Review of the Multicenter Trial Committee report : a prospective , randomized study on the prophylaxis of postoperative deep venous thrombosis . The etiology of postoperative deep venous thrombosis ( DVT ) is thought to be due to a combination of factors including stasis , a hypercoagulable state and venous endothelial damage . Methods of prophylaxis are directed toward correcting one or more of these pathologic events . Methods counteracting more than one of these factors can be expected to be even more effective . The combination of dihydroergotamine ( DHE ) and heparin was anticipated to minimize stasis and the hypercoagulable state respectively . Based upon current experimental evidence and current theory , an additional benefit might include minimizing venous endothelial injury by controlling venomotor tone . A prospective , randomized , double-blind , multicenter trial was designed and performed in the United States evaluating the prophylactic efficacy of DHE 0.5 mg plus heparin 5000 U , DHE 0.5 mg plus heparin 2500 U , heparin 5000 U , and DHE 0.5 mg versus placebo . General surgical patients including those undergoing noncardiac thoracic and pelvic operations who were identified at moderate to high risk for postop DVT were included . Study medications were injected subcutaneously two hours preoperatively and every 12 hours postoperatively for 5-7 days or until the 125I-fibrinogen-uptake test ( RFUT ) became positive . Eight hundred and eighty eight patients were entered into this trial and 744 ( 85 % ) completed the study . Results showed a statistically significant benefit from DHE/Hep 5000 compared to placebo ( p less than 0.01 ) and compared to other active agents ( p less than 0.05 ) . None of the other active agents showed a statistically significant prophylactic benefit . ( ABSTRACT TRUNCATED AT 250 WORDS )

dihydroergotamine ( DHE )

heparin

DHE

heparin

DHE

heparin

heparin

DHE

placebo .

DHE/Hep

placebo

United States

Eight hundred and eighty eight


[ The chemotherapy of advanced breast cancer . A report on the first 600 cases in a cooperative programme to carry out a systematic study ( 1974-1977 ) ( author 's transl ) ] . The authors explain the objectives and the structure of a programme evolved for the methodic study of advanced breast cancers which they have worked out and carried out in cooperation with the departments of medicine in eight French anticancer centres . They analyse the initial phases , which correspond to the three first years of work . They give the state of the results that have been obtained in 603 patients using three protocols for treatment . These consisted of the administration in interrupted doses of chemotherapy which consisted of vincristine associated for the one part with cyclophosphamide and 5-fluoro-uracil and on the other hand with doxorubicine or/and with methotrexate . From this study there emerged the value of combined therapy using doxorubicine as much because of the frequency with which results better than 50 % were obtained ( in a randomised trial ) as by their quality , which was made clear in an important series of 240 cases . They point out the conditions required to initiate the place of such a scheme in all complex therapy which aims as much at palliation as at cure , and point out how important it is to be methodical in the application of chemotherapy in order to ensure its development as an anticancer therapy .

chemotherapy

chemotherapy

vincristine

cyclophosphamide

doxorubicine

methotrexate .

doxorubicine

chemotherapy

quality

advanced breast cancer .

600 cases

advanced breast cancers

in eight French anticancer centres

603 patients


Ascaris and growth rates : a randomized trial of treatment . Three hundred forty-one Tanzanian preschool children were randomly assigned to levamisole or placebo treatment given at three-month intervals . Weights and heights were measured at the tri-monthly treatment visits for a period of one year . Among the 273 children who were seen and weighed at the one-year follow-up visit , the rate of weight gain was 8 per cent greater for those receiving levamisole than for placebo-treated controls ( p = .06 ) . In 78 children known to be infected with Ascaris at baseline , the rate of weight gain was 21 per cent greater in children treated with levamisole than in those receiving placebo ( p = .03 ) . The rate of height gain was no different for treatment and placebo groups .

levamisole

placebo

levamisole

placebo-treated

levamisole

placebo

placebo

Weights and heights

rate of weight gain

rate of weight gain

rate of height gain

Three hundred forty-one

Tanzanian

preschool children

children


Rapid tightening of blood glucose control leads to transient deterioration of retinopathy in insulin dependent diabetes mellitus : the Oslo study . In a study of retinopathy during one year of tight blood glucose control 45 type I ( insulin dependent ) diabetics without proliferative retinopathy were randomised to receive either continuous subcutaneous insulin infusion , multiple insulin injections , or conventional insulin treatment ( controls ) . Near normoglycaemia was achieved with continuous infusion and multiple injections but not with conventional treatment . Blind evaluation of fluorescein angiograms performed three monthly showed progression of retinopathy in the control group , transient deterioration in the continuous infusion group , and no change in the multiple injection group . Half the patients receiving continuous infusion and multiple injections developed retinal cotton wool spots after three to six months . These changes regressed in all but four patients after 12 months . Control patients did not develop cotton wool spots . Patients who developed cotton wool spots are characterised by a larger decrement in glycosylated haemoglobin and blood glucose values , more frequent episodes of hypoglycaemia , a longer duration of diabetes , and more severe retinopathy at onset . A large and rapid fall in blood glucose concentration may promote transient deterioration of diabetic retinopathy .

insulin infusion

insulin injections

insulin treatment

retinopathy

fluorescein angiograms

progression of retinopathy

cotton wool spots .

glycosylated haemoglobin

blood glucose values

episodes of hypoglycaemia

duration of diabetes

retinopathy

blood glucose concentration

insulin dependent diabetes mellitus :


Protection of man from natural infection with influenza A2 Hong Kong virus by amantadine : a controlled field trial . Prophylactic administration of amantadine in doses of 100 mg. twice a day offered statistically significant protection against influenza A2 infection in a double-blind field trial involving 391 medical student volunteers during the influenza A2 Hong Kong epidemic in Helsinki in the winter of 1969 . Serologically verified influenza , as measured by complement fixation and/or haemagglutination inhibition , occurred in 27 out of 192 students in the amantadine group against 57 out of 199 in the placebo group , giving a protection rate of 52 % .

amantadine

amantadine

amantadine

placebo

Serologically verified influenza


The treatment of asthma in adults using sodium cromoglycate pressurized aerosol : a double-blind controlled trial . Sodium cromoglycate formulated as a pressurized aerosol ( 2 mg 4-times daily ) and placebo were compared in 31 adult asthmatic patients in a double-blind crossover trial lasting 12 weeks . Sodium cromoglycate was superior to placebo in improving breathlessness at rest ( p less than 0.001 ) , breathlessness on exertion ( p less than 0.05 ) and the quality of sleep ( p less than 0.001 ) , and also in improving the morning peak expiratory flow rate value ( p less than 0.05 ) . Both the patients ' ( p less than 0.05 ) and the clinicians ' ( p less than 0.01 ) treatment opinions , and their treatment preferences ( p less than 0.05 ) , favoured sodium cromoglycate . Moreover , usage of bronchodilators ( theophylline and aerosol beta-stimulants combined ) declined significantly ( p less than 0.001 ) during sodium cromoglycate treatment compared to placebo . No side-effects were reported . The results of this study show that sodium cromoglycate delivered by pressurized aerosol was significantly superior to placebo , not only in improving asthmatic symptoms , but also in reducing the amount of concomitant bronchodilator therapy required .

