Treating the substance-abusing suicidal patient . Studies concerning the treatment of substance-abusing suicidal patients are scarce despite the frequent presence of suicidal behavior among this population . Indeed , suicidality ( ideation or behavior ) is generally an exclusion criterion for participation in treatment studies of subjects with alcohol or drug abuse . Consequently , to date , little is known about the optimal treatment of this population . The first study involving substance-abusing suicidal patients was an open-label trial conducted in the early 1990s . This study involved 12 patients , all of whom demonstrated recent suicidal ideations and had made a lifetime suicide attempt . The results of that open-label study demonstrated significant within-group improvement in both depressive symptoms ( including suicidal ideations ) and level of drinking . However , substantial residual depressive symptoms and drinking persisted at the end of the trial . Also , because no placebo control group was utilized , the authors of that study could not rule out the possibility that the apparent therapeutic effect from fluoxetine was the result of the placebo effect . To date , only one double-blind , placebo-controlled study of subjects with alcohol or substance abuse has included substantial numbers of suicidal patients . The study involved 51 subjects , of whom 20 ( 39 % ) had made a suicide attempt in the current depressive episode , 31 ( 61 % ) had made a suicide attempt in their lifetime , and 46 ( 90 % ) had reported suicidal ideations in the week before hospitalization . The results of that double-blind , placebo-controlled study suggest that fluoxetine was effective in decreasing but not eliminating both the depressive symptoms ( including suicidal ideations ) and the level of alcohol consumption among a study group of subjects with comorbid major depressive disorder and alcohol dependence , many of whom displayed suicidal ideations . A secondary data analysis from that study suggested that cigarette smoking is also significantly decreased by fluoxetine , but the magnitude of the decrease is limited and few of these patients totally quit smoking with fluoxetine treatment alone . Another secondary data analysis from that study suggested that marijuana smoking was also significantly decreased in a subgroup of subjects who demonstrated cannabis abuse and that the magnitude of this improvement was robust . A third secondary data analysis from that study suggested that cocaine abuse acts as a predictor of poor outcome for both depressive symptoms ( including suicidality ) and level of alcohol use in this population . The results of a 1-year naturalistic follow-up study involving the patients from that study suggest that the benefits of fluoxetine in decreasing depressive symptoms and level of drinking persist 1 year after entering the treatment program . To date , no other double-blind , placebo-controlled studies involving substantial numbers of substance-abusing suicidal patients have been reported to either confirm or refute these findings . Further studies are clearly warranted to evaluate the efficacy of various pharmacotherapeutic agents and various psychotherapies in the treatment of substance-abusing suicidal patients .

open-label study

placebo

fluoxetine

placebo

placebo-controlled

placebo-controlled

fluoxetine

fluoxetine

placebo-controlled

depressive symptoms and drinking

cigarette smoking

marijuana smoking

cocaine abuse

substance-abusing suicidal

substance-abusing suicidal

alcohol or drug abuse

substance-abusing suicidal

recent suicidal ideations

had made a lifetime suicide attempt

alcohol or substance abuse

suicide attempt in their lifetime

suicidal ideations

substance-abusing suicidal

substance-abusing suicidal


Gabapentin but not vigabatrin is effective in the treatment of acquired nystagmus in multiple sclerosis : How valid is the GABAergic hypothesis ? Acquired nystagmus occurs frequently in patients with multiple sclerosis and is often the cause of illusory motion of the environment ( oscillopsia ) , and blurring of vision . Based primarily on the beneficial effect of gabapentin on acquired pendular nystagmus ( APN ) , a GABAergic mechanism in controlling nystagmus has been hypothesised . If increasing GABA concentrations in the CNS are critical for the treatment of nystagmus , then a selective GABAergic drug should be highly successful . However , as gabapentin is not a selective GABAergic agent , vigabatrin , a " pure " GABAergic medication , and gabapentin , were compared in a single blind cross over trial in eight patients with definite multiple sclerosis . Patients were randomly assigned to begin with gabapentin ( 1200 mg daily ) or vigabatrin ( 2000 mg daily ) . Neuro-ophthalmological and electro-oculographic ( EOG ) evaluations were performed four and three times , respectively . Treatment efficacy was based on improving visual acuity and EOG indices ( amplitude or frequency of nystagmus , or both ) by at least 50 % of pretreatment values . Three out of eight patients dropped out due to adverse effects . In the remaining five patients gabapentin improved symptomatic pendular or gaze evoked jerk nystagmus in four . Three patients decided to continue gabapentin therapy . Importantly , vigabatrin proved useful in only one out of five patients , suggesting that gabapentin effectiveness may be related to additional non-GABAergic mechanisms of action . Interaction with cerebral glutamate transmission by inhibition of NMDA receptor might be an alternative hypothesis for the therapeutic action of gabapentin .

efficacy

visual acuity

adverse effects

acquired nystagmus

multiple sclerosis

eight

definite multiple sclerosis

dropped out due to adverse effects

Three


Four-year outcomes from adolescent alcohol and drug treatment . OBJECTIVE Knowledge of treatment response for alcohol and drug problems among adults is mounting ; less is known about long-term outcome for adolescents who receive treatment for alcohol and drug problems . The current study examined youth substance involvement over 4 years ( using five waves of data collection ) following treatment for alcohol and drug abuse . METHOD A cohort of youth ( N = 162 , 60 % male ) treated during adolescence ( mean age = 16 years ) was followed into young adulthood , a period associated with stabilization of alcohol use patterns and elevated risk for life problems secondary to both alcohol and drug use . Participants ( 14-18 years old ) were consecutive admissions to inpatient adolescent alcohol and drug treatment centers in San Diego that were abstinence focused and based on the 12-step approach . RESULTS Alcohol and other drug use were reduced during the 4 years posttreatment , with the exception of nicotine . The greatest prevalence reduction occurred for stimulants ; modest changes were evident in alcohol and marijuana use . Nicotine was the most commonly used substance throughout the 4 years after treatment . Several distinct substance involvement trajectories were evident during the 4 years following treatment . CONCLUSIONS Alcohol and drug use patterns during the 4 years following treatment highlight both changes and diversity in substance involvement as youth make the transitions from middle to late adolescence and into young adulthood . Findings demonstrate the importance of identifying transitional periods and the need for alternative intervention strategies that may help the progression of this population into young adulthood .

adolescent alcohol and drug treatment

treatment for alcohol and drug problems

treatment for alcohol and drug abuse

Alcohol and other drug use

prevalence reduction

adolescent

adolescents

alcohol and drug problems

youth

adolescence

16 years )

young adulthood

14-18 years old


Effect of ischaemic preconditioning , cardiopulmonary bypass and myocardial ischaemic/reperfusion on free radical generation in CABG patients . OBJECTIVE To investigate the free radicals ( FR ) generation after ischaemic preconditioning and cardiopulmonary bypass and during reperfusion in CABG patients , and the role of ischaemic preconditioning . METHODS Forty-three CABG patients were randomised into an ischaemic preconditioning and a control group . The protocol for ischaemic preconditioning was two cycles of 2-min ischaemia followed by 3-min reperfusion . Free radicals were measured using electron spin resonance spectroscopy . Global and right heart functions were collected . RESULTS The free radicals generation in coronary sinus blood in the ischaemic preconditioning group was 9.7 and 16.6 % after the ischaemic preconditioning protocol and 10 min after declamping , 6.8 and 13.3 % in the controls . The free radicals in arterial samples were , respectively , 21 , 14 , 10 and 9 % at 10 min , 1 , 2 and 24 h after reperfusion . Cardiac index ( CI ) and right ventricular ejection fraction ( RVEF ) were improved by ischaemic preconditioning . CONCLUSION Both ischaemic preconditioning and cardiopulmonary bypass induced free radicals generation . Although ischaemic preconditioning had no effect on free radicals generation after the operation , it protected against postoperative stunning .

ischaemic preconditioning

cardiopulmonary bypass

myocardial ischaemic/reperfusion

ischaemic preconditioning

cardiopulmonary bypass

ischaemic preconditioning

ischaemic preconditioning

ischaemic preconditioning

ischaemia

reperfusion

ischaemic preconditioning

ischaemic preconditioning

ischaemic preconditioning

ischaemic preconditioning

cardiopulmonary bypass

ischaemic preconditioning

free radical generation

Free radicals

Global and right heart functions

free radicals in arterial samples

Cardiac index ( CI )

free radicals generation

free radicals generation

CABG

CABG

Forty-three

CABG


Nicotine infusion acutely impairs insulin sensitivity in type 2 diabetic patients but not in healthy subjects . OBJECTIVES The aim of this study was to examine if an acute nicotine infusion alters insulin sensitivity to a similar degree in type 2 diabetic patients as in healthy control subjects . DESIGN . Double-blind , cross-over , placebo-controlled , randomized experimental study . Nicotine 0.3 microg kg-1 min ( -1 ) or NaCl was infused ( 2 h ) during a euglycaemic hyperinsulinaemic clamp ( 4 h ) to assess insulin sensitivity . SETTING University research laboratory . SUBJECTS Six male and female type 2 diabetic patients [ DM2 ; age 54 +/- 10 ( mean +/- SD ) years ; body mass index ( BMI ) 25.6 +/- 2.9 kg m ( -2 ) ] treated with diet or one oral hypoglycaemic agent and six age- and BMI-matched control subjects ( Ctr ) . MAIN OUTCOME MEASURE Insulin sensitivity ( rate of glucose infusion per kg fat free body mass and minute ) , nicotine and free fatty acid ( FFA ) levels , pulse rate and blood pressure . RESULTS The infusions produced similar nicotine levels in both groups . In the absence of nicotine , DM2 were more insulin resistant than Ctr ( 6.7 +/- 0.4 vs. 10.9 +/- 0.3 mg kg-1 LBM min ( -1 ) , respectively ; P < 0.0001 ) . This insulin resistance was further aggravated by the nicotine infusion in DM2 but not in Ctr ( 4.6 +/- 0.3 vs. 10.9 +/- 0.3 mg kg ( -1 ) LBM min ( -1 ) ; P < 0.0001 ) . Only minor differences were seen in FFA levels , pulse rates and blood pressure . CONCLUSIONS At this low infusion rate , nicotine aggravated the insulin resistance in DM2 but not in Ctr . This finding may be because of the ( dysmetabolic ) diabetic state per se or to an increased sensitivity to environmental factors associated with a genetic predisposition for type 2 diabetes . These results show that diabetic subjects are particularly susceptible to the detrimental effects of nicotine .

