tbuckley/cabot-search huggingface dataset:
Mutations in the mitochondrial GTPase mitofusin 2 cause Charcot-Marie-Tooth neuropathy type 2A
Authors: Stephan Züchner, Irina V Mersiyanova, Maria Muglia, Nisrine Bissar-Tadmouri, Julie Rochelle, Elena L Dadali, Mario Zappia, Eva Nelis, Alessandra Patitucci, Jan Senderek, Yesim Parman, Oleg Evgrafov, Peter De Jonghe, Yuji Takahashi, Shoij Tsuji, Margaret A Pericak-Vance, Aldo Quattrone, Esra Battologlu, Alexander V Polyakov, Vincent Timmerman, J Michael Schröder, Jeffery M Vance
Journal: Nature Genetics (2004)
Surgical Treatment of Parkinson Disease
Authors: Emad N. Eskandar, G. Rees Cosgrove, Leslie A. Shinobu
Journal: JAMA (2001)

SEVERAL EFFECTIVE NEUROSURGIcal treatments for Parkinson disease (PD) have been developed based on an improved understanding of basal ganglia circuitry and the continuing evolution of neurosurgical techniques. Currently, there are 3 surgical targets for the treatment of movement disorders, the globus pallidus interna (Gpi), the subthalamic nucleus (STN), and the Ventralis intermedius nucleus of the thalamus. The Gpi and the STN are the preferred targets for the treatment of PD while Ventralis intermedius is now primarily targeted in the treatment of tremor. Options for treatment include the placement of a deep brain stimulating (DBS) electrode in any of these areas or the creation of a small lesion in the Gpi (pallidotomy) or in the thalamus (thalamotomy).
Long-term propranolol administration alters myocyte and ventricular geometry in rat hearts with and without infarction.
Authors: M C Fishbein, L Q Lei, S A Rubin
Journal: Circulation (1988)

To determine the effects of long-term beta-adrenergic receptor blockade on adult rats with myocardial infarction, we studied 24 female Sprague-Dawley rats with myocardial infarction induced at 20-22 weeks of age. Two days after surgery, the animals were randomized to receive either propranolol (750 mg/l) in their drinking water or water alone for 5 weeks. Plastic, embedded, longitudinal and cross sections of septum (1 micron thick) were prepared for morphometric measurements. In untreated rats, infarction was followed by myocardial hypertrophy, as shown by significant increases in septal area (23%), myocyte length (19%), cross-sectional area (20%), and volume (43%) (p less than or equal to 0.05). In rats with and without infarction, beta-blockade resulted in decreased myocyte dimensions and increased left ventricular cavity dimensions. Propranolol had special effects in rats with infarction, resulting in significant blunting of increased cross-sectional area (15% less, p = 0.04) and a greater increase in left ventricular cavity dimensions (38% more, p = 0.04). Thus, propranolol blunts myocardial hypertrophy and increases left ventricular cavity dimensions in rats with myocardial infarction.
Decreasing the Adverse Effects of Cancer Therapy: National Cancer Institute Guidance for the Clinical Development of Radiation Injury Mitigators
Authors: Benjamin Movsas, Bhadrasain Vikram, Martin Hauer-Jensen, John E. Moulder, Ethan Basch, Stephen L. Brown, Lisa A. Kachnic, Adam P. Dicker, C. Norman Coleman, Paul Okunieff
Journal: Clinical Cancer Research (2010)

Recently, many agents have been identified that target molecular pathways that can mitigate radiation toxicity. To date, no drugs have been approved as radiation injury mitigators, which are defined as agents administered after irradiation but before toxicity is manifest. In order to accelerate the application of potential mitigators for cancer patients, a meeting sponsored by the National Cancer Institute (NCI) and National Institute of Allergy and Infectious Diseases (NIAID) was held in January 2010. This article presents an algorithm to guide clinical trials for such agents in patients receiving radiotherapy or radiochemotherapy. It reviews the mechanisms of radiation injury, the clinical problem, the preclinical and clinical development of candidate agents, and the design and conduct of clinical trials. The central role of patient reported outcomes is outlined, as well as key lessons learned from prior clinical trials. Ultimately, the goal is to be able to apply such promising agents to improve the quality of life for patients receiving radiotherapy or chemoradiotherapy for cancer.
Fashions in Medicine
Authors: J. R. Reynolds
Journal: BMJ (1871)

