tbuckley/cabot-search huggingface dataset:
Incidence of ovarian failure in systemic lupus erythematosus after treatment with pulse cyclophosphamide.
Authors: E M McDermott, R J Powell
Journal: Annals of the Rheumatic Diseases (1996)

OBJECTIVE: To investigate the incidence of ovarian failure after pulse cyclophosphamide treatment in systemic lupus erythematosus (SLE) and to compare this with two control groups: SLE patients treated with azathioprine, and a healthy age matched population. METHODS: All women patients with SLE treated with pulse cyclophosphamide in our department were identified and questioned concerning menstrual history. All the hospital notes were reviewed and details recorded on dose of cyclophosphamide, duration of treatment, side effects and lowest pretreatment neutrophil and leucocyte counts during the course of treatment. Disease controls were recruited from our department and healthy controls from the local family health services authority (FHSA) register. RESULTS: Incidence of ovarian failure in the premenopausal cyclophosphamide treated group was 54% and the incidence of premature menopause (occurring before age 40 years) was 41%. Increasing age at start of treatment showed a linear trend with incidence of ovarian failure (p = 0.01). Using logistic regression, increasing duration of treatment was related to incidence of ovarian failure (p = 0.047 in those treated age 35 years or younger). An association between the lowest neutrophil count throughout the treatment period, when taken immediately before each planned cyclophosphamide pulse, and the incidence of ovarian failure was also demonstrated (p = 0.04 in those treated before age 40 years). CONCLUSION: Ovarian failure--in particular, premature failure after treatment with pulse cyclophosphamide--is common. Factors associated with increased risk include greater age at start of treatment, longer period of treatment, and greater degree of marrow suppression as assessed by the neutrophil count immediately before each planned cyclophosphamide pulse.
Imperfect Gold Standards for Kidney Injury Biomarker Evaluation
Authors: Sushrut S. Waikar, Rebecca A. Betensky, Sarah C. Emerson, Joseph V. Bonventre
Journal: Journal of the American Society of Nephrology (2011)

Clinicians have used serum creatinine in diagnostic testing for acute kidney injury for decades, despite its imperfect sensitivity and specificity. Novel tubular injury biomarkers may revolutionize the diagnosis of acute kidney injury; however, even if a novel tubular injury biomarker is 100% sensitive and 100% specific, it may appear inaccurate when using serum creatinine as the gold standard. Acute kidney injury, as defined by serum creatinine, may not reflect tubular injury, and the absence of changes in serum creatinine does not assure the absence of tubular injury. In general, the apparent diagnostic performance of a biomarker depends not only on its ability to detect injury, but also on disease prevalence and the sensitivity and specificity of the imperfect gold standard. Assuming that, at a certain cutoff value, serum creatinine is 80% sensitive and 90% specific and disease prevalence is 10%, a new perfect biomarker with a true 100% sensitivity may seem to have only 47% sensitivity compared with serum creatinine as the gold standard. Minimizing misclassification by using more strict criteria to diagnose acute kidney injury will reduce the error when evaluating the performance of a biomarker under investigation. Apparent diagnostic errors using a new biomarker may be a reflection of errors in the imperfect gold standard itself, rather than poor performance of the biomarker. The results of this study suggest that small changes in serum creatinine alone should not be used to define acute kidney injury in biomarker or interventional studies.
HIGH SENSITIVE TROPONIN T CORRELATES WITH DIASTOLIC FUNCTION
Authors: Takuro Kubozono, Masaaki Miyata, Atsushi Kusumoto, Yoshiyuki Ikeda, Takuro Shinsato, So Kuwahata, Shoji Fujita, Kunitsugu Takasaki, Toshinori Yuasa, Hamasaki Shuichi, Chuwa Tei
Journal: Journal of the American College of Cardiology (2011)
Timing of New Black Box Warnings and Withdrawals for Prescription Medications
Authors: Karen E. Lasser
Journal: JAMA (2002)

