[ Therapeutic value of a combination of trimetazidine with a calcium inhibitor in the treatment of chronic coronary insufficiency ] . This double-blind , placebo-controlled study sought to examine the short-term benefit of adding 60 mg of trimetazidine to the daily therapeutic regimen of 29 male patients with coronary insufficiency who had persistent ST depression on exercise tolerance test ( greater than or equal to 1 mm ) , despite treatment with nifedipine 40 mg per day . As compared with the placebo group , after only 14 days , the patients treated with trimetazidine showed statistically significant increases in the maximum workload level attained before ST depression occurred ( 31 % versus - 6 % ; P = 0.009 ) , the total work performed ( 31 % versus 2 % ; P = 0.024 ) and a significant decrease in the systolic tension time ( double product ) /workload ratio ( -5 % versus +11 % ; P = 0.005 ) . Throughout the study the clinical acceptability was excellent , with no side effects attributable to trimetazidine being recorded . This study shows that the addition of trimetazidine to a calcium antagonist brings a valuable improvement in therapeutic results .

trimetazidine

trimetazidine

nifedipine

placebo

the total work performed

systolic tension time

chronic coronary insufficiency ]

male

coronary insufficiency

persistent ST depression


No effect of acetylsalicylic acid on B-thromboglobulin and platelet factor 4 plasma levels in patients with transient ischaemic attacks . We studied the effect of acetylsalicylic acid ( ASA ) versus placebo on B-thromboglobulin ( B-TG ) and platelet factor 4 ( PF4 ) plasma levels and ADP-induced platelet aggregation in 25 male patients with transient ischaemic attacks ( TIA ) . The patients were allocated randomly to two groups : 14 patients received oral treatment with ASA 500 mg b.i.d . for 14 days , 11 patients placebo b.i.d . for the same period . B-TG and PF4 plasma levels and ADP-induced platelet aggregation were determined in basal conditions , and two hours , and seven and fourteen days after starting with ASA or placebo . In addition , the same parameters were studied in a group of 20 healthy males of matched age . Basal levels of plasma B-TG and PF4 and the maximal amplitude of ADP-induced platelet aggregation were abnormally high in TIA patients . ASA caused a significant reduction of B-TG plasma levels in TIA patients 2 hours after the first administration , but no effect was observed at the 7th and 14th day of treatment . PF4 plasma levels were unaffected by ASA treatment . It is concluded that ASA , at the dose conventionally used in clinical trials , does not affect the release of two alpha-granule proteins .

acetylsalicylic acid

acetylsalicylic acid ( ASA )

placebo

ASA

placebo

Basal levels of plasma B-TG and PF4

B-TG plasma levels

PF4 plasma levels

transient ischaemic attacks

male

transient ischaemic attacks ( TIA )

males


Placebo-controlled study of oral enoximone in congestive heart failure with initial and final intravenous hemodynamic evaluation . Seventeen patients with stable congestive heart failure ( class II and III New York Heart Association ) received intravenous and oral enoximone in a 2-part study . Hemodynamic data were first obtained after intravenous administration of 0.75 mg/kg of enoximone ; data were again obtained after 12 weeks of therapy with either oral enoximone ( 150 mg 3 times daily ) or placebo . The efficacy and safety of oral enoximone were also studied in a 12-week , double-blind randomized format . In the intravenous study , enoximone was delivered over 5 minutes and hemodynamic data were measured for up to 12 hours after . Cardiac index increased 2.76 +/- 0.63 to 3.42 +/- 0.72 liters/min/m2 ) , pulmonary wedge pressure decreased ( 19.5 +/- 8.8 to 14.6 +/- 8.0 mm Hg ) as did mean arterial blood pressure ( 101 +/- 14.8 to 85 +/- 13.7 mm Hg ) and systemic vascular resistance ( 1,880 +/- 573 to 1,254 +/- 383 dynes s cm-5 ) . Heart rate increased slightly ( 82 +/- 17 to 86 +/- 14 beats/min ) . All these changes were maximal 1 to 2 hours after infusion and lasted 8 hours at least . Patients were then randomized double-blind to oral treatment . Baseline values showed that the 7 patients who received placebo had more severe CHF . Therefore , comparison might be biased . Patient overall assessment showed a continuous benefit in both groups . Ejection fraction improved from 30.1 +/- 6.8 % to 33.9 +/- 9.9 % in the enoximone group while it remained unchanged with placebo ( 23.4 +/- 6.5 % to 23.4 +/- 1.5 % ) . ( ABSTRACT TRUNCATED AT 250 WORDS )

oral enoximone

enoximone

0.75 mg/kg of enoximone

oral enoximone

placebo

oral enoximone

enoximone

placebo

Hemodynamic data

Cardiac index

pulmonary wedge pressure

mean arterial blood pressure

systemic vascular resistance

Heart rate

CHF

Seventeen patients


Bronchodilator effect of fenoterol and ipratropium bromide in infants with acute wheezing : use of MDI with a spacer device . Twenty-eight infants admitted to Exequiel González Cortes Children 's Hospital because of acute wheezing ( AW ) were randomly assigned to three study groups . Fenoterol ( FNT ) , ipratropium bromide ( IB ) , and placebo were administered respectively to children in the different groups by means of metered dose inhalers ( MDI ) with spacers , using doses of 3 puffs every hour , for 4 hours . The degree of bronchial obstruction was assessed clinically and scored with the single-blind method every hour prior to each treatment . The criterion of a bronchodilator effect was a significant decrease in the degree of bronchial obstruction at subsequent scorings . The scores of the three groups were compared using the Student 's t test for matched samples . The same test was also applied to the independent samples for determining the superiority of one treatment , FNT or IB , over the other . The results indicated a significant decrease in the scores of the groups receiving FNT and IB ( P less than 0.05 ) ; this did not occur in the group in which placebo was used . FNT produced a more rapid and sustained effect than IB ( P less than 0.05 ) . Significant bronchodilator effect was obtained in infants with AW when repeated doses of FNT or IB were administered with MDI and spacers . This effect was significantly greater in the group treated with FNT .

fenoterol

ipratropium bromide

Fenoterol ( FNT )

ipratropium bromide ( IB )

a bronchodilator effect


Flow-cytometric studies with eleutherococcus senticosus extract as an immunomodulatory agent . A placebo-controlled study of the effect of an Eleutherococcus senticosus extract ( Eleukokk ) on the immune system was performed with 36 healthy volunteers utilising quantitative multi-parameter flow cytometry with monoclonal antibodies directed against specific surface markers of human lymphocyte subsets . Volunteers in the verum group received 10 ml of an ethanolic ( vincamine free ) eleutherococcus senticosus preparation , 3 times daily for 4 weeks . In the placebo , the eleutherococcus extract was substituted by additional wine , resulting in identical final concentrations of ethanol in both preparations . The purpose of the double-blind study was the demonstration of possible effects on the cellular immune status , as determined by quantitative flow cytometry . The most salient feature in the verum group was a drastic increase in the absolute number of immunocompetent cells , with an especially pronounced effect on T lymphocytes , predominantly of the helper/inducer type , but also on cytotoxic and natural killer cells . In addition , a general enhancement of the activation state of T lymphocytes was observed . No side effects were observed during the trial or afterwards ( observation period 6 months ) .

eleutherococcus senticosus extract

placebo-controlled

cellular immune status

quantitative flow cytometry

T lymphocytes

helper/inducer type

cytotoxic and natural killer cells .

activation state of T lymphocytes

side effects

immune system


[ Effects of simvastatin on plasma lipids , lipoproteins and apoproteins ( A1 and B ) . 24 cases of major primary hypercholesterolemia ] . We studied the effects of simvastatin ( MK 733 ) , a new competitive inhibitor of HMG CoA reductase , alone and in combination with a bile acid sequestrant , cholestyramine , on serum levels of lipoproteins and apoproteins A1 and B , in 24 patients with familial hypercholesterolemia . After simvastatin treatment ( 40 mg/day ) alone for 12 weeks , serum total and low density lipoprotein cholesterol decreased by 31 and 36 percent respectively . With the addition of cholestyramine , there was a 41 per cent total decrease in serum cholesterol from the control value and a 50 percent decrease in low density lipoprotein cholesterol . After cholestyramine treatment alone for 12 weeks , serum total and low density lipoprotein cholesterol decreased by 20 percent and 29 percent respectively . With the addition of simvastatin ( 20 mg per day ) , there was a 32 percent total decrease in serum cholesterol from the control value and a 43 percent decrease in low density lipoprotein cholesterol . High density lipoprotein cholesterol remained unchanged . No major adverse effect was observed . If long term safety can be confirmed , the simvastatin-cholestyramine regimen may prove useful in heterozygous familial hypercholesterolemia .

simvastatin

simvastatin ( MK 733

bile acid sequestrant , cholestyramine

simvastatin treatment

cholestyramine

cholestyramine treatment

simvastatin

simvastatin-cholestyramine regimen

plasma lipids

lipoproteins

apoproteins

low density lipoprotein cholesterol

serum cholesterol

low density lipoprotein cholesterol

serum total

and low density lipoprotein cholesterol

serum cholesterol

density lipoprotein cholesterol

High density lipoprotein cholesterol

major adverse effect

hypercholesterolemia

familial hypercholesterolemia


Clinical significance and prognostic importance of left ventricular hypertrophy in non-Q-wave acute myocardial infarction . Left ventricular ( LV ) hypertrophy is known to be an independent risk factor for cardiac death , but its significance in non-Q-wave acute myocardial infarction ( AMI ) has not been assessed previously . In a randomized diltiazem-placebo-controlled therapeutic trial of non-Q-wave AMI confirmed by creatine kinase-MB ( CK-MB ) , 126 of 544 patients ( 23 % ) exhibited LV hypertrophy using standard voltage criteria . Compared to patients without LV hypertrophy , patients with LV hypertrophy were significantly older ( 65 vs 60 years , p less than 0.0001 ) and had smaller peak adjusted CK levels ( 490 +/- 376 vs 666 +/- 726 IU/liter , p less than 0.001 ) than patients without LV hypertrophy . Patients with and without LV hypertrophy did not differ significantly in acute mortality during hospitalization , progression to Q waves , reinfarction by CK-MB criteria or angina associated with transient electrocardiographic changes . Compared with patients without LV hypertrophy , those patients with non-Q-wave AMI and LV hypertrophy had a 2-fold higher incidence of reinfarction ( 24 vs 12 % , p less than 0.005 ) and death ( 19 vs 9 % , p = 0.044 ) during the first year of follow-up . Multivariate regression analysis revealed that the relative risk of death and reinfarction during the initial year after AMI was increased by a factor of 1.7 and 2.1 among patients with LV hypertrophy , respectively . It was therefore concluded that , although patients with LV hypertrophy and non-Q-wave AMI have smaller enzymatic infarcts and the same short-term prognosis as do patients without LV hypertrophy , their reinfarction and mortality rates are significantly increased during the first year of follow-up . ( ABSTRACT TRUNCATED AT 250 WORDS )

