The tension-free hernioplasty in a randomized trial . BACKGROUND The tension-free hernioplasty as introduced by Lichtenstein has gained increasing acceptance during the last decade although the technique has not been evaluated in a randomized trial . METHODS This randomized study compares the 2-year follow-up results after 102 tension-free hernioplasties with implantation of a prolene mesh in all groin hernias to 53 Cooper ligament repairs in direct hernias and 53 abdominal ring repairs in indirect hernias . RESULTS After tension-free repairs five hernias recurred ( 5 % ) , and after either Cooper ligament or abdominal ring repair , 16 recurrences were found ( 15 % ) ( P = 0.025 ) . No indirect hernias recurred after a tension-free repair ; 2 recurred after abdominal ring repair ( 4 % ; NS ) . The recurrence rate after tension-free repairs for primary direct inguinal hernias was 7 % as compared with 30 % after Cooper ligament repair ( P = 0.0081 ) . No difference in complication rate between the tested methods was found . CONCLUSION Recurrence rate is reduced to one-third after tension-free herniotomies as compared with the conventionel herniotomies without increase in complication rate .

tension-free hernioplasty

tension-free hernioplasty

tension-free repairs

tension-free repair

abdominal ring repair

tension-free repairs

Cooper ligament repair

tension-free herniotomies

conventionel herniotomies

hernias recurred

recurrences

indirect hernias recurred

complication rate

Recurrence rate

complication rate

hernioplasties

groin hernias

direct hernias

indirect hernias

tension-free herniotomies


Adjvant treatment of tongue and floor of the mouth cancers . Since January 1974 , 95 patients with anterior tongue and floor of the mouth cancers were included in a randomized trial . After stratification according to staging and initial treatment , one-third of the patients received chemotherapy for 2 years ( methotrexate 400 mg followed by citrovorum factor 100 mg + bleomycin 60 mg/week , during the first 15 weeks ) , one-third of the patients received immunotherapy with weekly C. parvum injections during 2 years , while the remaining third did not receive any treatment . If adjuvant treatment seems to delay recurrence it did not significantly decrease the recurrence rate . Survival is also not signigicantly modified by adjuvant treatment and was better for patients with small tumors . Patients who previously received radiotherapy did not benefit from adjuvant therapy .

Adjvant treatment

adjuvant

radiotherapy

adjuvant therapy

delay recurrence

recurrence rate

Survival

mouth cancers

one-third

one-third

third


Baseline characteristics of participants in the Appropriate Blood Pressure Control in Diabetes trial . The ABCD ( Appropriate Blood Pressure Control in Diabetes ) trial is a large , prospective , randomized clinical trial designed to compare the effects of intensive with moderate blood pressure control on the prevention and progression of diabetic nephropathy , retinopathy , cardiovascular disease , and neuropathy in non-insulin-dependent diabetes ( NIDDM ) . The secondary objective is to determine equivalency of the effects of a calcium channel blocker ( nisoldipine ) and of an angiotensin-converting enzyme inhibitor ( enalapril ) as a first-line antihypertensive agent in the prevention and/or progression of these diabetic vascular complications . The study consists of two study populations : a hypertensive one ( diastolic blood pressure of > or = 90.0 mm Hg at the time of randomization ) and a normotensive one ( diastolic blood pressure of 80.0-89.0 mm Hg at the time of randomization ) . A total of 950 men and women aged 40-74 years were randomized and are being followed for 5 years at a single center . There were 470 randomized participants in the hypertensive population and 480 randomized participants in the normotensive population . This report summarizes the demographic , biochemical , and clinical characteristics of the randomized patients at the time of entry into the trial and evaluates the balance between the treatment groups within each population .

moderate blood pressure control

calcium channel blocker

nisoldipine

angiotensin-converting enzyme inhibitor

enalapril

diastolic blood pressure

diastolic blood pressure


Using a choice assessment to predict reinforcer effectiveness . A choice assessment has been found to be a more accurate method of identifying preferences than is single-item presentation . However , it is not clear whether the effectiveness of reinforcement varies positively with the degree of preference ( i.e. , whether the relative preference based on the results of a choice assessment predicts relative reinforcer effectiveness ) . In the current study , we attempted to address this question by categorizing stimuli as high , middle , and low preference based on the results of a choice assessment , and then comparing the reinforcing effectiveness of these stimuli using a concurrent operants paradigm . High-preference stimuli consistently functioned as reinforcers for all 4 clients . Middle-preference stimuli functioned as reinforcers for 2 clients , but only when compared with low-preference stimuli . Low-preference stimuli did not function as reinforcers when compared to high- and middle-preference stimuli . These results suggest that a choice assessment can be used to predict the relative reinforcing value of various stimuli , which , in turn , may help to improve programs for clients with severe to profound disabilities .

choice assessment

A choice assessment

choice assessment

concurrent operants paradigm

choice assessment

stimuli


Injection pain with propofol . Reduction with aspiration of blood . A randomised , controlled , single-blind study was performed on 100 patients to investigate a new method of reducing pain on propofol injection . Aspiration of 2 ml of the patient 's blood into a syringe of propofol immediately before injection was compared with the addition of lignocaine 20 mg or normal saline 2 ml to the propofol before injection . The addition of blood was significantly more effective in reducing pain on injection than the addition of saline ( p < 0.001 ) , but was not significantly more effective than the addition of lignocaine .

propofol .

propofol

propofol

lignocaine 20 mg

normal saline

2 ml to the propofol before injection

Injection pain

pain

reducing pain on injection

effective


Effects of perioperative indomethacin on intracranial pressure , cerebral blood flow , and cerebral metabolism in patients subjected to craniotomy for cerebral tumors . This study was carried out to evaluate the effects of perioperative indomethacin on intracranial pressure ( ICP ) , cerebral blood flow ( CBF ) , and cerebral metabolism . Twenty patients subjected to craniotomy for supratentorial cerebral tumors were anesthetized with thiopental , fentanyl , nitrous oxide , and isoflurane . A PaCO2 level averaging 4.8 kPa ( median ) was achieved . The patients were randomized to intravenous indomethacin 50 mg or placebo administrated after exposure of the dura . ICP was measured continuously subdurally with a 22-gauge canula connected to a transducer . CBF and the arteriovenous difference of oxygen ( AVDO2 ) were measured twice , before and after indomethacin/placebo administration . A significant decrease in ICP from 6.5 to 1.5 mm Hg ( median ) was found after indomethacin administration . This decrease was caused by a significant decrease in CBF associated with a significant increase in AVDO2 . Indomethacin did not affect the cerebral metabolic rate of oxygen , the arteriovenous difference of lactate , or the lactate/oxygen index , suggesting that indomethacin did not provoke global cerebral ischemia . In the indomethacin group , dura was sufficiently relaxed in eight of nine patients and dura was opened without the occurrence of cerebral swelling . In one patient , mannitol treatment was necessary to prevent dural tightness . In the placebo group , mannitol supplemented with hypocapnia was applied in five patients . These findings suggest that perioperative treatment with indomethacin is an excellent treatment of intracranial hypertension during normocapnic isoflurane anesthesia for craniotomy .

indomethacin

intravenous indomethacin 50 mg

indomethacin

intracranial pressure

cerebral blood flow

cerebral metabolism

effects

intracranial pressure ( ICP )

cerebral blood flow ( CBF )

cerebral metabolism

ICP

CBF

arteriovenous difference of oxygen

ICP

CBF

cerebral metabolic rate of oxygen

arteriovenous difference of lactate ,

lactate/oxygen index

cerebral swelling

dural tightness

craniotomy for cerebral tumors

Twenty

five


Efficacy and safety of triamcinolone acetonide aqueous nasal spray in patients with seasonal allergic rhinitis . BACKGROUND In order to accommodate increasing patient preferences a new aqueous formulation of triamcinolone acetonide nasal spray was developed for the relief of symptoms associated with seasonal and perennial allergic rhinitis . OBJECTIVE This multicenter , randomized , double-blind study was designed to compare the efficacy and safety of once-daily triamcinolone acetonide aqueous nasal spray ( 220 micrograms/day ) with placebo in relieving the symptoms of seasonal allergic rhinitis due to ragweed . METHODS One hundred forty patients received either a once daily 220-microgram dose of triamcinolone acetonide aqueous nasal spray or placebo for 2 weeks . Patients evaluated the severity of seasonal allergic rhinitis symptoms daily for 2 weeks according to a 4-point scale ( 0 = absent , 1 = mild , 2 = moderate , 3 = severe ) . Physician and patient global evaluations of overall treatment effectiveness were assessed at the end of the treatment period . RESULTS Patients receiving triamcinolone acetonide aqueous nasal spray , 220 micrograms/day , had significantly ( P < .05 ) greater improvements in all rhinitis symptoms at weeks 1 and 2 and overall for the 2-week treatment period compared with the placebo group . A significant ( P = .006 ) improvement in the nasal index occurred as early as 12 hours after the first dose of triamcinolone acetonide aqueous nasal spray . Both patients and physicians reported a greater overall improvement in symptoms for the triamcinolone acetonide aqueous nasal spray group . There were no differences between the two treatment groups in the incidence of adverse events . CONCLUSIONS This study confirmed that a 220-microgram dose of triamcinolone acetonide aqueous nasal spray , administered once daily for 2 weeks , is well tolerated and reduces effectively the severity of symptoms of seasonal allergic rhinitis due to ragweed .

of triamcinolone acetonide

placebo

placebo

seasonal allergic rhinitis

seasonal allergic rhinitis symptoms

improvements

rhinitis symptoms

improvement in the nasal index occurred

adverse events .

seasonal allergic rhinitis

seasonal allergic rhinitis

One hundred forty

seasonal allergic rhinitis


Effect of hydrochlorothiazide therapy on cardiac arrhythmias in African-American men with systemic hypertension and moderate to severe left ventricular hypertrophy . The effect of hydrochlorothiazide therapy on ventricular arrhythmias was studied in 45 hypertensive African-American men with moderate to severe left ventricular ( LV ) hypertrophy . After medication washout , patients were treated with placebo followed by hydrochlorothiazide . Clinical , biochemical , and 48-hour ambulatory electrocardiographic data was collected after each treatment phase . Signal-averaged electrocardiograms were recorded in a subgroup of 24 patients . Average LV posterior wall thickness was 15 +/- 1.1 mm , septum 16 +/- 2 mm , LV mass 420 +/- 90 g , and LV mass index 212 = 51 g/m2 . Systolic blood pressure ( BP ) was 168 +/- 18 mm Hg after the placebo phase and 146 +/- 15 mm Hg after hydrochlorothiazide ; diastolic BP was 103 +/- 6 mm Hg and 89 +/- 9 mm Hg , respectively . Serum potassium decreased significantly from 4.2 +/- 0.4 mmol/L to 3.7 +/- 0.6 mmol/L after hydrochlorothiazide therapy . The average hourly incidence of ventricular premature contractions was 22 with placebo and 25 with hydrochlorothiazide . There were 3 and 1 couplets and 0.2 and 0.2 runs of ventricular tachycardia per patient per hour , respectively . Variables of signal-averaged electrocardiography did not differ between the 2 treatments . Thus , in hypertensive African-American men with moderate to severe LV hypertrophy , hydrochlorothiazide does not worsen ventricular arrhythmias or signal-averaged electrocardiographic variables .

