Pruritus in HIV-1 disease : therapy with drugs which may modulate the pattern of immune dysregulation . BACKGROUND Pruritus in HIV-1+ patients is common and increases with disease progression . The causes of pruritus are numerous including xerosis , drug and photoeruptions , follicular and papular eruptions as well as infestations and infections by a wide range of organisms . One other possible factor contributing to pruritus is the pattern of immune dysregulation . With advancing HIV-1 disease there is Th1 to Th2 cytokine switching . METHODS After some positive results with prostaglandin inhibitors , we undertook a study in which we randomly placed patients on four different forms of therapy for their pruritus . The therapies included hydroxyzine with or without doxepin at night , pentoxifylline , indomethacin and topical moisturization with medium-strength topical steroids . All patients were evaluated for both subjective relief as well as side effects . RESULTS Patients placed on indomethacin obtained relief more consistently and more completely . Patients on pentoxifylline had the fewest side effects of all oral therapies . Patients on antihistamines with or without doxepin had the highest incidence of side effects , although more of these patients reported a greater degree of relief than patients on pentoxifylline . All patients on oral therapy overall had greater relief than patients using topical steroids . CONCLUSION The systemic therapies which may modulate the pattern of immune dysregulation seen in HIV-1 disease may be beneficial in the pruritus seen in late-stage patients .

pentoxifylline

immune dysregulation

subjective relief

side effects

relief

side effects

incidence of side effects

degree of relief

greater relief

immune dysregulation

beneficial

Pruritus

four different forms of therapy

pruritus


Impact of surgical staging in evaluating the radiotherapeutic outcome in RTOG # 77-06 , a phase III study for T1BN0M0 ( A2 ) and T2N0M0 ( B ) prostate carcinoma . PURPOSE To evaluate survival and time to metastatic disease in patients treated for localized prostatic carcinoma in a Phase III radiotherapy ( RT ) protocol , Radiation Therapy Oncology Group ( RTOG ) 77-06 . Patients with T18N0M0 ( A2 ) or T2N0M0 ( B ) disease after lymphangiogram ( LAG ) or staging laparotomy ( SL ) were randomized between prophylactic radiation to the pelvic lymph nodes and prostatic bed vs. prostatic bed alone . The outcome of both treatment arms , as well as a comparison of the LAG group , to that of the SL group , are updated . METHODS AND MATERIALS A total of 449 eligible males were entered into RTOG protocol 7706 between 1978 and 1983 . Lymph node staging was mandatory but at the physician 's discretion ; 117 ( 26 % ) patients had SL , while 332 ( 74 % ) had LAG . Follow-up was a median of 12 years and a maximum of 16 years . For those randomized to receive prophylactic pelvic lymph nodal irradiation , 45 Gy of megavoltage RT was delivered via multiple portals in 4.5-5 weeks , while all patients received 65 Gy in 6.5-8 weeks to the prostatic bed . RESULTS There was no significant difference in survival whether treatment was administered to the prostate or prostate and pelvic lymph nodes . The SL group had greater 12-year survival than the LAG group ( 48 % vs. 38 % , p = 0.02 ) . Disease-free survival was statistically significant , with 38 % for the SL group vs. 26 % for the LAG group ( p = 0.003 ) . Bone metastasis was less common in the SL group ( 14 % ) than the LAG group ( 27 % ) ( p = 0.003 ) . CONCLUSION At 12-year median follow-up , there still was no survival difference in those patients treated prophylactically to the pelvic nodes and prostatic bed vs. the prostatic bed alone . Those patients not surgically staged with only LAG for lymph node evaluation were less accurately staged , as reflected by a statistically significant reduced survival and earlier metastases .

surgical staging

Phase III radiotherapy

Radiation Therapy Oncology Group

survival

12-year survival

Disease-free survival

Bone metastasis


Interfering with the central executive by means of a random interval repetition task . Four dual-task experiments are reported in which a short-term memory task is performed concurrently with a random interval repetition task , which was designed to interfere with functions normally attributed to the central executive in the working memory model of Baddeley and Hitch ( 1974 ) . The task was found to interfere with supra-span serial recall and with backward memory span , but did not disrupt performance on a forward-memory-span task . The effects were observed in dissociation with effects of articulatory suppression and matrix tapping , so that the locus of the effects of the new task is not due to the slave systems . In addition , single-task random-interval repetition performance was sampled and compared to performance in the dual-task conditions of all four experiments . Although quality of tapping performance differed between the single-task and the dual-task conditions , it was not related to recall performance . All the results are discussed with reference to the working memory model .

random interval repetition task

short-term memory task

random interval repetition task

task

forward-memory-span task

single-task random-interval

dual-task

single-task

dual-task

backward memory span

forward-memory-span

tapping performance

recall performance

short-term memory

central executive


The reliability of catheter-tip transducers for the measurement of intrauterine pressure in the third stage of labour . In order to assess the reliability of intrauterine pressure measurements in the third stage of labour , catheter-tip transducers were used in 20 women randomly allocated into two groups of 10 . In each case in the first group two catheters were tied together and introduced transcervically into the uterine cavity after delivery of the placenta . In each case in the second group two catheters were inserted independently into the same uterine cavity . The active and cumulative active pressures recorded from the pairs of catheters within each uterine cavity were compared . Comparison of individual active pressure readings from separate transducers revealed good agreement whether the catheters were tied together or were separate . Cumulative active pressure was very similar when assessed by each catheter in the same uterus . Intrauterine catheter-tip transducers can be used reliably to measure uterine activity in the third stage of labour although there may be minor contraction by contraction differences in recordings of individual active pressures .

