A comparative study of the safety and efficacy of FemCap , a new vaginal barrier contraceptive , and the Ortho All-Flex diaphragm . The FemCap Investigators ' Group . The FemCap is a new silicone rubber barrier contraceptive shaped like a sailor 's hat , with a dome that covers the cervix , a rim that fits into the fornices , and a brim that conforms to the vaginal walls around the cervix . It was designed to result in fewer dislodgments and less pressure on the urethra than the cervical cap and diaphragm , respectively , and to require less clinician time for fitting . This was a phase II/III , multicenter , randomized , open-label , parallel group study of 841 women at risk for pregnancy . A subset of 42 women at one site underwent colposcopy . Women were randomized to use the FemCap or Ortho All-Flex contraceptive diaphragm , both with 2 % nonoxynol-9 spermicide , for 28 weeks . The objectives were to compare the two devices with regard to their safety and acceptability and to determine whether the probability of pregnancy among FemCap users was no worse than that of the diaphragm ( meaning not more than 6 percentage points higher ) . The 6-month Kaplan-Meier cumulative unadjusted typical use pregnancy probabilities were 13.5 % among FemCap users and 7.9 % among diaphragm users . The adjusted risk of pregnancy among FemCap users was 1.96 times that among diaphragm users , with an upper 95 % confidence limit of 3.01 . Clinical equivalence ( noninferiority ) of the FemCap compared with the diaphragm , as defined in this study , would mean that the true risk of pregnancy among FemCap users was no more than 1.73 times the pregnancy risk of diaphragm users . Because the observed upper 95 % confidence limit ( and even the point estimate ) exceeded 1.73 , the probability of pregnancy among FemCap users , compared with that among diaphragm users , did not meet the definition of clinical equivalence used in this study . The FemCap was believed to be safe and was associated with significantly fewer urinary tract infections . More women reported problems with the FemCap with regard to insertion , dislodgement , and especially removal , although their general assessments were positive . The two devices were comparable with regard to safety and acceptability , but a 6-point difference in the true 6-month pregnancy probabilities of the two devices could not be ruled out . Further studies are needed to determine whether design modifications can simplify insertion and removal .

Ortho All-Flex diaphragm

FemCap

FemCap

Ortho All-Flex contraceptive diaphragm

nonoxynol-9 spermicide

FemCap

diaphragm

FemCap

diaphragm

FemCap

diaphragm

FemCap

FemCap

diaphragm

FemCap

diaphragm

FemCap

FemCap

probability of pregnancy

6-month Kaplan-Meier cumulative

adjusted risk of pregnancy

Clinical equivalence ( noninferiority )

true risk of pregnancy

pregnancy risk

probability of pregnancy among FemCap

clinical equivalence

safe

urinary tract infections

safety and acceptability

6-month pregnancy probabilities

women

risk for pregnancy

42 women

colposcopy


Cholesterol-lowering effect of stanol ester in a US population of mildly hypercholesterolemic men and women : a randomized controlled trial . OBJECTIVE To determine the efficacy of stanol esters in lowering cholesterol in a US population . SUBJECTS AND METHODS After a run-in phase , 318 subjects were randomized to receive one of the following margarine-like spreads containing stanol ester or placebo for 8 weeks : EU 3 G : 1 g of stanol ( ester form ) per 8-g serving of a European formula 3 times a day ; US 3 G : 1 g of stanol ( ester form ) per 8-g serving of a US reformulation 3 times a day ; US 2 G : 0.67 g of stanol ( ester form ) per 8-g serving of a US reformulation 3 times a day ; or placebo spread . RESULTS Mean +/- SD baseline total cholesterol ( TC ) and low-density lipoprotein cholesterol ( LDL-C ) levels were 233+/-20 and 153+21 mg+/-dL , respectively . In the US 3 G group , 3 g daily of stanol esters lowered TC and LDL-C levels by 6.4 % and 10.1 % , respectively . There was a dose-dependent response compared with 2 g daily ( US 2 G ) . Triglyceride and high-density lipoprotein cholesterol levels were unchanged . The incidence of adverse effects was not different from placebo . Serum vitamin A and 25-hydroxyvitamin D levels were not affected . CONCLUSIONS Stanol esters lowered TC and LDL-C levels in a mildly hypercholesterolemic US population without evidence of adverse effects . It may be a useful dietary adjunct to lower cholesterol .

stanol ester

stanol esters

stanol ester

placebo

stanol ( ester form )

stanol ( ester form )

stanol

placebo

stanol esters

placebo

Stanol esters

TC

LDL-C levels

adverse effects

TC

LDL-C levels

mildly hypercholesterolemic

men

women

mildly hypercholesterolemic


Ursodeoxycholic acid has no influence on function after restorative proctocolectomy in ulcerative colitis . BACKGROUND Poor pouch function is associated with impaired bile acid absorption and increased faecal loss of bile acids . Bile acid replacement therapy might therefore be of clinical benefit , provided that diarrhoea is not aggravated by therapy . AIM To investigate the role of exogenous bile acid therapy in patients with poor pouch function after restorative proctocolectomy for ulcerative colitis . PATIENTS AND METHODS Twenty ulcerative colitis patients with poor pouch function ( score > 4 on a 12-point score ) were recruited for inclusion to a prospective , randomized , double-blind crossover , placebo-controlled trial of ursodeoxycholic acid ( 10 mg/kg per day in two divided doses for 1 month ) . RESULTS A total of 16 patients completed the study . There was no significant difference in the functional score or bowel frequency following treatment irrespective of whether the active treatment was given before or after placebo . CONCLUSIONS We conclude that ursodeoxycholic acid given over 4 weeks had no influence on functional score or bowel frequency after restorative proctocolectomy for U.C .

Ursodeoxycholic acid

Bile acid replacement therapy

exogenous bile acid therapy

placebo-controlled

ursodeoxycholic acid

ursodeoxycholic acid

proctocolectomy

functional score or bowel frequency

functional score or bowel frequency

U.C .

ulcerative colitis

patients with poor pouch function

Twenty

ulcerative colitis

poor pouch function


Standard-dose lansoprazole is more effective than high-dose ranitidine in achieving endoscopic healing and symptom relief in patients with moderately severe reflux oesophagitis . The Dutch Lansoprazole Study Group . BACKGROUND In the treatment of reflux oesophagitis , H2-receptor antagonists are still widely used in spite of the apparent higher efficacy of proton pump inhibitors . In an attempt to compensate for the lower efficacy , H2-receptor antagonists are now increasingly being used at a higher dose . OBJECTIVE To assess whether or not standard-dose lansoprazole ( 30 mg o.d . ) is more effective than high-dose ranitidine ( 300 mg b.d . ) in moderately severe reflux oesophagitis ( grades II-III ) . METHODS Lansoprazole or ranitidine was given to 133 patients for 4-8 weeks in a double-blind , randomized , parallel group , multicentre trial . RESULTS The percentage of patients with endoscopically-verified healing was significantly higher on lansoprazole than on ranitidine both after 4 weeks ( 79 % vs. 42 % ) and 8 weeks ( 91 % vs. 66 % ) , though smoking had a negative impact on oesophagitis healing with lansoprazole . Heartburn , retrosternal pain and belching improved significantly better with lansoprazole than with ranitidine , as did the patient-rated overall symptom severity . Relief of heartburn appeared somewhat faster with ranitidine , but was more pronounced with lansoprazole . The number of patients with adverse events was similar in both treatment groups . CONCLUSION Standard-dose lansoprazole is better than high-dose ranitidine in moderately severe reflux oesophagitis .

Standard-dose lansoprazole

high-dose ranitidine

Lansoprazole

standard-dose lansoprazole

high-dose ranitidine

Lansoprazole

ranitidine

lansoprazole

ranitidine

lansoprazole

lansoprazole

ranitidine

ranitidine

lansoprazole

Standard-dose lansoprazole

high-dose ranitidine

Relief of heartburn

number of patients with adverse events

reflux oesophagitis


Enalapril ( 10 mg/day ) in systemic sclerosis . One year , double blind , randomised study ( ESS-1 ) : echocardiographic substudy -- three months follow-up . The ESS-1 study was designed to evaluate the long-term effects of the angiotensin converting enzyme inhibitor ( ACEI ) enalapril ( 10 mg per day ) on the cardio-pulmonary system in patients with scleroderma ( SSc ) . We estimated changes in heart diameters , systolic and diastolic left ventricle function and mean values of pulmonary artery pressure after 3 months treatment . The study group comprise 41 patients with SSc . 18 patients received placebo and 23 ones were given enalapril . After 3 months of treatment we did not observe statistically significant differences in heart diameters and left ventricle systolic function parameters between treated group and placebo . Enalapril therapy did not affect left ventricle diastolic function , nevertheless differences in MVA were almost of statistical significance . Echocardiographic signs of pulmonary hypertension were found in 4 patients .

Enalapril

enalapril

placebo

enalapril

Enalapril

heart diameters

left ventricle diastolic function

MVA

pulmonary hypertension

scleroderma ( SSc )


Ciprofloxacin , lomefloxacin , or levofloxacin as treatment for chronic osteomyelitis . The efficacy and safety of three oral fluoroquinolones ( lomefloxacin , levofloxacin , and ciprofloxacin ) for the treatment of chronic osteomyelitis were analyzed . Twenty-seven patients had documented infections with quinolone-sensitive organisms and received either lomefloxacin , levofloxacin , or ciprofloxacin . Levofloxacin was effective therapy for 9 of 15 ( 60 % ) patients . Lomefloxacin was effective therapy for five of seven ( 71 % ) patients , and ciprofloxacin was effective therapy for two of five patients ( 40 % ) . Average follow-up was 11.8 months for patients who completed the course of therapy , and the average duration of therapy was 60.6 days . Gram-positive bacteria were isolated from 18 patients , and 11 patients were cured . Oral fluoroquinolones can be safe , effective therapy if they are given for a prolonged course as treatment for infections caused by susceptible gram-positive as well as gram-negative organisms and in combination with adequate surgical debridement .

