Acute hemodynamic effects of conivaptan , a dual V ( 1A ) and V ( 2 ) vasopressin receptor antagonist , in patients with advanced heart failure . BACKGROUND Arginine vasopressin may contribute to abnormalities in hemodynamics and fluid balance in heart failure through its actions on V ( 1A ) ( vascular and myocardial effects ) and V ( 2 ) receptors ( renal effects ) . Inhibiting the action of vasopressin may be beneficial in patients with heart failure . METHODS AND RESULTS A total of 142 patients with symptomatic heart failure ( New York Heart Association class III and IV ) were randomized to double-blind , short-term treatment with conivaptan , a dual V ( 1a ) /V ( 2 ) vasopressin receptor antagonist , at a single intravenous dose ( 10 , 20 , or 40 mg ) or placebo . Compared with placebo , conivaptan at 20 and 40 mg significantly reduced pulmonary capillary wedge pressure ( -2.6+/-0.7 , -5.4+/-0.7 , and -4.6+/-0.7 mm Hg for placebo and 20 and 40 mg groups , respectively ; P < 0.05 ) and right atrial pressure ( -2.0+/-0.4 , -3.7+/-0.4 , and -3.5+/-0.4 mm Hg for placebo and 20 and 40 mg groups , respectively ; P < 0.05 ) during the 3- to 6-hour interval after intravenous administration . Conivaptan significantly increased urine output in a dose-dependent manner ( -11+/-17 , 68+/-17 , 152+/-19 , and 176+/-18 mL/hour for placebo and 10 , 20 , and 40 mg groups , respectively ; P < 0.001 ) during the first 4 hours after the dose . Changes in cardiac index , systemic and pulmonary vascular resistance , blood pressure , and heart rate did not significantly differ from placebo . CONCLUSIONS In patients with advanced heart failure , vasopressin receptor antagonism with conivaptan resulted in favorable changes in hemodynamics and urine output without affecting blood pressure or heart rate . These data suggest that vasopressin is functionally significant in advanced heart failure and that further investigations are warranted to examine the effects of conivaptan on symptom relief and natural history in such patients .

conivaptan

conivaptan

vasopressin

placebo

Conivaptan

conivaptan

Acute hemodynamic effects

pulmonary capillary wedge pressure

right atrial pressure

urine output

hemodynamics and urine output

blood pressure or heart rate .

advanced heart failure

heart failure .

142 patients

symptomatic heart failure

advanced heart failure


Does temporary clamping of drains following knee arthroplasty reduce blood loss ? A randomised controlled trial . In a randomised , blinded study 76 patients undergoing primary total knee arthroplasty were assigned to either immediate drain opening ( n = 45 ) or drains opened at 2 h ( n = 31 ) . No significant differences were found between the groups for the volume of drained blood , transfusion requirements , knee motion or wound status . The authors conclude that the practice of clamping drains has no benefit in routine knee arthroplasty . However , when faced with immediate brisk blood loss , the results suggest that drains can be clamped without any excess morbidity .

temporary clamping of drains

immediate drain opening ( n = 45 )

drains opened at 2 h

clamping drains

drains

volume of drained blood

transfusion requirements

knee motion

wound status

blood loss

morbidity

primary total knee arthroplasty


Evaluation of a new computer intervention to teach people with autism or Asperger syndrome to recognize and predict emotions in others . This randomized controlled trial looked at the effect of a new computer program designed to teach people with autistic spectrum disorders to better recognize and predict emotional responses in others . Two groups of 11 children ( age 12-18 ) with autism or Asperger syndrome at two special schools participated : one group used the computer program for 10 half-hour sessions over 2 weeks . Within-program data showed a significant reduction in errors made from first to last use . Students were assessed pre- and post-intervention using facial expression photographs , cartoons depicting emotion-laden situations , and non-literal stories . Scores were not related to age or verbal ability . The experimental group made gains relative to the control group on all three measures . Gains correlated significantly with the number of times the computer program was used and results suggest positive effects . Further research could assess whether these gains generalized into real life or improved performance on theory of mind measures .

new computer intervention

new computer program

computer program

facial expression photographs

, and

non-literal stories

autism or Asperger syndrome

autistic spectrum disorders

children

age 12-18

autism

Asperger syndrome


Absence of cervical radiation myelitis after hyperfractionated radiation therapy with and without concurrent chemotherapy for locally advanced , unresectable , nonmetastatic squamous cell carcinoma of the head and neck . PURPOSE To evaluate the risk of developing radiation myelitis after a cervical spinal cord dose of 50.6 Gy given via 1.1 Gy b.i.d . fractionation during a prospective , randomised trial of hyperfractionated radiation therapy ( HFX RT ) to a total dose of 77 Gy given in 70 fractions of 1.1 Gy b.i.d. , with and without concurrent low-dose , daily cisplatin ( CDDP ) for head and neck cancer . METHODS Of 130 patients with locally advanced , unresectable , nonmetastatic squamous cell carcinoma of the head and neck ( SCC H & N ) who entered a prospective , randomised trial , 101 patients received 50.6 Gy to a portion of their spinal cord and survived > 1 year following the beginning of therapy . Forty-five patients were treated with HFX RT alone and fifty-six patients also received CDDP . RESULTS None of these 101 patients developed cervical radiation myelitis . Therefore , it was not possible to investigate the influence of potentially contributing factors on the occurrence of radiation myelitis , such as interfraction interval , cord length , and administration of concurrent CDDP . CONCLUSIONS Given the increasing number of studies with both altered fractionated regimens and concurrent radio-chemotherapy in SCC H & N , new studies with more patients are needed to gain better insight into the risks of developing cervical radiation myelitis .

hyperfractionated radiation therapy

concurrent chemotherapy

Gy

hyperfractionated radiation therapy

Gy

cisplatin ( CDDP )

50.6 Gy

HFX RT

CDDP

CDDP

radio-chemotherapy

cervical radiation myelitis

risk of developing radiation myelitis

cervical radiation myelitis .

occurrence of radiation myelitis

cervical radiation myelitis

head and neck cancer


Social support and abstinence from opiates and cocaine during opioid maintenance treatment . Social support may play an important role in helping drug users achieve abstinence ; however these benefits may depend on the type of support experienced . In this prospective observational study , we examined the extent to which general and abstinence-specific support , both structural and functional , predicted opiate and cocaine abstinence in 128 opioid maintenance patients receiving either methadone or LAAM . A new multidimensional self-report instrument assessing abstinence-specific functional support was developed for the study . Previously validated measures were used to assess the remaining types of support . With baseline abstinence and other statistically important covariates adjusted , hierarchical logistic regression analyses demonstrated that the associations between social support at study baseline and biochemically confirmed abstinence 3 months later varied by type of support and by drug . Greater abstinence-specific structural support ( operationalized as fewer drug users in the social network ) and decreases in three types of negative abstinence-specific functional support ( Complaints about Drug Use , Drug Exposure , and Demoralization ) predicted cocaine , but not opiate abstinence . There were no effects for general support , whether structural or functional , on abstinence from either drug . Interventions that focus on modifying patients ' abstinence-specific support may be helpful in reducing the high rates of cocaine use disorders in this population .

Social support

abstinence

opioid maintenance treatment

Social support

general and abstinence-specific support

both structural and functional

methadone

LAAM

abstinence-specific

abstinence-specific

abstinence-specific

abstinence-specific

Social support

abstinence

abstinence ;

social support

abstinence-specific structural support

opiate abstinence .

general support

abstinence

rates of cocaine use disorders

opioid maintenance treatment

drug users

opioid maintenance patients


Relationship between endogenous estrogen concentrations and serum cholesteryl ester transfer protein concentrations in Chinese women . BACKGROUND CETP plays an important role in HDL metabolism and in the reverse cholesterol transport pathway . METHODS The relationship between the changes of endogenous estrogen and the concentration of cholesteryl ester transfer protein ( CETP ) in the serum of Chinese women was investigated . Serum concentrations of estradiol ( E ( 2 ) ) , follicle-stimulating hormone ( FSH ) , CETP and lipid profile were determined in 196 Chinese women ( 52 premenopausal with ages ranging from 18 to 40 years , 57 perimenopausal from 41 to 60 years , and 87 postmenopausal from 61 to 81 years ) . RESULTS Serum CETP concentration was significantly lower in postmenopausal women compared with those in perimenopausal and premenopausal women ( 1.39+/-1.06 , 2.36+/-1.50 and 2.31+/-1.25 mg/l , respectively , P < 0.0001 ) . Even in the women around the menopausal , CETP concentration in postmenopause was significantly lower than that in premenopause ( 1.93+/-1.33 vs. 3.42+/-1.35 mg/l , P < 0.01 ) . In addition , CETP concentration had a highly positive correlation with serum concentration of E ( 2 ) ( r=0.243 , P < 0.001 ) , while negative correlation of CETP concentration with serum concentration of FSH was found ( r=-0.273 , P < 0.001 ) . CONCLUSIONS Estrogen may affect the concentration of CETP .

endogenous estrogen concentrations

serum cholesteryl ester

follicle-stimulating hormone ( FSH )

CETP

lipid profile

Serum CETP concentration

CETP concentration

serum concentration

CETP concentration

serum concentration of FSH

concentration of CETP

Chinese

women

Chinese

women

premenopausal

ages ranging from 18 to 40 years

perimenopausal

41 to 60 years

postmenopausal

61 to 81 years


Prognostic significance of the dobutamine echocardiography test in idiopathic dilated cardiomyopathy . Dobutamine stress echo provides potentially useful information on idiopathic dilated cardiomyopathy ( IDC ) . From February 1 , 1997 , to October 1 , 1999 , 186 patients ( 131 men and 55 women , mean age 56 +/- 12 years ) with IDC , ejection fraction < 35 % , and angiographically normal coronary arteries were studied by high-dose ( up to 40 micro/kg/min ) dobutamine echo in 6 centers , all quality controlled for stress echo reading . In all patients , wall motion score index ( WMSI ) ( from 1 = normal to 4 = dyskinetic in a 16- segment model of the left ventricle ) was evaluated by echo at baseline and peak dobutamine . One hundred eighty-four patients were followed up ( mean 15 +/- 13 months ) and only cardiac death was considered as an end point . There were 29 cardiac deaths . Significant parameters for survival prediction at univariate analysis are : DeltaWMSI ( chi-square 20.1 ; p < 0.0000 ) , New York Heart Association ( NYHA ) class ( chi-square 17.57 ; p < 0.0000 ) , rest ejection fraction ( chi-square 10.41 ; p = 0.0013 ) , angiotensin-converting enzyme inhibitors ( chi-square 8.23 ; p = 0.0041 ) , and hypertension ( chi-square 8.08 , p = 0.0045 ) . In the multivariate stepwise analysis only DeltaWMSI and NYHA were independent predictors of outcome ( DeltaWMSI = hazard ratio 0.02 , p < 0.0000 ; NYHA class = hazard ratio 3.83 , p < 0.0000 ) . Kaplan-Meier survival estimates showed a better outcome for patients with a large inotropic response ( DeltaWMSI > or =0.44 , a cutoff identified by receiver-operating characteristic curves analysis ) than for those with a small or no myocardial inotropic response to dobutamine ( 93.6 % vs 69.4 % , p = 0.00033 ) . Thus , in patients with IDC , an extensive contractile reserve identified by high-dose dobutamine stress echocardiography is associated with a better survival .