catheter-tip transducers

catheter-tip transducers

catheters

Intrauterine catheter-tip transducers

intrauterine pressure

intrauterine pressure

active and cumulative active pressures

individual active pressure

Cumulative active pressure

uterine activity

individual active pressures


Amoxicillin/metronidazole/omeprazole/clarithromycin : a new , short quadruple therapy for Helicobacter pylori eradication . BACKGROUND Triple therapy regimens including two antibiotics plus acid suppression have become the new standard therapy in Helicobacter pylori eradication because of success rates of about 90 % . However , these regimens are still costly , duration is about one week or less , and side-effects are not negligible . We therefore evaluated a new quadruple therapy , because theoretically a shorter duration of treatment may result in reduced costs , fewer side-effects , and possibly in a lower potential for antibiotic resistances . METHODS Controlled , prospective pilot study including H. pylori-positive patients with gastric or duodenal ulcers or erosive gastritis , treated after failure of dual therapy ( proton-pump-inhibitors or ranitidine plus amoxicillin ) or for the first time . They were assigned to a one week triple standard therapy , consisting of metronidazole 400 mg bid + omeprazole 20 mg bid + clarithromycin 250 mg bid , or a newly created quadruple-regimen , which adds amoxicillin ( 1 g bid ) to the above triple regimen . Each of the four drugs was given for 5 days . H. pylori status was checked by 13C urea breath test before and after four weeks of therapy . RESULTS A total of 71 patients were treated by quadruple therapy , and 42 patients were treated by triple therapy . The eradication rate of H. pylori for patients under quadruple treatment , without vs. with previous dual therapy , were 96 % vs. 92 % ( 42/44 vs. 22/24 ) by per protocol and 91 % vs. 88 % ( 42/46 vs. 22/25 ) by intention to treat analysis ( comparisons not significant ) . No major side-effects were reported . CONCLUSIONS Five-day quadruple therapy ( with omeprazole , metronidazole , clarithromycin and amoxicillin ) represents an effective and safe new regimen for H. pylori eradication .

Helicobacter pylori eradication

13C urea breath test

eradication rate

Helicobacter pylori

H. pylori-positive


Simulating a memory impairment : can amnesics implicitly outperform simulators ? OBJECTIVES The purpose of this study was to examine the effectiveness of a variety of tests in differentiating simulating test performances from genuine memory-impaired and normal ( control ) test performances . DESIGN A simulation design was implemented , based on an analogue design in which normal participants were given experimental instructions to feign a mental impairment and are compared to ( a ) other normal participants with instructions to perform honestly , and ( b ) a comparison group , for example , acquired brain-injured persons , with similar instructions . METHOD Forty individuals comprised the simulating and control group and all participants were randomly assigned to the simulating and control groups . Twenty memory-impaired patients , all of whom had been diagnosed as suffering from a memory impairment following acquired brain damage , participated as the memory-impaired control group . The simulation group was directed to imitate a person with a memory impairment . The primary outcome measure involved identifying those tests , if any , where simulators were significantly different from normal and memory-impaired participants . RESULTS On 5 of the 15 tasks administered , simulators performed significantly differently from normal and memory-impaired participants . Of these 5 tasks , the coin-in-the-hand , when administered in conjunction with the autobiographical interview , identified 95 per cent of the simulators without misclassifying any of the memory-impaired or normal participants . CONCLUSION It is suggested that these two tests , when administered jointly , might be of use in clinical settings to assist in the detection of malingerers .

A simulation design

assigned to the simulating

control groups

simulators

effectiveness

simulating test performances

memory-impaired

amnesics

memory-impaired

acquired brain-injured

Forty

Twenty

memory-impaired

memory impairment

acquired brain damage ,


The role of pneumatic compression in the treatment of postmastectomy lymphedema . A randomized phase III study . BACKGROUND Pneumatic compression is a frequently prescribed physical therapy for patients affected by postmastectomy lymphedema but , despite its wide use , its efficacy has not been demonstrated in phase III studies . We performed a randomized study comparing pneumatic compression versus no treatment in patients with postmastectomy lymphedema . PATIENTS AND METHODS Patients with monolateral postmastectomy lymphedema were randomized to receive two cycles of intermittent pneumatic compression ( PC group ) , i.e. , five two-hour sessions per week for two weeks , to be repeated after a five-week interval , or to no treatment ( control group ) . The patients in both groups were instructed as to the prophylactic hygienic care of the limb . Lymphedema was assessed by the sum of differences in circumference measurements between affected and normal limbs ( 'delta ' ) . Response was defined as a > or = 25 % reduction in delta value . RESULTS Eighty patients entered the study . No statistically significant differences in response rates between the two groups were observed : 20 % in the control group ( 95 % CI : 9 % -36 % ) , 25 % in the PC group ( 95 % CI : 13 % -41 % , P = 0.59 ) . The absolute mean decrease in delta value was 1.9 +/- 3.7 cm in the PC group and 0.5 +/- 3.3 cm in the control group . CONCLUSIONS We demonstrated that intermittent pneumatic compression has a limited clinical role in the treatment of postmastectomy lymphedema . Efforts to prevent this complication should be undertaken .