ContextRecently approved drugs may be more likely to have unrecognized adverse drug reactions (ADRs) than established drugs, but no recent studies have examined how frequently postmarketing surveillance identifies important ADRs.Objective To determine the frequency and timing of discovery of new ADRs described in black box warnings or necessitating withdrawal of the drug from the market. Design and SettingExamination of the Physicians' Desk Reference for all new chemical entities approved by the US Food and Drug Administration between 1975 and 1999, and all drugs withdrawn from the market between 1975 and 2000 (with or without a prior black box warning). Main Outcome Measures Frequency of and time to a new black box warning or drug withdrawal.Results A total of 548 new chemical entities were approved in 1975-1999; 56 (10.2%) acquired a new black box warning or were withdrawn.Forty-five drugs (8.2%) acquired 1 or more black box warnings and 16 (2.9%)were withdrawn from the market.In Kaplan-Meier analyses, the estimated probability of acquiring a new black box warning or being withdrawn from the market over 25 years was 20%.Eighty-one major changes to drug labeling in the Physicians' Desk Reference occurred including the addition of 1 or more black box warnings per drug, or drug withdrawal.In Kaplan-Meier analyses, half of these changes occurred within 7 years of drug introduction; half of the withdrawals occurred within 2 years.Conclusions Serious ADRs commonly emerge after Food and Drug Administration approval.The safety of new agents cannot be known with certainty until a drug has been on the market for many years.
Operations Indices for Community Mental Health Centers
Authors: LUCY D. OZARIN, CARL TAUBE, FRED E. SPANER
Journal: American Journal of Psychiatry (1972)

Data obtained from a survey of federally funded mental health centers in operation for more than two months in 1969 revealed that the 205 centers provided care for an estimated 372,000 persons, with 23 percent on inpatient and 73 percent on outpatient status. Children and elderly people were underserved. Onethird of the patients sought help directly, without professional or agency intermediaries. Currently, public financing of mental health centers appears essential. Improved recordkeeping of program operations is urgently needed.
A study in post-Flexner survival. The Medical College of the State of South Carolina, 1913
Authors: W. C. Worthington
Journal: JAMA (1991)

The Flexner report of 1910 resulted in the closing of many marginal medical schools and opened a new era in medical education in the United States. Caught in Abraham Flexner's net were several old schools with long histories and, as he said, "traditions and a certain present dignity" that lacked the minimum resources needed to meet the standards of the Council on Medical Education of the American Medical Association. One example was the Medical College of the State of South Carolina. It was consigned to oblivion in Flexner's plan, but survived. Dean Robert Wilson, MD, in his efforts to save his school, turned politician, enlisted the aid of the state's highly controversial governor, and initiated an effective lobbying campaign in the state legislature. The Council on Medical Education became involved unofficially in the person of its secretary, Nathan P. Colwell, MD. His presence in South Carolina was turned to advantage by Wilson and others and contributed substantially to the success of their efforts. (<i>JAMA</i>. 1991;266:981-984)
Incremental Predictive Value of Carotid Ultrasonography in the Assessment of Coronary Risk in a Cohort of Asymptomatic Type 2 Diabetic Subjects
Authors: Sophie Bernard, André Sérusclat, François Targe, Sybil Charrière, Olivier Roth, Jacques Beaune, François Berthezène, Philippe Moulin
Journal: Diabetes Care (2005)

Consensus guidelines recommend cardiovascular risk assessment as the initial step of primary prevention. The aim of this study was to evaluate the incremental predictive value for coronary events conferred by carotid ultrasonography in addition to risk assessment by Framingham score and screening for silent myocardial ischemia in a cohort of type 2 diabetic patients.We prospectively studied 229 patients free of any cardiovascular complication with at least one additional cardiovascular risk factor. At baseline, all patients had an exercise treadmill test, carotid intima-media thickness (IMT) measurement, and coronary risk assessment by Framingham score. Cardiovascular events were registered during a 5-year follow-up period.Age, carotid IMT, carotid plaques, number of risk factors, Framingham score, and suboptimal exercise electrocardiogram were associated with incident cardiovascular events (P < 0.05). Carotid IMT was an independent predictor of cardiovascular events (P = 0.045). The predictive value for coronary events was similar for carotid IMT and Framingham score as assessed by area under the receiver operating characteristic curves. An improvement in risk prediction was conferred by addition of carotid IMT in a Cox model (global chi(2) increased from 14.1 to 18.1, P = 0.035).This prospective study confirms that carotid IMT is a marker of cardiovascular risk in this type 2 diabetic cohort, establishes that carotid IMT provides a similar predictive value for coronary events than Framingham score, and suggests that the combination of these two indexes significantly improves risk prediction for these patients.
Calcium pyrophosphatase dihydrate (CPPD) crystal deposition disease in a teaching hospital in Kuwait
Authors: A N Malaviya, I M Al-Shari, A R Al-Shayeb, D Shehab, M A S Hussain, M Al-Mutairy, O M Roberts, S Al-Ghuriear
Journal: Annals of the Rheumatic Diseases (2001)

