tbuckley/cabot-search huggingface dataset:
The revision of axis V in DSM-III-R: should symptoms have been included?
Authors: A E Skodol, B G Link, P E Shrout, E Horwath
Journal: American Journal of Psychiatry (1988)

The authors studied the relationship of psychological symptoms to clinicians' ratings on DSM-III's axis V. A total of 355 patients received multiaxial assessments and were reinterviewed under blind conditions with the Psychiatric Epidemiology Research Interview, which contains scales to measure aspects of social and occupational functioning and various symptom dimensions. The majority of symptom scales were correlated significantly with axis V ratings. Axis I diagnosis explained 19.0% of the variance in axis V; demographics, 6.5%; and symptoms, 7%. Symptoms had a larger effect, in terms of explained variance, than adaptive functioning variables and tended to detract from the latter's significance. These results have implications for axis V in DSM-III-R and for planning DSM-IV.
Induction of GvL after allogeneic stem cell transplantation
Authors: M. L. Arellano, W. Harris, A. Langston, S. McMillan, H. Rosenthal, E. K. Waller
Journal: Journal of Clinical Oncology (2008)

18004 Background: Bone marrow or blood stem cell transplantation remains the only potentially curative therapy for patients with high-risk leukemia, but relapse remains the major cause of treatment failure. We hypothesized that the combination of GM-CSF and IFN-alfa-2b upregulates co-stimulatory molecule expression and down-regulates counter-regulatory signals, leading to a graft vs. leukemia effect. We report on correlative laboratory data from an ongoing prospective clinical trial to assess the efficacy and toxicity of GM-IFN in patients with acute leukemia relapsed after allogeneic transplantation. Methods: Pilot study, target enrollment of 15 patients. Eligible patients are older than 1 year of age, with acute leukemia/MDS relapsed after allogeneic transplantation; adequate organ function, lack of GVHD after withdrawal of immunosuppression, and > 20% donor chimerism in CD3+ cells. Patients with > 5% circulating blasts receive cyto-reductive therapy with either hydroxyurea, or cytarabine 0.5–1gm/m2 IV daily for 5 days. GM 250mg/m2 3x/week and pegylated IFN 1.5mcg/kg weekly are administered to patients who lack significant GVHD after cyto-reductive therapy and after recovery of toxicities. Cytokines are continued until development of GVHD, progression of disease, or limiting toxicity. Study samples collected pre and post-therapy are assessed for co- stimulatory molecules on blasts & T-cells, enumeration of immune cells (Tregs, DCs, and NK cells), intracellular cytokines, and cytotoxicity assays. Results: 6 patients with AML relapsed after allogeneic transplant have been enrolled, median age 20. Median time to relapse 5 months. Paired samples were obtained on 4 patients. One patient progressed and expired prior to therapy, and 1 patient withdrew prior to cytokines. 2 pts. developed GVHD. Three pts. survive at 3, 4, and 5 mos. CD80 was upregulated in blasts, and CTLA4 was downregulated in CD4+T cells and NK cells in all pts. post-therapy. PDL1 was upregulated on blasts in 3/4 pts. post-therapy. Conclusions: Immune therapy with GM-IFN appears to upregulate co-stimulatory molecules on leukemic blasts, but this seems to be tempered by upregulation of counter-regulatory signals on T-cells. Cytotoxicity assays are being evaluated will be presented. Accrual is ongoing and will be expanded to other centers. No significant financial relationships to disclose.
Obstetric Complications Associated with the Lupus Anticoagulant
Authors: D. Ware Branch, James R. Scott, Neil K. Kochenour, Edward Hershgold
Journal: New England Journal of Medicine (1985)