pneumatic compression

Pneumatic compression

pneumatic compression

pneumatic compression

no treatment

intermittent pneumatic compression

Lymphedema

response rates

decrease in delta value

postmastectomy lymphedema

postmastectomy lymphedema

postmastectomy lymphedema

monolateral postmastectomy lymphedema

Eighty


Determinants of total and specific IgE in infants with atopic dermatitis . ETAC Study Group . Early Treatment of the Atopic Child . ETAC ( Early Treatment of the Atopic Child ) , a multi-centre predominantly European study to investigate the potential for cetirizine to prevent the development of asthma in infants with atopic dermatitis has completed enrollment : 817 children have been randomised to 18 months ' treatment with either active or placebo and a subsequent 18 months of post-treatment follow-up . Results of the therapeutic effects will not be available for some time , but the study has provided an opportunity to investigate influences on sensitization to allergens in a large cohort of 1-2 years olds with already established atopic dermatitis , resident in different countries and in different environments . The study shows that in infants with atopic dermatitis , raised serum total IgE has significantly different determinants from that a specific allergen sensitization . In infancy , increased total IgE is more affected by factors increasing risk of intercurrent infection and non-specific airway inflammation , such as environmental tobacco smoke exposure ( p < 0.001 ) and the use of gas cookers ( p = 0.02 ) . Specific allergen sensitization as represented by detectable IgE antibodies is influenced primarily by allergen exposure . In Sweden , low level exposure to allergens is associated with reduced specific allergen sensitization rates even though the infants already have atopic dermatitis .

cetirizine

active

placebo

sensitization to allergens

serum total IgE

specific allergen sensitization

total IgE

allergen sensitization

IgE antibodies

specific allergen sensitization


[ Clinical benefits of normothermic cardiopulmonary bypass on postoperative systemic metabolism ] . To evaluate the influence of body temperature during cardiopulmonary bypass ( CPB ) on postoperative systemic metabolism , 32 patients undergoing elective cardiac surgery were randomly assigned to either hypothermia ( n = 16 ) or normothermia ( n = 16 ) . Serial hemodynamic parameters and blood samples were obtained after surgery . CPB and operation times were significantly shorter and the platelet reduction ratio during CPB [ = ( platelets before CPB-platelets after CPB ) /platelets before CPB ] was significantly lower in normothermic patients than in hypothermic patients . The platelet reduction ratio was dependent on the minimum rectal temperature during CPB , the operation time , and the CPB time . In the early postoperative period , hypothermic patients had abnormally high systemic vascular resistance and a reduced cardiac index compared with the normothermic patients . There were no differences between 2 groups in postoperative hepatic and renal functions , changes in oxygen consumption , arterial-venous PCO2 or arterial-venous pH gradient . This study suggested a beneficial influence of normothermic CPB on postoperative hemodynamics . Normothermic CPB was not associated with adverse effects on postoperative metabolic recovery .

normothermic cardiopulmonary bypass

cardiopulmonary bypass ( CPB )

hypothermia

normothermia

CPB

CPB

normothermic CPB

Normothermic CPB

postoperative systemic metabolism

CPB and operation times

platelet reduction ratio

platelet reduction ratio

operation time

CPB time

normothermic patients

changes in oxygen consumption

postoperative hemodynamics

adverse effects

elective cardiac surgery

hypothermia

n = 16

normothermia


[ Prevention of vascular complications following cerebral ischemia of arterial origin ; the ESPRIT trial : mild anticoagulant therapy , combination treatment with acetylsalicylic acid plus dipyridamole or treatment with acetylsalicylic acid alone ? ] . The European and Australian Stroke Prevention in Reversible Ischaemia Trial ( ESPRIT ) is a randomised clinical trial in which patients with cerebral ischaemia of arterial origin will be randomised between oral anticoagulation ( international normalized ratio ( INR ) : 2.0-3.0 ) , the combination of acetylsalicylic acid ( in any dose between 30 and 325 mg per day ) plus dipyridamole ( 400 mg daily ) and acetylsalicylic acid only ( in any dose between 30 and 325 mg per day ) . It is planned to enroll 4500 patients with a mean follow-up of three years . Primary outcome is the composite event of vascular death , stroke , myocardial infarction , or major bleeding complication ; outcome assessment will be blinded . ESPRIT is an international , multicentre study in which 60-80 hospitals in the Netherlands and other countries in Europe and Australia will participate .

mild anticoagulant therapy

acetylsalicylic acid

dipyridamole

acetylsalicylic acid

oral anticoagulation

acetylsalicylic acid

dipyridamole

acetylsalicylic acid

vascular complications

composite event of vascular death ,

stroke

myocardial infarction

, or

major bleeding complication


The problem of measurement error in multisite clinical trials . The implementation of a multisite , randomized , clinical psychopharmacologic trial involves a substantial investment of time and effort on the part of all participants . Because of their complexity , such clinical trials present unique methodological and design challenges . Indeed , it is not uncommon for such studies to conclude with uninterpretable results , due in part to such methodological pitfalls . It has been suggested that clarification of such methodologic dilemmas is one of the most important challenges facing the future of industry-sponsored psychopharmacologic drug development . Among the many factors that may contribute to problematic clinical trial results , error in measuring the phenomena being studied is of particular concern . In this article , we describe the outcome of an intensive series of interrater reliability training sessions for the 17-item Hamilton Depression Rating Scale conducted at the start of a Phase II multisite clinical drug trial . The data underscore the magnitude of error present in such a test setting and provide preliminary evidence for the potential effect of this problem on the detection of clinical change .

