tbuckley/cabot-search huggingface dataset:
Impact of rice based oral rehydration solution on stool output and duration of diarrhoea: meta-analysis of 13 clinical trials.
Authors: S. M. Gore, O. Fontaine, N. F. Pierce
Journal: BMJ (1992)

OBJECTIVE--To define the benefit of rice oral rehydration salts solution in relation to the glucose based World Health Organisation oral rehydration salts solution for treating and preventing dehydration in patients with severe dehydrating diarrhoea. DESIGN--Meta-analysis using data from 13 available randomised trials that compared these two formulations. SUBJECTS--The studies compared 1367 patients with cholera, severe cholera-like diarrhoea, or acute non-cholera diarrhoea. 668 received the standard WHO solution and 699 the rice based solution. INTERVENTION--Each trial report was reviewed to determine patient eligibility, the number of patients who were randomised and the number of these excluded from analysis, details of the randomisation procedure, and the precise timing of the outcome measurements. MAIN OUTCOME MEASURES--Stool output during the first 24 hours; weighted estimates of the difference in mean stool output between treatments. RESULTS--The rice solution significantly reduced the rate of stool output during the first 24 hours by 36% (95% confidence interval 28 to 44%) in adults with cholera and by 32% (19 to 45%) in children with cholera. The rate of stool loss in infants and children with acute non-cholera diarrhoea was reduced by only 18% (6 to 30%). CONCLUSIONS--The benefit of rice oral rehydration salts solution for patients with cholera is sufficiently great to warrant its use in such patients. The benefit is considerably smaller for children with acute, noncholera diarrhoea and should be more precisely defined before its practical value can be judged.
Dominance of memory over naive T cells in contact dermatitis is due to differential tissue immigration
Authors: W. STERRY, SILKE BRUHN, N. KuNNE, BEATE LICHTENBERG, K. WEBER-MATTHIESEN, J. BRASCH, V. MIELKE
Journal: British Journal of Dermatology (1990)

CD4+ T cells include a naive (CD4-, CD45RO-, CD29-, CD45RA+) as well as a memory subpopulation (CD4+, CD45RO+, CD29+, CD45RA-). These subpopulations represent different stages in T-cell development and function. Recently, it has been shown that inflammatory and neoplastic CD4+ T-cell infiltrates are dominated by the memory subpopulation, whereas both subpopulations are about the same size in the peripheral blood. This was thought to be the result of in situ maturation of naive into memory T cells. We analysed early positive patch-test reactions 1-2 days after antigen challenge and found that most of the CD4+ T cells that had freshly immigrated into the tissue carried the memory phenotype. Their preferential migration may be mediated by at least five adhesion molecules expressed on their cell surface. This observation has important pathogenetic implications, since memory T cells can be rapidly activated by antigens and secrete a wide variety of pro-inflammatory cytokines.
Animals bearing malignant grafts reject normal grafts that express through gene transfer the same antigen.
Authors: G A Perdrizet, S R Ross, H J Stauss, S Singh, H Koeppen, H Schreiber
Journal: The Journal of Experimental Medicine (1990)

Breaking the state of immunological unresponsiveness of tumor-bearing individuals to cancer is a prerequisite for active or passive tumor-specific immunotherapy. To study this problem the immunogenic MHC class I antigen, K216 was transfected into a progressor tumor. The transfected tumors were regularly rejected by normal mice but grew progressively in mice bearing nontransfected tumors. In addition, transgenic mice were derived to obtain normal cells and tissues expressing the same K216 gene product. Normal mice rejected K216-positive normal or malignant tissue grafts and generated K216-specific CTL in vitro and in vivo in response to these challenges. In contrast, mice bearing nontransfected tumors, though rejecting K216-positive nonmalignant tissue grafts, did not reject K216-positive tumors nor generate K216-specific CTL in response to K216-positive tumor cells. Mice bearing K216-positive tumors also rejected the nonmalignant K216-positive tissue grafts, but this in vivo response failed to lead to rejection of the simultaneously present tumor graft expressing the same antigen; in fact, immunity had no measurable effect whatsoever on tumor size or incidence and caused no selection for antigen loss variants. Taken together, the present findings suggest that transfer of expression of a target antigen into nonmalignant cells provides a way for obtaining effective stimulation of antigen-specific CTL in tumor-bearing mice, but that additional manipulations will be required to cause immunological rejection of established tumors.
Albuminuria According to Status of Autoimmunity and Insulin Sensitivity Among Youth With Type 1 and Type 2 Diabetes
Authors: Amy K. Mottl, Abigail Lauer, Dana Dabelea, David M. Maahs, Ralph B. D’Agostino, Larry M. Dolan, Lisa K. Gilliam, Jean M. Lawrence, Beatriz Rodriguez, Santica M. Marcovina, Giuseppina Imperatore, Roopa Kanakatti Shankar, Maryam Afkarian, Kristi Reynolds, Angela D. Liese, Michael Mauer, Elizabeth J. Mayer-Davis
Journal: Diabetes Care (2013)

