tbuckley/cabot-search huggingface dataset:
Gastrointestinal transit in cirrhotic patients: Effect of hepatic encephalopathy and its treatment
Authors: David H. van Thiel, Stefano Fagiuoli, Harlan I. Wright, Mei-Chen Chien, Judith S. Gavaler
Journal: Hepatology (1994)

Chronic hepatic encephalopathy is highly responsive to changes in diet, to antibiotic therapy and to ingestion of nondigestible disaccharides. The precise pathophysiology of chronic hepatic encephalopathy in individual cases is highly variable, although ammonia toxicity and production of neurotransmitterlike substances in the gut have been proposed to contribute to the overall syndrome of chronic hepatic encephalopathy. The support for this hypothesis is based on the empiric observation that reduction in protein intake, a catharsis or both are effective treatments for chronic hepatic encephalopathy. This study was performed to evaluate the effect of mild subclinical and low-grade (grade 0 to 1) chronic hepatic encephalopathy on gastric emptying and oral-cecal transit times. Thirty patients were studied. Ten had no evidence of chronic hepatic encephalopathy, as determined with a battery of neuropsychiatric studies (group 1); 10 had subclinical hepatic encephalopathy, as judged on the basis of abnormal neuropsychiatric test performance but normal neurological examination (group 2); and 10 had grade 1 hepatic encephalopathy. Each underwent a liquid gastric emptying study and a lactulose oral-cecal transit time study. No significant differences between groups were evident in the results of the gastric emptying studies. In contrast, the time required for a lactulose load to reach the cecum was significantly greater in the patients with hepatic encephalopathy (p < 0.01) and increased as a function of the hepatic encephalopathy grade.(ABSTRACT TRUNCATED AT 250 WORDS)
Association Between Nonrandom X-Chromosome Inactivation and BRCA1 Mutation in Germline DNA of Patients With Ovarian Cancer
Authors: R. E. Buller, A. K. Sood, T. Lallas, T. Buekers, J. S. Skilling
Journal: JNCI Journal of the National Cancer Institute (1999)

Most human female cells contain two X chromosomes, only one of which is active. The process of X-chromosome inactivation, which occurs early in development, is usually random, producing tissues with equal mixtures of cells having active X chromosomes of either maternal or paternal origin. However, nonrandom inactivation may occur in a subset of females. If a tumor suppressor gene were located on the X chromosome and if females with a germline mutation in one copy of that suppressor gene experienced nonrandom X-chromosome inactivation, then some or all of the tissues of such women might lack the wild-type suppressor gene function. This scenario could represent a previously unrecognized mechanism for development of hereditary cancers. We investigated whether such a mechanism might contribute to the development of hereditary ovarian cancers.Patterns of X-chromosome inactivation were determined by means of polymerase chain reaction amplification of the CAG-nucleotide repeat of the androgen receptor (AR) gene after methylation-sensitive restriction endonuclease digestion of blood mononuclear cell DNA from patients with invasive (n = 213) or borderline (n = 44) ovarian cancer and control subjects without a personal or family history of cancer (n = 50). BRCA1 gene status was determined by means of single-strand conformational polymorphism analysis and DNA sequencing. All statistical tests were two-sided.Among individuals informative for the AR locus, nonrandom X-chromosome inactivation was found in the DNA of 53% of those with invasive cancer versus 28% of those with borderline cancer (P = .005) and 33% of healthy control subjects (P = .016). Nonrandom X-chromosome inactivation can be a heritable trait. Nine of 11 AR-informative carriers of germline BRCA1 mutations demonstrated nonrandom X-chromosome inactivation (.0002 < P < .008, for simultaneous occurrence of both).Nonrandom X-chromosome inactivation may be a predisposing factor for the development of invasive, but not borderline, ovarian cancer.
Shear stress induces angiotensin converting enzyme expression in cultured smooth muscle cells: possible involvement of bFGF
Authors: W Gosgnach
Journal: Cardiovascular Research (2000)