Dobutamine stress echo

idiopathic dilated cardiomyopathy

dobutamine echo

idiopathic dilated cardiomyopathy .

cardiac death

better outcome

large inotropic response

better survival .


Capsular contracture around saline-filled fine textured and smooth mammary implants : a prospective 7.5-year follow-up . In a previous prospective randomized clinical study comparing in the same patient textured and smooth saline-filled mammary implants ( Biocell ) with large pore size ( 300 to 600 microm ) , we saw no difference in capsular contracture . This study was undertaken in a similar way to compare capsular contracture around smooth and textured saline-filled prostheses with pores of small size . During a period of 7.5 years , the breast hardness was followed up , and at the end of the study patient satisfaction was evaluated . Twenty healthy women with a mean age of 30 years were operated on for breast augmentation . Two surgeons performed all operations in a standardized way . Each patient received subglandularly a Siltex textured saline-filled prosthesis with a pore size of 30 to 70 microm in one breast , and a smooth saline-filled prosthesis in the other . The hardness of the breasts was evaluated after 0.5 , 1 , and 7.5 years using Baker grading and applanation tonometry . Eighteen patients completed 1-year and 7.5-year follow-up . Two breasts with smooth prostheses were contracted after 6 months ( Baker III or IV ) . After 1 year , four patients with smooth prostheses and one with a textured prosthesis had capsular contracture ( p = 0.34 ) . Seven and one-half years after surgery , six patents with smooth and four with textured implants had contracture ( p = 0.66 ) . On two patients with smooth prostheses and one patient with a textured prosthesis , the capsule around the implant hardened between 6 and 12 months . Between 1 year and 7.5 years , three breasts with smooth and textured implants contracted and one with a textured implant softened.The patients reported on a Visual Analogue Scale ( 1 to 10 ) the impact of the augmentation on their quality of life to be 9 +/- 1 . Four patients preferred the breast with the smooth prosthesis , three preferred the breast with the textured prosthesis , and the others found both breasts equal . This study showed no significant difference of contracture with smooth versus fine textured implants . The majority of the patients preferred the smooth implants . The patients reported that the breast augmentation had had an extremely high impact on their quality of life .

saline-filled prostheses

implants

The hardness of the breasts

Baker grading and applanation tonometry

capsular contracture

contracture

capsule around the implant hardened

smooth and textured implants contracted

quality of life

significant difference

contracture

preferred the smooth implants

Twenty

healthy

women

mean age of 30 years

breast augmentation

Eighteen patients


Evaluating the impact of peer , nurse case-managed , and standard HIV risk-reduction programs on psychosocial and health-promoting behavioral outcomes among homeless women . Investigators examined the 6-month impact of three cognitive-behavioral HIV risk-reduction programs on behavioral factors ( substance use and sexual risk behaviors ) and cognitive and psychological resources of 325 women who resided in emergency or sober-living shelters and their 308 intimate sexual partners . Participants were randomized by shelter to a peer-mentored , a nurse case-managed , or a standard care HIV risk-reduction program . Significant improvements were observed in all groups in all behavioral factors and cognitive and psychological resources except for self-esteem . Participants in the peer-mentored and nurse case-managed groups did not differ significantly from the standard group in self-esteem , life satisfaction , psychological well-being , use of noninjection drugs , sex with multiple partners , and unprotected sex at 6 months ( n = 633 ) . It was concluded that a standard approach by health care professionals appears to effectively modify HIV risk behaviors for a majority of homeless participants and may have important economic and policy implications . Further , the impact of short-term programs that address psychological vulnerabilities of impoverished populations needs to be studied further .

peer-mentored , a nurse case-managed

peer-mentored and nurse case-managed

standard group

behavioral factors

cognitive and psychological resources

self-esteem

modify HIV risk behaviors

women

women

homeless

impoverished


Fibrin application for preventing lymphocysts after retroperitoneal lymphadenectomy in patients with gynecologic malignancies . OBJECTIVE We performed a randomized , prospective trial to assess the impact of fibrin glue on the incidence of lymphocysts after systematic pelvic or pelvic and paraaortic lymphadenectomy in patients with gynecologic malignancies . METHODS Ninety-three consecutive patients with gynecologic pelvic malignancies who underwent surgery including pelvic or pelvic and paraaortic lymphadenectomy were randomized during surgery to be treated with fibrin glue or not . Serial computed tomography ( CT ) scans were performed during follow-up . CT findings of a smooth and thin-walled cavity filled with a water-equivalent fluid , sharply demarcated from its surroundings and without signs of infiltration were interpreted as lymphocysts . RESULTS Forty-seven patients ( 51 % ) were treated with fibrin glue and 46 ( 49 % ) were not . All 93 patients underwent pelvic lymphadenectomy ; 15 patients ( 32 % ) of the fibrin group and 12 ( 26 % ) of the controls also underwent paraaortic lymphadenectomy . We found no significant differences between patients who received fibrin glue and those who did not . CONCLUSION Intraoperative application of fibrin glue did not reduce the rate of postoperative lymphocysts after lymphadenectomy and had no impact on any follow-up parameter . Its use seems not to be indicated in systematic gynecologic pelvic or pelvic and paraaortic lymphadenectomy .

Fibrin application

fibrin glue

treated with fibrin glue

not

Serial computed tomography ( CT ) scans

fibrin glue

lymphocysts

no significant differences

no impact

follow-up parameter

gynecologic malignancies

gynecologic malignancies

Ninety-three

gynecologic pelvic malignancies


Once-daily versus twice-daily intravenous administration of vancomycin for infections in hospitalized patients . The efficacy and toxicity of once-daily ( od ) versus twice-daily ( bd ) dosing of vancomycin was compared in 121 hospitalized patients . Eighteen patients were then withdrawn from the study . Clinical and bacteriological responses were evaluated in all patients ( n = 103 ) . Nephrotoxicity was assessed in patients who did not receive nephrotoxic agents ( n = 76 ) . Ototoxicity was assessed in patients who completed two audiograms and were not receiving ototoxic agents ( n = 63 ) . No significant difference was found between the two groups for favourable clinical response : 47/51 ( 92.1 % ) and 49/52 ( 94.2 % ) in the od and bd groups , respectively . In 34 patients vancomycin was the only effective antibiotic . Fifteen of 18 ( 83.3 % ) evaluated episodes in the od and 12/16 ( 75.0 % ) evaluated episodes in the bd group showed a favourable bacteriological response . There were no significant differences between the od and bd groups for all adverse events . Nephrotoxicity developed in 4/37 ( 10.8 % ) and 3/39 ( 7.7 % ) patients , respectively . Hearing loss developed in 1/31 ( 3.2 % ) and 5/32 ( 15.6 % ) . Phlebitis occurred in 7/51 ( 13.7 % ) and 12/52 ( 23.0 % ) . Red man syndrome occurred in 7/51 ( 13.7 % ) and 5/52 ( 9.6 % ) in od and bd groups , respectively . The efficacy and safety profile of od administration of vancomycin is similar to that of the customary , but less convenient , bd administration .

vancomycin

vancomycin

vancomycin

vancomycin

Nephrotoxicity

Ototoxicity

only effective antibiotic

favourable bacteriological response

all adverse events

Nephrotoxicity

Hearing loss

Phlebitis

Red man syndrome

efficacy and safety profile

infections in hospitalized patients

hospitalized

Eighteen


Controlled prospective trial of prednisolone and cytotoxics in progressive IgA nephropathy . In a single-center , multiple-referral source study , 38 patients with progressive IgA nephropathy and controlled hypertension were randomized to treatment with prednisolone and cytotoxic agents , to therapy with low-dose cyclophosphamide then azathioprine , and to control groups . The follow-up period lasted 2 to 6 yr. Renal survival , as assessed by Kaplan-Meier analysis annually to 5 yr , showed significant preservation of function from 3 yr in the treatment group and 82 , 82 , 72 , and 72 % for 2 , 3 , 4 , and 5 yr , respectively , compared with 68 , 47 , 26 , and 6 % in controls . Rate of loss of renal function , evaluated objectively by least-squares analyses of reciprocal serum creatinine , was reduced-and in one-third of the patients , arrested-during immunosuppressive treatment . Proteinuria , present in all patients at the time of entry into the trial , was reduced by treatment from 12 mo , compared with pretreatment levels or controls ; erythrocyturia was reduced from 6 mo . Histologic activity and chronicity indexes were determined in renal biopsies performed at trial entry . Multivariate analysis demonstrated that mesangial cell proliferation and matrix scores were highest in those patients with more rapidly progressive disease . No morphologic variable or residual renal function predicted response to immunosuppressive therapy at entry . Mean arterial pressures did not differ significantly between treatment and control groups . There was thus no explanation other than treatment for the improved outcome in patients who received immunosuppressive therapy . Morbidity attributable to treatment or to renal failure occurred in both groups ; an audit showed that benefits of therapy outweighed expected or minor side effects of drugs in this population at risk of end-stage renal failure . Patients selected for moderately progressive IgA nephropathy benefit from treatment with prednisolone and cytotoxic agents ; results are consistent with modulation of systemic immune response or nephritic injury , thus explaining improved outcome , and indicate that this therapy has an acceptably low risk of side effects .

prednisolone and cytotoxics

prednisolone and cytotoxic agents

low-dose cyclophosphamide

azathioprine

control groups .

prednisolone

cytotoxic agents ;

loss of renal function

Proteinuria

erythrocyturia

Histologic activity

chronicity indexes

Multivariate analysis

Mean arterial pressures

Morbidity

renal failure

benefits of therapy

progressive IgA nephropathy

side effects

progressive IgA nephropathy

progressive IgA nephropathy

hypertension

Proteinuria

moderately progressive IgA nephropathy


Physical activity in first-degree relatives of breast cancer patients . This study sought to evaluate physical activity in women at moderate risk for breast cancer , the correlates of engaging in regular physical activity , and whether physical activity relates to psychological well-being . The results revealed that 55 % of women were regularly active . Logistic regression models indicated that positive affect was associated with increased and negative affect was associated with decreased overall and leisure activity . Older , married , and employed women were more likely to engage in household/occupational activity , whereas women who perceived their risk for breast cancer as high were less likely . More educated women and those with higher perceived risk were more likely to engage in leisure activity , and married women were less likely . These results suggest a need to increase activity levels in women at moderate risk for breast cancer , provide variables upon which interventions can be tailored to promote activity , and point to psychological benefits of activity in this population .

Physical activity

physical activity

physical activity

physical activity

increase activity levels

psychological well-being

leisure activity

household/occupational activity

leisure activity

breast cancer

women

moderate risk for breast cancer

women

women

moderate risk for breast cancer


Metformin therapy improves ovulatory rates , cervical scores , and pregnancy rates in clomiphene citrate-resistant women with polycystic ovary syndrome . OBJECTIVE To evaluate the effect of metformin therapy on hyperandrogenism , insulin resistance , cervical scores , ovulation , and pregnancy rates in clomiphene citrate-resistant women with polycystic ovary syndrome ( PCOS ) . DESIGN Prospective , randomized , double-blind , placebo-controlled study . SETTING Infertility clinic of a tertiary referral center . PATIENT ( S ) Fifty-six women with clomiphene citrate-resistant PCOS . INTERVENTION ( S ) Two cycles of oral metformin therapy ( 850 mg , twice daily ) in group I and placebo therapy ( twice daily ) in group II . Clomiphene citrate ( 100 mg/day ) on cycle days 3-7 of the second cycle in both groups . MAIN OUTCOME MEASURE ( S ) Insulin , T , DHEAS , FSH , LH , body mass index ( BMI ) , waist-to-hip ratio , endometrial thickness , cervical score , ovulation , and pregnancy rates in clomiphene-induced cycles after metformin therapy . RESULT ( S ) Metformin therapy resulted in a significant decrease in total T , LH level , LH/FSH ratio , insulin resistance , and mean BMI . No difference in waist-to-hip ratio , DHEAS level , and fasting insulin level was observed . Clomiphene citrate induction resulted in higher ovulation rates and thicker endometrium in the metformin group than in the placebo group . There was higher cumulative pregnancy rate in the metformin group ; however , there was no significant difference in the pregnancy rate between the two groups . CONCLUSION ( S ) Metformin therapy not only decreases hyperandrogenism and insulin resistance but also improves ovulation rates , cervical scores , and pregnancy rates in clomiphene citrate-resistant women with PCOS .

