tbuckley/cabot-search huggingface dataset:
Polyclonal Gammopathy and Lymphoproliferation after Transfer Factor in Severe Combined Immunodeficiency Disease
Authors: Erwin W. Gelfand, Reuben Baumal, Johannes Huber, Marie C. Crookston, Kenneth H. Shumak
Journal: New England Journal of Medicine (1973)

Transfer factor was administered to a 10-month-old infant with severe combined immunodeficiency disease in an attempt to stimulate cell-mediated immunity. No change in thymus-dependent lymphocyte function was observed. However, three weeks after transfer factor there was a marked increase in the leukocyte count, with the appearance of mature plasma cells in the peripheral blood and bone marrow. The serum IgM rose to 2000 mg per 100 ml; several blood-group antibodies, including anti-i, became detectable. Although the relation of transfer factor to the polyclonal gammopathy may be coincidental, the administration of transfer factor to patients with severe combined immunodeficiency disease may induce uncontrolled B-cell proliferation. (N Engl J Med 289:1385–1389, 1973)
High Titer of Autoantibodies to GAD Identifies a Specific Phenotype of Adult-Onset Autoimmune Diabetes
Authors: Raffaella Buzzetti, Antonio Petrone, Marco Capizzi, Emanuele Bosi
Journal: Diabetes Care (2007)

In our article (1) on adult-onset autoimmune diabetes, titers of antibodies to GAD (GADA) are reported in arbitrary units, i.e., they are elaborated in-house; therefore, they are unsuitable for comparison with other studies. However, as anticipated by Kobayashi et al. (2), the participation in the Diabetes Antibody Standardization Program (3) allows us to convert these measurements into World Health Organization (WHO) units. The value of 32 units, which in our study …
Effect of D-Thyroxine on Thyrotoxicosis and on the Associated Exophthalmos
Authors: W. D. Alexander, D. A. Koutras, W. W. Buchanan, J. Crooks
Journal: BMJ (1961)

<h3>Abstract</h3> Circadian clock is a cell-autonomous time-keeping mechanism established gradually during embryonic development. Here we generated a transgenic zebrafish line carrying a destabilized fluorescent protein driven by the promoter of a core clock gene, <i>nr1d1</i>, to report <i>in vivo</i> circadian rhythm at the single-cell level. By time-lapse imaging of this fish line, we observed the sequential initiation of the reporter expression starting at photoreceptors in pineal gland then spreading to cells in other brain regions. Even within pineal gland, we found heterogeneous onset of <i>nr1d1</i> expression in which each cell undergoes circadian oscillation superimposed over cell-type specific developmental trajectory. Furthermore, we found that single-cell expression of <i>nr1d1</i> showed synchronous circadian oscillation under light-dark cycle. Remarkably, single-cell oscillations were lost in animals raised under constant darkness while developmental trend still persists. It suggests that light exposure in early clock development initializes cellular clocks rather than synchronizes existing individual oscillators as previously believed.
Evidence of comparative efficacy should have a formal role in European drug approvals
Authors: C. Sorenson, H. Naci, J. Cylus, E. Mossialos
Journal: BMJ (2011)

Despite methodological concerns, comparative efficacy evidence should be required at the time of drug approval, <b>says Corinna Sorenson and colleagues</b>, to allow patients, clinicians, and other healthcare decision makers to determine whether a new drug is superior, equivalent, or inferior to its existing alternatives
Apoptotic and non-apoptotic programmed cardiomyocyte death in ventricular remodelling
Authors: G. W. Dorn
Journal: Cardiovascular Research (2008)

A defining cellular event in the transition from compensated hypertrophy to dilated cardiomyopathy is cardiomyocyte drop-out due to apoptosis, programmed necrosis, and autophagy. The importance of apoptosis in heart failure has been recognized for over a decade, while other forms of programmed cell death have more recently been appreciated, and their pathophysiological roles continue to be defined in experimental and clinical heart failure. The major focus of this review is on apoptosis in heart failure, with a discussion of molecular cross-talk between apoptosis, autophagy, and programmed necrosis.
HYPOHIDROTIC (OR ANHIDROTIC) ECTODERMAL DYSPLASIA—AN APPRAISAL OF DIAGNOSTIC METHODS*
Authors: JULIAN VERBOV
Journal: British Journal of Dermatology (1970)