diltiazem-placebo-controlled

mortality

hospitalization

progression to Q waves

reinfarction by CK-MB criteria

angina

reinfarction

risk of death

reinfarction

non-Q-wave acute myocardial infarction


Lack of effect of warfarin on the restenosis rate or on clinical outcome after balloon coronary angioplasty . Between September 1985 and April 1987 , 110 consecutive patients who had successful coronary angioplasty were included in a randomised prospective controlled evaluation of the effects of warfarin on restenosis . The warfarin ( n = 56 ) and the control ( n = 54 ) groups were not different in terms of age , sex , previous coronary bypass surgery or coronary balloon angioplasty , severity of symptoms , and frequency of multivessel disease or of total coronary occlusions . Warfarin was started on the day of the procedure and the dosage was adjusted to maintain the thromboplastin international normalised ratio greater than or equal to 2.5 . One hundred and five ( 96 % ) of the patients were given verapamil and other antianginal drugs were prescribed as needed . Low molecular weight dextran and heparin were given during the procedure and heparin was continued for 24 hours in all patients . One hundred and eight ( 98 % ) of patients were followed up clinically after a median of five months ( range 1-20 ) . Eighty five ( 77 % ) had follow up angiography at five months . In the warfarin group symptoms improved in 46 ( 85 % ) patients by at least 1 angina class and 31 ( 57 % ) were symptom free ; the exercise test remained positive in 20 ( 36 % ) patients and the angiographic restenosis rate was 25 % per lesion and 29 % per patient . There were no major bleeding complications . In the control group 46 ( 85 % ) patients were improved by at least 1 angina class and 31 ( 57 % ) were symptom free ; the exercise test was positive in 11 ( 21 % ) patients and the angiographic restenosis rate was 33 % per lesion and 37 % per patient . Although the incidence of angiographic restenosis tended to be lower with warfarin , none of these differences was significant . These data suggest that the combination of verapamil and warfarin , in the absence of aspirin , is not significantly better than verapamil alone in preventing symptom recurrence or angiographic restenosis after coronary angioplasty .

warfarin

warfarin

warfarin

control

Warfarin

verapamil

other antianginal drugs

heparin

warfarin

warfarin

verapamil

warfarin

aspirin

restenosis rate

symptoms

symptom free

angiographic restenosis rate

major bleeding complications

exercise test

angiographic restenosis rate

angiographic restenosis


Arginine vasopressin dissociates the diuresis and natriuresis due to atrial natriuretic factor in man . The possible interaction between arginine vasopressin ( AVP ) and atrial natriuretic factor ( ANF ) in the control of urinary sodium and water excretion was investigated in man . Nine healthy male volunteers undergoing stable maximal water diuresis were studied on four separate occasions . Atrial natriuretic factor 15 pmol kg-1 min-1 or placebo ( P ) was concomitantly administered against a background infusion of either AVP 0.003 pmol kg-1 min-1 or P ; thus the combinations P + P , AVP + P , P + ANF and AVP + ANF were studied . Atrial natriuretic factor caused a significant increase in sodium excretion ( UNaV ) [ +56 % ] , urinary flow rate ( V ) [ +17 % ] and free water clearance ( CH2O ) [ +23 % ] ; creatinine clearance ( Ccr ) did not change . Arginine vasopressin reduced V ( -58 % ) and CH2O ( -68 % ) but did not alter UNaV or Ccr . On the AVP + ANF study day , UNaV increased ( +64 % ) as with P + ANF , but V ( -44 % ) and CH2O ( -52 % ) continued to decrease below baseline levels ; analysis of variance showed this antidiuresis reflected the prevalent effect of AVP rather than any specific interaction . These results show that AVP is able to dissociate the natriuretic and diuretic effects of ANF .

Arginine vasopressin

arginine vasopressin ( AVP )

Atrial natriuretic factor

placebo

AVP

P

ANF

Atrial natriuretic factor

Arginine vasopressin

AVP

ANF

diuresis and natriuresis

sodium excretion ( UNaV )

urinary flow rate ( V )

free water clearance ( CH2O )

creatinine clearance ( Ccr )

V

UNaV or Ccr

UNaV

P + ANF

V

natriuretic and diuretic effects

man .

man .


Intensive induction chemotherapy for small cell anaplastic carcinoma of the lung . The role of intensive induction chemotherapy in small cell cancer of the lung remains unclear . Twenty-eight newly diagnosed patients with small cell lung cancer were randomized to receive either high-dose or standard-dose cyclophosphamide , vincristine , and semustine in a trial where the dose of induction chemotherapy was the sole treatment variable . Complete responses ( CR ) were achieved in 57 % of patients receiving high-dose therapy as compared to 21 % of patients receiving standard-dose therapy ( P less than 0.05 ) . There was a higher rate of severe toxicity in the high-dose group ( P less than 0.01 ) . The overall median survival was not improved ( 36 weeks for the high-dose group vs 43 weeks for the standard-dose group ) ; however , the median survival in patients achieving CR was prolonged ( 92 weeks for the high-dose group vs 50 weeks for the standard-dose group ) . These effects were most pronounced in patients with extensive disease ; a CR after induction was achieved in five of nine patients treated with high doses but not in any of those treated with standard doses ( P less than 0.05 ) . A small group of patients appear to benefit by achieving a long-term remission with intensive induction chemotherapy , but this effect may be offset by increased morbidity .

Intensive induction chemotherapy

intensive induction chemotherapy

cyclophosphamide

vincristine

semustine

Complete responses ( CR )

severe toxicity

overall median survival

median survival

CR

Twenty-eight

small cell lung cancer


Treatment of varicella-zoster virus infection in severely immunocompromised patients . A randomized comparison of acyclovir and vidarabine . In a prospective , randomized trial , we compared intravenous acyclovir and vidarabine in the treatment of varicella-zoster virus infection in severely immunocompromised patients who presented within 72 hours of onset of the infection . Eleven patients were treated in each group . Cutaneous dissemination of infection occurred in none of the 10 acyclovir recipients and in 5 of the 10 vidarabine recipients who had presented with localized dermatomal disease ( P = 0.016 ) . As compared with vidarabine , acyclovir treatment shortened the median periods during which cultures were positive for the virus ( four vs. seven days , P = 0.004 ) and new lesions formed ( three vs. six days , P = 0.03 ) . Acyclovir also shortened the median interval until the first decrease in pain ( 4 vs. 7 days , P = 0.005 ) , the pustulation of all lesions ( 4 vs. 7 days , P = 0.0004 ) , the crusting of all lesions ( 7 vs. 17 days , P = 0.0003 ) , and the complete healing of lesions ( 17 vs. 28 days , P = 0.003 ) . In addition , acyclovir reduced the incidence of fever ( two vs. eight patients , P = 0.015 ) . We conclude that acyclovir is better than vidarabine for the treatment of varicella-zoster infection in immunocompromised patients .

acyclovir

vidarabine

intravenous acyclovir

vidarabine

acyclovir

vidarabine

Acyclovir

acyclovir

acyclovir

vidarabine

Cutaneous dissemination of infection

new lesions

pustulation of all lesions

crusting of all lesions

fever


Intravenous hyperimmune globulin prophylaxis against cytomegalovirus interstitial pneumonitis after allogenic bone marrow transplantation . In an attempt to reduce the incidence of lethal cytomegalovirus ( CMV ) interstitial pneumonitis after allogenic bone marrow transplantation 49 patients were randomized in a multicenter controlled study to receive either CMV-hyperimmune globulin or a control immune globulin with low anticytomegalovirus titer . Immune globulin was administered intravenously 6 times with 20 days interval , starting on day 7 before transplantation . Patients receiving CMV hyperimmune globulin or control immune globulin were comparable with regard to age , diagnosis , pretransplant anti-CMV titer , incidence of graft-versus-host disease and transfusions . In each group , the incidence of histologically proven CMV interstitial pneumonitis during the first 110 days post BMT was recorded . Six of 23 patients in the control group versus 1 of 26 in the CMV hyperimmune globulin group died of CMV interstitial pneumonitis ( p less than 0.05 ) . No significant effect on idiopathic pneumonitis or survival was observed .

allogenic bone marrow transplantation

CMV-hyperimmune globulin

Immune globulin

CMV hyperimmune globulin

control immune globulin

control

CMV hyperimmune globulin

CMV interstitial pneumonitis

died of CMV interstitial pneumonitis

idiopathic pneumonitis

survival

allogenic bone marrow transplantation .


Antihypertensive effect of single doses of enalapril in hypertensive patients treated with bendrofluazide . This study was designed to investigate the validity of the then current recommendations for initiation of therapy with enalapril in hypertensive patients on treatment with a diuretic . Enalapril in single doses of 10 and 20 mg was given to 13 hypertensive patients on treatment with bendrofluazide 5 mg daily in a randomised , crossover , placebo controlled study . The mean maximal reduction in blood pressure was similar with both doses ( 35/20 mmHg supine , 38/20 mmHg standing ) , occurred on average within 6 h of tablet ingestion , and was not accompanied by any significant change in heart rate . Three patients experienced symptomatic hypotension . In one patient this was incapacitating after 10 mg and precluded exposure to 20 mg . This study shows that in hypertensive patients receiving treatment with diuretics , the addition of enalapril should be undertaken with caution . An optimal starting dose of enalapril in such patients remains to be confirmed .

enalapril

bendrofluazide

enalapril

Enalapril

bendrofluazide

placebo

Antihypertensive effect

heart rate

symptomatic hypotension

incapacitating

hypertensive patients

hypertensive


Comparison of four continuously administered progestogen plus oestradiol combinations for climacteric complaints . Sixty women with climacteric complaints who had not menstruated for at least 1 year were randomly allocated to receive one of four hormonal replacement regimens . All four formulations were administered daily and continuously and each contained 2 mg of micronized oestradiol-17 beta in combination with either norethisterone acetate 1 mg ( group A ) or 0.5 mg ( group B ) or megestrol acetate 5 mg ( group C ) or 2.5 mg ( group D ) . The clinical efficacy was the same although the alleviation of vasomotor symptoms was somewhat slower in those women receiving preparation A . The endometrium was atrophied in nearly all biopsies . Irregular uterine bleeding was almost entirely confined to the earlier phase of the study and was substantially less with the formulation containing 1 mg norethisterone acetate . It is concluded that a continuous oestradiol-progestogen combination can be used for long-term treatment of climacteric complaints in postmenopausal women and that after 4 months the clinical efficacy is the same irrespective of the type and dose of progestogen administered .

progestogen plus oestradiol

or megestrol acetate 5 mg

norethisterone acetate

oestradiol-progestogen combination

progestogen

climacteric complaints .

clinical efficacy

vasomotor symptoms

endometrium

biopsies .

Irregular

uterine

bleeding

climacteric complaints

clinical efficacy

Sixty

not menstruated


[ Whole gut irrigation with isotonic mannitol solution in the treatment of gastrointestinal bleeding due to cirrhosis : a controlled study ( author 's transl ) ] .

gastrointestinal bleeding


Comparison of 5-aminosalicylic acid ( 3 g ) and prednisolone phosphate sodium enemas ( 30 mg ) in the treatment of distal ulcerative colitis . A prospective , randomized , double-blind trial . Twenty-nine patients with attacks of distal ulcerative colitis were treated randomly with 3 g 5-aminosalicylic acid ( 5-ASA ) or 30 mg of prednisolone phosphate sodium ( PP ) enemas ( 40 ml ) . Endoscopic , clinical , and histologic improvement were comparable in the two treatment groups . Our study showed that topical treatment with 5-ASA is as efficacious as PP in improving distal ulcerative colitis .