Metformin therapy

metformin therapy

placebo-controlled

oral metformin therapy

placebo therapy

Clomiphene citrate

metformin

Metformin

metformin

placebo

Metformin

ovulation rates and thicker endometrium

cumulative pregnancy rate

pregnancy rate

hyperandrogenism and insulin resistance


A randomized , double-blind , placebo-controlled MRI study of anti-herpes virus therapy in MS . OBJECTIVE To evaluate the effect of treatment with the antiherpes drug valacyclovir on MRI-evident lesions in patients with relapsing-remitting MS in a phase 2 , randomized , double-blind , placebo-controlled study . BACKGROUND It has been postulated from virologic studies that herpesvirus infection could play a role in the progression of MS. METHODS Patients were eligible for the study if they had had two or more MS relapses in the 2-year period before enrollment . Seventy patients with Expanded Disability Status Scale scores of 0 to 5.5 were randomly assigned to receive 1 gram of valacyclovir ( n = 36 ) or placebo ( n = 34 ) three times daily for 24 weeks . Patients underwent MRI every fourth week for 32 weeks : twice during pretreatment , six times during treatment , and once after treatment . Scoring of neurologic disability was performed at the start and end of the treatment period . The primary endpoint was the number of new active MRI-evident lesions over 24 weeks of treatment . Secondary endpoints included other MRI measures and clinical endpoints . RESULTS The mean number of new active lesions +/- SD per patient during 24 weeks of treatment with valacyclovir was 11.9 +/- 17.6 and that during placebo treatment was 14.5 +/- 21.4 . A protocol-planned exploratory analysis stratified patients according to baseline activity ; this analysis showed that patients with high levels of disease activity in the valacyclovir treatment group ( n = 17 ) developed fewer new active lesions per scan than did those in the placebo treatment group ( n = 11 ) . The median number ( Q ( 1 ) , Q ( 3 ) range ) of active lesions was 2.0 ( 1.38 , 3.96 ) in the valacyclovir treatment group and 6.5 ( 2.63 , 9.0 ) in the placebo treatment group . CONCLUSIONS Valacyclovir treatment did not reduce the formation of active lesions in patients with relapsing-remitting MS who had two or more relapses during the previous 2-year period . In a subgroup of patients with high levels of disease activity who had more than one active MRI-evident lesion during 4 weeks , valacyclovir treatment was associated with a reduced number of new active MRI-evident lesions and with an increase in the number of scans free of new active lesions . The results of the exploratory subgroup analysis provide support for further studies of antiherpes therapy for patients with MS and high levels of MRI-evident disease activity .

anti-herpes virus therapy

antiherpes drug valacyclovir

placebo-controlled

valacyclovir

placebo

valacyclovir

placebo

valacyclovir

Valacyclovir

valacyclovir

antiherpes therapy

MRI-evident lesions

Scoring of neurologic disability

other MRI measures

clinical endpoints

new active lesions

new active lesions

active lesions

active lesions

new active MRI-evident lesions

new active lesions

anti-herpes

MS

MS

MS

Seventy

MS

MS

MRI-evident disease activity


[ Clinical study on retarding aging effect of tongbu recipe to traditional Chinese medicine ] . OBJECTIVE To study the mechanism of Tongbu No . 1 ( TB1 , a prescription for reinforcing Kidney and Spleen , clearing up the bowel viscera to send Turbid downward and regulating Qi and blood ) in retarding aging . METHODS A controlled , multiple indexes study was conducted in 56 old subjects randomized into 3 groups . RESULTS TB1 ( containing ginseng leaf , cistanche , fleeceflower root , immature bitter orange , rhubarb , etc ) could improve various symptoms of aging , and had the effect in regulating immune and endocrinal function , scavenging free radicals and adjusting coli flora . The effects of TB1 and TB2 ( containing ginseng leaf , cistanche and fleeceflower root ) were different significantly ( P < 0.05 , P < 0.01 ) . CONCLUSION TB1 has a good comprehensive effect in retarding aging .

Tongbu No

retarding aging effect

retarding aging

scavenging free radicals

adjusting coli flora

retarding aging

old


Dronabinol versus megestrol acetate versus combination therapy for cancer-associated anorexia : a North Central Cancer Treatment Group study . PURPOSE To determine whether dronabinol administered alone or with megestrol acetate was more , less , or equal in efficacy to single-agent megestrol acetate for palliating cancer-associated anorexia . PATIENTS AND METHODS Four hundred sixty-nine assessable advanced cancer patients were randomized to ( 1 ) oral megestrol acetate 800 mg/d liquid suspension plus placebo , ( 2 ) oral dronabinol 2.5 mg twice a day plus placebo , or ( 3 ) both agents . Eligible patients acknowledged that loss of appetite or weight was a problem and reported the loss of 5 pounds or more during 2 months and/or a daily intake of less than 20 calories/kg of body weight . RESULTS Groups were comparable at baseline in age , sex , tumor type , weight loss , and performance status . A greater percentage of megestrol acetate-treated patients reported appetite improvement and weight gain compared with dronabinol-treated patients : 75 % versus 49 % ( P =.0001 ) for appetite and 11 % versus 3 % ( P =.02 ) for > or = 10 % baseline weight gain . Combination treatment resulted in no significant differences in appetite or weight compared with megestrol acetate alone . The Functional Assessment of Anorexia/Cachexia Therapy questionnaire , which emphasizes anorexia-related questions , demonstrated an improvement in quality of life ( QOL ) among megestrol acetate-treated and combination-treated patients . The single-item Uniscale , a global QOL instrument , found comparable scores . Toxicity was also comparable , with the exception of an increased incidence of impotence among men who received megestrol acetate . CONCLUSION In the doses and schedules we studied , megestrol acetate provided superior anorexia palliation among advanced cancer patients compared with dronabinol alone . Combination therapy did not appear to confer additional benefit .

Dronabinol

dronabinol

megestrol acetate

megestrol acetate

megestrol acetate

liquid suspension

plus placebo

dronabinol

placebo

megestrol acetate-treated

dronabinol-treated

megestrol acetate

megestrol acetate-treated

megestrol acetate

megestrol acetate

dronabinol

appetite improvement and weight gain

differences in appetite or weight

quality of life ( QOL )

QOL

Toxicity

impotence

Four hundred sixty-nine

men


Quantitative angiographic methods for appropriate end-point analysis , edge-effect evaluation , and prediction of recurrent restenosis after coronary brachytherapy with gamma irradiation . OBJECTIVES The study was done to investigate the relationship between clinical restenosis and the relative angiographic location of the recurrent restenotic lesion , after treatment of in-stent restenosis with vascular brachytherapy in the Washington Radiation for In-Stent Restenosis Trial ( WRIST ) . BACKGROUND Intracoronary radiation therapy reduces recurrence of in-stent restenosis . We investigated the above objective in patients enrolled in WRIST . METHODS The WRIST study randomized 130 patients to double-blinded therapy with gamma irradiation ( iridium-192 [ ( 192 ) Ir ] ) versus placebo after interventional treatment of diffuse in-stent restenosis . After the intervention and at follow-up , three vessel segments were individually analyzed with quantitative coronary angiography : 1 ) the " stent , " 2 ) the " radiation ribbon , " and 3 ) the " ribbon+margin " segment ( including 5 mm on either end of the injured or radiation-ribbon segment ) . Receiver operator curves ( ROC ) were used to assess the value of the follow-up percent diameter stenosis ( DS ) for each of the three analyzed segments in predicting target vessel revascularization ( TVR ) . RESULTS ( 192 ) Ir reduced recurrent restenosis ( 23.7 % vs. 60.7 % , p < 0.001 ) and the length of recurrent restenosis ( 8.99 +/- 4.34 mm vs. 17.54 +/- 10.48 mm , p < 0.001 ) at follow-up compared to placebo . Isolated stent edge ( 3.4 % ) and ribbon edge ( 1.7 % ) restenoses were infrequent in both groups . The best angiographic surrogate of TVR was the 50 % follow-up DS obtained from the ribbon+margin analysis ( ROC area 0.806 ) . CONCLUSIONS In WRIST , not only was ( 192 ) Ir therapy effective in reducing restenosis , but it also reduced the lesion length of treatment failures by 50 % , and it was not associated with edge proliferation . The restenosis rate obtained from the vessel segment inclusive of the dose fall-off zones was the best correlate of TVR and should become a standard analysis site in all vascular brachytherapy trials .

coronary brachytherapy

vascular brachytherapy

Intracoronary radiation therapy

placebo

( 192 ) Ir therapy

prediction of recurrent restenosis

recurrent restenosis

length of recurrent restenosis

Isolated stent edge

ribbon edge

restenoses


[ Statins in the treatment of patients with arterial occlusive disease of the lower extremities ] . In patients with advanced atherosclerosis manifested by arterial occlusion in the lower extremities without a baseline blood lipid disorder statin treatment caused improvement of the efficiency , i.e . prolongation of the claudication interval , while in a comparable control group without statins the efficiency deteriorated further . In patients with arterial occlusion of the lower extremities with baseline dyslipidaemia statin treatment proved protective , i.e . at least it retarded the patients ' complaints . The authors recorded improvement of the prooxidation state which followed after the dynamics of improvement of the impaired blood lipid spectrum . The results admit a possible part played by the pleiotropic effect of statins .

Statins

statin

statin

efficiency , i.e .

protective

the prooxidation state

blood lipid spectrum


1999 WHO/ISH Guidelines applied to a 1999 MONICA sample from northern Sweden . BACKGROUND Treating hypertension with drugs is so far the most cost-effective way to reduce this important risk factor for cardiovascular disease ( CVD ) . It is , however , important to determine absolute risk , and thereby estimate indication for drug treatment , in order to maintain a cost-effective drug treatment . WHO/ISH Hypertension Guidelines from 1999 propose a risk stratification for estimating absolute risk for CVD based on blood pressure and additional risk factors , target organ damage ( TOD ) and CVD . OBJECTIVES We studied the consequences of applying the recent WHO/ISH risk stratification scheme to a MONICA sample of 6000 subjects from a geographically defined population in northern Sweden , regarding indications for treatment , target blood pressure and risk distribution . METHODS We have risk-classified each of these patients using a computer program , according to the WHO/ISH scheme . Data on TOD were not available . RESULTS In all , 917 ( 15 % ) had drug-treated hypertension . Three-quarters ( n = 737 ) were inadequately treated , with blood pressure levels at or above 140 or 90 mmHg . 1773 ( 30 % of 5997 ) untreated subjects had a blood pressure of 140/90 or above ; 16 % in the low- , 62 % in the medium- , 8 % in the high- , and 14 % in the very-high-risk group . The corresponding risk-group pattern for the inadequately treated hypertensives ( n = 737 ) was 5.5 , 48.3 , 11.1 and 35.2 % , respectively . If we shifted the target blood pressure from below 140/90 to below 130/85 for drug-treated subjects under 60 ( n = 278 ) the number of inadequately treated subjects increased by 34 ( 12.2 % of 278 ) ; 14 in the low-risk group , 15 in the medium-risk group , and only five in the high- or very-high-risk groups . CONCLUSIONS Only one-fifth of the drug-treated hypertensives were well controlled . Moreover , the incidence of newly detected blood pressure elevation was high . The majority of younger subjects with high blood pressure had low risk , but in those aged 45-54 this had already risen to a medium risk . Changing the target blood pressure to below 130/85 , for subjects aged below 60 , as recommended by WHO/ISH , affects predominantly low- and medium-risk groups .

