Intraspecific variability of dihydrochalcone, chromenes and benzoic acid derivatives in leaves of Piper aduncum L.(Piperaceae)

Chemical analysis carried out in leaves of 18 specimens of Piper aduncum L. (Piperaceae) occurring at Ripasa Reserve, Araraquara, SP, Brazil indicated two distinct populations when investigated over aperiod of 14 months (January 2000 to February 2001) and then submitted to cluster analysis. The two groups were characterized by accumulation of prenylated benzoic acids, chromenes and dihydrochalcone, respectively. A total of seven compounds were identified by HPLC analysis and compared with standards including two prenylated benzoic acid [aduncumene (1) and 3-(3’-7’-dimethyl- 2’-6’-octadienyl)-4-methoxy-benzoic acid (5)], four chromenes [methyl 2,2-dimethyl-8-(3’-methyl-2’-butenyl)-2H-1-chromene-6-carboxylate (4), methyl 2,2-dimethyl-2H-1-chromene-6-carboxylate (2b), methyl 8-hydroxy-2,2-dimethyl-2H-1-chromene-6-carboxylate (3) and 2,2-dimethyl-2H-1-chromene-6- carboxylic acid (2a)] and one dihydrochalcone [2’,6’-dihydroxy-4’-methoxy- dihydrochalcone (6)]

Glibenclamide—10-h Treatment Window in a Clinically Relevant Model of Stroke

Glibenclamide improves outcomes in rat models of stroke, with treatment as late as 6 h after onset of ischemia shown to be beneficial. Because the molecular target of glibenclamide, the sulfonylurea receptor 1 (Sur1)-regulated NCCa-ATP channel, is upregulated de novo by a complex transcriptional mechanism, and the principal pathophysiological target, brain swelling, requires hours to develop, we hypothesized that the treatment window would exceed 6 h. We studied a clinically relevant rat model of stroke in which middle cerebral artery occlusion (75% < reduction in LDF signal ≤90%) was produced using an intra-arterial occluder. Recanalization was obtained 4.5 h later by removing the occluder. At that time, we administered recombinant tissue plasminogen activator (rtPA; 0.9 mg/kg IV over 30 min). Immunolabeling showed modest expression of Sur1 5 h after onset of ischemia, with expression increasing 7- to 11-fold (P < 0.01) by 24 h. Rats were administered either vehicle or glibenclamide (10 μg/kg IP loading dose plus 200 ng/h by constant subcutaneous infusion) beginning 4.5 or 10 h after onset of ischemia. In rats treated at 4.5 or 10 h, glibenclamide significantly reduced hemispheric swelling at 24 h from (mean ± SEM) 14.7 ± 1.5% to 8.1 ± 1.6% or 8.8 ± 1.1% (both P < 0.01), respectively, and significantly reduced 48-h mortality from 53% to 17% or 12% (both P < 0.01), and improved Garcia scores at 48 h from 3.8 ± 0.62 to 7.6 ± 0.70 or 8.4 ± 0.74 (both P < 0.01). We conclude that, in a clinically relevant model of stroke, the treatment window for glibenclamide extends to 10 h after onset of ischemia

Integrative care for the management of low back pain: use of a clinical care pathway

<p>Abstract</p> <p>Background</p> <p>For the treatment of chronic back pain, it has been theorized that integrative care plans can lead to better outcomes than those achieved by monodisciplinary care alone, especially when using a collaborative, interdisciplinary, and non-hierarchical team approach. This paper describes the use of a care pathway designed to guide treatment by an integrative group of providers within a randomized controlled trial.</p> <p>Methods</p> <p>A clinical care pathway was used by a multidisciplinary group of providers, which included acupuncturists, chiropractors, cognitive behavioral therapists, exercise therapists, massage therapists and primary care physicians. Treatment recommendations were based on an evidence-informed practice model, and reached by group consensus. Research study participants were empowered to select one of the treatment recommendations proposed by the integrative group. Common principles and benchmarks were established to guide treatment management throughout the study.</p> <p>Results</p> <p>Thirteen providers representing 5 healthcare professions collaborated to provide integrative care to study participants. On average, 3 to 4 treatment plans, each consisting of 2 to 3 modalities, were recommended to study participants. Exercise, massage, and acupuncture were both most commonly recommended by the team and selected by study participants. Changes to care commonly incorporated cognitive behavioral therapy into treatment plans.</p> <p>Conclusion</p> <p>This clinical care pathway was a useful tool for the consistent application of evidence-based care for low back pain in the context of an integrative setting.</p> <p>Trial registration</p> <p>ClinicalTrials.gov NCT00567333</p

Pancreatic hyperamylasemia during acute gastroenteritis: incidence and clinical relevance