THERE are " fashions" in medical science as well as in medical practice; and, like fashions in other quarters, they have their uses and abuses,- they effect some good, and they do some harm.The use of fashion in scientific matters is this, that great attention is bestowed upon the object that may be said to be " fashionable," whether that be a method of work, a direction of work, or the employment of some agent which is believed to be capable of effecting certain results; and that this great attention resolves itself, as times goes on, into a sifting process, which enables those who fall in with the popular method, direction, or agency, to separate the useful from the useless, and to " throw away the worser half."The evil of fashion in matters medical is this, that, by the indi- vidual, the sifting process is ignored; there is often easy acquiescence in, and unquestioning adoption of, the principle or agent which is felt to be in vogue; and thus either or both may be employed to the exclusion or neglect of means and agencies which we can ill afford to lose.All multitudes, masses, or sets of men have a tendency to run into extremes, and individuals who make up such masses are not free from the influ- ences to which classes are exposed.It is bard work for any one to set himself against, and make way against, the current by which he finds himself surrounded; he too often finds it easy and convenient, and thinks it wise, to fall into the wake of others, and thus add force to the stream by which he and they are carried onwards.The result may be
Splenic cyst carcinoma presenting in pregnancy
Authors: L. Elit, B. Aylward
Journal: American Journal of Hematology (1989)

Abstract A case report of squamous cell carcinoma in an epidermoid cyst of the spleen is diagnosed in a pregnant female. Elaboration on the clinical, radiological, and pathological findings is presented to emphasize the distinguishing features of benign and malignant cysts.
The benefits and harms of intravenous thrombolysis with recombinant tissue plasminogen activator within 6 h of acute ischaemic stroke (the third international stroke trial [IST-3]): a randomised controlled trial
Authors: Peter Sandercock, Joanna M Wardlaw, Richard I Lindley, Martin Dennis, Geoff Cohen, Gordon Murray, Karen Innes, Graham Venables, Anna Czlonkowska, Adam Kobayashi, Stefano Ricci, Veronica Murray, Eivind Berge, Karsten Bruins Slot, Graeme J Hankey, Manuel Correia, Andre Peeters, Karl Matz, Phillippe Lyrer, Gord Gubitz, Stephen J Phillips, Antonio Arauz
Journal: The Lancet (2012)
Human immunodeficiency virus and liver disease: An update
Authors: Kenneth E. Sherman, Juergen Rockstroh, David Thomas
Journal: Hepatology (2015)

Human immunodeficiency viral (HIV) infection affects approximately 1.2 million persons in the United States and 35 million worldwide. Progression to advanced liver disease remains a leading cause of death among HIV‐infected persons in the United States and elsewhere. Though mortality from HIV complications has been dramatically reduced wherever effective combination antiretroviral therapy is used, there has been little impact on liver‐related mortality. Causes of liver disease in the setting of HIV infection include viral hepatitis, nonalcoholic fatty liver disease/nonalcoholic steatohepatitis, drug‐associated toxicities, and other metabolic/genetic disorders which interact in an environment modulated by persistent immune activation and altered cytokine display. Conclusion: Despite significant advances in treatment of hepatitis C virus and suppression of hepatitis B virus, treatment and management principles for liver disease in HIV‐infected patients remain challenging; limited resources, fragmented health care, and high levels of injection drug use, alcohol use, and depression remain relevant issues in the HIV‐infected patient .(H epatology 2015;62:1871–1882)
Prevalence of NIDDM and Impaired Glucose Tolerance in Aborigines and Malays in Malaysia and Their Relationship to Sociodemographic, Health, and Nutritional Factors
Authors: Osman Ali, T T Tan, O Sakinah, B A K Khalid, L L Wu, M L Ng
Journal: Diabetes Care (1993)