sodium cromoglycate

Sodium cromoglycate

placebo

Sodium cromoglycate

placebo

sodium cromoglycate .

sodium cromoglycate

placebo .

sodium cromoglycate

placebo

breathlessness at rest

breathlessness on exertion

quality of sleep

morning peak expiratory flow rate value

treatment preferences

side-effects

asthmatic symptoms

asthma

adults

adult

asthmatic


Effects of mild physical exercise on serum lipoproteins and metabolites of arachidonic acid : a controlled randomised trial in middle aged men . To study the effects of physical exercise on biochemical risk factors for ischaemic heart disease 31 healthy middle aged men undertook regular physical exercise for two months and 29 served as controls in a randomised trial . In the men taking regular exercise serum cholesterol concentrations increased 26 % more in the high density lipoprotein subfraction two ( HDL2 ) and decreased 31 % more in the subfraction three ( HDL3 ) and 9 % more in the low density lipoprotein fraction than in the control group . A tendency towards increased plasma 6-keto-prostaglandin F1 alpha concentration and decreased serum thromboxane B2 concentration was found during the period of regular exercise , but prostaglandin E2 concentrations remained unchanged . The increase in plasma 6-keto-prostaglandin F1 alpha concentration was associated with an increase in serum HDL2 cholesterol concentration in the group taking regular exercise . Our data suggest that mild regular physical exercise favourably influences cholesterol distribution in serum lipoproteins in healthy middle aged men and may have beneficial effects on circulating metabolites of arachidonic acid .

mild physical exercise

physical exercise

regular physical exercise

exercise

exercise .

mild regular physical exercise

serum lipoproteins

metabolites of arachidonic acid :

serum cholesterol concentrations

subfraction three ( HDL3 )

low density lipoprotein fraction

serum thromboxane B2 concentration

prostaglandin E2 concentrations

serum HDL2 cholesterol concentration

serum lipoproteins

middle aged men .

healthy

middle aged men

healthy

middle aged men


Experimental hyaline membrane disease in the premature monkey : effects of antenatal dexamethasone . A blind , randomized trial of antenatal glucocorticoid treatment was conducted using the premature monkey ( Macaca nemestrina ) model of hyaline membrane disease ( HMD ) . Twelve dams received dexamethasone ( 2 mg/dose ) 72 , 48 , and 24 h before abdominal delivery at 135 +/- 1 days of gestation . Twelve control animals received saline . Infants of dexamethasone-treated dams had significantly lower incidence and severity of HMD than did infants of control animals ( 50 versus 92 % , p less than 0.05 ) . Improvement with treatment was markedly greater for males than for females . Differences in volume-pressure behavior of the excised lungs included greater distensibility in the infants from dexamethasone-treated dams ( 20.6 +/- 7.1 ml/g dry lung versus 14.7 +/- 6.1 , p less than 0.05 ) and enhanced deflation stability with treatment . Accelerated production of surface active material ( SAM ) phospholipids in infants from dexamethasone-treated dams was indicated by increases in total lung phospholipid ( 84.5 +/- 8.1 mg/g dry lung versus 75.1 +/- 9.9 , p less than 0.025 ) , alveolar lavage fluid phospholipid ( 5.65 +/- 3.33 mg/g dry lung versus 3.01 +/- 1.84 , p less than 0.05 ) , and alveolar lavage fluid disaturated phosphatidylcholine ( DPC ) ( 2.47 +/- 1.84 mg/g dry lung versus 1.06 +/- 1.05 , p less than 0.05 ) . Incorporation of 14C-palmitate into lung lipid was not influenced by dexamethasone , but a significantly greater portion of the label appeared in the DPC fraction with treatment . Antenatal dexamethasone treatment was successful in reducing the incidence and severity of experimental HMD in this animal model ; the beneficial effects of treatment were associated with accelerated maturation of fetal pulmonary functions , including , but not limited to , synthetic metabolism of SAM phospholipid .

dexamethasone .

glucocorticoid

dexamethasone

saline .

dexamethasone-treated

dexamethasone-treated

dexamethasone-treated

dexamethasone

dexamethasone

incidence and severity of HMD

volume-pressure behavior

distensibility

deflation stability

total lung phospholipid

alveolar lavage fluid phospholipid

lung lipid

fetal pulmonary functions

the premature monkey :

Twelve dams

Twelve control animals


EORTC protocols in prostatic cancer . An interim report . Two parallel prospective randomized studies have been undertaken by the EORTC Urological Group in previously untreated patients with prostatic cancer in order to compare low dose Stilboestrol versus Cyproterone acetate versus Medroxyprogesterone acetate in the first trial , and Stilboestrol versus Estracyt in the second trial . Although the follow up is still short , no superiority of the other drugs over Stilboestrol had appeared so far with regard to either objective response or significant side effects apart from gynaecomastia . In the third trial , patients with advanced disease no longer responsive to hormonal treatment were randomized to either Adriamycin or Procarbazine . Toxicity and early death were particularly frequent in Procarbazine treated patients , whereas most patients progressed in both treatment groups .

Stilboestrol

Cyproterone acetate

Medroxyprogesterone acetate

Stilboestrol

Estracyt

Stilboestrol

Adriamycin

Procarbazine .

Procarbazine

side effects

gynaecomastia

Toxicity and early death

prostatic cancer .


A controlled study of psychiatric hospital versus community treatment - the effect on relatives . One hundred and twenty patients presenting at Macquarie Hospital for admission were randomly allocated into two groups . The control group patients received standard hospital care and follow-up . The project group patients were not admitted if this could be avoided ; instead they were taken back to the community by the project team who provided them and their relatives with comprehensive , assertive and prolonged follow-up treatment backed by a 24-hour crisis service . The majority ( 63 % ) of the project group had no admission during the 10 month study period . Initially , the burden on the relatives of the project group was higher , but by one month it was somewhat lower and by four months it was significantly lower than the burden on the control group relatives . Relatives of the project group patients were significantly more satisfied with the treatment than control group relatives . It is clearly feasible to treat most psychiatric patients in the community without increasing the burden on their relatives .

psychiatric hospital

community treatment

standard hospital care and follow-up .

back to the community

follow-up treatment

effect on relatives

burden on the relatives

satisfied

burden on their relatives .

