tbuckley/cabot-search huggingface dataset:
Antitussive and antibronchoconstriction actions of fenspiride in guinea-pigs
Authors: EA Laude, D Bee, O Crambes, P Howard
Journal: European Respiratory Journal (1995)

Fenspiride is a nonsteroidal anti-inflammatory agent, which we have previously shown to have an in vivo antibronchoconstrictor action in guinea pigs. We have currently studied this action using the constrictors Substance P, neurokinin A, citric acid and capsaicin in anaesthetized guinea-pigs. Fenspiride has also been reported to produce a subjective improvement in cough in patients. We have used a conscious guinea-pig model of cough as a more definitive method to study the effect of fenspiride on capsaicin- and citric acid-induced cough. Aerosolized fenspiride (1 mg.mL-1) caused a 58% reversal of capsaicin-induced bronchoconstriction; and i.v. fenspiride (1mg.kg-1) a 45% reversal of citric acid induced bronchoconstriction. Substance P- and neurokinin A-induced bronchoconstriction were unaffected by 1 mg.kg-1 i.v. fenspiride. Aerosolized fenspiride (1, 3 and 10 mg.mL-1) administered for 4 min reduced citric acid (300 mM) induced cough, but 0.1 mg.mL-1 was without effect. Pretreatment with aerosolized fenspiride (10 mg.mL-1) caused a shift in the citric acid dose response curve to the right. For citric acid-induced cough, the duration of action of aerosolized fenspiride (10 mg.mL-1) was found to be 5 and 15 min post-treatment. Aerosolized capsaicin (30 microM) induced cough was also reduced by 3 and 10 mg.mL-1 aerosolized fenspiride, but no significant effect was found with 1 mg.mL-1. We conclude that aerosolized fenspiride reduces capsaicin- and citric acid-induced bronchoconstriction as well as induced cough in guinea-pigs in vivo. Whether a pathway common to both cough and bronchoconstriction is the site of action of fenspiride remains to be established. We postulate that fenspiride, acting as an antitussive and antibronchoconstrictor agent, would be beneficial in the clinical situation for those patients with hyperresponsive airways.
Antagonists of Neuronal Calcium Channels: Structure, Function, and Therapeutic Implications
Authors: G P Miljanich, J Ramachandran
Journal: The Annual Review of Pharmacology and Toxicology (1995)

This article reviews the structural and functional diversity of neuronal calcium channels and the therapeutic potential of antagonizing such channels. Through spatial and temporal control of intracellular calcium concentration, voltage-sensitive calcium channels regulate a host of neuronal processes, including neurotransmitter secretion, electrical activity, cytoskeletal function, cell metabolism and proliferation, and gene expression. Several genes elaborate a number of calcium channel isoforms or subtypes--each tailored to specific roles in neuronal function and possessing distinct biophysical properties, distribution, modulation, and pharmacological sensitivity. This diversity has raised the possibility that subtype-specific antagonists could provide novel treatments for some neuropathologies. In fact, neuroprotective and analgesic actions of N-type channel blockers in animals appear to confirm this supposition. These properties prompted human clinical studies evaluating these agents for prevention of neuronal degeneration following ischemic brain trauma and for relief of pain. Future medical applications for these blockers and antagonists of other channels subtypes are discussed.
Intervention Synthesis: A Missing Link between a Systematic Review and Practical Treatment(s)
Authors: Paul P. Glasziou, Iain Chalmers, Sally Green, Susan Michie
Journal: PLoS Medicine (2014)

Effective delivery of treatments requires clear procedural details of the essential elements of treatment.Hence, if a systematic review finds that a class of interventions is effective, then the users of the review will want to know: ''Which version of the intervention should I use?''N Current methods to guide selection or synthesis from the variations of a treatment used across trials in a systematic review are poorly developed, and absent from most instructions on systematic review methods.N We identify three basic approaches: (i) single-trial-based choice, where criteria such as feasibility, cost, effectiveness, or familiarity guide which trial's treatment to adopt; (ii) common components hybrid, which extracts then combines-based on frequency and importance-components of several trials; and (iii) model-guided synthesis, where a model of the mechanisms of effect is used to code and assess the importance of components for the version(s) recommended.N Whichever method is used, we suggest review authors provide an ''intervention options table'', which describes the pros and cons of some intervention alternatives used in an individual trial or set of trials.N If clinicians and policymakers are to be expected to base their practices on the results of systematic reviews in practice, these three approaches will need to be more widely adopted.
All healthcare staff--not just GPs--should have a role in commissioning consortiums, MPs hear
Authors: A. O'Dowd
Journal: BMJ (2011)

The bill currently going through parliament to reform the NHS should spell out a guaranteed role for the whole general practice team on the new commissioning consortiums and not just for GPs, MPs have been told.