Nicotine

nicotine

placebo-controlled

Nicotine

or NaCl was infused

nicotine

nicotine

nicotine

pulse rate

blood pressure

insulin resistant

insulin resistance

FFA levels

pulse rates

blood pressure

insulin resistance

type 2 diabetic patients


The clinical and biochemical effects of propofol infusion with and without EDTA for maintenance anesthesia in healthy children undergoing ambulatory surgery . UNLABELLED We conducted this randomized , double-blinded , comparative , parallel-group study to determine whether adding EDTA to propofol would affect the clinical profile , calcium and magnesium homeostasis , or renal function in healthy children . After the induction of anesthesia with halothane , 69 ambulatory surgical patients ( 1 mo to < 17 yr old ) , received propofol without EDTA ( n = 33 ) or propofol with EDTA ( n = 36 ) . Blood samples were obtained for the measurement of ionized calcium , ionized magnesium , and laboratory indicators of renal function . Hemodynamic measurements , recovery , and adverse events were recorded . Propofol with EDTA produced no significant effects on clinical efficacy or renal function . Propofol and propofol EDTA produced a statistically significant decrease from baseline in serum concentrations of ionized calcium and magnesium during infusion ( P < 0.05 ) , but with no apparent clinical effect . Hemodynamic measurements generally remained stable and were similar for both groups . Statistically significant changes in systolic blood pressure , mean arterial pressure , and heart rate were not considered clinically significant . Adverse events were mild or moderate . The addition of EDTA does not alter the clinical profile of propofol in pediatric ambulatory surgical patients . With or without EDTA , propofol is associated with a decrease in ionized calcium with no apparent clinical effect . IMPLICATIONS The addition of EDTA does not alter the clinical profile of propofol in pediatric ambulatory surgical patients . With or without EDTA , propofol is associated with a decrease in ionized calcium with no apparent clinical effect .

propofol

with and without EDTA

EDTA to propofol

induction of anesthesia with halothane

propofol without EDTA

propofol with EDTA

Propofol with EDTA

Propofol

propofol EDTA

EDTA

EDTA

propofol

Blood samples

Hemodynamic measurements , recovery

adverse events

clinical efficacy or renal function .

Hemodynamic measurements

ionized calcium

ionized calcium

children

ambulatory surgery

children

ambulatory surgical

1 mo to < 17 yr old

ambulatory surgical

ambulatory surgical


Patient positioning influences oxygen saturation in the acute phase of stroke . We evaluated arterial oxygen saturation ( SaO ( 2 ) ) and heart rate in acute stroke patients to determine whether routine positioning affected these physiological parameters . Measurements were recorded at the bedside non-invasively in five different positions assigned in random order each maintained for 10 min . One hundred and twenty-nine patients examined within a median of 72 h , lying on the left side resulted in slightly lower SaO ( 2 ) than lying on the right side , which was statistically significant in the patients with a right ( n = 66 ) , but not left , hemiparesis . Patients able to sit in a chair ( n = 65 ) , who mostly had less severe strokes , had a significantly higher mean SaO ( 2 ) and heart rate when sitting in the chair than when placed in any other position . About 10 % of patients , especially those with a severe stroke , with right hemiparesis and concomitant chest disease , experienced falls in SaO ( 2 ) to 90 % or less for > /=2 min in certain positions ; the hypoxia was more likely when they were lying on their left side . These results may have implications for current practice and for future patient positioning strategies to improve outcome after stroke .

five different positions

median

lying on the left side

lying on the right side

sit in a chair

lying on their left side

oxygen saturation

heart rate

SaO ( 2 )

mean SaO ( 2 )

heart rate

SaO ( 2 )

hypoxia

acute phase

stroke

One hundred and twenty-nine


Brief report : case reports on naltrexone use in children with autism : controlled observations regarding benefits and practical issues of medication management .

naltrexone

benefits

practical issues

autism :


Risk factors for malnutrition in patients undergoing gastroenterological and hernia surgery : an analysis of 374 patients . OBJECTIVE The aim of this study was to assess the nutritional status of 374 surgical patients with gastrointestinal disease and hernias of the abdominal wall ; to identify risk factors associated with a poorer nutritional status in this group of patients and to assess awareness of the patient 's nutritional status by medical teams . SUMMARY BACKGROUND DATA Malnutrition is prevalent among surgical patients and is associated with higher surgical complication rates and mortality . The major causes of poor nutritional status are related to the underlying disease , socio-economic factors , age , and length of hospitalization . Despite its high prevalence , medical teams often overlook malnutrition , and screening of these patients is not routine . It is of utmost importance to identify patients at risk for malnutrition in order to prevent related complications . METHODS The 374 patients evaluated in this study were a subgroup of a larger multicenter , cross-sectional , randomized study that was carried out in 1996 . Nutritional status was assessed by using Subjective Global Assessment . RESULTS Malnutrition was present in 55 % of the patients , with 19 % of the patients severely malnourished . The presence of cancer , infection , age over 60 years , upper gastrointestinal disease , and longer length of hospital stay all negatively influenced nutritional status . Despite the high prevalence of malnutrition , the medical teams only assessed the nutritional status of a few patients . CONCLUSION Malnutrition was highly prevalent in this setting of patients . Therefore , patients with the risk factors above presented should routinely undergo nutritional screening and/or assessment in order to be able to early diagnose or prevent malnutrition and its correlated morbidity and mortality .

gastroenterological and hernia surgery

Nutritional status

Subjective Global Assessment .

Malnutrition

nutritional status

malnutrition

nutritional

Malnutrition


Comparison of enoxaparin and standard heparin in gynaecologic oncologic surgery : a randomised prospective double-blind clinical study . OBJECTIVE This study aimed to compare the haemorrhagic complications and efficacy of enoxaparin , a low molecular weight heparin ( LMWH ) , and conventional standard heparin ( SH ) in gynaecological oncologic surgery . MATERIALS METHODS A double blind , randomised trial was performed on 102 consecutive women undergoing gynaecologic cancer surgery with pelvic and paraaortic lymphadenectomy . The women were separated into those who were given 2,500 IU enoxaparin once daily and SH in a dose of 5,000 IU three times daily . The groups were analysed for intraoperative blood loss , drainage , transfusion requirements , perioperative haemoglobin decrease , wound haematoma , and clinical deep venous thrombosis . RESULTS The two groups were well matched for age , weight , and other factors , which could predispose to the development of deep venous thrombosis ( DVT ) and haemorrhage . No patient developed clinical significant DVT , wound haematoma or intra-abdominal bleeding . There was no significant difference in bleeding complications between the two regimens . The antiFXa level in the plasma was correlated strongly with patient weight . CONCLUSIONS A dose of 2,500 IU enoxaparin/day does not cause more bleeding complications than SH 5,000 IU three times daily when used to prevent thrombosis . However , the dose of enoxaparin must be adjusted to the patient 's weight .

enoxaparin

standard heparin

enoxaparin

standard heparin ( SH )

enoxaparin

SH

enoxaparin/day

haemorrhage

DVT

wound haematoma

intra-abdominal bleeding

bleeding complications

antiFXa level

gynaecologic oncologic surgery :


Lamotrigine therapy for autistic disorder : a randomized , double-blind , placebo-controlled trial . In autism , glutamate may be increased or its receptors up-regulated as part of an excitotoxic process that damages neural networks and subsequently contributes to behavioral and cognitive deficits seen in the disorder . This was a double-blind , placebo-controlled , parallel group study of lamotrigine , an agent that modulates glutamate release . Twenty-eight children ( 27 boys ) ages 3 to 11 years ( M = 5.8 ) with a primary diagnosis of autistic disorder received either placebo or lamotrigine twice daily . In children on lamotrigine , the drug was titrated upward over 8 weeks to reach a mean maintenance dose of 5.0 mg/kg per day . This dose was then maintained for 4 weeks . Following maintenance evaluations , the drug was tapered down over 2 weeks . The trial ended with a 4-week drug-free period . Outcome measures included improvements in severity and behavioral features of autistic disorder ( stereotypies , lethargy , irritability , hyperactivity , emotional reciprocity , sharing pleasures ) and improvements in language and communication , socialization , and daily living skills noted after 12 weeks ( the end of a 4-week maintenance phase ) . We did not find any significant differences in improvements between lamotrigine or placebo groups on the Autism Behavior Checklist , the Aberrant Behavior Checklist , the Vineland Adaptive Behavior scales , the PL-ADOS , or the CARS . Parent rating scales showed marked improvements , presumably due to expectations of benefits .

Lamotrigine therapy

lamotrigine

received either placebo

lamotrigine twice daily

lamotrigine

placebo

improvements in language

communication

socialization

Parent rating scales

autistic disorder :

Twenty-eight

children

ages 3 to 11 years


Children 's attitudes and behavioral intentions toward a peer with autistic behaviors : does a brief educational intervention have an effect ? This study examined children 's ratings of attitudes and behavioral intentions toward a peer presented with or without autistic behaviors . The impact of information about autism on these ratings was investigated as well as age and gender effects . Third- and sixth-grade children ( N = 233 ) were randomly assigned to view a video of the same boy in one of three conditions : No Autism , Autism , or Autism/Information . Children at both grade levels showed less positive attitudes toward the child in the two autism conditions . In rating their own behavioral intentions , children showed no differences between conditions . However , in attributing intentions to their classmates , older children and girls gave lower ratings to the child in the autism conditions . Information about autism did not affect ratings of either attitudes or behavioral intentions as ascribed to self or others .

educational intervention

attitudes and behavioral intentions

attitudes and behavioral intentions

less positive attitudes

behavioral intentions

lower ratings

attitudes or behavioral intentions


Ipratropium bromide nasal spray for treatment of rhinorrhea in the laryngectomized patient : a pilot study . Many who have had a total laryngectomy complain of unrelenting rhinorrhea that is often very difficult to control . This study was undertaken to evaluate the effect of ipratropium bromide ( IB ) , an anticholinergic nasal spray , on rhinorrhea in these patients . This was designed as a prospective , randomized , double-blind , placebo-controlled , crossover pilot study . Participants were selected if they had a total laryngectomy and complained of rhinorrhea . They were asked to rate the severity and duration of their rhinorrhea each day throughout the study on a scale from zero to six . Each participant was initially given a saline nasal spray for one week . They were then randomized to use either IB or saline for the double-blinded portion of the study . Two sprays of IB at a dose of 42 micrograms/spray ( 0.06 % ) , or saline , were administered intranasally twice daily for two weeks , after which time the participants were given another nasal spray ( either IB or saline ) for the crossover portion of the study . Six patients entered and completed the study . Those patients using the IB recorded a mean 55 % decline in severity and a mean 51 % decline in duration of the rhinorrhea as compared to placebo . The relief in both severity and duration of rhinorrhea obtained by patients was analyzed using the Wilcoxon signed-rank test and found to be highly significant ( p < 0.001 ) . Despite the limitations of a small sample size in this study , ipratropium bromide nasal spray significantly reduced both the severity and duration of rhinorrhea in laryngectomized patients . We suggest ipratropium nasal spray as a safe , effective way to treat chronic rhinorrhea in laryngectomized patients , improving their quality of life .

