Adjuvant subcutaneous interleukin-2 in patients with resected renal cell carcinoma : a pilot study . BACKGROUND A pilot study was conducted to investigate the toxicity and tolerance to low-dose subcutaneous interleukin-2 ( IL-2 ) for patients with resected renal cell carcinoma ( RCC ) at high risk for recurrent disease ( TNM stages III and IV resected distant metastases ) . PATIENTS AND METHODS Patients with surgically resected locally advanced ( T3-4 or N1-2 ) or metastatic RCC were randomly assigned to 1 of 4 treatment groups that received different dose levels and schedules of subcutaneous IL-2 as follows : dose level 1 , 4 MIU/m2 per day , every other week for 24 weeks ( n = 10 ) ; dose level 2 , 8 MIU/m2 per day , every other week for 24 weeks ( n = 9 ) ; dose level 3 , 4 MIU/m2 per day , weeks 1-4 , 9-12 , and 17-20 ( n = 11 ) ; and dose level 4 , 8 MIU/m2 per day , weeks 1-4 , 9-12 , and 17-20 ( n = 10 ) . Interleukin-2 was administered in 2 daily doses on days 1-5 of each week indicated . A dose level was considered tolerable if no more than 2 patients experienced grade 3/4 toxicity . RESULTS Forty-one patients were entered in the study and 40 were evaluable for toxicity . Therapy was well tolerated at all dose levels and schedules , with most patients ( 98 % ) experiencing mild-to-moderate constitutional symptoms . Grade 3/4 toxicity was seen in 8 patients ( 20 % ) . Interleukin-2 dose reductions were required in 7 patients , and no patient discontinued therapy secondary to toxicity . Of 39 patients evaluable for efficacy , 31 have experienced relapse ( 79 % ) , and 15 have died ( 38 % ) . Median survival was 1.4 years , and the 3-year disease-free survival rate was 33 % . Median overall survival has not been reached ; however , the 3-year survival rate was 70 % . There was no statistically significant difference between any of the treatment arms with respect to disease-free survival or 3-year survival ( P > 0.54 and P > or= 0.09 for all pairwise comparisons ) , schedules ( dose level 1/2 vs. 3/4 ; P = 0.46 and P = 0.5 ) , or dose of IL-2 administered ( dose level 1/3 vs. 2/4 ; P = 0.99 and P = 0.1 ) . CONCLUSION Subcutaneous IL-2 was well tolerated for 6 months in patients with surgically resected RCC at high risk of recurrence . Future adjuvant trials in this setting are not likely to include IL-2 in view of the clinical efficacy and favorable toxicity profiles of selected multitargeted kinase inhibitors .

subcutaneous interleukin-2 ( IL-2 )

Subcutaneous IL-2

toxicity

tolerance

tolerable

grade 3/4 toxicity .

toxicity .

tolerated

Grade 3/4 toxicity

Interleukin-2 dose reductions

toxicity .

relapse

died

Median survival

3-year disease-free survival rate

Median overall survival

3-year survival rate

tolerated

clinical efficacy

favorable toxicity


Long-term follow-up of the Stockholm randomized trials of postoperative radiation therapy versus adjuvant chemotherapy among 'high risk ' pre- and postmenopausal breast cancer patients . For many years , loco-regional radiotherapy was the standard postoperative treatment for node positive breast cancer patients in Sweden . Because of encouraging results from trials of adjuvant chemotherapy in the mid 1970s , the Stockholm Breast Cancer Study Group decided to directly compare postoperative radiation ( RT ) with adjuvant CMF-type chemotherapy ( CT ) . Long-term results are presented from two randomized trials of RT versus CT in pre- ( n = 547 ) and postmenopausal ( n = 679 ) patients , respectively , with node positive disease or a tumour diameter > 30 mm . RT substantially reduced loco-regional recurrences among both pre- and postmenopausal patients ( relative hazard RT versus CT : 0.67 and 0.43 , respectively ) . Among premenopausal patients distant metastases occurred less frequently in the CT group ( relative hazard : 1.68 , p > 0.001 ) resulting in an improved recurrence-free survival ( p = 0.04 ) . Overall survival was also better with CT ( cumulative survival at 15 years : 50 % and 44 % in the CT and RT groups , respectively ) but the difference was not statistically significant . Among the postmenopausal patients there were no substantial differences in terms of recurrence-free or overall survival between the treatment groups . The risk of a second primary malignancy , however , was doubled in the RT group ( p > 0.01 ) . The most pronounced excess concerned second lung cancers occurring after 10 years . The cumulative incidence at 20 years was estimated at 0.3 % and 3.7 % in the CT and RT groups , respectively . The trials illustrate the role of radiotherapy in preventing loco-regional recurrences among high-risk patients , as well as the need for systemic treatment to control the disease systemically .

postoperative radiation therapy

adjuvant chemotherapy

adjuvant chemotherapy

postoperative radiation

adjuvant CMF-type chemotherapy

RT

CT

loco-regional recurrences

distant metastases

recurrence-free survival

Overall survival

recurrence-free or overall survival

risk of a second primary malignancy

second lung cancers

cumulative incidence at 20 years

loco-regional recurrences


A fenbendazole oral drench in addition to an ivermectin pour-on reduces parasite burden and improves feedlot and carcass performance of finishing heifers compared with endectocides alone . Two studies utilizing 1,862 yearling heifers were conducted to determine the effects of a fenbendazole oral drench in addition to an ivermectin pour-on ( SG+IVPO ) , compared with an ivermectin pour-on ( IVPO ) or a doramectin injectable ( DMX ) alone , on parasite burden , feedlot performance , and carcass merit of feedlot cattle . In the first study , heifers receiving the SG+IVPO had fewer ( P = 0.02 ) cattle retreated for disease and 73 % fewer ( P = 0.06 ) worm eggs per fecal sample 98 d after treatment than heifers treated with IVPO . Heifers treated with SG+IVPO consumed more DM , had greater ADG , were heavier at slaughter , and had heavier carcasses than IVPO-treated heifers ( P < 0.05 ) . Heifers treated with SG+IVPO also had more ( P = 0.07 ) carcasses grading USDA Prime or Choice than IVPO-treated heifers . In the second study , heifers treated with SG+IVPO had fewer ( P < 0.01 ) worm eggs per fecal sample 35 d after treatment and had fewer numbers of adult and larval Cooperia and Trichostrongylus spp . in the small intestine at slaughter ( P < 0.10 ) compared with heifers treated with DMX . Heifers treated with SG+IVPO consumed more DM , were heavier at slaughter , and had heavier carcasses than DMX-treated heifers ( P < 0.01 ) . The SG+IVPO-treated heifers also had greater ADG ( P < 0.10 ) . The broad-spectrum effectiveness of a combination of a fenbendazole oral drench and an ivermectin pour-on reduced parasite burden and increased feed intake , ADG , and carcass weight in feedlot heifers compared with treatment with an endectocide alone .

fenbendazole

ivermectin

fenbendazole oral drench

ivermectin pour-on ( SG+IVPO

ivermectin pour-on ( IVPO )

doramectin injectable ( DMX ) alone

SG+IVPO-treated

reduces parasite burden

improves feedlot

carcass performance

parasite burden

feedlot performance

carcass merit of feedlot cattle

cattle retreated for disease

heavier at slaughter

heavier carcasses

carcasses

in the small intestine

greater ADG

parasite burden

increased

feed intake

carcass weight

parasite burden


Enhanced bioavailability of zeaxanthin in a milk-based formulation of wolfberry ( Gou Qi Zi ; Fructus barbarum L. ) . The carotenoid zeaxanthin is concentrated within the macula . Increased macular zeaxanthin is suggested to lower the risk of age-related macular degeneration . The small red berry , wolfberry ( Fructus barbarum L. ; Gou Qi Zi and Kei Tze ) , is one of the richest natural sources of zeaxanthin . However , carotenoid bioavailability is low , and food-based products with enhanced bioavailability are of interest . The present study investigated zeaxanthin bioavailability from three wolfberry formulations . Berries were homogenised in hot ( 80 degrees C ) water , warm ( 40 degrees C ) skimmed milk and hot ( 80 degrees C ) skimmed milk , with freeze drying of each preparation into a powdered form . A zeaxanthin-standardised dose ( 15 mg ) of each was consumed , in randomised order , together with a standardised breakfast by twelve healthy , consenting subjects in a cross-over trial , with a 3-5-week washout period between treatments . Blood samples were taken via a venous cannula immediately before ( fasting ) and 2 , 4 , 6 , 7 , 8 and 10 h post-ingestion . Zeaxanthin concentration in the triacylglycerol-rich lipoprotein fraction of plasma was measured by HPLC . Results showed that triacylglycerol-rich lipoprotein zeaxanthin peaked at 6 h post-ingestion for all formulations . Zeaxanthin bioavailability from the hot milk formulation was significantly higher ( P < 0.001 ) than from the others . Mean area under the curve ( n 12 ) results were 9.73 ( sem 2.45 ) , 3.24 ( sem 0.72 ) and 3.14 ( sem 1.09 ) nmol x h/l for the hot milk , warm milk and hot water formulations , respectively . Results showed clearly that homogenisation of wolfberry in hot skimmed milk results in a formulation that has a 3-fold enhanced bioavailability of zeaxanthin compared with both the 'classical ' hot water and warm skimmed milk treatment of the berries .

zeaxanthin

zeaxanthin

zeaxanthin

zeaxanthin .

zeaxanthin

zeaxanthin-standardised dose

Zeaxanthin

zeaxanthin

Zeaxanthin

zeaxanthin

Enhanced bioavailability of zeaxanthin

carotenoid bioavailability

bioavailability

zeaxanthin bioavailability

Zeaxanthin concentration

HPLC .

Mean area under the curve

twelve

healthy


Nuclear fragments and holes in grading of breast cancer aspirates .

grading of breast cancer aspirates


Effect of enamel preparation method on in vitro marginal microleakage of a flowable composite used as pit and fissure sealant . OBJECTIVES The aim of this in vitro study was to evaluate the microleakage in occlusal surfaces , after preparation with Er : YAG laser and compared to the diamond-bur conventional technique . METHODS Thirty premolars were divided into three groups : I - high-speed handpiece + 37 % phosphoric acid ; II - Er : YAG laser ( 350 mJ , 4 Hz and 112 J/cm ( 2 ) ) + 37 % phosphoric acid ; and III - Er : YAG laser ( 350 mJ , 4 Hz and 112 J/cm ( 2 ) ) + Er : YAG laser ( 80 mJ , 4 Hz , and 25 mJ/cm ( 2 ) ) . All cavities received the same adhesive system and were restored with flowable composite according to manufacturer 's instructions . Teeth were submitted to thermal cycling and immersed in 50 % silver nitrate solutions for 8 h in total darkness . Specimens were sectioned longitudinally in the bucco-lingual direction , in slices of 1 mm thick . Each slice was immersed into photo developing solution and was photographed , and microleakage was scored from 0 to 7 , by three calibrated examiners . RESULTS A statistically significant difference ( P < 0.0001 ) was observed between Er : YAG laser prepared and etched specimens and those in the other groups . CONCLUSIONS It can be concluded that no significant difference was noted between the two types of enamel preparation when etching was performed . Preparing and treating the enamel surface exclusively by Er : YAG laser resulted in the highest degree of leakage .

enamel preparation method

Er : YAG laser

diamond-bur conventional technique

high-speed handpiece

37 % phosphoric acid

Er : YAG laser ( 350 mJ

37 % phosphoric acid

Er : YAG laser

thermal cycling

silver nitrate solutions

enamel preparation

Er : YAG laser

marginal microleakage

microleakage in occlusal surfaces

microleakage

degree of leakage .