hydrochlorothiazide therapy

hydrochlorothiazide therapy

placebo

hydrochlorothiazide

hydrochlorothiazide therapy

placebo

hydrochlorothiazide

hydrochlorothiazide

Effect

cardiac arrhythmias

ventricular arrhythmias

Signal-averaged electrocardiograms

Average LV posterior wall thickness

Systolic blood pressure ( BP )

Serum potassium

ventricular premature contractions

ventricular tachycardia

signal-averaged electrocardiography

ventricular arrhythmias

45 hypertensive African-American

men

subgroup of 24 patients


Levosulpiride in functional dyspepsia : a multicentric , double-blind , controlled trial . Abnormalities in gastrointestinal motility have been reported in a substantial proportion of patients with functional dyspepsia , supporting the use of prokinetic drugs for treatment of dyspeptic symptoms . To evaluate efficacy and safety of levosulpiride in short-term treatment , 1298 patients were enrolled in a double-blind multicentric study carried out in 45 Italian Gastroenterology Departments . Patients were randomly assigned to either levosulpiride ( 25 mg tid ) , domperidone ( 10 mg tid ) , metoclopramide ( 10 mg tid ) or placebo ( 1 tablet tid ) for 4 weeks . Patients were selected on the basis of : a ) occurrence in the last 4 weeks of at least 5/10 selected symptoms ( anorexia , nausea , vomiting , upper abdominal pain , postprandial bloating , abdominal fullness , early satiety , belching , heartburn , regurgitation ) , severity of which should reach/exceed a total score of 8 , as assessed by a specific scale ranging from 0 ( absent ) to 3 ( severe ) ; b ) normal results of routine biochemical , ultrasound and endoscopic examinations . In addition , each patient subjectively evaluated efficacy of treatment by a visual analogue scale . Significant improvement was recorded for all symptoms at days 10 and 28 in all groups ( p < 0.001 ) , but levosulpiride was significantly ( p < 0.01 ) superior to domperidone , metoclopramide and placebo both in the overall clinical improvement scale as well as in a subgroup of symptoms ( postprandial bloating , epigastric pain , heartburn ) . Active treatments and placebo were comparable as far as concerns occurrence of side-effects ( 12-20 % ) including galactorrhoea , breast tenderness and menstrual changes .

Levosulpiride

prokinetic drugs

levosulpiride

levosulpiride

domperidone

metoclopramide

placebo

levosulpiride

domperidone

metoclopramide

placebo

Active treatments

placebo

efficacy and safety

efficacy

postprandial bloating

epigastric pain

heartburn

functional dyspepsia

functional dyspepsia ,

dyspeptic symptoms


The evolving clinical status of patients after a myocardial infarction : the importance of post-hospital data for mortality prediction . Studies predicting mortality after myocardial infarction ( MI ) usually rely on in-hospital data , and combine patients admitted for the first MI with recurrent MI patients . Since treatment decisions are often made or modified at the first outpatient clinic visit , this study was designed to evaluate the importance of post-hospital data on mortality prediction after a first myocardial infarction ( MI ) . An inception cohort of patients enrolled in the Beta-Blocker in Heart Attack Trial ( n = 2830 ) was included . Forty-three variables ( including in-hospital and post-hospital data ) were evaluated using stepwise logistic regression . Ten variables were independently associated with 1-year mortality : five used in-hospital data ( history of hypertension , hypercholesterolemia , congestive heart failure [ CHF ] , ventricular tachycardia , and age ) ; and five variables depended on post-hospital data collected at the first outpatient visit ( CHF after discharge , New York Heart Association functional class , heart rate , pulmonary rates , and smoking ) . Two predictive systems were developed that partitioned patients into one of four classes with distinct mortality risks : a composite system using the 10 in- and post-hospital variables , and a system using only the 5 in-hospital variables . Mortality risk for the composite system classes ranged from 0.6 to 20.0 % ( I [ n = 861 ] , 0.6 % ; II [ n = 1151 ] , 2.3 % ; III [ n =698 ] , 4.3 % ; IV [ n = 120 ] , 20.0 % ) . In contrast , the range of mortality risk using the in-hospital data only system was less ( 1 to 8.3 % ) . Most importantly , a distinct gradient within each class of the in-hospital data only system was created by the addition of the post-hospital data . This study demonstrates that risk stratification after an acute first MI is improved by the addition of post-hospital data .

post-hospital data

in-hospital data

post-hospital data

in-hospital and post-hospital data )

post-hospital data

in-hospital data

in-hospital data

post-hospital data

post-hospital data

Mortality risk

range of mortality

myocardial infarction ( MI


Intrathecal immunoactivation in patients with HIV-1 infection is reduced by zidovudine but not by didanosine . The effect of zidovudine and didanosine on the cerebrospinal fluid ( CSF ) concentrations of neopterin was studied in 12 patients with human immunodeficiency virus type-1 ( HIV-1 ) infection 3-12 months after initiation of antiretroviral therapy . Ten treatment periods on zidovudine and 7 on didanosine were analysed . The CSF concentrations of neopterin decreased by 63 % ( from 29.6 to 12.9 nmol/l , p < 0.01 ) during zidovudine but increased by 15 % ( from 22.6 to 25.9 nmol/l , not significant during didanosine treatment . The CSF monocytic cell count decreased during zidovudine but increased during didanosine treatment . The results suggest that zidovudine but not didanosine reduces intrathecal immunoactivation during HIV-1 infection .

zidovudine

didanosine

zidovudine

didanosine

antiretroviral therapy

zidovudine

didanosine

zidovudine

didanosine

zidovudine

didanosine

zidovudine

didanosine

Intrathecal immunoactivation

CSF concentrations of neopterin

CSF monocytic cell count

patients with HIV-1 infection

human immunodeficiency virus type-1


Impact of triiodothyronine on the survival of high-risk patients undergoing open heart surgery . Experimental and clinical studies have shown the beneficial effects of triiodothyronine ( T3 ) following myocardial revascularization on cardiopulmonary bypass ( CPB ) . In this study , open-label T3 was administered to 68 high-risk patients undergoing open heart surgery . The New Jersey Risk Assessment was used to calculate the preoperative estimated surgical mortality . A loading dose of T3 was administered : ( a ) at release of the aortic cross-clamp , ( b ) whenever the patient became CPB dependent , ( c ) if the patient exhibited low cardiac output after discontinuing CPB and ( d ) as pretreatment before initiating CPB . All therapeutic modalities were followed by a continuous T3 infusion . Following T3 therapy , CPB was discontinued in all patients . Based upon discriminant analysis , a total of 26 deaths were expected from the entire group , but only 7 patients died , therefore , the observed mortality was reduced by 72 % ( p < 0.007 ) . The use of T3 had a major impact on reducing surgical mortality , and may be advocated as a new therapeutic modality in patients with high estimated mortality undergoing open heart surgery .

triiodothyronine

open heart surgery .

triiodothyronine ( T3 )

cardiopulmonary bypass ( CPB ) .

T3 therapy

CPB

survival of high-risk patients

beneficial effects

New Jersey Risk Assessment

deaths

died

observed mortality

reducing surgical mortality

estimated mortality

undergoing open heart surgery

open heart surgery


Ganciclovir use during mild renal failure in heart transplantation .

Ganciclovir

heart transplantation

renal failure


Final report of a randomized controlled study with streptococcal preparation OK-432 as a supplementary immunopotentiator for laryngeal cancer . We conducted a randomized controlled study of streptococcal preparation OK-432 on 120 newly identified cases of laryngeal squamous cell carcinoma who were registered at 10 participating institutions between November 1984 and October 1989 . The patients were divided into two groups : those in early stages ( stage I or II ) and those in advanced stages ( stage III or IV ) ; these groups were further subdivided into an immunotherapy group ( receiving OK-432 ) and a control group ( who did not receive OK-432 ) . The usefulness of OK-432 was studied using the sealed envelope method . The basic therapy for all cases was radiotherapy and , when required , surgery . As adjuvant therapy , 5Fu or derivatives were administered to all cases from the beginning of the treatment period to one year after the basic therapy , with the exception of cases in whom side effects were serious enough to contraindicate use of the drug . The target administration period was 5 years . Of the initial 120 cases , 11 cases were disqualified ( 3 cases of double cancer and 8 of incomplete primary therapy ) and the remaining 109 were used for evaluation . The 5-year survival rate and the 5-year recurrence-free rate were 76 % and 84 % , respectively , in the immunized groups ( both the early and advanced groups ) , whereas the same rates for the control groups were 78 % and 75 % . There was a tendency for the immunized groups to enjoy a slightly longer recurrence-free period . Over a 24-month observation period the immunized group always had higher levels of peripheral leukocytes and peripheral lymphocytes ; this difference was significant for the first 21 months . Inhibition of bone marrow function is sometimes observed with radiotherapy . It is hoped that , if this inhibition can be mitigated , it will be possible to assist the compromised immune system and maintain a certain level of immune performance which will prevent recurrence and improve survival rate . In the present study we observed a tendency of the lower recurrence rate in the immunized group , and we hypothesize that OK-432 is effective in extending the recurrence-free period .

control

slightly longer recurrence-free period

Inhibition of bone marrow function

certain level of immune performance

improve survival rate


The impact of a psychological intervention on quality of life in non-metastatic breast cancer . The aim of this study was to determine whether psychological intervention had a beneficial effect on the quality of life and behaviour of women diagnosed with breast cancer . 36 consecutive patients with non-metastatic breast cancer assigned to surgery and systemic chemotherapy were randomised to receive either psychological intervention ( weekly cognitive individual psychotherapy and bimonthly family counselling ) or standard follow-up . Personality ( 16-PF and IIQ ) , quality of life ( FLIC ) , and depression ( BDI ) scores were the endpoints for this study , and the questionnaires were completed by the patients at diagnosis , and up to 9 months after diagnosis . Cognitive psychotherapy and family counselling improved both depression and quality of life indexes compared with the control group . Better emotional coping behaviours were also revealed by some changes in personality traits in the intervention group .

psychological intervention

standard follow-up

quality of life

quality of life

behaviour

Personality ( 16-PF and IIQ )

quality of life ( FLIC )

depression ( BDI ) scores

depression

quality of life indexes

emotional coping behaviours

non-metastatic breast cancer

women

breast cancer

non-metastatic breast cancer


Ranitidine improves lymphocyte function after severe head injury : results of a randomized , double-blind study . OBJECTIVE To study the immunomodulatory effect of the histamine receptor antagonist , ranitidine , in patients admitted to the intensive care unit after severe head injury . DESIGN Randomized , prospective , double-blind study . SETTING Surgical intensive care unit of a university Level I trauma center . PATIENTS Twenty patients admitted with a Glasgow Coma Scale score of < 10 who were enrolled as part of a prospective , multicenter trial to assess the impact of multiple risk factors and ranitidine prophylaxis on the development of stress-related upper gastrointestinal bleeding . INTERVENTIONS Continuous infusion of ranitidine at 6.25 mg/hr ( n = 9 ) or placebo ( n = 11 ) for a maximum of 5 days . MEASUREMENTS AND MAIN RESULTS Before the patients were enrolled in the study and on completion of treatment , lymphocyte cell-surface antigen expression was determined by flow cytometry ( n = 14 patients ) ; mitogen-stimulated interferon-gamma and interleukin-2 production were measured by enzyme-linked immunosorbent assay ( n = 19 patients ) . Treatment with ranitidine , but not placebo , was associated with a significant increase in CD4+ lymphocytes ( 33 % to 49 % ; p < .05 ) and a significant decrease in CD8+ lymphocytes ( 41 % to 27 % ; p < .05 ) . Also , the mitogen-stimulated interferon-gamma production increased from 121 to 269 pg/mL ( p < .05 ) in patients treated with ranitidine , but not in patients treated with placebo . There were no significant differences in interleukin-2 production or circulating B-cell concentrations between both groups . CONCLUSION This study demonstrates an immunostimulatory effect of the histamine-2-receptor antagonist , ranitidine , both at the cellular and mediator levels in patients after head injury .

placebo

ranitidine

placebo

ranitidine

placebo

mitogen-stimulated interferon-gamma

interleukin-2 production

CD4+ lymphocytes

CD8+ lymphocytes

interleukin-2 production

circulating B-cell concentrations

severe head injury :

patients after head injury .