Ipratropium bromide nasal spray

ipratropium bromide ( IB )

placebo-controlled

saline nasal spray

IB

saline

IB

saline

IB

saline

severity

duration of their rhinorrhea

decline in severity

decline in duration of the rhinorrhea

severity and duration of rhinorrhea

Wilcoxon signed-rank test

severity and duration of rhinorrhea

quality of life

rhinorrhea

laryngectomized patient

total laryngectomy

rhinorrhea

Six


Uncomplicated moderate coronary artery dissections after balloon angioplasty : good outcome without stenting . OBJECTIVE To study the relation between moderate coronary dissections , coronary flow velocity reserve ( CFVR ) , and long term outcome . METHODS 523 patients undergoing balloon angioplasty and sequential intracoronary Doppler measurements were examined as part of the DEBATE II trial ( Doppler endpoints balloon angioplasty trial Europe ) . After successful balloon angioplasty , patients were randomised to stenting or no further treatment . Dissections were graded at the core laboratory by two observers and divided into four categories : none , mild ( type A-B ) , moderate ( type C ) , severe ( types D to F ) . Patients with severe dissections ( n = 128 ) or without available reference vessel CFVR ( n = 139 ) were excluded . The remaining 256 patients were divided into two groups according to the presence ( group A , n = 45 ) or absence ( group B , n = 211 ) of moderate dissection . RESULTS Following balloon angioplasty , there was no difference in CFVR between the two groups . At 12 months follow up , a higher rate of major adverse cardiac events was observed overall in group A than in group B ( 10 ( 22 % ) v 23 ( 11 % ) , p = 0.041 ) . However , the risk of major adverse events was similar in the subgroups receiving balloon angioplasty ( group A , 6 ( 19 % ) v group B , 16 ( 16 % ) , NS ) . Among group A patients , the adverse events risk was greater in those randomised to stenting ( odds ratios 6.603 v 1.197 , p = 0.046 ) , whereas there was no difference in risk if the group was analysed according to whether the CFVR was < 2.5 or > /= 2.5 after balloon angioplasty . CONCLUSIONS Moderate dissections left untreated result in no increased risk of major adverse cardiac events . Additional stenting does not improve the long term outcome .

stenting

balloon angioplasty

balloon angioplasty

stenting

or no further treatment

CFVR

major adverse cardiac events

risk of major adverse events

adverse events risk

risk of major adverse cardiac events

256 patients


Famotidine treatment of children with autistic spectrum disorders : pilot research using single subject research design . Using single subject research design , we performed pilot research to evaluate the safety and efficacy of famotidine for the treatment of children with autistic spectrum disorders . We studied 9 Caucasian boys , 3.8-8.1 years old , with a DSM-IV diagnosis of a pervasive developmental disorder , living with their families , receiving no chronic medications , and without significant gastrointestinal symptoms . The dose of oral famotidine was 2 mg/kg/day ( given in two divided doses ) ; the maximum total daily dose was 100 mg . Using single-subject research analysis and medication given in a randomized , double-blind , placebo-controlled , cross-over design , 4 of 9 children randomized ( 44 % ) had evidence of behavioral improvement . Primary efficacy was based on data kept by primary caregivers , including a daily diary ; daily visual analogue scales of affection , reciting , or aspects of social interaction ; Aberrant Behavior Checklists ( ABC , Aman ) ; and Clinical Global Improvement scales . Children with marked stereotypy ( meaningless , repetitive behaviors ) did not respond . Our subjects did not have prominent gastrointestinal symptoms and endoscopy was not part of our protocol ; thus , we can not exclude the possibility that our subjects improved due to the effective treatment of asymptomatic esophagitis . The use of famotidine for the treatment of children with autistic spectrum disorders warrants further investigation .

Famotidine

famotidine

famotidine

behavioral improvement

Clinical Global Improvement scales

gastrointestinal symptoms

autistic spectrum disorders

autistic spectrum disorders

9 Caucasian

3.8-8.1 years


Valsartan alone or with a diuretic or ACE inhibitor as treatment for African American hypertensives : relation to salt intake . Previous clinical trials have demonstrated the important influence of ethnicity and dietary salt on the antihypertensive efficacy of drugs that block the renin angiotensin system . Angiotensin II receptor blockers are a new therapeutic entity that have not been widely studied in African American hypertensives , either alone , or in combination with other therapies such as diuretics or angiotensin converting enzyme inhibitors . We performed a pilot , prospective , open label , randomized design clinical trial to evaluate the effects of the angiotensin II receptor blocker valsartan ( 160 mg once a day ) on systolic and diastolic blood pressure in hypertensive African Americans ( n = 88 ) on a low salt ( 100 mEq Na+/day ) for 2 weeks and the same diet supplemented by 100 mEq Na+ for 4 weeks . After this evaluation , while continuing the Na+ supplementation , patients were randomized to valsartan 320 mg/day ( n = 28 ) , or the addition of hydrochlorothiazide ( HCTZ ) 12.5 mg/day ( n = 30 ) , or benazepril 20 mg/day to the valsartan 160 mg/day for an additional 6 weeks . Valsartan ( 160 mg/day ) lowered blood pressure significantly in African American patients on both low salt ( -6.4/-4.8 mm Hg : P < .001 ) and a high salt diet ( -4.9/-3.8 mm Hg : P = .01 ) . The high salt diet attenuated the antihypertensive effect slightly ( 1.6/1.3 mm Hg , P = not significant ) . When comparing the efficacy of the three randomized therapeutic regimens while on the Na+ supplement , the valsartan 160 mg/HCTZ 12.5 mg was the most effective therapy with an incremental reduction in blood pressure of -10.5/-6.9 mm Hg ( P < .01 ) , compared to valsartan 160 mg/day alone . Doubling the dose of valsartan to 320 mg incrementally lowered blood pressure by -3.8/-3.3 mm Hg ( P = not significant ) . The least effective approach was adding benazepril 20 mg/day to valsartan 160 mg/day with no incremental reduction in systolic blood pressure and diastolic blood pressure reduction of only 1.7 mm Hg ( P = not significant ) . We conclude that in our open label pilot study , the antihypertensive activity of valsartan is not significantly attenuated by supplemented salt diet in hypertensive African Americans . Moreover , adding a low dose of HCTZ appears to be the most effective strategy in enhancing the antihypertensive activity of this angiotensin II receptor blocker in contrast to either doubling the dose or adding an angiotensin converting enzyme inhibitor .

inhibitor

systolic and diastolic blood pressure

blood pressure

antihypertensive effect

blood pressure

blood pressure

African American hypertensives

hypertensive African Americans

hypertensive African Americans .


There are some benefits for eradicating Helicobacter pylori in patients with non-ulcer dyspepsia . BACKGROUND The relationship between Helicobacter pylori infection and non-ulcer dyspepsia is not established . AIM To determine whether eradication of H. pylori might be of benefit in non-ulcer dyspepsia patients . METHODS We randomly assigned 129 H. pylori infected patients with severe epigastric pain , without gastro-oesophageal reflux symptoms , to receive twice daily treatment with 300 mg of ranitidine , 1000 mg of amoxicillin , and 500 mg of clarithromycin for 7 days and 124 such patients to receive identical-appearing placebos . RESULTS Treatment was successful ( decrease of symptoms at 12 months ) in 62 % of patients in the active-treatment group and in 60 % of the placebo group ( N.S. ) . At 12 months , the rate of eradication of H. pylori was 69 % in the active-treatment group and 18 % in the placebo group ( P < 0.001 ) . Complete relief of symptoms occurred significantly more frequently in patients on the active treatment ( 43 % ) than in placebo-treated patients ( 31 % , P=0.048 ) . Within the active-treatment group , therapeutic success was significantly more frequent in the non-infected patients ( 84 % vs. 64 % , P=0.04 ) . CONCLUSIONS Although eradicating H. pylori is not likely to relieve symptoms in the majority of patients with non-ulcer dyspepsia , a small proportion of H. pylori-infected patients may benefit from eradication treatment .

ranitidine

amoxicillin

clarithromycin

placebos .

rate of eradication of H. pylori

Complete relief of symptoms

therapeutic success

non-ulcer dyspepsia

non-ulcer dyspepsia

pylori infected

severe epigastric pain

without gastro-oesophageal reflux

non-infected

non-ulcer dyspepsia

pylori-infected


Clomipramine versus haloperidol in the treatment of autistic disorder : a double-blind , placebo-controlled , crossover study . Clomipramine , haloperidol , and placebo were compared with baseline in the treatment of autism , and overall outcome , specific symptoms , and side effects were examined . It was hypothesized that clomipramine would be better tolerated than haloperidol and prove superior on a measure of stereotypy . Individuals with a DSM-IV diagnosis of autistic disorder ( mean age , 16.3 years ; range , 10-36 years ) were randomly assigned , by using a Latin square design , to the following 7-week trials : placebo , clomipramine ( mean daily dose , 128.4 mg ; range , 100-150 mg ) , or haloperidol ( mean daily dose , 1.3 mg ; range , 1-1.5 mg ) . Data on 36 subjects were analyzed and taken together ; the results favored haloperidol . In those patients who were able to complete a full therapeutic trial , clomipramine proved comparable to haloperidol in terms of improvement compared with baseline . However , significantly fewer individuals receiving clomipramine versus haloperidol were able to complete the trial ( 37.5 % vs. 69.7 % , respectively ) for reasons related to both side effects and efficacy or behavior problems . In the intent-to-treat sample , which is perhaps more clinically relevant , only haloperidol proved superior to baseline on a global measure of autistic symptom severity , as well as specific measures for irritability and hyperactivity . Clomipramine did not seem more effective on a measure of stereotypy , nor was it better tolerated .

Clomipramine versus haloperidol

placebo-controlled

Clomipramine , haloperidol

placebo

clomipramine

haloperidol

placebo

clomipramine

haloperidol

haloperidol .

clomipramine

haloperidol

clomipramine

haloperidol

haloperidol

Clomipramine

overall outcome

specific symptoms

side effects

improvement

side effects

efficacy

behavior problems

autistic symptom severity

irritability and hyperactivity

autistic disorder :

autism


Sulfasalazine decreases acute gastrointestinal complications due to pelvic radiotherapy . BACKGROUND Radiation-induced gastrointestinal toxicity is a significant concern for patients who are treated with this modality for pelvic malignancies . Eicosanoids and free radicals are thought to be among the reasons for this effect . Sulfasalazine is an inhibitor of their synthesis in the mucosa . OBJECTlVE : To determine whether sulfasalazine can reduce the radiation-induced acute gastrointestinal complications . METHODS In this prospective , double-blind study , 31 patients receiving pelvic radiotherapy were randomized to receive two sulfasalazine 500-mg tablets twice daily or placebo , administered orally from the first day of irradiation . Patients were evaluated weekly , and gastrointestinal toxicities were graded according to the Late Effect of Normal Tissue-Subjective Objective Management Analytic ( LENT-SOMA ) toxicity table during pelvic radiotherapy . On the last day of week 5 , the subjects were graded endoscopically , and biopsies taken from the rectum were classified histopathologically . RESULTS Groups did not differ in age , gender , tumor site , or irradiation procedure . During radiotherapy , grade 2 or higher gastrointestinal toxicity occurred in 20 % ( 3/15 ) and 63 % ( 10/16 ) of the sulfasalazine and placebo groups , respectively . This difference was significant ( p = 0.017 ) . No statistically significant differences were found in endoscopic and histopathologic evaluations . CONCLUSIONS Sulfasalazine is effective in decreasing clinically acute gastrointestinal toxicities . Long-term follow-up with the subjects will help to determine the net effect of sulfasalazine on the radiation-induced gastrointestinal injuries .