Thirty


Pharmacokinetic-pharmacodynamic relationship of rocuronium under stable nitrous oxide-fentanyl or nitrous oxide-sevoflurane anesthesia in children . BACKGROUND The aim of this study was to compare pharmacokinetics and pharmacokinetic-pharmacodynamic ( PK-PD ) relationship of rocuronium in children anesthetized with nitrous oxide ( N2O ) and fentanyl or with N2O and sevoflurane . METHODS Twenty-four children ( 3-11 years old , ASA PS I or II ) were randomized to receive N2O/O2-fentanyl or N2O/O2-sevoflurane ( one MAC ) anesthesia . Neuromuscular transmission was monitored electromyographically . Initial bolus dose of rocuronium , 0.6 mg x kg ( -1 ) was followed by continuous infusion , targeting at steady-state 95 % T1 depression . Neuromuscular transmission was allowed to recover spontaneously . Plasma samples were collected at the moment of discontinuation of infusion , and 10 , 20 , 30 , 50 , 60 and 75 min afterwards . Concentrations of rocuronium were measured using high-performance liquid chromatography with electrochemical detection ( HPLC-EC ) . Rocuronium PK was described by a two-compartment model and PD parameters were estimated using effect compartment and sigmoidal E ( max ) models . RESULTS No differences in rocuronium PK parameters were observed between study groups . Clearance was 3.91 +/- 2.07 and 3.62 +/- 0.80 ml x min ( -1 ) x kg ( -1 ) in sevoflurane and fentanyl groups , respectively ( P < 0.65 ) . Effect compartment concentrations corresponding to 50 % inhibition of T1 ( EC50 ) were 1.41 +/- 0.45 and 2.32 +/- 1.00 microg x ml ( -1 ) ( P < 0.02 ) , and rate constants for equilibration between plasma and effect compartment ( k ( e0 ) ) values were 0.10 +/- 0.04 and 0.24 +/- 0.14 min ( -1 ) ( P < 0.009 ) in sevoflurane and fentanyl groups , respectively . CONCLUSIONS Disposition of rocuronium was similar under stable N2O-fentanyl and N2O-sevoflurane anesthesia . Sevoflurane reduced rocuronium requirements as well as decreased EC50 relevant to inhibition of T1 and rocuronium transfer to effect compartment . Therefore , the potentiating effect of sevoflurane seems to be mainly of PD origin , probably due to an increased sensitivity of the neuromuscular junction .

rocuronium

nitrous oxide-fentanyl

nitrous oxide-sevoflurane

rocuronium

nitrous oxide ( N2O ) and fentanyl

N2O and sevoflurane

N2O/O2-fentanyl or N2O/O2-sevoflurane

electromyographically

rocuronium

rocuronium PK parameters

Clearance

Disposition of rocuronium

rocuronium transfer

anesthesia

children

children

Twenty-four

children

3-11 years old

ASA PS I or II


Efficacy and safety of zoledronic acid in patients with breast cancer metastatic to bone : a multicenter clinical trial . PURPOSE This study evaluated the efficacy and safety of zoledronic acid in breast cancer patients with newly diagnosed bone metastases . MATERIALS AND METHODS Patients diagnosed with bone metastases < or = 6 weeks prior to first visit were enrolled . Zoledronic acid ( 4 mg ) was administered via a 15-minute infusion every 3 or 4 weeks for 12 infusions . Skeletal-related events ( SREs ) were defined as pathologic bone fractures , spinal cord compression , surgery to bone , radiation therapy to bone , and hypercalcemia of malignancy . Primary efficacy end points were the proportion of patients with at least one SRE and the time to first SRE . Secondary end points included pain , analgesic use , and quality of life . RESULTS Among 312 patients enrolled , 30 % experienced at least one SRE during the 12-month study , and 22 % experienced only one SRE . The median time to first SRE was not reached in the intent-to-treat population . Mean pain and analgesic scores declined from baseline , and quality-of-life scores remained stable to study end . The most frequently reported adverse events , regardless of relationship to study drug , were pyrexia ( 22 % ) and bone pain ( 10 % ) . Serum creatinine levels did not significantly increase from baseline throughout the study . CONCLUSIONS Breast cancer patients with newly diagnosed bone metastases who were treated with zoledronic acid had a low incidence of SREs compared with patients who received placebo in randomized phase III trials , and pain was decreased from baseline . This study demonstrated the favorable risk : benefit ratio of zoledronic acid for the prevention of skeletal complications .

zoledronic acid

zoledronic acid

Zoledronic acid

zoledronic acid

placebo

zoledronic acid

efficacy and safety

Skeletal-related events ( SREs )

pain

analgesic use

quality of life

SRE

SRE

SRE

Mean pain

analgesic scores

quality-of-life scores remained stable

pyrexia

bone pain

Serum creatinine levels

SREs

breast cancer

breast cancer

bone metastases

bone metastases

Breast cancer

bone metastases


Effects of sensory-level high-volt pulsed electrical current ondelayed-onset muscle soreness . Ten healthy males and ten healthy females aged 21.5 +/- 3.2 years ( mean +/- s ) participated in the study , which was designed to evaluate the effectiveness of sensory level-high volt pulsed electrical current ( HVPC ) on delayed-onset muscle soreness ( DOMS ) . Arm discomfort , elbow extension range of motion and isometric elbow flexion strength were obtained as baseline measurements . Delayed-onset muscle soreness was induced in the participants ' dominant or non-dominant arm using two sets of 20 maximal eccentric elbow flexion contractions . After the induction of DOMS , the participants were randomly divided into an experimental condition ( HVPC ) or a placebo condition . The experimental condition consisted of 20 min of HVPC immediately after the induction of DOMS , and 20 min every 24 h for three consecutive days thereafter . The participants in the placebo condition received an intervention similar in design ; however , no electrical current was administered . Baseline measurements were reevaluated at 24 , 48 , 72 and 96 h after the induction of DOMS . Three weeks later , the participants returned and the protocol was repeated on the contralateral limb , using the opposite intervention ( HVPC or placebo ) . Repeated-measures analysis of variance revealed a significant increase in overall arm discomfort , decrease in elbow extension and decrease in isometric strength for both conditions over time . No significant main effect of treatment , or time-by-treatment interaction , was found for the HVPC condition when compared with the placebo condition for any variable . Sensory-level HVPC , as utilized in our application , was ineffective in reducing the measured variables associated with DOMS .

experimental condition ( HVPC )

placebo

HVPC

placebo

HVPC

placebo

HVPC

placebo

ondelayed-onset muscle soreness .

delayed-onset muscle soreness ( DOMS )

Delayed-onset muscle soreness

DOMS

DOMS

Baseline measurements

DOMS

overall arm discomfort

elbow extension

isometric strength

both conditions

No significant main effect of treatment

time-by-treatment interaction

DOMS

Ten

males

females


Coenzyme Q10 and exercise training in chronic heart failure . AIMS There is evidence that plasma coenzyme Q ( 10 ) ( CoQ ( 10 ) ) levels decrease in patients with advanced chronic heart failure ( CHF ) . However , it is not known whether oral CoQ ( 10 ) supplementation may improve cardiocirculatory efficiency and endothelial function in patients with CHF . METHODS AND RESULTS We studied 23 patients in NYHA class II and III ( 20 men , three women , mean age 59+/-9 years ) with stable CHF secondary to ischaemic heart disease [ ejection fraction 37+/-7 % ] , using a double-blind , placebo-controlled cross-over design . Patients were assigned to each of the following treatments : oral CoQ ( 10 ) ( 100 mg tid ) , CoQ ( 10 ) plus supervised exercise training ( ET ) ( 60 % of peak VO ( 2 ) , five times a week ) , placebo , and placebo plus ET . Each phase lasted 4 weeks . Both peak VO ( 2 ) and endothelium-dependent dilation of the brachial artery ( EDDBA ) improved significantly after CoQ ( 10 ) and after ET as compared with placebo . CoQ ( 10 ) main effect was : peak VO ( 2 ) +9 % , EDDBA +38 % , systolic wall thickening score index ( SWTI ) -12 % ; ET produced comparable effects . CoQ ( 10 ) supplementation resulted in a four-fold increase in plasma CoQ ( 10 ) level , whereas the combination with ET further increased it . No side effects were reported with CoQ ( 10 ) . CONCLUSIONS Oral CoQ ( 10 ) improves functional capacity , endothelial function , and LV contractility in CHF without any side effects . The combination of CoQ ( 10 ) and ET resulted in higher plasma CoQ ( 10 ) levels and more pronounced effects on all the abovementioned parameters . However , significant synergistic effect of CoQ ( 10 ) with ET was observed only for peak SWTI suggesting that ET amplifies the already described effect of CoQ ( 10 ) on contractility of dysfunctional myocardium .

Coenzyme Q10

( CoQ ( 10 ) )

CoQ ( 10 )

oral CoQ ( 10 ) ( 100 mg tid ) ,

supervised exercise training ( ET )

placebo

placebo plus ET

CoQ ( 10 )

ET

placebo

CoQ ( 10 )

ET

CoQ ( 10 )

CoQ ( 10 )

ET

CoQ ( 10 ) .

Oral CoQ ( 10 )

CoQ ( 10 )

ET

CoQ ( 10 )

CoQ ( 10 )

ET

ET

CoQ ( 10 )

coenzyme Q ( 10 ) ( CoQ ( 10 ) ) levels

peak VO

EDDBA

plasma CoQ ( 10 ) level

functional capacity

endothelial function

LV contractility

side effects

SWTI

chronic heart failure

CHF

men

three

women

59+/-9 years

CHF


Left thoracoabdominal approach versus abdominal-transhiatal approach for gastric cancer of the cardia or subcardia : a randomised controlled trial . BACKGROUND Because of the inaccessibility of mediastinal nodal metastases , the left thoracoabdominal approach ( LTA ) has often been used to treat gastric cancer of the cardia or subcardia . In a randomised phase III study , we aimed to compare LTA with the abdominal-transhiatal approach ( TH ) in the treatment of these tumours . METHODS Between July , 1995 , and December , 2003 , 167 patients were enrolled from 27 Japanese hospitals and randomly assigned to TH ( n=82 ) or LTA ( n=85 ) . The primary endpoint was overall survival , and secondary endpoints were disease-free survival , postoperative morbidity and hospital mortality , and postoperative symptoms and change of respiratory function . The projected sample size was 302 . After the first interim analysis , the predicted probability of LTA having a significantly better overall survival than TH at the final analysis was only 3.65 % , and the trial was closed immediately . Analysis was by intention to treat . This study is registered with , number NCT00149266 . FINDINGS 5-year overall survival was 52.3 % ( 95 % CI 40.4-64.1 ) in the TH group and 37.9 % ( 26.1-49.6 ) in the LTA group . The hazard ratio of death for LTA compared with TH was 1.36 ( 0.89-2.08 , p=0.92 ) . Three patients died in hospital after LTA but none after TH . Morbidity was worse after LTA than after TH . INTERPRETATION Because LTA does not improve survival after TH and leads to increased morbidity in patients with cancer of the cardia or subcardia , LTA can not be justified to treat these tumours .