We identified eight patients with the lupus anticoagulant (an autoantibody acquired by some patients with systemic lupus erythematosus), by observation of an increased activated partial thromboplastin time and abnormal results on a tissue thromboplastin-inhibition test. The patients had experienced a total of 30 spontaneous abortions and fetal deaths in 31 previous pregnancies (96.8 per cent). During their next pregnancy, the patients were treated with 40 to 50 mg of prednisone per day and 81 mg of aspirin per day. The therapy shortened their activated partial thromboplastin times, produced normal values for tissue thromboplastin inhibition, and reduced the rate of pregnancy loss to 37.5 per cent. However, preeclampsia developed in the five patients who gave birth to live infants, and fetal growth retardation occurred in three cases. The corticosteroid and low-dose aspirin regimen appears to improve perinatal outcome in cases in which the mother has the lupus anticoagulant, but such practices as careful fetal surveillance and preterm delivery when appropriate are also important to successful obstetric management of such cases.
172P: Antacid and de novo brain metastases in EGFR-mutant NSCLC patients treated with first-line, first-generation EGFR-TKIs
Authors: Y.-M. Chen, M.-C. Lin, C.-H. Lai, W.-F. Fang, H.-C. Chang, C.-C. Wang, C.-C. Tseng
Journal: Journal of Thoracic Oncology (2016)
Case 17-2010
Authors: Daniel Tarsy, Kathleen J. Sweadner, Phillip C. Song
Journal: New England Journal of Medicine (2010)

A 29-year-old right-handed woman was seen in the neurology clinic of this hospital because of a 3-year history of involuntary flexion of the left hand and increasing difficulty moving the left foot. Examination revealed dystonic movements and posturing of the left arm, hand, and foot. Brain imaging was normal. During the next 2.5 years, symptoms gradually worsened, and difficulty swallowing and speaking developed. A diagnostic test was performed.
Treatment of Chronic Hepatitis C in Active Drug Users
Authors: G L Davis, J R Rodrigue
Journal: New England Journal of Medicine (2001)

It is currently estimated that between 2.7 million and 4.0 million persons in the United States have chronic hepatitis C virus (HCV) infection.1 Many of these persons have potentially progressive disease. Studies suggest that mortality and health care costs from complications of chronic hepatitis C and cirrhosis, such as hepatocellular carcinoma and liver failure, will increase dramatically over the next 10 to 20 years.2,3 Several reports indicate that this increase has already begun to occur.4,5 Thus, the development of more effective interferon-based treatments is particularly encouraging. A standard regimen of interferon and ribavirin results in sustained eradication of . . .
Aldosterone-Receptor Deficiency in Pseudohypoaldosteronism
Authors: Decio Armanini, Ursula Kuhnle, Thomas Strasser, Helmuth Dorr, Ina Butenandt, Peter C. Weber, Jan R. Stockigt, Paul Pearce, John W. Funder
Journal: New England Journal of Medicine (1985)

Pseudohypoaldosteronism, a syndrome characterized by salt wasting and failure to thrive, usually presents in infancy as high urinary levels of sodium despite hyponatremia, hyperkalemia, hyperreninemia, and elevated aldosterone levels. We have investigated this syndrome for the possibility of abnormal Type I or "mineralocorticoid-like" receptors, which have intrinsic steroid specificity indistinguishable from that of renal mineralocorticoid receptors and are found in many tissues and cells, including mononuclear leukocytes. We have studied three patients with pseudohypoaldosteronism: the 28-year-old index case in Melbourne (Patient 1) and two siblings in Munich, eight and two years of age (Patients 2 and 3); clinically, Patient 3 had a less severe case than his sister. Percoll-separated control monocytes bound [3H]aldosterone with high affinity (Kd approximately 3 nM) and limited capacity (150 to 600 sites per cell). On repeated examination, no [3H]aldosterone binding was found in monocytes from Patients 1 and 2; in Patient 3, the levels were 62 sites per cell, more than 2 S.D. below those of the control. Levels in the parents of the Munich patients (first cousins) were normal. It appears that pseudohypoaldosteronism is caused by a Type I receptor defect, that the defect may be complete or partial, that transmission may be autosomal recessive, and that the study of patients with pseudohypoaldosteronism may indicate physiologic roles for Type I receptors in nonepithelial tissues.
A phase II prospective study of standardized steroid dosing for patients with brain metastases undergoing whole brain radiotherapy
Authors: A. E. Sturdza, A. Bezjak, G. R. Pond, K. Brrows, B. Millar, C. Garraway, N. Laperriere, L. Dawson, R. K. Wong
Journal: Journal of Clinical Oncology (2008)

