Outcome of children with centrally reviewed low-grade gliomas treated with chemotherapy with or without radiotherapy on Children 's Cancer Group high-grade glioma study CCG-945 . BACKGROUND The objectives of the current study were to determine the outcome of children who were treated with chemotherapy and radiotherapy on the Children 's Cancer Group ( CCG ) high-grade glioma protocol ( CCG-945 ) who were diagnosed with low-grade gliomas on post hoc central pathologic review and to identify clinical and biologic features associated with prognosis . METHODS Between 1985 and 1991 , 250 children with institutionally classified high-grade gliomas were enrolled on CCG-945 . Patients older than 24 months with intracranial lesions were assigned randomly to receive either lomustine , vincristine , and prednisone ( control regimen ) or the 8-drugs-in-1-day regimen ( experimental regimen ) ; younger patients and those with primary spinal cord tumors were assigned nonrandomly to the experimental regimen . Central independent review by 5 neuropathologists led to a reclassification of low-grade glioma in 70 patients , who were the focus of the current study . RESULTS The study involved 42 males and 28 females ( median age , 7.7 years ) with a median follow-up of 10.4 years . At 5 years , the progression-free survival ( PFS ) rate was 63 % +/- 6 % , and the overall survival ( OS ) rate was 79 % +/- 5 % , compared with a PFS rate of 19 % +/- 3 % ( P < 0.0001 ) and an OS rate of 22 % +/- 3 % ( P < 0.0001 ) in the remainder of the cohort . Significantly poorer 5-year PFS was seen in children younger than 24 months , those with fibrillary astrocytoma , and those with posterior fossa tumors . Patients demonstrated a modest improvement in PFS but no improvement in OS compared with children with low-grade gliomas who were treated with contemporary chemotherapy-alone approaches . CONCLUSIONS The current report calls attention to the importance of central pathologic review in large multiinstitutional trials of children with gliomas and suggests that aggressive front-line combined chemoradiotherapy does not confer a survival advantage in this highly selected population of patients .

chemotherapy and radiotherapy

clinical and biologic features

progression-free survival ( PFS ) rate

overall survival ( OS ) rate

PFS rate

OS rate

5-year PFS

PFS

OS

survival advantage

children

low-grade gliomas

children

chemotherapy

radiotherapy

high-grade glioma

low-grade gliomas

central pathologic review

children

high-grade gliomas

24 months

intracranial lesions

younger

primary spinal cord tumors

low-grade glioma

males

females

7.7 years

10.4 years


Abrasive wear on eroded root dentine after different periods of exposure to saliva in situ . The effect of salivary exposure time on the abrasive wear of acid-eroded dentine was evaluated in situ . One-hundred and twenty bovine root dentine slabs were randomly assigned into six groups ( A-F ) and placed in intraoral palatal devices , which were worn by 10 volunteers for 4 d. On the first day , no erosive/abrasive procedures were carried out . On the following 3 d , erosive challenges were performed extraorally , two times per day , by immersing the device for 90 s in a soft drink . Subsequently , the group A specimens were immediately brushed ( 40 strokes ) , and the others were brushed after the following times : B , 20 min ; C , 40 min ; and D , 60 min . Group E specimens were only acid-eroded and those of group F were only brushed . Dentine wear was measured with a profilometer . anova and Dunnett 's test showed that groups A-D did not differ statistically from the control group E but differed from the control group F. The lowest mean value was found for group F. Regression analysis was unable to show salivary effect on dentine wear reduction . The data suggest that the exposure time of saliva of up to 60 min has no effect on reducing the eroded dentine wear by toothbrushing .

saliva

salivary

erosive challenges

salivary

Abrasive wear

abrasive wear

Dentine wear

dentine wear reduction

eroded dentine wear

eroded root dentine

acid-eroded dentine


T lymphocyte subsets and NK cell cytotoxicity in chronic hemodialysis patients . The effect of recombinant human erythropoietin ( rHu-EPO ) treatment . We investigated subpopulations of T lymphocytes , NK cell number and cytotoxic activity in 14 chronic uremic patients on regular hemodialysis treatment . We observed a significantly decreased absolute lymphocyte number and percentage of CD3 cells . Relative numbers of CD16 cells were significantly elevated , but NK cell cytotoxic activity was within a normal range . Nine patients with chronic renal anemia on maintenance hemodialysis were enrolled in rHu-EPO treatment trial . The treatment was continued till the hematocrit level reached 30 % . Each of the patients had corrected anemia and well-being . After 12 weeks of the treatment we observed in these patients decreases in CD3 , CD4 , CD8 and CD16 cell numbers and elevation of CD4/CD8 ratio . Cytotoxic activity of NK cells did not change significantly . Presented results indicate that chronic hemodialysis patients have significantly diminished lymphocyte number . rHu EPO treatment affects the T lymphocyte subsets inducing a deep decrease of CD8 and CD16 cell percentage leading to normalisation of the CD4/CD8 ratio .

regular hemodialysis treatment

rHu-EPO

rHu EPO

T lymphocytes

NK cell number

cytotoxic activity

absolute lymphocyte number

percentage of CD3 cells

CD16 cells

NK cell cytotoxic activity

hematocrit level

anemia

CD3 , CD4 , CD8 and CD16 cell numbers

CD4/CD8 ratio

Cytotoxic activity of NK cells

lymphocyte number

CD8 and CD16 cell percentage

CD4/CD8 ratio

hemodialysis

Nine

renal anemia


Shorter treatment for vaginal candidosis : comparison between single-dose oral fluconazole and three-day treatment with local miconazole . Fluconazole is an effective , simple and safe , although slightly expensive , agent for the treatment of vaginal candidosis . Single-dose fluconazole ( 150 mg ) administered orally in capsule form was compared with three-day local treatment with miconazole pessaries in the treatment of vaginal candidosis in a randomized study in Finland . Cure rates were good ( > 80 % ) in randomized patient groups assessed both clinically and by the results of yeast cultures . Oral administration was preferred to local therapy by patients in both the miconazole and fluconazole groups . For the time being , fluconazole is not recommended for use during pregnancy or lactation .

fluconazole

miconazole

Fluconazole

miconazole pessaries

miconazole

fluconazole

fluconazole

Cure rates

vaginal candidosis :

vaginal candidosis

vaginal candidosis


[ Myocardial ischemia with stable angina pectoris : clinico-ergometric evaluation after the use of diltiazem ] . PURPOSE To evaluate the efficacy of diltiazem versus placebo in patients with stable angina . METHODS Eight-seven angina pectoris patients , mean age of 57 +/- 9 , 82 white and 79 male were evaluated in a randomized , double-blind trial of two groups of patients diltiazem and placebo , 3 to 4 tablets a day ( diltiazem 180 to 240 mg daily ) . The patients were evaluated after laboratory tests and clinical-ergometric examinations . A coronary arteriography was performed on study entry . RESULTS The average of anginal attacks , number of weekly sublingual nitrate , heart rate , systolic and diastolic pressure at rest and at the end of diltiazem period were significantly lower ( p < 0.05 ) regarding same periods on placebo . The percentage of depression for ST-segment was lower for diltiazem when compared with placebo ( p < 0.05 ) and the percentage of patients that reach higher stages in the ergometric test was significantly better for diltiazem . Heart rate and systolic plus diastolic pressures after exercise did not differ in both groups . CONCLUSION Diltiazem reduced the clinical and electrocardiographical aspects and raises the effort tolerance during the ergometric test in patients with stable angina .

diltiazem ]

diltiazem

placebo

diltiazem

placebo

diltiazem

placebo

diltiazem

placebo

diltiazem

Diltiazem

average of anginal attacks

number of weekly sublingual nitrate

heart rate

depression for ST-segment

Heart rate

systolic plus diastolic pressures

stable angina

Eight-seven

angina pectoris

mean age of 57 +/- 9

82 white

79 male


A controlled clinical trial of a muscle relaxant analgesic combination in the treatment of acute lumbago .

muscle relaxant analgesic combination

analgesic

acute lumbago


Effects of temafloxacin and ciprofloxacin on the pharmacokinetics of caffeine . A number of quinolone antibacterial agents , particularly enoxacin , pefloxacin , pipemidic acid and ciprofloxacin , are known to decrease the clearance of methylxanthines . The effects of temafloxacin and ciprofloxacin on the pharmacokinetics of caffeine were therefore compared in a 3-way crossover study in 12 healthy young volunteers . Each volunteer received 183mg once-daily doses of caffeine in conjunction with twice-daily placebo , temafloxacin 600mg and ciprofloxacin 750mg in 3 separate phases according to a randomised sequence . A doubling of the area under the plasma concentration-time curve ( 77.8 vs 31.8 mg/L.h ) and terminal-phase half-life ( 9.7 vs 4.5h ) of caffeine were observed in the presence of ciprofloxacin . The magnitude of the reduction in the intrinsic clearance of caffeine produced by ciprofloxacin was greater than that described in the literature for ciprofloxacin and theophylline . This may partly be explained by intertrial differences in dosage and study design . Coadministration of temafloxacin did not have any effect on the pharmacokinetics of caffeine , confirming results of other studies suggesting that this agent does not affect methylxanthine clearance . Accordingly , it appears that restriction of caffeine intake during temafloxacin therapy is not necessary .

temafloxacin

ciprofloxacin

ciprofloxacin

temafloxacin

ciprofloxacin

183mg once-daily doses of caffeine

placebo

temafloxacin 600mg

ciprofloxacin 750mg

caffeine

ciprofloxacin

ciprofloxacin

theophylline

temafloxacin

temafloxacin

terminal-phase half-life

pharmacokinetics of caffeine

methylxanthine clearance

healthy

young


The use of adrenocorticotrophic hormone ( 4-9 ) analog ORG 2766 in autistic children : effects on the organization of behavior . In a double-blind placebo-controlled crossover trial , 14 autistic children were treated with the neuropeptide ORG 2766 , a synthetic analog of adrenocorticotrophic hormone ( ACTH ) ( 4-9 ) . ORG 2766 treatment ( 20 mg per day during 4 weeks ) was associated with an increased amount and an improved quality of the social interaction of the autistic children with a familiar experimenter . These changes in interaction were clinically relevant . Following treatment with ORG 2766 gaze and smile behaviors of child and experimenter showed stronger temporal contingencies . Further , after ORG 2766 , stereotypies were temporally disconnected from verbal initiatives . The data supported the notion of a stimulating effect of ORG 2766 on social interaction . The implications of these findings for the endogenous opioid theory of autism are discussed .

neuropeptide ORG 2766

ORG 2766 treatment

ORG 2766

ORG 2766

ORG 2766

gaze and smile behaviors

stronger temporal contingencies .

verbal initiatives .

autistic children :