Improved local control of invasive bladder cancer by concurrent cisplatin and preoperative or definitive radiation . The National Cancer Institute of Canada Clinical Trials Group . PURPOSE A prospective randomized trial was conducted to determine whether the addition of concurrent cisplatin to preoperative or definitive radiation therapy in patients with muscle-invasive bladder cancer improved local control or survival . PATIENTS AND METHODS Ninety-nine eligible patients with T2 to T4b transitional cell bladder cancer participated , 64 % with cT3b or cT4 . Patients and their physicians selected either definitive radiotherapy or precystectomy radiotherapy ; patients were then randomly allocated to receive intravenous cisplatin 100 mg/m2 at 2-week intervals for three cycles concurrent with pelvic radiation , or to receive radiation without chemotherapy . Patients were stratified by clinical tumor stage and by radiation plan . The median follow-up duration is 6.5 years . RESULTS The occurrence of distant metastases was the same in both study arms . However , 25 of 48 control patients have had a first recurrence in the pelvis , compared with 15 of 51 cisplatin-treated patients ( P = .036 ) . The pelvic relapse rate in the two groups was significantly reduced by concurrent cisplatin ( P = .038 , log-rank test ) and this effect was preserved in a stepwise Cox regression model of prognostic factors ( hazards ratio , 0.50 ; 90 % confidence interval [ CI ] , 0.29 to 0.86 ; P = .036 ) . The hazard reduction was similar for both radiation plans . Pretreatment leukocytosis and high clinical stage were independent adverse factors in a Cox model of overall survival , but the effect of cisplatin was not significant . CONCLUSION Concurrent cisplatin may improve pelvic control of locally advanced bladder cancer with preoperative or definitive radiation , but has not been shown to improve overall survival . The use of concurrent cisplatin had no detectable effect on distant metastases .

concurrent cisplatin

and

preoperative

definitive radiation

concurrent cisplatin to preoperative

radiotherapy

precystectomy radiotherapy

intravenous cisplatin

concurrent with pelvic radiation

receive radiation without chemotherapy

cisplatin-treated

concurrent cisplatin

cisplatin

Concurrent cisplatin

preoperative or definitive radiation

concurrent cisplatin

local control or survival

occurrence of distant metastases

first recurrence

pelvic relapse rate

hazard reduction

overall survival

pelvic control

overall survival

muscle-invasive bladder cancer

Ninety-nine

64 %


Effect of supplementary antioxidant vitamin intake on carotid arterial wall intima-media thickness in a controlled clinical trial of cholesterol lowering . BACKGROUND There is accumulating experimental , epidemiological , and clinical evidence of an association between anti-oxidant vitamin intake and reduced risk of coronary heart disease . Using data from the Cholesterol Lowering Atherosclerosis Study ( CLAS ) , we explored the association of self-selected supplementary antioxidant vitamin intake on the rate of progression of early preintrusive atherosclerosis . METHODS AND RESULTS CLAS was an arterial imaging trial in which nonsmoking 40- to 59-year-old men with previous coronary artery bypass graft surgery were randomized to colestipol/niacin plus diet or placebo plus diet . The rate of progression of early preintrusive atherosclerosis was determined in 146 subjects using high-resolution B-mode ultrasound quantification of the distal common carotid artery far wall intima-media thickness ( IMT ) . From the nutritional supplement database , 22 subjects had an on-trial average supplementary vitamin E intake of > or = 100 IU per day ( high users ) and 29 subjects had an average on-trial supplementary vitamin C intake of > or = 250 mg per day ( high users ) . Within the placebo group , less carotid IMT progression was found for high supplementary vitamin E users when compared with low vitamin E users ( 0.008 versus 0.023 mm/y , P = .03 ) . No effect of vitamin E within the drug group was found . No effect of vitamin C within the drug or placebo group was found . CONCLUSIONS Supplementary vitamin E intake appears to be effective in reducing the progression of atherosclerosis in subjects not treated with lipid-lowering drugs while the process is still confined to the arterial wall ( early preintrusive atherosclerosis ) .

supplementary antioxidant vitamin

anti-oxidant vitamin

antioxidant vitamin

colestipol/niacin

placebo plus diet .

vitamin E

vitamin C

placebo

vitamin E

vitamin E

vitamin E

vitamin C

placebo

Supplementary vitamin E

lipid-lowering drugs

less carotid IMT progression

vitamin

progression of atherosclerosis

early preintrusive atherosclerosis .

nonsmoking

40- to 59-year-old

men


Age and autonomic effects on interrelationships between lung volume and heart rate . To determine effects of aging and autonomic input on interrelationships between respiratory and heart rate variability , we collected 5 min of lung volume of R-R interval data from 7 young [ 27 +/- 3 ( SD ) yr ] and 10 older ( 69 +/- 6 yr ) healthy supine humans before and after double pharmacological autonomic blockade with propranolol ( 0.2 mg/kg iv ) and atropine ( 0.04 mg/kg iv ) . Estimates of respiratory and heart rate power spectra and linear transfer functions between the two groups were generated by Fourier analysis . Age , double blockade effects , the age-drug interactions were determined by analysis of variance for repeated measures . Basal R-R intervals were unaffected by age . Double blockade decreased R-R intervals and variability in both age groups ( P < 0.0001 ) , but R-R intervals decreased less in older than in young subjects ( P < 0.0001 ) . In contrast , basal respiratory intervals and standard deviation were greater in older subjects ( P = 0.05 ) and were unaffected by double blockade in young and older subjects . Lung volume-to-heart rate spectral coherence was highest at frequencies associated with respiration and greater in young than in older subjects ( P < 0.07 ) . Double blockade decreased lung volume-to-heart rate variability transfer function magnitude ( P < 0.007 ) and increased phase angle ( P < 0.02 ) without age effects or age-drug interactions . In conclusion , heart rate , respiration , and respiration-heart rate interrelations are altered by aging , and double autonomic pharmacological blockade does not eliminate all age-related differences .

propranolol

atropine

R-R intervals

variability

basal respiratory intervals

phase angle

heart rate

respiration

respiration-heart rate interrelations

young [ 27 +/- 3 ( SD ) yr ]

older ( 69 +/- 6 yr )

young and older subjects .


Differential effects of angiotensin converting enzyme inhibitors on the vasodepressor and prostacyclin responses to bradykinin . Angiotensin converting enzyme ( ACE ) inhibitors block degradation of bradykinin and bradykinin stimulates prostacyclin production . ACE inhibitors are reported to increase prostaglandins . Therefore , we set out to determine 1 ) the contribution of prostacyclin to the bradykinin-mediated vasodepressor effects of ACE inhibitors , 2 ) whether ACE inhibitors alter the effect of bradykinin on prostacyclin , and 3 ) whether the effects of ACE inhibitors on bradykinin and prostaglandins are class effects or dependent on ACE inhibitor structure . To address these questions , we compared the effects of captopril , quinapril and placebo on blood pressure , urinary excretion of 2,3-dinor-6-keto-PGF1 alpha , and the vasodepressor response to i.v . bradykinin in 21 salt-replete normal-to-high renin hypertensive patients . Captopril and quinapril doses were titrated to lower pressure similarly . Captopril , but not quinapril , increased excretion of prostacyclin metabolite ( 217 +/- 50 vs. 135 +/- 21 pg/mg Cr base line , P < .05 ) . Both ACE inhibitors dramatically , equally potentiated the vasodepressor response to bradykinin ; the bradykinin dose required to decrease mean arterial pressure 15 mm Hg or increase pulse 20 bpm was 50-fold lower in ACEI-treated than in placebo-treated subjects ( 10 +/- 0 and 12.1 +/- 2.1 ng/kg/min in captopril and quinapril groups vs. 567 +/- 109 ng/kg/min in the placebo group ; P < .005 ) . ACE inhibition significantly attenuated the prostacyclin response to bradykinin at any given level of hypotensive response . Indomethacin abolished the prostacyclin response to bradykinin but did not alter the vasodepressor response . These data demonstrate that ACE inhibitors potentiate bradykinin-mediated vasodepression through a prostaglandin-independent mechanism . They suggest that although ACE inhibitors increase prostaglandins by increasing bradykinin , ACE inhibitors may attenuate prostaglandin production through a second bradykinin-independent mechanism .

bradykinin .

Angiotensin converting enzyme ( ACE )

ACE

ACE inhibitors

ACE inhibitors

ACE inhibitors

ACE

captopril , quinapril

placebo

bradykinin

Captopril and quinapril

Captopril

ACE

ACEI-treated

placebo-treated

captopril

quinapril

placebo

ACE

Indomethacin

ACE

prostacyclin metabolite

vasodepressor response

mean arterial pressure

prostacyclin response to bradykinin

prostacyclin response

vasodepressor response .


