The nature and importance of changes in toe-brachial pressure indices following percutaneous transluminal angioplasty for leg ischaemia . OBJECTIVES To document changes in toe-brachial pressure indices ( TBPI ) during the 6 months following percutaneous transluminal angioplasty ( PTA ) and relate these changes to restenosis . Furthermore , to ascertain the effect of administering a vasodilator , glyceryl trinitrate ( GTN ) , immediately following PTA . DESIGN Eighty-three technically successful PTA procedures were studied . Fifty-six were for intermittent claudication , 14 for ischaemic rest pain , and 13 for non-healing ulcers . Immediately following balloon dilatation an intra-arterial bolus of either 150 micrograms GTN , with or without a 10 mg GTN patch for 24 h , or a saline placebo was administered . TBPI were measured before and for 6 h after PTA and then at 24 h , 1 week , 1 month and 6 months . At this time , patency at the PTA site was determined by arteriography . RESULTS There was continuing TBPI improvement over 1 month in patients given saline following PTA . In patients given GTN , peak TBPI was achieved by 1 week , and corresponded with the TBPI observed immediately following GTN administration . Restenosis occurred in 27 ( 33 % ) patients , and was significantly more frequent following the procedures for rest pain or ulceration , or where a TBPI increase of more than 0.15 by 1 week was observed . CONCLUSIONS Haemodynamic changes following PTA continue for at least 1 month , can be modified by GTN administration , and are predictive of subsequent restenosis . Measuring the TBPI increase during the first week following PTA underestimates total improvement , and may give false reassurance with respect to recurrent disease .

percutaneous transluminal angioplasty

glyceryl trinitrate ( GTN )

PTA

150 micrograms GTN

GTN patch

saline placebo

saline

GTN

GTN

GTN

toe-brachial pressure indices ( TBPI )

effect

TBPI

TBPI

peak TBPI

TBPI

Restenosis

TBPI

PTA procedures

ischaemic rest pain

non-healing ulcers


Design of a cost-effectiveness study within a randomized trial : the LIPID Trial for Secondary Prevention of IHD . Long-term Intervention with Pravastatin in Ischemic Heart disease . The Long-term Intervention with Pravastatin in Ischemic Heart Disease ( LIPID ) trial is a double-blind , randomized , placebo-controlled trial evaluating the long-term effect of pravastatin on coronary mortality in patients with a previous myocardial infarction or unstable angina-ischemic heart disease ( IHD ) . It is planned to run for at least five years with 9014 patients from 85 centers in Australia and New Zealand . The trial will monitor cause-specific mortality and major clinical events associated with each treatment . Running in parallel with the main study is a prospective economic analysis , the objectives of which are ( 1 ) to estimate the effectiveness of pravastatin compared with placebo in terms of survival , quality of life ( QOL ) , and quality-adjusted life-years ( QALY ) ; ( 2 ) to estimate the resource usage associated with pravastatin compared with placebo-in particular , to study whether it alters resource usage through prevention of disease progression ; and ( 3 ) to use this information for a cost-utility analysis with cost per quality-adjusted life-year as the unit of analysis . A novel aspect of the design is the use of a preliminary cost-effectiveness analysis , based on " best-guess " values , and a sensitivity analysis over plausible ranges to guide the choice of subsample size . Some data , such a mortality , days spent in hospital , major clinical events , and drug use , are being collected within the main LIPID trial . However , additional subsamples for the cost-effectiveness study will include information on quality of life , time off work , and resources used , such as time in hospital , procedures , and medications taken . The methods and sample sizes for these substudies have been a crucial issue in validity and feasibility .

Pravastatin

Pravastatin

placebo-controlled

pravastatin

pravastatin

pravastatin

placebo-in

survival

quality of life ( QOL )

quality-adjusted life-years ( QALY )

mortality

days spent in hospital

major clinical events

drug use

cost-effectiveness

quality of life

time off work

resources used

time in hospital

procedures

medications taken

IHD .


Nimodipine pharmacotherapeutic adjuvant therapy for inpatient treatment of cocaine dependence . Recent preclinical studies suggest utility for voltage-sensitive calcium channel blockers ( VSCCBs ) in the treatment of cocaine addiction . The following double-blind placebo-controlled study examined the role of the VSCCB nimodipine in attenuating cocaine craving in 66 recently abstinent cocaine-dependent patients on an inpatient substance abuse treatment unit utilizing an intensive 12-step milieu-oriented psychosocial therapy . While the medication was well tolerated , the dose of nimodipine used in this study ( 90 mg q.d . ) was not superior to placebo in reducing background or cue-induced cocaine craving over the 3 weeks of the study . There was the suggestion that nimodipine might attenuate the severity of some cocaine-induced brain deficits , as detected by evaluation of smooth pursuit eye movement function . A rationale for evaluating higher doses of nimodipine for the treatment of cocaine addiction is presented . As nimodipine might have anticraving and mood-stabilizing properties and cardio- and neuroprotective properties in the face of cocaine intoxication and might possibly even reverse some cocaine-induced brain deficits , further investigation of the role of nimodipine ( and other VSCCBs ) in cocaine addiction appears an attractive avenue of future medication development .

Nimodipine

placebo-controlled

nimodipine

nimodipine

placebo

nimodipine

nimodipine

nimodipine

nimodipine

smooth pursuit eye movement function .

cocaine addiction .


Acute rejection and heart infection rates in FK 506- versus cyclosporine A-treated heart transplant recipients : an endomyocardial biopsy pathologic study .

FK 506-

cyclosporine A-treated

heart transplant recipients


A comparison of intermittent vaginal administration of misoprostol with continuous dinoprostone for cervical ripening and labor induction . OBJECTIVE Our purpose was to compare the effect of vaginal administration of misoprostol ( Cytotec ) with that of dinoprostone ( Cervidil ) on cervical ripening and labor induction . STUDY DESIGN Two hundred patients with indications for induction of labor and unfavorable cervical examinations were randomly assigned to receive vaginally administered misoprostol ( prostaglandin E1 ) or the dinoprostone ( prostaglandin E2 ) vaginal insert . Twenty-five microgram tablets of misoprostol were placed in the posterior vaginal fornix every 4 hours for a maximum of six doses . Additional misoprostol was not given after either spontaneous rupture of membranes , adequate cervical ripening ( Bishop score of > or = 8 or cervical dilatation of > or = 3 cm ) , or beginning of active labor . The vaginal insert , Cervidil , containing 10 mg of dinoprostone in a timed-release preparation was placed in the posterior vaginal formix for a maximum period of 24 hours . The vaginal insert was removed for spontaneous rupture of membranes , entry into active labor , adequate cervical ripening , or abnormality of uterine contractile pattern or fetal cardiac activity . RESULTS Of the 200 patients enrolled , 99 were randomized to misoprostol and 101 to dinoprostone . The average interval from start of induction to vaginal delivery was 1 hour shorter in the misoprostol group ( 1296.7 +/- 722.1 minutes ) than in the dinoprostone group ( 1360.0 +/- 792.0 minutes ) , but this difference was not statistically significant ( p = 0.97 ) . Oxytocin augmentation of labor was used in 50 ( 50.5 % ) misoprostol-treated patients and 43 ( 43.5 % ) dinoprostone-treated patients ( relative risk 1.14 , 95 % confidence interval 0.86 to 1.51 , p = 0.35 ) . There were no significant differences between routes of delivery with misoprostol or dinoprostone . Overall , 38 patients ( 19.3 % ) had cesarean deliveries . There was a significantly lower prevalence of tachysystole ( six or more uterine contractions in a 10-minute window for two consecutive 10-minute periods ) in the misoprostol group ( 7.1 % ) than in the dinoprostone group ( 18.4 % ) ( relative risk 0.52 , 95 % confidence interval 0.31 to 0.89 , p = 0.02 ) . There were no significant differences in frequency of uterine hyperstimulation or hypertonus . Abnormal fetal heart rate tracings were found in 23 ( 23.2 % ) of misoprostol-treated patients and 35 ( 35.7 % ) of dinoprostone-treated patients ( relative risk 0.73 , 95 % confidence interval 0.52 to 1.01 , p = 0.0546 ) . No significant differences were found in meconium passage , 1- or 5-minute Apgar scores < 7 , neonatal resuscitations , or admissions to the neonatal intensive care unit between the two groups . CONCLUSIONS Vaginally administered misoprostol is as effective as dinoprostone for cervical ripening and the induction of labor . Mean time intervals to delivery , need for oxytocin augmentation , and routes of delivery were similar between the two groups . Incidence of uterine tachysystole with misoprostol every 4 hours was significantly less than with dinoprostone .

dinoprostone ( Cervidil )

misoprostol ( prostaglandin E1 )

dinoprostone ( prostaglandin E2 )

misoprostol

misoprostol

Cervidil

dinoprostone

misoprostol

dinoprostone

misoprostol

dinoprostone

Oxytocin

misoprostol-treated

dinoprostone-treated

misoprostol

dinoprostone

misoprostol

dinoprostone

misoprostol-treated

dinoprostone-treated

misoprostol

oxytocin

misoprostol

dinoprostone

cervical ripening and labor induction .

cervical ripening and labor induction .

Oxytocin augmentation of labor

routes of delivery

cesarean deliveries .

tachysystole

meconium passage

Apgar scores

neonatal resuscitations

effective

uterine tachysystole

Two hundred patients

misoprostol

dinoprostone

cesarean deliveries


An open , parallel group comparison of quinapril and captopril , when added to diuretic therapy , in the treatment of elderly patients with heart failure . This study aimed to compare the efficacy , tolerability and first-dose blood-pressure response of once-daily quinapril and twice-daily captopril when added to diuretic therapy in elderly patients with heart failure . The study was performed at a single centre as an open randomised parallel-group study , patients being selected for inclusion from the outpatient population . Following a starting dose of either 2.5 mg once-daily quinapril , or 6.25 mg twice-daily captopril , patients were reviewed at two-weekly intervals , and following clinical assessment a decision was made either to titrate up to the next medication stage or to enter the patient into the 16-week maintenance phase . Efficacy was assessed using a six-minute walking test , the New York Heart Association ( NYHA ) class , a functional lifescale ( FLS ) questionnaire and the cardiothoracic ratio ( CTR ) -at study entry and at the end of the maintenance phase . Blood pressure was measured for 5 h post-first-dose of medication . Sixty-one patients were randomised to treatment : 30 to quinapril and 31 to captopril . Following withdrawals , data from 36 patients ( 20 on quinapril , 16 on captopril ) were available for analysis . The distance walked during the six-minute walking test improved in both groups ; the difference between the treatment groups was not statistically significant . There were no significant changes in the FLS or CTR . An analysis of change in the NYHA status from study entry to study end showed a statistically significant difference between the two groups ( p = 0.02 ) in favour of quinapril . Five patients in each group experienced hypotension during the 5 h following the first dose of medication . This study has shown heart failure to be as well controlled by once-daily quinapril as by twice-daily captopril , with comparable effects on first-dose blood-pressure response .

quinapril

captopril

diuretic therapy

quinapril

captopril

diuretic therapy

quinapril

captopril

quinapril

captopril

quinapril

captopril

quinapril

quinapril

captopril

Efficacy

assessed

Blood pressure

statistically significant .

