tbuckley/cabot-search huggingface dataset:
VSL#3 for the prevention of antibiotic associated diarrhoea (AAD) and clostridium difficile associated diarrhoea (CDAD): an interim analysis
Authors: C. Selinger, M. Lockett, A. Bell, S. Sebastian, N. Haslam
Journal: Gut (2011)

<h3>Introduction</h3> CDAD is the most common health care-acquired infection in the United Kingdom and causes significant morbidity and mortality. Previous studies have reported incidences of CDAD as high as 17%. Prevention of CDAD by Probiotics co-administration during antibiotic exposure is an appealing concept, but the few previously published trials showed inconclusive data and were hindered by flaws in trial design. This trial aims to investigate whether VSL#3 will prevent AAD and CDAD in hospitalised patients exposed to systemic antibiotics. <h3>Methods</h3> This multi-centre, randomised, double-blind, placebo-controlled trial will recruit 445 patients. One sachet of VSL#3 or placebo is given twice daily for the length of the antibiotics course and 7 days thereafter with follow-up for 28 days after the last antibiotic dose. Primary outcomes are occurrence of AAD and CDAD and secondary outcomes are length of stay (LOS) and 30-day mortality. <h3>Results</h3> This interim analysis reports on 124 patients enrolled in the trial so far. 62 patients were randomised to the active and 62 to the placebo group. Both groups were well matched for baseline demographic patient data. The study drug was generally well tolerated, and there was no difference in the rate of serious adverse events (3 in each group). Exposure to high risk antibiotic regimens was 85.5% (active) and 74.4% (placebo), respectively. No statistically significant differences were found in primary and secondary outcomes between the active and the placebo group at interim analysis. There was, however, a trend towards less AAD in the active group on per protocol analysis (active 0%, placebo 11.4%, p = 0.11). Assuming CDAD incidences of 5% in the placebo group and 0.1% in the active group 175 participants per group (350 in total) would give 90% power to detect a difference at a significance level of 0.05. <h3>Conclusion</h3> VSL#3 is well tolerated, and no drug-related SAE were reported. The incidences of both AAD and CDAD are much lower than previously reported. This may reflect improved infection control measures (hygiene, isolation rooms, and antibiotic policy) at the participating sites. Updated power calculations based on the lower incidences find that the original sample size is still suitable to confirm or refute the primary hypothesis.
microRNAs: What the Clinician Should Know About This New Frontier
Authors: Derek LeRoith
Journal: Diabetes Care (2014)

As clinicians, we are often overwhelmed by the explosion of new discoveries in technology. When investigators of various aspects of obesity and diabetes moved from physiologic studies of β-cell function and insulin action in metabolic tissues, they moved into the realm of gene expression, gene array, and other laboratory techniques. These techniques were readily included in our understanding of the disorders. For example, enhanced hepatic glucose production secondary to impaired insulin release from the pancreas and hepatic insulin resistance was often associated with increased expression of important regulatory enzymes, such as glucose-6-phosphatase and PEPCK. The exquisite regulation of their gene expression is commonly measured as mRNA, a step before translation into the protein. More recently, we have had to come to grips with large-scale genome-wide association studies that relate the disease with single nucleotide polymorphisms—often only associations without definitive or identifiable causal relationships. Thus, while we could readily understand genetic mutations resulting in disease states, it was often less apparent how single nucleotide polymorphisms could explain diseases in the absence of genetic mutations (1).

If that wasn’t enough, we now are becoming overwhelmed by new physiologic and pathologic processes discovered more recently as the sequence of the whole genome is no longer …
Targeted oxygen therapy in the prehospital management of patients with chronic obstructive pulmonary disease
Authors: W. M. Ricketts
Journal: Thorax (2011)

Although guidelines recommend targeted oxygen therapy for patients with hypoxia and exacerbations of chronic obstructive pulmonary disease (COPD), there is no strong evidence that this strategy is effective. In this study, Austin and colleagues perform the first randomised controlled trial, in the prehospital setting, of oxygen therapy titrated to target saturations in patients at risk of …
Intestinal deletion of<i>Claudin-7</i>enhances paracellular organic solute flux and initiates colonic inflammation in mice
Authors: Hiroo Tanaka, Maki Takechi, Hiroshi Kiyonari, Go Shioi, Atsushi Tamura, Sachiko Tsukita
Journal: Gut (2015)