WHO/ISH risk stratification scheme

computer program

blood pressure levels

number of inadequately treated subjects

newly detected blood pressure elevation

drug-treated hypertension

aged 45-54

subjects aged below 60


Improved responsiveness of PCOS patients to clomiphene after CYP17a inhibitor . PURPOSE To study the effect of CYP17a inhibitor , " ketoconazole , " on clomiphene responsiveness in PCOS patients . METHODS Prospective analysis was employed with the setup at Alexandria IVF/ICSI center . Ninety-seven insulin-resistant PCOS patients undergoing ovulation induction using clomiphene citrate were randomly divided , by random number table , into two groups . The first group ( n = 49 ) received ketoconazole ( 400 mg daily ) till correction of metabolic syndrome followed by clomiphene ( 100 mg/day ) ; the second group ( n = 48 ) receiving clomiphene without ketoconazole pretreatment . Main outcome measures were incidence of clomiphene resistance , monofollicular response , fasting insulin/glucose ratio , serum testosterone , and pregnancy rates . RESULTS The ketoconazole group showed significantly ( p < 0.05 ) higher incidence of monofollicular response ( 38 % ) , higher pregnancy rates , and significantly less marked antiestrogenic manifestations than did the control group . They also had significantly lower incidence of clomiphene resistance ( 11.6 % ) , lower serum testosterone levels , less hyperinsulinaemia , than did the control group . CONCLUSION Ketoconazole improved clomiphene responsivenss in PCOS patients and attenuated its untoward biological effects .

clomiphene

CYP17a inhibitor .

CYP17a inhibitor , " ketoconazole , "

clomiphene citrate

ketoconazole

clomiphene

clomiphene

ketoconazole pretreatment

ketoconazole

Ketoconazole

incidence of monofollicular response

higher pregnancy rates

incidence of clomiphene resistance

lower serum testosterone levels

hyperinsulinaemia

untoward biological effects .

PCOS patients


Small-dose selective spinal anesthesia for short-duration outpatient laparoscopy : recovery characteristics compared with desflurane anesthesia . UNLABELLED We conducted a randomized controlled trial to compare the recovery characteristics of selective spinal anesthesia ( SSA ) and desflurane anesthesia ( DES ) in outpatient gynecological laparoscopy . Twenty ASA physical status I patients undergoing gynecological laparoscopy were randomized to receive either SSA with lidocaine 10 mg + sufentanil 10 microg or general anesthesia with DES and N ( 2 ) O. Intraoperative conditions , recovery times , postanesthesia recovery scores , and postoperative outcomes were recorded . Intraoperative conditions were comparable in both groups . All patients in the SSA group were awake and oriented at the end of surgery , whereas patients in the DES group required 7 +/- 2 min for extubation and orientation . SSA patients had a significantly shorter time to straight leg raising ( 3 +/- 1 min versus 9 +/- 4 min ; P < 0.0001 ) and to ambulation ( 3 +/- 0.9 min versus 59 +/- 16 min ; P < 0.0001 ) compared with the DES group . SSA patients had significantly less postoperative pain than DES patients ( P < 0.05 ) . We concluded that SSA was an effective alternative to DES for outpatient gynecological laparoscopy . IMPLICATIONS This study compared the use of a desflurane general anesthetic to a small-dose spinal anesthetic in ambulatory gynecological laparoscopy . Using the spinal technique , patients can walk from the operating room table to a stretcher on completion of surgery . Their recovery time was similar to that of the desflurane group .

spinal anesthesia

desflurane anesthesia

selective spinal anesthesia ( SSA )

desflurane anesthesia ( DES )

gynecological laparoscopy

SSA

lidocaine 10 mg + sufentanil 10 microg

SSA

DES

SSA

DES

SSA

DES

DES

desflurane

desflurane

shorter time to straight leg raising

ambulation

postoperative pain

recovery time

Twenty

ASA physical status I


Marginal biotin deficiency during normal pregnancy . BACKGROUND Biotin deficiency is teratogenic in several mammalian species . Approximately 50 % of pregnant women have an abnormally increased urinary excretion of 3-hydroxyisovaleric acid ( 3-HIA ) , which probably reflects decreased activity of the biotin-dependent enzyme methylcrotonyl-CoA carboxylase . However , increased 3-HIA excretion could result from pregnancy per se ( eg , from an effect of pregnancy on renal handling of organic acids ) . OBJECTIVE We tested the hypothesis that biotin supplementation significantly decreases 3-HIA excretion in pregnant women with abnormally increased 3-HIA excretion . DESIGN Twenty-six pregnant women with increased 3-HIA excretion were studied in a randomized , placebo-controlled trial ; 10 women were studied during early pregnancy ( 6-17 wk gestation ) and 16 women during late pregnancy ( 21-37 wk gestation ) . Urine samples were collected before and after 14 d of supplementation with 300 microg ( 1.2 micromol ) biotin/d or placebo . RESULTS In the early-pregnancy group , 3-HIA excretion decreased ( P < 0.006 ) by 11.7 +/- 3.6 mmol/mol creatinine ( mean +/- SEM ) in the 5 women who received biotin supplements , whereas 3-HIA excretion increased by 1.6 +/- 0.6 mmol/mol creatinine in the 5 women who received placebo . In the late-pregnancy group , 3-HIA excretion decreased ( P < 0.002 ) by 7.1 +/- 1.2 mmol/mol creatinine in the 8 women who received biotin supplements , whereas 3-HIA excretion increased by 0.9 +/- 1.8 mmol/mol creatinine in the 8 women who received placebo . CONCLUSIONS This study provides evidence that the increased excretion of 3-HIA seen frequently in normal pregnancy reflects reduced biotin status . The conclusion that marginal biotin deficiency occurs frequently in the first trimester further raises concern about potential human teratogenicity .

placebo-controlled

300 microg ( 1.2 micromol ) biotin/d

placebo

3-hydroxyisovaleric acid ( 3-HIA )

Urine samples

3-HIA excretion

3-HIA excretion

3-HIA excretion

3-HIA excretion

excretion of 3-HIA

biotin status .

normal pregnancy

pregnant

women

pregnant

women

increased 3-HIA excretion

Twenty-six

pregnant

women

increased 3-HIA excretion


Liposome-encapsulated doxorubicin compared with conventional doxorubicin in a randomized multicenter trial as first-line therapy of metastatic breast carcinoma . BACKGROUND The objective of this study was to compare the efficacy and toxicity of the liposome-encapsulated doxorubicin , TLC D-99 ( Myocet , Elan Pharmaceuticals , Princeton , NJ ) , and conventional doxorubicin in first-line treatment of metastatic breast carcinoma ( MBC ) . METHODS Two hundred twenty-four patients with MBC and no prior therapy for metastatic disease were randomized to receive either TLC D-99 ( 75 mg/m ( 2 ) ) or doxorubicin ( 75 mg/m ( 2 ) ) every 3 weeks , in the absence of disease progression or unacceptable toxicity . The primary efficacy endpoint was response rate . Responses were assessed using World Health Organization criteria and were required to be of at least 6 weeks ' duration . The primary safety endpoint was cardiotoxicity . Cardiac function was monitored by multiple-gated radionuclide cardioangiography scan , and the left ventricular ejection fraction ( LVEF ) was scored at a central laboratory . Patients were removed from study if LVEF declined 20 or more EF units from baseline to a final value of greater than or equal to 50 % , or by 10 or more units to a final value of less than 50 % , or onset of clinical congestive heart failure ( CHF ) . RESULTS Median age was 54 years in both treatment groups . All relevant prognostic factors were balanced , with the exception that there were significantly more progesterone receptor positive patients in the doxorubicin-treated group . Protocol-defined cardiotoxicity was observed in 13 % of TLC D-99 patients ( including 2 cases of CHF ) compared to 29 % of doxorubicin patients ( including 9 cases of CHF ) . Median cumulative doxorubicin dose at onset of cardiotoxicity was 785 mg/m ( 2 ) for TLC D-99 versus 570 mg/m ( 2 ) for doxorubicin ( P = 0.0001 ; hazard ratio , 3.56 ) . The overall response rate was 26 % in both treatment groups . The median TTP was 2.9 months on TLC D-99 versus 3.1 months on doxorubicin . Median survival was 16 versus 20 months with a nonsignificant trend in favor of doxorubicin ( P = 0.09 ) . Clinical toxicities , commonly associated with doxorubicin , appeared less common with TLC D-99 , although the difference was not statistically significant . There was only one report of palmar-plantar erythrodysesthesia ( Grade 2 ) with this liposomal formulation of doxorubicin . CONCLUSIONS Single-agent TLC D-99 produces less cardiotoxicity than doxorubicin , while providing comparable antitumor activity .

Liposome-encapsulated doxorubicin

conventional doxorubicin

liposome-encapsulated doxorubicin

conventional doxorubicin

TLC D-99 ( 75 mg/m ( 2 ) )

doxorubicin

doxorubicin-treated

doxorubicin

doxorubicin

TLC D-99

doxorubicin

doxorubicin

doxorubicin

doxorubicin

TLC D-99

doxorubicin

Protocol-defined

cardiotoxicity

cardiotoxicity

overall response rate

median TTP

Median survival

toxicities

palmar-plantar erythrodysesthesia

metastatic breast carcinoma

Two hundred twenty-four

MBC

54 years


[ Intravesical instillation of doxorubicin or epirubicin for chemoprophylaxis of superficial bladder cancer -- the fifth study of the Japanese Urological Cancer Research Group for Adriamycin/Farumorubicin ] . A total of 465 patients with primary and multiple or recurrent , stages Ta and T1 superficial bladder cancer were included in this randomized multicenter trial to compare the prophylactic effect by 17 times instillation of 40 mg doxorubicin or 40 mg epirubicin with no instillation after transurethral resection of tumor ( s ) . The primary endpoint was first recurrence after transurethral resection . Endoscopic examination as well as urinary cytology was performed in each case every three months . It became evident that the recurrence rate in the doxorubicin or epirubicin instillation arm was lower that in the no instillation arm . Toxicity was mainly restricted to bladder irritation in about 10 % of patients in each instillation arm .