FLS or CTR

statistically significant difference

hypotension

first-dose blood-pressure response

elderly patients with heart failure .


Lack of effect of food on the steady state pharmacokinetics of BMS-181101 , an antidepressant , in healthy subjects . The effect of food on the pharmacokinetics of BMS-181101 , a new anti-depressant under development , was investigated in 12 healthy male volunteers at steady state . Each subject received a 15 mg oral dose of BMS-181101 twice a day ( q 12 h ) for 11 days and a morning dose of BMS-181101 on day 12 . Six subjects were randomly assigned to receive BMS-181101 under fasted conditions from days 1 to 6 and then crossed over to fed conditions from days 7 to 12 . The other six subjects received the reverse conditions , fed for days 1-6 and fasted for days 7-12 . Serial blood samples were collected up to 12 h on days 6 and 12 following the administration of the morning dose . In addition , trough blood samples were collected on days 4 , 5 , 10 , and 11 prior to the morning dose . Plasma samples were analyzed for intact BMS-181101 using a validated high-performance liquid chromatography method with an electrochemical detector . BMS-181101 was well tolerated both with and without ingestion of food . The statistical evaluation of the Cmin values indicated that steady state of BMS-181101 was achieved by the fourth day of dosing regardless of whether the subject was fasted or fed . When BMS-181101 was administered with food , Cmax was reduced by about 25 % and tmax was prolonged by 1 h. However , AUCtau , t1/2 , and time to attain steady state of BMS-181101 were not altered by ingestion of food . In summary , BMS-181101 can be given with food without adversely impacting the safety or pharmacokinetic profiles of the drug .

food

Serial blood samples

trough blood samples

Plasma samples

intact BMS-181101

tolerated

Cmin values

steady state

Cmax

was reduced

tmax

was prolonged

AUCtau

, and

time to attain steady state

of BMS-181101

safety

pharmacokinetic profiles

healthy

healthy

male

Six


Intravenous magnesium sulfate in acute severe asthma not responding to conventional therapy . OBJECTIVE To evaluate the effectiveness of early administration of intravenous Magnesium sulfate ( i.v . MgSO4 ) in children with acute severe asthma not responding to conventional therapy . DESIGN Randomized double-blind , placebo-controlled trial . SETTING Pediatric emergency service of a large teaching hospital . SUBJECTS 47 children aged between 1-12 years with acute severe asthma showing inadequate or poor response to 3 doses of nebulized salbutamol given at an interval of 20 min each . INTERVENTION The MgSO4 group received 0.2 ml/kg of 50 % MgSO4 as intravenous ( i.v . ) infusion over 35 minutes and the placebo group received normal saline infusion in the same dose and at the same rate . MgSO4 solution and normal saline were coded and dispensed in identical containers . Decoding was done at the completion of the study . All the patients received oxygen , nebulized salbutamol , i.v . aminophylline and corticosteroids . RESULTS MgSO4 group showed early and significant improvement as compared to placebo group in PEFR and SaO2 at 30 min and 1 , 2 , 3 and 7 hours after stopping the infusion ( p ranging from < 0.05 to < 0.01 ) . The clinical asthma score also showed significant improvement in the MgSO4 group 1 , 2 , 3 and 11 hours after stopping the infusion ( p < 0.01 ) . CONCLUSION Addition of MgSO4 to conventional therapy helps in achieving earlier improvement in clinical signs and symptoms of asthma and PEFR in patients not responding to conventional therapy alone .

Intravenous magnesium sulfate

conventional therapy

conventional therapy

placebo-controlled

nebulized salbutamol

placebo

normal saline infusion

MgSO4 solution

normal saline

corticosteroids .

placebo

conventional therapy

acute severe asthma

inadequate or poor response

early and significant improvement

PEFR

clinical asthma score

improvement in clinical signs

symptoms of asthma and PEFR

children

47 children

aged between 1-12 years


Exhaled NO during graded changes in inhaled oxygen in man . BACKGROUND Nitric oxide ( NO ) is present in the exhaled air of animals and humans . In isolated animal lungs the amount of exhaled NO is decreased during hypoxia . A study was undertaken to determine whether changes in arterial oxygen tension affect levels of exhaled NO in humans . METHODS Sixteen healthy subjects were randomised to inhale different gas mixtures of oxygen and nitrogen in a double blind crossover study . Eight gas mixtures of oxygen and nitrogen ( fractional inspired oxygen concentration ( FiO2 ) 0.1 to 1.0 ) were administered . Exhaled NO was measured with a chemiluminescence detector from end expiratory single breath exhalation . RESULTS A dose-dependent change in exhaled NO during graded oxygen breathing was observed ( p = 0.0012 ) . The mean ( SE ) exhaled NO concentration was 31 ( 3 ) ppb at baseline , 39 ( 4 ) ppb at an FiO2 of 1.0 , and 26 ( 3 ) ppb at an FiO2 of 0.1 . CONCLUSIONS The NO concentration in exhaled air in healthy humans is dependent on oxygen tension . Hyperoxia increases the level of exhaled NO , which indicates increased NO production . The mechanism behind this phenomenon remains to be elucidated .

Nitric oxide

mixtures of oxygen and nitrogen

gas mixtures of oxygen and nitrogen

Exhaled NO

exhaled NO

mean ( SE ) exhaled NO concentration

NO concentration

man .

Sixteen


Effect of esmolol pretreatment on EEG seizure morphology in RUL ECT . Intravenous beta-blockers are an effective means of controlling heart rate and blood pressure during electroconvulsive therapy ( ECT ) , but have been shown to decrease seizure duration . While the importance of seizure duration to the antidepressant response of ECT grows less certain , there is growing evidence that seizure morphology predicts the antidepressant effect of ECT . This study examined the impact of esmolol pretreatment on seizure morphology . Eighteen depressed patients ( 6 men , 12 women ; 69 +/- 12.8 years old ) received ECT with and without esmolol pretreatment in a randomized , blinded crossover design . The seizures were blindly rated for duration of motor convulsion , duration of electroencephalogram ( EEG ) seizure , degree of seizure regularity , and degree of postictal EEG suppression . Esmolol shortened the duration of the motor convulsion and degraded the quality of the ictal regularity . Routine administration of intravenous esmolol before ECT may cause a decrease in ictal regularity . Careful consideration should be given to the potential benefits of esmolol versus the deleterious effect on the electrophysiologic process . Esmolol may still be indicated on a case-by-case basis for extreme tachycardia or hypertension associated with ECT , and presumably poses no problem for the therapeutic effect of ECT if given after the seizure is over .

esmolol

electroconvulsive therapy ( ECT )

esmolol

ECT

with and without esmolol pretreatment

EEG seizure morphology

heart rate and blood pressure

seizure morphology .

quality of the ictal regularity .

Eighteen

depressed

men

women

69 +/- 12.8


A drug interaction study between ticlopidine and cyclosporin in heart transplant recipients . OBJECTIVES Previous uncontrolled studies have suggested an interaction between ticlopidine , a major antiplatelet agent , and cyclosporin in heart- and kidney-transplant recipients . The aims of this study were to examine in a randomised , double-blind fashion , the possible interaction between cyclosporin A and ticlopidine ( 250 mg per day ) and the tolerability of this combination in heart-transplant recipients . METHODS Twenty heart-transplant recipients were randomised into either a treated or a placebo group . Blood samples were drawn for time-course evaluation of cyclosporin blood levels over a period of 12 h , following the morning intake of cyclosporin and , for platelet aggregation studies , before and after 14 days of ticlopidine administration . Twenty four-hour urine samples were collected for 6-beta-hydroxycortisol measurements , before and after 14 days of ticlopidine . RESULTS Although given at half the recommended daily dosage , ticlopidine significantly reduced platelet aggregation . Pharmacokinetic parameters indicate that the bioavailability of cyclosporin A was not significantly modified by ticlopidine . However , one patient in the ticlopidine group was withdrawn because of a major fall in cyclosporin blood level within 3 days of treatment . Urinary excretion of 6-beta-hydroxycortisol was augmented after treatment in the ticlopidine group compared with the placebo group , suggesting that induction of drug metabolism might have occurred . Data also show quite a large intra-individual variability in cyclosporin bioavailability in the placebo group , suggesting that poor absorption of the drug formulation and/or poor compliance might have contributed to the decreased cyclosporin blood levels in the patient withdrawn from this study and in previous uncontrolled studies . CONCLUSION Cyclosporin bioavailability was not clearly modified by a half dosage of ticlopidine in this study . We , however , recommend closely monitoring cyclosporin blood levels when prescribing ticlopidine . Further studies will be needed with new formulations of cyclosporin or when using the full dosage of ticlopidine .

ticlopidine

cyclosporin

ticlopidine

cyclosporin

cyclosporin A and ticlopidine

placebo

cyclosporin

ticlopidine

cyclosporin A

ticlopidine

ticlopidine

placebo

cyclosporin

placebo

cyclosporin

ticlopidine

ticlopidine

cyclosporin

ticlopidine

platelet aggregation .

bioavailability of cyclosporin A

fall in cyclosporin blood level

cyclosporin bioavailability

cyclosporin blood levels

heart transplant recipients .

Twenty


Dose-response comparison of RRR-alpha-tocopherol and all-racemic alpha-tocopherol on LDL oxidation . Much data have accrued in support of the concept that oxidation of LDL is a key early step in atherogenesis . The most consistent data with respect to micronutrient antioxidants and atherosclerosis appear to relate to alpha-tocopherol ( AT ) , the predominant lipid-soluble antioxidant in LDL . There are scant data on the direct comparison of RRR-AT and all-racemic ( rac ) -AT on LDL oxidizability . Hence , the aim of the present study was to examine the relative effects of RRR-AT and all-rac-AT on plasma antioxidant levels and LDL oxidation in healthy persons in a dose-response study . The effect of RRR-AT and all-rac-AT at doses of 100 , 200 , 400 , and 800 IU/d on plasma and LDL AT levels and LDL oxidation was tested in a randomized , placebo-controlled study of 79 healthy subjects . Copper-catalyzed oxidation of LDL was monitored by measuring the formation of conjugated dienes and lipid peroxides over an 8-hour time course at baseline and again after 8 weeks . Plasma AT , lipid-standardized AT , and LDL AT levels rose in a dose-dependent fashion in both the RRR-AT and all-rac-AT groups compared with baseline . There were no significant differences in plasma , lipid-standardized , and LDL AT levels between RRR-AT and all-rac-AT supplementation at any dose comparison . The lag phases of oxidation were significantly prolonged with doses > or = 400 IU/d of RRR-AT and all-rac-AT , as measured by conjugated-dienes assay and at 400 IU/d of RRR-AT and 800 IU/d of both forms of AT by lipid peroxide assay . Again , there were no significant differences in the lag phase of oxidation at each dose for RRR-AT when compared with all-rac-AT . Also , there were no significant differences in LDL oxidation after in vitro enrichment of LDL with RRR-AT and all-rac-AT . Thus , supplementation with either RRR-AT or all-rac-AT resulted in similar increases in plasma and LDL AT levels at equivalent IU doses , and the degree of protection against copper-catalyzed LDL oxidation was only evident at doses > or = 400 IU/d for both forms .

