Absolute bioavailability of a new high dose methylprednisolone tablet formulation . This was a single-blind , single-dose , randomized crossover study to determine the absolute bioavailability of Medrol , a new high dose ( 100 mg ) methylprednisolone tablet product , by comparing it with 100 mg methylprednisolone from an intravenous formulation , Solu-Medrol . Fourteen healthy , non-smoking , Caucasian male volunteers took part . On treatment days volunteers remained recumbent for 4 hours after drug administration , with food and fluid intake standardized over this period . Serial blood samples were drawn over a 14-hour period after drug administration . Plasma methylprednisolone concentrations were determined by high performance liquid chromatography . The geometric means of AUCi.v . and AUCtablet were 4,049 and 3,334 ng.h/ml , respectively . The absolute bioavailability of the tablet product was 82 % , which is in agreement with published data for other oral dosage forms of methylprednisolone . Volunteers displayed the expected rise in peripheral blood neutrophil count , but no other clinically relevant changes in hematology or clinical chemistry were observed . No adverse drug reactions were recorded . It is concluded that the tablet product can be used as a substitute for parenteral methylprednisolone in situations requiring high-dose therapy .

methylprednisolone

Medrol

methylprednisolone

methylprednisolone

Solu-Medrol

methylprednisolone

methylprednisolone

methylprednisolone

peripheral blood neutrophil count

Fourteen

male


Immune response in healthy volunteers vaccinated with BCG plus killed leishmanial promastigotes : antibody responses to mycobacterial and leishmanial antigens . Antibody ( IgG ) responses to mycobacterial ( BCG ; PPD ; Mycobacterium leprae soluble antigen , MLSA ) and leishmanial ( Leishmania mexicana LV4 ) antigens were measured in 208 initially PPD and leishmanin skin-test negative volunteers divided into four vaccine groups as follows : 68 received BCG plus killed promastigotes ( group A ) , 47 received BCG alone ( group B ) , 47 received killed promastigotes alone ( group C ) , and 46 formed the diluent control ( placebo , group D ) . Three vaccine doses were administered at 8-12 week intervals . Vaccinees were bled immediately prior to each vaccination , and again at 3- and 12-month follow-up . Skin tests were performed prevaccination , and again at the 3- and 12-month follow-up . Anti-BCG , anti-PPD and anti-MLSA IgG levels increased significantly in groups A and B receiving BCG . The presence of leishmanial antigen ( with BCG ) in the inoculum suppressed the IgG response to Mycobacterium tuberculosis/Mycobacterium bovis-related ( PPD and BCG ) , but not M. leprae-related ( MLSA ) -related , antigens . A small but significant increase ( relative to prevaccination level ) in response to MLSA , but not to BCG or PPD was observed in the non-BCG-vaccinated groups . The background level of response to mycobacterial and leishmanial antigens was higher in the Venezuelan vaccinees than in non-endemic ( British ) volunteers . Responses to leishmanial antigen were not enhanced in the two vaccine groups receiving killed promastigotes ( with/without BCG ) compared with the BCG alone and placebo groups . Instead , all vaccine groups showed a pattern of response consistent with either ( i ) a response to the skin-test antigen or , more likely , ( ii ) seasonal endemic exposure to leishmanial antigen . Interestingly , this endemic response to leishmanial antigen was enhanced in the vaccine groups receiving BCG , despite the fact that group B received no leishmanial antigen in the vaccine inoculum . When prevaccination IgG levels ( mean + 3 standard deviations ) were used to determine a negative cut-off , a low percentage ( < 38 % ) of vaccinees converted to responder status for either anti-mycobacterial or anti-leishmanial responses , and those who did would be classified as 'low-responder ' status compared with titres observed in severe forms of disease . Hence , although there was evidence for a background endemic response to both leishmanial and mycobacterial antigens , there was no evidence that vaccination per se led to a potentially disease exacerbatory level of TH2-associated antibody response especially with respect to the anti-leishmanial response . ( ABSTRACT TRUNCATED AT 400 WORDS )

BCG plus

BCG plus killed promastigotes

BCG alone

promastigotes alone

diluent control

Immune response

Antibody ( IgG ) responses

Skin tests

leishmanial antigen

Venezuelan vaccinees


A comparison of the systemic bioactivity of inhaled budesonide and fluticasone propionate in normal subjects . 1 . The aim of this study was to compare the systemic bioactivity of low and high doses of inhaled budesonide and fluticasone propionate given by respective dry powder inhaler devices . 2 . A randomised , single blind cross-over design was used in nine healthy subjects who were given 800 micrograms day-1 of budesonide Turbohaler ( B800 ) for 1 week , followed by 1 week of 1600 micrograms day-1 ( B1600 ) , or fluticasone Diskhaler 750 micrograms day-1 ( F750 ) for 1 week followed by 1 week of 1500 micrograms day-1 ( F1500 ) . There was a 1 week washout between treatments with fluticasone or budesonide . A twice daily dosing regime was used and mouth-rinsing was employed to reduce gut bioavailability as well as to obviate local adverse effects . 3 . Parameters of hypothalmic-pituitary adrenal ( HPA ) axis activity and bone metabolism were measured at baseline ( B0/F0 ) , at the end of each week of treatment and after the 1 week washout ( F0 or B0 ) . 4 . Both fluticasone and budesonide significantly ( P < 0.05 ) attenuated the post tetracosactrin serum cortisol at low and high doses whilst early morning cortisol was unchanged . No dose-response effect was observed with either drug , and there was no significant difference between treatment with fluticasone or budesonide . 5 . Neither budesonide nor fluticasone produced significant suppression of plasma osteocalcin , although the higher doses of both drugs significantly reduced fasting urinary calcium levels . ( ABSTRACT TRUNCATED AT 250 WORDS )

budesonide

fluticasone propionate

inhaled budesonide

fluticasone propionate

fluticasone

budesonide

fluticasone

budesonide

bone metabolism

post tetracosactrin serum cortisol

dose-response effect

difference

normal subjects .

nine healthy subjects


Long-stay versus short-stay hospital treatment of children suffering from severe protein-energy malnutrition . OBJECTIVE To contrast early discharge versus attempted full nutritional rehabilitation in hospital of children suffering from severe protein-energy malnutrition ( PEM ) . DESIGN Field experiment , two-way analysis of variance with one between group ( short- versus long-stay ) and one repeated measures factor ( admission , then 12 , 18 , 24 , 30 and 36 months post-admission ) . Covariates introduced . SETTING Primary health care , Kingston , Jamaica . SUBJECTS n = 81 ; mean age 11 months ; 79 contribute longitudinal data ; 44 every measurement . INTERVENTIONS When concurrent illnesses had been treated and normal feeding re-established ( weight gain 5 g/kg.day-1 ) , subjects were randomly allocated to short-stay ( SS ) or long-stay ( LS ) group . LS retained in hospital for full nutritional rehabilitation mean 40 days ) . SS discharged immediately ( mean 18 days ) for standard Health Service care at home for 6 months plus high-energy supplement ( 3.31 MJ with 20.6 g protein daily ) for first 3 months . After discharge LS received 6 months home care , but without supplementation . RESULTS Significant advantages for LS group on NCHS weight & length for age at discharge , and at 12 , 18 , 24 and for length also 30 months ( P < 0.05 to P < 0.001 ) . Weight advantage peaked at 12 and 18 months , length later at 18 and 24 months . CONCLUSIONS Contrary to earlier reports , full nutritional rehabilitation can be achieved in hospital for children suffering from PEM . Although in the long-term both groups move towards expected levels in their home community , a significant advantage maintained for approximately 2 years is developmentally advantageous during the critical time after weaning .

Long-stay

short-stay hospital treatment

early discharge

short-

long-stay

short-stay ( SS )

long-stay ( LS )

LS

SS

LS

children

PEM

11 months


Changes in beta-carotene levels by long-term administration of natural beta-carotene derived from Dunaliella bardawil in humans . Long-term administration of a beta-carotene preparation derived from Dunaliella bardawil , a beta-carotene-rich algae , was studied in healthy young male volunteers . The daily administration of 60 mg of the beta-carotene preparation ( 30 mg of all-trans beta-carotene and 30 mg of 9-cis beta-carotene ) was performed and beta-carotene concentrations were determined in the plasma , red blood cells ( RBC ) , platelets ( PLT ) , and mononuclear cells ( MN ) . The all-trans beta-carotene level increased four- , two- , and threefold the baseline in plasma , PLT , and MN , respectively . Basal levels of 9-cis beta-carotene in plasma , PLT , and MN were low and found as one-tenth , one-fifth , and one-fifth of all-trans beta-carotene , which increased three- , two- , and 1.5-fold the baseline , respectively . Plasma and RBC alpha-tocopherol levels were not changed by the intake of beta-carotene . No side effects or toxicities were documented in any of the subjects during the administration period . In conclusion , the bioavailability of beta-carotene derived from Dunaliella bardawil was preferential for all-trans beta-carotene , although a small amount of the 9-cis form was detected in the plasma and blood cells .

natural beta-carotene

beta-carotene preparation

beta-carotene-rich algae

60 mg of the beta-carotene preparation

plasma

red blood cells ( RBC )

platelets ( PLT ) ,

mononuclear cells ( MN )

all-trans beta-carotene level

plasma

PLT

MN

Plasma and RBC alpha-tocopherol levels

No side effects or toxicities

humans


Peritonsillar infiltration with bupivacaine for paediatric tonsillectomy . In a double-blind study forty-two children scheduled for elective adenotonsillectomy were randomized to receive peritonsillar infiltration , following induction of anaesthesia , with either 0.25 % plain bupivacaine or 0.9 % saline , 0.5 ml/kg to a maximum of 10 ml . The children were assessed on awakening , and then 10 minutes , 1 hour , 4 hours and 24 hours later . On each occasion the observer gave the child a pain score from 1 ( no pain ) to 5 ( severe pain ) . The scores on awakening and after 10 minutes were significantly lower in the bupivacaine group ( P < 0.05 , Mann-Whitney U test ) . Thereafter there was no difference between the groups . The authors conclude that peritonsillar infiltration with bupivacaine is only moderately useful as analgesia for children having tonsillectomy .

bupivacaine

infiltration

bupivacaine

bupivacaine

awakening

pain score

scores on awakening

paediatric tonsillectomy

forty-two

children

children

children

tonsillectomy


Angiotensin converting enzyme inhibition does not affect the response to exogenous angiotensin II in the human forearm . Suppression of endogenous levels of angiotensin II by angiotensin converting enzyme inhibition , may result in up-regulation of vascular AT1 receptors . We have evaluated the effects of orally administered enalapril on angiotensin II induced vasoconstriction in the human forearm . Subjects received in random order , enalapril ( 20 mg ) or matched placebo daily for 2 weeks . Forearm blood flow response to increasing doses of angiotensin II was measured using venous occlusion plethysmography at the beginning of the study and at the end of each 2 week treatment period . Treatment with enalapril significantly reduced plasma angiotensin II levels and supine blood pressure compared with placebo . The percentage reductions in forearm blood flow in the infused arm , in response to the maximum dose of angiotensin II ( 50,000 fmol min-1 ) were 48.1 +/- 3.6 % at baseline , 57.5 +/- 3.6 % on placebo and 54.5 +/- 4.2 % on enalapril . The differences were not significantly different . This demonstrates that suppression of plasma angiotensin II for a 14 day period does not enhance the response to exogenous intra-arterial angiotensin II in the human forearm of healthy salt replete subjects .

enalapril

enalapril

placebo

Forearm blood flow

plasma angiotensin II levels

supine blood pressure

reductions in forearm blood flow

healthy salt replete


Aspirin in coronary heart disease . The Coronary Drug Project Research Group .