One hundred and twenty

psychiatric patients


Changes in the fatty acid composition of the plasma lipid esters during lipid-lowering treatment with diet , clofibrate and niceritrol . Reduction of the proportion of linoleate by clofibrate but not by niceritrol . The fatty acid composition of the plasma lipid esters has been studied during lipid-lowering treatment of 95 patients with atherosclerotic disease . During the first two months of the trial only a diet was prescribed . During the ensuing two months either clofibrate or niceritrol , a nicotinic acid ester , was added in a randomized order . During the last two months the second drug was added . The combined treatment with diet , clofibrate and niceritrol caused highly significant serum lipid reductions . The fatty acid composition in the plasma lipid esters was determined in samples from each trial period to measure the degree of dietary adherence . During dietary treatment the relative content of saturated and monounsaturated fatty acids secreased and the polyunsaturated fatty acids increased with an increasing ratio between pulyunsaturated and saturated fatty acids ( P/S ratio ) in the cholesterol esters and triglycerides . Only minor changes were seen in the phospholipids . The changes caused by the diet were partly reversed by clofibrate while niceritrol did not cause any major changes of the fatty acid composition . Clofibrate treatment coincided with increasing amounts of monounsaturated fatty acids , especially oleate ( 18 : 1 ) , in the cholesterol esters , triglycerides and phospholipids while there were significant reductions of the content of linoleic ( 18 : 2 ) acid in both the cholesterol esters and triglycerides . The 18 : 2/18 : 1 ratio decreased significantly in all the lipid esters analyzed . However , the P/S ratio was not significantly affected , partly because the relative content of saturated fatty acids also tended to decrease during clofibrate treatment . It is concluded that addition of clofibrate treatment to patients who are on a diet enriched with polyunsaturated fats is associated with a change from polyunsaturated to monounsaturated fatty acids in the plasma lipid esters but does not significantly effect the ratio between polyunsaturated and saturated fatty acids . The fatty acid changes caused by clofibrate treatment and counteracted by an increased amount of polyunsaturated fat in the diet .

diet

clofibrate

niceritrol .

clofibrate

niceritrol

diet

clofibrate

niceritrol

diet

clofibrate

niceritrol

Clofibrate

clofibrate

diet .

linoleate

serum lipid

polyunsaturated fatty acids

phospholipids .

fatty acid composition .

monounsaturated fatty acids

oleate

triglycerides and phospholipids

content of linoleic ( 18 : 2 ) acid

P/S ratio

saturated fatty acids

acid changes


The efficacy of prophylactic ondansetron , droperidol , perphenazine , and metoclopramide in the prevention of nausea and vomiting after major gynecologic surgery . The prophylactic antiemetic efficacy of intravenous ( i.v . ) ondansetron , droperidol , perphenazine , and metoclopramide was evaluated in a prospective , double-blind study of 360 ASA physical status I-III patients undergoing total abdominal hysterectomy ( TAH ) . Subjects were randomized to receive i.v. , one of ondansetron 4 mg , droperidol 1.25 mg , perphenazine 5 mg , metoclopramide 10 mg , or placebo prior to induction of anesthesia . Hypotension immediately after administration of metoclopramide was observed in two patients and four patients given ondansetron developed profound systolic hypotension at induction of anesthesia . Twenty-two percent of patients receiving droperidol became sedated . Postoperatively , patients developing severe nausea , retching , or vomiting , defined as severe emetic sequelae ( SES ) , were deemed to have failed antiemetic prophylaxis and received antiemetic rescue . A significantly larger number of patients who received i.v . ondansetron ( 63 % ) , droperidol ( 76 % ) , and perphenazine ( 70 % ) were free of SES when compared to placebo ( 43 % ) ; P < 0.05 . Metoclopramide was ineffective . Although ondansetron , droperidol , and perphenazine were effective in providing antiemetic prophylaxis , only i.v . perphenazine was free of side effects . Hence , we conclude that perphenazine is the best choice for antiemetic prophylaxis after TAH .

ondansetron

droperidol

perphenazine

metoclopramide

ondansetron

droperidol

perphenazine

metoclopramide

ondansetron

droperidol

perphenazine

metoclopramide

placebo

metoclopramide

Hypotension

severe nausea , retching , or vomiting

severe emetic sequelae ( SES )

SES

effective

side effects .


Effects of individualized breast cancer risk counseling : a randomized trial . BACKGROUND Studies have shown that a majority of women with a family history of breast cancer have exaggerated perceptions of their own risk of this disease and experience excessive anxiety . In response to the need to communicate more accurate risk information to these women , specialized programs for breast cancer risk counseling have been initiated in medical centers across the United States . PURPOSE Our purpose was 1 ) to evaluate the impact of a standardized protocol for individualized breast cancer risk counseling on comprehension of personal risk among first-degree relatives of index breast cancer patients and 2 ) to identify women most and least likely to benefit from such counseling . METHODS This study is a prospective randomized trial comparing individualized breast cancer risk counseling to general health counseling ( control ) . We studied 200 women aged 35 years and older who had a family history of breast cancer in a first-degree relative . Women with a personal history of cancer were excluded . Risk comprehension was assessed as the concordance between perceived " subjective " lifetime breast cancer risk and estimated " objective " lifetime risk . RESULTS The results of logistic regression analysis showed that women who received risk counseling were significantly more likely to improve their risk comprehension , compared with women in the control condition ( odds ratio [ OR ] = 3.5 ; 95 % confidence interval [ CI ] = 1.3-9.5 ; P = .01 ) . However , in both groups , about two thirds of women continued to overestimate their lifetime risks substantially following counseling . Examination of subjects by treatment interaction effects indicated that risk counseling did not produce improved comprehension among the large proportion of women who had high levels of anxious preoccupation with breast cancer at base line ( P = .02 ) . In addition , white women were less likely to benefit than African-American women ( OR = 0.34 ; 95 % CI = 0.11-0.99 ; P = .05 ) . CONCLUSION Efforts to counsel women about their breast cancer risks are not likely to be effective unless their breast cancer anxieties are also addressed . IMPLICATIONS Attention to the psychological aspects of breast cancer risk will be critical in the development of risk-counseling programs that incorporate testing for the recently cloned breast cancer susceptibility gene , BRCA1 ( and BRCA2 when that gene has also been cloned ) .

general health counseling ( control ) .

risk counseling

risk counseling

risk-counseling programs

comprehension of personal risk

Risk comprehension

risk comprehension

lifetime risks

comprehension

women

aged 35 years and older

Women

personal history of cancer


[ Double-blind placebo-controlled study of the effectiveness and tolerability of 10 and 30 mg ketorolac tromethamine suppositories in post-cholecystectomy pain ] . OBJECTIVE To evaluate the efficacy and tolerability of ketorolac tromethamine 10 mg and 30 mg suppositories in comparison to placebo , after single dose administration in patients suffering from post-operative pain after cholecystectomy . DESIGN Double-blind , randomized , controlled study . SETTING Anaesthesia Service . PATIENTS 99 patients with severe pain following surgery . INTERVENTIONS Cholecystectomy . MEASUREMENTS AND MAIN RESULTS The analgesia activity of ketorolac tromethamine 10 mg and 30 mg suppositories were evaluated after single dose administration by assessing pain intensity and pain relief using a 4 point scale ( VRS ) . At the end of the treatment period overall assessment of safety and efficacy were recorded by physician and patient . The results show that in both active groups after 30 ' and until 4 hours , pain intensity decreased significantly with respect to the baseline . However a statistically significant difference between groups of p < 0.02 , p < 0.01 and p < 0.05 was found in favour of the 30 mg dose respectively at 30 ' , 6 and 8 hours after administration . All the patients treated with placebo suppositories required another rescue analgesic drug and withdrew from the trial . Three patients complained adverse events not related to treatment : two on placebo and one on ketorolac 10 mg . The systemic and local tolerability of the drug was good . CONCLUSIONS This study shows that ketorolac 30 mg suppositories are effective in clinical conditions , such as after surgery , in which pain control must be achieved within the shortest time interval and maintained or improved by means of a single route of administration .

