The effect of nebivolol treatment on oxidative stress and antioxidant status in patients with cardiac syndrome-X . BACKGROUND Free radical-mediated oxidative stress has been implicated in the etiopathogenesis of several disorders . The aim of this study was to elucidate the effect of treatment with nebivolol on the metabolic state of oxidative stress , and antioxidant status markers in patients with cardiac syndrome-X ( CSX ) , additionally , to compare with the effect of metoprolol treatment . METHODS Thirty patients , 17 female and 13 male , with CSX were enrolled in the study . Nebivolol ( 5 mg/day ) or metoprolol ( 50 mg/day ) was administrated for 12 weeks . Twelve hour fasting blood samples , taken at the initiation and on the third month of therapy , were analyzed for the levels of malondialdehyde ( MDA ) , nitrite+nitrate ( NOx ) , and the activity of myeloperoxidase ( MPO ) , superoxide dismutase ( SOD ) . No patient presented additional risk factors for increased reactive oxygen species levels . RESULTS Compared with sixteen control participants , patients with CSX had significantly higher activity of MPO and levels of MDA , but significantly lower SOD activity and levels of NOx before treatment . After treatment , MPO activity and MDA levels were significantly reduced ; SOD activity and NOx levels were significantly increased with nebivolol but remained unchanged with metoprolol . CONCLUSION We have shown that patients with CSX who taken nebivolol have lower serum MPO activity , levels of MDA and higher serum SOD activity , NOx levels when compared with metoprolol treatment . Exercise stress test parameters were also ameliorated in patients who had taken nebivolol in contrast to metoprolol . Nebivolol treatment may be a novel treatment strategy in cases with CSX in the future .

nebivolol treatment

nebivolol

metoprolol treatment

Nebivolol

metoprolol

nebivolol

metoprolol

nebivolol

metoprolol

nebivolol

metoprolol

Nebivolol

levels of malondialdehyde ( MDA

nitrite+nitrate ( NOx )

the activity of myeloperoxidase ( MPO )

superoxide dismutase ( SOD )

activity of MPO

levels of MDA

lower SOD activity

levels of NOx

MPO activity

MDA levels

SOD activity

NOx levels

MPO activity

levels of MDA

serum SOD activity

NOx levels

cardiac syndrome-X

cardiac syndrome-X ( CSX )

Thirty

female

male

CSX

CSX


Pulse oximeter perfusion index as an early indicator of sympathectomy after epidural anesthesia . BACKGROUND The pulse oximeter perfusion index ( PI ) has been used to indicate sympathectomy-induced vasodilatation . We hypothesized that pulse oximeter PI provides an earlier and clearer indication of sympathectomy following epidural anesthesia than skin temperature and arterial pressure . METHODS Forty patients received lumbar epidural catheters . Patients were randomized to receive either 10 ml 0.5 % bupivacaine or 10 ml 0.25 % bupivacaine . PI in the toe , mean arterial pressure ( MAP ) and toe temperature were all assessed at baseline and at 5 , 10 and 20 min following epidural anesthesia . The effect of epidural anesthesia over time was assessed by repeated measures analysis of variance . Additionally , we defined clinically evident sympathectomy criteria ( a 100 % increase in the PI , a 15 % decrease in MAP and a 1 degrees C increase in toe temperature ) . The numbers of patients demonstrating these changes for each test were compared using the McNemar test for each time point . RESULTS Twenty-nine subjects had photoplethysmography signals that met a priori signal quality criteria for analysis . By 20 min , PI increased by 326 % , compared with a 10 % decrease and a 3 % increase in MAP and toe temperature , respectively . For PI 15/29 , 26/29 and 29/29 of the subjects met the sympathectomy criteria at 5 , 10 and 20 min , respectively , compared with 4/29 , 6/29 and 18/29 for MAP changes and 3/29 , 8/29 and 14/29 for toe temperature changes . CONCLUSIONS PI was an earlier , clearer and more sensitive indicator of the development of epidural-induced sympathectomy than either skin temperature or MAP .

lumbar epidural catheters

receive either 10 ml 0.5 % bupivacaine

10 ml 0.25 % bupivacaine

epidural anesthesia

epidural anesthesia

measures analysis of variance

McNemar test

photoplethysmography signals

PI

MAP and toe temperature

sympathectomy criteria

MAP

temperature changes

skin temperature

MAP

Forty

Twenty-nine


Perioperative fever and outcome in surgical patients with aneurysmal subarachnoid hemorrhage . OBJECTIVE We examined the incidence of perioperative fever and its relationship to outcome among patients enrolled in the Intraoperative Hypothermia for Aneurysm Surgery Trial . METHODS One thousand patients with initial World Federation of Neurological Surgeons grades of I to III undergoing clipping of intracranial aneurysms after subarachnoid hemorrhage were randomized to intraoperative normothermia ( 36 degrees C-37 degrees C ) or hypothermia ( 32.5 degrees C-33.5 degrees C ) . Fever ( > or =38.5 degrees C ) and other complications ( including infections ) occurring between admission and discharge ( or death ) were recorded . Functional and neuropsychologic outcomes were assessed 3 months postoperatively . The primary outcome variable for the trial was dichotomized Glasgow Outcome Scale ( good outcome versus all others ) . RESULTS Fever was reported in 41 % of patients . In 97 % of these , fever occurred in the postoperative period . The median time from surgery to first fever was 3 days . All measures of outcome were worse in patients who developed fever , even in those without infections or who were World Federation of Neurological Surgeons grade I. Logistic regression analyses were performed to adjust for differences in preoperative factors ( e.g. , age , Fisher grade , initial neurological status ) . This demonstrated that fever continued to be significantly associated with most outcome measures , even when infection was added to the model . An alternative stepwise model selection process including all fever-related measures from the preoperative and intraoperative period ( e.g. , hydrocephalus , duration of surgery , intraoperative blood loss ) resulted in the loss of significance for dichotomized Glasgow Outcome Scale , but significant associations between fever and several other outcome measures remained . After adding postoperative delayed ischemic neurological deficits to the model , only worsened National Institutes of Health Stroke Scale score , Barthel Activities of Daily Living index , and discharge destination ( home versus other ) remained independently associated with fever . CONCLUSION These findings suggest that fever is associated with worsened outcome in surgical subarachnoid hemorrhage patients , although , because the association between fever and the primary outcome measure for the trial is dependent on the covariates used in the analysis ( particularly operative events and delayed ischemic neurological deficits ) , we can not rule out the possibility that fever is a marker for other events . Only a formal trial of fever treatment or prevention can address this issue .

intraoperative normothermia

Perioperative

Fever

death

Functional

Fever

fever

median time from surgery to first fever

infections

fever

infection

fever-related

fever

delayed ischemic neurological deficits

fever

fever

fever

fever


Ambulatory blood pressure control with bedtime aspirin administration in subjects with prehypertension . BACKGROUND Aspirin has been found to prevent angiotensin II-induced hypertension and to induce nitric oxide ( NO ) release from vascular endothelium . Low-dose aspirin has also been shown to reduce blood pressure ( BP ) when administered at bedtime , as opposed to upon awakening , in untreated hypertensive patients and high-risk pregnant women . Accordingly , we investigated the effects on ambulatory BP of aspirin administered at different times of the day in prehypertension . METHODS We studied 244 subjects with prehypertension , 43.0 +/- 13.0 years of age , randomly divided in three groups : nonpharmacological hygienic-dietary recommendations ; the same recommendations and aspirin ( 100 mg/day ) on awakening ; or the same recommendations and aspirin at bedtime . BP was measured for 48 consecutive hours before and after 3 months of intervention . RESULTS Ambulatory BP was unchanged in subjects randomized to either nonpharmacological intervention or aspirin on awakening . A significant ambulatory BP reduction was , however , observed in the subjects who received aspirin at bedtime ( decrease of 6/3 mm Hg in the 24-h mean of systolic ( SBP ) /diastolic BP ( DBP ) , respectively ; P < 0.001 ) , without changes in heart rate ( HR ) from baseline . BP was homogeneously controlled along the 24 h after bedtime aspirin administration ( 6/4 mm Hg reduction in activity mean of SBP/DBP ; 6/3 mm Hg reduction in sleep-time mean , respectively ) . CONCLUSIONS This prospective trial documents a significant effect on BP of low dose aspirin only when ingested at bedtime by prehypertensive subjects . The timed administration of low-dose aspirin could thus provide a valuable and cost-effective approach for BP control in subjects at elevated risk of developing hypertension .

aspirin administration

Aspirin

aspirin

aspirin

aspirin

aspirin

nonpharmacological intervention

aspirin

aspirin

aspirin

aspirin

aspirin

blood pressure

blood pressure ( BP )

ambulatory BP

BP

Ambulatory BP

ambulatory BP

systolic ( SBP ) /diastolic BP ( DBP )

heart rate ( HR )

BP

BP

BP control


Randomized , double-blind , multicenter , controlled trial of ibuprofen versus acetaminophen ( paracetamol ) and placebo for treatment of symptoms of tonsillitis and pharyngitis in children .

ibuprofen

acetaminophen ( paracetamol )

placebo

symptoms of tonsillitis and pharyngitis

children .


Pilot study of Panax quinquefolius ( American ginseng ) to improve cancer-related fatigue : a randomized , double-blind , dose-finding evaluation : NCCTG trial N03CA . PURPOSE This pilot trial sought to investigate whether any of three doses of American ginseng ( Panax quinquefolius ) might help cancer-related fatigue . A secondary aim was to evaluate toxicity . METHODS Eligible adults with cancer were randomized in a double-blind manner , to receive American ginseng in doses of 750 , 1,000 , or 2,000 mg/day or placebo given in twice daily dosing over 8 weeks . Outcome measures included the Brief Fatigue Inventory , vitality subscale of the Medical Outcome Scale Short Form-36 ( SF-36 ) , and the Global Impression of Benefit Scale at 4 and 8 weeks . RESULTS Two hundred ninety patients were accrued to this trial . Nonsignificant trends for all outcomes were seen in favor of the 1,000- and 2,000-mg/day doses of American ginseng . Area under the curve analysis of activity interference from the Brief Fatigue Inventory was 460-467 in the placebo group and 750 mg/day group versus 480-551 in the 1,000- and 2,000-mg/day arms , respectively . Change from baseline in the vitality subscale of the SF-36 was 7.3-7.8 in the placebo and the 750-mg/day arm , versus 10.5-14.6 in the 1,000- and 2,000-mg/day arms . Over twice as many patients on ginseng perceived a benefit and were satisfied with treatment over those on placebo . There were no significant differences in any measured toxicities between any of the arms . CONCLUSION There appears to be some activity and tolerable toxicity at 1,000-2,000 mg/day doses of American ginseng with regard to cancer-related fatigue . Thus , further study of American ginseng is warranted .