<h3>Objective</h3> To design novel anti-inflammation treatments, it is important to recognise two distinct steps of inflammation: initiation and acceleration. In IBDs, intestinal inflammation is reported to be accelerated by dysfunction in the epithelial paracellular barrier formed by tight junctions (TJs). However, it is unclear whether changes in paracellular barrier function initiate inflammation. Some of the intestinal claudin-family proteins, which form the paracellular barrier, show aberrant expression levels and localisations in IBDs. We aimed to elucidate the role of paracellular-barrier change in initiating colonic inflammation. <h3>Design</h3> We generated intestine-specific conditional knockout mice of <i>claudin-7 (Cldn7)</i>, one of the predominant intestinal claudins. <h3>Results</h3> The intestine-specific <i>Cldn7</i> deficiency caused colonic inflammation, even though TJ structures were still present due to other claudins. The paracellular flux (pFlux), determined by measuring the paracellular permeability across the colon epithelium, was enhanced by the <i>Cldn7</i> deficiency for the small organic solute Lucifer Yellow (457 Da), but not for the larger organic solute FITC-Dextran (4400 Da). Consistent with these results, the intestine-specific <i>claudin-7</i> deficiency enhanced the pFlux for <i>N</i>-formyl-l-methionyl-l-leucyl-l-phenylalanine (fMLP) (438 Da), a major bacterial product, to initiate colonic inflammation. <h3>Conclusions</h3> These findings suggest that specific enhancement of the pFlux for small organic solutes across the claudin-based TJs initiates colonic inflammation.
Plasma renin activity in psychosocial hypertension of CBA mice.
Authors: A J Vander, J P Henry, P M Stephens, L L Kay, D R Mouw
Journal: Circulation Research (1978)

We studied plasma renin activity (PRA) in male full-color brown Agouti (CBA) mice subjected to varying degrees of psychosocial stress induced by manipulation of their housing patterns.Blood samples were obtained from unanesthetized mice by retro-orbital puncture; blood pressure (BP) was measured by tail plethysmography.At 4 months of age, PRA was lower in mice isolated since weaning (isolates) than in mice housed together in standard cages (boxed sibs).Isolation of boxed sibs for 7 days also decreased PRA.PRA did not change in isolates during a 10-month period.In contrast, PRA and BP changed markedly after 4-month-old isolates were placed in an interconnected box system [population cage (PC)] which increased social interaction and competition; values at all times were greater than those of isolated controls.PRA increased rapidly during the first 1-2 days, declined from these high values over the next 3 weeks to values similar to those of boxed sibs (but higher than control isolates), and then rose again progressively during the next 5-6 months.BP was elevated within 1 week (particularly in subordinate mice), then rose slowly throughout the experiment.During the first 2 months, PRA and BP were inversely correlated; no significant correlation existed after 2 months.Hematocrit tended to be lower in PC mice from 7 days on.Blood urea was increased in 10-month-old PC mice.Increased PRA and BP also occurred in boxed sibs placed in PC for 3-10 weeks.The pattern of PRA changes in these mice is analogous to that observed in certain forms of human essential hypertension and is further evidence that psychosocial hypertension in CBA mice may be an appropriate model for the study of essential hypertension.SUSTAINED hypertension can be induced in CBA mice by placing them in complex population cages which facilitate social interactions and competition for territory. 1' 2 This psychosocially induced hypertension may result in part from repeated activation of the sympathetic nervous system and release of pituitary-adrenocortical hormones. 3' 4 The possible participation of the renin-angiotensin system in the initiation and maintenance of the hypertension has
Generation of polarized antigen-specific CD8 effector populations: reciprocal action of interleukin (IL)-4 and IL-12 in promoting type 2 versus type 1 cytokine profiles.
Authors: M Croft, L Carter, S L Swain, R W Dutton
Journal: The Journal of Experimental Medicine (1994)

