tbuckley/cabot-search huggingface dataset:
Impaired early left ventricular relaxation in coronary artery disease: effects of intracornary nifedipine.
Authors: M F Rousseau, C Veriter, J M Detry, L Brasseur, H Pouleur
Journal: Circulation (1980)

It has been shown that the maximal rate of left ventricular (LV) relaxation is impaired in patients with coronary artery disease (CAD) under basal conditions. To test the hypothesis that this impaired LV relaxation could be related to viable but metabolically abnormal myocardium, we studied the time course of isovolumic LV pressure fall in 21 patients with CAD and in 13 control subjects under basal conditions. This study was repeated after intracoronary injection of the calcium antagonist nifedipine (N) in 11 patients with CAD and in eight controls. Our data showed that isovolumic pressure fall was biexponential in 20 of 21 CAD patients and in six of 13 controls. Moreover, the time constant of isovolumic pressure fall during the first 40 msec after peak (negative) dP/dt (T1) was significantly greater in CAD patients than in controls (62 +/- 3 vs 44 +/- 1 msec, p < 0.002); the time constant of pressure fall during the 40-80 msec after peak (negative) dP/dt (T2) was similar in both groups ( 42 +/- 2 vs 39 +/- 2 msec, NS). Thirty seconds after injection of nifedipine, T1 and T2, were significantly prolonged in patients with CAD (14 msec and 16 msec, respectively, p < 0.005) and in controls 12 msec and 14 msec, respectively, p < 0.05), and a negative inotropic effect was observed in both groups (peak (positive) dP/dt - 16% in controls and -23% in CAD patients, p < 0.01). At rest, impairment of isovolumic relaxation in CAD patients is mainly limited to the first 40 msec after peak (negative) dP/dt, suggesting a dyssynchronous wall motion. This impairment of LV relaxation is better identified by T1 than by peak (negative) dP/dt in individual patients, and cannot be improved by administration of a calcium antagonist.
Randomised controlled trial of labouring in water compared with standard of augmentation for management of dystocia in first stage of labour
Authors: Elizabeth R Cluett, Ruth M Pickering, Kathryn Getliffe, Nigel James St George Saunders
Journal: BMJ (2004)

<h3>Abstract</h3> <b>Objectives</b> To evaluate the impact of labouring in water during first stage of labour on rates of epidural analgesia and operative delivery in nulliparous women with dystocia. <b>Design</b> Randomised controlled trial. <b>Setting</b> University teaching hospital in southern England. <b>Participants</b> 99 nulliparous women with dystocia (cervical dilation rate &lt; 1 cm/hour in active labour) at low risk of complications. <b>Interventions</b> Immersion in water in birth pool or standard augmentation for dystocia (amniotomy and intravenous oxytocin). <b>Main outcome measures</b> Primary: epidural analgesia and operative delivery rates. Secondary: augmentation rates with amniotomy and oxytocin, length of labour, maternal and neonatal morbidity including infections, maternal pain score, and maternal satisfaction with care. <b>Results</b> Women randomised to immersion in water had a lower rate of epidural analgesia than women allocated to augmentation (47% <i>v</i> 66%, relative risk 0.71 (95% confidence interval 0.49 to 1.01), number needed to treat for benefit (NNT) 5). They showed no difference in rates of operative delivery (49% <i>v</i> 50%, 0.98 (0.65 to 1.47), NNT 98), but significantly fewer received augmentation (71% <i>v</i> 96%, 0.74 (0.59 to 0.88), NNT 4) or any form of obstetric intervention (amniotomy, oxytocin, epidural, or operative delivery) (80% <i>v</i> 98%, 0.81 (0.67 to 0.92), NNT 5). More neonates of women in the water group were admitted to the neonatal unit (6 <i>v</i> 0, P = 0.013), but there was no difference in Apgar score, infection rates, or umbilical cord pH. <b>Conclusions</b> Labouring in water under midwifery care may be an option for slow progress in labour, reducing the need for obstetric intervention, and offering an alternative pain management strategy.
The Incidence of Type 1 Diabetes in the Age Group 0–39 Years Has Not Increased in Antwerp (Belgium) Between 1989 and 2000
Authors: Ilse Weets, Ivo H. De Leeuw, Marc V.L. Du Caju, Raoul Rooman, Bart Keymeulen, Chantal Mathieu, Raoul Rottiers, Jean-Claude Daubresse, Danielle Rocour-Brumioul, Daniel G. Pipeleers, Frans K. Gorus
Journal: Diabetes Care (2002)