Ciprofloxacin

lomefloxacin

levofloxacin

oral fluoroquinolones

lomefloxacin

levofloxacin

ciprofloxacin

lomefloxacin

levofloxacin

ciprofloxacin

chronic osteomyelitis .

efficacy and safety

duration of therapy

Gram-positive bacteria

cured

safe , effective

chronic osteomyelitis

Twenty-seven


Partial depletion of tissue factor pathway inhibitor during subcutaneous administration of unfractionated heparin , but not with two low molecular weight heparins . Tissue factor pathway inhibitor ( TFPI ) is released to circulating blood after intravenous ( i.v . ) and subcutaneous ( s.c. ) injections of heparins , and may thus contribute to the antithrombotic effect of heparins . We have recently shown that total TFPI activity , plasma free TFPI antigen , and heparin releasable TFPI were partially depleted during repeated and continuous i.v . infusion of unfractionated heparin ( UFH ) , but not during s.c. treatment with a low molecular weight heparin ( LMWH ) . The difference may be attributed to a different mode of action or the different mode of administration . In the present randomized cross-over study , s.c. administration of therapeutic doses of UFH was compared with s.c. administration of two LMWHs . 12 healthy male volunteers were treated for 3 d with UFH , 250 U/kg twice daily , dalteparin , 200 U/kg once daily , and enoxaparin , 1.5 mg/kg once daily . Six participants were also treated with UFH , 300 U/kg once daily . On day 5 a single dose of either drug was given . Peak levels of total TFPI activity and free TFPI antigen were detected 1 h after injection , whereas maximal prolongation of activated partial thromboplastin time ( APTT ) and peak levels of anti-factor Xa activity and anti-factor IIa activity were detected after 4 h. On UFH administered twice daily , free TFPI antigen decreased by 44 % from baseline level before the first injection on day 1 to pre-injection level on day 5 . On UFH administered once daily , basal free TFPI antigen decreased by 50 % , 56 % and 27 % on day 2 , 3 and 5 respectively , compared with day 1 . Minimal depletion of TFPI was detected during treatment with LMWHs . The study demonstrates the different modes of action of LMWHs and UFH and may help to explain the superior antithrombotic efficacy of LMWHs .

heparin

unfractionated heparin

UFH

administration of two LMWHs

UFH

dalteparin , 200 U/kg once daily

enoxaparin

UFH

UFH

UFH

LMWHs

UFH

heparin releasable TFPI

free TFPI antigen

basal free TFPI antigen

Minimal depletion of TFPI

12 healthy male volunteers


Quantitative monitoring of serum hepatitis B virus DNA and blood lymphocyte subsets during combined prednisolone and interferon-alpha therapy in patients with chronic hepatitis B . Several investigators have reported a significantly reduced CD4/CD8 ratio , as defined by monoclonal antibodies , in the peripheral blood of Caucasian patients with chronic active hepatitis B ( CAHB ) . In Asian patients with chronic hepatitis B , quantitative analyses of subpopulations of peripheral blood lymphocytes have not been able to confirm these findings . In this work , we analysed the frequency of peripheral blood lymphocyte subsets in 10 Chinese patients with histologically proven CAHB and seven healthy Chinese individuals . Four of the 10 CAHB patients received combined prednisolone/interferon-alpha2b ( IFN-alpha2b ) therapy . Peripheral blood samples were consecutively collected for analysis of lymphocyte subpopulations using an indirect immunofluorescence ( IF ) method , and hepatitis B virus ( HBV ) DNA was quantified by a chemiluminescent , molecular-hybridization assay . Peripheral blood mononuclear cells from seven Chinese control individuals comprised 63 +/- 3 % CD3+ cells , of which 41 +/- 4 % were of CD4+ and 23 +/- 2 % of CD8+ subsets . The mean CD4/CD8 ratio in the healthy controls was 1.9 ( 95 % confidence interval = 1.1-2.7 ) . The CD4/CD8 ratios were significantly reduced ( P < 0.01 ) in the 10 patients with chronic hepatitis B , compared with those of the controls , owing to a significant increase in the number of CD8+ cells ( P < 0.005 ) . During the treatment with prednisolone , a significant increase in the CD4/CD8 ratio was observed in all treated patients . This increase was mainly caused by a decrease in the number of CD8+ cells and was accompanied by an increase in serum HBV DNA levels , which peaked during the latter part of the prednisolone cycle . During the treatment with IFN-alpha2b , a second increase in the CD4/CD8 ratio was observed , which was caused by an increase in CD4+ cells . A marked decrease in viral load was observed , during treatment with IFN-alpha2b , in patients with HBV DNA levels below 10 000 pg ml-1 . Our data indicate that the CD4/CD8 ratios in Chinese CAHB patients do not differ from those of Caucasian patients with CAHB , when analysed using similar methods for the enumeration of lymphocyte subsets . Profound effects on cellular distribution and viral replication were noted during the combined prednisolone/IFN-alpha2b therapy . Additional studies of the modulatory effect of the combined therapy on the distribution of lymphocyte subsets and cytokine profiles in relation to the therapeutic outcome of HBV infection are warranted .

combined prednisolone

interferon-alpha therapy

prednisolone

serum hepatitis B virus DNA

blood lymphocyte subsets

CD4/CD8 ratio

Peripheral blood samples

Peripheral blood mononuclear cells

mean CD4/CD8 ratio

CD4/CD8 ratios

number of CD8+ cells

CD4/CD8 ratio

number of CD8+ cells

increase in serum HBV DNA levels

viral load


Early immunisation with hepatitis B vaccine : a five-year study . We evaluated the response to the recombinant Hepatitis B vaccine using an accelerated schedule versus the traditional schedule by studying the immunologic memory induced in 200 children with HBs-Ag negative mothers . At seroconversion , the traditional schedule presented a higher percentage of children with serum HBs-Ag concentrations over 100 mIU/ml than the accelerated schedule . After five years this difference was no longer statistically significant and children who presented anti-HBsAg concentrations below 10 mUI/ml received an additional booster dose which stimulated the antibody concentration to exceed 100 mIU/ml in all cases . Recombinant HBV vaccine induced better long term immunologic memory when it was administered earlier .

hepatitis B vaccine :

recombinant Hepatitis B vaccine

Recombinant HBV vaccine

immunologic memory

children

HBs-Ag


Gastric carcinoma : expression of c-erbB-2/neu oncoprotein , epidermal growth factor receptor , cathepsin D , progesterone receptor and tumor associated glycoprotein-72 in different histological types . OBJECTIVE Gastric carcinoma can be divided into two main histological and clinical types : diffuse and intestinal . The aim of this study was to investigate the expression of neu/c-erbB-2 oncoprotein , epidermal growth factor receptor ( EGFR ) , cathepsin D ( catD ) , progesterone receptor ( PR ) and tumor-associated glycoprotein-72 ( TAG-72 ) in gastric carcinoma of these histological types . METHOD In this randomized , prospective study we analyzed 85 biopsy samples from patients with gastric adenocarcinoma . The control group consisted of 40 specimens from normal gastric mucosa . Neu oncoprotein and PR were determined by ELISA . CatD and TAG-72 were quantified with immunoradiometric ( IRMA ) methods , and EGFR were studied by radioimmunoassay ( RIA ) . RESULTS Neu , EGFR , catD and TAG-72 concentrations were higher in the tumoral group ( p = 0.02 , p = 0.00001 , p = 0.002 and p = 0.007 , respectively ) . In diffuse adenocarcinomas , catD and PR expression was increased ( p = 0.01 and p = 0.04 respectively ) , whereas TAG-72 concentration , which correlated with neu ( r = 0.57 ) , was higher in the intestinal type ( p = 0.04 ) . No significant differences in EGFR and neu concentrations were seen between the two histological types . CONCLUSIONS The higher PR and catD concentrations in diffuse adenocarcinomas , and the overexpression of TAG-72 in the intestinal type , support the existence of two modes of gastric carcinogenesis .

neu/c-erbB-2 oncoprotein

ELISA

expression of c-erbB-2/neu oncoprotein

epidermal growth factor receptor

cathepsin D , progesterone receptor

tumor associated glycoprotein-72

expression of neu/c-erbB-2 oncoprotein

cathepsin D ( catD )

progesterone receptor ( PR )

Neu oncoprotein

PR

ELISA

CatD

immunoradiometric ( IRMA ) methods

EGFR

radioimmunoassay ( RIA )

Neu

EGFR

catD

catD

PR expression

TAG-72 concentration

neu

EGFR

neu

PR

catD concentrations

Gastric carcinoma

Gastric carcinoma

gastric adenocarcinoma


Prediction of metabolic and cardiopulmonary responses to maximum cycle ergometry : a randomised study . All of the most widely-cited studies for the prediction of maximum exercise responses have utilized either volunteers or referred subjects . Therefore , selection bias , with overestimation of the reference values , is a likely consequence . In order to establish a set of predictive equations for the gas exchange , ventilatory and cardiovascular responses to maximum ramp-incremental cycle ergometry , this study prospectively evaluated 120 sedentary individuals ( 60 males , 60 females , aged 20-80 ) , randomly-selected from > 8,000 subjects . Regular physical activity pattern by questionnaire , body composition by anthropometry and dual energy X-ray absorptiometry ( n = 75 ) and knee strength by isokinetic dynamometry were also assessed . Previously reported equations typically overestimated the subjects ' peak oxygen uptake ( p < 0.05 ) . Prediction linear equations for the main variables of clinical interest were established by backward stepwise regression analysis including : sex , age , knee extensor peak torque , bone-free lean leg mass , total and lean body mass , height , and physical activity scores . Reference intervals ( 95 % confidence limits ) were calculated : some of these values differed markedly from those formerly recommended . The results therefore might provide a more appropriate frame of reference for interpretation of the responses to symptom-limited ramp incremental cycle ergometry in sedentary subjects ; i.e . those usually referred for clinical cardiopulmonary exercise tests .

maximum cycle ergometry

dual energy X-ray absorptiometry

ramp incremental cycle ergometry

maximum exercise responses

peak oxygen uptake

Reference intervals

either volunteers or referred subjects

sedentary individuals

males

females

aged 20-80

randomly-selected from > 8,000 subjects


Focal therapeutic efficacy of transcatheter arterial infusion of styrene maleic acid neocarzinostatin for hepatocellular carcinoma . We evaluated the focal therapeutic effect of oily carcinostatic agents administered by transcatheter arterial infusion ( TAI ) as the initial therapy in patients with hepatocellular carcinoma in a randomized controlled clinical trial . Group A ( 19 patients ) received 4 mg of styrene maleic acid neocarzinostatin in 4 ml of Lipiodol , and group B ( 18 patients ) received 100 mg of epirubicin in 4 ml of Lipiodol via the tumor feeding arteries as peripherally as possible . The grade of Lipiodol accumulation and the tumor regression rate were determined 2 weeks after TAI by computerized tomography . Adverse effects within 2 weeks after TAI were evaluated by subjective signs and symptoms such as fever ( maximum body temperature ) and the frequency of shaking chills and abdominal pain , and by biochemical parameters such as albumin , prothrombin time , and aspartate and alanine aminotransferases . Lipiodol accumulation in the tumor was significantly greater in group A ( 12/19 ; 63.2 % showing grade IV Lipiodol accumulation ) than in group B ( 3/18 ; 16.7 % showing grade IV ) ( P < 0.05 ) . The tumor regression rate was also significantly greater in group A ( 8/17 ; 47.1 % showing more than 25 % tumor regression ) than in group B ( 1/13 ; 7.7 % showing more than 25 % tumor regression ) ( P < 0.05 ) . Although clinically significant elevations of aminotransferases and reductions of cholinesterase , and shaking chills were observed more often in group A than in group B ( P < 0.0001 ) , these factors had little influence on the clinical outcome . Our results suggest that styrene maleic acid neocarzinostatin in Lipiodol exerts a more favorable focal therapeutic effect than does epirubicin in Lipiodol in the initial treatment of hepatocellular carcinoma .

styrene maleic acid

oily carcinostatic agents

styrene maleic acid neocarzinostatin

epirubicin

Lipiodol

Focal therapeutic efficacy

focal therapeutic effect

fever ( maximum body temperature )

frequency of shaking chills

abdominal pain

Lipiodol accumulation in the tumor

tumor regression rate

elevations of aminotransferases

reductions of cholinesterase

shaking chills

more favorable focal therapeutic effect

patients with hepatocellular carcinoma

Group A ( 19 patients

group B ( 18 patients )


Randomised controlled trial of patient triggered and conventional fast rate ventilation in neonatal respiratory distress syndrome . AIM To compare patient triggered , with conventional fast rate , ventilation in a randomised controlled trial using the incidence of chronic lung disease as the primary outcome measure . METHODS Three hundred and eighty six preterm infants with birthweights from 1000 to 2000 g , and requiring ventilation for respiratory distress syndrome within 24 hours of birth , were randomised to receive either conventional or trigger ventilation with the SLE 2000 ventilator . RESULTS There were no significant differences in the incidence of chronic lung disease ( 28 day and 36 week definitions ) , death , pneumothorax , intraventricular haemorrhage , number of ventilator days , or length of oxygen dependency between groups . CONCLUSIONS Patient triggered ventilation in preterm infants with respiratory distress syndrome is feasible . No significant differences , when compared with conventional fast rate ventilation in important medium and longer term outcome measures , were evident .