doxorubicin

40 mg doxorubicin

40 mg epirubicin

doxorubicin

epirubicin

first recurrence

Endoscopic examination

urinary cytology

recurrence rate

Toxicity

bladder irritation

superficial bladder cancer


Helicobacter pylori and gastric cancer : current status of the Austrain Czech German gastric cancer prevention trial ( PRISMA Study ) . AIM To test the hypothesis that Helicobacter pylori eradication alone can reduce the incidence of gastric cancer in a subgroup of individuals with an increased risk for this fatal disease . METHODS It is a prospective , randomized , double blind , placebo controlled multinational multicenter trial . Men between 55 and 65 years of age with a gastric cancer phenotype of Helicobacter pylori gastritis are randomized to receive a 7 day course of omeprazole 2 X 20mg , clarithromycin 2 X 500mg , and amoxicillin 2 X 1g for 7 days , or omeprazole 2 X 20mg plus placebo . Follow-up endoscopy is scheduled 3 months after therapy , and thereafter in one-year intervals . Predefined study endpoints are gastric cancer , precancerous lesions ( dysplasia , adenoma ) , other cancers , and death . RESULTS Since March 1998 , 1524 target patients have been screened , 279 patients ( 18.3 % ) had a corpus dominant type of H. pylori gastritis , and 167 of those were randomized ( 58.8 % ) . In the active treatment group ( r = 86 ) , H. pylori infection infection was cured in 88.9 % of patients . Currently , the cumulative follow-up time is 3046 months ( 253.38 patient years , median follow up 16 months ) . So far , none of the patients developed gastric cancer or any precancerous lesion . Three ( 1.8 % ) patients reached study endpoints other than gastric cancer . CONCLUSION Among men between 55 and 65 years of age , the gastric cancer phenotype of H. pylori gastritis appears to be more common than expected . Further follow up and continuing recruitment are necessary to fulfil the main aim of the study .

placebo

omeprazole 2 X 20mg

clarithromycin 2 X 500mg

amoxicillin 2 X 1g

omeprazole 2 X 20mg

placebo

gastric cancer

gastric cancer

death

cured

gastric cancer

any precancerous lesion

gastric cancer

Austrain Czech German gastric cancer


A double-blind , placebo-controlled crossover study investigating the effect of porcine secretin in children with autism . OBJECTIVES A recent patient series reported the incidental findings of improved social and language skills in 3 children with autistic spectrum disorders after the administration of secretin , a peptide hormone . However , a subsequent study did not find evidence for a drug effect . Parents are seeking treatment with secretin despite the absence of empirical investigations demonstrating amelioration in autism symptomology . In order to more precisely measure the effects of secretin , this study investigated the effect of a single intravenous dose of porcine secretin on 12 autistic children through a randomized , double-blind , placebo-controlled , crossover study . Children were assessed on objective language and on social , neuropsychological , and gastrointestinal measures to evaluate drug effects . The study was conducted over a 16-week trial . The results indicated that significant differences were not observed on the majority of the dependent variables . Statistically significant differences were observed on measures of positive affect and activity level following secretin infusion . In general , the autistic children did not demonstrate the improvements described in the initial retrospective report .

placebo-controlled

porcine secretin

secretin

secretin

secretin

intravenous dose of porcine secretin

placebo-controlled

secretin

gastrointestinal measures

children

autism

children

autistic spectrum disorders

children

children


Carpal tunnel release by limited palmar incision vs traditional open technique : randomized controlled trial . AIM To compare a limited palmar incision for carpal tunnel release ( CTR ) with a traditional open technique , which is still considered the gold standard . METHODS Seventy-two patients with a carpal tunnel syndrome were individually randomized into the trial ( limited incision CTR ) ( n=36 ) and control group ( traditional technique CTR ) ( n=36 ) . In the trial group , skin incision parallel to the thenar crease was made up to 2.5 cm in length , under an operating microscope and endoscopic transillumination . Skin incision in the control group began at the distal border of the carpal ligament , followed the longitudinal crease of the palm , and crossed the base of the palm in a zigzag fashion . Three months after surgery , the patients were asked about symptomatic relief and intervals between the operation and return to their daily activities and work , and examined for scar tenderness and esthetic outcome . Distal motor latency , conduction velocity , scar length , scar width , and operation time were measured . RESULTS There were no differences between the two groups in symptomatic relief and electrophysiological parameters . Intervals between the operation and return to daily activities ( median 5 days , range 2-15 ) were shorter in the trial group than in the control group ( median 10 days , range 2-21 ; p < 0.001 ) , as well as the intervals between the operation and return to work ( median 15 days , range 5-45 vs median 30 days , range 10-60 ; p < 0.001 ) . Scar/pillar tenderness , scar length and width , esthetic outcome , and operation time were significantly better in the trial group . CONCLUSION Limited palmar incision CTR is as effective and safe as traditional CTR technique , but with better postoperative recovery and cosmetic results .

limited palmar incision

traditional open technique

limited palmar incision

for

carpal tunnel release ( CTR )

traditional open technique

limited incision CTR

( traditional technique CTR )

Skin incision

Limited palmar incision CTR

traditional CTR technique

Seventy-two patients


Changes in selected fitness parameters following six weeks of snowshoe training . BACKGROUND Recently , there has been an increase in popularity and participation in the sport of snowshoeing . While the sport has gained considerable recognition , to date there is little or no scientific research regarding training responses to snowshoeing as a form of exercise . Therefore , the purpose of this study was to determine whether snowshoe training could improve fitness measures . A further purpose was to compare responses from a snowshoe training program to a similarly designed run training program . METHODS This prospective , comparative study was conducted with healthy males and females between the ages of 19 and 24 . These subjects were recruited from the University of Vermont population and surrounding community . Following baseline measurements in VO2max , running time to exhaustion ( RTE ) , and anthropometry , 17 subjects ( 10 snowshoers and 7 runners ) participated in a six week conditioning program . Both groups exercised for 30 min at 75-85 % age predicted maximum heart rate , 3-4 times per week , for a total of 18 sessions . RESULTS VO2max improved significantly in both running and snowshoeing groups , 6.3 and 8.5 % , respectively . Run time to exhaustion also improved significantly in both groups , 23.3 and 33.5 % , respectively . There were no changes in anthropometry for either group . With the exception of RTE , there were no statistically significant differences between groups in any other measurements at baseline . CONCLUSIONS These results support the acceptability of snowshoeing as a valid means to improve or maintain cardiovascular endurance .

snowshoe training

snowshoeing

snowshoe training program

run training program

fitness parameters

training responses

fitness measures .

VO2max ,

running time to exhaustion ( RTE )

, and anthropometry

anthropometry

cardiovascular endurance .

healthy

males

females

19 and 24


The Low Energy Safety Study ( LESS ) : rationale , design , patient characteristics , and device utilization . BACKGROUND A 10-J energy safety margin has traditionally been used in programming implantable cardioverter defibrillators ( ICDs ) . The Low Energy Safety Study ( LESS ) tests the hypothesis that programming shocks to lower energy margins is safe and effective . METHODS Patients with standard ICD indications undergo defibrillation threshold testing ( DFT ) at the time of ICD implant , with reconfirmation of lowest successful energy twice ( DFT++ ) . Patients are randomized to 2 groups : the first has the initial 2 shocks for ventricular fibrillation conversion programmed at 2 energy steps above DFT++ ( typically 4-6 J , maximum 10 J ) with subsequent shocks at maximum energy , and the second has all shocks programmed at maximum energy . Patients are followed up every 3 months for 2 years to assess shock conversion efficacy of spontaneous arrhythmias . In a subgroup of patients , there is a second randomization to energy levels of 0 , 1 , 2 , 3 , or 4 steps above implant DFT++ for conversion testing of 3 induced ventricular fibrillation episodes at prehospital discharge , 3 months , and 12 months after implant . RESULTS Enrollment is complete ( 702 patients ) , but follow-up results are pending . There were no significant variations in implant indications and baseline antiarrhythmic drug use over the 3-year enrollment period , although an increase in the percentage of dual-chamber ICDs implanted occurred , with the majority ( 65 % ) of implanted ICDs being dual-chamber devices by the end of the enrollment period . CONCLUSION The results of LESS should facilitate the development of algorithms for programming ICD energy safety margins .

Low Energy Safety Study

implantable cardioverter defibrillators

( ICDs )

Low Energy Safety Study

ICD implant

all shocks programmed at maximum energy

DFT++

antiarrhythmic drug

energy safety margins

implantable cardioverter defibrillators

ICDs

Patients with standard ICD indications

ICD implant


Multicenter randomized controlled trial of the management of unresectable malignant mesothelioma proposed by the British Thoracic Society and the British Medical Research Council . Malignant mesothelioma is almost invariably fatal . The incidence of the disease is rising rapidly in many countries , and there is no generally accepted standard treatment for patients with unresectable disease . According to current British Thoracic Society ( BTS ) guidelines , patients should be treated with active symptom control ( ASC ) , involving ( 1 ) regular follow-up in a specialist clinic ; ( 2 ) structured assessments of physical , psychological and social problems with appropriate action ; ( 3 ) rapid involvement of additional specialists ; and ( 4 ) parallel nursing support . Although many nonrandomized studies have reported tumor responses to anticancer chemotherapy , few have studied palliation and it is not known whether chemotherapy prolongs survival or provides clinically worthwhile palliation with acceptable toxicity when given in addition to ASC . We therefore plan to conduct a multicenter randomized controlled trial comparing ( 1 ) ASC alone , ( 2 ) ASC plus mitomycin vinblastine and cisplatin ( MVP ) , and ( 3 ) ASC plus vinorelbine ( N ; Navelbine , Pierre Fabre Oncology , Winchester , UK ) . We chose these chemotherapy regimens because they have been shown in nonrandomized studies to provide good symptom control as recorded by patients . The outcome measures are overall survival , palliation of symptoms , performance status , analgesic usage , toxicity , quality of life , tumor response , and recurrence/progression-free survival . In a preliminary feasibility study , we are assessing the acceptability of the trial design to patients and the suitability of two standard quality-of-life instruments in mesothelioma . Data will help us to decide the final details of the large multicenter trial .

ASC alone

ASC plus vinorelbine

overall survival

palliation of symptoms

performance status

analgesic usage

toxicity

quality of life

tumor response

recurrence/progression-free survival

quality-of-life

Malignant mesothelioma


Pacifier as a risk factor for acute otitis media .

Pacifier

acute otitis media


Glibenclamide vs gliclazide in reducing oxidative stress in patients of noninsulin dependent diabetes mellitus -- a double blind randomized study . OBJECTIVE Parameters of oxidative stress were quantitated in 50 patients with type 2 diabetes mellitus in uncontrolled state and after control using oral glibenclamide or gliclazide . The estimates were further compared between the two groups irrespective of drug used to evaluate the difference , if any . METHODS The study was a double blind , uncontrolled , noncrossover and randomized trial . Fifty patients of uncontrolled type 2 diabetes were divided in to two groups . Group I ( 25 patients ) received capsule A ( glibenclamide ) while Group II ( 25 patients ) received capsule B ( gliclazide ) . The parameters studied were Superoxide dismutase ( SOD ) , malonyl-dialdehyde ( MDA ) and reduced glutathione ( GSH ) . They were done at ( a ) uncontrolled stage ( FBS -- 165 +/- 16.7 mg/dl , PP -- 240 +/- 30.1 mg/dl and HbA1 -- 10.5 +/- 0.9 % in group I and FBS -- 150 +/- 15.8 mg/dl , PP -- 246 +/- 29.1 mg/dl HbA1 10.6 +/- 0.8 % in group II ) and during controlled stage at 12 weeks ( FBS -- 120 +/- 18.5 mg/dl , PP -- 180 +/- 19.1 mg/dl and HbA1 -- 8.4 +/- 0.29 % in group I and FBS -- 118 +/- 17.6 mg/dl , PP -- 176 +/- 20.1 mg/dl and HbA1 -- 8.5 +/- 0.39 % in group II patients ) . RESULTS The significantly raised levels of MDA and SOD , and decreased levels of reduced glutathione ( GSH ) during uncontrolled stage of diabetes indicated free radical stress induced lipid peroxidation . The significant fall of MDA and SOD and increased levels of GSH in blood in both groups after control revealed beneficial effects of glycemic control on oxidative stress . The levels were not normalized and stayed higher than those in controls . On intergroup comparison ; the control of diabetes with gliclazide ( group II ) showed improvement in oxidative stress ( MDA , GSH ) better ( p < 0.001 ) than glibenclamide ( group I ) . CONCLUSION Oxidative stress in uncontrolled diabetes is decreased with glycemic control . The control of diabetes with gliclazide reduced oxidative stress more than glibenclamide , indicating higher antioxidant properties of gliclazide . Normalization of oxidative stress was not achieved . Further studies are required to see long-term effect of drug therapy in combating oxidative stress after achieving acceptable control of diabetes .