5-aminosalicylic acid

prednisolone phosphate sodium

5-aminosalicylic acid ( 5-ASA )

prednisolone phosphate sodium ( PP )

PP

distal ulcerative colitis

distal ulcerative colitis

distal ulcerative colitis

Twenty-nine patients

attacks of distal ulcerative colitis

distal ulcerative colitis


Comparison of endocrine and radiation therapy in locally advanced prostatic cancer . 151 patients with locally advanced prostatic cancer ( T3-4 M0 ) , representing 38 % of the 404 cancer patients in a Finnish multicenter study , were randomly assigned to one of three treatment arms : orchiectomy , estrogens or radiotherapy . During the 4-year follow-up period there were no significant differences in the progression rates ( appearance of metastases in bone scan ) between the therapy groups . The frequency of thromboembolic and other cardiovascular complications was highest in the estrogen group ( 13/50 patients ) . In the radiotherapy group , 19 of 45 patients had bowel or bladder complications . On the other hand , orchiectomy has few , if any , complications . The high risk of complications associated with estrogens and radiotherapy has to be taken into consideration in the selection of treatment .

endocrine

radiation therapy

orchiectomy

estrogens

radiotherapy

progression rates

bowel or bladder complications

locally advanced prostatic cancer .

( T3-4 M0 )


[ Vulvovaginal Candida mycoses -- treatment with clotrimazole . Comparison of single-dose treatment with 6-day therapy ] .

clotrimazole


[ Controlled study of the quinidine-amiodarone combination in the reversal of auricular fibrillation ] .

quinidine-amiodarone combination

reversal of auricular fibrillation ]

auricular fibrillation ]


Plasma 3,4-dihydroxyphenylethyleneglycol and 3-methoxy-4-hydroxyphenylethyleneglycol as indicators of central noradrenergic activity . A comparative study on control subjects and depressed patients . Animal studies have suggested interspecies differences in brain norepinephrine ( NE ) metabolism , especially with regard to the relative proportions of 3,4-dihydroxyphenylethyleneglycol ( DOPEG ) compared to 3-methoxy-4-hydroxyphenylethyleneglycol ( MOPEG ) . In order to question the value of both glycol metabolites as peripheral indices of central noradrenergic activity , a comparative study of plasma DOPEG and MOPEG ( measured by HPLC ) related to depression , sex , age and diagnostic categories ( DSM-III ) was carried out on depressed and control subjects . In addition , two groups of 8 patients were randomly submitted to a desipramine 150 mg/day , or a metapramine 450 mg/day antidepressant treatment influencing the formation of DOPEG and MOPEG in a different way . The study did not demonstrate any difference between DOPEG and MOPEG for most of the experimental factors . We found also a significant positive correlation between plasma levels of DOPEG and MOPEG . Our results support the idea that each of these two biological indices can be used in the assessment of central noradrenergic activity .

desipramine 150 mg/day

central noradrenergic activity

central noradrenergic activity

depressed


Comparative effects of pinacidil and nifedipine in the treatment of arterial hypertension .

pinacidil

nifedipine

arterial hypertension .


Combined use of vasopressin and synthetic hypothalamic releasing factors as a new test of anterior pituitary function . Nine normal volunteers and 15 patients with pituitary disorders were given a combined test of anterior pituitary function using four hypothalamic releasing factors and arginine vasopressin . Rapid sequential intravenous infusions of human corticotrophin releasing factor 100 micrograms , growth hormone releasing factor 100 micrograms , luteinising hormone releasing hormone 100 micrograms , and thyrotrophin releasing hormone 200 micrograms were administered . Arginine vasopressin ( 10 pressor units ) was given intramuscularly at the same time . Plasma or serum samples were assayed for concentrations of cortisol , growth hormone , luteinising hormone , follicle stimulating hormone , prolactin , and thyroid stimulating hormone at multiple times for 120 minutes . No troublesome side effects occurred . The results of the releasing factor combined test with arginine vasopressin were compared in the same subjects with a conventional combined test using insulin together with thyrotrophin releasing hormone and luteinising hormone releasing hormone . No difference was observed in the basal and peak concentrations of luteinising hormone , follicle stimulating hormone , thyroid stimulating hormone , and prolactin . Both cortisol and growth hormone responses to the releasing factors with arginine vasopressin were much greater than those seen with insulin induced hypoglycaemia or the combined releasing factors without arginine vasopressin . Patients with pituitary hypo-function were similarly recognised in both studies . There was a rapid increase in all hormone values with a peak usually by 60 minutes . In most people adequate assessment of individual hormone reserves may be achieved using basal , 30 minute , and 60 minute samples . This new combined releasing factor test appears to be a safe , rapid , and useful test of anterior pituitary function .

vasopressin

arginine vasopressin .

human corticotrophin

growth hormone

luteinising hormone

thyrotrophin

Arginine vasopressin

side effects

cortisol and growth hormone responses

pituitary hypo-function

hormone values


Effects of mecamylamine on human cigarette smoking and subjective ratings . Multiple measures of cigarette smoking , subjective effect and physiological effect were collected during 90-min test sessions in normal volunteers . Before sessions subjects received oral doses of mecamylamine ( 2.5 , 5.0 , 10 , 20 mg ) or placebo . Each dose and placebo was given three times in a randomized block sequence . Mecamylamine increased several measures of cigarette smoking , including number of cigarettes , number of puffs per cigarette , and expired air carbon monoxide level . Mecamylamine also produced modest , dose-related decreases in standing blood pressure and increases in standing heart rate . The subjective effects produced by mecamylamine were not characteristic of those of psychoactive drugs . Mecamylamine appears to have increased cigarette smoking by decreasing the effective dose level of nicotine available from cigarette smoking .

mecamylamine

placebo

Mecamylamine

Mecamylamine

mecamylamine

Mecamylamine

number of cigarettes

number of puffs per cigarette

expired air carbon monoxide level

blood pressure

standing heart rate

cigarette smoking

normal


Caudal analgesia for perianal surgery . A comparison between bupivacaine and diamorphine . Seventy-three patients undergoing elective perianal surgery were randomly divided into a control group , a group who received a caudal injection of 20 ml bupivacaine 0.5 % plain and a group who received diamorphine 2.5 mg in 10 ml normal saline by caudal injection ; a comparison was then made of postoperative analgesia requirements . The bupivacaine group had better analgesia than the control group for the first 8 hours , after which there was no difference . The diamorphine group had better analgesia than the control group for the first 24 hours postoperatively . Side effects were less in the diamorphine group than the control , or the bupivacaine group . In particular , 41 % of the bupivacaine group complained of some degree of urinary retention and one patient required temporary catheterisation . It is concluded that caudal diamorphine gives good postoperative analgesia for perianal operations , particularly when motor blockade is not wanted by the surgeon .

bupivacaine

diamorphine

bupivacaine

diamorphine

caudal injection

bupivacaine

diamorphine

diamorphine

bupivacaine

bupivacaine

diamorphine

analgesia

analgesia

Side effects

some degree of urinary retention

temporary catheterisation

Seventy-three

elective perianal surgery


Comparison of amiodarone and disopyramide in the control of paroxysmal atrial fibrillation and atrial flutter ( interim report ) .

amiodarone and disopyramide


Dose dependent response of symptoms , pituitary , and bone to transdermal oestrogen in postmenopausal women . The effect of the plasma oestradiol concentration on climacteric symptoms , gonadotrophin release , and bone resorption was studied in three groups of postmenopausal women given 0.025 mg , 0.05 mg , or 0.1 mg transdermal oestradiol daily . There was a dose related reduction in symptoms , plasma follicle stimulating hormone concentration , and urinary calcium and hydroxyproline excretion . The relation of the response to plasma oestradiol values was similar for each variable with an initial large reduction and little change in response to increases in the plasma oestradiol concentration above 150 pmol/l ( 41 pg/ml ) . Hormone replacement therapy producing an effect equivalent to higher oestradiol concentrations is likely to increase the risk of side effects without conferring any additional benefit .

transdermal oestradiol

oestradiol

climacteric symptoms

gonadotrophin release

bone resorption

reduction in symptoms

side effects

additional benefit

postmenopausal women .


Effects of resistive exercise on skeletal muscle in marrow transplant recipients receiving total parenteral nutrition . Skeletal muscle protein loss occurs during marrow transplantation despite total parenteral nutrition . To determine if muscle atrophy could be minimized with exercise therapy , 30 patients undergoing marrow transplantation for acute leukemia completed a prospective randomized trial to receive : ( 1 ) no therapy ( controls ) , ( 2 ) physical therapy thrice weekly ( PT3 ) , or ( 3 ) physical therapy five times weekly ( PT5 ) . Patients were studied through 35 days posttransplant . Muscle protein status and turnover was assessed by weekly nitrogen balance , and creatinine and 3-methylhistidine excretion . Results favored a muscle protein-sparing effect of exercise , as a significant decrease in creatinine excretion in controls only suggested muscle protein loss associated with inactivity . Changes in arm muscle area correlated with energy , but not protein intake . Large individual variation , inadequate nutritional support and differences in admission arm muscle area may have clouded these results .

resistive exercise

exercise therapy

no therapy ( controls )

exercise

Skeletal muscle protein loss

muscle atrophy

Muscle protein status and turnover

weekly nitrogen balance

creatinine

3-methylhistidine excretion

creatinine excretion

muscle protein loss

arm muscle area


Chemotherapy of advanced gastric carcinoma ( stage IV ) : a randomized study of FAM versus 5-FU plus BCNU . Forty-six patients with advanced gastric carcinoma ( Stage IV ) were evaluated in a prospective randomized comparison of two chemotherapy regimens ( FAM versus 5-FU plus BCNU ) to identify therapeutic activity . Treatment groups were well balanced with respect to known prognostic factors . Thirty-three patients had measurable disease and thirteen had only microscopic residual disease in the resection margins . The overall median survival of the entire group was 13.2 months . Two ( 6 % ) patients with measurable disease reached complete response ( CR ) , 1 ( 3 % ) partial response ( PR ) , 12 ( 36 % ) had stable disease ( SD ) and 18 ( 56 % ) had progressive disease ( PD ) . The responders had not reached the median survival yet , the patients with SD had a median survival of 14.7 months and the PD 9.5 months . In the FAM arm there were 3 ( 18 % ) responders ( 2 CR and 1 PR ) , 7 ( 41 % ) SD and 7 ( 41 % ) PD , versus O responders , 5 ( 31 % ) SD and 11 ( 69 % ) PD in the 5-FU plus BCNU arm . In the FAM arm the median survival was 15.7 months versus 9.9 months in the other therapeutic arm . The statistical analysis indicated that survival associated with FAM regimen was superior to that reached with the 5-FU plus BCNU regimen . Thirteen patients with unmeasurable disease had a median survival of 15.9 months .

