tbuckley/cabot-search huggingface dataset:
Getting the best possible evidence from observational studies of treatment of multidrug-resistant tuberculosis patients
Authors: Dennis Falzon, Richard (Dick) Menzies, Charles L. Daley, Christian Lienhardt, Aamir Khan, Michael L. Rich, Mohammed A. Aziz, Catharina S.B. van Weezenbeek, Carole D. Mitnick
Journal: European Respiratory Journal (2013)

Background: The development of clinical recommendations by the World Health Organization (WHO) requires the systematic review of evidence and the grading of its quality. There is no high-quality evidence on treatment for multidrug-resistant tuberculosis (MDR-TB) patients using only standard second-line anti-TB drugs, as results of randomized controlled trials are not available. Well executed observational studies can meanwhile provide useful information that is applicable to clinical practice. For observational data to provide the best possible guidance, measures need to be taken to limit bias, imprecision, and heterogeneity.  Intervention: WHO has established an expert Working Group to develop principles that national TB control programmes and other implementers could use to ensure the quality of observational study data.  Results: Based on past experience, the group identified a number of critical points that need to be improved upon. Patient and programme-related data should be captured and reported in a standardized manner. These include bacteriological endpoints, proxies of disease severity, information on adverse drug reactions, the duration of current and past use of individual drugs, reason for change of regimen, use of accompanying medications, costs, hospitalization, patient support and type and extent of surgery.  Conclusions: The Working Group recommends that programmes undertaking observational studies record most of these parameters, that they register data electronically, that they strive to publish their work, and that they share anonymous, individual patient data so as to update the knowledge base on MDR-TB patient outcomes.
Glucagon levels and metabolic effects in fasting man
Authors: Errol B. Marliss, Thomas T. Aoki, Roger H. Unger, J. Stuart Soeldner, George F. Cahill
Journal: Journal of Clinical Investigation (1970)

The role of glucagon in the metabolic adaptation to prolonged fasting in man has been examined. Plasma immunoreactive glucagon was determined during 6-wk fasts and during infusion of exogenous glucagon using an assay which minimized nonpancreatic immunoreactivity.
Hematological features of patients with myelodysplastic syndromes associated with a chromosome 5q deletion
Authors: S. Lewis, D. Oscier, J. Boultwood, F. Ross, M. Fitchett, K. Rack, G. Abrahamson, V. Buckle, J. S. Wainscoat
Journal: American Journal of Hematology (1995)

Abstract The hematological and clinical features of 26 patients with myelodysplasia and a chromosome 5q deletion in the bone marrow are presented. We have examined the relationship of French‐American‐British Co‐operative Group (FAB) 1982 classification and bone marrow karyotype at diagnosis with patient outcome and the presence or absence of the classical features of the 5q‐ syndrome. Those patients classified as refractory anemia (RA) with no additional karyotypic abnormalities have the typical features of the 5q‐ syndrome and a good prognosis. None of the patients in this group transformed to acute leukemia during the period of follow‐up. Patients with either refractory anemia and excess blasts (RAEB) or additional karyotypic abnormalities show many of the hematologic features of the 5q‐ syndrome but do not share the good prognosis. We conclude that the 5q‐ syndrome may be best defined as primary MDS of the FAB type RA with a 5q deletion as the sole karyotypic abnormality. This simple definition will distinguish patients with a good prognosis and all the classical features of the 5q‐ syndrome.
Activation of Protein Kinase C Isoforms and Its Impact on Diabetic Complications
Authors: Pedro Geraldes, George L. King
Journal: Circulation Research (2010)

Both cardio- and microvascular complications adversely affect the life quality of patients with diabetes and have been the leading cause of mortality and morbidity in this population. Cardiovascular pathologies of diabetes have an effect on microvenules, arteries, and myocardium. It is believed that hyperglycemia is one of the most important metabolic factors in the development of both micro- and macrovascular complications in diabetic patients. Several prominent hypotheses exist to explain the adverse effect of hyperglycemia. One of them is the chronic activation by hyperglycemia of protein kinase (PK)C, a family of enzymes that are involved in controlling the function of other proteins. PKC has been associated with vascular alterations such as increases in permeability, contractility, extracellular matrix synthesis, cell growth and apoptosis, angiogenesis, leukocyte adhesion, and cytokine activation and inhibition. These perturbations in vascular cell homeostasis caused by different PKC isoforms (PKC-alpha, -beta1/2, and PKC-delta) are linked to the development of pathologies affecting large vessel (atherosclerosis, cardiomyopathy) and small vessel (retinopathy, nephropathy and neuropathy) complications. Clinical trials using a PKC-beta isoform inhibitor have been conducted, with some positive results for diabetic nonproliferative retinopathy, nephropathy, and endothelial dysfunction. This article reviews present understanding of how PKC isoforms cause vascular dysfunctions and pathologies in diabetes.
Aseptic meningitis, trimethoprim, and Sjogren's syndrome
Authors: S. M. de la Monte
Journal: JAMA (1985)

