tbuckley/cabot-search huggingface dataset:
Dantrolene is neuroprotective in Huntington's disease transgenic mouse model
Authors: Xi Chen, Jun Wu, Svetlana Lvovskaya, Emily Herndon, Charlene Supnet, Ilya Bezprozvanny
Journal: Molecular Neurodegeneration (2011)

Abstract Background Huntington's disease (HD) is a progressive neurodegenerative disorder caused by a polyglutamine expansion in the Huntingtin protein which results in the selective degeneration of striatal medium spiny neurons (MSNs). Our group has previously demonstrated that calcium (Ca 2+ ) signaling is abnormal in MSNs from the yeast artificial chromosome transgenic mouse model of HD (YAC128). Moreover, we demonstrated that deranged intracellular Ca 2+ signaling sensitizes YAC128 MSNs to glutamate-induced excitotoxicity when compared to wild type (WT) MSNs. In previous studies we also observed abnormal neuronal Ca 2+ signaling in neurons from spinocerebellar ataxia 2 (SCA2) and spinocerebellar ataxia 3 (SCA3) mouse models and demonstrated that treatment with dantrolene, a ryanodine receptor antagonist and clinically relevant Ca 2+ signaling stabilizer, was neuroprotective in experiments with these mouse models. The aim of the current study was to evaluate potential beneficial effects of dantrolene in experiments with YAC128 HD mouse model. Results The application of caffeine and glutamate resulted in increased Ca 2+ release from intracellular stores in YAC128 MSN cultures when compared to WT MSN cultures. Pre-treatment with dantrolene protected YAC128 MSNs from glutamate excitotoxicty, with an effective concentration of 100 nM and above. Feeding dantrolene (5 mg/kg) twice a week to YAC128 mice between 2 months and 11.5 months of age resulted in significantly improved performance in the beam-walking and gait-walking assays. Neuropathological analysis revealed that long-term dantrolene feeding to YAC128 mice significantly reduced the loss of NeuN-positive striatal neurons and reduced formation of Htt exp nuclear aggregates. Conclusions Our results support the hypothesis that deranged Ca 2+ signaling plays an important role in HD pathology. Our data also implicate the RyanRs as a potential therapeutic target for the treatment of HD and demonstrate that RyanR inhibitors and Ca 2+ signaling stabilizers such as dantrolene should be considered as potential therapeutics for the treatment of HD and other polyQ-expansion disorders.
Unmatched bone marrow transplants successfully treat leukaemia
Authors: J. Siegel-Itzkovich
Journal: BMJ (1998)

A new method of bone marrow transplantation using donors matched for only one HLA haplotype has proved successful in leukaemia, increasing the prospects of finding suitable donors.

Italian and Israeli researchers have developed a technique that can make mismatched transplants as effective as those in which the tissue type of the donor and recipient are identical …
Lesson of the week Child sexual abuse enquiries and unrecognised vulval lichen sclerosus et atrophicus
Authors: P L Wood, T Bevan
Journal: BMJ (1999)

Unrecognised vulval dystrophy in young girls may wrongly suggest childhood sexual abuse

Lichen sclerosus et atrophicus in young girls can present as haemorrhagic areas on the vulva. Failure to consider this diagnosis and to treat the condition appropriately may lead to a misdiagnosis of child sexual abuse, resulting in a lengthy and distressing investigation for all concerned, particularly the parents. There was extensive publicity surrounding these issues in the United Kingdom after events in Cleveland in 1987. We present three patients with lichen sclerosis et atrophicus. In each case, investigations into child sexual abuse had been instigated before an appropriate referral and correct diagnosis were made.

### Case 1

A 6 year old girl was admitted to hospital as an emergency under the care of the paediatricians. There was a history of a suspected accidental fall, after which the girl's mother noticed blood staining on her daughter's underwear The girl lived with her mother and her mother's partner and visited her natural father once a week.

