tbuckley/cabot-search huggingface dataset:
Abnormalities in Parathyroid Hormone Secretion and 1,25-Dihydroxyvitamin D<sub>3</sub>Formation in Women with Osteoporosis
Authors: Shonni J. Silverberg, Elizabeth Shane, Luz de la Cruz, Gino V. Segre, Thomas L. Clemens, John P. Bilezikian
Journal: New England Journal of Medicine (1989)

We investigated the parathyroid hormone–1,25-dihydroxyvitamin D3 (1,25(OH)2D) axis in osteoporosis by administering phosphate to 8 postmenopausal women with osteoporosis (49 to 78 years old) and to 10 normal women matched for age (50 to 74 years). All subjects responded with a similar increase in the serum phosphorus concentration (women with osteoporosis, 1.15±0.06 to 1.79±0.09 mmol per liter; controls, 1.14±0.05 to 1.73±0.08 mmol per liter) and a fall in the ionized calcium concentration (women with osteoporosis, 1.12±0.03 to 1.06±0.03 mmol per liter; controls, 1.17±0.01 to 1.11 ±0.02 mmol per liter). Parathyroid hormone levels rose 2.5-fold in the control group (15.4±2.2 to 37.9±6.1 pg per milliliter) but increased by only 43 percent in the group with osteoporosis (14.8±2.8 to 21.2±4.1 pg per milliliter), an increase similar to that previously reported in young normal subjects (53 percent). In healthy older and younger subjects, the levels of 1,25(OH)2D did not change; in the subjects with osteoporosis, however, they decreased significantly (50 percent). We conclude that older women require a greater parathyroid hormone stimulus than younger women to maintain vitamin D homeostasis, because of an age-related decline in the formation of 1,25(OH)2D in response to parathyroid hormone, and that in osteoporosis the age-appropriate parathyroid hormone response to the same hypocalcemic signal is diminished. Our results are consistent with the presence of an abnormality in parathyroid hormone secretory function in osteoporosis in addition to the universal decline in 1,25(OH)2D responsiveness associated with aging. (N Engl J Med 1989; 320:277–81.)
Nonparathyroid Humoral Hypercalcemia in Patients with Neoplastic Diseases
Authors: David Powell, Frederick R. Singer, Timothy M. Murray, Cedric Minkin, John T. Potts
Journal: New England Journal of Medicine (1973)

Eleven patients had hypercalcemia and hypophosphatemia associated with various nonparathyroid neoplasms in the absence of bony metastases (pseudohyperparathyroidism). In nine patients surgical ablation or other antitumor therapy resulted in remission of the biochemical abnormalities. Parathyroid hormone was undetectable both in peripheral blood and in tumor tissue from all patients when assessed with multiple immunoassays that detect not only intact parathyroid hormone but proparathyroid hormone and biologically active and inactive parathyroid hormone fragments in addition. However, extracts of tissues caused active calcium resorption from bone in vitro. The chemical nature of the presumed humoral substance (or substances) is unknown. The findings suggest that in many patients with neoplasms and clinical and biochemical features typical of pseudohyperparathyroidism some humoral substance other than parathyroid hormone must be responsible for hypercalcemia and other features of their disease. (N Engl J Med 289:176–181, 1973)
Madelung's Disease: Inherited from an Ancient Mediterranean Population?
Authors: C Feliciani, P Amerio
Journal: New England Journal of Medicine (1999)