<h3>OBJECTIVE</h3> A Medline electronic search showed a paucity of reports on calcium pyrophosphate dihydrate crystal deposition disease (CPPD-CDD) from the Gulf region. To date only a single case report has been published from this region. Therefore, this study aimed, firstly, at finding out the prevalence of chondrocalcinosis in adult Arabs in Kuwait presenting with knee arthritis and, secondly, at carrying out an observational study of CPPD-CDD among Arabs in Kuwait. <h3>METHODS</h3> For the study of the prevalence of chondrocalcinosis 100 consecutive adult patients presenting with knee arthritis were radiologically examined. For the observational study the clinical, laboratory, and radiological findings were analysed in patients with CPPD-CDD seen over a period of five years. <h3>RESULTS</h3> This study showed the presence of chondrocalcinosis in two (2%) of the 100 adult Kuwaiti and other Middle-Eastern Arab patients (70 men, 30 women, median age 50 (range 45–80)) who presented to the rheumatology clinic for the evaluation of knee pain. When the younger age of the group (only three patients aged &gt;70) is taken into account the figure was comparable with that reported from Western countries. Over a period of five years a total of 2726 new patients were evaluated at the rheumatology clinic of this institution. A diagnosis of crystal arthritis was made in 85 patients (3%). Fourteen of these 85 (that is, 16.5%, but 0.5% of the total cases) were diagnosed with definite (eight patients) or probable (six patients) CPPD-CDD. Different clinical presentations, including that of acute monarthritis (that is, pseudogout), premature generalised osteoarthritis, and polyarticular rheumatoid-like presentations, were seen in different patients. Overlap with true gout, with the additional presence of monosodium urate crystals in the joint aspirate, was seen in two patients. <h3>CONCLUSION</h3> The present report shows that CPPD-CDD may not be uncommon among Arabs in the Gulf region. A high degree of clinical awareness and routine examination of joint aspirates with careful analysis for crystals may make it a more common diagnosis in this part of the world. In this regard it is interesting to note that cases and case series including familial cases have been reported from North Africa, especially Tunisia, indicating that the disease has been well described in Arabs of other geographical regions.
Why collapse morphological concepts?
Authors: Wolfgang U. Dressler
Journal: Behavioral and Brain Sciences (1999)

Clahsen's conception of inflectional rules – as being not only regular, but simultaneously only concatenative (combinatorial), general and productive, representing the default, not occurring in interfixation within German compounds, and identical to the first rules to be acquired in first-language acquisition – involves an unwarranted collapsing of morphological concepts.
Cognitive Deficits in Adolescents With Schizophrenia Undergoing Antipsychotic Treatment
Authors: H. Chabrol, G. Peresson, D. Bonnet, J. T. Kenny, L. Friedman, R. L. Findling, T. P. Swales, M. E. Strauss, J. A. Jesberger, S. C. Schulz
Journal: American Journal of Psychiatry (1999)
Rapid Eye Movement Sleep Behavior Disorder and Neurodegenerative Disease
Authors: Michael Joseph Howell, Carlos Hugh Schenck
Journal: JAMA Neurology (2015)

The dream enactment of rapid eye movement sleep behavior disorder (RBD) is often the first indication of an impending α-synuclein disorder, such as Parkinson disease, multiple-system atrophy, or dementia with Lewy bodies.To provide an overview of RBD from the onset of dream enactment through the emergence of a parkinsonian disorder.Peer-reviewed articles, including case reports, case series, retrospective reviews, prospective randomized trials, and basic science investigations, were identified in a PubMed search of articles on RBD from January 1, 1986, through July 31, 2014.Under normal conditions, vivid dream mentation combined with skeletal muscle paralysis characterizes rapid eye movement sleep. In RBD, α-synuclein abnormalities in the brainstem disinhibit rapid eye movement sleep motor activity, leading to dream enactment. The behaviors of RBD are often theatrical, with complexity, aggression, and violence; fighting and fleeing actions can be injurious to patients as well as bed partners. Rapid eye movement sleep behavior disorder is distinguished from other parasomnias by clinical features and the demonstration of rapid eye movement sleep without atonia on polysomnography. Consistent with early neurodegeneration, patients with RBD demonstrate subtle motor, cognitive, and autonomic impairments. Approximately 50% of patients with spontaneous RBD will convert to a parkinsonian disorder within a decade. Ultimately, nearly all (81%-90%) patients with RBD develop a neurodegenerative disorder. Among patients with Parkinson disease, RBD predicts a non-tremor-predominant subtype, gait freezing, and an aggressive clinical course. The most commonly cited RBD treatments include low-dose clonazepam or high-dose melatonin taken orally at bedtime.Treatment of RBD can prevent injury to patients and bed partners. Because RBD is a prodromal syndrome of Parkinson disease (or related disorder), it represents a unique opportunity for developing and testing disease-modifying therapies.
Physiological regulation of early and late stages of megakaryocytopoiesis by thrombopoietin.
Authors: F J de Sauvage, K Carver-Moore, S M Luoh, A Ryan, M Dowd, D L Eaton, M W Moore
Journal: The Journal of Experimental Medicine (1996)

