tbuckley/cabot-search huggingface dataset:
Major contribution of tubular secretion to creatinine clearance in mice
Authors: Christoph Eisner, Robert Faulhaber-Walter, Yaohui Wang, Asada Leelahavanichkul, Peter S.T. Yuen, Diane Mizel, Robert A. Star, Josephine P. Briggs, Mark Levine, Jurgen Schnermann
Journal: Kidney International (2009)
The Metabolism of Angiotensin II
Authors: Robert L. Wolf, Milton Mendlowitz, Stanley E. Gitlow, Nosrat Naftchi
Journal: Circulation Research (1962)

1. I 131 -labeled angiotensin II has been employed to study the metabolism of this polypeptide. 2. Following the intravenous administration of angiotensin II-I 131 to normotensive and untreated primary benign hypertensive subjects, a slower angiotensin II degradation rate and a larger final volume of distribution of angiotensin II-I 131 was found in the hypertensive than in the normotensive patients. The slow rate of degradation of angiotensin II may be responsible for the increased quantity and concentration of this polypeptide in the body fluids. 3. Greater quantities of angiotensin II-I 131 are degraded in vitro by sera from untreated primary benign hypertensive patients than from normotensive or secondary renal hypertensive patients. There is evidence for the presence of a serum factor or factors enhancing angiotensin II-I 131 degradation and for the presence of a heat labile inhibitor.
Evidence that type I diabetes and thyrogastric autoimmunity have different genetic determinants.
Authors: A N Gorsuch, B M Dean, G F Bottazzo, J Lister, A G Cudworth
Journal: BMJ (1980)

The prevalences of autoimmune endocrine disease and relevant organ-specific autoantibodies were determined in 141 patients with type I (insulin-dependent) diabetes and their families. All available members of the families were genotyped for HLA. Islet-cell antibody was found in 10 (4%) out of 248 unaffected siblings, all of whom were genetically potential cases of diabetes. One developed classical symptoms six months later. In contrast, thyroid and gastric parietal-cell antibodies occurred independent of the HLA-linked susceptibility to diabetes. These results suggest that different genes control the production of these autoantibodies and the susceptibility to type I diabetes.
FILM VS. TLD WHOLE BODY MONITORS IN NUCLEAR MEDICINE
Authors: E. L. McGuire, P R. Jollos, G. L. Purnell, K. L. Thomas
Journal: Clinical Nuclear Medicine (1992)

S: APRIL 9–12, 1992 San Antonio Convention Center & Hyatt Regency Hotel SAN ANTONIO, TEXAS Southwestern Chapter Society of Nuclear Medicine SPECT/PET Nuclear Cardiology Symposium and 37th Annual Meeting: PDF Only
The American Society of Anesthesiologists Physical Status Score and Risk of Perioperative Infection
Authors: Marc A. Rozner
Journal: JAMA (1996)

<h3>To the Editor.</h3> —As an anesthesiologist who administers "prophylactic" antibiotics to patients in the perioperative period, I welcome and applaud the recent article by Dr Goldmann and colleagues<sup>1</sup>about the emergence and spread of resistant microorganisms in hospitals. I agree with Goldmann et al that reducing routine use of broad-spectrum antibiotics will involve a multidisciplinary approach, and this approach will take place only when hospital leadership demands it. However, I must criticize the authors' use of the physical status score, as determined by criteria from the American Society of Anesthesiologists (ASA), to determine a patient's susceptibility to a perioperative infection. The system in use today was originally published by Saklad in 1941,<sup>2</sup>modified to its current form by Dripps et al in 1961,<sup>3</sup>and remains essentially unchanged today. Although many studies have been performed to determine the accuracy of this scoring system with regard to surgical mortality,
Immunoglobulin gene usage and immunohistochemical characteristics of human monoclonal antibodies to the mitochondrial autoantigens of primary biliary cirrhosis induced in the XenoMouse
Authors: Motoko Sasaki, Judy Van De Water, Thomas P. Kenny, Michael L. Gallo, Patrick S. C. Leung, Yasuni Nakanuma, Aftab A. Ansari, Ross L. Coppel, James Neuberger, Eric M. Gershwin
Journal: Hepatology (2001)