Aspirin

coronary heart disease .

coronary heart disease .


Naltrexone in young autistic children : a double-blind , placebo-controlled crossover study . OBJECTIVE This study evaluated the efficacy and safety of naltrexone , an opiate blocker , in the treatment of autism . METHOD Thirteen children with autistic disorder , aged 3.4 to 8.3 years ( mean 5.4 ) , were studied in home , school , and outpatient laboratory . Naltrexone , 1.0 mg/kg , was given daily in a randomized , double-blind , placebo-controlled crossover design . Dependent measures included parent and teacher Clinical Global Impressions ( CGI ) , Conners Rating Scales , and Naltrexone Side-Effects ( SE ) Rating Scale ; laboratory CGI , movement actometer readings , and a 10-second interval recording system analysis of on-task , communication initiations , disruptive behavior , and self-stimulation . RESULTS Eight of 13 subjects improved in two or more settings . Changes in parent measures ( CGI , Conners Impulsivity-Hyperactivity Factor , and SE-Restlessness ) and Teacher CGI achieved statistical significance . Teacher SE-Restlessness and initiation of communication in the clinic showed a trend toward improvement . Actometer readings improved in two children who were very active at baseline . Adverse side effects were behavioral , mild , and transient . Administering the bitter tablet was a challenge . CONCLUSIONS Naltrexone offers promise as an agent for modest improvement of behavior and social communication in young children with autism . Parent and teacher measures can be useful in outpatient trials to evaluate change .

Naltrexone

placebo-controlled

naltrexone

Naltrexone , 1.0 mg/kg

placebo-controlled crossover design

communication initiations

disruptive behavior ,

and

self-stimulation

Naltrexone

efficacy and safety

Clinical Global Impressions ( CGI )

Conners Rating Scales

laboratory CGI

movement actometer readings

communication initiations

disruptive behavior

self-stimulation

parent measures ( CGI

SE-Restlessness

Teacher CGI

Teacher SE-Restlessness

initiation of communication

Actometer readings

Adverse side effects

social communication

young

autistic children

autism .

Thirteen

autistic disorder

aged 3.4 to 8.3 years

young children

autism


Evaluation of an intervention to change benzodiazepine-prescribing behavior in a prepaid group practice setting . To determine the effect of two levels of educational intervention on benzodiazepine-prescribing behavior in an elderly population in a controlled prepaid group practice ( PPGP ) setting , we designed a prospective controlled trial , with six-month follow-up . Our setting was a 270,000 member group-model PPGP in Colorado , from 1990 to 1991 . Participants included 91 physicians , 62 men and 29 women ; median age was 38.7 years . Group 1 received a one-on-one educational presentation by a clinical pharmacist , written educational materials , a brief follow-up visit , and feedback with recommendations . Group 2 received only a face-to-face presentation , given to departmental groups , as well as the same written educational materials used in group 1 . Controls received no intervention . Our primary outcome measure was the benzodiazepine " on/off " status of the elderly PPGP members . The secondary outcome measure was the median change ( preintervention minus postintervention ) in a standardized amount of benzodiazepines prescribed per physician . Logistic regression analysis failed to show a significant effect on postintervention benzodiazepine on/off status between study groups , when controlling for preintervention on/off status , PPGP-member age , PPGP-member gender , and all possible interactions . Analysis of variance failed to demonstrate an effect of either intervention on the median change in standardized amount of benzodiazepines prescribed per physician , with groups 1 , 2 , and controls yielding values of -278 ( range : -4,137 , 2,844 ) , -330 ( -1,531 , 1,358 ) , and -541 ( range : -3,716 , 2,185 ) , respectively . We conclude that strategies effective in changing physician prescribing behavior in other settings may not be effective in a PPGP setting with benzodiazepines in the elderly as the target for change .

no intervention .

benzodiazepine on/off status


Warfarin versus aspirin for prevention of thromboembolism in atrial fibrillation : Stroke Prevention in Atrial Fibrillation II Study . Warfarin is an established treatment for prevention of ischaemic stroke in patients with atrial fibrillation , but the value of this agent relative to aspirin in unclear . In the first Stroke Prevention in Atrial Fibrillation ( SPAF-I ) study , direct comparison of warfarin with aspirin was limited by the small number of thromboembolic events . SPAF-II aims to address this issue and also to assess the differential effects of the two treatments according to age . We compared warfarin ( prothrombin time ratio 1.3-1.8 , international normalised ratio 2.0-4.5 ) with aspirin 325 mg daily for prevention of ischaemic stroke and systemic embolism ( primary events ) in two parallel randomised trials involving 715 patients aged 75 years or less and 385 patients older than 75 ; we sought reductions in the absolute rate of primary events by warfarin compared with aspirin of 2 % per year and 4 % per year , respectively . In the younger patients , warfarin decreased the absolute rate of primary events by 0.7 % per year ( 95 % CI-0.4 to 1.7 ) . The primary event rate per year was 1.3 % with warfarin and 1.9 % with aspirin ( relative risk [ RR ] 0.67 , p = 0.24 ) . The absolute rate of primary events in low-risk younger patients ( without hypertension , recent heart failure , or previous thromboembolism ) on aspirin was 0.5 % per year ( 95 % CI 0.1 to 1.9 ) . Among older patients , warfarin decreased the absolute rate of primary events by 1.2 % per year ( 95 % CI-1.7 to 4.1 ) . The primary event rate per year was 3.6 % with warfarin and 4.8 % with aspirin ( RR 0.73 , p = 0.39 ) . In this older group , the rate of all stroke with residual deficit ( ischaemic or haemorrhagic ) was 4.3 % per year with aspirin and 4.6 % per year with warfarin ( RR 1.1 ) . Warfarin may be more effective than aspirin for prevention of ischaemic stroke in patients with atrial fibrillation , but the absolute reduction in stroke rate by warfarin is small . Younger patients without risk factors had a low rate of stroke when treated with aspirin . In older patients the rate of stroke ( ischaemic and haemorrhagic ) was substantial , irrespective of which agent was given . Patient age and the inherent risk of thromboembolism should be considered in the choice of antithrombotic prophylaxis for patients with atrial fibrillation .

Warfarin

aspirin

Warfarin

warfarin

aspirin

warfarin

aspirin 325 mg daily

warfarin

aspirin

warfarin

warfarin

aspirin

aspirin

warfarin

warfarin

aspirin

thromboembolism

ischaemic stroke

systemic embolism

absolute rate of primary events

primary event rate per year

ischaemic stroke

rate of stroke

atrial fibrillation

75 years or less

older than 75


Exposure reduced agoraphobia but not panic , and cognitive therapy reduced panic but not agoraphobia . Earlier studies showed that cognitive therapy has anti-panic effects and exposure has anti-agoraphobic effects while other studies suggest that agoraphobia is a secondary complication of panic disorder . It was therefore hypothesized that cognitive therapy not only reduces panic but also agoraphobia and that it potentiates the effects of exposure in vivo . Two groups of 12 severe agoraphobics were treated with 4 sessions of cognitive therapy followed by 8 sessions of cognitive therapy combined with in vivo exposure . The other 12 received 4 sessions of 'associative therapy ' , a presumably inert treatment that controls for therapist attention , followed by 8 sessions of in vivo exposure that was framed in common behavioral terms . The initial cognitive therapy produced a significant reduction in panic frequency , while associative therapy did not affect panic . Neither cognitive therapy alone , nor associate therapy alone significantly reduced depression , state or trait anxiety , self-rated agoraphobia or behavioral avoidance . After adding exposure however , these parameters were clearly and significantly reduced . Cognitive therapy did not potentiate exposure effects . The results are discussed .

cognitive therapy

cognitive therapy

cognitive therapy

cognitive therapy

'associative therapy

cognitive therapy

associate therapy

Cognitive therapy

panic frequency

depression

state or trait anxiety

self-rated agoraphobia

behavioral avoidance

Two groups of

severe agoraphobics were treated


[ Postlaparoscopic pain syndrome . Results of a prospective , randomized study ] . The so-called post-laparoscopic algesia is a specific impairment of about 63 % of the patients who undergo laparoscopic surgical operations . This impairment takes the form of mild to moderate shoulder pain . Eliminating the causes of pain has a clear advantage over symptomatic treatment using analgetics , a fact worth a good consideration especially with the post-operative sojourn at the hospital becoming shorter and shorter . In a prospective controlled study , involving 42 patients subdivided into four groups namely , higher or lower insufflation pressures , chemically inert insufflation gas and control groups ; the use of analgetics , lung function , operation duration , amount of insufflated gas , intraperitoneal pH-values and post-operative complications in the various subgroups were compared to each other with regard to post-operative pain perception . The results did not show any significant differences among the groups regarding the main parameters like pH-value or different insufflation pressures etc . These results led to the termination of the study based on the raised criteria since we anticipated the actual cause of the shoulder pain to be due to an unknown factor . By the evaluation of the individual data , it became apparent that , the pains increase with increasing gas consumption , a fact which led to assumption that the pains are caused by a physical effect such as the cooling of the peritoneum .

laparoscopic surgical operations

higher or lower insufflation pressures

chemically inert insufflation gas

control

analgetics

lung function

operation duration

amount of insufflated gas

intraperitoneal pH-values

post-operative complications

pains increase

pains

laparoscopic surgical operations


[ Effect of acupuncture on T-lymphocyte and its subsets from the peripheral blood of patients with malignant neoplasm ] . Effect of acupuncture on the T-lymphocyte and its subsets from the peripheral blood of patients with malignant neoplasm has been researched in this study . 51 patients were divided into two groups : one in acupuncture treatment and the other without any treatment . 48 healthy adults were also studied as normal control group . The results showed that the percentages of OKT3+ , OKT4+ , OKT8+ cells in the peripheral blood of the 51 patients were lower than those of the normal adults respectively . After the acupuncture treatment , the percentages of OKT3+ , OKT4+ , OKT8+ cells were obviously higher than those before acupuncture ; the control group of patients showed no significant variation . This result revealed that acupuncture seemed to have more affect on OKT4+ cells than on OKT8+ cells . From our study we believe that acupuncture can be used as one of the many treatments for patients with cancer .

acupuncture

acupuncture

acupuncture treatment

acupuncture

acupuncture ;

acupuncture

acupuncture

T-lymphocyte and its subsets

T-lymphocyte

subsets

OKT4+ cells

OKT8+ cells .

malignant neoplasm

malignant neoplasm

51 patients

adults

cancer


Decreased sensitivity to dexamethasone in lymphocytes from patients with Alzheimer 's disease . Cortisol levels in patients with Alzheimer 's disease ( AD ) are relatively unaffected by a challenge with dexamethasone ( DEX ) in vivo . The present study demonstrates that DEX is less inhibitory for phytohemagglutinin ( PHA ) -induced T cell proliferation in AD patients as compared to age-matched controls . Since no significant differences were found between AD patients and age-matched controls with regard to the fraction of CD45RA+ or CD45RO+ CD4+ T cells nor the ability of peripheral blood mononuclear cells to produce IL-2 or IL-4 , it is unlikely that the difference in DEX sensitivity is due to a changed lymphokine profile or a changed composition of the CD4+ T cell population . Sensitivity to DEX was negatively correlated with the ability to produce IL-2 and IL-4 in the controls but not in AD patients . This suggests that IL-2 and IL-4 synthesis in AD patients is less sensitive to regulation by glucocorticoids .

dexamethasone

dexamethasone

DEX

DEX

DEX

glucocorticoids

Decreased sensitivity to dexamethasone

Cortisol levels

ability to produce IL-2 and IL-4

IL-2 and IL-4 synthesis in AD patients

patients with Alzheimer 's disease .


