tbuckley/cabot-search huggingface dataset:
Blood Donation by the Elderly
Authors: Johanna Pindyck
Journal: JAMA (1987)

At present, healthy potential blood donors older than the age of 66 years often leave the donor pool for reasons of age alone, despite the fact that this demographic group is growing, is a potentially willing source of blood products, and constitutes the cohort with highest per capita use of blood and its derivatives. There is no clinical or physiological rationale for this. We performed a controlled study to measure the feasibility and safety of blood donation by healthy elderly donors aged 66 years and older, compared with a younger cohort aged 55 to 65 years of age. A study group of prior donors aged 66 years and older and a control group of prior donors between the ages of 50 and 65 were sent letters inviting them to donate blood. The volume donated did not differ between the two groups. In the older group, there were eight immediate reactions, seven mild and one moderate. The control population experienced seven immediate reactions, six mild and one severe. We conclude that it is both clinically feasible and efficient to recruit healthy prior donors older than the age of 66 years for blood donation. As a group, this population is potentially able to donate large volumes of blood and do so without any difference in immediate or short-term reactions. Further study of hemodynamic variables as more objective markers of safety is needed.
Whole Body Gallium-67 Citrate Scintigraphy in a Patient with Sarcoidosis and Biopsy-proven Erythema Nodosum
Authors: GARY G. WINZELBERG, JERRY RABINOWITZ
Journal: Clinical Nuclear Medicine (1984)

A 26-year-old man presented with clinical findings of painful arthritis of the knees and tender nodules over the shins. Chest radiography demonstrated hilar and paratracheal adenopathy which, on biopsy, proved to be sarcoidosis. A whole body Ga-67 citrate scintiscan identified the gallium-avid adenopathy and abnormal soft tissue activity in the knees and shins. The gallium-avid skin nodules, while clinically thought to be consistent with sarcoidosis, on biopsy proved to be erythema nodosum.
Abstract 240: Transcriptional knockdown of urokinase-type plasminogen activator receptor (uPAR) induces apoptosis in glioblastoma xenograft cells via activation of p53
Authors: Chandramu Chetty, Shivani Ponnala, Krishna Kumar Veeravalli, Meena Gujrati, Dzung H. Dinh, Jasti S. Rao
Journal: Cancer Research (2012)

Abstract Elevated levels of urokinase plasminogen activator receptor (uPAR), a glycoprotein tethered to the cell membrane with a glycosylphosphotidylinositol (GPI) anchor, is associated with tumor malignancy in a variety of cancers including glioblastoma (GBM). In this study, we show that inhibition of uPAR via RNA interference (puPAR-Si) induced p53-mediated massive cell death in human GBM xenograft cell lines, 4910 and 5310. Induction of Fas expression and cleavage of caspases-8, -9 and -3 and PARP (poly (ADP-ribose) polymerase) revealed induction of the extrinsic apoptotic pathway. Inhibition of Fas death receptor blocked puPAR-Si-induced apoptosis. Further, uPAR inhibition induced the expression of tumor suppressor p53 and its downstream target gene p21. Transcriptional knockdown of p53 rescued cells from apoptosis, thereby indicating that p53 was critical for induction of apoptosis. Moreover, puPAR-Si treatment inhibited pre-established tumor growth in an intracranial model. Indeed, histological analysis of tumor sections collected from mice that were treated with uPAR siRNA revealed increased immunoreactivity of phosphorylated p53, Fas, active caspase 3 and induction of programmed cell death. These data suggest a novel function of uPAR acting as a survival factor for GBM by downregulating p53; inhibition of uPAR induces a pro-apoptotic signaling pathway via p53. These findings may offer new treatment strategies for GBM. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 240. doi:1538-7445.AM2012-240
Hepatitis B Virus Vaccine An Opportunity for Control
Authors: Donald P. Francis
Journal: JAMA (1983)