American ginseng

placebo

American ginseng

placebo

placebo

ginseng

placebo

American ginseng

American ginseng

Brief Fatigue Inventory

Global Impression of Benefit Scale

vitality subscale

satisfied

toxicities

cancer-related fatigue

cancer-related fatigue

adults

cancer

Two hundred ninety

cancer-related fatigue


The influence of dietary fibre source and gender on the postprandial glucose and lipid response in healthy subjects . BACKGROUND Consumption of soluble dietary fibre is correlated with decreased postprandial glucose and insulin responses and hence has beneficial effects on the metabolic syndrome . AIM OF THE STUDY To investigate the effects on postprandial glucose , insulin and triglyceride concentrations of meals enriched with soluble dietary fibres from oats , rye bran , sugar beet fibre or a mixture of these three fibres . METHODS Thirteen healthy human volunteers ( 6 men and 7 women , aged 20-28 years ) were included in the study . The subjects came to the study centre once a week after an overnight fast to ingest test meals and a control meal in random order . The meals contained either oat powder ( 62 g , of which 2.7 soluble fibre ) , rye bran ( 31 g , of which 1.7 g soluble fibre ) , sugar beet fibre ( 19 g , of which 5 g soluble fibre ) , a mixture of these three fibres ( 74 g , of which 1.7 g soluble fibre from each source , giving 5 g soluble fibre ) or no added fibre ( control ) and were all adjusted to contain the same total amount of available carbohydrates . Blood samples were drawn before and every 30 min up to 180 min after the meals . RESULTS Meals with rye bran gave a lower postprandial glucose peak when compared with the control meal , and this effect was more pronounced in women compared to men . Oat powder , containing a low amount of total fibre and a high amount of carbohydrates in liquid matrix , gave a higher incremental glucose peak concentration compared to rye bran and sugar beet fibre and higher insulin incremental area under curve compared to control . The oat powder also influenced the effects of the mixed meal , diminishing the glucose-lowering effects . Postprandial triglyceride levels tended to be higher after all fibre-rich meals , but only significant for oat powder and the mixed meal when compared with the control meal . CONCLUSIONS Postprandial glucose , insulin and triglyceride concentrations are influenced by dietary fibre-rich meals , depending on fibre source , dose of soluble and total fibre and possibly gender .

dietary fibre source

soluble dietary fibre

meals

oat powder

rye bran

sugar beet fibre

a mixture of these three fibres

or

no added fibre

( control )

carbohydrates

Meals with rye bran

Oat powder

oat powder

meal

meal

dietary fibre-rich meals

postprandial glucose

lipid response

postprandial glucose

insulin

triglyceride concentrations

postprandial glucose peak

incremental glucose peak concentration

insulin incremental area under curve

glucose-lowering effects

Postprandial triglyceride levels

Postprandial glucose

insulin

triglyceride concentrations

healthy

Thirteen

healthy

6 men and 7 women

aged 20-28 years )


Topical administration of diclofenac ( 1 % ) in the prevention of miosis during vitrectomy . PURPOSE A prospective , randomized clinical trial was conducted to assess the usefulness of preoperative diclofenac eye drops in maintaining mydriasis during vitrectomy and in reducing postoperative inflammation . METHODS Fifty consecutive patients undergoing vitrectomy were randomly assigned to diclofenac ( n = 24 ) or control ( n = 26 ) groups . All patients received a standard preoperative regimen of cyclopentolate ( 2 % ) and phenylephrine hydrochloride ( 2.5 % ) . The diclofenac group also received diclofenac ( 1 % ) preoperatively . Pupillary diameter was recorded at four time points during surgery . Inflammatory indices were measured postoperatively using slit-lamp examination . RESULTS After induction of anesthesia , the decrease in pupil size was not significantly different between the two groups ( P = 0.112 ) , but for the next two stages , it was significantly less in the diclofenac group ( P = 0.012 and P = 0.003 , respectively ) . No significant differences were found between the two groups for anterior chamber cells and redness in the eye postoperatively ( P = 0.609 and P = 0.123 , respectively ) . However , anterior chamber flare was significantly greater in the control group ( P = 0.035 ) , and patients felt significantly more pain in this group ( P = 0.001 ) . CONCLUSIONS Topical administration of diclofenac was effective in maintaining mydriasis during vitrectomy and in reducing postoperative pain and anterior chamber flare as determined by slit-lamp evaluations .

diclofenac

diclofenac

diclofenac

control

cyclopentolate

phenylephrine hydrochloride

diclofenac

diclofenac

diclofenac

diclofenac

miosis

postoperative inflammation .

Pupillary diameter

Inflammatory indices

decrease in pupil size

anterior chamber cells

redness in the eye

anterior chamber flare

pain

maintaining mydriasis

postoperative pain

anterior chamber flare


Adjuvant therapy with pegylated interferon alfa-2b versus observation in resected stage III melanoma : a phase III randomized controlled trial of health-related quality of life and symptoms by the European Organisation for Research and Treatment of Cancer Melanoma Group . PURPOSE Interferon ( IFN ) -based adjuvant therapy in melanoma is associated with significant side effects , which necessitates evaluation of health-related quality of life ( HRQOL ) . Our trial examined the HRQOL effects of adjuvant pegylated IFN-alpha-2b ( PEG-IFN-alpha-2b ) versus observation in patients with stage III melanoma . METHODS A total of 1,256 patients with stage III melanoma were randomly assigned after full lymphadenectomy to receive either observation ( n = 629 ) or PEG-IFN-alpha-2b ( n = 627 ) : induction 6 micrograms/kg/wk [ DOSAGE ERROR CORRECTED ] for 8 weeks then maintenance 3 micrograms/kg/wk [ DOSAGE ERROR CORRECTED ] for an intended total duration of 5 years . The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 was used to assess HRQOL . RESULTS At 3.8 years of median follow-up , for the primary end point , recurrence-free survival ( RFS ) , risk was reduced by 18 % ( hazard rate = 0.82 ; P = .01 ) in the PEG-IFN-alpha-2b arm compared with observation . Significant and clinically meaningful differences occurred with the PEG-IFN-alpha-2b treatment arm compared with the observation group , showing decreased global HRQOL at month 3 ( -11.6 points ; 99 % CI , -8.2 to -15.0 ) and year 2 ( -10.5 points ; 99 % CI , -6.6 to -14.4 ) . Many of the other scales showed statistically significant differences between scores when comparing the two arms . From a clinical point of view , important differences were found for five scales : two functioning scales ( social and role functioning ) and three symptom scales ( appetite loss , fatigue , and dyspnea ) , with the PEG-IFN-alpha-2b arm being most impaired . CONCLUSION PEG-IFN-alpha-2b leads to a significant and sustained improvement in RFS . There is an expected negative effect on global HRQOL and selected symptoms when patients undergo PEG-IFN-alpha-2b treatment .

health-related quality of life

recurrence-free survival ( RFS )

HRQOL

social

and

role functioning

appetite loss

fatigue

dyspnea

global HRQOL

stage III melanoma

stage III melanoma

after full lymphadenectomy


The ADDITION-Cambridge trial protocol : a cluster -- randomised controlled trial of screening for type 2 diabetes and intensive treatment for screen-detected patients . BACKGROUND The increasing prevalence of type 2 diabetes poses a major public health challenge . Population-based screening and early treatment for type 2 diabetes could reduce this growing burden . However , the benefits of such a strategy remain uncertain . METHODS AND DESIGN The ADDITION-Cambridge study aims to evaluate the effectiveness and cost-effectiveness of ( i ) a stepwise screening strategy for type 2 diabetes ; and ( ii ) intensive multifactorial treatment for people with screen-detected diabetes in primary care . 63 practices in the East Anglia region participated . Three undertook the pilot study , 33 were allocated to three groups : no screening ( control ) , screening followed by intensive treatment ( IT ) and screening plus routine care ( RC ) in an unbalanced ( 1:3:3 ) randomisation . The remaining 27 practices were randomly allocated to IT and RC . A risk score incorporating routine practice data was used to identify people aged 40-69 years at high-risk of undiagnosed diabetes . In the screening practices , high-risk individuals were invited to take part in a stepwise screening programme . In the IT group , diabetes treatment is optimised through guidelines , target-led multifactorial treatment , audit , feedback , and academic detailing for practice teams , alongside provision of educational materials for newly diagnosed participants . Primary endpoints are modelled cardiovascular risk at one year , and cardiovascular mortality and morbidity at five years after diagnosis of diabetes . Secondary endpoints include all-cause mortality , development of renal and visual impairment , peripheral neuropathy , health service costs , self-reported quality of life , functional status and health utility . Impact of the screening programme at the population level is also assessed through measures of mortality , cardiovascular morbidity , health status and health service use among high-risk individuals . DISCUSSION ADDITION-Cambridge is conducted in a defined high-risk group accessible through primary care . It addresses the feasibility of population-based screening for diabetes , as well as the benefits and costs of screening and intensive multifactorial treatment early in the disease trajectory . The intensive treatment algorithm is based on evidence from studies including individuals with clinically diagnosed diabetes and the education materials are informed by psychological theory . ADDITION-Cambridge will provide timely evidence concerning the benefits of early intensive treatment and will inform policy decisions concerning screening for type 2 diabetes . TRIAL REGISTRATION Current Controlled trials ISRCTN86769081 .

intensive multifactorial treatment

no screening ( control )

screening plus routine care

effectiveness

cost-effectiveness

all-cause mortality

peripheral neuropathy

health service costs

self-reported quality of life

functional status

health utility

mortality

cardiovascular morbidity


Osteoporosis and gait and balance disturbances in older sarcopenic obese New Zealanders . UNLABELLED Bone , muscle , and fat may affect gait and balance in older adults . Osteoporosis was prevalent in low muscle mass participants and related to gait and balance deficits . Low muscle combined with high fat mass had more functional deficits and poorer bone health , which has implications for falls risk and fractures . INTRODUCTION Decreasing bone density and muscle mass and increasing fat mass may act synergistically to affect gait and balance in older adults . METHODS One hundred eighty-three older adults ( age 72.7 +/- 6 years , range 56-93 ; body mass index 28.2 +/- 4.9 , range 16.6-46.0 ) were recruited from a New Zealand falls prevention intervention trial . Total and appendicular skeletal muscle mass ( ASM ) , percent fat , and bone mineralization were assessed by dual energy X-ray absorptiometry and used to characterize normal lean ( NL , n = 51 ) , sarcopenic ( SS , n = 18 ) , sarcopenic obese ( SO , n = 29 ) , and obese ( OO , n = 85 ) phenotypes . Functional performance was assessed using timed up and go , chair stand , single leg stand , and step test . Regression models were adjusted for age , sex , medications , and physical activity . RESULTS Femoral neck osteoporosis was present in 22 % SS , 17 % SO , 12 % NL , and 7 % OO . Femoral neck osteoporosis with low ASM predicted poor chair stand performance ( beta -3.3 , standard error 1.6 , p = 0.04 ) . SO scored lowest on the chair stand ( p = 0.03 ) and step test ( p = 0.03 ) . Higher ASM predicted faster timed up and go performance ( p = 0.001 ) . CONCLUSIONS Osteoporosis was prevalent in low ASM groups ( SS and SO ) and related to gait and balance deficits , particularly in the SO . This has implications for falls risk , fractures , and interventions .

