Randomized trial of a " stage-of-change " oriented smoking cessation intervention in infertile and pregnant women . OBJECTIVE To assess a " stage-of-change " oriented smoking cessation intervention for infertile and pregnant women , compared with standard of care . DESIGN Randomized controlled trial . SETTING Three university teaching hospitals in Hamilton , Ontario , Canada . PATIENT ( S ) Infertile women at their first visit to a tertiary referral infertility clinic ( n = 94 ) and new patients seeking pre-natal care ( n = 110 ) who had smoked > /= 3 cigarettes in the past six months . INTERVENTION ( S ) A three to five minute scripted intervention and booklet specific to the woman 's " stage-of-change " in the smoking continuum , versus standard of care . Exhaled carbon-monoxide ( CO ) monitoring was used to validate exposure in both groups . MAIN OUTCOME MEASURE ( S ) Delta " stage-of-change " and rate of maintained cessation at 12 months post follow-up . RESULT ( S ) Intervention and control were similarly effective for infertile women : the rate of maintained cessation rose significantly from 4 % to 24 % over twelve months , with a mean delta " stage-of-change " 0.28 . In prenatal women , neither approach was effective . Maintained cessation did not significantly change from 0 to 12 months ( 19 % to 18 % ) . Mean delta " stage-of-change " declined by -0.62 . CONCLUSION ( S ) For infertile women , basic information describing the impact of smoking on fertility , along with exhaled CO monitoring and a more intensive intervention were both highly effective . In pregnant women neither approach was beneficial , with some evidence of post-partum relapse .

standard of care

rate of maintained cessation

mean delta " stage-of-change "

Maintained cessation

Mean delta " stage-of-change

infertile and pregnant

women


Effect of L-ornithine-L-aspartate on patients with and without TIPS undergoing glutamine challenge : a double blind , placebo controlled trial . BACKGROUND AND AIM An oral glutamine load in cirrhotic patients awaiting liver transplantation was shown to cause a rise in blood ammonia and psychometric abnormalities which were reversed by hepatic transplantation . L-Ornithine-L-aspartate ( LOLA ) has been shown to reduce ammonia and improve psychometric function in patients with hepatic encephalopathy . The aim of the present study was to assess the effect of LOLA in healthy patients with cirrhosis and no evidence of clinical encephalopathy after challenging the central nervous system by administration of oral glutamine . PATIENTS AND METHODS Eight cirrhotics ( Child 's B or C ) without transjugular intrahepatic portosystemic shunts ( TIPS ) and seven with TIPS underwent two oral glutamine ( 20 g ) challenges , receiving LOLA ( 5 g intravenously ) on one occasion and placebo on the other in random order . Psychometric tests , including choice reaction time ( CRT ) and number connection test , were performed before and after glutamine , together with electroencephalography and blood ammonia . RESULTS Mean basal ammonia was 27 ( SEM 5 ) micromol/l in non-TIPS and 76 ( 10 ) micromol/l in TIPS patients ( p < 0.05 ) . Basal CRT 2 was 0.643 ( 0.033 ) s in non-TIPS and 0.825 ( 0.076 ) s in TIPS patients ( p < 0.02 ) . In non-TIPS patients , ammonia increased to 36 ( 10 ) micromol/l when LOLA was administered and to 62 ( 13 ) micromol/l with placebo ( p < 0.02 ) . There was no alteration in psychometric function in non-TIPS patients after glutamine when LOLA was given but when placebo was given , glutamine caused prolongation of CRT ( p=0.02 ) . Glutamine did not affect psychometric function in TIPS patients with or without LOLA . CONCLUSION This study showed that LOLA ameliorated the deleterious psychometric effects of glutamine in Child 's grade B and C patients with cirrhosis without TIPS and supports its use in clinical practice in hepatic encephalopathy .

L-ornithine-L-aspartate

L-Ornithine-L-aspartate ( LOLA )

LOLA

oral glutamine ( 20 g ) challenges

LOLA

placebo

LOLA

LOLA

placebo

LOLA

blood ammonia

psychometric abnormalities

ammonia

psychometric function

Mean basal ammonia

Basal CRT 2

ammonia

psychometric function

CRT

psychometric function

psychometric effects


Superior modulation of activation levels of stimulus representations does not underlie superior discrimination in autism . The performance of children with and without autism was compared in object-based positive and negative priming tasks within a visual search procedure . Object-based positive and negative priming effects were found in both groups of children . This result provides the first evidence for the activation of object-based representations during visual search task performance and further supports the notion that both excitatory and inhibitory guidance mechanisms are involved in target location in visual search . The children with autism were overall better than the typically developing children at visual search , thus replicating demonstrations of superior discrimination in autism . Furthermore , there was no difference between the magnitude of the positive nor the negative priming effects of the groups . This finding suggests that excitatory and inhibitory control operate comparably in autism and normal development . These results are discussed in the light of the superior ability of individuals with autism to discriminate between items . More specifically , it is argued that superior discrimination in autism does not result from enhanced top-down excitatory and inhibitory control .

visual search procedure .

visual search task performance

positive and negative priming effects

object-based representations

visual search

priming effects

normal development


Onset/offset characteristics and intubating conditions of rapacuronium : a comparison with rocuronium . We compared onset and offset of action and tracheal intubating conditions after rapacuronium and rocuronium in 60 patients in a randomized , assessor-blinded study . Following induction of anaesthesia with propofol 2.5 mg kg-1 , either rapacuronium 1.5 mg kg-1 ( n = 30 ) or rocuronium 0.6 mg kg-1 ( n = 30 ) was administered to facilitate tracheal intubation . Anaesthesia was maintained with either a propofol infusion ( 100 micrograms kg-1 min-1 ) or sevoflurane ( 1 % end-tidal ) with 66 % nitrous oxide ( N2O ) , n = 15 in each subgroup . Neuromuscular monitoring was performed using an electromyographic ( EMG ) device ( Datex Relaxograph ) . The lag times ( mean 42 ( SD 11 ) s and 44 ( 16 ) s ) , maximum block ( 99 ( 2 ) % and 98 ( 3 ) % ) and intubating conditions at 60 s ( good-to-excellent in 86 % and 84 % of patients ) were similar for rapacuronium and rocuronium , respectively . The onset time of rapacuronium was shorter than rocuronium ( 87 ( 20 ) vs 141 ( 65 ) s , P < 0.001 ) , and the degree of block at 60 s was greater ( 69 ( 26 ) vs 50 ( 27 ) % , P < 0.05 ) . Twenty-five per cent recovery was shorter with rapacuronium than rocuronium during propofol ( 15.0 ( 3.2 ) vs 39.1 ( 14.2 ) min , P < 0.001 ) and sevoflurane ( 15.1 ( 4.2 ) vs 47.8 ( 19.0 ) min , P < 0.001 ) anaesthesia . We conclude that rapacuronium 1.5 mg kg-1 had a more rapid onset , similar intubating conditions , and shorter recovery times than rocuronium 0.6 mg kg-1 .

rapacuronium

rocuronium

propofol

rapacuronium

rocuronium

propofol infusion ( 100

micrograms

kg-1 min-1 )

Neuromuscular monitoring

electromyographic

Neuromuscular monitoring

lag times

maximum block

intubating conditions at 60 s

onset time

degree of block at 60 s

recovery

intubating conditions

tracheal intubating conditions

patients


Comparison of succinylcholine with two doses of rocuronium using a new method of monitoring neuromuscular block at the laryngeal muscles by surface laryngeal electromyography . We compared the onset of neuromuscular block with succinylcholine ( 1 mg kg-1 ) and two doses of rocuronium ( 0.6 and 0.9 mg kg-1 ) at the adductor pollicis muscle using electromyography ( EMG ) and acceleromyography ( AMG ) , and at the adductor laryngeal muscles with a new electromyographic method using a disposable surface electrode attached to the cuff of a tracheal tube . At the larynx , the mean ( +/- SD ) time to 90 % block and the onset time of succinylcholine ( 38 +/- 15 and 47 +/- 19 s , respectively ) were significantly shorter ( P < 0.01 ) than for rocuronium 0.6 mg kg-1 ( 92 +/- 42 and 106 +/- 38 s ) and rocuronium 0.9 mg kg-1 ( 52 +/- 31 and 64 +/- 30 s ) . We found that , with comparable degrees of neuromuscular block , the onset time of succinylcholine at the adductor pollicis was significantly shorter ( P < 0.01 ) than for rocuronium 0.6 mg kg-1 and 0.9 mg kg-1 ( EMG , 80 +/- 39 vs 145 +/- 48 s and 99 +/- 31 s ; AMG , 90 +/- 39 vs 124 +/- 53 s and 106 +/- 38 s ) . Clinical duration at the adductor pollicis ( AMG ) was significantly longer ( P < 0.01 ) for both rocuronium groups than for succinylcholine ( T4 : T1 = 0.7 , 54 +/- 18 and 77 +/- 21 vs 8 +/- 6 min ) . The surface laryngeal electrode proved non-invasive , easy to use and reliable in measuring onset of the neuromuscular block at the larynx .

succinylcholine

rocuronium

electromyographic method

succinylcholine

rocuronium

rocuronium

succinylcholine

rocuronium

succinylcholine

neuromuscular block

onset of neuromuscular block

mean ( +/- SD ) time to 90 % block

succinylcholine

neuromuscular block

onset of the neuromuscular block

surface laryngeal electromyography


Sublingual administration of micronized estradiol and progesterone , with and without micronized testosterone : effect on biochemical markers of bone metabolism and bone mineral density . OBJECTIVES The purpose of this investigation was to evaluate the relative efficacy of the sublingual administration of micronized estradiol ( E2 ) , progesterone ( P4 ) , and testosterone ( T ) on bone mineral density and biochemical markers of bone metabolism . DESIGN In this double-blind , prospective study , postmenopausal women were randomly assigned to one of four treatment groups : hysterectomized women were assigned to either 1 ) micronized E2 ( 0.5 mg ) or 2 ) micronized E2 ( 0.5 mg ) + micronized T ( 1.25 mg ) . Women with intact uteri were assigned to either 3 ) micronized E2 ( 0.5 mg ) + micronized P4 ( 100 mg ) or 4 ) micronized E2 ( 0.5 mg ) + micronized P4 ( 100 mcg ) + micronized T ( 1.25 mg ) . For the purpose of this study , the four treatment groups were combined into two groups for all comparisons . The E2 and E2+P4 groups were combined into the HRT alone group ( n=30 ) , and the E2+T and E2+P4+T groups were combined into the HRT + T group ( n=27 ) . Hormones were administered sublingually as a single tablet twice a day for 12 months . Bone mineral density was measured in the anterior-posterior lumbar spine and total left hip via dual energy x-ray absorptiometry . Bone metabolism was assessed via serum bone-specific alkaline phosphatase and urinary deoxypyridinoline and cross-linked N-telopeptide of type I collagen , both normalized to creatinine . Data were analyzed via a repeated measures analysis of variance and a Student 's t test ( alpha=0.05 ) . RESULTS The subjects were of similar age ( 54.0 +/- 0.8 years ) , height ( 64.0 +/- 0.3 in ) , weight ( 157.6 +/- 4.2 lb ) , and had similar baseline follicle-stimulating hormone ( 66.4 +/- 3.2 mIU/L ) , E2 ( 26.4 +/- 1.5 pg/ml ) , P4 ( 0.3 +/- 0.1 ng/ml ) , total T ( 19.0 +/- 1.5 ng/dL ) , and bioavailable T ( 3.7 +/- 0.3 ng/dL ) levels . During therapy , serum levels increased ( p < 0.05 ) for each hormone . Bone mineral density and bone markers at baseline were similar for each treatment group . Bone-specific alkaline phosphatase decreased ( p < 0.05 ) by -14.3 +/- 4.1 % in the HRT alone group and by -8.2 +/- 4.6 % in the HRT + T group . Deoxypyridinoline levels decreased significantly in the HRT alone and HRT + T groups , - 14.4 +/- 6.8 % and -26.9 +/- 7.6 % , respectively . Significant reductions ( p < 0.05 ) in cross-linked N-telopeptide of type I collagen were also observed in both groups , -24.4 +/- 6.5 % and -39.5 +/- 8.6 % , respectively . Bone mineral density in the lumbar spine increased ( p < 0.05 ) by +2.2 +/- 0.5 % the HRT alone group and by + 1.8 +/- 0.6 % in the HRT + T group . Total hip bone mineral density was maintained in the HRT alone group ( +0.4 +/- 0.4 % ) and increased ( p < 0.05 ) in the HRT + T group ( + 1.8 +/- 0.5 % ) . CONCLUSIONS Sublingual micronized HRT favorably decreases serum and urine markers of bone metabolism , prevents bone loss , and results in a slight increase in spine and hip bone mineral density . Although the addition of testosterone to HRT for 1 year did not result in added benefit to the spine bone mineral density , it did result in a significant increase in hip bone mineral density . Longer duration of therapy may have further improved these outcomes .