OBJECTIVE—A worldwide increase in the incidence of childhood type 1 diabetes has been observed. Because in various countries the majority of new type 1 diabetic patients are diagnosed in adulthood, we investigated whether the rising incidence of this disorder in children reflects a global increase in the incidence of diabetes or a shift toward earlier clinical presentation. RESEARCH DESIGN AND METHODS—The incidence of type 1 diabetes presenting before age 40 years was prospectively measured in the Antwerp district over a 12-year period (1989–2000). The completeness of ascertainment was evaluated by the capture-recapture method. Trends in incidence during the study period were analyzed by Poisson regression. RESULTS—The incidence of type 1 diabetes diagnosed before age 40 years remained constant over the 12-year period, averaging 9.9 cases per 100,000 individuals per year. The incidence was similar in both sexes under age 15 years, but a marked male excess was noted for adult-onset disease, in particular after age 20 years, resulting in a male-to-female ratio of 0.9 under age 15 years vs. 1.6 thereafter (P = 0.001). During the 12-year observation period, there was a significant tendency toward increasing incidence under age 15 years at the expense of a decreasing incidence between ages 15 and 40 years (P = 0.025). The annual increase in incidence averaged 1.8% under age 15 years and 5.0% under age 5 years (P = 0.06). CONCLUSIONS—Our results indicate that in Belgium, the increasing incidence of childhood type 1 diabetes—especially for children under age 5 years—is not attributable to a global increase in disease incidence, but rather to earlier clinical manifestation. The results suggest that an environmental factor may preferentially accelerate the subclinical disease process in young diabetes-prone subjects.
Pathways of processing of the gastrin precursor in rat antral mucosa.
Authors: A Varro, S Voronina, G J Dockray
Journal: Journal of Clinical Investigation (1995)

The precursor of the acid-stimulating hormone gastrin gives rise to multiple peptides differing markedly in biological activity, but the relevant biosynthetic pathways are poorly understood. We have used antibodies to amidated gastrins, gastrins with COOH-terminal glycine (Gly) gastrins with COOH-terminal hydroxyglycine (GlyOH) and to the COOH terminus of progastrin, to immunoprecipitate peptides labeled with [35S]sulfate or [3H]tyrosine during incubation of rat antral mucosa in vitro. Labeled progastrin was detectable after 30 min of continuous incubation with isotopic precursors, G34 and G34-Gly after 60 min, and G17 and G17-Gly after 120 min. Pulse chase experiments indicated that progastrin is converted to G34-Gly which then follows one of two pathways: (a) hydroxylation of COOH-terminal Gly and conversion to G34 followed by cleavage yielding G17, or (b) cleavage to G17-Gly. The kinetics of G17-Gly and G17 labeling were similar, suggesting that G17-Gly is a product in its own right, and not simply an intermediate in G17 synthesis. Since the two peptides are reported to have distinct biological activities, they appear to be alternative mature products of progastrin processing.
A Preoperative Nomogram for Disease Recurrence Following Radical Prostatectomy for Prostate Cancer
Authors: Michael W. Kattan, James A. Eastham, Alan M. F. Stapleton, Thomas M. Wheeler, Peter T. Scardino
Journal: JNCI Journal of the National Cancer Institute (1998)

Few published studies have combined clinical prognostic factors into risk profiles that can be used to predict the likelihood of recurrence or metastatic progression in patients following treatment of prostate cancer. We developed a nomogram that allows prediction of disease recurrence through use of preoperative clinical factors for patients with clinically localized prostate cancer who are candidates for treatment with a radical prostatectomy.By use of Cox proportional hazards regression analysis, we modeled the clinical data and disease follow-up for 983 men with clinically localized prostate cancer whom we intended to treat with a radical prostatectomy. Clinical data included pretreatment serum prostate-specific antigen levels, biopsy Gleason scores, and clinical stage. Treatment failure was recorded when there was clinical evidence of disease recurrence, a rising serum prostate-specific antigen level (two measurements of 0.4 ng/mL or greater and rising), or initiation of adjuvant therapy. Validation was performed on a separate sample of 168 men, also from our institution.Treatment failure (i.e., cancer recurrence) was noted in 196 of the 983 men, and the patients without failure had a median follow-up of 30 months (range, 1-146 months). The 5-year probability of freedom from failure for the cohort was 73% (95% confidence interval = 69%-76%). The predictions from the nomogram appeared accurate and discriminating, with a validation sample area under the receiver operating characteristic curve (i.e., comparison of the predicted probability with the actual outcome) of 0.79.A nomogram has been developed that can be used to predict the 5-year probability of treatment failure among men with clinically localized prostate cancer treated with radical prostatectomy.
The role of submucosal oedema in increased peripheral airway resistance by intravenous volume loading in dogs
Authors: GJ Tang, AN Freed
Journal: European Respiratory Journal (1994)