14 autistic children


Randomized phase II trial of high-dose 4'-epi-doxorubicin + cyclophosphamide versus high-dose 4'-epi-doxorubicin + cisplatin in previously untreated patients with extensive small cell lung cancer . One hundred and eleven previously untreated patients with extensive small cell lung cancer were included in a prospective randomized study with the aim to assess the efficacy and tolerance of high-dose epirubicin ( 120 mg/m2 ) in combination with either cyclophosphamide ( 800 mg/m2 ; arm 1 ) or cisplatin ( 60 mg/m2 ; arm 2 ) . Ninety-six patients were evaluable for response and toxicity and additional 12 patients for toxicity only . The overall response rate ( CR+PR ) in arm 1 and 2 were 61.4 ( 27/44 ) and 67.3 % ( 35/52 ) , respectively . The mean duration of remission was 4.4 months ( arm 1 ) and 4.9 months ( arm 2 ) . The mean survival time was 6.6 months in arm 1 and 7.7 months in arm 2. WHO grade 4 toxicity was encountered in 25.5 and 15.8 % of patients in arm 1 and 2 , respectively . One case of cardiotoxicity resulting in the patient 's death was observed in arm 1 . Both combinations showed considerable antitumor activity . Toxicity was acceptable .

cyclophosphamide

cisplatin

high-dose epirubicin

cyclophosphamide

cisplatin

efficacy

tolerance

response

toxicity

toxicity

overall response rate ( CR+PR )

mean duration of remission

mean survival time

WHO grade 4 toxicity

cardiotoxicity

death

antitumor activity

Toxicity

extensive small cell lung cancer

One hundred and eleven

extensive small cell lung cancer

Ninety-six patients

12 patients


The adrenocorticotrophic hormone ( 4-9 ) analog ORG 2766 benefits autistic children : report on a second controlled clinical trial . In a second controlled crossover trial , 20 autistic children received 40 mg/day of the neuropeptide ORG 2766 , a synthetic analog of ACTH ( 4-9 ) , for 8 weeks . Parents ' checklist ratings ( ABC ) as well as clinicians ' ratings ( CGI ) pointed to significant improvements after the course of treatment ; improvements were clearest on the ABC social withdrawal subscale . The analysis of individual target symptoms and the parents ' treatment preferences substantiated the beneficial effects of ORG 2766 . In an ethologically analyzed playroom session , ORG 2766 treatment was associated with an improvement in the children 's play behavior and a significant increase in the social interaction between child and experimenter . Gaze coordination between child and experimenter also was improved .

ORG 2766 .

Parents ' checklist ratings ( ABC )

clinicians ' ratings ( CGI )

ABC social withdrawal subscale .

children 's play behavior


Role of memory B-cell responses in serum and mucosal fluids of swine for protective immunity against pseudorabies virus . We examined primary and memory isotype-specific antibody responses directed against pseudorabies virus in serum and mucosal fluids of pigs with and without passively acquired maternal antibody , and we studied the relationship between these responses and protection against virus challenge . Pigs were inoculated intranasally with the virulent NIA-3 strain or the avirulent Bartha strain , or they were inoculated IM with an inactivated vaccine containing the Phylaxia strain . Ten weeks later , all pigs were challenge-exposed intranasally with strain NIA-3 . Only pigs that were without passively acquired antibody at the time they were inoculated with virulent virus appeared to have complete protective immunity against challenge exposure , as evidenced by lack of clinical signs of pseudorabies and lack of virus excretion . In contrast , pigs inoculated with strain Bartha or with the inactivated vaccine developed fever , had a period of growth arrest , and excreted virus after challenge exposure . In pigs without passively acquired antibody , intranasal inoculation with strains NIA-3 or Bartha was followed by primary IgM and IgA responses in serum and in oropharyngeal fluid as well as primary IgG1 and IgG2 responses in serum . Intramuscular inoculation with the inactivated vaccine induced primary serum IgM , IgG1 , and IgG2 responses , but no mucosal responses . Challenge exposure of pigs that had been inoculated with the Bartha strain or the inactivated vaccine was followed by clear memory responses in serum and in oropharyngeal fluid . In contrast , challenge exposure of pigs that had been inoculated by the virulent NIA-3 strain was not followed by memory responses . ( ABSTRACT TRUNCATED AT 250 WORDS )

virulent

NIA-3 strain

avirulent Bartha strain

challenge-exposed

intranasally with strain NIA-3

complete protective immunity

clinical signs of pseudorabies

virus excretion

fever

period of growth arrest

excreted virus

IgM and IgA responses

serum

oropharyngeal fluid

mucosal responses

memory responses

Pigs


Erythema migrans : comparison of treatment with azithromycin , doxycycline and phenoxymethylpenicillin . Azithromycin , doxycycline and phenoxymethylpenicillin were compared in a prospective , randomized study of 64 patients with typical erythema migrans . Twenty patients were treated with oral azithromycin , 250 mg bd for two days followed by 250 mg od for eight days , 21 patients were given phenoxymethylpenicillin 1 million IU tds for 14 days and 23 patients received doxycycline , 100 mg bd for 14 days . All patients were followed up for 24 months . There were no significant differences between the groups with respect to the persistence of cutaneous lesions after starting treatment ; the mean durations were 10.5 days in the penicillin group , 8.8 days in the doxycycline group and 8.6 days in the azithromycin group . There were statistically significant differences in terms of the resolution of associated local and/or systemic symptoms . The response time was shortest in patients treated with azithromycin . Two patients who received phenoxymethylpenicillin and two given doxycycline subsequently developed major manifestations of Lyme borreliosis ; these did not occur in patients receiving azithromycin . Although azithromycin has been shown to be effective in the treatment of erythema migrans , further studies will be needed to determine the optimal dosage and duration of therapy .

azithromycin

doxycycline

phenoxymethylpenicillin

Azithromycin

doxycycline

phenoxymethylpenicillin

oral azithromycin

phenoxymethylpenicillin

doxycycline

penicillin

doxycycline

azithromycin

azithromycin

phenoxymethylpenicillin

doxycycline

azithromycin

azithromycin

cutaneous lesions

mean durations

response time

Lyme borreliosis

Erythema migrans

erythema migrans


Long-term anticoagulant treatment after acute myocardial infarction . The Warfarin Re-Infarction Study . High levels of fibrinogen and clotting factor VII are associated with an increased risk for subsequent death and cardiovascular disease in apparently healthy individuals . Furthermore , pathoanatomic studies and coronary angiography have confirmed a relationship between coronary thrombus formation and acute Q-wave infarction . Effective antithrombotic agents may prevent or limit thrombus formation and events related to thrombosis . The Warfarin Re-Infarction Study ( WARIS ) studied the effect of warfarin in survivors of acute myocardial infarction . Patients aged 75 years or less were randomized in a double-blind , placebo-controlled study to test whether long-term treatment with warfarin reduces the risk of death , reinfarction , and thromboembolic morbidity . A total of 1918 patients were screened for participation ; 1214 were recruited . The mean follow-up was 37 months . Analyzed on an intention-to-treat basis , 123 ( 20 % ) in the placebo group died , versus 94 ( 15 % ) in the warfarin group , a risk reduction of 24 % ( P = 0.026 ) . Considering patients on treatment or within 28 days after discontinuing the test medication , 92 in the placebo group died , as compared with 60 of the warfarin-treated patients , a risk reduction of 35 % ( P = 0.005 ) . Relapsing myocardial infarction ( fatal and nonfatal ) was reduced by 43 % ( P = 0.0001 ) . The incidence of cerebrovascular attacks was lower in the warfarin group ( 16 patients ) than the placebo group ( 41 patients ) , a highly significant reduction of 61 % ( P = 0.0003 ) . Serious bleeding occurred in 11 patients taking warfarin , an incidence of 0.6 % per year . In conclusion , long-term anticoagulant therapy may be recommended after acute myocardial infarction .

anticoagulant treatment

warfarin

placebo-controlled

warfarin

placebo

warfarin

warfarin-treated

warfarin

placebo

warfarin

increased risk

subsequent death

cardiovascular disease

thrombus formation

events related to thrombosis .

risk

death , reinfarction

thromboembolic morbidity

died

risk reduction

died

risk reduction

incidence of cerebrovascular attacks

Serious bleeding

acute myocardial infarction


Topical anti-inflammatory drugs in the treatment of allergic pollinosic conjunctivitis : a comparative double-blind study . Anti-inflammatory drugs , i.e . glucocorticosteroids and NSAIDs ( nonsteroidal anti-inflammatory drugs ) , are often included in the treatment of allergic conjunctivitis . The present study compares the clinical efficacy and safety of topical hydrocortisone , acetylsalicylic acid ( ASA ) and piroxicam compared to placebo . The trial , designed as a double-blind , randomized and parallel-group treatment , was carried out in a group of 40 patients suffering from seasonal allergic conjunctivitis due to Parietaria pollen , during the pollen season ( June-July , 1990 ) . Patients received hydrocortisone 0.1 % solution , ASA 1 % solution , piroxicam 0.5 % solution or placebo as eye drops , all one drop in each eye q.i.d . for 14 days . The symptoms were evaluated at baseline and at the end of treatment by the clinician and by patients on a diary card . The hydrocortisone group showed a rapid and significant improvement during the first week of treatment , while ASA and piroxicam reduced symptomatology during the second week of treatment ; this difference was statistically significant . At the end of the trial , the active drugs were comparable with regard to clinical efficacy . A statistically significant difference was observed between the active drugs and placebo , while no statistically significant difference was observed among the three drugs . No serious side-effects were observed . The results demonstrate the clinical efficacy of anti-inflammatory drugs in the treatment of pollen-induced allergic conjunctivitis ; they also suggest the use of NSAIDs in long-term treatment , as their efficacy has been shown to be closely comparable to that of steroids , while avoiding the well-known side-effects of the latter in prolonged treatment .

Topical anti-inflammatory drugs

glucocorticosteroids and NSAIDs

nonsteroidal anti-inflammatory drugs

hydrocortisone

acetylsalicylic acid ( ASA )

piroxicam

placebo

hydrocortisone 0.1 % solution

ASA 1 % solution

piroxicam 0.5 % solution

placebo

efficacy and safety

symptomatology

clinical efficacy .

serious side-effects

allergic pollinosic conjunctivitis :

allergic conjunctivitis .


Amisulpride versus bromocriptine in infantile autism : a controlled crossover comparative study of two drugs with opposite effects on dopaminergic function . An alteration of dopaminergic ( DA ) function much more complex than simple hyperactivity has been evoked in infantile autism . We therefore compared the clinical efficacy of a DA antagonist ( amisulpride ) and a DA agonist ( bromocriptine ) in a randomized , double-blind , crossover trial in 9 children with autism , likely severely mentally retarded . Amisulpride acts preferentially on specific autistic symptoms whereas bromocriptine acts more on motor hyperactivity and attention symptoms . These findings raise the specificity of these two drugs which appear to act preferentially on some target symptoms and are consistent with some clinical and pharmacological observations showing a sedative effect with low doses of DA agonists and a stimulant effect with low doses of DA antagonists such as the benzamides .