To evaluate whether etiologic diabetes type is associated with the degree of albuminuria in children with diabetes. RESEARCH DESIGN AND METHODS SEARCH: is an observational, longitudinal study of children with diabetes. Youth with newly diagnosed diabetes were classified according to diabetes autoantibody (DAA) status and presence of insulin resistance. We defined insulin resistance as an insulin sensitivity score <25th percentile for the United States general youth population. DAA status was based on positivity for the 65-kD isoform of glutamate decarboxylase and insulinoma-associated protein 2 antigens. The four etiologic diabetes type groups were as follows: DAA(+)/insulin-sensitive (IS) (n = 1,351); DAA(+)/insulin-resistant (IR) (n = 438); DAA(-)/IR (n = 379); and DAA(-)/IS (n = 233). Urinary albumin:creatinine ratio (UACR) was measured from a random urine specimen. Multivariable regression analyses assessed the independent relationship between the four diabetes type groups and magnitude of UACR.
Mild Recessive Mutations in Six Fraser Syndrome–Related Genes Cause Isolated Congenital Anomalies of the Kidney and Urinary Tract
Authors: Stefan Kohl, Daw-Yang Hwang, Gabriel C. Dworschak, Alina C. Hilger, Pawaree Saisawat, Asaf Vivante, Natasa Stajic, Radovan Bogdanovic, Heiko M. Reutter, Elijah O. Kehinde, Velibor Tasic, Friedhelm Hildebrandt
Journal: Journal of the American Society of Nephrology (2014)

Congenital anomalies of the kidney and urinary tract (CAKUT) account for approximately 40% of children with ESRD in the United States. Hitherto, mutations in 23 genes have been described as causing autosomal dominant isolated CAKUT in humans. However, >90% of cases of isolated CAKUT still remain without a molecular diagnosis. Here, we hypothesized that genes mutated in recessive mouse models with the specific CAKUT phenotype of unilateral renal agenesis may also be mutated in humans with isolated CAKUT. We applied next-generation sequencing technology for targeted exon sequencing of 12 recessive murine candidate genes in 574 individuals with isolated CAKUT from 590 families. In 15 of 590 families, we identified recessive mutations in the genes FRAS1, FREM2, GRIP1, FREM1, ITGA8, and GREM1, all of which function in the interaction of the ureteric bud and the metanephric mesenchyme. We show that isolated CAKUT may be caused partially by mutations in recessive genes. Our results also indicate that biallelic missense mutations in the Fraser/MOTA/BNAR spectrum genes cause isolated CAKUT, whereas truncating mutations are found in the multiorgan form of Fraser syndrome. The newly identified recessive biallelic mutations in these six genes represent the molecular cause of isolated CAKUT in 2.5% of the 590 affected families in this study.
How predictive and productive is animal research?
Authors: F. Godlee
Journal: BMJ (2014)

It’s more than 20 years since Doug Altman wrote his scorching editorial in The BMJ on “the scandal of medical research” (doi:10.1136/bmj.308.6924.283). Earlier this year The BMJ ’s former editor Richard Smith summarised why the same editorial could be published today with little change (http://bit.ly/1rHnWbL), referencing the recent Lancet series on waste in medical research and John Ioannidis’s PLoS Medicine article entitled, “Why most published research findings are false.” The medical literature remains beset with academic and commercial biases caused by overinterpretation of small, poorly designed, and badly implemented studies, many of them erroneously or selectively reported or not reported at all. The result is an evidence base …
Bcl-2 antagonist killer 1 (<i>BAK1</i>) polymorphisms influence the risk of developing autoimmune rheumatic diseases in women
Authors: A M Delgado-Vega, J Castiblanco, L M Gómez, L-M Diaz-Gallo, A Rojas-Villarraga, J-M Anaya
Journal: Annals of the Rheumatic Diseases (2009)