micronized estradiol

progesterone

micronized testosterone

micronized estradiol ( E2 )

progesterone ( P4 )

testosterone ( T )

micronized E2

micronized E2

micronized T

micronized E2

micronized P4

micronized E2

+ micronized P4

+ micronized T

HRT + T

HRT

HRT + T

HRT alone

HRT + T

HRT alone

HRT + T

HRT alone

HRT + T

HRT

HRT

bone

and bone mineral density .

Bone mineral density

Bone metabolism

Bone mineral density and bone markers

Bone-specific alkaline phosphatase

levels

Total hip bone mineral density

bone loss

spine and hip bone mineral density .

spine bone mineral density

hip bone mineral density .


Paclitaxel ( 175 mg/m2 ) plus carboplatin ( 6 AUC ) versus paclitaxel ( 225 mg/m2 ) plus carboplatin ( 6 AUC ) in advanced non-small-cell lung cancer ( NSCLC ) : a multicenter randomized trial . Hellenic Cooperative Oncology Group ( HeCOG ) . PURPOSE The combination of paclitaxel and carboplatin has become a widely used regimen in NSCLC due to phase II reports of moderate toxicity , reasonable activity and easy outpatient administration . Purpose of our present prospective study was to evaluate the dose response relationship of paclitaxel . PATIENTS AND METHODS Since July 1996 , 198 patients with non-operable NSCLC and measurable disease without previous chemotherapy entered the trial . Ninety nine patients ( group A ) were randomized to receive paclitaxel 175 mg/m2 in three-hour infusion plus carboplatin dosed to an area under the concentration-time curve of 6 every 3 weeks and 99 ( group B ) to receive the same regimen with paclitaxel increased to 225 mg/m2 . Eligibility criteria included WHO performance status 0-2 , documented inoperable stage IIIA and IIIB , IV , no brain metastasis , no prior chemotherapy and adequate renal and hepatic function . Patients in both groups were well-matched with baseline disease characteristics . RESULTS In group A with 90 evaluable patients , the response rate was 25.6 % ( 6 CR , 17 PR ) whereas in group B with 88 evaluable patients , the response rate was 31.8 % ( 3 CR , 25 PR ) , P = 0.733 . Median time to progression favored the high-dose paclitaxel ( 4.3 vs. 6.4 months , P = 0.044 ) . The median survival was 9.5 months for group A versus 11.4 months for group B ( P = 0.16 ) . The one-year survival was 37 % for group A and 44 % for group B ( P = 0.35 ) . The best prognostic factor for one-year survival was the response rate ( P < 0.0001 ) . With a relative dose intensity of paclitaxel 0.94 in both groups , neurotoxicity ( P = 0.025 ) and leucopenia ( P = 0.038 ) were more pronounced in group B patients . No toxic death was observed . CONCLUSIONS Higher dose paclitaxel prolongs the median time to progression but causes more neurotoxicity and leucopenia . The better response rate , the longer overall and better one-year survival seen with the higher dose of paclitaxel are not statistically significant .

Paclitaxel

carboplatin

paclitaxel

plus carboplatin

paclitaxel

carboplatin

chemotherapy

paclitaxel

plus carboplatin

paclitaxel

chemotherapy

dose response

response rate

response rate

Median time to progression

median survival

one-year survival

one-year survival

response rate

neurotoxicity

leucopenia

toxic death

non-small-cell lung cancer ( NSCLC )

non-operable NSCLC

Ninety nine


Analysis of treatment in childhood leukaemia . I. Predisposition to methotrexate-induced neutropenia after craniospinal irradiation . Report to the Medical Research Council of the Working Party on Leukaemia in Childhood . The degree of drug-induced neutropenia resulting from a controlled trial ( UKALL I ) of treatment in acute lymphoblastic leukaemia was analysed . The main agent associated with severe neutropenia was methotrexate , and methotrexate-induced neutropenia was significantly greater in patients who had received craniospinal irradiation . The synergistic toxic effect of irradiation followed by methotrexate treatment seems to have contributed to three of the five deaths which occurred in complete remission in this trial ; all deaths in remission occurred in patients who had received central nervous system prophylaxis . Analysis of patients who subsequently relapsed compared with those still in remission after 18 months of treatment indicated that the former , on average , had slightly lower neutrophil counts . This suggests that the children who relapsed did not receive any less aggressive treatment than those who remained in remission .

methotrexate

Analysis of treatment

neutropenia

severe neutropenia

methotrexate-induced neutropenia

synergistic toxic effect of irradiation

deaths

remission

neutrophil counts .


The effect of systemic lidocaine on pain and secondary hyperalgesia associated with the heat/capsaicin sensitization model in healthy volunteers . UNLABELLED Although effective in neuropathic pain , the efficacy of systemic lidocaine in non-neuropathic pain remains uncertain . We investigated the analgesic effect of systemic lidocaine on the heat/capsaicin sensitization model of experimental pain in 24 volunteers . Sensitization was produced by heating the skin to 45 degrees C for 5 min , followed by a 30-min application of 0.075 % capsaicin cream , and maintained by periodically reheating the sensitized skin . Subjects received IV lidocaine ( bolus 2 mg/kg , then infusion 3 mg. kg . h ) , or saline for 85 min . Areas of secondary hyperalgesia , heat pain detection thresholds , and painfulness of stimulation with 45 degrees C for 1 min ( long thermal stimulation ) were quantified . Systemic lidocaine reduced the area of secondary hyperalgesia to brush , but not to von Frey hair stimulation . Lidocaine did not alter heat pain detection thresholds or painfulness of long thermal stimulation in normal skin . We conclude that , at infusion rates in the low- to mid-antiarrhythmic range , lidocaine has no effect on acute nociceptive pain but does have a limited and selective effect on secondary hyperalgesia . IMPLICATIONS The efficacy of systemic lidocaine in nonneuropathic pain remains uncertain . This study investigates the effect of systemic lidocaine on experimental-induced hyperalgesia in 25 volunteers . Hyperalgesia was induced by using an experimental pain model that uses heat and capsaicin in combination . Systemic lidocaine showed a selective effect on secondary hyperalgesia .

lidocaine

lidocaine

systemic lidocaine

heating the skin

capsaicin cream

lidocaine

saline

lidocaine

Lidocaine

lidocaine

lidocaine

lidocaine

pain

secondary hyperalgesia

secondary hyperalgesia

heat pain detection thresholds

painfulness of long thermal stimulation

acute nociceptive pain

secondary hyperalgesia

efficacy

nonneuropathic pain

experimental-induced hyperalgesia

Hyperalgesia

pain and secondary hyperalgesia

in healthy volunteers .

non-neuropathic pain

experimental pain in 24 volunteers .


Phase III comparative study of high-dose cisplatin versus a combination of paclitaxel and cisplatin in patients with advanced non-small-cell lung cancer . PURPOSE New effective chemotherapy is needed to improve the outcome of patients with advanced non-small-cell lung cancer ( NSCLC ) . Paclitaxel administered as a single agent or in combination with cisplatin has been shown to be a potentially new useful agent for the treatment of NSCLC . PATIENTS AND METHODS Between January 1995 and April 1996 , 414 patients with stage IIIB or IV NSCLC were randomized to received either a control arm of high-dose cisplatin ( 100 mg/m ( 2 ) ) or a combination of paclitaxel ( 175 mg/m ( 2 ) , 3-hour infusion ) and cisplatin ( 80 mg/m ( 2 ) ) every 21 days . RESULTS Compared with the cisplatin-only arm , there was a 9 % improvement ( 95 % confidence interval , 0 % to 19 % ) in overall response rate for the paclitaxel/cisplatin arm ( 17 % v 26 % , respectively ; P=.028 ) . Median time to progression was 2.7 and 4.1 months in the control and paclitaxel/cisplatin arm , respectively ( P=.026 ) . The study , however , failed to show a significant improvement in median survival for the paclitaxel/cisplatin arm ( 8.6 months in the control arm v 8.1 months in the paclitaxel/cisplatin arm , P=.862 ) . There was more hematotoxicity , peripheral neuropathy , and arthralgia/myalgia on the paclitaxel/cisplatin arm , whereas the high-dose cisplatin arm produced more ototoxicity , nausea , vomiting , and nephrotoxicity . Quality of life ( QOL ) was similar overall between the two arms . CONCLUSION This large randomized phase III trial failed to show a significant improvement in survival for the paclitaxel/cisplatin combination compared with high-dose cisplatin in patients with advanced NSCLC . However , the paclitaxel/cisplatin combination did produce a better clinical response , resulting in an increased time to progression while providing a similar QOL .

high-dose cisplatin

paclitaxel and cisplatin

Paclitaxel

cisplatin

high-dose cisplatin

combination of paclitaxel

cisplatin

paclitaxel/cisplatin

paclitaxel/cisplatin

paclitaxel/cisplatin

paclitaxel/cisplatin

cisplatin

paclitaxel/cisplatin

cisplatin

paclitaxel/cisplatin

overall response rate

Median time to progression

median survival

Quality of life ( QOL )


Treatment of brain metastases of small-cell lung cancer : comparing teniposide and teniposide with whole-brain radiotherapy -- a phase III study of the European Organization for the Research and Treatment of Cancer Lung Cancer Cooperative Group . PURPOSE Approximately 60 % of patients with small-cell lung cancer ( SCLC ) develop brain metastases . Whole-brain radiotherapy ( WBRT ) gives symptomatic improvement in more than 50 % of these patients . Because brain metastases are a sign of systemic progression , and chemotherapy was found to be effective as well , it becomes questionable whether WBRT is the only appropriate therapy in this situation . PATIENTS AND METHODS In a phase III study , SCLC patients with brain metastases were randomized to receive teniposide with or without WBRT . Teniposide 120 mg/m ( 2 ) was given intravenously three times a week , every 3 weeks . WBRT ( 10 fractions of 3 Gy ) had to start within 3 weeks from the start of chemotherapy . Response was measured clinically and by computed tomography of the brain . RESULTS One hundred twenty eligible patients were randomized . A 57 % response rate was seen in the combined-modality arm ( 95 % confidence interval [ CI ] , 43 % to 69 % ) , and a 22 % response rate was seen in the teniposide-alone arm ( 95 % CI , 12 % to 34 % ) ( P < .001 ) . Time to progression in the brain was longer in the combined-modality group ( P=.005 ) . Clinical response and response outside the brain were not different . The median survival time was 3.5 months in the combined-modality arm and 3.2 months in the teniposide-alone arm . Overall survival in both groups was not different ( P=.087 ) . CONCLUSION Adding WBRT to teniposide results in a much higher response rate of brain metastases and in a longer time to progression of brain metastases than teniposide alone . Survival was poor in both groups and not significantly different .

