tbuckley/cabot-search huggingface dataset:
The risk of comorbidity: Table 1
Authors: J C Peterson, S A Paget, M S Lachs, M C Reid, M E Charlson
Journal: Annals of the Rheumatic Diseases (2012)

The field of rheumatology has shown great interest in comorbidity-related risk among patients with rheumatoid arthritis (RA). A recent paper reported that a person with RA has a similar risk of sustaining a myocardial infarction as a person with diabetes mellitus (DM), and this risk is comparable to that of a healthy person 10 years older.1 Several other papers have also recently reported that people with RA and DM share a similar cardiovascular risk.2 3 These findings are strikingly similar to those of the Charlson Index published 25 years ago.4

The Charlson Comorbidity Index is the most commonly used prognostic measure of illness burden in contemporary clinical research.5 Cited in nearly 7000 studies, it is considered the gold standard to assess comorbid risk in clinical research.6 Over time the Charlson Index has increased in use and relevance, likely related to increased rates of chronic disease, supporting the need to measure and adjust for these conditions in research.

The original objective was to develop a prognostic taxonomy for comorbid conditions that could singly or in combination prognosticate …
Elevation of homocysteine and excitatory amino acid neurotransmitters in the CSF of children who receive methotrexate for the treatment of cancer.
Authors: C T Quinn, J C Griener, T Bottiglieri, K Hyland, A Farrow, B A Kamen
Journal: Journal of Clinical Oncology (1997)

PURPOSE Folate deficiency, either by diet or drug, increases plasma homocysteine (Hcy). Hcy damages cerebrovascular endothelium, and hyperhomocysteinemia is a risk factor for stroke. Hcy is metabolized to excitatory amino acid (EAA) neurotransmitters, such as homocysteic acid (HCA) and cysteine sulfinic acid (CSA), which may cause seizures and excitotoxic neuronal death. We postulated that excess Hcy and EAA neurotransmitters may partly mediate methotrexate (MTX)-associated neurotoxicity. PATIENTS AND METHODS In this retrospective analysis, we used high-performance liquid chromatography (HPLC) to measure Hcy, HCA, and CSA in CSF from two groups of children: (1) a control group of patients with no MTX exposure, and (2) a treatment group of patients who had received MTX no more than 7 days before a scheduled lumbar puncture. RESULTS The treatment group had a significantly (P = .0255) greater concentration of Hcy in CSF (0.814 micromol/L +/- 0.215 [mean +/- SEM], n = 23) than the control group (0.210 micromol/L +/- 0.028, n = 34). HCA and CSA were not detected in CSF from control patients (n = 29); however, MTX caused marked accumulation of CSF HCA (119.1 micromol/L +/- 32.0, n = 16) and CSA (28.4 micromol/L +/- 7.7, n = 16) in the treatment group. Patients with neurologic toxicity at the time of lumbar puncture had many of the highest concentrations of Hcy, HCA, and CSA. CONCLUSION These data support our hypothesis that MTX-associated neurotoxicity may be mediated by Hcy and excitotoxic neurotransmitters.
Enkephalinase inhibition increases plasma atrial natriuretic peptide levels, glomerular filtration rate, and urinary sodium excretion in rats with reduced renal mass.
Authors: H M Lafferty, M Gunning, P Silva, M B Zimmerman, B M Brenner, S Anderson
Journal: Circulation Research (1989)

To investigate the in vivo effects of inhibition of endopeptidase 24.11, an enkephalinase enzyme shown to be involved in atrial natriuretic peptide (ANP) breakdown in vitro, we infused phosphoramidon, a specific inhibitor of endopeptidase 24.11, into rats with reduced renal mass (and chronic extracellular volume expansion) and into normal rats. Relative to baseline values in rats with remnant kidneys, phosphoramidon led to elevations of plasma ANP levels and concomitant increases in urinary sodium excretion, fractional excretion of sodium, glomerular filtration rate, filtration fraction, and urinary cyclic GMP excretion. Similar changes in renal function and urinary cyclic GMP excretion were obtained with thiorphan, another endopeptidase 24.11 inhibitor. These enhanced ANP levels and renal actions were not observed with phosphoramidon in normal rats. These results show that plasma ANP levels can be modulated in rats with reduced renal mass by inhibition of endopeptidase 24.11.
Brain Swelling and Death in Children with Cerebral Malaria
Authors: Karl B. Seydel, Samuel D. Kampondeni, Clarissa Valim, Michael J. Potchen, Danny A. Milner, Francis W. Muwalo, Gretchen L. Birbeck, William G. Bradley, Lindsay L. Fox, Simon J. Glover, Colleen A. Hammond, Robert S. Heyderman, Cowles A. Chilingulo, Malcolm E. Molyneux, Terrie E. Taylor
Journal: New England Journal of Medicine (2015)