Objective: Bcl-2 antagonist killer 1 ( BAK1 ) is a Bcl-2 family proapoptotic member suggested as a candidate gene for autoimmune diseases. The influence of BAK1 polymorphisms on the risk of developing autoimmune rheumatic diseases (AIRDs) in women was investigated. Methods: A total of 719 Colombian women were included in the present study: 209 had systemic lupus erythematosus, 99 primary Sjögren syndrome, 159 rheumatoid arthritis and 252 were healthy matched controls. Tag single nucleotide polymorphisms (SNPs) and potentially functional variants were typed by TaqMan allele discrimination assays. HLA-DRB1 and HLA-DQB1 typing was performed by reverse dot-blot hybridisation and linkage disequilibrium (LD) with BAK1 SNPs was assessed. Results: SNPs rs513349 (odds ratio (OR) 0.57, 95% CI 0.46 to 0.72, p = &lt;0.001) and rs5745582 (OR 1.61, 95% CI 1.26 to 2.04, p = &lt;0.001) were associated with the AIRDs included in this study. There was a significant increase of the rs513349G-rs561276C-rs5745582A (GCA) haplotype in each patient cohort as compared to controls (OR 1.95, 95% CI 1.50 to 2.54, p = &lt;0.001). These SNPs were not in LD with HLA-DRB1 or HLA-DQB1 genes. Conclusions: The results indicate that the BAK1 polymorphisms influence the risk of acquiring AIRDs in the population studied and are consistent with the paradigm that autoimmune diseases are likely to share common susceptibility variants.
Perioperative Activation of Disseminated Tumor Cells in Bone Marrow of Patients With Prostate Cancer
Authors: Dorothea Weckermann, Bernhard Polzer, Thomas Ragg, Andreas Blana, Günter Schlimok, Hans Arnholdt, Simone Bertz, Rolf Harzmann, Christoph A. Klein
Journal: Journal of Clinical Oncology (2009)

The outcome of prostate cancer is highly unpredictable. To assess the dynamics of systemic disease and to identify patients at high risk for early relapse we followed the fate of disseminated tumor cells in bone marrow for up to 10 years and genetically analyzed such cells isolated at various stages of disease.Nine hundred bone marrow aspirates from 384 patients were stained using the monoclonal antibody A45-B/B3 directed against cytokeratins 8, 18, and 19. Log-rank statistics and Cox regression analysis were applied to determine the prognostic impact of positive cells detected before surgery (244 patients) and postoperatively (214 patients). Samples from primary tumors (n = 55) and single disseminated tumor cells (n = 100) were analyzed by comparative genomic hybridization.Detection of cytokeratin-positive cells before surgery was the strongest independent risk factor for metastasis within 48 months (P < .001; relative risk [RR], 5.5; 95% CI, 2.4 to 12.9). In contrast, cytokeratin-positive cells detected 6 months to 10 years after radical prostatectomy were consistently present in bone marrow with a prevalence of approximately 20% but had no influence on disease outcome. Characteristic genotypes of cytokeratin-positive cells were selected at manifestation of metastasis.Cytokeratin-positive cells in the bone marrow of prostate cancer patients are only prognostically relevant when detected before surgery. Because we could not identify significant genetic differences between pre- and postoperatively isolated tumor cells before manifestation of metastasis, we postulate the existence of perioperative stimuli that activate disseminated tumor cells. Patients with cytokeratin-positive cells in bone marrow before surgery may therefore benefit from adjuvant therapies.
Haemorrhagic hypersensitivity pneumonitis due to naphthylene-1,5-diisocyanate
Authors: R. Merget, B. Marczynski, Z. Chen, K. Remberger, M. Raulf-Heimsoth, P.O. Willroth, X. Baur
Journal: European Respiratory Journal (2002)

