Memory monitoring by animals and humans . The authors asked whether animals and humans would use similarly an uncertain response to escape indeterminate memories . Monkeys and humans performed serial probe recognition tasks that produced differential memory difficulty across serial positions ( e.g. , primacy and recency effects ) . Participants were given an escape option that let them avoid any trials they wished and receive a hint to the trial 's answer . Across species , across tasks , and even across conspecifics with sharper or duller memories , monkeys and humans used the escape option selectively when more indeterminate memory traces were probed . Their pattern of escaping always mirrored the pattern of their primary memory performance across serial positions . Signal-detection analyses confirm the similarity of the animals ' and humans ' performances . Optimality analyses assess their efficiency . Several aspects of monkeys ' performance suggest the cognitive sophistication of their decisions to escape .

serial probe recognition tasks

Memory

response

used the escape option

Signal-detection analyses

Optimality analyses

efficiency

animals and humans .


Leptin levels in protracted critical illness : effects of growth hormone-secretagogues and thyrotropin-releasing hormone . Prolonged critical illness is characterized by feeding-resistant wasting of protein , whereas reesterification , instead of oxidation of fatty acids , allows fat stores to accrue and associate with a low-activity status of the somatotropic and thyrotropic axis , which seems to be partly of hypothalamic origin . To further unravel this paradoxical metabolic condition , and in search of potential therapeutic strategies , we measured serum concentrations of leptin ; studied the relationship with body mass index , insulin , cortisol , thyroid hormones , and somatomedins ; and documented the effects of hypothalamic releasing factors , in particular , GH-secretagogues and TRH . Twenty adults , critically ill for several weeks and supported with normocaloric , continuously administered parenteral and/or enteral feeding , were studied for 45 h. They had been randomized to receive one of three combinations of peptide infusions , in random order : TRH ( one day ) and placebo ( other day ) ; TRH + GH-releasing peptide ( GHRP ) -2 and GHRP-2 ; TRH + GHRH + GHRP-2 and GHRH + GHRP-2 . Peptide infusions were started after a 1-microgram/kg bolus at 0900 h and infused ( 1 microgram/kg.h ) until 0600 h the next morning . Serum concentrations of leptin , insulin , cortisol , T4 , T3 , insulin-like growth factor ( IGF ) -I , IGF-binding protein-3 and the acid-labile subunit ( ALS ) were measured at 0900 h , 2100 h , and 0600 h on each of the 2 study days . Baseline leptin levels ( mean +/- SEM : 12.4 +/- 2.1 micrograms/L ) were independent of body mass index ( 25 +/- 1 kg/m2 ) , insulin ( 18.6 +/- 2.9 microIU/mL ) , cortisol ( 504 +/- 43 mmol/L ) , and thyroid hormones ( T4 : 63 +/- 5 nmol/L , T3 : 0.72 +/- 0.08 nmol/L ) but correlated positively with circulating levels of IGF-I [ 86 +/- 6 micrograms/L , determination coefficient ( R2 ) = 0.25 ] and ALS ( 7.2 +/- 0.6 mg/L , R2 = 0.32 ) . Infusion of placebo or TRH had no effect on leptin . In contrast , GH-secretagogues elevated leptin levels within 12 h. Infusion of GHRP-2 alone induced a maximal leptin increase of +87 % after 24 h , whereas GHRH + GHRP-2 elevated leptin by up to +157 % after 24 h. The increase in leptin within 12 h was related ( R2 = 0.58 ) to the substantial rise in insulin . After 45 h , and having reached a plateau , leptin was related to the increased IGF-I ( R2 = 0.37 ) . In conclusion , circulating leptin levels during protracted critical illness were linked to the activity state of the GH/IGF-I axis . Stimulating the GH/IGF-I axis with GH-secretagogues increased leptin levels within 12 h. Because leptin may stimulate oxidation of fatty acids , and because GH , IGF-I , and insulin have a protein-sparing effect , GH-secretagogue administration may be expected to result in increased utilization of fat as preferential substrate and to restore protein content in vital tissues and , consequently , has potential as a strategy to reverse the paradoxical metabolic condition of protracted critical illness .

growth hormone-secretagogues

thyrotropin-releasing hormone .

TRH

( one day )

placebo

placebo

TRH

GH-secretagogue

Serum concentrations of leptin

insulin

cortisol

insulin-like growth factor ( IGF ) -I

IGF-binding protein-3

acid-labile subunit ( ALS )

Baseline leptin levels

leptin

leptin levels

maximal leptin increase

leptin

leptin within 12

leptin

increased IGF-I

circulating leptin levels

leptin levels


Braced for impact : reducing military paratroopers ' ankle sprains using outside-the-boot braces . BACKGROUND Ankle injuries account for 30 to 60 % of all parachuting injuries . This study was designed to determine if outside-the-boot ankle braces could reduce ankle sprains during Army paratrooper training . METHODS The randomized trial involved 777 volunteers from the U.S. Army Airborne School , Fort Benning , Ga. Of this group , 745 completed all study requirements ( 369 brace-wearers and 376 non-brace-wearers ) . Each volunteer made five parachute jumps , for a total of 3,674 jumps . RESULTS The incidence of inversion ankle sprains was 1.9 % in non-brace-wearers and 0.3 % in brace-wearers ( risk ratio , 6.9 ; p = 0.04 ) . Other injuries appeared unaffected by the brace . Overall , 5.3 % of the non-brace group and 4.6 % of the brace group experienced at least one injury . The risk ratio for injured individuals was 1.2:1 ( non-brace to brace groups ; p = 0.65 ) . CONCLUSION Inversion ankle sprains during parachute training can be significantly reduced by using an outside-the-boot ankle brace , with no increase in risk for other injuries .

outside-the-boot braces

brace-wearers

non-brace-wearers )

incidence of inversion ankle sprains

risk ratio for injured individuals

Inversion ankle sprains

paratroopers

369 brace-wearers

376 non-brace-wearers


Atrioventricular conduction during long-term follow-up of patients with sick sinus syndrome . BACKGROUND It has been claimed that patients with sick sinus syndrome have an increased risk of developing AV block , but this has never been assessed prospectively . The aim of the present study was to evaluate in a prospective trial AV conduction during the long-term follow-up of patients with sick sinus syndrome . METHODS Two hundred twenty-five consecutive patients with sick sinus syndrome and intact AV conduction were randomized to undergo single-chamber atrial pacing ( 110 patients ) or single-chamber ventricular pacing ( 115 patients ) . Follow-up after 3 months and then yearly included measurement of the PQ interval and , in patients with atrial pacemakers , determination of the atrial stimulus-Q intervals at pacing rates of 100 and 120 bpm . The occurrence of AV block in the atrial group was recorded . During follow-up ( mean , 5.5+/-2.4 years ) , there was no change in PQ interval in either group and no change in atrial stimulus-Q intervals or Wenckebach block point in the atrial group . Four of 110 patients in the atrial group developed grade 2 to 3 AV block that required upgrading of the pacemaker ( 0.6 % per year ) . Two of these 4 patients had right bundle-branch block at pacemaker implantation . CONCLUSIONS AV conduction , estimated as PQ interval and atrial stimulus-Q interval at atrial pacing rates of 100 and 120 bpm and the Wenckebach block point , remains stable during long-term follow-up . Thus , treatment with single-chamber atrial pacing is safe and can be recommended to patients with sick sinus syndrome without bundle-branch block .

single-chamber atrial pacing

single-chamber ventricular pacing

single-chamber atrial pacing

risk of developing AV block

PQ interval

occurrence of AV block

PQ interval

atrial stimulus-Q intervals

Wenckebach block point

grade 2 to 3 AV block

right bundle-branch block

PQ interval

atrial stimulus-Q interval

safe

sick sinus syndrome

sick sinus syndrome

sick sinus syndrome

Two hundred twenty-five

sick sinus syndrome

sick sinus syndrome


Compliance with depot medroxyprogesterone acetate : a randomized , controlled trial of intensive reminders . We enrolled women in a prospective , randomized study to determine whether an intensive reminder system would improve compliance in women receiving depot medroxyprogesterone injections . Women selecting this treatment were assigned to a group that received both mail and telephone reminders or to a second group that received only a scheduled appointment at the time of the previous injection . The rate of continuation and the rate of on-time injections did not differ between groups . Women who had prolonged bleeding were more likely to discontinue depot medroxyprogesterone injections .

depot medroxyprogesterone acetate

depot medroxyprogesterone

mail and telephone reminders

scheduled appointment

rate of continuation

rate of on-time injections

prolonged bleeding

women

depot medroxyprogesterone


Epileptogenic activity of folic acid after drug induces SLE ( folic acid and epilepsy ) OBJECTIVE To study the effect of folic acid-containing multivitamin supplementation in epileptic women before and during pregnancy in order to determine the rate of structural birth defects and epilepsy-related side effects . STUDY DESIGN First a randomised trial , later periconception care including in total 12225 females . RESULTS Of 60 epileptic women with periconceptional folic acid ( 0.8 mg ) -containing multivitamin supplementation , no one developed epilepsy-related side effects during the periconception period . One epileptic woman delivered a newborn with cleft lip and palate . Another patient exhibited with a cluster of seizures after the periconception period using another multivitamin . This 22-year-old epileptic woman was treated continuously by carbamazepine and a folic acid ( 1 mg ) -containing multivitamin from the 20th week of gestation . She developed status epilepticus and later symptoms of systemic lupus erythematodes . Her pregnancy ended with stillbirth . CONCLUSIONS The epileptic pregnant patient 's autoimmune disease ( probably drug-induced lupus ) could damage the blood-brain barrier , therefore the therapeutic dose ( > or =1 mg ) of folic acid triggered a cluster of seizures . Physiological dose ( < 1 mg ) of folic acid both in healthy and 60 epileptic women , all without any autoimmune disease , did not increase the risk for epileptic seizures .

periconceptional folic acid

carbamazepine and a folic acid

-containing multivitamin

cluster of seizures

status epilepticus

stillbirth

cluster of seizures

risk for epileptic seizures


Oxidative DNA damage measured in human lymphocytes : large differences between sexes and between countries , and correlations with heart disease mortality rates . The 'antioxidant hypothesis ' proposes that vitamin C , vitamin E , carotenoids , and other antioxidants occurring in fruit and vegetables afford protection against heart disease and cancer by preventing oxidative damage to lipids and to DNA , respectively . To test elements of this hypothesis , we have measured blood levels of dietary antioxidants , and 8-oxodeoxyguanosine ( 8-oxo-dG ) concentrations in lymphocyte DNA , in healthy men and women from five European countries : France , Ireland , The Netherlands , Spain , and the U.K . Volunteers , aged 25 45 , all nonsmokers , gave blood samples before and after a 12-wk carotenoid supplementation regime . Vitamin C was measured in plasma and vitamin E and carotenoids were measured in serum by high-performance liquid chromatography ( HPLC ) . 8-oxo-dG was assayed by HPLC ( with coulometric detection ) in DNA isolated from lymphocytes from the same blood samples . Mean values were calculated for groups of volunteers at each sampling time according to country , sex , and supplementation ( between 9 and 24 individual samples contributing to each mean ) . We found that 8-oxo-dG levels in lymphocyte DNA vary significantly according to sex and country . A low mean 8-oxo-dG concentration is seen in DNA of women from all five countries , and of men from France and Spain . 8-oxo-dG is significantly higher ( up to about threefold ) in lymphocyte DNA from men in Ireland and the U.K. Oxidative DNA damage is not significantly affected by carotenoid supplementation ; nor is there any association with mean baseline levels of antioxidants , which are generally similar in the five countries . The five countries sampled lie on an axis from northern to southern Europe with a steep gradient in terms of premature heart disease . There is a strong association between premature coronary heart disease mortality in men and the mean levels of 8-oxo-dG for the five countries ( r = 0.95 , P < 0.01 ) . Women have low coronary heart disease mortality rates , which do not correlate with 8-oxo-dG . In terms of cancer deaths , only colorectal cancer in men shows a significant positive correlation ( r = 0.91 , P < 0.05 ) , and stomach cancer in women is negatively correlated with DNA oxidation ( r = -0.92 , P = 0.01 ) .