alpha-tocopherol

RRR-AT and all-rac-AT

lag phases of oxidation

lag phase of oxidation

LDL oxidation


Postoperative pain relief following laparoscopic tubal sterilization with silastic bands . OBJECTIVE To evaluate postoperative pain relief of intramuscular ketorolac , topical bupivacaine , and placebo in patients undergoing laparoscopic tubal sterilization with silastic bands . METHODS One hundred five women undergoing laparoscopic tubal sterilization with silastic bands were randomized to one of three groups : one received intramuscular ketorolac and topical placebo applied to the fallopian tubes , the second received intramuscular placebo and topical bupivacaine , and the third received intramuscular placebo and topical placebo . Surgical procedures , anesthesia , and recovery were conducted with standardized protocols . Postoperative pain perception was graded using the modified McGill pain intensity scale at 30 minutes postoperatively , at discharge from the recovery room , and the next morning by telephone interview . Other measured variables included postoperative vomiting , additional analgesia requirement , and length of time spent in the recovery room . RESULTS Only topical bupivacaine was found to decrease postoperative pain scores significantly over those with placebo , at 30 minutes postoperatively ( median score 2 compared with 4 , P = .002 ) and at discharge from the recovery room ( median score 2 compared with 3 , P = .03 ) . There was no significant decrease in pain scores with intramuscular ketorolac compared with placebo . No differences in pain scores were found between the three groups at the next morning phone call . There were no significant differences between the three groups with respect to requirements for supplemental pain medications in the recovery room , incidence of postoperative vomiting , or length of time spent in the recovery room . CONCLUSION Topical bupivacaine decreases postoperative pain scores significantly compared with placebo in women undergoing laparoscopic tubal sterilization with silastic bands .

ketorolac , topical bupivacaine

placebo

intramuscular placebo and

topical bupivacaine

placebo

ketorolac

placebo

bupivacaine

placebo

postoperative pain scores

pain scores

pain scores

incidence of postoperative vomiting

laparoscopic tubal sterilization

laparoscopic tubal sterilization

One hundred five

women

laparoscopic tubal sterilization


Effectiveness of norgestimate and ethinyl estradiol in treating moderate acne vulgaris . BACKGROUND An excess of androgen is believed to contribute to development of acne in some patients . Because oral contraceptives ( OCs ) may reduce the active androgen level , hormonal therapy with OCs has been used successfully to treat patients with acne , although this treatment has previously not been studied in placebo-controlled trials . OBJECTIVE Our purpose was to evaluate the efficacy of a triphasic , combination OC ( ORTHO TRI-CYCLEN [ Ortho-McNeil Pharmaceutical , Raritan , N.J. ] , norgestimate/ethinyl estradiol ) compared with placebo in the treatment of moderate acne vulgaris . METHODS Two hundred fifty-seven healthy female subjects , 15 to 49 years of age with moderate acne vulgaris , were enrolled in a multicenter , randomized , double-blind , placebo-controlled clinical trial . Each month for 6 months , subjects received either 3 consecutive weeks of the OC ( i.e. , tablets containing a fixed dose of ethinyl estradiol [ 0.035 mg ] and increasing doses of norgestimate [ 0.180 mg , 0.215 mg , 0.250 mg ] ) followed by 7 days of inactive drug or placebo ( color-matched tablets ) . Efficacy was assessed by facial acne lesion counts , an investigator 's global assessment , a subject 's self-assessment , and an analysis of within-cycle variation ( cycle 6 ) in lesion counts . RESULTS Of the 160 subjects in whom efficacy could be evaluated , the OC group showed a statistically significantly greater improvement than the placebo group for all primary efficacy measures . The mean decrease in inflammatory lesion count from baseline to cycle 6 was 11.8 ( 62.0 % ) versus 7.6 ( 38.6 % ) ( p = 0.0001 ) , and the mean decrease in total lesion count was 29.1 ( 53.1 % ) versus 14.1 ( 26.8 % ) ( p = 0.0001 ) in the OC and placebo groups , respectively . In the investigator 's global assessment , 93.7 % of the active treatment group versus 65.4 % of the placebo group were rated as improved at the end of the study ( p < 0.001 ) . Six of the seven secondary efficacy measures ( total comedones , open comedones , closed comedones , papules , pustules , and the subject 's self-assessment of study treatment ) were also significantly more favorable in the OC group compared with the placebo group . CONCLUSION An OC containing 0.035 mg of ethinyl estradiol combined with the triphasic regimen of norgestimate is a safe and effective treatment of moderate acne vulgaris in women with no known contraindication to OC therapy .

norgestimate

ethinyl estradiol

oral contraceptives

triphasic , combination OC

ORTHO TRI-CYCLEN

Ortho-McNeil Pharmaceutical

Raritan

norgestimate/ethinyl estradiol )

placebo

OC

ethinyl estradiol

norgestimate

inactive drug

placebo

ethinyl estradiol

Effectiveness

efficacy

Efficacy

facial acne lesion counts

global assessment

subject 's self-assessment

improvement

mean decrease in total lesion count

investigator 's global assessment

moderate acne vulgaris

acne

Two hundred fifty-seven

healthy

female

15 to 49 years of age

moderate acne vulgaris

women


Maximal bioavailability of digoxin from tablets and oral solution in steady state . Comparison has been made between the absorption of digoxin from Lanoxin tablets and the absorption of international chemical reference substance digoxin from an oral solution . Plasma levels , areas under 24-hour plasma concentration curves and urinary excretion were similar by both formulations in steady state . 78 % of the digoxin administered was absorbed from the tablets and 76 % from the solution . Rapid dissolution in the intestinal fluids accounts for the high digoxin bioavailability of the tablets .

digoxin

digoxin

Lanoxin

digoxin from an oral solution .

digoxin

digoxin

Maximal bioavailability

absorption of digoxin

digoxin

digoxin

digoxin bioavailability


The influence of preoperative antibiotics on success of endosseous implants up to and including stage II surgery : a study of 2,641 implants . According to the American College of Surgeons , complex oral surgical procedures , including the transoral placement of endosseous implants , are of the type that may require prophylactic antibiotics . However , the routine use of prophylactic antibiotics in the field of dental implantology continues to be controversial , and their utilization varies widely . No data from a randomized prospective clinical study of the prophylactic use of antibiotics in implant surgery have been previously published . As part of the comprehensive Dental Implant Clinical Research Group clinical implant study , the preoperative or postoperative use of antibiotics , the type used , and the duration of coverage was left to the discretion of the surgeon . These data were recorded and correlated with failure of osseointegration during healing ( stage I ) and at stage II surgery ( uncovering ) . The results showed that significantly fewer failures occurred when preoperative antibiotics were used .

antibiotics

endosseous implants

prophylactic antibiotics

prophylactic antibiotics

antibiotics

antibiotics

antibiotics

success

failures


The influence of type of incision on the success rate of implant integration at stage II uncovering surgery . In 1991 , the Dental Implant Clinical Research Group comprising 30 Department of Veterans Affairs medical centers and two dental schools initiated a long-term clinical study to investigate the clinical performance of implants within the Spectra-System ( Core-Vent Corporation , Las Vegas , NV ) . This article focuses on a portion of the study database related to incision type , implant success rates , and response of crestal bone up to the time of surgical uncovering . The crestal incision was used for 1,705 implants ( 381 patients ) and the remote incision for 593 implants ( 141 patients ) . No statistically significant difference ( P = .092 chi-square statistic ) was found in implant integration or the response of crestal bone .

type of incision

surgery

implants

surgical uncovering

crestal incision

remote incision

implant integration

response of crestal bone

implant integration

stage II uncovering surgery

implants within the Spectra-System

1,705 implants

381 patients

593 implants

141 patients


Naltrexone in young autistic children : replication study and learning measures . OBJECTIVE This study expanded upon previous work on naltrexone efficacy and safety in young autistic children and assessed performance on learning measures . METHOD Eleven children with autistic disorder , aged 3.0 to 8.3 years , were studied in home , school , and outpatient laboratory , bringing to 24 the combined study sample . Naltrexone , 1.0 mg/kg , was given daily in a randomized , double-blind , crossover design . Dependent measures were parent and teacher Clinical Global Impressions ( CGI ) and Naltrexone Side Effects Rating Scale ( SE ) , Conners Parent Impulsivity/Hyperactivity Factor , Teacher Hyperactivity Factor , laboratory CGI , and analysis of videotaped behavior . Learning measures were the Early Intervention Developmental Profile-Language and paired-associate learning . RESULTS Comparisons between naltrexone and baseline , but not naltrexone and placebo , on parent and teacher ratings showed statistical significance . Three of 11 subjects improved in two or more settings . Side effects were mild . Administering naltrexone was a challenge . The combined study sample showed improvement on all parent measures and on Teacher CGI and SE-Restlessness compared with baseline and placebo . Eleven of the 24 children improved in two or more settings . Scores on learning measures did not change across conditions . CONCLUSIONS Naltrexone was associated with modest improvement of behavior in 11 of 24 children , but learning did not improve .

Naltrexone

naltrexone

Naltrexone

naltrexone

naltrexone

placebo

naltrexone

placebo

Naltrexone

Clinical Global Impressions ( CGI )

Teacher Hyperactivity Factor

paired-associate learning

Side effects

parent measures

Teacher CGI

SE-Restlessness

learning measures

behavior

learning


Long-term follow-up of three randomized trials comparing idarubicin and daunorubicin as induction therapies for patients with untreated acute myeloid leukemia . BACKGROUND Most clinical trials for acute leukemia have reported results after 2-3 years of follow-up . Comparisons between the original data and longer-term follow-up data may be of interest , particularly with regard to promising new therapies . METHODS In 1996 , survival data were updated from three prospective , randomized comparisons of idarubicin and daunorubicin that began in 1984 and 1985 . These were trials of the Memorial Sloan-Kettering Cancer Center ( MSKCC ) , the U.S. Multicenter Study Group , and the Southeastern Cancer Study Group ( SEG ) . The original results of these trials were reported in 1991 and 1992 . RESULTS The original results of the SEG trial demonstrated no significant difference between idarubicin and daunorubicin . The updated survival analysis showed similar results . The MSKCC trial revealed a significant advantage of idarubicin compared with daunorubicin in both the original and the updated analyses . The U.S. Multicenter trial found a significant difference favoring idarubicin in the original analysis , but the difference was not significant in the updated analysis . CONCLUSIONS It is essential that the median length of follow-up be clearly stated in any clinical trial . When the results obtained with a particularly promising new drug or procedure are presented early in the course of study ( within 1-2 years ) , the investigators should strongly consider a repeat evaluation after an additional 3-5 years of follow-up .

idarubicin

daunorubicin

idarubicin and daunorubicin

survival analysis

advantage of idarubicin

untreated acute myeloid leukemia .