Hamilton Depression Rating Scale


A prospective randomized study of amoxycillin and omeprazole with and without metronidazole in the eradication treatment of Helicobacter pylori . A combination of amoxycillin and omeprazole is often used to treat Helicobacter pylori infection . A three-drug regimen comprising metronidazole , amoxycillin and omeprazole has been proposed as an alternative therapy . In a prospective , randomized , comparative study , we evaluated these two regimens with respect to safety and efficacy in patients with H. pylori infection . Sixty patients with peptic ulcer ( gastric , 32 patients ; duodenal , 28 patients ) who had a history of ulcer recurrence were randomly assigned to dual therapy with amoxycillin ( 500 mg three times daily for 2 weeks ) and omeprazole ( 20 mg once daily for 8 weeks ) or to triple therapy with metronidazole ( 500 mg twice daily for 2 weeks ) plus amoxycillin and omeprazole , given in the same dosages as dual therapy . Forty-eight patients completed the protocol ; treatment was discontinued because of side effects in nine patients , and three patients dropped out of the study . On the basis of all patients treated , the rate of H. pylori eradication was significantly higher for triple therapy 20/23 cases , 87.0 % ; 95 % confidence interval ( CI ) , 0.664-0.972 ) than for dual therapy 13/25 , 52.0 % ; 0.313-0.722 ; P < 0.05 ) . On an intention-to-treat basis , the difference between the groups in the rate of H. pylori eradication was marginally significant ( P = 0.06 [ 0.028-0.512 ] ) . Side effects were reported by five patients receiving triple therapy ( skin rash , one ; nausea , two ; headache , one ; abdominal pain , one ) , and four patients receiving dual therapy ( skin rash , two ; abdominal pain , one ; diarrhoea , one ) . All side effects resolved spontaneously after termination of treatment . There was no significant difference in safety between the two regimens . Triple therapy with metronidazole , amoxycillin , and omeprazole was significantly more effective for the eradication of H. pylori than dual therapy with amoxycillin and omeprazole alone . The safety of these regimens was similar , and triple therapy was found to be clinically acceptable .

amoxycillin and omeprazole

metronidazole

amoxycillin and omeprazole

amoxycillin

omeprazole

metronidazole

plus amoxycillin and omeprazole

amoxycillin and omeprazole alone

the

rate of H. pylori eradication

rate of H. pylori eradication

was marginally significant

skin rash

nausea

headache

abdominal pain

four patients receiving dual therapy (

skin rash

abdominal pain

diarrhoea

safety

eradication of H. pylori

Helicobacter pylori

H. pylori infection

Sixty

peptic ulcer

gastric

duodenal

history of ulcer recurrence

Forty-eight


Effect of L-carnitine on myocardial metabolism : results of a balanced , placebo-controlled , double-blind study in patients undergoing open heart surgery . The effects of L-carnitine on cardiac performance after open heart surgery were evaluated in a balanced , placebo-controlled , double-blind study in 38 patients . Preoperative haemodynamic status was good in all of them . Seventeen subjects underwent mitral valve replacement and 19 patients coronary artery bypass grafting . Five grams L-carnitine were given intravenously over 2 h , twice daily for 5 consecutive days ; moreover , 10 g L-carnitine in 1500 ml cardioplegia were administered through the aortic root after aortic cross-clamping . Surgery was always planned on treatment day 3 . The post-ischaemic functional recovery of the heart was assessed by clinical parameters , as well as by biochemical and ultrastructure evaluations on biopsy specimens . No differences were found between the control and the treatment group with respect to all clinical parameters of cardiac performance after cardiopulmonary bypass . At anaesthesia induction , serum carnitine was significantly increased in treated patients , but carnitine concentrations in the right atrial biopsy obtained just before aortic declamping were similar in the two groups . In patients with mitral valve replacement , L-carnitine therapy was associated with significantly higher concentrations of pyruvate , ATP and creatine phosphate in papillary muscle . Glycogen levels were also higher in the treated group , but the difference was not statistically significant . Myocardial ultrastructure on septal biopsies , obtained within 5 min from weaning from extracorporeal circulation , showed better preservation scores for all considered parameters ( nucleus , sarcoplasmic reticulum , mitochondria and cellular oedema ) in the treated subjects , although the difference reached statistical significance only for nuclei . When biochemical and ultrastructural data are considered , these findings suggest that L-carnitine improves myocardial metabolism . However , it can not be concluded that L-carnitine provides an advantageous support therapy for well-compensated patients requiring cardiac surgery . In contrast , the positive effects of L-carnitine on cardiac recovery after bypass might become clinically relevant in the surgical setting for haemodynamically compromised patients , in which further investigations are required .