Case fatality rates among African children with cerebral malaria remain in the range of 15 to 25%. The key pathogenetic processes and causes of death are unknown, but a combination of clinical observations and pathological findings suggests that increased brain volume leading to raised intracranial pressure may play a role. Magnetic resonance imaging (MRI) became available in Malawi in 2009, and we used it to investigate the role of brain swelling in the pathogenesis of fatal cerebral malaria in African children.
Subclinical Seizure Activity and Prophylactic Phenytoin Infusion in Acute Liver Failure: A Controlled Clinical Trial
Authors: Antony J. Ellis, Julia A. Wendon, Roger Williams
Journal: Hepatology (2000)

Subclinical seizure activity in the patient with encephalopathy and on ventilation with acute liver failure (ALF) is a poorly recognized entity. Its importance lies in the likely exacerbation of cerebral hypoxia and the contribution of such seizure activity to the development of cerebral edema. The aim of the present study was to document the frequency of subclinical seizure activity in a cohort of patients with ALF by using a cerebral function and activity monitor that allows continuous recording of electroencephalogram activity at the bedside and to determine whether the prophylactic administration of the antiepileptic agent phenytoin would reduce its occurrence. Forty-two patients were enrolled in a controlled clinical trial: 20 patients were given phenytoin and 22 acted as controls. Subclinical seizure activity was recorded in 3 and 10 patients, respectively, of the treated and control groups. Pupillary abnormalities indicative of seizure activity and/or raised intracranial pressure (ICP) were also seen less frequently in the phenytoin-treated group compared with the controls (5 and 11 patients, respectively). Autopsy examinations available in 19 patients showed signs of cerebral edema in only 2 (22%) of the phenytoin-treated patients compared with 7 (70%) of the controls (P <.033). Based on these findings, we recommend that patients with ALF, on reaching the stage of grade III or IV encephalopathy, should be routinely monitored for subclinical seizure activity. In this study, prophylaxis with phenytoin reduced the frequency of such seizure activity and its effects, and proved to be safe with the regimen used.
Remnant-like particle cholesterol, triglycerides, and insulin resistance in nonobese Japanese type 2 diabetic patients.
Authors: A Taniguchi, M Fukushima, M Sakai, K Miwa, T Makita, I Nagata, S Nagasaka, K Doi, T Okumura, A Fukuda, H Kishimoto, T Fukuda, S Nakaishi, K Tokuyama, Y Nakai
Journal: Diabetes Care (2000)

The aim of the study was to investigate the relationships between remnant-like particle (RLP) cholesterol, triglycerides, and insulin resistance in nonobese Japanese type 2 diabetic patients.A total of 86 nonobese Japanese type 2 diabetic patients (72 men and 14 women, aged 40-83 years, BMI 20.1-26.6 kg/m2) were studied. BMI, HbA1c levels, and fasting concentrations of plasma glucose, serum lipids (RLP cholesterol, total cholesterol, HDL cholesterol, and triglycerides), and serum insulin were measured. Insulin resistance was estimated by the homeostasis model assessment (HOMA-IR). The subjects were divided into two groups according to the value of HOMA-IR. Values >2.5 were indicative of the insulin-resistant state, and values <2.5 were indicative of the insulin-sensitive state.The insulin-resistant group had significantly higher RLP cholesterol and triglyceride levels and lower HDL cholesterol levels compared with the insulin-sensitive group. Univariate regression analysis showed that insulin resistance was positively correlated with BMI (r = 0.254, P = 0.019), HbA1c levels (r = 0.278, P = 0.011), RLP cholesterol levels (r = 0.315, P = 0.004), and triglyceride levels (r = 0.332, P = 0.002) and was negatively correlated with HDL cholesterol levels (r = -0.301, P = 0.006) in our diabetic patients. Multiple regression analysis showed that insulin resistance was independently associated with serum triglyceride levels, which explained 13.5% of the variability of insulin resistance in our nonobese Japanese type 2 diabetic patients.These results indicate that 1) nonobese Japanese type 2 diabetic patients with insulin resistance are characterized by high RLP cholesterol and triglyceride levels, and low HDL cholesterol levels; and 2) the level of serum triglycerides is an independent predictor of insulin resistance in these patients.
Alternative and complementary medicine for asthma.
Authors: A F Kalyoncu, Z T Selcuk, A Iskendarani, L Coplu, S Emri, A A Sahin, Y I Baris
Journal: Thorax (1992)