Objective: Hemodynamic stresses are considered to be important regulators of gene expression in vascular cells. In this study, we have investigated the role of shear stress on ACE expression in cultured rat vascular cells, and focused on the regulation of ACE expression in smooth muscle cells. Methods: Rat aortic endothelial cells, smooth muscle cells and fibroblasts isolated from Wistar rats were submitted to shear stress using a laminar shear flow parallel chamber. Results: A 10 dynes/cm2 shear rate for 24 h increased ACE activity in the three vascular cell types (× 2.14 in endothelial cells, × 2.9 in smooth muscle cells, × 3.33 in fibroblasts). This induction was blocked by a 24 h pre-incubation with a translation blocker (10−4M cycloheximide) showing the role of protein neosynthesis. Therefore the study was focused on smooth muscle cells and we demonstrated that the increase in ACE activity was due to an elevation in ACE mRNA level in response to a 10 dynes/cm2 shear stress for 24 h. This induction was dependent on the shear intensity (P<0.0001). Six hours of a 15 dynes/cm2 shear stress showed no effect on ACE activity or mRNA expression. In contrast, the same duration of shear significantly increased bFGF mRNA level (×3.7). Conversely, bFGF dose dependently increased ACE mRNA expression and activity in smooth muscle cells. This result suggests that bFGF could be one of the potential inductors of ACE expression in the stressed smooth muscle cells. Conclusions: Mechanical stress increases ACE expression in vascular cells. bFGF could be one of the potential factors involved in this activation. This phenomenon could participate in the role of ACE activity in vascular wall remodeling.
HMGB1 Contributes to Kidney Ischemia Reperfusion Injury
Authors: Huiling Wu, Jin Ma, Peng Wang, Theresa M. Corpuz, Usha Panchapakesan, Kate R. Wyburn, Steven J. Chadban
Journal: Journal of the American Society of Nephrology (2010)

High-mobility group box 1 (HMGB1), a nuclear factor released extracellularly as an inflammatory cytokine, is an endogenous ligand for Toll-like receptor 4 (TLR4). TLR4 activation mediates kidney ischemia-reperfusion injury (IRI), but whether HMGB1 contributes to IRI is unknown. Here, treating wild-type mice with neutralizing anti-HMGB1 antibody protected them against kidney IRI, evidenced by lower serum creatinine and less tubular damage than untreated mice. Mice treated with anti-HMGB1 had significantly less tubulointerstitial infiltration by neutrophils (day 1) and macrophages (day 5) and markedly reduced apoptosis of tubular epithelial cells. Furthermore, anti-HMGB1 antibody-treated IRI kidneys had significantly lower levels of IL-6, TNFα, and monocyte chemoattractant protein 1 (MCP1). mRNA, which are downstream of HMGB1. Conversely, administration of rHMGB1 after reperfusion exacerbated kidney IRI in wild-type mice. TLR4 deficient (TLR4−/−) mice were protected against kidney IRI; administration of neither anti-HMGB1 antibody nor rHMGB1 affected this renoprotection. In conclusion, endogenous HMGB1 promotes kidney damage after IRI, possibly through the TLR4 pathway. Administration of a neutralizing antibody to HMGB1 either before or soon after ischemia-reperfusion affords significant protection, suggesting therapeutic potential for acute kidney injury.
Outcomes in children treated for persistent bacterial bronchitis
Authors: D. Donnelly, A. Critchlow, M. L Everard
Journal: Thorax (2006)

<b>Background:</b> Persistent bacterial bronchitis (PBB) seems to be under-recognised and often misdiagnosed as asthma. In the absence of published data relating to the management and outcomes in this patient group, a review of the outcomes of patients with PBB attending a paediatric respiratory clinic was undertaken. <b>Methods:</b> A retrospective chart review was undertaken of 81 patients in whom a diagnosis of PBB had been made. Diagnosis was based on the standard criterion of a persistent, wet cough for &gt;1 month that resolves with appropriate antibiotic treatment. <b>Results:</b> The most common reason for referral was a persistent cough or difficult asthma. In most of the patients, symptoms started before the age of 2 years, and had been present for &gt;1 year in 59% of patients. At referral, 59% of patients were receiving asthma treatment and 11% antibiotics. <i>Haemophilus influenzae</i> and <i>Streptococcus pneumoniae</i> were the most commonly isolated organisms. Over half of the patients were completely symptom free after two courses of antibiotics. Only 13% of patients required ⩾6 courses of antibiotics. <b>Conclusion:</b> PBB is often misdiagnosed as asthma, although the two conditions may coexist. In addition to eliminating a persistent cough, treatment may also prevent progression to bronchiectasis. Further research relating to both diagnosis and treatment is urgently required.
Soluble ST2 plasma concentrations predict mortality in severe sepsis
Authors: Jacobien J. Hoogerwerf, Michael W. T. Tanck, Marieke A. D. van Zoelen, Xavier Wittebole, Pierre-François Laterre, Tom van der Poll
Journal: Intensive Care Medicine (2010)