L-carnitine

L-carnitine

placebo-controlled

mitral valve replacement

coronary artery bypass grafting

L-carnitine

L-carnitine in 1500 ml cardioplegia

aortic cross-clamping

L-carnitine therapy

L-carnitine

serum carnitine

carnitine concentrations

pyruvate

ATP

creatine phosphate

Glycogen levels

myocardial metabolism

advantageous support therapy

cardiac recovery


Scintigraphic evaluation of a new capsule-type colon specific drug delivery system in healthy volunteers . Colonic drug delivery is intended for local or systemic therapies . The lack of predictive in vitro or animal model leads to considerable time delays in colonic product development . The objective of this scintigraphic study was to provide " proof of concept " for a novel capsule-type colonic delivery system ( Colon-Targeted Delivery Capsule ) in healthy volunteers . The human data validates the design concept behind the release mechanism , in that capsule disintegration , and hence drug release , did not start until 5 h after gastric emptying , irrespective of whether the product was administered to fasted or fed subjects . However , the potential for prolonged gastric residence for large enteric coated products intended for intestinal targeting was also observed ; overall , the study provides a focus for subsequent product development and highlights the role of scintigraphy in dynamically visualizing the drug delivery process .

Colonic drug delivery

healthy volunteers .


Comparison of single- and dual-coil active pectoral defibrillation lead systems . OBJECTIVES The purpose of this study was to compare defibrillation thresholds with lead systems consisting of an active left pectoral electrode and either single or dual transvenous coils . BACKGROUND Lead systems that include an active pectoral pulse generator reduce defibrillation thresholds and permit transvenous defibrillation in nearly all patients . A further improvement in defibrillation efficacy is desirable to allow for smaller pulse generators with a reduced maximal output . METHODS This prospective study was performed in 50 consecutive patients . Each patient was evaluated with two lead configurations with the order of testing randomized . Shocks were delivered between the right ventricular coil and either an active can alone ( single coil ) or an active can with the proximal atrial coil ( dual coil ) . The right ventricular coil was the cathode for the first phase of the biphasic defibrillation waveform . RESULTS Delivered energy at the defibrillation threshold was 10.1+/-5.0 J for the single-coil configuration and 8.7+/-4.0 J for the dual-coil configuration ( p < 0.02 ) . Moreover , 98 % of patients had low ( < 15 J ) thresholds with the dual-coil lead system , compared with 88 % of patients with the single-coil configuration ( p=0.05 ) . Leading edge voltage ( p < 0.001 ) and shock impedance ( p < 0.001 ) were also decreased with the dual-coil configuration , although peak current was increased ( p < 0.001 ) . CONCLUSIONS A dual-coil , active pectoral lead system reduces defibrillation energy requirements compared with a single-coil , unipolar configuration .

single

dual transvenous coils

lead configurations

( single coil )

( dual coil )

single-coil

dual-coil

dual-coil

single-coil

dual-coil

dual-coil

single-coil

defibrillation efficacy

Delivered energy

defibrillation threshold

thresholds

Leading edge voltage

shock impedance

peak current

defibrillation energy requirements

98 %

88 %


Quantifying oral analgesic consumption using a novel method and comparison with patient-controlled intravenous analgesic consumption .

oral analgesic

analgesic


Evaluation of lidocaine in human inferior alveolar nerve block . The purpose of this study was to measure the degree of anesthesia following the administration of 3.6 ml of 2 % lidocaine solutions with either 1:50,000 , 1:80,000 , or 1:100,000 for inferior alveolar nerve block and to compare the results with those obtained following the administration of 1.8 ml of the same solutions ( 1 ) . With the use of a repeated measures design , 30 subjects randomly received an inferior alveolar injection at three successive appointments . The first molar , first premolar , lateral incisor , and contralateral canine ( control ) were blindly tested with an Analytic Technology pulp tester at 3-min cycles for 50 min . The degree of anesthesia was comparable for the three solutions following the administration of 3.6 ml of each solution . Retrospective evaluation showed that the volume of the solution influenced the degree of anesthesia .

lidocaine

lidocaine solutions

inferior alveolar injection

degree of anesthesia

degree of anesthesia

human inferior alveolar nerve block


Anti-tumor necrosis factor alpha : Crohn 's disease guided missile .

Anti-tumor necrosis factor alpha

Crohn 's disease


[ Treatment of irresectable hepatocellular carcinoma with repeated transient dearterialization ] . A joint clinical prospective study between SUMS and Lund university was reported . 40 patients with the irresectable hepatocellular carcinoma ( HCC ) admitted to the department of HPB surgery in the First Affiliated Hospital of SUMS were randomized into two groups : ( 20 each ) from Feb. 1994 to April , 1995 . The patients were treated with hepatic artery ligation ( HAL ) and repeated transient dearterialization ( RTD ) respectively . Postoperative response to treatment , liver function change ( ALT ) , AFP , imaging examination of the tumor , patient 's survival were evaluated . It has been shown that RTD is superior to HAL in terms of the objective response to the therapy , reduction of tumor size , patient 's symptom relief , liver function and AFP changes and patient 's survival . In the RTD group , the effective rate was 70 % , the mean survival time was 8.2 months , and the 6-month survival rate was 79.7 % . In HAL group , the effective rate was only 5 % , the mean survival time was 5.1 months , 6 months survival rate was 35.8 % . It has been postulated that RTD may prevent the rapid development of collateral circulation and increase the production of oxygen-derived free radicals , which may be the responsible factors for the ischemic treatment of hepatic tumours . We consider that RTD would be a promising polliative method for HCC .