Figure 1. A 44-year-old man was evaluated for symmetric deposits of fat on his arms and legs. At the age of 26 years, he had been hospitalized because of axonal polyneuropathy of the legs and alcoholic fatty liver. Subsequently, fat deposits characteristic of multiple symmetric lipomatosis slowly developed (Panel A). In addition to the fat deposits, the patient had macrocytic anemia, peripheral neuropathy, and alcoholic fatty liver. Glucose and lipid metabolism was normal. No other family members had a similar distribution of fat. Multiple symmetric lipomatosis, also known as Madelung's disease or the Launois–Bensaude syndrome, is characterized by painless, diffuse, . . .
Viral Induced Disease in Mild Atopic Asthmatics: Dynamics of Pulmonary Function, Speed of Symptom Onset and Implications for Drug Intervention in HRV Inoculated Volunteers
Authors: Alex Mann, Ganesh Balaratnam, Jane Gunter, Pawel Rucki, Chris Poll, Martin Johnson, Tony Lockett
Journal: Journal of Allergy and Clinical Immunology (2016)
Experimental Treatment of Ebola Virus Disease with TKM-130803: A Single-Arm Phase 2 Clinical Trial
Authors: Jake Dunning, Foday Sahr, Amanda Rojek, Fiona Gannon, Gail Carson, Baimba Idriss, Thomas Massaquoi, Regina Gandi, Sebatu Joseph, Hassan K. Osman, Timothy J. G. Brooks, Andrew J. H. Simpson, Ian Goodfellow, Lucy Thorne, Armando Arias, Laura Merson, Lyndsey Castle, Rebecca Howell-Jones, Raul Pardinaz-Solis, Benjamin Hope-Gill, Mauricio Ferri, Jennifer Grove, Mark Kowalski, Kasia Stepniewska, Trudie Lang, John Whitehead, Piero Olliaro, Mohammed Samai, Peter W. Horby
Journal: PLoS Medicine (2016)

Background TKM-130803, a small interfering RNA lipid nanoparticle product, has been developed for the treatment of Ebola virus disease (EVD), but its efficacy and safety in humans has not been evaluated. Methods and Findings In this single-arm phase 2 trial, adults with laboratory-confirmed EVD received 0.3 mg/kg of TKM-130803 by intravenous infusion once daily for up to 7 d. On days when trial enrolment capacity was reached, patients were enrolled into a concurrent observational cohort. The primary outcome was survival to day 14 after admission, excluding patients who died within 48 h of admission. After 14 adults with EVD had received TKM-130803, the pre-specified futility boundary was reached, indicating a probability of survival to day 14 of ≤0.55, and enrolment was stopped. Pre-treatment geometric mean Ebola virus load in the 14 TKM-130803 recipients was 2.24 × 109 RNA copies/ml plasma (95% CI 7.52 × 108, 6.66 × 109). Two of the TKM-130803 recipients died within 48 h of admission and were therefore excluded from the primary outcome analysis. Of the remaining 12 TKM-130803 recipients, nine died and three survived. The probability that a TKM-130803 recipient who survived for 48 h will subsequently survive to day 14 was estimated to be 0.27 (95% CI 0.06, 0.58). TKM-130803 infusions were well tolerated, with 56 doses administered and only one possible infusion-related reaction observed. Three patients were enrolled in the observational cohort, of whom two died. Conclusions Administration of TKM-130803 at a dose of 0.3 mg/kg/d by intravenous infusion to adult patients with severe EVD was not shown to improve survival when compared to historic controls. Trial registration Pan African Clinical Trials Registry PACTR201501000997429
Bortezomib With High-Dose Melphalan, Arsenic Trioxide, and Ascorbic Acid In a Preparative Regimen For Multiple Myeloma: 5-Year Follow Up
Authors: A. Megan Cornelison, Yvonne Dinh, Manish Sharma, Nina Shah, Qaiser Bashir, Simrit Parmar, Chitra M. Hosing, Uday R Popat, Richard E Champlin, Muzaffar H. Qazilbash
Journal: Blood (2013)
Case 2-1999
Authors: Keith J. Benkov, Carolyn C. Compton
Journal: New England Journal of Medicine (1999)

Presentation of CaseA 15-year-old girl was referred to the hospital because of abdominal pain and bloody stools.The patient had been in excellent health until 26 weeks earlier, when she began to have mild periumbilical pain, usually after the evening meal, without radiation to the back. She passed small amounts of blood with several stools and sometimes noted blood dripping into the toilet bowl. She continued to have periumbilical pain. The results of laboratory studies performed at that time and on four subsequent occasions before admission are shown in Table 1 and Table 2. A stool culture was negative; Clostridium difficile toxin . . .
Is there a role for early chemotherapy in the management of pituitary adenomas?
Authors: Andrew L. Lin, Melissa W. Sum, Lisa M. DeAngelis
Journal: Neuro-Oncology (2016)