FAM

5-FU plus BCNU

chemotherapy

FAM

5-FU plus BCNU

FAM

FAM

FAM

5-FU plus BCNU

overall median survival

complete response ( CR )

partial response ( PR )

stable disease ( SD )

progressive disease ( PD )

median survival

survival

median survival

survival

Thirty-three

thirteen

Thirteen


Antibiotic prophylaxis in high-risk head and neck surgery : one-day vs. five-day therapy . Patients who undergo major contaminated surgery of the head and neck benefit from perioperative antibiotic prophylaxis . This study was developed to determine if 5 days of antibiotic administration would be more effective than 1 day . A multi-institutional prospective randomized double-blind study was designed . Patients who were identified as requiring pedicled flap reconstruction were potential candidates for the study . Later , patients were randomly assigned to receive cefoperazone sodium for either 24 hours or 120 hours . In each case , the drug was administered intravenously , beginning 1 to 2 hours preoperatively and continued for the prescribed period . One hundred nine patients were evaluable . Fifty-three patients were assigned to 1 day of perioperative prophylaxis . Wound infection developed in ten patients ( 18.9 % ) . Fifty-six patients were assigned to 5 days of perioperative antibiotic prophylaxis . Wound infection developed in 14 ( 25 % ) of these patients ( P greater than .05 ) . These data suggest that no beneficial effect from administration of antibiotics for longer than 24 hours postoperatively can be achieved in patients who undergo myocutaneous flap reconstruction .

Antibiotic prophylaxis

one-day

five-day therapy

antibiotic prophylaxis

antibiotic administration

cefoperazone sodium

perioperative antibiotic prophylaxis

antibiotics

antibiotic administration

Wound infection

Wound infection

high-risk head and neck surgery

One hundred nine


Postoperative pain control for outpatient oral surgery . 16 healthy patients requiring removal of bilateral symmetrically-impacted mandibular third molars participated in a double-blind randomised crossover trial to test the effectiveness of postoperative pain control using a long-acting anti-inflammatory agent ( diflunisal ) in combination with a long-acting local anaesthetic agent ( bupivacaine ) . Results were compared to the more traditional method of using an oral analgesic with shorter duration of action ( paracetamol with codeine ) with lignocaine as the local anaesthetic . Using a visual analogue pain scale , patients reported that significantly reduced pain was experienced over the first 4 days postoperatively with the diflunisal/bupivacaine treatment and patient preference for this treatment was highly significant . This report represents the first such study of diflunisal used for an extended course in oral surgery with pain assessment over the same period . No significant side-effects or adverse reactions were encountered .

diflunisal

( bupivacaine )

( paracetamol with codeine )

lignocaine

diflunisal/bupivacaine treatment

diflunisal

Postoperative pain control

visual analogue pain scale

pain

patient preference

pain

side-effects or adverse reactions

oral surgery

healthy


Transdermal nitroglycerin in angina pectoris : efficacy of intermittent application . Continuous application of transdermal nitroglycerin appears to result in tolerance to the antianginal effect . In a double-blind study the effects of continuous ( 24 h/day ) and intermittent ( 16 h/day ) application of transdermal nitroglycerin in a dosage of 10 mg/day were compared with the effects of placebo in 12 patients with chronic stable angina receiving treatment with beta-adrenergic blocking or calcium channel blocking agents . Exercise performance was assessed 2 to 4 hours after initial application and after 1 week of each treatment given in random order with a 3 day interval between treatments . Exercise time to onset of angina , total exercise duration and time to 1 mm ST segment depression were all significantly increased after initial application during the continuous and intermittent treatment periods . These increases were maintained after 1 week of intermittent but not continuous treatment . Thus the benefit of initial application of transdermal nitroglycerin is maintained with intermittent treatment and a daily nitrate-free interval , whereas tolerance to antianginal effect occurs with continuous treatment .

Transdermal nitroglycerin

transdermal nitroglycerin

transdermal nitroglycerin in

placebo

beta-adrenergic blocking

calcium channel blocking agents

transdermal nitroglycerin

tolerance to the antianginal effect

Exercise performance

tolerance to antianginal effect

angina pectoris


[ Bupivacaine-CO2 and bupivacaine-HCl at various injection temperatures in peridural anesthesia for extracorporeal shock wave lithotripsy ] . INTRODUCTION The effect of different injection temperatures on carbonated anesthetics has been controversial since 1965 . The current study was undertaken to determine onset times of sensory and motor blockade after epidural anesthesia with 0.5 % bupivacaine-CO2 and 0.5 % bupivacaine-HCl at various injection temperatures . MATERIALS AND METHODS The study was performed on 90 ASA class I-II urologic patients during extracorporeal shock wave lithotripsy . The patients were randomized in six groups to receive either 0.5 % bupivacaine-CO2 or 0.5 % bupivacaine-HCl at temperatures of 4 degrees , 20 degrees , or 36 degrees C. The six groups were comparable in age , height , and weight . Epidural anesthesia was performed at the L2-3 interspace with an 18-gauge Tuohy needle using loss of resistance . A catheter was advanced 4 cm in the epidural space and 4 ml 0.5 % bupivacaine with adrenaline 1:200,000 was given as a test dose . After 4 min the full anesthetic dose , based on body size , was injected with the patient supine . Sensory blockade was determined by the pinprick method and motor blockade by the Bromage method at 2-min intervals for the first 20 min , at 5-min intervals for the next 10 min , and then every 15 min to a total of 240 min . Statistical analysis was done by the Mann-Whitney test , with P less than 0.05 considered significant . RESULTS Spread of sensory blockade was significantly faster with bupivacaine-CO2 and -HCl at a temperature of 36 degrees C as compared to 4 degrees or 20 degrees C ( P less than 0.05 ) ( Figs . 1 , 2 and Table 2 ) . ( ABSTRACT TRUNCATED AT 250 WORDS )

bupivacaine-HCl

peridural anesthesia

epidural anesthesia

bupivacaine-HCl

extracorporeal shock wave lithotripsy .

bupivacaine-HCl

Epidural anesthesia

18-gauge Tuohy

bupivacaine with adrenaline

-HCl

Sensory blockade

motor blockade

Spread of sensory blockade

ASA class I-II urologic


Metabolic and ventilatory responses during very low level exercise . 1 . Nine male and six female healthy subjects were studied during supine bicycle exercise at workloads of 12 and 37 W ; pedalling rates varied between 30 and 50 cycles/min at each workload . Measurements were made of oxygen consumption ( VO2 ) , carbon dioxide production ( VCO2 ) , minute ventilation ( VE ) , tidal volume ( VT ) , respiratory frequency ( fR ) , inspiratory and expiratory time ( TI , TE ) and mean inspiratory flow ( VT/TI ) using a non-invasive canopy-computer-spirometer system . 2 . At rest , males had greater values of VE , VT , TI , inspiratory duty cycle ( TI/TTOT ) , VCO2 and VO2 , and a lower fR , than females . 3 . At the lower workload , VO2 , VCO2 , VE , VT and VT/TI increased linearly with increasing pedalling rate , whereas at the higher workload there was a decrease in VO2 and little or no change in ventilatory parameters from 30 to 50 cycles/min except for an increase in fR in females . 4 . While performing supine exercise , there was an effect of pedalling rate on ventilatory and metabolic parameters at the low workload ( 12 W ) which diminished at the higher workload ( 37 W ) . An increase in pedalling rate appears to enhance efficiency at these low workloads . 5 . Differences between the sexes during exercise generally include : ( a ) a higher breathing frequency , ( b ) a greater mechanical efficiency , and ( c ) lower ventilatory equivalents of O2 and CO2 ( VE/VO2 and VE/VCO2 ) during the higher workload in females than males .

very low level exercise

supine bicycle exercise

supine exercise

respiratory frequency ( fR ) ,

mean inspiratory flow ( VT/TI )

VE

VT

TI

inspiratory duty cycle

( TI/TTOT )

lower fR

VE

VT

VT/TI

ventilatory parameters

fR

pedalling rate

higher breathing frequency

a greater mechanical efficiency


Effect of fenfluramine on autistic symptoms .

fenfluramine

autistic symptoms


Effects of misoprostol on human circulation . Prostaglandins ( PGs ) of the E-type are potent vasodilators in most species and in most vascular beds . However , vasoconstrictor effects of PGEs have also been noted at selected sites . This study examined the effects of misoprostol , a PGE1 analog with antiulcer activity , on the human cardiovascular system . Twenty healthy subjects participated in this double-blind , placebo-controlled , parallel group study . Following a 12 hour fast , heart rate , arterial blood pressure , light reflex plethysmography of the finger , resting blood flow volume in the lower arm and leg and peripheral vascular resistance were measured at 10 min . intervals for 1 hour prior to drug administration , to permit calculating baseline values . Misoprostol ( 400 mcg ) or its matching placebo were administered orally , and the measurements were repeated at 10 min . intervals over the next 2 hours . A decrease in leg blood flow volume and a corresponding increase in leg peripheral vascular resistance were noted in the misoprostol group . A statistically significant decrease in heart rate between the two treatment groups was also noted . These small changes were not considered to be of clinical importance . No adverse experiences were reported . In conclusion , a single dose of misoprostol ( 400 mcg ) has no clinically significant vasoconstrictive or vasodilative properties in man .

misoprostol

misoprostol

Misoprostol

placebo

misoprostol

misoprostol

misoprostol

misoprostol

peripheral vascular resistance

leg blood flow volume

heart rate

adverse experiences

vasoconstrictive or vasodilative

human circulation

Twenty


Serum C-peptide after 6 months on glibenclamide remains higher than during insulin treatment . Serum C-peptide was measured fasting and 6 minutes after glucagon ( 1 mg given intravenously ) in 49 patients with non-insulin-dependent diabetes mellitus , after 4 and 6 months of successive periods of treatment with insulin and oral hypoglycaemics ( glibenclamide and metformin ) , given in random order . Glycaemic control was not significantly different on the two treatments , but C-peptide was much higher while the patients were on glibenclamide . We conclude that glibenclamide stimulates pancreatic insulin production even after 6 months treatment .

glibenclamide

6 minutes after glucagon

glibenclamide

Serum C-peptide

Serum C-peptide

Glycaemic control

C-peptide

non-insulin-dependent diabetes mellitus


Prospective controlled study of androgen therapy in the anemia of chronic renal disease : effects on iron kinetics . Ferrokinetic and RBC mass determinations were made at 3-month intervals in iron-replete hemodialysis patients randomized to a control group or to nandrolone decanoate therapy . After 3 months , RBC mass increased in two of 4 androgen-treated patients . Erythron iron turnover , an index of RBC production , increased in the one responder studied but not in the two nonresponders . Similarly , in a fifth subject , who was not restudied until 6 months of androgen therapy were completed , an increase in RBC mass was associated with an increase in erythron iron turnover . However , between 3 and 6 months , RBC mass increased in all 4 androgen-treated patients studied even though erythron iron turnovers remained unchanged and dialysis-associated blood losses did not decrease . Thus , at least two androgen-treated patients had increases in RBC mass without ever increasing their erythron iron turnover . Two of three control subjects also had increased erythron iron turnovers , which in one case was related to increased dialysis-associated blood losses . Changes in RBC mass were not consistently paralleled by changes in Hb . These findings suggest that increases in RBC mass during nandrolone decanoate therapy result from two mechanisms : increased erythropoiesis ( shown by simultaneous increases in RBC mass and erythron iron turnover ) and increased RBC survival ( indirectly shown by increases in RBC mass without increases in erythron iron turnover ) . The importance of control groups , RBC mass determinations and the monitoring of dialysis-associated blood losses in studying the effects of androgens on erythropoiesis in chronic hemodialysis patients is also demonstrated .