The immunodominant antimitochondrial antibody (AMA) response in primary biliary cirrhosis (PBC) is directed against the E2 component of pyruvate dehydrogenase (PDC-E2). The nature of the clonal selection process is unclear, and to address this issue, we took advantage of a transgenic technology, XenoMouse, that contains 80% of the human immunoglobulin (Ig) variable gene repertoire and can produce high-affinity human antibodies to virtually any immunogen without evidence of clonal bias. We immunized mice with PDC-E2 to obtain 13 HmAbs, including 4 IgG 2 and 9 IgM isotypes. Immunoglobulin gene analysis was unique and demonstrated a clonal bias; the immunoglobulin gene usage was considerably different from other antibody responses analyzed in XenoMouse systems. Four of the 13 mAbs recognized the inner lipoyl domain of PDC-E2, 2 of 13 recognized the entire PDC-E2 molecule, 4 of 13 recognized PDC-E2 and OGDC-E2, 1 of 13 recognized OGDC only, 1 recognized BCOADC-E2 only, and 1 recognized an unidentified 100-kd mitochondrial protein. Immunohistochemical staining using these HmAbs produced mitochondrial staining of septal bile ducts in both PBC and control livers. Ig gene analysis showed that 7 of 13 HmAbs used the V H 3 and 4 of 13 used VH4 gene repertoire, respectively. Three of 7 V H 3 antibodies used the same Ig VH3-21 gene family found in human AMA from patients with PBC. The CDRs of these autoantibodies were slightly mutated when compared with the sequences present within the Ig germline genes. In conclusion, the XenoMouse not only recapitulates the unique specificity and restriction of PBC patients, but indicates that the autoantibodies are derived from a restricted clonal selection process. Such data suggest that the original immunogen leads to somatic mutation without subsequent development of determinant spreading. (Hepatology 2001;34:631-637.)
Nathan Smith Davis
Authors: Whitfield J. Bell
Journal: JAMA (1973)

Nathan Smith Davis (1817-1904), physician, teacher, author, and editor, was one of the most influential and powerful figures in the American medical profession for more than half a century. He inaugurated the movement that led to the founding of the American Medical Association, served as the Association's president in 1864, and was the first editor of its<i>Journal</i>. Not inappropriately, he has been called "the father of the American Medical Association." In 1875, in response to a query from Dr. Joseph M. Toner of Washington (himself a president of the Association and an indefatigable collector of biographical lore), Dr. Davis wrote a long autobiographical letter, valuable for its account of his early years and as interesting for what it omits as for what it relates of his later career. The letter, not previously published, is preserved in volume 73 of the Toner Papers in the Library of Congress; in the
Phototoxic blisters from high frusemide dosage
Authors: JOHN N. BURRY, JAMES R. LAWRENCE
Journal: British Journal of Dermatology (1976)

Blistering of exposed areas has appeared in patients suffering from chronic renal failure treated with high doses of frusemide. The blistering, which resembles that occurring in nalidixic acid phototoxicity and in porphyria cutanea tarda, is considered phototoxic in nature.
Superficial Accumulation of Plasminogen During Plasma Clot Lysis
Authors: Dmitry V. Sakharov, Dingeman C. Rijken
Journal: Circulation (1995)