A study has been carried out in 20 members of 5 unrelated families to confirm the diagnosis of hypohidrotic ectodermal dysplasia (HED) in 5 young males, and to detect possible female carriers. The history and the clinical examination were supplemented by sweat testing and plastic imprinting over selected areas of the palm, pore-counting, and dermatoglyphic analysis. Findings of importance include definitely abnormal imprints in 3 mothers and in 4 affected individuals, good sweat gland function in one of the affected individuals, and unilateral or bilateral high maximal and angles in all affected individuals and in 4 mothers.
Unexplained iron deficiency in idiopathic and heritable pulmonary arterial hypertension
Authors: E. Soon, C. M. Treacy, M. R. Toshner, R. MacKenzie-Ross, V. Manglam, M. Busbridge, M. Sinclair-McGarvie, J. Arnold, K. K. Sheares, N. W. Morrell, J. Pepke-Zaba
Journal: Thorax (2011)

<h3>Background</h3> Anaemia is common in left heart failure and is associated with a poorer outcome. Many patients with pulmonary arterial hypertension (PAH) are anaemic or iron-deficient. This study was performed to investigate the prevalence of iron deficiency in PAH and to identify possible causes. <h3>Methods</h3> All patients with idiopathic or heritable PAH diagnosed in 1995–2008 were identified. Controls were selected from patients with chronic thromboembolic pulmonary hypertension (CTEPH). Full blood counts were examined and any abnormality was investigated. Patients were excluded if they had a cause for iron deficiency. The prevalence study was based on 85 patients with idiopathic PAH and 120 with CTEPH. A separate group of 20 patients with idiopathic PAH and 24 with CTEPH with matching haemodynamics were prospectively investigated for serum factors affecting iron metabolism. <h3>Results</h3> The prevalence study identified a point prevalence of unexplained iron deficiency of 50% in premenopausal women with idiopathic PAH compared with 8% in premenopausal women with CTEPH (p=0.002); 14% in postmenopausal women with idiopathic PAH compared with 6% in postmenopausal women with CTEPH (p=0.16); 28% in men with idiopathic PAH men compared with 2% in men with CTEPH (p=0.002); and 60% in patients with heritable PAH. The serum study showed that patients with idiopathic PAH had lower serum iron and transferrin saturations than those with CTEPH. Interleukin-6 levels correlated with iron levels(r=−0.6, p=0.006) and transferrin saturations (r=−0.68, p=0.001) in idiopathic PAH but not in CTEPH. <h3>Conclusions</h3> The prevalence of unexplained iron deficiency is significantly higher in idiopathic PAH than in CTEPH. This may be linked to interleukin-6.
Mechanism of Postoperative Limitation in Sodium Excretion: The Role of Extracellular Fluid Volume and of Adrenal Cortical Activity1
Authors: Russell E. Randall, Solomon Papper
Journal: Journal of Clinical Investigation (1958)

Decreased renal excretion of sodium is a wellknown feature of the immediate postoperative state (1-3). The mechanisms responsible have, however, not been clearly defined. While increased adrenal cortical secretion such as is generally associated with major surgical procedures (4-9) has been causally implicated by many investigators (1, 3, 10-13), there is considerable evidence that the changes in sodium excretion are independent of variations in the supply of adrenal cortical hormones (14-18). The extracellular fluid volume, or more precisely that portion of it which is physiologically effective, has been shown to be a major determinant of renal sodium excretion in normal individuals (19-21). Therefore variation in this volume warrants consideration as a possible etiological factor in the decreased postoperative excretion of sodium. The observations that fluid sequestration occurs in and about the traumatized tissues both in animals and in man indeed suggests that a dislocation of the body fluids may occur in the surgical patient and result in a contraction of the effective extracellular fluid volume. The present study was designed to investigate the effect of isotonic expansion of the extracellular fluid volume on the postoperative response to the administration of sodium chloride. The data indicate that the usually observed impairment in natriuretic response is corrected by isotonic extracellular fluid volume expansion. In addition, studies in a patient with Addison's disease suggest that decreased natriuresis postoperatively occurs independently of enhanced adrenal cortical hormone secretion.
141 EXTENDED TREATMENT DURATION IN CHRONIC HEPATITIS C GENOTYPE 1-INFECTED SLOW RESPONDERS: FINAL RESULTS OF THE SUCCESS STUDY
Authors: M. Buti, Y. Lurie, N.G. Zakharova, N.P. Blokhina, A. Horban, C. Sarrazin, L. Balciuniene, R. Chen, X. Yu, R. Faruqi, R. Esteban
Journal: Journal of Hepatology (2009)
Keratinocyte growth factor protects murine hepatocytes from tumor necrosis factor-induced apoptosis in vivo and in vitro
Authors: Giorgio Senaldi, Christine L. Shaklee, Bernadett Simon, Christopher G. Rowan, David L. Lacey, Thomas Hartung
Journal: Hepatology (1998)