repeated transient dearterialization ]

hepatic artery ligation ( HAL )

and

RTD

RTD

RTD

RTD

patient 's survival

tumor size

symptom relief

liver function

AFP

survival

effective rate

survival time

survival rate

effective rate

survival time

survival rate

irresectable hepatocellular carcinoma

irresectable hepatocellular carcinoma


Transcutaneous electrical nerve stimulation in the treatment of myofascial pain dysfunction . The effect of transcutaneous electrical nerve stimulation ( TENS ) plus conservative therapy ( ibuprofen , bite plate , self-physiotherapy ) on myofascial pain dysfunction ( MPD ) was determined . A single-blind trial as done in 10 patients with MPD with subthreshold TENS ( frequency 35 Hz , pulse width 100 milliseconds , modulation 50 % ) compared with sham TENS at 8 visits over 14 weeks . Pain was assessed on a visual analogue scale before and after TENS at each visit and the data were analysed with the analysis of variance ( ANOVA ) for repeated measures . A highly significant effect was seen for time ( F = 4.80 , P = 0.0003 ) but not for TENS . Subthreshold TENS did not increase the symptom relief produced by conservative treatment with the protocol used .

self-physiotherapy

subthreshold TENS

sham TENS

TENS

TENS

Subthreshold TENS

Pain

visual analogue scale

time

myofascial pain dysfunction

MPD


Humoral immune response to tetanus-diphtheria vaccine given during extended use of chloroquine or primaquine malaria chemoprophylaxis . Immune suppression resulting from prolonged chemoprophylaxis and potential drug-vaccine interaction were investigated within the context of a randomized placebo-controlled trial that compared daily primaquine or weekly chloroquine administration for malaria prevention . After 11 months of prophylaxis , adult male subjects received a tetanus-diphtheria ( Td ) vaccination . Prophylaxis continued 4 weeks longer . Anti-tetanus and anti-diphtheria antibody levels were measured by ELISA at baseline and at 1 , 3 , 7 , and 14 months after Td vaccination . All groups were comparable at baseline . Immunization triggered significant increases in anti-tetanus and anti-diphtheria IgG levels over each group 's pre-Td baseline levels and those of an unvaccinated control group . Geometric mean anti-tetanus titers ( GMTs ) in the primaquine group were significantly higher than those of the placebo group at 1 , 3 , and 14 months . Anti-tetanus GMTs in placebo and chloroquine groups declined over 14 months to levels comparable to those of unvaccinated controls , but levels in the primaquine group remained significantly higher than in controls .

tetanus-diphtheria vaccine

chloroquine

primaquine malaria chemoprophylaxis

placebo-controlled

primaquine

chloroquine

tetanus-diphtheria ( Td ) vaccination

ELISA

placebo

placebo

Humoral immune response

Immune suppression

ELISA

Anti-tetanus GMTs

adult

male


Long-term evaluation of tamsulosin in benign prostatic hyperplasia : placebo-controlled , double-blind extension of phase III trial . Tamsulosin Investigator Group . OBJECTIVES To evaluate the long-term efficacy and safety of once-daily tamsulosin ( 0.4 and 0.8 mg ) , a unique selective alpha1A-adrenoceptor antagonist in patients with benign prostatic hyperplasia ( BPH ) . METHODS This trial extended a 13-week , Phase III multicenter placebo-controlled , double-blind outpatient trial for an additional 40 weeks . Of 618 patients , 418 ( 68 % ) continued into the extension phase on the same double-blind medication and dose . The primary efficacy parameters were total American Urological Association ( AUA ) symptom score and maximum urinary flow ( Qmax ) . RESULTS The mean changes in AUA symptom score from baseline to end point were statistically significant in all groups ( P < 0.001 ) . Significant improvements were observed in Qmax for both tamsulosin groups but not for the placebo group . The statistically significant improvements from baseline in efficacy parameters observed for each tamsulosin group at the end of the 13-week Phase III trial were maintained during the long-term extension phase . Tamsulosin at both dosages was well tolerated as maintenance therapy . Clinically significant orthostatic hypotension was not observed . Vital sign changes in either hypertensive or normotensive patients were not clinically significantly different across the three groups . CONCLUSIONS Tamsulosin once-daily at 0.4 or 0.8 mg was shown to be effective , safe , and well tolerated in the target BPH population during long-term use .

tamsulosin

placebo-controlled

tamsulosin

tamsulosin

placebo

tamsulosin

Tamsulosin

maximum urinary flow ( Qmax )