Amisulpride

bromocriptine

DA antagonist ( amisulpride )

DA agonist ( bromocriptine )

Amisulpride

bromocriptine

DA agonists

DA antagonists

benzamides

dopaminergic ( DA ) function

clinical efficacy

sedative effect

stimulant effect

infantile autism :

infantile autism

children

autism

mentally retarded


Oral ondansetron in the prevention of postoperative nausea and vomiting . The effect of three times daily oral ondansetron in preventing postoperative nausea and vomiting was investigated in two randomized , double-blind , placebo-controlled , multi-centre studies . The first study compared ondansetron 1 , 8 and 16 mg to placebo , and the second study compared 8 mg ondansetron to placebo . Both studies included ASA Class I-III female patients about to undergo major abdominal gynaecological surgery or vaginal hysterectomy . In the first study , the 8 and 16 mg ondansetron groups had a significantly lower incidence of nausea and vomiting in the 0-24 h period following recovery from anaesthesia than the placebo group . Ondansetron 8 mg three times daily was also significantly better than placebo in the second study . Side-effects mainly consisted of constipation , headache , and asymptomatic elevation of liver enzymes . The incidence of side-effects was similar in ondansetron- and placebo-treated patients . There appeared to be no clinically important benefit of the 16 mg three times daily ondansetron regimen over the 8 mg three times daily dose , therefore 8 mg three times daily is recommended as the optimal oral dose in the prevention of postoperative nausea and vomiting .

ondansetron

placebo-controlled

ondansetron 1 , 8 and 16 mg

placebo

8 mg ondansetron

placebo

8 and 16 mg ondansetron groups

placebo

Ondansetron

ondansetron

postoperative nausea and vomiting

incidence of nausea and vomiting

Side-effects

side-effects

clinically important benefit

postoperative nausea and vomiting

ASA Class I-III

female


Effect of enalapril on myocardial infarction and unstable angina in patients with low ejection fractions . An association between raised renin levels and myocardial infarction has been reported . We studied the effects of enalapril , an angiotensin-converting enzyme ( ACE ) inhibitor , on the development of myocardial infarction and unstable angina in 6797 patients with ejection fractions < or = 0.35 enrolled into the two Studies of Left Ventricular Dysfunction ( SOLVD ) trials . Patients were randomly assigned to placebo ( n = 3401 ) or enalapril ( n = 3396 ) at doses of 2.5-20 mg per day in two concurrent double-blind trials with the same protocol . Patients with heart failure entered the treatment trial ( n = 2569 ) and those without heart failure entered the prevention trial ( n = 4228 ) . Follow-up averaged 40 months . In each trial there were significant reductions in the number of patients developing myocardial infarction ( treatment trial : 158 placebo vs 127 enalapril , p < 0.02 ; prevention trial : 204 vs 161 p < 0.01 ) or unstable angina ( 240 vs 187 p < 0.001 ; 355 vs 312 , p < 0.05 ) . Combined , there were 362 placebo group patients with myocardial infarction compared with 288 in the enalapril group ( risk reduction 23 % , 95 % CI 11-34 % ; p < 0.001 ) . 595 placebo group patients developed unstable angina compared with 499 in the enalapril group ( risk reduction 20 % , 95 % CI 9-29 % , p < 0.001 ) . There was also a reduction in cardiac deaths ( 711 placebo , 615 enalapril ; p < 0.003 ) , so that the reduction in the combined endpoint of deaths , myocardial infarction , and unstable angina was highly significant ( 20 % risk reduction , 95 % CI 14-26 % ; p < 0.0001 ) . Enalapril treatment significantly reduced myocardial infarction , unstable angina , and cardiac mortality in patients with low ejection fractions .

enalapril

enalapril

placebo

enalapril

placebo

enalapril

placebo

enalapril

placebo

enalapril

placebo

enalapril

Enalapril

unstable angina

reduction in cardiac deaths

deaths

myocardial infarction

unstable angina

myocardial infarction

unstable angina

cardiac mortality

patients with low ejection fractions


Amphotericin versus pentamidine in antimony-unresponsive kala-azar . We compared the efficacy of amphotericin B and pentamidine isethionate in a prospective randomised trial in 120 uncomplicated and parasitologically confirmed cases of antimony-unresponsive kala-azar . Doses were twenty intramuscular injections of pentamidine 4 mg/kg on alternate days or fourteen definitive doses of amphotericin 0.5 mg/kg infused in 5 % dextrose on alternate days . 48 ( 80 % ) patients given pentamidine showed initial cure and 46 ( 77 % ) showed definitive cure compared with 60 ( 100 % ) and 59 ( 98 % ) cases , respectively , on amphotericin ( p < 0.001 ) . Amphotericin also brought about quicker abatement of fever and more complete spleen regression .

Amphotericin

pentamidine

amphotericin B

pentamidine isethionate

pentamidine

amphotericin

pentamidine

amphotericin

Amphotericin

initial cure

definitive cure

abatement of fever

complete spleen regression

antimony-unresponsive kala-azar

antimony-unresponsive kala-azar


Dexmedetomidine infusion for maintenance of anesthesia in patients undergoing abdominal hysterectomy . The usefulness of intravenous dexmedetomidine infusion for maintenance of anesthesia was studied in patients anesthetized with thiopental , fentanyl , nitrous oxide , and oxygen . Isoflurane was added as needed . The study was conducted in two parts , the first of which was an open dose-response study that comprised 14 women undergoing abdominal hysterectomy . After a suitable infusion regimen of dexmedetomidine was determined according to hemodynamic criteria , 20 patients were included in a double-blind , randomized placebo-controlled trial ( 10 receiving dexmedetomidine , 10 saline solution ) . Dexmedetomidine was administered as a two-step infusion to rapidly achieve a steady-state plasma concentration . The infusion was started with an initial dose given over 10 min before the induction of anesthesia ; at induction the maintenance rate was begun and continued until closure of the abdominal fascia . The infusion regimens of dexmedetomidine tested in the dose-response study ranged from 120 ng.kg-1 x min-1 , followed by 6 ng.kg-1 x min-1 , to 270 + 13.5 ng.kg-1 x min-1 . In the second part of the study , an initial infusion of 170 ng.kg-1 x min-1 was chosen , followed by 10 ng.kg-1 x min-1 for maintenance . Anesthesia was induced with thiopental ( 4.0 mg/kg ) and maintained with isoflurane in 70 % nitrous oxide and oxygen . Isoflurane was administered according to predetermined hemodynamic criteria . Dexmedetomidine infusion did not completely abolish the need for isoflurane but diminished its requirement by > 90 % ( P = 0.02 ) . The heart rate response to endotracheal intubation was significantly blunted .

Dexmedetomidine

dexmedetomidine

dexmedetomidine

placebo-controlled

dexmedetomidine

saline solution

Dexmedetomidine

dexmedetomidine

Dexmedetomidine

was significantly blunted

abdominal hysterectomy


Different aprotinin applications influencing hemostatic changes in orthotopic liver transplantation . The effect of different aprotinin applications on hemostatic changes and blood product requirements in orthotopic liver transplantation was investigated in a prospective , open , and randomized study . From November 1989 to June 1990 , 13 patients received aprotinin as a bolus of 0.5 Mill . Kallikrein inactivator units ( KIU ) on three occasions in the course of an OLT , whereas 10 other patients were treated with continuous aprotinin infusion of 0.1-0.4 Mill . KIU/hr . Before and after reperfusion of the graft liver , signs of hyperfibrinolysis , measured by thrombelastography , were significantly lower in the infusion group . Tissue-type plasminogen activator ( t-PA ) activity increased during the anhepatic phase but to a significantly lesser extent in the infusion group . Blood product requirements during OLT were tendentiously higher in the bolus group but not significantly so . However , the use of packed red blood cells was significantly lower in the postoperative period , whereas there was no significant difference in fresh frozen plasma requirements between the two groups . All 23 patients have survived , and only one woman of each group required retransplantation due to severe host-versus-graft reactions . Furthermore , we investigated the perfusate of the graft liver in both groups and detected signs of a decreased t-PA release in the infusion group . Our results demonstrate an advantage of aprotinin given as continuous infusion over bolus application in OLT .

Different aprotinin applications

aprotinin applications

aprotinin

bolus of 0.5 Mill

aprotinin

Blood product requirements

packed red blood cells

plasma requirements

survived

retransplantation

host-versus-graft reactions

t-PA release

orthotopic liver transplantation .


Induction chemotherapy in head and neck cancer : results of a phase III trial . Between December 1982 and October 1986 , 131 patients with stage II-III-IV squamous cell carcinoma of the oropharynx or oral cavity were randomized to induction chemotherapy , consisting of bleomycin ( 10 mg/m2/day in continuous infusion from day 1 to day 5 ) , methotrexate ( 120 mg/m2 on day 2 ) followed by folinic acid , 5-fluorouracil ( 5 FU ) ( 600 mg/m2 on day 2 ) , and cisplatin ( 120 mg/m2 on day 4 ) every 4 weeks for a total of three cycles followed by definitive locoregional treatment versus locoregional treatment alone . The modalities of definitive treatment ( radiotherapy +/- surgery ) were chosen prior to randomization . A total of 116 patients were evaluable . Of 55 patients in the chemotherapy arm , four ( 7 % ) had a complete response ( CR ) and 23 ( 42 % ) a partial response ( PR ) following the induction regimen . At the completion of locoregional treatment , 76 % ( 42 of 55 ) of patients in the experimental group were in CR compared to 89 % ( 54 of 61 ) in the control group . There was no difference in survival , cause-specific survival , and pattern of relapse between both groups . The median survival was 22 months in the chemotherapy group and 29 months in the control group . Responders to chemotherapy did not fare better than nonresponders . Chemotherapy-related toxicities were few and most of them related to cisplatin which was reduced to 100 mg/m2 for 35 patients . There were no treatment-related deaths and , in the experimental arm of the trial , no increased morbidity from locoregional treatment . This induction regimen does not offer any advantages over standard treatment .

Induction chemotherapy

locoregional treatment

radiotherapy

surgery

chemotherapy

survival

cause-specific survival

pattern of relapse

median survival

Chemotherapy-related toxicities

deaths

morbidity

head and neck cancer

116 patients were evaluable


Iloprost in cardiopulmonary bypass procedures . The inhibition of platelet aggregation during cardiopulmonary bypass and effects on post-operative placebo-controlled study of 145 patients . Significant preservation of platelet numbers and function were shown without significant haemodynamic problems , but no effect on cerebral deficits could be found . The use of iloprost in patients with severe thrombocytopenia seems justified , but the clinical benefits from its use in routine cardiopulmonary bypass remain to be shown .