The relatively short history of the inactivated  to prevent hepatitis B virus (HBV) infection has been marked by alternating excitement and concern. Initially, there was excitement when Krugman and colleagues showed that a boiled plasma vaccine could induce protective antibody. There was still more excitement when large-scale production of plasmaderived HBV  became feasible and the final product was shown to induce antibody. But later, concern arose regarding the safety of such a vaccine. The question then was, Can inactivation of HBV and non A—non B agent(s) be guaranteed in the absence of cell-culture detection systems? 1 As evidence for inactivation accumulated through chimpanzee and early human studies, confidence returned, and enthusiasm grew as additional studies demonstrated both safety and high efficacy. 2,3 The tide has now turned again as we consider the potential risks of transmitting an as yet to be identified agent of the acquired immune deficiency syndrome.
Cooperative loss of RAS feedback regulation drives myeloid leukemogenesis
Authors: Zhen Zhao, Chi-Chao Chen, Cory D Rillahan, Ronglai Shen, Thomas Kitzing, Megan E McNerney, Ernesto Diaz-Flores, Johannes Zuber, Kevin Shannon, Michelle M Le Beau, Mona S Spector, Scott C Kogan, Scott W Lowe
Journal: Nature Genetics (2015)
Protease-resistant form of insulin-like growth factor-binding protein 5 is an inhibitor of insulin-like growth factor-I actions on porcine smooth muscle cells in culture.
Authors: Y Imai, W H Busby, C E Smith, J B Clarke, A J Garmong, G D Horwitz, C Rees, D R Clemmons
Journal: Journal of Clinical Investigation (1997)

IGFs are pleiotrophic mitogens for porcine smooth muscle cells (pSMC) in culture. The effects of IGFs on cells are modulated by various insulin-like growth factor-binding proteins (IGFBP). IGFBP-5 is synthesized by pSMC and binds to the extracellular matrix. However, IGFBP-5 is also secreted into conditioned medium of cultured cells and is cleaved into fragments by a concomitantly produced protease. These fragments have reduced affinity for the IGFs and cleavage makes it difficult to assess the role of intact IGFBP-5. To study the consequence of accumulation of intact IGFBP-5 in medium, we determined the cleavage site in IGFBP-5 and prepared a protease resistant mutant. Amino acid sequencing of purified IGFBP-5 fragments suggested Arg138-Arg139 as the primary cleavage site. Arg138-Arg139-->Asn138-Asn139 mutations were introduced to create protease-resistant IGFBP-5, which has the same affinity for IGF-I as the native protein. This mutant IGFBP-5 remained intact even after 24 h of incubation and it inhibited several IGF-I actions when added to pSMC culture medium. The mutant IGFBP-5 (500 ng/ml) decreased IGF-I stimulated cellular DNA synthesis by 84%, protein synthesis by 77%, and it inhibited IGF-I stimulated migration of pSMC by 77%. It also inhibited IGF-I stimulation of IRS-1 phosphorylation. In contrast, the same amount of native IGFBP-5 did not inhibit IGF-I actions. The significance of inhibitory effects of the protease resistant IGFBP-5 was further demonstrated in pSMC transfected with mutant or native IGFBP-5 cDNAs. The mutant IGFBP-5 accumulated in culture medium of transfected cells, while native IGFBP-5 was degraded into fragments, PSMC overexpressing the mutant IGFBP-5 also responded poorly to IGF-I compared with mock transfected cells. IGF-I (5 ng/ml) increased [35S]methionine incorporation into control cells by 36% above the basal level, but it did not significantly change (4%) in pSMC cultures that were producing the mutant IGFBP-5. In conclusion, the accumulation of protease-resistant IGFBP-5 in the medium was inhibitory to IGF-I actions on pSMC. This suggests that proteolysis can prevent IGFBP-5 from acting as an inhibitor of IGF-I-stimulated effects and that it serves as an important mechanism for regulating cellular responsiveness to IGF-I.
THE PREVALENCE OF MALNUTRITION
Authors: NORMAN JOLLIFFE
Journal: JAMA (1942)