2050 Background: This study is aimed to prospectively investigate whether lower doses of Dexamethasone (DXM) control neurological symptoms with less side-effects in patients with brain metastases undergoing whole brain radiation therapy (WBRT). Methods: This phase II study had a planned sample size of 50 pts. Pts diagnosed with brain metastases that were on DXM for less than 2 weeks prior to seeing a oncologist and consented to WBRT were eligible. Those with neurological symptoms related to brain metastases were given DXM 8mg qAM, asymptomatic pts received 4mg qAM. First assessment: day 3, then WBRT (20 Gy/5fr). Reassessment: last day of RT, and 2, 4, 8 weeks (w) post RT for symptomatic (1, 3, 8 w for asymptomatic) patients. Neurological symptoms and steroid related side- effects, as reported by patients, were documented. DXM was tapered at the end of WBRT using a pre-established protocol: over 3 w for symptomatic (2 w for asymptomatic) cohort. Primary study outcome was the percentage of pts with significant deviation from the protocol (those who needed higher doses of steroids or to be restarted after tapering). Results: 49 pts were accrued, 40 fully evaluable. 62% of pts deviated from protocol, 95% CI: 46%-77% (56% of asymptomatic, 73% of symptomatic pts); thus, the primary study endpoint was met, and the tapering schedule was deemed inappropriate for clinical use. 24/25 deviations involved an increase in dose or reintroduction of DXM after tapering. Most deviation (15) occurred during or after tapering; 4 were needed for subsequent chemotherapy. Presence of cerebellar metastases was the only statistically significant predictor of pts requiring steroid modification (p value 0.0063). Predominant steroid side-effects graded by patients as little, moderately or very disturbing were increased appetite (73%), peripheral myopathy (58%), insomnia (55%), irritability (50%). Conclusions: Although lower doses of steroids may control neurological symptoms prior to WBRT, the majority of pts required an increase in steroid dose and/or were not able to be tapered according to a pre-determined schedule. Given the side-effects of prolonged steroid use, further attempts at managing and likely individualizing steroid dosing and taper are needed. No significant financial relationships to disclose.
Effects of Somatostatin on Hemostasis in Baboons
Authors: Donna J. Koerker, Laurence A. Harker, Charles J. Goodner
Journal: New England Journal of Medicine (1975)

Because some baboons repeatedly infused with somatostatin died we reviewed available autopsy material. All six animals chronically treated with somatostatin displayed gross or microscopical pulmonary hemorrhage and increased hemosiderin in lung and liver whereas only one of six untreated animals had a similar abnormality. We therefore examined the hemostatic system in living baboons. Thrombocytopenia (mean platelet count of 84,000 per microliter) was noted in six of seven baboons chronically treated with somatostatin; platelet survival was normal. Clotting factors were unaffected. Fibrinogen concentration and survival were unchanged. The acute effects of intravenous somatostatin (0.8 μg per kilogram per minute for two hours) in previously untreated animals transiently decreased platelet count, reduced retention of platelets on glass-bead columns and inhibited aggregation induced by ADP, collagen and epinephrine. Bleeding times were not prolonged. Somatostatin added to platelet-rich plasma in vitro was without effect. These data suggest that prolonged administration of somatostatin should be undertaken with caution. (N Engl J Med 293:476–479,1975)
The Treatment of Pruritus and Hypercholesteremia of Primary Biliary Cirrhosis with Cholestyramine
Authors: Theodore B. Van Itallie, Sami A. Hashim, Richard S. Crampton, David M. Tennent
Journal: New England Journal of Medicine (1961)