Iloprost

placebo-controlled

iloprost

cardiopulmonary bypass

placebo-controlled

severe thrombocytopenia


Cone biopsy : has endocervical sampling a role ? OBJECTIVE To investigate the sensitivity , specificity and predictive value of endocervical sampling in women with abnormal cervical smears . DESIGN A randomized study of two methods of endocervical sampling . SETTING Colposcopy clinic at Aberdeen Royal Infirmary . SUBJECTS 100 women with abnormal cervical smears selected for cone biopsy according to current colposcopy criteria . INTERVENTIONS 53 women were randomized to have endocervical sampling with the Kevorkian curette and 47 to have sampling with the Medscand endocervical brush . MAIN OUTCOME MEASURES Cytology and histology results from endocervical sampling compared with cone biopsy histology . RESULTS The overall sensitivity of endocervical sampling was 56 % , with a false negative rate of 44 % and a negative predictive value of 26 % . CONCLUSIONS Endocervical sampling should not influence management when colposcopy is unsatisfactory .

endocervical sampling

endocervical sampling

endocervical sampling

endocervical sampling

endocervical sampling

Endocervical sampling

cone biopsy histology

sensitivity of endocervical sampling

false negative rate

negative predictive value

women

abnormal cervical smears .

women

abnormal cervical smears


Treatment of peptic ulcer disease with furazolidone . Furazolidone ( FZ ) has been used in China as a treatment of peptic ulcer disease for about 20 years . Clinical and experimental studies suggest that it has good short-term and long-term effects on both human and animal ulcers . The ulcer healing rate is related to the dosage and course of treatment . The healing rate of a high dose , 2 week course is about 70-75 % and the relapse rate after 3 years is 9.5 % . The adverse reactions to FZ are not severe , and are well tolerated in most patients . However the mutagenic studies of several biological systems indicate that it has a mutagenic effect , but the mutagenic and carcinogenic effects on humans and animals remain questionable , because FZ has been biotransformed into other metabolites . The mechanisms of FZ in the treatment of peptic ulcer disease are not fully understood , perhaps partly due to the monoamine oxidase ( MAO ) inhibitory reaction and partly to the antibacterial activity to Helicobacter pylori ( HP ) . The long-term effects of FZ are still not clear .

furazolidone . Furazolidone

peptic ulcer disease

peptic

animal ulcers .

ulcer healing

tolerated

mutagenic

carcinogenic

peptic ulcer disease

peptic ulcer disease

human

animal ulcers

peptic ulcer disease


Perioperative immunotherapy with recombinant interleukin 2 in patients undergoing surgery for colorectal cancer . Major surgery impairs the cellular immune response . We have therefore studied the immunological effects of low-dose recombinant interleukin 2 given to patients undergoing surgery for colorectal cancer to determine whether this agent has potential in perioperative adjuvant immunotherapy . Patients were randomly allocated to control ( n = 13 ) or treatment groups ( n = 12 ) . Immunological studies of both lymphocyte function and subset number were performed preoperatively and on Days 1 , 4 , 7 , and 10 . Treatment with recombinant interleukin 2 prevented the postoperative fall in both natural killer and lymphokine-activated killer cell cytotoxicity , clearly demonstrated in the control group . The treatment group also showed in vivo T-cell activation with an initial lymphopenia followed by a rebound lymphocytosis and upregulation of the subset markers CD25 ( interleukin 2 receptor ) and CD45RO ( T-memory cells ) . These combined effects may have important consequences in controlling metastatic dissemination of tumor during the vulnerable perioperative period .

recombinant interleukin 2

low-dose recombinant interleukin 2

control

recombinant interleukin 2

lymphocyte function

vivo T-cell activation

rebound lymphocytosis

CD45RO ( T-memory cells )


Buprenorphine alone and in combination with naloxone in non-dependent humans . This study evaluated the effects of concurrent naloxone on the opioid agonist effects of buprenorphine , a mixed agonist-antagonist marketed as an analgesic and under development as a treatment for drug abuse . In a residential laboratory seven non-physically-dependent opioid abuser volunteers received intramuscular buprenorphine ( 0.4 mg or 0.8 mg/70 kg ) alone and in combination with naloxone ( 0.4 mg or 0.8 mg/70 kg ) versus placebo . Buprenorphine produced dose-related opioid agonist effects on physiological and subjective measures . Concurrent naloxone attenuated the opioid agonist effects of buprenorphine . Thus , a combination product of buprenorphine and naloxone may have lower abuse liability than buprenorphine alone .

naloxone

buprenorphine

placebo

physiological and subjective measures

the opioid agonist effects

abuse liability

seven

opioid abuser


A randomized trial of a health care program for first-time adolescent mothers and their infants . To test the effectiveness of a special health care program for adolescent mothers ( 17 years old or younger ) and their infants , 243 mother-infant pairs were randomly assigned to one of two groups . All of the mothers were unwed , on Medicaid , and black . The control group received routine well-baby care . The experimental group received routine care and services that included rigorous follow-up , discussions with the mother about her plans for return to school and use of family planning methods , and extra health teaching . The dropout rate in the experimental group ( 60 % ) was significantly less after 18 months than the control group ( 82 % ) . In spite of the high dropout rate , 91 % of the mothers were located for the 18 month follow-up interview . The repeat pregnancy rate in the experimental group was 12 % after 18 months , and 28 % in the control group . There was no significant difference in the percentage returning to school . After 12 months , the infants in the experimental group were more likely to be fully immunized ( 33 % ) than the infants in the control group ( 18 % ) . Mothers in the special care program who continued to attend clinic used the emergency room less than the mothers who continued to attend in the control group . These results suggest that a comprehensive health care program is one way to bring about better outcomes for both adolescent mothers and their infants .

special health care program

extra health teaching

special care program

comprehensive health care program

repeat pregnancy rate

percentage returning to school

fully immunized

used the emergency room less

first-time

adolescent

and their

infants

adolescent

mothers

were randomly assigned


The cumulative dose response effect of eicosapentaenoic and docosahexaenoic acid on blood pressure , plasma lipid profile and diet pattern in mild to moderate essential hypertensive black patients . In this study eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) were given in a cumulative manner , every 6 weeks , starting with 10 mg , then 100 mg , 1000 mg and 10,000 mg EPA daily to mild to moderate essential hypertensive black patients . The corresponding DHA doses were 3 , 33 , 333 and 3333 mg. A control group was given olive oil as placebo for the entire 24 weeks . The placebo group had lower diastolic and systolic blood pressures after 24 weeks than the EPA and DHA group . No effect was seen on plasma triglycerides , cholesterol , HDL-cholesterol and gamma-glutamyltranspeptidase at any stage of the trial . In the EPA group plasma free-EPA increased significantly from 1000 mg onwards and plasma free-arachidonic acid ( AA ) decreased after 1000 mg EPA . No other plasma free essential fatty acid changed during the trial , although the HDL : cholesterol increased slightly but non-significantly with an increase in EPA and DHA . No significant changes in diet pattern or body mass was observed . It is therefore concluded that EPA and DHA supplementation had no beneficial effects in mild to moderate essential hypertensive black patients except for a lowering of plasma AA .

eicosapentaenoic

docosahexaenoic acid

eicosapentaenoic acid ( EPA )

docosahexaenoic acid ( DHA )

EPA

DHA

olive oil as placebo

placebo

EPA

DHA

EPA

EPA

EPA

DHA

EPA

DHA supplementation

plasma free-EPA

plasma free-arachidonic acid ( AA )

plasma free essential fatty acid

HDL : cholesterol

EPA and DHA

diet pattern or body mass

lowering of plasma AA


The radial forearm flap : a biomechanical study of donor-site morbidity utilizing sheep tibia . The use of vascularized bone grafts to reconstruct extremity and mandibular defects is now commonplace in reconstructive surgery . Fibula , scapula , iliac crest , rib , and metatarsal as well as the radial forearm osseocutaneous flaps have all been utilized for this purpose . Troublesome spiral fractures of the distal radius are the most common fractures associated with the use of the distal radius as a vascularized bone-graft donor site . This study was proposed to investigate the effect of donor-site bone loss on the strength of the radius under torsional ( rotational ) loading . Previous clinical series and experimental studies have not examined this aspect of distal radius loading after harvesting the bone graft . Fifty pairs of sheep tibiae were utilized in the experiment . Five pairs were used in a pilot study and 45 pairs were used in the main experiment . Five pairs of human radii were used for the control in the pilot study . The pilot study attempted to make a comparison between the human radius and the sheep tibia for experimental purposes . For the biomechanical study of donor-site defects , four study groups were examined with random assignment and matched pairs . The control group ( group 1 ) had no alteration to the bone . Each test condition included five matched pairs of sheep tibiae . Experiment 1 compared the difference in the depth of the osteotomy defect . In doing this , one-third of the total length of the bone was removed in each of the following specimens to include ( 1a ) 30 percent of the cross-sectional area of the total bone , ( 1b ) 37 percent of the cross-sectional area of the total bone , and ( 1c ) 50 percent of the cross-sectional area of the total bone . In experiment 2 , the osteotomy shape was varied . Instead of the ends of the cuts being squared , the ends were beveled or rounded . Experiment 3 compared different lengths of bone removed in the osteotomy defect and included the following : In experiment 3a the diameter of the sheep tibia was measured at the incisura fibularis . This dimension was one diameter of bone , and a one-diameter length of bone was removed . In experiment 3b , a two-diameter length of bone was removed . In experiment 3c , a three-diameter length of bone was removed . In experiment 3d , a four-diameter length of bone was removed . ( ABSTRACT TRUNCATED AT 400 WORDS )

vascularized bone grafts

no alteration to the bone

osteotomy shape

osteotomy defect .

osteotomy shape

Fifty

Five

Five


[ Physical performance and sedation : comparative study of the effects of a benzodiazepine ( temazepam ) and of a non-benzodiazepine hypnotic ( zolpidem ) ] . It is well-known that many athletes experience some form of precompetition stress that may result in insomnia during the night before their competition . Yet , sleep withdrawal even if only partial , has a negative influence on performance , particularly when the type of exercise requires good psychomotor performance The purpose of the present study was to investigate whether the intake of a hypnotic drug would have negative effects on physical performance capacity . The authors have compared the effects of oral temazepam , a medium half-life benzodiazepine vs oral zolpidem , a short half-life non-benzodiazepine drug , vs placebo . A randomized double-blind trial was used to assess endurance , resistance , strength and coordination in 26 athletes . The results did not show any differences between the three groups , neither in physical performance characteristic nor in coordination . It is concluded that as regards the performance capacity , there is no risk for stressed athletes to use sleep inducers the night before their competition .

benzodiazepine ( temazepam )

oral temazepam

medium half-life benzodiazepine

oral zolpidem

placebo

endurance

resistance

strength

and

coordination

26 athletes

stressed


Desmopressin has no beneficial effect on excessive postoperative bleeding or blood product requirements associated with cardiopulmonary bypass . Cardiopulmonary bypass during open-heart surgery is sometimes associated with excessive perioperative bleeding . Following a non-randomized study suggesting that desmopressin acetate ( desmopressin ) reduced blood product requirements in these patients , we conducted a double-blind , placebo-controlled randomized trial of desmopressin ( 0.3 micrograms/kg , i. v. ) in 92 patients with overt bleeding and a prolonged bleeding time . Mean blood loss during the first 24 h post-treatment was similar in the desmopressin and placebo groups ( 582 vs 465 ml , respectively ; p = 0.15 ) . Red-cell ( p = 0.76 ) , fresh frozen plasma ( r = 0.66 ) and platelet unit ( p = 0.74 ) requirements were also similar . The haemostatic effect of desmopressin has been attributed to the release of von Willebrand factor ( vWF ) and a reduced bleeding time . In our study , vWF and factor VIII : C levels increased while the bleeding time decreased significantly at 90 min and 24 h in both groups and , although vWF and factor VIII : C levels were slightly higher in desmopressin-treated patients at 90 min , the difference was not significant . Thrombin-antithrombin III complex , fibrinogen degradation product and tissue plasminogen activator levels , reflecting activation of the coagulation and fibrinolytic systems , respectively , decreased uniformly in both groups . We conclude that desmopressin is not useful in reducing blood loss or blood product requirements in patients with excessive immediate postoperative bleeding .