Glibenclamide

gliclazide

glibenclamide

gliclazide

glibenclamide

gliclazide

gliclazide

glibenclamide

gliclazide

glibenclamide

oxidative stress

oxidative stress

Superoxide dismutase ( SOD )

malonyl-dialdehyde ( MDA )

reduced glutathione ( GSH )

levels of MDA and SOD

levels of reduced glutathione ( GSH )

fall of MDA and SOD

increased levels of GSH in blood

oxidative stress .

oxidative stress ( MDA , GSH )

Oxidative stress

oxidative stress

oxidative stress

oxidative stress

noninsulin dependent diabetes mellitus

uncontrolled type 2 diabetes


Methodological issues in designing a multisite trial of risperidone in children and adolescents with autism . OBJECTIVE To describe the methodological challenges and decisions made in developing a multisite , controlled study of risperidone in children and adolescents with autism . METHODS Review the design considerations for clinical trials in children with autistic disorder accompanied by severe tantrums , aggressive and/or self-injurious behaviors . These design considerations include the definition of inclusion criteria that are relevant to clinical practice and matching study design to the goal of evaluating short- and long-term effects . Additional ethical and scientific issues concern the length of trial and sample size . RESULTS We undertook a short-term , placebo-controlled study to evaluate the efficacy and safety of risperidone in children and adolescents with autistic disorder . This trial design was followed by an extended open-label maintenance on risperidone to confirm durability of treatment effects and to monitor safety . Finally , a placebo-controlled discontinuation study tested the need for continuous treatment . CONCLUSIONS In the absence of standard pharmacological treatment for children with autistic disorder , a placebo-controlled study remains the most appropriate method of testing efficacy and safety . The clinical relevance of this study is enhanced by the addition of an extended maintenance phase followed by a placebo discontinuation .

risperidone

risperidone

placebo-controlled

risperidone

risperidone

placebo

efficacy

safety

durability

safety

children and adolescents with autism .


Effects of glucagon-like peptide-1 ( 7-36 ) amide on motility and sensation of the proximal stomach in humans . BACKGROUND Glucagon-like peptide-1 ( 7-36 ) amide ( GLP-1 ) retards gastric emptying , reduces food intake , and inhibits antroduodenal and stimulates pyloric motility . AIMS To assess the effects of synthetic GLP-1 on fundus tone and volume waves , gastric compliance , and perception of gastric distension . SUBJECTS Eleven healthy male volunteers . METHODS Background infusions were saline , or GLP-1 at 0.3 or 0.9 pmol/ kg/min on separate days in random order . Interdigestive fundus motility was recorded by barostat ( maximum capacity of intragastric bag 1200 ml ) during basal and peptide periods of 60 minutes each . Thereafter stepwise isobaric distensions were performed with ongoing peptide infusion , and gastric sensation was scored . RESULTS Low and high loads of GLP-1 induced physiological and supraphysiological plasma immunoreactivities , respectively . GLP-1 dose dependently diminished fundus tone ( 162.9 ( 15.0 ) and 259.5 ( 17.2 ) v 121.1 ( 6.0 ) ml with saline ; p < 0.0001 ) . It greatly reduced volume waves and total volume displaced by these events ( p < 0.0001 ) . Gastric compliance derived from isobaric distension rose in a dose related manner ( 42.6 ( 5.5 ) and 63.6 ( 7.7 ) v 27.0 ( 3.5 ) ml/mm Hg ; p=0.0004 ) with a concomitant reduction of the pressure at half maximum bag volume ( 6.4 ( 0.4 ) and 5.5 ( 0.4 ) v 7.2 ( 0.1 ) mm Hg ; p < 0.0001 ) . GLP-1 did not change perception of isobaric distension but reduced the perception score related to corresponding bag volume ( p < 0.0001 ) . CONCLUSIONS GLP-1 is a candidate physiological inhibitory regulator of fundus motility . It allows the stomach to afford a larger volume without increase in sensation .

glucagon-like peptide-1 ( 7-36 ) amide

synthetic GLP-1

saline

fundus tone and volume waves

gastric compliance

perception of gastric distension

Interdigestive fundus motility

gastric sensation

fundus tone

volume waves and total volume displaced

Gastric compliance

pressure

isobaric distension

perception score

fundus motility

increase in sensation

Eleven

healthy

male


Immune status of infants fed soy-based formulas with or without added nucleotides for 1 year : part 2 : immune cell populations . BACKGROUND Infants fed a soy protein isolate-based formula have immunization responses similar to breast-fed infants . However , cellular aspects of the immunologic development of soy-fed infants have not been studied extensively . Nucleotides added to milk-based formula benefit infant immune status , but reports of the immunologic effects of adding nucleotides to soy-based formula are not available . This study examines immune cell populations of infants fed soy protein isolate formulas with and without added nucleotides for 1 year . METHODS Newborn , term infants studied in a masked 12-month feeding trial were assigned randomly to soy formula groups with and without added nucleotides ( n = 94 , n = 92 ) . A nonrandomized human milk/formula-fed cohort ( n = 81 ) , was concurrently enrolled . Blood samples were collected at 6 , 7 , and 12 months . Thirty-two immune cell populations were characterized using three-color flow cytometry . Cellular markers were chosen to assess general pediatric immune status , emphasizing maturation and activation of B , T , and NK lymphocytes . RESULTS All cell populations , number and percentages , were within age-related normal ranges . The only significant difference found between soy formula and human milk/formula-fed infants was the percentage of CD57 + NK T cells at 12 months ( human milk/formula > soy formula , P = 0.034 ) . There were significant differences at some time points between human milk/formula-fed and nucleotide-supplemented soy formula-fed infants in populations of lymphocytes , eosinophils , total T , helper T , naive helper , memory/effector helper , CD57 - T , and CD11b + CD8 + NK cells . None of the cell populations differed between infants fed soy formula versus soy plus nucleotides . CONCLUSIONS Infants fed this commercial soy formula demonstrated immune cell status similar to human milk/formula-fed infants , consistent with normal immune system development . The addition of nucleotides to soy formula did not significantly change specific individual immune cell populations but tended to increase numbers and percentages of T cells and decreased numbers and percentages of NK cells .

soy-based formulas

added nucleotides

soy protein isolate-based formula

Nucleotides

nucleotides

soy-based formula

soy protein isolate formulas

nucleotides

soy formula

nucleotides

human milk/formula-fed cohort

soy formula

human milk/formula-fed

nucleotide-supplemented

nucleotides

nucleotides

immunization responses

immunologic effects

immune cell populations

general pediatric immune status

percentage of CD57 + NK T cells

cell populations

immune cell status

immune system development

immune cell populations

numbers and percentages of T cells

numbers and percentages of NK cells


Prophylactic use of amifostine to prevent radiochemotherapy-induced mucositis and xerostomia in head-and-neck cancer . PURPOSE To determine the prophylactic properties of amifostine against acute and late toxicities from radiochemotherapy in patients with head-and-neck cancer . METHODS AND MATERIALS Fifty patients were randomized to receive conventional radiotherapy ( RT ) ( 2-Gy fractions , 5 days weekly , to a total of 60-74 Gy , depending on the tumor localization and TNM classification ) and carboplatin ( 90 mg/m ( 2 ) infusion once per week before RT ) . Amifostine ( 300 mg/m ( 2 ) ) was administered in the study group only 15-30 min before RT for 6-7.5 weeks . The primary study end point was the grading of acute and late nonhematologic toxicities ( mucositis , dysphagia , xerostomia ) induced by radiochemotherapy . Secondary end points included treatment duration , hematologic toxicity , and clinical outcome . RESULTS The treatment duration was significantly shorter in the amifostine-treated group ( p = 0.013 ) , because treatment interruptions were more frequent in the control group . Acute toxicities ( mucositis and dysphagia ) were less severe in the amifostine-treated group . By Week 3 , all in the control group experienced Grade 2 mucositis compared with only 9 % in the amifostine-treated group ( p < 0.0001 ) . By Week 5 , 52.2 % of the patients in the control group experienced Grade 4 mucositis compared with 4.5 % in the amifostine-treated group ( p = 0.0006 ) . Similar results were obtained for dysphagia . At 3 months of follow-up , only 27 % of patients in the study group experienced Grade 2 xerostomia compared with 73.9 % in the control group ( p = 0.0001 ) . Eighteen months after cessation of therapy , the proportion of patients with Grade 2 xerostomia was 4.5 % vs. 30.4 % for each respective treatment group ( p = 0.047 ) . Cytoprotection with amifostine did not affect treatment outcome , with 90.9 % complete responses in the amifostine-treated group compared with 78.3 % in the control group ( p = 0.414 ) . CONCLUSION Amifostine was effective in reducing mucositis and dysphagia resulting from radiochemotherapy in patients with head-and-neck cancer . Furthermore , amifostine reduced the severity of late xerostomia , a side effect of RT with long-lasting consequences . Amifostine treatment did not affect the clinical outcome .

amifostine

amifostine

conventional radiotherapy

carboplatin

Amifostine

radiochemotherapy

Cytoprotection

amifostine

Amifostine

amifostine

Amifostine

mucositis

dysphagia

xerostomia

treatment duration

hematologic toxicity

clinical outcome

treatment duration

Acute toxicities

mucositis

dysphagia

Grade 2 mucositis

dysphagia

Grade 2 xerostomia


Laparoscopically assisted vaginal hysterectomy versus abdominal hysterectomy in stage I endometrial cancer . The purpose of this study was to evaluate and compare laparoscopic treatment for stage I endometrial cancer with the traditional transabdominal approach . From July 1996 to July 1998 , 61 patients with clinical stage I endometrial cancer were treated at the Gynaecology Oncology Unit at the Royal North Shore of Sydney , Australia . Twenty-nine patients were treated with laparoscopic assisted vaginal hysterectomy ( LAVH ) and bilateral salpingo-oophrectomy ( BSO ) plus minus laparoscopic pelvic lymphadenectomy ( LPLA ) , while 32 patients were treated with the traditional laparotomy and underwent total abdominal hysterectomy ( TAH ) and BSO plus minus pelvic lymphadenectomy ( PLA ) . The main outcomes studied were operative time , blood loss , blood transfusion , intraoperative complications , postoperative complications , duration of hospital stay , and number of lymph nodes obtained . In conclusion , laparoscopic treatment of endometrial cancer is safe in the hands of experienced operators with minimal intraoperative and postoperative complications . This procedure is associated with significantly less blood loss and shorter hospitalization ; however , it is associated with significantly longer operating time . Proper selection of patients for the laparoscopic procedure is the vital step in achieving the major goals of this approach .