We have generated primary effector populations from naive CD8 T cells in response to antigen and determined their patterns of cytokine secretion upon restimulation. The effect of exogenous factors on the effector generation was examined and compared with responses of antigen-specific CD4 effectors generated under comparable conditions. CD8 cells from bm1 mice were stimulated with C57BL/6 (B6) antigen presenting cells (APCs) bearing allogeneic class I and CD8 cells from female severe combined immunodeficiency (SCID) B6 mice, transgenic for a T cell receptor alpha/beta (TCR-alpha/beta) that recognizes H-Y on Db, were stimulated with APCs from male mice. In parallel, CD4 cells from bm12 mice were stimulated with alloantigen and CD4 cells from V beta 3/V alpha 11 TCR transgenics were stimulated with a peptide of pigeon cytochrome c on IEk. T cells from both transgenic mice were of naive phenotype whereas normal mice contained 10-20% memory cells. Effector CD8 populations generated were L-selectin low, CD45RB high, and CD44 high. Naive CD8 cells from SCID anti-H-Y mice made little or no cytokine immediately upon stimulation in contrast to naive CD4 which produced large amounts of interleukin 2 (IL-2). Both populations, however, generated primary effectors over 4-5 d that made substantial quantities of many cytokines upon restimulation. Both CD8 and CD4 effectors produced similar patterns of cytokines with alloantigen or specific antigen. Cytokines present during naive CD8 stimulation influenced the cytokine secretion profile of the effectors, as previously shown for CD4 cells, although secretion by CD8 effectors was generally lower than that of CD4 effectors. CD8 cells cultured with IL-2 alone made predominantly interferon gamma (IFN-gamma) and no IL-4 or IL-5, similar to CD4 cells. Priming with IFN-gamma increased IFN-gamma secretion from CD4 effectors, but had little if any effect on CD8 cells. In contrast, priming with IL-12 generated CD8 effectors, as well as CD4 effectors, producing elevated quantities of IFN-gamma, with similar levels from both the CD4 and CD8 populations. The presence of IL-4 during effector cell generation promoted synthesis of IL-4 and IL-5 from both CD8 and CD4 cells while downregulating IFN-gamma secretion. CD8 cells made only small amounts of IL-4, more than 100-fold less than CD4 cells, whereas significant levels of IL-5 were induced, only 3-10-fold lower than from CD4.(ABSTRACT TRUNCATED AT 400 WORDS)
Definition of COPD: based on evidence or opinion?
Authors: R. Pellegrino, V. Brusasco, G. Viegi, R. O. Crapo, F. Burgos, R. Casaburi, A. Coates, C. P. M. van der Grinten, P. Gustafsson, J. Hankinson, R. Jensen, D. C. Johnson, N. MacIntyre, R. McKay, M. R. Miller, D. Navajas, O. F. Pedersen, J. Wanger
Journal: European Respiratory Journal (2008)

FVC, without recommending any numerical cut-off point.
Impact of Restricted Maternal Weight Gain on Fetal Growth and Perinatal Morbidity in Obese Women With Type 2 Diabetes
Authors: Björg Ásbjörnsdóttir, Signe S. Rasmussen, Louise Kelstrup, Peter Damm, Elisabeth R. Mathiesen
Journal: Diabetes Care (2012)

OBJECTIVE Since January 2008, obese women with type 2 diabetes were advised to gain 0–5 kg during pregnancy. The aim with this study was to evaluate fetal growth and perinatal morbidity in relation to gestational weight gain in these women. RESEARCH DESIGN AND METHODS A retrospective cohort comprised the records of 58 singleton pregnancies in obese women (BMI ≥30 kg/m2) with type 2 diabetes giving birth between 2008 and 2011. Birth weight was evaluated by SD z score to adjust for gestational age and sex. RESULTS Seventeen women (29%) gained ≤5 kg, and the remaining 41 gained &amp;gt;5 kg. The median (range) gestational weight gains were 3.7 kg (−4.7 to 5 kg) and 12.1 kg (5.5–25.5 kg), respectively. Prepregnancy BMI was 33.5 kg/m2 (30–53 kg/m2) vs. 36.8 kg/m2 (30–48 kg/m2), P = 0.037, and median HbA1c was 6.7% at first visit in both groups and decreased to 5.7 and 6.0%, P = 0.620, in late pregnancy, respectively. Gestational weight gain ≤5 kg was associated with lower birth weight z score (P = 0.008), lower rates of large-for-gestational-age (LGA) infants (12 vs. 39%, P = 0.041), delivery closer to term (268 vs. 262 days, P = 0.039), and less perinatal morbidity (35 vs. 71%, P = 0.024) compared with pregnancies with maternal weight gain &amp;gt;5 kg. CONCLUSIONS In this pilot study in obese women with type 2 diabetes, maternal gestational weight gain ≤5 kg was associated with a more proportionate birth weight and less perinatal morbidity.
“Expert Opinion” Software for Medical Diagnosis and Treatment
Authors: Robert M. Ross
Journal: JAMA Internal Medicine (2014)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Fibrolamellar hepatocellular carcinoma complicating ulcerative colitis with primary sclerosing cholangitis.
Authors: J A Snook, P Kelly, R W Chapman, D P Jewell
Journal: Gut (1989)