The effects of the angiotensin-converting enzyme inhibitor imidapril on plasma plasminogen activator inhibitor activity in patients with acute myocardial infarction . This study sought to determine whether early treatment with angiotensin-converting enzyme ( ACE ) inhibitors in patients with acute myocardial infarction ( AMI ) is useful for the improvement of fibrinolytic function , as well as left ventricular function . This study was designed to examine the levels of plasma plasminogen activator inhibitor ( PAI ) activity and serum ACE activity during the course of 2 weeks in 40 patients with AMI within 12 hours after the onset of the symptom and who randomly received early treatment with either the ACE inhibitor imidapril or a placebo ( 20 patients in the imidapril group and 20 in the placebo group ) . The levels of serum ACE activity in the imidapril group decreased significantly ( p < 0.01 ) 8 hours after the administration of imidapril , and the levels 24 hours after administration were significantly lower than those in the placebo group ( 3.6 +/- 0.6 IU/L vs 7.4 +/- 0.8 IU/L ; p < 0.001 ) . The plasma PAI activity increased gradually to peak levels 16 hours after the administration of imidapril and placebo . The levels in the placebo group decreased gradually but remained high during the study period . On the other hand , the levels of PAI activity in the imidapril group decreased rapidly and those 48 hours after administration were significantly lower than those in the placebo group ( 7.9 +/- 1.9 IU/ml vs 18.4 +/- 3.5 IU/ml ; p < 0.01 ) . The levels of left ventricular ejection fraction about 2 weeks after admission were significantly higher in the imidapril group than in the placebo group ( 65.9 % +/- 2.5 % vs 49.1 % +/- 4.4 % ; p < 0.01 ) . This study showed that imidapril , an ACE inhibitor , might be useful for the improvement of fibrinolytic function and left ventricular function in the acute phase of myocardial infarction .

ACE inhibitor imidapril

placebo

imidapril

imidapril

placebo

placebo

imidapril

fibrinolytic function

left ventricular function

serum ACE activity

levels of serum ACE activity

plasma PAI activity

levels of PAI activity

fibrinolytic function

left ventricular function

acute myocardial infarction

AMI


Evaluation of hypertensive patients after care provided by community pharmacists in a rural setting . We evaluated blood pressure control , quality of life , quality of care , and satisfaction of patients who were monitored by specially trained community pharmacists in a group medical practice . After participating in an intensive skill development program , pharmacists performed in an interdisciplinary team in a rural clinic . The primary objective was assessed by evaluating outcome variables at 6 months compared with baseline in 25 patients randomly assigned to a study group . A control group of 26 patients was also evaluated to determine if outcome variables remained constant from baseline to 6 months . Systolic blood pressure was reduced in the study group ( 151 mm Hg baseline , 140 mm Hg at 6 mo , p < 0.001 ) and diastolic blood pressure was significantly lower at 2 , 4 , and 5 months compared with baseline . Ratings from a blinded peer review panel indicated significant improvement in the appropriateness of the blood pressure regimen , going from 8.7 +/- 4.7 to 10.9 +/- 4.5 in the study group ( p < 0.01 ) , but they did not change in the control group . Several quality of life scores improved significantly in the study group after 6 months ( p < 0.05 ) . These included physical functioning ( 61.6 vs 70.7 ) , physical role limitations ( 56.8 vs 72.8 ) , and bodily pain ( 60.0 vs 71.7 ) at baseline and 6 months , respectively . There were no significant changes in the control group . Patient satisfaction scores were consistently higher in the study group at the end of the study . Our results indicate that when community pharmacists in a clinic setting are trained and included as members of the primary care team , significant improvements in blood pressure control , quality of life , and patient satisfaction can be achieved .

community pharmacists

specially trained community pharmacists

intensive skill development program

community pharmacists

blood pressure control

quality of life

quality of care

satisfaction of patients

Systolic blood pressure

diastolic blood pressure

quality of life scores

physical functioning

physical role limitations

bodily pain

Patient satisfaction scores

blood pressure control

quality of life

patient satisfaction

hypertensive

rural setting


Radiotherapy and CCNU in the treatment of high-grade supratentorial astrocytomas . Forty-one consecutive patients with supratentorial primary brain tumors ( 38 Grade III and IV astrocytomas , one giant-cell astrocytoma , and two cases with insufficient tissue for diagnosis ) were randomly allocated within 2 weeks of surgery to one of three therapeutic groups . Group 1 ( 15 patients ) received radiation therapy totaling 4000 to 4500 rads in 4 to 5 weeks . Group 2 ( 13 patients ) received 1- ( 2-chloroethyl ) -3-cyclohexyl-1-nitrosourea CCNU ) 130 mg/sq m orally every 6 weeks . Group 3 ( 13 patients ) received radiation therapy plus CCNU as for Groups 1 and 2 . When the disease progressed , patients in Groups 1 and 2 were crossed over to receive CCNU and irradiation respectively . The median survival time in these groups was 188 , 259 , and 252 days , and the mean survival 263 , 262 , and 329 days . The median time from diagnosis to crossover ( Groups 1 and 2 ) or to progression ( Group 3 ) was 163 , 99 , and 220 days , and the mean time was 172 , 108 , and 231 days . There was no statistically significant difference between the means or medians in any of these situations .

Radiotherapy

CCNU

radiation therapy

radiation therapy plus CCNU

CCNU

median survival time

survival

means or medians

Forty-one

supratentorial primary brain tumors

Grade III and IV astrocytomas

one

giant-cell astrocytoma

two


MSL-109 adjuvant therapy for cytomegalovirus retinitis in patients with acquired immunodeficiency syndrome : the Monoclonal Antibody Cytomegalovirus Retinitis Trial . The Studies of Ocular Complications of AIDS Research Group . AIDS Clinical Trials Group . OBJECTIVE To evaluate the efficacy and safety of an intravenous human monoclonal antibody to cytomegalovirus ( CMV ) , MSL-109 , as adjuvant treatment for CMV retinitis . METHODS Two hundred nine patients with acquired immunodeficiency syndrome and active CMV retinitis were enrolled in a multicenter , phase 2/3 , randomized , placebo-controlled clinical trial . Patients received adjuvant treatment with MSL-109 , 60 mg intravenously every 2 weeks , or placebo . Randomization was stratified on the basis of whether patients had untreated or relapsed retinitis . Primary drug therapy for CMV retinitis was determined by the treating physician . RESULTS The rates of retinitis progression , as evaluated in a masked fashion , were 3.04/person-year in the MSL-109-treated group and 3.05/person-year in the placebo-treated group ( P=.98 ; Wald test ) ; the median times to progression were 67 days in the MSL-109-treated group and 65 days in the placebo-treated group . No differences between the 2 groups were noted in the rates of increase in retinal area involved by CMV , visual field loss , or visual acuity outcomes . The mortality rate in the MSL-109-treated group was 0.68/person-year , and in the placebo-treated group , 0.31/person-year ( P=.01 ) . The mortality difference was not explained by differences in baseline variables or in concurrent antiretroviral therapy . Among patients with newly diagnosed retinitis , mortality rates were similar ( MSL-109 , 0.41/person-year ; placebo , 0.42/person-year ; P=.95 ) , whereas among patients with relapsed retinitis the MSL-109-treated group had a greater mortality rate ( MSL-109 , 0.83/person-year ; placebo , 0.24/person-year ; P=.003 ) . However , the mortality rate in the placebo-treated patients with relapsed CMV retinitis was lower than that in the placebo-treated patients with newly diagnosed CMV retinitis and lower than that in other trials of patients with relapsed CMV retinitis . CONCLUSIONS Intravenous MSL-109 , 60 mg every 2 weeks , appeared to be ineffective adjuvant therapy for CMV retinitis . The mortality rate was higher in the MSL-109-treated group , but the reasons for this difference remain uncertain .

MSL-109 adjuvant therapy

placebo-controlled

placebo

Primary drug therapy

placebo-treated

placebo-treated

placebo

placebo-treated

efficacy and safety

rates of retinitis progression

mortality rate

mortality

mortality rates

mortality rate

mortality rate

ineffective

mortality rate

cytomegalovirus retinitis

Ocular Complications

Two hundred nine

acquired immunodeficiency syndrome

CMV retinitis


Lower extremity deep vein thrombosis : a prospective , randomized , controlled trial in comatose or sedated patients undergoing femoral vein catheterization . OBJECTIVES To determine the rate of lower extremity deep vein thrombosis after the use of femoral catheters in intensive care unit ( ICU ) comatose or sedated adults . Results were then compared with results of patients undergoing superior vena cava catheterization . DESIGN Prospective , randomized , controlled , unblinded study . SETTING A mixed medical/surgical ICU in a university hospital . PATIENTS Sixty-one comatose or sedated patients admitted to the ICU who underwent central venous catheterization . INTERVENTIONS Patients were monitored for signs of thrombotic complications . On catheter removal , a lower-extremity bilateral phlebographic examination was performed in each patient . MEASUREMENTS AND MAIN RESULTS After randomization , 31 patients underwent femoral vein catheterization and 30 patients underwent superior vena cava catheterization , either by axillary ( 21 patients ) or internal jugular vein ( 10 patients ) cannulation . Single lumen polyurethane catheters were inserted for a mean duration of 7.1 +/- 4.6 ( SD ) days in the femoral vein group and 9.9 +/- 5.5 days in the superior vena cava group ( p = NS ) . No patient had clinical signs of leg venous thrombosis or pulmonary embolism during the study period . In each patient , lower extremity bilateral phlebography was performed at the time of catheter removal . Leg phlebographies were normal in 18 ( 60 % ) patients in the femoral vein group and 26 ( 84 % ) patients in the superior vena cava group . Fibrin sleeves which developed around the femoral catheters were seen in seven ( 23.3 % ) patients in the femoral vein group and in no patients in the superior vena cava cannulation group . Three patients had femoral vein thrombosis , two ( 6.6 % ) patients in the femoral vein group ( two nonobstructive thromboses , adherent to the common femoral vein wall ) and one ( 3.0 % ) patient in the superior vena cava group ( nonobstructive thrombosis which developed in the superficial femoral vein ) ( p = NS ) . Lower deep extremities thrombosis developed in five ( 16.7 % ) patients in the femoral vein group and in five ( 16 % ) patients in the superior vena cava group ( p = NS ) . CONCLUSIONS Femoral vein catheterization with a polyurethane catheter is associated with a lower rate of extremity deep vein thrombosis which is similar to the rate observed after superior vena cannulation in comatose or sedated patients . Femoral vein thrombosis was observed at a rate of 6.6 % after femoral vein cannulation and a rate of 3 % after superior vena cava cannulation . Given the acceptable rate of this clinically important complication , femoral vein cannulation offers an attractive alternative to insertion via the vena cava in the critically ill .

femoral vein catheterization

femoral catheters

superior vena cava catheterization

central venous catheterization

femoral vein catheterization

superior vena cava catheterization

Single lumen polyurethane catheters

femoral vein group

superior vena cava

lower extremity bilateral phlebography

femoral vein

superior vena cava cannulation

femoral vein

superior vena cava

Femoral vein catheterization

femoral vein cannulation

superior vena cava cannulation

femoral vein cannulation

vena cava

Lower extremity deep vein thrombosis :

thrombotic complications .