Desmopressin

desmopressin acetate ( desmopressin )

placebo-controlled

desmopressin

desmopressin

placebo

postoperative bleeding

perioperative bleeding

blood loss

bleeding time

vWF and factor VIII : C levels

bleeding time

vWF and factor VIII : C levels

Thrombin-antithrombin III complex

fibrinogen degradation product

and

tissue plasminogen activator levels

bleeding

blood product requirements

cardiopulmonary bypass

overt bleeding

prolonged bleeding time


Isoflurane and propofol for long-term sedation in the intensive care unit . A crossover study . Propofol and isoflurane have been reported recently to offer better sedation than alternative agents in patients who require long-term ventilation in the Intensive Care Unit . This is the first report of a direct comparison between propofol and isoflurane . Twenty-four patients predicted to require artificial ventilation for at least 48 h were entered into a randomised crossover study to monitor sedation quality and time to recovery from sedation . There were no significant differences between the two agents in either end-point , with over 95 % optimal sedation achieved by the use of each drug . Few adverse events were noted . Technological advances in the administration of volatile agents as long-term sedatives in the Intensive Care Unit may facilitate their more widespread use .

Propofol

isoflurane

propofol

isoflurane

sedation

sedation quality

time to recovery from sedation

optimal sedation

adverse events

Twenty-four


Prevention of acute postoperative pressure rises in glaucoma patients undergoing cataract extraction with posterior chamber lens implant . Acute elevations in intraocular pressure ( IOP ) commonly follow extracapsular cataract extraction and lens implant in glaucoma patients . Thirty six patients with glaucoma undergoing cataract extraction and posterior chamber lens implantation received one of three treatments . Group 1 : 500 mg of Diamox Sustets ( acetazolamide ) 1 hour preoperatively ( 10 patients ) ; Group 2 : peroperative intracameral Miochol ( acetylcholine ) ( 11 patients ) ; Group 3 : the above treatments combined ( 15 patients ) . IOPs were measured at 3 , 6 , 9 , and 24 hours postoperatively . The average of the maximum pressure rises above the preoperative level over the 24 hour period was greatest for the group receiving acetazolamide only at 8.9 mm Hg ; for the acetylcholine group the average maximum rise was 6.3 mm Hg ; while the combined treatment group showed a decrease of 0.7 mm Hg . IOP rises of > 6 mm Hg were seen in 7 % of patients ( one of 15 ) in the combined treatment group , 45 % ( five of 11 ) of the acetylcholine group , and 70 % ( seven of 10 ) of the acetazolamide group . IOP rises of > 10 mm Hg were seen in 7 % of the combined treatment group , in 18 % of the acetylcholine only group , and in 50 % of the acetazolamide only group . A pressure rise > 20 mm Hg was seen in one patient receiving acetazolamide only and one patient receiving acetylcholine only . The difference between the acetylcholine group and the combined group for rises > 6 mm Hg was significant using the chi 2 test while the acetazolamide group showed a significant difference for rises > 6 and 10 mm Hg compared with the combined group . All acute pressure rises were recorded before or at 9 hours following operation except in the combined treatment patient where the rise occurred at 24 hours . To prevent the acute IOP rises seen following cataract surgery with lens implant in glaucoma patients we recommend combined ocular hypotensive therapy .

Diamox Sustets ( acetazolamide )

treatments combined

acetazolamide

acetylcholine

acetylcholine

acetazolamide

acetylcholine

acetazolamide

acetazolamide

acetylcholine

acetylcholine

acetazolamide

combined treatment

intraocular pressure ( IOP )

IOPs

average of the maximum pressure rises

IOP rises

IOP rises

pressure rise > 20 mm Hg

rises > 6 mm Hg

rises > 6

acute pressure rises

acute IOP

glaucoma

posterior chamber lens implant

Thirty six


Pharmacokinetics and pharmacodynamics of intravenous diltiazem in patients with atrial fibrillation or atrial flutter . BACKGROUND Diltiazem , a calcium channel blocker , has been shown to be safe and effective in the treatment of patients in atrial fibrillation and/or atrial flutter . However , there have been no pharmacokinetic/pharmacodynamic studies of diltiazem in these patients . METHODS AND RESULTS The pharmacokinetics and pharmacodynamics of intravenous diltiazem were determined in 32 patients with atrial fibrillation or atrial flutter ( mean +/- SD age , 66 +/- 7 years ; mean baseline heart rate , 131 +/- 10 beats per minute ) after 20 mg or 20 mg followed by 25-mg bolus doses and a 10 and 15 mg/hr infusion for 24 hours . After the 10 and 15 mg/hr infusions of diltiazem , mean +/- SD elimination half-life was 6.8 +/- 1.8 and 6.9 +/- 1.5 hours , volume of distribution was 411 +/- 151.8 and 299 +/- 70.8 I , and systemic clearance was 42 +/- 12.4 and 31 +/- 8.3 l/hr , respectively . Percentages of the plasma concentrations of the principal metabolites desacetyldiltiazem and N-desmethyldiltiazem to diltiazem were < 15 % and < 10 % , respectively . Thirty of 32 patients maintained response throughout the 24-hour infusion of diltiazem . Using a sigmoidal Emax pharmacodynamic model , a strong relation ( mean +/- SD r2 , 0.78 +/- 0.2 ) was observed between plasma diltiazem concentration and percent heart rate reduction . Mean +/- SD Emax ( maximum percent reduction in heart rate from baseline ) and EC50 ( plasma diltiazem concentration that achieves half Emax ) were 52 +/- 17 % and 110 +/- 84 ng/ml , respectively . The model predicts that mean plasma diltiazem concentration of 79 , 172 , and 294 ng/ml are required to produce a 20 % , 30 % , and 40 % reduction in heart rate , respectively . A relation between plasma diltiazem concentration and percent change in systolic blood pressure ( SBP ) or diastolic blood pressure ( DBP ) from baseline was not observed ( mean +/- SD r2 , SBP/DBP : 0.35 +/- 0.24/0.36 +/- 0.2 ) . There were no untoward side effects observed . CONCLUSIONS First , the pharmacokinetics of diltiazem in patients with atrial fibrillation or atrial flutter is nonlinear with an apparent dose-dependent decrease in systemic clearance with increasing infusion rate . Second , using a sigmoidal Emax model , there is a strong relation between plasma diltiazem concentration and percent heart rate reduction . Third , the plasma concentrations of the principal metabolites desacetyldiltiazem and N-desmethyldiltiazem are low and are not expected to contribute significantly to the pharmacodynamics of intravenous diltiazem in these patients .

diltiazem

Diltiazem

intravenous diltiazem

diltiazem

diltiazem

plasma diltiazem concentration

percent heart rate reduction

plasma diltiazem concentration

heart rate

systolic blood pressure ( SBP )

diastolic blood pressure ( DBP )


Interferon alfa in acute posttransfusion hepatitis C : a randomized , controlled trial .

Interferon alfa

acute posttransfusion hepatitis C :


The relationship between the response of Plasmodium falciparum malaria to mefloquine in African children and its sensitivity in vitro . The clinical efficacy of two doses of mefloquine ( 15 and 25 mg/kg body weight ) was evaluated in 85 children suffering from acute symptomatic falciparum malaria . The cure rate on day 28 was 100 % in both groups . There was no significant difference ( P > 0.05 ) in the mean parasite and fever clearance times in both groups ( 48.5 +/- 14.6 and 32.0 +/- 12.7 h respectively for the 25 mg/kg group and 49.0 +/- 15.1 and 30.0 +/- 13.3 h respectively for the 15 mg/kg group ) . There was also no significant difference ( P > 0.05 ) in these values between children with hyperparasitaemia ( 53.6 +/- 11.1 and 36.0 +/- 17.0 h respectively ) and those without hyperparasitaemia ( 49.1 +/- 13.6 and 31.8 +/- 14.6 h respectively ) . Recurrence of parasitaemia was observed after day 30 in 2 patients in the 15 mg/kg group and in 1 patient in the 25 mg/kg group . In vitro , 3 of 21 isolates showed reduced susceptibility to mefloquine , with minimum inhibitory concentrations ( MIC ) > 67 nM/litre . The MIC and 50 % , 90 % and 99 % inhibitory concentrations were 200.8 , 6.27 , 31.7 and 119.6 nM/litre respectively . Four of 22 isolates were resistant to chloroquine ( MIC > 108 nM/litre ) . Isolates that showed low sensitivity to mefloquine in vitro were sensitive to chloroquine in vitro , and the 4 that were resistant to chloroquine were sensitive to mefloquine . Irrespective of MIC and dose of mefloquine , parasitaemia cleared in all subjects in 96 h or less . ( ABSTRACT TRUNCATED AT 250 WORDS )

mefloquine

mefloquine

mefloquine

chloroquine

mefloquine

cure rate

mean parasite and fever clearance times

Recurrence of parasitaemia

susceptibility to mefloquine

inhibitory concentrations

resistant

sensitivity

children

acute symptomatic falciparum malaria .


[ Mitoxantrone ( MTX ) versus mitomycin C ( MMC ) in the ablative treatment of Ta , T1 superficial bladder tumors . Phase III , randomized prospective study ] . A prospective randomized study was conducted to determine the ablation capacity of mitoxantrone in Ta-T1 superficial bladder tumors versus mitomycin C , a drug whose intravesical ablation properties are well-known . Fifty-seven patients comprised the study . The tumor was not completely resected when the patient underwent TUR . This residual tumor was used as control . The patients were treated with either 20 mg Mitoxantrone or 40 mg mitomycin C weekly for 8 weeks and two other instillations every 15 days in 50 ml saline solution . Response to therapy was evaluated between the 4th and 8th week and classified as complete response ( CR ) , defined as no gross and microscopic evidence of residual tumor , or no response ( NR ) or therapeutic failure . CR was observed in 77.7 % of the patients treated with mitomycin C and in 50 % in those that had been treated with Mitoxantrone . Treatment was discontinued because of side effects in 15 % of the patients treated with mitomycin C and in 63.4 % of those who received Mitoxantrone . We can conclude from the results of the present study that Mitoxantrone is a useful agent for ablation therapy of superficial bladder tumors , although the high incidence of severe side effects warrants its limited use and at high dilutions .

mitoxantrone

mitomycin C

Mitoxantrone

mitomycin C

mitomycin C

Mitoxantrone

mitomycin C

Mitoxantrone

Mitoxantrone

ablation capacity

Response to therapy

complete response ( CR )

no response ( NR )

therapeutic failure

side effects

side effects

Ta , T1 superficial bladder tumors

Fifty-seven


[ Unstable angina : comparison of the effects of diltiazem and propranolol ] . PURPOSE To evaluate the effects of diltiazem and propranolol in patients with unstable angina . METHODS Fifty-six patients with unstable angina , mean age of 55.4 +/- 8.5 , 41 men and 15 women , were evaluated in a randomized , double-blind study of two groups of patients treated with diltiazem or propranolol at total daily doses of 180 mg and 120 mg respectively during the first 48 hours . After that the total daily doses was adjusted to 240 mg and 160 mg , respectively , until the 7th day . The first 48 hours , four times daily , clinical evaluation , CKMB data , ECG were obtained and two times daily until 7th day . A coronary arteriography was done on study entry . RESULTS A significative reduction of angina crisis number , duration , intensity and the number of sublingual nitrates doses were observed equally in both groups . The SAP , DAP , HR and RR did not show statistical differences between groups . Individual groups analysis showed significative reductions of SAP , DAP and HR in propranolol group . The CKMB data , ECG alterations and coronary arteriography characteristics were similar . CONCLUSION Both drugs were effective for the unstable angina treatment .