Alternative and complementary medicine for asthma Readers of the review by D J Lane and T V Lane (November 1991;46:787-97) might conclude that hypnosis has little to offer asthmatic patients.Although the report of Ewer and Stewart' is quoted as showing improvement in symptom scores and some peak expiratory flow rates and decreased use of bronchodilators, no mention is made of a 74-9% improvement (p < 0-01) in the degree of bronchial hyperresponsiveness to a stan- dardised methacholine challenge test.These authors state that "while our hypnotic tech- nique does not eliminate bronchial hyperresponsiveness it does provide a clinically useful and non-toxic adjuvant to drug treat- ment that might benefit about half of the asthmatic population."This approach could well reduce the use of the toxic drugs, such as troleandomycin, gold, azathioprine, and methotrexate, mentioned as steroid sparing agents by Shiner and Geddes.2The British Tuberculosis Association's study3 did not report negative results as stated in the review.On the contrary, "independent clinical assessors considered the asthma to be much better in 59% of the hypnosis groups and in 43% of the control group, the difference being significant."These results were obtained by using only direct suggestion under hypnosis plus autohypnosis daily; more advanced methods, such as reciprocal inhibition, were not used.In my own study4 it was possible to with- draw oral prednisolone or to reduce the dose in 14 of the 16 patients treated by hypnosis.The number of hospital admissions during the first year of hypnotherapy fell to 13, compared with 44 during the previous year.This represented a reduction of 249 hospital days, which, at 1988 costs (£170 per day), saved the NHS £42 330.As some 55 000 adults are admitted each year for asthma, savings to the NHS could be considerable if hypnotherapy were to be used more widely.
Serum N-Terminal Pro–Brain Natriuretic Peptide Is a Sensitive Marker of Myocardial Dysfunction in AL Amyloidosis
Authors: Giovanni Palladini, Carlo Campana, Catherine Klersy, Alessandra Balduini, Giovanbattista Vadacca, Vittorio Perfetti, Stefano Perlini, Laura Obici, Edoardo Ascari, Gianvico Melzi d’Eril, Remigio Moratti, Giampaolo Merlini
Journal: Circulation (2003)

Background— Brain natriuretic peptide (BNP) is a marker of ventricular dysfunction and can be used to assess prognosis in heart failure and after myocardial infarction. Heart involvement is the most important prognostic factor and causes death in almost all patients with light-chain amyloidosis (AL). We investigated the prognostic value of NT-proBNP and its utility in monitoring amyloid heart dysfunction. Methods and Results— NT-proBNP was quantified at diagnosis in 152 consecutive patients seen at the coordinating center of the Italian Amyloidosis Study Group (Pavia) from 1999 throughout 2001. Heart involvement was estimated on the basis of clinical signs, electrocardiography, and echocardiography. NT-proBNP concentrations differed in patients with (n=90, 59%) and without (n=62, 41%) heart involvement (median: 507.8 pmol/L versus 22.1 pmol/L, P =10 −7 ). The best cutoff for heart involvement was at 152 pmol/L (sensitivity: 93.33%, specificity: 90.16%, accuracy: 92.05%) and distinguished two groups with different survival ( P &lt;0.001). The Cox multivariate model including NT-proBNP was better than models including echocardiographic and clinical signs of heart involvement. NT-proBNP appeared to be more sensitive than conventional echocardiographic parameters in detecting clinical improvement or worsening of amyloid cardiomyopathy during follow-up. Conclusions— NT-proBNP appeared to be the most sensitive index of myocardial dysfunction and the most powerful prognostic determinant in AL amyloidosis. It adds prognostic information for newly diagnosed patients and can be useful in designing therapeutic strategies and monitoring response. NT-proBNP is a sensitive marker of heart toxicity caused by amyloidogenic light chains.
SM-10 * ANTI-EPILEPTIC DRUGS AND CORTICAL IRRITABILITY IN PATIENTS WITH TUMORAL EPILEPSIES
Authors: P. Warren, J. Szaflarski, L. Nabors
Journal: Neuro-Oncology (2014)