Osteoporosis

dual energy X-ray absorptiometry

step test

percent fat

bone mineralization

Femoral neck osteoporosis

ASM

chair stand performance

Higher ASM

Osteoporosis

One hundred eighty-three older adults

ASM


Effects of dietary coconut oil on the biochemical and anthropometric profiles of women presenting abdominal obesity . The effects of dietary supplementation with coconut oil on the biochemical and anthropometric profiles of women presenting waist circumferences ( WC ) > 88 cm ( abdominal obesity ) were investigated . The randomised , double-blind , clinical trial involved 40 women aged 20-40 years . Groups received daily dietary supplements comprising 30 mL of either soy bean oil ( group S ; n = 20 ) or coconut oil ( group C ; n = 20 ) over a 12-week period , during which all subjects were instructed to follow a balanced hypocaloric diet and to walk for 50 min per day . Data were collected 1 week before ( T1 ) and 1 week after ( T2 ) dietary intervention . Energy intake and amount of carbohydrate ingested by both groups diminished over the trial , whereas the consumption of protein and fibre increased and lipid ingestion remained unchanged . At T1 there were no differences in biochemical or anthropometric characteristics between the groups , whereas at T2 group C presented a higher level of HDL ( 48.7 +/- 2.4 vs. 45.00 +/- 5.6 ; P = 0.01 ) and a lower LDL : HDL ratio ( 2.41 +/- 0.8 vs. 3.1 +/- 0.8 ; P = 0.04 ) . Reductions in BMI were observed in both groups at T2 ( P < 0.05 ) , but only group C exhibited a reduction in WC ( P = 0.005 ) . Group S presented an increase ( P < 0.05 ) in total cholesterol , LDL and LDL : HDL ratio , whilst HDL diminished ( P = 0.03 ) . Such alterations were not observed in group C. It appears that dietetic supplementation with coconut oil does not cause dyslipidemia and seems to promote a reduction in abdominal obesity .

soy bean oil

coconut oil

( group C ; n = 20 )

walk for 50 min per day

biochemical and anthropometric profiles

biochemical and anthropometric profiles

consumption of protein and fibre

Reductions in BMI

WC

HDL

abdominal obesity .

women

abdominal obesity

waist circumferences ( WC )

women

aged 20-40 years


Local anaesthetic use for the iliac crest-donor site : pharmacokinetic and pharmacodynamic evaluations . During orthopaedic surgery of the limb , we performed a prospective , double blind controlled study on three parallel groups in 30 patients to evaluate the pharmacokinetic and pharmacodynamic effect of infiltration of the iliac crest bone graft harvest site with 20 ml of bupivacaine ( 100 mg ) , ropivacaine ( 150 mg ) or saline as control group ( n = 10 in each group ) . Then , in a sheep model of iliac crest infiltration , we compared the pharmacokinetics of single administration of plain bupivacaine ( 100 mg ) and bupivacaine ( 500 mg ) -loaded microspheres . In the clinical control group , pain from the iliac crest was worse than pain from the primary surgical site . Pain from the iliac crest was significantly reduced during the first 12 postoperative hours in local anaesthetic groups compared to the control group . However , during this period , pain from the primary surgical site was increased compared to the control group . Finally , there was no difference between the three groups in the average intake of PCA morphine . There was no significant pharmacokinetic and pharmacodynamic difference between plain bupivacaine and ropivacaine . The maximal plasma concentration ( Cmax ) of ropivacaine and bupivacaine were 964 ( 282 ) ng ml ( -1 ) and 638 ( 366 ) ng ml ( -1 ) , respectively . In the sheep model , it was clearly shown that the release of bupivacaine from microspheres was controlled and prolonged despite the largest dose of bupivacaine used ( 500 mg ; n = 4 ) . Wound infiltration of iliac crest harvest site with local anaesthetic is an easy technique for postoperative analgesia . However , this effect lasts only 12 hours without reducing the morphine consumption due to an increase of pain from the primary surgical site . The local anaesthetic infiltration produced a significant peak of plasma level , which could be dangerous if another infiltration or regional anaesthetic technique was associated with it . Experimentally , as a drug delivery system , the use of local anaesthetic-loaded microspheres could be an interesting alternative .

orthopaedic surgery

20 ml of bupivacaine ( 100 mg )

ropivacaine ( 150 mg )

bupivacaine

bupivacaine

morphine

bupivacaine

ropivacaine

ropivacaine

bupivacaine

bupivacaine

bupivacaine

anaesthetic-loaded microspheres

Pain from the iliac crest

significantly reduced

no difference

no significant

pharmacokinetic and pharmacodynamic

difference

maximal plasma concentration ( Cmax )

morphine consumption

significant peak of plasma level

orthopaedic surgery

three parallel groups


Efficacy of chlorhexidine gluconate use in the prevention of perirectal infections in patients with acute leukemia . The frequency of rectal infections is increased in patients with acute leukemia . Complications associated with rectal lesions may be severe enough to cause life-threatening septicemia . Clinical research evaluating the effects of preventive perirectal skin care is scarce . This study 's purpose was to determine whether using chlorhexidine gluconate ( CHG ) in a prophylactic perirectal skin-care regimen decreases perirectal infections and whether it produces more skin irritation than a nonmedicated skin cleanser . The sample consisted of 40 patients , 16 of whom were randomized to use chlorhexidine and 24 of whom were randomized to use nonmedicated skin cleanser . Chi-square and t-tests were used to analyze the incidence of skin breakdown and rectal infections ; the correlation between the two factors ; a positive history of rectal infections , fissures , or hemorrhoids ; presence of hemorrhoids ; severity of diarrhea ; and duration and severity of granulocytopenia . A positive relationship was found between the severity of granulocytopenia and the incidence of rectal infections ( p = 0.02 ) . No significant difference was seen in the occurrence of perirectal infections ( p = 0.35 ) or skin breakdown ( p = 0.18 ) between the two groups . The data suggest that CHG does not offer increased protection against perirectal infections in patients undergoing intensive chemotherapy , nor is it more irritating than a nonmedicated skin cleanser . Further studies are needed to examine the efficacy of hygienic measures such as using skin disinfectants to prevent infections in patients who are immunocompromised .

chlorhexidine gluconate

chlorhexidine gluconate ( CHG )

chlorhexidine

nonmedicated skin cleanser

Efficacy

rectal infections

skin breakdown

rectal infections

severity of granulocytopenia

incidence of rectal infections

occurrence of perirectal infections

skin breakdown

acute leukemia

rectal infections

acute leukemia


Gamma-hydroxybutyric acid versus clomethiazole for the treatment of alcohol withdrawal syndrome in a medical intensive care unit : an open , single-center randomized study . BACKGROUND Clomethiazole ( CLO ) has been shown to be effective in treating alcohol withdrawal syndrome ( AWS ) . Gamma-Hydroxybutyric acid ( GHB ) has also been introduced in the treatment of alcoholic patients and is effective in surgical intensive care unit ( ICU ) patients in preventing and treating AWS . There are no comparative studies between CLO and GHB in a medical ICU setting . METHODS Twenty-six alcoholic patients with severe AWS and concomitant medical diseases were randomally enrolled in the study . CLO was given orally to 12 patients in a dosage of 250 mg every 4 hours as a liquid ; GHB ( initially 30 mg/kg body weight ( BW ) followed by 15 mg/kg BW ) was administered intravenously to 14 patients . Four major AWS symptoms ( tremor , sweating , nausea , restlessness ) were scored , and the administration of additional medication was registered . RESULTS GHB was more effective in treating AWS symptoms . In the GHB group , AWS score dropped from 6.6 +/- 2.6 to 1.8 +/- 2.1 ( p < .01 ) , while in the CLO group , the score dropped from 6 +/- 2.5 to 4.1 +/- 2.4 ( n. s. ) . Differences between groups were significant ( p =.021 , two-way ANOVA ) . The treatment did not alter outcome or the duration of ICU stay . No serious side effects were detected . CONCLUSION GHB effectively controls AWS symptoms in medical ICU patients . The rapid initial treatment response of GHB in contrast to CLO has no influence on duration of patient withdrawal .

Gamma-hydroxybutyric acid

clomethiazole

Clomethiazole ( CLO )

Gamma-Hydroxybutyric acid ( GHB )

CLO

GHB

GHB

GHB

GHB

CLO

GHB

CLO

alcohol withdrawal syndrome

AWS

AWS

AWS symptoms

tremor

sweating

nausea

restlessness

additional medication

AWS

duration of ICU stay

No serious side effects

AWS symptoms

duration of patient withdrawal

alcohol withdrawal syndrome

alcohol withdrawal syndrome ( AWS )

Twenty-six

alcoholic


Noninvasive detection of candidate molecular biomarkers in subjects with a history of insulin resistance and colorectal adenomas . We have developed novel molecular methods using a stool sample , which contains intact sloughed colon cells , to quantify colonic gene expression profiles . In this study , our goal was to identify diagnostic gene sets ( combinations ) for the noninvasive classification of different phenotypes . For this purpose , the effects of a legume-enriched , low glycemic index , high fermentable fiber diet was evaluated in subjects with four possible combinations of risk factors , including insulin resistance and a history of adenomatous polyps . In a randomized crossover design controlled feeding study , each participant ( a total of 23 ; 5-12 per group ) consumed the experimental diet ( 1.5 cups of cooked dry beans ) and a control diet ( isocaloric average American diet ) for 4 weeks with a 3-week washout period between diets . Using prior biological knowledge , the complexity of feature selection was reduced to perform an exhaustive search on all allowable feature ( gene ) sets of size 3 , and among these , 27 had ( unbiased ) error estimates of 0.15 or less . Linear discriminant analysis was successfully used to identify the best single genes and two- to three-gene combinations for distinguishing subjects with insulin resistance , a history of polyps , or exposure to a chemoprotective legume-rich diet . These results support our premise that gene products ( RNA ) isolated from stool have diagnostic value in terms of assessing colon cancer risk .

novel molecular methods

control diet

history of adenomatous polyps

total of 23 ;

insulin resistance

history of polyps


Randomized clinical trial of balance-based torso weighting for improving upright mobility in people with multiple sclerosis . BACKGROUND Torso weighting has sometimes been effective for improving upright mobility in people with multiple sclerosis , but parameters for weighting have been inconsistent . OBJECTIVE To determine whether balance-based torso weighting ( BBTW ) has immediate effects on upright mobility in people with multiple sclerosis . METHODS This was a 2-phase randomized clinical trial . In phase 1 , 36 participants were randomly assigned to experimental and control groups . In phase 2 , the control group was subsequently randomized into 2 groups with alternate weight-placement . Tests of upright mobility included : timed up and go ( TUG ) , sharpened Romberg , 360-degree turns , 25-foot walk , and computerized platform posturography . Participants were tested at baseline and again with weights placed according to group membership . In both phases , a physical therapist assessed balance for the BBTW group and then placed weights to decrease balance loss . In phase 1 , the control group had no weights placed . In phase 2 , the alternate treatment group received standard weight placement of 1.5 % body weight . RESULTS People with BBTW showed a significant improvement in the 25-foot walk ( P = .01 ) over those with no weight , and the TUG ( P = .01 ) over those with standard weight placement . BBTW participants received an average of 0.5 kg , less than 1.5 % of any participant 's body weight . CONCLUSION BBTW can have immediate advantages over a nonweighted condition for gait velocity and over a standardized weighted condition for a functional activity in people with multiple sclerosis ( MS ) who are ambulatory but have balance and mobility abnormalities .