diltiazem

propranolol

diltiazem

propranolol

diltiazem

propranolol

coronary arteriography

propranolol

clinical evaluation

CKMB data

ECG

number of sublingual nitrates doses

SAP , DAP , HR and RR

SAP , DAP and HR

CKMB data

ECG alterations

coronary arteriography


Controlled study on the therapeutic efficacy of propionyl-L-carnitine in patients with congestive heart failure . A double-blind phase II study of propionyl-L-carnitine ( CAS 17298-37-2 ) versus placebo was carried out on a group of 60 patients with mild to moderate ( II and III NYHA class ) congestive heart failure . The group was made up of men and women aged between 48 and 73 years in chronic treatment with digitalis and diuretics for at least 3 months and who still displayed symptoms . Thirty of these patients were chosen randomly and for 180 days , 500 mg of propionyl-L-carnitine was orally administered , 3 times a day in addition to their usual treatment . At basal conditions and after 30 , 90 and 180 days the maximum exercise time was evaluated using an exercise tolerance test performed on an ergometer bicycle and the left ventricular ejection fraction was tested by means of bidimensional echocardiography . After one month of treatment , the patients treated with propionyl-L-carnitine , compared to the control group , showed significant increases in the values of both tests , increases which became even more evident after 90 and 180 days . At the stated times the increases in the maximum exercise time were 16.4 % , 22.9 % , and 25.9 % , respectively . The ventricular ejection fraction increased by 8.4 % , 11.6 % and 13.6 % , respectively . On the basis of these results , having studied the particular mechanism of action of propionyl-L-carnitine the authors conclude that it represents a drug of undoubted therapeutic interest in patients with congestive heart failure , in whom it could be efficaciously administered along with a standard pharmacological therapy .

500 mg of propionyl-L-carnitine

exercise tolerance test

bidimensional echocardiography

therapeutic efficacy

maximum exercise time

exercise tolerance test

left ventricular ejection fraction

bidimensional echocardiography

values of both tests

maximum exercise time

ventricular ejection fraction

efficaciously

congestive heart failure

mild

men

women

between 48 and 73 years

chronic treatment

congestive heart failure


A controlled trial of trimethoprim-sulfamethoxazole or aerosolized pentamidine for secondary prophylaxis of Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome . AIDS Clinical Trials Group Protocol 021 . BACKGROUND Pneumocystis carinii pneumonia ( PCP ) continues to be the most common index diagnosis in the acquired immunodeficiency syndrome ( AIDS ) , but it is not clear which of several available agents is the most effective in preventing a recurrence of PCP . METHODS We conducted a comparative , open-label trial in 310 adults with AIDS who had recently recovered from an initial episode of PCP and had no treatment-limiting toxic effects of trimethoprim-sulfamethoxazole or pentamidine . All the patients were treated with zidovudine and were randomly assigned to receive either 800 mg of sulfamethoxazole and 160 mg of trimethoprim once daily or 300 mg of aerosolized pentamidine administered every four weeks by jet nebulizer . The participants were followed for a median of 17.4 months . RESULTS In the trimethoprim-sulfamethoxazole group ( n = 154 ) there were 14 recurrences of PCP , as compared with 36 recurrences ( including 1 extrapulmonary recurrence ) in the aerosolized-pentamidine group ( n = 156 ) . The estimated recurrence rates at 18 months were 11.4 percent with trimethoprim-sulfamethoxazole and 27.6 percent with pentamidine ( P < 0.001 ) . The risk of a recurrence ( adjusted for initial CD4 cell count ) was 3.25 times higher in the pentamidine group ( P < 0.001 , 95 percent confidence interval , 1.72 to 6.16 ) . There were no significant differences between the groups in survival or in hematologic or hepatic toxicity . Crossovers from trimethoprim-sulfamethoxazole to aerosolized pentamidine were more common than the reverse ( 27 vs. 4 percent ) , partly because of the study protocols for the management of leukopenia . There were 19 serious bacterial infections in the trimethoprim-sulfamethoxazole group and 38 in the pentamidine group . The time to a first bacterial infection was significantly greater for those assigned to trimethoprim-sulfamethoxazole ( P = 0.017 ) . CONCLUSIONS In patients with AIDS who are receiving zidovudine , trimethoprim-sulfamethoxazole is more effective than aerosolized pentamidine in conventional doses for the prevention of recurrent pneumocystis infection .

trimethoprim-sulfamethoxazole

aerosolized pentamidine

trimethoprim-sulfamethoxazole

pentamidine

zidovudine

300 mg of aerosolized pentamidine

jet nebulizer

trimethoprim-sulfamethoxazole

trimethoprim-sulfamethoxazole

pentamidine

pentamidine

trimethoprim-sulfamethoxazole

pentamidine

zidovudine

trimethoprim-sulfamethoxazole

aerosolized pentamidine

preventing a recurrence of PCP

recurrences of PCP

recurrence rates

recurrence

survival

hematologic or hepatic toxicity .

bacterial infections

time to a first bacterial infection

acquired immunodeficiency syndrome

adults

AIDS

AIDS


Oestrogen replacement after oophorectomy : comparison of patches and implants .

Oestrogen replacement

patches

implants

Oestrogen replacement

oophorectomy


Biodistribution of three photosensitizers in dogs with spontaneous tumors . Photodynamic therapy ( PDT ) has been considered a potential method for tumor eradication . The present study was designed to assess the efficacy of PDT as an alternative treatment approach . Photosensitizers , such as porfimer sodium , tin ethyl etiopurpurin , and aluminum chlorophthalocyanine , were administered i.v . to dogs , and tissue samples were harvested 24 to 300 hours later . The uptake of the photosensitizers in tumor ( fibrosarcoma ) and adjacent normal tissue biopsies was quantified by tissue solubilization technique and fluorimetry . In addition , the pharmacokinetics and selectivity of the photosensitizers were addressed by two-phase exponential function and specific uptake ratio , respectively . Porfimer sodium exhibited a longer elimination half-life ( 175.3 hr ) , slower clearance ( 0.0028 L/kg/hr ) , and a larger area under the curve ( 1075 microg/g/hr ) in tumors than did tin ethyl etiopurpurin or aluminum chlorophthalocyanine . As a result , porfimer sodium showed a good selectivity in tumors located in muscle and skin . The study provided clinical information for determination of the efficacy of different PDT alternatives .

tin ethyl etiopurpurin

aluminum chlorophthalocyanine .

longer elimination half-life

slower clearance

larger area under the curve

efficacy

dogs with spontaneous tumors .


A prospective , placebo-controlled , randomized trial of intravenous streptokinase and angioplasty versus lone angioplasty therapy of acute myocardial infarction . BACKGROUND The value of routine administration of intravenous thrombolytic agents during percutaneous transluminal coronary angioplasty ( PTCA ) therapy of acute myocardial infarction ( MI ) has not been determined . Therefore , we prospectively randomized 122 patients with evolving MI to PTCA therapy with or without adjunctive intravenous streptokinase therapy . METHODS AND RESULTS Patients with ECG ST segment elevation who presented within 4 hours of symptom onset , had no contraindication to thrombolytic therapy , and were not in cardiogenic shock were enrolled . They were treated immediately with intravenous heparin ( 10,000 units ) and oral aspirin ( 325 mg ) and randomized to treatment with placebo or streptokinase ( 1.5 M units ) administered intravenously over 30 minutes . Patients then were taken immediately to the catheterization laboratory , and those with suitable coronary anatomy underwent immediate PTCA . Subsequent clinical course , serial radionuclide ventriculography , and 6-month repeat angiography were analyzed . A total of 106 patients were treated with PTCA . Use of PTCA was similar for placebo ( 92 % ) and streptokinase ( 83 % ) groups . Angioplasty was successful in 95 % of patients , with no difference in placebo ( 93 % ) and streptokinase ( 98 % ) groups . Serial radionuclide ventriculography demonstrated no difference in 24-hour ( 52 +/- 12 % versus 50 +/- 12 % ) or 6-week ( 51 +/- 12 % versus 51 +/- 13 % ) ejection fraction values for placebo and streptokinase groups , respectively . Contrast ventriculography demonstrated improvement in immediate ( 54 +/- 12 % ) versus 6-month ( 60 +/- 15 % , p < 0.05 ) values for the overall group . No differences in 6-month values were present ( 58 +/- 15 % versus 62 +/- 15 % , p = NS ) for placebo and streptokinase groups , respectively . Coronary angiography was performed in 75 % of the 90 patients eligible for restudy . Arterial patency was 87 % at 6 months , and coronary restenosis was present in 38 % of patients . No differences in chronic patency or restenosis were detected for the two treatment groups . Although adjunctive intravenous streptokinase therapy did not improve outcome , it did complicate the hospital course . Hospitalization was longer ( 9.3 +/- 5.0 versus 7.7 +/- 4.4 days , p = 0.046 ) and more costly ( $ 25,191 +/- 15,368 versus $ 19,643 +/- 7,250 , p < 0.02 ) . Transfusion rate was higher ( 39 % versus 8 % , p = 0.0001 ) and need for emergency coronary bypass surgery was greater ( 10.3 % versus 1.6 % , p = 0.03 ) for the streptokinase-treated patients . CONCLUSIONS Adjunctive intravenous streptokinase therapy does not enhance early preservation of ventricular function , improve arterial patency rates , or lower restenosis rates after PTCA therapy of acute MI . Hospital course is longer , more expensive , and more complicated . For these reasons , PTCA therapy of acute MI should not be routinely performed with adjunctive intravenous streptokinase therapy .