The local social services department had already been involved about six months previously because of a history of suspected, unexplained perineal trauma. At that time, after a visit to her father, the girl had complained of soreness around the vulva, and a brown discharge had been noticed on her underwear. The girl's mother had described continuing vaginal ulceration which did not heal completely. The symptoms had persisted despite antibiotic treatment, acyclovir for suspected genital herpes simplex infection (which prompted further investigation because of the association with child sexual abuse), and reassurance. …
Menopausal Estrogen Therapy and Hip Fractures
Authors: Annlia Paganini-Hill, Ronald K. Ross, Vibeke R. Gerkins, Brian E. Henderson, Mary Arthur, Thomas M. Mack
Journal: Annals of Internal Medicine (1981)

The association between menopausal estrogen therapy and hip fracture was studied in a retirement community. Ninety-one hip fracture cases during a 5-year period in female residents under age 80 were compared to age-and race-matched community controls. Estrogen use was recorded from the medical records of the outpatient care facility and personal interviews. The estimated risk ratio for use of oral estrogens in excess of 60 months was 0.42. This protective effect was largely limited to oophorectomized women for whom the risk ratio for a comparable duration of use was 0.14; the risk significantly decreased with increased duration, but no such trend existed with increased dosage. Diabetes mellitus, low Quetelet's index, tallness, prolonged immobilization or physical inactivity, use of corticosteroids, early age at menopause, low levels of sunlight exposure, and heavy cigarette smoking were each independent risk factors for hip fracture but none confounded the observed association with estrogen use.
Selective Forelimb Impairment in Rats Expressing a Pathological TDP-43 25 kDa C-terminal Fragment to Mimic Amyotrophic Lateral Sclerosis
Authors: Robert D Dayton, Michael A Gitcho, Elysse A Orchard, Jon D Wilson, David B Wang, Cooper D Cain, Jeffrey A Johnson, Yong-Jie Zhang, Leonard Petrucelli, J Michael Mathis, Ronald L Klein
Journal: Molecular Therapy (2013)

Pathological inclusions containing transactive response DNA-binding protein 43 kDa (TDP-43) are common in several neurodegenerative diseases including amyotrophic lateral sclerosis (ALS). TDP-43 normally localizes predominantly to the nucleus, but during disease progression, it mislocalizes to the cytoplasm. We expressed TDP-43 in rats by an adeno-associated virus (AAV9) gene transfer method that transduces neurons throughout the central nervous system (CNS). To mimic the aberrant cytoplasmic TDP-43 found in disease, we expressed a form of TDP-43 with mutations in the nuclear localization signal sequence (TDP-NLS). The TDP-NLS was detected in both the cytoplasm and the nucleus of transduced neurons. Unlike wild-type TDP-43, expression of TDP-NLS did not induce mortality. However, the TDP-NLS induced disease-relevant motor impairments over 24 weeks. We compared the TDP-NLS to a 25 kDa C-terminal proaggregatory fragment of TDP-43 (TDP-25). The clinical phenotype of forelimb impairment was pronounced with the TDP-25 form, supporting a role of this C-terminal fragment in pathogenesis. The results advance previous rodent models by inducing cytoplasmic expression of TDP-43 in the spinal cord, and the non-lethal phenotype enabled long-term study. Approaching a more relevant disease state in an animal model that more closely mimics underlying mechanisms in human disease could unlock our ability to develop therapeutics.
Dopamine Reward Pathway in Adult ADHD
Authors: Samuele Cortese, F. Xavier Castellanos
Journal: JAMA (2010)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Endoscopic Hemostasis in Acute Diverticular Bleeding
Authors: C. Prakash, H. Chokshi, D. T Walden, G. Aliperti
Journal: Endoscopy (1999)

Endoscopic hemostasis is the standard care in acute upper gastrointestinal bleeding [1] [2], and can be extended to bleeding angiodysplasia in the lower intestinal tract [3]. With the emerging role of urgent colonoscopy in acute lower intestinal bleeding [4] [5] [6], it is conceivable that actively bleeding diverticula will be identified with increasing frequency. Case reports suggest a limited role for endoscopic hemostasis of bleeding diverticula [7] [8], though techniques of localization and therapy are not well characterized. We describe our experience with endoscopic management of bleeding diverticula and review the literature pertinent to this procedure.
ANTIBODY FORMATION
Authors: Jonathan W. Uhr, Martin S. Finkelstein, Joyce B. Baumann
Journal: The Journal of Experimental Medicine (1962)