Treatment of acute asthma . Lack of therapeutic benefit and increase of the toxicity from aminophylline given in addition to high doses of salbutamol delivered by metered-dose inhaler with a spacer . We conducted a randomized , double-blind , placebo-controlled study to determine if intravenous aminophylline adds any benefit to high doses of inhaled salbutamol in patients who presented for treatment of acute asthma . We studied 94 patients ( mean age , 35.6 +/- 11.2 years ) with moderate to severe acute asthma . All patients received therapy with salbutamol delivered with metered-dose inhaler ( MDI ) into a spacer device ( Volumatic ) in four puffs ( 400 micrograms ) at 10-min interval , and intravenous hydrocortisone ( 500 mg ) . Patients were randomly assigned to receive either a loading dose of intravenous aminophylline followed by a routine infusion ( n = 45 ) or an equal volume of placebo as a loading dose and infusion ( n = 49 ) . The two groups showed no differences in measurements of peak expiratory flow , FEV1 , and FVC at baseline and at the end of treatment . However , the patients treated with aminophylline had significantly more adverse effects ( p < 0.05 ) . There were no differences in the final mean dose of salbutamol ( 6.3 +/- 44.5 mg for the placebo group and 5.8 +/- 4.2 mg for the aminophylline group ) , hospital admission rate ( 10.2 percent for the placebo group and 9.0 percent for the aminophylline group ) , and mean duration of Emergency Department treatment ( 2.5 +/- 1.83 h for the placebo group and 2.37 +/- 1.75 h for the aminophylline group ) . The results were similar when the patients were divided in accord with the degree of respiratory obstruction ( baseline FEV1 < 30 percent of predicted ) and theophylline level at 30 min of treatment ( placebo group patients with theophylline level < 10 mg/L vs aminophylline group patients with theophylline level > or = 10 mg/L ) . We conclude that intravenous aminophylline adds to the toxicity but not the efficacy of inhaled salbutamol in the treatment of acute exacerbations of asthma .

aminophylline

salbutamol

placebo-controlled

aminophylline

salbutamol

salbutamol

intravenous hydrocortisone

aminophylline

placebo

aminophylline

placebo

aminophylline

placebo

aminophylline

theophylline

theophylline

aminophylline

salbutamol

therapeutic benefit

increase of the toxicity

peak expiratory flow

FVC

adverse effects

respiratory obstruction

theophylline level

toxicity

efficacy

acute asthma

moderate to severe acute asthma


[ Report of a controlled clinical trial of a new synthetic drug , parsalmide , in rheumatic arthropathies ( inflammatory and degenerative ) ] . The anti-inflammatory , analgesic and tranquillizing activity of a synthetic compound called parsalmide was investigated in patients suffering from inflammatory and degenerative rheumatic arthropathies . The study was carried out in 30 subjects using the controlled experiment technique according to the " between patient " pattern , attributing parsalmide and indomethacin at random to two groups . Both preparations were found to possess good anti-inflammatory and analgesic action , comparable clinically and statistically . Tolerance was very good , particularly at gastroenteric level ( no side and/or undesired effects were observed ) and at the level of haemopoietic , renal and hepatic function .

parsalmide

parsalmide

parsalmide

indomethacin

anti-inflammatory and analgesic action

Tolerance


The effect of a culture-specific education program to promote breastfeeding among Vietnamese women in Sydney . The rate of breastfeeding among immigrant Vietnamese women in Western countries is low compared to those in Vietnam . To counteract this trend , a language and culture specific education program was developed . An experimental design was used to test the effectiveness of this program . The sample consisted of 182 prenatal Vietnamese women . Data collection included questionnaires and interviews . Results suggested that the education program had significant effects on knowledge , attitudes , planned and actual behaviour towards breastfeeding . However , the effect did not sustain until 6 months postpartum . Implications for nursing practice and further research are discussed .

language and culture specific education

knowledge

attitudes

actual behaviour towards breastfeeding

Vietnamese

women

immigrant Vietnamese

women

prenatal Vietnamese

women


[ Effect of dopexamine in splanchnic perfusion during surgery of the abdominal aorta ] . Abdominal aortic surgery has significant effects on cardiac and splanchnic perfusion . The purpose of this study was to examine the effects of dopexamine , an inodilator drug , on hemodynamic and splanchnic perfusion with measurement of gastric intramucosal pH , by the method of gastric tonometry , during abdominal aneurysm resection . Twenty-five patients undergoing excision of an aortic abdominal aneurysm were randomly divided into two groups . During aortic cross-clamping Group II patients received dopexamine infusion , at a dose of 1 microgram/kg/m , and at a dose of 0.5 micrograms/kg/m from declamping to the end of the surgery . Whereas Group I patients did not receive a dopexamine infusion . During aortic cross-clamping the intramucosal pH value decreased in Group I patients , but did not change in Group II patients . Heart rate , cardiac index , and mixed venous oxygen saturation increased significantly during dopexamine infusion , whereas systemic vascular resistance was reduced . During aortic cross-clamping dopexamine was a useful agent in improving splanchnic blood flow , cardiac index venous saturation . Also , since the drug produces dose related hemodynamic changes of rapid onset and reversibility , it is possible to interrupt the infusion before aortic declamping to avoid the decrease in the intramucosal pH value .

dopexamine

dopexamine

did not receive a dopexamine infusion

dopexamine

intramucosal pH value

systemic vascular resistance


Management of the thyroid isthmus in tracheostomy : a prospective and retrospective study . The thyroid isthmus is often encountered while a tracheostomy is being performed . This study details retrospective and prospective comparison of electrocautery division of the isthmus with older techniques . In this study , electrocautery division of the thyroid isthmus during tracheostomy is faster and as safe as other techniques with respect to blood loss , perioperative complications , and airway outcome .

tracheostomy

tracheostomy

electrocautery division of the isthmus

thyroid isthmus

faster and as safe


Influence of ball weight on junior high school girls ' volleyball performance . This study was designed to investigate the influence of a lighter ball ( Tachikara Volley Lite ) on 72 seventh-grade girls ' tournament game play and pretest-to-posttest improvement for a 16-day volleyball practice period . Two intact classes were randomly assigned to groups , one of whom used lighter balls during skills progressions while a second used regulation balls . All students used regulation balls during tournament game play and skills tests . Both groups significantly improved the forearm pass from pretest to posttest . Analysis of covariance indicated no significant differences between groups on posttest means for any skill . A 2 x 6 ( treatment x game day ) analysis of variance indicated that the group practicing with lighter balls had significantly more correct sets and a higher average daily success rate for the set and underhand serve on game days than the group using a regulation ball .

ball weight

lighter balls

regulation balls

regulation balls

lighter balls

regulation ball

performance

influence

forearm pass

Analysis of covariance

correct sets

higher average daily success rate

junior high school

girls

seventh-grade

girls


Promoting health in schools through a board game . Primary prevention and health promotion have become salient topics in Canadian society and in nursing during the past two decades . The noncommunicable chronic diseases , such as heart disease and cancer , have been linked to specific lifestyle behaviors or habits , which often develop early in life . The success of public health efforts to improve the health status of all Canadians depends substantially on the success of educational programs directed toward children . Effective teaching strategies that seek to promote health and wellness in children need to be developed and empirically evaluated . Educational games may provide an efficient vehicle for carrying out developmentally specific nursing interventions in school settings . This article begins with a brief overview of the historical origins of games , along with their advantages and disadvantages as educational strategies . The results of a pretest-posttest control group design study that evaluated the effectiveness of a board game as a primary prevention teaching strategy with 23 sixth grade children in Winnipeg , Manitoba are presented . The experimental group had significant gains in knowledge related to anatomy and physiology , diet , and lifestyle risk factors associated with the development of heart disease and cancer .

board game

lifestyle behaviors

children .

in children


Effects of a fish-oil and vegetable-oil formula on aggregation and ethanolamine-containing lysophospholipid generation in activated human platelets and on leukotriene production in stimulated neutrophils . The effects of consuming a liquid formula containing either fish oil enriched in omega-3 fatty acids or vegetable oil enriched in oleic acid was evaluated in 20 male subjects randomly allocated into two groups over a 42-d period . A decrease in collagen-induced aggregation by using washed platelet suspensions was found in both groups after nutritional supplementation . A considerable rise in omega-3 and a decrease in omega-6 fatty acids occurred in the platelet phospholipid with fish-oil consumption . The degree of eicosapentaenoic acid ( EPA , 20:5n-3 ) enrichment ( fish-oil group ) was dramatically greater in the ether-containing plasmenylethanolamine ( 13.5 mol % of fatty acids ; mol % of fatty acids = moles per 100 moles of total fatty acids ) than in phosphatidylethanolamine ( 2.8 mol % ) or phosphatidylcholine ( 2.9 mol % ) . Neither treatment significantly influenced the agonist-induced accumulation of lysoplasmenylethanolamine as derived via phospholipase A2 hydrolysis of plasmenylethanolamine . HPLC measurements of eicosanoid production in A23187-stimulated neutrophils revealed a considerable decrease in the formation of arachidonic acid-derived leukotriene B4 ( LTB4 ) , by 41 % , and 5-HETE ( 5-hydroxyeicosatetraenoic acid ) , by 30 % , in the fish-oil group along with the appearance of the corresponding EPA-derived products [ LTB5 and 5-HEPE ( 5-hydroxyeicosapentaenoic acid ) ] . No such alterations in the formation of lipoxygenase products were found with the vegetable oil treatment .