Sulfasalazine

Sulfasalazine

sulfasalazine

sulfasalazine

500-mg tablets twice daily

placebo

gastrointestinal toxicities

difference

pelvic malignancies .

pelvic radiotherapy


Comparison of the acute effects of salbutamol and terbutaline on heart rate variability in adult asthmatic patients . This study investigated the effects of beta2-adrenergic agonist therapy on heart rate variability ( HRV ) in adult asthmatic patients by using frequency domain measures of HRV . A randomized crossover design was used . Twenty adult patients with asthma were studied . All patients showed a mild-to-moderate decrease in baseline forced expiratory volume in one second . Any diseases that might have influenced the autonomic function were excluded . All patients had a complete physical examination and medical history that revealed no cardiovascular disease or medication . The study used 200 microg inhaled salbutamol and 500 microg inhaled terbutaline . HRV analysis was performed for each 5-min segment , 5 min before inhalation of the study drug and 5 , 10 , 15 , 20 , 25 and 30 min after inhalation . Total power ( TP : < 0.40 Hz ) , high-frequency power ( HF : 0.15-0.40 Hz ) , low-frequency power ( LF : 0.04-0.15 Hz ) and LF/HF ratio were calculated . The LF and LF/HF ratio increased and TP decreased at 5 , 10 , 15 and 20 min after the salbutamol and the terbutaline inhalation , HF did not change significantly after the salbutamol and terbutaline inhalation . Acute salbutamol and terbutaline inhalation produce similar effects on heart rate variability and increase sympathetic modulation in the cardiac autonomic activity .

salbutamol and terbutaline

salbutamol

inhaled terbutaline

salbutamol

terbutaline

salbutamol

terbutaline

effects

heart rate variability

heart rate variability ( HRV )

forced expiratory volume in one second

Total power

( TP : < 0.40 Hz )

high-frequency power

( HF : 0.15-0.40 Hz )

LF/HF ratio

LF and LF/HF ratio

TP

HF

heart rate variability

sympathetic modulation

adult

asthmatic

Twenty


Does short-term treatment with proton pump inhibitors cause rebound aggravation of symptoms ? BACKGROUND Rebound acid hypersecretion might occur after treatment with proton pump inhibitors . This study looks for a rebound aggravation of symptoms after short-term treatment with lansoprazole . STUDY Sixty-two patients ( 19 men and 43 women ; mean age , 54 years ; range , 32-77 years ) with heartburn and regurgitation and normal upper endoscopy findings were studied in a randomized , double-blind , placebo-controlled trial with a crossover design . There were two 5-day treatment periods with lansoprazole 60 mg once daily or placebo in random order , separated by a 9-day washout period . Reflux , total , and antacid scores were calculated for each of the treatment periods . Higher scores during the placebo period in the group given lansoprazole first than in the group given placebo first indicated a rebound aggravation of symptoms . RESULTS The mean symptom scores during the placebo period in the groups given lansoprazole first and placebo first were as follows : reflux score , 21.5 and 17.6 , respectively ( not significant ) ; total score , 11.2 and 10.3 , respectively ( not significant ) ; and antacid score , 8.2 and 7.2 , respectively ( not significant ) . CONCLUSIONS There is no indication of a rebound aggravation of symptoms 12 to 14 days after a 5-day treatment with lansoprazole 60 mg once daily in patients with reflux symptoms .

proton pump inhibitors

proton pump inhibitors

lansoprazole .

placebo-controlled

lansoprazole 60 mg once daily

placebo

placebo

lansoprazole

placebo

lansoprazole

Reflux , total , and antacid scores

symptom scores

reflux score

total score

antacid score

patients with reflux symptoms .


Olanzapine versus haloperidol in children with autistic disorder : an open pilot study . OBJECTIVES Conventional neuroleptics ameliorate symptoms in children with autistic disorder ; however , they are known to cause dyskinesias . Atypical neuroleptics , including olanzapine , may have less risk for dyskinesia , but their efficacy in autistic disorder is not established . This study was designed to investigate the safety and effectiveness of open-label olanzapine as a treatment for children with autistic disorder by using haloperidol as a standard comparator treatment . METHOD In a parallel groups design , 12 children with DSM-IV autistic disorder ( mean age 7.8+/-2.1 years ) were randomized to 6 weeks of open treatment with olanzapine or haloperidol . Mean final dosages were 7.9+/-2.5 mg/day for olanzapine and 1.4+/-0.7 mg/day for haloperidol . Outcome measures included the Clinical Global Impressions ( CGI ) and the Children 's Psychiatric Rating Scale ( CPRS ) . RESULTS Both groups had symptom reduction . Five of six in the olanzapine group and three of six in the haloperidol group were rated as responders according to the CGI Improvement item . Subjects showed improvement on the CPRS Autism Factor ( F1,9 = 24.4 , p = .0008 ) . Side effects included drowsiness and weight gain . CONCLUSIONS The findings suggest that olanzapine is a promising treatment for children with autistic disorder . Further placebo-controlled and long-term studies of olanzapine in autistic disorder are required .

Olanzapine

haloperidol

neuroleptics

Atypical neuroleptics

olanzapine

haloperidol

open treatment with olanzapine

haloperidol

olanzapine

haloperidol

olanzapine

haloperidol

olanzapine

olanzapine

Clinical Global Impressions ( CGI )

symptom reduction

CGI

CPRS Autism Factor

drowsiness and weight gain

children

autistic disorder

children

autistic disorder ;

children

autistic disorder

DSM-IV autistic disorder

mean age 7.8+/-2.1 years

children

autistic disorder


The effect of neighborhood-based community organizing : results from the Seattle Minority Youth Health Project . OBJECTIVE To evaluate the effect of a community mobilization and youth development strategy to prevent drug abuse , violence , and risky sexual activity . DATA SOURCES/STUDY SETTING Primary surveys of youth , parents , and key neighborhood leaders were carried out at baseline ( 1994 ) and at the end of the intervention period ( 1997 ) . The study took place in four intervention and six control neighborhoods in Seattle . STUDY DESIGN The study was designed as a randomized controlled trial with neighborhood as the unit of randomization . The intervention consisted of a paid community organizer in each neighborhood who recruited a group of residents to serve as a community action board . Key variables included perceptions of neighborhood mobilization by youth , parents , and key neighborhood leaders . DATA COLLECTION/EXTRACTION METHODS Youth surveys were self-administered during school hours . Parent and neighborhood leader surveys were conducted over the phone by trained interviewers . PRINCIPAL FINDINGS Survey results showed that mobilization increased to the same degree in both intervention and control neighborhoods with no evidence of an overall intervention effect . There did appear to be a relative increase in mobilization in the neighborhood with the highest level of intervention activity . CONCLUSION This randomized study failed to demonstrate a measurable effect for a community mobilization intervention . It is uncertain whether the negative finding was because of a lack of strength of the interventions or problems detecting intervention effects using individual-level closed-end surveys .

neighborhood-based community organizing

community mobilization intervention

drug abuse

violence

risky sexual activity

mobilization

mobilization

level of intervention activity

mobilization intervention

Seattle Minority

Youth

Health Project

youth

parents

six


Comparison of thiopentone/guaifenesin , ketamine/guaifenesin and ketamine/midazolam for the induction of horses to be anaesthetised with isoflurane . Forty-eight horses subjected to elective surgery were randomly assigned to three groups of 16 horses . After premedication with 0.1 mg/kg acepromazine intramuscularly and 0.6 mg/kg xylazine intravenously , anaesthesia was induced either with 2 g thiopentone in 500 ml of a 10 per cent guaifenesin solution , given intravenously at a dose of 1 ml/kg ( group TG ) , or with 100 mg/kg guaifenesin and 2.2 mg/kg ketamine given intravenously ( group KG ) , or with 0.06 mg/kg midazolam , and 2.2 mg/kg ketamine given intravenously ( group KM ) . Anaesthesia was maintained with isoflurane . The mean ( sd ) end tidal isoflurane concentration ( per cent ) needed to maintain a light surgical anaesthesia ( stage III , plane 2 ) was significantly lower in group KM ( 0.91 [ 0.03 ] ) than in groups TG ( 1.11 [ 0.03 ] ) and KG ( 1.14 [ 0.03 ] ) . The mean ( sd ) arterial pressure ( mmHg ) was significantly lower in group KG ( 67.4 [ 2.07 ] ) than in groups TC ( 75.6 [ 2.23 ] ) and KM ( 81.0 [ 2.16 ] ) . There were no significant differences in the logarithm of the heart rate , recovery time or quality of recovery between the three induction groups . However , pronounced ataxia was observed in the horses of group KM , especially after periods of anaesthesia lasting less than 75 minutes .

acepromazine

xylazine

thiopentone

guaifenesin

guaifenesin and 2.2 mg/kg ketamine

midazolam

ketamine

isoflurane .

isoflurane

Anaesthesia

light surgical anaesthesia

mean ( sd ) arterial pressure ( mmHg )

anaesthesia

Forty-eight

horses subjected to elective surgery


Relationships between age at diagnosis , clinical features , and outcome of therapy in children treated in the Medical Research Council AML 10 and 12 trials for acute myeloid leukemia . Between May 1988 and June 2000 , 698 children were treated in the Medical Research Council acute myeloid leukemia 10 and 12 trials . The presenting features and outcomes of therapy in these children were compared by age . Although there was no single cutoff in age , younger children were more likely to have intermediate risk and less likely to have favorable cytogenetics ( P < .001 ) , and they had a higher incidence of translocations involving chromosome 11q23 ( P < .001 ) . The distribution of French-American-British ( FAB ) types also varied with age ; FAB types M5 ( P < .001 ) and M7 ( P < .001 ) were more common in early childhood , whereas older children were more likely to have FAB types M0 ( P =.03 ) , M1 ( P =.04 ) , M2 ( P =.005 ) , and M3 ( P < .001 ) . Involvement of the central nervous system at diagnosis was also more common in the youngest children ( P =.01 ) . Younger children had more severe diarrhea ( P =.002 ) , whereas older children had worse nausea and vomiting ( P =.01 ) after chemotherapy . When adjusted for other important factors , complete remission rates were similar ( P =.5 ) and although there was less resistant disease in younger children ( P =.003 ) , this was partially balanced by a slight increase in deaths during induction therapy in younger patients ( P =.06 ) . On multivariate analysis overall survival ( P =.02 ) , event-free survival ( P =.02 ) , and disease-free survival were better ( P =.06 ) in younger children due to a lower relapse rate ( P =.02 ) especially in the bone marrow ( P =.02 ) .

