tbuckley/cabot-search huggingface dataset:
No evidence of persisting measles virus in the intestinal tissues of patients with inflammatory bowel disease
Authors: Y. D'Souza, S. Dionne, E. G Seidman, A. Bitton, B. J Ward
Journal: Gut (2007)

and increased body weight appropriately.Tissue samples showed a progressive increase in the amount of cell infiltrate in the matrix (table 1, fig 1).After 2 weeks, acute inflammation was replaced by full-thickness ingrowths of capillaries and myofibroblasts.Epithelial regeneration into the anastomosis was first seen at 2 weeks, and well-formed branching crypts were seen at 4 weeks of transplantation.Goblet cells and absorptive cells with brush border were present at 4 months of transplantation.Morphologically intact regenerated mucosa extending across the anastomosis to the grafts was observed at 6 months of transplantation.To date, there is limited literature on the bioengineered intestine.Vacanti et al, 6-8 developed a cystic structure in which neomucosa forms in a biodegradable polymer in rodents.Once formed, the neointestinal cyst is anastomosed in continuity with the native bowel without causing feeding problems, but some animals had small bare areas of the cysts that lacked neomucosa. 7 We did not report such bare areas in our model; furthermore, there was progressive growth of the neomucosa in the ADM over time.It is possible that immediate contact of the ADM scaffold with the intestinal structures and with luminal content provided trophic stimuli for the new intestinal segment. 9Another possible factor for the observed growth in our model may be the effects of small-bowel resection on the development of neointestine.It is well known that post resection gut mucosa growth factors have a stimulatory effect on intestinal regeneration. 10 In conclusion, we have demon- strated that ADM can be successfully used as a scaffold to generate a bioartificial new intestinal segment in vivo, and we propose this method as a basis for developing new intestinal elongation techniques.
Acupuncture for Chronic Knee Pain
Authors: Rana S. Hinman, Paul McCrory, Marie Pirotta, Ian Relf, Andrew Forbes, Kay M. Crossley, Elizabeth Williamson, Mary Kyriakides, Kitty Novy, Ben R. Metcalf, Anthony Harris, Prasuna Reddy, Philip G. Conaghan, Kim L. Bennell
Journal: JAMA (2014)

<h3>Importance</h3> There is debate about benefits of acupuncture for knee pain. <h3>Objective</h3> To determine the efficacy of laser and needle acupuncture for chronic knee pain. <h3>Design, Setting, and Participants</h3> Zelen-design clinical trial (randomization occurred before informed consent), in Victoria, Australia (February 2010-December 2012). Community volunteers (282 patients aged ≥50 years with chronic knee pain) were treated by family physician acupuncturists. <h3>Interventions</h3> No acupuncture (control group, n = 71) and needle (n = 70), laser (n = 71), and sham laser (n = 70) acupuncture. Treatments were delivered for 12 weeks. Participants and acupuncturists were blinded to laser and sham laser acupuncture. Control participants were unaware of the trial. <h3>Main Outcomes and Measures</h3> Primary outcomes were average knee pain (numeric rating scale, 0 [no pain] to 10 [worst pain possible]; minimal clinically important difference [MCID], 1.8 units) and physical function (Western Ontario and McMaster Universities Osteoarthritis Index, 0 [no difficulty] to 68 [extreme difficulty]; MCID, 6 units) at 12 weeks. Secondary outcomes included other pain and function measures, quality of life, global change, and 1-year follow-up. Analyses were by intention-to-treat using multiple imputation for missing outcome data. <h3>Results</h3> At 12 weeks and 1 year, 26 (9%) and 50 (18%) participants were lost to follow-up, respectively. Analyses showed neither needle nor laser acupuncture significantly improved pain (mean difference; −0.4 units; 95% CI, −1.2 to 0.4, and −0.1; 95% CI, −0.9 to 0.7, respectively) or function (−1.7; 95% CI, −6.1 to 2.6, and 0.5; 95% CI, −3.4 to 4.4, respectively) compared with sham at 12 weeks. Compared with control, needle and laser acupuncture resulted in modest improvements in pain (−1.1; 95% CI, −1.8 to −0.4, and −0.8; 95% CI, −1.5 to −0.1, respectively) at 12 weeks, but not at 1 year. Needle acupuncture resulted in modest improvement in function compared with control at 12 weeks (−3.9; 95% CI, −7.7 to −0.2) but was not significantly different from sham (−1.7; 95% CI, −6.1 to 2.6) and was not maintained at 1 year. There were no differences for most secondary outcomes and no serious adverse events. <h3>Conclusions and Relevance</h3> In patients older than 50 years with moderate or severe chronic knee pain, neither laser nor needle acupuncture conferred benefit over sham for pain or function. Our findings do not support acupuncture for these patients. <h3>Trial Registration</h3> anzctr.org.au Identifier:ACTRN12609001001280
Hepatitis C screening: Getting it right
Authors: Brian R. Edlin
Journal: Hepatology (2012)