AUA symptom score

Qmax

significant improvements

tolerated

orthostatic hypotension

Vital sign changes

benign prostatic hyperplasia :

target BPH population


A double-blind , placebo-controlled trial of nefazodone in the treatment of patients hospitalized for major depression . BACKGROUND There are few published placebo-controlled clinical trials demonstrating the efficacy of the newer antidepressants in markedly or severely depressed hospitalized patients . This study demonstrates the efficacy of nefazodone compared with placebo in the treatment of patients hospitalized for major depression . METHOD Nefazodone and placebo treatment were compared in a 6-week trial of 120 patients hospitalized for DSM-III-R diagnosed major depression ( without psychosis ) at 2 study centers . Efficacy was evaluated using standard psychiatric rating scales , and patients were monitored for safety . RESULTS Nefazodone treatment resulted in a significant reduction ( p < .01 ) of the 17-item Hamilton Rating Scale for Depression ( HAM-D-17 ) total score compared with placebo from the end of the first treatment week through the end of the study ( -12.2 nefazodone vs. -7.7 placebo ) . At the end of the trial , significantly more nefazodone-treated patients ( 50 % ) than placebo-treated patients ( 29 % ) had responded , as indicated by their Clinical Global Impressions-Improvement score ( p = .021 ) or by a > or = 50 % reduction in their HAM-D-17 scores ( p = .017 ) . Significantly more patients treated with nefazodone ( 36 % ) than placebo-treated patients ( 14 % ) had a HAM-D-17 score < or = 10 at the end of treatment ( p = .004 ) . Significant treatment differences ( p < .01 ) in favor of nefazodone were also seen in the Montgomery-Asberg Depression Rating Scale ; the HAM-D retardation , anxiety , and sleep disturbance factors ; and HAM-D item 1 ( depressed mood ) . Patients with dysthymia in addition to major depression also showed significant improvement ( p < .05 ) when treated with nefazodone , with significant differences in response rates seen as early as week 2 and through the end of the trial . The mean nefazodone dose was 491 mg/day at the end of week 2 and 503 mg/day at the end of treatment . Nefazodone was well tolerated , and the number of patients discontinuing owing to adverse events was small , with no significant safety issues noted in either treatment group . Fewer nefazodone-treated than placebo-treated patients discontinued owing to lack of efficacy . CONCLUSION Nefazodone was superior to placebo in the treatment of marked to severe major depression in patients requiring hospitalization . The clinical benefit of nefazodone was evident as early as the first week of treatment as judged by several measures of efficacy , with significant differences from placebo sustained throughout the trial .

placebo-controlled

nefazodone

placebo-controlled

nefazodone

placebo

Nefazodone

placebo treatment

placebo

nefazodone

placebo

nefazodone-treated

placebo-treated

nefazodone

placebo-treated

nefazodone-treated

placebo-treated

Nefazodone

nefazodone

standard psychiatric rating scales

HAM-D-17 scores

HAM-D-17 score

dysthymia

major depression

nefazodone

well tolerated

adverse events

efficacy

major depression

severely depressed

major depression

dysthymia

major depression

major depression


Proposed synergistic effect of calcium channel blockers with lipid-lowering therapy in retarding progression of coronary atherosclerosis . Lipid-lowering therapy now has undoubtedly proven to be an effective therapeutic modality to retard the progression of coronary atherosclerosis . An additional approach for prevention of the progression of atherosclerosis is calcium channel blocker ( CCB ) treatment . Evidence indicating that CCBs inhibit atherosclerosis is less unequivocal than the clear evidence for lipid-lowering therapy . Many investigations support the view that a number of key processes in atherosclerosis may be influenced by CCBs . From the " negative " and " positive " studies with CCBs performed in animals and humans we must conclude that apparently some , but not all , types or stages of the atherosclerotic process are inhibited by CCBs . To assess whether lipid-lowering therapy and CCB treatment may have an additive or synergistic beneficial effect on human atherosclerosis , which is conceivable because their anti-atherosclerotic properties differ , data from the angiographic lipid-lowering trial REGRESS ( pravastatin vs. placebo ) were reviewed . In REGRESS , patients in the pravastatin group had significantly less progression if cotreated with CCBs as compared with those with no CCB cotreatment , whereas in the placebo ( no pravastatin ) group no effect of CCB treatment was observed . With respect to angiographic new lesion formation , in the pravastatin group there were 50 % less patients with new angiographic lesions if cotreated with CCBs as compared with no CCB cotreatment , whereas in the placebo ( no pravastatin ) group , again , no significant effect of CCB treatment was observed . No beneficial effects of CCB treatment on clinical events were observed during the 2-year study follow-up . In view of the correlation between angiographic progression and subsequent clinical events as demonstrated in several large trials , it is not unrealistic to also anticipate in this population , a beneficial effect on clinical events with longer follow-up . Although the REGRESS trial was not designed to evaluate combination therapy , the results suggest that addition of CCBs to HMG-CoA reductase inhibitor therapy ( pravastatin ) acts synergistically in retarding the progression of established coronary atherosclerosis . These results appear to warrant prospective randomized trials to determine in a more definitive manner the merits of this combination in the prevention of progression of coronary atherosclerosis . Currently a number of studies in these fields are being designed or are already underway .

calcium channel blockers

lipid-lowering therapy

Lipid-lowering therapy

calcium channel blocker ( CCB )

CCBs

lipid-lowering therapy .