Left thoracoabdominal approach

abdominal-transhiatal approach

left thoracoabdominal approach ( LTA )

compare

overall survival

disease-free survival

postoperative morbidity

hospital mortality

postoperative symptoms

change of respiratory function

5-year overall survival

hazard ratio of death

for LTA

died

Morbidity


[ Pilot results of using tamsulone-FS in patients with prostatic adenoma according to the results of a randomized multicenter comparative trial ] . Tamsulone-FS -- a novel Russian alpha1A/D-adrenoblocker ( Farm-Syntez ) -- was studied in a randomized multicenter comparative trial in patients with prostatic adenoma . Pilot results agreed with other trials published in the literature and demonstrated tamsulone-FS efficacy and safety for management of lower urinary tract symptoms caused by prostatic adenoma . The efficacy and safety of tamsulone-FS was comparable to those of omnik . This drug can be recommended for wide clinical practice in prostatic adenoma . It is registered by Roszdravnadzor ( certificate N LC-000859 of 03.11.2005 ) and allowed for production and sale .

tamsulone-FS

Tamsulone-FS --

tamsulone-FS

tamsulone-FS

prostatic adenoma .

prostatic adenoma

prostatic adenoma


The efficacy of conventional PCNL and two modifications to standard procedure . OBJECTIVE To compare the efficacy of conventional Percutaneous Nephrolithotomy ( PCNL ) with two of its modified procedures . METHODS A randomized controlled trial , was performed on 60 patients undergoing PCNL . Cases of renal stone regardless of stone size and configuration , having pre-operative negative urine culture , no coagulopathy , and no visible residual stone in intra-operative fluoroscopy , were included . They were randomly divided into 3 groups of 20 cases each with nephrostomy tube ( NT ) and temporary ureteral catheter ( TU ) in group A , only TU in group B and only indwelling ureteral catheter ( IU ) in group C. Mean age of cases were 43.2 ( 25-70 ) , 40.1 ( 25-73 ) , and 44 ( 25-70 ) years in groups A , B and C , respectively ( P = 0.6 ) . Procedures were performed under general anaesthesia , using standard techniques for access and lithotomy . Forty-eight hours , 2 weeks and 3 months after PCNL , plain X-ray abdomen , ultrasonography and IVP were performed for each case . RESULTS Only one case in group A had urinary leakage after removal of nephrostomy tube . No cases in the other two groups encountered this problem . There was no haemorrhagic episode . Ultrasonic evaluation showed mild residue in 3 , 1 and 1 cases of groups A , B and C , respectively ( P = 0.2 ) . No collective fluid was found in these groups . IVP showed dilatation without obstruction in 3 subjects of group A and none in group B or C ( P = 0.03 ) . CONCLUSION Tubeless PCNL seems to be accompanied by better outcome . So , further evaluation on more patients seems necessary .

conventional PCNL

PCNL

nephrostomy tube ( NT )

temporary ureteral catheter ( TU )

only TU

PCNL

Tubeless PCNL

urinary leakage

haemorrhagic episode

mild residue

collective fluid

dilatation without obstruction

PCNL

Cases of renal stone


Effectiveness of a clinical intervention in improving pain control in outpatients with cancer treated by radiation therapy . PURPOSE To determine the effectiveness of a multicomponent clinical intervention to reduce pain in outpatients with cancer . METHODS AND MATERIALS Sixty-four patients were randomly assigned to receive either a clinical intervention including an information session , the use of a pain diary , and the possibility to contact a physician to adjust the pain medication , or the usual treatment of pain by the staff radiation oncologist . All patients reported their average and worst pain levels at baseline and 2 and 3 weeks after the start of the intervention . RESULTS The study groups were similar with respect to their baseline characteristics and pain levels at randomization . After 3 weeks , the average and worst pain experienced by patients randomized to the clinical intervention group was significantly inferior to the average pain experienced by patients in the control group ( 2.9/10 vs. 4.4/10 and 4.2/10 vs. 5.5/10 , respectively ) . Results showed that the experimental group patients decreased their pain levels more than the control group patients did over time . CONCLUSION An intervention including patient education , a pain diary , and defining a procedure for therapeutic adjustments can be effective to improve pain relief in outpatients with cancer .

clinical intervention

radiation therapy

multicomponent clinical intervention

clinical intervention

information session

pain diary

contact a physician

clinical intervention group

patient education

a pain diary

therapeutic adjustments

pain levels

a pain diary

improve pain relief

cancer

cancer

Sixty-four patients

cancer


Oxytocin increases retention of social cognition in autism . BACKGROUND Oxytocin dysfunction might contribute to the development of social deficits in autism , a core symptom domain and potential target for intervention . This study explored the effect of intravenous oxytocin administration on the retention of social information in autism . METHODS Oxytocin and placebo challenges were administered to 15 adult subjects diagnosed with autism or Asperger 's disorder , and comprehension of affective speech ( happy , indifferent , angry , and sad ) in neutral content sentences was tested . RESULTS All subjects showed improvements in affective speech comprehension from pre- to post-infusion ; however , whereas those who received placebo first tended to revert to baseline after a delay , those who received oxytocin first retained the ability to accurately assign emotional significance to speech intonation on the speech comprehension task . CONCLUSIONS These results are consistent with studies linking oxytocin to social recognition in rodents as well as studies linking oxytocin to prosocial behavior in humans and suggest that oxytocin might facilitate social information processing in those with autism . These findings also provide preliminary support for the use of oxytocin in the treatment of autism .

Oxytocin

Oxytocin

oxytocin

Oxytocin

placebo

placebo

oxytocin

oxytocin

retention of social cognition

affective speech comprehension

social recognition

prosocial behavior

adult

autism or Asperger 's disorder


Patient-reported outcomes after inguinal herniorrhaphy . BACKGROUND Patient-reported outcomes ( PRO ) reflect the functional outcomes of inguinal herniorrhaphy . We studied the effect of hernia recurrence and complications on PRO for participants in the Veterans Affairs trial of Open or Laparoscopic Repair of Inguinal Hernia . METHODS Analyzed PRO included ( 1 ) the Medical Outcomes Study Short Form 36 , version 2 , ( 2 ) the Surgical Pain Scale , ( 3 ) the Activities Assessment Scale , and ( 4 ) patient satisfaction . Recurrences and complications were recorded at follow-up visits . Complications were categorized by ( 1 ) hematoma/seroma , ( 2 ) orchitis , ( 3 ) neuralgia , and ( 4 ) other . Univariate and multivariable regression analyses identified variables significantly associated with postoperative PRO . RESULTS Of the 1603 patients with PRO data , 105 had a recurrence and 342 had a complication at 2 years . Multivariable analyses showed neuralgia ( P < .0005 ) adversely affected all PRO , and recurrence ( P < .05 ) affected patient-reported pain , activity , and satisfaction , but not the score for the Medical Outcomes Study Short Form 3 . Patients with a recurrence after open repair had more pain than those with a recurrence after laparoscopic repair ( P = .0001 ) . Patients with other complications after laparoscopic repair reported more pain and less activity than those with other complications after open repair ( P = .003 and P = .009 , respectively ) . CONCLUSIONS The effectiveness of inguinal herniorrhaphy should be measured by the rate of recurrence and neuralgia . Postoperative neuralgias have a deleterious effect on all patient-reported outcomes .

inguinal herniorrhaphy .

inguinal herniorrhaphy .

hematoma/seroma

orchitis

neuralgia

neuralgia

patient-reported pain

activity

satisfaction

Medical Outcomes Study Short Form 3

pain

pain

less activity

recurrence

neuralgia


Atorvastatin and quinapril inhibit blood coagulation in patients with coronary artery disease following 28 days of therapy . BACKGROUND We evaluated the antithrombotic effects of statins and angiotensin-converting enzyme inhibitor ( ACEI ) drugs in patients with coronary artery disease ( CAD ) . METHODS AND RESULTS Blood coagulation at the site of microvascular injury was assessed in 26 males with CAD before and after treatment with quinapril ( 10 mg day-1 ; n=13 ) or atorvastatin ( 40 mg day-1 ; n=13 ) for 4 weeks and an additional 4 weeks of combined therapy ( quinapril+atorvastatin ) . Rates of prothrombin and factor V activation ( FVa ) , fibrinogen ( Fbg ) cleavage and FVa inactivation showed that both quinapril and atorvastatin decreased the rates of : formation of thrombin B-chain ( by 30.6 % , P=0.007 ; and by 34.3 % , P=0.003 ) , formation of thrombin-antithrombin complexes ( by 30.4 % , P=0.0002 ; and by 40 % , P=0.001 ) , FV activation ( by 19.1 % , P=0.03 ; and by 21.8 % , P=0.005 ) and Fbg depletion ( by 29.2 % , P=0.004 ; and by 32.7 % , P=0.001 ) . Atorvastatin alone accelerated FVa inactivation ( P=0.005 ) . A further 4 weeks of combined therapy enhanced most anticoagulant effects only when atorvastatin was added to quinapril . CONCLUSIONS In CAD patients , atorvastatin and quinapril slowed blood clotting at the site of microvascular injury after 28 days of therapy . Addition of atorvastatin to quinapril , but not quinapril to the statin , enhanced the anticoagulant effects . Our findings might help explain the reduced risk of myocardial infarction or stroke in patients treated with statins and/or ACEIs and the lack of clinical benefits from ACEI added to prior statin therapy in patients at cardiovascular risk .

Atorvastatin

quinapril

statins

quinapril

atorvastatin

atorvastatin

quinapril

quinapril

statin

statins

fibrinogen ( Fbg ) cleavage

FVa inactivation

formation of thrombin B-chain

FV activation

Fbg depletion

FVa inactivation

anticoagulant effects

patients with coronary artery disease

males

CAD patients


A randomized comparison of the effect of two prelinguistic communication interventions on the acquisition of spoken communication in preschoolers with ASD . PURPOSE This randomized group experiment compared the efficacy of 2 communication interventions ( Responsive Education and Prelinguistic Milieu Teaching [ RPMT ] and the Picture Exchange Communication System [ PECS ] ) on spoken communication in 36 preschoolers with autism spectrum disorders ( ASD ) . METHOD Each treatment was delivered to children for a maximum total of 24 hr over a 6-month period . Spoken communication was assessed in a rigorous test of generalization at pretreatment , posttreatment , and 6-month follow-up periods . RESULTS PECS was more successful than RPMT in increasing the number of nonimitative spoken communication acts and the number of different nonimitative words used at the posttreatment period . Considering growth over all 3 measurement periods , an exploratory analysis showed that growth rate of the number of different nonimitative words was faster in the PECS group than in the RPMT group for children who began treatment with relatively high object exploration . In contrast , analogous slopes were steeper in the RPMT group than in the PECS group for children who began treatment with relatively low object exploration .

communication interventions

( Responsive Education

Prelinguistic Milieu Teaching [ RPMT ]

the

Picture Exchange Communication System

[ PECS ] )

was faster in the PECS

analogous slopes

ASD

autism spectrum disorders ( ASD )


A comparative study of the pharmacokinetics of ibuprofen arginate versus dexibuprofen in healthy volunteers . OBJECTIVE Ibuprofen arginate is a salt formulation of ibuprofen designed to reach target concentrations rapidly . The primary objective of this study was to compare the 12-h pharmacokinetic profile of S ( + ) -ibuprofen following administration of single doses of ibuprofen arginate ( 600 mg ) and dexibuprofen ( 400 mg ) in healthy volunteers . METHODS Twenty-four volunteers were recruited into an open-label , randomised , two-period , single-centre study with crossover design . RESULTS Both treatments were well tolerated . Ibuprofen arginate and dexibuprofen showed similar bioavailability for S ( + ) -ibuprofen . Compared with dexibuprofen , ibuprofen arginate demonstrated a 45 % higher maximum concentration ( C ( max ) ) , and a time to peak concentration ( T ( max ) ) 2 h sooner . CONCLUSION Ibuprofen arginate approaches maximum concentrations of S ( + ) -ibuprofen faster and higher than dexibuprofen .