features and outcomes of

in these children were compared by age

favorable cytogenetics

FAB types M5

FAB types M0

severe diarrhea

nausea and vomiting

complete remission rates

deaths

overall survival

event-free survival

disease-free survival

relapse rate

children

children

acute myeloid leukemia


[ Comparison between anterior rhinomanometry and impulse-oscillometric rhinometry found within nasal allergen provocation ] . UNLABELLED Besides the standard method of anterior rhinomanometry ( aR ) , the impulse-oscillometric rhinometry ( IOS ) is available for measurements of the nasal resistance . The aR is a procedure dependent on the cooperation of the patient , whereas IOS is measured regardless from the breathing activities of the patient . We examined weather the resistance-measurement by means of IOS in comparison to the aR is a more suitable method for nasal allergic provocation . METHOD 17 patients with anamnestic known rhinokonjunktivitis ( 6 f , 11 m ) had a pricktest and then a nasal provocation testing with an allergen which provoked a reaction on the skin . The complete resistance of the nose was measured in a randomized order by means of aR and IOS . RESULTS The complete resistance showed neither in the basic measurement ( aR 0,38 +/- 0,14 kPa/l/s ; IOS 0,38 +/- 0,11 kPa/l/s ) nor in the control solution ( aR 0,38 +/- 0,14 ; IOS 0,39 +/- 0,14 ) nor after application of the allergenic solution ( 15 min : aR 0,69 +/- 0,27 ; IOS 0,77 +/- 0,42 ; 30 min : aR 0,65 +/- 0,29 ; IOS 0,6 +/- 0,38 ) a significant difference between the two methods . The results of the measurement of aR and IOS after the allergenic solution showed a positive correlation ( 15 min : r = 0,63 , p < 0,01 ; 30 min : r = 0,67 , p < 0,01 ) . We found by means of clinic and measurement methods in the aR of 7 patients a positive reaction , within 7 patient a negative reaction , 3 patients had a unspecific nasal hyperreactivity . There was a correspondence in 6 of the 7 patients with positive reaction in aR between both methods . 4 of the 7 results with negative reaction in the aR would have been positive then underlying the same criteria in the IOS without announcing the symptomscore a relevant clinical symptomatic while testing . CONCLUSION IOS is a suitable procedure for nasal provocation testing and provides results similar to the aR . In comparison to aR IOS is not dependent on the patients cooperation . Due to its higher sensitivity the valid limits of the aR at provocation testings can not be transferred to IOS to avoid a false positive reaction .

anterior rhinomanometry

impulse-oscillometric rhinometry

aR and IOS .

nasal allergen provocation

nasal resistance

nasal allergic provocation

resistance

complete resistance

measurement of aR and IOS

unspecific nasal hyperreactivity

symptomscore

false positive reaction

nasal allergen

rhinokonjunktivitis


Penetration of ofloxacin and ciprofloxacin into the aqueous humor of eyes with functioning filtering blebs : a randomized trial . OBJECTIVE To determine concentrations of ofloxacin and ciprofloxacin hydrochloride in aqueous humor after topical or combined topical and oral administration in eyes with filtering blebs . DESIGN A prospective , investigator-masked , randomized , controlled comparative study involving 36 eyes of 34 patients with functioning filtering blebs who were to undergo cataract surgery . Treatment groups received either topical ofloxacin or topical ciprofloxacin ( instillation of 0.3 % ophthalmic solution every 30 minutes for 4 hours before surgery ) , or a combined topical plus oral regimen ( ciprofloxacin hydrochloride , four 100-mg tablets , or ofloxacin , one 400-mg tablet , administered 24-26 , 12-14 , and 2 hours preceding surgery ) . The main outcome measure was antibiotic concentration measured by chromatographic separation and mass spectrometry of aqueous samples obtained during surgery . RESULTS Topical antibiotic treatment yielded mean concentrations of ofloxacin , 0.75 microg/mL , and ciprofloxacin , 0.21 microg/mL , in aqueous . With combined topical and oral therapy , significantly more ofloxacin was measured than ciprofloxacin ( 3.84 microg/mL vs 0.35 microg/mL [ P < .001 ] ) . The combination regimen produced significantly greater ofloxacin levels than did topical therapy alone ( P =.007 ) . CONCLUSIONS Ofloxacin penetrates better than ciprofloxacin into the aqueous of eyes with filtering blebs , particularly after combined topical and oral administration , by which ofloxacin reaches more than a 10-fold greater concentration than does ciprofloxacin . Combined topical and oral therapy with ofloxacin may be beneficial in the treatment of bleb-associated infections .

ofloxacin

ciprofloxacin

topical ofloxacin

topical ciprofloxacin

surgery

ofloxacin , one 400-mg tablet

surgery

ofloxacin

ciprofloxacin

topical and oral therapy with ofloxacin

antibiotic concentration

concentrations of ofloxacin

greater ofloxacin levels

ciprofloxacin

36 eyes of 34 patients


A randomized effectiveness trial of collaborative care for patients with panic disorder in primary care . BACKGROUND Effectiveness studies have tested interventions to improve quality of care for depression in primary care , but none , to our knowledge , have been completed for panic disorder ( PD ) in this setting . This study sought to test the clinical effectiveness of PD pharmacotherapy embedded in a disease management framework of " collaborative care " ( CC ) . METHODS One hundred fifteen patients with PD from 3 primary care clinics were randomized to CC or " usual care " ( UC ) . Patients in CC ( n = 57 ) received educational videotapes and pamphlets ; pharmacotherapy with the selective serotonin reuptake inhibitor paroxetine ; 2 psychiatrist visits and 2 telephone calls in the first 8 weeks ; and up to 5 telephone calls between 3 and 12 months ' follow-up . Usual care patients ( n = 58 ) were treated by their primary care physician . Telephone assessments of panic , anxiety sensitivity , depression , and disability variables were performed at 3 , 6 , 9 , and 12 months ' follow-up . Adequacy of pharmacotherapy was assessed with an algorithm based on a review of efficacy studies . RESULTS Patients in CC were more likely to receive adequate ( type , dose , duration ) medication and more likely to adhere to this medication at 3 and 6 months . Random regression analyses showed that CC patients improved significantly more over time compared with UC patients on anxiety , depression , and disability measures , with the greatest effects at 3 and 6 months . CONCLUSIONS Compared with UC , CC interventions significantly improved both quality of care and clinical and functional outcomes in primary care PD patients . Clinical differences were greatest in the first 6 months , corresponding to the greater quality of care and the greater intensity of intervention .

collaborative care

PD pharmacotherapy

CC

educational videotapes and pamphlets

effectiveness

Effectiveness

clinical effectiveness

panic

anxiety sensitivity

depression

disability variables

Adequacy of pharmacotherapy

algorithm

adhere to this medication

improved

anxiety

depression

disability measures

intensity

panic disorder

One hundred fifteen

PD

PD


Matched-pair analysis of all-polyethylene versus metal-backed tibial components . Forty-eight matched pairs of osteoarthritic knees from patients who underwent primary total knee arthroplasty with a round-on-round , Apollo Knee System were studied to evaluate the outcome between all-polyethylene and metal-backed tibial components . Patients were matched for patient factors , preoperative deformities , cruciate salvage or sacrifice , and surgical technique . At the last follow-up ( average , 38.4 months ) , there was no statistically significant difference in terms of knee scores , patient self-assessment , and radiographic outcomes . No component required revision , and no revisions were pending . Maintenance of these results over time would project into better long-term success for all-polyethylene tibial components because of the amount of wear and osteolysis with current modular metal-backed tibial components . We advocate the use of a more cost-effective all-polyethylene tibial component in elderly patients ( > 70 years old ) who are not likely to need the versatility of exchange of a modular polyethylene insert because of wear .

all-polyethylene tibial components

metal-backed tibial components

all-polyethylene tibial component

knee scores

patient self-assessment

radiographic outcomes

Forty-eight

osteoarthritic

deformities

elderly

> 70


Dipyridamole in chronic stable angina pectoris ; a randomized , double blind , placebo-controlled , parallel group study . BACKGROUND Oral dipyridamole induces accumulation of endogenous adenosine , which in a hypoxic milieu exerts experimentally an angiogenic effect on coronary collateral circulation . A meta-analysis of 13 randomized placebo-controlled trials published between 1960 and 1992 showed evidence of benefit for dipyridamole in the treatment of angina pectoris , especially with longer duration of treatment . Aim To assess the efficacy and safety of dipyridamole in the treatment of patients with chronic stable angina in a large scale , international , randomized , placebo-controlled , parallel group study . METHODS Four hundred patients with chronic stable angina pectoris and a positive treadmill exercise test were randomized to receive either modified release dipyridamole ( 200 mg b.i.d . p.o. , n=198 ) or corresponding placebo ( n=202 ) , for 24 weeks as an add-on to conventional antianginal therapy and for 4 additional weeks as monotherapy -- the latter after withdrawal of standard treatment with calcium antagonists and/or beta-blockers and/or long-acting ( prophylactic ) nitrates . RESULTS Of the 198 patients randomized to dipyridamole , 134 completed the add-on and only 12 the monotherapy phase . Of the 202 patients randomized to placebo , 162 reached the add-on and only 12 the monotherapy phase . Serious adverse events occurred in 15 patients with dipyridamole and in 12 with placebo ( 7.6 % vs 6.0 , P=0.52 ) . Increase over the baseline treadmill exercise test was similar in the treatment groups at each stage of the trial for all the main efficacy parameters : total treadmill exercise test duration ; time to first anginal pain ( except for a -13 s difference in favour of placebo at week 24 ; P=0.040 ) ; time to ST segment depression > 0.1 mVolt ( except for a +21 s difference in favour of dipyridamole at week 8 ; P=0.024 ; this latter difference was totally attributable to patients with lower exercise tolerance -- Bruce stage II at study entry ) . CONCLUSION In patients with chronic stable angina treated with regular antianginal background medication , the use of oral dipyridamole is safe and well tolerated . Antianginal and antiischaemic efficacy , as assessed by exercise testing , is comparable to placebo , except for a beneficial effect on time to ischaemia after 2 months , totally attributable to patients with lower exercise tolerance at study entry .

Dipyridamole

dipyridamole

dipyridamole

modified release dipyridamole

corresponding placebo

conventional antianginal therapy

dipyridamole

placebo

efficacy and safety

Serious adverse events

total treadmill exercise test duration

time to first anginal pain

time to ST segment depression

safe

tolerated

chronic stable angina pectoris

Four hundred


Effect of antioxidant supplementation on ozone-induced lung injury in human subjects . To determine whether antioxidants can influence human susceptibility to ozone ( O ( 3 ) ) -induced changes in lung function and airway inflammation , we placed 31 healthy nonsmoking adults ( 18 to 35 yr old ) on a diet low in ascorbate for 3 wk . At 1 wk , subjects were exposed to filtered air for 2 h while exercising ( 20 L/min/m ( 2 ) ) , and then underwent bronchoalveolar lavage ( BAL ) and were randomly assigned to receive either a placebo or 250 mg of vitamin C , 50 IU of alpha-tocopherol , and 12 oz of vegetable cocktail daily for 2 wk . Subjects were then exposed to 0.4 ppm O ( 3 ) for 2 h and underwent a second BAL . On the day of the O ( 3 ) exposure , supplemented subjects were found to have significantly increased levels of plasma ascorbate , tocopherols , and carotenoids as compared with those of the placebo group . Pulmonary function testing showed that O ( 3 ) -induced reductions in FEV ( 1 ) and FVC were 30 % and 24 % smaller , respectively , in the supplemented cohort . In contrast , the inflammatory response to O ( 3 ) inhalation , as represented by the percent neutrophils and the concentration of interleukin-6 recovered in the BAL fluid at 1 h after O ( 3 ) exposure was not different for the two groups . These data suggest that dietary antioxidants protect against O ( 3 ) -induced pulmonary function decrements in humans .

antioxidant supplementation

antioxidants

diet low in ascorbate

bronchoalveolar lavage ( BAL )

placebo

250 mg of vitamin C

50 IU of alpha-tocopherol

vegetable cocktail daily for 2 wk

BAL

dietary antioxidants

lung function

airway inflammation

inflammatory response to O ( 3 )