Hepatitis C is the most prevalent bloodborne viral disease in the United States and the deadliest. This year, the U.S. Preventive Services Task Force (USPSTF) will update its 2004 hepatitis C guideline, which recommends against screening asymptomatic adults for hepatitis C. This guideline has hampered public health efforts to encourage screening and identify and refer infected persons for care by declaring that such interventions were not supported by the evidence. A draft revision of the guideline, released on November 26, 2012, concludes that testing persons born between 1945 and 1965 probably has at least a small net benefit, but stops short of definitively recommending that this cohort be screened. This article examines the Task Force's process for writing its guidelines. It recommends that the Task Force adopt a balanced approach to evaluating the benefits and harms of screening; use the preponderance of the evidence as a standard for evaluating interventions that target serious public health problems; be transparent about the value judgments that go into its decisions; consider the wide variation in disease prevalence in diverse patient populations; and recommend screening asymptomatic adults for hepatitis C.By taking a broader view of the evidence, the Task Force can write new guidelines that will serve efforts to curb the hepatitis C epidemic, rather than frustrate them.
Uterine peristalsis during the follicular phase of the menstrual cycle: effects of oestrogen, antioestrogen and oxytocin
Authors: G Kunz
Journal: Human Reproduction Update (1998)

Uterine peristalsis directing sustained and rapid sperm transport from the external cervical os or the cervical crypts to the isthmic part of the tube ipsilateral to the dominant follicle, changes in direction and frequency during the menstrual cycle, with lowest activity during menstruation and highest activity at mid cycle. It was therefore suggested that uterine peristalsis is under the control of the dominant follicle with the additional involvement of oxytocin. To test this hypothesis, vaginal sonography of uterine peristalsis was performed in the early, mid and late proliferative phases, respectively, of cycles of women treated with oestradiol valerate and with human menopausal gonadotrophin following pituitary downregulation, with clomiphene citrate and with intravenous oxytocin, respectively. Administration of oestradiol valerate resulted in oestradiol serum concentrations comparable with the normal cycle with a simulation of the normal frequency of peristaltic contractions. Elevated oestradiol concentrations and bolus injections of oxytocin resulted in a significant increase in the frequency of peristaltic contractions in the early and mid follicular phases, respectively. Clomiphene tended, though insignificantly so, to suppress the presence of elevated oestradiol concentrations. In the late follicular phase of the cycle extremely elevated oestradiol concentrations as well as the injection of oxytocin resulted only in an insignificant further increase of peristaltic frequency. In the normal cycles, as well as during extremely elevated oestradiol concentrations and following oxytocin administration, the peristaltic contractions were always confined to the subendometrial layer of the muscular wall. The results and the review of the literature indicate that uterine peristalsis during the follicular phase of the menstrual cycle is controlled by oestradiol released from the dominant follicle with the probable involvement of oxytocin, which is presumably stimulated together with its receptor within the endometrial-subendometrial unit and therefore acting in an autocrine/paracrine fashion. Since unphysiological stimulation with oestradiol and oxytocin did not significantly increase the frequency of uterine peristalsis in the late follicular phase of the cycle it is assumed that normal preovulatory frequency of uterine peristalsis is at a level which cannot be significantly surpassed due to phenomena of refractoriness of the system.
No Downstaging After Short-Term Preoperative Radiotherapy in Rectal Cancer Patients
Authors: C.A.M. Marijnen, I.D. Nagtegaal, E. Klein Kranenbarg, J. Hermans, C.J.H. van de Velde, J.W.H. Leer, J.H.J.M. van Krieken
Journal: Journal of Clinical Oncology (2001)