ketorolac tromethamine

ketorolac tromethamine

placebo

ketorolac tromethamine

placebo

ketorolac

effectiveness

tolerability

efficacy

tolerability

pain intensity and pain relief

4 point scale ( VRS )

safety

efficacy

pain intensity

rescue analgesic drug

adverse events

systemic and local tolerability


Efficacy of intramuscular oxytetracycline as a dry cow treatment for Staphylococcus aureus mastitis . To determine the efficacy of intramuscular oxytetracycline as a supplemental dry cow treatment for Staphylococcus aureus mastitis , 37 Holstein cows were randomly assigned to two treatment groups : intracisternal infusion with a commercial preparation of cephapirin benzathine at drying off ( 20 cows ) and infusion with cephapirin benzathine at drying off and intramuscular oxytetracycline at 11 mg/kg once daily on d 7 , 8 , 9 , and 10 after drying off ( 17 cows ) . Milk samples collected 7 , 14 , 30 , and 60 d after calving were plated for bacterial isolation within 24 h after collection and after 24 to 72 h of storage at -20 degrees C. Quarters were defined as infected if S. aureus was isolated from the fresh and frozen cultures from any one sample collected before drying off . An infected quarter was defined as cured if S. aureus was not isolated from the fresh or frozen culture from milk samples obtained following calving . The rate of cure by 30 d after calving for systemic oxytetracycline ( in combination with cephapirin treatment ) was 29.4 % for infected quarters and 29.4 % for infected cows , compared with 27.5 and 25.0 % , respectively , for the cephapirin treatment only . Results including the culture at 60 d after calving were 21.2 and 22.5 % , respectively , for combination therapy and cephapirin therapy only . Systemic oxytetracycline , in combination with intramammary dry cow treatment , did not improve the rate of cure for S. aureus mastitis .

oxytetracycline

oxytetracycline

cephapirin benzathine

cephapirin benzathine

oxytetracycline

oxytetracycline

cephapirin

cephapirin

cephapirin

oxytetracycline

rate of cure

rate of cure

Holstein cows


Epidemiology of stroke . Importance of preventive pharmacological strategies in elderly patients and associated costs . Stroke is a major cause of death and disability in developed countries . The incidence of stroke increases exponentially with age , yet , traditionally , many medical practitioners have been reluctant to treat hypertension in older patients . Since 1991 , the results of 3 major trials -- the British Medical Research Council ( MRC ) trial of treatment in older adults , the Swedish Trial in Old Patients with Hypertension ( STOP-Hypertension ) and the Systolic Hypertension in the Elderly Program ( SHEP ) -- have conclusively established the benefits of treating older patients ( > 60 years ) with both diastolic and isolated systolic hypertension . International guidelines for the management of hypertension -- including the Fifth Report of the Joint National Committee , the 1993 report of the World Health Organization and the International Society of Hypertension and the second report of the British Hypertension Society Working Party -- have all been modified to reflect the emerging evidence concerning the benefits of treating older patients . Cost-effectiveness data are similarly in accord with giving high priority to the treatment of older individuals with hypertension .

preventive pharmacological strategies

Cost-effectiveness data

elderly patients

older patients

Old Patients with Hypertension

older individuals with hypertension .


Measurement of transfer factor during constant exhalation . BACKGROUND Transfer factor of the lung for carbon monoxide ( TLCO ) was measured by a new method based on analysis of the ratio of the concentrations of carbon monoxide to an inert gas ( methane ) relative to lung volume during a constant exhalation . Since this new technique is based solely upon exhalation , anomalies associated with inspiration and breath holding do not affect results . Additionally , because prolonged breath holding is not required , measurements can readily be made in dyspnoeic patients . METHODS Exhalation TLCO ( TLCO , ex ) was compared with the standard ( Jones and Meade ) 10 second breath holding TLCO ( TLCO , bh ) in 100 consecutive patients . Patients did not practise the exhalation manoeuvre prior to testing . RESULTS The comparative results were very close ; mean difference ( bias ) +/- standard deviation ( precision ) was 0.05 ( 0.84 ) mmol/min/kPa . The relation was equally strong in patients with severe pulmonary disease ; for patients with FEV1 < 1.51 the mean difference was 0.21 ( 0.80 ) mmol/min/kPa . CONCLUSIONS Since the results were essentially identical between the techniques , it seems that comparable pathophysiological factors affect TLCO during breath holding and constant exhalation . Constant exhalation may therefore be a useful alternative to the breath holding technique for clinical measurement of TLCO .

TLCO ( TLCO

standard ( Jones and Meade )

TLCO ( TLCO

Exhalation TLCO ( TLCO , ex )

relation


The effect of two types of teacher training on implementation of Smart Choices : a tobacco prevention curriculum . This study examined the implementation phase of a four-year research project to test the effectiveness of strategies to increase diffusion of Smart Choices , a school-based tobacco prevention program . The impact on curriculum implementation of two approaches to teacher training are compared . School districts were randomly assigned to a live workshop training or video training condition . The outcome of the evaluation was teachers ' implementation of Smart Choices . Results show a lower proportion of video-trained teachers implemented the curriculum , but overall completeness and fidelity of implementation for those teachers who did teach the curriculum were comparable for the two groups . Video-trained teachers , however , were less likely to use brainstorming and student presentations/role plays , two of the methods prescribed by the curriculum . Implications of the results for teacher training are discussed .

teacher training

live workshop training

video training condition

video-trained

Video-trained

effectiveness

diffusion of Smart Choices

completeness

and

fidelity of implementation

School districts


Necessary but not sufficient : the effect of screening and feedback on outcomes of primary care patients with untreated anxiety . OBJECTIVE To consider the impact on primary care patient outcomes of using both a screener to determine elevated anxiety levels among patients with previously undetected anxiety and a physician intervention to inform physicians of their patients ' conditions . DESIGN Participating physicians were randomized to either the demonstration or the control arm , and patients were assigned to a study arm based on the randomization of their physicians . The patients were followed for change in outcome measures during the five-month study period . SETTING A mixed-model health maintenance organization serving approximately 110,000 enrollees in central Colorado . PATIENTS/PARTICIPANTS 573 patients who had unrecognized and untreated anxiety identified from the approximately 8,000 patients who completed the waiting room screening questionnaire . INTERVENTIONS A physician intervention served the dual function of 1 ) providing an educational demonstration of anxiety in the primary care setting and 2 ) providing a reporting system for summarizing the anxiety symptom levels and functioning status of the patients enrolled in the study . MEASUREMENTS AND MAIN RESULTS Patient outcomes were measured as changes in global anxiety scores , functioning and well-being , and patients ' reports of global improvements . CONCLUSIONS The findings indicate that this method of reporting symptoms and functioning status to primary care physicians did not significantly change patient outcomes . Improvement in outcomes appeared to be more closely associated with the patient 's severity of psychological distress .