To the Editor.—  The CASE REPORT, Trimethoprim-Induced Aseptic Meningitis, by Dr Derbes 1 published recently inThe Journaldescribes a patient with Sjorgen's syndrome who, on several well-documented occasions, exhibited an allergic response or hypersensitivity to trimethoprimsulfamethoxazole. While the patient clearly manifested central nervous system (CNS) signs and symptoms after taking sulfa drugs, the author does not demonstrate that the exudate in the cerebrospinal fluid (CSF) was related to or caused by its administration. The abruptness and rapidity of onset of neurologic symptoms following the use of trimethoprim strongly suggest that her response was probably vascular in origin. In contrast to Dr Derbes' statement, our recent studies demonstrated that aseptic meningitis occurs commonly in patients with Sjogren's syndrome. 2,3 Patients with Sjogren's syndrome frequently have polymorphous inflammatory infiltrates in the leptomeninges, and characteristic atypical mononuclear cells are usually present in CSF. The neurologic symptoms associated with the polymorphous meningitis of
ASIP and TYR pigmentation variants associate with cutaneous melanoma and basal cell carcinoma
Authors: Daniel F Gudbjartsson, Patrick Sulem, Simon N Stacey, Alisa M Goldstein, Thorunn Rafnar, Bardur Sigurgeirsson, Kristrun R Benediktsdottir, Kristin Thorisdottir, Rafn Ragnarsson, Steinunn G Sveinsdottir, Veronica Magnusson, Annika Lindblom, Konstantinos Kostulas, Rafael Botella-Estrada, Virtudes Soriano, Pablo Juberías, Matilde Grasa, Berta Saez, Raquel Andres, Dominique Scherer, Peter Rudnai, Eugene Gurzau, Kvetoslava Koppova, Lambertus A Kiemeney, Margret Jakobsdottir, Stacy Steinberg, Agnar Helgason, Solveig Gretarsdottir, Margaret A Tucker, José I Mayordomo, Eduardo Nagore, Rajiv Kumar, Johan Hansson, Jon H Olafsson, Jeffrey Gulcher, Augustine Kong, Unnur Thorsteinsdottir, Kari Stefansson
Journal: Nature Genetics (2008)
Influence of childhood growth on asthma and lung functioning in adolescence
Authors: A.M.M. Sonnenschein-van der Voort, L.D. Howe, R. Granell, L. Duijts, J.A.C. Sterne, K. Tilling, A.J. Henderson
Journal: European Respiratory Journal (2013)

Background Low birth weight and rapid infant growth are associated with increased risks of childhood asthma but little is known about the role of growth in childhood with asthma.

Aims To examine the associations of children’s growth patterns with asthma, bronchodilator responsiveness, and lung function in adolescence.

Methods Individual growth trajectories from birth until 10 years were estimated using multilevel linear spline models and standard deviation (SD) scores were calculated among 7,882 children participating in a population-based prospective cohort study. Weight trajectories were adjusted for height. Current asthma at 14 and 17 years was based on questionnaires. Lung function (z-scores of FVC, FEV1, and FEV1/FVC (%)), and bronchodilator responsiveness were measured during clinic visits at age 15 years.

Results Weight but not height gain during early childhood was associated with asthma at 14 and 17 years. Weight gain between 0-3 and 3-12 months was associated with salbutamol reversibility (Odds ratio (OR): 1.14 (95% CI: 1.00, 1.30), and 1.23 (1.07, 1.42) per SD increase in weight, respectively). We found little evidence of associations with height gain. Increased weight gain (per SD) between 3-7 years was the most strongly associated with higher FVC (0.16 (0.12, 0.20)) and FEV1 (0.19 (0.08, 0.16)), and reduced FEV1/FVC (-0.35 (-0.67, -0.04)). Height gain in all periods of childhood was consistently associated with lower FVC and tended to be associated with a lower FEV1 and FEV1/FVC.