O ( 3 ) -induced pulmonary function


Is psychotherapy more effective when therapists disclose information about themselves ? Theorists have long debated the wisdom of therapists disclosing personal information during psychotherapy . Some observers have argued that such therapist self-disclosure impedes treatment , whereas others have suggested that it enhances the effectiveness of therapy . To test these competing positions , therapists at a university counseling center were instructed to increase the number of self-disclosures they made during treatment of one client and refrain from making self-disclosures during treatment of another client . Analyses revealed that clients receiving psychotherapy under conditions of heightened therapist disclosure not only reported lower levels of symptom distress but also liked their therapist more . Such findings suggest that self-disclosure by the therapist may improve both the quality of the therapeutic relationship and the outcome of treatment .

psychotherapy

psychotherapy

increase the number of self-disclosures

treatment

psychotherapy

therapist disclosure

disclosing personal information

effectiveness of therapy .

lower levels of symptom distress

liked their therapist more .

quality of the therapeutic relationship

and the outcome of treatment .

therapists


Comparison of tropisetron and granisetron in the control of nausea and vomiting in children receiving combined cancer chemotherapy . Tropisetron and granisetron are selective serotonin ( 5-HT3 ) antagonists that have been proven effective in the prevention of nausea and vomiting in adults and children receiving cancer chemotherapy . This prospective , randomised study was designed to compare the efficacy of the two agents in the prevention of vomiting and nausea in children receiving highly emetogenic chemotherapy for various malignancies . A total of 51 children ( mean age : 7.7 +/- 4.8 year ) were studied in 133 chemotherapy cycles . In 66 chemotherapy cycles , the children received tropisetron as an antiemetic agent in a dose of 0.2 mg/kg/24 h intravenously and , in 67 cycles , they received granisetron 40 micrograms/kg/24 h intravenously before cytotoxic drug administration during the days they received chemotherapy . The response per 24 h of chemotherapy was defined as complete ( no nausea and vomiting ) , partial ( 1-4 events of vomiting and/or nausea ) , and failure ( more than 4 events of vomiting and/or nausea ) . Efficacy of antiemetic therapy was evaluated as acute ( Day 1 ) and overall was based on the worst day during the chemotherapy . Complete control of acute vomiting was achieved in 74 % of tropisetron and 88 % of granisetron patients ( P = 0.04 ) , and complete control of acute nausea in 56 % and 82 % respectively ( p = 0.002 ) . Overall response by means of complete control of both vomiting and nausea during the whole therapy period was 29 % of tropisetron group and 55 % of granisetron group ( p = 0.007 ) . The statistical analysis ( depending on the emetogenicity of the chemotherapy cycles ) showed increased efficacy of granisetron in highly ( grade 3 ) emetogenic chemotherapy cycles ( p = 0.002 ) , whereas there was no difference in the very highly emetogenic cycles ( p = 0.7 ) . Also , granisetron was found to be more effective than tropisetron , especially in patients heavier than 25 kg ( p = 0.02 ) . The adverse reactions were few and mild . There were no differences in the tolerability of the two antiemetic therapy modalities . In conclusion , granisetron was found to be more effective than tropisetron in controlling nausea and vomiting in children receiving highly emetogenic chemotherapy . This increased antiemetic efficacy of ganisetron might have been related to maximal dose differences according to body weight .

tropisetron and granisetron

Tropisetron

granisetron

tropisetron

granisetron

chemotherapy

tropisetron

granisetron

tropisetron

granisetron

granisetron

tropisetron

granisetron

ganisetron

nausea and vomiting

nausea

vomiting

vomiting and nausea

Complete control of acute vomiting

acute nausea

Overall response

vomiting

nausea

effective

adverse reactions

tolerability

nausea

vomiting

antiemetic efficacy

body weight

children

cancer chemotherapy

adults

children

cancer chemotherapy

children

highly emetogenic chemotherapy

malignancies

7.7 +/- 4.8 year

children

highly emetogenic chemotherapy


Dose dependent pharmacokinetics of theophylline : Michaelis-Menten parameters for its major metabolic pathways . Dose Dependency for pharmacokinetics of theophylline and the formation of its major metabolites , 3-methylxanthine ( 3-MX ) ; 1-methyluric acid ( 1-MU ) ; 1,3-dimethyluric acid ( DMU ) , were examined by administering three single oral doses ( 250 , 375 , 500 mg ) of theophylline to six healthy adult volunteers . The serum and urine concentrations of theophylline and the metabolites in serum and urine were determined by high-performance liquid chromatography . Total clearance of theophylline decreased and its half life increased over the range of doses administered ( p < 0.01 ) . There was a significant dose related decrease in the fractional recovery of 3-MX and 1-MU ( p < 0.001 ) and a dose related increase in fractional excretion of DMU and unchanged theophylline ( p < 0.01 and p < 0.001 respectively ) . No significant dose related changes were observed in the renal clearance of 3-MX , 1-MU and DMU , indicating linear urinary excretion kinetics of the metabolites . Theophylline metabolic clearance to 3-MX as well as to 1-MU decreased with increasing dose but clearance to DMU remained unnaffected by the size of dose . The individual Michaelis-Menten parameters Km and Vmax were estimated for six subjects receiving three different single doses . The Km values for theophylline metabolism to 3-MX , 1-MU and DMU were 2.4+/-0.6 , 5.1+/-1.8+/- and 112.3+/-36.8 mg/L respectively and the Vmax values were 3.5+/-0.7 , 7.5+/-2.6 and 112.3+/-36.8 mg/hr respectively . The Km values for the N-demethylation pathways ( 3MX and 1-MU ) were lower corresponding to therapeutic serum concentrations of drug . These results suggest that the elimination kinetics of theophylline is nonlinear in the human in the therapeutic range of serum concenntrations and can be explained by saturable formation kinetics of 3-MX and 1-MU . In contrast to previous studies we did n't find obvious indication for nonlinear formation of DMU at therapeutic concentration range .

theophylline

theophylline

theophylline

theophylline

Theophylline

theophylline

theophylline

Total clearance

fractional excretion of DMU

renal clearance of 3-MX

DMU

Michaelis-Menten parameters Km and Vmax

DMU

Vmax values

serum concenntrations

six

adult


Epidural analgesia compared with intravenous morphine patient-controlled analgesia : postoperative outcome measures after mastectomy with immediate TRAM flap breast reconstruction . BACKGROUND AND OBJECTIVES Epidural analgesia has been shown to provide superior pain control compared with intravenous ( IV ) opioids after major surgical procedures . In this study , we compared the effect of epidural analgesia and IV morphine patient-controlled analgesia ( PCA ) on pain relief , duration of hospitalization , oral nutrition , ambulation , and side effects in patients undergoing a major surgical procedure ( i.e. , unilateral mastectomy with immediate transverse rectus abdominis musculocutaneous flap reconstruction ) . METHODS Eighteen patients were prospectively randomized to receive either epidural analgesia or PCA during the postoperative period . The intensity of pain was assessed daily by a 100-mm visual analog scale . The total length of hospital stay , time to ambulation , and time to oral nutrition were recorded . RESULTS The epidural group had significantly lower pain scores at 3 evaluation times through postoperative day number 4 ( P < .05 ) . The total length of hospitalization for the epidural group ( median , 101 hours ) was significantly less than the PCA group ( median , 126 hours ; P = .0498 ) . The time to first ambulation , time to first bowel sounds , time to tolerating oral nutrition , incidence of nausea/vomiting or pruritus , and time to first flatus were not statistically different between the groups . CONCLUSIONS These results show that epidural analgesia compared with PCA offered improved pain control after breast reconstruction with immediate transverse rectus abdominis musculocutaneous flap reconstruction . It also resulted in a 25-hour reduction in time of hospitalization .

Epidural analgesia

intravenous morphine

patient-controlled analgesia ( PCA )

epidural analgesia or PCA

intensity of pain

total length of hospital stay

time to ambulation

time to oral nutrition

pain scores

total length of hospitalization

time to first ambulation

time to first bowel sounds

time to tolerating oral nutrition

time to first flatus

major surgical procedure ( i.e.

Eighteen


A randomized intervention to improve ongoing participation in mammography . OBJECTIVE To test the effectiveness of interventions intended to increase rates of regular breast cancer screening , according to recommended guidelines . STUDY DESIGN A randomized controlled trial of 2 outreach interventions ( a mail reminder and a telephone reminder plus appointment scheduling ) compared with a routine publicity campaign to encourage continued participation in mammography screening . PARTICIPANTS AND METHODS Participants were 1908 women aged 50 to 75 years continuously enrolled in a large group-model HMO during the study who underwent a bilateral mammogram during the first quarter of 1994 and no subsequent mammogram during the next 18 to 21 months . Data were obtained from health plan administrative data files supplemented by medical chart review . Women were randomly assigned to receive ( 1 ) a mail reminder , ( 2 ) a telephone reminder , or ( 3 ) routine publicity on mammography for all women . The outcome measure was a mammogram received after the intervention period and within 2 years of the initial mammogram date . RESULTS Bivariate and multivariate statistical analyses showed that participation was significantly higher for women contacted by telephone than through routine publicity . Mail reminders were no more effective than a routine publicity campaign . Primary care physician and gynecologist visits increased the likelihood of a subsequent mammogram for women in all intervention groups . CONCLUSIONS Telephone contact by regular health plan staff was more successful than publicity in encouraging continued participation in mammography screening in women enrolled in a group-model managed health care plan . Because mailings did not influence participation in mammography screening , health plans should be cautious about investing in member mailings without first evaluating their effectiveness in the context of existing outreach efforts .

interventions intended

routine publicity campaign

mammography

routine publicity campaign .

Telephone contact

ongoing participation in mammography

subsequent mammogram

mammography screening

mammography screening


Benefit of FSH priming of women with PCOS to the in vitro maturation procedure and the outcome : a randomized prospective study . The aim of this study was to determine whether the rates of in vitro oocyte maturation , fertilization and cleavage , as well as implantation rate and pregnancy rate , could be improved by low-dose priming with FSH in vivo before retrieval of immature oocytes in patients with polycystic ovary syndrome ( PCOS ) . From March 1998 to June 2000 , a total of 28 women underwent 36 completed treatment cycles , randomized sequentially in one of two groups . Women in group 1 ( n = 12 cycles ) received no stimulation and women in group 2 ( n = 24 cycles ) received 150 iu recombinant FSH day ( -1 ) for 3 days , initiated on day 3 after menstruation . Aspiration was performed transvaginally between day 9 and day 17 in the unstimulated group and on day 8 or day 9 in the FSH-primed group after FSH deprivation for 2 or 3 days . All cumulus-enclosed oocytes of healthy appearance were matured in culture medium ( TCM-199 ) in vitro for 28-36 h before intracytoplasmic sperm injection ( ICSI ) . After oocyte retrieval the women were given oestradiol ( 6 mg day ( -1 ) ) and progesterone administration ( 300 mg day ( -1 ) ) was initiated 2 days later . Suitable embryos ( maximum two embryos ) were transferred on day 3 after ICSI . The percentage of oocytes reaching metaphase II was significantly higher ( P < 0.05 ) in the FSH-primed group ( 59 % , 92/156 ) compared with the non-primed group ( 44 % , 36/81 ) . There were no significant differences in the rates of oocyte fertilization and cleavage between these groups . No pregnancies were obtained in group 1 ( 0 % , 0/12 ) , whereas seven clinical pregnancies were obtained in group 2 ( 29 % , 7/24 ) ( P < 0.05 ) . In group 2 , 37 embryo transfers resulted in eight implantations ( 21.6 % ) . Three healthy singleton children have been born at term ; the remaining pregnancies ended with spontaneous abortions in the first trimester . These results indicate that priming with recombinant FSH before harvesting of immature oocytes from patients with PCOS may improve the maturational potential of the oocytes and the implantation rate of the cleaved embryos .