PURPOSE: In retrospective studies, total mesorectal excision (TME) surgery has been demonstrated to result in a reduction in the number of local recurrences of rectal cancer. Reports on improved local control after preoperative, hypofractionated radiotherapy have led to the introduction of a randomized multicenter trial to evaluate the effect of TME surgery with and without preoperative radiotherapy. Treatment with preoperative radiotherapy might have an effect on the pathologic characteristics that determine staging of rectal cancer. We investigated the occurrence of downstaging in rectal cancer patients treated with and without preoperative radiotherapy. PATIENTS AND METHODS: We analyzed the differences in tumor size, number of examined lymph nodes, tumor-node-metastasis stage, and histopathologic features in 1,321 patients entered onto a randomized trial. The trial compared preoperative radiotherapy (5 × 5 Gy) followed by TME surgery with TME surgery alone. Patients who had an interval of more than 10 days between the start of radiotherapy and surgery were excluded from analysis. RESULTS: Differences were observed in tumor size (P &lt; .001) and total number of examined lymph nodes (P &lt; .001). No difference in tumor or node classification was detected. The irradiated group demonstrated more poorly differentiated tumors as well as more mucinous tumors. CONCLUSION: In rectal cancer patients, short-term, preoperative radiotherapy with 5 × 5 Gy does not lead to downstaging if the interval between the start of radiotherapy and surgery does not exceed 10 days.
Simvastatin suppresses glomerular cell proliferation and macrophage infiltration in rats with mesangial proliferative nephritis.
Authors: A Yoshimura, K Inui, T Nemoto, S Uda, Y Sugenoya, S Watanabe, N Yokota, T Taira, S Iwasaki, T Ideura
Journal: Journal of the American Society of Nephrology (1998)

Inhibition of 3-hydro-3-methylglutaryl coenzyme A reductase inhibits the production of mevalonate and has been shown to suppress proliferation in many cell types. Therefore, 3-hydro-3-methylglutaryl coenzyme A reductase inhibitors may have a beneficial effect in glomerular disease, because glomerular cell proliferation is a central feature in the active glomerular injury. This study examines the effect of simvastatin on glomerular pathology in a rat mesangial proliferative glomerulonephritis (GN) induced by anti-thymocyte antibody (anti-Thy 1.1 GN). There was no difference in the degree of the antibody and complement-mediated initial injuries between simvastatin-treated and control GN rats. The most pronounced feature of simvastatin-treated GN was the suppression of the early glomerular cell proliferation. The proliferative activity was maximal at day 4 after disease induction (26.5+/-7.0 of proliferating cell nuclear antigen-positive cells/glomerulus); however, approximately 70% of proliferation was suppressed by simvastatin treatment. At day 4 after disease induction, simvastatin administration also decreased alpha-smooth muscle actin expression in the glomerulus, which is a marker for mesangial cell activation. Inhibition of monocyte/macrophage recruitment into glomeruli by simvastatin was also a prominent feature. There was a 30% decrease in the number of glomerular ED-1+ cells by simvastatin treatment at day 2 after disease induction. Furthermore, simvastatin remarkably suppressed subsequent mesangial matrix expansion and type IV collagen accumulation in glomeruli. We also found that the platelet-derived growth factor expression was reduced in simvastatin-treated nephritic rats, which might simply reflect the reduction in mesangial cell proliferation and mesangial cellularity. There was no significant difference in plasma cholesterol or triglyceride levels between simvastatin- and vehicle-treated nephritic rats at day 2 and day 4, which corresponded to the times when simvastatin treatment resulted in a reduction in mesangial cell proliferation. In conclusion, this is the first report to find that mesangial cell proliferation and matrix expansion have been blocked by simvastatin in vivo. The protective effect of simvastatin in the matrix expansion in anti-Thy1.1 GN was partly by inhibition of mesangial cell proliferation and monocyte/ macrophage recruitment into glomeruli, which were independent of a change in circulating lipids.
An inhaled steroid improves markers of airway inflammation in patients with mild asthma
Authors: A Jatakanon, S Lim, KF Chung, PJ Barnes
Journal: European Respiratory Journal (1998)