torso weighting

balance-based torso weighting ( BBTW )

computerized platform posturography

BBTW

BBTW

upright mobility

upright mobility

parameters for weighting

upright mobility

timed up and go ( TUG )

sharpened Romberg

360-degree turns

25-foot walk ,

computerized platform posturography

balance loss

25-foot walk

gait velocity

functional activity

multiple sclerosis

multiple sclerosis

multiple sclerosis

multiple sclerosis

MS


MDM2 and Ki-67 predict for distant metastasis and mortality in men treated with radiotherapy and androgen deprivation for prostate cancer : RTOG 92-02 . PURPOSE MDM2 regulates p53 , which controls cell cycle arrest and apoptosis . Both proteins , along with Ki-67 , which is an established strong determinant of metastasis , have shown promise in predicting the outcome of men treated with radiation therapy ( RT ) with or without short-term androgen deprivation ( STAD ) . This report compares the utility of abnormal expression of these biomarkers in estimating progression in a cohort of men treated on RTOG 92-02 . PATIENTS AND METHODS Adequate tissue for immunohistochemistry was available for p53 , Ki-67 , and MDM2 analyses in 478 patient cases . The percentage of tumor nuclei staining positive ( PSP ) was quantified manually or by image analysis , and the per-sample mean intensity score ( MIS ) was quantified by image analysis . Cox regression models were used to estimate overall mortality ( OM ) , and Fine and Gray 's regressions were applied to the end points of distant metastasis ( DM ) and cause-specific mortality ( CSM ) . Results In multivariate analyses that adjusted for all markers and treatment covariates , MDM2 overexpression was significantly related to DM ( P = .02 ) and OM ( P = .003 ) , and Ki-67 overexpression was significantly related to DM ( P < .0001 ) , CSM ( P = .0007 ) , and OM ( P = .01 ) . P53 overexpression was significantly related to OM ( P = .02 ) . When considered in combination , the overexpression of both Ki-67 and MDM2 at high levels was associated with significantly increased failure rates for all end points ( P < .001 for DM , CSM , and OM ) . CONCLUSION Combined MDM2 and Ki-67 expression levels were independently related to distant metastasis and mortality and , if validated , could be considered for risk stratification of patients with prostate cancer in clinical trials .

radiotherapy

androgen deprivation

radiation therapy ( RT )

distant metastasis

mortality

tumor nuclei staining positive

per-sample mean intensity score

( MIS )

overall mortality ( OM )

distant metastasis ( DM )

cause-specific mortality ( CSM )

MDM2 overexpression

DM

DM

CSM

OM

P53 overexpression

OM

overexpression of both Ki-67

significantly increased failure rates

Ki-67 expression levels

distant metastasis

mortality


Effects of weight-bearing versus nonweight-bearing exercise on function , walking speed , and position sense in participants with knee osteoarthritis : a randomized controlled trial . OBJECTIVE To investigate whether weight-bearing ( WB ) exercise enhances functional capacity to a greater extent than nonweight-bearing ( NWB ) exercise in participants with knee osteoarthritis . DESIGN Randomized controlled trial . SETTING Kinesiology laboratory . PARTICIPANTS Participants ( N=106 ) were randomly assigned to WB exercise , NWB exercise , or a control group ( no exercise ) . INTERVENTION WB exercise and NWB exercise groups underwent an 8-week knee extension-flexion exercise program . MAIN OUTCOME MEASURES Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) function scale , walking speed , muscle torque , and knee reposition error were assessed before and after intervention . RESULTS Equally significant improvements were apparent for all outcomes after WB exercise and NWB exercise , except for reposition error , for which improvement was greater in the WB exercise group . In contrast , there were no improvements in the control group . CONCLUSIONS Simple knee flexion and extension exercises ( WB and NWB ) performed over 8 weeks resulted in significant improvement in the WOMAC function scale and knee strength compared with the control group . NWB exercise alone may be sufficient enough to improve function and muscle strength . The additional benefit of WB exercise was improved position sense , which may enhance complex walking tasks ( walking on figure of 8 route and spongy surface ) .

weight-bearing

nonweight-bearing exercise

weight-bearing ( WB ) exercise

nonweight-bearing ( NWB ) exercise

WB exercise

NWB exercise

control group ( no exercise )

WB exercise

WB

NWB

NWB exercise

WB exercise

functional capacity

reposition error

WOMAC function scale and knee strength

function and muscle strength .

position sense

complex walking tasks


Clinical impact of leak compensation during non-invasive ventilation . BACKGROUND This study aimed to assess the impact of leak compensation capabilities during pressure- and volume-limited non-invasive positive-pressure ventilation ( NPPV ) in COPD patients . METHODS Fourteen patients with stable hypercapnic COPD who were receiving long-term NPPV were included in the study . For both modes of NPPV , a full face mask and an artificial leak in the ventilatory circuit were used at three different settings , and applied during daytime NPPV , either without leakage ( setting I ) , with leakage during inspiration only ( setting II ) , and with leakage during inspiration and expiration ( setting III ) . Ventilation pattern was pneumotachy-graphically recorded . RESULTS NPPV was feasible with negligible leak volumes , indicating optimal mask fitting during the daytime ( setting I ) . In the presence of leakage ( settings II and III ) , the attempt to compensate for leak was only evident during pressure-limited NPPV , since inspiratory volumes delivered by the ventilator increased from 726+/-129 ( setting I ) to 1104+/-164 ( setting II ) , and to 1257+/-166 ( setting III ) ml during pressure-limited NPPV , respectively ( all p < 0.001 ) ; however , they remained stable during volume-limited NPPV . Leak compensation resulted in a decrease in leakage-induced dyspnea . However , 83 % /87 % ( setting II/III ) of the additionally-delivered inspiratory volume during pressure-limited NPPV was also lost via leakage . Expiratory volume was higher in setting II compared to setting III ( both p < 0.001 ) , indicating the presence of significant expiratory leakage . CONCLUSIONS The attempt at leak compensation largely feeds the leakage itself and only results in a marginal increase of tidal volume . However , pressure-limited -- but not volume-limited -- NPPV results in a clinically-important leak compensation in vivo . TRIAL REGISTRATION www.uniklinik-freiburg.de/zks/live/uklregister/Oeffentlich.html Identifier : UKF001272 .

Ventilation pattern

leak volumes

leakage

leakage-induced dyspnea .

Expiratory volume

Fourteen

stable hypercapnic COPD

receiving long-term NPPV


Lack of efficacy of citalopram in children with autism spectrum disorders and high levels of repetitive behavior : citalopram ineffective in children with autism . CONTEXT Selective serotonin reuptake inhibitors are widely prescribed for children with autism spectrum disorders . OBJECTIVES To determine the efficacy and safety of citalopram hydrobromide therapy for repetitive behavior in children with autism spectrum disorders . DESIGN National Institutes of Health-sponsored randomized controlled trial . SETTING Six academic centers , including Mount Sinai School of Medicine , North Shore-Long Island Jewish Health System , University of North Carolina at Chapel Hill , University of California at Los Angeles , Yale University , and Dartmouth Medical School . PARTICIPANTS One hundred forty-nine volunteers 5 to 17 years old ( mean [ SD ] age , 9.4 [ 3.1 ] years ) were randomized to receive citalopram ( n = 73 ) or placebo ( n = 76 ) . Participants had autistic spectrum disorders , Asperger disorder , or pervasive developmental disorder , not otherwise specified ; had illness severity ratings of at least moderate on the Clinical Global Impressions , Severity of Illness Scale ; and scored at least moderate on compulsive behaviors measured with the Children 's Yale-Brown Obsessive Compulsive Scales modified for pervasive developmental disorders . INTERVENTIONS Twelve weeks of citalopram hydrobromide ( 10 mg/5 mL ) or placebo . The mean ( SD ) maximum dosage of citalopram hydrobromide was 16.5 ( 6.5 ) mg/d by mouth ( maximum , 20 mg/d ) . MAIN OUTCOME MEASURES Positive response was defined by a score of much improved or very much improved on the Clinical Global Impressions , Improvement subscale . An important secondary outcome was the score on the Children 's Yale-Brown Obsessive Compulsive Scales modified for pervasive developmental disorders . Adverse events were systematically elicited using the Safety Monitoring Uniform Report Form . RESULTS There was no significant difference in the rate of positive response on the Clinical Global Impressions , Improvement subscale between the citalopram-treated group ( 32.9 % ) and the placebo group ( 34.2 % ) ( relative risk , 0.96 ; 95 % confidence interval , 0.61-1.51 ; P > .99 ) . There was no difference in score reduction on the Children 's Yale-Brown Obsessive Compulsive Scales modified for pervasive developmental disorders from baseline ( mean [ SD ] , -2.0 [ 3.4 ] points for the citalopram-treated group and -1.9 [ 2.5 ] points for the placebo group ; P = .81 ) . Citalopram use was significantly more likely to be associated with adverse events , particularly increased energy level , impulsiveness , decreased concentration , hyperactivity , stereotypy , diarrhea , insomnia , and dry skin or pruritus . CONCLUSION Results of this trial do not support the use of citalopram for the treatment of repetitive behavior in children and adolescents with autism spectrum disorders . Trial Registration clinicaltrials.gov Identifier : NCT00086645 .

citalopram

citalopram

Selective serotonin reuptake inhibitors

citalopram hydrobromide therapy

citalopram

placebo

citalopram hydrobromide

placebo

citalopram hydrobromide

citalopram-treated

placebo

citalopram-treated

placebo

Citalopram

citalopram

efficacy

Adverse events

developmental disorders

energy level , impulsiveness

children with autism .


Safety and efficacy of a new 3.3 g b.i.d . tablet formulation in patients with mild-to-moderately-active ulcerative colitis : a multicenter , randomized , double-blind , placebo-controlled study . OBJECTIVES To evaluate the safety and efficacy of a new twice-daily balsalazide disodium 1.1 g tablet dosing regimen ( 6.6 g/day , three tablets twice daily ) for the treatment of mild-to-moderately-active ulcerative colitis ( UC ) . METHODS In a double-blind , multicenter study patients with symptoms of acute UC and a baseline Modified Mayo Disease Activity Index ( MMDAI ) score between 6 and 10 , inclusive , with a subscale rating of > or =2 for both rectal bleeding and mucosal appearance were randomized to receive 3.3 g of balsalazide or placebo tablets twice daily for 8 weeks . The primary end point was the proportion of patients achieving clinical improvement ( > or =3 point improvement in MMDAI ) and improvement in rectal bleeding ( > or =1 point improvement ) at 8 weeks . Safety assessments were conducted from baseline through 2-weeks post-treatment . RESULTS A total of 249 patients ( 166 balsalazide , 83 placebo ) received at least 1 dose of study medication . The mean MMDAI score at baseline was 7.9 ; 62 % of patients had a score > or =8.0 ( moderate disease ) . A significantly larger proportion of patients achieved clinical improvement and improvement in rectal bleeding in the balsalazide group vs. the placebo group ( 55 vs. 40 % , P=0.02 ) . The most common adverse events reported were worsening of UC and headache ; both were reported more often in the placebo group . CONCLUSIONS Balsalazide disodium 1.1 g tablets administered as 3.3 g twice daily are effective , well tolerated and significantly better than placebo for improving signs and symptoms of mild-to-moderately-active UC . This new formulation with a reduced pill and dosing burden offers the potential to improve convenience and compliance in patients with active UC .

new 3.3 g b.i.d . tablet formulation

balsalazide disodium 1.1 g tablet

balsalazide

placebo

balsalazide

placebo

balsalazide

placebo

placebo

Balsalazide disodium

placebo

Safety and efficacy

safety and efficacy

mean MMDAI score

clinical improvement

improvement in rectal bleeding

worsening of UC

headache

effective

well tolerated

better

convenience

compliance

ulcerative colitis

acute UC

active UC


Transdermal scopolamine patch in addition to ondansetron for postoperative nausea and vomiting prophylaxis in patients undergoing ambulatory cosmetic surgery . STUDY OBJECTIVE To determine the efficacy of transdermal scopolamine in addition to ondansetron in decreasing the incidence of postoperative nausea and vomiting ( PONV ) . DESIGN Randomized controlled trial . SETTING Academic hospital . PATIENTS 126 ASA physical status I and II patients undergoing outpatient plastic surgery with three or more risk factors for PONV . INTERVENTIONS Patients were randomly assigned to one of two groups to receive ( Group 1 ) a transdermal scopolamine ( TDS ) patch or ( Group 2 ) , a placebo patch two hours before surgery . MEASUREMENTS Occurrence of vomiting , severity of nausea using a visual analog scale ( VAS ) , rescue medication , pain intensity and pain medications , and side effects were recorded every hour until discharge from hospital , then every 4 hours thereafter for a total of 24 hours . MAIN RESULTS A statistically significant reduction in postoperative nausea between 8 and 24 hours in patients receiving TDS was noted . CONCLUSIONS Transdermal scopolamine in addition to ondansetron benefits patients at high risk for PONV undergoing outpatient plastic surgery for up to 20 hours after surgery .