Binding of plasminogen to partially degraded fibrin is an important step in fibrinolysis, influencing its rate and fibrin specificity. Little is known about the spatial distribution of plasminogen and of plasminogen-binding sites inside thrombi during lysis. In the present study, we investigated this problem, which is important for a better understanding of the local regulation of fibrinolysis and the rate-limiting factors of therapeutic thrombolysis.An experimental system was used that allowed continuous visualization and quantification by fluorescence microscopy of the spatial distribution of fluorescein-labeled plasminogen inside and outside model thrombi. Strong superficial accumulation of plasminogen was observed during lysis of a plasma clot induced by tissue-type or urokinase-type plasminogen activators in the surrounding plasma. A distinctly visible plasminogen-accumulating shell moved continuously with the reducing surface of the clot. The accumulation decreased in conditions of exhaustive activation of plasminogen in the outer plasma. It was found in a purified system that a thin superficial layer (approximately 50 microns wide) of a plasmin-treated fibrin clot exposes about 2.5 plasminogen-binding sites per fibrin monomer with a Kd of 2.2 mumol/L. At a physiological concentration of plasminogen (1.5 mumol/L) in the outer medium, plasminogen was concentrated about 10-fold in this layer. The binding was dose-dependently inhibited by epsilon-aminocaproic acid.We conclude that the generation of potent surface-associated plasminogen-binding sites during thrombolysis results in a strikingly high plasminogen concentration at the dynamically changing surface of a lysing clot. The necessity of a continuous plasminogen supply from the plasma supports the use of fibrin-specific and plasminogen-sparing agents for thrombolytic therapy.
Concurrent Temozolomide and Dose-Escalated Intensity-Modulated Radiation Therapy in Newly Diagnosed Glioblastoma
Authors: Christina I. Tsien, Doris Brown, Daniel Normolle, Matthew Schipper, Morand Piert, Larry Junck, Jason Heth, Diana Gomez-Hassan, Randall K. Ten Haken, Thomas Chenevert, Yue Cao, Theodore Lawrence
Journal: Clinical Cancer Research (2011)

To determine the maximum-tolerated dose (MTD) of radiation (RT) with concurrent temozolomide in patients with newly diagnosed glioblastoma (GBM), to estimate their progression-free (PFS) and overall survival (OS), and to assess the role of (11)C methionine PET (MET-PET) imaging in predicting recurrence.Intensity-modulated RT (IMRT) doses of 66 to 81 Gy, assigned to patients by the time-to-event continual reassessment method, were delivered over 6 weeks with concurrent daily temozolomide (75 mg/m(2)) followed by adjuvant cyclic temozolomide (200 mg/m(2) d1-5 q28d ×6 cycles). Treatment was based on gadolinium-enhanced MRI. Pretreatment MET-PET scans were obtained for correlation with eventual sites of failure.A total of 38 patients were analyzed with a median follow-up of 54 months for patients who remain alive. Late CNS grade ≥III toxicity was observed at 78 (2 of 7 patients) and 81 Gy (1 of 9 patients). None of 22 patients receiving 75 or less Gy developed RT necrosis. Median OS and PFS were 20.1 (14.0-32.5) and 9.0 (6.0-11.7) months, respectively. Twenty-two of 32 patients with pretreatment MET-PET uptake showed uptake beyond the contrast-enhanced MRI. Patients whose treatment did not include the region of increased MET-PET uptake showed an increased risk of noncentral failure (P < 0.001).Patients with GBM can safely receive standard temozolomide with 75 Gy in 30 fractions, delivered using IMRT. The median OS of 20.1 months is promising. Furthermore, MET-PET appears to predict regions of high risk of recurrence not defined by MRI, suggesting that further improvements may be possible by targeting metabolically active regions.
Health Care Workers With AIDS
Authors: M E Chamberland, L J Conley, T J Bush, C A Ciesielski, T A Hammett, H W Jaffe
Journal: JAMA (1991)