vitamin C , vitamin E , carotenoids

antioxidants

lymphocyte DNA

12-wk carotenoid supplementation regime

liquid chromatography

8-oxo-dG levels in lymphocyte DNA

mean 8-oxo-dG concentration

Oxidative DNA damage

mean baseline levels of antioxidants

coronary heart disease mortality rates

significant positive correlation

stomach cancer

men

women

25 45


Efficacy of dose-intensified MEC ( methotrexate , epirubicin and cisplatin ) chemotherapy for advanced urothelial carcinoma : a prospective randomized trial comparing MEC and M-VAC ( methotrexate , vinblastine , doxorubicin and cisplatin ) . Japanese Urothelial Cancer Research Group . BACKGROUND To evaluate the antitumor activity in patients with T3b , T4 or metastatic urothelial carcinoma treated with MEC or M-VAC chemotherapy , by performing a multi-center randomized prospective study . METHODS From 1991 to 1995 , 89 patients with T3b , T4 or metastatic urothelial carcinoma were randomly allocated to a methotrexate , epirubicin and cisplatin chemotherapy group ( arm 1 : S-MEC therapy ; n = 29 ) , a dose-intensified MEC therapy combined with G-CSF group ( arm 2 : I-MEC therapy ; n = 30 ) or a methotrexate , vinblastine , doxorubicin and cisplatin chemotherapy ( arm 3 : M-VAC therapy ; n = 30 ) . At the registration center , the patients were stratified into previously untreated patients and patients with recurrence after radical operation and then randomly allocated to the treatment groups . In each arm , two or more courses of chemotherapy ( 4-week cycles ) were performed . RESULTS Of the 88 eligible patients , four treated with S-MEC therapy and two treated with I-MEC therapy showed CR . The response rates ( CR + PR ) were 52 % ( 15/29 ) with S-MEC therapy , 76 % ( 22/29 ) with I-MEC therapy and 47 % ( 14/30 ) with M-VAC therapy . The response rate with I-MEC therapy was significantly higher than that with M-VAC therapy ( P = 0.02 ) . Although the incidence of leukopenia was low with I-MEC therapy , the incidence of thrombocytopenia was high with this therapy . CONCLUSION MEC therapy used in this study is promising in terms of the antitumor effects .

MEC

methotrexate

epirubicin

cisplatin

MEC

M-VAC

methotrexate

vinblastine

doxorubicin

cisplatin

MEC

M-VAC

methotrexate

epirubicin

cisplatin

MEC therapy

G-CSF

methotrexate

vinblastine

doxorubicin

cisplatin

M-VAC therapy

S-MEC therapy

I-MEC

S-MEC therapy

I-MEC

M-VAC

I-MEC

M-VAC

I-MEC

MEC therapy

Efficacy

antitumor activity

response rates

response rate with I-MEC therapy

I-MEC therapy

thrombocytopenia

antitumor effects

advanced urothelial carcinoma

Urothelial Cancer


Involvement of cholecystokininA receptors in transient lower esophageal sphincter relaxations triggered by gastric distension . OBJECTIVE Transient lower esophageal sphincter relaxations ( TLESRs ) are the main mechanism underlying gastroesophageal reflux . In the present study we evaluated the effect of loxiglumide , a specific cholecystokininA ( CCKA ) -receptor antagonist , on the occurrence of TLESRs evoked by gastric distension . METHODS Eight healthy subjects underwent esophageal manometry using a 10-lumen sleeve assembly during placebo or loxiglumide ( 10 mg/kg/h ) in a randomized double-blind order . Gastric distension was induced by inflation of 400 ml of air . RESULTS Basal lower esophageal pressure ( LESP ) and swallow-induced relaxation were not affected by loxiglumide . Loxiglumide significantly reduced the number of TLESRs , from 11.5 ( 5.8-18.3 ) to 6.0 ( 3.3-14.3 ) during the total recording period of 1 h , and from 5.5 ( 4.25-7.5 ) to 2.0 ( 0.5-6.8 ) during the first 15 min . The number of common cavities was significantly decreased by loxiglumide , from 8.0 ( 4.0-20.0 ) to 5.0 ( 2.0-7.8 ) . TLESRs represented the main mechanism ( 60 % during placebo , 74 % during loxiglumide ) underlying common cavities , followed by swallow-induced relaxation . CONCLUSIONS Loxiglumide significantly reduces the number of TLESRs triggered by gastric distension without interfering with swallow-related relaxation of the lower esophageal sphincter , suggesting the involvement of CCKA receptors in the reflex pathway mediating TLESRs .

10-lumen sleeve assembly during placebo

loxiglumide

swallow-induced relaxation

TLESRs

number of common cavities

TLESRs

TLESRs

Eight


Functional modification of agonist-antagonist electromyographic activity for rapid movement inhibition . Subjects made a fast elbow extension movement to designated target in response to a go signal . In 45 % of trials a stop signal was presented after the go signal , to which subjects were asked to stop the movement as rapidly as possible . The interstimulus interval ( ISI ) , or time interval between the go and stop signals , was randomly varied between 0 and 200 ms. Electromyographic ( EMG ) activity was recorded from biceps brachii and triceps brachii . Subjects could sometimes completely inhibit initiation of the movements when the ISI was 0 ms , but could rarely do so when the ISI exceeded 100 ms. For responses that were initiated but stopped on the way , the amplitude of the movement decreased linearly as the time interval ( =modification time ) from the stop signal to EMG onset increased . The peak velocity increased linearly as the movement amplitude increased . This tendency was similar to those previously reported in step-tracking movements with various amplitudes . In spite of the similarity in the kinematics of the movement , the EMG pattern was different from that of step-tracking movement . While the initial agonist burst ( AG1 ) decreased linearly after the modification time exceeded 100 ms , the antagonist burst ( ANT ) increased compared with the go trial for the modification time from 0 to 200 ms and decreased after the modification time exceeded 300 ms . This change of activation is analogous to functional modification of middle-latency reflex EMG response to load , or cutaneous perturbation . In conclusion , it is suggested that adaptive mechanisms , which would functionally modify the reflex responses , are also continuously working during voluntary movements in response to sudden changes in environmental information .

go signal

interstimulus interval ( ISI )

Electromyographic ( EMG )

Electromyographic ( EMG ) activity

amplitude of the movement

peak velocity

EMG pattern

step-tracking movement

initial agonist burst ( AG1 )

antagonist burst ( ANT )

EMG response


Evaluation of the safety , immunogenicity , and pharmacokinetic profile of a new , highly purified , heat-treated equine rabies immunoglobulin , administered either alone or in association with a purified , Vero-cell rabies vaccine . A clinical evaluation of a new , purified , heat-treated equine rabies immunoglobulin ( PHT-Erig ) , F ( ab ' ) 2 preparation , was carried out in Thailand and in the Philippines-two countries where rabies is endemic . An initial prospective , randomised , controlled trial ( Study 1 ) , compared the safety and pharmacokinetics ( serum concentrations of rabies antibodies ) after administration either of PHT-Erig or of a commercially-available , equine rabies immune globulin ( Erig PMC ) . A second trial ( Study 2 ) simulated post-exposure rabies prophylaxis by using a reference cell culture vaccine , the purified Vero-cell rabies vaccine ( PVRV ) , administered in association with either Erig PMC or PHT-Erig . In Study 1 , 27 healthy , Thai adults received a 40 IU kg ( -1 ) dose of either Erig PMC ( n = 12 ) or PHT-Erig ( n = 15 ) via the intramuscular ( i.m . ) route ; half of the dose was injected into the deltoid area and the other half into the buttocks . Serum for rabies antibody determination and F ( ab ' ) 2 concentration was collected at hours ( H ) 0 , 6 and 12 , and on day ( D ) 2 , 3 , 4 , 6 , 8 , 10 , 12 and 15 . Both products were safe , with no serious adverse events , and in particular , no anaphylactic reactions or serum sickness was reported . A statistical comparison of the pharmacokinetic parameters did not demonstrate bioequivalence of the two products . Nonetheless , the relative bioavailability of 93 % and the similar absorption rates suggest the pharmacokinetic profiles of Erig and PHT-Erig are similar . The antibody level in either group were low throughout the 15-day study period . The geometric mean titer ( GMT ) values ranged from group 0.027-0.117 IU ml ( -1 ) in the Erig group and from 0.029 to 0.072 IU ml ( -1 ) in the PHT-Erig . There was no significant difference between the evolution of GMT values for the two groups . In Study 2 , 71 healthy volunteers received 40 IU kg ( -1 ) via the intramuscular route of either Erig PMC ( n = 36 ) or PHT-Erig ( n = 35 ) on D0 , in association with five doses of PVRV on D0 , D3 , D7 , D14 and D28 . The safety evaluation was performed during the 28-day follow-up and serum samples for anti-rabies antibody titration were collected on D0 ( before injection ) D3 , D7 , D14 and D28 . No serious reactions were reported in either group . In particular , no immediate ( anaphylactic type ) or delayed ( serum sickness ) allergic reactions were observed . Over the 28-day follow-up period , GMT profiles of the two groups were statistically equivalent . On D14 , 100 % of the subjects had protective antibody titers ( anti-rabies antibodies > or = 0.5 IU ml ( -1 ) , which is the WHO-recommended level of seroconversion ) , and Erig PMC and PHT-Erig were indistinguishable according to the clinical definition chosen . On D28 , the GMT values were 33.2 IU ml ( -1 ) ( 95 % CI , 23.8-46.1 IU ml ( -1 ) ) in the Erig PMC/PVRV group and 31.4 IU ml ( -1 ) ( 95 % confidence interval , CI , 23.4-42.2 IU ml ( -1 ) ) in the PHT-Erig/PVRV group , showing evidence of adequate vaccine-induced antibody responses in both groups . The increased purity , the heat-treatment step introduced in the manufacturing process of PHT-Erig , and the good clinical results substantiate the use of this new generation , purified equine F ( ab ' ) 2 preparation in the post-exposure prophylaxis of rabies .

Vero-cell rabies vaccine .