Objective— To determine the prevalence of diabetes mellitus and IGT in different ethnic groups living in the same physical environment and to find their relationship to nutritional status and dietary intake. Research Design and Methods— The study was conducted among Malays and Orang Asli in six rural and urban locations in Malaysia. OGTTs were performed on 706 adult subjects ≥ 18 yr of age. WHO criteria were used for diagnosing diabetes mellitus and IGT. Results— The overall prevalence of diabetes mellitus and IGT among Orang Asli was 0.3 and 4.4% compared with 4.7 and 11.3%, respectively, among Malays. This increased prevalence of glucose intolerance among Malays was associated with higher levels of social development. Among rural Malays, the crude prevalence of diabetes in a traditional village was 2.8% and in the land scheme was 6.7%, whereas urban Malays had a prevalence of 8.2%. In contrast, the prevalence of IGT (10.5–14.8%) was higher among rural Malays, compared with 9.6% among urban Malays. Ethnic group, ≥ 40 yr of age, an income &amp;gt; M$250, fewer daily activity, and obesity were associated with a higher prevalence of diabetes. Conclusions— Diabetes mellitus and IGT, which were more common among Malays than Orang Asli, were associated with more affluent life-styles and modernization.
Phase III Comparison of Standard Doxorubicin and Cyclophosphamide Versus Weekly Doxorubicin and Daily Oral Cyclophosphamide Plus Granulocyte Colony-Stimulating Factor As Neoadjuvant Therapy for Inflammatory and Locally Advanced Breast Cancer: SWOG 0012
Authors: Georgiana K. Ellis, William E. Barlow, Julie R. Gralow, Gabriel N. Hortobagyi, Christy A. Russell, Melanie E. Royce, Edith A. Perez, Danika Lew, Robert B. Livingston
Journal: Journal of Clinical Oncology (2011)

Patients with inflammatory breast cancer (IBC) or locally advanced breast cancer (LABC) were randomly assigned to 21-day doxorubicin and cyclophosphamide administered for five cycles (standard arm) versus weekly doxorubicin and daily oral cyclophosphamide administered with granulocyte colony-stimulating factor support for 15 weeks (continuous arm). All patients had subsequent weekly paclitaxel for 12 weeks before surgery.Patients (n = 372) were randomly assigned to the standard arm (n = 186) or the continuous arm (n = 186) stratified by disease type (LABC, n = 256; IBC, n = 116). The primary outcome was microscopic pathologic complete response (pCR) at surgery. Secondary outcomes included disease-free survival, overall survival, and toxicity.More patients in the standard arm had grade 3 to 4 leukopenia and neutropenia, but there were more instances of stomatitis/pharyngitis and hand-foot skin reaction in the continuous arm. Assessed among 356 eligible patients, pCR was not different between the treatment groups stratified by disease type (P = .42). In subset analysis, higher pCR rates were observed in the continuous arm versus the standard arm only for stage IIIB disease (P = .0057) and in IBC (P = .06). Comparison of overall survival and disease-free survival showed no difference between treatment groups (P = .37 and P = .87, respectively).No significant clinical benefit was seen for the investigational arm in this trial overall.
A Model-Based Method for Assessing Insulin Sensitivity From the Oral Glucose Tolerance Test
Authors: Andrea Mari, Giovanni Pacini, Elaine Murphy, Bernhard Ludvik, John J. Nolan
Journal: Diabetes Care (2001)

OBJECTIVE—Available insulin sensitivity (IS) methods based on the oral glucose tolerance test (OGTT) are empirical. We used a glucose-insulin model to derive an OGTT-based IS (oral glucose insulin sensitivity [OGIS]) index, which predicts glucose clearance in a glucose clamp. We validated OGIS against clamp data. RESEARCH DESIGN AND METHODS—OGIS requires glucose and insulin concentrations from a 75-g OGTT at 0, 2, and 3 h (3-h OGTT) or at 0, 1.5, and 2 h (2-h OGTT). The formula includes six constants optimized to match the clamp results. For this purpose, 15 lean nondiabetic subjects (BMI &amp;lt; 25 kg/m2), 38 obese nondiabetic subjects (BMI &amp;gt; 25 kg/m2), and 38 subjects with type 2 diabetes randomly underwent an OGTT and a 120 mU · min−1 · m−2 insulin infusion euglycemic clamp. Glucose clearance (ClCLAMP), calculated as the ratio of glucose infusion to concentration during the last hour of the clamp, was compared with OGIS. OGIS was also tested on an independent group of 13 subjects with impaired glucose tolerance (IGT). RESULTS—OGIS and ClCLAMP were correlated in the whole group (R = 0.77, P &amp;lt; 0.0001), in the subgroups (lean: R = 0.59; obese: R = 0.73; type 2 diabetes: R = 0.49; P &amp;lt; 0.02), and in the independent IGT group (R = 0.65, P &amp;lt; 0.02). Reproducibility of OGIS and ClCLAMP were similar (coefficients of variation: OGIS 7.1%, ClCLAMP 6.4%). OGIS was as effective as ClCLAMP in discriminating between groups (for OGIS, lean vs. obese: 440 ± 16 vs. 362 ± 11 ml · min−1 · m−2, P &amp;lt; 0.001; lean vs. type 2 diabetes: 440 ± 16 vs. 239 ± 7, P &amp;lt; 0.0001; obese vs. type 2 diabetes: 362 ± 11 vs. 239 ± 7, P &amp;lt; 0.0001; results were similar for ClCLAMP). The relationships between IS and BMI, fasting plasma insulin, and insulin secretion (calculated from the OGTT insulin concentration) were examined. OGIS yielded results similar to ClCLAMP and fully consistent with established physiological principles. The performance of the index for the 3-h and 2-h OGTT was similar. CONCLUSIONS—OGIS is an index of IS in good agreement with the clamp. Because of its simplicity (only three blood samples required), this method has potential use for clinical investigation including large-scale epidemiological studies.
Phylogeny Unites Animal Sodium Leak Channels with Fungal Calcium Channels in an Ancient, Voltage-Insensitive Clade
Authors: Benjamin J. Liebeskind, David M. Hillis, Harold H. Zakon
Journal: Molecular Biology and Evolution (2012)