Conclusion Rapid weight gain in early childhood is associated with bronchodilator responsiveness and increased lung capacity in adolescence, while rapid height gain seems to be associated with smaller lungs.
Abnormalities of Thalamic Volume and Shape in Schizophrenia
Authors: John G. Csernansky, Mathew K. Schindler, N. Reagan Splinter, Lei Wang, Mohktar Gado, Lynn D. Selemon, Devna Rastogi-Cruz, Joel A. Posener, Paul A. Thompson, Michael I. Miller
Journal: American Journal of Psychiatry (2004)

OBJECTIVE: Postmortem and neuroimaging studies of schizophrenia have reported deficits in the volume of the thalamus and its component nuclei. However, the pattern of shape change associated with such volume loss has not been investigated. In this study, alterations in thalamic volume, shape, and symmetry were compared in subjects with and without schizophrenia. METHOD: T1-weighted magnetic resonance scans were collected in 52 schizophrenia and 65 comparison subjects matched for age, gender, race, and parental socioeconomic status. High-dimensional (large-deformation) brain mapping was used to assess thalamic morphology. RESULTS: Significant differences in thalamic volume, deformities of thalamic shape at the anterior and posterior extremes of the structure, and a significant exaggeration of thalamic asymmetry (i.e., left smaller than right) were found in the schizophrenia subjects. After covarying for total cerebral volume, the difference in thalamic volume became insignificant. When information about thalamic shape was combined with previously collected information about hippocampal shape, the discrimination between schizophrenia patients and comparison subjects was improved. CONCLUSIONS: Thalamic volume was smaller than normal in schizophrenia patients, but only proportionate to reductions in reduced total cerebral volume. The presence of changes in thalamic shape and asymmetry suggest greater pathologic involvement of individual nuclei at its anterior and posterior extremes of the thalamic complex.
Prospectively Randomized Comparison of Different Mechanical Aortic Valves
Authors: R. Autschbach, T. Walther, V. Falk, M. Kostelka, A. Rosler, G. Langebartels, M. Kruger, A. Diegeler, F. W. Mohr
Journal: Circulation (2000)

The aim of this prospectively randomized study was to evaluate the hemodynamic and functional outcomes after aortic valve replacement with 3 different bileaflet mechanical valves.Three hundred consecutive patients were randomly assigned to receive ATS (n=100), Carbomedics (n=100), or St Jude Medical Hemodynamic Plus (n=100) mechanical aortic valve replacement. There were no significant differences regarding patient age (average 61+/-8 years), body surface area (1.9+/-0.2 m(2)), left ventricular function (ejection fraction 0.59+/-0.17), and presence of aortic stenosis (90%, 89%, and 91%), respectively. All patients had postoperative as well as 6-month and 1-year follow-ups that included transthoracic echocardiography. Multivariate statistical analysis was performed. Implanted valve sizes were comparable at 24+/-2 (ATS), 23.7+/-1.6 (CM), and 23.6+/-1.9 (SJMHP) mm (NS). At 1-year follow-up, the following incidence of events was noted: death 3/1/1, all non-valve related; stroke 0/1/1; trivial transvalvular incompetence 3/3/2; paravalvular leak 2/3/2; and reoperation 0/1/1, respectively (NS). Transvalvular flow velocities were 2.5/2.6/2.4 m/s postoperatively (P:=0.03) and 2.4/2.4/2.3 m/s at 6-month follow-up, respectively (NS). There was a significant decrease in left ventricular mass for all patients but no significant differences among the groups.There are no clinically relevant differences among the tested bileaflet aortic valves. Regardless of valve type, there was a low complication rate. On the basis of these findings, all 3 bileaflet prostheses are well suited for aortic valve replacement.
Aldose Reductase Gene Polymorphisms and Peripheral Nerve Function in Patients With Type 2 Diabetes
Authors: Katariina Sivenius, Jussi Pihlajamäki, Juhani Partanen, Leo Niskanen, Markku Laakso, Matti Uusitupa
Journal: Diabetes Care (2004)

OBJECTIVE—We screened the human aldose reductase (ALR) gene for DNA sequence variants in type 2 diabetic and nondiabetic subjects and investigated whether the previously reported and novel polymorphisms were associated with neurophysiologic deterioration and clinical peripheral neuropathy. RESEARCH DESIGN AND METHODS—The study population included 85 Finnish type 2 diabetic and 126 nondiabetic subjects. The genetic analyses were performed using the PCR, single-strand conformation polymorphism, restriction fragment-length polymorphism, and automated laser fluorescence scanning analyses. A detailed neurologic examination and neurophysiologic analyses were performed at the time of diagnosis and at the 10-year examination. RESULTS—The genetic screening identified four polymorphisms: C-106T, C-11G, A11370G, and C19739A. The C and Z-2 alleles of the C-106T polymorphism and the previously reported (CA)n repeat marker were more frequent in type 2 diabetic subjects than in nondiabetic subjects. At baseline, the diabetic subjects with the T allele of the C-106T polymorphism had lower sensory response amplitude values in the peroneal (P = 0.025), sural (P = 0.007), and radial (P = 0.057) nerves and, during follow-up, a greater decrease in the conduction velocity of the motor peroneal nerve than those with the C-106C genotype. No associations were found between the polymorphisms examined and clinical polyneuropathy. CONCLUSIONS—The C-106T polymorphism of the ALR gene may contribute to an early development of neurophysiologic deterioration in type 2 diabetic patients.
Effect of Sympathetic Nerve Stimulation on Pulmonary Vascular Resistance in the Dog
Authors: PHILIP J. KADOWITZ, ALBERT L. HYMAN
Journal: Circulation Research (1973)