F ( ab ' ) 2 preparation

PHT-Erig

Erig PMC

PHT-Erig

Erig PMC

PHT-Erig

safety

immunogenicity

pharmacokinetic profile

safety

pharmacokinetics

pharmacokinetic parameters

relative bioavailability

absorption rates

antibody level

geometric mean titer ( GMT ) values

evolution of GMT values

safety evaluation

serious reactions

GMT profiles

protective antibody titers

GMT values

antibody responses

adults


Preventing disability and managing chronic illness in frail older adults : a randomized trial of a community-based partnership with primary care . BACKGROUND Effective new strategies that complement primary care are needed to reduce disability risks and improve self-management of chronic illness in frail older people living in the community . OBJECTIVE To evaluate the impact of a 1-year , senior center-based chronic illness self-management and disability prevention program on health , functioning , and healthcare utilization in frail older adults . DESIGN A randomized controlled trial . SETTING A large senior center located in a northeast Seattle suburb . The trial was conducted in collaboration with primary care providers of two large managed care organizations . PARTICIPANTS A total of 201 chronically ill older adults seniors aged 70 and older recruited through medical practices . INTERVENTION A targeted , multi-component disability prevention and disease self-management program led by a geriatric nurse practitioner ( GNP ) . MEASUREMENTS Self-reported Physical function , physical performance tests , health care utilization , and health behaviors . RESULTS Each of 101 intervention participants met with the GNP from 1 to 8 times ( median = 3 ) during the study year . The intervention group showed less decline in function , as measured by disability days and lower scores on the Health Assessment Questionnaire . Other measures of function , including the SF-36 and a battery of physical performance tests , did not change with the intervention . The number of hospitalized participants increased by 69 % among the controls and decreased by 38 % in the intervention group ( P = .083 ) . The total number of inpatient hospital days during the study year was significantly less in the intervention group compared with controls ( total days = 33 vs 116 , P = .049 ) . The intervention led to significantly higher levels of physical activity and senior center participation and significant reductions in the use of psychoactive medications . CONCLUSIONS This project provides evidence that a community-based collaboration with primary care providers can improve function and reduce inpatient utilization in chronically ill older adults . Linking organized medical care with complementary community-based interventions may be a promising direction for research and practice .

A targeted , multi-component

disability

managing chronic illness

improve self-management

chronic illness

chronic illness

self-management

disability prevention program on health

functioning

healthcare utilization

Self-reported Physical function

physical performance tests

health care utilization

health behaviors

less decline in

function

disability days

lower scores

Health Assessment Questionnaire

number of hospitalized participants

total number of inpatient hospital days

physical activity

senior center participation

use of psychoactive medications

function

inpatient utilization

frail

older adults

frail

older people

70 and older

chronically ill

older adults


Acute effects of caffeine ingestion on signal-averaged electrocardiograms . BACKGROUND Although moderate caffeine ingestion has not been shown to be arrhythmogenic , caffeine toxicity can cause severe cardiac arrhythmias , including atrial fibrillation and ventricular tachycardia . Atrial fibrillation and ventricular tachycardia have been associated with prolongation of P-wave and QRS complex durations on signal-averaged electrocardiograms . This study investigated acute effects of caffeine ingestion on signal-averaged P-wave and QRS complexes . METHODS AND RESULTS Signal-averaged electrocardiograms were obtained from 12 normal subjects ( 6 men , 6 women ; ages 21 to 26 years ) before and after ingestion of caffeine ( 5 mg/kg body weight ) or placebo in a randomized , double-blind , crossover fashion . Electrocardiograms for signal averaging were recorded from electrodes left in a constant location . After bandpass filtering ( 30 to 300 Hz ) and amplification , signals were sampled over 7.2 minutes at 2000 Hz . Signal-averaged P-wave and QRS complex durations did not significantly change after placebo ingestion . After caffeine ingestion QRS duration prolonged in 9 of 11 subjects at 90 minutes ( mean +/- SEM = 0.8+/-0.3 ms , P < .02 ) and in 8 of 9 after 3 hours ( 1.1+/-0.2 ms , P < .001 ) . No significant change in P-wave duration or heart rate was found after caffeine ingestion at any test interval . Average caffeine level in saliva 90 minutes after ingestion was 6.6+/-1.6 ( SD ) microg/dL . CONCLUSIONS Although probably not arrhythmogenic in normal subjects , moderate caffeine ingestion does produce a small but statistically significant prolongation of signal-averaged QRS complexes . Further prolongation caused by excessive caffeine intake may be a factor in the genesis of arrhythmias associated with caffeine toxicity .

caffeine ingestion

caffeine

placebo

signal-averaged electrocardiograms .

signal-averaged P-wave

P-wave duration or heart rate

Average caffeine level in saliva


Pharmacokinetics of cefuroxime in healthy volunteers : an update .

cefuroxime

healthy volunteers :

healthy volunteers :


Preoperative irradiation versus the use of nonsteroidal anti-inflammatory drugs for prevention of heterotopic ossification following total hip replacement : the results of a randomized trial . PURPOSE Previous studies showed the effectiveness of early preoperative ( 4 h before operation ) irradiation for prevention of heterotopic ossification ( HO ) after total hip replacement . This procedure can result in logistic problems , if there is a great distance between the department of radiotherapy and the orthopedic clinic . To avoid these organizational problems a prospective study was undertaken to analyze the effectiveness of preoperative irradiation on the day preceding surgery ( 16-20 h before operation ) . METHODS AND MATERIALS Between 1995 and 1996 , 100 patients were randomized to receive a prophylactic therapy for prevention of heterotopic ossification . Forty-six patients were irradiated with 7 Gy single dose within 16-20 h before operation . Fifty-four patients were treated with nonsteroidal anti-inflammatory drugs ( NSAID ) ( Voltaren resinat 2 x 75 mg/day for 2 weeks ) . Heterotopic ossification was scored according to the Brooker Grading system . One hundred patients receiving no prophylactic therapy after total hip arthroplasty between 1988 and 1992 were analyzed and defined as the historical control group . RESULTS Incidence of heterotopic ossification was 47.8 % in the 7 Gy preoperative group ( Brooker Score I : 36.9 % ; II : 8.7 % ; III : 2.2 % ; IV : 0 % ) and 11.1 % in the NSAID group ( Brooker Score I : 9.3 % ; II : 1.8 % ; III : 0 % ; IV : 0 % ) . Regarding overall heterotopic ossification there was a significant difference between the NSAID group and the 7 Gy group ( p < 0.01 ) . Analyzing the clinically significant heterotopic ossification ( Brooker Score III and IV ) there was no significant difference between the two treatment arms ( p > 0.05 ) . In the untreated historical control group the incidence of heterotopic ossification was 65 % ( Brooker Score I : 26 % ; II : 15 % ; III : 19 % ; IV : 5 % ) . Referring to overall and to clinically relevant heterotopic ossification the incidence of HO was greater in the control group than in the prophylactically treated groups ( p < 0.05 ) . CONCLUSION Irradiation within 16-20 h before operation and use of NSAID ( Voltaren resinat ) can reduce the incidence of clinically relevant heterotopic ossification after total hip replacement .

heterotopic ossification

heterotopic ossification

Heterotopic ossification

Brooker Grading system

heterotopic ossification

Brooker Score

Brooker Score

heterotopic ossification

heterotopic ossification (

Brooker Score III and IV

heterotopic ossification

Brooker Score

heterotopic ossification

HO

total hip replacement

100 patients

heterotopic ossification


Efficacy and safety relative to placebo of an oral formulation of cetirizine and sustained-release pseudoephedrine in the management of nasal congestion . BACKGROUND The aim of this study was to assess the clinical efficacy of an oral formulation of cetirizine 5 mg with sustained-release pseudoephedrine ( PSE ) 120 mg relative to placebo in patients with nasal congestion . METHODS Twenty-four patients with perennial rhinitis due to house-dust-mite ( HDM ) allergy were recruited in this crossover study . A treatment period of 1 week , in which cetirizine/PSE was administered twice daily , was followed by a washout period of at least 2 weeks and a further period of 1 week in which the alternative treatment was given to each patient . Immediately after the first dose of each medication ( day 1 ) , nasal congestion and related symptoms were assessed during a 7-h challenge with HDM feces , with the Vienna Challenge Chamber ( VCC ) , to investigate onset of action of the preparation . A second challenge of 3-h duration , carried out at least 12 h after the final dose , was undertaken after 1 week ( mean ) of twice-daily treatment to assess residual effects of the formulation after achievement of steady state . RESULTS The oral formulation of cetirizine/PSE was significantly ( P < 0.001 ) superior to placebo in improving nasal obstruction during both challenges . The improvement in nasal airflow and nasal patency was significantly greater with cetirizine/PSE than with placebo ( P < 0.02 ) . In addition , subjective assessment of nasal symptoms showed that cetirizine/PSE was significantly superior to placebo in both challenges for the sum of nasal obstruction scores ( P < 0.01 ) . Both medications were well tolerated , and no serious adverse events occurred during the study . CONCLUSIONS In this study , cetirizine/PSE relieved nasal congestion and other objective and subjective symptoms to a significantly greater extent than placebo . No serious adverse events occurred , and both regimens were equally well tolerated .

placebo

cetirizine

pseudoephedrine

cetirizine

pseudoephedrine

placebo

cetirizine/PSE

cetirizine/PSE

placebo

cetirizine/PSE

placebo

placebo

cetirizine/PSE

Efficacy

safety

management of nasal congestion

clinical efficacy

nasal congestion

effects

nasal obstruction

nasal airflow

nasal patency

sum of nasal obstruction scores

tolerated

adverse events

nasal congestion

adverse events

tolerated

nasal congestion

patients with nasal congestion .

Twenty-four


The " SPEM " ( Studio Policentrico Elettrocateteri Membrane ) : a multicenter study on membrane leads . SPEM is a multicenter randomized double-blind study performed to test the acute and chronic electrophysiological behavior of three different ventricular leads : ( 1 ) an ion exchange membrane with 30-microgram dexamethasone elution in a contoured activated carbon tip lead ( Membrane 1400T , 30 patients ) ; ( 2 ) the same lead design without steroid ( Membrane 1401T , 24 patients ) ; and ( 3 ) the same lead design without steroid or membrane ( control group , 27 patients ) . Twenty-three of the 81 patients were women ; the mean age for all patients was 74 +/- 10 years . Parameters are calculated both in uni- and bipolar configuration at implant and at follow-up after 1 , 5 , 15 , 30 , 90 , 180 , and 360 days . Implant threshold ( chronaxie = 0.413 +/- 0.280 ms , rheobase = 0.264 +/- 0.099 V ) , signal amplitude ( 13.45 +/- 5.87 mV ) , and slew rate ( 2.05 +/- 1.38 V/s ) reveal no significant differences . Pacing impedance values both at implant ( unipolar 571 +/- 165 omega ; bipolar 605 +/- 123 omega ) and at follow-ups ( unipolar 480 +/- 72 omega ; bipolar 518 +/- 75 omega ) are slightly lower in the unipolar configuration . At 15 and 30-day follow-ups , control group and nonsteroid leads show a higher threshold value growth ( in unipolar from 0.16 +/- 0.11 to 1.19 +/- 0.85 microJ ; in bipolar from 0.18 +/- 0.13 to 1.24 +/- 0.88 microJ ) than the membrane steroid leads ( in unipolar from 0.13 +/- 0.11 to 0.70 +/- 0.39 microJ ; in bipolar from 0.23 +/- 0.32 to 0.76 +/- 0.36 microJ ) ; the threshold of nonsteroid leads decreases after 1-3 months and it settles at the same threshold level of the leads with membrane and steroid ( in unipolar 0.60 +/- 0.33 microJ ; in bipolar 0.55 +/- 0.26 microJ ) , which has been stable since the first month . The ion exchange membrane is effective in reducing the chronic pacing threshold like acute steroid elution at low doses , but membrane alone does not prevent an acute pacing threshold increase through the first month postimplant .