Tumor-associated seizures and epilepsy in patients with primary malignant brain tumors constitute a major healthcare challenge. Seizures and antiepileptic drugs (AEDs) used in their management significantly impact patients' quality of life; there is a dearth of information regarding the actual effects of AEDs on cortical irritability, as measured by electroencephalograms (EEGs). Herein, we investigated the effects of various AEDs on the presence or absence of epileptiform discharges (EDs) in glioma patients. METHODS: We identified 210 patients with a pathologically confirmed diagnosis of primary glioma and who had at least 1 EEG at our institution from 01/01/2009 to 12/31/2013. EEGs were independently reviewed and scored for the presence of EDs and current AEDs were recorded. RESULTS: "Last available" EEGs were reviewed on 149 patients (M = 75, F = 74, mean age at time of EEG = 51 SD-14.2). Eighty-five percent of patients had high-grade glioma (HGG) and 15% had low-grade glioma (LGG). EDs were identified in 34.2% of all patients; in 27.3% of those with LGG and in 35.8% of those with HGG. We noted that patients with HGG had a higher incidence of EDs in the EEG than those with LGG, however this difference was not significant (35.8% vs. 27.3%, p = 0.44). Further, we did not observe a specific effect of any of the AEDs used on the presence/absence of EDs (p > 0.05 for levetiracetam, phenytoin, valproate, lacosamide, zonisamide, or topiramate). CONCLUSIONS: Our retrospective data indicate that there is no correlation between AED(s) used and cortical irritability as measured by EEG in patients with gliomas. This is an interesting and important observation. Prospective clinical trials are needed to assess the role of EEG in guiding treatment decisions, as related to AED therapy and choice in this population and the value of pre-treatment EEG as a possible biomarker for the development of tumor-related epilepsy needs to be evaluated.
PROPERTIES OF THE CAUSATIVE AGENT OF A CHICKEN TUMOR
Authors: James B. Murphy, Ernest Sturm, Giovanni Favilli, Donald C. Hoffman, Albert Claude
Journal: The Journal of Experimental Medicine (1932)

The injection of tumor extracts and their active protein fractions into rabbits induced the formation of precipitins and neutralizing antibodies. When the major portion of proteins in the tumor extract had been eliminated it induced the formation of neutralizing antibodies, but not of precipitins. The tumor agent, more highly purified by removal of the viscous fraction, did not induce precipitins, and only 2 out of the 15 sera gave any evidence of neutralizing bodies. After the removal of the major portion of protein, the extracts showed insufficient interaction with the sera to fix complement.
Childhood asthma in a rural county
Authors: D. Holmgren, N. ÅRberg, U. Lindberg, I. Engström
Journal: Allergy (1989)

As part of a questionnaire study of allergic diseases in Swedish children, information about asthma reported in a rural county was evaluated. Of a total population of approx. 9,000 children 4, 7, 10 and 14 years of age, 5.1% reported a history of asthma and 2.4% reported symptoms during the last year. The incidence was highest during the first 2 years of life. A higher incidence in boys than in girls was found only during the first 4 years of life. Cessation of symptoms was most common in children with onset during the first 2 years of life. By checking the medical case records, a high accuracy of the reported information was confirmed.
Bone mineral density in rheumatoid arthritis patients 1 year after adalimumab therapy: arrest of bone loss
Authors: C A Wijbrandts, R Klaasen, M G W Dijkgraaf, D M Gerlag, B L F van Eck-Smit, P P Tak
Journal: Annals of the Rheumatic Diseases (2008)