Inhibition of histamine-induced skin wheal and flare after 5 days of mizolastine . Mizolastine is a new , nonsedating antihistamine providing satisfactory symptomatic relief in allergic rhinitis and urticaria . The purpose of this study was to use inhibition of wheal and flare formation after 2-mu g intradermal histamine injections as a measure of the antihistamine effect of repeated doses of mizolastine . Eight volunteers were enrolled in this four-arm , double-blind , cross-over , randomized study . Three dose levels of once-daily mizolastine ( 5 mg , 10 mg , and 15 mg ) were compared with placebo during 5-day dose periods . Histamine tests were performed before drug intake on days 1 and 5 , and then 2 , 3 , 4 , 6 , 8 , 10 , 12 , 14 , and 24 hours after drug intake on day 5 . All 3 doses of mizolastine were more effective than placebo in suppressing wheal and flare reactions , and the antihistamine activity was highest at both the 10- and 15-mg dose levels . The effect on the flare reaction appeared within 1 hour , reached a maximum effect 4 hours after administration , and persisted for as long as 24 hours . The relative changes in wheal and flare areas were correlated with mizolastine trough plasma levels on day 5 . Safety was satisfactory in all groups . This study confirms that mizolastine is a rapid and potent antihistamine ; and its long-lasting effectiveness indicates that a once-daily regimen is acceptable for clinical use .

histamine-induced

mizolastine

Mizolastine

once-daily mizolastine

placebo

Histamine tests

mizolastine

placebo

mizolastine

mizolastine

more effective

wheal and flare reactions

antihistamine activity

effect on the flare reaction

Safety

antihistamine

allergic rhinitis and urticaria

Eight

volunteers


Durability of central venous catheters . A randomized trial in children with malignant diseases . In a prospective randomized study the durability of tunnelled and non-tunnelled central venous catheters was investigated in children with malignant diseases . Twenty children were included in the study but four ( two in each group ) had to be excluded ; three because the entry criteria turned out not to be fulfilled and one because of lack of data . The median duration of the tunnelled catheters was 224 days with a range of 25-846 days which was significantly longer than that of conventional catheters ( 39.5 days , range 9-228 days ) . In addition six of eight conventional catheters were accidentally removed whereas all catheters in the tunnelled group had to be removed via a small incision . Three cases of catheter related sepsis , two in the tunnelled group and one in the conventional group , were registered . The corresponding number of infections per catheter days were 1 in 1189 days and 1 in 522 days , respectively . In conclusion cuffed , tunnelled central venous catheters are less prone to displacement than traditional percutaneous central venous catheters when used in children with malignant diseases .

central venous catheters

tunnelled catheters

conventional catheters

Durability

durability

median duration

significantly longer

catheter related sepsis

number of infections per catheter days

displacement

children

with malignant diseases .

children

with malignant diseases .

Twenty

four

two

three

one

malignant diseases


The immunogenicity of three Haemophilus influenzae type B conjugate vaccines after a primary vaccination series in Philippine infants . Serum antibody responses to three Haemophilus influenzae type b ( Hib ) capsular polysaccharide-protein conjugate vaccine ( PRP-OMP , PRP-T , and HbOC ) were evaluated in 174 Philippine infants after a primary vaccination series . Children were randomized to receive one of the Hib vaccines ( Hib groups ) or into a control group . Vaccination was carried out at six , 10 and 14 weeks of age based on the local Expanded Program of Immunization schedule . Sera were collected at six weeks of age for the Hib groups and one month after the third dose for all subjects . Anti-Hib concentrations were determined by the Farr-type radioimmunoassay . There were no significant differences ( P = 0.3626 ) in the prevaccination anti-Hib geometric mean concentration ( GMC ) among the three Hib groups . Differences in the GMC after the primary series of three doses were significant ( P < 0.0001 ) ; GMC was highest for PRP-T ( 6.62 micrograms/ml ) , followed by HbOC ( 1.9 micrograms/ml ) , then PRP-OMP ( 1.06 micrograms/ml ) , and lowest for the control group ( 0.11 microgram/ml ) . We conclude that all three Hib conjugate vaccines ( PRP-T , HbOC , and PRP-OMP ) were immunogenic after three primary doses among Philippine infants .

Hib vaccines ( Hib groups )

control group

Hib conjugate vaccines

PRP-T

HbOC

PRP-OMP

immunogenicity

Serum antibody responses

Anti-Hib concentrations

GMC

GMC

immunogenic

infants

primary vaccination


Is there a difference ? A prospective study comparing lateral and standard SMAS face lifts with extended SMAS and composite rhytidectomies . Presented is a prospective study comparing limited SMAS ( lateral SMASectomy ) , conventional SMAS , extended SMAS , and composite rhytidectomies . Randomized patients received either a limited SMAS or conventional SMAS face lift on one side and an extended SMAS or composite rhytidectomy on the other . All procedures were performed at Manhattan Eye , Ear and Throat Hospital in accordance with their well-defined surgical descriptions . Postoperative courses were followed clinically for at least 1 year . Photographs were taken preoperatively and at 6 and 12 months postoperatively . Photographs were reviewed by three independent experienced face lift surgeons . The study comprises 21 patients , 20 women and 1 man , with a mean age of 59 years ( range 47 to 70 years ) . Nineteen patients underwent primary rhytidectomies ; two underwent secondary face lifts . For the first 12 patients , each had an extended SMAS procedure performed on one side ; on the other , 7 had a conventional SMAS and 5 had a limited SMAS ( lateral SMASectomy ) face lift . In the last 9 patients , a conventional SMAS was carried out on one side in 8 , a limited SMAS in 1 , and on the opposite side , a composite rhytidectomy was performed . Complications were few . Temporary weakness of the buccal branch of the facial nerve occurred in 2 patients on the side of the more extensive surgery . On the operating table at completion of the surgery , there was more improvement in reversal of midfacial ptosis and flattening of the nasolabial folds with both extended SMAS and composite rhytidectomies . The composite flap had the most dramatic effect on the nasolabial folds and oral commissure . After 24 hours , once swelling developed and facial motion became reactivated , the noticeable differences in the midface and nasolabial folds were lost . No discernible differences in facial halves were noted again . Differences between facial sides on the 6- and 12-month postoperative photographs were not detectable . We conclude that for routine facial plasty , comparable clinical outcomes are obtained at 6 months and 1 year with limited ( lateral SMASectomy ) and conventional SMAS face lifts compared with extended SMAS and composite rhytidectomies . All procedures are lacking in their improvement of midface ptosis and the nasolabial folds . The increased surgical risks , morbidity , and convalescence associated with those more extensive procedures do not seem to be warranted in the average patient .

lateral and standard SMAS face lifts

extended SMAS

composite rhytidectomies .

composite rhytidectomies .

limited SMAS

conventional SMAS

extended SMAS

composite rhytidectomy

primary rhytidectomies ;

secondary face lifts .

conventional SMAS

limited SMAS

conventional SMAS

limited SMAS

composite rhytidectomy

extended SMAS

composite rhytidectomies .

extended SMAS

women

man


Thoracoscopic talc insufflation versus talc slurry for symptomatic malignant pleural effusion . BACKGROUND Talc has been generally accepted to be the most effective sclerosant for chemical pleurodesis , although the optimal route of administration remains unclear . METHODS We designed a prospective , randomized study to compare video-assisted thoracoscopic talc insufflation with bedside talc slurry in the treatment of malignant pleural effusion . From September 1993 to November 1995 , 57 patients were recruited and randomized to either video-assisted thoracoscopic talc insufflation under general anesthesia ( n = 28 ) or talc slurry by the bedside ( n = 29 ) . Patients with poor general condition ( Karnofsky score less than 30 % ) , poor pulmonary function ( forced expiratory volume in 1 second less than 0.5 L ) , or trapped lungs were excluded from this study . Five grams of purified talc was used for either video-assisted thoracoscopic talc insufflation or talc slurry . RESULTS There was no statistically significant difference between the two groups of patients with respect to age , sex ratio , chest drainage duration , postprocedural hospital stay , parenteral narcotics requirement , complications , or procedure failure ( ie , recurrence ) . CONCLUSIONS Video-assisted thoracoscopic talc insufflation has not been shown to be a superior approach compared with talc slurry in our study . Because the former demands more resources , we advocate that talc slurry should be considered as the procedure of choice in the treatment of symptomatic malignant pleural effusion in patients who do not have trapped lungs .

Thoracoscopic talc insufflation

talc slurry

bedside talc slurry

general anesthesia

parenteral narcotics requirement

complications

procedure failure ( ie , recurrence )

malignant pleural effusion

poor general condition

poor pulmonary function

trapped lungs

trapped lungs


Dental bacteremia in children . Bacteremia resulting from dental extraction is regarded as an important cause of bacterial endocarditis , and it is therefore recommended that patients undergoing tooth extraction be given prophylactic antibiotics . As dental procedures other than extractions may also cause bacteremias , we studied a variety of dental procedures routinely used in pediatric dentistry . Blood samples for cultures were obtained 30 s after each of 13 dental operative procedures in 735 anesthetized children aged 2-16 years . Four procedures used for conservative dentistry caused bacteremias significantly more often than the baseline value of 9.4 % : polishing teeth 24.5 % , intraligamental injection 96.6 % , rubber dam placement 29.4 % , and matrix band with wedge placement 32.1 % . In comparison , toothbrushing alone caused a bacteremia on 38.5 % of occasions . The organisms isolated were typical of odontogenic bacteremias in that 50 % of the isolates were identified as varieties of viridans streptococci . These data show that a wider variety of dental procedures than was previously documented cause bacteremia .

dental extraction is

prophylactic antibiotics

polishing teeth

intraligamental injection

rubber dam placement

matrix band with wedge placement

Blood samples

bacteremias

bacteremia

odontogenic bacteremias

bacteremia

in children

patients undergoing tooth extraction

children aged 2-16 years


Modulation of oxidant stress in vivo in chronic cigarette smokers . BACKGROUND Free radical-induced oxidative damage is thought to be involved in the pathogenesis of diseases associated with cigarette smoking . We examined the production of 8-epi-prostaglandin ( PG ) F2 alpha , a stable product of lipid peroxidation in vivo , and its modulation by aspirin and antioxidant vitamins in chronic cigarette smokers . METHODS AND RESULTS We performed the following studies : ( 1 ) a cross-sectional comparison of smokers and control subjects , ( 2 ) an examination of the dose-response relationship , ( 3 ) an exploration of the effect of smoking cessation ( 3 weeks ) and nicotine patch supplementation , ( 4 ) the effect of aspirin consumption , and ( 5 ) the effects of 5 days ' dosing with vitamin E ( 100 and 800 U ) , vitamin C ( 2 g ) , and their combination . 8-epi-PGF2 alpha excretion ( in pmol/mmol , mean +/- SEM ) was 176.5+/-30.6 in heavy smokers , 92.7+/-4.8 ( P < .05 ) in moderate smokers , and 54.1+/-2.7 ( P < .005 ) in nonsmokers . Urinary levels fell from 145.5+/-24.9 to 114.6+/-27.1 ( week 2 , P < .05 ) and 112.6+/-24.9 ( week 3 , P < .05 ) on cessation of smoking . Aspirin treatment failed to suppress urinary levels of 8-epi-PGF2 alpha despite a significant reduction in urinary 11-dehydro-TxB2 production and suppression of 8-epi-PGF2 alpha and TxB2 in serum . Vitamin C ( pre , 194.6+/-40.9 ; post , 137.2+/-34.1 ; P < .05 ) and a combination of vitamin C and E ( pre , 171.0+/-39.8 ; post , 133.5+/-29.6 P < .05 ) suppressed urinary 8-epi-PGF2 alpha , whereas vitamin E alone had no effect . CONCLUSIONS Urinary 8-epi-PGF2 alpha may represent a noninvasive , quantitative index of oxidant stress in vivo . Elevated levels of 8-epi-PGF2 alpha in smokers may be modulated by quitting cigarettes and switching to nicotine patches or by antioxidant vitamin therapy .