androgen therapy

control group

or to

nandrolone decanoate

therapy

androgen therapy

androgen-treated

androgen-treated

anemia

RBC mass

Erythron iron turnover

RBC mass

RBC mass

dialysis-associated blood losses

RBC mass

erythron iron turnover

erythron iron turnovers

dialysis-associated blood losses

RBC mass

RBC mass

RBC mass

erythron iron turnover

RBC survival

RBC mass

erythron iron turnover

RBC mass

dialysis-associated blood losses

anemia

chronic renal disease


[ Supplementary treatment with Esberitox of female patients undergoing curative adjuvant irradiation following breast cancer ] . 1 . The study was supposed to investigate a possible prevention or reduction of the toxicity of radiotherapy by an additional treatment with Esberitox . This question arose when performing an investigation about the effect of Esberitox in a combined chemo-radiotherapy . Whereas the latter induces above all a systemic damage to the hemopoietic system , radiotherapy is a regional noxa . 2 . The present prospective , randomized study was conducted with 50 patients submitted to curative adjuvant irradiation following surgery for mammary carcinoma . The radiotherapy was performed in the same way in all patients with irradiations of the thoracic wall and the regional lymph nodes . Two groups were built by randomization . The study group received an additional treatment with Esberitox , the control group did not receive an additional treatment . 3 . As a result , no protective influence of Esberitox could be demonstrated . The parameters investigated were the peripheral blood count ( leucocytes , granulocytes , lymphocytes , monocytes , thrombocytes , hemoglobin , hematocrit ) and the incidence of infections . 4 . This result diverging from literature is discussed . It is probably affected by volume and extension of the injury induced by a hematotoxic noxa and furthermore by the ability of regeneration . If this ability is exhausted , the protective effect of Esberitox can act no longer . Therefore the essential factor seems to be the duration of exposure to the noxa . Esberitox was effective in case of a short toxicity , it was ineffective in case of prolonged toxicity , if the treatment continuity ( noxa ) was not broken up by some regeneration intervals . The radiotherapy studied in this trial had a duration of 50 days , and its effect was that of a longterm injury .

Esberitox

curative adjuvant irradiation

radiotherapy

Esberitox .

Esberitox

curative adjuvant irradiation

radiotherapy

Esberitox

radiotherapy

prevention or reduction of the toxicity


[ Total parenteral nutrition in colon surgery ] .

parenteral nutrition

colon surgery

parenteral nutrition

colon surgery ]


The therapeutic efficacy and cost-effectiveness of aggressive tocolysis for premature labor associated with premature rupture of the membranes . We conducted a randomized trial comparing bed rest with tocolysis to determine the therapeutic efficacy , safety , and cost-effectiveness of tocolysis for the treatment of preterm labor after membrane rupture . One hundred nine women participated over a 26-month interval . Treatment groups did not differ significantly in terms of gestational age at membrane rupture , gestational age at delivery , birth weight , maternal or fetal infectious morbidity , respiratory distress syndrome , necrotizing enterocolitis , or perinatal mortality . Prolongation of intrauterine time after the onset of uterine contractions was seen in women receiving tocolysis ( 105.2 +/- 157 hours versus 62.1 +/- 77 hours , p = 0.06 ) . This prolongation was not associated with a significant reduction in the total cost per surviving infant ( tocolysis , $ 38,593 +/- $ 40,887 versus bed rest , $ 43,158 +/- $ 37,116 ; p = 0.445 ) . The cost difference was artifactual . The number of very premature infants born ( less than 28 weeks ' gestation ) was unequal in the two groups ( 12 in the bed rest group and 5 in the tocolysis group ) and skewed the results . Before 28 weeks ' gestation tocolysis was associated with a significant increase in intrauterine time after the onset of regular contractions ( p = 0.05 ) . However , there was no identifiable perinatal benefit garnered from the additional 5 days . After 28 weeks there were no significant differences between treatment groups in terms of intrauterine time after the onset of regular contractions and total cost per surviving infant . Because tocolysis does not improve perinatal outcome and can itself be associated with major maternal morbidity , it should be avoided after 28 weeks ' gestation . Before 28 weeks ' gestation tocolysis may greatly increase intrauterine time , but the benefit of this prolongation is not clear .

bed rest with tocolysis

tocolysis

tocolysis

tocolysis

tocolysis

therapeutic efficacy

cost-effectiveness

therapeutic efficacy

safety

cost-effectiveness

gestational age at membrane rupture

gestational age at delivery

birth weight

perinatal mortality

total cost

cost difference

very premature infants born

increase in intrauterine time

regular contractions

intrauterine time

regular contractions

preterm labor after membrane rupture

One hundred nine women


Control of perioperative hypertension during coronary artery surgery . A randomised double-blind study comparing isosorbide dinitrate and nitroglycerin . A reduction in the causes of myocardial ischaemia remains of prime importance during coronary artery surgery . Hypertension with the ensuing increase in myocardial oxygen demand is a major factor in the aetiology of perioperative myocardial ischaemia . Nitroglycerin ( NTG ) has long been used beneficially to reduce myocardial oxygen demand by its effects on the systemic and peripheral vascular resistances . An alternative nitrate , isosorbide dinitrate ( ISDN ) is now available as an intravenous preparation , and may offer technical advantages , both due to its stability in solution and also its longer in vivo half-life . We designed and carried out a multi-centre study to compare and evaluate the efficacy of ISDN and NTG in the management of perioperative hypertension in 85 patients undergoing elective coronary artery surgery . A total of 288 events in which the systolic blood pressure ( SBP ) exceeded a predetermined trigger value were observed . ISDN was successful in treating hypertension in 63 % of the events , whereas NTG had an 83 % success . The SBP was significantly lowered after treatment with either ISDN , 155 mmHg to 138 mmHg , or NTG , 160 mmHg to 130 mmHg . The mean successful dose rate for ISDN was 6.5 micrograms kg-1 min-1 , whereas for NTG this was 3.8 micrograms kg-1 min-1 . In the ISDN group less events took place possibly due to the longer duration of this drug . In many previous studies NTG has been found to be effective in controlling hypertension ; ISDN offers and alternative approach in reducing hypertension .

coronary artery surgery

isosorbide dinitrate

nitroglycerin

Nitroglycerin ( NTG )

nitrate

isosorbide dinitrate ( ISDN )

ISDN

NTG

elective coronary artery surgery

ISDN

NTG

ISDN

NTG

ISDN

NTG

hypertension

myocardial ischaemia

Hypertension

myocardial oxygen demand

myocardial ischaemia

myocardial oxygen demand

efficacy of ISDN and NTG

systolic blood pressure ( SBP )

successful

hypertension

SBP

mean successful dose rate

events

hypertension

reducing hypertension

coronary artery surgery

85 patients


Comparison of mastectomy with tamoxifen for treating elderly patients with operable breast cancer . STUDY OBJECTIVE Comparison of tamoxifen and mastectomy in treatment of breast cancer in elderly patients . DESIGN Randomised trial of treatment of operable breast cancer by wedge mastectomy or tamoxifen , with median follow up 24 and 25 months respectively ( range 1-63 ) . SETTING University hospital ; most patients from primary catchment area . PATIENTS 135 consecutive patients with breast cancer aged over 70 with operable tumours ( less than 5 cm maximum diameter ) ; 68 were allocated to tamoxifen group and 67 to mastectomy group . Histological diagnosis by biopsy . Two incorrect randomisations in each group . Patient characteristics similar in the two groups and all under care of one surgical team . INTERVENTIONS Mastectomy group received wedge mastectomy plus excision of symptomatic axillary lymph nodes . Tamoxifen group received continuous treatment with tamoxifen 20 mg twice daily . Patients in tamoxifen group received wedge mastectomy if there was sign of local progression . Those in mastectomy group received further excision or radiotherapy for locoregional recurrence and when local treatments had been exhausted or metastatic disease diagnosed they received tamoxifen . END POINT Treatment efficacy was assessed by local control of disease and by survival . MAIN RESULTS Mortality from metastatic cancer in tamoxifen group was 7 ( 10.6 % ) and in mastectomy group 10 ( 15.3 % ) ( NS ) . There was no difference in survival between the two groups . In mastectomy group 70 % remained alive and free of local recurrence at 24 months ; in tamoxifen group only 47 % remained alive and free of local progression . In mastectomy group locoregional recurrence occurred in 16 patients and metastatic disease in 13 ; in tamoxifen group locoregional progression occurred in 29 patients and metastatic disease in seven . CONCLUSIONS As a high proportion of patients treated with tamoxifen eventually required surgery treatment of elderly patients with breast cancer should include mastectomy . Optimum treatment may include both mastectomy and tamoxifen .

mastectomy

tamoxifen

tamoxifen

mastectomy

wedge mastectomy

tamoxifen

tamoxifen group

mastectomy group .

Tamoxifen

tamoxifen 20 mg

wedge mastectomy

radiotherapy

tamoxifen

tamoxifen

mastectomy

Treatment efficacy

local control of disease and by

survival

Mortality

survival

free of local recurrence

locoregional recurrence

locoregional progression

elderly

breast cancer

breast cancer

elderly

breast cancer

tumours

elderly

breast cancer


[ Complaints in the postoperative phase related to anesthetics ] . In two prospective , randomized studies the frequency of headache , nausea , vomiting , and analgesic requirement during the first postoperative 24 h was observed in order to study differences between the sexes and the inhalation anesthetics halothane , enflurane , isoflurane , or balanced anesthesia with enflurane/alfentanil . Nausea and vomiting were more frequent after enflurane than after halothane or isoflurane . There was no significant difference between anesthetics and frequency of headache , but there were significant differences in postoperative analgesic requirements which were highest after halothane and lowest after isoflurane . Postoperative complaints were always significantly greater among women than among men . The second study indicated that balanced anesthesia did not reduce the analgesic requirement compared to enflurane without alfentanil , but lead to a higher incidence of vomiting . After premedication with flunitrazepam and atropine and combined with 70 % N2O/30 % O2 , isoflurane was the most favorable anesthetic agent with regard to the parameters studied . Balanced anesthesia with enflurane/alfentanil did not show any advantages for patients in the postoperative phase under the given conditions .

anesthetics halothane

enflurane

isoflurane

enflurane

halothane

isoflurane

halothane

isoflurane

enflurane

alfentanil

isoflurane

Nausea and vomiting

frequency of headache

postoperative analgesic requirements

Postoperative complaints

analgesic requirement

vomiting

anesthetics

women

men

postoperative phase


[ Trial of a calcium antagonist in dysmenorrhea ] .

calcium antagonist

dysmenorrhea ]

dysmenorrhea ]


Psoriasis of the scalp treated with Grenz rays or topical corticosteroid combined with Grenz rays . A comparative randomized trial . To investigate the effect of Grenz ray therapy alone compared with Grenz rays combined with a topical corticosteroid ( betamethasone dipropionate ) in psoriasis of the scalp , 40 patients were randomized into two groups . One group received 4 Gy of Grenz rays administered on six occasions at intervals of 1 week and the other group was given the same Grenz ray treatment plus topical corticosteroid . The patients were assessed before and after Grenz ray therapy and were followed-up for 6 months . Of the 37 patients who completed the trial 16 out of 19 ( 84 % ) of the patients in the Grenz ray group , and 13 out of 18 ( 72 % ) of the patients in the combination group healed . The remission time did not differ significantly between the two groups . Of the patients who healed , 5 of 16 patients in the Grenz ray only group and 4 of 13 patients in the combination group remained healed at 6 months . We conclude that Grenz ray therapy is a useful treatment modality for scalp psoriasis , but that the addition of a topical corticosteroid has only a minor effect .