Witnesses appearing before MPs on the parliamentary health select committee on 8 February said the current proposal for GPs to lead the consortiums alone was unfairly exclusive to the general practice team.

There was also a danger of creating “tribalism” between GPs and hospital doctors, said witnesses speaking during the first evidence session of the committee’s follow-up inquiry into commissioning.

Committee chair Stephen Dorrell, Conservative MP for Charnwood, asked about the relationship between …
Adherence by Medical-Surgical Inpatients to Recommendations for Outpatient Psychiatric Treatment
Authors: William W. Weddington, Jr.
Journal: Psychotherapy and Psychosomatics (1983)

A records review of medical-surgical inpatients at a university hospital reveals that only 20% of patients seen in psychiatric consultation followed recommendations to seek psychiatric outpatient treatment. The study is unique in that immediate appointments with the consulting psychiatrists were offered prior to patients' discharge. The low rate is similar to the findings by others. Diagnosis of depression was associated with patients' keeping appointments, although social class may have been an indirect factor. Transformation of the medical-surgical inpatient to psychiatric outpatient remains a poorly understood process.
A high potency nonformylated peptide agonist for the phagocyte N-formylpeptide chemotactic receptor.
Authors: J L Gao, E L Becker, R J Freer, N Muthukumaraswamy, P M Murphy
Journal: The Journal of Experimental Medicine (1994)

Analysis of synthetic tri- and tetrapeptides has previously indicated that N-formylation is required for high biological activity when they react with the phagocyte N-formylpeptide receptor, suggesting that the natural ligand for the receptor is from bacterial and/or mitochondrial sources. To explore this requirement further, we synthesized the pentapeptide methionyl-norleucyl-leucyl-phenylalanyl-phenylalanine (MNleLFF) and studied the effects of different NH2-terminal modifications on its activity. N-formyl-MNleLFF induced transient alterations of [Ca2+]i and superoxide production in human neutrophils with 10- and 100-fold greater potency, respectively, than the proto-type N-formylpeptide, N-formylmethionyl-leucyl-phenylalanine (fMLF). Surprisingly, N-acetyl-MNleLFF was a potent as N-formyl-MNleLFF. Moreover, the unacylated counterpart H-MNleLFF was also highly active, having an EC50 for calcium mobilization of 10 nM, and for respiratory burst activation of 100 nM. All three pentapeptides could completely desensitize calcium transients elicited by stimulation of neutrophils with fMLF, whereas the neutrophil chemoattractants C5a and interleukin 8 only weakly affected fMLF-induced transients, suggesting that they activate neutrophils via the same receptor as fMLF. Finally, all three pentapeptides activated the recombinant human N-formylpeptide receptor expressed in frog oocytes, but did not effectively activate related phagocyte receptors. These data broaden the potential sources of natural ligands for the N-formyl-peptide receptor from N-formylated bacterial and mitochondrial products to other nonformylated endogenous peptides.
Treatment of Helicobacter pylori infection favourably affects gastric mucosal superoxide dismutases.
Authors: J M Gotz, J L Thio, H W Verspaget, G J Offerhaus, I Biemond, C B Lamers, R A Veenendaal
Journal: Gut (1997)