Pituitary adenomas are benign intracranial neoplasms that are frequently well-controlled with standard treatments that include surgical resection, radiotherapy, and agents that modulate hormonal excess. Unfortunately, a subset of patients remains uncontrolled or develops complications from these interventions. For these patients, chemotherapy is an additional treatment option that could improve outcomes. Temozolomide is an oral chemotherapy with a favorable side-effect profile that has shown activity against pituitary adenomas. Its non-overlapping toxicity and ability to induce rapid tumor regression renders it a potentially important adjunctive treatment. In patients with tumors that cannot be optimally addressed with standard treatments, there may be a role for early initiation of temozolomide.
Effect of Intervals between Doses on the Development of Tolerance to Isosorbide Dinitrate
Authors: John O. Parker, Bernice Farrell, Karen A. Lahey, Gordon Moe
Journal: New England Journal of Medicine (1987)

We studied the development of tolerance to isosorbide dinitrate in 12 patients with chronic stable angina pectoris. The effect of 30 mg of isosorbide dinitrate on treadmill exercise performance was assessed before and at one, three, and five hours after a single dose. As compared with placebo, the drug increased treadmill walking time until the onset of angina and until the development of moderate angina over the five-hour observation period (P<0.05). The patients then received 30 mg of isosorbide dinitrate twice, three times, and four times daily for a period of one week, and exercise performance was assessed before and at one, three, and five hours after the final morning dose. During sustained treatment two and three times daily, treadmill walking time was longer throughout the five-hour testing period than during the placebo phase (P<0.05). In contrast, during treatment four times daily, treadmill walking time was prolonged at one hour (P<0.05) but not at three and five hours after the last dose. We conclude that tolerance to the clinical effects of isosorbide dinitrate develops with a sustained dosage of 30 mg four times daily, but not when the drug is given two or three times daily. (N Engl J Med 1987; 316: 1440–4.)
A New Variant of Heavy-Chain Disease (μ-Chain Disease)
Authors: Harold S. Ballard, Louise M. Hamilton, Aaron J. Marcus, Clarise H. Illes
Journal: New England Journal of Medicine (1970)

A pathologic immunoglobulin was found in the serum of a man who had the clinical signs of a malignant lymphoproliferative disorder. It represents a new variant of heavy-chain disease (μ-chain disease). Additional findings included radiographic evidence of skeletal involvement, amyloidosis and morphologic abnormalities of the plasma cells. Although serum electrophoresis did not reveal an M component, immunoelectrophoresis showed an anomalous protein that appeared to be a rapidly migrating IgM. This protein was subsequently identified as a heavy-chain fragment of IgM. The urinary findings were unique in that the μ-chain fragment demonstrated in the serum was absent and a light chain (kappa type) was present.
SAT0324 ABCG2 Dysfunction Leads to Renal Urate Underexcretion Type Hyperuricemia in Addition to Extra-Renal Urate Underexcretion Type Hyperuricemia
Authors: K. Ichida, H. Matsuo, A. Nakayama, M. Sakiyama, T. Chiba, S. Shimizu, H. Nakashima, T. Nakamura, Y. Takada, T. Takada, H. Nakaoka, K. Wakai, Y. Sakurai, T. Shimizu, H. Suzuki, N. Shinomiya
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Hyperuricemia induces common diseases, gout and kidney stones, and accelerates the progression of renal diseases. Hyperuricemia has been clinically classified into the urate overproduction type (the renal urate overload type) including the extra-renal urate underexcretion type, the renal underexcretion type, and the combined type. We have reported that the dysfunction of ATP-binding cassette transporter, sub-family G, member 2 (ABCG2) is the major cause of hyperuricemia, especially extra-renal urate underexcretion type hyperuricemia. But its involvement in renal underexcretion type hyperuricemia, the most prevalent subtype, is not clearly explained so far. <h3>Objectives</h3> The aim of present study is to determine the contribution of ABCG2 to the onset of each type of hyperuricemia. <h3>Methods</h3> We performed the association analysis with hyperuricemia patients and controls in male Japanese. <h3>Results</h3> ABCG2 dysfunction significantly increased the risk of the whole hyperuricemia and renal urate overload type hyperuricemia, according to the severity of impairment. Furthermore, slight and moderate ABCG2 dysfunction significantly increased the risk of renal underexcretion type hyperuricemia. ABCG2 dysfunction caused renal urate underexcretion and induced hyperuricemia even if the renal urate overload was not remarkable. <h3>Conclusions</h3> These results show that ABCG2 plays physiologically important roles in both renal and extra-renal urate excretion mechanisms. <h3>References</h3> Matsuo H, Takada T, Ichida K, et al: Common defects of ABCG2, a high-capacity urate exporter, cause gout: a function-based genetic analysis in a Japanese population. Sci Transl Med 1:5ra11, 2009 Ichida K, Matsuo H, Takada T, et al: Decreased extra-renal urate excretion is a common cause of hyperuricemia. Nat Commun 3:764, 2012 Matsuo H, Nakayama A, Sakiyama M, et al: ABCG2 dysfunction causes hyperuricemia due to both renal urate underexcretion and renal urate overload. Sci Rep 4:3755, 2014 <h3>Disclosure of Interest</h3> None declared
Coronary-Plaque Rupture in Acute Coronary Syndromes Triggered by Snow Shoveling
Authors: Ayman J. Hammoudeh, Jacob I. Haft
Journal: New England Journal of Medicine (1996)