Modulation of oxidant stress in vivo

aspirin

antioxidant vitamins

smoking cessation

nicotine patch supplementation

aspirin consumption

vitamin E

vitamin C

Aspirin treatment

Vitamin C

combination of vitamin C and E

vitamin E

quitting cigarettes

switching to nicotine patches

antioxidant vitamin therapy

8-epi-PGF2 alpha excretion

Urinary levels fell

urinary levels of 8-epi-PGF2 alpha

urinary 11-dehydro-TxB2 production

urinary 8-epi-PGF2 alpha

Urinary 8-epi-PGF2 alpha

chronic cigarette smokers .

moderate smokers

nonsmokers


[ Therapy of metastatic endocrine tumors of the gastrointestinal tract ] .

[ Therapy


A randomised open multicentre comparative trial of lamotrigine and carbamazepine as monotherapy in patients with newly diagnosed or recurrent epilepsy . The efficacy and safety of lamotrigine and carbamazepine as monotherapy in patients with untreated , newly diagnosed or recurrent partial and/or generalised tonic-clonic seizures , were compared in a randomised , open , multicentre study . Patients received 24 weeks ' treatment with oral lamotrigine 100 mg ( LTG 100 , n = 115 ) or 200 mg ( LTG 200 , n = 111 ) or carbamazepine 600 mg ( CBZ 600 , n = 117 ) . Efficacy measurements were comparable between the three treatment groups , although the higher lamotrigine dose was possibly most effective , with 60.4 % completing seizure free compared with 51.3 % ( LTG 100 ) and 54.7 % ( CBZ 600 ) . Both dosage regimens of lamotrigine were well tolerated . More patients on CBZ 600 reported adverse experiences , 66 % versus 53 % ( LTG 100 ) and 58 % ( LTG 200 ) , and of these a greater proportion were attributed to CBZ 600 treatment , 53 % versus 23 % ( LTG 100 ) and 28 % ( LTG 200 ) . Similarly , a greater proportion of the CBZ 600 group required a change in dose , 47 % versus 20 % ( LTG 100 ) and 17 % ( LTG 200 ) or withdrew completely due to adverse experiences , 10.3 % versus 4.3 % ( LTG 100 ) and 4.5 % ( LTG 200 ) . The most common adverse experience leading to withdrawal was rash , with approximately double the proportion of reports occurring in patients on CBZ 600 ( 5.1 % ) compared with lamotrigine ( 1.7 % on LTG 100 and 2.7 % on LTG 200 ) . Overall lamotrigine appeared equally effective but better tolerated compared with carbamazepine .

lamotrigine

carbamazepine

lamotrigine

carbamazepine

200 mg ( LTG 200 , n = 111 )

carbamazepine 600 mg ( CBZ

lamotrigine

lamotrigine

CBZ

LTG

LTG

CBZ

CBZ

LTG

LTG

LTG

LTG

CBZ

lamotrigine

LTG

LTG

lamotrigine

carbamazepine

efficacy and safety

Efficacy measurements

tolerated .

adverse experiences

adverse experiences

adverse experience

rash


Effects of fenoterol on inspiratory effort sensation and fatigue during inspiratory threshold loading . We studied the effects of a single dose of fenoterol on the relationship between inspiratory effort sensation ( IES ) and inspiratory muscle fatigue induced by inspiratory threshold loading in healthy subjects . The magnitude of the threshold was 60 % of maximal static inspiratory mouth pressure ( PI , mmax ) at functional residual capacity , and the duty cycle was 0.5 . Subjects continued the threshold loaded breathing until the target mouth pressure could no longer be maintained ( endurance time ) . The intensity of the IES was scored with a modified Borg scale . Either fenoterol ( 5 mg ) or a placebo was given orally 2 h before loading in a randomized double-blind crossover protocol . The endurance time with fenoterol ( 34.4 +/- 8.6 min ) was longer than that with the placebo ( 22.2 +/- 7.1 min ; P < 0.05 ) . The ratio of high- to low-frequency power of the diaphragmatic electromyogram ( EMGdi ) decreased during loading ; the decrease was less with fenoterol ( P < 0.05 ) . The EMGdi also decreased with loading ; the decrease was greater on fenoterol treatment ( P < 0.01 ) . The PI , mmax and maximal transdiaphragmatic pressure ( Pdi ) were similarly decreased after loading on either treatment . The intensity of the IES rose with time during loading in both groups but was lower with fenoterol than with the placebo ( P < 0.05 ) . The ratio of Pdi to integrated activity of the EMGdi increased with fenoterol ( P < 0.05 ) . Fenoterol treatment increased both superimposed Pdi twitch and Pdi twitch of relaxed diaphragm and decreased the value of ( 1-superimposed Pdi twitch/Pdi twitch of relaxed diaphragm ) . Thus we conclude that in normal subjects fenoterol reduces diaphragmatic fatigue and decreases the motor command to the diaphragm , resulting in a decrease in IES during inspiratory threshold loading and a prolongation of endurance .

fenoterol

fenoterol

fenoterol

placebo

fenoterol

fenoterol

endurance time

EMGdi

intensity of the IES rose with time

ratio of Pdi

healthy subjects .


[ Drug therapy of condylomata acuminata ] . This study seeks to evaluate two candidate regimens ( 5-fluorouracil and interferon ) as adjuvants to optimally performed laser surgery in the treatment of condylomata acuminata . Skillful laser ablation can remove any volume of human papillomavirus-associated vulvar disease but can not prevent reactivation of the surrounding latent viral reservoir during postoperative healing . Conversely , interferon and 5-fluorouracil are relatively ineffective as primary therapies . This study involves 118 evaluable patients : 32 in the laser-CO2 group , 34 in the 5-fluorouracil group and 52 in the interferon group . At assessment of final outcome , it was found that 43 of 52 ( 82 % ) assessable patients in the adjuvant interferon arm were controlled by a single laser ablation as compared with only 17 of 34 ( 50 % ) in the 5-fluorouracil group and 13 of 32 ( 40 % ) in the laser alone group . There was no statistical difference in outcome within the 5-fluorouracil and laser only arms . Conversely , a relatively low dose of recombinant interferon , used in combination with effective surgical deleulking , can markedly reduce the risk of postoperative recurrence .

interferon

laser surgery

interferon

interferon

interferon

laser alone

interferon

surgical deleulking

condylomata acuminata

controlled

single laser ablation

postoperative recurrence

condylomata acuminata


Treatment of men with flat ( FC ) or acuminata ( CA ) condylomata with interferon alpha-2a . This study was undertaken to assess the effect of CO2 laser vaporization , 5-fluorouracil 5 % ( 5-FU ) topical application and Interferon alpha-2a ( IFA alpha-2a ) in the treatment of C.A . or F.C . of the male genital tract . From March 1986 to September 1991 , 1372 men , sexual partners of women with F.C . or C.A . or cervical intraepithelial neoplasia , were submitted to peoscopy . One thousand and nineteen ( 74.27 % ) men presented with various penile lesions caused by HPV ( histologically confirmed ) ; of these 505 were treated for C.A . or F.C . or a combination of F.C . and C.A . The best treatment modalities , irrespective of the kind of lesion , were found to be the combination of 5-FU plus IFN alpha-2a ( high dose ) ( 98.27 % ) , the combination of CO2 laser vaporization plus 5-FU plus IFN alpha-2a ( high dose ) ( 93.93 % ) and the combination of CO2 laser vaporization plus 5-FU ( 87.23 % ) . In conclusion we believe that IFN alpha-2a can be used with excellent results as first line treatment in combination with CO2 laser vaporization or/plus 5-FU in patients with C.A . or F.C . or combined condylomata .

interferon alpha-2a

CO2 laser vaporization

Interferon alpha-2a ( IFA alpha-2a )

5-FU plus IFN alpha-2a

IFN alpha-2a

CO2 laser vaporization

One thousand and nineteen

combined condylomata


Trunk exercise combined with spinal manipulative or NSAID therapy for chronic low back pain : a randomized , observer-blinded clinical trial . OBJECTIVES To study the relative efficacy of three different treatment for chronic low back pain ( CLBP ) . Two preplanned comparisons were made : ( a ) Spinal manipulative therapy ( SMT ) combined with trunk strengthening exercises ( TSE ) vs. SMT combined with trunk stretching exercises , and ( b ) SMT combined with TSE vs. nonsteroidal anti-inflammatory drug ( NSAID ) therapy combined with TSE . STUDY DESIGN Interdisciplinary , prospective , observer-blinded , randomized clinical trial with a 1-yr follow-up period . The trial evaluated therapies in combination only and was not designed to test the individual treatment components . SETTING Primary contact , college out-patient clinic . PATIENTS In total , 174 patients aged 20-60 yr were admitted to the study . MAIN OUTCOME MEASURES Patient-rated low back pain , disability , and functional health status at 5 and 11 wk . INTERVENTIONS Five weeks of SMT or NSAID therapy in combination with supervised trunk exercise , followed by and additional 6 wk of supervised exercise alone . RESULTS Individual group comparisons after 5 and 11 wk of intervention on all three main outcome measures did not reveal any clear clinically important or statistically significant differences . There seemed to be a sustained reduction in medication use at the 1-yr follow-up . in the SMT/TSE group . Continuance of exercise during the follow-up year , regardless of type , was associated with a better outcome . CONCLUSION Each of the three therapeutic regimens was associated with similar and clinically important improvement over time that was considered superior to the expected natural history of long-standing CLBP . For the management of CLBP , trunk exercise in combination with SMT or NSAID therapy seemed to be beneficial and worthwhile . The magnitude of nonspecific therapeutic ( placebo ) effects , cost-effectiveness and relative risks of side effects associated with these types of therapy need to be addressed in future studies .

NSAID therapy

SMT combined with TSE

SMT

NSAID

supervised exercise alone .

SMT

NSAID therapy

( placebo )

Patient-rated low back pain

disability

functional health status

chronic low back pain

chronic low back pain


Colonoscopic miss rates of adenomas determined by back-to-back colonoscopies . BACKGROUND & AIMS The miss rate of colonoscopy for neoplasms is poorly understood . The aim of this study was to determine the miss rate of colonoscopy by same day back-to-back colonoscopy . METHODS Two consecutive same day colonoscopies were performed in 183 patients . The patients were randomized to undergo the second colonoscopy by the same or a different endoscopist and in the same or different position . RESULTS The overall miss rate for adenomas was 24 % , 27 % for adenomas < or = 5 mm , 13 % for adenomas 6-9 mm , and 6 % for adenomas > or = 1 cm . Patients with two or more adenomas at the first examination were more likely than patients with no or one adenoma detected at the first examination to have one or more adenomas at the second examination ( odds ratio , 3.3 ; 95 % confidence interval , 1.69-6.46 ) . Right colon adenomas were missed more often ( 27 % ) than left colon adenomas ( 21 % ) , but the difference was not significant . There was evidence of variation in sensitivity between endoscopists , but significant miss rates for small adenomas were found among essentially all endoscopists . CONCLUSIONS Using current colonoscopic technology , there are significant miss rates for adenomas < 1 cm even with meticulous colonoscopy . Miss rates are low for adenomas > or = 1 cm . The results suggest the need for improvements in colonoscopic technology .

colonoscopy

colonoscopies

second colonoscopy

colonoscopic technology

overall miss rate for adenomas

adenomas

variation in sensitivity

miss rates

miss rates

Miss rates

adenomas

183 patients .