fish-oil and vegetable-oil formula

vegetable oil enriched in oleic acid

fish-oil consumption

vegetable oil treatment

lysophospholipid generation

leukotriene production

collagen-induced aggregation

omega-6 fatty acids

eicosapentaenoic acid

HPLC measurements

eicosanoid production

male


Effect of interferon gamma on infection-related death in patients with severe injuries . A randomized , double-blind , placebo-controlled trial . OBJECTIVE To assess the efficacy of interferon gamma in reducing infection and death in patients sustaining severe injury . DESIGN Multicenter , randomized , double-blind , placebo-controlled trial with observation for 60 days and until discharge for patients with major infection on day 60 . SETTING Nine university-affiliated level 1 trauma centers . PATIENTS Four hundred sixteen patients with severe injuries , assessed by Injury Severity Score and degree of contamination . INTERVENTION Recombinant human interferon gamma , 100 micrograms , was administered subcutaneously once daily for 21 days ( or until patient discharge if prior to 21 days ) as an adjunct to standard antibiotic and supportive therapy . MAIN OUTCOME MEASURES Incidence of major infection , death related to infection , and death . RESULTS Infection rates were similar in both treatment groups ; however , patients treated with interferon gamma experienced fewer deaths related to infection ( seven [ 3 % ] vs 18 [ 9 % ] ; P = .008 ) and fewer overall deaths ( 21 [ 10 % ] vs 30 [ 14 % ] ; P = .17 ) . While 12 early deaths ( days 1 through 7 ) occurred in each treatment group , late death occurred in 18 placebo-treated patients and nine in interferon gamma-treated patients . The results were dominated by findings at one center , which had the highest enrollment and higher infection and death rates . Statistical analysis did not eliminate the possibility of an unidentified imbalance between arms as an explanation for the results . CONCLUSION Further evaluation is required to determine the validity of the observed reduction in infection-related deaths in patients treated with interferon gamma .

interferon gamma

supportive therapy

interferon gamma-treated

interferon gamma

deaths

deaths

early deaths

death

patients with severe injuries .

patients sustaining severe injury .


Aerosolized pentamidine as primary prophylaxis for Pneumocystis carinii pneumonia : efficacy , mortality and morbidity . OBJECTIVE Primary prophylaxis against Pneumocystis carinii pneumonia ( PCP ) for patients with HIV infection has been recommended by the Centers for Disease Control and Prevention . We evaluated alternatives to routine primary PCP prophylaxis with aerosolized pentamidine . METHODS A total of 121 HIV-infected patients with CD4+ cell counts < or = 200 x 10 ( 6 ) /l or an AIDS diagnosis were enrolled in a controlled study of aerosolized pentamidine as primary PCP prophylaxis . Patients were randomly assigned to treatment ( n = 61 ) with aerosolized pentamidine once every month or to no treatment ( n = 60 ) . Patients were evaluated for PCP , mortality , morbidity and progression of HIV disease . Morbidity was estimated from the number of days patients were unable to work due to illness , number of days hospitalized and AIDS events . RESULTS Baseline characteristics were similar in the treatment and control groups and mean CD4+ cell counts were 116 and 107 x 10 ( 6 ) /l , respectively . Eight incidents of PCP and 19 deaths were observed in the treatment group during a median follow-up of 16.4 months ( range , 2.3-32.4 months ) . Nineteen incidents of PCP and 13 deaths , of which one was related to an acute episode of PCP , were noted in the control group . Median follow-up of controls was 18.5 months ( range , 3.1-32.9 months ) . Patients in the treatment group were unable to work 19 % of the observation time and were hospitalized for 4.3 % of that time . Corresponding figures were 20 and 3.0 % , respectively , in the control group . CONCLUSIONS Aerosolized pentamidine had significant prophylactic efficacy , but we could not detect any major effect on mortality and morbidity . The overall mortality and morbidity were not markedly influenced by PCP . Clinical check-ups and treatment of acute PCP could be a justifiable alternative to drug prophylaxis with aerosolized pentamidine in selected patients .

Aerosolized pentamidine

aerosolized pentamidine .

aerosolized pentamidine

aerosolized pentamidine

no treatment

Aerosolized pentamidine

aerosolized pentamidine

Pneumocystis carinii pneumonia :

PCP ,

mortality

CD4+ cell counts

deaths

deaths

Median follow-up

observation time

prophylactic efficacy

mortality and morbidity .

mortality

morbidity

justifiable

patients with HIV infection

A total of


Enhanced small group instruction using choral responding and student interaction for children with autism and developmental disabilities . The use of effective instructional strategies in small groups was investigated to determine learning effects for 24 elementary age students with autism and developmental disabilities . Effective strategies included ( a ) the use of choral responding ; ( b ) the use of student-to-student responding ; ( c ) the rotation of materials every 5 minutes during the 30-minute group while teaching 2 to 3 concepts ; and ( d ) the use of random , unpredictable trials for student responding . Thirty-minute language groups were targeted to teach receptive and expressive skills using pictures and common objects across five categories ( e.g. , household items , foods ) . Results showed increased opportunities to respond , increased levels of responding and academic engagement , higher gains on weekly criterion-referenced pre- and posttests , and decreased passive and inappropriate student behavior during interventions .

effective instructional strategies

the use of choral responding ;

small group


Use and limitations of Holter electrocardiography in assessing drug therapy of myocardial ischemia during the peri-PTCA period . Incidence and pattern of myocardial ischemia during the peri-PTCA ( percutaneous transluminal coronary angioplasty ) period and the possible role of continuous intravenous isosorbide dinitrate in its prevention were examined prospectively in 30 patients . Holter electrocardiographic monitoring was performed for 21 +/- 3 h before PTCA and continued during and for 41 +/- 8 h after the procedure . Before PTCA , 19 ischemic episodes were present in 10 ( 33 % ) of 30 patients . PTCA produced an abrupt decrease in number ( p = 0.015 ) and duration ( p = 0.03 ) of spontaneous ischemic episodes . The rarity of recurrent myocardial ischemic events by Holter monitoring after PTCA negated any attempt at assessing the efficacy of intravenous isosorbide dinitrate in their prevention . Holter monitoring could not be used as an early predictor of late coronary restenosis .

Holter electrocardiography

Holter electrocardiographic monitoring

Holter monitoring

isosorbide dinitrate

Holter monitoring

Use and limitations

Holter electrocardiographic monitoring

spontaneous ischemic episodes .

recurrent myocardial ischemic events


Late hemodynamic effects of the preserved papillary muscles during mitral valve replacement . BACKGROUND The late hemodynamic effects of preserving the papillary muscles during mitral valve replacement have not been evaluated . METHODS AND RESULTS Sixteen patients who had chronic mitral regurgitation due to myxomatous degeneration were randomized to preservation ( Pres group , n = 8 ) or no preservation ( No Pres group , n = 8 ) of the chordae tendineae and papillary muscles during mitral valve replacement . Rest and exercise nuclear ventriculograms were performed early ( 3 months ) and late ( 5 years ) after surgery . Early after surgery , the No Pres group had lower ejection fractions and stroke work indexes ( P < .05 by repeated-measures [ rm ] ANOVA ) than the Pres group did at similar end-diastolic volume indexes . The No Pres group had similar cardiac indexes after exercise because heart rate increased ( P < .005 by rm ANOVA ) . Late after surgery , ejection fraction was greater at similar end-diastolic volume indexes ( P < .005 by rm ANCOVA ) , and preload recruitable stroke work indexes ( P < .001 by rm ANCOVA ) were better in the Pres group . CONCLUSIONS Preserving chordal attachments enhanced the late hemodynamic recovery after mitral valve replacement for mitral regurgitation .

mitral valve replacement

preservation

no preservation

lower ejection fractions

stroke work indexes

cardiac indexes

heart rate increased

ejection fraction

end-diastolic volume indexes

preload recruitable stroke work indexes

mitral valve replacement .

Sixteen

preservation

no preservation


Effect of TENS on pain , medications , and pulmonary function following coronary artery bypass graft surgery . The efficacy of transcutaneous electrical nerve stimulation ( TENS ) as an adjunct to narcotic medications for the management of postoperative pain was assessed in a prospective , randomized , controlled study of patients following coronary artery bypass graft ( CABG ) surgery with the right or left internal thoracic artery ( ITA ) . Forty-five male patients ( mean age , 57 +/- 6 years ) were randomly assigned to ( 1 ) TENS , ( 2 ) placebo TENS , or ( 3 ) control treatments ( n = 15 each ) , following extubation and during the 24- to 72-h postoperative period . Two-way analysis of variance tests indicated no significant differences among treatment groups for ( 1 ) pain with cough , ( 2 ) narcotic medication intake , ( 3 ) FVC , ( 4 ) FEV1 , and ( 5 ) PEFR ( p > 0.05 ) . However , pain at rest reported by the TENS group was significantly lower than that reported by the control group ( treatment main effect ; p < 0.04 ) , although no significant differences were observed between the TENS and placebo or between the placebo and control groups ( p > 0.05 ) . All six criterion measures were characterized by significant changes over time for the entire group ( n = 45 ; time main effect ; p < 0.01 ) , as follows : pain and medication intake were similar on days 1 and 2 , but were significantly less on day 3 , and pulmonary functions were significantly lower than preoperatively on day 1 , decreased further on day 2 , and despite an improvement on day 3 , remained significantly lower than preoperative values ( p < 0.01 ) . This study suggests that the addition of TENS , applied continuously during the immediate postoperative period following CABG with ITA , may not be advantageous in pain management or the prevention of pulmonary dysfunction .

TENS

placebo TENS

control treatments

TENS

pain

medications

pulmonary function

postoperative pain

pain with cough

narcotic medication intake

FVC

PEFR

pain at rest

pain

medication intake

pulmonary functions

pulmonary dysfunction


A cost-benefit comparison of intensive diabetes management with implantable pumps versus multiple subcutaneous injections in patients with type I diabetes . OBJECTIVE To investigate if intraperitoneal ( IP ) insulin infusion via programmable implantable pumps is a potential alternative to subcutaneous ( SC ) insulin via multiple injections . RESEARCH DESIGN AND METHODS We compared the cost-benefits of the two methods using a randomized , prospective , 6-month , crossover design in 10 adult type I diabetic patients . RESULTS When judged on the last month of IP versus SC periods in the nine patients who completed the study , metabolic data showed better glycemic control ( HbA1c : 7.2 +/- 0.2 IP vs. 8.5 +/- 0.7 % SC , mean +/- SE , P = 0.02 ) , reduced glycemic fluctuations ( SD of capillary glucose values : 3.4 +/- 0.2 IP vs. 4.6 +/- 0.2 mM SC , P < 0.01 ) , and fewer mild hypoglycemic events ( 5.7 +/- 2.0 IP vs. 10.0 +/- 3.1 events/month SC , P = 0.02 ) . Quality of life , judged by Diabetes Control and Complications Trial questionnaires , was unaffected by pump therapy . Direct costs , including pump acquisition , implantation , and follow-up , were 2.6-fold higher with IP than with SC delivery . CONCLUSIONS The implantable pump is more effective in the short term , equally accepted , but more costly than multiple injections and should be limited to patients with unsatisfactory glycemic control despite intensive diabetes management with SC insulin . In addition , longer-term , larger-scale , and comparative evaluation is required .