<h3>Objectives.</h3> —To characterize health care workers with the acquired immunodeficiency syndrome (AIDS) in the United States and to evaluate the role of occupational transmission of the human immunodeficiency virus (HIV). <h3>Data Source.</h3> —National AIDS surveillance data. <h3>Methods.</h3> —Health care workers with AIDS are reported to the Centers for Disease Control by state and local health departments. Health care workers who do not report a nonoccupational risk for HIV infection are termed<i>undetermined risk</i>cases and are investigated by health departments using a standard protocol. <h3>Results.</h3> —Through June 30,1990, there were 5425 cases of AIDS in health care workers reported in the United States. Three of these workers developed AIDS following well-documented occupational exposure to HIV-infected blood. Of the 539 health care workers initially reported without a nonoccupational risk, follow-up investigations were completed for 303. Nonoccupational risk factors were established for 237 (78.2%) of the 303 investigated health care workers; 66 workers (21.8%) remained in the undetermined category. Follow-up information was incomplete for 236 health care workers who also remained in the undetermined category, resulting in 5120 health care workers (94.4%) with AIDS with nonoccupational risks for HIV infection. Overall, health care workers were more likely than non—health care workers with AIDS to have an undetermined risk for HIV infection (5.6% vs 2.8%;<i>P</i>&lt;.001). While many of the 66 investigated health care workers had jobs involving contact with patients and/or potential contact with blood, none reported percutaneous, mucous membrane, or cutaneous exposures to blood or body fluids known to be infected with HIV. <h3>Conclusion.</h3> —Surveillance data suggest that most health care workers with AIDS acquired their HIV infection through a nonoccupational route. (<i>JAMA</i>. 1991;266:3459-3462)
BMJ joins campaign to put "science into assessment of research," as its impact factor rises
Authors: S. Mayor
Journal: BMJ (2013)

The BMJ ’s impact factor has risen from 14 in 2011 to 17 in 2012, placing it fourth among the world’s top general medical journals and first among open access, general medical journals, latest figures show.

The impact factor is a measure of the average number of citations to articles that a journal has recently published. The 2012 impact factor was calculated from the number of times articles published in a journal during 2010 and 2011 were cited by articles in other indexed journals during 2012. This figure was divided by the total number of “citable items” (mainly research and clinical review articles) published in 2010-11.

The BMJ ’s …
Massive splenic infarction in Saudi patients with sickle cell anemia: A unique manifestation
Authors: Ali Hassan Al Jama, Ahmed Hassan Al Salem, Ibrahim Abdalla Al Dabbous
Journal: American Journal of Hematology (2002)

Splenic infarcts are common in patients with sickle cell anemia (SCA), but these are usually small and repetitive, leading ultimately to autosplenectomy. Massive splenic infarcts on the other hand are extremely rare. This is a report of our experience with 8 (4 males and 4 females) cases of massive splenic infarction in patients with SCA. Their ages ranged from 16 to 36 years (mean 22 years). Three presented with left upper quadrant abdominal pain and massive splenic infarction on admission, while the other 5 developed massive splenic infarction while in hospital. In 5 the precipitating factors were high altitude, postoperative, postpartum, salmonella septicemia, and strenuous exercise in one each, while the remaining 3 had severe generalized vasoocclusive crises. Although both ultrasound and CT scan of the abdomen were of diagnostic value, we found CT scan more accurate in delineating the size of infarction. All our patients were managed conservatively with I.V. fluids, analgesia, and blood transfusion when necessary. Diagnostic aspiration under ultrasound guidance was necessary in two patients to differentiate between massive splenic infarction and splenic abscess. Two patients required splenectomy during the same admission because of suspicion of secondary infection and abscess formation, while a third patient had splenectomy 2 months after the attack because of persistent left upper quadrant abdominal pain. In all the 3 histology of the spleen showed congestive splenomegaly with massive infarction. All of our patients survived. Two patients subsequently developed autosplenectomy while the remaining 3 continue to have persistent but asymptomatic splenomegaly. Massive splenic infarction is a rare and unique complication of SCA in the Eastern Province of Saudi Arabia, and for early diagnosis and treatment, physicians caring for these patients should be aware of such a complication.
Predictive and Prognostic Roles of <i>BRAF</i> Mutation in Stage III Colon Cancer: Results from Intergroup Trial CALGB 89803
Authors: Shuji Ogino, Kaori Shima, Jeffrey A. Meyerhardt, Nadine J. McCleary, Kimmie Ng, Donna Hollis, Leonard B. Saltz, Robert J. Mayer, Paul Schaefer, Renaud Whittom, Alexander Hantel, Al B. Benson, Donna Spiegelman, Richard M. Goldberg, Monica M. Bertagnolli, Charles S. Fuchs
Journal: Clinical Cancer Research (2011)