Injection of a small bacteriophage phiX 174 into guinea pigs results in an accelerated elimination of phage detectable as early as 24 hours after injection. The immune nature of the accelerated elimination is indicated by its specificity, by the appearance of excess specific serum antibody after phage elimination, and by the prevention of accelerated elimination by 400 r whole body x-irradiation of guinea pigs prior to injection of phage. The early antibody response is considered to be a primary one since an analogous response occurs in newborn guinea pigs, antibody is not detectable in the sera of non-immunized animals, and the second challenge with phiX stimulates a serum antibody response 100-fold greater than that after primary immunization. The early detection of immune elimination appears to be due, in part, to the small amounts of phage employed, since larger doses of phage delay the time of onset of detectable immune elimination. The early rise of serum antibody in the primary and secondary response appears exponential with a similar rate constant of antibody formation. The rate constant is also independent of dose. These findings have led to the suggestion that during this exponential phase, the relative rate of antibody formation at a cellular level may be constant for a given antigen.
Treatment of Massive Intrathecal Methotrexate Overdose by Ventriculolumbar Perfusion
Authors: Robert J. Spiegel, Paul R. Cooper, Ronald H. Blum, James L. Speyer, Duncan McBride, John Mangiardi
Journal: New England Journal of Medicine (1984)

INTRATHECAL chemotherapy is now widely used in the prophylaxis and treatment of neoplasms that metastasize to the central nervous system. Over 20 years of experience with intrathecal methotrexate therapy has resulted not only in improved survival rates in some cancers1 2 3 but also in the recognition of a number of acute and chronic toxicities. Exposure to methotrexate in high concentrations or for sustained periods is clearly neurotoxic, and various dosage recommendations have been suggested to avoid neurotoxicity.4 , 5 Clinical studies indicate that adults should receive a maximal intrathecal dose of 12.5 mg of methotrexate to avoid acute clinical neurotoxicity.Cases of inadvertent . . .
New Tool Measures 10-Year Fracture Risk
Authors: Bridget M. Kuehn
Journal: JAMA (2008)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
312 DEFINING THE IMPACT OF ORGAN DYSFUNCTION IN CIRRHOSIS: SURVIVAL AT A COST?
Authors: D.L. Shawcross, M.J. Austin, R.D. Abeles, M. McPhail, A. Yeoman, A.J. Portal, W. Bernal, G. Auzinger, E. Sizer, J.A. Wendon
Journal: Journal of Hepatology (2008)
Pattern of insulin delivery after intravenous glucose injection in man and its relation to plasma glucose disappearance.
Authors: E Ferrannini, A Pilo
Journal: Journal of Clinical Investigation (1979)

Plasma insulin concentrations after pulse intravenous injection of glucose show an early rise, which declines towards the prestimulation level smoothly. This pattern is the effect of both continuing secretion and hormone disappearance from the plasma. To reconstruct the time-course of the acutal secretory response, we measured insulin disappearance from the plasma of 17 healthy volunteers by means of a bolus intravenous injection of 125I-insulin, and then performed an intravenous glucose tolerance test with frequent blood sampling. The data were analyzed by deconvolution, which made it possible to compute the glucose-induced posthepatic insulin delivery rate minute by minute. Under basal conditions, 2.64 +/- 0.28 (mean +/-SEM) mU/min.m2 reaches the systemic circulation. In the 90 min that follow acute glucose stimulation, 0.86 +/- 0.11 U/m2, a 270% increment over the basal production rate, is made available to the periphery. A wide individual variability was found to exist in both the basal and the glucose-stimulated delivery. They were strongly (P less than 0.001) related to each other in a direct fashion. A first spike of insulin release (107 +/- 12 mU/min) occurred in all the subjects at 2.2 +/- 0.2 min followed, in 16 subjects, by a second spike (38 +/- 6 mU/min), at 11.3 +/- 0.9 min. Two-thirds of the total postglucose insulin output were associated with the initial, oscillatory phase (from 0 to 25 min, on average), and one-third with the "tail" phase (from 25 to 90 min), during which the average delivery rate was 5.0 +/- 0.9 mU/min.m2. The delivery curves were closely (mean squared deviation of 4.5 +/- 0.5 mU/min) reproduced by computer stimulation upon assuming that insulin secretion is a function of both glucose concentration and glucose rate of change. Both the first and the second spike of insulin delivery, but not the total insulin output during the test, showed a significant, positive correlation with the plasma glucose disappearance rate computed between 10 and 60 min. Furthermore, with a time shift of approximately equal to 15 min, a significant relationship between the phases of insulin secretion and the glucose decay rates, computed over corresponding time intervals, was evident throughout the test.
Updated Results of the Randomized Phase 2 Impact Trial: Maintenance with TLR-9 Agonist Mgn1703 Vs Placebo in Patients with Metastatic Colorectal Carcinoma (MCRC)
Authors: Hans-Joachim Schmoll, Jorge Riera-Knorrenschild, Hendrik Kroening, Frank Mayer, Dieter Nitsche, Reinhard Ziebermayr, Johannes Andel, Dirk Arnold, Burghardt Wittig, Werner Scheithauer
Journal: Annals of Oncology (2013)
Treatment for Pain in Terminal Illness
Authors: Gary D. Salkind
Journal: JAMA (1984)