Airway inflammation can be demonstrated in mildly asthmatic patients who are not treated with inhaled steroids. Current guidelines recommend that inhaled steroids should be introduced in mild asthmatics who use an inhaled beta2-agonist more than once daily. It was postulated that inhaled steroids can have anti-inflammatory effects in patients with even milder disease. The effect of 4 weeks of treatment with budesonide (800 microg twice daily by Turbohaler) was studied in 10 steroid-naive mildly asthmatic patients (forced expiratory volume in one second (FEV1) = 96+/-1.4% predicted) who required an inhaled beta2-agonist less than one puff daily, in a double-blind, placebo-controlled, crossover fashion. Spirometry, exhaled nitric oxide (NO), bronchial responsiveness (provocative concentration causing a 20% fall in FEV1 (PC20)), and sputum induction were performed before and after each treatment period. Following budesonide treatment, there were significant improvements in FEV1, and PC20, in association with a significant reduction in the percentage of eosinophils in induced sputum. Exhaled NO levels tended towards reduction, but the change was nonsignificant. There were also nonsignificant reductions in sputum eosinophil cationic protein and tumour necrosis factor-alpha levels. In conclusion inhaled budesonide can lead to improvements in noninvasive markers of airway inflammation, in association with a small improvement in lung function, even in mildly asthmatic patients who require an inhaled beta2-agonist less than once daily. This suggests a potential benefit of inhaled corticosteroids, even in relatively asymptomatic asthma.
Prospective Study of Fluoxetine Treatment and Suicidal Behavior in Affectively Ill Subjects
Authors: Andrew C. Leon, Martin B. Keller, Meredith G. Warshaw, Timothy I. Mueller, David A. Solomon, William Coryell, Jean Endicott
Journal: American Journal of Psychiatry (1999)

There has been speculation in the literature about a link between fluoxetine use and suicidal behavior. The authors of this study hypothesized that there is no elevation in risk of suicidal behavior associated with use of fluoxetine.The data come from the National Institute of Mental Health Collaborative Depression Study, a prospective, naturalistic follow-up of persons who presented for treatment of affective disorders. The analyses included data on 643 subjects who were followed up after fluoxetine was approved by the Food and Drug Administration in December 1987 for the treatment of depression.Nearly 30% (N = 185) of the study group was treated with fluoxetine at some point during the follow-up period. Relative to the other subjects, those who were subsequently treated with fluoxetine had onset of affective illness at a younger age and, after intake into the study and before 1988, had elevated rates of suicide attempts before fluoxetine treatment. A mixed-effects survival analysis that incorporated treatment exposure time, multiple treatment trials, and multiple suicide attempts per subject showed that relative to no treatment, use of fluoxetine and use of other somatic antidepressants were associated with nonsignificant reductions in the likelihood of suicide attempts or completions. Severity of psychopathology was strongly associated with elevated risk, and each suicide attempt after intake into the Collaborative Depression Study was associated with a marginally significant increase in risk of suicidal behavior.The results do not support the speculation that fluoxetine increases the risk of suicide. Rather, there was a nonsignificant reduction in risk of suicidal behavior among patients treated with fluoxetine, even though those subjects were more severely ill before treatment with fluoxetine.
The cost effectiveness of behavioural graded activity in patients with osteoarthritis of hip and/or knee
Authors: V. M H Coupe, C. Veenhof, M. W van Tulder, J. Dekker, J. W J Bijlsma, C. H M Van den Ende
Journal: Annals of the Rheumatic Diseases (2006)

To evaluate whether exercise treatment based on behavioural graded activity comprising booster sessions is a cost-effective treatment for patients with osteoarthritis of the hip and/or knee compared with usual care.
Inducible Podocyte Injury and Proteinuria in Transgenic Zebrafish
Authors: Weibin Zhou, Friedhelm Hildebrandt
Journal: Journal of the American Society of Nephrology (2012)

Damage or loss of podocytes causes glomerulosclerosis in murine models, and mutations in podocyte-specific genes cause nephrotic syndrome in humans. Zebrafish provide a valuable model for kidney research, but disruption of pronephroi leads to death within a few days, thereby preventing the study of CKD. In this study, we generated an inducible model of podocyte injury in zebrafish (pod::NTR-mCherry) by expressing a bacterial nitroreductase, which converts metronidazole to a cytotoxin, specifically in podocytes under the control of the zebrafish nphs2/podocin promoter. Application of the prodrug metronidazole to the transgenic fish induces acute damage to the podocytes in pronephroi of larval zebrafish and the mesonephroi of adult zebrafish, resulting in foot-process effacement and podocyte loss. We also developed a functional assay of the glomerular filtration barrier by creating transgenic zebrafish expressing green fluorescent protein (GFP)-tagged vitamin D-binding protein (VDBP) as a tracer for proteinuria. In the VDBP-GFP and pod::NTR-mCherry double-transgenic fish, induction of podocyte damage led to whole-body edema, and the proximal tubules reabsorbed and accumulated VDBP-GFP that leaked through the glomeruli, mimicking the phenotype of human nephrotic syndrome. Moreover, expression of wt1b::GFP, a marker for the developing nephron, extended into the Bowman capsule in response to podocyte injury, suggesting that zebrafish have a podocyte-specific repair process known to occur in mammalian metanephros. These data support the use of these transgenic zebrafish as a model system for studies of glomerular pathogenesis and podocyte regeneration.
Insulin resistance associated with lower rates of weight gain in Pima Indians.
Authors: B A Swinburn, B L Nyomba, M F Saad, F Zurlo, I Raz, W C Knowler, S Lillioja, C Bogardus, E Ravussin
Journal: Journal of Clinical Investigation (1991)