Grenz rays

Grenz ray therapy

Gy of Grenz rays

Grenz ray

Grenz ray

Grenz ray therapy

corticosteroid

healed

remission time

healed

remained healed

treatment

scalp psoriasis

minor effect

Psoriasis of the scalp


The influence of adult intervention on infants ' level of attention . The effects of adult intervention on infants ' level of attention to objects were studied with 10-month-old infants . After a baseline measure of spontaneous attention was obtained , infants were randomly assigned to 1 of 4 conditions ( low , medium , high intervention , or no-intervention control ) . Level of intervention was controlled by systematically varying the manner and frequency with which objects were presented , the extent to which the experimenter talked to the infant , and physical proximity . Infant attention was defined as duration of time spent examining objects . The overall duration of infant attention increased during medium intervention when compared to the control group . Baseline attention was then used to separate low and high attenders . Low attending infants attended more in medium and high intervention than in the low condition , while high attending infants were unaffected by intervention . The results show that level of intervention interacts with the child 's spontaneous tendency to focus attention on objects .

adult intervention

adult intervention

low , medium , high intervention

no-intervention

physical proximity

intervention

infants ' level of attention

level of attention

overall duration of infant attention

attended

infants


Mecamylamine reduces some EEG effects of nicotine chewing gum in humans . Spontaneous EEG was recorded in nine cigarette smokers who had been abstinent from tobacco for 12 hr . Subjects were treated with a capsule containing either centrally acting nicotine blocker , mecamylamine ( 10 mg ) , or placebo . At each of three 60-min intervals after the capsule was ingested , the subjects chewed two pieces of gum containing a total of 0 , 4 or 8 mg of nicotine . Nicotine and mecamylamine dose combinations were randomized across subjects . Two three-minute periods of spontaneous EEG were recorded before the capsule and before and after gum chewing from bipolar electrode montages at the following positions : Cz-T5 , Cz-T6 , Cz-F7 and Cz-F8 . During one period the subjects relaxed with eyes closed , in the other period they performed a math task with eyes open . When the drugs were given individually , mecamylamine decreased beta power and nicotine gum ( 4 and 8 mg ) increased alpha frequency . Mecamylamine pretreatment prevented the increase in alpha frequency caused by the 4 mg gum dose but not the 8 mg dose . Alpha power was increased by the 8 mg gum dose and that increase was prevented by mecamylamine . Self-reported ratings of the " strength " of the gum were significantly diminished by mecamylamine pretreatment . The data are consistent with the results of earlier studies which indicate that the effects of tobacco administration and withdrawal are mediated by central actions of nicotine .

Mecamylamine

or placebo .

Nicotine and mecamylamine

mecamylamine

Mecamylamine

mecamylamine .

beta power

alpha frequency .

alpha frequency

Alpha power

" strength "

nine

cigarette smokers


Heparin plus dipyridamole in childhood hemolytic-uremic syndrome : a prospective , randomized study . From 1976 to 1985 , a total of 58 infants and children with the hemolytic-uremic syndrome were randomly assigned to treatment either with heparin and dipyridamole or with supportive management only . In the treatment group , two patients died in the early weeks of the disease . Analysis of clinical and laboratory data showed no significant difference between either group of patients as to the evolution of their illness except for a significantly higher incidence of anuria and a significantly faster recovery from hypertension in the treated group . Renal biopsy studies showed no differences between the two groups in terms of incidence and severity of the histologic lesions . The long-term data on blood pressure and creatinine clearance values in the survivors were similar in both groups . This study indicates that treatment with heparin and dipyridamole has no benefit over symptomatic therapy alone in the typical form of childhood hemolytic-uremic syndrome .

Heparin plus dipyridamole

heparin and dipyridamole

heparin

dipyridamole

symptomatic therapy

incidence of anuria

faster recovery from hypertension

blood pressure

creatinine clearance values

heparin

dipyridamole

benefit over symptomatic therapy

childhood

infants and children

hemolytic-uremic syndrome


Educational intervention for altering water-sanitation behavior to reduce childhood diarrhea in urban Bangladesh : impact on nutritional status . We evaluated whether an educational intervention that was effective in reducing childhood diarrhea also improved childhood nutritional status . Fifty-one communities of 38 families each were randomized to receive the intervention or no intervention . During 1 y of follow-up the rate of diarrhea ( per 100 wk ) in children less than 6 y in the intervention group was 5.89 episodes whereas that in the nonintervention group was 7.55 episodes ( protective efficacy 22 % ; p less than 0.0001 ) . During the same follow-up period children in both groups exhibited comparable patterns of weight gain ; 1 y after the intervention the mean weight for age of children in both groups was 76 % of the NCHS standard . No significant differences were observed in the proportion of each group that experienced a major deterioration or improvement of nutritional status . We conclude that an intervention that reduces rates of childhood diarrhea may not necessarily also improve nutritional status .

Educational intervention

educational intervention

intervention

no intervention

diarrhea

childhood nutritional status .

rate of diarrhea

weight gain ;

mean weight for age

childhood diarrhea

nutritional status .

diarrhea

children less than 6 y


Surgery of aphakic retinal detachment . In a prospective study 84 patients with aphakic retinal detachment were treated either by local scleral buckling alone or combined with an encirclement . The rate of surgical reattachment of the retina was found to be similar with either technique over a minimum follow-up period of one year . Simplicity and a low incidence of serious complications of the local procedure merit its application as the initial method of repairing aphakic detachments .


Argon laser trabeculoplasty in primary open-angle glaucoma -- results in black Jamaican population . A controlled , randomised , prospective trial of Argon laser trabeculoplasty ( ALT ) was carried out on 48 eyes of 30 black Jamaican patients with primary open-angle glaucoma . All eyes had uncontrolled intra-ocular pressures ( greater than or equal to 22 mm Hg ) despite medical therapy . Treatment was successful in controlling intraocular pressure in 68 % of eyes after 12 months follow-up ( p = 0.004 ) . The average drop in intraocular pressure attributable to ALT was 6.6 mmHg . Argon laser trabeculoplasty is an effective adjunct in managing to control intraocular pressure in black Jamaican glaucoma patients .

Argon laser trabeculoplasty

Argon laser trabeculoplasty ( ALT )

ALT

Argon laser trabeculoplasty

intra-ocular pressures

controlling intraocular pressure

drop in intraocular pressure

intraocular pressure

primary open-angle glaucoma

primary open-angle glaucoma

glaucoma


Lack of antihistamine properties of single dose cinnarizine in man . A simple way to study a histamine antagonist in man is to observe the effect it has on the magnitude of the skin reaction to intradermal histamine . The aim of the present study was to evaluate the antihistamine activity of single oral doses of 75 mg cinnarizine using 75 mg diphenhydramine as control , both being compared to placebo . The study was performed with two groups of 5 healthy subjects , each group receiving one of the active treatments or placebo randomly under blind conditions . All subjects received intradermal injections on the forearm of a 0.05 ml saline solution containing 5 micrograms of histamine before and at different times after drug intake . The histamine-induced wheal area was measured and , after drug administration , the percent decrease of the wheal area was calculated . Results showed that diphenhydramine produced a significant inhibition of the histamine-induced wheal size at 1.5 h which lasted up to 4 h after drug administration , reaching maximum inhibition at 2.5 h. After cinnarizine treatment no significant decrease of the histamine-induced wheal area was observed at any time .

cinnarizine

histamine .

cinnarizine using

diphenhydramine as control

placebo .

placebo

saline solution

diphenhydramine

cinnarizine

wheal area

inhibition of the

histamine-induced wheal size

histamine-induced wheal area

man .


[ Propofol infusion for the maintenance of short-term anesthesia ] . The administration of propofol by infusion for maintenance of anesthesia has attracted much attention recently . We investigated the necessary infusion rate of propofol to maintain anesthesia for short surgical procedures without loss of the evident advantages of this substance . Forty unpremedicated female patients aged 18-59 , scheduled for minor gynecological procedures , were randomly assigned to four groups . Anesthesia was induced with 2.0 mg/kg propofol i.v . and simultaneously an infusion of 0.05 , 0.10 , 0.15 , or 0.20 mg propofol/kg per minute was started . The patients were breathing N2O/O2 with FIO2 33 % . Additional propofol was administered as a bolus of 10 to 20 mg when the patients moved . With 0.05 mg propofol/kg per minute all patients required additional bolus injections of propofol ; with 0.10 mg 8 patients , with 0.15 mg 5 patients , and with 0.20 mg 1 patient required bolus injection . Therefore , 0.15 mg/kg per minute can be considered as an approximate ED50 value . The total propofol consumption ( infusion + bolus ) increased from 0.102 +/- 0.028 ( +/- SD ) with the lowest infusion rate to 0.202 +/- 0.006 mg/kg per minute with the highest infusion rate and recovery time from 5.2 +/- 1.4 to 9.9 +/- 2.6 min . There was a significant correlation between propofol consumption and recovery time . After induction , arterial blood pressure decreased by systolic/diastolic 20/10-15 mmHg . With the low infusion rate , arterial pressure increased to its control value during operation ; it remained at the postinduction value with high infusion rates . Side-effects : 10 patients had salivation that in some instances lead to coughing , 9 reported pain at the injection site during induction , and 9 reported dreams of a pleasant nature . ( ABSTRACT TRUNCATED AT 250 WORDS )

[ Propofol

propofol

propofol

2.0 mg/kg propofol i.v .

propofol/kg

N2O/O2 with FIO2

propofol

propofol/kg

propofol ;

propofol

propofol

anesthesia

total propofol consumption

infusion rate

infusion rate

recovery time

propofol consumption

recovery time

arterial blood pressure

arterial pressure

short-term anesthesia ]


Randomized study of six umbilical cord care regimens . Comparing length of attachment , microbial control , and satisfaction . Two hundred and seventy one infants were enrolled in a study to compare six different methods of treating the umbilical cord . Antimicrobial control was equal for all methods . Repeated triple dye application was considered least acceptable by staff and parents and had the longest attachment time . Povidone-iodine was associated with the shortest attachment time and was most liked . If there is no special need to treat a specific nosocomial outbreak , duration of cord attachment and satisfaction of staff and parents can help clinicians decide on a cord care regimen .

umbilical cord care regimens

triple dye application

Povidone-iodine

least acceptable

longest attachment time .

attachment time

six umbilical cord care regimens .