To the Editor: The acute coronary syndromes — myocardial infarction, unstable angina, and sudden cardiac death — have been shown to be triggered by heavy physical exertion, including snow shoveling...
Hashimoto's Thyroiditis
Authors: Leslie J. De Groot, Reginald Hall, William V. McDermott, Ann M. Davis
Journal: New England Journal of Medicine (1962)

Though a diagnosis rarely made a decade ago, Hashimoto's disease is now recognized with considerable frequency. This change is due to the wider use of the needle biopsy and, more importantly, to the demonstration of autoimmunization in this disease by Witebsky, Rose and Shulman1 and by Roitt et al.2 The circulating autoantibodies were initially thought to be the cause of the inflammatory process, but this now seems unlikely. The thyroid lesions are not necessarily correlated with the level of circulating antibodies, and passive transfer by means of serum has failed. It now seems that the initial event in the experimental . . .
Immune Endothelial-Cell Injury in Heparin-Associated Thrombocytopenia
Authors: Douglas B. Cines, Ann Tomaski, Susan Tannenbaum
Journal: New England Journal of Medicine (1987)

We studied the possibility that immune injury to endothelial cells may have a role in the development of thrombosis in some patients with heparin-associated thrombocytopenia. Serum samples from each of 27 patients who had this clinical diagnosis contained heparindependent platelet antibodies and deposited more than normal amounts of IgG, IgA, or IgM on endothelial cells, stimulating the production of tissue factor. Binding of immunoglobulins to endothelial cells was no longer detected when the patients were studied after heparin was withdrawn, but reappeared within several days upon reexposure to heparin in a patient who experienced a clinical recurrence. Binding of immunoglobulin to endothelial cells was partially reduced by the preadsorption of serum samples with heparin or heparan sulfate bound to Sepharose or by enzymatic cleavage of cell-bound heparan sulfate, and was augmented by the addition of heparan sulfate. Thus, serum from some patients with heparin-associated thrombocytopenia may contain antibodies that react with heparin bound to endothelial cells or with heparan sulfate synthesized by endothelial cells. Immune injury to both platelets and endothelial cells may play a part in the development of thrombosis in some patients after heparin therapy. (N Engl J Med 1987; 316: 581–9.)
Socioeconomic and clinical outcome of occupational and work-related asthma in exposed to isocyanates
Authors: Gabriella Guarnieri, Giovanni Scattolin, Grazia Barbetta, Ilaria Cattoni, Filippo Liviero, Giuliana Maran, Paola Mason, Maria Cristina Scarpa, Piero Maestrelli
Journal: European Respiratory Journal (2014)

Occupational asthma induced by isocyanates is relatively common and is associated with adverse socioeconomic consequences. Work exposure cessation is the most recommendable strategy after diagnosis, but often is not sufficient for the patient9s recovery.  Our aim was to assess the long-term impact of diagnosis of asthma on employment status in patients exposed to isocyanates and with work-related respiratory symptoms.  We compared 32 subjects with isocyanate induced occupational asthma (OA+) confirmed by positive specific inhalation challenge (SIC), 14 subjects with work-exacerbated asthma (WEA, active asthma but negative SIC) and 18 non-asthmatic subjects (NA, respiratory symptoms, but no objective signs of asthma and negative SIC).Job history, asthmatic symptoms by Asthma Control Test (ACT), lung function by spirometry and use of anti-asthma drugs were evaluated in each subject at diagnosis and after 10-year follow-up.  Clinical and functional features were comparable in the three groups at diagnosis. At follow-up, there were no differences among groups in the percentage of subjects who had changed job (OA+ 56%, WEA 58%, NA 61%). A minority of OA+ remained exposed to isocyanates (9%), while this occurred more frequently in WEA (29%) and NA (22%). The rate of subjects who recovered was 66.7%, 43.5% and 22% for NA, OA+ and WEA, respectively. In all groups, the greatest proportion of recovery was observed in subjects removed from exposure.  In conclusion, work-related respiratory symptoms were associated with a moderate work disability regardless of diagnosis of OA. The avoidance of exposure to isocyanates was associated with better prognosis irrespective of the initial diagnosis.
Human Granulocyte Colony-Stimulating Factor after Induction Chemotherapy in Children with Acute Lymphoblastic Leukemia
Authors: Ching-Hon Pui, James M. Boyett, Walter T. Hughes, Gaston K. Rivera, Michael L. Hancock, John T. Sandlund, Timothy Synold, Mary V. Relling, Raul C. Ribeiro, William M. Crist, William E. Evans
Journal: New England Journal of Medicine (1997)