Patients with sepsis-after surviving the initial hyperinflammatory phase-display features consistent with immunosuppression, including hyporesponsiveness of immunocompetent cells to bacterial agents. Immunosuppression is thought to be facilitated by negative regulators of toll-like receptors, including membrane-bound ST2. We investigated the release of soluble ST2 (sST2), a decoy receptor that inhibits membrane-bound ST2 signaling, during sepsis.The study population comprised 95 patients with severe sepsis admitted to one of two intensive care units (ICUs) at the day the diagnosis of severe sepsis was made. Blood was obtained daily from admission (day 0) until day 7 and finally at day 14. Twenty-four healthy subjects served as controls. sST2 and cytokines were measured in serum.Mortality among patients was 34% in the ICU and 45% in the hospital. On admission, sepsis patients had higher sST2 levels [10,989 (7,871-15,342) pg/ml, geometric mean (95% confidence interval, CI)] than controls [55 (20-145) pg/ml, P < 0.0001]. Serum sST2 remained elevated in patients from day 0 to 14 and correlated with disease severity scores (P < 0.001) and cytokine levels on day 0 and during course of disease (P < 0.0001). Nonsurvivors displayed elevated sST2 levels compared with survivors of the intensive care unit (P < 0.0001).Sepsis results in sustained elevation of serum sST2 levels, which correlates with disease severity and mortality.
Time course of pulmonary artery pressure during sleep in sleep apnoea syndrome: role of recurrent apnoeas
Authors: E Sforza, L Laks, RR Grunstein, J Krieger, CE Sullivan
Journal: European Respiratory Journal (1998)

Recent results in animals have suggested that repetition of hypoxaemic stimuli may result in a progressive increase in pulmonary arterial pressure (Ppa). The purpose of the present study was to investigate the effects of recurrent obstructive apnoeas on Ppa. We have, therefore, examined the nocturnal trend of Ppa in seven obstructive sleep apnoea syndrome (OSAS) patients and in five snorers. Mean Ppa was measured before, at the start, at the end and after the selected apnoeas. The analysis was performed for each 1 h period for at least 7 h throughout the night on at least 10 randomly selected apnoeas per hour. In snorers, 100 randomly chosen values were measured during every hour of the night. In the morning after the nocturnal study, the Ppa responses to acute hypoxia and hypercapnia were measured. No Ppa changes throughout the 7 h were found during sleep in snorers [Ppa slope:-0.002+/-0.10 mmHg x h(-1)]. In OSAS patients a small but significant increase in Ppa throughout the night was noted, affecting the values before [Ppa slope: 0.7+/-0.16 mmHg x h(-1)], at the start of apnoea [Ppa slope: 0.530.1 mmHg x h(-1)] as well as at the end [Ppa slope: 0.44+/-0.08 mmHg x h(-1)] and in the postapnoeic period [Ppa slope: 0.55+/-0.1 mmHg x h(-1)]. When we limited the analysis to nonrapid eye movement (NREM) sleep, a trend in progressive Ppa was also present, irrespective of changes in apnoea duration and apnoea desaturation. The Ppa rise during the night was not affected by diurnal Ppa pulmonary vascular response to hypoxia and hypercapnia or indices of sleep apnoea severity. We conclude that in obstructive sleep apnoea, pulmonary artery pressure progressively increases during the night, reflecting the cumulative effects of apnoeas and nocturnal hypoxaemia.
Diagnostic Errors—The Next Frontier for Patient Safety
Authors: David E. Newman-Toker
Journal: JAMA (2009)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Interleukin-27 inhibits ectopic lymphoid-like structure development in early inflammatory arthritis
Authors: Gareth W. Jones, Michele Bombardieri, Claire J. Greenhill, Louise McLeod, Alessandra Nerviani, Vidalba Rocher-Ros, Anna Cardus, Anwen S. Williams, Costantino Pitzalis, Brendan J. Jenkins, Simon A. Jones
Journal: The Journal of Experimental Medicine (2015)