Transdermal scopolamine patch

ondansetron

transdermal scopolamine

ondansetron

transdermal scopolamine ( TDS ) patch

placebo patch

scopolamine

postoperative nausea and vomiting

Occurrence of vomiting

severity of nausea

visual analog scale ( VAS )

rescue medication

pain intensity

pain medications

side effects

postoperative nausea

postoperative nausea and vomiting

PONV

three or more risk factors for PONV


One-year follow-up of the outcome of a randomized controlled trial of a home-based intervention programme for children with autism and developmental delay and their families . INTRODUCTION There is debate about the type and intensity of early childhood intervention that is most helpful for children with developmental problems . The aim of the study was to determine whether a home-based programme provided over 12 months resulted in sustained improvement in development and behaviour 12 months after the intervention ceased . The characteristics of the children and families who benefited most from the intervention were also studied . METHOD Randomized controlled trial . Participants A total of 59 children , aged 3-5 years , attending two early childhood intervention centres in Melbourne , Australia . Intervention Half of the subjects received an additional home-based programme consisting of 40 weekly visits . MAIN OUTCOME MEASURES Bayley Scales of Infant Development and Wechsler Preschool and Primary Scale of Intelligence Revised , Preschool Behaviour Checklist , Bayley Behaviour Rating Scale and Behaviour Screening Questionnaire . All tests administered pre-intervention , following the intervention and 12 months later . Secondary outcome measures Family stress , support and empowerment . RESULTS Fifty-four children completed the assessments 12 months after conclusion of the intervention . Compared with the control group , improvement in aspects of cognitive development in the children who received the extra intervention was sustained 1 year later ( P= 0.007 ) while significant behavioural differences post intervention were not . Analyses of the data by the Reliable Change Index indicated improvement of clinical significance occurred in non-verbal areas . In contrast to the control group who deteriorated , language skills in the intervention group remained stable . Improvements were significantly associated with higher stress in the families . CONCLUSION Improvements following the provision of a home-based programme to preschool children with developmental disabilities were sustained 1 year later . Children from highly stressed families appeared to benefit most , reinforcing the importance of involving families in early childhood intervention programmes .

home-based intervention programme

early childhood intervention

behavioural differences

Reliable Change Index

non-verbal areas .

language skills

stress

children

autism and developmental delay

children

developmental problems

3-5 years

Fifty-four

children


Loss of bone mineral density after antiretroviral therapy initiation , independent of antiretroviral regimen . BACKGROUND Decreased bone mineral density ( BMD ) has been described in HIV-infected patients initiating antiretroviral therapy ( ART ) , but the contributions of ART and immunologic and/or virologic factors remain unclear . METHODS We compared total BMD changes over 96 weeks in 106 ART-naive HIV-infected subjects who were randomized to receive efavirenz ( EFV ) + zidovudine/lamivudine ( n = 32 ) or lopinavir/ritonavir ( LPV/r ) + zidovudine/lamivudine induction ( n = 74 ) for 24-48 weeks followed by LPV/r monotherapy . We also sought to identify factors associated with BMD loss , including markers of systemic inflammation [ soluble tumor necrosis factor-alpha receptors ( sTNFR I and II ) ] . RESULTS After 96 weeks , the mean percent change from baseline in total BMD was -2.5 % ( LPV/r ) and -2.3 % ( EFV ) ( P < 0.01 for within-group changes in either arm ; P = 0.86 for between-group differences ) . No alteration in the rate of BMD change was observed upon simplification to LPV/r monotherapy . Although soluble tumor necrosis factor-alpha receptor II concentrations at baseline and 24 weeks were at least marginally associated with subsequent changes in BMD ( P = 0.06 and P = 0.028 , respectively ) , these associations were no longer significant after adjustment for CD4 T cell count . Subjects with lower baseline CD4 T cell count , non-black race , and higher baseline glucose demonstrated a higher risk for > 5 % decrease in BMD . CONCLUSIONS Similar decreases in BMD over 96 weeks occurred in ART-naive subjects receiving either EFV-based regimen or LPV/r-based regimen , which was not altered by simplification to LPV/r monotherapy and was unrelated to markers of tumor necrosis factor-alpha activity .

antiretroviral therapy initiation

LPV/r monotherapy .

bone mineral density

bone mineral density ( BMD )

BMD

rate of BMD change

BMD

BMD

BMD

ART-naive HIV-infected subjects

ART-naive


Folic acid-based intervention in non-ST elevation acute coronary syndromes . Homocysteinemia is a risk factor for cardiovascular diseases . Folic acid combined with vitamins B ( 6 ) and B ( 12 ) is effective in lowering homocysteine levels . This randomized placebo-controlled study was designed to determine the effect of a folic acid-based supplement on secondary prevention of clinical events in non-ST-segment elevation acute coronary syndromes . The study comprised 240 patients with either unstable angina or non-ST-elevation myocardial infarction in the previous 2 weeks who were randomized to a folate group ( n =116 ) or a placebo group ( n =124 ) . The folate group received 1 mg folic acid , 400 microg vitamin B ( 12 ) , and 10 mg vitamin B ( 6 ) daily . Clinical outcomes within 6 months were assessed . The composite endpoint of death , nonfatal acute coronary syndrome , and serious re-hospitalization was significantly higher in the folate group ; serious re-hospitalization alone was significantly higher in this group . Advanced age and diabetes increased susceptibility to the composite outcome . Folic acid-based supplementation is not beneficial and may even be harmful in the secondary prevention of cardiovascular events in patients with unstable angina and non-ST-elevation myocardial infarction . Further studies on the safety of such supplements are suggested . Controlled Clinical Trials Registry no . ISRCTN30249553 .

Folic acid-based intervention

Folic acid

vitamins B ( 6 ) and B ( 12 )

placebo-controlled

folic acid-based supplement

folate

placebo group

folic acid

vitamin B ( 12 )

vitamin B ( 6 )

Folic acid-based supplementation

homocysteine levels

Clinical outcomes

death

nonfatal acute coronary syndrome

serious re-hospitalization

Advanced age and diabetes

prevention of cardiovascular events


Aerobic and strength training reduces adiposity in overweight Latina adolescents . PURPOSE To date , no study has examined the synergistic effects of a nutrition and combination of aerobic and strength training ( CAST ) on both adiposity and metabolic parameters in overweight Latina adolescent females . The goal was to assess if a 16-wk nutrition plus CAST pilot study had stronger effects on reducing adiposity and on improving glucose/insulin indices compared with control ( C ) , nutrition only ( N ) , and a nutrition plus strength training ( N + ST ) groups . METHODS In a 16-wk randomized trial , 41 overweight Latina girls ( 15.2 +/- 1.1 yr ) were randomly assigned to C ( n = 7 ) , N ( n = 10 ) , N + ST ( n = 9 ) , or N + CAST ( n = 15 ) . All intervention groups received modified carbohydrate nutrition classes ( once a week ) , whereas the N + ST also received strength training ( twice a week ) and the N + CAST received a combination of strength and aerobic training ( twice a week ) . The following were measured before and after intervention : strength by one repetition maximum , physical activity by the 7-d accelerometry and the 3-d physical activity recall , dietary intake by 3-d records , body composition by dual-energy x-ray absorptiometry ( DEXA ) , glucose/insulin indices by oral glucose tolerance test , and intravenous glucose tolerance test with minimal modeling . Across intervention group , effects were tested using ANCOVA with post hoc pairwise comparisons . RESULTS There were significant overall intervention effects for all adiposity measures ( weight , body mass index [ BMI ] , BMI z-scores , and DEXA total body fat ) , with a decrease of 3 % in the N + CAST group compared with a 3 % increase in the N + ST group ( P < or = 0.05 ) . There was also an intervention effect for fasting glucose with the N group increasing by 3 % and the N + CAST group decreasing by 4 % ( P < or = 0.05 ) . CONCLUSION The CAST was more effective than nutrition alone or nutrition plus strength training for reducing multiple adiposity outcomes and fasting glucose in overweight Latina girls . However , further research investigating and identifying intervention approaches that improve both adiposity and insulin indices , particularly in high-risk populations , are warranted .

Aerobic and strength training

nutrition

nutrition

CAST

nutrition

nutrition

strength training

C

N

N + ST

N + CAST

modified carbohydrate nutrition classes

N + ST

received strength training

N + CAST

N + CAST

N + ST

N

N + CAST

CAST

nutrition

nutrition

strength training

adiposity

adiposity

metabolic parameters

adiposity

glucose/insulin indices

strength

3-d physical activity recall

dietary intake

body composition

glucose/insulin indices

fasting glucose

multiple adiposity outcomes

fasting glucose

adiposity

insulin indices

overweight Latina

adolescents

females

overweight

girls

15.2 +/- 1.1 yr

overweight

girls


Randomized placebo controlled human volunteer trial of a live oral cholera vaccine VA1.3 for safety and immune response . A live oral cholera vaccine developed from a non-toxigenic Vibrio cholerae O1 El Tor strain VA1.3 was tested in a double-blind randomized placebo controlled study for safety and immunogenicity in 304 men aged between 16 and 50 years from Kolkata , India . A dose of 5 x 10 ( 9 ) CFU ( n=186 ) or a placebo ( n=116 ) containing the diluent buffer was administered . The vaccine did not elicit adverse events except in two vaccine recipients with mild diarrhoea and vomiting . None excreted the vaccine strain . Vibriocidal antibody response developed in 105/186 ( 57 % ) and 5/116 ( 4 % ) in vaccine and placebo recipients , respectively . In a subgroup , anti-CT antibody rose ( > or =2-folds ) in 23/30 ( 77 % ) and 6/19 ( 32 % ) in vaccine and placebo recipients , respectively . These studies demonstrate that VA1.3 at a dose of 5 x 10 ( 9 ) is safe and immunogenic in adults from a cholera endemic region .