Thrombopoietin (TPO) has recently been cloned and shown to regulate megakaryocyte and platelet production by activating the cytokine receptor c-mpl. To determine whether TPO is the only ligand for c-mpl and the major regulator of megakaryocytopoiesis, TPO deficient mice were generated by gene targeting. TPO-/- mice have a >80% decrease in their platelets and megakaryocytes but have normal levels of all the other hematopoietic cell types. A gene dosage effect observed in heterozygous mice suggests that the TPO gene is constitutively expressed and that the circulating TPO level is directly regulated by the platelet mass. Bone marrow from TPO-/- mice have decreased numbers of megakaryocyte-committed progenitors as well as lower ploidy in the megakaryocytes that are present. These results demonstrate that TPO alone is the major physiological regulator of both proliferation and differentiation of hematopoietic progenitor cells into mature megakaryocytes but that TPO is not critical to the final step of platelet production.
An open phase I study assessing the feasibility of the triple combination: oxaliplatin plus irinotecan plus leucovorin/ 5-fluorouracil every 2 weeks in patients with advanced solid tumors
Authors: M. Ychou, T. Conroy, J.F. Seitz, S. Gourgou, A. Hua, D. Mery-Mignard, A. Kramar
Journal: Annals of Oncology (2003)
Gefitinib Radiosensitizes Non–Small Cell Lung Cancer Cells by Suppressing Cellular DNA Repair Capacity
Authors: Toshimitsu Tanaka, Anupama Munshi, Colin Brooks, Jenny Liu, Marvette L. Hobbs, Raymond E. Meyn
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Overexpression of the epidermal growth factor receptor (EGFR) promotes unregulated growth, inhibits apoptosis, and likely contributes to clinical radiation resistance of non–small cell lung cancer (NSCLC). Molecular blockade of EGFR signaling is an attractive therapeutic strategy for enhancing the cytotoxic effects of radiotherapy that is currently under investigation in preclinical and clinical studies. In the present study, we have investigated the mechanism by which gefitinib, a selective EGFR tyrosine kinase inhibitor, restores the radiosensitivity of NSCLC cells. Experimental Design: Two NSCLC cell lines, A549 and H1299, were treated with 1 μmol/L gefitinib for 24 h before irradiation and then tested for clonogenic survival and capacity for repairing DNA double strand breaks (DSB). Four different repair assays were used: host cell reactivation, detection of γ-H2AX and pNBS1 repair foci using immunofluorescence microscopy, the neutral comet assay, and pulsed-field gel electrophoresis. Results: In clonogenic survival experiments, gefitinib had significant radiosensitizing effects on both cell lines. Results from all four DNA damage repair analyses in cultured A549 and H1299 cells showed that gefitinib had a strong inhibitory effect on the repair of DSBs after ionizing radiation. The presence of DSBs was especially prolonged during the first 2 h of repair compared with controls. Immunoblot analysis of selected repair proteins indicated that pNBS1 activation was prolonged by gefitinib correlating with its effect on pNBS1-labeled repair foci. Conclusions: Overall, we conclude that gefitinib enhances the radioresponse of NSCLC cells by suppressing cellular DNA repair capacity, thereby prolonging the presence of radiation-induced DSBs.
Frame Count Reserve
Authors: Martin G. Stoel, Felix Zijlstra, Cees A. Visser
Journal: Circulation (2003)