BACKGROUND: Many case reports of acute pancreatitis have been reported but, up to now, pancreatic abnormalities during acute gastroenteritis have not been studied prospectively. OBJECTIVES: To evaluate the incidence and the clinical significance of hyperamylasemia in 507 consecutive adult patients with acute gastroenteritis. METHODS: The clinical significance of hyperamylasemia, related predisposing factors and severity of gastroenteritis were assessed. RESULTS: Hyperamylasemia was detected in 10.2 % of patients studied. Although amylasemia was found over four times the normal values in three cases, the clinical features of acute pancreatitis were recorded in only one case (0.1%). Hyperamylasemia was more likely (17%) where a microorganism could be identified in the stools (p < 0.01). Among patients with positive stool samples, Salmonella spp. and in particular S. enteritidis, was the microorganism most frequently associated with hyperamylasemia [17/84 (20.2 %) and 10/45 (22.2%), respectively], followed by Rotavirus, Clostridium difficile and Campylobacter spp. Patients with hyperamylasemia had more severe gastroenteritis with an increased incidence of fever (80 % vs 50.6 %, O.R. 3.0; P < 0.01), dehydration (18% vs 8.5%; O.R. 2.5; P < 0.05), and a higher mean number of evacuations per day (9.2 vs 7.5; P < 0.05) than those with amylasemia in the normal range. Hyperamylasemia was significantly associated with cholelithiasis, (30.0 % vs 10.7%, O.R. 3.5; P < 0.01) and chronic gastritis or duodenal ulceration (22.0 % vs 10.2%, O.R. 2.4, P < 0.05). CONCLUSIONS: Hyperamylasemia is relatively frequent, and is associated with severe gastroenteritis. However, acute pancreatitis in the setting of acute gastroenteritis, is a rare event

Prospective study on the mismatch concept in acute stroke patients within the first 24 h after symptom onset - 1000Plus study

<p>Abstract</p> <p>Background</p> <p>The mismatch between diffusion weighted imaging (DWI) lesion and perfusion imaging (PI) deficit volumes has been used as a surrogate of ischemic penumbra. This pathophysiology-orientated patient selection criterion for acute stroke treatment may have the potential to replace a fixed time window. Two recent trials - DEFUSE and EPITHET - investigated the mismatch concept in a multicenter prospective approach. Both studies randomized highly selected patients (n = 74/n = 100) and therefore confirmation in a large consecutive cohort is desirable. We here present a single-center approach with a 3T MR tomograph next door to the stroke unit, serving as a bridge from the ER to the stroke unit to screen all TIA and stroke patients. Our primary hypothesis is that the prognostic value of the mismatch concept is depending on the vessel status. Primary endpoint of the study is infarct growth determined by imaging, secondary endpoints are neurological deficit on day 5-7 and functional outcome after 3 months.</p> <p>Methods and design</p> <p>1000Plus is a prospective, single centre observational study with 1200 patients to be recruited. All patients admitted to the ER with the clinical diagnosis of an acute cerebrovascular event within 24 hours after symptom onset are screened. Examinations are performed on day 1, 2 and 5-7 with neurological examination including National Institute of Health Stroke Scale (NIHSS) scoring and stroke MRI including T2*, DWI, TOF-MRA, FLAIR and PI. PI is conducted as dynamic susceptibility-enhanced contrast imaging with a fixed dosage of 5 ml 1 M Gadobutrol. For post-processing of PI, mean transit time (MTT) parametric images are determined by deconvolution of the arterial input function (AIF) which is automatically identified. Lesion volumes and mismatch are measured and calculated by using the perfusion mismatch analyzer (PMA) software from ASIST-Japan. Primary endpoint is the change of infarct size between baseline examination and day 5-7 follow up.</p> <p>Discussions</p> <p>The aim of this study is to describe the incidence of mismatch and the predictive value of PI for final lesion size and functional outcome depending on delay of imaging and vascular recanalization. It is crucial to standardize PI for future randomized clinical trials as for individual therapeutic decisions and we expect to contribute to this challenging task.</p> <p>Trial Registration</p> <p>clinicaltrials.gov NCT00715533</p

Individualized chiropractic and integrative care for low back pain: the design of a randomized clinical trial using a mixed-methods approach

<p>Abstract</p> <p>Background</p> <p>Low back pain (LBP) is a prevalent and costly condition in the United States. Evidence suggests there is no one treatment which is best for all patients, but instead several viable treatment options. Additionally, multidisciplinary management of LBP may be more effective than monodisciplinary care. An integrative model that includes both complementary and alternative medicine (CAM) and conventional therapies, while also incorporating patient choice, has yet to be tested for chronic LBP.</p> <p>The primary aim of this study is to determine the relative clinical effectiveness of 1) monodisciplinary chiropractic care and 2) multidisciplinary integrative care in 200 adults with non-acute LBP, in both the short-term (after 12 weeks) and long-term (after 52 weeks). The primary outcome measure is patient-rated back pain. Secondary aims compare the treatment approaches in terms of frequency of symptoms, low back disability, fear avoidance, self-efficacy, general health status, improvement, satisfaction, work loss, medication use, lumbar dynamic motion, and torso muscle endurance. Patients' and providers' perceptions of treatment will be described using qualitative methods, and cost-effectiveness and cost utility will be assessed.</p> <p>Methods and Design</p> <p>This paper describes the design of a randomized clinical trial (RCT), with cost-effectiveness and qualitative studies conducted alongside the RCT. Two hundred participants ages 18 and older are being recruited and randomized to one of two 12-week treatment interventions. Patient-rated outcome measures are collected via self-report questionnaires at baseline, and at 4, 12, 26, and 52 weeks post-randomization. Objective outcome measures are assessed at baseline and 12 weeks by examiners blinded to treatment assignment. Health care cost data is collected by self-report questionnaires and treatment records during the intervention phase and by monthly phone interviews thereafter. Qualitative interviews, using a semi-structured format, are conducted with patients at the end of the 12-week treatment period and also with providers at the end of the trial.</p> <p>Discussion</p> <p>This mixed-methods randomized clinical trial assesses clinical effectiveness, cost-effectiveness, and patients' and providers' perceptions of care, in treating non-acute LBP through evidence-based individualized care delivered by monodisciplinary or multidisciplinary care teams.</p> <p>Trial registration</p> <p>ClinicalTrials.gov NCT00567333</p