Recent estimates of the prevalence of malnutrition in the United States have varied so greatly that the Food and Nutrition Board of the National Research Council has assigned to us, as a subcommittee, the task of evaluating existing evidence on this question. Among the reasons for the widely varying estimates is the lack of criteria for the diagnosis of malnutrition. It is therefore necessary before discussion of the evidence that terms be defined. <h3>DEFINITIONS</h3> "Nutritional failure" exists as soon as adequate amounts of an essential nutritional factor or factors fail to reach the "milieu interne." "Dietary inadequacy" means the failure to ingest an essential nutritional factor or factors in amounts sufficient to meet the existing requirement of the body. "Nutritional inadequacy" means not only the failure to ingest, i. e. dietary inadequacy, but failure to absorb, to retain and to utilize an essential nutritional factor or factors in amounts sufficient
Low-dose dobutamine echocardiography detects reversible dysfunction after thrombolytic therapy of acute myocardial infarction.
Authors: S C Smart, S Sawada, T Ryan, D Segar, L Atherton, K Berkovitz, P D Bourdillon, H Feigenbaum
Journal: Circulation (1993)

BACKGROUND Dysfunction after thrombolytic therapy of acute myocardial infarction (MI) may be reversible. Early after myocardial infarction, both reversible and irreversible injury may be manifested by regional wall motion abnormalities. Improved wall thickening during dobutamine infusion (dobutamine-responsive wall motion) may accurately identify reversibly injured segments. METHODS AND RESULTS To determine whether dobutamine-responsive wall motion accurately detects reversible postischemic dysfunction irrespective of infarct location, multistage (baseline, 4 and 12 micrograms.kg-1.min-1, and peak) dobutamine echocardiography (DE) was performed within 7 days of thrombolytic therapy. Resting echocardiography was repeated &gt; or = 4 weeks after MI, and reversible dysfunction was defined as improved wall motion. The accuracy of dobutamine-responsive wall motion was compared with that of signs of early reperfusion, non-Q-wave MI, and peak creatine kinase (CK). Sixty-three patients underwent DE without complications. Follow-up echocardiograms were done in 51 (81%) of these patients, and wall motion improved in 22 (41%). Dobutamine-responsive wall motion during all stages of DE was very specific for reversible dysfunction (90% to 93%) but sensitive (86%) only when hemodynamics were not altered (low dose, 4 micrograms.kg-1.min-1). Non-Q-wave MI and a low peak CK (&lt; 1000 IU/mL) were also specific (89% to 93%) but less sensitive (64% [P = .16] and 55% [P &lt; .05], respectively). Signs of early reperfusion did not identify postischemic dysfunction. Low-dose dobutamine-responsive wall motion and non-Q-wave MI independently identified reversible dysfunction, but only dobutamine-responsive wall motion was sensitive in all infarct locations. Non-Q-wave MI was sensitive only in anterior infarction. CONCLUSIONS Multistage dobutamine echocardiography can be performed safely early after thrombolytic therapy. Low-dose dobutamine-responsive wall motion accurately detected reversible dysfunction in all infarct locations. Dobutamine-responsive wall motion and non-Q-wave infarction may be very useful for accurately identifying reversible dysfunction early after thrombolytic therapy for acute MI.
Trends in Status Epilepticus—Related Hospitalizations and Mortality
Authors: John P. Betjemann, S. Andrew Josephson, Daniel H. Lowenstein, James F. Burke
Journal: JAMA Neurology (2015)