leg venous thrombosis

pulmonary embolism

lower extremity bilateral phlebography

Leg phlebographies

Fibrin sleeves

femoral vein thrombosis

Lower deep extremities thrombosis

rate of extremity deep vein thrombosis

Femoral vein thrombosis

Sixty-one


Biochemical markers as predictors of bone mineral density changes after GnRH agonist treatment . To evaluate bone biochemical markers as predictors of the efficacy of a hormone replacement therapy ( HRT ) , we studied the bone changes induced by the cessation and return of ovarian function in 28 patients treated for 6 months with a GnRH agonist . This model reproduced the effects observed in postmenopausal women with high bone turnover treated with HRT . At the end of the treatment , Z scores were 1.8 +/- 0.3 for Crosslaps ( CTx ) and deoxypyridinoline ( D-Pyr ) , and 1.1 +/- 0.2 for bone alkaline phosphatase ( B-ALP ) and osteocalcin ( OC ) . This indicated an imbalance in bone remodeling with a high bone resorption . Bone mineral density ( BMD ) fell by 4.2 +/- 2.5 % . The changes in BMD between the 6th and 12th months were 0 . 34 +/- 2.24 and -1.73 +/- 3.25 % at the lumbar spine and the femoral neck , respectively . Biochemical markers except urinary calcium and hydroxyproline measured at 6 months were positively correlated with the BMD changes at the lumbar spine . After the resumption of menstruation , 13 of 28 women displayed positive spine BMD changes between the 6th and 12th months ; in this group , bone biochemical markers measured at 6 months were significantly higher ( P = 0.02 ) . Stepwise regression analysis showed that the association of B-ALP and D-Pyr measured at 6 months explained 40 % of BMD variance and the association of B-ALP , PTH , and estradiol 56 % . We conclude that measuring individual biochemical bone markers can help to predict the bone effect of an increase in the circulating estradiol in women with ovarian deficiency .

GnRH agonist

hormone replacement therapy ( HRT )

GnRH agonist

efficacy

Z scores

bone alkaline phosphatase ( B-ALP )

osteocalcin ( OC )

imbalance in bone remodeling

high bone resorption

Bone mineral density ( BMD )

changes in BMD

Biochemical markers

urinary calcium and hydroxyproline

BMD changes at the lumbar spine

positive spine BMD changes

bone biochemical markers

association of B-ALP and D-Pyr

BMD variance

of B-ALP

PTH

estradiol

biochemical bone markers

bone effect

after GnRH agonist treatment .

hormone replacement therapy


Effects of creatine supplementation on repetitive sprint performance and body composition in competitive swimmers . In a double-blind and randomized manner , 18 male and female junior competitive swimmers supplemented their diets with 21 g.day-1 of creatine monohydrate ( Cr ) or a maltodextrin placebo ( P ) for 9 days during training . Prior to and following supplementation , subjects performed three 100-m freestyle sprint swims ( long course ) with 60 s rest/recovery between heats . In addition , subjects performed three 20-s arm ergometer maximal-effort sprint tests in the prone position with 60 s rest/recovery between sprint tests . Significant differences were observed among swim times , with Cr subjects swimming significantly faster than P subjects following supplementation in Heat 1 and significantly decreasing swim time in the second 100-m sprint . There was also some evidence that cumulative time to perform the three 100-m swims was decreased in the Cr group . Results indicate that 9 days of Cr supplementation during swim training may provide some ergogenic value to competitive junior swimmers during repetitive sprint performance .

creatine supplementation

creatine monohydrate ( Cr )

maltodextrin placebo ( P )

Cr

swim times

swim time


A comparison of antiarrhythmic-drug therapy with implantable defibrillators in patients resuscitated from near-fatal ventricular arrhythmias . The Antiarrhythmics versus Implantable Defibrillators ( AVID ) Investigators . BACKGROUND Patients who survive life-threatening ventricular arrhythmias are at risk for recurrent arrhythmias . They can be treated with either an implantable cardioverter-defibrillator or antiarrhythmic drugs , but the relative efficacy of these two treatment strategies is unknown . METHODS To address this issue , we conducted a randomized comparison of these two treatment strategies in patients who had been resuscitated from near-fatal ventricular fibrillation or who had undergone cardioversion from sustained ventricular tachycardia . Patients with ventricular tachycardia also had either syncope or other serious cardiac symptoms , along with a left ventricular ejection fraction of 0.40 or less . One group of patients was treated with implantation of a cardioverter-defibrillator ; the other received class III antiarrhythmic drugs , primarily amiodarone at empirically determined doses . Fifty-six clinical centers screened all patients who presented with ventricular tachycardia or ventricular fibrillation during a period of nearly four years . Of 1016 patients ( 45 percent of whom had ventricular fibrillation , and 55 percent ventricular tachycardia ) , 507 were randomly assigned to treatment with implantable cardioverter-defibrillators and 509 to antiarrhythmic-drug therapy . The primary end point was overall mortality . RESULTS Follow-up was complete for 1013 patients ( 99.7 percent ) . Overall survival was greater with the implantable defibrillator , with unadjusted estimates of 89.3 percent , as compared with 82.3 percent in the antiarrhythmic-drug group at one year , 81.6 percent versus 74.7 percent at two years , and 75.4 percent versus 64.1 percent at three years ( P < 0.02 ) . The corresponding reductions in mortality ( with 95 percent confidence limits ) with the implantable defibrillator were 39+/-20 percent , 27+/-21 percent , and 31+/-21 percent CONCLUSIONS Among survivors of ventricular fibrillation or sustained ventricular tachycardia causing severe symptoms , the implantable cardioverter-defibrillator is superior to antiarrhythmic drugs for increasing overall survival .

antiarrhythmic-drug therapy

implantable defibrillators

Antiarrhythmics

Implantable Defibrillators

implantable cardioverter-defibrillator

antiarrhythmic drugs

class III antiarrhythmic drugs

amiodarone

implantable cardioverter-defibrillators

antiarrhythmic-drug therapy .

implantable defibrillator

antiarrhythmic-drug

implantable defibrillator

implantable cardioverter-defibrillator

antiarrhythmic drugs

overall mortality .

survival

mortality


Randomised trial of efficacy and safety of oral ganciclovir in the prevention of cytomegalovirus disease in liver-transplant recipients . The Oral Ganciclovir International Transplantation Study Group [ corrected ] . BACKGROUND Cytomegalovirus ( CMV ) disease is a frequent cause of serious morbidity after solid-organ transplantation . The prophylactic regimens used to prevent CMV infection and disease have shown limited benefit in seronegative recipients . We studied the safety and efficacy of oral ganciclovir in the prevention of CMV disease following orthotopic liver transplantation . METHODS Between December , 1993 , and April , 1995 , 304 liver-transplant recipients were randomised to receive oral ganciclovir 1000 mg or matching placebo three times a day . Seronegative recipients of seronegative livers were excluded . Study drug was administered as soon as the patient was able to take medication by mouth ( no later than day 10 ) until the 98th day after transplantation . Patients were assessed at specified times throughout the first 6 months after surgery for evidence of CMV infection , CMV disease , rejection , opportunistic infections , and possible drug toxicity . FINDINGS The Kaplan-Meier estimate of the 6-month incidence of CMV disease was 29 ( 18.9 % ) of 154 in the placebo group , compared with seven ( 4.8 % ) of 150 in the ganciclovir group ( p < 0.001 ) . In the high-risk group of seronegative recipients ( R- ) of seropositive livers ( D+ ) , incidence of CMV disease was 11 ( 44.0 % ) of 25 in the placebo group , three ( 14.8 % ) of 21 in the ganciclovir group ( p = 0.02 ) . Significant benefit was also observed in those receiving antibodies to lymphocytes , where the incidence of CMV disease was 12 ( 32.9 % ) of 37 in the placebo group and two ( 4.6 % ) of 44 in the ganciclovir group ( p = 0.002 ) . Oral ganciclovir reduced the incidence of CMV infection ( placebo 79 [ 51.5 % ] of 154 ; ganciclovir 37 [ 24.5 % ] of 150 ; p < 0.001 ) and also reduced symptomatic herpes-simplex infections ( Kaplan-Meier estimates : placebo 36 [ 23.5 % ] of 154 ; ganciclovir five [ 3.5 % ] of 150 ; p < 0.001 ) . INTERPRETATION Oral ganciclovir is a safe and effective method for the prevention of CMV disease after orthotopic liver transplantation .

oral ganciclovir

Ganciclovir

oral ganciclovir

oral ganciclovir 1000

placebo

ganciclovir

placebo

ganciclovir

placebo

ganciclovir

placebo

ganciclovir

placebo

ganciclovir

efficacy and safety

safety and efficacy

6-month incidence of CMV disease

incidence of CMV disease

CMV disease

incidence of CMV infection

symptomatic herpes-simplex infections

liver-transplant

seronegative livers

liver transplantation


The effect of valaciclovir on cytomegalovirus viremia and viruria detected by polymerase chain reaction in patients with advanced human immunodeficiency virus disease . AIDS Clinical Trials Group Protocol 204/Glaxo Wellcome 123-014 International CMV Prophylaxis Study Group . Samples of blood and urine were collected at baseline , week 4 , and week 8 and then every 8 weeks from 310 patients entering a controlled trial of prophylaxis with valaciclovir versus acyclovir . Samples were tested under code by polymerase chain reaction ( PCR ) in one laboratory . The median number of samples collected from each patient was 5 for blood ( range , 0-15 ) and 5 for urine ( range , 0-15 ) . Both baseline PCR viremia and PCR viruria were significantly associated with future cytomegalovirus ( CMV ) disease ( P = .002 and P = .02 , respectively ) . The greatest effect of valaciclovir on CMV disease was seen in patients who were PCR-positive in blood at baseline ( P = .002 ) , although a significant effect was also seen in those who were PCR-negative in urine ( P = .02 ) . Thus , PCR viremia provides prognostic information about CMV disease in AIDS patients , and valaciclovir showed activity as both a preemptive and prophylactic agent .

valaciclovir

prophylaxis

valaciclovir

acyclovir

valaciclovir

valaciclovir

cytomegalovirus viremia

number of samples

PCR viremia and PCR viruria

CMV

PCR viremia


Safety and immunogenicity of a combined pentavalent diphtheria , tetanus , acellular pertussis , inactivated poliovirus and Haemophilus influenzae type b-tetanus conjugate vaccine in infants , compared with a whole cell pertussis pentavalent vaccine . BACKGROUND We compared the safety and immunogenicity of two combined diphtheria-tetanus-pertussis-inactivated poliovirus vaccines containing either acellular ( Pa , SmithKline Beecham Biologicals ) or whole cell ( Pw , Pasteur Merieux Connaught ) pertussis components , mixed with a Haemophilus influenzae type b polysaccharide polyribosylribitol phosphate-tetanus conjugate vaccine in an open , randomized study in healthy infants . DESIGN The combined vaccines were given at 2 , 4 , 6 and 12 months of age , and serum samples were obtained at ages 2 , 6 , 7 , 12 and 13 months . Adverse events were obtained by diary cards . RESULTS The Pa group ( n = 101 ) had a clearly lower incidence of both local and systemic adverse events than the Pw group ( n = 100 ) . Immunogenicity was comparable for the diphtheria and tetanus components , but significantly superior for pertussis toxin , filamentous hemagglutinin , pertactin and polioviruses 1 , 2 and 3 in the Pa group . Both groups had an appropriate response with regard to H. influenzae type b polysaccharide polyribosylribitol phosphate , but the dynamics of the response were significantly different : geometric mean concentrations ( micrograms per ml ) after the second , third and booster doses were 1.27 , 5.06 and 23.12 in the Pa group and 2.72 , 6.66 and 13.59 in the Pw group , respectively ( P = 0.0002 after second dose ; P = 0.0005 after booster ) . CONCLUSION The presently studied diphtheria , tetanus , acellular pertussis-H. influenzae b vaccine conjugated to tetanus toxoid combination was at least as immunogenic as the diphtheria , tetanus , whole cell pertussis-H. influenzae b vaccine conjugated to tetanus toxoid combination , with a significantly better safety profile . This is of obvious importance in countries where inactivated poliovirus vaccine is part of the routine infant immunization programs .