Ectopic lymphoid-like structures (ELSs) reminiscent of secondary lymphoid organs often develop at sites of chronic inflammation where they contribute to immune-mediated pathology. Through evaluation of synovial tissues from rheumatoid arthritis (RA) patients, we now show that low interleukin-27 (IL-27) expression corresponds with an increased incidence of ELS and gene signatures associated with their development and activity. The presence of synovial ELS was also noted in mice deficient in the IL-27 receptor (IL-27R) after the onset of inflammatory arthritis. Here, pathology was associated with increased synovial expression of pro-inflammatory cytokines, homeostatic chemokines, and transcriptional regulators linked with lymphoid neogenesis. In both clinical and experimental RA, synovial ELS coincided with the heightened local expression of cytokines and transcription factors of the Th17 and T follicular helper (Tfh) cell lineages, and included podoplanin-expressing T cells within lymphoid aggregates. IL-27 inhibited the differentiation of podoplanin-expressing Th17 cells, and an increased number of these cells were observed in IL-27R–deficient mice with inflammatory arthritis. Thus, IL-27 appears to negatively regulate ELS development in RA through control of effector T cells. These studies open new opportunities for patient stratification and treatment.
Tumor-Producing Capabilities of Hyperplastic Alveolar Nodules in Virgin and Hormone-Stimulated BALB/c &lt;italic&gt;f&lt;/italic&gt;. C3H and C3Hf Mice&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Daniel Medina, K. B. DeOme, L. Young
Journal: JNCI Journal of the National Cancer Institute (1970)

Experiments were designed to delineate the role of hormone stimulation in mouse mammary noduligenesis and tumorigenesis in mammary tumorvirus-positive BALB/c f. C3H mice and in nodule-inducing virus-positive C3Hf mice. The temporal pattern of noduligenesis and tumorigenesis was examined both in untreated virgins and in mice bearing pituitary isografts. In BALB/c f. C3H virgins, hyperplastic alveolar nodules (HAN) appeared sporadically and infrequently, whereas in C3Hf virgins, HAN appeared only after 19 months of age. In similar mice bearing pituitary isografts, HAN arose after 2 months of hormone stimulation in BALB/c f. C3H and after 6 months of hormone stimulation in C3Hf. Nodules were transplanted into 3-week-old syngeneic mice from both untreated virgin and hormone-stimulated BALB/c f. C3H and C3Hf mice to determine their relative tumor-producing capabilities. Recipient mice of each strain were separated into 2 groups; one group was maintained as untreated mice and the other received pituitary isografts. The results indicated that the HAN arising in virgin mice and mice bearing pituitary isografts did not differ from each other with regard to their tumor-producing capabilities. Furthermore, prolonged hormone stimulation of hosts bearing BALB/c f. C3H nodule transplants decreased the mean latent period of tumorigenesis but did not alter the final tumor incidence. These results indicate that prolonged hormone stimulation of mouse mammary glands by pituitary isografts exerts its influence on both noduligenesis and tumorigenesis, and its effect on noduligenesis is a quantitative, not a qualitative, phenomenon.
Mineralized bone loss at different sites in dialysis patients
Authors: H C Schober, Z H Han, A J Foldes, M S Shih, D S Rao, R Balena, A M Parfitt
Journal: Journal of the American Society of Nephrology (1998)

To characterize the magnitude and location of mineralized bone loss, 40 patients (20 men, 20 women, 29 white, 11 black) with clinically significant renal osteodystrophy who could be unambiguously classified based on histologic criteria as having osteitis fibrosa (OF; 20 cases) or osteomalacia (OM; 20 cases) were studied; they had been on maintenance hemodialysis for 4.6 +/- 3.0 yr. One hundred forty-two healthy women of similar age and ethnic composition served as control subjects. In all subjects, the proportions of mineralized bone, osteoid, and porosity (nonbone soft tissue) were measured separately in cortical and cancellous bone tissue, from intact full-thickness biopsies of the ilium, representative of the axial skeleton. The results were related to the volumes of cortical and cancellous bone tissue separately and to the volume of the entire biopsy core. Approximately three-quarters of the patients had measurements in the appendicular skeleton by single photon absorptiometry of the radius and morphometry of the metacarpal. Disease effects did not differ significantly between ethnic groups. Mineralized cortical bone volume (per unit of core volume) was reduced by approximately 45% in both patient groups. Mineralized cancellous bone volume was significantly increased by 36% in the patients with OF and nonsignificantly reduced by 9% in the patients with OM; however, the reduction in the latter patients was significant in relation to tissue volume. The combined total deficit for both types of iliac bone was approximately 20% in the patients with OF and approximately 40% in the patients with OM. Significant reductions in appendicular cortical bone were demonstrated in both patient groups at both measurement sites. Regardless of the current histologic classification, the major structural abnormality in the skeleton is generalized thinning of cortical bone due to increased net endocortical resorption, the most characteristic effect on bone of hyperparathyroidism. Protection of the skeleton from the adverse consequences of renal failure will require therapeutic intervention in patients with no symptoms of either renal or bone disease.
Newton and Darwin: Can this marriage be saved?
Authors: William M. Baum, Suzanne H. Mitchell
Journal: Behavioral and Brain Sciences (2000)