same lead design without steroid

ion exchange membrane

Pacing impedance values

threshold

threshold

threshold

chronic pacing threshold

acute pacing threshold

membrane leads

ventricular leads

Twenty-three

women

74 +/- 10 years


A search for serologic correlates of immunity to Bordetella pertussis cough illnesses . In a pertussis vaccine efficacy trial in Germany we collected sera from vaccinees ( DTaP or DTP ) after the third and fourth doses of vaccine or at comparable time periods in DT vaccine recipients . In addition , sera were collected from a randomized sample of subjects in each vaccine group at approximately 3-month intervals from which antibody kinetic curves were constructed , which allowed us to estimate specific antibody values to pertussis toxin ( PT ) , filamentous hemagglutinin ( FHA ) , pertactin and fimbriae-2 at the time of exposure in the household setting . The imputed geometric mean antibody values to PT , pertactin and fimbriae-2 at the time of household exposure to Bordetella pertussis infection were higher ( p < 0.07 or lower ) in non-cases compared with cases . A multivariate ( classification tree ) analysis found that only pertactin and PT were significant in protection . Subjects with an imputed pertactin value of < 7 EU ml-1 had a 67 % ( 18/27 ) chance of infection regardless of the PT value . If the pertactin value was > or = 7 EU ml-1 and the PT value > or = 66 EU ml-1 all subjects were non-cases . If the pertactin value was > or = 7 and the PT value was < 66 EU ml-1 the predicted probability of being a case was 31 % ( 15/49 ) . Logistic regression analysis also found that high versus low pertactin values were associated with illness prevention following household exposure . In the presence of antibody to pertactin , PT and fimbriae-2 , the additional presence of antibody to FHA did not contribute to protection . Our data support historical data indicating that agglutinating antibodies are associated with protection and also recent serologic correlates data and clinical efficacy data which indicate that multicomponent vaccines containing pertactin and fimbriae have better efficacy than PT or PT/FHA vaccines .

vaccinees ( DTaP or DTP )

pertussis

Logistic regression analysis


Blind versus open approach to laparoscopic cholecystectomy : a randomized study . Intraabdominal structures may be damaged during blind introduction of the first trocar for laparoscopic operations . In this study , 150 patients with gallbladder lithiasis who underwent laparoscopy were randomly assigned to two groups , a blind ( V group ) or an open ( H group ) , in order to compare the results and the rate of complications . No mortality was observed . Major complications occurred in 3/75 ( 4 % ) patients of the V group and in 1/75 ( 1.3 % ) patient of the H group ( p < 0.05 ) . Minor complications occurred in 5/75 ( 6.7 % ) patients of either group . The achievement of pneumoperitoneum required 4.5+/-0.4 min in the V group and 3.2+/-0.2 min in the H group ( p < 0.05 ) . The open laparoscopic technique is safer and faster than the blind approach ; therefore , it is proposed that this approach be routinely used in all laparoscopic procedures .

laparoscopic

open laparoscopic technique

blind approach

rate of complications

mortality

Major complications

Minor complications

achievement of pneumoperitoneum

gallbladder lithiasis

laparoscopy


A comparison of the recovery times of desflurane and isoflurane in outpatient anesthesia . The low solubility of desflurane has been shown to contribute to faster awakening from anesthesia when compared with other anesthetics in common use . However , research has failed to consistently demonstrate faster discharge times from the postanesthesia care unit following the use of desflurane . This study was undertaken to compare the recovery and discharge times of outpatients undergoing procedures greater than 2 hours in length . Thirty-three patients aged 18 to 70 years were randomized to receive either desflurane or isoflurane following a standard intravenous induction with propofol . Patients received premedication and opioids consistent with institutional practice , and inhalation agents were titrated to effect during anesthetic maintenance . Following surgery , patients were evaluated for time to emergence and time to meeting discharge criteria . The results demonstrated no differences between the emergence or discharge times following desflurane or isoflurane . In addition , measured parameters , such as intraoperative vital signs and postoperative emesis and opioid requirements , were not different between the groups . The use of desflurane as part of a balanced anesthetic technique did not speed the emergence or discharge time when compared with isoflurane .

desflurane

isoflurane

desflurane

desflurane

desflurane

isoflurane

propofol

desflurane

isoflurane

desflurane

isoflurane

recovery times

recovery and discharge times

discharge time

outpatient anesthesia

Thirty-three

patients

18 to 70


Sunbathing and sunbed use related to self-image in a randomized sample of Swedish adolescents . In 1996 a randomized sample of 4,020 Swedish adolescents from three birth cohorts were sent a questionnaire consisting of 50 items concerning habitual sun-related behaviours and attitudes , knowledge about melanoma , risk perception and self-image . A total of 2,615 questionnaires were returned . Girls sunbathed and used sunbeds more than boys at all ages . Sunbathing and sunbed use increased with age . Boys who were most satisfied and girls least satisfied with themselves sunbathed most . Those who were least satisfied with themselves used sunbeds most frequently . Girls reported a higher perceived susceptibility to melanoma than did boys . The perception of susceptibility increased with age . Those who were least satisfied with themselves reported feeling most susceptible . The overall main reason for sunbathing was appearance , both for own sunbathing , and to an even higher degree , as a supposed reason for other adolescents ' behaviour , and was reported most frequently by girls and the older age groups . The second most 'important ' reason for sunbathing was 'feeling warm and comfortable ' . Preventive programmes aimed at a change of sun related behaviours among Swedish adolescents have to be tailored to the climate and cultural conditions and must take into account that having a tan , and the warmth of the sun , are highly valued by most adolescents .

questionnaire

questionnaires

Sunbathing and sunbed use

most satisfied

least satisfied

sunbathed

used sunbeds

perception of susceptibility

most susceptible .

reason for sunbathing

'feeling warm and comfortable

adolescents

adolescents

Girls

boys


Oral ganciclovir dosing in transplant recipients and dialysis patients based on renal function . BACKGROUND An oral formulation of ganciclovir ( GCV ) was recently approved for the prevention of cytomegalovirus disease in solid organ transplant recipients . This study was designed to determine the bioavailability of GCV and to test a dosing algorithm in transplant and dialysis patients with different levels of renal function . METHODS Pharmacokinetic studies were carried out in 23 patients who were either a recipient of an organ transplant or on hemodialysis . Drug dosing was established by the following algorithm based on calculated creatinine clearance ( CrCl ) : CrCl = [ ( 140-age ) x body weight ] / ( 72 x Cr ) x 0.85 for women that is , CrCl > 50 ml/min , 1000 mg every 8 hr ; CrCl of 25-50 ml/min , 1000 mg every 24 hr ; CrCl of 10-24 ml/ min , 500 mg every day ; CrCl < 10 ml/min ( or on dialysis ) , 500 mg every other day after dialysis . GCV was taken within 30 min after a meal . The patients received oral GCV for between 12 days and 14 weeks . Serum specimens ( or plasma from patients on hemodialysis ) obtained at steady state were analyzed for GCV concentrations by high-performance liquid chromatography . In nine of the transplant recipients , absolute bioavailability was determined by comparing GCV levels after single oral and intravenous doses of GCV . RESULTS The following GCV concentrations ( mean +/-SD ) were determined : with CrCl of > or =70 ml/min , the minimum steady-state concentration ( Cmin ) and maximum concentration ( Cmax ) were 0.78+/-0.46 microg/ml and 1.42+/-0.37 microg/ml , respectively , with a 24-hr area under the concentration time curve ( AUC0-24 ) of 24.7+/-7.8 microg x hr/ml ; with CrCl of 50-69 ml/min , the Cmin and Cmax were 1.93+/-0.48 and 2.57+/-0.39 microg/ml , respectively , with an AUC0-24 of 52.1+/-10.1 microg x hr/ml ; with CrCl of 25-50 ml/min , the Cmin and Cmax were 0.41+/-0.27 and 1.17+/-0.32 microg/ml , respectively , with an AUC0-24 of 14.6+/-7.4 microg x hr/ml . For one patient with a CrCl of 23.8 ml/min , the Cmin and Cmax were 0.32 and 0.7 microg/ml , respectively , with an AUC0-24 of 10.7 microg x hr/ml . With CrCl of < 10 ml/min , the mean Cmin and Cmax were 0.75+/-0.42 and 1.59+/-0.55 microg/ml , respectively , with a mean AUC0-24 of 64.6+/-18.8 microg x hr/ml . Absolute bioavailability , for the nine patients so analyzed , was 7.2+/-2.4 % . For those patients with end-stage renal failure , GCV concentrations fell during dialysis from a mean of 1.47+/-0.48 microg/ml before dialysis to 0.69+/-0.38 microg/ml after dialysis . CONCLUSIONS The bioavailability of oral GCV in transplant patients was similar to that observed in human immunodeficiency virus-infected patients . However , levels between 0.5 and 1 microg/ml ( within the IC50 of most cytomegalovirus isolates ) could be achieved with tolerable oral doses . The proposed dosing algorithm resulted in adequate levels for patients with CrCl greater than 50 ml/min and for patients on dialysis . For patients with CrCl between 10 and 50 ml/min , the levels achieved were low and these patients would likely benefit from increased doses .

GCV

oral GCV

oral GCV

absolute bioavailability

GCV levels

GCV concentrations

Absolute bioavailability

GCV concentrations

23 patients

end-stage renal failure

human immunodeficiency virus-infected


Treatment of children with autism : a randomized controlled trial to evaluate a caregiver-based intervention program in community day-care centers . This study reports on the results of a randomized controlled trial that evaluated a caregiver-based intervention program for children with autism in community day-care centers . Thirty-five preschool children with a DSM III-R diagnosis of autism or pervasive developmental disorder were randomized to an experimental or control group . Children in the experimental group were enrolled in day care and their parents and child care workers received a 12-week intervention consisting of lectures and on-site consultations to day-care centers . In addition , supportive work was undertaken with families . Control subjects received day care alone . In the experimental group , there were greater gains in language abilities , significant increases in caregivers ' knowledge about autism , greater perception of control on the part of mothers , and greater parent satisfaction . We conclude that this research design demonstrated that the intervention was significantly superior to day care alone .

caregiver-based intervention program

day care alone

language abilities

caregivers ' knowledge about autism

parent satisfaction .


Accuracy and feasibility of contrast echocardiography for detection of perfusion defects in routine practice : comparison with wall motion and technetium-99m sestamibi single-photon emission computed tomography . The Nycomed NC100100 Investigators . OBJECTIVES We sought to assess the feasibility and accuracy of myocardial contrast echocardiography ( MCE ) using standard imaging approaches for the detection of perfusion defects in patients who had a myocardial infarction ( MI ) . BACKGROUND Myocardial contrast echocardiography may be more versatile than perfusion scintigraphy for identifying the presence and extent of perfusion defects after MI . However , its reliability in routine practice is unclear . METHODS Fundamental or harmonic MCE was performed with continuous or triggered imaging in 203 patients with a previous MI using bolus doses of a perfluorocarbon-filled contrast agent ( NC100100 ) . All patients underwent single-photon emission computed tomography ( SPECT ) after the injection of technetium-99m ( Tc-99m ) sestamibi at rest . Quantitative and semiquantitative SPECT , wall motion and digitized echocardiographic data were interpreted independently . The accuracy of MCE was assessed for detection of segments and patients with moderate and severe sestamibi-SPECT defects , as well as for detection of patients with extensive perfusion defects ( > 12 % of left ventricle ) . RESULTS In segments with diagnostic MCE , the segmental sensitivity ranged from 14 % to 65 % , and the specificity varied from 78 % to 95 % , depending on the dose of contrast agent . Using both segment- and patient-based analysis , the greatest accuracy and proportion of interpretable images were obtained using harmonic imaging in the triggered mode . For the detection of extensive defects , the sensitivity varied from 13 % to 48 % , with specificity from 63 % to 100 % . Harmonic imaging remained the most accurate approach . Time since MI and SPECT defect location and intensity were all determinants of the MCE response . The extent of defects on MCE was less than the extent of either abnormal wall motion or SPECT abnormalities . The combination of wall motion and MCE assessment gave the best balance of sensitivity ( 46 % to 55 % ) and specificity ( 82 % to 83 % ) . CONCLUSIONS Although MCE is specific , it has limited sensitivity for detection of moderate or severe perfusion defects , and it underestimates the extent of SPECT defects . The best results are obtained by integration with wall motion . More sophisticated methods of acquisition and interpretation are needed to enhance the feasibility of this technique in routine practice .