screening

feedback

demonstration

physician intervention

global anxiety scores

functioning and well-being


Double-blind randomized evaluation of intercostal nerve blocks as an adjuvant to subarachnoid administered morphine for post-thoracotomy analgesia . BACKGROUND AND OBJECTIVES Thoracotomy is associated with pain and compromised pulmonary function . Intercostal nerve blocks ( INB ) and subarachnoid morphine ( SM ) act on different portions of the pain pathway . Each is effective for post-thoracotomy pain relief . The combination of these two modalities in relieving post-thoracotomy pain and improving postoperative pulmonary function has not been investigated . METHODS In a double-blind study , 20 patients undergoing lateral thoracotomy for lung resection were randomized to receive 0.5 mg SM preoperatively and INB with bupivacaine ( INB+ ) prior to wound closure or 0.5 mg SM with INB using saline ( INB- ) . Visual analog scale pain scores at rest , with cough , and with movement of the ipsilateral arm , forced expiratory volume in 1 second ( FEV1 ) , and forced vital capacity ( FVC ) were measured at 4 , 24 , 48 , and 72 hours after the operation . Opioid use was measured during the initial 24 hours after the operation . RESULTS At 4 hours , the INB+ group demonstrated better FEV1 ( 56.6 % vs. 40.4 % of baseline , P < .05 ) and FVC values ( 54.6 % vs. 39.6 % of baseline , P < .05 ) and less resting and cough pain ( P < .05 ) . However , FEV1 continued to decline in the INB+ group at 24 hours to lower than the INB- group although pain scores were similar beyond 4 hours . Opioid usage during the first 24 hours was similar ( INB- , 16.7 mg vs. INB+ , 13.2 mg , P = .7 ) . CONCLUSIONS Although postoperative INB provided modest improvements in pain and pulmonary function when used as an adjuvant to 0.5 mg SM for post-thoracotomy analgesia , the benefits were transient . The authors do not recommend adding INB for patients undergoing lateral thoracotomy who receive 0.5 mg SM .

intercostal nerve blocks

morphine

Intercostal nerve blocks ( INB )

subarachnoid morphine ( SM )

SM

INB with bupivacaine ( INB+ )

SM

INB using saline ( INB- )

INB+

INB+

INB-

INB-

INB+

INB

SM

INB

SM

pain

post-thoracotomy pain

postoperative pulmonary function

Visual analog scale pain scores

forced vital capacity ( FVC )

Opioid use

FVC

pain scores

Opioid usage


The effects of sevoflurane and isoflurane on recovery from outpatient surgery . This randomized , open-label study compared the investigational inhalational anesthetic sevoflurane with isoflurane in 47 healthy women undergoing elective ambulatory surgery . The women were randomized to receive either sevoflurane or isoflurane in 60 % nitrous oxide-oxygen . Induction with thiopental 3-6 mg/kg was followed by vecuronium 0.1 mg/kg and fentanyl 0-200 micrograms . Duration of anesthesia , time to emergence , orientation , length of stay in the surgical unit , and hospital discharge were recorded . The emergence , length of stay , and discharge times after discontinuation of sevoflurane were 9.7 +/- 0.7 , 120.6 +/- 8.0 , and 244 +/- 15 minutes , respectively , and for isoflurane were 11.9 +/- 1.4 , 106.8 +/- 7.1 , and 282 +/- 24 minutes , respectively ( NS ) . The isoflurane group had a higher frequency of postoperative cough . At the end of surgery , the sevoflurane group received a deeper level of anesthesia ( minimum alveolar concentration 1.5 vs 1.3 ) , however , these patients were oriented earlier ( 13.6 +/- 1.1 min vs 17.0 +/- 1.5 min isoflurane ; p = 0.02 ) after discontinuation of anesthesia , although this difference is of little clinical significance .

sevoflurane

isoflurane

sevoflurane

isoflurane

sevoflurane

isoflurane

thiopental

vecuronium

fentanyl

sevoflurane

isoflurane

Duration of anesthesia

time to emergence

orientation

length of stay in the surgical unit

emergence ,

length of stay

, and

discharge times

postoperative cough

anesthesia

outpatient surgery .

healthy

women

undergoing elective ambulatory surgery

women


Fluoroscopic functional evaluation of bileaflet prostheses : effect of different intraoperative valve orientation . Fluoroscopy is a reliable , easy , and readily available technique to follow-up prosthesis functioning after heart valve surgery . The different orientation given to the prosthesis may represent a limitation of the technique accounting for unsatisfactory results in 10 % to 40 % of the cases . The aim of the study was to evaluate whether and to what extent different intraoperative valve orientation influence feasibility and accuracy of postoperative fluoroscopic evaluation of bileaflet prostheses . We prospectively evaluated 90 patients who had aortic , mitral , and/or tricuspid valve replacement with Sorin Bicarbon or CarboMedics bileaflet prostheses . Fifty percent of the patients in each group were randomly assigned to receive prostheses oriented in a perpendicular or a parallel position with respect to the ventricular septum . Fluoroscopic evaluation was considered appropriate when the prosthesis ' " tilting disk " projection was obtained . The valve 's hemodynamic performance was investigated through Doppler study . A proper fluoroscopic evaluation was rapidly ( 15 +/- 5 seconds ) achieved in all patients with the former orientation , whereas it was impossible to obtain it in 8 of 20 ( 40 % ) , 19 of 20 ( 95 % ) , and 4 of 5 ( 80 % ) of patients with the latter orientation . In the remaining patients extremely angulated , uneasy projection was often required to get a correct fluoroscopic image . The Doppler study showed a similarly favorable hemodynamic performance regardless of valve orientation . Prosthesis orientation crucially affects the rate of success of the fluoroscopic evaluation . The orientation perpendicular to the ventricular septum greatly facilitates the postoperative feasibility and accuracy of fluoroscopy , and it is not detrimental to the valve 's hemodynamic performance . This valve orientation may provide a better fluoroscopic window whenever a valve dysfunction is suspected .

bileaflet prostheses :

bileaflet prostheses .

prostheses

Prosthesis

feasibility

accuracy

hemodynamic performance

fluoroscopic evaluation

hemodynamic performance

feasibility

accuracy of fluoroscopy

valve 's hemodynamic performance .

fluoroscopic


The effect of tunnelling on epidural catheter migration . A prospective , randomised study of 82 patients having postoperative epidural analgesia was performed to determine whether the tunnelling of an epidural catheter influences its migration . Tunnelling of the catheter subcutaneously for a distance of 5 cm reduced the incidence of inward migration of 1 cm or more ( p < 0.01 ) compared to a standard method of fixation with a transparent adhesive dressing . This effect was more marked if the epidural catheter was sited in the thoracic rather than the lumbar area . Sixty two percent ( n = 26 ) of tunnelled catheters remained within 0.5 cm of their original position compared to 38 % ( n = 16 ) of non-tunnelled catheters , although this difference was not statistically significant . Outward catheter migration was not reduced by subcutaneous tunnelling .

tunnelling

tunnelling

Tunnelling

tunnelled catheters

non-tunnelled catheters

tunnelling .

migration .