Alterations in the RAS-RAF-MAP2K (MEK)-MAPK signaling pathway are major drivers in colorectal carcinogenesis. In colorectal cancer, BRAF mutation is associated with microsatellite instability (MSI), and typically predicts inferior prognosis. We examined the effect of BRAF mutation on survival and treatment efficacy in patients with stage III colon cancer.We assessed status of BRAF c.1799T>A (p.V600E) mutation and MSI in 506 stage III colon cancer patients enrolled in a randomized adjuvant chemotherapy trial [5-fluorouracil and leucovorin (FU/LV) vs. irinotecan (CPT11), FU and LV (IFL); CALGB 89803]. Cox proportional hazards model was used to assess the prognostic role of BRAF mutation, adjusting for clinical features, adjuvant chemotherapy arm, and MSI status.Compared with 431 BRAF wild-type patients, 75 BRAF-mutated patients experienced significantly worse overall survival [OS; log-rank P = 0.015; multivariate HR = 1.66; 95% CI: 1.05-2.63]. By assessing combined status of BRAF and MSI, it seemed that BRAF-mutated MSS (microsatellite stable) tumor was an unfavorable subtype, whereas BRAF wild-type MSI-high tumor was a favorable subtype, and BRAF-mutated MSI-high tumor and BRAF wild-type MSS tumor were intermediate subtypes. Among patients with BRAF-mutated tumors, a nonsignificant trend toward improved OS was observed for IFL versus FU/LV arm (multivariate HR = 0.52; 95% CI: 0.25-1.10). Among patients with BRAF wild-type cancer, IFL conferred no suggestion of benefit beyond FU/LV alone (multivariate HR = 1.02; 95% CI: 0.72-1.46).BRAF mutation is associated with inferior survival in stage III colon cancer. Additional studies are necessary to assess whether there is any predictive role of BRAF mutation for irinotecan-based therapy.
Development of contraceptive vaccines for humans using antigens derived from gametes (spermatozoa and zona pellucida) and hormones (human chorionic gonadotrophin): current status
Authors: Rajesh K. Naz, Anthony Sacco, Om Singh, Rahul Pal, Gursharan P. Talwar
Journal: Human Reproduction Update (1995)

Contraceptive research has entered a new phase of development with the advent of hybridoma and DNA recombinant technologies. During the past 5 years, significant advances have been made in this area and now it seems that realistic prospects exist for the development of contraceptive vaccines for use in humans and animals (veterinary, wild and domestic), applicable to both the female and male sexes. Contraceptive vaccines will be valuable supplements to the presently available methods of family planning, and, due to high specificity, the occurrence of limited side-effects if any, low cost and infrequent administration, contraceptive vaccines may have greater acceptability than the currently available methods. Mammalian reproduction starts with the unison of gametes contributed by the male and female partners. Both spermatozoon and oocyte have antigens on the cell surface that are unique, tissue-specific, immunogenic and accessible to antibodies, and binding of the antibodies to these antigens can cause inhibition of gamete function, resulting in a failure of fertilization. Fertilization is followed by embryogenesis, with the early embryo producing several proteins, some of which, eg. human chorionic gonadotrophin (HCG), have a vital role in the establishment and maintenance of early pregnancy. Again, these proteins are accessible to antibodies, and their immunoneutralization can cause anti-fertility effects with loss of early embryo. Thus, the antigens derived from proteins on spermatozoa, oocyte and early embryo, especially HCG, constitute interesting molecules for the development of contraceptive vaccines. The aim of the present article is to review the current status of development of contraceptive vaccines based on antigens derived from sperm cell, oocyte zona pelluci-da and HCG, and to discuss their relative merits and future development.
Transfer of Unstable Patients: Dumping or Duty?
Authors: Olga Jonasson
Journal: JAMA (1987)