teniposide

teniposide

with whole-brain radiotherapy

Whole-brain radiotherapy ( WBRT )

WBRT

teniposide

WBRT

Teniposide

WBRT

chemotherapy

teniposide-alone

teniposide-alone

WBRT

teniposide

clinically

computed tomography of the brain

response rate

response rate

Time to progression

in the brain

longer

Clinical response

median survival time

response rate

Survival

One hundred twenty eligible patients


[ Effectiveness of morphine by periarticular injections after shoulder arthroscopy ] . Peripheral opioid receptors have been found in inflamed synovia and the analgesic effect of intra-articularly administered morphine after arthroscopic knee surgery has been proven . There is controversy about efficacy of intraarticular morphine after shoulder arthroscopy . Thirty-two patients with impingement syndrome underwent subacromial decompression in the course of arthroscopic shoulder surgery . At the end of the operation morphine ( 5 mg ) or saline was injected periarticularly . Pain intensity ( rest and passive mobilisation ) was recorded after recovery and after 1,2,4 , and 24 hours ( Numeric Rating Scale ) ; the use of rescue medication ( piritramide by patient controlled analgesia ) was noted . No relevant pain reduction was apparent in the morphine group . Piritramide consumption was identical in both groups ( 19.7 +/- 16 mg vs. 19.8 +/- 19 mg ) . We conclude that periarticularly administered morphine in arthroscopic subacromial decompression in the dosage applied in this study does exert no relevant analgesic effect . This is possibly due to the fact that either subacromial tissue , despite of chronic inflammation , does not show the same reagibility as synovia or it is a problem of the nearly complete resection of the subacromial bursa .

morphine

morphine

morphine

arthroscopic shoulder surgery

operation morphine ( 5 mg )

saline

piritramide

Piritramide

morphine

rescue medication

piritramide

patient controlled analgesia

pain reduction

Piritramide consumption

analgesic effect


Cost-effectiveness of clozapine compared with conventional antipsychotic medication for patients in state hospitals . BACKGROUND An open-label , randomized controlled trial compared clozapine with physicians'-choice medications among long-term state hospital inpatients in Connecticut . The goal was to examine clozapine 's cost-effectiveness in routine practice for people experiencing lengthy hospitalizations . METHODS Long-stay patients with schizophrenia in a state hospital were randomly assigned to begin open-label clozapine ( n = 138 ) or to continue receiving conventional antipsychotic medications ( n = 89 ) . We interviewed study participants every 4 months for 2 years to assess psychiatric symptoms and functional status , and we collected continuous measures of prescribed medications , service utilization , and other costs . We used both parametric and nonparametric techniques to examine changes in cost and parametric analyses to examine changes in effectiveness . We used bootstrap techniques to estimate incremental cost-effectiveness ratios and create cost-effectiveness acceptability curves . RESULTS Both groups incurred similar costs during the 2-year study period , with a trend for clozapine to be less costly than usual care in the second study year . Clozapine was more effective than usual care on many but not all measures . With the use of effectiveness measures that favored clozapine ( extrapyramidal side effects , disruptiveness ) , bootstrap techniques indicated that , even when a payer is unwilling to incur any additional cost for gains in effectiveness , the probability that clozapine is more cost-effective than usual care is at least 0.80 . These findings were not as evident when outcomes where clozapine was not clearly superior ( psychotic symptoms , weight gain ) were examined . CONCLUSION Clozapine demonstrated cost-effectiveness on some but not all measures of effectiveness when the alternative was a range of conventional antipsychotic medications .

clozapine

clozapine

Clozapine

clozapine

Clozapine

cost-effectiveness

assess psychiatric symptoms

functional status

changes in cost

parametric analyses

changes in effectiveness

cost-effectiveness acceptability curves

effective

effectiveness measures

more cost-effective

psychotic symptoms

weight gain

cost-effectiveness

patients in state hospitals

long-term state hospital inpatients


Beta radiation as an adjunct to low-risk trabeculectomy . PURPOSE To assess a single dose of intraoperative beta radiation used to enhance the success rate of trabeculectomy in a population of low-risk glaucoma patients in whom antimetabolites might not be indicated . METHODS A prospective randomized trial of 65 eyes was designed , with 31 eyes receiving 750 rads of intraoperative beta radiation ( group 1 ) , and 34 eyes receiving no supplementation ( group 2 ) . RESULTS Mean follow-up time was 24 months . Mean postoperative intraocular pressure was 12.2 mmHg in group 1 , and 13.7 mmHg in group 2 ( P = 0.16 ) . Mean decrease in intraocular pressure was 10.3 mmHg in group 1 , and 9.3 mmHg in group 2 ( P = 0.49 ) . The two groups were not significantly different in terms of surgical complications . CONCLUSION For this population of low-risk patients , there was no significant difference in outcome after applications of a single intraoperative dose of beta radiation .

Beta radiation

intraoperative beta radiation

receiving no supplementation

beta radiation

Mean postoperative intraocular pressure

intraocular pressure

surgical complications

trabeculectomy

glaucoma

low-risk patients


Outcomes of early endovascular versus surgical treatment of ruptured cerebral aneurysms . A prospective randomized study . BACKGROUND AND PURPOSE This prospective study was conducted to compare the outcomes of surgical clipping and endovascular treatment in acute ( < 72 hours ) aneurysmal subarachnoid hemorrhage ( SAH ) . METHODS One hundred nine consecutive patients were randomly assigned to either surgical ( n=57 ) or endovascular ( n=52 ) treatment . Clinical and neuropsychological outcome was assessed at 3 and 12 months after treatment ; MRI of the brain was performed at 12 months . Follow-up angiography was scheduled after clipping and 3 and 12 months after endovascular treatment . RESULTS One year postoperatively , 43/41 ( surgical/endovascular ) patients had good or moderate recovery , 5/4 had severe disability or were in a vegetative state , and 9/7 had died ( NS ) according to intention to treat . Patients with good clinical recovery did not differ in their neuropsychological test scores . Symptomatic vasospasm ( OR 2.47 ; 95 % CI 1.45 to 4.19 ; P < 0.001 ) , poorer Hunt and Hess grade ( OR 2.50 ; 95 % CI 1.31 to 4.75 ; P=0.005 ) , need for permanent shunt ( OR 8.90 ; 95 % CI 1.80 to 44.15 ; P=0.008 ) , and larger size of the aneurysm ( OR 1 . 22 ; 95 % CI 1.02 to 1.45 ; P=0.032 ) independently predicted worsened clinical outcome regardless of the treatment modality . In MRI , superficial brain retraction deficits ( P < 0.001 ) and ischemic lesions in the territory of the ruptured aneurysm ( P=0.025 ) were more frequent in the surgical group . Kaplan-Meier analysis ( mean+/-SD follow-up 39+/-18 months ) revealed equal survival in both treatment groups . No late rebleedings have occurred . CONCLUSIONS One-year clinical and neuropsychological outcomes seem comparable after early surgical and endovascular treatment of ruptured intracranial aneurysms . The long-term efficacy of endovascular treatment in preventing rebleeding remains open .

surgical treatment

surgical

endovascular

Follow-up angiography

MRI

cerebral aneurysms .

recovery

died

recovery

neuropsychological test scores

. Symptomatic vasospasm

Hunt and Hess grade

need for permanent shunt

larger size of the aneurysm

clinical outcome

superficial brain retraction deficits

ischemic lesions

ruptured aneurysm

survival

late rebleedings

rebleeding

One hundred nine


Short- and long-term results after thrombolytic treatment of deep venous thrombosis . OBJECTIVES The goal of this study was to assess the short- and long-term efficacy of different thrombolytic therapy regimens in patients with leg or pelvic deep venous thrombosis ( DVT ) . BACKGROUND It is unclear whether locoregional or systemic thrombolysis is superior in treating acute leg DVT or even whether lysis is more effective than anticoagulation therapy in preventing postthrombotic syndrome . METHODS A total of 250 patients averaging 40 years of age with acute DVT were randomized into five groups to receive full heparinization ( 1,000 IU/h ) and compression treatment , with four groups also administered locoregional tissue plasminogen activator ( 20 mg/day ) or urokinase ( 100,000 IU/day ) or systemic streptokinase ( 3,000,000 IU daily ) or urokinase ( 5,000,000 IU daily ) . All groups then received anticoagulation and compression treatment for one year . Primary efficacy criteria included the change after one year in the number of closed vein segments and the occurrence of postthrombotic syndrome . RESULTS Systemic thrombolytic therapy significantly reduced the number of closed vein segments after 12 months in patients with acute DVT compared with conventional treatment ( p < 0.05 ) . Postthrombotic syndrome also occurred with less frequency in systemically treated patients versus controls ( p < 0.001 ) . High-dose thrombolysis led to better rates of complete recanalization after seven days ( p < 0.01 ) than locoregional lysis . However , 12 patients receiving thrombolysis ( 9 systemic , 3 local ) suffered major bleeding complications ; 9 patients on systemic treatment developed pulmonary emboli . CONCLUSIONS Systemic thrombolytic treatment for acute DVT achieved a significantly better short- and long-term clinical outcome than conventional heparin/anticoagulation therapy but at the expense of a serious increase in major bleeding and pulmonary emboli . Given the inherent risks for such serious complications , systemic thrombolysis , although effective , should be used selectively in limb-threatening thrombotic situations .

thrombolytic treatment

thrombolytic therapy

urokinase ( 100,000 IU/day )

urokinase ( 5,000,000 IU daily )

Systemic thrombolytic therapy

Systemic thrombolytic treatment

closed vein segments

closed vein segments

Postthrombotic syndrome

complete recanalization

major bleeding complications

pulmonary emboli


Tromethamine buffer modifies the depressant effect of permissive hypercapnia on myocardial contractility in patients with acute respiratory distress syndrome . In patients with acute respiratory distress syndrome ( ARDS ) , permissive hypercapnia is a strategy to decrease airway pressures to prevent ventilator-induced lung damage by lowering tidal volumes and tolerating higher arterial carbon dioxide tension . However , in experimental studies hypercapnia impairs myocardial contractility and hemodynamic function . We investigated the effect of short-term permissive hypercapnia on myocardial contractility and hemodynamics in patients with ARDS . We hypothesized that the administration of tromethamine ( THAM ) , a buffer which does not increase carbon dioxide production , would modify these changes . In 12 patients with ARDS , permissive hypercapnia was implemented for 2 h with a target Pa ( CO ( 2 ) ) of 80 mm Hg . Patients were randomized to have respiratory acidosis corrected by THAM ( pH-corrected group ) , or not corrected ( pH-uncorrected group ) . Hemodynamic responses were measured , and transesophageal echocardiography ( TEE ) was used to determine myocardial contractility . Permissive hypercapnia resulted in significant decreases in systemic vascular resistance ( SVR ) and increases in cardiac output ( Q ) . Myocardial contractility decreased in both groups but significantly less in the pH-corrected group ( approximately 10 % ) than in the pH-uncorrected group ( approximately 18 % , p < 0.05 ) . Mean arterial pressure decreased and mean pulmonary arterial pressure increased significantly only in the pH-uncorrected group . All values returned to baseline conditions 1 h after permissive hypercapnia was terminated . Our study demonstrates a reversible depression of myocardial contractility and hemodynamic alterations during rapid permissive hypercapnia which were attenuated by buffering with THAM . This may have applicability to the clinical strategy of permissive hypercapnia and allow the benefit of decreased airway pressures to be realized while minimizing the adverse hemodynamic effects of hypercapnic acidosis .