placebo-controlled

streptokinase

thrombolytic agents

PTCA therapy

intravenous streptokinase therapy

thrombolytic therapy

intravenous heparin

oral aspirin

placebo

streptokinase

PTCA

placebo

streptokinase

streptokinase

streptokinase

streptokinase

Coronary angiography

streptokinase

streptokinase therapy

streptokinase therapy

ejection fraction values

Contrast ventriculography

6-month values

Coronary angiography

Arterial patency

coronary restenosis

chronic patency or restenosis

Hospitalization

costly

Transfusion rate

ventricular function

evolving MI to PTCA therapy

ECG ST segment elevation

treated with PTCA


Improved acidosis correction and recovery of mesothelial cell mass with neutral-pH bicarbonate dialysis solution among children undergoing automated peritoneal dialysis . Acid-base balance and peritoneal membrane longevity are of utmost relevance for pediatric patients undergoing peritoneal dialysis ( PD ) . PD fluids with neutral pH and reduced glucose degradation product contents are considered more biocompatible , because they preserve peritoneal cell functions in vitro . To investigate the clinical effects of a novel PD fluid buffered with 34 mM pure bicarbonate at neutral pH , a randomized , prospective , crossover comparison with conventional , acidic , 35 mM lactate PD fluid was performed for two consecutive 12-wk periods with 28 children ( age , 6 mo to 15 yr ) undergoing automated PD ( APD ) . Blood bicarbonate levels and arterial pH were significantly higher after 3 mo of bicarbonate PD ( 24.6 +/- 2.3 mM and 7.43 +/- 0.06 , respectively ) , compared with lactate PD ( 22.8 +/- 3.9 mM and 7.38 +/- 0.05 , respectively ; P < 0.05 ) . This effect was reversible among patients who returned from bicarbonate to lactate fluid . Low initial pH and young patient age independently predicted increased blood pH during bicarbonate APD . Peritoneal equilibration tests revealed subtle changes in solute transport , with a less steep creatinine equilibration curve during bicarbonate dialysis , suggesting reduced peritoneal vasodilation . The peritoneal release of carcinogen antigen-125 increased twofold during bicarbonate APD ( 29 +/- 15 versus 15 +/- 8 U/ml per 4 h , P < 0.01 ) , which is consistent with recovery of the mesothelial cell layer . This effect was fully reversed when the patients returned to lactate fluid . Effluent carcinogen antigen-125 levels were inversely correlated with peritoneal glucose exposure during lactate but not bicarbonate APD , indicating improved in vivo mesothelial cell tolerance of high-dose glucose with the neutral-pH PD fluid with reduced glucose degradation product content . Among children undergoing APD , neutral-pH , bicarbonate-buffered PD fluid provides more effective correction of metabolic acidosis and better preservation of peritoneal cell mass than do conventional , acidic , lactate-based fluids .

automated peritoneal dialysis

peritoneal dialysis ( PD )

automated PD ( APD )

bicarbonate PD

lactate PD

effects

Blood bicarbonate levels

arterial pH

higher

bicarbonate PD

lactate PD

initial pH

blood pH

bicarbonate APD

subtle changes in solute transport

steep creatinine equilibration curve

Effluent carcinogen antigen-125 levels

children

automated peritoneal dialysis

pediatric

peritoneal dialysis

PD

children

6 mo to 15 yr

automated PD

APD

children

APD


Selenium supplementation and secondary prevention of nonmelanoma skin cancer in a randomized trial . The Nutritional Prevention of Cancer Trial was a double-blind , randomized , placebo-controlled clinical trial designed to test whether selenium as selenized yeast ( 200 microg daily ) could prevent nonmelanoma skin cancer among 1312 patients from the Eastern United States who had previously had this disease . Results from September 15 , 1983 , through December 31 , 1993 , showed no association between treatment and the incidence of basal and squamous cell carcinomas of the skin . This report summarizes the entire blinded treatment period , which ended on January 31 , 1996 . The association between treatment and time to first nonmelanoma skin cancer diagnosis and between treatment and time to multiple skin tumors overall and within subgroups , defined by baseline characteristics , was evaluated . Although results through the entire blinded period continued to show that selenium supplementation was not statistically significantly associated with the risk of basal cell carcinoma ( hazard ratio [ HR ] = 1.09 , 95 % confidence interval [ CI ] = 0.94 to 1.26 ) , selenium supplementation was associated with statistically significantly elevated risk of squamous cell carcinoma ( HR = 1.25 , 95 % CI = 1.03 to 1.51 ) and of total nonmelanoma skin cancer ( HR = 1.17 , 95 % CI = 1.02 to 1.34 ) . Results from the Nutritional Prevention of Cancer Trial conducted among individuals at high risk of nonmelanoma skin cancer continue to demonstrate that selenium supplementation is ineffective at preventing basal cell carcinoma and that it increases the risk of squamous cell carcinoma and total nonmelanoma skin cancer .

Selenium supplementation

secondary prevention

placebo-controlled

selenium as selenized yeast

selenium supplementation

selenium supplementation

selenium supplementation

time to multiple skin tumors

risk of basal cell carcinoma

total nonmelanoma skin cancer

basal cell carcinoma

squamous cell carcinoma

total nonmelanoma skin cancer .

nonmelanoma skin cancer

nonmelanoma skin cancer

Eastern United States

previously had this disease


Analgesic efficacy of low-dose diclofenac versus paracetamol and placebo in postoperative dental pain . AIMS To compare the efficacy and safety of diclofenac-K ( 12.5 mg ) vs paracetamol ( 500 mg ) and placebo given in a flexible dosage regimen to treat pain resulting from extraction of impacted third molar teeth . METHODS This was a 2-day , double-blind , double-dummy , randomized , parallel-group , placebo-controlled study of diclofenac-K ( 12.5 mg ) tablets vs paracetamol ( 500 mg ) tablets and placebo in patients with moderate or severe pain within 8 hours of extraction of impacted third molars . RESULTS After the first 2-tablet dose , patients took on average 2.5 additional tablets of diclofenac-K or 2.4 tablets of paracetamol , almost all as 1-tablet doses . Most placebo patients discontinued by taking rescue medication ( ibuprofen 200 mg ) on the first day . Pain relief after the initial dose of diclofenac-K ( 2 x 12.5 mg ) was superior to placebo ( P < .01 for all efficacy outcomes ) and comparable to paracetamol ( 2 x 500 mg ) . About 30 % of patients in each active treatment group took rescue medication during the study , compared to 78 % on placebo . About 70 % in each active treatment group considered the overall pain relief to be " some , " " a lot , " or " complete " compared to only 15 % on placebo . The incidence of adverse events in each active treatment group was low and comparable between the treatments . CONCLUSION An initial double-dose of diclofenac-K ( 2 x 12.5 mg ) or paracetamol ( 2 x 500 mg ) adequately relieved the most intense postoperative pain , and the flexible multiple dose regimen ( 1 or 2 tablets ) maintained adequate pain relief thereafter . Most patients needed only 1-tablet doses following the initial 2-tablet dose .

diclofenac

paracetamol

placebo

diclofenac-K

paracetamol

placebo

placebo-controlled

placebo

diclofenac-K

paracetamol

placebo

diclofenac-K

placebo

paracetamol

placebo

placebo

diclofenac-K

paracetamol

Pain relief

overall pain relief

incidence of adverse events

postoperative pain

pain relief

postoperative dental pain

pain

moderate or severe pain

extraction of impacted third molars

postoperative pain


Randomized controlled trial of education and feedback for implementation of guidelines for acute low back pain . OBJECTIVE The effect of clinical guidelines on resource utilization for complex conditions with substantial barriers to clinician behavior change has not been well studied . We report the impact of a multifaceted guideline implementation intervention on primary care clinician utilization of radiologic and specialty services for the care of acute low back pain . DESIGN Physician groups were randomized to receive guideline education and individual feedback , supporting patient education materials , both , or neither . The impact on guideline adherence and resource utilization was evaluated during the 12-month period before and after implementation . PARTICIPANTS Fourteen physician groups with 120 primary care physician and associate practitioners from 2 group model HMO practices . INTERVENTIONS Guideline implementation utilized an education/audit/feedback model with local peer opinion leaders . The patient education component included written and videotaped materials on the care of low back pain . MAIN RESULTS The clinician intervention was associated with an absolute increase in guideline-consistent behavior of 5.4 % in the intervention group versus a decline of 2.7 % in the control group ( P =.04 ) . The patient education intervention produced no significant change in guideline-consistent behavior , but was poorly adopted . Patient characteristics including duration of pain , prior history of low back pain , and number of visits during the illness episode were strong predictors of service utilization and guideline-consistent behavior . CONCLUSIONS Implementation of an education and feedback-supported acute low back pain care guideline for primary care clinicians was associated with an increase in guideline-consistent behavior . Patient education materials did not enhance guideline effectiveness . Implementation barriers could limit the utility of this approach in usual care settings .

neither

Guideline implementation

clinician intervention

guideline-consistent behavior

guideline-consistent behavior

duration of pain

prior history of low back pain

Fourteen


Safety of injectable opioid maintenance treatment for heroin dependence . BACKGROUND There is a growing debate about injectable opioid treatment programs in many Western countries . This is the first placebo-controlled study of the safety of injectable opioids in a controlled treatment setting . METHODS Twenty-five opioid-dependent patients on intravenous ( IV ) heroin or IV methadone maintenance treatment were randomly assigned to either their individual prescribed IV maintenance dose or placebo . Acute drug effects were recorded , focusing on electrocardiography , respiratory movements , arterial blood oxygen saturation , and electroencephalography ( EEG ) . RESULTS After heroin injection , marked respiratory depression progressing to a Cheyne-Stokes pattern occurred . Peripheral arterial blood oxygenation decreased to 78.9 +/- 8.7 % ( mean +/- SD ) ranging from 52 % -90 % . During hypoxia , 7 of the 16 subjects experienced intermittent and somewhat severe bradycardia . Five subjects exhibited paroxysmal EEG patterns . After methadone injection , respiratory depression was less pronounced than after heroin injection . No relevant bradycardia was noted . CONCLUSIONS Opioid doses commonly prescribed in IV opioid treatment induce marked respiratory and circulatory depression , as well as occasionally irregular paroxysmal EEG activity . Further studies are needed to optimize the clinical practice of IV opioid treatment to prevent serious complications . Moreover , the extent of the observed effects raises questions about the appropriateness of IV opioid treatment in the present form .

injectable opioid maintenance treatment

injectable opioid treatment programs

placebo-controlled

injectable opioids

intravenous ( IV ) heroin

IV methadone maintenance treatment

placebo

heroin injection

methadone injection

heroin injection

Opioid

IV opioid treatment

IV opioid treatment

IV opioid treatment

Acute drug effects

electrocardiography

respiratory movements

arterial blood oxygen saturation

electroencephalography ( EEG )

respiratory depression

Cheyne-Stokes pattern

Peripheral arterial blood oxygenation

hypoxia

bradycardia

paroxysmal EEG patterns

respiratory depression

bradycardia

respiratory and circulatory depression

irregular paroxysmal EEG activity

heroin dependence

Twenty-five

opioid-dependent patients

16 subjects


GnRH agonist treatment before total laparoscopic hysterectomy for large uteri . STUDY OBJECTIVE To evaluate whether uterine shrinkage induced by gonadotropin-releasing hormone ( GnRH ) agonists in women with a large uterus ( > 14 wks ) may facilitate total laparoscopic hysterectomy . DESIGN Randomized , prospective study ( Canadian Task Force classification I ) . SETTING University-affiliated hospital . PATIENTS Sixty-two women with symptomatic uterine myomas ( size 16-20 wks ) . INTERVENTIONS Total laparoscopic hysterectomy for benign pathology . MEASUREMENTS AND MAIN RESULTS Before surgery , women were assigned , at a ratio of 1:1 by random selection , to receive injections of triptorelin depot 11.25 mg 3 months before surgery ( group A ) or no treatment ( group B ) . Uterine volume , mean operating time , uterine weight , drop in hemoglobin , intraoperative complications , conversions to laparotomy , and hospital stay were recorded . Triptorelin decreased uterine volume , calculated by ultrasonography , by 26.5 % in group A , whereas the volume remained unchanged in group B . Statistical differences were found between groups concerning uterine weight , operating time , and drop in hemoglobin level . Three patients in group B were converted to laparotomy because of uterine size . CONCLUSION In women with a large uterus , a 3-month preoperative course of GnRH may facilitate laparoscopic hysterectomy , decreasing uterine size , operating time , and blood loss .