ibuprofen arginate

dexibuprofen

Ibuprofen arginate

ibuprofen

S ( + ) -ibuprofen

ibuprofen arginate

dexibuprofen

Ibuprofen arginate

dexibuprofen

S ( + ) -ibuprofen

dexibuprofen

ibuprofen arginate

Ibuprofen arginate

dexibuprofen

pharmacokinetic profile

bioavailability for S ( + ) -ibuprofen

maximum concentration ( C ( max ) )


Topical adrenaline in the control of intraoperative bleeding in adenoidectomy : a randomised , controlled trial . OBJECTIVES To evaluate the efficacy of topical racemic adrenaline ( RA ) ( Micronefrin ; Bird Products , Palm Springs , CA , USA ) in the control of intraoperative bleeding and the prevention of postoperative bleeding , laryngeal spasm and postoperative pain in adenoidectomy among children < 6 years of age . DESIGN Prospective , randomised , blinded and placebo-controlled trial . SETTING Kanta-Hame Central Hospital , a district referral center in Finland . PATIENTS A consecutive sample of 93 children undergoing outpatient adenoidectomy . INTERVENTION Patients were randomised to receive topical gauze sponges soaked in either 1:500 RA or 0.9 % sodium chloride ( physiological saline ) for 3 min after adenoidectomy . MAIN OUTCOME MEASURES Amount of intraoperative bleeding ( surgeons ' subjective estimate ) , need for additional packings , need for electrocautery , laryngeal spasm , postoperative bleeding and pain , duration of procedure and duration of patients ' stay in the operation room ( OR ) . RESULTS Adrenaline significantly decreased surgeons ' subjective estimate of the amount of intraoperative bleeding ( proportion of patients with significant decrease 67 versus 21 % , P < 0.001 ) , reduced the mean number of packings needed ( 0.6 versus 1.2 , P < 0.001 ) and use of electrocautery ( 22 versus 45 % , P = 0.015 ) , and shortened the mean duration of the procedure ( 13 versus 18 min , P = 0.043 ) and the mean stay in the OR ( 31 versus 35 min , P = 0.058 ) . The impact of adrenaline was even more pronounced among patients with extensive adenoids and/or profuse intraoperative bleeding . A slight elevation of heart rate was observed more often in the adrenaline group ( P = 0.043 ) . CONCLUSIONS Use of topical adrenaline can be recommended in adenoidectomy among children . It helps control the intraoperative bleeding , reduces the use of electrocautery and shortens the durations of procedure and stay in the OR .

adrenaline

racemic adrenaline ( RA )

topical gauze sponges soaked

RA

0.9 %

adenoidectomy

Adrenaline

adrenaline

adrenaline

adrenaline

intraoperative bleeding

intraoperative bleeding

prevention of postoperative bleeding

laryngeal spasm and postoperative pain

intraoperative bleeding

amount of intraoperative bleeding

number of packings needed

use of electrocautery

duration of the procedure

stay in the OR

adenoids

intraoperative bleeding

elevation of heart rate

intraoperative bleeding

electrocautery

procedure and stay in the OR

adenoidectomy

children < 6 years

children

extensive adenoids

profuse intraoperative bleeding

children


Cardiac safety of formoterol 12 microg twice daily in patients with chronic obstructive pulmonary disease . BACKGROUND Some evidence suggests an increased risk of myocardial infarction and dysrhythmia events associated with beta ( 2 ) -agonist use in patients with chronic obstructive pulmonary disease ( COPD ) . This prospective , multicenter , randomized , double-blind , placebo-controlled study compared the cardiac safety of formoterol and placebo in patients with COPD . METHODS After a 3-14-day run-in , 204 patients were randomized to receive formoterol 12 microg dry powder inhalation or matching placebo twice daily for 8 weeks . Twenty four-hour continuous electrocardiography ( Holter monitoring ) was performed at screening and after 2 and 8 weeks of treatment . RESULTS Only a small number of patients met the predefined criteria for a proarrhythmic event ( 4 formoterol and 2 placebo patients ) . No patients had sustained postbaseline ventricular tachycardia events , postbaseline run of ventricular ectopic beats associated with relevant symptoms ( e.g . hypotension , syncope ) , or an episode of ventricular flutter or fibrillation . Holter monitoring data were variable but showed no clinically meaningful differences between the formoterol and placebo groups , respectively , for variables such as ( mean+/-SD at end of treatment ) : heart rate ( 80+/-8.6 vs. 80+/-10.6 bpm ) , number and rate of ventricular premature beats ( total 732+/-2685.4 vs. 650+/-2090.6 ; rate 35+/-131.0 vs. 30+/-101.3 per h ) , ventricular tachycardia events ( total 0.4+/-1.70 vs. 1.0+/-9.23 ; rate 0.02+/-0.082 vs. 0.05+/-0.479 per h ) , and supraventricular premature beats ( total 504+/-1844.1 vs. 823+/-2961.8 ; rate 22+/-80.6 vs. 37+/-129.6 per h ) . Vital signs and electrocardiogram data , including corrected QT intervals ( Bazett and Fridericia ) , were similar across treatment groups . The overall adverse event experience was similar in the formoterol ( n=26 [ 27 % ] ) and placebo ( n=33 [ 31 % ] ) groups . The most common adverse events , infections and respiratory events , were expected for this patient population . The incidence of cardiac adverse events was low ( 1 formoterol and 4 placebo patients ) . CONCLUSIONS The results of this study confirm the good cardiovascular safety profile of formoterol in patients with COPD .

formoterol

formoterol

placebo

placebo

formoterol

placebo

Cardiac

myocardial infarction

dysrhythmia events

proarrhythmic event

hypotension , syncope

heart rate

ventricular tachycardia events

supraventricular premature beats

Vital signs

overall adverse event experience

cardiac adverse events

good cardiovascular safety

chronic obstructive pulmonary disease

COPD

COPD


Control of the lumbar neutral zone decreases low back pain and improves self-evaluated work ability : a 12-month randomized controlled study . STUDY DESIGN A randomized controlled study with 12 months intervention . OBJECTIVE To study the effectiveness of a training intervention with emphases on the control of lumbar neutral zone ( NZ ) and behavior modeling as secondary prevention of low back pain ( LBP ) and disability . SUMMARY OF BACKGROUND DATA Improving the control of lumbar NZ and enhancing muscle activation patterns ensuring spinal stability have been proposed as means for secondary prevention of LBP and disability . In addition , cognitive behavior interventions have been shown to lower the risk of recurrence of LBP and long-term disability . METHODS Middle-aged working men with recent LBP but without severe disability were randomly allocated to either a training ( TG , n = 52 ) or control group ( CG , n = 54 ) . The aim was to exercise twice a week for 12 months , once guided and once independently . The outcome measures were the changes in intensity of LBP , disability , self-evaluated future work ability , and neuromuscular fitness . RESULTS The intensity of LBP decreased significantly more ( 39 % ) in the TG than in CG at 12 months . The proportion of subjects with negative expectations about their future work ability decreased in both groups at 6 and 12 months ; however , the proportion was significantly bigger in TG compared with CG ( P = 0.028 ) . There effects on disability indexes and fitness were not statistically significant . CONCLUSIONS Controlling lumbar NZ is a specific form of exercise and daily self-care with potential for prevention of recurrent nonspecific LBP and disability among middle aged working men .

behavior modeling

cognitive behavior interventions

training

control group

exercise and daily self-care

low back pain

improves

self-evaluated work ability

low back pain ( LBP )

disability

LBP

disability

recurrence of LBP

long-term disability

changes in intensity of LBP

disability

self-evaluated future work ability

neuromuscular fitness

intensity of LBP

disability indexes and fitness

low back pain

low back pain ( LBP ) and disability .

Middle-aged

men

training


Randomized controlled trial of melatonin for children with autistic spectrum disorders and sleep problems . BACKGROUND Melatonin is often used for autistic children with sleep disorders , despite a lack of published evidence in this population . METHODS A randomized , placebo-controlled double-blind crossover trial of melatonin was undertaken in 11 children with autistic spectrum disorder ( ASD ) . RESULTS Seven children completed the trial . Sleep latency was 2.6 h [ 95 % confidence intervals ( CI ) 2.28-2.93 ] baseline , 1.91 h ( 95 % CI 1.78-2.03 ) with placebo and 1.06 h ( 95 % CI 0.98-1.13 ) with melatonin . Wakings per night were 0.35 ( 95 % CI 0.18-0.53 ) baseline , 0.26 ( 95 % CI 0.20-0.34 ) with placebo and 0.08 ( 95 % CI 0.04-0.12 ) with melatonin . Total sleep duration was 8.05 h ( 95 % CI 7.65-8.44 ) baseline , 8.75 h ( 95 % CI 8.56-8.98 ) with placebo and 9.84 h ( 95 % CI 9.68-9.99 ) with melatonin . CONCLUSIONS Although the study was small owing to recruitment difficulties , it still provides evidence of effectiveness of melatonin in children with sleep difficulties and ASD , which we predict a larger study would confirm .

melatonin

placebo-controlled

melatonin

placebo

Sleep latency

Wakings per night

Total sleep duration

effectiveness

children

autistic spectrum disorders

sleep problems

autistic

children

sleep disorders

children

autistic spectrum disorder ( ASD )

Seven

children

children

sleep difficulties

ASD


Omega-3 fatty acids supplementation in children with autism : a double-blind randomized , placebo-controlled pilot study . BACKGROUND There is increasing evidence that fatty acid deficiencies or imbalances may contribute to childhood neurodevelopmental disorders . METHODS We conducted a randomized , double-blind , placebo-controlled 6-week pilot trial investigating the effects of 1.5 g/d of omega-3 fatty acids ( .84 g/d eicosapentaenoic acid , .7 g/d docosahexaenoic acid ) supplementation in 13 children ( aged 5 to 17 years ) with autistic disorders accompanied by severe tantrums , aggression , or self-injurious behavior . The outcome measure was the Aberrant Behavior Checklist ( ABC ) at 6 weeks . RESULTS We observed an advantage of omega-3 fatty acids compared with placebo for hyperactivity and stereotypy , each with a large effect size . Repeated-measures ANOVA indicated a trend toward superiority of omega-3 fatty acids over placebo for hyperactivity . No clinically relevant adverse effects were elicited in either group . CONCLUSIONS The results of this study provide preliminary evidence that omega-3 fatty acids may be an effective treatment for children with autism .

