-fold to as much as 136-fold more SN-38 to tumors than irinotecan, with tumor:blood ratios favoring IMMU-132 by 20- to 40-fold. Intestinal concentrations of SN-38/SN-38G also were 9-fold lower with IMMU-132.These studies confirm a superior SN-38 tumor delivery by IMMU-132 compared with irinotecan.