abdominal hysterectomy

laparoscopic treatment

traditional transabdominal approach

laparotomy

total abdominal hysterectomy ( TAH )

pelvic lymphadenectomy

laparoscopic treatment

laparoscopic procedure

operative time

blood loss

blood transfusion

intraoperative complications

postoperative complications

duration of hospital stay

number of lymph nodes

blood loss

hospitalization

operating time

stage I endometrial cancer

stage I endometrial cancer

stage I endometrial cancer

Twenty-nine

LAVH

bilateral salpingo-oophrectomy

BSO

laparoscopic pelvic lymphadenectomy

LPLA


[ Efficacy and immune memory of plasma-derived hepatitis B vaccine 11 years after primary immunization ] . OBJECTIVE To evaluate the long-term efficacy of hepatitis B vaccine 10 years after primary immunization to provide scientific basis for the time of revaccination . METHODS The study was strictly designed with randomization , double-blinding , and placebo-controlled method to observe the efficacy and immune memory 11 years following hepatitis B vaccination . RESULTS Immunogenicity and protective rate of vaccine were still kept well 11 years after immunization with a protective rate against HBV infection of 73.5 % . But , there was no significant difference in HBV infection rates between vaccine group and placebo-controlled group ( 7.89 % vs. 13.25 % , P > 0.1 ) nine to 11 years following immunization . There still existed immune memory 11 years after immunization , but it was significantly weaker than that within the first 10 years after immunization . CONCLUSION The efficacy of the vaccine had begun to drop 11 years after immunization , which should be followed up further to reach a clear conclusion .

plasma-derived hepatitis B vaccine

hepatitis B vaccine

placebo-controlled

hepatitis B vaccination

Efficacy

immune memory

long-term efficacy

immune memory

protective rate

HBV infection rates

immune memory

efficacy


Effect of oxolamine on cough sensitivity in COPD patients .

oxolamine

cough sensitivity

COPD patients


Effect of delayed cord clamping on iron stores in infants born to anemic mothers : a randomized controlled trial . OBJECTIVE To study the effects of cord clamping on iron stores of infants born to anemic mothers at 3 months of age . DESIGN Randomized controlled trial . SETTING Teaching hospital . METHODS Infants born to mothers with hemoglobin ( Hb ) < 100 g/L were randomized at delivery to either immediate cord clamping ( early group ) or cord clamping delayed till descent of placenta into vagina ( delayed group ) . The outcome measures were infant 's hemoglobin and serum ferritin 3 months after delivery . RESULTS There were 102 neonates randomized to early ( n = 43 ) or delayed cord clamping ( n = 59 ) . The groups were comparable for maternal age , parity , weight and supplemental iron intake , infant s birth weight , gestation and sex . The mean infant ferritin and Hb at 3 months were significantly higher in the delayed clamping group ( 118.4 microg/L and 99 g/L ) than in the early clamping group ( 73 microg/L and 88 g/L ) . The mean decrease in Hb ( g/L ) at 3 months adjusted for co-variates was significantly less in the delayed clamping group compared to the early clamping group ( -1.09 , 95 % CI-1.58 to -0.62 , p > 0.001 ) . The odds for anemia ( < 100 g/L ) at 3 months was 7.7 ( 95 % CI 1.84-34.9 ) times higher in the early compared to the delayed clamping group . CONCLUSION Iron stores and Hb in infancy can be improved in neonates born to anemic mothers by delaying cord clamping at birth .

delayed cord clamping

immediate cord clamping

delayed clamping

early clamping

delayed clamping

early clamping

delayed clamping

delaying cord clamping

iron stores

mean infant ferritin and Hb at 3 months

Hb

anemia

Iron stores

Hb

infants

born to anemic mothers :


Effectiveness of two quadruple , tetracycline- or clarithromycin-containing , second-line , Helicobacter pylori eradication therapies . BACKGROUND There are no guidelines on second-line therapies for Helicobacter pylori eradication failures of omeprazole-clarithromycin-amoxicillin triple therapy . AIM To compare the efficacy of two second-line therapies for persistent H. pylori infection . METHODS Over a 6-year period , patients with persistent H. pylori infection following omeprazole-clarithromycin-amoxicillin eradication therapy were randomized to receive omeprazole , 20 mg twice daily , bismuth , 120 mg four times daily , metronidazole , 500 mg twice daily , and either tetracycline , 500 mg four times daily , or clarithromycin , 500 mg twice daily , given for 7 days . Before therapy , patients underwent endoscopy with biopsies for histology , culture and antibiotic susceptibility tests . H. pylori infection was confirmed by histology . RESULTS Of the 95 randomized patients , 88 ( 93 % ) completed the study . Age , sex , smoking , ulcer/non-ulcer dyspepsia ratio and antibiotic resistance were not significantly different between the treatment groups . On intention-to-treat analysis , eradication was achieved in 41 of the 49 patients ( 84 % ; 95 % confidence interval , 70.4-92.7 % ) and 27 of the 46 patients ( 59 % ; 95 % confidence interval , 43.3-73.0 % ) of the tetracycline- and clarithromycin-containing groups , respectively ( P=0.007 ) . On multivariate regression analysis , the sensitivity of H. pylori to metronidazole had a likelihood ratio of 5.2 ( P=0.022 ) , followed by the type of quadruple therapy ( likelihood ratio , 4.4 ; P=0.036 ) . CONCLUSIONS Tetracycline-containing quadruple rescue therapy is highly effective in treating H. pylori eradication failures of the omeprazole-amoxicillin-clarithromycin regimen .

tetracycline-

clarithromycin-containing

omeprazole-clarithromycin-amoxicillin

omeprazole , 20 mg twice daily

bismuth , 120 mg four times daily

metronidazole , 500 mg twice daily

tetracycline , 500 mg

clarithromycin , 500 mg

eradication

sensitivity of H.


[ Clinical application of irradiated drug-containing porcine-cornea to patients with ocular burns ] . OBJECTIVE To explore a new method for the management of patients with ocular burns . METHODS Fifty-five cases of patients with ocular burns ( in 88 eyes ) were randomly divided into treatment and control groups . Thirty cases in treatment group with 49 eyes were transplanted with irradiated drug-containing ( ofloxacin , acetyl cysteine and reduced glutathione ) porcine-cornea . 25 cases in control group with 39 eyes were treated with routine program . RESULTS Thirty-two eyes were rescued in treatment group with the cure rate of 65.3 % . But only 17 eyes were saved in control group with the cure rate of 43.59 % , indicating significant difference of the cure rate between the two groups ( P < 0.05 ) . CONCLUSION Irradiated drug-containing porcine-cornea might well be an ideal therapeutic material for the management of patients with ocular burns .

drug-containing porcine-cornea

ofloxacin

acetyl cysteine

reduced glutathione

porcine-cornea

eyes were rescued

eyes were saved

cure rate

ocular burns

ocular burns

Fifty-five

ocular burns

ocular burns


Benefits , morbidity , and mortality associated with long-term administration of oral anticoagulant therapy to patients with peripheral arterial bypass procedures : a prospective randomized study . BACKGROUND The benefits of the long-term administration of oral anticoagulant therapy remain unclear in patients with lower extremity arterial bypass surgery . We studied the effect of warfarin plus aspirin therapy ( WASA ) versus aspirin therapy alone ( ASA ) on patient mortality , morbidity and bypass patency rates in a randomized clinical trial . METHODS In a multicenter , prospective , nonmasked clinical trial , 831 patients who underwent peripheral arterial bypass surgery were compared in a long-term treatment program of WASA ( target international normalized ratio of 1.4 to 2.8 ; 325 mg/day ) with ASA ( 325 mg/day ) . The primary end point was bypass patency , and mortality and morbidity were the secondary endpoints . RESULTS There were 133 deaths in the WASA group ( 31.8 % ) and 95 deaths in the ASA group ( 23.0 % ; risk ratio , 1.41 ; 95 % confidence interval , 1.09 to 1.84 ; P =.0001 ) . Major hemorrhagic events occurred more frequently in the WASA group ( WASA , n = 35 ; ASA , n = 15 ; P =.02 ) . In the prosthetic bypass group , there was no significant difference in patency rate in the 8-mm bypass subgroup , but there was a significant difference in patency rate in the 6-mm bypass subgroup ( femoral-popliteal ; 71.4 % in the WASA group versus 57.9 % in the ASA group ; P =.02 ) . In the vein bypass group , patency rate was unaffected ( 75.3 % in the WASA group versus 74.9 % in the ASA group ) . CONCLUSION The long-term administration of warfarin therapy when combined with aspirin therapy has only a few selected indications for improvement of bypass patency and is associated with an increased risk of morbidity and mortality .

oral anticoagulant therapy

oral anticoagulant therapy

warfarin plus aspirin therapy ( WASA )

aspirin therapy alone ( ASA )

WASA

ASA

WASA

ASA

WASA

ASA

WASA

ASA

WASA

warfarin therapy

Benefits

morbidity

mortality

patient mortality

morbidity

bypass patency rates

bypass patency

mortality

morbidity

deaths

deaths

Major hemorrhagic events

patency rate

patency rate

patency rate

bypass patency

morbidity

mortality


Comparison of comfort and local complications after cardiac catheterization . The purpose of this study was to compare the effects of 4 hours of bed rest versus 6 hours of bed rest on patients ' safety , comfort , and satisfaction levels . Using a quasi-experimental design , the authors studied 118 left-heart catheterization patients who were randomly assigned to 4 hours or 6 hours of bed rest . Among the study participants , only 1 in the 6-hour group had significant bleeding . There were no complications in the 4-hour group . There were no statistically significant differences between the two groups on any of the other study variables . Given the lack of significant complications for the 4-hour group and similar comfort levels for both study groups , these findings suggest the feasibility of reducing the standard period of postcatheterization bed rest from 6 hours to 4 hours , thereby possibly lowering the cost of the outpatient procedure .

cardiac catheterization

bed rest

bed rest

left-heart catheterization

comfort

local complications

safety

comfort

satisfaction levels

significant bleeding

complications

comfort levels

cost of the outpatient procedure

cardiac catheterization

left-heart catheterization patients


Amiodarone versus digoxin and metoprolol combination for the prevention of postcoronary bypass atrial fibrillation . OBJECTIVE This prospective randomized study aims at evaluation and comparison of the prophylactic effects of amiodarone versus digoxin and metoprolol combination in postcoronary bypass atrial fibrillation . METHODS A total of 241 consecutive patients undergoing elective coronary artery bypass grafting were randomly allocated into three groups . Patients in Group1 ( n=77 ) received metoprolol 100 mg/24 h per oral ( P.O . ) , preoperatively , 2x0.5 mg digoxin intravenously on the operating day and digoxin 0.25 mg P.O.+metoprolol 100 mg P.O . on the first postoperative day until discharge . Patients in Group 2 ( n=72 ) received totally 1200 mg intravenous/24 h amiodarone which the 300 mg - bolus dose/1 h was given as soon as the operation had been finished . On the next day patients were administered 450 mg/24 h amiodarone i.v . and 600 mg/day in three doses P.O . were given until discharge . Group 3 ( n=92 ) was the control group with no antiarrhythmic prophylaxis . RESULTS Preoperative patient characteristics and operative parameters were similar in three groups . Atrial fibrillation occurred in 13 patients ( 16.8 % ) in Group 1 , six patients ( 8.3 % ) in Group 2 and 31 patients ( 33.6 % ) in Group 3 . CONCLUSION Both study groups were effective in the prevention of postcoronary bypass atrial fibrillation with respect to control ( P < 0.01 in Group 1 and P < 0.001 in Group 2 ) .