Omega-3 fatty acids supplementation

placebo-controlled

omega-3 fatty acids

placebo

omega-3 fatty acids

omega-3 fatty acids

Aberrant Behavior Checklist ( ABC )

hyperactivity and stereotypy

hyperactivity

adverse effects

autism

neurodevelopmental disorders .

aged 5 to 17 years


Rationale and design of the Folic Acid for Vascular Outcome Reduction In Transplantation ( FAVORIT ) trial . BACKGROUND Patients with chronic kidney disease , including kidney transplant recipients , are at high risk for cardiovascular disease ( CVD ) . In addition to the constellation of traditional CVD risk factors in chronic kidney disease , elevated total homocysteine ( tHcy ) is notably more prevalent among the general population . The Folic Acid for Vascular Outcome Reduction In Transplantation ( FAVORIT ) trial is designed to evaluate whether lowering tHcy using vitamin supplementation reduces CVD events in renal transplant recipients . METHODS FAVORIT is a multicenter double-blind randomized controlled clinical trial . Participants are clinically stable renal transplant recipients who are 6 months or longer posttransplant with elevated tHcy . Patients are randomized to a multivitamin that includes either a high-dose or low-dose of folic acid ( 5 or 0 mg ) , vitamin B6 ( 50 or 1.4 mg ) , and vitamin B12 ( 1000 or 2 microg ) . The primary end point is a composite of incident or recurrent CVD outcomes , that is , coronary heart , cerebrovascular , or abdominal aortic/lower extremity arterial events . A sample size of 4000 is estimated to provide 87 % power to detect a 20 % treatment effect . Recruitment is expected to continue until July 2006 , with follow-up through June 2010 . RESULTS From August 2002 through December 2004 , 2234 of the target 4000 patients were enrolled . In accordance with trial design , mean ( SD ) screening tHcy was elevated ( 17.4 +/- 6.2 micromol/L ) , and mean ( SD ) estimated creatinine clearance was consistent with stable renal function ( 58.0 +/- 18.6 mL/min ) . Evaluating baseline results to date , 42 % of the randomized participants had a history of diabetes mellitus , and 21 % had prevalent CVD . CONCLUSIONS The FAVORIT trial is designed with sufficient power and follow-up time to detect a clinically relevant change in CVD risk between renal transplant recipients receiving a high or low tHcy-lowering folic acid multivitamin . Preliminary screening and baseline data support the trial 's objectives .

Folic Acid

The Folic Acid

vitamin supplementation

vitamin B6

and vitamin B12

folic acid multivitamin

cardiovascular disease ( CVD )

total homocysteine ( tHcy )

CVD events

mean ( SD ) screening tHcy

history of diabetes mellitus

chronic kidney disease

kidney transplant recipients

renal transplant recipients

renal transplant recipients

elevated tHcy

renal transplant recipients


Children 's Yale-Brown Obsessive Compulsive Scale modified for pervasive developmental disorders . OBJECTIVE To examine the psychometric properties of the Children 's Yale-Brown Obsessive Compulsive Scales ( CYBOCS ) modified for pervasive developmental disorders ( PDDs ) . METHOD Raters from five Research Units on Pediatric Psychopharmacology ( RUPP ) Autism Network were trained to reliability . The modified scale ( CYBOCS-PDD ) , which contains only the five Compulsion severity items ( range 0-20 ) , was administered to 172 medication-free children ( mean 8.2 +/- 2.6 years ) with PDD ( autistic disorder , n = 152 ; Asperger 's disorder , n = 6 ; PDD not otherwise specified , n = 14 ) participating in RUPP clinical trials . Reliability was assessed by intraclass correlation coefficient ( ICC ) and internal consistency by Cronbach 's alpha coefficient . Correlations with ratings of repetitive behavior and disruptive behavior were examined for validity . RESULTS Eleven raters showed excellent reliability ( ICC = 0.97 ) . The mean CYBOCS score was 14.4 ( +/- 3.86 ) with excellent internal consistency ( alpha = .85 ) . Correlations with other measures of repetitive behavior ranged from r = 0.11 to r = 0.28 and were similar to correlations with measures of irritability ( r = 0.24 ) and hyperactivity ( r = 0.25 ) . Children with higher scores on the CYBOCS-PDD had higher levels of maladaptive behaviors and lower adaptive functioning . CONCLUSIONS The five-item CYBOCS-PDD is reliable , distinct from other measures of repetitive behavior , and sensitive to change .

CYBOCS-PDD

five Compulsion severity items

Reliability

reliability

mean CYBOCS score

internal consistency

measures of irritability

hyperactivity

maladaptive behaviors

lower adaptive functioning


Heart rate variability and QT dispersion in patients with subclinical hypothyroidism . UNLABELLED The effect of subclinical hypothyroidism ( SH ) on cardiovascular autonomic function and ventricular repolarization has not been yet elucidated . The aim of the present study was to evaluate the dispersion of QT interval , i.e . an index of inhomogeneity of repolarization , and heart rate variability ( HRV ) , i.e . a measure of cardiac autonomic modulation , in SH patients . METHODS The study included 42 patients ( 29 women and 13 men ; mean age 53.2+/-14.2 years ; body surface area 1.76+/-0.14 m2 ) with SH , as judged by elevated serum TSH levels ( > 3.6 mIU/l ; range , 3.8-12.0 ) and normal free thyroid hormones ( FT4 and FT3 ) and 30 euthyroid volunteer . Subjects with cardiac , metabolic , neurological disease or any other systemic disease that could affect autonomic activity were excluded from the study . Patients with SH and control subjects underwent a full history , physical examination , standard 12-lead ECG , and 24-h ambulatory ECG monitoring . To evaluate the effect of treatment with L-thyroxine on QT dispersion and HRV , 15 patients with SH were randomly assigned to receive therapy with L-thyroxine . All the subjects were evaluated at enrolment and after 6 months . RESULTS Patients with SH showed higher QT dispersion and lower HRV measures than healthy controls ( P < 0.01 for all ) . In SH patients , the standard deviation of N-Ns ( SDNN ) was negatively related to TSH ( r=-0.42 , P=0.006 ) , while low frequency ( LF ) /high frequency ( HF ) ratio was positively related to TSH ( r=0.42 , P=0.006 ) . Moreover , in SH patients both QT dispersion and QTc dispersion were positively related to TSH ( r=0.64 and r=0.63 , P < 0.001 for both ) . After 6 months , the patients treated with L-tiroxine exhibited a reduction of QT dispersion and an increase of HRV parameters . CONCLUSION The results of the present study demonstrated that SH can alter autonomic modulation of heart rate and cause increased inhomogeneity of ventricular recovery times . Accordingly , early L-thyroxine treatment may be advised not only to prevent progression to overt hypothyroidism but also to improve abnormal cardiac autonomic function and ventricular repolarization inhomogeneity .

L-thyroxine

L-thyroxine

L-tiroxine

L-thyroxine

Heart rate variability

QT dispersion

QT dispersion

lower HRV measures

standard deviation of N-Ns ( SDNN )

QT dispersion

QTc dispersion

QT dispersion

HRV parameters

heart rate

subclinical hypothyroidism

subclinical hypothyroidism

SH

42 patients

women

men

SH

systemic disease

SH

SH

SH


Preventing paclitaxel-induced peripheral neuropathy : a phase II trial of vitamin E supplementation . A randomized , controlled trial was performed to assess the efficacy and safety of vitamin E supplementation for prophylaxis against paclitaxel-induced peripheral neuropathy ( PIPN ) . Thirty-two patients undergoing six courses of paclitaxel-based chemotherapy were randomly assigned to receive either chemotherapy with vitamin E ( 300 mg twice a day , Group I ) or chemotherapy without vitamin E supplementation ( Group II ) . A detailed neurological examination and electrophysiological study was performed during and 3 months after chemotherapy . The severity of PIPN was summarized by means of a modified Peripheral Neuropathy ( PNP ) score . The incidence of neurotoxicity differed significantly between groups , occurring in 3/16 ( 18.7 % ) patients assigned to the vitamin E supplementation group and in 10/16 ( 62.5 % ) controls ( P=0.03 ) . The relative risk ( RR ) of developing PIPN was significantly higher in controls than in vitamin E group patients ( RR=0.3 , 95 % confidence interval ( CI ) =0.1-0.9 ) . Mean PNP scores were 2.25+/-5.1 ( range 0-15 ) for patients in Group I and 11+/-11.63 ( range 0-32 ) for those in Group II ( P=0.01 ) . Vitamin E supplementation was well tolerated and showed an excellent safety profile . This study shows that vitamin E effectively and safely protects patients with cancer from the occurrence of paclitaxel-induced peripheral nerve damage . A double-blind , placebo-controlled trial is needed to confirm these results .

vitamin E supplementation

vitamin E supplementation

paclitaxel-based chemotherapy

chemotherapy with vitamin E

chemotherapy

vitamin E supplementation

vitamin E

Vitamin E supplementation

vitamin E

placebo-controlled

efficacy and safety

severity of PIPN

was summarized

incidence of neurotoxicity

relative risk ( RR ) of developing PIPN

Mean PNP scores

tolerated

safety profile

Thirty-two

chemotherapy

cancer


A double-blind randomized controlled trial of oral misoprostol and intramuscular syntometrine in the management of the third stage of labor . BACKGROUND The aim of this study was to compare the efficacy and safety of oral misoprostol 400 mug with intramuscular syntometrine in the management of the third stage of labor . MATERIAL AND METHODS This was a double-blind randomized controlled trial conducted in a tertiary care hospital . Three hundred and fifty-five women randomized to receive either oral misoprostol 400 mug or intramuscular syntometrine in the third stage of labor were studied . The change in hemoglobin level from before to 48 h after delivery , use of additional oxytocics and treatment related side effects were the main outcome measures . RESULTS There were no significant differences between the two groups in terms of the change in hemoglobin level and mean blood loss . The incidence of shivering was significantly higher in the misoprostol group whilst that of vomiting was significantly higher in the syntometrine group . There were no differences in the incidence of nausea , headache , diarrhea and pyrexia between the two groups . CONCLUSION Orally administered misoprostol at a dose of 400 mug is an acceptable alternative in preventing post-partum blood loss , as measured by the peri-partum change in hemoglobin level and was not associated with an increased incidence of side effects .

misoprostol

misoprostol

syntometrine

misoprostol

hemoglobin level

hemoglobin level

mean blood loss

shivering

blood loss

hemoglobin level

third stage of labor

Three hundred and fifty-five

women

third stage of labor


Virtual reality exposure therapy and standard ( in vivo ) exposure therapy in the treatment of fear of flying . This controlled clinical trial tested virtual reality exposure ( VRE ) therapy for the fear of flying ( FOF ) , a relatively new and innovative way to do exposure therapy , and compared it to standard ( in vivo ) exposure therapy ( SE ) and a wait list ( WL ) control with a 6- and 12-month follow-up . Eighty-three participants with FOF were randomly assigned to VRE , SE , or WL . Seventy-five participants , 25 per group , completed the study . Twenty-three WL participants completed randomly assigned treatment following the waiting period . Treatment consisted of 4 sessions of anxiety management training followed either by exposure to a virtual airplane ( VRE ) or an actual airplane at the airport ( SE ) conducted over 6 weeks . Results indicate that VRE was superior to WL on all measures , including willingness to fly on the posttreatment flight ( 76 % for VRE and SE ; 20 % for WL ) . VRE and SE were essentially equivalent on standardized questionnaires , willingness to fly , anxiety ratings during the flight , self-ratings of improvement , and patient satisfaction with treatment . Follow-up assessments at 6 and 12 months indicated that treatment gains were maintained , with more than 70 % of respondents from both groups reporting continued flying at follow-up . Based on these findings , the use of VRE in the treatment of FOF was supported in this controlled study , suggesting that experiences in the virtual world can change experiences in the real world .