Randomized study of 13-cis retinoic acid v placebo in the myelodysplastic disorders . A double-blind , placebo-controlled randomized trial of 13-cis retinoic acid was performed to determine if the drug has a therapeutic effect in patients with myelodysplastic syndromes ( MDS ) . Sixty-eight evaluable patients with MDS were randomized to receive a single , daily oral dose of either 13-cis retinoic acid ( 13-CRA , 100 mg/m2 ) or matching placebo . Treatment was continued , when possible , for a period of 6 months . Determination of response to treatment was based on clinical course , repeat bone marrow biopsies , and aspirates and blood counts ( CBC ) with WBC differential , platelet , and reticulocyte numbers at specified intervals . No significant difference was noted between the two treatment groups in response to test drug ( P = .66 ) . One patient ( 3 % ) in the 13-CRA group and two patients ( 6 % ) in the placebo group had a minor response . Approximately 30 % of patients in both groups had progression of their disease , and progression-free survival was nearly identical . Greater than 90 % of the patients receiving 13-CRA developed mild or moderate skin toxicity that was reversible with decreasing or discontinuing the drug . Our study did not find that 13-CRA exerts a beneficial therapeutic effect in patients with MDS .

13-cis retinoic acid

placebo

13-cis retinoic acid

13-cis retinoic acid ( 13-CRA

matching placebo .

therapeutic effect

response

progression of their disease

progression-free survival

mild or moderate skin toxicity

therapeutic effect

myelodysplastic disorders .


Comparison of intermittent or continuous methotrexate plus 6-mercaptopurine in regimens for standard-risk acute lymphoblastic leukemia in childhood ( JCCLSG-S811 ) . The Japanese Children 's Cancer and Leukemia Study Group . From 1981 to 1983 , 131 previously untreated patients with acute lymphoblastic leukemia ( ALL ) standard-risk group were entered to the protocol JCCLSG-S811 . Of 119 eligible patients , 115 ( 96.6 % ) attained complete remission by treatment with prednisone ( PRD ) plus vincristine ( VCR ) or vindesine ( VDS ) . After preventive central nervous system ( CNS ) therapy including 18 Gy cranial irradiation and three doses of intrathecal methotrexate ( MTX ) , the patients were assigned randomly to the two maintenance chemotherapies , Regimen A and Regimen B . Regimen A ( intermittent regimen ) consisted of PRD ( 120 mg/m2/day by mouth for 5 days ) plus 6-mercaptopurine ( 6MP ) ( 175 mg/m2/day by mouth for 5 days ) plus VCR ( 2.0 mg/m2 intravenously ) alternating biweekly with MTX ( 225 mg/m2 intravenously ) . Regimen B ( continuous regimen ) consisted of 6MP ( 50 mg/m2/day by mouth ) plus MTX ( 20 mg/m2/week by mouth ) combined with pulses of PRD and VCR ( the same dosages as Regimen A ) every 4 weeks . As the late intensification therapy ( LIT ) , five courses of high-dose MTX ( 2000 mg/m2 per dose per week intravenously for three doses every 12 weeks ) with leucovorin rescue were administered to all patients who were in continuous complete remission ( CCR ) for more than 2 years . Sixty and 55 patients , respectively , were registered in Regimen A and B . The CCR rates in Regimen A and B were 75.1 % +/- 5.8 % ( mean +/- 1 SE ) and 49.7 % +/- 7.3 % ( P less than 0.01 ) at 4 years , and 72.1 % +/- 6.3 % and 49.7 % +/- 7.3 % ( P less than 0.05 ) at 5 years , respectively . In Regimen B , CNS and testicular relapses increased after 3 years of CCR . In addition , the patients in Regimen B had a much higher incidence of infections than Regimen A . The LIT did not seem to have important effects on the duration of CCR . From these data we conclude that the intermittent cyclic regimen of 6MP and MTX may be more effective as compared to the continuous administration of these drugs in the maintenance chemotherapy .

intermittent or continuous methotrexate

18 Gy cranial irradiation

intrathecal methotrexate ( MTX )

PRD

plus 6-mercaptopurine ( 6MP )

plus VCR ( 2.0

biweekly with MTX

plus MTX

combined with pulses of PRD and VCR

MTX

MTX

pulses of PRD and VCR

CCR rates

CNS and testicular relapses

incidence of infections

duration of CCR

lymphoblastic leukemia

childhood


BCG ( RIVM ) versus mitomycin intravesical therapy in superficial bladder cancer . First results of randomized prospective trial . This study presents the preliminary results of a randomized prospective two-arm study in which bacillus Calmette-Guérin ( BCG ) RIVM , a Dutch BCG preparation , is compared with mitomycin C ( MMC ) in patients with primary or recurrent superficial bladder tumors , including carcinoma in situ ( CIS ) . Therapeutic regimens were as follows : after complete transurethral resection of all visible tumors , BCG RIVM ( 1 x 10 ( 9 ) bacilli in 50 mL saline ) was instilled once a week for six consecutive weeks , and mitomycin C ( 30 mg in 50 mL saline ) was administered once a week for one month ( weeks 1 to 4 ) and thereafter once a month for a total of six months . Reported are the incidence of side effects in 165 patients and the recurrence rate of tumors in 308 patients after a follow-up period of twelve months . Drug-induced , or chemical cystitis was observed in 13 ( 16.7 % ) of 78 BCG-treated patients and in 12 ( 13.8 % ) of 87 MMC-treated patients . In the same groups bacterial cystitis occurred in 17 ( 21.8 % ) patients and in 16 ( 18.4 % ) patients , respectively . In the BCG-treated group ( N = 148 ) , 44 ( 29.8 % ) had recurrent tumors , while in the MMC-treated group ( N = 160 ) , 40 ( 25.0 % ) had a recurrence . The recurrence rate for BCG-treated patients was 0.33 ; the recurrence rate for MMC-treated patients was 0.29 ( P = 0.560 , not significant ) . These preliminary data demonstrated no statistically significant difference between the two arms with regard to toxicity and recurrence of tumors .

BCG ( RIVM )

mitomycin intravesical therapy

incidence of side effects

recurrence rate of tumors

Drug-induced , or chemical cystitis

bacterial cystitis

recurrent tumors

bladder cancer


Dysthymia : a randomized study of cognitive marital therapy and antidepressants . Preliminary data from a randomized study of the effectiveness of combined marital therapy and antidepressant medication in the treatment of dysthymic married women is presented . The study compares doxepin with placebo , and a marital therapy designed to enhance intimacy through facilitating self-disclosure between spouses with a more supportive and educational therapeutic approach . After ten weeks of combined treatment , the dysthymic women show statistically significant improvement on all the depression measures as well as on the intimacy scale . A trend is developing for greater reduction of depressive symptomatology in the group treated with self-disclosure . The evidence appears to suggest the possibility that the presence of a patient 's husband as a supportive figure may of itself be a potent therapeutic manoeuvre in the treatment of dysthymic women .

combined marital therapy

and antidepressant medication

doxepin with

placebo

, and a

marital therapy

depression measures

intimacy scale .

depressive symptomatology

treatment of dysthymic

women

dysthymic

women


Pulsatile insulin delivery is more efficient than continuous infusion in modulating islet cell function in normal subjects and patients with type 1 diabetes . The respective modulating effects of continuous and intermittent insulin delivery on pancreatic islet cell function were studied in seven normal men and nine insulin-dependent ( type 1 ) diabetic patients . In the normal men , saline or continuous ( 0.8 mU kg-1 min-1 ) or pulsatile ( 5.2 mU kg-1 min-1 , with a switching on/off length of 2/11 min ) human insulin were delivered on different days and in random order . Despite hyperinsulinemia , blood glucose was kept close to its basal value by the glucose clamp technique . The diabetic patients also were infused in random order and on different days with either saline or a smaller amount of insulin delivered continuously ( 0.15 mU kg-1 min-1 ) or in a pulsatile manner ( 0.97 mU kg-1 min-1 for 2 min , followed by 11 min during which no insulin was infused ) . In all experiments , 5 g arginine were given iv as a bolus dose 30 min before the end of the study , and plasma C-peptide and glucagon levels were determined to assess islet cell function . In the normal men , insulin administration resulted in a significant decline of basal plasma glucagon and C-peptide levels and in a clear-cut decrease in the arginine-induced glucagon response . These effects of insulin were significantly more marked when insulin was delivered in a pulsatile rather than a continuous manner . In the insulin-dependent diabetic patients , the lower dose of insulin infused continuously did not alter the basal or arginine-stimulated glucagon response . In contrast , when the same amount of insulin was delivered intermittently , arginine-induced glucagon release was greatly reduced . Thus , these data support the concept that insulin per se is a potent physiological modulator of islet A- and B-cell function . Furthermore , they suggest that these effects of insulin are reinforced when the hormone is administered in an intermittent manner in an attempt to reproduce the pulsatile physiological release of insulin .

Pulsatile insulin delivery

continuous infusion

saline

continuous

pulsatile

human insulin

saline

in a

pulsatile

manner

arginine

Pulsatile insulin delivery

plasma C-peptide

glucagon levels

basal plasma glucagon

C-peptide levels

arginine-induced glucagon response

arginine-induced glucagon release


[ Prevention of thromboembolism in patients operated on for hip prosthesis ] . The latest research into the prevention of peri- and postoperative thromboembolic disease has found orthopaedic surgery patients to be most at risk . As the genesis of deep venous thrombosis ( DVT ) is due to haemodynamic , hemorheologic and parietal factors , various prophylactic measures have been considered in the past , measures which have not proved able to provide satisfactory protection in orthopaedics . The results obtained with Defibrotide in a random and controlled clinical study versus calcium heparin involving 211 patients of both sexes candidates to receive total hip arthroplasty and presenting at least one major thromboembolic risk factor are reported . The patients were assigned at random to one of the following treatments : 1 ) Defibrotide at a dose of 400 mg b.i.d . i.v . in 50 ml phleboclysis in 5 minutes ( n = 108 ) ; 2 ) calcium heparin at a dose of 5000 IU t.i.d . subcutaneously ( n = 103 ) . The treatment began the day before operation and continued on average up to the eighth day for the Defibrotide group . With the control group it continued until discharge ( usually on the 15th day ) and at home for about three weeks until the completion of the physiotherapy cycle . In the 108 patients treated with Defibrotide only one case of DVT was reported and in none of these patients were symptoms or signs of pulmonary embolism encountered . In the group treated with calcium heparin 2 cases of clinically and radiologically diagnosed pulmonary embolism and 4 cases of DVT were observed . Although the differences were not statistically significant , the tendency favours Defibrotide . Statistically significant ( p less than 0.01 ) was the difference in postoperative bleeding evaluated with particular attention in patients of advanced age . Further , in the Defibrotide group , scarring was considered excellent in 96 % of cases while in the heparin group scarring was excellent in 85 % ( p less than 0.05 ) . To conclude , the sure clinical effectiveness , tolerance , handiness and lack of interference with clotting functions make Defibrotide a really useful drug for the prevention of thromboembolic episodes in patients undergoing major orthopaedic surgery .