The effect of sympathetic nerve stimulation on the pulmonary circulation was studied in a hemodynamically separated dog lung in which blood flow was maintained constant with a pump. Electrical stimulation of the stellate ganglia at 3, 10, and 30 cps produced a significant increase in mean lobar arterial perfusion pressure. Since lobar blood flow and left atrial pressure did not change during nerve excitation, the increase in lobar arterial pressure reflected an increase in vascular resistance across the lung. The increase in pulmonary vascular resistance was dependent on the stimulus frequency, and the time from the onset of stimulation to the attainment of the peak response was inversely related to the stimulus frequency. The response to nerve stimulation was decreased by alpha-receptor blocking agents. Lobar perfusion with a roller pump had an effect similar to perfusion with a piston pump. The response to nerve stimulation was independent of changes in rate, rhythm, and volume of respiration, changes in aortic blood pressure, and changes in airway resistance. The effects of stellate stimulation and of injected norepinephrine on vascular resistance were similar in the hemodynamically separated lobe. In essence, sympathetic nerve stimulation produced an active increase in vascular resistance in the pulmonary circulation, and the contribution of passive factors such as changes in respiration, bronchomotor tone, and bronchial circulation was minimal. Since the response was blocked by phentolamine, the increase in pulmonary vascular resistance in response to nerve stimulation was attributed to activation of alpha receptors in the pulmonary vascular bed by neurally released norepinephrine. These results demonstrate that pulmonary vascular resistance can be increased at stimulus frequencies in the physiological range of discharge for the sympathetic nervous system.
A new generation of starch products as excipient in pharmaceutical tablets. II. High surface area retrograded pregelatinized potato starch products in sustained-release tablets
Authors: G.Henk P Te Wierik, Anko C Eissens, Jack Bergsma, A.Willemien Arends-Scholte, Coenraad F Lerk
Journal: Journal of Controlled Release (1997)
Biomarker discovery in human cerebrospinal fluid: the need for integrative metabolome and proteome databases
Authors: Emanuel Schwarz, E Fuller Torrey, Paul C Guest, Sabine Bahn
Journal: Genome Medicine (2012)

The number of metabolites identified in human cerebrospinal fluid (CSF) has steadily increased over the past 5 years, and in this issue of Genome Medicine David Wishart and colleagues provide a comprehensive update that brings the number of metabolites listed in the CSF metabolome database to 476 compounds. There is now a need for an integrative metabolome-proteome CSF database to maximize the impact of this achievement in biomedical research. Only by such efforts can we hope to unravel the complexity of molecular pathophysiological processes.
Physiology of B cells in mice with X-linked immunodeficiency (xid). III. Disappearance of xid B cells in double bone marrow chimeras.
Authors: J Sprent, J Bruce
Journal: The Journal of Experimental Medicine (1984)