conventional fast rate ventilation

trigger ventilation

incidence of chronic lung disease

incidence of chronic lung disease

death


Randomised controlled study of clinical outcome following trophic feeding . AIMS To determine the effect of trophic feeding on clinical outcome in ill preterm infants . METHODS A randomised , controlled , prospective study of 100 preterm infants , weighing less than 1750 g at birth and requiring ventilatory support and parenteral nutrition , was performed . Group TF ( 48 infants ) received trophic feeding from day 3 ( 0.5-1 ml/h ) along with parenteral nutrition until ventilatory support finished . Group C ( 52 infants ) received parenteral nutrition alone . " Nutritive " milk feeding was then introduced to both groups . Clinical outcomes measured included total energy intake and growth over the first six postnatal weeks , sepsis incidence , liver function , milk tolerance , duration of respiratory support , duration of hospital stay and complication incidence . RESULTS Groups were well matched for birthweight , gestation and CRIB scores . Infants in group TF had significantly greater energy intake , mean difference 41.4 ( 95 % confidence interval 9 , 73.7 ) kcal/kg p=0.02 ; weight gain , 130 ( CI 1 , 250 ) g p = 0.02 ; head circumference gain , mean difference 0.7 ( CI 0.1 , 1.3 ) cm , p = 0.04 ; fewer episodes of culture confirmed sepsis , mean difference -0.7 ( -1.3 , -0.2 ) episodes , p = 0.04 ; less parenteral nutrition , mean difference -11.5 ( CI -20 , -3 ) days , p = 0 . 03 ; tolerated full milk feeds ( 165 ml/kg/day ) earlier , mean difference -11.2 ( CI -19 , -3 ) days , p = 0.03 ; reduced requirement for supplemental oxygen , mean difference -22.4 ( CI-41.5 , -3.3 ) days , p = 0.02 ; and were discharged home earlier , mean difference -22.1 ( CI -42.1 , -2.2 ) days , p = 0.04 . There was no significant difference in the relative risk of any complication . CONCLUSIONS Trophic feeding improves clinical outcome in ill preterm infants requiring parenteral nutrition .

trophic feeding .

trophic feeding

ventilatory support

Trophic feeding

parenteral nutrition .

sepsis incidence

liver function

milk tolerance

duration of respiratory support

duration of hospital stay

complication incidence

energy intake

weight gain

head circumference gain

episodes of culture confirmed sepsis

parenteral nutrition

tolerated full milk feeds

requirement for supplemental oxygen

discharged

risk of any complication

ill preterm

infants


Treatment of hypertension with ascorbic acid . In a randomised , double-blind , placebo-controlled study we showed that treatment of hypertensive patients with ascorbic acid lowers blood pressure . Further studies of ascorbic acid to treat hypertension , with clinical endpoints , are warranted .

ascorbic acid

placebo-controlled

ascorbic acid

ascorbic acid

blood pressure .

hypertension

clinical endpoints

hypertension

hypertensive


Comparison of chemotherapy with chemohormonal therapy as first-line therapy for metastatic , hormone-sensitive breast cancer : An Eastern Cooperative Oncology Group study . PURPOSE Although hormonal therapy represents standard therapy for metastatic hormone-sensitive disease , many patients receive initial chemotherapy because of the location , bulk , or aggressiveness of their disease . It is uncertain whether simultaneous hormonal therapy provides additional benefit compared with chemotherapy alone . Eastern Cooperative Oncology Group trial E3186 was initiated to explore this question . PATIENTS AND METHODS Between January 1988 and December 1992 , 231 patients with estrogen receptor ( ER ) -positive or ER-unknown metastatic breast cancer were randomized to receive either chemotherapy ( cyclophosphamide , doxorubicin , and fluorouracil ¿CAF ) or chemohormonal therapy ( CAF plus tamoxifen and Halotestin ¿fluoxymesterone ; Pharmacia-Upjohn , Kalamazoo , MI ¿CAFTH ) as front-line therapy for metastatic breast cancer . Patients who experienced a complete response to induction therapy either received or did not receive maintenance cyclophosphamide , methotrexate , fluorouracil , prednisone , and TH as a secondary randomization . RESULTS The response rates ( complete response and partial response ) of patients who received CAF and CAFTH were similar ( 69.2 % v 68.9 % , respectively ; P =.99 ) . Time to treatment failure ( TTF ) was slightly longer for patients who received chemohormonal therapy compared with chemotherapy alone patients ( 13.4 months v 10.3 months , respectively ; P =.087 ) , and TTF was significantly longer in ER-positive compared with ER-negative patients ( 17.4 months v 10.3 months , respectively ; P =.048 ) . However , ER status had no effect on overall survival ( 30.0 months for CAF v 29.3 months for CAFTH ) . CONCLUSION In patients with potentially hormone-sensitive metastatic breast cancer , chemohormonal therapy prolongs TTF for ER-positive patients without improving overall survival .

chemotherapy

chemohormonal therapy

chemotherapy

simultaneous hormonal therapy

response rates

Time to treatment failure ( TTF )

TTF

overall survival


The effect of body weight changes and endurance training on 24h substrate oxidation . OBJECTIVE To investigate the effect of exercise training and dietary macronutrient composition on 24 h substrate oxidation in male , obese subjects . DESIGN A 16 month exercise intervention study was executed , including a weight loss period with a very low energy diet ( VLED ) for 2 months at the start of the study . SUBJECTS Twelve male , obese subjects ( age 36.3+/-5.1 y ; body weight 94.6+/-13.9 kg ; body mass index , BMI 30.8+/-3.0 kg/m2 ) and in an additional study 15 lean , well-trained subjects ( age 36.2+/-7.2 y ; body weight 72.2+/-5.9 kg ; BMI 22.3+/-1.7 kg/m2 ) participated . MEASUREMENTS Substrate oxidation was measured during a standardized 36 h stay in the respiration chamber at the start of the study ( 0 months ) , and at 4 , 10 and 16 months . In the respiration chamber subjects were randomly assigned to a high-fat ( Hi.F ) diet ( 60 % of energy ( En % ) fat ) or a reduced-fat ( Red.F ) diet ( 30 En % fat ) . The well-trained group was measured once in the respiration chamber for 36 h according to the same protocol . RESULTS At any time point , independent of the diet consumed , the 24 h carbohydrate ( CHO ) balances in the chamber were mostly negative ( means ranging from +31 to -98 g/d ) and the fat balances mostly positive ( means ranging from -26 to +38 g/d ) for the obese a well as for the lean , well-trained group . For both diets an increased shortage of 70 g of CHO was found at 16 months compared with 4 months , and an increase in fat balance of 33 g during the same time period in the obese subjects , indicating that CHO oxidation had increased with 12 months endurance training . In the well-trained group the 24h CHO balance was even more negative for both types of diet ( -103 to -185 g/d for the Red.F and Hi.F diet , respectively ) under similar conditions compared with the trained obese group . CONCLUSION The changes in 24 h substrate utilization in the obese , as well as in the well-trained group , suggest that endurance training increased the reliance on carbohydrate oxidation and therefore did not increase 24 fat oxidation .

exercise training and

dietary macronutrient composition

exercise intervention

very low energy diet ( VLED

high-fat ( Hi.F ) diet

( 60 % of energy ( En % ) fat ) or a

reduced-fat ( Red.F ) diet

( 30 En % fat

24h substrate oxidation

24 h substrate oxidation

Substrate oxidation

24 h carbohydrate ( CHO ) balances

fat balances

shortage of 70 g of CHO

fat balance

CHO oxidation

24h CHO balance

24 h substrate utilization

carbohydrate oxidation

24 fat oxidation

male

obese

Twelve

male

obese


The relationship between repetitive behaviors and growth hormone response to sumatriptan challenge in adult autistic disorder . Autism is heterogeneous with respect to clinical symptoms and etiology . To sort out this heterogeneity in autism , we investigated whether specific neurobiological markers vary in parallel to core symptomatology . Specifically , we assessed growth hormone response to the 5-HT 1d agonist , sumatriptan , and linked this measure of serotonergic function to the severity of repetitive behaviors in adult autistic patients . Eleven adult patients with autism or Asperger 's disorder were randomized to single dose sumatriptan ( 6 mg SQ ) and placebo challenges , separated by a one-week interval . In adult autistic disorders , severity of repetitive behaviors at baseline , as measured by YBOCS-compulsion score , significantly positively correlated with both peak delta growth hormone response and area under the curve growth hormone response to sumatriptan . Thus , the severity of a specific behavioral dimension in autism ( repetitive behaviors ) parallels the sensitivity of the 5-HT 1d receptor , as manifest by sumatriptan elicited GH response .

sumatriptan

5-HT 1d agonist , sumatriptan

sumatriptan

placebo

sumatriptan

5-HT 1d receptor

sumatriptan

repetitive behaviors

growth hormone response

specific neurobiological markers

core symptomatology

growth hormone response

severity of repetitive behaviors

severity of repetitive behaviors

at baseline

measured by

YBOCS-compulsion score

significantly positively correlated

peak delta growth hormone response

( repetitive behaviors )

parallels the sensitivity

sumatriptan elicited GH response

adult

autistic disorder

adult

autistic

Eleven

adult

autism

Asperger 's disorder


Effectiveness of manual physical therapy and exercise in osteoarthritis of the knee . A randomized , controlled trial . BACKGROUND Few investigations include both subjective and objective measurements of the effectiveness of treatments for osteoarthritis of the knee . Beneficial interventions may decrease the disability associated with osteoarthritis and the need for more invasive treatments . OBJECTIVE To evaluate the effectiveness of physical therapy for osteoarthritis of the knee , applied by experienced physical therapists with formal training in manual therapy . DESIGN Randomized , controlled clinical trial . SETTING Outpatient physical therapy department of a large military medical center . PATIENTS 83 patients with osteoarthritis of the knee who were randomly assigned to receive treatment ( n = 42 ; 15 men and 27 women [ mean age , 60 +/- 11 years ] ) or placebo ( n = 41 ; 19 men and 22 women [ mean age , 62 +/- 10 years ] ) . INTERVENTION The treatment group received manual therapy , applied to the knee as well as to the lumbar spine , hip , and ankle as required , and performed a standardized knee exercise program in the clinic and at home . The placebo group had subtherapeutic ultrasound to the knee at an intensity of 0.1 W/cm2 with a 10 % pulsed mode . Both groups were treated at the clinic twice weekly for 4 weeks . MEASUREMENTS Distance walked in 6 minutes and sum of the function , pain , and stiffness subscores of the Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) . A tester who was blinded to group assignment made group comparisons at the initial visit ( before initiation of treatment ) , 4 weeks , 8 weeks , and 1 year . RESULTS Clinically and statistically significant improvements in 6-minute walk distance and WOMAC score at 4 weeks and 8 weeks were seen in the treatment group but not the placebo group . By 8 weeks , average 6-minute walk distances had improved by 13.1 % and WOMAC scores had improved by 55.8 % over baseline values in the treatment group ( P < 0.05 ) . After controlling for potential confounding variables , the average distance walked in 6 minutes at 8 weeks among patients in the treatment group was 170 m ( 95 % CI , 71 to 270 m ) more than that in the placebo group and the average WOMAC scores were 599 mm higher ( 95 % CI , 197 to 1002 mm ) . At 1 year , patients in the treatment group had clinically and statistically significant gains over baseline WOMAC scores and walking distance ; 20 % of patients in the placebo group and 5 % of patients in the treatment group had undergone knee arthroplasty . CONCLUSIONS A combination of manual physical therapy and supervised exercise yields functional benefits for patients with osteoarthritis of the knee and may delay or prevent the need for surgical intervention .