Tromethamine buffer

tromethamine ( THAM )

THAM

THAM

depressant effect

Hemodynamic responses

Mean arterial pressure

mean pulmonary arterial pressure

myocardial contractility

hemodynamic alterations

airway pressures

acute respiratory distress syndrome


Epidural fentanyl-bupivacaine compared with clonidine-bupivacaine for analgesia in labour . Alpha-adrenergic agonists produce pain relief through an opioid independent mechanism and may be alternatives to opioids for combination with local anaesthetics for analgesia during labour . We studied 41 pregnant women . Epidural block was performed with 75 microg clonidine ( n = 20 ) or 50 microg fentanyl ( n = 21 ) combined with 0.125 % bupivacaine ( 10 mL ) . Maternal vital parameters were measured . Analgesia was evaluated using a visual analogue scale ( VAS ) ; sedation was scored using a five-point scale . There were no differences in maternal vital parameters , fetal heart rate ( FHR ) or Apgar scores between the groups . Analgesia lasted longer in the bupivacaine-clonidine group ( 139.4 +/- 31 min ) compared with the bupivacaine-fentanyl group ( 127.9 +/- 48 min ) ( P = 0.42 ) . Additional analgesic requirement was more often in the fentanyl-bupivacaine group and total bupivacaine requirement was less in the clonidine-bupivacaine group ( 22.5 +/- 12.5 mg vs. 30.9 +/- 12.8 mg ) ( P = 0.04 ) . This small study confirms that this combination of bupivacaine and clonidine provides satisfactory analgesia for first-stage labour , and of longer duration than bupivacaine-fentanyl .

Epidural fentanyl-bupivacaine

clonidine-bupivacaine

clonidine

50 microg fentanyl

combined with 0.125 % bupivacaine

bupivacaine-clonidine

bupivacaine-fentanyl

fentanyl-bupivacaine

clonidine-bupivacaine

bupivacaine

clonidine

bupivacaine-fentanyl

pain relief

Maternal vital parameters

Analgesia

sedation

Additional analgesic requirement

satisfactory analgesia

duration

analgesia in labour

women


Randomized , placebo-controlled trial of oral phytonadione for excessive anticoagulation . STUDY OBJECTIVE To compare the efficacy of managing excessive anticoagulation in the absence of bleeding by either omitting warfarin therapy alone or administering oral phytonadione in addition to omitting warfarin therapy . DESIGN Randomized , double-blind , placebo-controlled study . SETTING Clinical pharmacy anticoagulation service in a group model health maintenance organization . SUBJECTS Thirty nonbleeding patients with international normalized ratios ( INRs ) ranging from 6.0-10.0 . INTERVENTIONS Patients were randomized to receive either a single oral dose of phytonadione 2.5 mg or placebo . Both groups omitted warfarin doses until the INR became less than or equal to 4.0 . MEASUREMENTS AND RESULTS The mean calculated time to reach an INR of 4.0 was significantly greater in the placebo than the phytonadione group ( 2.6 vs 1.4 days , p=0.006 ) . Overcorrection of anticoagulation was significantly more common in patients receiving phytonadione . Overt warfarin resistance was not observed in either group after reinitiating warfarin therapy . No major bleeding or thromboembolic complications occurred , and minor bleeding episodes were similar in both groups . CONCLUSION The addition of oral phytonadione 2.5 mg reduced the time to achieve an INR of 4.0 by approximately 1 day compared with omitting warfarin therapy alone . Adverse events did not differ between the two groups . Both strategies were effective in managing asymptomatic patients with INRs of 6.0-10.0 . Oral phytonadione may be most appropriate for patients at high risk for bleeding in whom the benefit of prompt INR reduction would outweigh the thromboembolic risk associated with INR overcorrection .

phytonadione

phytonadione

single oral dose of phytonadione 2.5 mg

placebo

excessive anticoagulation .

Overcorrection of anticoagulation

Overt warfarin resistance

bleeding

INR reduction

INR overcorrection .

Thirty


VLDL , apolipoproteins B , CIII , and E , and risk of recurrent coronary events in the Cholesterol and Recurrent Events ( CARE ) trial . BACKGROUND Plasma triglyceride concentration has been an inconsistent independent risk factor for coronary heart disease , perhaps because of the metabolic heterogeneity among VLDL particles , the main carriers of triglycerides in plasma . METHODS AND RESULTS We conducted a prospective , nested case-control study in the Cholesterol and Recurrent Events ( CARE ) trial , a randomized placebo-controlled trial of pravastatin in 4159 patients with myocardial infarction and average LDL concentrations at baseline ( 115 to 174 mg/dL , mean 139 mg/dL ) . Baseline concentrations of VLDL-apolipoprotein ( apo ) B ( the VLDL particle concentration ) , VLDL lipids , and apoCIII and apoE in VLDL+LDL and in HDL were compared in patients who had either a myocardial infarction or coronary death ( cases , n=418 ) with those in patients who did not have a cardiovascular event ( control subjects , n=370 ) in 5 years of follow-up . VLDL-cholesterol , VLDL-triglyceride , VLDL-apoB , apoCIII and apoE in VLDL+LDL and apoE in HDL were all interrelated , and each was a univariate predictor of subsequent coronary events . The significant independent predictors were VLDL-apoB ( relative risk [ RR ] 3.2 for highest to lowest quintiles , P : =0.04 ) , apoCIII in VLDL+LDL ( RR 2.3 , P : =0.04 ) , and apoE in HDL ( RR 1.8 , P : =0.02 ) . Plasma triglycerides , a univariate predictor of coronary events ( RR 1.6 , P : =0.03 ) , was not related to coronary events ( RR 1.3 , P : =0.6 ) when apoCIII in VLDL+LDL was included in the model , whereas apoCIII remained significant . Adjustment for LDL- and HDL-cholesterol did not affect these results . CONCLUSIONS The plasma concentrations of VLDL particles and apoCIII in VLDL and LDL are more specific measures of coronary heart disease risk than plasma triglycerides perhaps because their known metabolic properties link them more closely to atherosclerosis .

placebo-controlled

pravastatin

VLDL

apolipoproteins B

CIII

E

recurrent coronary events

VLDL-apolipoprotein

B ( the VLDL particle concentration )

VLDL lipids

apoCIII and apoE in VLDL+LDL and in HDL

VLDL-cholesterol , VLDL-triglyceride

VLDL-apoB

apoCIII and apoE in VLDL+LDL

apoE in HDL

VLDL-apoB

apoCIII in VLDL+LDL

apoE in HDL

Plasma triglycerides

coronary events

coronary events

apoCIII in VLDL+LDL

apoCIII

LDL- and HDL-cholesterol


An evaluation of chemical arthrodesis of the proximal interphalangeal joint in the horse by using monoiodoacetate . The use of monoiodoacetate ( MIA ) for arthrodesis of the proximal interphalangeal joint ( PIJ ) and the effect of exercise on the degree of fusion were investigated . Eight horses received 3 injections ( Weeks 0 , 3 , 6 ) of MIA ( 2 mL ; 60 mg/mL ) into the right or left front PIJ . Peri-operatively , the horses received phenylbutazone , butorphanol , and abaxial sesamoidean nerve blocks to relieve pain . During the study , the horses were monitored for general health , lameness , and swelling around the injection area . Radiographs were taken biweekly to evaluate bony fusion . Horses were randomly divided into non-exercised and exercised groups . Exercise consisted of 20 minutes of trotting on a treadmill ( 4 m/s ) , 3 days per week for 13 weeks . The horses were euthanized at 24 weeks . Slab sections of the PIJ were evaluated grossly and radiographically for bony fusion . Histologic examinations were performed to evaluate articular cartilage . Three horses were excluded from the study after developing soft tissue necrosis around the injection site , septic arthritis , and necrotic tendinitis . The remaining horses remained healthy , developed a grade 1 to 4 lameness with minimal to severe swelling in the PIJ region . All 5 horses showed radiographic evidence of bony fusion , however , no fusion was present when injected joints were examined on postmortem examination . Histologic examination revealed thinning of the cartilage , diffuse necrosis of chondrocytes , with the calcified zone intact . Subjectively , exercise did not influence the degree of cartilage destruction . Based on this study , chemical arthrodesis can not be advocated in clinical cases because of the high complication rate and lack of bony fusion .

monoiodoacetate

monoiodoacetate ( MIA )

MIA

phenylbutazone

butorphanol

abaxial sesamoidean

nerve blocks

Exercise

chemical arthrodesis

bony fusion

thinning of the cartilage

diffuse necrosis of chondrocytes

degree of cartilage destruction

complication rate

bony fusion

Eight

horses


Randomized trial of fenretinide in superficial bladder cancer using DNA flow cytometry as an intermediate end point . Retinoids have shown a potential activity in preventing tumor recurrence in superficial bladder cancer . We assessed the activity of the synthetic retinoid fenretinide in superficial bladder cancer using DNA flow cytometry and conventional cytology as surrogate biomarkers . A total of 99 subjects with resected superficial bladder cancer ( pTa , pT1 ) were randomized to either fenretinide ( 200 mg day p.o . for 24 months ) or no intervention . Cystoscopy and bladder washing for DNA flow cytometry end points ( proportion of DNA aneuploid histograms , hyperdiploid fraction , and percentage of apoptotic cells ) and proportion of abnormal cytological examinations were repeated every 4 months for up to 36 months . The primary study end point was the proportion of DNA aneuploid histograms after 12 months . This figure was 48.9 % in the fenretinide arm and 41.9 % in the control arm ( odds ratio , 1.16 ; 95 % confidence interval , 0.44-3.07 ) . There was no difference in any other response biomarker between the two groups up to 36 months , nor was any biomarker able to predict recurrence risk . Recurrence-free survival was comparable between the arms ( 27 events in the fenretinide arm versus 21 in the control arm ; P = 0.36 ) . Twelve subjects in the fenretinide arm complained of diminished dark adaptability , and nine subjects in the fenretinide arm versus one control subject had mild dermatological alterations . We conclude that fenretinide showed a lack of effect on the DNA content distribution and the morphology of urothelial cells obtained in serial bladder washings . Recurrence-free survival was comparable between groups . Because our data are hampered by the lack of predictivity of the selected biomarkers , additional studies are necessary to assess the activity of fenretinide in preventing bladder cancer .

fenretinide

synthetic retinoid fenretinide

fenretinide ( 200 mg day p.o .

no intervention

fenretinide

abnormal cytological examinations

proportion of DNA aneuploid histograms

response biomarker

Recurrence-free survival

dark adaptability

mild dermatological alterations

content distribution

morphology of urothelial cells

Recurrence-free survival

superficial bladder cancer


Effect of systemic nitric oxide synthase inhibition on postexercise hypotension in humans . An acute bout of aerobic exercise results in a reduced blood pressure that lasts several hours . Animal studies suggest this response is mediated by increased production of nitric oxide . We tested the extent to which systemic nitric oxide synthase inhibition [ N ( G ) -monomethyl-L-arginine ( L-NMMA ) ] can reverse the drop in blood pressure that occurs after exercise in humans . Eight healthy subjects underwent parallel experiments on 2 separate days . The order of the experiments was randomized between sham ( 60 min of seated upright rest ) and exercise ( 60 min of upright cycling at 60 % peak aerobic capacity ) . After both sham and exercise , subjects received , in sequence , systemic alpha-adrenergic blockade ( phentolamine ) and L-NMMA . Phentolamine was given first to isolate the contribution of nitric oxide to postexercise hypotension by preventing reflex changes in sympathetic tone that result from systemic nitric oxide synthase inhibition and to control for alterations in resting sympathetic activity after exercise . During each condition , systemic and regional hemodynamics were measured . Throughout the study , arterial pressure and vascular resistances remained lower postexercise vs. postsham despite nitric oxide synthase inhibition ( e.g. , mean arterial pressure after L-NMMA was 108.0+/-2.4 mmHg postsham vs. 102.1+/-3.3 mmHg postexercise ; P < 0.05 ) . Thus it does not appear that postexercise hypotension is dependent on increased production of nitric oxide in humans .