placebo

live oral cholera vaccine VA1.3

placebo

placebo

safety

adverse events

mild diarrhoea and vomiting

Vibriocidal antibody response

anti-CT antibody rose

safe and immunogenic

volunteer trial


Loss of autonomy among elderly patients after a stay in a medical intensive care unit ( ICU ) : a randomized study of the benefit of transfer to a geriatric ward . In order to evaluate changes in the functional autonomy of elderly patients after a stay in a medical intensive care unit ( ICU ) , and the impact of post-ICU management in geriatric ward , we included in a randomized controlled trial 45 patients aged > or=75 years . They were assessed for functional autonomy before ICU stay , just after ICU discharge , just after hospital discharge , and 6 months later . The patients were randomly divided into two post-ICU management groups : " geriatric ward " and " standard care " . Autonomy was usually recovered rapidly , but the degree of recovery depended on the patient 's previous autonomy ( p < 0.0001 ) . At the last assessment , 41 % of the patients had recovered their previous autonomy . The mean Barthel indexes were 81.5+/-30.4 in the geriatric management arm and 70.5+/-33.4 in the standard management arm ( p=0.4 ) . The study was prematurely ended due to insufficient recruitment flow . These results underline the rapid loss of autonomy after a stay in a medical ICU . Early specific intervention to improve the autonomy of elderly patients seems an attractive solution that could be assessed by randomized controlled trial . Above all , our results should also serve as a basis for further controlled randomized studies in this setting .

post-ICU management

geriatric ward

post-ICU management

" geriatric ward "

" standard care "

elderly

aged > or=75 years

elderly patients


Leucocyte depletion of perioperative blood transfusion does not affect long-term survival and recurrence in patients with gastrointestinal cancer . BACKGROUND Perioperative red blood cell ( RBC ) transfusion may be associated with a poor prognosis in cancer surgery . Allogeneic leucocytes are assumed to play a causal role . This study evaluated the long-term effect of transfusion with leucocyte-depleted ( LD ) blood in patients with gastrointestinal cancer . METHODS The Transfusion Associated Complications = Transfusion Induced Complications ? ( TACTIC ) study is a multicentre randomized controlled trial evaluating the short-term benefits of LD versus non-LD RBC transfusions . The present study evaluated 5-year survival and cancer recurrence among 512 patients with gastrointestinal cancer included in the TACTIC study . RESULTS Some 89.2 per cent of patients had a primary tumour and 79.7 per cent underwent surgery with curative intent ; 243 patients received perioperative RBC transfusion ( median 3 units ) . The 5-year overall survival rate of patients with any type of gastrointestinal cancer was 50.8 per cent in the LD group and 45.8 per cent in the non-LD group ( P = 0.191 ) . Corresponding 5-year disease-free survival rates were 60.0 and 56.6 per cent ( P = 0.482 ) , and recurrence rates 32.9 and 34.3 per cent ( P = 0.864 ) . CONCLUSION Leucocyte depletion is not associated with better long-term survival and lower recurrence rates in patients with gastrointestinal cancer .

perioperative blood transfusion

transfusion with leucocyte-depleted

LD versus

non-LD RBC transfusions

surgery

perioperative RBC transfusion

long-term survival

leucocyte-depleted

perioperative RBC transfusion

5-year disease-free survival rates

recurrence rates

long-term survival

lower recurrence rates

gastrointestinal cancer

gastrointestinal cancer

gastrointestinal cancer

primary tumour

gastrointestinal cancer


Quick change versus double pump while changing the infusion of inotropes : an experimental study . BACKGROUND Quick change ( QC ) and double pumping ( DP ) are common methods of substituting the infusion of inotropes given through intravenous pump . AIMS The aim of the study was to compare two methods in respect with the variation in mean arterial pressure ( MAP ) . The hypothesis was that the DP method could be the most effective in achieving haemodynamic stability . DESIGN The study is a randomized research in an open randomized clinical trial . METHODS The study took place at the Paediatric Intensive Care Unit of Padua Hospital . It considered patients of 0-36 months , not premature , treated with inotropic infusion with monitoring of blood pressure . The research obtained the approval of the Hospital Research Ethics committee and parents signed informed consent . Comparison of the two groups made use of the Wilcoxon test for the continuous variables and the Fisher 's exact test for the comparison of frequencies , at significance value of 5 % . The data were registered in an Excel spreadsheet and analysed with SAS . RESULTS The sample comprised 30 patients of age between 1 and 27 months , of whom 13 ( 43 % ) were male . They were all affected by cardiac , respiratory or infective pathology , all of them intubated and on artificial respiratory support , sedated and infused with dopamine . The characteristics of the patients of the two groups did not differ significantly . The percentage variation of the baseline value of MAP after 30 min from starting the treatment between the two methods was not statistically significant ( p = 0.85 ) . The 95 % confidence interval for the difference in the percentage variation of MAP between the two groups was ( -3.1 , +3.7 ) . From a clinical perspective , the methods are to be considered equivalent . CONCLUSIONS The study was conducted on a limited sample ; no statistically significant differences were detected ; QC is the quickest and more cost-effective method .

Quick change

versus

double pump

Quick change ( QC )

and

double pumping ( DP )

DP

inotropic infusion

QC

mean arterial pressure ( MAP )

haemodynamic stability

blood pressure

MAP

MAP

quickest

cost-effective

Hospital Research Ethics committee


Emotional , motivational and interpersonal responsiveness of children with autism in improvisational music therapy . Through behavioural analysis , this study investigated the social-motivational aspects of musical interaction between the child and the therapist in improvisational music therapy by measuring emotional , motivational and interpersonal responsiveness in children with autism during joint engagement episodes . The randomized controlled study ( n = 10 ) employed a single subject comparison design in two different conditions , improvisational music therapy and toy play sessions , and DVD analysis of sessions . Improvisational music therapy produced markedly more and longer events of 'joy ' , 'emotional synchronicity ' and 'initiation of engagement ' behaviours in the children than toy play sessions . In response to the therapist 's interpersonal demands , 'compliant ( positive ) responses ' were observed more in music therapy than in toy play sessions , and 'no responses ' were twice as frequent in toy play sessions as in music therapy . The results of this exploratory study found significant evidence supporting the value of music therapy in promoting social , emotional and motivational development in children with autism .

improvisational music therapy

musical interaction

improvisational music therapy

Improvisational music therapy

toy play sessions

music therapy

music therapy

'compliant ( positive ) responses

'no responses '

children

autism

child

children

autism

children

autism


[ Clinilal study of medical ozone therapy in chronic hepatitis B of 20 patients ] . OBJECTIVE To study the effect of medical ozone in the treatment of chronic hepatitis B . METHODS 42 patients with chronic hepatitis B were divided randomly into two groups . 22 patients treated with basic therapy were as a control group . 20 patients treated with basic therapy plus ozone therapy were taken as a treatment group . Index of biochemistry and virology were studied at initial and post-treatment 8 weeks . RESULTS After the treatment , liver function of the treatment group and the control group had more significant improvement . The treatment group complete effective and partial effective were 10 % and 35 % difference . The control group complete effective and partial effective were 4.6 % and 13.6 % ( P < 0.05 ) . CONCLUSION Treatment of medical ozone on patients with chronic hepatitis B is effective .

medical ozone therapy

medical ozone

basic therapy

basic therapy plus ozone therapy

Index of biochemistry

virology

complete effective

partial effective

effective

chronic hepatitis B

chronic hepatitis B

chronic hepatitis B

chronic hepatitis B


Gemcitabine combined with either pemetrexed or paclitaxel in the treatment of advanced non-small cell lung cancer : a randomized phase II SICOG trial . PURPOSE To estimate the safety , activity , and impact on quality of life of a combination of gemcitabine and pemetrexed in patients with locally advanced or metastatic non-small cell lung cancer ( NSCLC ) in the context of a randomized two-stage phase II study . PATIENTS AND METHODS Patients in stage IIIB or IV NSCLC were randomly allocated to receive either gemcitabine 1250 mg/m ( 2 ) on day 1 , and pemetrexed ( Alimta ) 500 mg/m ( 2 ) followed by gemcitabine 1250 mg/m ( 2 ) on day 8 of a 3-weekly cycle ( GA arm ) , or paclitaxel 120 mg/m ( 2 ) followed by gemcitabine 1000 mg/m ( 2 ) , both given on days 1 and 8 of a 3-weekly cycle ( PG arm ) . RESULTS 105 ( GA arm , 51 ; PG arm , 54 ) eligible patients ( stage IV , 32 and 30 , respectively ) were enrolled into this study ; thereafter , accrual was stopped due to first-stage analysis . The response rate was 20 % ( 95 % confidence interval [ CI ] , 10-33 % ) in the GA arm , and 32 % ( 95 % CI , 20-46 % ) in the PG arm . Median progression-free survival was 5.1 ( 95 % CI , 3.7-6.5 ) months in the GA arm , and 8.3 ( 95 % CI , 5.9-10.7 ) months in the PG arm , while median overall survival was 10.5 ( 95 % CI 7.1-13.9 ) , and 13.3 ( 95 % CI 11.7-14.9 ) months , respectively . Severe neutropenia ( 36 % vs 22 % ) , and febrile neutropenia ( 14 % vs 7 % ) were more common with the GA regimen , while hair loss ( 52 % vs 16 % ) and any grade peripheral neuropathy ( 31 % vs 2 % ) occurred more frequently with PG regimen . Other severe side effects of GA regimen were diarrhoea ( 10 % ) , liver enzyme derangement ( 10 % ) , and fatigue ( 8 % ) . CONCLUSION The GA regimen was tolerated and moderately active in advanced or metastatic NSCLC . However , this combination did not yield any advantage in comparison with the PG regimen , and does not deserve further evaluation .

Gemcitabine

pemetrexed

paclitaxel

combination of gemcitabine

pemetrexed

gemcitabine

pemetrexed

gemcitabine

paclitaxel

gemcitabine

PG

PG regimen

GA regimen

safety ,

activity

, and impact on quality of life

response rate

Median progression-free survival

median overall survival

Severe neutropenia

febrile neutropenia

hair loss

any grade peripheral neuropathy

severe side effects

diarrhoea

liver enzyme derangement

fatigue

advanced non-small cell lung cancer

NSCLC


Pharmacokinetic- pharmacodynamic analysis of the role of CYP2C19 genotypes in short-term rabeprazole-based triple therapy against Helicobacter pylori . AIMS The aim was to explore the role of CYP2C19 polymorphism in short-term rabeprazole-based triple therapy against Helicobacter pylori infection . METHODS Patients with H. pylori infection were tested for CYP2C19 genotype as poor metabolizers ( PMs ) or extensive metabolizers ( EMs , homozygous EM or heterozygous EM ) and given rabeprazole for 7 days . Antibiotics ( clarithromycin and amoxicillin ) were given on days 1-4 , days 4-7 , or days 1-7 . A direct link model with an effect compartment was used in the population pharmacokinetic-pharmacodynamic analysis . The status of H. pylori infection was evaluated . RESULTS Rabeprazole clearance was lower in CYP2C19 PMs than in EMs ( with average values of 10.7 vs. 16.8 l h ( -1 ) in PMs and EMs , respectively ) , resulting in higher plasma levels in the former group . The values of EC ( 50 ) and k ( eo ) of gastrin response increased with multiple doses of rabeprazole . The k ( eo ) values were lower in CYP2C19 PMs than in EMs on day 1 ( 0.012 vs. 0.017 x 10 ( -4 ) l min ( -1 ) ) , and higher than in EMs on day 4 ( 0.804 vs. 0.169 x 10 ( -4 ) l min ( -1 ) ) of rabeprazole treatment . The predicted gastrin-time profile showed a higher response in CYP2C19 PMs than in EMs on days 4 and 7 . Helicobacter pylori was eradicated in all CYP2C19 PMs except in one patient infected by a resistant strain . In contrast , in CYP2C19 EMs the eradication rates ranged from 58 to 85 % . CONCLUSIONS CYP2C19 genotypes play a role in H. pylori eradication therapy . Rabeprazole-based short-term triple therapy may be applicable in CYP2C19 PMs for H. pylori eradication .