FSH priming

FSH

no stimulation

recombinant FSH

rates of in vitro oocyte maturation

fertilization

cleavage

implantation rate

pregnancy rate

pregnancies

clinical pregnancies

implantations

healthy singleton children

born

spontaneous abortions

women

PCOS

polycystic ovary syndrome ( PCOS ) .

women

PCOS


Induction versus noninduction in renal transplant recipients with tacrolimus-based immunosuppression . BACKGROUND The aim of this study was to compare the efficacy and safety of induction treatment with antithymocyte globulins ( ATG ) followed by tacrolimus therapy with immediate tacrolimus therapy in renal transplant recipients . METHODS This 12-month , open , prospective study was conducted in 15 centers in France and 1 center in Belgium ; 309 patients were randomized to receive either induction therapy with ATG ( n=151 ) followed by initiation of tacrolimus on day 9 or immediate tacrolimus-based triple therapy ( n=158 ) . In both study arms , the initial daily tacrolimus dose was 0.2 mg/kg . Steroid boluses were given in the first 2 days and tapered thereafter from 20 mg/day to 5 mg/day . Azathioprine was administered at 1-2 mg/kg per day . RESULTS At month 12 , biopsy-confirmed acute rejections were reported for 15.2 % ( induction ) and 30.4 % ( noninduction ) of patients ( P=0.001 ) . The incidence of steroid-sensitive acute rejections was 7.9 % ( induction ) and 22.2 % ( noninduction ) ( P=0.001 ) . Steroid-resistant acute rejections were reported for 8.6 % ( induction ) and 8.9 % ( noninduction ) of patients . A total of nine patients died . Patient survival and graft survival at month 12 was similar in both treatment groups ( 97.4 % vs. 96.8 % and 92.1 % vs. 91.1 % , respectively ) . Statistically significant differences in the incidence of adverse events were found for cytomegalovirus ( CMV ) infection ( induction , 32.5 % vs. noninduction , 19.0 % , P=0.009 ) , leukopenia ( 37.3 % vs. 9.5 % , P < 0.001 ) , fever ( 25.2 % vs. 10.1 % , P=0.001 ) , herpes simplex ( 17.9 % vs. 5.7 % , P=0.001 ) , and thrombocytopenia ( 11.3 % vs. 3.2 % , P=0.007 ) . In the induction group , serum sickness was observed in 10.6 % of patients . The incidence of new onset diabetes mellitus was 3.4 % ( induction ) and 4.5 % ( noninduction ) . CONCLUSION Low incidences of acute rejection were found in both treatment arms . Induction treatment with ATG has the advantage of a lower incidence of acute rejection , but it significantly increases adverse events , particularly CMV infection .

noninduction

antithymocyte globulins ( ATG )

tacrolimus

induction therapy with ATG

tacrolimus

tacrolimus-based triple therapy

tacrolimus

Steroid boluses

Azathioprine

ATG

efficacy and safety

biopsy-confirmed acute rejections

Steroid-resistant acute rejections

incidence of adverse events

cytomegalovirus ( CMV ) infection

leukopenia

fever

herpes simplex

thrombocytopenia

serum sickness

new onset diabetes mellitus

adverse events

renal transplant recipients

309 patients


Safety and efficacy of PNU-142633 , a selective 5-HT1D agonist , in patients with acute migraine . In this randomized , double-blind , placebo-controlled , parallel-group study , patients received a single 50-mg oral dose of a 5-HT ( 1D ) agonist , PNU-142633 ( n = 34 ) , or matching placebo ( n = 35 ) during an acute migraine attack . No statistically significant treatment effects were observed at 1 and 2 h after dosing , even after stratifying by baseline headache intensity . At 1 and 2 h post-dose , 8.8 % and 29.4 % of the PNU-142633 group , respectively , and 8.6 % and 40.0 % of the placebo group , respectively , experienced headache relief ; 2.9 % and 8.8 % of the PNU-142633 group and 0 % and 5.7 % of the placebo group were free of headache pain . Adverse events associated with PNU-142633 treatment included chest pain ( two patients ) and QTc prolongation ( three patients ) . Results from this study suggest that anti-migraine efficacy is not mediated solely through the 5-HT ( 1D ) receptor subtype , although this receptor may contribute , at least in part , to the adverse cardiovascular effects observed with 5-HT agonist medications .

PNU-142633 , a selective 5-HT1D agonist

matching placebo

5-HT agonist

headache relief

free of headache pain .

Adverse events

chest pain

QTc prolongation

acute migraine

acute migraine


Caffeine eliminates psychomotor vigilance deficits from sleep inertia . STUDY OBJECTIVES This study sought to establish the effects of caffeine on sleep inertia , which is the ubiquitous phenomenon of cognitive performance impairment , grogginess and tendency to return to sleep immediately after awakening . DESIGN 28 normal adult volunteers were administered sustained low-dose caffeine or placebo ( randomized double-blind ) during the last 66 hours of an 88-hour period of extended wakefulness that included seven 2-hour naps during which polysomnographical recordings were made . Every 2 hours of wakefulness , and immediately after abrupt awakening from the naps , psychomotor vigilance performance was tested . SETTING N/A . PARTICIPANTS N/A . INTERVENTIONS N/A . MEASUREMENTS AND RESULTS In the placebo condition , sleep inertia was manifested as significantly impaired psychomotor vigilance upon awakening from the naps . This impairment was absent in the caffeine condition . Caffeine had only modest effects on nap sleep . CONCLUSIONS Caffeine was efficacious in overcoming sleep inertia . This suggests a reason for the popularity of caffeine-containing beverages after awakening . Caffeine 's main mechanism of action on the central nervous system is antagonism of adenosine receptors . Thus , increased adenosine in the brain upon awakening may be the cause of sleep inertia .

Caffeine

caffeine

low-dose caffeine

placebo

placebo

Caffeine

psychomotor vigilance deficits

sleep inertia

psychomotor vigilance performance

sleep inertia

psychomotor vigilance

nap sleep

sleep inertia

sleep inertia

sleep inertia


Equivalent efficacy of mitomycin C plus doxorubicin instillation to bacillus Calmette-Guerin therapy for carcinoma in situ of the bladder . BACKGROUND To elucidate the most efficient topical therapy for carcinoma in situ of the bladder , the efficacy of intravesical mitomycin C plus doxorubicin therapy was compared with bacillus Calmette-Guerin ( BCG ) therapy . The clinical behavior of the tumor was analysed according to the histological grade . METHODS Forty-two patients with carcinoma in situ of the bladder were randomized to intravesical BCG ( 21 patients ) or mitomycin C plus doxorubicin sequential therapy ( 21 patients ) as first line treatment . The non-responders underwent the subsequent instillation of the other intravesical therapy alternately . Of the patients , 27 had grade 2 and 15 had grade 3 cancer . RESULTS Both topical therapies were equally effective with initial response rates of 86 % ( 18/21 ) for BCG and 81 % ( 17/21 ) for mitomycin C plus doxorubicin , irrespective of the tumor grade . Of seven initial non-responders , five patients achieved a complete response by subsequent instillation , resulting in a total response rate of 95 % . After a mean follow-up of 47 months , five patients ( 12 % ) developed disease progression . The progression rates were not different between the topical therapies , but were significantly higher in grade 3 than in grade 2 cases . CONCLUSION It appears likely that mitomycin C plus doxorubicin instillation has an equivalent efficacy to BCG as the initial therapy of carcinoma in situ and the combination of them would be the most efficient treatment for the disease . Moreover , histological grading would be clinically useful in defining the tumor characteristics and behavior of carcinoma in situ of the bladder .

mitomycin C plus doxorubicin

intravesical BCG

efficacy

response rates

total response rate

disease progression

progression rates

efficacy to BCG

carcinoma


Potentiation of bradykinin-induced tissue plasminogen activator release by angiotensin-converting enzyme inhibition . OBJECTIVES The aim of the present study was to determine the effect of angiotensin-converting enzyme ( ACE ) inhibition on the local stimulated release of tissue plasminogen activator ( t-PA ) from the endothelium . BACKGROUND Angiotensin-converting enzyme inhibitor therapy may exert a beneficial effect on the endogenous fibrinolytic balance . METHODS Blood flow and plasma fibrinolytic factors were measured in both forearms of eight healthy males who received unilateral brachial artery infusions of the endothelium-dependent vasodilators substance P ( 2 to 8 pmol/min ) and bradykinin ( 100 to 1,000 pmol/min ) , and the endothelium-independent vasodilator sodium nitroprusside ( 2 to 8 microg/min ) . These measurements were performed on each of three occasions following one week of matched placebo , quinapril 40 mg or losartan 50 mg daily administered in a double-blind randomized crossover design . RESULTS Sodium nitroprusside , substance P and bradykinin produced dose-dependent increases in the blood flow of infused forearm ( analysis of variance [ ANOVA ] , p < 0.001 for all ) . Although sodium nitroprusside did not affect plasma t-PA concentrations , they were increased dose-dependently in the infused forearm by substance P and bradykinin infusion ( ANOVA , p < 0.001 for both ) . Bradykinin-induced release of active t-PA was more than doubled during treatment with quinapril in comparison to placebo or losartan ( two-way ANOVA : p < 0.003 for treatment group , p < 0.001 for t-PA response and p = ns for interaction ) , whereas the substance P response was unaffected . CONCLUSIONS We have shown a selective and marked augmentation of bradykinin-induced t-PA release during ACE inhibition . These findings suggest that the beneficial clinical and vascular effects of ACE inhibition may , in part , be mediated through local augmentation of bradykinin-induced t-PA release .