Virtual reality exposure therapy

standard ( in vivo ) exposure therapy

VRE

WL

VRE

SE

standardized questionnaires

willingness to fly

anxiety ratings during the flight

self-ratings of improvement

patient satisfaction with treatment

fear of flying

fear of flying ( FOF

Eighty-three participants

with FOF

Seventy-five participants

25 per group

Twenty-three


Risperidone in children with autism : randomized , placebo-controlled , double-blind study . Some open-label studies suggest that risperidone can be useful in the treatment of certain target symptoms in children with autism . We aimed to study whether the use of risperidone in comparison with placebo improved functioning in children with autism with regard to behavior ( aggressiveness , hyperactivity , irritability ) , social and emotional responsiveness , and communication skills . We conducted a randomized , double-blind , placebo-controlled trial with 40 consecutive children with autism , whose ages ranged from 2 to 9 years , who were receiving either risperidone or placebo given orally at a dose of 1 mg/day for 6 months . Autism symptoms were monitored periodically . The outcome variables were total scores on the Childhood Autism Rating Scale ( CARS ) and the Children 's Global Assessment Scale ( CGAS ) after 6 months . Of the 40 children enrolled , 39 completed the trial over a period of 18 months ; 19 received risperidone , and 20 received placebo . In the risperidone group , 12 of 19 children showed improvement in the total Childhood Autism Rating Scale score and 17 of 19 children in the Children 's Global Assessment Scale score compared with 0 of 20 children for the Childhood Autism Rating Scale score and 2 of 20 children for the Children 's Global Assessment Scale score in the placebo group ( P < .001 and P = .035 , respectively ) . Risperidone also improved social responsiveness and nonverbal communication and reduced the symptoms of hyperactivity and aggression . Risperidone was associated with increased appetite and a mild weight gain , mild sedation in 20 % , and transient dyskinesias in three children . Risperidone improved global functioning and social responsiveness while reducing hyperactivity and aggression in children with autism and was well tolerated .

Risperidone

risperidone

risperidone

placebo

placebo-controlled

risperidone

placebo

risperidone

placebo

risperidone

placebo

Risperidone

Risperidone

Risperidone

total

Childhood Autism Rating Scale

score

Childhood Autism Rating Scale score

social responsiveness

and

nonverbal communication

symptoms of

hyperactivity

and

aggression

appetite

weight gain

mild sedation

transient dyskinesias

global functioning

social responsiveness

reducing

hyperactivity

and

aggression

children

autism

children

autism

children

autism

children

autism

ages ranged from 2 to 9 years

children

children

autism


A controlled , randomized , double-blind trial to evaluate the effect of a supplement of cocoa husk that is rich in dietary fiber on colonic transit in constipated pediatric patients . OBJECTIVE Although a diet that is rich in fiber is widely recommended for preventing and treating constipation , the efficacy of fiber supplements have not been tested sufficiently in children . Our aim with this pilot study was to evaluate if fiber supplementation is beneficial for the treatment of children with idiopathic chronic constipation . METHODS Using a parallel , randomized , double-blind , controlled trial , we conducted an interventional study to evaluate the efficacy of a supplement of cocoa husk rich in dietary fiber on intestinal transit time and other indices of constipation in children with constipation . After screening , the patients were randomly allocated to receive , for a period of 4 weeks , either a cocoa husk supplement or placebo plus standardized toilet training procedures . Before and after 4 weeks of treatment , we ( 1 ) performed anthropometry , a physical examination , and routine laboratory measurements , ( 2 ) determined total and segmental colonic transit time , ( 3 ) evaluated bowel movement habits and stool consistency using a diary , and ( 4 ) received a subjective evaluation from the parents regarding the efficacy of the treatment . The main variable for verifying the efficacy of the treatment was the total colonic transit time . RESULTS Fifty-six chronically constipated children were randomly assigned into the study , but only 48 children completed it . These children , who were aged between 3 and 10 years , had a diagnosis of chronic idiopathic constipation . With respect to total , partial colon , and rectum transit time , there seemed to be a trend , although statistically nonsignificant , toward faster transit times in the cocoa husk group than in the placebo group . When we analyzed the evolution of the intestinal transit time throughout the study of children whose total basal intestinal transit time was > 50th percentile , significant differences were observed between the groups . The total transit time decreased by 45.4 +/- 38.4 hours in the cocoa husk group and by 8.7 +/- 28.9 hours in the placebo group ( -38.1 hours ) . In the case of the right colon , changes in transit time also were significant between groups . Mean changes tended toward faster transit times in the left colon and the rectum , although the differences were not statistically significant . The children who received cocoa husk supplements tended to increase the number of bowel movements by more than that of the children of the placebo group . We also observed a reduction in the percentage of patients who reported hard stools ( hard scybalous or pebble-like stools ) , although this reduction was significantly greater in the cocoa husk group . At the end of the intervention , 41.7 % and 75.0 % of the patients who received cocoa husk supplementation or placebo , respectively , reported having hard stools . Moreover , a significantly higher number of children ( or their parents ) reported a subjective improvement in stool consistency . No significant adverse effects were reported during the study . CONCLUSIONS This study confirms the beneficial effect of a supplement of cocoa husk that is rich in dietary fiber on chronic idiopathic constipation in children . These benefits seem to be more evident in pediatric constipated patients with slow colonic transit time .

cocoa husk supplement or

anthropometry

cocoa husk supplements

supplement of cocoa husk

colonic transit

idiopathic chronic constipation

constipation

total colonic transit time

transit times

intestinal transit

basal intestinal transit time

total transit time

changes in transit time

Mean changes

number of bowel movements

hard scybalous or pebble-like stools

reported having hard stools

improvement in stool consistency

No significant adverse effects

chronic idiopathic constipation

constipated

pediatric

patients .

children

children with constipation .

Fifty-six

children completed it .

3 and 10 years

chronic idiopathic constipation


Effects of monotherapy and combination therapy on blood pressure control and target organ damage : a randomized prospective intervention study in a large population of hypertensive patients . This prospective , randomized trial evaluated the effect of monotherapy and different combination therapies on cardiovascular target organ damage and metabolic profile in 520 hypertensive patients . Patients were allocated to a single agent : carvedilol 25 mg , amlodipine 10 mg , enalapril 20 mg , or losartan 50 mg ( groups C , A , E , and L , respectively ) . After 2 months ( level 2 ) , nonresponders received a low-dose thiazide diuretic , and after 4 months ( level 3 ) , amlodipine ( groups E , C , and L ) and carvedilol ( group A ) . Twenty-four-hour blood pressure was significantly lowered in all treatment groups . Blood pressure control was more pronounced in patients receiving two or three drugs . At the end of the study , the carotid intima-media thickness decreased in group L ( P < .01 ) , left ventricular mass index in groups E and L ( P < .05 and P < .001 , respectively ) , with a concomitant reduction in cholesterol in group L ( P < .03 ) . Diastolic function improved significantly in group L ( P < .05 ) . This study describes the need to control blood pressure with two or more drugs in most hypertensive patients and illustrates good clinical outcomes , independent of blood pressure lowering , using combination therapy with losartan , low-dose thiazide , and amlodipine .

monotherapy and combination therapy

low-dose thiazide diuretic

amlodipine

carvedilol

losartan

low-dose thiazide

amlodipine

Twenty-four-hour blood pressure

Blood pressure control

carotid intima-media thickness

left ventricular mass index

cholesterol

Diastolic function

blood pressure

hypertensive patients


Albumin-glutaraldehyde bioadhesive ( " Bioglue " ) for prevention of postoperative complications after stapled hemorrhoidopexy : A randomized controlled trial . BACKGROUND Hemorrhoidopexy using the circumferential stapler is an established method for surgical treatment of patients with prolapsing hemorrhoids . Despite its advantages , complications such as anal canal stenosis , hemorrhage and anastomosis leak with eventual intrapelvic sepsis can cause serious postoperative problems . The aim of this study was to evaluate the utility of a surgical adhesive , the biological albumin-glutaraldehyde glue " Bioglue " , in reduction of these postoperative complications . PATIENTS AND METHODS Between January 2002 and November 2004 , 200 patients undergoing stapled hemorrhoidopexy were enrolled in a prospective , randomized clinical trial . One hundred patients were randomly assigned to the control group ; the study group consisted of 100 patients who received Bioglue in the mucosa anastomosis area . All patients received standardized postoperative analgesic , laxative and antibiotic treatment . We then evaluated the two groups for postoperative complications ( after surgery and 6 months postoperatively ) . RESULTS From the control group ( no Bioglue application ) , two patients presented with anal stenosis , two with hemorrhage , three had anastomosis leak and one had thrombosis , whereas none of the patients from the Bioglue group had any of these complications . Both groups had patients with severe postoperative pain ( 3 each ) and fecal incontinence ( 1 patient each ) . The overall difference in the number of complications in the two groups was statistically significant ( p < 0.05 ) . CONCLUSION In this first study using Bioglue in patients undergoing circumferential stapled hemorrhoidopexy we have shown that application of the glue is effective in reducing postoperative complications .

stapled hemorrhoidopexy

control group ;

Bioglue in the mucosa anastomosis area

postoperative complications

postoperative complications

anal stenosis

hemorrhage

anastomosis leak

thrombosis

complications .

severe postoperative pain

fecal incontinence

overall difference

number of complications

effective

reducing postoperative complications .

200 patients

stapled hemorrhoidopexy

One hundred patients


Effectiveness of written guidelines on the appropriateness of thromboprophylaxis prescriptions for medical patients : a prospective randomized study . OBJECTIVE To assess the effectiveness of providing doctors with written thromboprophylaxis prescription aids based on current recommendations . DESIGN A prospective trial of specific anticoagulant prescription forms : a 1-day survey before and after the intervention in each centre . SETTING 30 Internal Medicine departments of Assistance Publique-Hôpitaux de Paris . SUBJECTS All inpatients were included , except those who were either admitted or discharged on the day of the survey , and those receiving curative anticoagulant treatment . INTERVENTIONS The study included three parts : ( i ) a 1-day baseline survey ; ( ii ) over the following 3-month period , departments were randomized into two groups : all practitioners in wards allocated to the intervention group were required to systematically use specific anticoagulant prescription forms , whilst doctors in the control group continued prescribing according to their usual practices and ( iii ) a 1-day postintervention survey . MAIN OUTCOME MEASURE The proportion of prescriptions in accordance with the recommendations . RESULTS 1,469 patients were included . The intervention produced a significant reduction in the frequency of over-prescriptions , from 25 % to 14 % of the patients who did not meet the guideline criteria ( adjusted OR : 0.3 ; 95 % CI : 0.1-0.8 ) . Using specific forms did not improve under-prescription of anticoagulants . A little over 60 % of the patients who met guideline criteria for thromboprophylaxis were prescribed anticoagulants in both intervention and control wards , either at baseline or after intervention . CONCLUSIONS Multitargeted interventions using a variety of means and strategies should still be considered to improve prescriptions that may have a significant impact on health expenses and , most importantly , on patients outcomes .

thromboprophylaxis prescriptions

thromboprophylaxis prescription aids

Effectiveness

effectiveness


Anecortave acetate treatment for retinal angiomatous proliferation : a pilot study . PURPOSE The purpose of this study was to evaluate anecortave acetate treatment of retinal angiomatous proliferation ( RAP ) , a neovascular form of age-related macular degeneration , with specific regard to inhibition of neovascularization and maintenance of vision . METHODS Thirty-four patients with RAP with any stage of neovascularization were randomized 1:1:1 for treatment with three different quantities ( 30 mg , 15 mg , 3 mg ) of anecortave acetate sterile suspension for juxtascleral administration . Best-corrected visual acuity ( Early Treatment Diabetic Retinopathy Study chart ) , intraocular pressure measurement , biomicroscopy , funduscopy , digital fluorescein , and indocyanine green angiography were recorded at baseline and at 3 months . A 6-month retreatment interval was established for this study with a follow-up of 12 months . In selected patients optical coherence tomography was performed . The outcomes were mean changes in visual acuity and lesion size at 1 year . RESULTS The detachment of the neurosensory retina and retinal pigment epithelium improved in all eyes , but all neovascular lesions increased in size . Vision loss occurred in the majority of study eyes ( 22 out of 34 eyes , 64.7 % ) independent of the concentration administered . CONCLUSION The results suggest that a posterior juxtascleral injection of anecortave acetate reduces capillary permeability in patients with RAP . However , in spite of improvement of the exudation there is a progression of neovascularization and a significant loss of vision in all these patients . Like other monotherapeutic methods used to treat this variant of neovascular age-related macular degeneration , anecortave acetate alone does not appear to benefit these patients . Future studies should investigate a combination form of therapy .