The insights described by Nevin &amp; Grace may be summarized without reference to the Newtonian concepts they suggest. The metaphor to Newtonian mechanics seems dubious in three ways: (1) extensions seem to lead to paradoxes; (2) many well-known phenomena are ignored; (3) the Newtonian concepts seem difficult to reconcile with the larger framework of evolutionary theory.
Relief of Expressed Suicidal Intent by ECT: A Consortium for Research in ECT Study
Authors: Charles H. Kellner, Max Fink, Rebecca Knapp, Georgios Petrides, Mustafa Husain, Teresa Rummans, Martina Mueller, Hilary Bernstein, Keith Rasmussen, Kevin O’Connor, Glenn Smith, A. John Rush, Melanie Biggs, Shawn McClintock, Samuel Bailine, Chitra Malur
Journal: American Journal of Psychiatry (2005)

OBJECTIVE: This study assessed the incidence, severity, and course of expressed suicidal intent in depressed patients who were treated with ECT. The data are from the first phase of an ongoing, collaborative multicenter study, the overall aim of which was to compare continuation ECT with pharmacotherapy in the prevention of relapse after a successful course of ECT. METHOD: Suicidal intent, as expressed by patients during an interview, was scored at baseline and before each ECT session with item 3 on the 24-item Hamilton Depression Rating Scale in 444 patients with unipolar depression. RESULTS: One hundred thirty-one patients (29.5%) reported suicidal thoughts and acts (score of 3 or 4) at baseline. Scores decreased to 0 after 1 week (three ECT sessions) in 38.2% of the patients, after 2 weeks (six ECT sessions) in 61.1%, and in 80.9% at the end of the course of treatment. CONCLUSIONS: Expressed suicidal intent in depressed patients was rapidly relieved with ECT. Evidence-based treatment algorithms for major depressive mood disorders should include dichotomization according to suicide risk, as assessed by interview. For patients at risk, ECT should be considered earlier than at its conventional "last resort" position.
Benefits of immunotherapy with a standardized <i>Dermatophagoides pteronyssinus</i> extract in asthmatic children: a three‐year prospective study
Authors: M. Pifferi, G. Baldini, G. Marrazzini, M. Baldini, V. Ragazzo, A. Pietrobelli, A.L. Boner
Journal: Allergy (2002)

Background: Although widely practiced for over 80 years, the role of specific immunotherapy (SIT) in pediatric asthma treatment is still controversial. We assessed the effects of a 3‐year period of subcutaneous administration of a standardized preparation of Dermatophagoides pteronyssinus ( D pt ) on the respiratory health in a group of asthmatic children monosensitized to house dust mite (HDM). Methods: A randomized clinical trial was performed after 1‐year run‐in period. Fifteen children receiving SIT for HDM and 14 controls (four drop‐outs), matched for age, allergen sensitization, asthma severity, lung function, and non‐specific bronchial reactivity (BHR), were studied during the 3‐year treatment period. During the whole trial, respiratory symptoms, pharmacological and respiratory function parameters were regularly evaluated. Skin prick tests and methacholine challenge were performed at the beginning and end of the study. Results: In the SIT group significant improvement in asthmatic symptoms and marked reduction in drug intake was observed. The SIT group also showed a significant decrease in non‐specific bronchial BHR. No new sensitivity occurred during the study period in the SIT group only. No major local or systemic side‐effects were reported during the study. Conclusions: Our results confirm that SIT is effective in asthmatic children sensitive to mites. It is associated with a decrease in BHR and it may prevent the development of new sensitizations in monosensitized subjects.