multiple subcutaneous injections

pump

implantable pump

multiple injections

cost-benefit

cost-benefits

metabolic data

glycemic control

glycemic fluctuations

mild hypoglycemic events

Quality of life

effective

accepted

costly

glycemic control

type I diabetes

adult

type I diabetic


Assessing drug use prevalence in the workplace : a comparison of self-report methods and urinalysis . A random sample of 800 employees of a steel manufacturing company were randomly assigned to one of four self-report methods of assessing illicit drug use : 1 ) Individual interview in the workplace , 2 ) group-administered questionnaire in the workplace , 3 ) telephone interview , and 4 ) individual interview off the worksite . All 621 subjects participating in the research were also tested by urinalysis . Rates of drug use self-report were highest in the workplace interview condition and lowest in the overall group questionnaire condition . Although the overall prevalence rates produced by self-reports and urinalysis were similar , there was little concordance between urinalysis positives and self-report positives . The results indicated that self-reports and urinalysis are complementary methods of drug use assessment , and are best used in combination .

self-report methods

Individual interview in the workplace

telephone interview

individual interview off the worksite

Rates of drug use self-report

overall prevalence rates

urinalysis positives

self-report positives

drug use assessment


Brief report : a controlled evaluation of facilitated communication using open-ended and fill-in questions .

open-ended and fill-in questions


The degrees of UVB-induced erythema and pigmentation correlate linearly and are reduced in a parallel manner by topical anti-inflammatory agents . To examine whether it is possible to evaluate the degree of ultraviolet B ( UVB ) -induced inflammation by measuring the degree of hyperpigmentation , we investigated the relationship between UVB-induced erythema and the subsequent pigmentation quantitatively . At 24 h and 7 d after irradiation with erythemogenic doses of UVB to the backs of 16 Japanese subjects , the degree of induced erythema ( delta erythema index ) and that of pigmentation ( delta melanin index ) were examined by an image analytic method using a videomicroscope interfaced with a computer . The relationship between two indices was linear in each subject , and the correlation coefficient was 0.83 when evaluated using whole data . The slope of the regression line for the delta melanin index against delta erythema index tended to become steeper as non-irradiated skin color became darker ( r = 0.63 ) , suggesting that more efficient melanogenesis takes place after the same level of inflammation in the subject with darker skin . Both erythema and hyperpigmentation were suppressed significantly and in a parallel manner by corticosteroids and indomethacin applied topically immediately after UVB irradiation . These results imply that the post-inflammatory hyperpigmentation correlates closely with the severity of the prior inflammation and that chemical mediators released in the inflammatory process have considerable influence on the melanogenesis . We conclude that the measurement of UVB-induced hyperpigmentation can be utilized for the assessment of topical anti-inflammatory agents , unless these have direct actions on the tyrosinase activity of melanocytes .

topical anti-inflammatory agents .

corticosteroids

indomethacin

topical anti-inflammatory agents

erythema and hyperpigmentation

post-inflammatory hyperpigmentation

UVB-induced hyperpigmentation


Therapy for progressive supranuclear palsy : past and future . Dysfunction of multiple brain systems in progressive supranuclear palsy ( PSP ) has complicated attempts to treat the disease . Neurotransmitter replacement strategies targeting the dopaminergic , cholinergic , and serotonergic systems have been unsuccessful . In order to bypass the degenerated cortico-striato-pallidal loop , we administered the adrenergic agonist idazoxan ( IDA ) to treat PSP in two randomized double-blind , placebo controlled , crossover studies . Approximately one half of patients enrolled in these studies showed statistically significant improvement in balance and manual dexterity while taking IDA compared to placebo . These results suggest that new therapies that target structures outside of the basal ganglia may be useful for symptomatic treatment of PSP . Applying this strategy and developing treatments that arrest or reverse clinical deterioration in PSP will require improved understanding of the process underlying the illness .

Neurotransmitter replacement strategies

adrenergic agonist idazoxan ( IDA )

placebo

placebo

therapies

statistically significant

progressive supranuclear palsy

progressive supranuclear palsy


Randomized double-blind , placebo-controlled evaluation of oral ondansetron in the prevention of nausea and vomiting associated with fractionated total-body irradiation . PURPOSE To evaluate oral ondansetron in the prevention of total-body irradiation ( TBI ) -induced nausea and vomiting . METHODS Twenty patients who received 4 days of TBI as part of their preparative regimen before bone marrow transplantation were randomized to receive either 8-mg oral doses of ondansetron or placebo . Administration of drug was double-blinded . Initial rescue therapy consisted of intravenous ( i.v . ) ondansetron 0.15 mg/kg following two or more emetic episodes between successive fractions of TBI or five total emetic episodes during the 4 days of therapy . If , after receipt of i.v . ondansetron , patients had two or more emetic episodes between fractions of TBI or five total emetic episodes , additional antiemetics were administered . RESULTS Patients who received oral ondansetron had significantly fewer emetic episodes compared with those who received placebo ( P = .005 ) over the entire 4-day study period . Oral ondansetron was also significantly superior to placebo with respect to the time of onset of emesis or rescue ( P = .003 ) . Six of 10 patients treated with oral ondansetron completed the study without additional antiemetic therapy , while none of 10 patients who received placebo completed the study without rescue antiemetic therapy . Six placebo patients who received initial rescue therapy with i.v . ondansetron required no additional antiemetics . No relationships were apparent between peak ondansetron concentration ( Cmax ) or area under the concentration versus time curve ( AUC ) and number of emetic episodes . CONCLUSION Oral ondansetron is an effective therapy for the prevention of emesis induced by TBI .

placebo-controlled

oral ondansetron

oral ondansetron

oral doses of ondansetron

placebo

ondansetron

ondansetron

ondansetron

placebo

ondansetron

placebo

ondansetron

antiemetic therapy

placebo

antiemetic therapy

placebo

initial rescue therapy

ondansetron

Oral ondansetron

emetic episodes

time of onset of emesis or rescue

rescue antiemetic therapy .

additional antiemetics .

nausea

vomiting

fractionated total-body irradiation

Twenty


Osteocalcin in patients with rheumatoid arthritis . A one-year followup study . OBJECTIVE To analyze clinical , radiological , and drug ( disease modifying antirheumatic drug , DMARD ) dependent factors influencing bone turnover in patients with rheumatoid arthritis ( RA ) . METHODS We investigated in a one-year double blind randomized study comparing intramuscular ( im ) gold with im methotrexate ( MTX ) , whether the variation of inflammatory activity or functional capacity , the ascending anatomic stage , or DMARD treatments have an influence on bone formation ( osteocalcin ) in patients with RA . RESULTS Patients ( n = 48 ) enrolled at the beginning of our study had significantly increased osteocalcin levels ( 3.45 +/- 0.93 -- > 4.42 +/- 1.39 ng/ml p < 0.02 ) after one year if inflammatory activity decreased ( > or = 1 SD : erythrocyte sedimentation rate ( ESR ) 26.4 mm/h , C-reactive protein ( CRP ) 3.8 mg/dl ) . We found a significant negative correlation of the one-year CRP- ( r = -0.44 , p < 0.001 ) or ESR differences ( r = -0.45 , p < 0.001 ) with the corresponding osteocalcin differences . This was also evident if these patients were pooled with 15 patients excluded from the double blind study as already receiving DMARD treatment ( n = 63 ; p < 0.01 ) . Patients with impaired functional capacity also had significantly reduced osteocalcin levels ( p < 0.01 ) . In both cases , alkaline phosphatase showed no significant differences . CONCLUSIONS Our data suggest that osteocalcin , a useful followup variable of bone turnover , is changed significantly ( p < 0.02 ) in patients with RA regarding inflammatory activity and functional capacity . In contrast to alkaline phosphatase , a fall in inflammatory activity stimulated and impairment of functional capacity significantly decreased osteocalcin levels in patients with RA .

Osteocalcin

DMARD treatment

inflammatory activity

functional capacity

osteocalcin levels

inflammatory activity

erythrocyte sedimentation rate ( ESR )

C-reactive protein ( CRP )

CRP-

ESR

differences

functional capacity

osteocalcin levels

alkaline phosphatase

bone turnover

inflammatory activity

functional capacity

alkaline phosphatase

functional capacity

rheumatoid arthritis

rheumatoid arthritis ( RA )

RA

RA


Naltrexone , an opiate antagonist , fails to modify motor symptoms in patients with Parkinson 's disease . One month of adjunct treatment with naltrexone ( 100 mg/day ) was compared with placebo in a double-blind , randomized , cross-over design in two groups of patients with Parkinson 's disease . The first group was composed of 10 patients with a moderate motor impairment insufficiently controlled by monotherapy with bromocriptine . The second group was composed of eight patients with L-dopa-induced peak-dose dyskinesia . Naltrexone as compared with placebo did not demonstrate any significant change in motor function in either group . These negative clinical results do not support a significant role of endogenous opioid systems in the pathophysiology of motor impairment in Parkinson 's disease .

Naltrexone

opiate antagonist

naltrexone

placebo

bromocriptine

Naltrexone

placebo

motor symptoms

motor impairment

motor function

motor impairment

patients with Parkinson 's disease .


A prospective randomized study concerning the point A dose in high-dose rate intracavitary therapy for carcinoma of the uterine cervix . The final results . PURPOSE High-dose rate ( HDR ) remote afterloading intracavitary therapy has been recognized as an effective and safe treatment modality for carcinoma of the uterine cervix . Since 1983 , a prospective randomized study was started in order to investigate the more advantageous treatment schedule with keeping the local control rate . This paper reports the final results in terms of survival , local control and complications . PATIENTS AND METHODS Between January 1983 and February 1989 , a total of 165 patients with carcinoma of the uterine cervix was entered in a prospective randomized study concerning the point A dose of HDR therapy ( 6 Gy/fraction vs 7.5 Gy/fraction ) and external irradiation dose at Department of Radiation Therapy , The Center for Adult Diseases , Osaka . UICC [ 20 ] stage distribution of patients was as follows : stage IA = 4 , stage IB = 33 , stage IIA = 18 , stage IIB = 38 , stage III = 57 , stage IV = 15 . RESULTS Overall 5-year cause specific survivals were as follows : stage IA = 100 % , stage IB = 96 % , stage IIA = 92 % , stage IIB = 79 % , stage III = 57 % , stage IV = 27 % . In each stage , 5-year survival rates in groups A and B were 100 % , 93 % in stage I , 82 % and 85 % in stage II , 62 % and 52 % in stage II and 22 % and 31 % in stage IV , respectively . There were no statistically significant differences among these survival curves in each stage . Five-year local failure rates were 16 % in group A and 16 % in group B ( p = 0.9096 ) , and corresponding distant failure rates were 23 % in group A and 19 % in group B ( p = 0.2955 ) . Moderate-to-severe complications requiring treatment ( Kottmeier 's grade 2 or more ) were noted in 6 patients ( 7 % ) in group A and 6 patients ( 7 % ) in group B . All of the bladder and rectal complications needed medical treatment ( Kottmeier 's grade 2 ) . Severe complications receiving surgery were noted in 4 patients ( A : 1 ; B : 3 ) , i.e. , small intestine 3 and sigmoid colon 1 patient . Another 1 patient ( A ) was dead of ileus . CONCLUSIONS There were no statistically significant differences between 2 treatment schedules in survival rates , failure patterns and complications rates . This fact suggests that small number of fractions ( 7.5 Gy/fraction ) may be advantageous because of short duration and a low load of treatment .