To explore the effects of anti-tumour necrosis factor (TNF)alpha antibody therapy on bone mineral density (BMD) of the lumbar spine and femur neck in patients with rheumatoid arthritis (RA).A total of 50 patients with active RA (DAS28> or =3.2) who started adalimumab (40 mg subcutaneously/2 weeks) were included in an open label prospective study. All patients used stable methotrexate and were allowed to use prednisone (< or =10 mg/day). The BMD of the lumbar spine and femur neck was measured before and 1 year after start of treatment.Disease activity at baseline (28-joint Disease Activity Score (DAS28)) and disease duration were inversely correlated with femoral neck BMD and lumbar spine BMD (p<0.05). Mean BMD of lumbar spine and femur neck remained unchanged after 1 year of adalimumab therapy (+0.3% and +0.3%, respectively). Of interest, a beneficial effect of prednisone on change in femur neck BMD was observed with a relative increase with prednisone use (+2.5%) compared to no concomitant prednisone use (-0.7%), (p = 0.015).In contrast to the progressive bone loss observed after conventional disease-modifying antirheumatic drug therapy, TNF blockade may result in an arrest of general bone loss. Consistent with previous observations, the data also suggest that the net effect of low-dose corticosteroids on BMD in RA may be beneficial, possibly resulting from their anti-inflammatory effects.
Activation of the Glutamate Receptor GRM1 Enhances Angiogenic Signaling to Drive Melanoma Progression
Authors: Yu Wen, Jiadong Li, Jasmine Koo, Seung-Shick Shin, Yong Lin, Byeong-Seon Jeong, Janice M. Mehnert, Suzie Chen, Karine A. Cohen-Sola, James S. Goydos
Journal: Cancer Research (2014)

Abstract Glutamate-triggered signal transduction is thought to contribute widely to cancer pathogenesis. In melanoma, overexpression of the metabotropic glutamate receptor (GRM)-1 occurs frequently and its ectopic expression in melanocytes is sufficient for neoplastic transformation. Clinical evaluation of the GRM1 signaling inhibitor riluzole in patients with advanced melanoma has demonstrated tumor regressions that are associated with a suppression of the mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) pathways. Together, these results prompted us to investigate the downstream consequences of GRM1 signaling and its disruption in more detail. We found that melanoma cells with enhanced GRM1 expression generated larger tumors in vivo marked by more abundant blood vessels. Media conditioned by these cells in vitro contained relatively higher concentrations of interleukin-8 and VEGF due to GRM1-mediated activation of the AKT–mTOR–HIF1 pathway. In clinical specimens from patients receiving riluzole, we confirmed an inhibition of MAPK and PI3K/AKT activation in posttreatment as compared with pretreatment tumor specimens, which exhibited a decreased density of blood vessels. Together, our results demonstrate that GRM1 activation triggers proangiogenic signaling in melanoma, offering a mechanistic rationale to design treatment strategies for the most suitable combinatorial use of GRM1 inhibitors in patients. Cancer Res; 74(9); 2499–509. ©2014 AACR.
Herpes Simplex Corneae in Malaria
Authors: J. G. Scott
Journal: BMJ (1944)

MEDICAL MEMORANDA MEDICALTI OURNAL213low or a negligible output of gonadotrophic hormone.This suggests that in this type of case there is a sudden functional reduction in pituitary activity to be followed later by the physi- cal symptoms of hypopituitarism.The suggestion that the picture of pituitary cachexia without structural changes in the pituitary itself can follow the menopause is supported by the resumption of normal pituitary function observed in this case after treatment.The physiological properties of corticotrophic hormone have been studied in hypophysectomized rats.It is known that sugar storage is much reduced after hypophysectomy, for the combustion of fed sugar is much higher than in normal animals.This condition has been corrected by cortico- trophic hormone (Reiss et al., 1938).The cholesterol and fat content in hypophysectomized rats can also be increased by corticotrophic hormone (Reiss et al., 1937).No doubt there were comparable actions in the case we have described.Summary A case of clinical pituitary cachexia in a nulliparous woman has been described.Clinical and hormone studies indicated extreme hypopituitarism.Treatment with corticotrophic hormone resulted in complete restoration of weight and cosmetic features.This was not a case of anorexia nervosa.The psychotic depression was not relieved until a considerable time after physical improvement was complete.The origin of this condition has been discussed.