Pulmonary congestion leads to an increase in airway resistance. It is still unknown whether this is due to vascular engorgement or to submucosal oedema. The present study was designed to determine the relative contribution of these two potential mechanisms. We examined the effect of intravenous volume loading on canine peripheral airway resistance (Rp). Bronchoscopes were wedged in contralateral sublobar segments and used to record Rp during rapid infusion of normal saline. Volume loading with normal saline increased pulmonary capillary wedge pressure (PCWP) and Rp. Unlike normal saline, dextran 70 did not increase Rp when infused at a rate that produced similar changes in PCWP. During infusion of normal saline, delta Rp was significantly enhanced in lung segments previously challenged with dry air when compared to contralateral control lungs, unexposed to dry air, and the use of dextran 70 significantly reduced this effect. Vasoconstriction with phenylephrine significantly decreased baseline Rp, but did not completely reverse the effect of fluid infusion. In addition, in lung segments exposed to dry air, delta Rp was significantly greater after volume loading and treatment with phenylephrine when compared to contralateral control lung. Finally, muscarinic receptor blockade was ineffective in preventing Rp from increasing during infusion of normal saline. Our results suggest that volume loading-induced increases in Rp are not caused by either vascular engorgement or the stimulation of muscarinic receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
Morbidity in nocturnal asthma: sleep quality and daytime cognitive performance.
Authors: M F Fitzpatrick, H Engleman, K F Whyte, I J Deary, C M Shapiro, N J Douglas
Journal: Thorax (1991)

Most patients with asthma waken with nocturnal asthma from time to time. To assess morbidity in patients with nocturnal asthma nocturnal sleep quality, daytime sleepiness, and daytime cognitive performance were measured prospectively in 12 patients with nocturnal asthma (median age 43 years) and 12 age and intellect matched normal subjects. The median (range) percentage overnight fall in peak expiratory flow rate (PEF) was 22 (15 to 50) in the patients with nocturnal asthma and 4 (-4 to 7) in the normal subjects. The patients with asthma had poorer average scores for subjective sleep quality than the normal subjects (median paired difference 1.1 (95% confidence limits 0.1, 2.3)). Objective overnight sleep quality was also worse in the asthmatic patients, who spent more time awake at night (median difference 51 (95% CL 8.1, 74) minutes), had a longer sleep onset latency (12 (10, 30) minutes), and tended to have less stage 4 (deep) sleep (-33 (-58, 4) minutes). Daytime cognitive performance was worse in the patients with nocturnal asthma, who took a longer time to complete the trail making tests (median difference 62 (22, 75) seconds) and achieved a lower score on the paced serial addition tests (-10 (-24, -3)). Mean daytime sleep latency did not differ significantly between the two groups (2 (-3, 7) minutes). It is concluded that hospital outpatients with stable nocturnal asthma have impaired sleep quality and daytime cognitive performance even when having their usual maintenance asthma treatment.
Glutamine synthetase expression as a valuable marker of epilepsy and longer survival in newly diagnosed glioblastoma multiforme
Authors: Anna Rosati, Pietro Luigi Poliani, Alice Todeschini, Manuela Cominelli, Daniela Medicina, Marco Cenzato, Edda Lucia Simoncini, Stefano Maria Magrini, Michela Buglione, Salvatore Grisanti, Alessandro Padovani
Journal: Neuro-Oncology (2013)