BACKGROUND AND AIMS: Excessive production of reactive oxygen metabolites (ROMs) by phagocytic cells is thought to contribute to the mucosal pathology of Helicobacter pylori infection. Previously, H pylori infection was shown to have a differential effect on some gastric mucosal scavenger enzymes of ROMs-namely, mitochondrial and cytoplasmic superoxide dismutases-reflected by a large increase in the cytokine inducible manganese superoxide dismutase and a marginal decrease in the constitutive copper/zinc superoxide dismutase. The present study was performed to evaluate whether these altered mucosal superoxide dismutase concentrations and activities in H pylori associated gastritis are reversed to normal by successful treatment of the infection. PATIENTS AND METHODS: In two different treatment groups-namely, omeprazole or ranitidine, in combination with clarithromycin and metronidazole (OME/AB (n = 33) and RAN/AB (n = 30))-manganese superoxide dismutase and copper/zinc superoxide dismutase concentrations were evaluated by enzyme linked immunosorbent assays in homogenates of gastric antrum and corpus biopsy specimens obtained before and eight weeks after successful treatment of H pylori infection. Superoxide dismutase activities in these homogenates were determined spectrophotometrically in eight patients of both groups before and after successful treatment. The concentrations of gastric mucosal superoxide dismutases were also determined in 12 patients with a persistent H pylori infection, with (n = 4) or without (n = 8) eradication therapy. Infection and eradication of H pylori were confirmed by a combination of culture and histology. RESULTS: Concentrations of manganese superoxide dismutase were significantly lower after than before therapy in antral (p &lt; 0.001 in both treatment groups) and corpus (p &lt; 0.001 in both treatment groups) mucosa. By contrast, copper/zinc superoxide dismutase concentrations were significantly higher (p &lt; 0.001) only in antral mucosa of the OME/AB treated group. Manganese superoxide dismutase activity was significantly lower after than before treatment in antral (OME/AB p &lt; 0.01, RAN/AB p &lt; 0.001), but not in corpus mucosa. Copper/zinc superoxide dismutase activity was not significantly altered by therapy. In the 12 patients with a persistent H pylori infection no major changes in the gastric mucosal superoxide dismutase concentrations were found. CONCLUSIONS: The raised manganese superoxide dismutase and reduced copper/ zinc superoxide dismutase concentrations and activities in H pylori associated gastritis were reversed towards normal by successful treatment of the infection.
Functional asymmetry in the lower limb professional soccer players
Authors: I Sannicandro, A Piccinno, R A Rosa, S De Pascalis
Journal: British Journal of Sports Medicine (2011)

Background Soccer, sports asymmetric, requiring different loads to the lower limbs as the player uses separately one leg to kick and the other one to jump and landing; in literature are studies that have described this asymmetry in terms of strength (Samadi et al ., 2009; Rahnama et al ., 2005) or ground reaction force in the landing (Sannicandro, 2008). Objective Analyzing the relationship between asymmetry of the strength of the lower capacity and ability to manage tasks in one-leg-standing balance in professional players. Design Descriptive research (correlation study which investigates the relationship between variables). Setting Soccer elite division in the off season. Participants 29 soccer players (25.3±2.7 year, 180.1±2.6 cm, 78.5±2.2 kg). Assessment of risk factors The maximal strength, the explosive strength and the balance test can be considered as indicators for to determine both the functional asymmetry of lower limbs both potential risk factors for soccer player. Main outcome measurements For each leg was assessed maximal strength (1RM) using a leg press (Technogym, Italy), explosive strength through hop test, the ability to balance by tilting platform electronics (DEB, Delos Italy). This instrument has provided the percentage of time that the player has complied with the assigned range of motion of ±2°. Results The assessment of maximal strength, explosive power and the balance returned respectively asymmetry averaged 9.9±7.2% to 6.6±5.3% and 11.4±3.2%. There was a correlation between 1RM and leg hop test for left and right respectively equal to r=0.55 and r=0.53 (p&lt;0.01), a correlation between test and hop balance equal respectively to r=0.49 and r=0.47 (p&lt;0.01). Conclusion The study describes the functional asymmetries of the lower limb in soccer players in relation to 1RM, the explosive strength and balance tasks in one-leg-standing. The correlation between values of explosive strength and balance tasks would suggest a functional relationship between two ability, as already hypothesised in literature (Gstöttner et al ., 2009).
Outcomes after Long-Term Acute Care
Authors: SHANNON S. CARSON, PETER B. BACH, LORAINE BRZOZOWSKI, ALAN LEFF
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