Anecortave acetate treatment

anecortave acetate treatment

anecortave acetate

anecortave acetate

inhibition of neovascularization

maintenance of vision

intraocular pressure measurement

mean changes in visual acuity

lesion size at 1 year

neovascular lesions

Vision loss

capillary permeability

neovascularization

loss of vision


Trials and tribulations in speech therapy .

speech therapy

Trials

tribulations

speech therapy


Use of an alpha 1-blocker , YM617 , in the treatment of benign prostatic hypertrophy . YM617 Clinical Study Group . A recently synthesized alpha 1-blocker , ( R ) ( - ) -5- [ 2- [ [ 2- ( o-ethoxyphenoxy ) ethyl ] amino ] propyl ] -2- methoxybenzenesulfonamide hydrochloride ( YM617 ) , was evaluated in 270 patients with benign prostatic hypertrophy in a double-blind study . After 2 weeks on placebo the patients were assigned at random to 4 groups : group P -- placebo , group L -- 0.1 mg. , group M -- 0.2 mg. and group H -- 0.4 mg. of YM617 . Comparing the placebo to the treatment period , subjective symptoms , such as nocturia and urgency , were significantly decreased in group H ( p less than 0.01 ) . The sensation of incomplete voiding was significantly improved in groups M and H ( p less than 0.01 ) . However , the differences among the groups were statistically insignificant . Residual urine volume was significantly decreased in groups L , M and H after instillation of saline into the bladder ( p less than 0.01 ) but not in group P. The maximum and average flow rates were significantly increased in groups L , M and H ( p less than 0.01 ) but not in group P. Average flow rate showed significant differences between groups M or H versus group P. Neither orthostatic hypotension nor a decrease in blood pressure was noted . Adverse side effects and changes in laboratory data were all slight and disappeared when the second tests were performed . In summary , the irritative and obstructive symptoms caused by benign prostatic hypertrophy were decreased and urodynamic studies were markedly improved by the alpha 1-blocker , YM617 . The drug seems to be useful in the treatment of patients with benign prostatic hypertrophy .

alpha 1-blocker , YM617

placebo

P -- placebo

placebo

nocturia and urgency

sensation of incomplete voiding

Residual urine volume

maximum and average flow rates

Average flow rate

orthostatic hypotension

blood pressure

irritative and obstructive symptoms

benign prostatic hypertrophy

urodynamic studies

benign prostatic hypertrophy

benign prostatic hypertrophy

benign prostatic hypertrophy


Long-term results of the MRC AML10 trial .

MRC AML10

Long-term results

MRC

trial


Lack of a pharmacokinetic interaction between steady-state roflumilast and single-dose midazolam in healthy subjects . AIMS The aim of this study was to investigate the effects of roflumilast , an investigational PDE4 inhibitor for the treatment of COPD and asthma , on the pharmacokinetics of the CYP3A probe drug midazolam and its major metabolites . METHODS In an open , randomized ( for midazolam treatment sequence ) study , 18 healthy male subjects received single doses of midazolam ( 2 mg oral and 1 mg i.v. , 1 day apart ) alone , repeated doses of roflumilast ( 500 microg once daily for 14 days ) alone , and repeated doses of roflumilast together with single doses of midazolam ( 2 mg oral and 1 mg i.v. , 1 day apart ) . RESULTS A comparison of clearance and peak and systemic exposure to midazolam following administration of roflumilast indicated no effect of roflumilast dosed to steady state on the pharmacokinetics of midazolam . Point estimates ( 90 % CI ) were 0.97 ( 0.84 , 1.13 ) for the AUC of i.v . midazolam and 0.98 ( 0.82 , 1.17 ) for that of oral midazolam with and without roflumilast . CONCLUSIONS Therapeutic steady state concentrations of roflumilast and its N-oxide do not alter the disposition of the CYP3A substrate midazolam in healthy subjects . This finding suggests that roflumilast is unlikely to alter the clearance of drugs that are metabolized by CYP3A4 .

roflumilast

midazolam

roflumilast

midazolam

midazolam

midazolam

roflumilast

pharmacokinetic interaction

pharmacokinetics of the CYP3A probe

pharmacokinetics of midazolam .

healthy

male

healthy


A stable prostacyclin analogue ( iloprost ) in the treatment of ischaemic ulcers of the lower limb . A Scandinavian-Polish placebo controlled , randomised multicenter study . The clinical efficacy of the prostacyclin analogue iloprost was studied during a 2 week treatment and 6 month follow-up period in 103 patients with ischaemic ulcers who were randomised to receive active treatment or placebo . Responders were defined as those patients who achieved healing of at least one third of the ulcer area during the study period . The overall responder rate was 41.3 % , compared with 25 % for the control group ( P = 0.086 ) . Side effects including flushing and headache , were common . The study population had a mortality of 23 % during the 6 month period , the amputation rate was 43.5 % for iloprost and 50 % for placebo treated patients . In this severely diseased population of patients a treatment period limited to 2 weeks did not sufficiently improve ulcer healing .

placebo

prostacyclin analogue iloprost

active treatment

placebo

iloprost

placebo

clinical efficacy

responder rate

flushing and headache

mortality

amputation rate

ulcer healing

ischaemic ulcers


Atomoxetine for hyperactivity in autism spectrum disorders : placebo-controlled crossover pilot trial . OBJECTIVE To explore placebo-controlled efficacy and safety of atomoxetine ( ATX ) for attention-deficit/hyperactivity disorder ( ADHD ) symptoms in children with autism spectrum disorders ( ASD ) . METHOD Children ages 5 to 15 with ASD and prominent ADHD symptoms were randomly assigned to order in a crossover of clinically titrated ATX and placebo , 6 weeks each , separated by 1-week washout . Slopes for each condition were compared by paired t test . RESULTS In 2004-2005 , 12 boys and 4 girls ( 7 with autistic disorder , 1 Asperger 's , 8 pervasive developmental disorder not otherwise specified ) all completed at least 3 weeks of each condition . On the primary outcome , the Hyperactivity subscale of the Aberrant Behavior Checklist , ATX was superior to placebo ( p =.043 , effect size d = 0.90 ) . It was also superior on a 0 to 3 rating of nine DSM-IV ADHD hyperactive/impulsive symptoms ( p =.005 , d = 1.27 ) , but missed significance on nine inattentive symptoms ( p =.053 , d= 0.89 ) . Nine subjects responded to ATX , four to placebo ( 25 % improvement on the Hyperactivity subscale plus Clinical Global Impressions-Improvement of 1-2 . One was rehospitalized for recurrent violence on ATX . Adverse events were otherwise tolerable , with no tendency to stereotypy . CONCLUSIONS ATX appears safe and effective for treating hyperactivity in some children with autism spectrum disorders . The effect appears as large as in a multisite methylphenidate trial in the same population , with fewer intolerable side effects . Further study in autism spectrum disorders is indicated .

Atomoxetine

atomoxetine ( ATX )

ATX

placebo

methylphenidate

rehospitalized

Adverse events

autism spectrum disorders ( ASD )

Children ages 5 to 15

boys

girls

children


Effect of hormone therapy on risk of hip and knee joint replacement in the Women 's Health Initiative . OBJECTIVE To determine the effect of hormone therapy on arthroplasty rates . METHODS We examined data from the Women 's Health Initiative placebo-controlled , double-blind , randomized trials . Community-dwelling women ages 50-79 years were enrolled at 40 US clinics . Women with prior arthroplasty were excluded , yielding a sample size of 26,321 subjects . Women who had had hysterectomies ( n = 10,272 ) were randomly assigned to receive 0.625 mg/day conjugated equine estrogens ( n = 5,076 ) , or placebo ( n = 5,196 ) , with a mean followup of 7.1 years . Those who had not had hysterectomies ( n = 16,049 ) were randomly assigned to receive estrogen plus progestin ( n = 8,240 ) , given as 0.625 mg/day conjugated equine estrogens plus 2.5 mg/day medroxyprogesterone acetate , or placebo ( n = 7,809 ) , with a mean followup of 5.6 years . Participants reported hospitalizations , and arthroplasties were identified by procedure codes . Arthroplasties due to hip fracture were censored . Cox proportional hazards regression was used to assess hazard ratios ( HRs ) and 95 % confidence intervals ( 95 % CIs ) using intent-to-treat methods and outcome of time to first procedure . RESULTS In the estrogen-alone trial , women receiving hormone therapy had significantly lower rates of any arthroplasty ( HR 0.84 [ 95 % CI 0.70-1.00 ] , P = 0.05 ) . However , this effect was borderline statistically significant for hip arthroplasty ( HR 0.73 [ 95 % CI 0.52-1.03 ] , P = 0.07 ) , and not significant for knee arthroplasty ( HR 0.87 [ 95 % CI 0.71-1.07 ] , P = 0.19 ) . In the estrogen-plus-progestin trial , there was no association for total arthroplasty ( HR 0.99 [ 95 % CI 0.82-1.20 ] , P = 0.92 ) or for individual hip ( HR 1.14 [ 95 % CI 0.83-1.57 ] , P = 0.41 ) or knee ( HR 0.91 [ 95 % CI 0.72-1.15 ] , P = 0.41 ) arthroplasties . CONCLUSION These data suggest that hormone therapy may influence joint health , but this observed decrease in risk may be limited to unopposed estrogen and may possibly be more important in hip than in knee osteoarthritis .

conjugated equine estrogens

estrogen plus progestin

conjugated equine estrogens

placebo

arthroplasty rates .

hospitalizations

arthroplasties

procedure codes

Arthroplasties

rates of any arthroplasty

total arthroplasty

individual hip

knee

arthroplasties

hip and knee joint replacement

Women 's

Women 's

Community-dwelling

women

50-79 years

Women

who had had hysterectomies

Those who had not had hysterectomies

women


Studies on leptin and leptin receptor gene expression in myometrium and uterine myomas of gnRH analogue-treated women . AIM To test if treatment with GnRH analogue , which leads to a significant reduction in myoma volume , changes expression of leptin genes and gene coding leptin receptor isoforms in uterine myomas and in the surrounding unaltered myometrium . METHODS Using RT-PCR , expression of leptin genes and leptin receptor genes was studied in myomas and in the surrounding myometrium in women with uterine myomas , untreated or treated with GnRH analogue . In the randomly selected cases presence of leptin protein and of leptin receptor proteins was examined also by Western blotting . RESULTS Expression of leptin genes was demonstrated both in myomas and in the surrounding myometrium , and a similar pattern of expression was found for leptin receptor isoforms . The results of RT-PCR were confirmed by Western blotting , which documented the identical distribution of leptin proteins and leptin receptor proteins in studied tissues . Treatment with GnRH analogue had no effect on the expression pattern of studied genes . CONCLUSION The results of the present study on the administration of GnRH analogue to females with myomas suggest that no direct or immediate inter-relationship exists between expression of leptin genes in uterine myomas on one hand and estrogen , progesterone and leptin levels in the blood on the other . Expression seems to be of a more durable nature but factors that induce such expression remain unknown .