manual physical therapy and exercise

physical therapy

treatment

placebo

manual therapy

standardized knee exercise program

placebo

subtherapeutic ultrasound

treatment

placebo

treatment

treatment

placebo

treatment

placebo

treatment

knee arthroplasty

disability

pain

6-minute walk distance

WOMAC score

6-minute walk distances

WOMAC scores

distance walked in 6 minutes

WOMAC scores

baseline WOMAC scores

walking distance

knee arthroplasty

functional benefits

surgical intervention

osteoarthritis of the knee

osteoarthritis of the knee

osteoarthritis of the knee

men

women

60 +/- 11

62 +/- 10

osteoarthritis of the knee


Regression of left ventricular hypertrophy after stentless versus conventional aortic valve replacement . The goal of this study was to analyze regression of left ventricular hypertrophy after randomization to conventional biological versus stentless aortic valve replacement . Stentless ( Freestyle , Toronto , n = 106 ) or conventional biological aortic valves ( Carpentier-Edwards , n = 74 ) were evaluated prospectively . Preoperatively there were no differences with regard to aortic valve pathology , left ventricular function , and pressure gradients between the two patient groups . The patient annulus index ( 13.55 vs. 13.46 mm ; NS ) measured intraoperatively was used as baseline for further comparison . Postoperatively , left ventricular mass index was 213+/-77 g/m2 ( stentless ) compared with 202+/-72 ( conventional group ) g/m2 ( NS ) , whereas after 6 months it was 141+/-41 g/m2 in the stentless and 170+/-43 g/m2 in the conventional group ( P < .05 ) . Regression of left ventricular hypertrophy occurs in all patients after aortic valve replacement . Nevertheless , the use of stentless bioprostheses leads to a significant enhancement , which may result in a reduction of the cardiac risk profile for the patient .

stentless

conventional aortic valve replacement

Stentless

conventional biological aortic valves

stentless bioprostheses

patient annulus index

left ventricular mass index

aortic valve replacement

aortic valve replacement


Changes in cardiac muscle mass and function in hemodialysis patients during growth hormone treatment . BACKGROUND Adult patients with chronic renal failure ( CRF ) often show symptoms as fatigue , wasting , and reduced working capacity with concomitant findings of reduced cardiac performance and muscle mass . This state may in part be caused by an imbalance in the somatostatin/somatomedine axis resulting in increased catabolism . During an attempt to correct this catabolic state by administration of exogenous growth hormone , cardiac muscle mass and performance were studied . METHODS In a double-blind , placebo-controlled 6-month study comprising 20 adult enfeebled hemodialysis patients , 9 patients were treated with a single daily subcutaneous injection of recombinant human growth hormone ( rhGH ) 4 IU/m2 and 11 with placebo injections . Left ventricular muscle mass ( LVM ) and ejection fraction ( EF ) were evaluated by echocardiography and the maximal working capacity ( MWC ) was measured by a bicycle exercise test performed before and after the treatment period . Supplementary electrocardiography ( ECG ) was performed before and after 6-month treatment . RESULTS Median LVM increased significantly from 172 to 220 g ( p = 0.03 ) in the rhGH-treated group , while an insignificant decrease was observed in the placebo group from 281 to 200 g ( p = 0.3 ) . The EF showed no significant changes in the two groups . MWC showed a slight , insignificant decrease in both groups . From ECG no significant ST deviations were found and no significant changes regarding B-Hb , blood pressure or pulse were observed in the two groups . Irregular heart rhythm aggravated in one patient during the first month of treatment with rhGH , but was overcome by a -blocking agent . CONCLUSION The treatment with rhGH of adult chronic hemodialysis patients for 6 months increased the left ventricular mass significantly , but without any effect on ejection fraction or maximal working capacity . No electrocardiographic signs of ischemia were associated with the increasing muscle mass and only one patient developed symptoms that might relate to ischemia . No changes in B-Hb , blood pressure or pulse were observed during the treatment period .

growth hormone treatment

exogenous growth hormone

placebo-controlled

hemodialysis

placebo

bicycle exercise test

cardiac muscle mass

Left ventricular muscle mass ( LVM )

ejection fraction ( EF )

electrocardiography ( ECG )

Median LVM

EF

MWC

ST deviations

Irregular heart rhythm

the left ventricular mass

B-Hb

blood pressure

hemodialysis

growth hormone treatment

Adult

chronic renal failure ( CRF )

adult

enfeebled hemodialysis


Randomized trial of the effects of risedronate on vertebral fractures in women with established postmenopausal osteoporosis . Vertebral Efficacy with Risedronate Therapy ( VERT ) Study Group . The purpose of this randomized , double-masked , placebo-controlled study was to determine the efficacy and safety of risedronate in the prevention of vertebral fractures in postmenopausal women with established osteoporosis . The study was conducted at 80 study centers in Europe and Australia . Postmenopausal women ( n = 1226 ) with two or more prevalent vertebral fractures received risedronate 2.5 or 5 mg/day or placebo ; all subjects also received elemental calcium 1000 mg/day , and up to 500 IU/day vitamin D if baseline levels were low . The study duration was 3 years ; however , the 2.5 mg group was discontinued by protocol amendment after 2 years . Lateral spinal radiographs were taken annually for assessment of vertebral fractures , and bone mineral density was measured by dual-energy X-ray absorptiometry at 6-month intervals . Risedronate 5 mg reduced the risk of new vertebral fractures by 49 % over 3 years compared with control ( p < 0.001 ) . A significant reduction of 61 % was seen within the first year ( p = 0.001 ) . The fracture reduction with risedronate 2.5 mg was similar to that in the 5 mg group over 2 years . The risk of nonvertebral fractures was reduced by 33 % compared with control over 3 years ( p = 0.06 ) . Risedronate significantly increased bone mineral density at the spine and hip within 6 months . The adverse-event profile of risedronate , including gastrointestinal adverse events , was similar to that of control . Risedronate 5 mg provides effective and well-tolerated therapy for severe postmenopausal osteoporosis , reducing the incidence of vertebral fractures and improving bone density in women with established disease .

risedronate

risedronate

placebo

elemental calcium 1000 mg/day

vitamin D

vertebral fractures

efficacy and safety of risedronate

vertebral fractures

vertebral fractures

bone mineral density

vertebral fractures

fracture reduction

nonvertebral fractures

bone mineral density

gastrointestinal adverse events

women

postmenopausal osteoporosis

postmenopausal

women

established osteoporosis

women

n = 1226

severe postmenopausal osteoporosis

women

with established disease


Bronchodilatory responses to formoterol , ipratropium , and their combination in patients with stable COPD . We studied 27 patients with stable chronic obstuctive pulmonary disease ( COPD ) in a randomised , single-blind , within-patient , placebo-controlled clinical study . Each patient was assigned on six separate days to receive one of the following drug regimens in random order : A . 40 micrograms ipratropium bromide ( Atrovent MDI , 20 micrograms/puff ) plus 2 puffs placebo ; B . 12 micrograms formoterol fumarate ( Foradil MDI , 12 micrograms/puff ) plus 3 puffs placebo ; C. 80 micrograms ipratropium ; D. 24 micrograms formoterol plus 2 puffs placebo ; E. 12 micrograms formoterol plus 40 micrograms ipratropium plus 1 puff placebo ; F. 4 puffs placebo . On each study day , spirometric indices and vital signs were measured at 5 , 10 , 15 and 60 minutes , and hourly thereafter up to and including 12 hours after study drug administration . Mean peak FEV1 change ( primary endpoint ) was maximum with the administration of the combination of ipratropium and formoterol ( 335.2 ml , SE 24.6 ) , and it differed significantly from the observed peak changes following single administration of the two tested doses of ipratropium ( p < 0.05 and p < 0.05 respectively ) . Safety and tolerability were satisfactory throughout the study .

formoterol

ipratropium

combination

placebo-controlled

2 puffs placebo

3 puffs placebo

80 micrograms ipratropium

12 micrograms formoterol

40 micrograms ipratropium

1 puff placebo

4 puffs placebo

ipratropium

formoterol

ipratropium

Bronchodilatory responses

spirometric indices and vital signs

Mean peak FEV1 change

Safety and tolerability

patients with stable COPD .


Granulocyte-macrophage colony-stimulating factor as immunomodulating factor together with influenza vaccination in stem cell transplant patients . The effect of granulocyte-macrophage colony-stimulating factor ( GM-CSF ) on the serological response at influenza vaccination was studied in 117 patients who had undergone stem cell transplantation ( SCT ) . The vaccine response was evaluated as significant increases in levels of influenza hemagglutination-inhibition ( HAI ) antibodies and of IgG antibodies measured by enzyme-linked immunosorbent assay ( ELISA ) . There was no difference in antibody response to either influenza A or B in 64 patients who received GM-CSF at vaccination , compared with the 53 who did not . In the subgroup of allogeneic SCT patients , HAI showed that the response rate to the influenza B vaccine was significantly higher in the treatment group ( P < .05 ) . ELISA showed that autologous SCT patients with breast cancer who received GM-CSF had a better response to influenza A ( P < .05 ) and B ( P < .01 ) . At early vaccination , 4-12 months after stem cell transplantation , these responses were more pronounced . GM-CSF appears to improve the response to influenza vaccination in some groups of SCT patients , but only to a limited extent .

influenza vaccination

influenza vaccination

GM-CSF

influenza B vaccine

GM-CSF

serological response

vaccine response

IgG antibodies

antibody response

ELISA

influenza A

influenza vaccination

stem cell transplant

undergone stem cell transplantation

SCT

SCT patients


Differential effects of amino acid and ketoacid on protein metabolism in humans . We examined the effects of insulin , amino acid ( AA ) , and branched-chain ketoacid ( KA ) availability on leucine kinetics in eight healthy volunteers ( age = 22 +/- 2 y , body mass index = 24 +/- 1 kg ) by using the euglycemic insulin clamp and [ 1-14C ] leucine turnover techniques . Four experimental conditions were studied : study I , hyperinsulinemia ; study II , hyperinsulinemia with maintenance of basal plasma AA and branched-chain KA concentrations ; study III , hyperinsulinemia with hyperaminoacidemia and basal plasma branched-chain KA concentrations ; and study IV , hyperinsulinemia plus basal plasma AA concentrations and elevated branched-chain KA levels . Basal endogenous leucine flux ( ELF ) averaged 1.20 +/- 0.05 ( mumol.kg-1.min-1 , mean +/- SE ) ; basal leucine oxidation ( LOX ) was 0.25 +/- 0.01 ; and basal non-oxidative leucine disposal ( NOLD ) was 0.95 +/- 0.04 . ELF significantly decreased in study I ( 0.77 +/- 0.06 mumol.kg-1.min-1 , P < 0.01 versus basal ) . When plasma AA and branched-chain KA were either maintained at their basal levels ( study II ) or increased above baseline values ( studies III and IV ) , ELF declined further ( 0.64 +/- 0.05 , 0.66 +/- 0.02 , and 0.66 +/- 0.03 mumol.kg-1.min-1 , respectively ; all Ps < 0.01 versus basal and P < 0.01 versus study I ) . LOX declined in study I ( 0.12 +/- 0.02 mumol.kg-1.min-1 , P < 0.01 versus basal ) but increased significantly in studies II , III , and IV ( 0.31 +/- 0.04 , 0.37 +/- 0.03 , and 0.40 +/- 0.03 mumol.kg-1.min-1 , respectively , all Ps < 0.01 versus basal , P < 0.05 study IV versus study II , and P < 0.05 study III versus study II ) . NOLD declined in study I ( 0.65 +/- 0.05 mumol/kg.min , P < 0.01 versus basal ) , whereas neither the maintenance of basal plasma AA/branched-chain KA levels ( study II ; 0.89 +/- 0.2 mumol.kg-1.min-1 ) nor the elevation of plasma branched-chain KA concentration ( study IV ; 0.96 +/- 0.1 mumol.kg-1.min-1 ) increased NOLD above baseline level . A stimulation of NOLD was observed only when plasma AA levels were increased ( study III ; 1.23 +/- 0.03 mumol/kg.min , P < 0.01 versus basal ) . In conclusion , the present data do not support the concept of a direct anabolic action of ketoanalogs but do provide additional evidence for the pivotal role of AA availability in the stimulation of whole-body protein synthesis .