Proteins in the superfamily of voltage-gated ion channels mediate behavior across the tree of life. These proteins regulate the movement of ions across cell membranes by opening and closing a central pore that controls ion flow. The best-known members of this superfamily are the voltage-gated potassium, calcium (Cav), and sodium (Nav) channels, which underlie impulse conduction in nerve and muscle. Not all members of this family are opened by changes in voltage, however. NALCN (NA+ leak channel nonselective) channels, which encode a voltage-insensitive "sodium leak" channel, have garnered a growing interest. This study examines the phylogenetic relationship among Nav/Cav voltage-gated and voltage-insensitive channels in the eukaryotic group Opisthokonta, which includes animals, fungi, and their unicellular relatives. We show that NALCN channels diverged from voltage-gated channels before the divergence of fungi and animals and that the closest relatives of NALCN channels are fungal calcium channels, which they functionally resemble.
Reciprocal expression of interferon gamma or interleukin 4 during the resolution or progression of murine leishmaniasis. Evidence for expansion of distinct helper T cell subsets.
Authors: F P Heinzel, M D Sadick, B J Holaday, R L Coffman, R M Locksley
Journal: The Journal of Experimental Medicine (1989)

We purified poly(A)+ mRNA from the spleen and lymph nodes at designated times after infection with Leishmania major in genetically susceptible BALB/c and resistant C57BL/6 mice. The steady-state levels of IL-2, IFN-gamma, IL-4, and IL-1 beta mRNA were determined using Northern hybridizations. IL-2 mRNA levels in the infected organs of BALB/c and C57BL/6 mice were comparable after infection, but IFN-gamma and IL-4 mRNA levels were reciprocally expressed. Levels of IFN-gamma mRNA in C57BL/6 draining nodes and spleen were significantly greater than in BALB/c mice except at 4 and 6 wk of infection, when splenic IFN-gamma mRNA levels were transiently comparable. In contrast, IL-4 mRNA was apparent only in BALB/c and not in C57BL/6 nodes and spleen. Tissue levels of IL-1 beta mRNA were 10-20-fold greater in BALB/c mice. BALB/c mice were pretreated with GK1.5 mAb, a manipulation that promotes healing of subsequent infection by transiently depleting L3T4+ cells. At 8 wk of infection, by which time lymphoid organs were repopulated with L3T4+ cells, GK1.5-pretreated BALB/c mice produced IFN-gamma, but not IL-4 message. Serum levels of IgE were markedly elevated in infected BALB/c, but not in infected C57BL/6 or GK1.5-pretreated BALB/c mice, consistent with in vivo biologic activity of IL-4 in nonhealing mice. Treatment of infected BALB/c mice with neutralizing anti-IL-4 antibody abolished the elevation of serum IgE and significantly attenuated the progression of disease as assessed by size and ulceration of the lesion, and by reduction in the number of tissue parasites. Both protective and deleterious responses to Leishmania infection have previously been shown to be L3T4+ cell dependent. Our findings are consistent with the differential expansion of protective, IFN-gamma-producing Th1 cells in healing mice, and the expansion of deleterious, IL-4-producing Th2 cells in nonhealing mice. The inverse relationship of IFN-gamma and IL-4 gene expression during leishmaniasis may underlie the divergence of cellular and humoral immunity that occurs during chronic infection with Leishmania and possibly other intracellular parasites.
Responses of asthmatic and non-asthmatic athletes to prolonged treadmill running.
Authors: W Freeman, M G Nute, S Brooks, C Williams
Journal: British Journal of Sports Medicine (1990)