patients with no or one adenoma


Single-dose pharmacokinetics of delavirdine mesylate and didanosine in patients with human immunodeficiency virus infection . Delavirdine is a nonnucleoside reverse transcriptase inhibitor with in vitro activity against human immunodeficiency virus type 1 ( HIV-1 ) that is currently being evaluated in combination regimens with various nucleoside analogs , including didanosine . Due to the pH-dependent solubility of delavirdine , the buffering agents in didanosine formulations may reduce delavirdine absorption . To evaluate the potential interaction between these agents , 12 HIV-infected patients ( mean [ +/- standard deviation ] CD4+ cell count , 304 +/- 213/mm3 ) were enrolled in a three-way crossover single-dose study . Didanosine ( 125 to 200 mg given as buffered tablets ) and delavirdine mesylate ( 400 mg ) pharmacokinetics were evaluated when each drug was given alone ( treatments A and B , respectively ) , when the two drugs were given concurrently ( treatment C ) , and when didanosine was given 1 h after delavirdine ( treatment D ) . Delavirdine exposure was reduced by concurrent administration of didanosine . The maximum drug concentration in serum ( Cmax ) was reduced from 7.22 +/- 4.0 to 3.51 +/- 1.9 microM , and the area under the concentration-time curve from 0 h to infinity ( AUC0 -- > infinity ) was reduced from 22.5 +/- 14 to 14 +/- 5.7 microM.h . The extent of N-dealkylation , as indicated by the ratio of the N-dealkylated delavirdine AUC0 -- > infinity to the delavirdine AUC0 -- > infinity , was unchanged across study treatments ( P = 0.708 ) . Reductions in didanosine exposure were observed during concurrent administration with delavirdine with a Cmax reduction from 4.65 +/- 2.0 to 3.22 +/- 0.59 microM and an AUC0 -- > infinity reduction from 7.93 +/- 3.9 to 6.54 +/- 2.3 microM.h . Thus , concurrent administration of delavirdine and didanosine may reduce the AUC0 -- > infinity of both drugs , although the clinical significance of this reduction is unknown . Administration of delavirdine 1 h before didanosine avoided the interaction . Due to the single-dose nature of this study , these findings require further evaluation at steady state .

delavirdine mesylate

didanosine

Didanosine

delavirdine mesylate

didanosine

delavirdine

Delavirdine

didanosine

delavirdine

didanosine

Delavirdine exposure

area under the concentration-time curve

extent of N-dealkylation

delavirdine AUC0 -- > infinity

didanosine exposure

Cmax

AUC0 -- > infinity

human immunodeficiency virus infection


Pedantic speaking style differentiates Asperger syndrome from high-functioning autism . Asperger syndrome ( AS ) is a pervasive developmental disorder recently introduced as a new diagnostic category in the ICD-10 and the DSM-IV . Along with motor clumsiness , pedantic speech has been proposed as a clinical feature of AS . However , few attempts have been made to define and measure this symptom . We studied 17 patients with AS ( ICD-10 ; 14 male , 3 female ; mean age 16.4 years , mean full-scale IQ 97 ) and compared them with a control group of 13 patients with normal-intelligence autism or high-functioning autism ( HFA ) ( ICD-10/DSM-III-R ; 12 male , 1 female ; mean age 15.5 years , mean full-scale IQ 81.2 ) . An operational definition of pedantic speech was formulated and a rating scale devised . 13 ( 76 % ) of the AS patients were rated as pedantic compared to 4 ( 31 % ) of the HFA group ( chi 2 = 6.3 ; p = .01 ) . Results suggest that pedantic speech is common in AS and may help differentiate AS from high-functioning autism .

Pedantic speaking

pedantic speech

pedantic

pedantic speech

AS

14 male

3 female

mean age 16.4 years

normal-intelligence autism

high-functioning autism ( HFA )

12 male

1 female

mean age 15.5 years

AS

HFA


Comparison of electromotive drug administration with ketorolac or with placebo in patients with pain from rheumatic disease : a double-masked study . This study was undertaken to assess the efficacy of ketorolac compared with placebo when delivered by electromotive drug administration ( EMDA ) in patients with pain from rheumatic disease . In EMDA , or iontophoresis , a low-intensity electric current is applied over the skin to deliver medication into body tissues . Although EMDA has been used to treat patients with various diseases , controlled studies are lacking in patients with rheumatic disease . This double-masked study included 60 patients ( 43 women and 17 men ) aged 31 to 80 years with the following conditions : 12 , epicondylitis ; 30 , scapulohumeral periarthritis ; 10 , gonalgia ; and 8 , metatarsalgia . They were divided randomly by a physician into 2 groups of 30 patients each for 5 sessions of active treatment ( 30 mg of ketorolac ) or placebo ( 5 mL of normal saline ) . Treatment took place every other day for 20 minutes . Immediately before and after the five treatment sessions and 7 days after treatment ended , both patient and physician measured the degree of pain using a categoric scale ( no pain , slight pain , intermediate pain , strong pain , and very strong pain ) and evaluated pain intensity using the Scott and Huskisson Visual Analogue Scale ( VAS ) . Seven days after treatment ended , both physician and patient judged the result of treatment using a second categoric scale ( no improvement or intermediate , good , or very good result ) . Both ketorolac and placebo provided immediate , significant pain relief when delivered by EMDA , but only those patients receiving ketorolac experienced a further reduction in pain 7 days after treatment ; those receiving placebo experienced a slight increase in pain . VAS values differed significantly between the two groups . Poor results ( no improvement ) were significantly higher in the placebo-treated group , while good results were significantly higher in the ketorolac-treated group . No patient reported any adverse effects during treatment . This study demonstrates that ketorolac relieves pain when delivered by EMDA and offers longer-lasting pain relief than does placebo .

ketorolac

placebo

ketorolac

placebo

EMDA

EMDA

30 mg of ketorolac

placebo

5 mL of normal saline

ketorolac

placebo

EMDA

ketorolac

placebo

placebo-treated

ketorolac-treated

ketorolac

EMDA

placebo

pain

efficacy

pain

degree of pain

pain intensity

pain relief

pain

pain

VAS values

Poor results ( no improvement )

good results

adverse effects

pain

pain

patients with rheumatic disease

women

men

aged 31 to 80 years

epicondylitis

scapulohumeral periarthritis


Topical beta-blockade with intrinsic sympathomimetic activity offers no advantage for the respiratory and cardiovascular function of elderly people . Topical therapy with beta-antagonists , such as timolol , may cause unrecognized impairment of respiratory and cardiovascular function in elderly people . Beta-antagonists with intrinsic sympathomimetic or cardioselective properties , such as carteolol or betaxolol , may cause less impairment . In a randomized , double-masked study of glaucoma patients , over 60 years of age , without history of bronchospasm and who were using timolol ( 0.5 % ) , 60 patients were allocated to betaxolol ( 0.5 % ) or carteolol ( 2 % ) or continued timolol ( 0.5 % ) treatment . Spirometry , pulse and blood pressure were measured on enrollment and after 4 weeks . In the timolol and carteolol groups there were no significant changes in mean spirometric values . Changing to betaxolol improved mean peak flow ( PF ) by 9.1 % , from 310 to 3411/min ( p < 0.05 ) and forced expiratory volume in 1 second ( FEV1 ) by 9.4 % , from 1.74 to 1.861 ( p < 0.05 ) . Differences in the changes in PF and FEV1 between betaxolol and timolol as well as betaxolol and carteolol groups were statistically significant ( p < 0.05 ) . Twenty-one per cent of those allocated to betaxolol showed clinically significant improvement in FEV1 . There was no change in pulse or blood pressure when carteolol was substituted for timolol but an increase of 10 beats per minute ( p < 0.05 ) in mean resting pulse in the betaxolol group . Therapy with cardioselective beta-blockade may offer significant advantages in respiratory function for elderly people with glaucoma over non-selective drugs , even if they have sympathomimetic activity .

timolol

carteolol

betaxolol

timolol

betaxolol

carteolol

timolol

Spirometry , pulse and blood pressure

mean spirometric values .

mean peak flow ( PF )

forced expiratory volume

changes in PF and FEV1

FEV1 .

pulse or blood pressure

mean resting pulse

elderly people .


Feasibility and effects of nurse run clinics for patients with epilepsy in general practice : randomised controlled trial . Epilepsy Care Evaluation Group . OBJECTIVE To test the feasibility and effect of nurse run epilepsy clinics in primary care . DESIGN A randomised controlled trial of nurse run clinics versus " usual care . " SETTING Six general practices in the South Thames region . SUBJECTS 251 patients aged over 15 years who were taking anti-epileptic drugs or had a diagnosis of epilepsy and an attack in the past two years who met specified inclusion criteria and had responded to a questionnaire . MAIN OUTCOME MEASURES Questionnaire responses and recording of key variables extracted from the clinical records before and after the intervention . RESULTS 127 patients were randomised to a nurse run clinic , of whom 106 ( 83 % ) attended . The nurse wrote 28 letters to the general practitioners suggesting changes in epilepsy management . For this intervention group compared with the usual care group there was a highly significant improvement in the level of advice recorded as having been given on drug compliance , adverse drug effects , driving , alcohol intake , and self help groups . CONCLUSIONS Nurse run clinics for patients with epilepsy were feasible and well attended . Such clinics can significantly improve the level of advice and drug management recorded .

nurse run epilepsy clinics

nurse run clinics

usual care

changes in epilepsy management .

usual care

Nurse run clinics

Feasibility and effects

feasibility and effect

level of advice recorded

feasible and well attended

15 years

epilepsy


Improving care givers ' satisfaction with information received during hospitalization . As competition for patient volume escalates among hospital providers , administrators must identify ways to attract new patients and maintain or increase patient volume . Family care givers are known to greatly influence individuals ' choices in these matters of selection of healthcare services and providers . The results of a successful nurse-initiated daily phone calls program , designed to improve family care giver satisfaction by enhancing the provision of patient-specific information , are presented . The components of the program , associated costs , and implications on delivery of care are discussed .

patient-specific information

components of the program

associated costs


The management of dermoid cysts -- a comparative study of laparoscopy and laparotomy . The aim of our study was to compare laparoscopy with laparotomy for the removal of ovarian dermoid cysts . Thirty-eight women with benign ovarian dermoid cyst were allocated for either laparoscopy ( 18 patients ) or laparotomy ( 20 patients ) . The two groups were compared for operative and hospitalization times and postoperative course . Operating time was longer ( 93.6 +/- 23.8 min ) and hospitalization time significantly shorter ( 22.4 +/- 6.6 h ) in the laparoscopy group . No complications were reported in either group . We conclude that operative laparoscopy is a safe procedure for the removal of dermoid ovarian cysts and is as effective as laparotomy .