GnRH agonist

triptorelin depot

GnRH

Uterine volume

mean operating time

uterine weight , drop in hemoglobin

intraoperative complications

conversions to laparotomy

hospital stay

uterine volume

uterine weight

operating time

drop in hemoglobin level .

women

large uterus ( > 14 wks )

Sixty-two

women

symptomatic uterine myomas

women

large uterus


Leukocyte-depleted reperfusion of transplanted human hearts : a randomized , double-blind clinical trial . Standard methods of myocardial preservation for heart transplantation have generally provided good results . Preservation times beyond 3 hours , however , have been associated with decreased survival . Leukocyte-mediated reperfusion injury is partly responsible for decreased graft function after prolonged graft ischemia . Leukocyte-depleted reperfusion has been shown experimentally to improve cardiac function after cold ischemic arrest . To determine the efficacy and safety of leukocyte-depleted reperfusion , 20 patients were enrolled in a randomized , double-blind clinical trial to be treated with either warm whole blood reperfusion ( group I ; n = 9 ) or warm leukocyte-depleted blood reperfusion ( group II ; n = 11 ) . Reperfusion with leukocyte-depleted blood or whole blood was carried out for 10 minutes , with enriched cardioplegic solution added for the first 3 minutes of reperfusion . The mean donor and recipient age and the ischemic time ( 142 versus 153 minutes ) were not significantly different between the two groups . Coronary sinus release of creatinine phosphokinase-MB 5 minutes after reperfusion was significantly less in group II ( 1.65 EU/min ) than in group I ( 3.83 units/min ; p = 0.05 ) . Thromboxane B2 release was also significantly less ( p = 0.05 ) in group II ( 33.6 pg/min ) than in group I ( 67.0 pg/min ) . All hearts functioned adequately in both groups . The duration of inotropic support was shorter in group II than in group I , but the difference was not statistically significant . Postoperative hemodynamics , rejection episodes , and infectious complications were also not significantly different between groups in a mean follow-up of 9 months . Mean ejection fraction 1 month after operation was 65 % in both groups . One early death occurred at 66 days secondary to infection ; two late deaths occurred in group II , both from rejection . Leukocyte-depleted reperfusion is safe and easily applied in the operating room . Furthermore , leukocyte-depleted reperfusion decreases biochemical evidence of reperfusion injury . Although not influencing postoperative cardiac function when the ischemic time is short , less than 3 hours , leukocyte-depleted reperfusion may prevent significant reperfusion injury and improve posttransplantation graft function when ischemic times are long . Safe extension of the ischemic time would expand the donor pool and allow for better crossmatching .

Leukocyte-depleted reperfusion

Leukocyte-depleted reperfusion

leukocyte-depleted reperfusion

warm whole blood reperfusion

whole blood

Leukocyte-depleted reperfusion

survival

graft function

cardiac function

efficacy and safety

ischemic time

Thromboxane B2 release

hearts functioned

duration of inotropic support

death

deaths

safe

biochemical evidence

cardiac function

reperfusion injury

posttransplantation graft function

ischemic times


EEG mapping and psychopharmacological studies with denbufylline in SDAT and MID . Computed tomography ( CT ) , electroencephalograms ( EEG ) , clinical and psychometric data were obtained in 96 mildly to moderately demented patients ( 72 women , 24 men ) , aged 61-96 years ( mean 82 ) , diagnosed according to DSM-III criteria . Patients were off drugs for at least 2 weeks and subdiagnosed according to the modified Marshall-Hachinski ischemic score and CT in 45 senile dementia of the Alzheimer type ( SDAT ) and 51 multiinfarct dementia ( MID ) patients . Evaluations were carried out before and 12 weeks after treatment with either 100 mg denbufylline BID or placebo and included EEG mapping , the Sandoz Clinical Assessment Geriatric ( SCAG ) score/factors , the Clinical Global Impression ( CGI ) , the Digit Symbol Substitution Test ( DSST ) , the Trail-Making Test ( TMT ) and the Digit Span Test ( DS ) . Descriptive data analysis including confirmatory statements found delta/theta activity enhanced , alpha and beta activity reduced , total power augmented , and the centroid slowed down over various brain regions in patients as compared with controls . The two subtypes of dementia could be differentiated in some conventional EEG variables but mostly by means of power asymmetry indices . Denbufylline induced a statistically significant and clinically relevant improvement in both SDAT and MID patients , whereas after placebo this was not the case in CGI , the TMT , and the DS , with interdrug differences being significant in all primary target variables such as the CGI , MMS , SCAG , and DSST . Thus , both the degenerative and vascular type of dementia exhibited a therapeutic benefit that could be objectified at the neurophysiological level by EEG mapping in an improvement of vigilance .

denbufylline

denbufylline

placebo

Denbufylline

placebo

delta/theta activity

alpha and beta activity

total power

centroid

improvement in both SDAT and MID

SDAT

MID

demented

women

men

aged 61-96 years ( mean 82 )

senile dementia

Alzheimer type

SDAT

multiinfarct dementia

MID


Prophylaxis with meropenem of septic complications in acute pancreatitis : a randomized , controlled trial versus imipenem . OBJECTIVES Prophylactic antibiotics are helpful in decreasing the incidence of septic complications in acute pancreatitis . The aim of this study was to compare the efficacy of meropenem , a new carbapenem antibiotic , with that of imipenem , which is the standard prophylactic treatment in patients with severe acute pancreatitis . METHODS One hundred seventy-six patients with necrotizing pancreatitis were prospectively randomized to prophylactic treatment with 0.5 g meropenem t.i.d . intravenously or 0.5 g imipenem q.i.d . intravenously . The occurrence of infection of pancreatic necrosis , rate of extrapancreatic infections , systemic and local complications , need for surgery , mortality rate , and length of hospitalization were recorded for each group . When a septic complication of pancreatic necrosis was suspected , fine needle aspiration with cultures of the sample was performed . Surgery was performed in cases of verified infected necrosis . CONCLUSION No difference was observed between patients treated with meropenem and those treated with imipenem in terms of incidence of pancreatic infection ( 11.4 % versus 13.6 % ) and extrapancreatic infections ( 21.6 % versus 23.9 % ) and clinical outcome . Meropenem is as effective as imipenem in preventing septic complications of patients with severe acute pancreatitis .

meropenem

imipenem

meropenem

new carbapenem antibiotic

imipenem

prophylactic treatment

prophylactic treatment

0.5 g meropenem t.i.d

imipenem

meropenem

imipenem

Meropenem

imipenem

septic complications

septic complications

rate of extrapancreatic infections

systemic and local complications

need for surgery

mortality rate

length of hospitalization

septic complication

incidence of pancreatic infection

extrapancreatic infections

clinical outcome

septic complications

severe acute pancreatitis

One hundred seventy-six

necrotizing pancreatitis


More is not necessarily better : Examining the nature of the temporal reference memory component in timing . Three experiments compared the timing performance of humans on a modified temporal generalization task with 1 , 3 , or 5 presentations of the standard duration . In all three experiments subjects received presentations of a standard duration at the beginning of a trial block and then had to judge whether each of a number of comparison stimuli was or was not the standard . The duration of the standard changed between blocks . The three experiments varied the experimental design ( between or within subjects ) , task difficulty ( how closely the comparison stimuli were spaced around the standards ) , and presence or absence of feedback on performance accuracy . Number of presentations of the standard never affected the proportion of identifications of the standard when it was presented , nor other features of the temporal generalization gradients observed . The implications for the operation of reference memories within the scalar timing system were explored via models that made different assumptions about how the individual presentations of the standard were stored and used .

experiments

standard duration

presence or absence of feedback

presentations of the standard

duration

task difficulty


Fake bad test response bias effects on the test of variables of attention . This study investigated the effects of faking bad ( FB ) on the Test of Variables of Attention ( TOVA ) using subjects randomly placed into two groups . Subjects in Group 1 took the TOVA under normal conditions ( NC ) first ; they were then requested to subtly fake bad . Group 2 subjects took the TOVA under the same fake bad instructions first , then took the test under normal conditions the second time . An analysis of the effects of test order yielded non-significant differences for basic TOVA variables across all four quarters , both halves and the total score . An analysis for group mean differences between the NC and the FB instructions yielded significant differences across the basic TOVA variables across the four quarters , two halves and total score . The FB group had excessive amounts of omission and commission errors , a greater response time mean ( i.e. , slower to respond ) and had greater variance around their mean response time . The study affirms that the professional using the TOVA needs to carefully eliminate a fake bad test-taking bias when subjects produce excessive test results .

TOVA under normal conditions ( NC )

subtly fake bad .

test of variables of attention

TOVA variables

basic TOVA variables

response time mean

Fake bad test response bias effects

variables of attention .

faking bad ( FB )

Test of Variables of Attention


The effects of treatment of urinary incontinence in general practice . A total of 110 women who had reported urinary incontinence to their general practitioners were randomly assigned to a treatment or control group . Treatment consisted of pelvic floor exercises in the case of stress incontinence and bladder training in the case of urge incontinence . The results were measured after 3 and 12 months by a research assistant on the basis of a constructed severity scale , an incontinence diary , and a comparison by the patients themselves of their previous and current conditions . After 3 months the control group were given the same treatment . After a further 3 and 12 months , they were assessed in exactly the same way as the treatment group . After 3 months about 60 % of the patients were either dry or only mildly incontinent ; the mean number of wet episodes had gone down from 20 to 7 , and 74 % of the women felt improved or cured . These results were later corroborated by the control group . After 12 months this successful outcome was improved slightly further . It may be concluded that the majority of women with incontinence can be successfully treated by the general practitioner . The effect of this treatment continues after one year .

pelvic floor exercises

bladder training

dry or only mildly incontinent ;

mean number of wet episodes

improved or cured .

treated

urinary incontinence


Including a 'no active intervention ' arm in surgical trials is possible : evidence from the CLasP randomised trial . OBJECTIVES To examine the impact of including a 'no active intervention ' arm ( called 'conservative management ' ) in a randomised controlled trial comparing treatments ( including surgery ) for men with lower urinary tract symptoms related to benign prostatic enlargement . METHODS Outcomes 7.5 months after randomisation were acceptability of randomisation , overall acceptability of and satisfaction with conservative management , impact on quality of life , perceived need for further treatment and treatment failure ( defined a priori ) . RESULTS In total , 177 ( out of 755 ) patients refused randomisation , including 31 % who did not want surgery and 22 % who wanted surgery . Most men randomised to conservative management were willing to undertake it as part of a trial but at the end of the trial they were divided between those who wanted to continue with it and those who expected surgery . At follow-up , 39 % of conservative management patients requested surgery , and interference of symptoms with life and an unsuccessful outcome were more commonly reported in this arm . There were no appreciable differences between treatment groups in terms of treatment failures . CONCLUSIONS Including a 'no active intervention ' arm did not appear to have a detrimental effect on patient recruitment or the completion of this trial in the short-term ; overall , conservative management was successfully completed by the majority of patients during the trial period , suggesting that researchers need not avoid including a no-intervention arm in surgical trials as long as they take care with its presentation .

surgery )

'no active intervention ' arm

interference of symptoms with life

unsuccessful outcome

treatment failures

patient recruitment

men

benign prostatic enlargement .