contrast echocardiography

Myocardial contrast echocardiography

perfusion scintigraphy

SPECT

MCE

segmental sensitivity

specificity

sensitivity

Time since MI

SPECT defect location and intensity

extent of defects on MCE

moderate or severe perfusion defects

SPECT defects


Recombinant human granulocyte and granulocyte-macrophage colony-stimulating factor ( G-CSF and GM-CSF ) administered following cytotoxic chemotherapy have a similar ability to mobilize peripheral blood stem cells . The availability of hematopoietic growth factors has greatly facilitated the mobilization and collection of peripheral blood stem cells ( PBSC ) . It was the aim of this double-blind study to compare the PBSC-mobilizing efficacy of recombinant human G-CSF and GM-CSF when administered post-chemotherapy . Twenty-six patients with relapsed Hodgkin 's disease were included in the study . Their median age was 31 years ( range , 22-59 ) and 14 patients were males and 12 were females . Patients were pretreated with a median of eight cycles of cytotoxic chemotherapy , while 18 patients had undergone extended field irradiation . The patients received dexamethasone 24 mg days 1-7 , melphalan 30 mg/m2 day 3 , BCNU 60 mg/m2 day 3 , etoposide 75 mg/m2 days 4-7 , Ara-C 100 mg/m2 twice daily days 4-7 ( Dexa-BEAM ) . Twelve patients were randomized to receive 5/microg/kg/day G-CSF and 14 patients to receive 5 microg/kg/day GM-CSF , both administered subcutaneously starting on day 1 after the end of Dexa-BEAM . Primary endpoints of the study were the number of CD34+ cells harvested per kg body weight on the occasion of six consecutive leukaphereses and the time needed for hematological reconstitution following autografting . Twenty-one patients completed PBSC collection , and six patients of the G-CSF group and nine of the GM-CSF group were autografted . No difference was observed with respect to the median yield of CFU-GM and CD34+ cells : 32.5 x 10 ( 4 ) /kg vs 31.3 x 10 ( 4 ) /kg CFU-GM , and 7.6 x 10 ( 6 ) /kg vs 5.6 x 10 ( 6 ) /kg CD34+ cells , for G-CSF and GM-CSF , respectively ( U test , P= 0.837 and 0.696 ) . High-dose chemotherapy consisted of cyclophosphamide 1.7 g/m2 days 1-4 , BCNU 150 mg/m2 days 1-4 , etoposide 400 mg/m2 days 1-4 . All patients transplanted with more than 5 x 10 ( 6 ) CD34+ cells/kg had a rapid platelet recovery ( 20 x 10 ( 9 ) /l ) between 6 and 11 days and neutrophil recovery ( 0.5 x 10 ( 9 ) /1 ) between 9 and 16 days , while patients transplanted with less than 5 x 10 ( 6 ) /kg had a delayed reconstitution , regardless of the kind of growth factor used for PBSC mobilization . In conclusion , our data indicate that in patients with Hodgkin 's disease G-CSF and GM-CSF given after salvage chemotherapy appear to be not different in their ability to mobilize PBSC resulting in a similar time needed for hematological reconstitution when autografted following high-dose therapy .

cytotoxic chemotherapy

recombinant human G-CSF

GM-CSF

post-chemotherapy

cytotoxic chemotherapy

receive 5/microg/kg/day G-CSF

5 microg/kg/day GM-CSF

Dexa-BEAM

G-CSF

GM-CSF

cyclophosphamide

BCNU

etoposide

median yield of CFU-GM and CD34+ cells

G-CSF

and

GM-CSF

platelet recovery

neutrophil recovery

ability to mobilize

PBSC

Twenty-six

relapsed Hodgkin 's disease

males

females

Hodgkin 's disease


Long-term outcome of migraine therapy : predictive value of the frontotemporal nitroglycerin test . We evaluated whether type of response to the migraine-induction test with a nitroglycerin ointment applied to the frontotemporal head region could predict the efficacy of antimigraine therapy . Forty-two patients with migraine without aura underwent the test before and 2 months after antimigraine therapy . Two and 4 months after treatment withdrawal , most subjects with a negative response to the post-treatment test maintained treatment benefit , whereas benefit was lost in patients with an early onset migraine response .

migraine therapy

frontotemporal nitroglycerin test

nitroglycerin ointment

antimigraine therapy

antimigraine therapy

maintained treatment benefit

early onset migraine response

migraine

Forty-two

migraine without aura


Yohimbine in neurally mediated syncope . Pathophysiological implications . In this study , we evaluated if increased sympathetic stimulation is an essential requirement for the development of neurally mediated syncope ( NMS ) by manipulating overall sympathetic outflow in subjects susceptible to tilt-induced syncope . Eight previously characterized patients with recurrent NMS ( five females and three males ; 34+/-2 yr ) were recruited from the Vanderbilt Syncope Unit and eight age-matched controls underwent initial administration of clonidine ( CLO ) or yohimbine ( YHO ) . This was done , prospectively , to determine doses of these agents that would increase or decrease plasma norepinephrine levels by > /= 30 % . On a different day , in all subjects we determined intraarterial blood pressure , EKG and muscle sympathetic nerve activity ( MSNA ) both supine and during upright tilt . After this , subjects randomly received either CLO or YHO , and 3 h later another tilt was performed . After 1 wk , a similar procedure with the other drug was performed . During the two basal tilts , all the control subjects completed the study , whereas all the NMS patients developed syncope . Reduction in sympathetic tone by CLO resulted in a decreased tolerance to tilt in three out of eight controls and in all the NMS patients . In contrast , YHO not only increased basal plasma NorEpi levels and MSNA , but also prevented syncope in seven out of eight patients . In a selected population of patients , increased sympathetic activity is not a prerequisite for the development of syncope . Yohimbine-induced enhancement of sympathetic tone in patients with NMS improves orthostatic tolerance and raises the possibility that this drug may be a useful agent in the treatment of NMS .

Yohimbine

clonidine ( CLO )

yohimbine

CLO

YHO

CLO

plasma norepinephrine levels

Reduction in sympathetic tone

tolerance to tilt

basal plasma NorEpi levels

MSNA

syncope

sympathetic activity

neurally mediated syncope

Eight

five

females

three

males

34+/-2 yr

eight

age-matched

controls


Basal cell carcinoma of the face : surgery or radiotherapy ? Results of a randomized study .

surgery

radiotherapy

Basal cell carcinoma of the face


Succinate sumatriptan evaluation by Doppler echocardiography in patients with migraine . Recent reports show that sumatriptan administration increases blood pressure and vascular resistance both in systemic and pulmonary circulation . This study was performed to evaluate by echo-Doppler technique the hemodynamic effects of subcutaneous sumatriptan administration . Forty-one migraine subjects ( 26 males , 15 females ) , mean age 36 +/- 2 years ( range 36-39 years ) , and 20 healthy control subjects ( 14 males , six females ) , mean age 36 +/- 2 years ( range 36-39 years ) were randomized ( double-blind ) to receiving sumatriptan ( group A ) or placebo ( group B ) . After a 2-week complete pharmacological washout , clinical examination , electrocardiogram , and Doppler echocardiography were performed at baseline , 15 , 30 , 45 , and 60 min after sumatriptan or placebo administration . No significant differences were found between the two groups regarding Doppler echocardiographic parameters ( aortic integral , pulmonary integral , end-systolic and end-diastolic diameters ) and heart rate ; only a slight but not significant increase in arterial blood pressure was observed in group A . Our data show that succinate sumatriptan can be used with safety in patients without hypertension and other cardiovascular disease .

Succinate sumatriptan

sumatriptan

sumatriptan ( group A )

placebo ( group B )

succinate sumatriptan

blood pressure and vascular resistance

hemodynamic effects

aortic integral

pulmonary integral

heart rate

patients with migraine .


High-intensity physical training in adults with asthma . A comparison between training on land and in water . The purpose of this study was to determine whether inactive asthmatic patients could perform high-intensity physical training equally well on land as in water , and to compare the effects of these training forms . Thirty-two adults with asthma , randomized into two groups , underwent a 10-week supervised rehabilitation program with emphasis on physical training . All patients , irrespective of training form , were able to exercise to maximal intensity ( 80-90 % of estimated maximal heart rate ) . No asthmatic attacks occurred in connection with the training sessions . Respiratory variables remained almost unchanged in both groups . The asthma symptoms declined during the rehabilitation period , and the subjects needed less acute asthma care after the rehabilitation . The cardiovascular condition improved significantly and similarly in the two groups . Ten patients , 5 in each group , had exercise-induced asthma at the start of the rehabilitation . Only 3 patients , 2 from the water group and 1 from the land group , had exercise-induced asthma after 10 weeks . We conclude that indoor training , either on land or in water , is beneficial . The effects of these two training forms are almost equivalent .

High-intensity physical training

training on land and in water

high-intensity physical training

on land as in water

asthmatic attacks

Respiratory variables

asthma symptoms

declined

cardiovascular condition

exercise-induced asthma

exercise-induced asthma

effects

adults

asthma

inactive asthmatic

Thirty-two

asthma

Ten


[ Radiotherapy for choroidal neovascularization in age-related macular degeneration . A pilot study using low- versus high-dose photon bean radiation ] . PURPOSE Several pilot studies have indicated that low-dose radiation therapy might have a beneficial effect on the course of choroidal neovascularization ( CNV ) in age-related macular degeneration ( AMD ) . This study aimed to ascertain whether such treatment might halt the progression of neovascular AMD and whether a low or a high radiation dose should be applied . PATIENTS The patients comprised some randomized to 0 vs 10 vs 36 Gy of radiation and ( after a change of the study protocol became necessary ) others who participated in a prospective , controlled non-randomized pilot study . Enclosed were eyes with visual acuity of > or = 0.1 and < or = 0.6 revealing a juxta-subfoveal CNV either of the occult type ( type 1 ) or the classic type ( isolated or as part of a predominantly occult lesion ) . RESULTS Eyes treated with 10 Gy for occult CNV ( n = 12 ) were subject to severe visual loss in 41.6 % of the cases compared to 38.5 % in the control group ( n = 13 ) at 12 months of follow-up . For eyes treated with 10 Gy because of classic CNV , the corresponding figures were 33 % ( n = 18 ) and 57 % ( n = 14 ) respectively . At 18 months of follow-up , the percentages were 63 % and 75 % respectively . Fluorescein angiographic growth of classic and occult CNV could not be halted by 10 Gy , while a temporary growth retardation was observed in cases irradiated with 36 Gy . CONCLUSION In the study presented , the natural course of occult CNV could not be improved by irradiation with 10 or 36 Gy . In cases of classic CNV , low-dose irradiation with 10 Gy postponed severe visual loss by a maximum of 18 months . A positive treatment effect was also observed in cases irradiated with 36 Gy ; however , a 25 % incidence of radiation retinopathy seems unacceptable .