laparoscopy

laparotomy

laparoscopy

laparotomy

laparoscopy

laparotomy

operative laparoscopy

laparotomy

Operating time

hospitalization time

complications

safe

effective

dermoid cysts

ovarian dermoid cysts

Thirty-eight

women

benign ovarian dermoid cyst

dermoid ovarian cysts


Effects of omeprazole and amoxycillin on the human oral and gastrointestinal microflora in patients with Helicobacter pylori infection . Fourteen patients with Helicobacter pylori infection were treated with omeprazole capsules 20 mg and amoxycillin capsules 1000 mg twice daily for 14 days and 14 patients with omeprazole capsules 20 mg and placebo twice daily for 14 days . Samples from saliva , dental plaque and faeces and biopsies from antrum and corpus were analysed in order to determine the ecological changes in the normal microflora . Several microorganisms were affected by both treatment regimens . Two patients were colonised with enterobacteria in the oral cavity and stomach during the omeprazole plus amoxycillin treatment . A general increase in the number of microorganisms from gastric mucosa was observed in both treatment groups . A selection of resistant enterobacteria and an increase in beta-lactamase production was observed in the faecal samples during the omeprazole plus amoxycillin treatment . Eradication of H. pylori in the omeprazole-amoxycillin group was 50 % and in the omeprazole placebo group 0 % four weeks after treatment . No viable H. pylori were cultivated in the saliva , dental plaque or faecal samples . Treatment with omeprazole 20 mg and amoxycillin 1000 mg twice daily for 14 days altered the normal microflora in the oral , gastric and intestinal tract and antibiotic resistant microorganisms increased in numbers in the intestinal microflora .

omeprazole

amoxycillin

omeprazole

amoxycillin

omeprazole

placebo

omeprazole plus amoxycillin

omeprazole plus amoxycillin

omeprazole-amoxycillin

selection of resistant enterobacteria

increase in beta-lactamase production

No viable H. pylori

saliva

dental plaque

faecal samples

intestinal microflora

Fourteen


Opioid-immune interactions in autism : behavioural and immunological assessment during a double-blind treatment with naltrexone . The emerging concept of opioid peptides as a new class of chemical messengers of the neuroimmune axis and the presence of a number of immunological abnormalities in infantile autism prompted us to correlate biological ( hormonal and immunological ) determinations and behavioural performances during treatment with the potent opiate antagonist , naltrexone ( NAL ) . Twelve autistic patients ranging from 7 to 15 years , diagnosed according to DSM-III-R , entered a double-blind crossover study with NAL at the doses of 0.5 , 1.0 and 1.5 mg/kg every 48 hours . The behavioural evaluation was conducted using the specific BSE and CARS rating scales NAL treatment produced a significant reduction of the autistic symptomatology in seven ( " responders " ) out of 12 children . The behavioural improvement was accompanied by alterations in the distribution of the major lymphocyte subsets , with a significant increase of the T-helper-inducers ( CD4+CD8- ) and a significant reduction of the T-cytotoxic-suppressor ( CD4-CD8+ ) resulting in a normalization of the CD4/CD8 ratio . Changes in natural killer cells and activity were inversely related to plasma beta-endorphin levels . It is suggested that the mechanisms underlying opioid-immune interactions are altered in this population of autistic children and that an immunological screening may have prognostic value for the pharmacological therapy with opiate antagonists .

naltrexone

naltrexone ( NAL )

NAL

BSE

CARS rating scales

NAL

opiate antagonists

BSE and CARS rating scales

autistic symptomatology

T-helper-inducers ( CD4+CD8- )

T-cytotoxic-suppressor ( CD4-CD8+ )

CD4/CD8 ratio .

natural killer cells and activity

autism

Twelve

autistic

7 to 15 years

children

autistic

children


Effects of preoperative intentional hemodilution on the extravasation rate of albumin and fluid . OBJECTIVE To evaluate the effects of preoperative intentional hemodilution with 4 % albumin solution on the extravasation rate of intravascular albumin and fluid in surgical patients . DESIGN A prospective , randomized , clinical study . SETTING University teaching hospital . PATIENTS Two groups ( control group [ group 1 ] and hemodiluted group [ group 2 ] ) of 13 healthy patients were studied during a long-term ( > 4 hrs ) surgical procedure . INTERVENTIONS Autologous technetium-99m ( 99mTc ) -labeled red blood cells and indium-oxine ( ( 111 ) In ) -labeled human serum albumin were injected intravenously during anesthesia at T = 0 min in the two groups for the determination of total blood volume and albumin diffusion space , respectively . In addition , body tetrapolar electrical impedance was used to assess extracellular fluid volume . In the hemodiluted group ( group 2 ) , 15 mL/kg of blood was withdrawn over 30 mins ( T = 20 mins to T = 50 mins ) and simultaneously replaced by an equal volume of 4 % albumin solution ( 0.6 g/kg ) . MEASUREMENTS AND MAIN RESULTS The albumin diffusion space , the colloid oncotic pressure , the plasma albumin concentration and the electrical impedance were measured before ( T = 10 mins ) and after ( T = 60 , 120 , and 240 mins ) hemodilution . Urine was collected from T = 10 mins to T = 240 mins . The total blood volume was calculated at T = 10 mins . No differences in the initial values were found between the two groups . In group 2 , hemodilution ( hematocrit 30 +/- 3 % ) resulted in a steeper increase in the albumin diffusion space ( p < .05 ) and a progressive decrease in the body electrical impedance ( p < .05 ) . The extravasation rate of albumin was 0.052 +/- 0.007 mL/kg/min in group 2 vs. 0.038 +/- 0.020 mL/kg/min in group 1 ( p < .05 ) . The value of calculated plasma volume at T = 0 min did not shown any difference between the two groups . This value was then lower than expected in group 2 , corresponding to a loss of plasma volume of > 3 mL/kg . Urine output was significantly lower in group 2 than in group 1 ( 0.7 +/- 0.4 vs. 1.4 +/- 1.0 mL/min , respectively ; p < .05 ) . A comparable decrease in colloid oncotic pressure and in plasma albumin concentration was observed in both groups . CONCLUSIONS These results suggest that preoperative hemodilution using 4 % albumin on a 1:1 volume basis for blood substitution during a prolonged surgical procedure with reduced blood losses enhances the extravasation rate of albumin and fluid to the interstitial tissues , impeding the maintenance of isovolemia . These findings support the use of a volume of infused colloid solution higher than that of withdrawn blood during preoperative hemodilution .

intentional hemodilution

albumin

extravasation rate of albumin and fluid

plasma albumin concentration

electrical impedance

total blood volume

albumin diffusion space

body electrical impedance

extravasation rate of albumin

value of calculated plasma volume

loss of plasma volume

Urine output

surgical


Marginal zone B cell lymphoma of the parotid glands : results of a randomised trial comparing radiotherapy to combined therapy . 39 patients with marginal zone B cell lymphoma ( MZBCL ) of the parotid glands ( stages I or II ) were studied . They were randomized to be treated with either radiotherapy alone ( extended fields , 4500 cGy ) or radiotherapy ( the same schedule ) plus adjuvant chemotherapy ( cyclophosphamide , vincristine and prednisone ) . The end points were survival and time to treatment failure ( TTF ) . Patients who received radiotherapy alone had a complete remission rate of 100 % , the TTF was 90 % at 5 years and overall survival at 5 years was 90 % with no statistical difference when compared with patients who received combined therapy [ 100 , 80 and 95 % , respectively ( P = 0.5 ) ] . Although adjuvant chemotherapy was well tolerated , the use of this therapeutic approach in patients with early stage MZBCL did not offer any advantage over radiotherapy alone as the initial treatment . Until now , radiotherapy was considered the treatment of choice in this clinical setting of patients .

radiotherapy

combined therapy

radiotherapy alone

radiotherapy

plus

radiotherapy

combined therapy

adjuvant chemotherapy

radiotherapy

end points

complete remission rate

TTF

overall survival

tolerated

marginal zone B cell lymphoma ( MZBCL )


Determining the trough-to-peak ratio in parallel-group trials . Systolic Hypertension in Europe ( SYST-EUR ) Trial Investigators . We explored how in parallel-group trials interindividual variability , correction for placebo effects , and smoothing of blood pressure profiles can be handled in measuring the trough-to-peak ratio in 244 individuals with isolated systolic hypertension ( > or = 60 years ) enrolled in the placebo-controlled Systolic Hypertension in europe Trial . Net treatment effects were computed by subtracting the mean changes from baseline during placebo ( n = 133 ) from those during active treatment ( n = 111 ) . At entry , systolic/diastolic pressures averaged 176/86 mm Hg in the clinic and 149/80 mm Hg on 24-hour ambulatory monitoring . With corrections applied for baseline and placebo , nitrendipine ( 10 to 40 mg/d ) , with the possible addition of enalapril ( 5 to 20 mg/d ) and/or hydrochlorothiazide ( 12.5 to 25 mg/d ) , reduced ( P < .001 ) these blood pressure values by 16.6/7.3 and 9.8/4.7 mm Hg , respectively . The net trough-to-peak ratios were first determined from blood pressure profiles ( 12 hours ) with 1-hour precision , synchronized by the morning and evening doses of the double-blind medication . According to the usual approach , disregarding interindividual variability , the systolic/diastolic net trough-to-peak ratios were 0.46/0.40 in the morning and 0.77/0.99 in the evening . In individual subjects , the baseline-adjusted trough-to-peak ratios were nonnormally distributed . We therefore used a nonparametric technique to calculate the net trough-to-peak ratios from the results in individual subjects . In the morning , these ratios averaged 0.25 systolic ( 95 % confidence interval , 0.09 to 0.41 ) and 0.15 diastolic ( 95 % confidence interval , 0.00 to 0.31 ) and in the evening , 0.19 and 0.36 ( 95 % confidence intervals , 0.00 to 0.38 and 0.14 to 0.56 ) , respectively . When the blood pressure profiles were smoothed by substituting the 1-hour averages by moving or fixed 2-hour averages or by Fourier modeling , the trough-to-peak ratios remained unchanged after the morning dose ( 0.20/0.13 , 0.20/0.14 , and 0.16/0.21 , respectively ) but tended to increase in the evening ( 0.32/0.38 , 0.28/0.40 , and 0.48/0.49 ) . In conclusion , the parallel-group analysis proposed makes it possible for one to correct the trough-to-peak ratio for baseline as well as placebo , to account for interindividual variability , and to calculate a confidence interval for the net trough-to-peak ratio . Accounting for interindividual variability reduces the trough-to-peak ratio . Smoothing affects the individualized net trough-to-peak ratios in an unpredictable way and should therefore be avoided .

nitrendipine

enalapril

hydrochlorothiazide

trough-to-peak ratio

trough-to-peak ratio

systolic/diastolic pressures

blood pressure values

net trough-to-peak ratios

blood pressure profiles

baseline-adjusted trough-to-peak ratios

net trough-to-peak ratios

blood pressure

trough-to-peak ratios

trough-to-peak ratio

trough-to-peak ratio

trough-to-peak ratio

trough-to-peak ratios

isolated systolic hypertension

> or = 60 years )

Systolic Hypertension


Dexamethasone in salbutamol-treated inpatients with acute bronchiolitis : a randomized , controlled trial . OBJECTIVE To determine the clinical benefit of oral dexamethasone in children admitted to the hospital with bronchiolitis treated with nebulized salbutamol . METHODS Randomized , double-blind , placebo-controlled trial in the inpatient wards of a pediatric tertiary care hospital . The participants , children aged 6 weeks to 15 months , admitted with first-time wheezing , were eligible if their oxygen saturation was less than 95 % on admission to the hospital and their Respiratory Distress Assessment Instrument ( RDAI ) score was greater than 6 . Patients were excluded if they had any one of the following : an underlying disease that might affect cardiopulmonary status , asthma , recent treatment with steroids ( within 2 weeks ) , or any history of adverse reaction to steroids . Patients were randomly assigned to receive either orally administered dexamethasone with 0.5 mg/kg as the first dose and 0.3 mg/kg for the next 2 mornings , or an equal volume of an orally administered placebo with an identical appearance . All patients received nebulized salbutamol at 0.15 mg/kg every 4 hours for the first 24 hours . The primary outcome measure was the change from baseline in the RDAI score at 24 hours . Secondary outcome measures were oxygen saturation , respiratory rate , RDAI measurement twice daily for the first 4 days , and the length of hospitalization . RESULTS At 24 hours the mean change ( SD ) from baseline in the RDAI score was 1.6 ( 2.3 ) in the placebo group ( n = 28 ) and 1.4 ( 2.0 ) in the dexamethasone group ( n = 33 ; p = 0.74 ) . There were no significant differences between the two groups in change in oxygen saturation , respiratory rate , and RDAI score at any assessment period . The median length of stay ( 95 % confidence interval ) for the placebo group was 48 ( 42 , 54 ) hours compared with 57 ( 38 , 76 ) hours in the dexamethasone group ( p = 0.19 ) . CONCLUSIONS Oral dexamethasone therapy does not affect the clinical course of children hospitalized with bronchiolitis and therefore can not be recommended in this clinical situation .