pentavalent diphtheria

tetanus

acellular pertussis

Pa , SmithKline Beecham Biologicals

tetanus toxoid combination

Immunogenicity

geometric mean concentrations

infants

healthy

infants

local and systemic adverse events


Postoperative analgesia by D-myo-inositol-1,2,6-trisphosphate in patients undergoing cholecystectomy . UNLABELLED D-myo-inositol-1,2,6-trisphosphate ( 1,2,6-IP3 ) possesses antiinflammatory properties , such as reduced eicosanoid synthesis and inhibition of inflammation-induced edema . These properties suggest possible analgesic effects . The analgesic effect of 1,2,6-IP3 was evaluated in a double-blind , randomized study in 24 patients undergoing cholecystectomy . Ten patients received 1,2,6-IP3 as an intravenous ( i.v . ) bolus dose of 240 mg , followed by a continuous i.v . infusion at 90 mg/h for 24 h. The placebo group ( n = 14 ) received corresponding volumes of isotonic saline . Postoperative pain ( visual analog pain scale ; VAS ) and opiate analgesic requirements ( ketobemidon ) were evaluated during five postoperative days . Results showed significantly reduced pain during the first five postoperative days in patients treated with 1,2,6-IP3 , as measured by using a VAS ( P < 0.05 ) . The requirements of opioid analgesics were significantly reduced during the first three postoperative days ( P < 0.05 ) . No drug-related side effects were observed . Results of the present study demonstrate a potent and long-lasting analgesic effect of 1,2,6-IP3 , possibly related to its antiinflammatory properties . IMPLICATIONS A new antiinflammatory drug under investigation , inositol-1,2,6-trisphosphate , was evaluated as a possible analgesic in a pilot study during the postoperative period in cholecystectomized patients . Results showed significantly lower pain assessment and opioid consumption , which should encourage further studies .

cholecystectomy

placebo

isotonic saline

ketobemidon

analgesic effects

analgesic effect

Postoperative pain

visual analog pain scale ; VAS

opiate analgesic requirements

ketobemidon

pain

VAS

requirements of

opioid analgesics

drug-related side effects

lower pain assessment

opioid consumption

patients undergoing cholecystectomy


A carbohydrate meal attenuates the forearm vasoconstrictor response to lower body subatmospheric pressure in healthy young adults . The cardiovascular ( CV ) responses to meal ingestion and orthostasis are well established . The effect of meal ingestion and meal composition on the CV responses to orthostasis are unknown . The effect of high carbohydrate ( HC ) and high fat ( HF ) meal ingestion on the CV responses to simulated orthostatic stress ( using graded lower body subatmospheric pressure ( LBSP ) ) was assessed in nine healthy young volunteers . Cardiac output ( CO ) , forearm blood flow ( FABF ) heart rate ( HR ) and blood pressure ( BP ) were measured before and during LBSP while fasted and after eating HC and HF meals . Ingestion of both meals led to an increase in CO and HR . Both meals resulted in a fall in total peripheral resistance but only HC led to a significant fall in BP ( p < 0.05 ) . HF had no effect on the CV responses to LBSP , whereas HC resulted in attenuated FABF and forearm vascular resistance responses ( p < 0.05 ) . Thus , ingestion of an HC meal significantly attenuates the forearm vascular response to orthostatic stress and the hypotensive effect of orthostasis is additive to that occurring after an HC meal .

carbohydrate meal

meal ingestion

high carbohydrate ( HC )

high fat ( HF

HC

HF

HC meal

blood pressure ( BP )

CO

HR

total peripheral resistance

BP

LBSP

adults

nine


The accuracy of clinical neurosensory testing for nerve injury diagnosis . PURPOSE The accuracy of the clinical neurosensory test to diagnose trigeminal nerve injuries has never been statistically evaluated . The purpose of this study was to determine the statistical efficacy of the clinical neurosensory test using surgical findings as the " gold " standard , and to determine whether a correlation existed between the sensory impairment score obtained by preoperative testing and the degree of nerve injury found at surgery . MATERIALS AND METHODS A multisite , randomized , prospective , blinded , clinical trial was conducted on 130 patients with inferior alveolar nerve ( IAN ) and lingual nerve ( LN ) injuries . Preoperatively , patients were provided a sensory impairment score using a three-level drop-out clinical neurosensory test ( NST ) , and blind comparisons were made with the surgical findings postoperatively . RESULTS The positive predictive and negative predictive values for LN-injured patients were 95 % and 100 % , respectively . The positive predictive and negative predictive values for IAN patients were 77 % and 60 % , respectively . There were statistically significant differences in the distribution of age , duration of injury , cause of injury , presence of neuropathic pain , presence of trigger pain , and degree of injury between the IAN and LN patient populations . There was a statistically significant positive relationship found between the sensory impairment score and the degree of nerve injury . CONCLUSIONS The NST is a clinically useful method to diagnose IAN and LN injuries . However , the NST results are less efficient for IAN injuries than LN injuries , and have a high incidence of false-positive ( 23 % ) and false-negative ( 40 % ) results when testing patients with IAN injuries . The different rates of statistical efficiency between the two groups of patients may be attributable to differences in prevalence and biologic covariates .

clinical neurosensory testing

clinical neurosensory test

NST

accuracy

clinical neurosensory testing

less efficient

high incidence of false-positive

false-negative

statistical efficiency

patients with IAN injuries .


Electrical sources of P300 event-related brain potentials revealed by low resolution electromagnetic tomography . 2 . Effects of nootropic therapy in age-associated memory impairment . In a double-blind , placebo-controlled study the effects of Actovegin on frontal and parietal electrical P300 sources revealed by low resolution electromagnetic tomography ( LORETA ) were studied in age-associated memory impairment ( AAMI ) patients . Actovegin is a protein-free metabolically active hemoderivative improving oxygen and glucose utilization . Each patient had , in randomized order , a treatment of 2 weeks with 250 ml 20 % Actovegin and 250 ml placebo daily . Auditory ERPs were recorded before and 5 h after drug administration on day 1 ( acute effect ) and on day 15 ( subacute and superimposed effect ) . Compared to age- and sex-matched normal controls , AAMI patients showed a trend towards P300 latency prolongation and a significantly reduced P300 global field power ( GFP ) . Maximal LORETA source strength did not differ from controls . After Actovegin parietal P300 scalp amplitudes increased , while frontal and temporal amplitudes decreased as compared to placebo . This increase in hilliness , measured by the GFP , was significant . Moreover , the parietal P300 source strength increased after acute , subacute and superimposed infusion of Actovegin as compared to placebo . This may reflect improved availability of cognitive processing resources in the parietal cortex , an area that on the one hand plays an important role in fundamental aspects of attention and on the other hand has been found to be functionally impaired in dementia .

nootropic therapy

Actovegin

2 weeks with 250 ml 20 % Actovegin

250 ml placebo

Auditory ERPs

placebo

placebo

P300 latency prolongation

P300 global field power

Maximal LORETA source strength

frontal and temporal amplitudes

hilliness

parietal P300 source strength

age-associated memory impairment


Randomised community-based trial of annual single-dose diethylcarbamazine with or without ivermectin against Wuchereria bancrofti infection in human beings and mosquitoes . BACKGROUND WHO has targeted lymphatic filariasis for elimination . Studies of vector-parasite relations of Wuchereria bancrofti suggest that a reduction in the microfilarial reservoir by mass chemotherapy may interrupt transmission and thereby eliminate infection . However , no field data exist on the impact of chemotherapy alone on vector efficiency and transmission intensity of W bancrofti . We compared the impact of an annual community-wide single-dose treatment with diethylcarbamazine alone or with ivermectin on rate and intensity of microfilaraemia , and transmission intensity in an area of Papua New Guinea endemic for intense W bancrofti transmission . METHODS We carried out clinical and parasitological surveys in 14 communities in matched pairs . People aged 5 years or older in seven communities received randomly assigned diethylcarbamazine 6 mg/kg and people in the other seven communities received diethylcarbamazine 6 mg/kg plus ivermectin 400 micrograms/kg . We made physical examinations for hydroceles and leg oedema and investigated microfilarial densities by membrane filtration before and after treatment . We selected five communities for monthly entomological surveys between September , 1993 , and September , 1995 . Mosquitoes were collected in these communities by the all-night landing catch method and were individually dissected to identify rates of infection and infectiveness . FINDINGS 2219 ( 87.6 % ) of 2534 eligible people received treatment . Microfilarial rate and density had decreased 1 year after treatment in all 14 communities ; this decrease was significantly higher in communities given combined therapy than in those given diethylcarbamazine alone ( mean decreases 57.5 % and 30.6 % , respectively ; p = 0.0013 ) . Greater decreases were also seen in community-specific microfilarial intensity with combined therapy ( mean reductions 91.1 % and 69.8 % , respectively ; p = 0.0047 ) . The rate of leg oedema was not altered , but the frequency of advanced hydroceles decreased by 47 % with combined therapy and 56 % with diethylcarbamazine alone . 26,641 Anopheles punctulatus mosquitoes were caught during 499 person-nights of landing catches . Exposure to infective third-stage larvae decreased in all monitored five communities . Annual transmission potential decreased by between 75.7 % and 98.8 % in combined-therapy communities and between 75.6 % and 79.4 % in communities given diethylcarbamazine alone . Transmission was almost interrupted in two communities treated with combined therapy . INTERPRETATION Annual single-dose community-wide treatment with diethylcarbamazine alone or with ivermectin is effective for the control of lymphatic filariasis in highly endemic areas , but combination therapy brings about greater decreases in rates and intensity of microfilaraemia .