Long-term acute-care (LTAC) hospitals are facilities exempt from the Medicare prospective payment system and which provide care to patients suffering from prolonged critical illness. From August 1, 1995 to July 31, 1996, we studied the outcomes of 133 mechanically ventilated patients who were consecutively admitted to a large urban LTAC hospital from intensive care units (ICUs) of acute-care hospitals. Survival and functional status within 1 yr after the index admission were measured, and specific patient variables were used to develop a predictive model for survival at 1 yr. Of the 133 patients studied, 66 (50%) died prior to discharge. Of discharged patients, 70% had been successfully liberated from mechanical ventilation. One year after LTAC hospital admission, 103 (77%) of the patients had expired, typically after spending the majority of their days in acute care or long-term care facilities. Eleven 1-yr survivors (8%) were fully functional, whereas the remainder had significantly reduced functional status. Patients older than 74 yr, and patients older than 64 yr and not functionally independent before admission, had a 95% (confidence interval [CI]: 84% to 99%) 1-yr mortality; patients without these characteristics had a 56% (CI: 41% to 71%) 1-yr mortality (p < 0.001). We demonstrate characteristics predicting the poorest prognoses for patients requiring prolonged mechanical ventilation. These characteristics may be identifiable before transfer to an LTAC hospital.
Malaria morbidity and mortality in Ebola-affected countries caused by decreased health-care capacity, and the potential effect of mitigation strategies: a modelling analysis
Authors: Patrick G T Walker, Michael T White, Jamie T Griffin, Alison Reynolds, Neil M Ferguson, Azra C Ghani
Journal: The Lancet Infectious Diseases (2015)

BackgroundThe ongoing Ebola epidemic in parts of west Africa largely overwhelmed health-care systems in 2014, making adequate care for malaria impossible and threatening the gains in malaria control achieved over the past decade. We quantified this additional indirect burden of Ebola virus disease.MethodsWe estimated the number of cases and deaths from malaria in Guinea, Liberia, and Sierra Leone from Demographic and Health Surveys data for malaria prevalence and coverage of malaria interventions before the Ebola outbreak. We then removed the effect of treatment and hospital care to estimate additional cases and deaths from malaria caused by reduced health-care capacity and potential disruption of delivery of insecticide-treated bednets. We modelled the potential effect of emergency mass drug administration in affected areas on malaria cases and health-care demand.FindingsIf malaria care ceased as a result of the Ebola epidemic, untreated cases of malaria would have increased by 45% (95% credible interval 43–49) in Guinea, 88% (83–93) in Sierra Leone, and 140% (135–147) in Liberia in 2014. This increase is equivalent to 3·5 million (95% credible interval 2·6 million to 4·9 million) additional untreated cases, with 10 900 (5700–21 400) additional malaria-attributable deaths. Mass drug administration and distribution of insecticide-treated bednets timed to coincide with the 2015 malaria transmission season could largely mitigate the effect of Ebola virus disease on malaria.InterpretationThese findings suggest that untreated malaria cases as a result of reduced health-care capacity probably contributed substantially to the morbidity caused by the Ebola crisis. Mass drug administration can be an effective means to mitigate this burden and reduce the number of non-Ebola fever cases within health systems.FundingUK Medical Research Council, UK Department for International Development, Bill & Melinda Gates Foundation.
In vivo visualisation of platelet involvement in infective endocarditis by targeting the glycoprotein IIb/IIIa receptor
Authors: F.M. Brouwers, W.J.G. Oyen, M.H.M. Kooistra, O.C. Boerman, J.A. Barrett, J.W.M. van der Meer, F.W.A. Verheugt, F.H.M. Corstens
Journal: Circulation (2000)
Impact of different endothelial nitric oxide synthase gene polymorphisms on endothelium-dependent vasodilation and response to exercise training in patients with coronary artery disease
Authors: Sandra Erbs, Volker Adams, Stephan Gielen, Sven Möbius-Winkler, Gerhard Schuler, Rainer Hambrecht
Journal: Journal of the American College of Cardiology (2002)
A crucial role of caldesmon in vascular development in vivo
Authors: Ping-Pin Zheng, Lies-Anne Severijnen, Marcel van der Weiden, Rob Willemsen, Johan M Kros
Journal: Cardiovascular Research (2008)