euglycemic insulin clamp

and [ 1-14C ]

leucine turnover

techniques

endogenous leucine flux ( ELF )

leucine oxidation ( LOX )

non-oxidative leucine disposal ( NOLD )

ELF

LOX

NOLD

NOLD

NOLD

healthy volunteers

age = 22 +/- 2 y

body mass index = 24 +/- 1 kg


Assessment of therapeutic response of Plasmodium falciparum to chloroquine and sulfadoxine-pyrimethamine in an area of low malaria transmission in Colombia . Although chloroquine ( CQ ) resistance was first reported in Colombia in 1961 and sulfadoxine-pyrimethamine ( SP ) resistance in 1981 , the frequency of treatment failures to these drugs in Colombia is unclear . A modified World Health Organization 14-day in vivo drug efficacy test for uncomplicated Plasmodium falciparum malaria in areas with intense malaria transmission was adapted to reflect the clinical and epidemiologic features of a low-intensity malaria transmission area in the Pacific Coast Region of Colombia . Patients > or =1 year of age with a parasite density > or =1,000 asexual parasites per microliter were enrolled in this study . Forty-four percent ( 24 of 54 ) of the CQ-treated patients were therapeutic failures , including 7 early treatment failures ( ETFs ) and 17 late treatment failures ( LTFs ) . Four ( 6 % ) of 67 SP-treated patients were therapeutic failures ( 2 ETFs and 2 LTFs ) . Therapeutic failure in the CQ-treated group was associated with an age < 15 years old ( P < 0.01 ) , but was not associated with initial parasite density , the presence of CQ or sulfa-containing drugs in urine , or a history of malaria . The high level of therapeutic failures to CQ detected in this study underscores the need and importance of drug efficacy evaluation in the development of a rational national antimalarial drug policy . The relatively low level of therapeutic failures to SP compared with other South American countries raises further questions regarding factors that might have prevented the rapid development of in vivo resistance to this drug combination .

chloroquine

sulfadoxine-pyrimethamine

chloroquine

sulfadoxine-pyrimethamine

CQ-treated

CQ-treated

CQ

CQ

therapeutic

therapeutic failures

early treatment failures ( ETFs

late treatment failures

( LTFs )

therapeutic failures

Therapeutic failure

therapeutic failures

efficacy

therapeutic failures

low malaria

> or =1 year of age

Forty-four


Efficacy of primaquine regimens for primaquine-resistant Plasmodium vivax malaria in Thailand . To define the current efficacy of Fansidar ( F. Hoffmann-La Roche Ltd. , Basel Switzerland ) ( pyrimethamine and sulfadoxine ) , primaquine in a high dose , and artesunate for treating acute Plasmodium vivax malaria , we conducted a comparative clinical trial of these 3 drugs in an open-label study . Patients ( 15-65 years old ) were assigned to 1 of 4 treatments regimens in a serial order . Ninety percent of the patients were infected at Thailand-Myanmar border . Patients in group I ( n = 23 ) received Fansidar ( 3 tablets , 75 mg of pyrimethamine and 1,500 mg of sulfadoxine , a single dose on the first day ) , group II ( n = 23 ) received Fansidar ( 3 tablets , 75 mg of pyrimethamine and 1,500 mg of sulfadoxine , a single dose on the first day ) and then received primaquine ( 30 mg a day for 14 days ) , group III ( n = 23 ) received primaquine ( 30 mg a day for 14 days ) , and group IV ( n = 23 ) received artesunate ( 200 mg once a day for 3 days ) and then primaquine ( 30 mg a day for 14 days ) . Cure rates on day 28 of follow-up were 40 % , 100 % , 100 % , and 100 % in groups I , II , II , and IV , respectively . There were 4 and 5 patients in group I showing post-treatment reappearance of parasitemia at < or = 16 days and between 17 and 28 days , respectively . Patients in the other 3 groups showed negative parasitemias within 7 days after treatment . Artesunate plus primaquine ( group IV ) cleared parasitemia faster than the other 3 regimens . There is a high proportion of ineffectiveness of Fansidar for treatment of P. vivax malaria and it should be no longer used for treatment of P. vivax malaria acquired at the Thailand-Myanmar border . A high dose of primaquine is safe and effective in the treatment of P. vivax malaria during the 28-day follow-up period .

primaquine regimens

Fansidar

Hoffmann-La Roche Ltd.

Basel Switzerland )

pyrimethamine

sulfadoxine

primaquine

artesunate

Fansidar

pyrimethamine

1,500 mg of sulfadoxine

primaquine ( 30 mg a day for 14 days )

artesunate

primaquine

Cure rates

negative parasitemias

parasitemia

ineffectiveness

safe and effective

Thailand .


Safety of the combination of valsartan and benazepril in patients with chronic renal disease . European Group for the Investigation of Valsartan in Chronic Renal Disease . OBJECTIVE Several experimental and clinical studies indicate that the renin system may play a pivotal role in progressing renal disease . The combination of an angiotensin-converting enzyme inhibitor and an angiotensin receptor blocker could provide a higher degree of blockade of the renin-angiotensin system than either agent alone . Such enhanced suppression might be of benefit for patients exhibiting a progressive decline in renal function because of chronic renal disease . METHODS A pilot multinational , multicentre , randomized , active-controlled , parallel group open-label study has been conducted in a group of patients with progressive chronic renal failure ( creatinine clearance 20-45 ml/min ) either with or without proteinuria and hypertension . The primary aim of the study was to investigate the safety and tolerability of the combination of valsartan and benazepril . Patients were randomly assigned to one of three groups : group 1 received valsartan 160 mg once daily ( n = 22 ) ; group 2 received valsartan 80 mg once daily plus benazepril 5 or 10 mg once daily ( n = 42 ) ; group 3 received valsartan 160 mg once daily plus benazepril 5 or 10 mg once daily ( n = 44 ) . The study lasted for 5 weeks , and in groups 2 and 3 benazepril was added on top of valsartan after the first week of therapy with the angiotensin receptor blocker . RESULTS Serum creatinine increased in all three groups ( mean change within a group : 11 micromol/l in group 1 , P= 0.045 ; 9 micromol/l in group 2 , P= 0.030 ; 15 micromol/l in group 3 , P= 0.0006 ) . Serum potassium also increased in all three groups of patients ( mean change within a group : 0.28 mmol/l in group 1 , P= 0.28 ; 0.48 mmol/l in group 2 , P= 0.0008 ; 0.36 mmol/l in group 3 , P= 0.02 ) . After 5 weeks of treatment , the largest decrease in blood pressure was observed in group 3 ( the mean change from baseline in seated diastolic blood pressure ( SDBP ) and seated systolic blood pressure ( SSBP ) , respectively , were : -2.0 and -11.5 mmHg in group 1 ; -7.6 and -15.4 mmHg in group 2 ; -12.6 and -21.6 mmHg in group 3 ) . In addition , both combination treatments resulted in the reduction of proteinuria . The total number of patients with adverse experiences were 10 ( 45.5 % ) , 14 ( 33.3 % ) and 11 ( 25 % ) in groups 1,2 and 3 , respectively . In six patients ( 5.6 % ) therapy was discontinued as a result of adverse experiences . Only one patient in each of the combined therapy groups withdrew from the study because of hyperkalaemia and no patients were forced to withdraw because of an increase in serum creatinine , acute renal failure or hospitalization . CONCLUSIONS These results indicate that short-term combination of an angiotensin-converting enzyme inhibitor and an angiotensin receptor blocker is safe and well tolerated in patients with moderate chronic renal failure .

combination of valsartan

benazepril

Valsartan

combination of valsartan

benazepril

valsartan 160 mg

valsartan 80 mg once daily

benazepril 5 or 10 mg once daily

valsartan 160 mg

benazepril 5 or 10 mg

Safety

safety and tolerability

Serum creatinine

Serum potassium

blood pressure

seated systolic blood pressure ( SSBP )

proteinuria

adverse experiences

hyperkalaemia

serum creatinine

acute renal failure

hospitalization

safe

well tolerated

chronic renal disease

progressive decline in renal function

chronic renal disease


[ Administration of tobramycin aerosols in patients with nosocomial pneumonia : a preliminary study ] . OBJECTIVE The aim of this study was to assess renal and respiratory tolerance of aerosolized tobramycin in intubated and mechanically ventilated patients with nosocomial pneumonia . PATIENTS AND METHODS This was a multicenter , randomized , double-blind , placebo controlled study . Thirty-eight mechanically ventilated patients with documented nosocomial pneumonia were included . Patients treated with intravenous betalactam and tobramycin were randomly allocated to receive aerosolized tobramycin ( 6 mg/kg/day , n = 21 ) or placebo ( n = 17 ) . The aerosol was administered via a pneumatic nebulizer once a day for 5 days . RESULTS Respiratory tolerance was good in all but two patients . No acute renal failure occurred . By day 10 , 7 patients in the tobramycin group ( 35 % ) had been extubated versus 3 in the placebo group ( 18.5 % , p = 0.18 ) . By day 28 , 6 patients had died ( 2 in the tobramycin group and 4 in the placebo group , p = 0.23 ) . CONCLUSION Aerosolized tobramycin was well tolerated in ventilated patients with documented nosocomial pneumonia .