Glutamine synthetase (GS) is an astrocytic enzyme catalyzing the conversion of glutamate and ammonia to glutamine. Its up-regulation has been related to higher tumor proliferation and poor prognosis in extra-cerebral tumors. We have previously reported a GS deficiency in patients with glioblastoma multiforme (GBM) who also developed epilepsy, which is a favorable prognostic factor in glioma. Here, we investigated the prognostic value of GS expression in patients with GBM with or without epilepsy and its correlation with survival. We conducted a clinical and histopathological study on 83 (52 males) consecutive patients with newly diagnosed GBM. Immunohistochemical expression of GS was scored semi-quantitatively on the basis of cell number, staining intensity, and distribution of immunoreactive cells. Several clinical and neuropathological variables were analyzed in relation to survival and GS expression. Median age at diagnosis was 62 years. At the last evaluation, with a median follow-up of 11.5 months (range, 1.5–58 months), 5 patients (6%) were still alive and 78 (94%) were dead. GS expression patterns in neoplastic cells were inversely correlated to the presence of epilepsy (P < .0001 for intensity and P < .009 for homogeneity of GS distribution, respectively). Univariate analysis showed that RPA score, epilepsy, O6-methylguanine-DNA methyltransferase (MGM)T status, application of Stupp protocol, and GS intensity pattern had a significant impact on survival. Absent/low intensity of GS expression was significantly associated with a longer survival in both uni- (19 vs 8 months; P < .0005) and multivariate (P = .003) analyses. Absent/low-intensity GS expression pattern represents a valuable biomarker of both epilepsy and overall survival in GBM.
Dose thresholds and duration of the local anhidrotic effect of botulinum toxin injections: measured by sudometry
Authors: C. Braune, F. Erbguth, F. Birklein
Journal: British Journal of Dermatology (2001)

Background Local injections of botulinum toxin type A (BTX-A) have been used successfully to treat focal hyperhidrosis, but because experimental data were lacking, doses have been chosen arbitrarily or empirically. Objectives To analyse dose dependency and duration of BTX-A-derived suppression of sweat gland activity. Methods Employing a standardized scheme (four injections, square 2 × 2 cm), different doses of BTX-A [Dysport®; 2·5–120 mouse units (MU)] were injected subcutaneously at the lateral aspects of both of the lower legs in 15 healthy volunteers. Sweat tests were performed before, and 3 weeks and 6 months after, BTX-A injections. Sweating was visualized by staining with iodine starch, and quantified by capacitance hygrometry after carbachol iontophoresis, the quantitative sudomotor axon reflex test (QSART). Results Iodine starch staining indicated a threshold dose of 10 MU (2·5 MU cm−2) leading to visible anhidrotic skin spots after 3 weeks in all subjects. This was maintained for 6 months with doses of 50 MU (12·5 MU cm−2) or higher, but the size of the anhidrotic skin area decreased over time (P < 0·001) indicating partial recovery at the edges. After 3 weeks QSART was significantly reduced (P < 0·02) and completely suppressed by doses of 80 MU (20 MU cm−2) or more, although after 6 months QSART increased again to pre-BTX-A levels (P < 0·001). Both methods indicated that the suppression of sweating is dose dependent (QSART: r = −0·70, P < 0·001; iodine starch staining: r = 0·74, P < 0·001). Conclusions Our findings suggest that BTX-A effectiveness can be quantified by testing sudomotor function. For the first time threshold doses for the suppression of sweating have been defined.
Sensitisation to airborne moulds and severity of asthma: cross sectional study from European Community respiratory health survey
Authors: M. Zureik
Journal: BMJ (2002)