We explored the in vivo effects of knockdown of caldesmon on vascular development in zebrafish.We investigated the effects of caldesmon knockdown on the vascular development in a zebrafish model with special attention for the trunk and head vessels including the aortic arches. We examined the developing fishes at various time points. The vascular abnormalities observed in the caldesmon morphants were morphologically and functionally characterized in detail in fixed and living embryos. The knockdown of caldesmon caused serious defects in vasculogenesis and angiogenesis in zebrafish morphants, and the vascular integrity and blood circulation were concomitantly impaired.The data provide the first functional assessment of the role of caldesmon in vascular development in vivo, indicating that this molecule plays a crucial role in vasculogenesis and angiogenesis in vivo. Interfering with caldesmon opens new therapeutic avenues for anti-angiogenesis in cancer and ischaemic cardiovascular disease.
Recurrence Patterns of Gastric-Type Adenocarcinoma (Gas) of the Uterine Cervix: a Subset Analysis of the Gynecologic Cancer Study Group of the Japan Clinical Oncology Group (Jcog) Gas Multicenter Study
Authors: S. Nishio, Y. Mikami, T. Otsuki, N. Yaegashi, T. Satoh, H. Yoshikawa, M. Saitoh, A. Okamoto, T. Kasamatsu, T. Miyamoto, T. Shiozawa, Y. Yoshioka, I. Konishi, A. Kojima, K. Takehara, E. Kaneki, H. Kobayashi, K. Ushijima, T. Kamura
Journal: Annals of Oncology (2014)
Renal screening in children after exposure to low dose melamine in Hong Kong: cross sectional study
Authors: H. S Lam, P. C Ng, W. C W Chu, W. Wong, D. F Y Chan, S. S Ho, K. T Wong, A. T Ahuja, C. K Li
Journal: BMJ (2008)

<b>Objective</b> To investigate the renal outcomes of children after exposure to low dose melamine in Hong Kong. <b>Design</b> Cross sectional study. <b>Setting</b> Special assessment centres, Hong Kong. <b>Participants</b> 3170 children (1422 girls and 1748 boys) aged 12 years or less referred from territory-wide primary care clinics after daily consumption for one month or more of milk products tainted with melamine. <b>Main outcome measures</b> Presence of renal stones and haematuria. <b>Results</b> One child had a confirmed renal stone, seven were suspected of having melamine related renal deposits, and 208 (6.6%) were positive for blood in urine by reagent strip. A proportion of these children were followed up at the special assessment centre, but only 7.4% of those positive for blood on reagent strip were confirmed by microscopy, suggesting an overall estimated prevalence of less than 1% for microscopic haematuria. <b>Conclusions</b> No severe adverse renal outcomes, such as acute renal failure or urinary tract obstruction, were detected in children after exposure to low dose melamine. Our results were similar to territory-wide findings in Hong Kong. Even including the seven children with suspected renal deposits, the prevalence of suspected melamine related abnormalities on ultrasonography was only 0.2%. None of these children required specific treatment. The prevalence of microscopic haematuria was probably overestimated by the reagent strip. These data suggest that large scale and urgent screening programmes may not be informative or cost effective for populations who have been exposed to low dose melamine.
Evidence that host size determines liver size: Studies in dogs receiving orthotopic liver transplants
Authors: Igal Kam, Steven Lynch, Gregory Svanas, Satori Todo, Lorenzo Polimeno, Antonio Francavilla, Ronald J. Penkrot, Sunichi Takaya, Bo G. Ericzon, Thomas E. Starzl, David H. Van Thiel
Journal: Hepatology (1987)

Orthotopic liver transplantation was performed in two groups of dogs; Group I animals consisted of large dogs that served as recipients of livers obtained from smaller dogs while Group II animals consisted of dogs that received liver from donor dogs of nearly the same size. The small-for-size livers transplanted into the Group I dogs rapidly increased in size over the course of 2 weeks until they achieved a size equal to that originally present in the larger recipient dogs. In contrast, the livers transplanted into dogs of the same size as the donors underwent some degree of atrophy. In both groups of animals, plasma levels of insulin and glucagon and hepatic (graft) activities of thymidine kinase and ornithine decarboxylase were followed serially. The only difference between the two groups of animals for these measures was that the ornithine decarboxylase activity rose to a greater degree in the liver that underwent graft enlargement. These data suggest that recipient size determines, at least in part, liver graft size once it is transplanted. These data also suggest that of the parameters followed, only ornithine decarboxylase activity parallels the finding of growth of the transplanted liver.