Amiodarone versus digoxin

metoprolol combination

amiodarone versus digoxin

metoprolol combination

metoprolol 100 mg/24 h per oral

amiodarone

amiodarone

control group

postcoronary bypass atrial fibrillation

postcoronary bypass atrial fibrillation

Atrial fibrillation

postcoronary bypass atrial fibrillation

Group1 ( n=77 )

Group 2 ( n=72 )

Group 3 ( n=92 )


Mediastinal lymphadenectomy in non-small cell lung cancer : effectiveness in patients with or without nodal micrometastases - results of a preliminary study . OBJECTIVES So far it has not clearly been demonstrated that systematic mediastinal lymphadenectomy improves survival in patients with non-small cell lung cancer . One explanation might be that in some patients an early spread of tumor cells has occurred which might not be curable by surgical means . To test this hypothesis lymph nodes of patients which were treated either by lymph node sampling or systematic lymphadenectomy were screened for micrometastatic spread of tumor cells and the influence of nodal micrometastases on the efficacy of lymphadenectomy was analyzed . METHODS Lymph nodes from patients ( n=94 ) which were included in a randomized trial of lymph node sampling ( LS , n=41 ) versus radical systematic lymphadenectomy ( LA , n=53 ) were screened by immunohistochemistry for disseminated tumor cells using the antibody Ber-Ep4 . The median observation time was longer than 5 years and follow-up data were available from all 94 patients . Kaplan-Meier curves were calculated and tested for statistical significance using the log-rank test . RESULTS Standard histopathological analysis revealed no lymph node involvement ( pN0 ) in 61 patients , pN1 disease in 13 patients and pN2 disease in 20 patients without significant differences between LA and LS with respect to T-stage , N-stage or age and sex of the patients . By immunohistochemistry a minimal nodal spread of tumor cells was detected in 21 out of 94 patients ( LS , n=10 ( 24 % ) ; LA , n=11 ( 21 % ) ) . Similar to the entire group of patients also in the subset of patients with nodal micrometastases the type of lymphadenectomy did not significantly influence the long-term survival ( P=0.27 and P=0.39 , respectively ) . In contrast , in patients with a negative immunohistochemical analysis systematic lymphadenectomy resulted in an improved overall survival ( P=0.044 ) . CONCLUSIONS Our data provide some evidence that systematic lymphadenectomy improves survival in patients without an early locoregional spread of cancer cells . As long as these patients can not be identified preoperatively all patients should undergo a systematic mediastinal lymphadenectomy .

lymphadenectomy

lymphadenectomy

lymph node sampling

systematic lymphadenectomy

lymphadenectomy

lymph node sampling ( LS

radical systematic lymphadenectomy ( LA

lymphadenectomy

systematic lymphadenectomy

lymphadenectomy

survival

median observation time

Kaplan-Meier curves

no lymph node involvement

nodal spread of tumor cells

long-term survival

improved overall survival

survival

locoregional spread of cancer cells


Supervisor tolerance-responsiveness to substance abuse and workplace prevention training : use of a cognitive mapping tool . Supervisor tolerance-responsiveness , referring to the attitudes and behaviors associated with either ignoring or taking proactive steps with troubled employees , was investigated in two studies . The studies were conducted to help examine , understand and improve supervisor responsiveness to employee substance abuse . Study 1 examined supervisor response to and tolerance of coworker substance use and ways of interfacing with the Employee Assistance Program ( EAP ) in two workplaces ( n = 244 and 107 ) . These surveys suggested that engaging supervisors in a dialogue about tolerance might improve their willingness to use the EAP . Study 2 was a randomized control field experiment that assessed a team-oriented training . This training adopted a cognitive mapping technique to help improve supervisor responsiveness . Supervisors receiving this training ( n = 29 ) were more likely to improve on several dimensions of responsiveness ( e.g . likely to contact the EAP ) than were supervisors who received a more didactic , informational training ( n = 23 ) or a no-training control group ( n = 17 ) . Trained supervisors also showed increases in their own help-seeking behavior . Procedures and maps from the mapping activity ( two-stage conversational mapping ) are described . Overall , results indicate that while supervisor tolerance of coworker substance use inhibits EAP utilization , it may be possible to address this tolerance using team-oriented prevention training in the work-site .

Supervisor tolerance-responsiveness

Employee Assistance Program ( EAP )

no-training control group

several dimensions of responsiveness

own help-seeking behavior .


The impact of different doses of medroxyprogesterone acetate on mood symptoms in sequential hormonal therapy . The aim of this study was to compare adverse mood effects of two different doses of medroxyprogesterone acetate ( MPA ) during postmenopausal hormone replacement therapy ( HRT ) in women with and without a history of premenstrual syndrome ( PMS ) . The study was designed as a randomized double-blind cross-over study and included 36 postmenopausal women at three health care areas in northern Sweden . The women received 2 mg estradiol continuously during five 28-day cycles and 10 mg or 20 mg MPA sequentially for 12 days during each cycle . The main outcome measures were mood and physical symptoms noted on a daily rating scale . We found that physical symptoms did not differ between 10 and 20 mg MPA . Both women with a history of PMS and women without responded with more negative mood symptoms with the lower dose of MPA . In women with previous PMS the higher dose of MPA enhanced positive mood symptoms . With respect to mood and physical symptoms , the aim to lower MPA doses in HRT is unwarranted .

medroxyprogesterone acetate

sequential hormonal therapy

medroxyprogesterone acetate ( MPA )

2 mg estradiol

mood symptoms

mood effects

physical symptoms

mood symptoms

positive mood symptoms

mood and physical symptoms

postmenopausal

women

premenstrual syndrome ( PMS ) .

postmenopausal

women


The interaction between propofol and clonidine for loss of consciousness . UNLABELLED Clonidine premedication reduces the intraoperative requirement for opioids and volatile anesthetics . Clonidine also reduces the induction dose of IV anesthetics . There is no information , however , regarding the effect of oral clonidine premedication on the propofol blood concentrations required for loss of consciousness , and the interaction between propofol and clonidine . We randomly administered target effect-site concentrations of propofol ranging from 0.5 to 5 . 0 microg/mL by using computer-assisted target-controlled infusion to 3 groups of healthy male patients : Control ( n = 35 ) , 2.5 microg/kg Clonidine ( n = 36 ) , and 5.0 microg/kg Clonidine ( n = 36 ) groups . Nothing was administered to the Control group . Clonidine ( 2.5 or 5.0 microg/kg ) was administered orally 90 min before the induction of anesthesia in the Clonidine groups . After equilibration between the blood and effect-site for 15 min , a verbal command to open their eyes was given two times to the patients . Arterial blood samples for analysis of the serum propofol and clonidine concentrations were taken immediately before verbal commands were given . Measured serum propofol concentrations in equilibrium with the effect-site at which 50 % of the patients did not respond to verbal commands ( EC50 for loss of consciousness ) were determined by logistic regression . The EC50 +/- SE values in the Control , 2.5 microg/kg Clonidine , and 5.0 microg/kg Clonidine groups were 2.67 +/- 0.18 , 1.31 +/- 0.12 , and 0.91 +/- 0.13 microg/mL , respectively . The EC50 in the 2.5 and 5.0 microg/kg clonidine groups was significantly smaller than that in the Control group ( P < 0.001 ) . The use of a response surface modeling analysis indicated that there was an additive interaction between measured arterial propofol and clonidine concentrations in relation to loss of consciousness . These results indicate that propofol and clonidine act additively for loss of consciousness . IMPLICATIONS Oral clonidine 2.5 and 5.0 microg/kg premedication decreases the propofol concentration required for loss of consciousness .

propofol and clonidine

Clonidine

Clonidine

clonidine

propofol

propofol and clonidine .

propofol

Control

Clonidine

Clonidine

Clonidine

Clonidine

propofol and clonidine

propofol

Clonidine

Clonidine

propofol and clonidine

clonidine

propofol

Arterial blood samples

additive interaction

loss of consciousness

loss of consciousness

healthy

male


Effects of enalapril and eprosartan on the renal vascular nitric oxide system in human essential hypertension . BACKGROUND Experimental data in humans on the contribution of angiotensin-converting enzyme inhibitors and angiotensin II type 1 receptor blockers to the nitric oxide system of the renal vasculature are inconsistent . Enalapril and eprosartan , alone and in combination , were used to determine their short-term effects on the renal nitric oxide system and renal hemodynamics of human subjects with essential hypertension . METHODS Twenty male , white patients ( 27 +/- 1 years ) with mild essential hypertension ( 143 +/- 11/95 +/- 6 mm Hg ) were included in a double-blind , randomized , placebo-controlled , fourfold cross-over study with placebo , enalapril ( 20 mg/day ) , eprosartan ( 600 mg/day ) , or combination of both drugs ( 10 and 300 mg/day , respectively ) each over a one week period followed by a two-week washout phase . After each study phase the glomerular filtration rate ( GFR ) and renal plasma flow ( RPF ) were determined . Basal nitric oxide synthesis of the renal vasculature was assessed by the decrease in RPF after inhibition of nitric oxide synthase with NG-monomethyl-L-arginine ( L-NMMA ; 4.25 mg/kg ) . RESULTS After one week of therapy , the combination therapy decreased casual blood pressure by 5 +/- 2/3 +/- 1 mm Hg versus placebo ( P < 0.01 ) . Neither enalapril alone ( -2 +/- 2/1 +/- 2 mm Hg , NS vs. placebo ) nor eprosartan alone ( -1 +/- 1/0 +/- 2 mm Hg , NS vs. placebo ) had a clear-cut significant effect on casual blood pressure . In the combination phase , RPF increased by 123 +/- 36 mL/min ( P < 0.01 ) . Neither enalapril alone ( +59 +/- 46 mL/min , P = 0.21 ) nor eprosartan alone ( +113 +/- 51 mL/min , P = 0.06 ) had a clear-cut significant effect on RPF . Changes of RPF induced by treatment correlated with the L-NMMA induced decrease in RPF in the combination ( r = 0.70 , P < 0.01 ) and eprosartan phase ( r = 0.86 , P < 0.001 ) , but not in the enalapril phase ( r = -0.44 , P = 0.10 ) . Renal vascular resistance was reduced by each active treatment with the most prominent reduction in the combination phase . GFR was unaffected by any treatment . CONCLUSIONS In contrast to the effects of either substance alone , a combination of half the dose of eprosartan with half the dose of enalapril had a prominent effect on renal perfusion . The effects of eprosartan on RPF are mediated , at least in part , by an increased bioavailability of nitric oxide in the renal vasculature .

enalapril

eprosartan

Enalapril

eprosartan

placebo-controlled

placebo

enalapril ( 20 mg/day )

eprosartan ( 600 mg/day )

combination of both drugs

combination therapy

enalapril

eprosartan

eprosartan

enalapril

eprosartan

effects

renal vasculature

RPF

casual blood pressure

casual blood pressure

RPF

RPF

RPF

Renal vascular resistance

GFR

renal perfusion

bioavailability of nitric oxide

human essential hypertension .