<h3>Abstract</h3> <b>Objective:</b> To assess whether the severity of asthma is associated with sensitisation to airborne moulds rather than to other seasonal or perennial allergens. <b>Design:</b> Multicentre epidemiological survey in 30 centres. <b>Setting:</b> European Community respiratory health survey. <b>Participants:</b> 1132 adults aged 20-44 years with current asthma and with skin prick test results. <b>Main outcome measure:</b> Severity of asthma according to score based on forced expiratory volume in one second, number of asthma attacks, hospital admissions for breathing problems, and use of corticosteroids in past 12 months. <b>Results:</b> The frequency of sensitisation to moulds (<i>Alternaria alternata</i> or <i>Cladosporium herbarum</i>, or both) increased significantly with increasing asthma severity (odds ratio 2.34 (95% confidence interval 1.56 to 3.52) for either for severe <i>v</i> mild asthma). This association existed in all of the study areas (gathered into regions), although there were differences in the frequency of sensitisation. There was no association between asthma severity and sensitisation to pollens or cats. Sensitisation to <i>Dermatophagoides pteronyssinus</i> was also positively associated with severity. In multivariable logistic regressions including sensitisation to moulds, pollens, <i>D pteronyssinus</i>, and cats simultaneously, the odds ratios for sensitisation to moulds were 1.48 (0.97 to 2.26) for moderate <i>v</i> mild asthma and 2.16 (1.37 to 3.35) for severe <i>v</i> mild asthma (P&lt;0.001 for trend). <b>Conclusions:</b> Sensitisation to moulds is a powerful risk factor for severe asthma in adults. This should be taken into account in primary prevention, management, and patients9 education.
Offering results to research participants
Authors: S Danielle MacNeil, Conrad V Fernandez
Journal: BMJ (2006)

effectiveness of screening in practice on the basis of this study, but it would probably be in the region of £1500-£2000 per successful treatment, based on a cost difference of £50 for testing and eradication and a response rate of 3% compared with no screening.In contrast, the CADET-Hp study found that a test and treat strategy reduced the cost per successful treatment by $C387 (£188; $333; €275) (-$C1707 to $C607). 12ane and colleagues provide further evidence that eradicating H pylori is beneficial.But their study does not greatly change the evidence base of the 2004 NICE guideline which recommended H pylori eradication as first choice in endoscopically proved peptic ulcer and functional dyspepsia and as a treatment option in uninvestigated dyspepsia.
Inhibition of granulocyte activation by surfactant in a 2‐yr-old female with meningococcus-induced ARDS
Authors: F.K. Tegtmeyer, J. Möller, P. Zabel
Journal: European Respiratory Journal (2002)

Activated polymorphonuclear neutrophils (PMNs) play a crucial role in acute respiratory distress syndrome (ARDS) via extracellular release of reactive cell products such as elastase. Surfactant has proved valuable in restoring lung function in ARDS. The significance of its immunomodulatory properties with respect to this effect has not yet been clarified. The aim of the present study was to determine the anti-inflammatory effects of surfactant administration in an infant with ARDS. During the acute phase of ARDS in a 2‐yr-old female, levels of PMN-derived elastase complexed with α 1 ‐protease inhibitor (E‐α 1 PI) were measured in both arterial and central venous blood samples obtained simultaneously. The results were correlated with oxygen demand and plasma concentrations of tumour necrosis factor‐α (TNF‐α) and interleukin‐6 (IL‐6) after endotracheal administration of surfactant (Alveofact® 60 mg·kg·body weight −1 ). In the present case, for the first time, a higher E‐α 1 PI concentration was detected in arterial blood (4.51 mg·L −1 ) than in central venous blood (2.28 mg·L −1 ). After administration of surfactant, these concentrations and the arteriovenous difference decreased, indicating that during ARDS, most PMN degranulation takes place in the pulmonary vascular bed and is inhibited by surfactant administration. Simultaneously, TNF‐α and IL‐6 plasma concentrations decreased within hours and lung function was restored. This local inhibition of polymorphonuclear neutrophil activation by exogenous surfactant may play a key role in the early improvement in lung function after surfactant administration.
A model of psychosocial hypertension showing reversibility and progression of cardiovascular complications.
Authors: J P Henry, P M Stephens, G A Santisteban
Journal: Circulation Research (1975)

The sequence of pathophysiological changes that can result from the stimulating effects of a sustained disturbance of the social environment was studied in ten colonies of socially deprived mice. Sixteen formerly isolated males were placed with 16 normal females in population cages consisting of seven intercommunicating boxes. Six of these socially disturbed 32-member colonies were terminated after periods of interaction ranging from 2 days to 9 months. The remaining four were terminated a month or more after the males had been returned to individual isolation. Indirect blood pressure measurements, body and heart weights, and sections of hearts and aortas were studied in the males. Following the shorter exposures, blood pressure reverted to normal in a few days. Exposure of 6 months or more were associated with unchanged body weights and sustained increases in heart weight and blood pressure readings. In addition, there was a significant development of aortic arteriosclerosis and myocardial fibrosis. These changes persisted despite prolonged return to isolation.