Radiotherapy

low-dose radiation therapy

0 vs 10 vs 36 Gy of radiation

10 Gy

10 Gy

36 Gy

10 or 36 Gy

10 Gy

36 Gy

severe visual loss

temporary growth retardation

severe visual loss


Mexiletine for HIV-infected patients with painful peripheral neuropathy : a double-blind , placebo-controlled , crossover treatment trial . Although mexiletine , an antiarrhythmic with local anesthetic properties , has been reported to relieve discomfort in diabetic neuropathy , its usefulness in the treatment of HIV-related painful peripheral neuropathy ( PPN ) has not been determined . The tolerance and effectiveness of mexiletine in HIV-related PPN were assessed in 22 patients who were randomized to receive mexiletine ( maximum dose , 600 mg/day ) or placebo for 6 weeks , followed by the alternative intervention for 6 weeks after a 1-week washout period . The daily pain response was assessed using a visual analogue scale card in 19 patients who received at least 2 weeks of the drug , 16 of whom were crossed-over to receive the alternate agent . No statistically significant difference was found between the mean daily pain scores for patients receiving mexiletine versus placebo , irrespective of the order in which the agents were received . Comparing the mean individual daily pain scores for each phase of study , 5 patients ( 31 % ) had significantly less pain while receiving mexiletine compared with their response to placebo , 5 patients ( 31 % ) had significantly less pain while receiving placebo , and no difference was noted in 6 patients ( 38 % ) . Crossover and multivariate analyses for repeated measures showed no apparent difference in the response to mexiletine versus placebo . Dose-limiting adverse events occurred in 39 % of those receiving mexiletine , but only 1 patient ( 5 % ) discontinued placebo . Mexiletine was only modestly well tolerated despite its relatively brief period of administration , and no evidence was found to support its benefit in HIV-related PPN . Although a first-drug effect was not demonstrated , a powerful placebo effect was seen in some patients .

Mexiletine

mexiletine

mexiletine

placebo

mexiletine

mexiletine

placebo

placebo

mexiletine

placebo

mexiletine

placebo

Mexiletine

tolerance and effectiveness

mean daily pain scores

mean individual daily pain scores

Crossover and multivariate analyses

Dose-limiting adverse events

HIV-infected

painful peripheral neuropathy


Marginal benefit/disadvantage of granulocyte colony-stimulating factor therapy after autologous blood stem cell transplantation in children : results of a prospective randomized trial . The Japanese Cooperative Study Group of PBSCT . In this prospective trial , a total of 74 children who were scheduled to undergo high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation ( PBSCT ) were prospectively randomized at diagnosis to evaluate the effectiveness of exogenous granulocyte colony-stimulating factor ( G-CSF ) treatment in accelerating hematopoietic recovery after PBSCT . The diagnosis included acute lymphoblastic leukemia ( ALL ) ( n = 27 ) , neuroblastoma ( n = 29 ) , and miscellaneous solid tumors ( n = 18 ) . Eligibility criteria included ( 1 ) primary PBSCT , ( 2 ) chemotherapy-responsive disease , and ( 3 ) collected cell number > 1 x 10 ( 5 ) colony-forming unit-granulocyte-macrophage ( CFU-GM ) /kg and > 1 x 10 ( 6 ) CD34 ( + ) cells/kg patient 's body weight . After applying the above criteria , 11 patients were excluded due to disease progression before PBSCT ( n = 6 ) or a low number of harvested cells ( n = 5 ) , leaving 63 patients for analysis ; 32 patients in the treatment group ( 300 microg/m2 of G-CSF intravenously over 1 hour from day 1 of PBSCT ) and 31 in the control group without treatment . Two distinct disease-oriented high-dose regimens without total body irradiation consisted of the MCVAC regimen using ranimustine ( MCNU , 450 mg/m2 ) , cytosine arabinoside ( 16 g/m2 ) , etoposide ( 1.6 g/m2 ) , and cyclophosphamide ( 100 mg/kg ) for patients with ALL , and the Hi-MEC regimen using melphalan ( 180 mg/m2 ) , etoposide ( 1.6 g/m2 ) , and carboplatinum ( 1.6 g/m2 ) for those with solid tumors . Five patients ( two in the treatment group and three in the control group ) were subsequently removed due to protocol violations . All patients survived PBSCT . The median numbers of transfused mononuclear cells ( MNC ) , CD34 ( + ) cells , and CFU-GM were , respectively , 4.5 ( range , 1 to 19 ) x 10 ( 8 ) /kg , 8.0 ( 1.1 to 25 ) x 10 ( 6 ) /kg , and 3.7 ( 1.2 to 23 ) x 10 ( 5 ) /kg in the treatment group ( n = 30 ) and 2.9 ( 0.8 to 21 ) x 10 ( 8 ) /kg , 6.3 ( 1.1 to 34 ) x 10 ( 6 ) /kg , and 5.5 ( 1.3 to 37 ) x 10 ( 5 ) /kg , respectively , in the control group ( n = 28 ) , with no significant difference . After PBSCT , the time to achieve an absolute neutrophil count ( ANC ) of > 0.5 x 10 ( 9 ) /L in the treatment group was less than that in the control group ( median , 11 v 12 days ; the log-rank test , P =.046 ) , although the last day of red blood cell ( RBC ) transfusion ( day 11 v day 10 ) and the duration of febrile days ( > 38 degrees C ) after PBSCT ( 4 v 4 days ) were identical in both groups . However , platelet recovery to > 20 x 10 ( 9 ) /L was significantly longer in treatment group than control group ( 26 v 16 days ; P =.009 ) and > 50 x 10 ( 9 ) /L tended to take longer in the treatment group ( 29 v 26 days ; P =.126 ) , with significantly more platelet transfusion-dependent days ( 27 v 13 days ; t-test , P =.037 ) . When patients were divided into two different disease cohorts , ALL patients showed no difference in engraftment kinetics between the G-CSF treatment and control groups , while differences were seen in those with solid tumors . We concluded that the marginal clinical benefit of 1 day earlier recovery of granulocytes could be offset by the delayed recovery of platelets . We recommend that the routine application of costly G-CSF therapy in children undergoing PBSCT should be seriously reconsidered .

high-dose chemotherapy

granulocyte colony-stimulating factor

primary PBSCT

PBSCT

G-CSF

PBSCT

control group

Hi-MEC regimen using melphalan

etoposide

carboplatinum

benefit/disadvantage

effectiveness

hematopoietic recovery

survived

CFU-GM

duration of febrile days

platelet recovery to > 20 x 10 ( 9 ) /L

platelet transfusion-dependent days

engraftment kinetics

recovery of granulocytes

recovery of platelets .

children

children

high-dose chemotherapy

acute lymphoblastic leukemia

neuroblastoma

miscellaneous solid tumors

primary PBSCT

chemotherapy-responsive disease

PBSCT

Five

two

three

children

PBSCT


Concurrent administration of donepezil HCl and digoxin : assessment of pharmacokinetic changes . AIM The aim of this study was to examine the pharmacokinetics of donepezil HCl and digoxin separately , and in combination , following administration of single oral doses . Changes in cardiac conduction parameters following drug administration were also assessed . METHODS This was an open-label , randomized , three-period crossover study in healthy male volunteers ( n=12 ) . During each treatment period , subjects received a single dose of either donepezil HCl ( 5 mg ) , digoxin ( 0.25 mg ) , or a combination of both drugs . Each treatment period was followed by a 2-week , drug-free washout period . RESULTS All 12 volunteers completed the study without incident . No statistically significant differences in donepezil pharmacokinetics ( Cmax , tmax , AUC ( 0-120 ) , AUC ( 0-infinity ) or t1/2 ) were observed when donepezil administered alone was compared with donepezil administered in combination with digoxin . Similarly , no statistically significant differences in digoxin pharmacokinetics were observed when digoxin was administered alone or in combination with donepezil . No clinically relevant changes in cardiac conduction ( lead II ECG ) were observed in any subject during any treatment period . CONCLUSIONS Co-administration of single doses of donepezil HCl ( 5 mg ) and digoxin ( 0.25 mg ) produced no changes in the pharmacokinetic profile of either drug . In addition , co-administration produced no changes in cardiac conduction parameters during the 24 h of telemetry monitoring following drug administration .

donepezil HCl and digoxin :

donepezil HCl ( 5 mg )

digoxin ( 0.25 mg )

donepezil administered alone

donepezil administered

digoxin

digoxin

donepezil pharmacokinetics

cardiac conduction

male


[ Clinical trial of 2 tobacco use cessation interventions in primary care ] . OBJECTIVE To study the efficacy of two types of intervention to stop tobacco dependency . DESIGN Randomised clinical trial . SETTING Primary care centre . PATIENTS AND OTHER PARTICIPANTS Smokers recruited from among the health centre users through the preventive activities and health promotion programme . INTERVENTIONS INDEPENDENT VARIABLE type of intervention . General variables : age , sex , marital status , educational level , work situation , cohabitation with children , smokers at home , number of years smoking , type of tobacco . There were two types of intervention : a ) Minimal Intervention ( MI ) . b ) Advanced Intervention ( AI ) . 54 patients were included , with 6 losses . 21 were assigned at random to the MI group and 27 to the AI group . Progress was measured at 15 days , 1 month , 3 months , 6 months and a year . RESULTS In the MI , 23.8 % were abstinent at 15 days ; the same percentage at one month and 3 months ; 19 % at 6 months ; and 14.3 % remained abstinent after a year . In the AI , 51.9 % were abstinent at 15 days ; 48.1 % at both one and 3 months ; 25.9 % at 6 months ; and 22.2 % were still not smoking after a year . No significant differences between the two interventions were found in any of the observations . CONCLUSIONS These data do not show that one intervention is better than the other . With the passage of time the effect of the intervention decreased in both groups .

cessation interventions

Minimal Intervention

Advanced Intervention

MI

AI

tobacco dependency .

abstinent

abstinent after a year .

not smoking after a year .

Smokers


Ten-year results of a randomised trial comparing cisplatin with cisplatin and cyclophosphamide in advanced , suboptimally debulked ovarian cancer . 176 eligible patients with advanced suboptimally operated ovarian carcinoma were randomly allocated to receive either cisplatin 75 mg/m2 or cisplatin 50 mg/m2 and cyclophosphamide 500 mg/m2 ( CP ) every 28 days for six courses . The overall clinical response rates ( complete response plus partial response ) were 52 and 63 % for CP and cisplatin , respectively ( non-significant ) . Including results obtained by second-look laparotomy , we did not observe a statistically significant difference in response rates in the two treatment groups . Median progression-free survival was 10 and 11.9 months for CP and cisplatin , respectively ( non-significant ) . No significant difference was observed in overall survival , with a median of 19.4 and 21.5 months for CP and cisplatin , respectively . Thirty-seven platinum-resistant and 27 platinum-sensitive tumours were treated with carboplatin or cisplatin as second-line therapy . Response rates to platinum second-line therapy were 6 and 50 % for resistant and sensitive tumours , respectively ( P < 0.001 ) . This difference in response rate was also confirmed by survival analysis . Patients with platinum-sensitive tumours survived longer when they were treated with platinum-containing chemotherapy ( P = 0.005 ) . Median survival was 22.8 and 8.5 months after initiation of second-line treatment for the platinum-containing and platinum-free regimens , respectively . In summary , we observed in suboptimally operated ovarian carcinoma patients similar response rates , progression-free interval , and overall survival for equitoxic cisplatin and CP . However , the doses of cisplatin and cyclophosphamide chosen were substantially lower than current standard doses of CP . Our study demonstrates , therefore , that a suboptimal dose of CP is as effective as optimal dose monotherapy cisplatin . Patients with recurrences considered as platinum-sensitive had a significantly higher response rate and improved survival when retreated with platinum-containing therapy .