ONE of the most frustrating features of primary biliary cirrhosis is pruritus, often so intense and unrelenting that the victim seriously contemplates suicide.1 Such patients suffer from chronic insomnia and irritability, and their bodies become covered with excoriations from uncontrollable scratching. Attempts to control the intolerable itching with sedatives, analgesics, glucocorticoids and methyltestosterone have met with little success. Recently, norethandrolone has been reported fairly effective in relieving the pruritus; however, its administration is associated with deepening jaundice and other side effects.2 3 4 Bile acids accumulate in the blood of patients with primary biliary cirrhosis, and it has been proposed that the . . .
Dendritic Cell–Based Immunotherapy: State of the Art and Beyond
Authors: Kalijn F. Bol, Gerty Schreibelt, Winald R. Gerritsen, I. Jolanda M. de Vries, Carl G. Figdor
Journal: Clinical Cancer Research (2016)

Abstract Dendritic cell (DC) vaccination in cancer patients aims to induce or augment an effective antitumor immune response against tumor antigens and was first explored in a clinical trial in the 1990s. More than two decades later, numerous clinical trials have been performed or are ongoing with a wide variety of DC subsets, culture protocols, and treatment regimens. The safety of DC vaccination and its ability to induce antitumor responses have clearly been established; however, although scattered patients with long-term benefit were reported, DC vaccines have not yet fulfilled their promise, perhaps mainly due to the lack of large-scale well-conducted phase II/III trials. To allow meaningful multicenter phase III trials, the production of DC vaccines should be standardized between centers which is now becoming feasible. To improve the efficacy of DC-based immunotherapy, it could be combined with other treatments. Clin Cancer Res; 22(8); 1897–906. ©2016 AACR. See all articles in this CCR Focus section, “Opportunities and Challenges in Cancer Immunotherapy.”
The Effect of Postmenopausal Estrogen Therapy on Bone Density in Elderly Women
Authors: David T. Felson, Yuqing Zhang, Marian T. Hannan, Douglas P. Kiel, Peter Wilson, Jennifer J. Anderson
Journal: New England Journal of Medicine (1993)

Estrogen therapy prevents bone loss in postmenopausal women who take it early in the postmenopausal period. The risk of fracture is highest much later in life, however. We studied whether bone mass in elderly women was affected by earlier estrogen use and how long women needed to take estrogen for it to have a beneficial effect on bone density later in life.In 1988 and 1989, we measured bone mineral density at the femur, spine, shaft of the radius, and ultradistal radius in 670 white women in the Framingham Study cohort (mean age, 76 years; range, 68 to 96). These women had been followed prospectively through menopause and had been asked repeatedly about estrogen therapy. After excluding women who began taking estrogen after a fracture, we investigated whether postmenopausal estrogen therapy affected bone density; in these analyses we adjusted for age, weight, height, cigarette smoking, physical activity, and age at menopause.A total of 212 women (31.6 percent) had received estrogen therapy (mean estimated duration of treatment, 5 years). Only women who had taken estrogen for 7 to 9 years or for 10 or more years had significantly higher bone mineral density than women who had not taken estrogen (7 to 9 years of treatment, P < 0.05 at sites in the femur and the spine; > or = 10 years, P < 0.05 at all sites except the spine). In the women less than 75 years of age who had taken estrogen for seven or more years, the bone density was, averaging all sites, 11.2 percent greater than in women who had never received estrogen. Among women 75 years of age and older in whom the duration of therapy was comparable, bone density was only 3.2 percent higher than in women who had never taken estrogen.For long-term preservation of bone mineral density, women should take estrogen for at least seven years after menopause. Even this duration of therapy may have little residual effect on bone density among women 75 years of age and older, who have the highest risk of fracture.
Somatic genomic alterations in urothelial cancer: Results of the Cancer Genome Atlas (TCGA) bladder cancer (BC) analysis.
Authors: Jonathan E. Rosenberg, Jaegil Kim, Andrew Cherniack, Carrie Sougnez, Matthew Meyerson, Gad Getz, John N. Weinstein, Seth P. Lerner, David J. Kwiatkowski
Journal: Journal of Clinical Oncology (2014)