high-dose rate intracavitary therapy

HDR therapy

5-year cause specific survivals

5-year survival rates

Five-year local failure rates

Moderate-to-severe complications

bladder and rectal complications

Severe complications

dead

failure patterns

complications rates

carcinoma of the uterine cervix

carcinoma of the uterine cervix

carcinoma of the uterine cervix


Correlation between in vivo humoral and in vitro cellular immune responses following immunization with hepatitis B surface antigen ( HBsAg ) vaccines . To study the regulation of the human immune response to hepatitis B surface antigen ( HBsAg ) we have carefully monitored the in vivo humoral and in vitro cellular immune responses to HBsAg in 50 subjects receiving four doses of hepatitis B vaccine according to a 0 , 1 , 2 , 12 month vaccination scheme . Twenty-three subjects were given a plasma-derived vaccine ( Hevac B ) and 27 received a recombinant HBsAg vaccine ( yeast-derived ; Engerix-B ) . The humoral and cellular immune responses were measured before vaccination ( day 0 ) ; 6 days after the second dose ( day 36 ) ; 6 days ( day 66 ) , 2 months ( day 120 ) and 10 months ( day 365 ) after the third dose and 1 month after the fourth dose ( day 395 ) . Based on the kinetics of the humoral immune responses , the vaccinees could be classified into fast , intermediate and slow/non-responders . Based on the magnitude of the immune response ( anti-HBs titre ) on day 395 , the vaccinees could be divided into high ( > or = 2000 U l-1 ) and low ( < or = 2000 U l-1 ) responders . A close correlation between the kinetics and the magnitude of the humoral immune response was observed . The in vivo anti-HBs response was measured using commercially available immunoradiometric assays . The in vitro cellular immune response was measured using an HBsAg-specific lymphoproliferation assay . Because of interassay variability the results were considered as dichotomous variables ( proliferation versus non-proliferation ) for further data analysis . A statistically significant correlation was observed between the kinetics and magnitude of the humoral immune response on the one hand and the in vitro anti-HBs response on the other hand . ( ABSTRACT TRUNCATED AT 250 WORDS )

hepatitis B surface antigen ( HBsAg )

hepatitis B vaccine

plasma-derived vaccine ( Hevac B )

humoral immune response

in vivo anti-HBs response

in vitro cellular immune response

dichotomous variables


Oesophageal intubation can be undetected by auscultation of the chest . Prompt detection of oesophageal intubation is a primary concern in anaesthetic practice . This blind , randomised study evaluates three widely used tests of intubation . Forty patients had both their trachea and oesophagus intubated , each patient was studied twice . Auscultation of the epigastrium , right and left axilla is more reliable than auscultation of the chest , and the anaesthetist 's feeling when he squeezes the bag . P = 0.001 and P = 0.048 , respectively . The tests were carried out after gastric distension with gas had occurred . We conclude that auscultation of epigastrium , right and left axilla , are recommended .

auscultation

oesophageal intubation

intubation

intubated

Auscultation of the epigastrium

Oesophageal intubation

Forty patients

anaesthetist 's


Preventing disability and falls in older adults : a population-based randomized trial . OBJECTIVES Because preventing disability and falls in older adults is a national priority , a randomized controlled trial was conducted to test a multicomponent intervention program . METHODS From a random sample of health maintenance organization ( HMO ) enrollees 65 years and older , 1559 ambulatory seniors were randomized to one of three groups : a nurse assessment visit and follow-up interventions targeting risk factors for disability and falls ( group 1 , n = 635 ) ; a general health promotion nurse visit ( group 2 , n = 317 ) ; and usual care ( group 3 , n = 607 ) . Data collection consisted of a baseline and two annual follow-up surveys . RESULTS After 1 year , group 1 subjects reported a significantly lower incidence of declining functional status and a significantly lower incidence of falls than group 3 subjects . Group 2 subjects had intermediate levels of most outcomes . After 2 years of follow-up , the differences narrowed . CONCLUSIONS The results suggest that a modest , one-time prevention program appeared to confer short-term health benefits on ambulatory HMO enrollees , although benefits diminished by the second year of follow-up . The mechanisms by which the intervention may have improved outcomes require further investigation .

general health promotion nurse visit

usual care

disability and falls in older adults

disability and falls in older adults

incidence of falls

short-term health benefits

benefits diminished

older adults

ambulatory HMO enrollees


Treatment of multiple myeloma according to the extension of the disease : a prospective , randomised study comparing a less with a more aggressive cystostatic policy . Cooperative Group of Study and Treatment of Multiple Myeloma . The purpose of the study was to ascertain whether the prognostic significance of staging in multiple myeloma ( MM ) is influenced by the aggressiveness of effective induction treatment and/or by continuing or discontinuing maintenance chemotherapy . Patients with untreated stage I MM ( defined according to Durie and Salmon ) were randomised between being followed without cytostatics until the disease progressed and receiving six courses of melphalan and prednisone ( MP-P ) just after diagnosis ; stage II patients were uniformly treated with MPH-P and stage III patients were randomised between MPH-P and four courses of combination chemotherapy with Peptichemio , vincristine and prednisone ( PTC-VCR-P ) . Within each stage , responsive patients were randomised between receiving additional therapy only until maximal tumour reduction was reached ( plateau phase ) and continuing induction therapy indefinitely until relapse . With resistant , progressive or relapsing disease , patients originally treated with MPH-P for induction received combination chemotherapy and vice versa . The overall first response rate was 43.8 % ( 42.2 % in 206 stage I , II and III patients treated with MPH-P and 48.0 % in 75 stage III patients treated with combination chemotherapy , P = NS ) . Combination chemotherapy was more myelotoxic than MPH-P and , in particular , caused more non-haematological side-effects . Both the less and the more aggressive induction policies gave the same disease control . Progression of disease was statistically similar in stage I patients who were initially left untreated and in t hose who received MPH-P just after diagnosis ; median duration of first response was similar in stage III patients receiving MPH-P and in those on combination chemotherapy . In all stages , discontinuing or continuing maintenance did not alter the median duration of first response . The overall second response rate was 28.5 % ( 34.0 % to MPH-P and 25.3 % to combination chemotherapy , P = NS ) . Median survival was greater than 78 months in stage I , was 46.3 months in stage II and was 24.3 months in stage III patients , still independent of both induction and post-induction policies . In MM , the significance of staging for survival is independent of both the aggressiveness of induction and of continuing or discontinuing maintenance chemotherapy after the maximal tumor reduction has been achieved . Both MPH-P and and the association of PTC , VCR and P are effective in inducing first response and also second response in patients failing on the alternative regimen , but PTC-VCR-P causes more side effects . Thus , the overwhelming majority of patients with MM can safely be given MPH-P as first therapy , and this treatment may be delayed in early diseases .

aggressive cystostatic

followed without cytostatics

melphalan and prednisone ( MP-P )

MPH-P

MPH-P

overall first response rate

myelotoxic

non-haematological side-effects

disease control

Progression of disease

duration of first response

median duration of first

response

overall second response rate

Median

survival

survival

first response

second response

side effects .

Multiple Myeloma

untreated stage I MM


A comparison of lisinopril and nifedipine in the treatment of mild to moderate hypertension . A multicentre study . Lisinopril has been compared with slow-release nifedipine in a 16-week double-blind , randomized , parallel-group study involving 102 patients with mild to moderate hypertension . Sitting systolic and diastolic blood pressures were reduced 6 and 5 mmHg more by lisinopril than by nifedipine over 12 weeks monotherapy . After 12 weeks a greater proportion of patients taking lisinopril was controlled ( sitting diastolic blood pressure below 95 mm Hg ) than in those taking nifedipine . As a result , 17 % of those taking lisinopril and 38 % of those taking nifedipine required additional therapy with hydrochlorothiazide . The addition of hydrochlorothiazide resulted in similar response rates in the lisinopril and nifedipine groups ( 89 % and 75 % respectively ) . The rate of reporting of adverse events considered to be drug-related and the rate of withdrawals were similar for both treatments . Cough was more often reported with lisinopril and headache , sweating , and hot flushes with nifedipine . We conclude that once-daily titrated doses of lisinopril produced better control of blood pressure than twice-daily titrated doses of nifedipine .

lisinopril and nifedipine

Lisinopril

nifedipine

lisinopril

nifedipine

lisinopril

nifedipine .

lisinopril

nifedipine

hydrochlorothiazide

lisinopril

nifedipine

lisinopril

nifedipine .

lisinopril

nifedipine .

hydrochlorothiazide

adverse events

Cough

headache , sweating

hot flushes

blood pressure

mild to moderate hypertension


The effects of single oral doses of 17 beta-oestradiol and progesterone on finger skin circulation in healthy women and in women with primary Raynaud 's phenomenon . The effects of sex , the menstrual cycle , oral contraceptives , pregnancy , and the menopause on skin perfusion in healthy women and in patients with Raynaud 's phenomenon suggest a role of female sex hormones . However , no clear relation between skin blood flow and circulating concentrations of oestrogens or progestogens has yet been found . The aim of this study was to investigate the effect of orally administered 17 beta-oestradiol and progesterone on finger skin blood flow before and during heat and cold challenge in 17 healthy normotensive women and in 12 women with Raynaud 's phenomenon . In each subject standardized finger heating ( 45 degrees C water bath , 10 min ) and cooling tests ( 15 degrees C water bath , 5 min and 20 min recovery ) were performed twice on the second ( or third ) day of two consecutive menstrual cycles . 17 beta-Oestradiol ( 9 mg ) or progesterone ( 300 mg ) were given before the second test , after a first test with placebo . Both hormonal doses resulted in ( high ) physiological concentrations . Fingertip skin temperature and laser Doppler flux were measured . There were no significant differences in the test results after placebo and after progesterone . Although values of fingertip skin temperature and laser Doppler flux after 17 beta-oestradiol tended to be higher only the precooling values in the healthy subjects reached significance : fingertip skin temperature respectively with placebo and with oestradiol ( mean ( SD ) ) : 32.7 ( 1.0 ) and 33.1 ( 0.8 ) degrees C ; laser Doppler flux with placebo and with oestradiol : 33.6 ( 11.7 ) and 42.2 ( 9.5 ) perfusion units ; both P < 0.05 ) . ( ABSTRACT TRUNCATED AT 250 WORDS )