nitric oxide synthase

( 60 min of seated upright rest

blood pressure

blood pressure

systemic and regional hemodynamics

nitric oxide synthase

mean arterial pressure after L-NMMA

postexercise hypotension

production of nitric oxide

postexercise hypotension

Eight


Depressive mood symptoms associated with ovarian suppression . OBJECTIVE To determine if sertraline is helpful in the management of depressive symptoms associated with ovarian suppression during GnRH agonist therapy as compared with a placebo-controlled group . DESIGN Double-blind placebo-controlled prospective study design . SETTING An obstetrics/gynecological office specializing in infertility in an academic environment . PATIENT ( S ) Premenstrual women with laparoscopically diagnosed endometriosis who required GnRH agonist therapy for treatment and did not have significant depressive or premenstrual mood symptoms at baseline . INTERVENTION ( S ) Participants were randomly assigned to either the sertraline treatment group or to the placebo group for the 3-month duration of the GnRH agonist therapy . MAIN OUTCOME MEASURE ( S ) The 21-item Hamilton Rating Scale for Depression ( HRSD ) , which is an instrument designed to assess depressive symptomatology . RESULT ( S ) A Hotellings T ( 2 ) test for repeated measure analysis indicated a statistically significant ( P < .05 ) between-group difference across time for the HRSD ( T ( 2 ) = 13.3 ; F [ 3 , 28 ] = 4.1 ; P=.02 ) with the sertraline treatment group manifesting significantly fewer depressive symptoms than the control group . CONCLUSION ( S ) The results indicate that sertraline is an effective option in the management of depressive mood symptoms associated with ovarian suppression during GnRH agonist therapy .

sertraline

GnRH agonist therapy

placebo-controlled

GnRH agonist therapy

sertraline treatment

GnRH agonist therapy .

sertraline

sertraline

GnRH agonist therapy .

depressive symptoms

women

required GnRH agonist therapy


Update on tamoxifen to prevent breast cancer . The Italian Tamoxifen Prevention Study .

tamoxifen

Tamoxifen

breast cancer

Italian Tamoxifen Prevention Study


Efficacy and safety of recombinant human nerve growth factor in patients with diabetic polyneuropathy : A randomized controlled trial . rhNGF Clinical Investigator Group . CONTEXT Nerve growth factor is a neurotrophic factor that promotes the survival of small fiber sensory neurons and sympathetic neurons in the peripheral nervous system . Recombinant human nerve growth factor ( rhNGF ) has demonstrated efficacy as treatment for peripheral neuropathy in experimental models and phase 2 clinical trials . OBJECTIVE To evaluate the efficacy and safety of a 12-month regimen of rhNGF in patients with diabetic polyneuropathy . DESIGN Randomized , double-blind , placebo-controlled phase 3 trial conducted from July 1997 through May 1999 . SETTING Eighty-four outpatient centers throughout the United States . PATIENTS A total of 1019 men and women aged 18 to 74 years with either type 1 or type 2 diabetes and a sensory polyneuropathy attributable to diabetes . INTERVENTIONS Patients were randomly assigned to receive either rhNGF , 0.1 microg/kg ( n = 504 ) , or placebo ( n = 515 ) by subcutaneous injection 3 times per week for 48 weeks . Patients were assessed at baseline , 12 weeks , 24 weeks , and 48 weeks . MAIN OUTCOME MEASURES The primary outcome measure was a change in neuropathy between baseline and week 48 , demonstrated by the Neuropathy Impairment Score for the Lower Limbs , compared between the 2 groups . Secondary outcome measures included quantitative sensory tests using the CASE IV System , the Neuropathy Symptom and Change questionnaire , the Patient Benefit Questionnaire ( PBQ ) , and a global symptom assessment , as well as nerve conduction studies and occurrence of new plantar foot ulcers . Patients also were evaluated for presence of adverse events . RESULTS Among patients who received rhNGF , 418 ( 83 % ) completed the regimen compared with 461 ( 90 % ) who received placebo . Administration of rhNGF was safe , with few adverse events attributed to treatment apart from injection site pain/hyperalgesia and other pain syndromes . However , neither the primary end point ( P =.25 ) nor most of the secondary end points demonstrated a significant benefit of rhNGF . Exceptions were the global symptom assessment ( P =.03 ) and 2 of 32 comparisons within the PBQ , which showed a modest but significant benefit of rhNGF ( P =.05 for severity of pain in the legs and P =.003 for 6-month symptoms in the feet and legs ) . CONCLUSION Unlike previous phase 2 trials , this phase 3 clinical trial failed to demonstrate a significant beneficial effect of rhNGF on diabetic polyneuropathy . JAMA . 2000 ; 284:2215-2221 .

recombinant human nerve growth factor

placebo-controlled

rhNGF

placebo

rhNGF

placebo

rhNGF

rhNGF

rhNGF

Efficacy and safety

efficacy and safety

adverse events .

adverse events

global symptom assessment

diabetic polyneuropathy

diabetic polyneuropathy

men

women

18 to 74

type 1 or type 2 diabetes

sensory polyneuropathy

diabetes


Commentary on " cytoreduction nephrectomy in metastatic renal cancer : the results of Southwest Oncology Group Trial 8949 " .

cytoreduction nephrectomy

Southwest Oncology Group Trial


Comparison of alfentanil , fentanyl and sufentanil for total intravenous anaesthesia with propofol in patients undergoing coronary artery bypass surgery . We have studied the pharmacokinetics and pharmacodynamics of alfentanil , fentanyl and sufentanil together with propofol in patients undergoing coronary artery bypass graft surgery ( CABG ) . Sixty patients ( age 40-73 yr , 56 male ) were assigned randomly to receive alfentanil , fentanyl or sufentanil and propofol . Plasma concentrations of these drugs and times for the plasma concentration to decrease by 50 % ( t50 ) and 80 % ( t80 ) after cessation of the infusion were determined . Times were recorded to awakening and tracheal extubation . Total dose and plasma concentrations of propofol were similar in all groups . Mean total doses of alfentanil , fentanyl and sufentanil were 443 , 45 and 4.4 micrograms kg-1 , respectively . Time to awakening did not differ significantly . In patients receiving fentanyl , the trachea was extubated on average 2 h later than in those receiving sufentanil and 3 h later than in those receiving alfentanil ( P < 0.05 ) . The t80 of fentanyl was longer ( P < 0.05 ) than that of alfentanil or sufentanil , and there was a linear correlation between the t80 of the opioid and the time to tracheal extubation ( r = 0.51 ; P < 0.01 ) . However , the t50 values for these opioids were similar and did not correlate with recovery time . In conclusion , patients undergoing CABG and who were anaesthetized with fentanyl and propofol needed mechanical ventilatory support for a significantly longer time than those receiving alfentanil or sufentanil and propofol . On the basis of the interindividual variation observed , the time to tracheal extubation was most predictable in patients receiving alfentanil and most variable in patients receiving fentanyl , a finding which may be important if the patients are transferred to a step-down unit on the evening of the operation .

alfentanil

fentanyl

sufentanil

propofol

alfentanil

fentanyl

sufentanil

propofol

alfentanil

fentanyl

sufentanil

propofol

alfentanil

fentanyl

sufentanil

fentanyl

sufentanil

alfentanil

fentanyl

alfentanil

sufentanil

fentanyl

propofol

alfentanil

sufentanil

propofol

alfentanil

fentanyl

pharmacokinetics and pharmacodynamics

Plasma concentrations

Total dose and plasma concentrations

Mean total doses

Time to awakening

trachea

time to tracheal extubation

t50 values

recovery time

mechanical ventilatory support

time to tracheal extubation


Magnetic resonance angiography for monitoring prophylactic endoscopic treatment of high risk esophageal varices . BACKGROUND AND STUDY AIMS Endoscopic injection sclerotherapy ( EIS ) and endoscopic variceal ligation ( EVL ) are used worldwide as the treatment for esophageal varices . We evaluated portal hemodynamics using magnetic resonance angiography ( MRA ) in these two forms of treatment . PATIENTS AND METHODS The study was carried out in 50 cirrhotic patients . MRA was performed to identify the hepatofugal supply vein selectively for esophageal varices . Those who showed a positive MR angiogram for the supply vein were randomly allocated to one of two groups , using the sealed envelope method , and underwent either EIS or EVL . On the other hand , those with a negative angiogram received only EVL . EIS was done to embolize esophageal varices as well as their feeders by intravariceal injection of sclerosant under fluoroscopic guidance . RESULTS A positive MR angiogram of the hepatofugal left gastric vein as the supply vein was observed in 41 patients . Nine patients showed negative MRA results . Among those with positive angiograms , the rate of eradication of the left gastric vein was higher in the EIS-treated group than in the EVL treated group ( 50 % vs. 8.6 % ) . After either treatment , the recurrence-free rate for high risk esophageal varices was higher in patients with complete eradication of the left gastric vein than in those without ( 88 % vs. 35 % ) . In patients with negative angiogram results , who only underwent EVL , high risk esophageal varices did not reappear over a long period . CONCLUSION MRA is useful for evaluating portal hemodynamics . With the aim of avoiding recurrence of esophageal varices , EIS was suitable for patients who had a hepatofugal supply vein for the varices because recurrence could be prevented by embolization of the supply vein . EVL may be expected to be efficacious in patients where no image of a hepatofugal supply vein is found on MRA .

endoscopic variceal ligation ( EVL )

EIS

EVL

EIS

risk esophageal varices

cirrhotic

esophageal varices .

Nine

negative MRA results .


Probiotics in the management of atopic eczema . BACKGROUND Over the last two decades the incidence of allergic diseases has increased in industrialized countries , and consequently new approaches have to be explored . OBJECTIVE The potential of probiotics to control allergic inflammation at an early age was assessed in a randomized double-blind placebo-controlled study . METHODS A total of 27 infants , mean age 4.6 months , who manifested atopic eczema during exclusive breast-feeding and who have had no exposure to any infant or substitute formula were weaned to probiotic-supplemented , Bifidobacterium lactis Bb-12 or Lactobacillus strain GG ( ATCC 53103 ) , extensively hydrolysed whey formulas or to the same formula without probiotics . The extent and severity of atopic eczema , the growth and nutrition of infants , and concentrations of circulating cytokines/chemokines and soluble cell surface adhesion molecules in serum and methyl-histamine and eosinophilic protein X in urine were determined . RESULTS The SCORAD score reflecting the extent and severity of atopic eczema was 16 ( 7-25 ) during breast-feeding , median ( interquartile range ) . After 2 months , a significant improvement in skin condition occurred in patients given probiotic-supplemented formulas , as compared to the unsupplemented group ; chi ( 2 ) = 12.27 , P = 0.002 . SCORAD decreased in the Bifidobacterium lactis Bb-12 group to 0 ( 0-3.8 ) , and in the Lactobacillus GG group to 1 ( 0.1-8.7 ) , vs unsupplemented 13.4 ( 4.5-18.2 ) , median ( interquartile range ) , in parallel with a reduction in the concentration of soluble CD4 in serum and eosinophilic protein X in urine . CONCLUSION The results provide the first clinical demonstration of specific probiotic strains modifying the changes related to allergic inflammation . The data further indicate that probiotics may counteract inflammatory responses beyond the intestinal milieu . The combined effects of these probiotic strains will guide infants through the weaning period , when sensitization to newly encountered antigens is initiated . The probiotic approach may thus offer a new direction in the search for future foods for allergy treatment and prevention strategies .