Status epilepticus is a common neurologic emergency with significant associated morbidity, mortality, and health care costs, yet limited data exist detailing trends in status epilepticus-related hospitalizations and mortality.To examine trends in status epilepticus-related hospitalizations and mortality.We performed 2 retrospective serial cross-sectional studies including 408 304 status epilepticus-related hospital visits using generalizable national data from January 1, 1999, to December 31, 2010, from the Centers for Disease Control and Prevention and the Nationwide Inpatient Sample. Centers for Disease Control and Prevention death certificate data, using International Statistical Classification of Diseases, Tenth Revision, codes, were used to determine nonstandardized and age-standardized rates of status epilepticus as the underlying cause of death in the United States. Data from the Nationwide Inpatient Sample were used to estimate population-standardized status epilepticus-related hospitalization rates using International Statistical Classification of Diseases, Ninth Revision, codes.Status epilepticus-related hospitalizations were categorized by whether status epilepticus was the principal diagnosis, whether the patient was intubated, and by primary insurance type. Temporal trends were tested using Poisson regression and summarized with quarterly incident rate ratios.In 2010, status epilepticus was the reported underlying cause of death in 613 deaths (approximately 2 per 1 000 000 persons). Age-standardized status epilepticus-related mortality per 1 000 000 persons increased by only 5.6% (incident rate ratio, 1.004; 95% CI, 1.002-1.006) from 1.79 in 1999 to 1.89 in 2010, while population-standardized hospitalizations for status epilepticus per 100 000 persons increased by 56.4% (incident rate ratio, 1.013; 95% CI, 1.012-1.013) from 8.86 in 1999 to 13.86 in 2010. The largest increase (181.6%; incident rate ratio, 1.030; 95% CI, 1.029-1.030) was seen among intubated patients with nonprincipal diagnoses of status epilepticus. Among varied insurance providers, the largest increase (81.3%) was seen in Medicare patients.A disconnect exists between the relatively stable status epilepticus-related mortality and the marked increase in status epilepticus hospitalizations, likely reflecting an increase in status epilepticus diagnoses through improved diagnostic sensitivity and changes in billing and coding. The definition and general approach to status epilepticus, including resource use, should evolve with these changing epidemiologic trends.
Non-European doctors feel penalised by change in UK policy
Authors: Adrian O'Dowd
Journal: BMJ (2006)

Doctors who trained outside the European Union are flooding the BMA with worried calls about a recent change in immigration policy that they fear will mean a forced exodus of medical staff from the United Kingdom. The BMA is seeking an urgent meeting with the government to try to resolve the matter and to establish some breathing space for foreign doctors who are already working in the UK to sort out their affairs.

The Department …
Lymphotoma—Symptomatic Lymph Leakage After Surgery
Authors: Edward Buonocore
Journal: JAMA (1965)

ALTERATION OF FLOW of lymphatic fluid in the pelvis and abdomen secondary to metastatic disease,<sup>1</sup>to trauma,<sup>2</sup>and to radiation<sup>3</sup>has been well documented; there are few reports, however, of the changes brought about by surgical transection of the lymphatic vessels of the abdomen. Dodd and his associates<sup>4</sup>demonstrated lymphangiographic evidence of pools of lymphatic fluid that had extravasated into the pelvis after transection of lymphatic vessels during pelvic surgery. The importance of the collections of lymph was emphasized by the occurrence of secondary urinarytract obstruction and sepsis. These collections of lymph were termed "lymphocysts" and "lymphoceles." These terms we consider misnomers because of the absence of a limiting endothelial lining. Since the masses described represent free lymphatic fluid, we believe that the term "lymphotoma," analogous to "hematoma" (a free collection of blood), is a more appropriate name. Despite the increased number of resections of aortic
Structural changes underlying compensatory increase of diffusing capacity after left pneumonectomy in adult dogs.
Authors: C C Hsia, F Fryder-Doffey, V Stalder-Nayarro, R L Johnson, R C Reynolds, E R Weibel
Journal: Journal of Clinical Investigation (1993)

To determine if the functional compensation in diffusing capacity of the remaining lung following pneumonectomy is due to structural growth, we performed morphometric analysis of the right lung in three adult foxhounds approximately 2 yr after left pneumonectomy (removal of 42% of lung) and compared the results to those in normal adult dogs previously studied by the same techniques. Diffusing capacity was calculated by an established morphometric model and compared to physiologic estimates at peak exercise in the same dogs after pneumonectomy. The major structural changes after left pneumonectomy are hyperinflation of the right lung, alveolar enlargement, and thinning of the alveolar-capillary tissue barrier. These changes confer significant functional compensation for gas exchange by reducing the overall resistance to O2 diffusion. The magnitude of compensation in diffusing capacity estimated either morphometrically or physiologically is similar. In spite of morphometric and physiologic evidence of functional compensation, there is no evidence of significant growth of structural components. After pneumonectomy, morphometric estimates of diffusing capacity are on average 23% higher than physiologic estimates in the same dogs at peak exercise. We conclude that the previously reported large differences between morphometric and physiologic estimates of diffusing capacity reflects the presence of large physiologic reserves available for recruitment.
Meningoradiculitis due to herpes simplex virus disclosing HIV infection.
Authors: P Dahan, B Haettich, J M Le Parc, J B Paolaggi
Journal: Annals of the Rheumatic Diseases (1988)