incidence of inward migration

catheter migration


Effects of tryptophan depletion in drug-free adults with autistic disorder . BACKGROUND The primary objective of this study was to investigate the behavioral and biochemical responses to acute tryptophan depletion in drug-free adult patients with autistic disorder . METHODS Twenty drug-free adults with autistic disorder ( 16 men and 4 women ) ( mean [ +/- SD ] age , 30.5 +/- 8.5 years ) underwent short-term tryptophan depletion in a double-blind , placebo-controlled , randomized crossover design . Patients received a 24-hour , low-tryptophan diet followed the next morning by an amino acid drink . Behavioral ratings were obtained on the morning of the amino acid drink ( baseline ) and 180 , 300 , and 420 minutes after the drink . Plasma free and total tryptophan levels were obtained at baseline and 5 hours after the drink . The active and sham testing sessions were separated by 7 days . RESULTS Eleven ( 65 % ) of the 17 patients who completed both test days showed a significant global worsening of behavioral symptoms with short-term tryptophan depletion , but none of the 17 patients showed any significant change in clinical status from baseline after sham depletion ( P = .001 ) . Tryptophan depletion led to a significant increase in behaviors such as whirling , flapping , pacing , banging and hitting self , rocking , and toe walking ( P < .05 ) . In addition , patients were significantly less calm and happy and more anxious . No significant change was observed in social relatedness or repetitive thoughts and behavior . Plasma total and free tryptophan levels were reduced 86 % and 69 % , respectively , 5 hours after the tryptophan-deficient amino acid drink . Patients who had a significant global exacerbation of symptoms had significantly higher baseline plasma total tryptophan levels ( P < .001 ) and Autism Behavior Checklist scores ( P = .005 ) than did patients who showed no significant change in symptoms after tryptophan depletion . CONCLUSIONS The results of this study are consistent with previous research that has implicated a dysregulation in serotonin function in some patients with autism . These data suggest that the short-term reduction of serotonin precursor availability may exacerbate some symptoms characteristic of autism in some patients . Continued investigation into the role of serotonin in the pathogenesis and treatment of autistic disorder is warranted .

tryptophan depletion

low-tryptophan diet

amino acid drink .

amino acid drink

Plasma free and total tryptophan levels

calm and happy

anxious .

Plasma total and free tryptophan levels

plasma total tryptophan levels

Autism Behavior Checklist scores

symptoms

drug-free

adults

autistic disorder

Twenty

drug-free adults with autistic disorder

16 men and 4 women

patients with autism .


A double-blind , placebo-controlled study of fluvoxamine in adults with autistic disorder . BACKGROUND Autistic disorder is characterized by a fundamental disturbance in social interaction , impairments in communication , and a markedly restricted repertoire of activities and interests . Abnormalities in the serotonin neurotransmitter system have been identified in some persons with autism . No consistently effective and safe drugs have been developed for treating the symptoms of autism . METHODS Thirty adults with autistic disorder completed a 12-week double-blind , placebo-controlled trial of the potent and selective serotonin uptake inhibitor fluvoxamine maleate . Behavioral ratings were obtained at baseline and after 4 , 8 , and 12 weeks of treatment . RESULTS Eight ( 53 % ) of 15 patients in the fluvoxamine-treated group were categorized as responders compared with none of 15 in the placebo group ( P = .001 ) . Fluvoxamine was superior to placebo in reducing repetitive thoughts and behavior ( P < .001 ) , maladaptive behavior ( P < .001 ) , and aggression ( P < .03 ) , and in improving some aspects of social relatedness ( P < .04 ) , especially language usage ( P < .008 ) . Treatment response was not correlated with age level of autistic behavior , or full-scale IQ . Other than mild sedation and nausea in a few patients , fluvoxamine was well tolerated . No dyskinesias , adverse cardiovascular events , or seizures occurred . CONCLUSIONS Fluvoxamine is more effective than placebo in the short-term treatment of the symptoms of autistic disorder in adults . Controlled studies of fluvoxamine and other potent and selective serotonin uptake inhibitors seem warranted in children and adolescents with autism .

placebo-controlled

fluvoxamine

placebo-controlled

fluvoxamine maleate .

fluvoxamine-treated

placebo

Fluvoxamine

placebo

fluvoxamine

Fluvoxamine

placebo

fluvoxamine

Behavioral ratings

repetitive thoughts and behavior

maladaptive behavior

aggression

social relatedness

language usage

mild sedation and nausea

adults with autistic disorder .

Thirty

adults

autistic disorder


Methodology of serial ECG classification using an adaptation of the NOVACODE for Q wave myocardial infarction in the Bypass Angioplasty Revascularization Investigation ( BARI ) . Serial electrocardiographic ( ECG ) changes are a critical component of the diagnostic algorithm for classification of myocardial ischemic events in large-scale clinical trials . This study describes a computerized serial ECG classification program developed at the St. Louis University Core ECG Laboratory for use in the Bypass Angioplasty Revascularization Investigation ( BARI ) trial , in which patients with multivessel coronary artery disease were randomized to receive either coronary artery bypass grafting or percutaneous transluminal coronary angioplasty . The St. Louis University program detects and codes serial changes in Q , ST , and T wave items according to Minnesota code ( MC ) criteria using a modified NOVACODE hierarchical classification system . Measurements using a seven-power calibrated coding loupe are used to generate the MC from a customized software program . Significant minor or major changes are detected by the serial comparison program and referred to a physician coder for verification . Serial comparison coding rules are used to adjust for weaknesses in the standard MC classification system resulting from instability at decision boundaries . Of 4,244 BARI randomized and registry study participants with follow-up ECGs received at the Core ECG Laboratory as of March 1995 , a grade 2 MC Q wave progression was noted in 568 participants ( 13.4 % ) using MC criteria alone , as compared with 367 ( 8.6 % ) after the St. Louis University coding rules were applied . The incidence of grade 1 MC Q wave progressions was 16.4 % ( 697/4,244 ) versus 6.1 % ( 259/4,244 ) when the St. Louis University program was applied . Intraobserver variability for grade 2 Q wave progression codes determined from a sample of 812 serial .

coronary artery bypass grafting


Analysis of prevention program effectiveness with clustered data using generalized estimating equations . Experimental studies of prevention programs often randomize clusters of individuals rather than individuals to treatment conditions . When the correlation among individuals within clusters is not accounted for in statistical analysis , the standard errors are biased , potentially resulting in misleading conclusions about the significance of treatment effects . This study demonstrates the generalized estimating equations ( GEE ) method , focusing specifically on the GEE-independent method , to control for within-cluster correlation in regression models with either continuous or binary outcomes . The GEE-independent method yields consistent and robust variance estimates . Data from project DARE , a youth substance abuse prevention program , are used for illustration .