Probiotics

probiotic-supplemented

Bifidobacterium lactis Bb-12

same formula without probiotics

allergic inflammation

SCORAD score

extent and severity of atopic eczema

skin condition

SCORAD

allergic inflammation

inflammatory responses

atopic eczema .

allergic inflammation at an early age


[ New therapeutic approaches in irritable bowel syndrome ] .

New therapeutic approaches

irritable bowel syndrome


Calcium and fibre supplementation in prevention of colorectal adenoma recurrence : a randomised intervention trial . European Cancer Prevention Organisation Study Group . BACKGROUND Some epidemiological studies have suggested that high dietary intake of calcium and fibre reduces colorectal carcinogenesis . Available data are not sufficient to serve as a basis for firm dietary advice . We undertook a multicentre randomised trial to test the effect of diet supplementation with calcium and fibre on adenoma recurrence . METHODS We randomly assigned 665 patients with a history of colorectal adenomas to three treatment groups , in a parallel design : calcium gluconolactate and carbonate ( 2 g elemental calcium daily ) , fibre ( 3.5 g ispaghula husk ) , or placebo . Participants had colonoscopy after 3 years of follow-up . The primary endpoint was adenoma recurrence . Analyses were by intention to treat . FINDINGS 23 patients died , 15 were lost to follow-up , 45 refused repeat colonoscopy , and five developed severe contraindications to colonoscopy . Among the 552 participants who completed the follow-up examination , 94 stopped treatment early . At least one adenoma developed in 28 ( 15.9 % ) of 176 patients in the calcium group , 58 ( 29.3 % ) of 198 in the fibre group , and 36 ( 20.2 % ) of 178 in the placebo group . The adjusted odds ratio for recurrence was 0.66 ( 95 % CI 0.38-1.17 ; p=0.16 ) for calcium treatment and 1.67 ( 1.01-2.76 , p=0.042 ) for the fibre treatment . The odds ratio associated with the fibre treatment was significantly higher in participants with baseline dietary calcium intake above the median than in those with intake below the median ( interaction test , p=0.028 ) INTERPRETATION Supplementation with fibre as ispaghula husk may have adverse effects on colorectal adenoma recurrence , especially in patients with high dietary calcium intake . Calcium supplementation was associated with a modest but not significant reduction in the risk of adenoma recurrence .

Calcium and fibre supplementation

calcium

fibre

fibre ( 3.5 g ispaghula husk )

placebo

colorectal adenoma recurrence

severe contraindications to colonoscopy

adenoma

recurrence

adenoma recurrence

colorectal adenomas

five

high dietary calcium intake


Effects of nicotine on regional cerebral glucose metabolism in awake resting tobacco smokers . Eleven healthy tobacco smoking adult male volunteers of mixed race were tobacco abstinent overnight for this study . In each subject , positron emission tomographic images of regional cerebral metabolism of glucose with [ 18F ] fluorodeoxyglucose were obtained in two conditions in the morning on different days : about 3min after approximately 1-2mg of nasal nicotine spray and after an equivalent volume of an active placebo spray of oleoresin of pepper in a random counterbalanced design . A Siemens/CTI 931/08-12 scanner with the capability of 15 horizontal brain slices was used . The images were further converted into a standard uniform brain format in which the mean data of all 11 subjects were obtained . Images were analysed in stereotactic coordinates using pixel-wise t statistics and a smoothed Gaussian model . Peak plasma nicotine levels varied three-fold and the areas under the curve ( 0-30min ) varied seven-fold among the individual subjects . Nicotine caused a small overall reduction in global cerebral metabolism of glucose but , when the data were normalized , several brain regions showed relative increases in activity . Cerebral structures specifically activated by nicotine ( nicotine minus pepper , Z score > 4.0 ) included : left inferior frontal gyrus , left posterior cingulate gyrus and right thalamus . The visual cortex , including the right and left cuneus and left lateral occipito-temporal gyrus fusiformis , also showed an increase in regional cerebral metabolism of glucose with Z scores > 3 . 6 . Structures with a decrease in regional cerebral metabolism of glucose ( pepper minus nicotine ) were the left insula and right inferior occipital gyrus , with Z scores > 3.5 . Especially important is the fact that the thalamus is activated by nicotine . This is consistent with the high density of nicotinic cholinoceptors in that brain region . However , not all brain regions affected by nicotine are known to have many nicotinic cholinoceptors . The results are discussed in relation to the cognitive effects of nicotine .

nicotine

tobacco abstinent

1-2mg of nasal nicotine spray

nicotine

Nicotine

nicotine

nicotine

nicotine

regional cerebral glucose metabolism

positron emission tomographic images

cerebral metabolism of glucose

Peak plasma nicotine levels

global cerebral metabolism of glucose

regional cerebral metabolism of glucose

nicotine


Effect of systemic penicillin on pain in untreated irreversible pulpitis . OBJECTIVE The purpose of this prospective , randomized , double-blind study was to determine the effect of penicillin on pain in untreated teeth diagnosed with irreversible pulpitis . STUDY DESIGN Forty emergency patients participated , and each had a clinical diagnosis of an irreversible pulpitis . Patients randomly received a 7-day oral dose ( 28 capsules , 500 mg each , to be taken every 6 hours ) of either penicillin or a placebo control in a double-blind manner . No endodontic treatment was performed . Each patient also received ibuprofen ; acetaminophen with codeine ( 30 mg ) ; and a 7-day diary to record pain , percussion pain , and number and type of pain medication taken . RESULTS The administration of penicillin did not significantly ( P > .05 ) reduce pain , percussion pain , or the number of analgesic medications taken by patients with untreated irreversible pulpitis . The majority of patients with untreated irreversible pulpitis had significant pain and required analgesics to manage this pain . CONCLUSION Penicillin should not be prescribed for untreated irreversible pulpitis because penicillin is ineffective for pain relief .

systemic penicillin

penicillin

penicillin

placebo

ibuprofen

acetaminophen with codeine

diary to record pain

penicillin

7-day diary to record pain

percussion pain

number and type of pain medication

pain

percussion pain

number of analgesic medications

significant pain

pulpitis

Forty


Percutaneous tracheostomy in critically ill patients : a prospective , randomized comparison of two techniques . OBJECTIVE To prospectively compare two commonly used methods for percutaneous dilational tracheostomy ( PDT ) in critically ill patients . DESIGN Prospective , randomized , clinical trial . SETTING Trauma and general intensive care units of a university tertiary teaching hospital , which is also a level 1 trauma center . PATIENTS One hundred critically ill patients with an indication for PDT . INTERVENTIONS PDT with the Ciaglia technique using the Ciaglia PDT introducer set and the Griggs technique using a Griggs PDT kit and guidewire dilating forceps . MEASUREMENTS AND MAIN RESULTS Surgical time , difficulties , and surgical and anesthesia complications were measured at 0-2 hrs , 24 hrs , and 7 days postprocedure . Groups were well matched , and there were no differences between the two methods in surgical time or in anesthesia complications . Major bleeding complications were 4.4 times more frequent with the Griggs PDT kit . With the Ciaglia PDT kit , both intraoperative and at 2 and 24 hrs , surgical complications were less common ( p = .023 ) and the procedure was more often completed without expert assistance ( p = .013 ) . Tracheostomy bleeding was not associated with either anticoagulant therapy or an abnormal clotting profile . Multivariate analysis identified the predictors of PDT complications as the Griggs PDT kit ( p = .027 ) and the Acute Physiology and Chronic Health Evaluation ( APACHE ) II score ( p = .041 ) . The significant predictors of time required to complete PDT were the APACHE II score ( p = .041 ) , a less experienced operator ( p = .0001 ) , and a female patient ( p = .013 ) . CONCLUSIONS Patients experiencing PDT with the Ciaglia PDT kit had a lower surgical complication rate ( 2 % vs. 25 % ) , less operative and postoperative bleeding , and less overall technical difficulties than did patients undergoing PDT with the Griggs PDT kit . Ciaglia PDT is , therefore , the preferred technique for percutaneous tracheostomy in critically ill patients .

PDT

Griggs technique using a Griggs PDT kit

guidewire dilating forceps

Griggs PDT

Ciaglia PDT

PDT

PDT

Griggs PDT

Ciaglia PDT

surgical time

anesthesia complications

Major bleeding complications

surgical complications

Tracheostomy bleeding

APACHE II score

lower surgical complication rate

overall technical difficulties

PDT

percutaneous tracheostomy


Somatostatin and ranitidine in the treatment of non-variceal upper gastrointestinal bleeding : a prospective , randomized , double-blind , controlled study . BACKGROUND/AIMS The aim of this study was to compare the efficacy of somatostatin vs. ranitidine in controlling acute non-variceal gastrointestinal bleeding . METHODOLOGY A total of 48 patients with acute upper gastrointestinal bleeding due to duodenal or gastric ulcer were divided into 2 groups . Group I consisted of 15 patients with Forrest IB and Group II consisted of 30 patients with Forrest II . Two regimens were randomly allocated to all patients within half an hour after the endoscopic procedure : 1 ) somatostatin-UCB 250 mcg i.v . bolus followed by continuous i.v . infusion at a rate of 6 mg/d for 72 h , or 2 ) ranitidine 300 mg/d by continuous i.v . infusion for 72 h. RESULTS In Group I , although mean blood transfusion requirements ( no . of units ) were lower in patients treated with somatostatin than in those treated with ranitidine , this was not statistically significant ( mean +/- SD : 2.56 +/- 3.05 vs. 5.17 +/- 4.96 , respectively ; P > 0.05 ) ; the time of bleeding stop was shorter in the somatostatin group than in the ranitidine group ( mean +/- SD : 3.24 +/- 2.45 vs. 11.25 +/- 11.63 , respectively ; P = 0.0383 ) . The rebleeding and the mortality rates did not differ between the treatment groups in both Group I and Group II . CONCLUSIONS Somatostatin is more effective than ranitidine in controlling acute non-variceal gastrointestinal bleeding in patients with Forrest IB bleeding activity . Somatostatin has no additional benefit in those with Forrest II bleeding activity .