Metabolic and cardio-respiratory responses of four asthmatic and four non-asthmatic athletes to two hours of treadmill running at 70 percent of maximal oxygen uptake are compared. The asthmatic group had pre-exercise airflow obstruction, as indicated by the lower forced expiratory volume in one second (FEV1) even after medication (2.90 +/- 0.661) compared to the non-asthmatic group (4.09 +/- 1.331). Changes in blood lactate, glucose and catecholamine concentrations as a result of the two hour run were similar for the two groups. However, the pattern of breathing was different. The asthmatics had a slower breathing frequency but a similar tidal volume to the non-asthmatics. Both groups had an increase in the ventilation rate over the two hour run. For the non-asthmatic group, this increase in ventilation was achieved by an increase in the breathing frequency (p less than 0.01), whereas tidal volume was reduced (p less than 0.05). The increase in the ventilation rate over the two hour run for the asthmatic group was brought about by a small increase in breathing frequency (p less than 0.05), whereas tidal volume was not changed. This maintenance of the tidal volume by the asthmatic athletes during endurance running may compensate for the airflow obstruction, and so allow successful participation in endurance running.
PWE-113 Diagnostic Benefit Of Mre Following Ct
Authors: S Dharmasiri, R Boud, A Dower, N Hennessy, L Standing, A Richards-Taylor, T Hollingworth, S Weaver, H Johnson, S McLaughlin
Journal: Gut (2014)

<h3>Introduction</h3> In patients presenting with symptoms suggestive of IBD (abdominal pain and/or diarrhoea) in common with ECCO guidelines colonoscopy is the first line test at our institution. In our practice magnetic resonance enterography (MRE) is then performed in those patients where there is a continuing clinical suspicion of small bowel Crohn’s disease. However in patients who present to non-IBD physicians Computed tomography of the abdomen and pelvis with contrast (CTAP) is often the first line investigation. In this situation MRE is commonly performed to exclude small bowel disease following review in the gastroenterology clinic. We are not aware of studies that have evaluated the additional diagnostic yield of MRE in this clinical scenario. <h3>Aim</h3> to establish the additional diagnostic yield of MRE in patients previously investigated with CTAP and ileo-colonoscopy. <h3>Methods</h3> Our radiology department maintain a prospective electronic database. We searched for all patients who underwent CTAP followed by MRE within the same 12 month period between February 2005 and February 2013. Electronic medical records were then reviewed. <h3>Results</h3> 80 patients were identified. The mean age at time of MRE was 49 (range 17–87), 45 (56%) were female. Indication for these investigations were: assessment of known Crohn’s disease; 18 (23%), abdominal pain; 34 (43%). Mean time between CTAP and MRE; 127 days (range 3–352). Final diagnosis was Crohn’s disease; 37 (45%), coeliac disease; 4(5%), irritable bowel syndrome 4(5%). In 11(14%) MRE added further information or changed the management for the patient. Of this group in 3 patients MRE identified terminal ileal (TI) inflammation that was not identified at CTAP. In two of these cases ileal-colonoscopy collaborated TI inflammation and in the third case capsule enteroscopy confirmed TI inflammation. In all three the final diagnosis was Crohn’s disease. Overall MRE identified one (1.25%) patient with possible CD that was missed at CTAP and ileo-colonoscopy. <h3>Conclusion</h3> In this study the diagnostic yield of MRE in patients previously investigated with ileo-colonoscopy and CTAP was low. This suggests that MRE has a limited diagnostic role in this specific situation and should be reserved for those patients where clinical suspicion remains high despite negative CTAP and ileo-colonoscopy or to further define complex disease. <h3>Disclosure of Interest</h3> None Declared.
ASSAY OF ANTI-ANDROGENS IN MAN BY THE SEBACEOUS GLAND RESPONSE
Authors: JOHN S. STRAUSS, PETER E. POCHI
Journal: British Journal of Dermatology (1970)

Journal Article ASSAY OF ANTI‐ANDROGENS IN MAN BY THE SEBACEOUS GLAND RESPONSE Get access JOHN S. STRAUSS, JOHN S. STRAUSS Department of Dermatology, Boston University School of Medicine, Boston University Medical Center, Boston, Massachusetts 02118 U.S.A Search for other works by this author on: Oxford Academic Google Scholar PETER E. POCHI PETER E. POCHI Department of Dermatology, Boston University School of Medicine, Boston University Medical Center, Boston, Massachusetts 02118 U.S.A Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 82, Issue s6, 1 June 1970, Page 33, https://doi.org/10.1111/j.1365-2133.1970.tb08003.x Published: 01 June 1970