Evidence is presented that B cells from mice with X-linked immunodeficiency (xid) differentiate at a slower rate than normal B cells. This conclusion stems from studies in which (B6 X CBA/J)F1 mice were heavily irradiated (1,000 rads) and reconstituted with a mixture of T-depleted marrow cells taken from (a) nondefective B6 mice (H-2b) and (b) xid CBA/N or nondefective CBA/Ca mice (both H-2k). With transfer of CBA/Ca plus B6 marrow cells, the irradiated recipients become repopulated with B cells derived from both parental marrow sources; except for an early imbalance (probably reflecting Hh resistance), the degree of chimerism remained relatively stable over a period of more than 6 months. Very different results occurred with transfer of a mixture of xid CBA/N and normal B6 marrow. Within the first 2 months after marrow reconstitution, a low but significant proportion of the B cells in both spleen and lymph nodes were of CBA/N origin. Thereafter the proportion of these cells fell progressively, and by 6-9 months virtually all of the B cells were of B6 origin. This gradual decline in CBA/N-derived cells did not apply to other cell types, i.e., T cells or pluripotential stem cells. Analogous results were obtained with transfer of CBA/N vs. CBA/Ca marrow cells into sublethally irradiated (750 rads) (CBA/N X DBA/2)F1 male vs. female mice. For example, CBA/N-marrow derived B cells differentiated effectively and survived for long periods in F1 male mice (xid----xid) but not in F1 female mice (xid----normal). The finding that xid B cells eventually disappear in the presence of normal B cells strengthens the view that xid B cells are an abnormal population not represented in normal mice.
A multivariate analysis of factors determining tumor progression in childhood low-grade glioma: a population-based cohort study (CCLG CNS9702)
Authors: T. Stokland, J.-F. Liu, J. W. Ironside, D. W. Ellison, R. Taylor, K. J. Robinson, S. V. Picton, D. A. Walker
Journal: Neuro-Oncology (2010)

The purpose of this study was to identify risk factors for the progression of low-grade glioma in children from a large population-based cohort. Patient and tumor details of a national cohort of children with low-grade glioma, recruited into an international multidisciplinary clinical strategy, were subjected to univariate and multivariate analyses of progression-free survival and overall survival. From the cohort of 798 patients, 639 patients were eligible, with a median age 6.71 years (0.26–16.75 years); 49% were males; 15.9% had neurofibromatosis type 1, 63.7% pilocytic astrocytoma, 5.9% fibrillary astrocytoma, 4.2% mixed neuronal-glial tumors, and 3.6% others; 21.1% were diagnosed clinically. Anatomically implicated were 31.6% cerebellum, 24.6% chiasma/hypothalamus, 16.0% cerebral hemispheres, 9.9% brain stem, 6.1% other supratentorial midline structures, 5.9% optic nerve only, 4.5% spinal cord, and 1.4% others. The 5-year overall survival and progression-free survival in the whole cohort were 94.6% and 69.4%, respectively. There was a significant association between age and site (P < .001) and extent of tumor resection and site (P < .001). Multivariate analysis identified young age, fibrillary astrocytoma, and extent of surgical resection as significant independent risk factors for progression. Hypothalamic/chiasmatic tumors demonstrated the most sustained tendency to progress. In conclusion, the influence of age and anatomical site upon the risk of tumor progression suggests that these factors strongly influence tumor behavior for the majority of pilocytic tumors. Age <1 year and 1–5 years, fibrillary histology, completeness of resection, and chiasmatic location are candidates for stratification in future studies.
Hydrocortisone Therapy for Patients with Septic Shock
Authors: Charles L. Sprung, Djillali Annane, Didier Keh, Rui Moreno, Mervyn Singer, Klaus Freivogel, Yoram G. Weiss, Julie Benbenishty, Armin Kalenka, Helmuth Forst, Pierre-Francois Laterre, Konrad Reinhart, Brian H. Cuthbertson, Didier Payen, Josef Briegel
Journal: New England Journal of Medicine (2008)

Hydrocortisone is widely used in patients with septic shock even though a survival benefit has been reported only in patients who remained hypotensive after fluid and vasopressor resuscitation and whose plasma cortisol levels did not rise appropriately after the administration of corticotropin.In this multicenter, randomized, double-blind, placebo-controlled trial, we assigned 251 patients to receive 50 mg of intravenous hydrocortisone and 248 patients to receive placebo every 6 hours for 5 days; the dose was then tapered during a 6-day period. At 28 days, the primary outcome was death among patients who did not have a response to a corticotropin test.Of the 499 patients in the study, 233 (46.7%) did not have a response to corticotropin (125 in the hydrocortisone group and 108 in the placebo group). At 28 days, there was no significant difference in mortality between patients in the two study groups who did not have a response to corticotropin (39.2% in the hydrocortisone group and 36.1% in the placebo group, P=0.69) or between those who had a response to corticotropin (28.8% in the hydrocortisone group and 28.7% in the placebo group, P=1.00). At 28 days, 86 of 251 patients in the hydrocortisone group (34.3%) and 78 of 248 patients in the placebo group (31.5%) had died (P=0.51). In the hydrocortisone group, shock was reversed more quickly than in the placebo group. However, there were more episodes of superinfection, including new sepsis and septic shock.Hydrocortisone did not improve survival or reversal of shock in patients with septic shock, either overall or in patients who did not have a response to corticotropin, although hydrocortisone hastened reversal of shock in patients in whom shock was reversed. (ClinicalTrials.gov number, NCT00147004.)