Defibrotide

calcium heparin

Defibrotide at a dose of 400 mg b.i.d

i.v

Defibrotide

Defibrotide

Defibrotide

thromboembolism

thromboembolic

DVT

pulmonary embolism

DVT

postoperative bleeding evaluated

scarring

scarring

thromboembolic


Analgesic efficacy of piroxicam in the treatment of postoperative pain . Two randomized , double-blind , single-dose studies were conducted to assess the analgesic efficacy and safety of piroxicam for the treatment of moderate or severe postoperative pain . Study 1 evaluated the analgesic efficacy of piroxicam 20 mg compared with that of codeine sulfate 60 mg and placebo . A final patient population of 149 subjects rated pain intensity and pain relief at one half hour and one hour following treatment and then hourly for six hours , with a global assessment made at the completion of 24 hours . Piroxicam 20 mg was significantly more efficacious than placebo for all analgesic variables , including the sum of the pain intensity differences ( SPID ) , total pain relief ( TOTAL ) , percent SPID , duration of effect , and time to remedication . Codeine 60 mg was significantly superior to placebo for percent SPID and some hourly measures . Piroxicam 20 mg was significantly more effective than codeine 60 mg for percent SPID and a few hourly measures including time to remedication . Study 2 assessed the efficacy of piroxicam 20 mg or 40 mg compared with aspirin 648 mg and placebo . Sixty patients rated their pain intensity and relief hourly for 12 hours and at 24 hours after administration of study medication . Both doses of piroxicam were significantly more effective than placebo from Hours 2 to 12 for pain intensity difference ( PID ) and relief scores , as well as for SPID and TOTAL . Aspirin was significantly more effective than placebo from Hours 2 to 8 for relief and Hours 2 to 10 for PID as well as SPID and TOTAL . Piroxicam 40 mg was significantly more effective than aspirin 648 mg for SPID , TOTAL , and hourly measures beginning with Hour 6 through Hour 12 . Piroxicam 20 mg was significantly better than aspirin for a few hourly measures : Hours 7 to 9 for relief and Hour 7 for PID . In addition , effects of piroxicam 20 mg had a significantly longer duration than aspirin . Similarly , piroxicam 20 mg had a significantly longer time to remedication compared with aspirin and placebo . The results of these studies provide evidence in support of the longer duration of analgesic efficacy of piroxicam compared with codeine or aspirin in patients with postoperative pain .

piroxicam

piroxicam

piroxicam

codeine sulfate

placebo

Piroxicam

placebo

Codeine

Piroxicam

codeine

piroxicam

aspirin

piroxicam

Piroxicam

aspirin

Piroxicam

aspirin

piroxicam

aspirin

piroxicam

codeine

aspirin

Analgesic efficacy

postoperative pain .

analgesic efficacy and safety

moderate or severe postoperative pain .

pain intensity and pain relief

efficacious

percent SPID

duration of effect

time to remedication

percent SPID

percent SPID

efficacy

pain intensity and relief

effective

SPID

TOTAL

effective

relief

PID

SPID

TOTAL

effective

SPID

TOTAL

hourly measures

PID

longer duration

longer time to remedication

duration of analgesic efficacy

postoperative pain


Transcutaneous electrical nerve stimulation after thoracotomy . Pain relief and peak expiratory flow rate -- a trial of transcutaneous electrical nerve stimulation . Forty patients scheduled to undergo thoracotomy were randomly allocated to receive either transcutaneous electrical nerve stimulation with intramuscular papaveretum ( 20 patients ) or intramuscular papaveretum alone ( 20 patients ) for postoperative pain relief . Total intramuscular analgesic requirements in the first 24 hours , time to satisfactory transfer to oral analgesia , antiemetic requirements and length of stay in hospital postoperatively were noted . Peak expiratory flow rate was compared pre- and postoperatively in the two groups . Use of nerve stimulation did not significantly alter the requirements for analgesia although there was a reduction in postoperative nausea and vomiting in the nerve stimulation group . There was no difference between the two groups with respect to changes in peak expiratory flow rate .

Pain relief

peak expiratory flow rate -- a

antiemetic requirements

postoperative nausea and vomiting

peak expiratory flow rate

Forty

thoracotomy


Antihypertensive efficacy of cetamolol : a dose-titrated study . This double-blind , placebo-controlled , randomized multicenter study evaluated the antihypertensive efficacy and safety of cetamolol hydrochloride in 108 patients diagnosed as having mild to moderate hypertension . After a placebo lead-in period , patients received either cetamolol 5-10-15 mg/d ( low dose ) , cetamolol 15-25-50 mg/d ( high dose ) , or placebo , once daily for four weeks . Patients began at the lowest dose and were titrated to higher doses based on the first two assessments of diastolic blood pressure and heart rate , which were conducted each week after double-blind treatment was dispensed . After four weeks of treatment 82.4 % , 81.3 % , and 93.3 % of the low-dose group , high-dose group , and placebo group , respectively , were titrated to the maximum dose level . After four weeks of treatment and 24 hours since the patient 's last dose , both cetamolol groups showed a significantly greater ( P less than or equal to .05 ) reduction in supine systolic/diastolic blood pressure ( -18.1 +/- 2.3/-9.2 +/- 1.5 mm Hg [ low dose ] and -17.3 +/- 2.3/-8.3 +/- 1.6 mm Hg [ high dose ] ) than the placebo group ( -9.9 +/- 2.5/-3.5 +/- 1.7 mm Hg ) . In general , the changes in standing ( stabilized ) systolic and diastolic blood pressure were similar to those seen in supine measurements . Significantly more patients receiving cetamolol than those receiving placebo showed a " good response " ( a decrease in diastolic blood pressure of 10 mm Hg or more or measuring less than 90 mm Hg with a decrease of at least 4 mm Hg ) . ( ABSTRACT TRUNCATED AT 250 WORDS )

cetamolol

placebo-controlled

cetamolol hydrochloride

placebo

cetamolol

cetamolol

placebo

placebo

cetamolol

Antihypertensive efficacy

antihypertensive efficacy and safety

diastolic blood pressure

heart rate


Need for insulin therapy in type II diabetes mellitus . A randomized trial . To identify patients with type II diabetes mellitus for whom insulin therapy is most beneficial , we conducted a randomized controlled trial in the general medicine clinic of a university hospital . Asymptomatic , obese , insulin-treated patients were given diet and diabetes education and , in half of these patients , insulin therapy was withdrawn . Over six months , patients developing hyperglycemic symptoms or acetonemia were counted as study failures . Failure criteria developed in 13 of 25 insulin-withdrawal patients , at a median of four weeks after withdrawal , compared with two of 24 control subjects . Elevated stimulated glucose levels predicted the need for insulin therapy . Hyperglycemia worsened in insulin-withdrawal patients who did not meet study failure criteria , but it improved in control patients . Study patients were insulin deficient as shown by low baseline C peptide values ( 0.43 +/- 0.05 nmol/L ) . The prompt metabolic decompensation precipitated by insulin withdrawal suggests that insulin-deficient patients may benefit from insulin therapy and may need it to prevent symptomatic hyperglycemia .

insulin therapy

insulin therapy

diet and diabetes education

insulin therapy

hyperglycemic symptoms or acetonemia

Failure criteria

Elevated stimulated glucose levels

Hyperglycemia

baseline C peptide values

symptomatic hyperglycemia

type II diabetes mellitus

type II diabetes mellitus

obese

25 insulin-withdrawal


[ Domperidone in the treatment of irritable colon . A placebo-controlled double-blind study ] .

[ Domperidone

placebo-controlled

irritable colon

irritable colon .


Nitrous oxide does not increase the incidence of nausea and vomiting after isoflurane anesthesia . A total of 110 patients undergoing elective abdominal hysterectomy were anesthetized in random order with either isoflurane in nitrous oxide and oxygen or isoflurane in air and oxygen . Fentanyl was used as an adjunct to isoflurane in all patients , 0.05 mg every 45 min . No difference was found between the two anesthetic techniques in the incidence of nausea , vomiting , or both during the first 24 hr after operation . The overall incidence was 62 and 67 % for air-O2 and N2O-O2 groups , respectively . Patients who had had nausea or vomiting after previous anesthetics had nausea or vomiting significantly more frequently than patients who did not . It is concluded that nitrous oxide does not contribute to the occurrence of nausea or vomiting after isoflurane anesthesia for gynecologic laparotomies .

Nitrous oxide

Fentanyl

nitrous oxide

incidence

nausea or vomiting

nausea or vomiting

nausea or vomiting

110 patients

all patients


Outpatient management of asthma with regular nebulized beta agonists : comparison of bitolterol mesylate and isoproterenol . Nebulized bitolterol solution and isoproterenol solution were compared when used on a regular basis , 2.5 mg three times a day for 1 month by patients with chronic asthma . In this multicenter , double-blind trial ; 130 nonsteroid-dependent patients were randomized to receive one of the two treatments concomitantly with their regular asthma medications . On study days , at the beginning of the study and after 2 and 4 weeks , treatments were given in the office or laboratory and patients were monitored with pulmonary function tests for eight hours . Both medications induced rapid bronchodilation that had a longer duration after bitolterol . The incidence of tremor was similar with the two medications . Tachycardia and palpitations were more frequent following isoproterenol . Bitolterol has a much longer duration of action and should be considered as a suitable bronchodilator for regular nebulizer treatment of chronic asthma .

bitolterol mesylate

isoproterenol

Nebulized bitolterol solution

isoproterenol solution

Bitolterol

pulmonary function tests

rapid bronchodilation

duration

incidence of tremor

Tachycardia and palpitations

duration of action

Outpatient management of asthma

patients with chronic asthma .


Prognostic significance and beneficial effect of diltiazem on the incidence of early recurrent ischemia after non-Q-wave myocardial infarction : results from the Multicenter Diltiazem Reinfarction Study . Of 576 patients with non-Q-wave acute myocardial infarction enrolled in the Diltiazem Reinfarction Study , 246 ( 43 % ) had 1 or more episodes of angina at rest or with minimal effort during 10.5 days of treatment with either diltiazem ( 90 mg every 6 hours ) or placebo . Reinfarction ( 12.2 % vs 3.6 % , p less than 0.0001 ) or death ( 6.1 % vs 1.5 % , p = 0.003 ) was more likely to occur within 2 weeks of randomization in patients with postinfarction angina than in those without angina . Based on serial electrocardiographic data , 115 of the 246 patients with angina had transient ST-T changes and 131 did not . Comparison of the 14-day event rates in these 2 groups showed that the 115 patients with electrocardiographic evidence of ischemia had a higher frequency of reinfarction ( 20 % vs 5.3 % , p less than 0.001 ) , more extensive damage as assessed by peak MB-creatine kinase levels ( 91 +/- 76 vs 37 +/- 19 IU/liter , p = 0.059 [ Wilcoxon rank sum ] ) and a higher mortality rate ( 11.3 % vs 1.5 % , p = 0.001 ) . Angina associated with transient ST-T changes occurred in 70 of the 289 patients in the placebo group but in only 45 of the 287 patients in the diltiazem group -- a 28 % reduction in cumulative life-table incidence ( p = 0.0103 [ 2-tail , log rank ] ; 95 % confidence interval , 9.3 to 53.8 % ) . It is concluded that patients with early postinfarction angina are at increased risk of reinfarction and death , and angina associated with transient electrocardiographic changes identified a very high risk subset . This subset appeared to have a larger area of viable but jeopardized myocardium and benefited from prophylactic therapy with diltiazem .

diltiazem

diltiazem

placebo

placebo

diltiazem

Prognostic significance

beneficial effect

early recurrent ischemia

Reinfarction

death

ST-T

reinfarction

extensive damage

peak MB-creatine kinase levels

higher mortality rate

Angina

transient ST-T changes

cumulative life-table incidence

risk of

reinfarction

death

changes

viable

jeopardized myocardium

early recurrent ischemia

non-Q-wave acute myocardial infarction

early postinfarction angina