tobramycin aerosols

tobramycin

intravenous betalactam

tobramycin

aerosolized tobramycin

aerosol

renal and respiratory tolerance

Respiratory tolerance

No acute renal failure

extubated

died

patients with nosocomial pneumonia

nosocomial pneumonia

Thirty-eight


Effect of sensory stimulation ( acupuncture ) on sympathetic and parasympathetic activities in healthy subjects . UNLABELLED It has been postulated that sensory stimulation ( acupuncture ) affects the cardiovascular system via the autonomic nervous system . Previously , skin temperature , thermography , plethysmography and blood pressure changes have been used in evaluation of sympathetic nerve activity following acupuncture . By using power spectral analysis , the low frequency and high frequency components of heart rate variability can be calculated reflecting the sympathetic and parasympathetic activity . The purpose of this study was to investigate to what extent acupuncture applied into the thenar muscle and into the cavum concha of the ear induced changes in the sympathetic and/or parasympathetic nervous system in healthy subjects . MATERIALS AND METHODS Twelve healthy volunteers , six men and six women , mean age 34.4 ( range 23-48 ) participated in three balanced , randomly distributed sessions . At an individual initial visit the 12 volunteers were introduced to the needle sensation by having a needle inserted into the point LI 11 . The needle sensation was evoked and the subject was trained to identify the characteristic needle sensation . The introduction was followed by three test sessions . SESSION A A short acupuncture needle , ( Seirin no 3 , & emptyv ; 0.20x15 mm ) was inserted perpendicular into the earpoint , Lu 1 , in the left inferior hemi-conchae . SESSION B An acupuncture needle ( Hwato , & emptyv ; 0.30x30 mm ) was inserted perpendicular into the Hegu point ( LI 4 ) in the middle of the right dorsal thenar muscle . SESSION C An acupuncture needle ( Hwato , & emptyv ; 0.30x30 mm ) was inserted perpendicular superficially into the skin overlying the Hegu point on the left hand . Results . Stimulation of the ear induced a significant increase in the parasympathetic activity during the stimulation period of 25 min ( P < 0.05 ) and during the post-stimulation period of 60 min ( P < 0.05 ) . No significant changes were observed in either the sympathetic activity , blood pressure or heart rate . Stimulation of the thenar muscle resulted in a significant increase in the sympathetic and the parasympathetic activity during the stimulation period ( P < 0.01 ) and during the post-stimulation period ( P < 0.01 and P < 0.001 , respectively ) . A significant decrease in the heart rate frequency ( P < 0.05 ) at the end of the post-stimulation period was also demonstrated . The superficial needle insertion into the skin overlaying the right thenar muscle caused a pronounced balanced increase in both the sympathetic and parasympathetic activity during the post stimulation period of 60 min ( P < 0.01 ) while no changes were observed during the stimulation period . CONCLUSION It is indicated that sensory stimulation ( acupunctura ) in healthy persons is associated with changed activity in the sympathetic and parasympathetic nervous system depending on site of stimulation and period of observation .

sensory stimulation

sensory stimulation ( acupuncture )

needle sensation

short acupuncture needle

skin temperature

thermography

plethysmography

blood pressure

parasympathetic activity

sympathetic activity

blood pressure

heart rate

heart rate frequency

sympathetic

parasympathetic activity

sympathetic

parasympathetic nervous

healthy subjects .

Twelve healthy volunteers

six

men

six

women

mean age 34.4 ( range 23-48 )


Effect of topical rh-TGF-beta 1 on second intention wound healing in horses . OBJECTIVE To investigate the effects on wound healing of transforming growth factor-beta 1 as a topical treatment to full-thickness , excisional wounds of the distal limb of horses . DESIGN A randomised block study using four horses , each with wounds assigned to four treatment groups . ANIMALS Four adult Standardbred geldings . PROCEDURE Four , 4 cm2 , full-thickness wounds were created on the dorsomedial and dorsolateral aspect of the metacarpus or metatarsus of each limb of four horses , giving a total of 64 wounds . For each limb , wounds were randomly assigned to four treatment groups : no treatment ( control ) , carrier ( Methyl Cellulose gel ) , 50 ng/wound rhTGF-beta 1 in carrier , and 500 ng/wound rhTGF-beta 1 in carrier . Wounds were treated on day 0 and day 8 . Effects of treatment were evaluated on the basis of the presence of exuberant granulation tissue requiring excision , number of times excision was required , total wound area , area of epithelialisation , area of granulation , and histological evaluation of biopsy samples of wounds on day 8 and excised wounds on day 21 . RESULTS Topical application of TGF-beta 1 at the two concentrations studied had no significant effect on the total area of wounds ( P = 0.7 ) , the area of granulation tissue ( P = 0.78 ) , the area of epithelialisation ( P = 0.92 ) , histological assessment or subjective clinical assessment of wounds . CONCLUSION TGF-beta 1 had no beneficial effects on wound healing . Additional trials are needed to test if it has value for wound treatment in horses .

rh-TGF-beta 1

growth factor-beta 1

no treatment

carrier ( Methyl Cellulose gel )

50 ng/wound rhTGF-beta 1 in carrier ,

500 ng/wound rhTGF-beta 1 in carrier

TGF-beta 1

second intention wound healing

total area of wounds

the area of granulation tissue

area of epithelialisation

wound healing

second intention wound healing

four


Efficacy and safety of a fixed low-dose perindopril/indapamide combination in essential hypertension . A randomised controlled study . This multicenter , double-blind , parallel-group study was designed to assess the efficacy and the safety of fixed low dose combination perindopril 2 mg/indapamide 0.625 mg ( Per/Ind ) versus atenolol 50 mg ( Ate ) . After a 4-week placebo run-in , 446 hypertensive patients ( mean age : 55.8 +/- 11.0 years ) were randomised to receive Per/Ind or Ate for 12 weeks . The primary outcome measures were the changes in trough supine systolic and diastolic blood pressure ( sSBP , sDBP ) between baseline and the last observation . Equivalence was assessed in an intention-to-treat analysis using a two one-sided tests procedure . Per/Ind and Ate decreased sSBP by -20.5 mmHg and -20.1 mmHg , respectively ; the 90 % confidence interval [ -2.3 ; 1.5 ] of the intertreatment difference ( -0.4 mmHg ) fell within the predefined equivalence interval [ -8 ; +8 mmHg ] . Similarly , the sDBP decreased by -15.1 mmHg ( Per/Ind ) and -16.2 mmHg ( Ate ) with an intertreatment difference of 1.1 mmHg whose 90 % confidence interval [ -0.1 ; 2.2 mmHg ] fell within the predefined equivalence interval [ -4 ; +4 mmHg ] ; thus antihypertensive efficacy of Per/Ind and Ate were equivalent ( P < 0.001 ) . In patients older than 65 , Per/Ind induces a statistically greater decrease in sSBP than Ate ( P < 0.05 ) . Per/Ind was well tolerated . Further controlled studies are needed to confirm these results on a long-term period .

perindopril/indapamide combination

atenolol

Per/Ind

Ate

Efficacy

safety

efficacy

safety

Equivalence

sSBP

confidence interval

sDBP decreased

equivalence interval

antihypertensive efficacy

sSBP

tolerated

essential hypertension

hypertensive

mean age : 55.8 +/- 11.0 years


Treatment of whiplash associated neck pain [ corrected ] with botulinum toxin-A : a pilot study . OBJECTIVE Up to 87 % of patients with whiplash associated disorder ( WAD ) have some degree of muscle spasm that is contributory to both pain and dysfunction . Botulinum toxin A ( BTX-A ) produces prolonged muscle relaxation that is dose-dependent and can be easily targeted to affected muscles . BTX-A therapy may be an effective form of therapy offering an alternative or adjunct to conventional modalities . We investigated BTX-A as therapy in patients with WAD . METHODS This randomized , double blind , placebo controlled study compares outcome measures in 26 patients with chronic neck pain ( WAD-II chronic ) subsequent to a motor vehicle accident . One-half of the patients received 100 units BTX-A , diluted in 1 ml saline , while the other half received just saline ( 1 ml ) . Five trigger points received 0.2 ml each of injectant via a 30 gauge needle . Outcome measures included total subjective neck , shoulder , and head pain based on visual analog scales ; objective total range of neck motion ( ROM ) , and the Vernon-Mior subjective function index . Followup assessments were carried out at 2 and 4 weeks post-treatment . RESULTS Fourteen subjects receiving BTX-A and 12 receiving saline completed the study . The treatment group showed a trend toward improvement in ROM and reduction in pain at 2 weeks post-injection . At 4 weeks post-injection the treatment group was significantly improved from preinjection levels ( p < 0.01 ) . The placebo group showed no statistically significant changes at any post-treatment time . The Vernon-Mior scale revealed a trend to improvement for both groups . CONCLUSION BTX-A treatment of subjects with chronic WAD II neck pain resulted in a significant ( p < 0.01 ) improvement in ROM and subjective pain compared to a placebo group , but only a trend to improvement in subjective functioning .

botulinum toxin-A :

Botulinum toxin A ( BTX-A )

BTX-A

placebo

other half received just saline

BTX-A

BTX-A

Vernon-Mior subjective function index

ROM

pain

Vernon-Mior scale

ROM

subjective pain

subjective functioning

WAD

chronic neck pain

Fourteen


Comparison of 0.25 % S ( - ) -bupivacaine with 0.25 % RS-bupivacaine for epidural analgesia in labour . We have compared the efficacy of 0.25 % S ( - ) -bupivacaine with 0.25 % RS-bupivacaine in providing epidural analgesia for labour in a randomized , multicentre , double-blind study . Analgesia was initiated with 10 ml of the study solution and maintained with 10-ml top-ups . We studied 137 women and treatments were found to be equivalent for onset , duration and quality of block . Median onset of pain relief was 12 min for both drugs and median duration was 49 ( range 3-129 ) min and 51 ( 7-157 ) min for S ( - ) -bupivacaine and RS bupivacaine , respectively . The estimated treatment difference for duration of pain relief was -4 ( 90 % CI -13 , 6 ) min . Thirty patients failed to achieve pain relief after the first injection ( 20 patients after S ( - ) -bupivacaine and 10 after RS-bupivacaine ; P = 0.039 ) . However , median duration of pain relief from the first top-up was 82 ( range 3-164 ) min for S ( - ) -bupivacaine and 76 ( 22-221 ) min for RS-bupivacaine . There were no significant differences in the quality of analgesia , as assessed by the investigators . There were no significant differences in the extent of sensory block , percentage of patients with motor block or incidence of adverse events .

S ( - ) -bupivacaine

RS-bupivacaine

analgesia

epidural analgesia

Median onset of pain relief

duration of pain relief

achieve pain relief

median duration of pain relief

quality of analgesia

or incidence of adverse events

in labour .

women


Hip protectors improve falls self-efficacy . OBJECTIVES To investigate the effect of use of external hip protectors on subjects ' fear of falling and falls self-efficacy ( belief in their own ability to avoid falling ) . DESIGN Randomized controlled trial . SETTING Aged-care health services in Sydney , Australia . PARTICIPANTS 131 women aged 75 years or older , who had two or more falls or one fall requiring hospital admission in the previous year and who live at home . Sixty-one subjects were in the intervention group and 70 in the control group . INTERVENTION Use of external hip protectors and encouragement to use the protectors by an adherence nurse . MEASUREMENTS At the time of enrolment into a wider study examining the effect of hip protectors on hip fractures , participants recruited at home completed an assessment of fear of falling and falls efficacy as measured by the Falls Efficacy Scale and the Modified Falls Efficacy Scale . At 4-month follow-up , these scales were readministered by an observer who was not aware of the allocation of the participant to intervention or control groups . RESULTS Fear of falling and falls self-efficacy , as measured by the Falls Efficacy and Modified Falls Efficacy Scales , were similar at baseline in both groups . Fear of falling was present at follow-up in 43 % of subjects using hip protectors and 57 % of the control group ( chi2 = 2.58 , P = 0.11 ) . Hip protector users had greater improvement in falls self-efficacy at follow-up as measured by the Falls Efficacy Scale ( t = 2.44 , P = 0.016 ) and the Modified Falls Efficacy Scale ( t = 2.08 , P = 0.039 ) . CONCLUSION Hip protectors improve falls self-efficacy . As users of hip protectors feel more confident that they can complete tasks safely , they may become more physically active and require less assistance with activities of daily living .