bradykinin

placebo

quinapril

losartan

quinapril

placebo

losartan

increases in the blood flow

plasma t-PA concentrations

release of active t-PA

substance P response was unaffected


Carotid sinus syndrome : a modifiable risk factor for nonaccidental falls in older adults ( SAFE PACE ) . OBJECTIVES The aim of the study was to determine whether cardiac pacing reduces falls in older adults with cardioinhibitory carotid sinus hypersensitivity ( CSH ) . BACKGROUND Cardioinhibitory carotid sinus syndrome causes syncope , and symptoms respond to cardiac pacing . There is circumstantial evidence for an association between falls and the syndrome . METHODS A randomized controlled trial was done of consecutive older patients ( > 50 years ) attending an accident and emergency facility because of a non-accidental fall . Patients were randomized to dual-chamber pacemaker implant ( paced patients ) or standard treatment ( controls ) . The primary outcome was the number of falls during one year of follow-up . RESULTS One hundred seventy-five eligible patients ( mean age 73 +/- 10 years ; 60 % women ) were randomized to the trial : pacemaker 87 ; controls 88 . Falls ( without loss of consciousness ) were reduced by two-thirds : controls reported 669 falls ( mean 9.3 ; range 0 to 89 ) , and paced patients 216 falls ( mean 4.1 ; range 0 to 29 ) . Thus , paced patients were significantly less likely to fall ( odds ratio 0.42 ; 95 % confidence interval : 0.23 , 0.75 ) than were controls . Syncopal events were also reduced during the follow-up period , but there were much fewer syncopal events than falls-28 episodes in paced patients and 47 in controls . Injurious events were reduced by 70 % ( 202 in controls compared to 61 in paced patients ) . CONCLUSIONS There is a strong association between non-accidental falls and cardioinhibitory CSH . These patients would not usually be referred for cardiovascular assessment . Carotid sinus hypersensitivity should be considered in all older adults who have non-accidental falls .

cardiac pacing

cardiac pacing .

standard treatment ( controls )

pacemaker

controls

nonaccidental falls

falls

falls

non-accidental fall

Falls ( without loss of consciousness )

fall

Syncopal events

syncopal events

Injurious events

non-accidental


Multisite , double-blind , placebo-controlled trial of porcine secretin in autism . OBJECTIVE To examine the efficacy of intravenous porcine secretin for the treatment of autistic disorder . METHOD Randomized , double-blind , placebo-controlled , crossover design . Fifty-six subjects with autistic disorder received either a secretin or placebo infusion at baseline and the other substance at week 4 . Subjects were given the Autism Diagnostic Observation Schedule ( ADOS ) and other pertinent developmental measures at baseline and at weeks 4 and 8 to assess drug effects . RESULTS For the primary efficacy analysis , change of ADOS social-communication total score from week 0 to week 4 , no statistically significant difference was obtained between placebo ( -0.8 +/- 2.9 ) and secretin groups ( -0.6 +/- 1.4 ; t54 = 0.346 , p < .73 ) . The other measures showed no treatment effect for secretin compared with placebo . CONCLUSION There was no evidence for efficacy of secretin in this randomized , placebo-controlled , double-blind trial .

placebo-controlled

porcine secretin

porcine secretin

placebo-controlled

secretin

placebo infusion

placebo

secretin

secretin

placebo

efficacy

treatment

autistic disorder

pertinent developmental measures

ADOS social-communication total score

treatment effect

efficacy

autism

autistic disorder .

Fifty-six

autistic disorder


Effect of a specific preparation of Chinese herbs ( " clear the way " ) on duration and severity of the common cold .

Chinese herbs

duration and severity of the

common cold

common cold


The role of radiography in primary care patients with low back pain of at least 6 weeks duration : a randomised ( unblinded ) controlled trial . OBJECTIVES To test the hypotheses that : ( 1 ) Lumbar spine radiography in primary care patients with low back pain is not associated with improved patient outcomes , including pain , disability , health status , sickness absence , reassurance , and patient satisfaction or belief in the value of radiography . ( 2 ) Lumbar spine radiography in primary care patients with low back pain is not associated with changes in patient management , including medication use , and the use of primary and secondary care services , physical therapies and complementary therapies . ( 3 ) Participants choosing their treatment group ( i.e . radiography or no radiography ) do not have better outcomes than those randomised to a treatment group . ( 4 ) Lumbar spine radiography is not cost-effective compared with usual care without lumbar spine radiography . DESIGN A randomised unblinded controlled trial . SETTING Seventy-three general practices in Nottingham , North Nottinghamshire , Southern Derbyshire , North Lincolnshire and North Leicestershire . Fifty-two practices recruited participants to the trial . SUBJECTS Randomised arm : 421 participants with low back pain , with median duration of 10 weeks . Patient preference arm : 55 participants with low back pain , with median duration of 11 weeks . INTERVENTION Lumbar spine radiography and usual care versus usual care without radiography . MAIN OUTCOME MEASURES Roland adaptation of the Sickness Impact Profile , visual analogue pain scale , health status scale , EuroQol , use of primary and secondary care services , and physical and complementary therapies , sickness absence , medication use , patient satisfaction , reassurance and belief in value of radiography at 3 and 9 months post-randomisation . RESULTS Participants randomised to receive an X-ray were more likely to report low back pain at 3 months ( odds ratio ( OR ) = 1.56 ; 95 % confidence interval ( CI ) , 1.02 to 2.40 ) and had a lower overall health status score ( p = 0.02 ) . There were no differences in health or functional status at 9 months . A higher proportion of participants consulted the general practitioner ( GP ) in the 3 months following an X-ray ( OR = 2.72 ; 95 % CI , 1.80 to 4.10 ) . There were no differences in use of any other services , medication use or sickness absence at 3 or 9 months . No serious spinal pathology was identified in either group . The commonest X-ray reports were of discovertebral degeneration and normal findings . Many patients did not perceive their information needs were met within the consultation . Satisfaction with care was greater in the group receiving radiography at 9 months . Participants randomised to receive an X-ray were not less worried , or more reassured about serious disease causing their low back pain . Satisfaction was associated with meeting participants ' information needs and reduced belief in the necessity for investigations for low back pain , including X-rays and blood tests . In both groups , at 3 and 9 months 80 % of participants would choose to have an X-ray if the choice was available . Participants in the patient preference group achieved marginally better outcomes than those randomised to a treatment group , but the clinical significance of these differences is unclear . Lumbar spine radiography was associated with a net economic loss at 3 and 9 months . CONCLUSIONS Lumbar spine radiography in primary care patients with low back pain of at least 6 weeks duration is not associated with improved functioning , severity of pain or overall health status , and is associated with an increase in GP workload . Participants receiving X-rays are more satisfied with their care , but are not less worried or more reassured about serious disease causing their low back pain . CONCLUSIONS - RECOMMENDATIONS FOR FURTHER RESEARCH : Further work is required to develop and test an educational package that educates patients and GPs about the utility of radiography and provides strategies for identifying and meeting the information needs of patients , and the needs of patients and GPs to be reassured about missing serious disease . Guidelines on the management of low back pain in primary care should be consistent about not recommending lumbar spine radiography in patients with low back pain in the absence of red flags for serious spinal pathology , even if the pain has persisted for at least 6 weeks .

radiography

Lumbar spine radiography

radiography

no radiography

X-ray

lumbar spine radiography

pain

satisfaction

belief

visual analogue pain scale

health status scale , EuroQol

physical and complementary therapies

sickness absence

medication use

patient satisfaction

low back pain

health status

health

functional status

any other services , medication use

sickness absence

serious spinal pathology

discovertebral degeneration

normal findings

Satisfaction

worried

reassured

outcomes

economic loss

functioning

severity of pain

overall health status

GP workload

Seventy-three

Fifty-two


Oral estrogen antagonizes the metabolic actions of growth hormone in growth hormone-deficient women . We have determined whether oral estrogen reduces the biological effects of growth hormone ( GH ) in GH-deficient ( GHD ) women compared with transdermal estrogen treatment . In two separate studies , eight GHD women randomly received either oral or transdermal estrogen for 8 wk before crossing over to the alternate route of administration . The first study assessed the effects of incremental doses of GH ( 0.5 , 1.0 , 2.0 IU/day for 1 wk each ) on insulin-like growth factor I ( IGF-I ) levels during each estrogen treatment phase . The second study assessed the effects of GH ( 2 IU/day ) on lipid oxidation and on protein metabolism using the whole body leucine turnover technique . Mean IGF-I level was significantly lower during oral estrogen treatment ( P < 0.05 ) and rose dose dependently during GH administration by a lesser magnitude ( P < 0.05 ) compared with transdermal treatment . Postprandial lipid oxidation was significantly lower with oral estrogen treatment , both before ( P < 0.05 ) and during ( P < 0.05 ) GH administration , compared with transdermal treatment . Protein synthesis was lower during oral estrogen both before and during GH administration ( P < 0.05 ) . Oral estrogen antagonizes several of the metabolic actions of GH . It may aggravate body composition abnormalities already present in GHD women and attenuate the beneficial effects of GH therapy . Estrogen replacement in GHD women should be administered by a nonoral route .

Oral estrogen

oral estrogen

transdermal estrogen

oral or transdermal estrogen

estrogen

oral estrogen

transdermal treatment

oral estrogen

estrogen

GH

Oral estrogen

GH therapy

Estrogen replacement

Mean IGF-I level

Postprandial lipid oxidation

Protein synthesis


Acute effect of pegvisomant on cardiovascular risk markers in healthy men : implications for the pathogenesis of atherosclerosis in GH deficiency . Cardiovascular risk is increased in GH deficiency ( GHD ) . GHD adults are frequently abdominally obese and display features of the metabolic syndrome . Otherwise healthy abdominally obese subjects have low GH levels and show features of the metabolic syndrome as well . We investigated in healthy nonobese males the effect of the GH receptor antagonist pegvisomant in different metabolic conditions . This is a model for acute GHD without the alterations in body composition associated with GHD . We compared the effect of pegvisomant with that of placebo before and after 3 d of fasting . In addition , we investigated the effect of pegvisomant under normal , i.e . fed , conditions . Three days of fasting as well as pegvisomant alone decreased serum free IGF-I levels ( 1.0 +/- 0.15 vs. 0.31 +/- 0.05 ng/ml and 0.86 +/- 0.23 vs. 0.46 +/- 0.23 ng/ml , respectively ) . Fasting in combination with pegvisomant also decreased serum free IGF-I levels ( 1.0 +/- 0.15 vs. 0.31 +/- 0.07 ng/ml ) . Treatment with pegvisomant had no additional influence on the decline of free IGF-I induced by fasting . Pegvisomant alone had no influence on insulin sensitivity . The increase in insulin sensitivity induced by fasting was comparable to the increase in insulin sensitivity induced by fasting combined with pegvisomant . Among serum lipid concentrations , only serum triglycerides increased significantly as a result of pegvisomant alone ( 1.0 +/- 0.2 vs. 1.6 +/- 0.4 mmol/liter ) . The changes in lipid concentrations induced by fasting alone or pegvisomant were not different from those induced by pegvisomant alone . von Willebrand factor antigen levels declined significantly under the influence of pegvisomant alone ( 1.1 +/- 0.07 vs. 0.8 +/- 0.06 U/ml ) . In conclusion , in different metabolic conditions the GH receptor antagonist pegvisomant induces no significant acute changes in the major risk markers for cardiovascular disease . These data suggest that the secondary metabolic changes , e.g . abdominal obesity or inflammatory factors , that develop as a result of long-standing GHD are of primary importance in the pathogenesis of atherosclerosis in patients with GHD .

pegvisomant

pegvisomant

pegvisomant

placebo

pegvisomant

pegvisomant

serum free IGF-I levels

serum free IGF-I levels

free IGF-I

insulin sensitivity .

insulin sensitivity

insulin sensitivity

serum lipid concentrations

serum triglycerides

changes in lipid concentrations

von Willebrand factor antigen levels

GHD adults

healthy nonobese males