The public tax-supported hospitals of this country were established primarily to ensure access to a decent minimum of health care for the poor. Unless and until a system is substituted whereby medical care to the poor in private hospitals is compensated by tax dollars, it is inevitable that indigent patients will be transferred from private to public institutions for financial reasons. The increasingly competitive financial climate of private health care and the inability of private hospitals any longer to shift the costs of uncompensated care to paying patients have resulted in dramatic increases in the numbers of patients transferred to public hospitals in recent years. To make the best of this situation, transfer policies designed to safeguard the patient's welfare have been implemented<sup>1</sup>; compliance is variable but, in general, most parties involved follow the rules. But should this practice be permitted when the patient is in an unstable condition and
Antibodies to GAD65 and a tyrosine phosphatase-like molecule IA-2ic in Filipino type 1 diabetic patients.
Authors: F Medici, M I Hawa, A Giorgini, A Panelo, C M Solfelix, R D Leslie, P Pozzilli
Journal: Diabetes Care (1999)

OBJECTIVE: Type 1 diabetes is more prevalent in Europeans than it is in Asians. The disease is associated with autoantibodies to GAD65 and a protein tyrosine phosphatase-like molecule (IA-2). The frequency of GAD antibodies in Asian patients with type 1 diabetes may be lower than that in Europeans. No data are available on IA-2 antibodies in Asians. We tested antibodies to GAD65 and IA-2ic (the intracellular fragment containing the antibody epitope) in Filipino diabetic patients because this population has mixed European and aboriginal racial origins. RESEARCH DESIGN AND METHODS: A cross-sectional study of antibodies to GAD65 and IA-2ic was performed on a consecutive series of 91 type 1 diabetic patients, 74 type 2 diabetic patients, and 100 control subjects attending a diabetes clinic in Manila, the Republic of the Philippines. All subjects were &amp;lt;40 years of age, with a mean age +/- SD of 24.8+/-9.8, 34.3+/-5.8, and 25.8+/-8.0 years, respectively. Diagnosis of type 1 diabetes was determined clinically and confirmed by baseline C-peptide. RESULTS: Of 91 type 1 diabetic patients, antibodies to GAD65 were detected in 25 (27.4%), but antibodies to IA-2ic were found in only 8 (8.8%) (P = 0.002); neither autoantibody was detected in either the type 2 diabetic or control subjects. Of the 25 recently diagnosed type 1 diabetic patients (disease duration &amp;lt;2.0 years), autoantibodies to GAD65 were detected in 14 (56%), but those to IA-2ic in only 4 (16%) (P = 0.007); GAD65 antibodies were detected in only 4 (6%) of 66 patients with a longer disease duration (P = 0.0004). Comparison with recently diagnosed European type 1 diabetic patients of age and disease duration similar to that of the Filipinos indicated that IA-2ic antibodies, unlike GAD antibodies, were significantly less prevalent in Filipino type 1 diabetic patients (P = 0.0007). CONCLUSIONS: This is the first study investigating the prevalence and pattern of humoral immune response in type 1 diabetic patients from the Philippines. Antibodies to IA-2ic, unlike GAD antibodies, were infrequent. Patterns of immune responses to type 1 diabetes-associated antigens may differ worldwide, with important implications for prediction of the disease and the potential for antigen-specific therapy.