Meningoradiculitis due to herpes simplex virus disclosing HIV infection SIR, A 37 year old Portuguese man with no significant previous illness was admitted to hospital for recent right sided sciatica associated with a vesicular eruption over the L5 dermatome.The pain had been present for five days and the eruption appeared a few hours after admission.His symptoms were worst during the night.His rectal temperature was 37-8°C.No spinal signs and no signs of intervertebral disc protrusion were noted.There was cervical, axillary, and inguinal lymphadenopathy.The vesicles were distributed along the posterolateral aspect of the thigh, the lower leg, and the dorsum of the foot, suggesting a herpes virus infection responsible for a spinal neuritis.Clinical examination was otherwise normal.A cerebrospinal fluid (CSF) analysis showed 36 lympho- cytes and protein 1-35 g/l.Routine haematological and hepatorenal tests were normal.On the eighth day herpes simplex virus antibodies (IgM) were detected by enzyme linked immunosorbent assay (ELISA) in the blood (6400) and the CSF (320); the ratio of CSF to serum titre of herpes simplex virus antibodies indicated intrathecal synthesis.On the other hand, cyto- megalovirus and herpes zoster antibodies were not found in the CSF but only in the serum.This unusual meningoradiculitis led to a search for an acquired cellular immunodeficiency.Chest radiography showed no abnormality.T4/T8 ratio was 1-31 with 2300 total lymphocytes, but the multitest was negative.Even though the patient was married with three children and no history of intravenous drug abuse, human immuno- deficiency virus (HIV) serology was positive (ELISA and Western blot); the patient admitted being bisexual.No antibody to HIV was found in his CSF.Complete resolution followed treatment with acyclovir 8 mg/kg three times daily for 10 days.The CSF on the 22nd day showed six lymphocytes and protein was 0-39 g/l.This 37 year old bisexual patient, with no previous significant medical history, developed a meningoradiculitis owing to recent herpes simplex virus infection.1 2 This unusual infection was associated with the presence of antibodies to HIV.3The patient had a normal lymphocyte count and T4/T8 ratio but a negative response to multitest suggestive of an immunosuppression.This rare neuro- logical involvement is seldom encountered as an oppor- tunistic infection.We think it suggests the possibility that the patient has an HIV infection.
Essential medicines in the Third World.
Authors: P F D'Arcy
Journal: BMJ (1984)

Dans beaucoup de pays du Tiers Monde les problemes de pauvrete, surpopulation, instabilite politique compliquent les problemes de sante. Les maladies infectieuses sont tres repandues et mal controlees. Questions: manque de medicaments, notamment des medicaments essentiels. Propositions de solutions: fabrication locale de medicaments, amelioration du stockage, de la distribution et du conditionnement
Effect of cirrhosis of the liver on the pharmacokinetics of chlormethiazole.
Authors: P J Pentikainen, P J Neuvonen, S Tarpila, E Syvalahti
Journal: BMJ (1978)

The pharmacokinetics of chlormethiazole were studied in eight patients with advanced cirrhosis of the liver and in six healthy volunteers after oral and intravenous administration of the drug. In the patients the systemic bioavailability of oral chlormethiazole was increased about tenfold, whereas its elimination was only slightly retarded. The increased bioavailability was clearly due to decreased first-pass metabolism of chlormethiazole in the cirrhotic liver. The results indicate that chlormethiazole should be used in reduced dosage when given by mouth to patients with cirrhosis of the liver.
Tropical Medicine
Authors: Peter A. Leggat
Journal: JAMA (2000)

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