Keratinocyte growth factor (KGF) promotes epithelial growth and differentiation and has potent effects on the liver. The coinjection of lipopolysaccharide (LPS) and D-galactosamine (GalN) results in hepatic failure in mice. Mechanistically, LPS-induced tumor necrosis factor (TNF) triggers hepatocyte apoptosis, which is enhanced by GalN-arrested transcription. Similarly, the combination of TNF and actinomycin D (ActD) causes hepatocyte apoptosis in vitro. We studied the effect of KGF on LPS and GalN-induced hepatic failure in vivo and on TNF- and ActD-induced hepatocyte apoptosis in vitro, where it was compared with those of hepatic growth factor (HGF) and epidermal growth factor (EGF). Mice treated with human recombinant KGF (1 mg/kg subcutaneously) 24 hours before intraperitoneal coinjection of LPS and GalN sustained prolonged survival compared with control mice, although overall mortality was not changed. The counts of apoptotic hepatocytes, serum alanine and aspartate transaminases, and DNA fragments in the cytosolic fraction of liver homogenates were higher in control mice than in treated mice 6 hours after LPS and GalN coinjection, before any mortality occurred. In vitro, hepatocytes pretreated with KGF exhibited reduced TNF- and ActD-induced cell damage and DNA fragmentation, similar to hepatocytes pretreated with HGF and EGF. In conclusion, KGF prolongs survival during LPS- and GalN-induced hepatic failure by temporarily protecting hepatocytes against apoptosis. It also protects hepatocytes in vitro against TNF- and ActD-induced apoptosis.
Combined Use of Urinary &amp;alpha;&lt;sub&gt;1&lt;/sub&gt;-Microglobulin and &lt;sup&gt;99m&lt;/sup&gt;Tc DMSA Scintigraphy in the Diagnosis and Follow-Up of Acute Pyelonephritis and Cystitis in Children
Authors: K. Everaert, A. Raes, P. Hoebeke, W. Samijn, J. Delanghe, C. Vande Wiele, J. Vande Walle
Journal: European Urology (1998)
Method for Cataract Extraction in Parkinsonism
Authors: John G. Bellows
Journal: JAMA (1965)

<h3>To the Editor:—</h3> The extraction of cataracts in patients with advanced stages of paralysis agitans has always presented serious problems to the eye surgeon. It is obviously impossible for him to perform intraocular surgery in the presence of head-shaking. Up to now, the ophthalmologist has had to rely on general anesthesia with the undesirable sequelae of retching, vomiting, and restlessness. These exertions sometimes cause rupture of the wound and intraocular hemorrhage. Most tranquilizers, such as the phenothiazine group, are contraindicated because they accentuate the extrapyramidal reactions, and increase the tremor in Parkinson's disease. The author found that a combination of diphenhydramine (Benadryl) hydrochloride and hydroxyzine pamoate (Vistaril) administered intravenously suppressed the trembling effects and headshaking in a patient with an advanced case of paralysis agitans, and allowed a successful intracapsular extraction to be performed with local anesthesia, thus prompting this report. A 63-year-old male with an advanced form of
Clinical Importance of Caffeine Withdrawal
Authors: John R. Hughes
Journal: New England Journal of Medicine (1992)