cisplatin

cyclophosphamide

CP and cisplatin

CP and cisplatin

CP and cisplatin

carboplatin or cisplatin

platinum-containing chemotherapy

platinum-containing

platinum-free

cisplatin and CP

cisplatin and cyclophosphamide

CP

cisplatin

platinum-containing therapy

overall clinical response rates

Median progression-free survival

overall survival

Response rates

response rate

Median survival

response rates

progression-free interval

overall survival

response rate

survival


BEACOPP , a new dose-escalated and accelerated regimen , is at least as effective as COPP/ABVD in patients with advanced-stage Hodgkin 's lymphoma : interim report from a trial of the German Hodgkin 's Lymphoma Study Group . PURPOSE The HD9 trial aims to evaluate whether moderate dose escalation and/or acceleration of standard polychemotherapy is beneficial for advanced-stage Hodgkin 's disease ( HD ) . Two variants of a novel bleomycin , etoposide , doxorubicin , cyclophosphamide , vincristine , procarbazine , and prednisone ( BEACOPP ) scheme ( standard and escalated dose ) are compared with cyclophosphamide , vincristine , procarbazine , and prednisone ( COPP ) /doxorubicin , bleomycin , vinblastine , and dacarbazine ( ABVD ) . PATIENTS AND METHODS The randomized , three-arm trial recruited patients in stages IIB and IIIA with risk factors and stages IIIB and IV . BEACOPP in baseline dose contains all drug dosages of COPP/ABVD ( except vincristine and procarbazine ) rearranged in a shorter , 3-week cycle . Escalated BEACOPP uses higher doses of cyclophosphamide , doxorubicin , and etoposide with granulocyte colony-stimulating factor ( G-CSF ) support . After eight chemotherapy cycles , initial bulky and residual disease is irradiated . The trial is monitored and analyzed by means of a sequential strategy . RESULTS An interim analysis with 505 assessable patients and a median follow-up of 23 months showed a significant inferiority ( according to sequential monitoring strategy ) of the COPP/ABVD regimen in progression rate and freedom from treatment failure ( FFTF ) compared with the pooled results of both BEACOPP variants . The 24-month FFTF rate was 75 % for COPP/ABVD and 84 % for BEACOPP pooled ( P = .034 ) . There was 12 % progressive disease with COPP/ABVD and 6 % with BEACOPP pooled . Differences in survival were not significant in sequential analysis . The acute toxicity of baseline BEACOPP resembled that of COPP/ABVD ; escalated BEACOPP showed increased but manageable hematologic toxicity . CONCLUSION Combined with local irradiation , BEACOPP in one or both variants shows superior disease control compared with COPP/ABVD , with acceptable acute toxicity . Further follow-up is required to assess the effect of dosage and the effect on survival and late toxicities .

dose-escalated and accelerated regimen

COPP/ABVD

standard polychemotherapy

novel bleomycin

etoposide , doxorubicin

cyclophosphamide

vincristine

procarbazine

prednisone

cyclophosphamide

vincristine

procarbazine

prednisone ( COPP ) /doxorubicin

bleomycin

vinblastine

dacarbazine ( ABVD )

COPP/ABVD

cyclophosphamide

doxorubicin

chemotherapy

COPP/ABVD

BEACOPP

BEACOPP

BEACOPP

BEACOPP

COPP/ABVD

BEACOPP

BEACOPP

COPP/ABVD

progression rate

freedom from treatment failure ( FFTF )

24-month FFTF rate

progressive disease

Differences in survival

acute toxicity of baseline BEACOPP

HD


Optimization of acid suppression for patients with peptic ulcer bleeding : an intragastric pH-metry study with omeprazole . OBJECTIVE To study whether an intravenous infusion dose of omeprazole ( 80 mg + 8 mg/h ) during 24 h can be subsequently reduced with maintained effect . Second , to study the effect of oral omeprazole 20 mg given once or twice daily up to day 10 , after cessation of a 3-day intravenous infusion ( 80 mg + 8 mg/h ) . DESIGN Prospective , randomized , partly blinded study . METHODS Twelve Helicobacter pylori ( + ) patients and 12 H. pylori ( - ) subjects were included . In part I the patients received omeprazole , 80 mg + 8 mg/h , during 24 h followed by 8 , 4 or 2 mg/h . In part II the subjects received 80 mg + 8 mg/h during 3 days followed by 20 mg omeprazole orally , once or twice daily until day 10 . Intragastric pH was measured . RESULTS All H. pylori ( + ) patients showed a rapid increase of intragastric pH with a mean intragastric pH of 6.7 during the second half of the first day . After the subsequent dose reduction , the mean pH decreased to 6.1-6.2 . Patients continuing on 8 mg/h showed the best results . Likewise , all H. pylori ( - ) subjects showed a rapid and sustained reduction of intragastric acidity during the infusion . Subsequent dose reduction to 20 mg once daily led to a stable fraction of time with pH > 3 of 72 % . CONCLUSIONS Omeprazole given as a continuous infusion of 80 mg + 8 mg/h for 72 h followed by omeprazole 20 mg once daily raised the intragastric pH to and above levels alleged to allow haemostasis in patients with peptic ulcer bleeding and subsequent healing of the ulcer .

omeprazole .

omeprazole

omeprazole

omeprazole

omeprazole

Omeprazole

omeprazole

Intragastric pH

mean pH

intragastric acidity

intragastric pH

peptic ulcer bleeding

Helicobacter pylori ( + ) patients

H. pylori ( - ) subjects

peptic ulcer bleeding


The economic impact of esophageal variceal hemorrhage : cost-effectiveness implications of endoscopic therapy . Esophageal variceal hemorrhage ( EVH ) is a serious and expensive sequela of chronic liver disease , leading to increased utilization of resources . Today , endoscopic sclerotherapy ( ES ) and endoscopic ligation ( EL ) are the accepted , community standards of endoscopic treatment of patients with EVH . However , there are no published studies comparing the economic costs of treating EVH using these interventions . As part of a prospective , randomized trial comparing ES and EL for the treatment of EVH , we estimated the direct costs of health care utilization and cost-effectiveness for the prevention of variceal rebleeding and patient survival at 1-year follow-up . Treatment groups were similar in incidence of variceal rebleeding ( 41.9 % vs. 42.9 % ) , variceal obliteration ( 41.9 % vs. 40.0 % ) , hospital days , blood transfusions , shunt requirements , and survival ( 71.0 % vs. 60.0 % ) . There were significantly more treatment failures for active bleeding using EL ( 42 % vs. 0 % ; P =.027 ) and esophageal stricture formation in the ES-treated patients ( 19.4 % vs. 2.9 % ; P = 0.03 ) . Median total direct cost outcomes were similar between groups ( EL = $ 9,696 and ES = $ 13,197 ; P =.46 ) . EL and ES had similar cost/variceal rebleeding prevented ( $ 28,678 vs. $ 29,093 ) and cost/survival ( $ 27,313 vs. $ 23,804 ) . In the subgroup of active bleeders , ES had a substantially lower cost/survival ( $ 28,523 vs. $ 51,696 ) . We conclude that resource utilization was similar between treatment groups and that the choice of endoscopic therapy for EVH must still rely on clinical grounds . Further studies comparing costs and resource utilization in this patient population are needed .

endoscopic sclerotherapy ( ES

endoscopic ligation

variceal rebleeding

variceal obliteration

survival

active bleeding

esophageal stricture formation

Median total direct cost

cost/survival

esophageal variceal hemorrhage :

Esophageal variceal hemorrhage ( EVH )


The tolerability of lactated Ringer 's solution and BSS plus for ocular irrigation with and without the Morgan therapeutic lens . OBJECTIVE To evaluate two solutions , lactated Ringer 's ( LR ) and a balanced salt solution ( BSS Plus , Alcon Laboratories , Ft. Worth , TX ) , compared with normal saline solution ( NSS ) , for ocular irrigation in healthy adult volunteers with and without the Morgan therapeutic lens ( MTL ) . METHODS This was a prospective , double-blind , randomized study of healthy volunteers who were at least 18 years of age . Exclusion criteria included the use of analgesics within four hours of the study . A complete ophthalmologic examination was performed at baseline and at the completion of the study . Following randomization and prior to any intervention , baseline discomfort scores were obtained by means of a verbally administered , horizontal , 100-mm , unnumbered analog discomfort scale . Both eyes of each volunteer were irrigated simultaneously for 15 minutes , with additional discomfort scores being recorded every 5 minutes using the same 100-mm , unnumbered analog discomfort scale . A global evaluation to assess the method of irrigation and the solutions used for irrigation was completed by both the physician blinded to the treatment groups and the volunteers . The volunteers were continuously monitored for any adverse effects resulting from the irrigation solutions or MTL . RESULTS Sixty-three volunteers were recruited into the study , with 61 entered in the final analysis . Age and gender were balanced within each group . There was no significant difference in discomfort scores between the two groups ; however , all discomfort scores decreased over time ( p = 0.008 ) . A lens-solution interaction was identified , with LR being the most tolerated when administered with the MTL . A statistically higher ocular pH difference was seen between the pre- and postirrigation readings for the control eye in volunteers irrigated with MTL ( p = 0.046 ) . Analysis of the global evaluations for each group revealed no difference in the distributions of physician and volunteer scores . No adverse event was reported in either group . CONCLUSION There does not appear to be any difference in discomfort scores between the ocular irrigation fluids when used without the MTL . Overall , the use of the MTL appears well tolerated by healthy , adult volunteers . However , there does appear to be a significant lens-solution effect on volunteers ' discomfort scores , with LR having significantly lower discomfort scores when used for ocular irrigation with the MTL . The authors conclude that the use of the MTL for ocular irrigation is well tolerated and recommend using LR as the irrigation solution for maximal patient comfort .

lactated Ringer 's solution

BSS plus

saline solution ( NSS )

discomfort scores

discomfort scores

unnumbered analog discomfort scale .

adverse effects

discomfort scores

discomfort scores

tolerated

ocular pH difference

physician and volunteer scores .

adverse event

discomfort scores

lens-solution effect


Comparative efficacy and safety of calcium carbasalate plus metoclopramide versus ergotamine tartrate plus caffeine in the treatment of acute migraine attacks . This randomized , double-blind , double-dummy , multicenter , parallel-group study aimed at comparing the efficacy and safety of calcium carbasalate ( equivalent to 900 mg aspirin ) plus metoclopramide 10 mg ( CM ) with ergotamine tartrate 1 mg plus caffeine 100 mg ( EC ) administered in the treatment of 2 acute migraine attacks . A total of 296 patients fulfilling the International Headache Society diagnostic criteria for migraine were enrolled . In total , one or two migraine attacks were treated in 268 and 235 patients , respectively . The primary endpoint for the first treated attack was headache relief , with intensity decreasing from moderate or severe to mild or absent 2 h after drug intake . Usual secondary efficacy endpoints were assessed . A superiority of CM over EC was observed for both treated attacks for the main endpoint : success in 54 versus 36 % , p = 0.003 for the first attack and 60 versus 44 % , p = 0.02 for the second attack . CM was also significantly superior to EC during the first attack for complete headache relief ( 20 vs. 8 % , p = 0.006 ) , nausea ( 42 vs. 63 % , p = 0 . 007 ) and willingness to take the drug again ( 90 vs. 80 % , p = 0.043 ) . The global efficacy evaluation , rated by the investigators , was significantly more favorable to CM for both attacks ( p = 0.001 for the first attack and p = 0.02 for the second ) . The patients ' evaluation was significant for the first attack ( p = 0.002 ) . The global incidence of adverse events was 45 % higher with EC , though not significant ( 32 vs. 22 % , p = 0.075 ) . They were most often unspecific and mild to moderate in intensity . Gastrointestinal side effects were significantly less frequent with CM than EC ( 7 vs. 21 % , p = 0.001 ) . Thus , CM is more effective and has a better gastrointestinal safety than EC in the acute treatment of migraine attacks .