Recombinant human granulocyte colony-stimulating factor (G-CSF, or filgrastim) hastens the recovery from neutropenia after intensive chemotherapy, but its role in the management of childhood leukemia is unclear.
AVE5026: A new hemisynthetic ultra low molecular weight heparin (ULMWH) with enriched anti-Xa activity and enhanced antithrombotic activity for management of cancer associated thrombosis
Authors: D. Hoppensteadt, W. Jeske, J. Walenga, J. Fareed
Journal: Journal of Clinical Oncology (2008)

14653 Background: AVE5026 is an ULMWH with a high anti-Xa activity associated with residual anti-IIa activity (ratio anti-Xa/IIa>30). This ratio may be favorable for use in cancer patients as it may have a higher therapeutic window. This agent is a polydisperse mixture of oligomeric heparin fragments (molecular weight 2000–3000 daltons) prepared by partial and controlled depolymerization of porcine mucosal heparin (UFH). The anticoagulant profile of AVE5026 has been previously reported (Hoppensteadt, et al. Blood 2007). Methods: To validate the hypothesis that AVE5026 is an appropriate antithrombotic in cancer, studies were carried out to determine its antithrombotic, bleeding, tumor growth, angiogenesis and apoptosis effects in animal models. Results: AVE5026 produced a dose-dependent antithrombotic response in the rat laser model of microvascular thrombosis (2.5 mg/kg IV, 9±1.7 laser shots; 5.0 mg/kg SC, 8±1.6 laser shots; control 3+0.8 laser shots). The relative bleeding effects of AVE5026 in a rat tail bleeding model were negligible in comparison to enoxaparin (E) and UFH (all 5 mg/kg IV; UFH >1000 sec; E 360±57 sec; AVE5026 209±29 sec; Control 215±32 seconds). Repeated administration of AVE5026 in dose ranges of 1–5 mg/kg od, SC for 14 days did not result in accumulation of the anti-Xa activity. Furthermore, in contrast to E, there was no enhancement of the hemorrhagic profile. Both E and AVE5026 inhibited tumor growth by regulating angiogenesis and apoptosis in a Lewis lung carcinoma (14% vs. 22% decrease) rat model and in a Walker 256 carcinosarcoma model (21% vs. 30% decrease) Conclusions: Although comparable results to E were demonstrated in animal models of arterial thrombosis, the bleeding effect of AVE5026 were disproportionately lower. This superior safety-efficacy ratio may translate into improved antithrombotic efficacy with decreased bleeding risk, suggesting that AVE5026 may provide the optimal treatment strategy for the management of cancer associated thrombosis. No significant financial relationships to disclose.
Acute Pericarditis Associated with Serum Sickness
Authors: Mervin J. Goldman, Francis Y. K. Lau
Journal: New England Journal of Medicine (1954)

ALTHOUGH carditis has been described as a manifestation of serum sickness in man, reports of acute pericarditis are uncommon. Davidson1 described an increase in cardiac dullness in 72 per cent of 50 cases of serum sickness, with an average increase of 1 cm. in transverse diameter of the heart. No subjective or objective evidence of heart disease was found in any of these patients, and it was assumed that the cardiac enlargement resulted from edema of the muscular wall of the heart. Clark and Kaplan2 reported 2 cases with endocardial and myocardial lesions, without pericardial involvement, after antipneumococcus serum. Clark . . .