Cessation of the use of products containing caffeine can cause a withdrawal syndrome of headaches, drowsiness, fatigue, decreased performance, and in some instances, nausea and vomiting.1 These symptoms begin within 12 to 24 hours after the last use, peak at 20 to 48 hours, and last approximately one week.1 Their occurrence is reproducible1 2 3 4 and has been validated in several placebo-substitution trials.1 2 3 4 Importantly, withdrawal effects appear to be a factor in the continued use of caffeinated substances.1 2 3 4 Effects have also been produced in animals.5 The neurochemical mechanism of caffeine withdrawal is not known.The study by Silverman et al. in this . . .
Mainstreams of Medicine: Essays on the Social and Intellectual Context of Medical Practice
Authors: Chester R. Burns
Journal: JAMA (1971)

To herald its entrance into the mainstreams of modern science, the University of Texas Medical School at San Antonio sponsored a series of lectures for freshman students in 1969. Conceived by David Kronick, professor of medical bibliography at the new medical school, the series received "obstetrical" assistance from Lester King who, as editor, now offers these lectures for those who wish "to appreciate new currents in medicine and to participate therein." Kronick introduces the volume with a plea for medical educators to include philosophy, sociology, and history—even music, art, poetry, literature, and drama—in their curricular aspirations. Social contexts of medical practice are discussed by Chauncey Leake, George Rosen, René Dubos, John Knowles, David Rutstein, and Thomas Ham. Some intellectual contexts of medical practice are analyzed by Harry Dowling, Douglas Bond, Lester King, and Henry Beecher. Collectively, the essays introduce patterns and problems within various streams of medical science, medical education,
Artesunate for the Treatment of Severe Falciparum Malaria
Authors: Philip J. Rosenthal
Journal: New England Journal of Medicine (2008)

A previously well, American-born 35-year-old man presents with a 5-day history of fever and progressive dyspnea and a 2-day history of jaundice.An evaluation 3 days before his presentation led to a diagnosis of a viral syndrome.The patient had returned 3 weeks earlier from a 1-month stay in West Africa.He reports receiving immunizations before travel and taking pills to prevent malaria weekly until his return to the United States.The physical examination shows moderate respiratory distress, diffuse pulmonary crackles, and mild jaundice.His vital signs include a temperature of 39.8°C, respiratory rate of 32 breaths per minute, and oxygen saturation of 87% while he is breathing ambient air.Abnormal results of laboratory tests include a hematocrit of 32.2%, platelet count of 78 per cubic millimeter, total bilirubin level of 4.2 mg per deciliter (71.8 μmol per liter), and creatinine level of 2.2 mg per deciliter (194.5 μmol per liter).A Giemsa-stained blood smear shows numerous ring forms of Plasmodium falciparum, with parasitemia estimated at 2%.He is immediately hospitalized, and an infectious-disease consultant recommends that the Centers for Disease Control and Prevention (CDC) be contacted to obtain intravenous artesunate for his treatment. The Cl inic a l Probl e mMalaria is one of the most important infectious diseases in the world, causing hundreds of millions of illnesses and an estimated 1 million deaths each year. 1 Malaria is endemic throughout most of the tropics, but it is most readily transmitted in sub-Saharan Africa.Nearly all serious illnesses and deaths from malaria are caused by P. falciparum.Severe malaria, which is much less common than uncomplicated disease, is difficult to define precisely, especially in regions where malaria is endemic, because other serious illnesses can coexist with malarial infection.Severe malaria is generally defined as acute malaria with major signs of organ dysfunction or high levels of parasitemia (Table 1). 2 In areas where malaria is endemic, young children are at high risk for severe malaria.Partial immunity develops in older children and adults after repeated infections, and they are thus at relatively low risk for severe disease.Pregnant women are also at increased risk for severe malaria. 4 Travelers to areas where malaria is endemic often contract the disease, mostly because of lack of compliance with preventive measures such as the avoidance of night-biting anopheline mosquitoes and use of chemoprophylaxis.Travelers generally have no previous exposure to malaria parasites and so are at high risk for pro-This Journal feature begins with a case vignette that includes a therapeutic recommendation.A discussion of the clinical problem and the mechanism of benefit of this form of therapy follows.Major clinical studies, the clinical use of this therapy, and potential adverse effects are reviewed.Relevant formal guidelines, if they exist, are presented.The article ends with the author's clinical recommendations.
What Role for Nurse Practitioners in Primary Care?
Authors: Jerome P. Kassirer
Journal: New England Journal of Medicine (1994)