diethylcarbamazine

ivermectin

chemotherapy

diethylcarbamazine

diethylcarbamazine

ivermectin

diethylcarbamazine

diethylcarbamazine

Microfilarial rate and density

rate of leg oedema

frequency of advanced hydroceles

Annual transmission potential

effective

Wuchereria bancrofti infection


Comparison of single-dose oral granisetron versus intravenous ondansetron in the prevention of nausea and vomiting induced by moderately emetogenic chemotherapy : a multicenter , double-blind , randomized parallel study . PURPOSE The antiemetic effectiveness and safety of single-dose oral granisetron were compared with intravenous ( I.V . ) ondansetron in chemotherapy-naive patients who received moderately emetogenic chemotherapy . PATIENTS AND METHODS In this double-blind , parallel-group study , patients naive to emetogenic chemotherapy ( N = 1,085 ) who were scheduled to receive cyclophosphamide- ( 500 to 1,200 mg/m2 ) or carboplatin ( > or = 300 mg/m2 ) based chemotherapy , were randomized to receive either oral granisetron ( n = 542 ) or I.V . ondansetron ( n = 543 ) . Efficacy assessments included the proportion of patients in each treatment group with total control over the 24 and 48 hours following chemotherapy initiation , as well as incidence and severity of nausea and emesis and use of antiemetic rescue medication . Prophylactic corticosteroids were allowed . Safety assessment was based on patients ' reports of adverse experiences . RESULTS Approximately 80 % of patients received prophylactic corticosteroids . Single-dose oral granisetron ( 2 mg ) and I.V . ondansetron ( 32 mg ) resulted in equivalent levels of total emetic control during the first 48 hours after chemotherapy . The proportion of nausea- and emesis-free patients at 24 and 48 hours were also approximately equivalent . The most commonly reported adverse experiences were headache , asthenia , and constipation . More patients who received ondonsetron than granisetron reported dizziness ( 9.6 % v 5.4 % , respectively ; P = .011 ) and abnormal vision ( 4.2 % v 0.6 % , respectively ; P < .001 ) . CONCLUSION A single oral dose of granisetron ( 2 mg ) resulted in equivalent levels of antiemetic protection as I.V . ondansetron ( 32 mg ) . Both agents were well tolerated , although more dizziness and abnormal vision were reported with ondansetron . Because the two antiemetic regimens exhibited equivalent efficacies , additional factors such as convenience and cost of therapy should be considered .

granisetron

ondansetron

granisetron

ondansetron

moderately emetogenic chemotherapy

emetogenic chemotherapy

carboplatin

granisetron

ondansetron

treatment group

control

chemotherapy

prophylactic corticosteroids

granisetron

ondansetron

chemotherapy

ondonsetron

granisetron

granisetron

ondansetron

ondansetron

nausea and emesis

total emetic control

dizziness

abnormal vision

antiemetic protection

dizziness and abnormal vision


Influence of special-effect contact lenses ( Crazy Lenses ) on visual function . PURPOSE Special-effect contact lenses ( opaque , tinted soft contact lenses that incorporate decorative images such as " cateyes , " stars , or hearts to alter eye color and structure ) have become increasingly popular . The purpose of this study was to investigate whether such lenses impair visual function . METHODS A clear soft contact lens and a special-effect soft contact lens ( Crazy lens , ) were fit in changing sequence in nine healthy subjects . The parameters studied included : visual acuity , contrast sensitivity ( with and without glare ) , visual field , and mesopic vision ( with and without glare ) . RESULTS The following parameters displayed a statistically significant difference ( P < 0.05 ) . Visual acuity was decreased to 0.9 +/- 0.23 in the Crazy lens group as compared with 1.2 +/- 0.13 in the clear lens group . Goldmann visual field displayed a significant constriction of the isopters : III/4 , I/4 , and I/3 . Mesopic vision without glare was reduced from 1:2.5 to 1:7.4 . Contrast sensitivity was significantly reduced in a photopic condition with and without glare and in a scotopic condition without glare . Furthermore , the special-effect lenses were associated with a decrease in lens wearing comfort . CONCLUSIONS Special-effect contact lenses were associated with a reduction of many visual functions , including visual acuity and contrast sensitivity . For some wearers this may interfere with activities where excellent vision is crucial , such as driving a car .

Special-effect contact lenses

A clear soft contact lens

clear lens

special-effect lenses

Special-effect contact lenses

visual function

visual function

visual acuity

visual field

Visual acuity

Goldmann visual field

constriction of the isopters

Mesopic vision without glare

Contrast sensitivity

lens wearing comfort

visual functions

visual acuity

contrast sensitivity

nine

healthy


Twice-a-day versus four-times-a-day ofloxacin treatment of external ocular infection . PURPOSE The purpose of this study was to compare the efficacies of 0.3 % ofloxacin eyedrops , when given twice-a-day ( BID ) versus four-times-a-day ( QID ) , for the treatment of external ocular disease . METHOD Fifty patients with blepharitis , conjuctivitis , or blepharoconjunctivitis were randomly assigned to treatment with 0.3 % ofloxacin eyedrops , BID or QID , for 10 days . Signs , symptoms , and cultures were evaluated at the beginning and at the end of the study . RESULTS The clinical outcome was virtually identical in the two groups . There was a significant decrease in clinical scores in the BID and QID groups by days 3 to 5 ( 2.6-3.0 points ) and a further decrease by day 11 ( 4.3-5.0 points ) . There was no significant difference between the two groups at any time interval . Microbiologic studies showed a reduction in colony-forming units in 87 % of the BID group and in 80 % of the QID group . CONCLUSION The treatment of external ocular disease with 0.3 % ofloxacin eyedrops was equally effective when given BID or QID .

efficacies

clinical scores

colony-forming units

external ocular disease

Fifty

blepharitis

conjuctivitis

blepharoconjunctivitis


Randomized controlled study of customized preventive medicine reminder letters in a community practice . OBJECTIVE To test the effectiveness of customized , family-oriented reminder letters in activating patients to seek appropriate preventive services . DESIGN Randomized clinical trial . One group received computer-generated , customized letters explaining recommended preventive procedures for each family member . A second group received a form letter listing recommendations for all preventive procedures for all age and sex groups . A third group ( control group ) received no letters . SETTING A private medical centre , without university affiliation , in rural Quebec . PARTICIPANTS From 8770 patients who met study criteria , 719 families were randomly selected . Data were available for 1971 of 1998 patients in these families . MAIN OUTCOME MEASURES The Family Received Index is the proportion of all procedures for which a family was overdue that they received . The Family End-of-study Up-to-date Index is the proportion of procedures for which the family was eligible and for which they were up-to-date at the end of the study . RESULTS The Family Received Index for families mailed customized letters was more than double the index for patients not mailed letters ( Kruskal-Wallis P = .0139 ) . Comparison of the Family End-of-study Up-to-date indices also demonstrated that families of patients sent customized letters were more likely to be up-to-date than families not sent letters ( Kruskal-Wallis P = .0054 ) . No statistically significant difference appeared between the number of preventive measures received by the control group and the form-letter group . CONCLUSIONS This study demonstrates a clinically small but statistically significant value to customizing reminder letters .

customized letters

customized letters

control

form-letter

customizing reminder letters .

effectiveness

The Family Received Index

Family End-of-study Up-to-date Index

Family Received Index

Family End-of-study Up-to-date indices


The cognitive , subjective , and physical effects of a ginkgo biloba/panax ginseng combination in healthy volunteers with neurasthenic complaints . We evaluated the effects of a Ginkgo biloba/ginseng combination on cognitive function in this 90-day , double-blind , placebo-controlled , parallel-group study . Sixty-four healthy volunteers ( aged 40 to 65 years ) , selected on the basis of fulfilling the ICD-10 F48.0 criteria for neurasthenia , were assigned randomly to four equal dosing groups , receiving 80 , 160 , or 320 mg of the combination b.i.d . or placebo . Assessments were performed on the day before dosing , and again at Days 1 , 30 , and 90 at 1 hour after the morning dose and 1 hour after the afternoon dose . The assessments included the Cognitive Drug Research ( CDR ) computerized assessment system , the Vienna Determination Unit , cycle ergometry , and various questionnaires . The treatments were well tolerated by all volunteers . On Day 90 at 1 hour post morning dosing , dose-related improvements were seen on the CDR tests , the 320 mg dose being significantly superior to placebo . These effects , however , were reversed 1 hour after the afternoon dose , possibly suggesting that a longer inter-dosing interval would be preferable . The 80-mg dose produced a significant benefit on the ergometry assessment of heart rate at maximum load . There were also several supporting changes from other assessments , including an advantage of 320 mg over placebo on the global score from the Symptom Checklist-90-revised ( SCL-90-R ) at Day 90 .

ginkgo biloba/panax ginseng combination

Ginkgo biloba/ginseng combination

placebo-controlled

placebo

placebo

effects

cognitive function

the Vienna Determination Unit

well tolerated

dose-related improvements

ergometry assessment of heart rate

Sixty-four healthy volunteers

aged 40 to 65 years )

criteria for neurasthenia


A plaque index for occlusal surfaces and fissures . Measurement of repeatability and plaque removal . Plaque indices have largely been developed for buccal and lingual tooth surfaces . There has been minimal interest in plaque accumulation on occlusal surfaces despite the predilection for caries at these sites . A numerical plaque index ( 0-5 ) is described based on the presence and distribution of plaque in the fissures and over the occlusal surfaces of permanent molar and premolar teeth . The repeatability of a single examiner in scoring the index was performed using 4 groups of 10 subjects . Each group of volunteers suspended tooth cleaning for 48 h and the index scored after disclosing plaque deposits . The index was rescored 60-90 min later . Plaque area was also determined by drawing the outline of plaque onto grids . Except for one condition of repeatability for one group , the 4 conditions of repeatability in scoring the index were met for all 4 groups of subjects . The sensitivity of the index and area recordings to detect plaque removed by brushing was then evaluated . A group of 10 subjects had plaque scored by index and area after suspending toothcleaning for 48 h. Subjects were then randomly allocated to brush or not brush their teeth and plaque rescored . The experiment was then repeated and brushing or not brushing crossed over . Highly significant differences between brushing and no brushing plaque indices and areas were determined . In conclusion , the occlusal fissure plaque index was easy to apply , repeatable and sufficiently sensitive to detect plaque removed by brushing . The index could find use as an additional measure of oral hygiene , in clinical trials on plaque control and possibly epidemiological studies relating to caries .

suspended tooth cleaning

plaque scored by index

brushing

not brushing

plaque indices

occlusal fissure plaque index

4 groups

plaque


The importance of the dual-switch valve for the treatment of adult normotensive or hypertensive hydrocephalus . Since the beginning of 1995 the new hydrostatic dual-switch valve ( DSV ) was implanted in 35 adult patients with hydrocephalus of different etiology . 26 patients suffered from normotensive hydrocephalus ( 10 idiopathic and 16 symptomatic ) , and 9 patients from hypertensive hydrocephalus of various origin . The first 21 cases of this cohort were compared in a randomized study with a comparable group of 21 hydrocephalic patients who received a conventional differential-pressure ( DP- ) valve . The clinical status and CT were assessed prior to shunting , 14 days and 3 and 6 months after the operation . The reduction of ventricular size was evaluated by the measurement of the Evans Index . The CT follow-up in the DSV group was characterized by an only minimal ( 14 ) or only slight ( 16 ) reduction of ventricular size in the vast majority of cases . A comparison of 21 patients with a DSV and the patients with DP valves , evaluated by measuring the reduction of the Evans Index , revealed a distinctly higher percentage of significant regressions in the DP valve collective , without doubt due to chronic overdrainage . The overall clinical result of our 35 patients with a DSV was excellent and good in 31 patients , but the outcome seems to be more dependent on the preshunt damage of the brain than on hydrocephalic aspects . A neglegible incidence of subdural effusions in the DSV group compared to 11 cases in the DP valve collective reflects the ability of the DSV to prevent overdrainage . The capability of the DSV to maintain the IVP within physiological limits after shunting , especially in the upright position , is documented by a comparison with possible unphysiological IVP variations in other valve constructions , which depend on the level of implantation , subcutaneous pressure or CSF flow through the valve .