calcium carbasalate

metoclopramide

ergotamine tartrate

caffeine

metoclopramide 10 mg ( CM )

CM

EC

CM

EC

CM

EC

CM

CM

EC

complete headache relief

nausea

willingness to take the drug again

global incidence of adverse events

Gastrointestinal side effects

acute migraine

migraine


A placebo-controlled trial of D-cycloserine added to conventional neuroleptics in patients with schizophrenia . BACKGROUND In a preliminary dose-finding study , D-cycloserine , a partial agonist at the glycine modulatory site of the glutamatergic N-methyl-D-aspartate ( NMDA ) receptor , improved negative symptoms and cognitive function when added to conventional neuroleptics at a dose of 50 mg/d . METHODS Forty-seven patients with schizophrenia meeting criteria for deficit syndrome were randomized to D-cycloserine , 50 mg/d ( n=23 ) or placebo ( n=24 ) added to their conventional neuroleptic for an 8-week , double-blind trial . Clinical assessments were performed at baseline and at weeks 1 , 2 , 4 , 6 , and 8 . Serum concentrations of D-cycloserine , relevant amino acids , and homovanillic acid were assayed at baseline and at weeks 4 and 8 . A cognitive battery was performed at baseline and at week 8 . RESULTS Thirty-nine patients completed the 8-week trial . Seven dropouts occurred in the D-cycloserine group and 1 in the placebo group . The mean reduction in negative symptoms with D-cycloserine ( 23 % ) was significantly greater than with placebo ( 7 % ) as calculated by slopes representing Scale for the Assessment of Negative Symptoms ( SANS ) total scores . Improvement of negative symptoms was predicted by low neuroleptic dose and low baseline SANS total score . No differences were found in performance on any cognitive test between groups or in changes in any other clinical measure . Clinical response did not correlate significantly with serum amino acid concentrations at baseline or with concentrations of D-cycloserine at weeks 4 and 8 . CONCLUSION These results support the hypothesis that agents acting at the glycine modulatory site of the NMDA receptor improve primary negative symptoms .

placebo-controlled

D-cycloserine

D-cycloserine

D-cycloserine

placebo

D-cycloserine

D-cycloserine

placebo

D-cycloserine

placebo

D-cycloserine

cognitive battery

performance on any cognitive test

schizophrenia

Forty-seven

schizophrenia

deficit syndrome

Thirty-nine


Herpes simplex virus vaccine in recurrent herpetic ocular infection . PURPOSE To evaluate the efficacy of an antiherpetic vaccine in recurrent herpetic ocular infections . METHODS Twenty patients with herpes simplex virus 1-related recurrent keratitis/keratouveitis were prospectively enrolled and randomly assigned to receive either a specific vaccination with heat shock-inactivated herpes simplex virus type 1 ( 10 patients ) or to be observed as controls ( 10 patients ) . The number , duration , and anatomic localization of relapses were recorded in all the patients for 12 months before inclusion in the study and for a similar period after the assignment of each subject to vaccine or control group . RESULTS In the vaccine group , we observed a reduction both in the number ( p = 0.016 ) and average duration ( p = 0.050 ) of recurrences , whereas in the control group , no significant change was found comparing a 12-month period before and after inclusion in the study . The comparison between the two groups highlighted a significant reduction in the number ( p = 0.013 ) and average duration ( p = 0.051 ) of relapses in treated subjects , who did not show any significant vaccine-induced side effects . CONCLUSION The use of a vaccination with heat shock-inactivated herpes simplex virus 1 seems to be able to reduce the number and duration of relapses in herpes simplex virus 1-related keratitis/keratouveitis .

Herpes simplex virus vaccine

antiherpetic vaccine

controls

vaccination

efficacy

number

average duration

recurrences

number

average duration

relapses

number and duration of relapses

recurrent herpetic ocular infection .


Total parenteral nutrition with glutamine dipeptide shortened hospital stays and improved immune status and nitrogen economy after major abdominal surgery .

hospital stays

immune status and nitrogen economy

major abdominal surgery


Study of cytosine arabinoside ( NSC-63878 ) synchronization plus vincristine ( NSC-67574 ) , prednisone ( NSC-10023 ) , and L-asparaginase ( NSC-109229 ) for remission induction in advanced acute leukemia in children . Cytosine arabinoside ( CA ) was utilized in efforts to synchronize leukemic cells in DNA synthesis for treatment with vincristine , prednisone , and L-asparaginase in children with acute leukemia in relapse . The results did not indicate any therapeutic advantage for patients treated with this combination compared to those treated without any attempt at CA synchronization .

cytosine arabinoside

synchronization plus vincristine

prednisone

L-asparaginase

Cytosine arabinoside ( CA )

vincristine

prednisone

L-asparaginase

CA synchronization .

therapeutic advantage

advanced acute leukemia

children

children

acute leukemia in relapse


Effects of atropine and scopolamine on bradycardia and emetic symptoms in otoplasty . OBJECTIVE To assess the effects of unilateral or bilateral otoplasty on bradycardia and postoperative nausea and vomiting ( PONV ) and the efficiency of transdermal scopolamine in the prophylaxis of PONV . STUDY DESIGN Post hoc assessment of the data from a double-blind , randomized study . METHODS Fifty otoplasty patients were studied ; half of them received randomly and in double-blind fashion a transdermal therapeutic system ( patch ) of scopolamine ( TTS-scopolamine ) as prophylaxis against PONV before general anesthesia . The placebo group received atropine 10 microg x kg ( -1 ) intravenously during induction . RESULTS The scopolamine-treated patients suffered more from moderate peroperative bradycardia ( 8/25 ; P < .05 ) than the atropine-treated patients ( 1/25 ) . Two patients wearing a half of the TTS-scopolamine patch needed intravenous atropine . After unilateral otoplasty , none of the TTS-scopolamine-treated patients and 50 % of the atropine-treated patients suffered from PONV . After bilateral operation , the respective incidences were 39 % and 81 % ( P < .01 ) . After unilateral otoplasty no patient needed droperidol , but after bilateral otoplasty , 12 of 19 of the atropine-treated and 4 of 18 ( P < .05 ) of the scopolamine-treated patients needed droperidol . The mean numbers of doses of droperidol were 0.8+/-0.9 and 0.3+/-0.6 ( P < .05 ) , respectively . Two additional patients , wearing half of the TTS-scopolamine patch , suffered from mild central anticholinergic syndrome . CONCLUSION TTS-scopolamine offers effective prophylaxis against PONV ( auriculoemetic reflex ) , but does not protect from bradycardia ( auriculocardiac reflex ) in otoplasty . Cutting of the TTS-scopolamine patch may lead to undesirable side effects .

atropine

scopolamine

unilateral or bilateral otoplasty

scopolamine

placebo

scopolamine-treated

atropine-treated

TTS-scopolamine

atropine

TTS-scopolamine-treated

atropine-treated

scopolamine-treated

droperidol

TTS-scopolamine

TTS-scopolamine

TTS-scopolamine

bradycardia

emetic symptoms

bradycardia

postoperative nausea

vomiting ( PONV )

prophylaxis of PONV .

moderate peroperative bradycardia

intravenous atropine

PONV

droperidol

mean numbers of doses of droperidol

mild central anticholinergic syndrome

prophylaxis

against PONV ( auriculoemetic reflex )

bradycardia ( auriculocardiac reflex )

side effects

bradycardia

emetic symptoms

Fifty

otoplasty


The preparation of patients for cardiac surgery . This study examines the impact of a preadmission telephone intervention on anxiety , knowledge , and readiness for discharge for patients attending a preadmission teaching program prior to cardiac surgery . The primary goal of the telephone intervention was to provide support by giving additional information about individual concerns . The telephone intervention did not have an effect on anxiety and knowledge . A significantly higher level of anxiety was found in the experimental group on admission , but this difference became nonsignificant when baseline level and length of waiting time were entered as covariates . The more anxious group rated their perceived knowledge level lower , despite the fact that both groups had similar scores in actual knowledge . Given the potential barrier that anxiety can pose for patient learning , nurses need to adapt their interventions to deal with the patients ' feelings of anxiety that accompany cardiac surgery to make the learning process effective .

preadmission telephone intervention

telephone intervention

anxiety

knowledge

readiness for discharge

anxiety

knowledge

level of anxiety

perceived knowledge

scores in actual knowledge

anxiety


Network support for drinking , Alcoholics Anonymous and long-term matching effects . AIMS ( 1 ) To examine the matching hypothesis that Twelve Step Facilitation Therapy ( TSF ) is more effective than Motivational Enhancement Therapy ( MET ) for alcohol-dependent clients with networks highly supportive of drinking 3 years following treatment ; ( 2 ) to test a causal chain providing the rationale for this effect . DESIGN Outpatients were re-interviewed 3 years following treatment . ANCOVAs tested the matching hypothesis . SETTING Outpatients from five clinical research units distributed across the United States . PARTICIPANTS Eight hundred and six alcohol-dependent clients . INTERVENTION Clients were randomly assigned to one of three 12-week , manually-guided , individual treatments : TSF , MET or Cognitive Behavioral Coping Skills Therapy ( CBT ) . MEASUREMENTS Network support for drinking prior to treatment , Alcoholics Anonymous ( AA ) involvement during and following treatment , percentage of days abstinent and drinks per drinking day during months 37-39 . FINDINGS ( 1 ) The a priori matching hypothesis that TSF is more effective than MET for clients with networks supportive of drinking was supported at the 3 year follow-up ; ( 2 ) AA involvement was a partial mediator of this effect ; clients with networks supportive of drinking assigned to TSF were more likely to be involved in AA ; AA involvement was associated with better 3-year drinking outcomes for such clients . CONCLUSIONS ( 1 ) In the long-term TSF may be the treatment of choice for alcohol-dependent clients with networks supportive of drinking ; ( 2 ) involvement in AA should be given special consideration for clients with networks supportive of drinking , irrespective of the therapy they will receive .

involved in AA ; AA involvement

3-year drinking outcomes

alcohol-dependent

Outpatients

Eight hundred and six

alcohol-dependent


[ Effect of alanyl-glutamine in postoperative total parenteral nutrition on postoperative immunosuppression and morbidity . Preliminary results of a prospective randomized study ] . The impact of glutamine substitution on postoperative immunosuppression and morbidity was investigated in patients with surgical interventions and total parenteral nutrition in a prospective randomized trial . To analyze immune competence , the expression of CD3 , CD4 , and CD8 on lymphocytes and of HLA-DR and CD14 on monocytes as well as the plasma levels of IL-6 and IL-10 was evaluated before , 1 , 2 , 4 , and 7 days after surgery . A total of 34 patients have been included ( with glutamine : n = 18 ; without glutamine : n = 16 ) . Patients with glutamine substitution showed decreased systemic inflammation , significant faster compensation for postoperative immunosuppression and a lower incidence of postoperative complications . Patients without postoperative complications showed no significant differences in postoperative immunosuppression .

alanyl-glutamine

glutamine substitution

glutamine substitution

immunosuppression

morbidity

decreased systemic inflammation

immunosuppression

glutamine

without glutamine

Patients with glutamine substitution