rabeprazole-based triple therapy

rabeprazole-based triple therapy

rabeprazole

Antibiotics

clarithromycin and amoxicillin

Rabeprazole

rabeprazole

rabeprazole

H. pylori infection

Rabeprazole clearance

values of EC ( 50 )

and

k ( eo ) of gastrin response

k ( eo ) values

predicted gastrin-time profile

Helicobacter pylori

eradicated

eradication rates


Short-term metformin treatment for clomiphene citrate-resistant women with polycystic ovary syndrome . OBJECTIVE To evaluate the effect of a short-course pretreatment with metformin on hyperandrogenism , insulin resistance , cervical scores , and pregnancy rates in women with clomiphene citrate ( CC ) -resistant polycystic ovary syndrome ( PCOS ) . METHODS Thirty-seven women with CC-resistant PCOS were randomly assigned to be pretreated with 500 mg of metformin or placebo 3 times per day for 2 cycles , and 100 mg of CC was given on days 5 through 9 of the second cycle in both groups . Luteinizing hormone ( LH ) , follicle stimulating hormone ( FSH ) , dehydroepiandrostendione sulfate ( DHEAS ) , total testosterone ( T ) , glucose , and insulin levels were measured at baseline and after the first cycle , as well as body mass index ( BMI ) , cervical score , and pregnancy rate . RESULTS After 1 cycle , BMI , total T level , and percentage of participants with insulin resistance were significantly decreased in the metformin group , without any significant decrease in LH , FSH , and DHEAS levels ; and in the second cycle , CC treatment resulted in a higher ovulation rate and a thicker endometrium in the metformin group . The pregnancy rate and cervical scores were also higher in that group . CONCLUSION The short-course pretreatment with metformin decreased hyperandrogenism and insulin resistance and improved cervical sores , ovulation rate , and pregnancy rate among women with CC-resistant PCOS .

metformin

metformin

clomiphene citrate

metformin

placebo

CC

metformin

CC

metformin

metformin

hyperandrogenism

insulin resistance

cervical scores

pregnancy rates

Luteinizing hormone ( LH )

follicle stimulating hormone ( FSH )

total testosterone ( T )

glucose

insulin levels

body mass index ( BMI

cervical score

pregnancy rate

BMI

total T level

LH

FSH

DHEAS levels

ovulation rate

thicker endometrium

pregnancy rate

cervical scores

hyperandrogenism

insulin resistance

cervical sores

ovulation rate

pregnancy rate

clomiphene citrate-resistant

women

polycystic ovary syndrome .

women

Thirty-seven

women

CC-resistant PCOS


Brief report : effects of cognitive behavioral therapy on parent-reported autism symptoms in school-age children with high-functioning autism . This pilot study tested the effect of cognitive behavioral therapy ( CBT ) on parent-reported autism symptoms . Nineteen children with autism spectrum disorders and an anxiety disorder ( 7-11 years old ) were randomly assigned to 16 sessions of CBT or a waitlist condition . The CBT program emphasized in vivo exposure supported by parent training and school consultation to promote social communication and emotion regulation skills . Parents completed a standardized autism symptom checklist at baseline and posttreatment/postwaitlist and 3-month follow-up assessments . CBT outperformed the waitlist condition at posttreatment/postwaitlist on total parent-reported autism symptoms ( Cohen 's d effect size = .77 ) . Treatment gains were maintained at 3-month follow-up . Further investigation of this intervention modality with larger samples and broader outcome measures appears to be indicated .

cognitive behavioral therapy

cognitive behavioral therapy ( CBT )

CBT

waitlist condition

CBT

parent-reported autism symptoms

standardized autism symptom checklist

total parent-reported autism symptoms

autism symptoms

school-age children

autism

autism

Nineteen

autism spectrum disorders

( 7-11 years old


A phase III clinical trial of exercise modalities on treatment side-effects in men receiving therapy for prostate cancer . BACKGROUND Androgen deprivation therapy ( ADT ) is accompanied by a number of adverse side effects including reduced bone mass and increased risk for fracture , reduced lean mass and muscle strength , mood disturbance and increased fat mass compromising physical functioning , independence , and quality of life . The purpose of this investigation is to examine the effects of long term exercise on reversing musculoskeletal-related side effects , and cardiovascular and diabetes risk factors in men receiving androgen deprivation for their prostate cancer . Specifically , we aim to investigate the effects of a 12-month exercise program designed to load the musculoskeletal system and reduce cardiovascular and diabetes disease progression on the following primary endpoints : 1 ) bone mineral density ; 2 ) cardiorespiratory function and maximal oxygen capacity ; 3 ) body composition ( lean mass and fat mass ) ; 4 ) blood pressure and cardiovascular function ; 5 ) lipids and glycemic control ; and 6 ) quality of life and psychological distress . METHODS/DESIGN Multi-site randomized controlled trial of 195 men ( 65 subjects per arm ) undergoing treatment for prostate cancer involving ADT in the cities of Perth and Brisbane in Australia . Participants will be randomized to ( 1 ) resistance/impact loading exercise , ( 2 ) resistance/cardiovascular exercise groups and ( 3 ) usual care/delayed exercise . Participants will then undergo progressive training for 12 months . Measurements for primary and secondary endpoints will take place at baseline , 6 and 12 months ( end of the intervention ) . DISCUSSION The principal outcome of this project will be the determination of the strength of effect of exercise on the well established musculoskeletal , cardiovascular and insulin metabolism side effects of androgen deprivation in prostate cancer patients . As this project is much longer term than previous investigations in the area of exercise and cancer , we will gain knowledge as to the continuing effects of exercise in this patient population specifically targeting bone density , cardiovascular function , lean and fat mass , physical function and falls risk as primary study endpoints . In terms of advancement of prostate cancer care , we expect dissemination of the knowledge gained from this project to reduce fracture risk , improve physical and functional ability , quality of life and ultimately survival rate in this population . CLINICAL TRIAL REGISTRY A Phase III clinical trial of exercise modalities on treatment side-effects in men receiving therapy for prostate cancer ; ACTRN12609000200280 .

exercise

Androgen deprivation therapy ( ADT )

exercise

androgen deprivation

exercise program

ADT

progressive training

exercise

musculoskeletal-related side effects

side effects

quality of life

ultimately survival rate

men

prostate cancer

men

androgen deprivation

men

prostate cancer involving ADT


A randomized double-blind placebo-controlled study of the long-term efficacy and safety of diethylpropion in the treatment of obese subjects . OBJECTIVE To evaluate the efficacy of diethylpropion on a long-term basis , with emphasis in cardiovascular and psychiatric safety aspects . DESIGN Randomized , double-blind , placebo-controlled trial . MEASUREMENTS Following a 2-week screening period , 69 obese healthy adults received a hypocaloric diet and were randomized to diethylpropion 50 mg BID ( n=37 ) or placebo ( n=32 ) for 6 months . After this period , all participants received diethylpropion in an open-label extension for an additional 6 months . The primary outcome was percentage change in body weight . Electrocardiogram ( ECG ) , echocardiography and clinical chemistry were performed at baseline and every 6 months . Psychiatric evaluation and application of Hamilton rating scales for depression and anxiety were also performed by experienced psychiatrists at baseline and every 3 months . RESULTS After 6 months , the diethylpropion group lost an average of 9.8 % ( s.d . 6.9 % ) of initial body weight vs 3.2 % ( 3.7 % ) in the placebo group ( P < 0.0001 ) . From baseline to month 12 , the mean weight loss produced by diethylpropion was 10.6 % ( 8.3 % ) . Participants in the placebo group who were switched to diethylpropion after 6 months lost an average of 7.0 % ( 7.7 % ) of initial body weight . The difference between groups at month 12 was not significant ( P=0.07 ) . No differences in blood pressure , pulse rate , ECG and psychiatric evaluation were observed . Dry mouth and insomnia were the most frequent adverse events . CONCLUSION Diethylpropion plus diet produced sustained and clinically significant weight loss over 1 year . It seems to be safe in relation to cardiovascular and psychiatric aspects in a well-selected population .

placebo-controlled

diethylpropion

diethylpropion

hypocaloric diet

diethylpropion 50 mg BID

placebo

diethylpropion

placebo

placebo

diethylpropion

Diethylpropion

body weight

mean weight loss

initial body weight

blood pressure , pulse rate , ECG

psychiatric evaluation

Dry mouth and insomnia

obese

69 obese healthy adults

hypocaloric diet


[ Clinical observation on acupuncture combined with Yizhi Jiannao granules for treatment of Alzheimer 's disease ] . OBJECTIVE To observe clinical therapeutic effect of acupuncture combined with Yizhi Jiannao Granules for treatment of Alzheimer 's disease and its effects on intelligence , daily life and social activity ability . METHODS Eighty-four cases were randomly divided into 3 groups , 28 cases in each group . The combined acupuncture and medication group was treated with acupuncture at Baihui ( GV 20 ) , Sishencong ( EX-HN 1 ) , Dazhui ( GV 14 ) , Guanyuan ( CV 4 ) , etc . and oral administration of Yizhi Jiannao Granules ; the Chinese herb group was treated with Yizhi Jiannao Granules , and the western medicine group with oral administration of Aricept . The scores for the Mini-Mental State Examination ( MMSE ) , Ability of Daily Life ( ADL ) and the therapeutic effects were assessed and compared before treatment and after treatment for 12 weeks among the groups . RESULTS After treatment , the scores for MMSE and ADL were improved in the combined acupuncture and medication group , the Chinese herb group and the western medicine group , which were better in the combined acupuncture and medication group ( P < 0.05 ) . The total effective rate of 85.7 % in the combined acupuncture and medication group was better than 71.4 % in the Chinese herb group and 67.9 % in the western medicine group . CONCLUSION Acupuncture combined with Yizhi Jiannao Granules has a significant therapeutic effect on Alzheimer 's disease , which is better than that of Yizhi Jiannao Granules or Aricept .