Background— The Doppler wire–derived (relative) coronary flow velocity reserve (CVR) that is used to evaluate functional significance of a coronary stenosis is a method performed only by interventional cardiologists. An angiographic method would be useful in the diagnostic catheterization laboratory. For this purpose, we investigated the relation between TIMI frame count reserve (FCR) and CVR. Methods and Results— In 38 patients, (relative) FCR of left anterior descending (LAD) and left circumflex coronary artery (LCx) was calculated by using manual, synchronized contrast agent injections and compared with (relative) CVR. In addition, vessel length was measured with an intracoronary guidewire and frame count flow velocity was calculated and compared with average peak velocity. There was a strong correlation between FCR and CVR ( r =0.62, P &lt;0.001) and between relative FCR and relative CVR ( r =0.84, P &lt;0.001). The LAD was significantly longer than the LCx (mean, 14.3±1.6 cm versus 11.4±1.8 cm, P &lt;0.001), and, therefore, TIMI frame count of LAD was significantly higher than of LCx (mean basal 32.5±15.1 versus 23.6±9.1 and hyperemic 12.1±6.6 versus 8.7±3.2, both P &lt;0.02). However, all flow velocity measurements and estimations of volume flow were not different for LAD compared with LCx. There were also no differences between mean FCR and CVR of LAD or LCx, of both vessels compared with each other and between mean relative FCR and relative CVR. Conclusion— The (relative) frame count reserve can be used to estimate (relative) coronary flow velocity reserve.
Relationship between the tissue-specificity of mouse gene expression and the evolutionary origin and function of the proteins.
Authors: Shiri Freilich, Tim Massingham, Sumit Bhattacharyya, Hannes Ponsting, Paul A Lyons, Tom C Freeman, Janet M Thornton
Journal: Genome biology (2005)

The combination of complete genome sequence information with expression data enables us to characterize the relationship between a protein's evolutionary origin or functional category and its expression pattern. In this study, mouse proteins were assigned into functional and phyletic groups and the gene expression patterns of the different protein groupings were examined by microarray analysis in various mouse tissues. Our results suggest that the proteins that are universally distributed in all tissues are predominantly enzymes and transporters. In contrast, the tissue-specific set is dominated by regulatory proteins (signal transduction and transcription factors). An increased tendency to tissue-specificity is observed for metazoan-specific proteins. As the composition of the phyletic groups highly correlates with that of the functional groups, the data were tested in order to determine which of the two factors - function or phyletic age - is dominant in shaping the expression profile of a protein. The observed differences in expression patterns of genes between functional groups were found mainly to reflect their different phyletic origin. The connection between tissue specificity and phyletic age cannot be explained by the recent rate of evolution. Finally, although metazoan-specific proteins tend to be tissue-specific compared with phyletically conserved proteins present in all domains of life, many such 'universal' proteins are also tissue-specific. The minimal cellular transcriptome of the metazoan cell differs from that of the ancestral unicellular eukaryote: new functions were added (metazoan-specific proteins), whilst other functions became specialized and no longer took place in all cells (tissue-specific pre-metazoan proteins).
Use of Interferon for Prevention of Hepatocellular Carcinoma in Cirrhotic Patients with Hepatitis B or Hepatitis C Virus Infection
Authors: Vicky Baffis, Ian Shrier, Averell H. Sherker, Andrew Szilagyi
Journal: Annals of Internal Medicine (1999)

The incidence of hepatocellular carcinoma in North America is increasing. Current debate focuses on whether interferon administered to cirrhotic patients—with or without biochemical or virologic response—delays or prevents cancer of the liver. Review of the literature revealed several studies that showed improvement in or delay in progression of histologic fibrosis in patients with hepatitis C virus (HCV) infection. In patients with hepatitis B virus (HBV) infection, conversion to the nonreplicative stage may be associated with histologic improvement. However, only 11 studies (6 of HCV, 3 of HBV, and 2 of HCV and HBV) compared development of hepatocellular carcinoma in interferon-treated patients with cirrhosis and cirrhotic patients who were not treated with interferon. Although no firm statistical conclusions could be drawn, the literature suggests that interferon therapy may prevent hepatocellular carcinoma in patients with cirrhosis, particularly those infected with HCV. Interferon treatment cannot be recommended for all persons with cirrhosis and HBV or HCV infection because the current evidence is only suggestive. Long-term randomized, controlled trials may provide definitive data; however, it will be difficult, if not impossible, to conduct such trials because of the improved efficacy of combination therapy with interferon and ribavirin in patients with chronic HCV infection and the development of new therapies for patients with HBV infection.