dual-switch valve

hydrostatic dual-switch valve ( DSV )

DSV

DSV

DP valves

DP valve

DSV

DSV

DP valve

DSV

DSV

ventricular size

Evans Index

preshunt damage of the brain

hydrocephalic aspects .

subdural effusions

overdrainage

IVP

possible unphysiological IVP variations


[ Value of absorbable clips in laparoscopic cholecystectomy . A randomized prospective study ] . Most surgeons use metal clips in laparoscopic cholecystectomy . The aim of this prospective randomized controlled study was to evaluate the efficacy of absorbable clips in elective laparoscopic cholecystectomy . One hundred consecutive patients with symptomatic gallstones without complications were randomized into groups ; group T had two metal clips ( titan clip ETHICONR ) , group R ( laproclipR Davis and Geck ) had one absorbable clip applied on the cystic duct and cystic artery . The patients were followed for one year . There was no difference between the two groups concerning operative time , hospital stay and postoperative complications . The absorbable clips seem to be as effective as metal clips in providing hemostasis in cystic artery and in cystic duct ligation .

absorbable clips

laparoscopic cholecystectomy

laparoscopic cholecystectomy

absorbable clips

elective laparoscopic cholecystectomy

two metal clips ( titan clip ETHICONR )

laproclipR Davis and Geck )

absorbable clips

metal clips

efficacy of absorbable clips

elective laparoscopic cholecystectomy

operative time , hospital stay

postoperative complications

hemostasis

One hundred

symptomatic gallstones


Incidence and clinical significance of false-negative sextant prostate biopsies . PURPOSE Since most patients do not undergo repeat sextant prostate biopsies after a biopsy is positive for prostate cancer , the true incidence of false-negative biopsies is not well defined . We assess the incidence and clinical significance of false-negative sextant prostate biopsies in patients undergoing radical prostatectomy . MATERIALS AND METHODS A total of 118 patients with biopsy proved prostate cancer underwent repeat sextant prostate biopsy before enrollment in a prospective randomized trial of radical prostatectomy with or without neoadjuvant hormonal therapy . Clinical parameters were assessed to determine potential sources of bias . Pathological parameters and prostate specific antigen relapse-free survival rates were compared to determine the clinical significance of false-negative biopsies . RESULTS Of the 118 patients 27 ( 23 % ) had a negative repeat sextant biopsy . Except for initial clinical stage , no differences were noted in the clinical or pathological parameters , or prostate specific antigen relapse rates in patients with negative versus positive repeat biopsies . CONCLUSIONS Our findings suggest that this 23 % incidence of false-negative biopsies represents significant cancer . This relatively high incidence is important to consider in treatment modalities in which prostate biopsy may be performed to determine response to therapy .

radical prostatectomy

radical prostatectomy

neoadjuvant hormonal therapy

clinical or pathological parameters

prostate specific antigen relapse rates


Primary glaucoma triple procedure in patients with primary open-angle glaucoma : the effect of mitomycin C in patients with and without prognostic factors for filtration failure . PURPOSE To investigate the effect of adjunctive mitomycin C on primary glaucoma triple procedure in patients with primary open-angle glaucoma with and without one or more of the prognostic factors for filtration failure of primary glaucoma triple procedure . Those factors include being of African-American race , having a preoperative intraocular pressure of 20 mm Hg or more on maximum tolerated medications , and being on two or more medications preoperatively . METHODS Study patients consisted of 197 consecutive patients with primary open-angle glaucoma who were randomly assigned to receive either no adjunctive mitomycin C ( 101 eyes of 101 patients ) or to receive adjunctive subconjunctival mitomycin C ( 96 eyes of 96 patients ) during the primary glaucoma triple procedure . Kaplan-Meier survival analysis comparisons were made between respective subgroups with and without prognostic indicators for filtration failures using a relatively stringent set of criteria for filtration success of primary glaucoma triple procedure . RESULTS There was no statistically significant ( P = .117 ) difference in filtration success of primary glaucoma triple procedure between the control and mitomycin C groups . Adjunctive mitomycin C significantly ( P < .05 ) improved the filtration outcome of the primary glaucoma triple procedure in the subgroups with each of the three prognostic factors for filtration failure of primary glaucoma triple procedure . On the other hand , in the subgroups without the prognostic factors , adjunctive mitomycin C did not significantly ( P > .05 ) change the filtration outcome of the primary glaucoma triple procedure . CONCLUSION These findings establish the basis for selective use of mitomycin C in patients with primary open-angle glaucoma undergoing primary glaucoma triple procedure .

mitomycin C

adjunctive mitomycin C

effect

effect

filtration success

filtration

filtration outcome


Treatment of hyperinsulinaemia in polycystic ovary syndrome ?


Efficacy of intravenous granisetron to control nausea and vomiting during multiple cycles of cisplatin-based chemotherapy . The safety and efficacy of granisetron ( 10 micrograms/kg and 40 micrograms/kg ) were evaluated during a second ( n = 393 ) and third ( n = 200 ) cycle of chemotherapy in this multicenter , double-blind , randomized , parallel-group study . Granisetron was administered as a single intravenous dose before the start of cisplatin chemotherapy ( > or = 60 mg/m2 ) . Total control ( no vomiting , no retching , no nausea , and no use of antiemetic rescue medication ) after the first 24 hr following chemotherapy was achieved in 40 % and 49 % of patients in Cycles 2 and 3 , respectively , for the 10 micrograms/kg group , and in 42 % and 38 % of patients in Cycles 2 and 3 , respectively , for the 40 micrograms/kg group . Both dose levels of granisetron were well tolerated . The results demonstrate comparable efficacy between the 10 micrograms/kg and 40 micrograms/kg doses of granisetron in preventing nausea and vomiting during repeat cycles of high-dose cisplatin-based chemotherapy . The results of this study show that granisetron 10 micrograms/kg is safe and well tolerated , and remains effective with repeat cycle use .

granisetron

cisplatin-based chemotherapy

granisetron

Granisetron

cisplatin chemotherapy

chemotherapy

granisetron

granisetron

cisplatin-based chemotherapy

granisetron

Total control

no vomiting

no retching , no nausea

no use of antiemetic rescue medication

dose levels of granisetron

nausea

vomiting


Histopathologic changes of the eyelid skin following trichloroacetic acid chemical peel . The use of trichloroacetic acid ( TCA ) as a periorbital and eyelid peel for skin rejuvenation is gaining significant acceptance among oculoplastic surgeons , dermatologists , and other surgery groups . In spite of the current enthusiasm , there remain potentially serious complications resulting from any periorbital peel . Cases of cicatricial ectropion have been reported in phenol-peeled patients , and lower eyelid ectropion has reportedly occurred in patients undergoing deep eyelid peel in conjunction with a blepharoplasty ( 1,2 ) . To avoid this complication , it is necessary to better understand the depth of the wound produced by different strengths and combinations of peeling agents applied to living eyelid tissue and , more important , to determine the concentrations of TCA that are likely to lead to cicatricial ectropion when applied in a consistent fashion . We chose upper-eyelid skin because it is easier to obtain for histopathologic study than lower-eyelid skin and , in our experience , is more sensitive to hypertrophic changes after chemical peeling or carbon dioxide laser resurfacing . We applied TCA to the preseptal skin of 10 patients 48 h before standard upper-eyelid blepharoplasty . The acid was applied to produce a " frost , " using varying concentrations of acid , ranging from 20 to 50 % . The treated skin removed at the time of blepharoplasty was reviewed in a masked fashion by a dermatopathologist to determine the depth of necrosis . We found that superficial peels with necrosis involving 30 % of the epidermis were produced by the lowest-concentration combination of TCA applied ( 20 % followed by 0 % ) . As the strength increased , so did the depth of peel . The combination of 50 % followed by a second application of 50 % produced the deepest peel , with necrosis into the papillary dermis . This finding would indicate that the chance of developing cicatricial ectropion with any of the tested combinations of TCA should be very remote .

trichloroacetic acid chemical peel

trichloroacetic acid ( TCA )

blepharoplasty

TCA

TCA

TCA

TCA

superficial peels with necrosis

applied

strength increased

deepest peel

eyelid skin

phenol-peeled

deep eyelid peel


Comparative dose efficacy study of atorvastatin versus simvastatin , pravastatin , lovastatin , and fluvastatin in patients with hypercholesterolemia ( the CURVES study ) The objective of this multicenter , randomized , open-label , parallel-group , 8-week study was to evaluate the comparative dose efficacy of the 3-hydroxy-3-methylglutaryl coenzyme A ( HMG-CoA ) reductase inhibitor atorvastatin 10 , 20 , 40 , and 80 mg compared with simvastatin 10 , 20 , and 40 mg , pravastatin 10 , 20 , and 40 mg , lovastatin 20 , 40 , and 80 mg , and fluvastatin 20 and 40 mg. Investigators enrolled 534 hypercholesterolemic patients ( low-density lipoprotein [ LDL ] cholesterol > or = 160 mg/dl [ 4.2 mmol/L ] and triglycerides < or = 400 mg/dl [ 4.5 mmol/L ] ) . The efficacy end points were mean percent change in plasma LDL cholesterol ( primary ) , total cholesterol , triglycerides , and high-density lipoprotein cholesterol concentrations from baseline to the end of treatment ( week 8 ) . Atorvastatin 10 , 20 , and 40 mg produced greater ( p < or = 0.01 ) reductions in LDL cholesterol , -38 % , -46 % , and -51 % , respectively , than the milligram equivalent doses of simvastatin , pravastatin , lovastatin , and fluvastatin . Atorvastatin 10 mg produced LDL cholesterol reductions comparable to or greater than ( p < or = 0.02 ) simvastatin 10 , 20 , and 40 mg , pravastatin 10 , 20 , and 40 mg , lovastatin 20 and 40 mg , and fluvastatin 20 and 40 mg. Atorvastatin 10 , 20 , and 40 mg produced greater ( p < or = 0.01 ) reductions in total cholesterol than the milligram equivalent doses of simvastatin , pravastatin , lovastatin , and fluvastatin . All reductase inhibitors studied had similar tolerability . There were no incidences of persistent elevations in serum transaminases or myositis .

atorvastatin

simvastatin

pravastatin

lovastatin

fluvastatin

simvastatin 10 , 20 , and 40 mg

pravastatin 10 , 20 , and 40 mg

lovastatin 20 , 40 , and 80 mg

fluvastatin 20 and 40 mg.

Atorvastatin

simvastatin

pravastatin

lovastatin

fluvastatin

Atorvastatin

simvastatin

pravastatin

lovastatin

fluvastatin

Atorvastatin

simvastatin

pravastatin

lovastatin

fluvastatin

efficacy

LDL cholesterol

LDL cholesterol

total cholesterol

tolerability

serum transaminases or myositis .

patients with hypercholesterolemia

multicenter