17 beta-oestradiol

progesterone

17 beta-oestradiol

progesterone

17 beta-Oestradiol

progesterone

placebo

finger skin circulation

skin blood flow

finger skin blood flow

physiological concentrations

Fingertip skin temperature

laser Doppler flux


Effect of simultaneous didanosine administration on itraconazole absorption in healthy volunteers . STUDY OBJECTIVE To investigate the effect of simultaneously administered didanosine ( ddI ) on the absorption of a single dose of itraconazole . DESIGN Randomized , crossover , unblinded single-dose pharmacokinetic study in healthy volunteers . Comparisons of itraconazole alone and itraconazole with simultaneous ddI were performed on days 1 and 15 . SETTING A university medical center . PATIENTS Seven healthy men and women . Six subjects ( 86 % ) completed the study ; one was removed due to the development of a rash . INTERVENTIONS Volunteers received a single 200-mg oral dose of itraconazole or itraconazole with concomitant oral ddI 300 mg ( two 150-mg tablets ) dispersed in 240 ml water . Each regimen was separated by a 2-week washout period . Serum samples were obtained frequently for 12 hours after the dose . MEASUREMENTS AND MAIN RESULTS Concentrations of itraconazole were determined using a microbiologic assay . Individual concentrations in serum versus time data were evaluated by linear regression analysis . Peak serum concentration and time to peak were determined by visual inspection of each individual 's serum concentration-time curve . A mean +/- SD peak serum itraconazole concentration of 0.90 +/- 0.30 micrograms/ml was observed at 3.0 +/- 0.7 hours when itraconazole was administered alone , compared with undetectable levels in all patients during therapy with ddI . CONCLUSIONS Simultaneous oral administration of ddI significantly decreases absorption of itraconazole . These drugs should not be administered concurrently .

didanosine ( ddI

itraconazole

itraconazole alone

itraconazole with simultaneous ddI

single 200-mg oral dose of itraconazole

itraconazole

itraconazole

oral administration of ddI

itraconazole

itraconazole absorption

serum versus time data

Peak serum concentration

time to peak

absorption of itraconazole

healthy volunteers .

Seven

men

women


Effect of intravenous fructose-1,6-diphosphate on myocardial contractility in patients with left ventricular dysfunction . STUDY OBJECTIVE To examine the effects of fructose-1,6-diphosphate on myocardial performance using nuclear scintigraphy . DESIGN Prospective , randomized , single-blind , parallel study . SETTING Urban teaching hospital clinical research center . PATIENTS Individuals with New York Heart Association functional class II-III heart failure ( mild to moderate ) . INTERVENTIONS Subjects received either intravenous fructose-1,6-diphosphate 125 mg/kg or normal saline 1.3 ml/kg every 12 hours over 10 minutes for four consecutive doses . Left ventricular performance was assessed by radionuclide ventriculography at baseline and within 60 minutes after the fourth infusion . Vital signs were monitored throughout the study period . MEASUREMENTS AND MAIN RESULTS Fructose-1,6-diphosphate resulted in a modest 7 % increase in left ventricular ejection fraction ( p < 0.05 ) . Peak ejection rate and peak diastolic filling rate did not change significantly . There were no changes in blood pressure or heart rate with either fructose-1,6-diphosphate or placebo . CONCLUSIONS Fructose-1,6-diphosphate produces a modest but significant increase in left ventricular ejection fraction in patients with mild to moderate heart failure .

intravenous fructose-1,6-diphosphate

normal saline

radionuclide ventriculography

placebo

myocardial contractility

myocardial performance

left ventricular ejection fraction

Peak ejection rate

peak diastolic filling rate

blood pressure

heart rate

left ventricular ejection fraction

left ventricular dysfunction

heart failure


Anaphylactoid reactions and histamine release by plasma substitutes : a randomized controlled trial in human subjects and in dogs [ proceedings ] .

Anaphylactoid

plasma substitutes :

in human


Early effects of continuous low-dosage all-norgestrel administered alone or with estrogen . Twenty-six postmenopausal women participated in a double-blind trial involving treatment according to a Latin square design with either ( i ) dl-norgestrel alone ( 0.075 mg/day ) continuously for two cycles , ( ii ) estradiol-17 beta alone ( 1 mg on 25 of 28 days ) for two cycles , or ( iii ) the combined hormones for six cycles . A placebo control cycle followed each hormonal treatment . Plasma triglycerides decreased by an average 22 % during treatment with either dl-norgestrel alone ( 123 +/- 11 vs. 160 +/- 10 mg/dl , n = 25 , P < 0.005 ) or combination therapy ( 126 +/- 11 vs. 162 +/- 11 , n = 25 , P < 0.005 ) as compared with control . Plasma total cholesterol fell by 5 % during two cycles of treatment with either dl-norgestrel alone ( 229 +/- 11 vs. 242 +/- 10 mg/dl , n = 25 , P < 0.02 ) or combination therapy ( 233 +/- 11 vs. 246 +/- 10 , n = 25 , P < 0.05 ) versus placebo . During the fifth and sixth cycles of combination therapy 94 % of cycles were free of flushing ( vs. 31 % for control , P < 0.01 ) , 64 % of cycles were free of spotting not requiring protection ( control 75 % ) , 96 % of cycles were free of vaginal bleeding ( control 100 % ) , endometrial biopsy showed inactive endometrium in nine of the 10 subjects re-biopsied , fasting blood pyruvate decreased by 20 % ( P < 0.05 ) and diastolic blood pressure fell by 4 % compared with control ( P < 0.05 ) , whereas glucose tolerance was unchanged . There was a significant reduction in vasomotor flushing beginning with the third to fourth cycles of combination therapy .

all-norgestrel

dl-norgestrel alone

estradiol-17 beta alone

combined hormones

placebo control

dl-norgestrel

dl-norgestrel

Plasma triglycerides decreased

Plasma total cholesterol

free of flushing

free of vaginal bleeding

inactive endometrium

fasting blood pyruvate decreased

diastolic blood pressure fell

glucose tolerance was unchanged

vasomotor flushing


Laser-aided external drainage of subretinal fluid : prospective randomized comparison with needle drainage . In a prospective randomized study of 50 consecutive eyes , we compared the safety and efficacy of draining subretinal fluid transchoroidally in primary scleral buckling for rhegmatogenous retinal detachment using a needle , with the safety and efficacy of the same procedure using an angulated endolaser probe set at 1 W for 0.2 seconds , using an average of 2.4 laser burns . There were no significant complications associated with the laser-aided drainage procedures ( 25 eyes ) . In the transchoroidal needle drainage procedures ( 25 eyes ) , subretinal hemorrhage occurred in three eyes and retinal incarceration in one . Thus , though our numbers are small , there appears to be some advantage of laser-assisted drainage in terms of a lower incidence of complications .

Laser-aided external drainage

subretinal fluid transchoroidally

needle

angulated endolaser probe

laser-aided drainage

transchoroidal needle drainage

safety

efficacy

safety

efficacy

complications

subretinal hemorrhage

incidence of complications

subretinal fluid


Endurance physical activity , diet and fibrinolysis . The impact of long-term , heavy exercise on recently established cardiovascular/thromboembolic risk factors of the fibrinolytic system , tissue plasminogen activator ( tPA ) and plasminogen activator inhibitor ( PAI-1 ) in relation to food composition was studied . Twenty healthy men , aged 18-55 years participated in a 14-day skiing tour through the Swedish mountains , carrying a pack load of 30 kg , and spending each night in self-dug igloos ( ambient temp -10 degrees to -25 degrees C ) , and were randomized to 2 food regimens having 30 or 40 energy percent of fat . Individual records were kept of all consumed food . Citrated plasma was obtained before and after 1 and 2 weeks of exercise : tPA release was assessed by a 10 min venous occlusion ( VO ) test . At baseline , daily dietary fiber intake correlated negatively with PAI-1 activity . Already after the first week of the skiing tour there were significant drops in PAI-1 activities , cholesterol and triglycerides . The tPA mass concentrations also dropped , both before and after VO , but tPA activities were unchanged , as were von Willebrand factor ( vWF ) levels . These changes were related mainly to the expenditure of energy , calculated from the food consumption , and appeared to be mediated through changed insulin sensitivity and decreased body fat mass . The energy percent of fat in the food had no differential impact . The effects receded a few weeks after cessation of the endurance exercise . Thus , endurance physical activity improves the fibrinolytic risk factor profile by reducing PAI-1 while leaving tPA activity unaffected , independently of food composition . A low dietary fiber intake appears to be associated with higher PAI-1 activities at baseline .

Endurance physical activity ,

diet

long-term , heavy exercise

daily dietary fiber intake

endurance physical activity

Citrated plasma

tPA release

daily dietary fiber intake

tPA mass concentrations

tPA activities

von Willebrand factor ( vWF ) levels

tPA

PAI-1 activities

Twenty

18-55 years


Interactive effects of indomethacin , angiotensin II and frusemide on renal haemodynamics and natriuresis in man . The responses of renal haemodynamic and natriuretic indices to the oral prostaglandin synthetase inhibitor indomethacin ( 200 mg ) , to infused angiotensin II ( 1 ng min-1 kg-1 ) and to the combination of the two were studies in placebo-controlled fashion in eight normal male subjects both prior to and following administration of intravenous frusemide ( 20 mg ) . As compared with placebo , angiotensin II infusion alone caused significant reductions in absolute rate of sodium excretion , fractional sodium excretion , urine flow rate and effective renal plasma flow ( all P < 0.001 vs placebo ) but had no effect on glomerular filtration rate . The only change observed in these parameters with indomethacin alone was a small but significant reduction in urine flow rate ( P < 0.005 vs placebo ) . As compared with the effects of angiotensin II alone , indomethacin pre-treatment followed by angiotensin II infusion led to much greater falls in absolute rate of sodium excretion , fractional sodium excretion , urine flow rate and effective renal plasma flow ( all P < 0.0001 vs placebo ) associated with a significant reduction in glomerular filtration rate ( P < 0.0001 ) not observed with angiotensin II alone . Frusemide administration at the midpoint of each study limb resulted in each case in a prompt 15 to 20 fold increase in natriuresis . The renal haemodynamic and natriuretic effects of angiotensin II , indomethacin and their combination were not qualitatively different from those observed in the pre-frusemide phase . Our findings provide a clear demonstration in man of the important homeostatic role of renal prostaglandins in preserving renal function , particularly glomerular filtration , under conditions of elevated circulating angiotensin II .

indomethacin

angiotensin II

frusemide

indomethacin ( 200 mg )

infused angiotensin II

placebo-controlled

intravenous frusemide

placebo

angiotensin II infusion

indomethacin

indomethacin

angiotensin II

placebo

Frusemide

pre-frusemide

absolute rate of sodium excretion

fractional sodium excretion

urine flow rate

effective renal plasma flow

glomerular filtration rate

urine flow rate

absolute rate of sodium excretion

fractional sodium excretion

urine flow rate

effective renal plasma flow

glomerular filtration rate

natriuresis

homeostatic role

eight

male


Relationship between subjective effects and drug preferences : ethanol and diazepam . The relationship between subjective effects and drug preferences in normal volunteers was explored in a meta-analysis of several previously published studies . Subjective effects of , and preference for , ethanol and diazepam vs. placebo were measured using a choice procedure . Subjects were grouped according to their drug choices : 'non-choosers ' never chose drug , whereas 'choosers ' always chose drug . The two groups were compared on their subjective responses to drug and on demographic variables . Ethanol decreased Arousal , Elation , Positive Mood and Vigor , and increased Anxiety , Depression and Fatigue in the non-choosers , whereas it increased Arousal and Vigor in the choosers . Ethanol choosers were also more likely to be males and/or full-time students than non-choosers . Diazepam produced sedative-like effects in both choosers and non-choosers , but markedly decreased Anxiety and increased Friendliness in choosers only . Diazepam choice was also associated with more frequent recreational use of marijuana and stimulants . Thus , both demographic variables and subjective drug effects were related to drug preference .