When the call went out recently for an increase in the number of primary care providers, nurse practitioners were prominent among the many professional groups that stepped forward. Now approximately 50,000 strong, they claim that their skills suit them ideally to fill the gap created by the shortage of primary care providers and gatekeepers. Already, 25 states have legislation authorizing the reimbursement of nurse practitioners by private and commercial insurers1,2; 21 states and the District of Columbia permit them to write prescriptions for drugs, and 15 of these give independent prescribing authority for controlled substances3. Is expansion . . .
Symptom-limited vs heart-rate-limited exercise testing soon after myocardial infarction.
Authors: R F DeBusk, W Haskell
Journal: Circulation (1980)

To develop guidelines for exercise testing soon after uncomplicated myocardial infarction, 93 men completed a heart-rate-limited (HRL) protocol and 107 completed a symptom-limited (SXL) protocol 3 weeks after the acute event. In the HRL protocol, effort terminated at a heart rate of 130 beats/min in the absence of a limiting symptom, exertional hypotension or ventricular tachycardia. Peak heart rate was not an end point in the SXL protocol. Despite a higher peak heart rate and work load in patients who completed the SXL protocol, the prevalence of exercise-induced ischemic ST-segment depression and ventricular ectopic activity was similar in the two groups. No complications occurred with either protocol. Twelve patients (6%) had cardiac events within the next 2 months. Regardless of the test protocol used, early events were more common in patients with ischemic ST-segment responses (15%) than in patients without ischemic responses (3%) (p less than 0.01). In contrast, exercise-induced ventricular arrhythmias were not predictive of early events. Eleven weeks after infarction, when all tests were SXL, the prevalence of exercise-induced ischemic ST-segment depression and premature ventricular complexes was similar to that at 3 weeks. We conclude that SXL and HRL exercise test protocols reveal a similar prevalence of ischemic ST-segment depression and ventricular ectopic activity soon after uncomplicated myocardial infarction.
KIR2DL3+NKG2A− natural killer cells are associated with protection from productive hepatitis C virus infection in people who inject drugs
Authors: Christine Thoens, Christoph Berger, Martin Trippler, Holger Siemann, Melanie Lutterbeck, Ruth Broering, Jörg Schlaak, Falko M. Heinemann, Andreas Heinold, Jacob Nattermann, Norbert Scherbaum, Galit Alter, Joerg Timm
Journal: Journal of Hepatology (2014)
All neuropathies great and small
Authors: E. B. Penny
Journal: Journal of Clinical Investigation (2005)

Autosomal-dominant pure hereditary spastic paraplegia (AD-HSP) is characterized by the degeneration of long axons in corticospinal tracts and dorsal columns, resulting in spasticity and difficulty walking. Mutations in the SPG4 gene product spastin are the predominant genetic lesions associated with this inherited disease. In this issue, Orso et al. examine and reconcile existing Drosophila mutants of spastin and generate a new model for HSP by overexpression of a fly spastin transgene that carries a mutation prevalent in human AD-HSP. Expression of this mutant spastin protein produces pathology in flies reminiscent of the human disease, including adult locomotion defects, in addition to causing aberrant synaptic morphology and altered microtubule stability. Both movement and synaptic defects in fly mutants were ameliorated by treatment with the microtubule-modifying agent vinblastine. The results are consistent with disease-causing mutations in human spastin producing dominant-negative proteins and confirm the usefulness of Drosophila genetic techniques to understand HSP and other neurodegenerative diseases.
Extrahepatic Biliary Obstruction Caused by Metastatic Breast Carcinoma
Authors: JOHN W. POPP
Journal: Annals of Internal Medicine (1979)

We describe our experience with seven patients who had extrahepatic biliary obstruction caused by metastatic breast cancer. The interval from the original diagnosis of breast cancer to the development of jaundice averaged 40 months, with a range of 9 months to 8 years. All patients were treated with surgical decompression, radiation, transhepatic catheter drainage, chemotherapy, or a combination of these modalities. Resolution of jaundice was achieved in six patients. Prolonged survival was realized in three; one patient lived for more than 6 years after surgical bypass, and two are alive and well at present (greater than 11 months after relief of biliary obstruction). Extrahepatic biliary obstruction by metastatic breast carcinoma should be distinguished from jaundice due to hepatic parenchymal destruction by this tumor; while the latter implies end-stage cancer, the former has the potential for significant palliation and prolonged survival.