GEE-independent

GEE-independent

prevention program

youth

substance abuse prevention program


Prevention of spinal anesthesia-induced hypotension in the elderly : comparison between preanesthetic administration of crystalloids , colloids , and no prehydration . The practice of routinely prehydrating patients by infusing a crystalloid or colloid solution ( up to 1.0 L/70 kg ) for prevention of spinal anesthesia-induced hypotension has been challenged recently , after several reports of failure to demonstrate its efficacy in young women . We compared the incidence and frequency of hypotension and vasopressor therapy after spinal anesthesia and no prehydration with crystalloid and colloid prehydration in elderly patients . Eighty-five ASA grade I or II patients ( aged 60-89 yr ) for elective total hip replacement were randomized to receive 500 mL crystalloid solution ( Hartmanns , n = 29 ) , 500 mL colloid ( Haemaccel , n = 28 ) , or no prehydration ( n = 28 ) over 10 min prior to spinal anesthesia . Hypotension was defined as a 30 % decrease from baseline systolic blood pressure ( BP ) or systolic < 90 mm Hg , and was treated with ephedrine 3-mg boluses . Although absolute systolic BP readings were significantly higher in the colloid group between 6 and 30 min ( P < 0.05 ) , the incidence of hypotension was not significantly different between the groups . The incidence of ephedrine use , incidence of nausea/vomiting , and median total dose of ephedrine were similar in all groups . We conclude that , in elderly patients undergoing elective procedures , withholding prehydration is not associated with any greater degree of hypotension or need for vasopressor therapy compared with crystalloid or colloid prehydration .

crystalloids

colloids

no prehydration .

crystalloid

colloid solution

no prehydration

crystalloid

colloid prehydration

crystalloid solution

colloid ( Haemaccel

no prehydration

colloid

crystalloid

colloid prehydration .

vasopressor therapy

Hypotension

systolic blood pressure

absolute systolic BP readings

incidence of hypotension

incidence of ephedrine use

incidence of nausea/vomiting

median total dose of ephedrine

hypotension

need for vasopressor therapy

the elderly

elderly patients

Eighty-five

elderly patients

undergoing elective procedures


[ Antazoline/tetryzoline eyedrops in comparison with levocabastine eyedrops in acute allergic conjunctivitis ] . BACKGROUND Allergic conjunctivitis is one of the most frequent allergic diseases of the anterior eye segment . METHODS This multicentre , clinical trial was an investigation to compare the antiallergic efficacy , local tolerance and safety of Antazolin/Tetryzolin eye drops and Levocabastine eye drops . 69 patients were treated over a 2 weeks course of therapy . The subjective and objective ocular symptoms were documented over the treatment period . RESULTS Both eye drops reduced subjective and objective ocular symptoms effective . The difference between the treatments ( p = 0.0395 ) was the faster onset of action of Antazolin/Tetryzolin 30 minutes after administration of the first drop of trial medication . CONCLUSION A fast and effective onset of action is of high clinical relevance . Therefore the benefits of using Antazolin/Tetryzolin eye drops was clearly outweigh .

Antazoline/tetryzoline

levocabastine

Antazolin/Tetryzolin

Levocabastine

Antazolin/Tetryzolin

Antazolin/Tetryzolin

onset of action

acute allergic conjunctivitis ]

69 patients


Effect of treatment with paromomycin on endotoxemia in patients with alcoholic liver disease -- a double-blind , placebo-controlled trial . The results of experimental and clinical studies support the hypothesis that gut-derived endotoxins might be of relevance for the development and course of alcoholic liver disease . The aim of this study was to test the effect of a nonabsorbable , broad-spectrum antibiotic on endotoxemia in patients with alcoholic liver disease . Fifty patients with alcoholic liver disease ( 27 with cirrhosis , 23 without cirrhosis ) were randomly assigned to receive either paromomycin sulfate ( 3 x 1 g/day ) or placebo in a double-blind fashion for at least 3 weeks , and if possible 4 weeks . Endotoxin concentration , liver function tests , and other laboratory parameters were determined in weekly intervals . Endotoxin concentration was also determined in 15 healthy controls . Groups receiving paromomycin or placebo were similar for clinical and biological items collected initially . Mean initial endotoxin concentrations were significantly elevated in both groups ( mean +/- SEM ; paromomycin , 16.7 +/- 5.3 pg/ml ; placebo , 17.5 +/- 6.9 pg/ml ; healthy controls , 2.3 +/- 0.4 pg/ml ) . Although the mean endotoxin concentration was lower in the verum group after 1 week ( paromomycin , 8.0 +/- 1.9 pg/ml ; placebo , 14.6 +/- 3.5 pg/ml ; p > 0.05 ) , paromomycin treatment had no significant effect on endotoxin concentration or liver function tests during the 4-week period . The beneficial effect of paromomycin treatment on endotoxemia in cirrhotics reported in earlier studies could not be reproduced under the conditions of this trial in patients with alcoholic liver disease .

paromomycin

placebo-controlled

paromomycin sulfate

placebo

paromomycin

placebo

paromomycin

placebo

paromomycin

placebo

paromomycin

paromomycin

endotoxemia

endotoxemia

Endotoxin concentration

liver function tests

Endotoxin concentration

endotoxin concentrations

endotoxin concentration

endotoxin concentration

liver function tests

patients with alcoholic liver disease

patients with alcoholic liver disease .

Fifty

patients with alcoholic liver disease (

with cirrhosis ,

without cirrhosis )

healthy controls

patients with alcoholic liver disease .


Effect of indomethacin phonophoresis on the relief of temporomandibular joint pain . The pain-relieving effect of indomethacin phonophoresis on temporomandibular ( TMJ ) joint pain was evaluated in a double-blind , placebo-controlled clinical trial . Twenty subjects , who have TMJ pain , were included for this study and randomly assigned to either the experimental group ( n = 10 ) or the control group ( n = 10 ) . Each treatment consisted of the application of ultrasound massage ( 1.0 MHz , 0.8 to 1.5 W/cm2 continuous output ) for 15 minutes to the painful temporomandibular joint . As a conducting medium , 1 % indomethacin cream was used for the experimental group and placebo cream for the control group respectively . Pre- and post-treatment pain levels and pain sensitivity were assessed with visual analogue scales ( VAS ) and pressure pain threshold ( PPT ) . Mean data indicated that post-treatment VAS was significantly decreased and post-treatment PPT was significantly increased in the experimental group , not in the control group . The results of this study suggest that indomethacin phonophoresis provides significant pain relieving effect over the TMJ pain .

indomethacin phonophoresis

indomethacin phonophoresis

placebo-controlled

indomethacin

placebo

indomethacin phonophoresis

pain-relieving

pain levels

pain sensitivity

visual analogue scales ( VAS )

pressure pain threshold ( PPT )

post-treatment VAS

post-treatment PPT

pain

temporomandibular joint pain .

Twenty

subjects , who have TMJ pain


Systemic hemodynamic , neurohormonal , and renal effects of a steady-state infusion of human brain natriuretic peptide in patients with hemodynamically decompensated heart failure . BACKGROUND Human brain natriuretic peptide ( hBNP ) is a promising agent for the treatment of decompensated cardiac failure . However , the systemic hemodynamic , neurohormonal , and renal effects of hBNP have been incompletely studied in human heart failure . METHODS AND RESULTS The effects of a continuous 4-hour infusion of hBNP were determined in 16 decompensated heart failure patients in an invasive , randomized , double-blind , placebo-controlled study . Patients were evaluated during three 4-hour study periods : baseline , treatment ( placebo [ n = 4 ] versus hBNP 0.025 or 0.05 microgram/kg/min [ n = 12 ] ) , and post-treatment . Urinary volume losses were replaced hourly to separate the vasodilatory and diuretic effects of hBNP . Two patients in the hBNP group were excluded from the analysis because of adverse events . hBNP significantly ( P < .001 ) reduced right atrial pressure and pulmonary capillary wedge pressure by approximately 30 % and 40 % , respectively . hBNP also significantly lowered systemic vascular resistance from 1722 +/- 139 to 1101 +/- 83 dynes.s.cm-5 ( P < .05 ) . These unloading effects of hBNP produced a 28 % increase in cardiac index ( P < .05 ) with no change in heart rate . Compared to placebo , hBNP decreased plasma norepinephrine and aldosterone . Renal hemodynamics were unaffected by hBNP ; however , most patients were resistant to its natriuretic effect . CONCLUSIONS 1 ) The predominant hemodynamic effects of hBNP were a decrease in cardiac preload and systemic vascular resistance . 2 ) hBNP also improved cardiac output without increasing heart rate . 3 ) Plasma norepinephrine and aldosterone levels decreased during hBNP infusion . 4 ) hBNP is pharmacologically active and has potential in the therapy for decompensated heart failure .