Insulin resistance is commonly associated with obesity and noninsulin-dependent diabetes. Whereas it predicts the development of diabetes, its effect on body weight change is unknown. We measured glucose disposal rates at submaximally- and maximally-stimulating insulin concentrations in 192 nondiabetic Pima Indians and followed their weight change over 3.5 +/- 1.8 y (mean +/- SD).(a) Insulin-resistant subjects gained less weight than insulin-sensitive subjects (3.1 vs. 7.6 kg, P less than 0.0001). (b) The percent weight change per year correlated with glucose disposal at submaximally-(r = 0.19, P less than 0.01) and maximally-stimulating (r = 0.34, P less than 0.0001) insulin concentrations independent of sex, age, initial weight, and 24-h energy expenditure; the correlations were stronger for glucose oxidation than for glucose storage. (c) Weight gain was associated with an increase in insulin resistance more than four times that predicted from the cross-sectional data. We conclude that insulin resistance is associated with a reduced risk of weight gain in nondiabetic Pima Indians.
Overexpression of Cd40 Ligand in Murine Epidermis Results in Chronic Skin Inflammation and Systemic Autoimmunity
Authors: Annette Mehling, Karin Loser, Georg Varga, Dieter Metze, Thomas A. Luger, Thomas Schwarz, Stephan Grabbe, Stefan Beissert
Journal: The Journal of Experimental Medicine (2001)

CD40–CD40 ligand (L) interactions play a pivotal role in immune-mediated inflammatory responses via the activation of antigen-presenting cells (APCs). To investigate the effects of continuous activation of resident tissue APCs, in this case the Langerhans cells (LCs) of the skin, CD40L expression was targeted to the basal keratinocytes of the epidermis of mice using the keratin-14 promoter. Approximately 80% of the transgenic (Tg) mice spontaneously developed dermatitis on the ears, face, tail, and/or paws. Compared with littermates, Tgs had a &amp;gt;90% decrease in epidermal LCs yet increased numbers within the dermis suggestive of enhanced emigration of CD40-activated LCs. Tgs also displayed massive regional lymphadenopathy with increased numbers of dendritic cells and B cells. Moreover, a decrease in IgM and an increase in IgG1/IgG2a/IgG2b/IgE serum concentrations was detectable. Screening for autoantibodies revealed the presence of antinuclear antibodies and anti-dsDNA antibodies implicative of systemic autoimmunity. Accordingly, renal Ig deposits, proteinuria, and lung fibrosis were observed. Adoptive transfer of T cells from Tgs to nonTg recipients evoked the development of skin lesions similar to those found in the Tgs. Dermatitis also developed in B cell–deficient CD40L Tg mice. These findings suggest that in situ activation of LCs by CD40L in the skin not only leads to chronic inflammatory dermatitis but also to systemic mixed-connective-tissue-like autoimmune disorders, possibly by breaking immune tolerance against the skin.
Highly malignant tumor variants retain tumor-specific antigens recognized by T helper cells.
Authors: C Van Waes, J L Urban, J L Rothstein, P L Ward, H Schreiber
Journal: The Journal of Experimental Medicine (1986)

We have studied the components of a complex of tumor-specific antigens to determine if all of the components of the complex were lost during progression from a rather benign regressor tumor to a highly malignant (HM) cancer. We find that the HM tumor cells have lost antigens recognized by CTL but retained antigens recognized by Th cells. Immunization with variants expressing Th-defined antigens induced tumor-specific immunity to challenge with a parental variant that expressed a CTL-recognized target antigen, but did not induce immunity to challenge with the variant that expressed the Th-defined antigen alone. Together, these findings suggested that Th cells fail to exert direct selective pressure upon the tumor, resulting in retention of "lineage-specific," Th-recognized antigens by highly immunoselected variants. Possible advantage could be taken of this fact for the development of specific immunotherapy.