Abstract This case report describes the previously undocumented association between fibrolamellar hepatocellular carcinoma and ulcerative colitis complicated by primary sclerosing cholangitis.
Prevention and management of knee osteoarthritis and knee cartilage injury in sports
Authors: Hideki Takeda, Takumi Nakagawa, Kozo Nakamura, Lars Engebretsen
Journal: British Journal of Sports Medicine (2011)

Articular cartilage defects in the knee of young or active individuals remain a problem in orthopaedic practice. These defects have limited ability to heal and may progress to osteoarthritis. The prevalence of knee osteoarthritis among athletes is higher than in the non-athletic population. The clinical symptoms of osteoarthritis are joint pain, limitation of range of motion and joint stiffness. The diagnosis of osteoarthritis is confirmed by the symptoms and the radiological findings (narrowing joint space, osteophyte formation and subchondral sclerosis). There is no strong correlation between symptoms and radiographic findings. The aetiology of knee osteoarthritis is multifactorial. Excessive musculoskeletal loading (at work or in sports), high body mass index, previous knee injury, female gender and muscle weakness are well-known risk factors. The high-level athlete with a major knee injury has a high incidence of knee osteoarthritis. Cartilage injuries are frequently observed in young and middle-aged active athletes. Often this injury precedes osteoarthritis. Reducing risk factors can decrease the prevalence of knee osteoarthritis. The prevention of knee injury, especially anterior cruciate ligament and meniscus injury in sports, is important to avoid progression of knee osteoarthritis.
The Swinging Pendulum of the Anemia of Cancer: Erythropoietin Trumps Hepcidin
Authors: Stanley Zucker
Journal: Journal of Clinical Oncology (2010)

TO THEEDITOR: More thanfive decades ago, Cartwright 1 popularizedtheconceptthatinadequatereleaseofironfromthereticuloendothelialsystem(REblockade),despiteadequatebodyironstores,was responsiblefortheanemiaofchronicdisease(ACD;cancer,infection, andinflammation).Themorerecentfindingofhighhepcidinlevelsin patients with cancer has provided a pathophysiologic explanation for the diminished iron reuse in patients with cancer. 2 Hohaus et al 3 recently reported on the role of interleukin (IL) -6 induction of hepcidinintheanemiaofHodgkin’slymphoma.Inpatientswithanemia, plasma hepcidin levels were inversely correlated with the hemoglobin concentration in blood. Consistent with the role of hepcidin in interfering with ferroportin export of iron out of enterocytes and macrophages into the blood stream, plasma levels of hepcidin positively correlated with serum ferritin levels (r0.62; P.0001) and inversely correlatedwithserumironandiron-bindingcapacity.Contrarytoexpectations, Hohaus et al further demonstrated that plasma hepcidin levels increasedinpatientswithnonanemicHodgkin’slymphomacomparable with patients with anemia. Hohaus et al concluded that increased hepcidin levels do not appear sufficient to induce anemia and that hepcidinindependent mechanisms induced by pro-inflammatory cytokines, in particular IL-6, are likely to be involved. 3
Long-term Follow-up of a Randomized Trial of Radiation With or Without Androgen Deprivation Therapy for Localized Prostate Cancer
Authors: Anthony V. D’Amico, Ming-Hui Chen, Andrew Renshaw, Marian Loffredo, Philip W. Kantoff
Journal: JAMA (2015)

This study uses long-term follow-up data from a randomized trial comparing radiation therapy with vs without androgen deprivation therapy for unfavorable-risk prostate cancer to compare survival and cause-specific mortality by severity of comorbidity.
Tracer Oxygen Distribution Is Barrier-Limited in the Cerebral Microcirculation
Authors: Ibrahim G. Kassissia, Carl A. Goresky, Colin P. Rose, Andreas J. Schwab, André Simard, Pierre-Michel Huet, Glen G. Bach
Journal: Circulation Research (1995)