Somatostatin and ranitidine

somatostatin vs. ranitidine

somatostatin-UCB

ranitidine

somatostatin

ranitidine

somatostatin

Somatostatin

Somatostatin

efficacy

blood transfusion requirements

time of bleeding stop

rebleeding

mortality rates

effective

additional benefit

duodenal or gastric ulcer


Perioperative enteral nutrition and quality of life of severely malnourished head and neck cancer patients : a randomized clinical trial . BACKGROUND AND AIMS This study evaluated the use of perioperative nutritional support on Quality of Life ( QOL ) in malnourished head and neck cancer patients undergoing surgery . METHODS 49 Malnourished ( weight loss > 10 % ) head and neck cancer patients who were included in a nutrition intervention trial were randomized to receive either no preoperative and standard postoperative tube-feeding ( group I ) , standard preoperative and postoperative tube-feeding ( group II ) or arginine-supplemented preoperative and postoperative tube-feeding ( group III ) . Of these patients , 31 completed a full QOL assessment on the first day of preoperative nutritional support , one day before surgery , and 6 months after surgery . Both a disease-specific ( EORTC QLQ-C30 ) and a generic questionnaire ( COOP-WONCA ) were used . One way analysis of variance ( ANOVA ) and the Kruskal-Wallis test were applied for testing differences in scores between groups . RESULTS Between baseline and the day before surgery , both preoperatively fed groups revealed a positive change for the dimensions physical and emotional functioning and dyspnea ( with significance in group II , P=0.050,0.031,0.045 respectively ) . Group III showed a negative change in appetite ( P=0.049 ) . Between baseline and 6 months after surgery , there were no differences between group I and both pre-fed groups . There were no differences in favour of group III compared to group II . CONCLUSION Enteral nutrition improves QOL of severely malnourished head and neck cancer patients in the period preceding surgery . No benefit of preoperative enteral feeding on QOL could be demonstrated 6 months after surgery .

perioperative nutritional support

arginine-supplemented preoperative

postoperative tube-feeding

preoperatively fed

both pre-fed groups

Enteral nutrition

preoperative enteral feeding

quality of life

Quality of Life ( QOL )

QOL assessment

physical and emotional functioning

dyspnea

appetite

QOL

QOL

head and neck cancer

head and neck cancer

head and neck cancer


Chemoprevention of gastric dysplasia : randomized trial of antioxidant supplements and anti-helicobacter pylori therapy . BACKGROUND Previous research has identified a high risk of gastric carcinoma as well as a high prevalence of cancer precursor lesions in rural populations living in the province of Nariño , Colombia , in the Andes Mountains . METHODS A randomized , controlled chemoprevention trial was conducted in subjects with confirmed histologic diagnoses of multifocal nonmetaplastic atrophy and/or intestinal metaplasia , two precancerous lesions . Individuals were assigned to receive anti-Helicobacter pylori triple therapy and/or dietary supplementation with ascorbic acid , beta-carotene , or their corresponding placebos . Gastric biopsy specimens taken at baseline were compared with those taken at 72 months . Relative risks of progression , no change , and regression from multifocal nonmetaplastic atrophy and intestinal metaplasia were analyzed with multivariate polytomous logistic regression models to estimate treatment effects . All statistical tests were two-sided . RESULTS All three basic interventions resulted in statistically significant increases in the rates of regression : Relative risks were 4.8 ( 95 % confidence interval [ CI ] = 1.6-14.2 ) for anti-H. pylori treatment , 5 . 1 ( 95 % CI = 1.7-15.0 ) for beta-carotene treatment , and 5.0 ( 95 % CI = 1.7-14.4 ) for ascorbic acid treatment in subjects with atrophy . Corresponding relative risks of regression in subjects with intestinal metaplasia were 3.1 ( 95 % CI = 1.0-9.3 ) , 3.4 ( 95 % CI = 1.1-9.8 ) , and 3.3 ( 95 % CI = 1.1-9.5 ) . Combinations of treatments did not statistically significantly increase the regression rates . Curing the H. pylori infection ( which occurred in 74 % of the treated subjects ) produced a marked and statistically significant increase in the rate of regression of the precursor lesions ( relative risks = 8.7 [ 95 % CI = 2.7-28.2 ] for subjects with atrophy and 5.4 [ 95 % CI = 1.7-17.6 ] for subjects with intestinal metaplasia ) . CONCLUSIONS In the very high-risk population studied , effective anti-H. pylori treatment and dietary supplementation with antioxidant micronutrients may interfere with the precancerous process , mostly by increasing the rate of regression of cancer precursor lesions , and may be an effective strategy to prevent gastric carcinoma .

for subjects with atrophy

subjects with intestinal metaplasia

the very high-risk population


Measurement of peptidase activity and evaluation of effectiveness of administration of minocycline for treatment of dogs with periodontitis . OBJECTIVE To determine clinical , enzymatic , and microbiologic effects of controlled-release localized administration of minocycline on dogs with periodontitis . ANIMALS Five adult Beagles with periodontitis . PROCEDURE After tooth scaling and root planing , 2 treatment , 1 placebo , and 1 control site were selected for each dog . Treatment sites ( n = 10 ) received a periodontal formulation of minocycline hydrochloride , placebo sites ( 5 ) received ointment without minocycline , and control sites ( 5 ) did not receive ointment . Treatments were administered 4 times at weekly intervals . Peptidase activity and clinical and microbiologic effects were evaluated and compared among sites for 17 weeks . RESULTS Bleeding of the gums on probing ( BOP ) and pocket depth ( PD ) improved at the treatment site and were maintained for 13 weeks after treatment . However , BOP and PD in placebo and control sites increased from weeks 9 to 17 Peptidase activity in the periodontal pocket decreased noticeably from week 1 to 17 , compared with baseline values for the treatment site . However , peptidase activity for placebo and control sites increased and were above baseline values on week 9 and week 13 , respectively . Total bacterial counts decreased by 90 % for treatment sites and remained at that value for 13 weeks . However , for placebo and control sites , bacterial counts increased and reached the baseline value on week 17 . CONCLUSIONS AND CLINICAL RELEVANCE Increased peptidase activity is correlated with the progression of periodontitis in dogs . Treatment with minocycline , using a localized delivery system , was effective in dogs for at least 13 weeks after cessation of drug administration .

minocycline

minocycline

placebo

received ointment without minocycline

minocycline

peptidase activity

clinical , enzymatic

microbiologic effects

BOP

PD

Peptidase activity

peptidase activity

Total bacterial counts

bacterial counts

Increased peptidase activity

dogs

periodontitis

dogs

periodontitis

Five

adult

Beagles

periodontitis

periodontitis

dogs


Effect of secretin on children with autism : a randomized controlled trial . To determine the effect of intravenous porcine secretin on autistic behaviours in children aged 2 to 7 years , the effects of secretin on ( 1 ) performance on a standardized language measure , and ( 2 ) autistic behaviours , as rated by parents and child development professionals was examined . Employing a randomized , double-blind , placebo-controlled design , 95 participants were assigned to one of two groups and administered a single dose of either secretin or placebo . A follow-up assessment was conducted 3 weeks after the injection . No significant differences in language or autistic behaviour measures were observed at the 3-week follow-up between the groups . Also , there was no significant difference in the proportion of individuals who improved by > or = 6 points on the language measure at follow-up . This study showed no significant effects of secretin on children with autism . Our results are consistent with a systematic review of randomized controlled trials evaluating the effect of secretin in children with autism .

secretin

intravenous porcine secretin

secretin

placebo

language or autistic behaviour measures

> or = 6 points on the language measure

children with autism

children aged 2 to 7 years

autism

autism


A randomized trial in simultaneous pancreas-kidney transplantation : portal versus systemic venous drainage of the pancreas allograft .

pancreas-kidney transplantation

systemic venous drainage


Cardiovascular effects of tamoxifen in women with and without heart disease : breast cancer prevention trial . National Surgical Adjuvant Breast and Bowel Project Breast Cancer Prevention Trial Investigators . BACKGROUND The overall effect of prophylactic tamoxifen in women depends on the balance between the effects of the drug , which include preventing breast cancer and altering cardiovascular risk . In a recent clinical trial , postmenopausal estrogen-progestin therapy was shown to increase the risk of early cardiovascular events among women with a history of coronary heart disease ( CHD ) . The cardiovascular effects of tamoxifen in women with and without CHD are not known . The National Surgical Adjuvant Breast and Bowel Project Breast Cancer Prevention Trial ( BCPT ) is the only clinical trial that provides data to assess the cardiovascular effects of tamoxifen in women with and without CHD . METHODS A total of 13 388 women at increased risk for breast cancer were randomly assigned in the BCPT to receive either tamoxifen ( 20 mg/day ) or placebo . Cardiovascular follow-up was available for 13 194 women , 1048 of whom had prior clinical CHD . Fatal and nonfatal myocardial infarction , unstable angina , and severe angina were tabulated ( mean follow-up : 49 months ) . All statistical tests were two-sided . RESULTS Cardiovascular event rates were not statistically significantly different between women assigned to receive tamoxifen and those assigned to receive placebo , independent of pre-existing CHD . Among women without CHD ( 6074 on tamoxifen versus 6072 on placebo ) , risk ratios ( 95 % confidence intervals [ CIs ] ) for tamoxifen users were 1.75 ( 0.44 to 8.13 ) for fatal myocardial infarction , 1.11 ( 0.55 to 2.28 ) for nonfatal myocardial infarction , 0.69 ( 0.29 to 1.57 ) for unstable angina , and 0.83 ( 0.32 to 2.10 ) for severe angina . In women with CHD ( 516 on tamoxifen versus 532 on placebo ) , risk ratios ( 95 % CIs ) for tamoxifen users were 0.00 ( 0 to 1.58 ) for fatal myocardial infarction , 1.25 ( 0.32 to 5.18 ) for nonfatal myocardial infarction , 2.26 ( 0.87 to 6.55 ) for unstable angina , and 1.39 ( 0.23 to 9.47 ) for severe angina . There was no evidence that the lack of association between tamoxifen and cardiovascular events was related to an early increase in risk that may have been offset by a late decrease in risk . CONCLUSION When used for breast cancer prevention in women with or without heart disease , tamoxifen is not associated with beneficial or adverse cardiovascular effects .

tamoxifen

tamoxifen ( 20 mg/day )

placebo

preventing breast cancer

cardiovascular risk

early cardiovascular events

cardiovascular effects

cardiovascular effects

unstable angina , and severe angina

Cardiovascular event rates

fatal myocardial infarction

nonfatal myocardial infarction

unstable angina

severe angina

risk ratios

fatal myocardial infarction

nonfatal myocardial infarction

unstable angina

severe angina

cardiovascular events

increase in risk

cardiovascular effects


Do heavier women benefit from a higher dose of leuprolide acetate for suppression of serum estradiol ? OBJECTIVE To determine if heavier women benefit from a higher dose of the gonadotropin-releasing hormone analogue leuprolide acetate ( LA ) depot in terms of suppression of serum estradiol . METHODS This was a retrospective analysis of the effect of LA depot 3.75 mg and 7.5 mg on serum estradiol from a multicenter , double-blind , parallel-group , 12-week study of women with anemia due to bleeding from uterine leiomyomata . Serum estradiol levels were obtained at baseline and at week 12 . Patients were divided into weight quartiles according to their baseline weight in kilograms : 46- < 64 , 64- < 72 , 72- < 89 , 89-159 ( pounds-102- < 140 , 140- < 159 , 159- < 196 , 196-350 ) . RESULTS At baseline there was no statistically significant difference in estradiol level between groups as a whole or within weight quartiles . Within each group there was no relationship between weight and baseline estradiol . At week 12 , whereas estradiol levels were significantly greater in the heavier patients in each of the groups ( LA 3.75 mg , p = 0.044 ; LA 7.5 mg , p = 0.002 ) , there was no significant difference in estradiol between groups as a whole or within any of the weight quartiles . Moreover , at week 12 there was no significant difference between groups in the percentage of patients with estradiol suppressed to the menopausal range . CONCLUSION Heavier women do not benefit from a higher dose of LA depot ( 7.5 vs. 3.75 mg ) for suppression of serum levels of estradiol .

leuprolide acetate

LA depot

serum estradiol

LA

Serum estradiol levels

no statistically significant difference

estradiol level

estradiol levels

significantly greater

no significant difference in estradiol

no significant difference

women

women

women

anemia

bleeding

uterine leiomyomata

women


Unopposed estrogen increases total plasma factor VII , but not active factor VII -- a short-term placebo-controlled study in healthy postmenopausal women . Estrogen therapy may increase the risk of arterial thromboembolism , at least in the short term . In a randomized , double-blind and placebo-controlled study in 25 healthy postmenopausal women ( 52.5 +/- 2.8 years ) , we therefore examined the short-term effect of unopposed estrogen on the fasting and fat-load-stimulated plasma levels of total factor VII versus active factor VII . Plasma total factor VII was measured by use of a chromogenic assay ; plasma active FVII by a recently developed method using truncated tissue factor . As compared to placebo , 8 weeks of oral 17beta-estradiol ( 2 mg daily ) increased the mean fasting and postprandial plasma levels of total factor VII by 17 and 21 % points , respectively ( both P < 0.01 ) , but did not affect the fasting and/or postprandial plasma levels of active factor VII ( mean change both 0.05 ng/mL ; P > 0.35 ) . Furthermore , the change in the fasting level of total factor VII after therapy was not associated with the change in the fasting level of active factor VII ( r = 0.27 ; P = 0.21 ) . These findings argue against the idea that elevated levels of total factor VII underlie an increased risk of arterial thromboembolism in postmenopausal women using unopposed estrogen replacement .