<h3>To the Editor.—</h3> We refer to the recent article by McGivney and Crooks<sup>1</sup>on treatment of pain in terminal illness. However, we believe that an important modality for provision of analgesic medications has been overlooked. The following case will illustrate this. <h3>Report of a Case.—</h3> On Feb 5, 1982, an 87-year-old woman was admitted to the hospital with a four-month history of epigastric pain and weight loss. She was found to be anemic at the time of admission, and upper gastrointestinal tract roentgenograms revealed a mass in the stomach. Endoscopy with biopsy produced the diagnosis of adenocarcinoma of the stomach. Surgery was considered but refused by the patient and her family. The patient was without much pain initially but gradually experienced epigastric pain. This was originally controlled with antacids and oral narcotics. However, during the next 1 1/2 years, the patient had increasing difficulty swallowing and episodes of nausea.
Clinicians need better access to ethics advice, report says
Authors: Susan Mayor
Journal: BMJ (2005)

Health professionals should have access to ethics support at a local level and be able to ask for advice on ethical dilemmas 24 hours a day, a report from the Royal College of Physicians has recommended this week.

The report recommends that healthcare institutions should review their existing arrangements for providing support on ethics and develop and implement guidelines on how to recognise and handle advice on ethical …
Natural History and Predictors of Outcome in Patients With Concomitant Functional Mitral Regurgitation at the Time of Aortic Valve Replacement
Authors: Marc Ruel, Varun Kapila, Joel Price, Alexander Kulik, Ian G. Burwash, Thierry G. Mesana
Journal: Circulation (2006)

Background— Concomitant functional mitral regurgitation (FMR) in patients undergoing aortic valve replacement (AVR) is frequently not corrected because it may improve after AVR; however, data supporting this assumption are sparse. We ascertained the impact of clinical and echocardiographic parameters on the outcome of patients with or without concomitant FMR at the time of AVR. Methods and Results— Clinical and echocardiographic follow-up was performed on 848 patients who underwent AVR after 1990. Risk factors for mortality and a composite outcome of heart failure (CHF) symptoms, CHF death, or subsequent mitral repair or replacement, were examined with bootstrapped Cox proportional hazard models. Follow-up was 4591 patient-years (mean 5.4±3.4 years; maximum 14.2 years). FMR ≥2+ had no independent adverse effect on survival in patients with aortic stenosis (AS) or insufficiency (AI). However, AS patients with FMR ≥2+ and 1 additional risk factor (left atrial diameter &gt;5 cm, preoperative peak aortic valve gradient &lt;60 mm Hg, or atrial fibrillation) were at increased risk for the composite outcome (hazard ratio [HR]: 2.7; P =0.004). AI patients with FMR ≥2+ and a left ventricular end-systolic diameter &lt;45 mm were also at risk (HR: 4.0; P =0.02). Clinical risk factors in the AS and AI subgroups were associated with an increased likelihood of mitral regurgitation ≥2+ at 18 months postoperatively. Conclusions— AS patients with FMR ≥2+ and a left atrial diameter &gt;5 cm, preoperative peak aortic valve gradient &lt;60 mm Hg, or atrial fibrillation have a significantly higher risk of CHF and persistent mitral regurgitation after AVR than other AS patients. AI patients with FMR ≥2+ and a left ventricular end-systolic diameter &lt;45 mm preoperatively are also at increased risk. Others fare well after AVR.
Platelet P-selectin plays an important role in arterial thrombogenesis by forming large stable platelet-leukocyte aggregates
Authors: Shinji Yokoyama, Hisao Ikeda, Nobuya Haramaki, Hideo Yasukawa, Toyoaki Murohara, Tsutomu Imaizumi
Journal: Journal of the American College of Cardiology (2005)
Prophylactic surgical uptake in a cohort of BRCA carriers: an Irish perspective.
Authors: PA Carroll, J Kennedy, T Boyle, EM Connolly
Journal: Cancer Research (2009)