gnRH analogue-treated

GnRH analogue

GnRH analogue

GnRH analogue

GnRH analogue

myoma volume

leptin receptor isoforms

Expression of leptin genes

expression pattern

leptin genes

women

uterine myomas

untreated or treated with GnRH analogue


Thrombus aspiration reduces microvascular obstruction after primary coronary intervention : a myocardial contrast echocardiography substudy of the REMEDIA Trial . OBJECTIVES The aim of this study was to clarify the role of microembolization in the genesis of microvascular obstruction ( MO ) after percutaneous coronary intervention ( PCI ) . BACKGROUND Fifty consecutive patients entered the myocardial contrast echocardiography ( MCE ) substudy of the REMEDIA ( Randomized Evaluation of the Effect of Mechanical Reduction of Distal Embolization by Thrombus Aspiration in Primary and Rescue Angioplasty ) trial , which defined the role of a new thrombus-aspirating device in preventing distal microembolization after PCI . METHODS A total of 25 patients were randomized to be pretreated with thrombus aspiration before PCI of the culprit lesion and 25 received standard PCI . At 24 h , 1 week , and 6 months after PCI , MCE was performed by Sonovue , and real-time imaging was performed by contrast pulse sequencing technology . Regional wall motion score index ( WMSI ) , contrast score index ( CSI ) , endocardial length of wall motion abnormality ( WML ) and contrast defect ( CDL ) , end-diastolic and end-systolic left ventricular ( LV ) volumes , and ejection fraction were calculated . RESULTS At each time point , in patients treated with a thrombus-aspiration filter device , WMSI , CSI , WML , and CDL were significantly lower and ejection fraction higher ( p < 0.05 vs. control patients ) , whereas LV volumes were slightly but not significantly smaller compared with control patients . In the overall study population , the extent of MO significantly correlated with temporal changes in LV volumes . CONCLUSIONS Thrombus aspiration used at the time of PCI significantly reduces the extent of MO and myocardial dysfunction , although it does not have a significant favorable effect in preventing LV remodeling . Thus , the beneficial effect of thrombus aspiration occurs at the microvascular level , but additional mechanisms may play a role in influencing the final extent of MO , which strictly correlates with post-infarct LV remodeling .

standard PCI .

microvascular obstruction

microvascular obstruction ( MO )

microembolization

ejection fraction

WMSI , CSI , WML , and CDL

ejection fraction

LV volumes

extent of MO

LV volumes

extent of MO

myocardial dysfunction

LV remodeling

MO

LV remodeling

primary coronary intervention :

Fifty


Nordic walking and chronic low back pain : design of a randomized clinical trial . BACKGROUND Low Back Pain is a major public health problem all over the western world . Active approaches including exercise in the treatment of low back pain results in better outcomes for patients , but it is not known exactly which types of back exercises are most beneficial or whether general physical activity provide similar benefits . Nordic Walking is a popular and fast growing type of exercise in Northern Europe . Initial studies have demonstrated that persons performing Nordic Walking are able to exercise longer and harder compared to normal walking thereby increasing their cardiovascular metabolism . Until now no studies have been performed to investigate whether Nordic Walking has beneficial effects in relation to low back pain . The primary aim of this study is to investigate whether supervised Nordic Walking can reduce pain and improve function in a population of chronic low back pain patients when compared to unsupervised Nordic Walking and advice to stay active . In addition we investigate whether there is an increase in the cardiovascular metabolism in persons performing supervised Nordic Walking compared to persons who are advised to stay active . Finally , we investigate whether there is a difference in compliance between persons receiving supervised Nordic Walking and persons doing unsupervised Nordic Walking . METHODS One hundred and fifty patients with low back pain for at least eight weeks and referred to a specialized secondary sector outpatient back pain clinic are included in the study . After completion of the standard back centre treatment patients are randomized into one of three groups : A ) Nordic Walking twice a week for eight weeks under supervision of a specially trained instructor ; B ) Unsupervised Nordic Walking for eight weeks after one training session with an instructor ; C ) A one hour motivational talk including advice to stay active . Outcome measures are pain , function , overall health , cardiovascular ability and activity level . RESULTS No results available at this point . DISCUSSION This study will investigate the effect of Nordic Walking on pain and function in a population of people with chronic LBP .

Nordic walking

Nordic Walking

Nordic Walking

Nordic Walking

supervised Nordic Walking

supervised Nordic Walking

advised to stay active .

supervised Nordic Walking

unsupervised Nordic Walking .

Nordic Walking

effects

reduce pain

improve function

compliance

pain

function

overall health

cardiovascular ability

activity level


Risperidone improves behavioral symptoms in children with autism in a randomized , double-blind , placebo-controlled trial . Subgroup analysis of children ( 5-12 years ) with autism enrolled in an 8-week , double-blind , placebo-controlled trial of risperidone for pervasive developmental disorders . The primary efficacy measure was the Aberrant Behavior Checklist-Irritability ( ABC-I ) subscale . Data were available for 55 children given risperidone ( n=27 ) or placebo ( n=28 ) ; mean baseline ABC-I ( +/- SD ) was 20.6 ( 8.1 ) and 21.6 ( 10.2 ) . Risperidone [ mean dose ( +/- SD ) : 1.37 mg/day ( 0.7 ) ] resulted in significantly greater reduction from baseline to endpoint in ABC-I versus placebo [ mean change ( +/- SD ) : -13.4 ( 1.5 ) vs. -7.2 ( 1.4 ) , P < 0.05 ; ES=-0.7 ] . The most common adverse effect with risperidone was somnolence ( 74 % vs. 7 % with placebo ) . Risperidone treatment was well tolerated and significantly improved behavioral problems associated with autism .

Risperidone

placebo-controlled

placebo-controlled

risperidone

risperidone

placebo

Risperidone

placebo

risperidone

placebo

Risperidone

behavioral symptoms

ABC-I

somnolence

tolerated

behavioral problems

children

autism

children ( 5-12 years )

autism


DTkid : interactive simulation software for training tutors of children with autism . Discrete-trial training ( DTT ) relies critically on implementation by trained tutors . We report three experiments carried out in the development of " DTkid " -- interactive computer simulation software that presents " SIMon " , a realistic virtual child with whom novice tutors can learn and practise DTT techniques . Experiments 1 and 2 exposed groups of participants either to DTkid training or to a control task . Participants in the former groups demonstrated significantly greater procedural and declarative knowledge of DTT . Experiment 3 confirmed this finding , further demonstrating that observation of DTkid training trials alone was sufficient to enhance participants ' declarative and procedural knowledge of DTT . Results indicate that DTkid offers the potential for an effective means of teaching DTT skills to novice tutors of children with autism .

Discrete-trial training

DTkid training

control task

DTkid training

declarative and procedural knowledge

children

autism

novice tutors

children

autism


Adenosinergic mechanisms contribute to individual differences in sleep deprivation-induced changes in neurobehavioral function and brain rhythmic activity . Large individual differences characterize the changes induced by sleep deprivation on neurobehavioral functions and rhythmic brain activity . To investigate adenosinergic mechanisms in these differences , we studied the effects of prolonged waking and the adenosine receptor antagonist caffeine on sustained vigilant attention and regional electroencephalogram ( EEG ) power in the ranges of theta activity ( 6.25-8.25 Hz ) in waking and the slow oscillation ( < 1 Hz ) in sleep . Activity in these frequencies is functionally related to sleep deprivation . In 12 subjectively caffeine-sensitive and 10 -insensitive young men , psychomotor vigilance task ( PVT ) performance and EEG were assessed at 3 h intervals before , during , and after one night without sleep . After 11 and 23 h waking , subjects received 200 mg caffeine and placebo in double-blind , cross-over manner . In the placebo condition , sleep deprivation impaired PVT speed more in caffeine-sensitive than in caffeine-insensitive men . This difference was counteracted by caffeine . Theta power in waking increased more in a frontal EEG derivation than in a posterior derivation . Caffeine attenuated this power gradient in caffeine sensitive subjects . Sleep loss also differently affected the power distribution < 1 Hz in non-rapid eye movement sleep between caffeine sensitive and insensitive subjects . Also , this difference was mirrored by the action of caffeine . The effects of sleep deprivation and caffeine on sustained attention and regional EEG power in waking and sleep were inversely related . These findings suggest that adenosinergic mechanisms contribute to individual differences in waking-induced impairment of neurobehavioral performance and functional aspects of EEG topography associated with sleep deprivation .

Adenosinergic mechanisms

adenosinergic mechanisms

caffeine

one night without sleep

caffeine

placebo

placebo

caffeine

Caffeine

caffeine

caffeine

adenosinergic mechanisms

Theta power in waking

Sleep loss

non-rapid eye movement sleep

sleep deprivation

waking and sleep

young

men


Comparison of the effectiveness of fennel and mefenamic acid on pain intensity in dysmenorrhoea . A study in Kerman , Islamic Republic of Iran in 2002 compared the effectiveness of fennel and mefenamic acid on pain relief in primary dysmenorrhoea . Two groups of high-school girls ( mean age 13 years ) suffering dysmenorrhoea were randomized to receive fennel extract ( n = 55 ) or mefenamic acid ( n = 55 ) for 2 months . In the fennel group , 80 % of girls and in the mefenamic acid group , 73 % of girls showed complete pain relief or pain decrease , while 80 % in the fennel group and 62 % in the mefenamic acid group no longer needed to rest . There was no significant difference between the 2 groups in the level of pain relief .

fennel

mefenamic acid

fennel

mefenamic acid

fennel extract

mefenamic acid

fennel

mefenamic acid

fennel

mefenamic acid

pain relief or pain decrease

level of pain relief


Enhanced baroreceptor control of the cardiovascular system by polyunsaturated Fatty acids in heart failure patients . OBJECTIVES The intention of this study was to test the hypothesis that , in heart failure patients , dietary supplementation of polyunsaturated fatty acids ( PUFA ) enhances arterial baroreceptor control of the cardiovascular system . BACKGROUND Administration of PUFA reduces the risk of life-threatening arrhythmias in patients surviving myocardial infarction . This might result from potentiation of arterial baroreflexes , but whether or not PUFA enhance baroreflex function has never been studied in humans . METHODS Patients with post-myocardial infarction left ventricular dysfunction underwent beat-to-beat blood pressure ( BP ) ( Finapres , Ohmeda Inc. , Englewood , Colorado ) and R-R interval ( electrocardiogram ) recording ; baroreceptor reflexes were assessed from the bradycardic and depressor responses to graded neck suction ( NS ) as well as by computation of the alpha " spontaneous " baroreflex sensitivity index . Assessments were repeated after prolonged treatment with PUFA ( 2 g/die , n = 15 ) or placebo ( n = 10 ) . RESULTS Baseline BP and R-R interval were unaffected by PUFA . Both reflex depressor and bradycardic responses to NS increased after PUFA ( respectively from -0.09 +/- 0.01 to -0.16 +/- 0.01 mm Hg x mm Hg ( -1 ) , p < 0.01 , and from 1.25 +/- 0.9 to 1.76 +/- 1.1 ms x mm Hg ( -1 ) , p < 0.04 ) but not after placebo . The spontaneous baroreflex sensitivity increased in the PUFA ( from 8.99 +/- 1.4 to 12.2 +/- 1.2 ms x mm Hg ( -1 ) , p < 0.02 ) but not in the placebo group . Polyunsaturated fatty acids ( but not placebo ) treatment also significantly increased R-R interval total variance and low-frequency and high-frequency spectral powers . CONCLUSIONS Dietary PUFA supplementation markedly potentiates baroreflex function and enhances heart rate variability in patients with stable congestive heart failure .

polyunsaturated Fatty acids

PUFA

PUFA

PUFA

placebo

PUFA .

PUFA

placebo .

PUFA

placebo

Polyunsaturated fatty acids

placebo

Dietary PUFA supplementation

Baseline BP

R-R interval

spontaneous baroreflex sensitivity

R-R interval total variance

heart rate variability

heart failure patients .

heart failure patients