285 Background: We report here an integrated analysis of mutation and somatic copy number alterations (SCNAs) in 131 BCs to provide a comprehensive landscape of molecular alterations. Methods: Exon capture, whole exome sequencing (WES), and SNP arrays were performed on 131 MIBCs with no prior chemotherapy treatment, analyzed using the Cancer Genome Atlas Firehose Pipeline, and validated using orthogonal methods. Significantly mutated genes (SMGs) were determined by MutSig v1.5. Recurrent SCNAs were identified via GISTIC 2.0. Consensus non-negative matrix factorization (CNMF) was used to identify SCNA and SMG clusters. Results: 32 genes showed statistically significant levels of recurrent somatic mutation. Known druggable SMGs included FGFR3 (12%), PIK3CA (20%), TSC1 (8%), and ERBB3 (11%). CDKN1A (14%), ERCC2 (12%), RXRA (9%), ELF3 (8%), KLF5 (8%), FOXQ1 (5%), RHOB (5%), PAIP1 (5%), and BTG2 (5%) were not previously reported as SMGs in any other TCGA cancer type. Truncating mutations in 4 SMGs involved in epigenetic regulation (MLL2, ARID1A, KDM6A, and EP300) were significantly enriched. Clustering of both SMGs and focal SNCAs in 125 samples identified three distinct groups. Group A is highly enriched in focal SCNAs in several genes, as well as mutations in MLL2. Group B is enriched in papillary histology, loss of CDKN2A, and alterations in FGFR3. Group C has TP53 mutations, enrichment with RB1 mutations, and amplifications of E2F3 and CCNE1. There were no statistically significant associations between smoking status and the mutational spectrum, frequency of mutation in any SMG, focal SCNAs, or CNMF subtype. Conclusions: Analyses identified potential therapeutic targets in 69% of BCs, including 42% with targets in the PI3K/AKT/mTOR pathway and 45% with targets (including ERBB2) in the RTK/MAPK pathway. Clustering reveals 3 groups with differences in pattern of genomic alteration suggesting the possibility of different pathogenic mechanisms of BC development. Epigenetic regulatory genes were more frequently mutated in urothelial carcinoma than in any common cancer studied to date, suggesting the future possibility of targeted therapy for chromatin abnormalities.
Guanidinosuccinic Acid in Renal Failure, Experimental Azotemia and Inborn Errors of the Urea Cycle
Authors: Israel M. Stein, Burton D. Cohen, Roger S. Kornhauser
Journal: New England Journal of Medicine (1969)

An Improved method of isolation and quantitation, using Dowex-1 ion-exchange chromatography and paper electrophoresis, has permitted efficient recovery of guanidinosuccinic acid from serum, urine and cerebrospinal fluid. Mean concentration of this acid in normal urine is 1.71 ± 1.60 (SD) mg/100 ml, and 5.35 ± 2.68 mg/100 ml in urine from uremic patients. Serum and cerebrospinal-fluid levels are also increased in uremia. In patients undergoing peritoneal dialysis, guanidinosuccinic acid was dialyzable. The metabolic pathway for synthesis of guanidinosuccinic acid is unknown. The increased excretion of this compound in rats treated with arginine, coupled with the failure to demonstrate the metabolite in the urine of patients suspected of having arginine deficiency resulting from genetic defects of the urea cycle, suggests that arginine is an intermediate in guanidinosuccinic acid synthesis.
The application of EEG sleep for the differential diagnosis of affective disorders
Authors: D J Kupfer, F G Foster, P Coble, R J McPartland, R F Ulrich
Journal: American Journal of Psychiatry (1978)