Symptoms of hypersensitivity pneumonitis and massive pulmonary haemorrhage occurred in a 24-yr-old male shortly after occupational exposure to naphthylene-1,5-diisocyanate (NDI). The present examination was performed ∼1-yr after the initial life-threatening haemoptysis and following an uneventful recovery after resection of the middle lobe, which had been identified bronchoscopically as the bleeding source. Histological re-examination of the lung was compatible with hypersensitivity pneumonitis. After a chamber challenge with NDI (5 parts per billion (ppb) for 10 min, 10 ppb for 110 min), rales were heard in both lungs, and a fall in vital capacity and partial pressure of arterial oxygen as well as a rise in body temperature were documented. Isocyanate-specific immunoglobulin-G antibodies could not be detected in the patient's serum, possibly due to the long period without exposure to isocyanates. The authors conclude that naphthylene-1,5-diisocyanate may cause immunological pulmonary haemorrhage. The underlying disease is consistent with hypersensitivity pneumonitis and may be triggered by low concentrations of the diisocyanate.
Investigation of an imported case of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection in Florence, Italy, May to June 2013
Authors: S Puzelli, A Azzi, M G Santini, A Di Martino, M Facchini, M R Castrucci, M Meola, R Arvia, F Corcioli, F Pierucci, S Baretti, A Bartoloni, D Bartolozzi, M de Martino, L Galli, M G Pompa, G Rezza, E Balocchini, I Donatelli
Journal: Eurosurveillance (2013)

On 31 May 2013, the first case of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection in Italy was laboratory confirmed in a previously healthy adult man, who developed pneumonia with moderate respiratory distress after returning from a holiday in Jordan. Two secondary cases were identified through contact tracing, among family members and colleagues who had not previously travelled abroad. Both secondary cases developed mild illness. All three patients recovered fully.
Safety and Efficacy of Ranibizumab in Diabetic Macular Edema (RESOLVE Study)
Authors: Pascale Massin, Francesco Bandello, Justus G. Garweg, Lutz L. Hansen, Simon P. Harding, Michael Larsen, Paul Mitchell, Dianne Sharp, U.E.K. Wolf-Schnurrbusch, Margarita Gekkieva, Andreas Weichselberger, Sebastian Wolf
Journal: Diabetes Care (2010)

The expression of vascular endothelial growth factor (VEGF) is elevated in diabetic macular edema (DME). Ranibizumab binds to and inhibits multiple VEGF variants. We investigated the safety and efficacy of ranibizumab in DME involving the foveal center.This was a 12-month, multicenter, sham-controlled, double-masked study with eyes (age>18 years, type 1 or 2 diabetes, central retinal thickness [CRT]≥300 μm, and best corrected visual acuity [BCVA] of 73-39 ETDRS letters [Early Treatment Diabetic Retinopathy Study]) randomly assigned to intravitreal ranibizumab (0.3 or 0.5 mg; n=51 each) or sham (n=49). The treatment schedule comprised three monthly injections, after which treatment could be stopped/reinitiated with an opportunity for rescue laser photocoagulation (protocol-defined criteria). After month 1, dose-doubling was permitted (protocol-defined criteria, injection volume increased from 0.05 to 0.1 ml and remained at 0.1 ml thereafter). Efficacy (BCVA and CRT) and safety were compared between pooled ranibizumab and sham arms using the full analysis set (n=151, patients receiving≥1 injection).At month 12, mean±SD BCVA improved from baseline by 10.3±9.1 letters with ranibizumab and declined by 1.4±14.2 letters with sham (P<0.0001). Mean CRT reduction was 194.2±135.1 μm with ranibizumab and 48.4±153.4 μm with sham (P<0.0001). Gain of ≥10 letters BCVA from baseline occurred in 60.8% of ranibizumab and 18.4% of sham eyes (P<0.0001). Safety data were consistent with previous studies of intravitreal ranibizumab.Ranibizumab is effective in improving BCVA and is well tolerated in DME. Future clinical trials are required to confirm its long-term efficacy and safety.
Vitamin D deficiency in alopecia areata
Authors: A. Aksu Cerman, S. Sarikaya Solak, I. Kivanc Altunay
Journal: British Journal of Dermatology (2014)

Alopecia areata (AA) is a T cell-mediated autoimmune disease that causes inflammation around anagen-stage hair follicles. Insufficient levels of vitamin D have been implicated in a variety of autoimmune diseases. Previous reports have described the effects of vitamin D on hair follicles.To evaluate the status of vitamin D in patients with AA, and the relationship between vitamin D levels and disease severity.A cross-sectional study of 86 patients with AA, 44 patients with vitiligo and 58 healthy controls was conducted. The serum vitamin D levels of the study group were determined by liquid chromatography/tandem mass spectrometry.Serum 25-hydroxyvitamin D [25(OH)D] levels in patients with AA were significantly lower than those of the patients with vitiligo and the healthy controls (P = 0·001 and P < 0·001, respectively). The prevalence of 25(OH)D deficiency was significantly higher in patients with AA (91%) compared with patients with vitiligo (71%) and healthy controls (33%) (P = 0·003 and P < 0·001, respectively). Furthermore, a significant inverse correlation was found between disease severity and serum 25(OH)D level in patients with AA (r = -0·409; P < 0·001).Deficient serum 25(OH)D levels are present in patients with AA and inversely correlate with disease severity. Accordingly, screening patients with AA for vitamin D deficiencies seems to be of value for the possibility of supplementing these patients with vitamin D.
Prenatal Cigarette Smoke Exposure Attenuates Recovery from Hypoxemic Challenge in Preterm Infants
Authors: Jennifer Schneider, Ian Mitchell, Nalini Singhal, Valerie Kirk, Shabih U. Hasan
Journal: American Journal of Respiratory and Critical Care Medicine (2008)