Abstract Abstract #3095 Introduction: Women with BRCA 1/2 mutations have a lifetime risk of approximately 45-87%1 for developing breast cancer and a 20-60% risk for ovarian cancer. The managment of these patients including prophylactic surgery is contorversial and presents difficult choices for patients. Uptake of prophylactic surgery in BRCA carriers in an Irish setting has not previously been investigated.&amp;#x2028; Methods: St. James hospital is a tertiary referral hospital for BRCA counselling and testing. All information was gathered and analysed from the Cancer genetics department database in our institution which provides a counselling service for a number of hereditary diseases.&amp;#x2028; Results: Deleterious BRCA 1/2 mutations have been identified in 57 families since testing began in 1992. There are a total of 109 women in this cohort.&amp;#x2028; 54% of these women were diagnosed with primary breast cancer. 23 (47.9%) women were symptomatic on presentation. Only 3 (6.3%) were detected during screening. Inital surgery and prophylactic surgery uptake in this group is displayed in table 1.&amp;#x2028; 31% (n=34) of our BRCA carrier cohort remain unaffected. Uptake of surgical prohylaxis is outlined in table 2. 17 women in this group opted for no form of prophylaxis. 88% of the women will require regular screening for breast cancer.&amp;#x2028; Age at bilateral prophylactic masectomy was 30.5 years. Of the 39 women in both groups who elected for bilateral salpingo oophorectomy, only 28% (11) women were under the age of 40 years.&amp;#x2028; &amp;#x2028; CPM Contralateral Prophylactic Mastectomy&amp;#x2028; TAH/BSO Total Abd Hysterectomy/Bilat Salpingo oopherectomy&amp;#x2028; &amp;#x2028; TAH/BSO Total Abd Hysterectomy/Bilat Salpingo oopherectomy&amp;#x2028; BPM Bilateral Prophylactic Mastectomy&amp;#x2028; Discussion: Prophylactic mastectomy offers a 95% risk reduction for breast cancer of 95%, despite this, a survival benefit has not been proven. Prophylactic oophorectomy before the age of 40 years has been associated with a reduction in breast cancer of 50% and up to 80% reduction in ovarian/peritoneal malignancy.There is also data to support that oophorectomy provides a survival benefit in BRCA carriers. The rates of uptake of prophylactic surgery in both the affected and unaffected groups in our cohort are lower than that of international standards2. The reasons for this are currently under investigation.&amp;#x2028; References:&amp;#x2028; 1. Ford D et al. Genetic heterogeneity and penetrance analysis of the BRCA1/2 genes in breast cancer families. Am J Hum Genet 1998;62(3):676-89.&amp;#x2028; 2. Metcalfe KA, et al.International variation in rates of uptake of preventive options in BRCA1/2 mutation carriers. Int J Cancer. 2008 May 1;122(9):2017-22. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3095.
TCTAP A-070 Impact of Hypertension on 5-Year Clinical Outcomes in Patients with Significant Coronary Artery Spasm; A Propensity Score Matching Study
Authors: Byoung Geol Choi, Seung-Woon Rha, Se Yeon Choi, Shaopeng Xu, Jabar Ali, Harris Ngow, Ji Bak Kim, Cheol Ung Choi, Eung Ju Kim, Dong Joo Oh
Journal: Journal of the American College of Cardiology (2015)