ethanol

diazepam

ethanol

diazepam

placebo

Ethanol

Ethanol

Diazepam

Diazepam

increased Anxiety

Depression

and Fatigue

increased Arousal

Vigor

sedative-like effects

drug preferences

normal

males


Effectiveness of a calculus scaling gel . This study evaluated the effect of a calculus scaling gel ( SofScale ) on time and ease of the scaling procedure in a double-blind , split-mouth clinical study of 32 subjects . The Volpe-Manhold calculus index was used to quantify the distribution and amount of calculus deposition on the lingual aspect of the mandibular 6 anterior teeth at baseline . The gel was applied directly to the calculus and subgingivally to the area to be scaled . Pre- and post-treatment gingival and stain indices were taken . Operator and subject questionnaires were completed immediately after treatment to determine ease of the scaling procedure . Results were analyzed with paired t-tests . The time difference in scaling between the product and placebo side was not significant . This study found that SofScale is safe to gingival tissues and does not promote tooth sensitivity . However , this study did not find significant differences in scaling time between product and placebo when using a 2-minute gel contact time .

calculus scaling gel

calculus scaling gel ( SofScale )

Volpe-Manhold calculus index

gel

SofScale

placebo

time and ease of the scaling procedure

Volpe-Manhold calculus index

Operator and subject questionnaires

time difference in scaling

gingival tissues

tooth sensitivity

32 subjects .


Paromomycin for cryptosporidiosis in AIDS : a prospective , double-blind trial . To test the effects of paromomycin , 10 patients with AIDS and cryptosporidiosis were randomized to paromomycin or placebo in a double-blind trial . After 14 days , patients were switched to the other treatment for 14 additional days . Measures included the number and character of each stool and weekly 24-h stool specimens for weight and oocyst excretion . During the paromomycin treatment phase , oocyst excretion decreased from 314 x 10 ( 6 ) to 109 x 10 ( 6 ) 24 h ( P < .02 ) . Oocyst excretion increased for the 4 patients initially on placebo compared to a median decrease of 128 x 10 ( 6 ) /24 h for the 6 initially treated with drug ( P < .02 ) . Stool frequency also decreased more in those treated with drug ( 3.6 fewer vs. 1.25 fewer/24 h , P < .05 ) . Trends favored drug over placebo for stool weight , stool character , and Karnofsky score . Paromomycin treatment resulted in improvement in both clinical and parasitologic parameters in cryptosporidiosis in AIDS .

Paromomycin

paromomycin

paromomycin

placebo

paromomycin

placebo

drug

placebo

Paromomycin

number and character of each stool

stool specimens for weight

oocyst excretion

oocyst excretion

Oocyst excretion

Stool frequency

stool weight , stool character

Karnofsky score

AIDS :


The biological factors in the etiopathogenesis and management of cervical spondylosis . Two hundred cases of cervical spondylosis were studied for 1 to 4 average ( 2 1/2 ) years . No co-relation could be established between the clinical features and the radiological findings in these cases . It was found that parasites play an important role in the multifactorial etiology of this condition and their eradication by deworming drugs gives better results than the traditional therapies . Many new hypotheses are proposed to explain the same .

deworming drugs

cervical spondylosis

Two hundred

cervical spondylosis


Surrogate and auxiliary endpoints in clinical trials , with potential applications in cancer and AIDS research . Surrogate endpoints have been defined by Prentice as response variables that can substitute for a 'true ' endpoint for the purpose of comparing specific interventions or treatments in a clinical trial . The applicability of this definition , and of related surrogate endpoint criteria , is discussed , with emphasis on cancer and AIDS research settings . Auxiliary endpoints are defined as response variables , or covariates , that can strengthen true endpoint analyses . Specifically , such response variables provide some additional information on true endpoint occurrence times for study subjects having censored values for such times . Auxiliary variables will very frequently be available , and they may be able to be used without making additional strong assumptions . Approaches to the use of auxiliary variables using ideas based on augmented score and augmented likelihood methods are described .

Surrogate

auxiliary endpoints

Surrogate endpoints

Auxiliary endpoints

Auxiliary variables

auxiliary variables

AIDS

cancer

AIDS


Deliberate mild intraoperative hypothermia for craniotomy . BACKGROUND Despite enthusiasm for the use of mild hypothermia during neurosurgical procedures , this therapy has not been evaluated systematically . This study examined the feasibility and safety of deliberate mild hypothermia and rewarming . METHODS Thirty patients scheduled for craniotomy were assigned to either a normothermic or mildly hypothermic group . Tympanic membrane temperature was monitored at anesthetic induction , throughout the isoflurane-fentanyl-N2O-O2 anesthetic , and for 18 h postoperatively . Normothermic patients were warmed to 36.5-37.0 degrees C after an initial temperature decrease , and hypothermic patients were cooled to 35 degrees C. In the hypothermic group temperatures were allowed to drift to 34.5 degrees C before rewarming was initiated . Water blankets and convective heating devices were used to cool and rewarm . RESULTS The minimum temperature achieved by the hypothermic group was 34.3 +/- 0.4 degrees C. Cooling occurred at a rate of 1.0 +/- 0.4 degrees C/h . Rewarming took place at a rate of 0.7 +/- 0.6 degrees C/h ( range 0.1-1.8 ) in the hypothermic group . Hypothermia did not delay emergence from anesthesia ( 20 +/- 15 min ) compared with normothermia ( 15 +/- 15 min , P = .45 ) . Mean temperature upon intensive care unit admission was 35.8 +/- 1.0 degrees C for the hypothermic group and 37.1 +/- 0.5 degrees C for the normothermic group ( P < 0.0001 ) . The hypothermic patients had more postoperative shivering . From 8 to 18 h postoperatively the temperatures of the two groups were similar except for a slightly greater temperature in the hypothermic patients at 12 h ( 37.6 +/- 0.5 vs. 37.3 +/- 0.4 degrees C , P = .029 ) . CONCLUSIONS Although deliberate mild hypothermia is easily achieved intraoperatively , complete rewarming may be difficult to attain during craniotomy with current methods . In addition to the need for determining whether deliberate mild hypothermia confers cerebral protection in humans , the potential risks of the therapy need to be further characterized .

mild intraoperative hypothermia

mild hypothermia

normothermic or mildly hypothermic

isoflurane-fentanyl-N2O-O2 anesthetic

Hypothermia

minimum temperature

Cooling

Rewarming

Hypothermia

anesthesia

postoperative shivering .

temperatures

temperature


Evolution of coronary stenoses is related to baseline severity -- a prospective quantitative angiographic analysis in patients with moderate coronary disease . INTACT Investigators . International Nifedipine Trial on Antiatherosclerotic Therapy . A correlation of the angiographic evolution of coronary stenoses ( stenosis diameter > or = 20 % ) with morphological stenosis parameters at baseline could help to identify the risk of progressive stenoses . Therefore , the data of the prospective INTACT study ( International Nifedipine Trial on Antiatherosclerotic Therapy ) were reviewed . In 348 patients with moderate coronary artery disease , standardized coronary angiograms were taken 3 years apart and were quantitatively analysed . Changes in the minimal diameter of the 1063 preexisting coronary stenoses compared between both angiograms were set in relation to a number of conventional stenosis parameters at baseline . Regression analysis demonstrated a significant correlation of the changes in minimal diameter with baseline % diameter stenosis ( r = 0.30 ; P < 0.001 ) , minimal diameter ( r = -0.28 ; P < 0.001 ) and reference diameter of stenoses ( r = -0.14 ; P < 0.001 ) . The changes were not correlated with stenosis length and plaque area . The baseline parameters of 22 preexisting stenoses progressing to occlusions differed from those remaining patent only with regard to the % diameter stenosis ( 43 +/- 9 % vs 39 +/- 11 % ; P < 0.05 ) . Additional progression of coronary disease became manifest through development of 228 stenoses and 19 occlusions at arterial sites free from definitive stenoses in the baseline angiograms . Thus , progression of atherosclerosis predominantly occurred in mild preexisting coronary stenoses and developed at previously angiographically normal sites . Since the conventional angiographic parameters analysed in this study failed to identify individual arterial sites with an increased risk for progression , definition of new angiographic parameters or application of new techniques seem mandatory to this end .

standardized coronary angiograms

minimal diameter

correlation

changes in minimal diameter

baseline % diameter stenosis

minimal diameter

reference diameter of stenoses

changes were not correlated

stenosis length and plaque area .

progressing to occlusions

remaining patent

% diameter stenosis

progression of coronary disease

stenoses

occlusions

moderate coronary disease

moderate coronary artery disease ,


A comparison of albuterol solution nebulized versus albuterol powder given by breath activated metered dose inhaler . The goal of the present study was to compare the efficacy of nebulized vs powdered albuterol in patients with exacerbated bronchial asthma who required hospitalization . From January to May 1990 known asthmatics admitted with acute exacerbation were included by established criteria . Two groups were randomized . Group I for Albuterol powder 200 micrograms inhaled q 4 hours . Group II with Albuterol nebulized solution 2.5 mg inhaled q 4 hrs . Force Vital Capacity and Force Expiratory Volume in one second were measured with a pressure differential transducer upon admission , 30 minutes and 24-hours following therapies . Absolute FEV1 improvement was calculated . Statistical analysis was performed using student 's T-Test and Fisher 's exact Test with significance established at p > 0.01 % . Fifteen patients enrolled in both groups , two patients of group I were excluded from the statistic analysis due to refusal to continue with the therapy . Both groups were comparable with respect to sex , asthma exacerbations/year , smoking history and hospital length of stay . FVC and FEV1 were comparable also . In contrast , there were significant difference when the absolute improvement were compared . The mean +/- SE for FEV1 absolute improvement at the first 30 min was 0.42 +/- 0.08 lts for the Group I versus 0.65 +/- 0.6 lts in the Group II . In the next 24 hours , Group I was 0.16 +/- 0.2 lts versus 0.30 +/- 0.7 lts in Group II ( p > .01 ) . We conclude that although the dose equivalence of both delivery systems have not been established in our study , the nebulized solution was more effective during the first 24 hours of hospitalization than the dry powder .

albuterol solution nebulized

albuterol powder

nebulized

powdered albuterol

Albuterol powder

Albuterol nebulized solution

nebulized solution

dry powder

Absolute FEV1 improvement

FVC and FEV1

mean +/- SE for FEV1

From January to May 1990

acute exacerbation

Fifteen