Hip protectors

external hip protectors

control

by an adherence nurse

hip protectors

Hip protector

Hip protectors

hip protectors

fear of falling

falls efficacy

Falls Efficacy Scale

Modified Falls Efficacy Scale

Fear of falling

falls self-efficacy

Falls Efficacy

Modified Falls Efficacy Scales

Fear of falling

self-efficacy

Falls Efficacy Scale

Modified Falls Efficacy Scale

Aged-care health services

women

aged 75 years or older

live at home

Sixty-one


Sun protection counseling for children : primary care practice patterns and effect of an intervention on clinicians . OBJECTIVES To describe current primary care sun protection advice for children and assess the effect on clinicians of an intervention to enhance their sun protection advocacy . SETTING Primary care practices caring for children in New Hampshire with special attention to clinicians serving 10 towns that were involved in a randomized controlled trial of the multicomponent SunSafe intervention involving schools , recreation areas , and primary care practices . DESIGN/INTERVENTION A statewide survey of all primary care clinicians serving children addressed their self-reported sun protection advocacy practices . Clinicians in 10 systematically selected rural towns were involved in the subsequent intervention study . The primary care intervention provided assistance to practices in establishing an office system that promoted sun protection advice to children and their parents during office visits . MAIN OUTCOME MEASURES Sun protection promotion activities of primary care clinicians as determined by their self report , research assistant observation , and parent interviews . RESULTS Of 261 eligible clinicians responding to the statewide survey , about half provide sun protection counseling " most of the time " or " almost always " during summer well care visits . Pediatricians do so more often than family physicians . Clinicians involved in the intervention increased their use of handouts , waiting room educational materials , and sunscreen samples . Compared with control town parents , parents in intervention towns reported an increase in clinician sun protection advice . CONCLUSIONS The SunSafe primary care intervention increased sun protection counseling activities of participating clinicians . A single-focus preventive service office system is feasible to include in community interventions to promote sun protection .

primary care sun protection

SunSafe

effect on clinicians

sun protection advocacy .

sun protection advocacy practices .

Sun protection promotion activities

clinician sun protection advice

sun protection counseling activities

feasible

sun protection

clinicians

261 eligible clinicians


Efficacy of a barrier cream and its vehicle as protective measures against occupational irritant contact dermatitis . The actual advantage of barrier creams over bland emollients for skin protection is still hotly debated . In a randomized , double-blinded study , a newly-introduced barrier cream and its moisturizing vehicle were compared regarding their skin compatibility , efficacy and resulting acceptance . Thus , 2 panels of 25 hospital nurses with mild signs of skin irritation were asked to use 1 of the test products provided ( verum or vehicle ) over a period of 4 weeks . Effects of both types of preparations were studied weekly by clinical examination and the instrumental assessment of bioengineering parameters . Results showed no significant differences between barrier cream and vehicle . In both groups , clinical skin status improved and stratum corneum hydration increased significantly during the study period . Both preparations were tolerated and accepted well , thus showing both skin protection and skin care . These results contribute to the debate as to whether a strict distinction between " skin care " and " skin protection " products is justified . The vehicle alone is capable of positively influencing skin status . Emphasis must be laid on regular , frequent , and correct application of a product for it to be effective .

barrier cream

its vehicle

barrier creams

barrier cream

barrier cream

vehicle

vehicle

Efficacy

clinical skin status

stratum corneum hydration

tolerated

and accepted well

skin protection and skin care .

2 panels

25 hospital

skin irritation


The effects of hormone replacement therapy on hemostatic variables in women with angiographically verified coronary artery disease : results from the estrogen in women with atherosclerosis study . Data on the effect of hormone replacement therapy on hemostasis are inconsistent , and there are few data in women with coronary artery disease . In a single-center , open , randomized study , 118 postmenopausal women with angiographically verified coronary artery disease were randomized to hormone replacement therapy , given as long-cycle transdermal 17-beta-estradiol ( 50 microg/24 hour ) for 3 months with sequential medroxy-progesterone acetate for 14 days , or to a control group receiving no therapy . Hemostatic parameters were measured at baseline and after 3 and 12 months of therapy . The coagulation inhibitors antithrombin , protein C , and protein S , but not tissue factor pathway inhibitor , decreased significantly from baseline in the hormone replacement therapy group at both 3 and 12 months as compared with the control group . The absolute decreases within the hormone replacement therapy group were 3 to 10 % . No significant differences between the two treatment groups were observed for the coagulation products prothrombin fragment 1+2 or thrombin-antithrombin complex or for D-dimer , although there were significant decreases in the levels within the hormone replacement therapy group . Levels of fibrinogen , activated factor VII , and factor VII antigen were not significantly influenced by hormone replacement therapy treatment . Similarly , nonsignificant changes were detected for the fibrinolytic parameters tissue plasminogen activator activity , tissue plasminogen activator antigen , and global fibrinolytic activity , but plasminogen activator inhibitor type 1 was significantly lower in the hormone replacement therapy group due to a questionable increase in the levels in the control group . In conclusion , treatment with transdermal estradiol combined with long-cycle progestins was associated with no net activation of coagulation despite reduced levels of coagulation inhibitors .

hormone replacement therapy

hormone replacement therapy

sequential medroxy-progesterone acetate

control

tissue factor pathway inhibitor

thrombin-antithrombin complex

D-dimer

Levels of fibrinogen

activated factor VII

factor VII antigen

tissue plasminogen activator antigen

global fibrinolytic activity

plasminogen activator inhibitor type 1

activation of coagulation

coagulation inhibitors

women

women

atherosclerosis


Treatment with metformin of non-diabetic men with hypertension , hypertriglyceridaemia and central fat distribution : the BIGPRO 1.2 trial . BACKGROUND In the BIGPRO 1 trial , one year of treatment with metformin in non-diabetic obese subjects with a central fat distribution had no significant effect on fasting plasma triglyceride concentration or on blood pressure despite a decrease in weight , fasting plasma insulin and glucose concentrations . To re-evaluate the effect of metformin on fasting triglyceride concentration and on blood pressure , the BIGPRO 1.2 trial included non-diabetic men ( n=168 ) with a fasting plasma triglyceride concentration > or =1.7 and < or =6.5 mmol/l , high blood pressure ( systolic > or =140 and < or =180 and/or diastolic > or =90 and < or =105 mmHg , or treatment for hypertension ) and a waist-to-hip ratio > or =0.95 . METHODS A randomised double-blind trial comparing metformin treatment ( 850 mg bid ) with placebo . RESULTS Metformin had no significant effect either on blood pressure or plasma triglyceride concentration . In comparison with the placebo group , fasting plasma insulin ( p < 0.04 ) , total cholesterol ( p < 0.05 ) and Apo B ( p < 0.008 ) concentrations decreased more in the metformin group in the BIGPRO 1 . 2 trial , confirming most of the previous results of the BIGPRO 1 trial . Tissue plasminogen activator antigen concentration decreased significantly ( p < 0.01 ) only in the metformin group , but this was not significantly different from the placebo group ( p < 0.12 ) ; further , there were no significant differences in the change in plasminogen activator inhibitor 1 . CONCLUSIONS The consistency of the two BIGPRO trials supports the conclusion that metformin affects several cardiovascular risk factors favourably in non-diabetic subjects with a central fat distribution .

metformin

metformin

metformin

metformin

placebo

Metformin

placebo

metformin

placebo

metformin

fasting plasma insulin

total cholesterol

Apo B

concentrations

non-diabetic

non-diabetic

men

treatment for hypertension

a waist-to-hip ratio > or =0.95 .


Study of the vaginal tolerance to Acidform , an acid-buffering , bioadhesive gel . Vaginal tolerance tests were performed with a new potential microbicidal and spermicidal product , an acid-buffering vaginal gel ( Acidform ) without or with nonoxynol-9 ( N-9 ) . The potential advantages over other vaginal products include keeping a low pH , decrease of the irritating effect of N-9 on the cervix or vaginal mucosa associated with greater retention of the product after application , and decreasing " messiness " as compared to other vaginal products . Three groups of six women were admitted and randomly assigned to use Acidform with 0 % , 2.5 % , and 5 % N-9 . Colposcopic evaluation for vulvar , vaginal , and cervical signs of irritation was performed and photographs were taken , following a specific World Health Organization protocol , at time 0 , and after 24 h and 6 days of application of the gel . No irritation or symptom was reported by users of Acidform without N-9 . A generalized and intense erythema in cervix was observed in 10 of 12 Acidform/N-9 users and abrasion occurred in nine of them . Vulvar irritation was seen in seven of these 10 volunteers . N-9 concentration in the gel ( 2.5 % or 5.0 % ) was not related to the findings . No ulcer , exulceration , or de-epithelialization was observed . Acidform without N-9 was well tolerated by volunteers , but it was unable to protect the cervix , vagina , and vulva from the N-9 effects .

Acidform

acid-buffering

bioadhesive gel

acid-buffering vaginal gel ( Acidform )

nonoxynol-9 ( N-9 )

Acidform

Acidform without N-9

Acidform without N-9

No irritation or symptom

Vulvar irritation

N-9 concentration in the gel

Three groups of six


Blood pressure biofeedback treatment of white-coat hypertension . OBJECTIVE The objective of the study was to compare blood pressure ( BP ) biofeedback treatment ( BF ) effects between white-coat hypertension and essential hypertension . METHODS Fifteen white-coat hypertensive out-patients and 23 essential hypertensive out-patients were randomly assigned to groups A or B . Subjects in group A underwent BF once a week for a total of four sessions . Those in group B visited the clinic only to measure BP and later underwent the same BF . RESULTS In group A , BPs of white-coat hypertensives and essential hypertensives were significantly reduced by 22/11 and 14/8 mmHg , respectively . In group B , they were unchanged during the same period but later suppressed by BF . Under BF , pulse and respiratory rates were significantly higher , and elevation of diastolic BP due to mental stress testing was better suppressed in white-coat hypertensives than in essential hypertensives . CONCLUSION This treatment was effective in both types of hypertension , and pressor response to stress seems to be important in the differentiated BF effect .