The kinetics of tracer oxygen distribution in the brain microcirculation of the awake dog were investigated with the multiple indicator dilution technique. A bolus containing 51Cr-labeled red blood cells, previously totally desaturated and then resaturated with [18O]2 (oxygen), 125I-albumin, 22Na, and [3H]water, was injected into the carotid artery, and serial anaerobic blood samples were collected from the sagittal sinus over the next 30 seconds. The outflow recovery curves were analyzed with a distributed-in-space two-barrier model for water and a one-barrier model for oxygen. The analysis provided an estimate of flow per gram brain weight as well as estimates for the tracer water and oxygen rate constants for blood-to-brain exchange and tracer oxygen parenchymal sequestration. Flow to tissue was found to vary between different animals, in concert with parallel changes in oxygen consumption. The 18O2 outflow curves showed an early peak, coincident with and more than half the magnitude of its vascular reference curve (labeled red blood cells), whereas the [3H]water curve increased abruptly to a low-in-magnitude curve at low flow values and to a small early peak at high flow values. Analysis indicates that the transfers of both 18O2 and [3H]water indicators from blood to brain are barrier-limited, with the former highly so because of the large red blood cell capacity for oxygen, and that the proportion of the tracer oxygen returning to the circulation from tissue is a small fraction of the total tracer emerging at the outflow.
Clinical impact of histologic subtypes in localized non-anaplastic nephroblastoma treated according to the trial and study SIOP-9/GPOH
Authors: A. Weirich, I. Leuschner, D. Harms, G.M. Vujanic, J. Tröger, U. Abel, N. Graf, D. Schmidt, R. Ludwig, P.A. Voûte
Journal: Annals of Oncology (2001)
2-adrenergic receptor polymorphisms, asthma and COPD: two large population-based studies
Authors: M. Thomsen, B.G. Nordestgaard, A.A. Sethi, A. Tybjærg-Hansen, M. Dahl
Journal: European Respiratory Journal (2011)

The β(2)-adrenergic receptor (ADRB2) is an important regulator of airway smooth muscle tone. We tested the hypothesis that three functional polymorphisms in the ADRB2 gene (Thr164Ile, Gly16Arg and Gln27Glu) are associated with reduced lung function, asthma or chronic obstructive pulmonary disease (COPD). We first genotyped 8,971 individuals from the Copenhagen City Heart Study for all three polymorphisms. To validate our findings, we genotyped an additional 53,777 individuals from the Copenhagen General Population Study for the Thr164Ile polymorphism. We identified 60,910 Thr164Ile noncarriers, 1,822 heterozygotes and 16 homozygotes. In the Copenhagen City Heart Study, the Thr164Ile genotype was associated with reduced forced expiratory volume in 1 s (FEV(1)) % predicted (trend p = 0.01) and FEV(1)/forced vital capacity (FVC) (p = 0.001): Thr164Ile heterozygotes had 3% and 2% reduced FEV(1) % pred and FEV(1)/FVC, respectively, compared with noncarriers. The odds ratio for COPD in Thr164Ile heterozygotes was 1.46 (95% CI 1.05-2.02). In the Copenhagen General Population Study, the Thr164 genotype associated with reduced FEV(1) % pred (p = 0.04) and FEV(1)/FVC (p < 0.001): Thr164Ile homozygotes and heterozygotes had 7% and 1% reduced FEV(1) % pred and 6% and 1% reduced FEV(1)/FVC, respectively, compared with noncarriers. The odds ratios for COPD in Thr164Ile homozygotes and heterozygotes were 4.53 (95% CI 1.54-13.3) and 1.07 (95% CI 0.92-1.25), respectively. Our results suggest that ADRB2 Thr164Ile is associated with reduced lung function and increased risk of COPD in the general population.
THE ROLE OF COMPLEMENT IN THE PASSIVE CUTANEOUS REACTION OF MICE
Authors: S. Ben-Efraim, B. Cinader
Journal: The Journal of Experimental Medicine (1964)

Intradermal injection of mice with ribonuclease antibody, followed by intravenous injection with ribonuclease, resulted in permeability increase, demonstrable by "blueing." The size of the blued area depends on the quantity of antibody injected and on the interval between the two injections. If antigen was injected first and antibody was injected subsequently, a similar increase in permeability was observed in animals having a complete complement system (MuB1-positive) and in animals which have a deficient complement system (MuB1-negative). Marked differences in response were observed between these two types of mice if antigen was injected some hours after the antibody. In MuB1-negative mice, a blueing reaction was not observed at intervals between injections (2(1/2) hours if 3 microg N antibody and 15 hours if 25 microg N antibody were injected intradermally) at which MuB1-positive animals showed a marked permeability increase. At these intervals, blueing did occur in MuB1-negative animals if they were injected with the serum of MuB1-positive mice or with fresh guinea pig serum. Blueing was not induced if the serum of MuB1-negative mice or heated guinea pig serum was injected. The occurrence of two distinct phases of the cutaneous reaction, of which only one involves the complete hemolytic complement system, was deduced from these observations.