Dexamethasone

dexamethasone with 0.5 mg/kg

placebo

salbutamol

clinical benefit

RDAI score

oxygen saturation

respiratory rate

RDAI measurement twice daily

length of hospitalization

mean change ( SD )

RDAI score

oxygen saturation

respiratory rate

RDAI score

median length of stay


Airway management training using the laryngeal mask airway : a comparison of two different training programmes . Nurses without prior experience in the use of the laryngeal mask airway ( LMA ) were randomly allocated to one of two groups to be trained in the emergency technique of insertion of an LMA . Group A ( 32 nurses ) were trained only on a manikin and group B ( 20 nurses ) were trained on a manikin and with live anaesthetised patient practice in theatre ( five successful insertions ) . Without further practice , both groups were asked to insert an LMA in a live patient in theatre 3 months after initial training . Three attempts per nurse were allowed . In group A , 75 % passed the LMA successfully at the first attempt , 22 % at the second attempt and 3 % ( one nurse ) at the third attempt . In group B , 80 % were successful at first attempt and 20 % at the second attempt . Skill performance and retention were shown to be high following either training method , with no significant difference between the performance of either group ( chi 2 ) . We have shown that manikin-only training in the emergency technique for LMA insertion is as effective as live patient training . It is proposed that manikin training alone may be adopted as a future training modality if , as is expected , the use of the LMA in resuscitation becomes more commonplace .

Airway management training

laryngeal mask airway

laryngeal mask airway ( LMA )

manikin

trained

on a manikin

and with

live anaesthetised patient practice

LMA

LMA

LMA

Airway management

LMA successfully

successful

Skill performance and retention

performance

effective

Nurses

nurses

nurses


Temporal variation in the effects of ophthalmic timolol on cardiovascular and respiratory functions in healthy men . This study examined the effects of ophthalmic timolol and time of administration on cardiovascular and respiratory functions in healthy young male volunteers . Eight participants ( mean age +/- standard deviation , 22 +/- 0.9 years ) received either 50 microL of 0.5 % timolol or placebo in the lower conjunctival sacs of both eyes in the morning or evening . Intraocular pressure , blood pressure , heart rate , and respiratory functions , including percent forced expiratory volume in 1 second and peak expiratory flow rate , were then measured for 3 hours after drug administration . Timolol reduced intraocular pressure and cardiovascular function at both administration times . However , a timolol-induced reduction in respiratory function was observed only in the evening : percent forced expiratory volume in 1 second , peak expiratory flow rate , and expiratory flow rate at 75 % vital capacity were reduced by 3 % , 7 % , and 12 % , respectively , 3 hours after administration . These results indicate that ophthalmic timolol reduces cardiovascular and respiratory functions in healthy young male subjects and that bronchial sensitivity to timolol differs between morning and evening .

ophthalmic timolol

ophthalmic timolol

timolol

placebo

Timolol

timolol-induced

ophthalmic timolol

effects

respiratory function

bronchial sensitivity

young

male

Eight


Pharmacokinetic properties of YM17E , an inhibitor of acyl coenzyme A : cholesterol acyl transferase , and serum cholesterol levels in healthy volunteers . We conducted a single and repeat oral dose study of YM17E , a novel inhibitor of acyl coenzyme A ( CoA ) : cholesterol acyltransferase , in healthy male volunteers to evaluate the pharmacokinetic profile , tolerability and effect of the drug on serum cholesterol . In the single administration study , YM17E was administered after a meal to two groups of subjects ( each containing six subjects taking the drug and three taking placebo ) receiving 3 , 60 and 300 mg or 15 , 60 and 450 mg YM17E , respectively . Plasma concentrations of unchanged drug following single oral administration at 3-300 mg after a meal increased with increasing dose . In contrast , plasma concentrations after administration of 450 mg were almost the same as after 300 mg . Unchanged YM17E was not detected in urine after single administration , suggesting that it was excreted via the bile or urine after metabolism . Five active metabolites ( M1 , M2-a , M2-b , M3 and M4 ) were observed in plasma at concentrations comparable to those of unchanged YM17E . Their plasma concentrations increased in a slightly greater than dose-dependent manner from 3 to 300 mg . The effect of food was studied in an open crossover design with a 1-week washout period . Twelve subjects received 150 mg YM17E in both the fasted and post-prandial states . The AUC and Cmax after fasting were closely similar to those after a meal , showing that bioavailability was not affected by food intake . In the repeated oral dose study , the subjects received test drug at 150 mg or 300 mg ( n = 6 each ) or placebo ( n = 3 ) twice a day ( after breakfast and after dinner ) for 7 days . On days 1 and 7 , the subjects received YM17E once a day ( after breakfast ) for evaluation of pharmacokinetic properties . After repeated oral administration of 150 mg b.d. , plasma concentrations reached steady state by day 5 ( mean Cmin 48.6 ng.ml-1 ) . After repeated administration of 300 mg b.d. , plasma concentrations prior to each daily morning dose increased up to the 5th day ( mean Cmin 166.6 ng.ml-1 ) and then tended to decrease until the 7th day . No significant signs , symptoms or changes in serum cholesterol levels were observed during the single and repeated oral dose studies at 150 mg b.d . Although statistical analysis was not conducted because of the small number of subjects , all subjects receiving repeated oral administration of 300 mg twice daily showed a 25 % decrease in serum cholesterol level on day 7 , but also the simultaneous occurrence of diarrhoea .

YM17E , an inhibitor of acyl coenzyme

dose study of YM17E

and three taking placebo

YM17E .

150 mg YM17E

test drug at 150 mg or 300 mg

placebo ( n = 3 ) twice a day

YM17E once a day

serum cholesterol levels

pharmacokinetic profile

Plasma concentrations

plasma concentrations

plasma concentrations

AUC and Cmax

plasma concentrations

plasma concentrations

serum cholesterol

diarrhoea

healthy

healthy

male

six

three


Outcome assessment for clinical trials : how many adjudicators do we need ? Canadian Lung Oncology Group . Considerable effort is often expended to adjudicate outcomes in clinical trials , but little has been written on the administration of the adjudication process and its possible impact on study results . As a case study , we describe the function and performance of an adjudication committee in a large randomized trial of two diagnostic approaches to potentially operable lung cancer . Up to five independent adjudicators independently determined two primary outcomes : tumor status at death or at final follow-up and the cause of death . Patients for whom there was any disagreement were discussed in committee until a consensus was achieved . We describe the pattern of agreement among the adjudicators and with the final consensus result . Additionally , we model the adjudication process and predict the results if a smaller committee had been used . We found that reducing the number of adjudicators from five to two or three would probably have changed the consensus outcome in less than 10 % of cases . Correspondingly , the effect on the final study results ( comparing primary outcomes in both randomized arms ) would have been altered very little . Even using a single adjudicator would not have affected the results substantially . About 90 minutes of person-time per patient was required for activities directly related to the adjudication process , or approximately 6 months of full time work for the entire study . This level of effort could be substantially reduced by using fewer adjudicators with little impact on the results . Thus , we suggest that when high observer agreement is demonstrated or anticipated , adjudication committees should consist of no more than three members . Further work is needed to evaluate if smaller committees are adequate to detect small but important treatment effects or if they compromise validity when the level of adjudicator agreement is lower .

adjudication committee

adjudication process

Outcome assessment

number of adjudicators

Outcome assessment for clinical trials

adjudicators

potentially operable lung cancer .

Up to five independent adjudicators


Soluble intercellular adhesion molecule-1 in primary biliary cirrhosis : effect of ursodeoxycholic acid and immunosuppressive therapy . OBJECTIVES Soluble intercellular adhesion molecule-1 ( sICAM-1 ) is thought to be released by a variety of cells at sites of inflammation , and their serum levels have been used as markers of inflammatory and immune activity . Our aim was to determine the effect of therapy with ursodeoxycholic acid alone and in combination with azathioprine and prednisone on serum sICAM-1 levels in primary biliary cirrhosis . DESIGN/METHODS Twenty-four patients with primary biliary cirrhosis and 17 healthy subjects were studied . Primary biliary cirrhosis patients received ursodeoxycholic acid for 12 months and were then randomized in a double-blind fashion to receive prednisone and azathioprine , or placebo in addition to ursodeoxycholic acid . RESULTS sICAM-1 levels were significantly higher in primary biliary cirrhosis patients than healthy subjects and fell by a median of 20 % after 12 months ' therapy with ursodeoxycholic acid ( P < 0.0004 ) . Addition of azathioprine and prednisone to ursodeoxycholic acid resulted in a further reduction of sICAM-1 levels by a median of 25 % ( P < 0.01 ) . Reductions in sICAM-1 were accompanied by improvement in liver function tests but not in the lymphocyte activation marker , soluble interleukin-2 receptor . CONCLUSION sICAM-1 levels in primary biliary cirrhosis are reduced by ursodeoxycholic acid . Further reductions were achieved by adding prednisone and azathioprine . These reductions probably reflect an improvement in hepatobiliary excretion and a reduction in cellular production of sICAM-1 .

ursodeoxycholic acid

immunosuppressive therapy

ursodeoxycholic acid alone

azathioprine and prednisone

ursodeoxycholic acid

prednisone

azathioprine

placebo

ursodeoxycholic acid

ursodeoxycholic acid

azathioprine

prednisone

ursodeoxycholic acid

ursodeoxycholic acid

prednisone

azathioprine

serum sICAM-1 levels

sICAM-1 levels

sICAM-1 levels

liver function tests

lymphocyte activation marker

soluble interleukin-2 receptor

sICAM-1 levels

hepatobiliary excretion

cellular production of sICAM-1

primary biliary cirrhosis :

Twenty-four

primary biliary cirrhosis

healthy subjects