On the basis of two EEG sleep criteria, REM latency and REM activity, the authors achieved 81% accuracy in distinguishing between 47 patients with primary depression and 48 patients with secondary depression using discriminant analysis. Sleep efficiency, the percentage of delta sleep, and the percentage of REM sleep discriminated between psychotic and nonpsychotic subgroups in the group with primary depression with 75% accuracy. REM activity and intermittent nocturnal awakening accurately discriminated two subtypes of patients with secondary depression at a level of 81%. These results suggest that EEG sleep measurements can yield significant data to aid in differential diagnosis in psychiatry.
Mitochondrial cardiotoxicity of a prototype HCV NS3-protease inhibitor is characterized by a specific electrocardiographic signature in mice
Authors: Thomas Vanwolleghem, Eva Van Braeckel, Joél Smet, Bi-Sheng Liu, Philip Meuleman, Harry L Janssen, Tania Roskams, Rudy Van Coster, Rita De Vos, Geert Leroux-Roels
Journal: Hepatology (2012)
S95 Peripheral blood CRTH2 positive cell count in patients with severe eosinophilic asthma
Authors: B Hilvering, L Stoeger, S Go, C Connelly, K Borg, S Thulborn, S Pahlke, ID Pavord, L Xue
Journal: Thorax (2015)

<h3>Background</h3> CRTH2 antagonism has been shown to reduce eosinophilic airway inflammation and improve lung function in patients with severe eosinophilic asthma. To better understand the role of CRTH2 in the pathogenesis of this asthma phenotype, we have carried out a cross-sectional study to investigate the CRTH2 positive cell counts in peripheral blood of patients with severe eosinophilic asthma. <h3>Methods</h3> Blood was taken from 12 controls and 33 patients with asthma, 21 of whom met the 2014 ERS/ATS guideline criteria for severe asthma and had historical evidence of eosinophilic airway inflammation as defined before (Pavord <i>et al</i>. Lancet 2012;380:651–9). Th2 were detected as CD3<sup>+</sup>CD4<sup>+</sup>CRTH2+, Tc2 as CD3<sup>+</sup>CD8<sup>+</sup>CRTH2+, eosinophils as SSC<sup>high</sup>CRTH2+, and basophils as CD123<sup>+</sup>CRTH2+ by flow cytometry, and numbers presented as total cell counts in peripheral blood. Data were analysed using one-way ANOVA followed by the Newman-Keuls test. <h3>Results</h3> CRTH2 cell counts were reasonably repeatable within patients (ICC 0.84; n = 9). Mean ± SD CRTH2+ cell counts were 168 ± 81, 322 ± 191, 710 ± 322 and 290 ± 179 × 10<sup>6</sup> cells/L in normal controls (n = 12), patients with mild to moderate asthma (n = 12), patients with severe asthma at BTS step 4 (n = 10), and patients with severe asthma at BTS step 5 (n = 11) respectively (Figure 1). Most CRTH2 + cells were eosinophils (Figure 1). <h3>Conclusion</h3> Blood CRTH2+ cells are increased in subjects with severe eosinophilic asthma, mainly because of increased CRTH2+ eosinophils. Eosinophils and basophils numbers are significantly increased in severe eosinophilic asthma at step 4 but not step 5. Th2 and Tc2 cell numbers are less clearly associated with severe asthma. CRTH2+ cell numbers are lower in patients treated with prednisolone.
Decreased Epinephrine Responses to Hypoglycemia during Sleep
Authors: Timothy W. Jones, Paul Porter, Robert S. Sherwin, Elizabeth A. Davis, Peter O'Leary, Fiona Frazer, Geoffrey Byrne, Stephen Stick, William V. Tamborlane
Journal: New England Journal of Medicine (1998)

In patients with type I diabetes mellitus, hypoglycemia occurs commonly during sleep and is frequently asymptomatic. This raises the question of whether sleep is associated with reduced counterregulatory-hormone responses to hypoglycemia.