human brain natriuretic peptide

hBNP

hBNP

placebo-controlled

placebo

hBNP

hBNP .

hBNP

hBNP

hBNP

hBNP

placebo

hBNP

hBNP ;

hBNP

hBNP

hBNP

hBNP

Systemic hemodynamic , neurohormonal

renal effects

systemic hemodynamic

neurohormonal

renal effects

adverse events .

systemic vascular resistance

cardiac index

heart rate .

natriuretic effect .

hemodynamic effects

cardiac output

heart rate .

decompensated heart failure patients


Salbutamol or mist in acute bronchiolitis . BACKGROUND The role of bronchodilators in the treatment of bronchiolitis remains controversial . METHODS A double-blind , placebo controlled trial was performed to evaluate the clinical response to nebulized salbutamol . One hundred and fifty-six infants aged between 7 weeks and 24 months who had had an episode of wheezing and other signs and symptoms of bronchiolitis were randomized to three groups as follows : ( i ) nebulized salbutamol was administered to 52 patients in group I at a dose of 0.15 mg/kg in 2 mL saline ; ( ii ) saline was nebulized to 52 patients in group II and ( iii ) in group III 52 patients received mist in a tent . All three groups were administered oxygen during the procedures . Treatment was repeated with the same agent after 30 min if the respiratory score was 5 or more . Respiratory rate , heart rate , oxygen saturation and presence of cyanosis , wheezing , retractions were recorded before and after each treatment . RESULTS The decrease in the respiratory score was 5.2 +/- 1.8 , 0.82 +/- 2.4 and 1.7 +/- 1.3 in group I , II and III , respectively . The decrease in group I was significantly higher than in the other groups . Heart rate was similar between groups . Oxygen saturation decreased in group I without reaching statistical significance . CONCLUSIONS Salbutamol was shown to be effective and safe in the treatment of acute bronchiolitis .

Salbutamol

mist

salbutamol

salbutamol

saline

saline

mist

oxygen

Salbutamol

respiratory score

Heart rate

Oxygen saturation

effective

safe

acute bronchiolitis .

One hundred and fifty-six


Inhaled fluticasone reduces sputum inflammatory indices in severe bronchiectasis . Although corticosteroid therapy might be clinically beneficial for bronchiectasis , very little is known of its effects on the inflammatory and infective markers in bronchiectasis . We have therefore performed a double-blind , placebo-controlled study to evaluate the effects of a 4-wk administration of inhaled fluticasone in bronchiectasis . Twenty-four patients ( 12 female ; mean age 51 yr ) were randomized into receiving either inhaled fluticasone ( 500 microgram twice daily ) via the Accuhaler device ( n = 12 ) or placebo . At each visit , spirometry , 24-h sputum volume , sputum leukocyte density , bacterial densities , and concentrations of interleukin ( IL ) -1beta , IL-8 , tumor necrosis factor-alpha ( TNF-alpha ) , and leukotriene B4 ( LTB4 ) were determined . There was a significant ( p < 0.05 ) decrease in sputum leukocyte density and IL-1beta , IL-8 , and LTB4 after fluticasone treatment . The fluticasone group had one and the placebo group three episodes of exacerbation . There were no significant changes in spirometry ( p > 0.05 ) or any reported adverse reactions in either group . The results of this study show that high-dose fluticasone is effective in reducing the sputum inflammatory indices in bronchiectasis . Large-scale and long-term studies are indicated to evaluate the effects of inhaled steroid therapy on the inflammatory components in bronchiectasis .

fluticasone

placebo-controlled

fluticasone

fluticasone

placebo .

fluticasone

fluticasone

placebo

sputum inflammatory indices

inflammatory and infective markers

leukotriene B4 ( LTB4 )

sputum leukocyte density

IL-1beta , IL-8

spirometry

adverse reactions

sputum inflammatory indices

severe bronchiectasis .

Twenty-four

mean age 51 yr

bronchiectasis .


Amonafide : An active agent in the treatment of previously untreated advanced breast cancer -- a cancer and leukemia group B study ( CALGB 8642 ) . Amonafide is a new imide derivative of naphthalic acid . The drug had demonstrated significant activity in preclinical studies and some activity in Phase I trials . The drug is extensively metabolized and detected in plasma and urine . Its toxicity has previously been correlated to the formation of an active metabolite , N-acetyl-amonafide . Amonafide was chosen for inclusion in the Cancer and Leukemia Group B ( CALGB ) master metastatic breast cancer protocol . CALGB 8642 randomizes previously untreated metastatic breast cancer patients either to one of several Phase II agents given for up to four cycles and then followed by standard cyclophosphamide-doxorubicin-5-fluorouracil , or to immediate treatment with standard cyclophosphamide-doxorubicin-5-fluorouracil . The end point of CALGB 8642 is to assess the difference in survival , toxicity , and overall response when limited exposure to Phase II agents precedes standard chemotherapy . This report deals only with amonafide as a Phase II agent . Comparisons with the cyclophosphamide-doxorubicin-5-fluorouracil arm will not be addressed . Patients had to have histologically documented measurable breast cancer and a performance status of 0-1 . Patients could not have had prior chemotherapy for metastatic disease . Prior adjuvant chemotherapy was permitted . Patients could not have visceral crisis . Amonafide was given at 300 mg/m2/day i.v . for 5 days , and repeated at 21-day intervals for a maximum of four cycles . Escalation and reduction in dose was mandated dependent on hematotoxicity or lack thereof . Toxicity was primarily hematological and bimodal : 32 % had grade 3 or 4 leukopenia and 24 % had grade 3 or 4 thrombocytopenia ; 22 % had no leukopenia and 44 % had no thrombocytopenia . The response rate was 18 % , including one complete response . When response was analyzed by hematological toxicity , there was a 35.7 % response if patients had leukopenia grade 3/4 ( versus 8.3 % , P = 0.08 ) . There was a 50 % response if patients had thrombocytopenia grade 3/4 ( versus 7.1 % , P = < 0.01 ) . We conclude that amonafide is somewhat active in previously untreated breast cancer patients . There may be a steep dose-response curve , based on the significant correlation between myelosuppression and response . Rates of responses in patients adequately dosed ( i.e. , with significant hematotoxicity ) with amonafide ranged from 35 to 50 % . Further studies will incorporate individualized dosing based on pretreatment acetylator phenotyping .

Amonafide :

Amonafide

Amonafide

amonafide

Amonafide

amonafide

survival

toxicity

overall response

Toxicity

leukopenia

thrombocytopenia

leukopenia

thrombocytopenia

response rate

hematological toxicity

leukopenia

thrombocytopenia

Rates of responses