Unopposed estrogen

placebo-controlled

Estrogen therapy

unopposed estrogen

placebo

oral 17beta-estradiol

unopposed estrogen replacement .

Plasma total factor VII

levels of total factor VII

risk of arterial thromboembolism

healthy postmenopausal

women

healthy postmenopausal

women

52.5 +/- 2.8

postmenopausal

women


Sertraline treatment of generalized social phobia : a 20-week , double-blind , placebo-controlled study . OBJECTIVE The authors evaluated the efficacy , safety , and tolerability of sertraline , a selective serotonin reuptake inhibitor , in the treatment of generalized social phobia . METHOD Adult outpatients with generalized social phobia ( N=204 ) from 10 Canadian centers were randomly assigned to receive sertraline or placebo in a 2:1 ratio for a 20-week double-blind study following a 1-week , single-blind , placebo run-in . The initial dose of sertraline was 50 mg/day with increases of 50 mg/day every 3 weeks permitted after the fourth week of treatment ( dosing was flexible up to a maximum of 200 mg/day ) . Primary efficacy assessments were the percentage of patients rated much or very much improved on the Clinical Global Impression ( CGI ) improvement item and the mean changes from baseline to study endpoint in total score on the social phobia subscale of the Marks Fear Questionnaire and total score on the Brief Social Phobia Scale . RESULTS In intent-to-treat endpoint analyses of 203 of the patients , significantly more of the 134 patients given sertraline ( N=71 [ 53 % ] ) than of the 69 patients receiving placebo ( N=20 [ 29 % ] ) were considered responders according to their CGI improvement scores at the end of treatment . The mean reductions in the social phobia subscale of the Marks Fear Questionnaire and in the total score on the Brief Social Phobia Scale were 32.6 % and 34.3 % in the sertraline group and 10.8 % and 18.6 % in the placebo group , respectively . Analysis of covariance showed superiority of sertraline over placebo on all primary and secondary efficacy measures . Sertraline was well tolerated : 103 ( 76 % ) of the 135 sertraline-treated patients and 54 ( 78 % ) of the 69 placebo-treated patients completed the study . CONCLUSIONS Sertraline is an effective treatment for patients with generalized social phobia .

Sertraline

sertraline

sertraline

placebo

sertraline

sertraline

placebo

sertraline

placebo

sertraline

placebo

Sertraline

sertraline-treated

placebo-treated

Sertraline

generalized social phobia :

generalized social phobia .

efficacy assessments

CGI improvement scores

efficacy measures .

generalized social phobia

generalized social phobia :

Adult

generalized social phobia


The effects of treatment with interleukin-1 receptor antagonist on the inflamed synovial membrane in rheumatoid arthritis . OBJECTIVE To evaluate the effects of treatment with interleukin-1 receptor antagonist ( IL-1Ra ) on synovial tissue in rheumatoid arthritis ( RA ) . METHODS Twelve patients with RA entering a randomized clinical trial of human recombinant IL-1Ra underwent synovial biopsies before and after treatment . Cellular infiltration and adhesion molecule expression were evaluated after immunohistochemical staining . RESULTS There was a notable reduction in intimal layer macrophages and subintimal macrophages and lymphocytes after treatment with IL-1Ra at 150 mg/day ( n=3 ) . Increased cellular infiltration was observed in all patients receiving placebo ( n=3 ) ; variable changes were observed after IL-1Ra 30 mg/day ( n=6 ) . In a limited study of adhesion molecule expression , down-regulation of E-selectin and vascular cell adhesion molecule-1 was observed after treatment with IL-1Ra 150 mg/day , but not after IL-1Ra 30 mg/day or placebo . The apparent arrest of progressive joint damage seen in four patients after treatment with IL-1Ra was associated with reduced intimal layer macrophage accumulation in all patients . CONCLUSION Treatment of RA with IL-1Ra resulted in reduced mononuclear cell infiltration of synovial membrane , which may represent the in vivo inhibition of biologically relevant IL-1ss-mediated pathogenic effects .

interleukin-1 receptor antagonist

human recombinant IL-1Ra

synovial biopsies

placebo

placebo

cellular infiltration

arrest of progressive joint damage

rheumatoid arthritis

Twelve patients


The response of neuropathic pain and pain in complex regional pain syndrome I to carbamazepine and sustained-release morphine in patients pretreated with spinal cord stimulation : a double-blinded randomized study . Forty-three patients with peripheral neuropathic pain , exclusively pain reduced by spinal cord stimulation ( SCS ) , were switched into a painful state after SCS inactivation . This mode was used to assess the pain-relieving effect of carbamazepine ( CMZ ) and opioids in a double-blinded , placebo-controlled trial . In Phase 1 , the patients were randomly allocated to receive either CMZ ( 600 mg/d ) or placebo during an SCS-free period of 8 days . In Phase 2 , after a CMZ elimination interval of 7 days , 38 patients received either sustained-release morphine ( 90 mg/d ) or placebo for 8 days . In cases of intolerable pain , the patients were authorized to reactivate their SCS . The pain intensity was rated on a numeric analog scale . In 38 patients who completed Phase 1 , significant delay in pain increase was observed in the CMZ group as compared with placebo ( P = 0.038 ) . In Phase 2 , the trend observed with morphine was insignificant ( P = 0.41 ) . Two CMZ patients and one morphine patient showed complete pain relief and preferred to continue the medication . Thirty-five patients returned to SCS . We conclude that CMZ is effective in peripheral neuropathic pain . Morphine obviously requires larger individually titrated dosages than those used in this study for results to be adequately interpreted .

carbamazepine

sustained-release morphine

carbamazepine ( CMZ )

opioids

placebo-controlled

CMZ ( 600 mg/d )

placebo

CMZ

sustained-release morphine ( 90 mg/d )

placebo

SCS .

neuropathic pain

pain in complex regional pain syndrome

intolerable pain

pain intensity

numeric analog scale

delay in pain increase

complete pain relief

neuropathic pain

complex regional pain syndrome

pretreated with spinal cord stimulation

Forty-three

peripheral neuropathic pain

painful state after SCS inactivation


Counselor and stimulus control enhancements of a stage-matched expert system intervention for smokers in a managed care setting . BACKGROUND Previous research has demonstrated the efficacy of an interactive expert system intervention for smoking cessation for a general population . The intervention provides individualized feedback that guides participants through the stages of change for cessation . Enhancing the expert system by adding proactive telephone counseling or a stimulus control computer designed to produce nicotine fading could produce preventive programs with greater population impacts . METHODS Four interventions were compared : ( a ) the interactive expert system intervention ; ( b ) the expert system intervention plus counselor calls ; ( c ) the expert system intervention plus the stimulus control computer ; and ( d ) an assessment only condition . A 4 ( intervention ) x 4 ( occasions ) ( 0,6,12 , and 18 months ) design was used . Smokers were contacted at home via telephone or mail . The initial subject pool was the 24,178 members of a managed care company . Screening was completed for 19,236 members ( 79.6 % ) , of whom 4,653 were smokers ; 85.3 % of the smokers were enrolled . RESULTS Thirty-eight percent were in the precontemplation stage , 45 % in the contemplation stage , and only 17 % in the preparation stage . At 18 months , the expert system resulted in 23.2 % point prevalence abstinence , which was 33 % greater than that of assessment only . The counselor enhancement produced increased cessation at 12 months but not at 18 months . The stimulus control computer produced no improvement , resulting in 20 % worse cessation rates than the assessment only condition . CONCLUSIONS The enhanced conditions failed to outperform the expert system alone . The study also demonstrated the ability of the interactive expert system to produce significantly greater cessation in a population of smokers than assessment alone .

interactive expert system intervention

assessment only condition

interactive expert system

efficacy

prevalence abstinence

cessation

improvement

cessation

outperform

expert system

cessation

smokers


Perioperative blood transfusions , with or without allogeneic leucocytes , relate to survival , not to cancer recurrence . BACKGROUND Perioperative blood transfusions are reported to be related to cancer recurrence and reduced survival . Different underlying mechanisms have been proposed , and allogeneic leucocytes in transfused blood have been suggested to contribute to this phenomenon . METHODS Packed red cells without buffy coat ( PC group ) were compared with filtered , leucoreduced , red cells ( LD group ) in a randomized trial of 697 patients with colorectal carcinoma . Five-year survival and cancer recurrence rates were determined , with special emphasis on the location of recurrence . RESULTS The intention-to-treat analysis showed a survival rate of 63.6 per cent in the PC group and 65.3 per cent in the LD group ( P = 0.69 ) , with recurrence rates of 27.8 and 27.9 per cent respectively . The observational analysis showed a significant difference in survival between transfused and non-transfused patients ( 59.6 versus 72.9 per cent ; P < 0.001 ) . The difference in cancer recurrence rate between transfused and non-transfused patients was not statistically significant ( 29.8 versus 24.3 per cent ; P = 0.13 ) . Local recurrences were more frequent in transfused than non-transfused patients ( 11.9 versus 7.6 per cent ; P = 0.09 ) . CONCLUSION Leucocyte depletion of perioperative transfused blood has no effect on long-term survival and/or cancer recurrence . Perioperative blood transfusions are associated with impaired survival , but not with cancer recurrence . The slight increase in local recurrence rate in transfused patients appears to be related to complicated , in particular rectal , surgery .

Perioperative blood transfusions

perioperative transfused blood

survival

cancer recurrence

cancer recurrence

reduced survival

Five-year survival

cancer recurrence rates

location of recurrence

survival rate

recurrence rates

difference in survival

difference in cancer recurrence rate

Local recurrences

long-term survival

cancer recurrence

recurrence rate


[ Diphtheria antitoxin level 2 years after booster vaccination ] . In a prospective , controlled , randomized , multicenter study the immunogenicity of a single ( day 0 ) and two ( day 0 , 28 ) booster vaccination against diphtheria were compared in subjects who had received their last diphtheria vaccination more than 10 years ago . Both short-term and long-term immunogenicity was assessed by determining diphtheria antitoxin levels four weeks after vaccination and after one and two years . 102 subjects received the first booster vaccination , and 83 were vaccinated twice . Prior to the first vaccination 27 % of the subjects had a diphtheria antitoxin level below 0.01 I.U./ml ; after the first booster only 5 % were unprotected . The second booster did not show a significant effect , however , in 1 of the 5 subjects who were still unprotected after the first booster the second elicited an antitoxin level of more than 0.01 I.U./ml . After one and two years 7 % and 8 % of the subjects had diphtheria antitoxin level below 0.01 I.U./ml . A serological effect of a second booster vaccination four weeks after the first one could not be demonstrated neither after one nor after two years .

booster vaccination

booster vaccination against diphtheria

diphtheria vaccination

diphtheria antitoxin

first booster vaccination

vaccinated

twice

booster

booster vaccination

diphtheria antitoxin levels

diphtheria antitoxin level

antitoxin level

diphtheria antitoxin level