Blood pressure biofeedback treatment

biofeedback treatment ( BF )

BF

visited the clinic

BF

BF

BF

Blood pressure

blood pressure

BP

pulse

respiratory rates

stress

Fifteen

white-coat hypertensive

essential hypertensive


Growth hormone ( GH ) responses to GH-releasing hormone alone or combined with arginine in patients with adrenal incidentaloma : evidence for enhanced somatostatinergic tone . Spontaneous and stimulated GH secretion is blunted in hypercortisolemic states due to increased hypothalamic somatostatinergic tone . However , no data are available on the characteristics of GH secretion in patients with incidentally discovered adrenal adenomas . They represent an interesting model for studying GH secretion , as a slight degree of cortisol excess may frequently be observed in such patients who do not present with any clear Cushingoid sign . In the present study , 10 patients ( 3 men and 7 women , aged 48-63 yr ) with an adrenal mass discovered serendipitously underwent , on separate occasions , a GHRH injection alone or combined with an infusion of the functional somatostatin antagonist , arginine . Thirteen age-matched healthy volunteers served as controls . Briefly , arginine ( 30 g ) was infused from -30 to 0 min , and GHRH ( 100 microg ) was injected as a bolus at 0 min , with measurement of serum GH [ immunoradiometric assay ( IRMA ) ] every 15 min for 150 min . Plasma IGF-I ( RIA after acid-ethanol extraction ) was measured in a morning sample . The diagnosis of cortical adenoma was based on computed tomography features and pattern of uptake on adrenal scintigraphy . Patients with obesity and/or diabetes were excluded . The study design included also an endocrine work-up aimed to study the hypothalamic-pituitary-adrenal axis [ urinary free cortisol ( UFC ) excretion , serum cortisol at 0800 h , plasma ACTH at 0800 h , morning cortisol after overnight 1 mg dexamethasone ] . Five of 10 patients showed abnormalities of the hypothalamic-pituitary-adrenal axis , including borderline or increased UFC excretion in 4 of them accompanied by blunted ACTH in 2 cases and failure of cortisol to suppress after dexamethasone in 1 ; the fifth patient displayed low ACTH and resistance to dexamethasone suppression . However , all patients had a unilateral uptake of the tracer on the side of the mass with suppression of the contralateral normal adrenal gland . As a group , the patients displayed greater UFC excretion and lower ACTH concentrations than the controls . GH release after GHRH treatment was blunted in patients bearing adrenal incidentaloma compared with controls ( GH peak , 5.7 +/- 5.2 vs. 18.0 +/- 7.0 microg/L ; P < 0.0001 ) , whereas GHRH plus arginine was able to elicit a comparable response in the 2 groups ( GH peak , 33.5 +/- 20.3 vs. 33.7 +/- 17.5 microg/L ; P = NS ) . The ratio between GH peaks after GHRH plus arginine and after GHRH plus saline was significantly greater in patients than in controls ( 751 +/- 531 % vs. 81 +/- 45 % ; P = 0.0001 ) . Similar data were obtained when comparing GH area under the curve after GHRH plus saline or GHRH plus arginine between the 2 groups . In summary , the present data suggest that in patients with incidental adrenal adenomas the GH response to GHRH is blunted due to increased somatostatinergic tone , as it can be restored to normal by pretreatment with the functional somatostatin antagonist arginine . The blunted GH release to GHRH may be an early and long lasting sign of autonomous cortisol secretion by the adrenal adenoma .

GH-releasing hormone alone

combined with arginine

GHRH injection alone

controls

arginine ( 30 g )

GHRH ( 100 microg )

GHRH treatment

GHRH plus arginine

GHRH plus arginine

Growth hormone ( GH ) responses

serum cortisol at 0800 h

plasma ACTH at 0800 h

borderline or increased UFC excretion

UFC excretion

lower ACTH concentrations

GH release after GHRH treatment

GH peaks after GHRH plus arginine

GHRH plus saline

GH response

somatostatinergic tone

adrenal incidentaloma

adrenal adenomas .

men

women

48-63 yr

Thirteen

healthy volunteers

controls

obesity and/or diabetes were excluded

adrenal incidentaloma

incidental adrenal adenomas


Evaluating a test protocol for predicting maximum lactate steady state . BACKGROUND Maximum lactate steady state ( MLSS ) is defined as the highest steady state exercise level one can maintain while also maintaining an equilibrium between the elimination of blood lactate and the diffusion of lactate into the blood . MLSS is an excellent tool for assessing fitness level , predicting endurance performance , and designing training programs . METHODS This investigation assesses the validity of the Lactate Minimum Test ( LMT ) , which consists of inducing lactic acidosis through a VO2peak test , followed by an eight-minute walking recovery and an incremental exercise test , to determine if the running velocity associated with the minimum lactate value predicts the MLSS velocity . Following this LMT , two constant velocity 28-minute runs were performed , one at the predicted MLSS velocity ( trial 1 ) and the other 0.13 m sec-1 ( 4-8 % ) above the predicted MLSS velocity ( trial 2 ) . Ten active female subjects participated ( 32 +/- 7 yrs ( mean +/- SD ) ; 65.7 +/- 16.4 kg ; VO2peak 40.0 +/- 7.5 ml.kg-1.min-1 ) . RESULTS During trial 1 , there was a -0.6 +/- 0.3 mmol l-1 ( mean +/- SE ) change in lactate . Based on a definition of lactate steady state ( LSS ) as less than a 0.5 mmol.l-1 increase , this value signified LSS . A similar comparison during trial 2 revealed a 1.8 +/- 0.3 mmol.l-1 increase in lactate , signifying a workload above LSS and therefore confirming trial 1 as the maximum LSS ( MLSS ) . CONCLUSIONS These results suggest that the test protocol accurately predicted the MLSS velocity .

Lactate Minimum Test ( LMT )

maximum lactate steady state .

change in lactate .

lactate steady state ( LSS )

lactate

MLSS velocity .

Ten

female

32 +/- 7 yrs ( mean +/- SD


Computer-assisted instruction : an effective instructional method for HIV prevention education ? PURPOSE To compare the effectiveness of a computer-assisted instruction ( CAI ) -based intervention to a more traditional lecture-based intervention for influencing psychosocial correlates of human immunodeficiency virus ( HIV ) preventive behaviors . METHODS Students enrolled in a Human Sexuality course ( N = 152 ) were randomly assigned to one of three groups : CAI , Lecture , or No Intervention group . Participants in the CAI group reviewed a 1-hour long CAI program , participants in the Lecture group were presented with a 1-hour long lecture , and participants in the No Intervention group received no intervention . After completing the respective interventions , all participants completed the HIV questionnaire , which measured selected Social Cognitive Theory constructs associated with HIV preventive behaviors . MANCOVA , ANCOVA and Post Hoc analyses were utilized to test for significant differences among the three groups . RESULTS The analyses disclosed that , compared to participants in the Lecture group , participants in the CAI group scored significantly higher on the scales measuring autoimmune deficiency syndrome ( AIDS ) knowledge , self-evaluative outcome motivation , and intention to practice HIV preventive behaviors with current partner . In addition , compared to the No Intervention group , the CAI group scored significantly higher on the scales measuring physical outcome motivation and social outcome motivation . CONCLUSIONS CAI-based programs can be effective for delivering instruction on HIV prevention . However , because of certain limitations , this type of program is best utilized as part of a more comprehensive intervention that uses several different delivery systems .

Computer-assisted instruction

computer-assisted instruction

traditional lecture-based intervention

CAI

Lecture

No Intervention

CAI program

HIV prevention

HIV questionnaire

Social Cognitive Theory

HIV preventive behaviors

self-evaluative outcome motivation

social outcome motivation

Students


A comparison of local anaesthetics for venepuncture . AIM To compare the effectiveness of EMLA cream and Ametop gel in providing analgesia for venous cannulation . METHODS Single blind study in 120 children . RESULTS Both anaesthetic agents produced adequate analgesia . However , Ametop gel was more effective , with a statistically significant difference in the pain scores of the two groups ( p < 0.05 ) .

local anaesthetics

EMLA cream

Ametop gel

Ametop gel

adequate analgesia

pain scores

venepuncture

venous cannulation

children


Use of recombinant human granulocyte colony-stimulating factor to increase chemotherapy dose-intensity : a randomized trial in very high-risk childhood acute lymphoblastic leukemia . PURPOSE To determine whether the use of a recombinant human granulocyte colony-stimulating factor ( [ G-CSF ] lenogastrim ) can increase the chemotherapy dose-intensity ( CDI ) delivered during consolidation chemotherapy of childhood acute lymphoblastic leukemia ( ALL ) . PATIENTS AND METHODS Sixty-seven children with very high-risk ALL were randomized ( slow early response to therapy , 55 patients ; translocation t ( 9 ; 22 ) or t ( 4 ; 11 ) , 12 patients ) . Consolidation consisted of six courses of chemotherapy ; the first , third , and fifth courses were a combination of high-dose cytarabine , etoposide , and dexamethasone ( R3 ) , whereas the second , fourth , and sixth courses included vincristine , prednisone , cyclophosphamide , doxorubicin , and methotrexate ( COPADM ) . G-CSF was given after each course , and the next scheduled course was started as soon as neutrophil count was > 1 x 10 ( 9 ) /L and platelet count was > 100 x 10 ( 9 ) /L . CDI was calculated using the interval from day 1 of the first course to hematologic recovery after the fifth course ( 100 % CDI = 105-day interval ) . RESULTS CDI was significantly increased in the G-CSF group compared with the non-G-CSF group ( mean +/- 95 % confidence interval , 105 +/- 5 % v 91 +/- 4 % ; P < .001 ) . This higher intensity was a result of shorter post-R3 intervals in the G-CSF group , whereas the post-COPADM intervals were not statistically reduced . After the R3 courses , the number of days with fever and intravenous antibiotics and duration of hospitalization were significantly decreased by G-CSF , whereas reductions observed after COPADM were not statistically significant . Duration of granulocytopenia was reduced in the G-CSF group , but thrombocytopenia was prolonged , and the number of platelet transfusions was increased . Finally , the 3-year probability of event-free survival was not different between the two groups . CONCLUSION G-CSF can increase CDI in high-risk childhood ALL . Its effects depend on the chemotherapy regimen given before G-CSF administration . In our study , a higher CDI did not improve disease control .

chemotherapy

consolidation chemotherapy

chemotherapy

high-dose cytarabine

etoposide

dexamethasone

vincristine

prednisone

cyclophosphamide

doxorubicin

methotrexate

G-CSF

G-CSF

non-G-CSF

G-CSF

post-COPADM

G-CSF

COPADM

G-CSF

G-CSF

G-CSF administration

CDI

CDI

post-R3 intervals

Duration of granulocytopenia

thrombocytopenia

event-free survival

childhood acute lymphoblastic leukemia

childhood

acute lymphoblastic leukemia

ALL

Sixty-seven

children

high-risk childhood ALL


Comparison of different long-term asthma treatments in subjects with mild-to-moderate asthma . In order to compare the efficacy of different asthma treatment in subjects with mild-to-moderate asthma , three groups of 11 patients were treated with nedocromil sodium ( NS ) , beclomethasone dipropionate ( BDP ) and beclomethasone dipropionate plus salmeterol ( BDP + S ) in an open , randomized study . Symptom score , peak expiratory flow ( PEF ) maximal amplitude , forced expiratory volume in one second ( FEV1 ) , and methacholine reactivity were measured at the baseline and at intervals of 3 months up to 12 months . After 3 months , symptoms reduced significantly in all treatment groups , while PEF variability improved in BDP and BDP + S groups ; FEV1 and bronchial responsiveness to methacholine were significantly improved in comparison with baseline value in the BDP + S group only . No significant difference was observed after 6 and 12 months of treatment in PEF variability , FEV1 or bronchial hyperreactivity in the NS group compared with baseline values , while a significant difference was observed in symptom score . BDP group showed a significant improvement in FEV1 and bronchial reactivity to methacholine after 6 and 12 months of treatment . In the BDP + S group , the improvement in symptoms and pulmonary function persisted until the end of the study . In conclusion , the combination of beclomethasone dipropionate and salmeterol improved pulmonary function and bronchial reactivity earlier than beclomethasone dipropionate alone , while nedocromil sodium improved symptoms but not pulmonary function . Assuming that bronchial reactivity could be an indirect measurement of airway inflammation , overtreatment of asthma in relationship with the classification of asthma severity of the International Guidelines could improve both airway inflammation and the prognosis of airway obstruction .

nedocromil sodium ( NS )

beclomethasone dipropionate ( BDP )

beclomethasone dipropionate

salmeterol

PEF variability

bronchial hyperreactivity

bronchial reactivity

symptoms

and

pulmonary function

pulmonary function

bronchial reactivity

bronchial reactivity

subjects with mild-to-moderate asthma .