acupuncture

Yizhi Jiannao granules

acupuncture

Yizhi Jiannao Granules

acupuncture

acupuncture

Yizhi Jiannao Granules

Yizhi Jiannao Granules

western medicine group

Aricept

combined acupuncture and medication

Chinese herb

western medicine

acupuncture and medication

combined acupuncture and medication

therapeutic effect

intelligence

daily life

social activity ability

Ability of Daily Life ( ADL )

the therapeutic effects

MMSE

ADL

total effective rate

therapeutic effect

Eighty-four

3 groups


Effects of tonabersat on migraine with aura : a randomised , double-blind , placebo-controlled crossover study . BACKGROUND Migraine with aura is thought likely to be caused by cortical spreading depression ( CSD ) . Tonabersat inhibits CSD , and we therefore investigated whether tonabersat has a preventive effect in migraine with aura . METHODS In this randomised , double-blind , placebo-controlled crossover trial , 40 mg tonabersat once daily was compared with matched placebo in patients who had at least one aura attack per month during the past 3 months . Randomisation was by computer-generated list . Patients kept a detailed diary to enable objective diagnosis of each attack as migraine with aura , migraine without aura , or other type of headache . Primary endpoints were a reduction in aura attacks with or without headache and a reduction in migraine headache days with or without an aura . Analysis was per protocol . This trial is registered , number NCT00332007 . FINDINGS 39 patients were included in the study , of whom 31 were included in the statistical analysis of efficacy . Median ( IQR ) attacks of aura were reduced from 3.2 ( 1.0-5.0 ) per 12 weeks on placebo to 1.0 ( 0-3.0 ) on tonabersat ( p=0.01 ) , whereas the other primary outcome measure , median migraine headache days with or without aura , was not significantly different between placebo and tonabersat groups ( 3.0 days in each group ; p=0.09 ) . Tonabersat was well tolerated but overall had more side-effects than placebo . INTERPRETATION Tonabersat showed a preventive effect on attacks of migraine aura but no efficacy on non-aura attacks , in keeping with its known inhibitory effect on CSD . The results support the theory that auras are caused by CSD and that this phenomenon is not involved in attacks without aura . FUNDING Minster Pharmaceuticals ; Lundbeck Foundation .

tonabersat

Tonabersat

tonabersat

compared with matched placebo

placebo

placebo

tonabersat

Tonabersat

Median ( IQR ) attacks of aura

tolerated

migraine with aura


Impact of preinduced quadriceps fatigue on exercise response in chronic obstructive pulmonary disease and healthy subjects . Exercise intolerance in chronic obstructive pulmonary disease ( COPD ) results from a complex interaction between central ( ventilatory ) and peripheral ( limb muscles ) components of exercise limitation . The purpose of this study was to evaluate the influence of quadriceps muscle fatigue on exercise tolerance and ventilatory response during constant-workrate cycling exercise testing ( CWT ) in patients with COPD and healthy subjects . Fifteen patients with COPD and nine age-matched healthy subjects performed , 7 days apart , two CWTs up to exhaustion at 80 % of their predetermined maximal work capacity . In a randomized order , one test was performed with preinduced quadriceps fatigue and the other in a fresh state . Quadriceps fatigue was produced by electrostimulation-induced contractions and quantified by maximal voluntary contraction and potentiated twitch force ( TwQ ( pot ) ) . Endurance time and ventilatory response during CWT were compared between fatigued and fresh state . Endurance time significantly decreased in the fatigued state compared with the fresh condition in COPD ( 356 +/- 69 s vs. 294 +/- 45 s , P < 0.05 ) and controls ( 450 +/- 74 s vs. 340 +/- 45 s , P < 0.05 ) . Controls showed significantly higher ventilation and end-exercise dyspnea scores in the fatigued condition , whereas , in COPD , fatigue did not influence ventilation or dyspnea during exercise . The degree of ventilatory limitation , as expressed by the Ve/maximum voluntary ventilation ratio , was similar in both conditions in patients with COPD . We conclude that it is possible to induce quadriceps fatigue by local electrostimulation-induced contractions . Our findings demonstrate that peripheral muscle fatigue is an additional important factor , besides intense dyspnea , that limits exercise tolerance in COPD .

CWTs

maximal voluntary contraction

potentiated twitch force ( TwQ ( pot )

Endurance time

and

ventilatory response

Endurance time

ventilatory limitation

Ve/maximum voluntary ventilation ratio

preinduced quadriceps fatigue

chronic obstructive pulmonary disease

Fifteen patients

COPD

patients with COPD

peripheral muscle fatigue


Comparison of arch dimension changes in 1-phase vs 2-phase treatment of Class II malocclusion . INTRODUCTION We compared arch dimension changes in 1-phase and 2-phase treatment of Class II malocclusion . This was a prospective randomized clinical trial conducted in the Department of Orthodontics at the University of Florida between 1990 and 2003 . METHODS During phase 1 treatment , 86 subjects were treated with a bionator , 93 were treated with headgear/biteplane , and 81 served as the observation group . For phase 2 , all subjects were then treated with full orthodontic appliances . Arch dimensions were followed ; maxillary and mandibular alginate impressions were taken at baseline , end of early Class II treatment or observation , beginning of fixed appliance treatment , end of orthodontic treatment , and approximately 3 years posttreatment . Alginate impressions were taken of each dental arch at each data collection point . These were poured in orthodontic stone , trimmed , and photocopied from the occlusal aspect . These images were then scanned and measured . RESULTS Although differences between the treatment groups were found in both the maxillary and mandibular arches after phase 1 , these differences were no longer evident by the end of full orthodontic treatment or after posttreatment retention . CONCLUSIONS There were no differences in arch dimensions after 1-phase or 2-phase treatment of Class II malocclusion .

bionator

headgear/biteplane

full orthodontic appliances

arch dimensions


Preparation and immune activity analysis of H5N1 subtype avian influenza virus recombinant protein-based vaccine . Avian influenza is a severe disease among farmed poultry and free-living birds and a constant threat to the commercial chicken industry around the world . Hemagglutinin ( HA ) is the major immunogen on the envelope of influenza A virus and is the predominant inducer of neutralizing antibody . To obtain the bioactive antigen proteins in large quantities , a new protein expression vector pBCX was constructed , which is based on the pET32a vector . The HA gene of the H5N1 subtype of avian influenza virus ( AIV ) was inserted into the pBCX vector and expressed efficiently in Escherichia coli BL21 ( DE3 ) . Fused expression of the exogenous gene and msyB produced a 97-kDa msyB-HA fusion protein . Sodium dodecyl sulfate-PAGE combined with scanning analysis demonstrated that the msyB-HA fusion protein accounted for 29.5 % of the total bacterial protein , 90.5 % being soluble . The msyB-HA fusion protein was purified with nondenaturing 50 % Ni-NTA column chromatography , and the result showed that 24 mg of purified msyB-HA fusion protein could be obtained from 1 L of induced expression bacterial culture medium . The comparative results in the present study showed that pBCX was superior to pET32a as a protein expression vector . Western blotting showed the recombinant msyB-HA ( rHA ) to have better antigenic activity , which may be the result from the better posttranslation protein modification and folding in the pBCX expression system . With the rHA fusion protein as antigen , we successfully prepared and screened specific monoclonal antibodys against the H5N1 subtype AIV , which indicated that the rHA had antigen epitopes and biofunctions . The immune test confirmed that the rHA protein vaccine could also induce high neutralizing antibodies , and the AIV challenge test proved that the rHA protein-based vaccine could prevent the corresponding infection . This study demonstrates that the recombinant HA protein produced by the pBCX expression system could be used as a recombinant protein-based vaccine and has potential for further development for diagnosis .

Sodium dodecyl sulfate-PAGE

scanning analysis

antigenic activity

pBCX vector


Excimer laser trabeculotomy vs 180 degrees selective laser trabeculoplasty in primary open-angle glaucoma . A 2-year randomized , controlled trial . PURPOSE To compare the effectiveness and safety of excimer laser trabeculotomy ( ELT ) ab interno vs selective laser trabeculoplasty ( SLT ) over 24 months of follow-up in patients with primary open-angle glaucoma ( POAG ) refractory to medical therapy . PATIENTS AND METHODS This prospective , randomized study included 30 consecutive eyes assigned randomly to either ELT or SLT group . ELT was carried out using a XeCl Excimer Laser with an emission wavelength of 308 nm . Eight spots were equally distributed at a distance of 500 microm from one another over the anterior trabeculum . The SLT patients were treated with a frequency-doubled q-switched neodymium : yytrium-aluminum-garnet laser ( wavelength 532 nm ) . Approximately 50 adjacent , but not overlapping , laser spots were distributed over 180 degrees of the trabecular meshwork , using an energy level ranging from 0.7 to 1.0 mJ per pulse . The main outcome measure was intraocular pressure ( IOP ) lowering after ELT and SLT . Success was defined as > or=20 % reduction in IOP without further glaucoma intervention . RESULTS At 24 months , complete success rates were 53.3 % for the ELT group and 40 % for the SLT group ( P=0.35 , Fisher 's exact test ) ; qualified success rates were 33.3 % for the ELT and 26.6 % for the SLT group ( P=0.5 , Fisher 's exact test ) .Mean IOP decreased from 25.0+/-1.9 to 17.6+/-2.2 mmHg ( -29.6 % ; P < 0.0001 ) in the ELT group and from 23.9+/-0.9 to 19.1+/-1.8 mmHg ( -21 % ; P < 0.0001 ) in the SLT group . CONCLUSIONS Both ELT and SLT proved to be effective techniques in the treatment of POAG refractory to medical therapy .

Excimer laser trabeculotomy

excimer laser trabeculotomy ( ELT )

selective laser trabeculoplasty ( SLT )

ELT

SLT

ELT

was carried out using a

XeCl Excimer Laser

with an emission

wavelength of 308 nm

effectiveness and safety

reduction in IOP

success rates

qualified success rates

test ) .Mean IOP decreased


Polycystic ovary syndrome and cardiovascular risk in young patients treated with drospirenone-ethinylestradiol or contraceptive vaginal ring . A prospective , randomized , pilot study . OBJECTIVE To compare the effects of a pill containing drospirenone with those of a combined contraceptive vaginal ring on the lipid and carbohydrate metabolism and on the surrogate markers of arterial function . SETTING Bologna University School of Medicine . PATIENT ( S ) Thirty-seven women with polycystic ovary syndrome ( PCOS ) were randomly submitted to drospirenone+ethinylestradiol ( group I ; n=19 ) or combined contraceptive vaginal ring ( group II ; n=18 ) therapy . The duration of the study was 6 months . INTERVENTION ( S ) The effect of treatments was assessed after 6 months of therapy . MAIN OUTCOME MEASURE ( S ) Utero-ovarian ultrasound analysis and color Doppler evaluation of uterine and stromal ovarian arteries . In addition , analysis of brachial artery flow-mediated vasodilatation and 24-hour ambulatory blood pressure monitoring were performed . Fasting blood samples were drawn for testing biochemical and hormonal parameters and nitrites/nitrates . RESULT ( S ) Both treatments improved hirsutism , hyperandrogenemia , and ultrasound and color Doppler ovarian parameters . Both drospirenone+ethinylestradiol or contraceptive vaginal ring induced a slight but significant increase of diurnal and 24-hour blood pressure . Although both therapies worsened the lipid profile , the oral pill administration was associated with a more evident increase of circulating triglycerides . The 6-month treatment with the vaginal ring significantly improved the area under the curve for glucose , insulin , and C-peptide , whereas the drospirenone+ethinylestradiol pill induced an increase in the insulinogenic index and homeostatic model assessment estimate for insulin resistance values . CONCLUSION ( S ) Vaginal hormonal contraception appears to be preferable to oral ethinylestradiol + drospirenone administration in hyperinsulinemic patients with PCOS .

drospirenone-ethinylestradiol

contraceptive vaginal ring

pill containing drospirenone

combined contraceptive vaginal ring

drospirenone+ethinylestradiol

combined contraceptive vaginal ring

therapy

therapy

hirsutism

hyperandrogenemia

diurnal and 24-hour blood pressure

lipid profile

circulating triglycerides

insulinogenic index