The effects of prenatal cigarette smoke (CS) exposure and hypoxemia on cardiorespiratory control have been investigated in full-term infants. However, few data are available in preterm infants, who form a particularly vulnerable population, with developmentally immature cardiorespiratory control.To investigate the effects of prenatal CS exposure on the duration and recovery of breathing pauses and oxygen saturation levels under baseline and hypoxemic conditions in preterm infants.The study was performed on 22 (12 born to smoking and 10 to nonsmoking mothers) spontaneously breathing preterm infants between 28 and 36 weeks' gestation. Cardiorespiratory variables were recorded under baseline normoxemic and hypoxemic conditions.Breathing pauses, pause indices, time to recovery, percent pause recovery, oxygen saturation (Sp(O2)), periods of wakefulness, and cardiorespiratory rates were compared between the two groups. Spontaneous recovery of breathing pauses (P = 0.03) and Sp(O(2)) levels (P = 0.017) were attenuated in CS-exposed infants as compared with the control group during the hypoxemic and posthypoxemic periods, respectively. The episodes of wakefulness during the hypoxemic challenge were similar between the two groups. Furthermore, CS-exposed infants showed a greater increase in heart rate (P < 0.001) during the hypoxemic challenge when compared with control infants.We provide evidence of how prenatal CS exposure and hypoxemic episodes affect the duration and recovery of breathing pauses in preterm infants. These observations could help explain why these infants are at a particularly high risk for sudden infant death syndrome.
The meaning of baselines
Authors: David Lee Robinson
Journal: Behavioral and Brain Sciences (1995)

Abstract Images of mind superbly summarizes work on cognitive neuroscienee using PET scanning. Some of the data emphasized suggests that parietal cortex is involved in the disengagement of attention. We have discovered neurons in awake monkeys which could perform this function. Another point of emphasis is the concept of neutral cues. Although an appealing concept, it is extremely difficult to define what is actually neutral.
Parallel Anticancer Drug Development and Molecular Stratification to Qualify Predictive Biomarkers: Dealing with Obstacles Hindering Progress
Authors: Victor Moreno Garcia, Philippe A. Cassier, Johann de Bono
Journal: Cancer Discovery (2011)

Abstract Current anticancer drug development still largely follows the classic designs developed for chemotherapeutic agents over the past 4 to 5 decades, remaining slow, costly, and inefficient, with continuing high risks of costly late drug attrition. A Pharmacologic Audit Trail has been described to decrease these risks, incorporating pharmacokinetic, pharmacodynamic, intermediate efficacy endpoints, as well as patient stratification molecular biomarkers. Molecular biomarker–based patient selection in hypothesis-testing early clinical trials is critical to clinically qualify putative predictive biomarkers for rationally designed, molecularly targeted drugs as early as possible. Nevertheless, major concerns have been raised about the impact of using such biomarkers in early trials, in view of the costs and time involved to develop multiple certified assays for clinical use. The rapid evolution of novel technologies of utility to this field, such as next-generation sequencing and circulating tumor-cell isolation, makes these valid concerns of critical importance. We therefore propose a more efficient parallel predictive biomarker and clinical anticancer drug development process to deal with the obstacles hindering progress. Cancer Discovery; 1(3); 207–12. © 2011 AACR.
[<sup>18</sup>F]Fluorodeoxyglucose Positron Emission Tomography–Guided Therapy in Metastatic Adrenocortical Carcinoma: An Illustrative Case
Authors: Hubert H. Chuang, Ferhat Deniz, Kanishka Sircar, Camilo Jimenez, Carlos Rubin De Celis, Christopher G. Wood, Mouhammed Amir Habra
Journal: Journal of Clinical Oncology (2012)