CCBs

CCBs

CCBs

lipid-lowering therapy

CCB

pravastatin

placebo

pravastatin

CCBs

CCB

placebo ( no pravastatin )

CCB

pravastatin

CCBs

CCB

placebo ( no pravastatin )

CCB

CCB

CCBs

pravastatin

progression of coronary atherosclerosis

atherosclerosis

progression of atherosclerosis

atherosclerosis

progression

angiographic new lesion formation

angiographic lesions

clinical events

angiographic progression

clinical events

progression of coronary atherosclerosis


Effect of aldose reductase inhibition on cardiovascular reflex tests in patients with definite diabetic autonomic neuropathy over a period of 2 years . The potential of the aldose reductase inhibitor tolrestat to ameliorate definite diabetic autonomic neuropathy ( DAN ) , as defined by standard cardiovascular autonomic function tests , was evaluated in 35 patients over a period of 2 years , with repeated measurements at 3-month intervals . The effect of tolrestat ( 200 mg a day ) was compared with that of placebo on 35 controls with diabetes mellitus , of similar age , gender , and glycemic control . In the placebo group , a significant deterioration of the indices , with the exception of Valsalva ratio , was recorded , while tolrestat induced a significant beneficial change in the values of most standard cardiovascular reflex tests , in comparison to baseline and placebo . The deep breathing tests ( expiration-inspiration ratio , standard deviation , and mean circular resultant of R-R intervals ) , postural index , and postural hypotension were favorably affected . Three of 35 patients on tolrestat ( 8.6 % ) developed high transaminases levels ( more than threefold the upper normal limit ) and were withdrawn from the study . In conclusion , tolrestat improved autonomic nervous system function in patients with definite DAN , in comparison to baseline and placebo . The clinical importance of this finding needs further investigation .

aldose reductase

tolrestat

tolrestat

placebo

placebo

tolrestat

tolrestat

tolrestat

cardiovascular reflex tests

Valsalva ratio

deep breathing tests

expiration-inspiration ratio

standard deviation

postural index

postural hypotension

high transaminases levels

autonomic nervous system function


Prevention of a first stroke by transfusions in children with sickle cell anemia and abnormal results on transcranial Doppler ultrasonography . BACKGROUND Blood transfusions prevent recurrent stroke in children with sickle cell anemia , but the value of transfusions in preventing a first stroke is unknown . We used transcranial Doppler ultrasonography to identify children with sickle cell anemia who were at high risk for stroke and then randomly assigned them to receive standard care or transfusions to prevent a first stroke . METHODS To enter the study , children with sickle cell anemia and no history of stroke had to have undergone two transcranial Doppler studies that showed that the time-averaged mean blood-flow velocity in the internal carotid or middle cerebral artery was 200 cm per second or higher . The patients were randomly assigned to receive standard care or transfusions to reduce the hemoglobin S concentration to less than 30 percent of the total hemoglobin concentration . The incidence of stroke ( cerebral infarction or intracranial hemorrhage ) was compared between the two groups . RESULTS A total of 130 children ( mean [ +/-SD ] age , 8.3+/-3.3 years ) were enrolled ; 63 were randomly assigned to receive transfusions and 67 to receive standard care . At base line , the transfusion group had a slightly lower mean hemoglobin concentration ( 7.2 vs. 7.6 g per deciliter , P=0.001 ) and hematocrit ( 20.4 vs. 21.7 percent , P=0.002 ) . Ten patients dropped out of the transfusion group , and two patients crossed over from the standard-care group to the transfusion group . There were 10 cerebral infarctions and 1 intracerebral hematoma in the standard-care group , as compared with 1 infarction in the transfusion group -- a 92 percent difference in the risk of stroke ( P < 0.001 ) . This result led to the early termination of the trial . CONCLUSIONS Transfusion greatly reduces the risk of a first stroke in children with sickle cell anemia who have abnormal results on transcranial Doppler ultrasonography .

Blood transfusions

standard care or transfusions

Transfusion

mean hemoglobin concentration

hematocrit

cerebral infarctions

intracerebral hematoma

infarction

risk of a first stroke

sickle cell anemia

children

sickle cell anemia

sickle cell anemia

stroke

children

sickle cell anemia

stroke

8.3+/-3.3 years

children

sickle cell anemia


Bronchodilator response to salbutamol after spontaneous recovery from nonspecific bronchial provocation tests in asthma . Assessment of airway responsiveness by bronchoprovocation and bronchodilatation tests is important in the diagnostic work-up protocol of bronchial asthma and it would be convenient to undertake both tests on the same occasion . However , it is not known whether this can be done accurately . Therefore , this study evaluated the effect of a prior bronchial provocation test on the bronchodilator response to salbutamol after spontaneous recovery of the forced expiratory volume in one second ( FEV1 ) in a group of asthmatic subjects . On two separate occasions at the same time of day , concentration-response studies with inhaled histamine or methacholine , or a sham challenge with normal saline were carried out in a blinded , randomized manner . Changes in airway calibre were followed as FEV1 and agonist responsiveness expressed as the provocative concentration causing a 20 % fall in FEV1 ( PC20 ) . After either spontaneous recovery or a fixed-duration wait of 45 min ( when appropriate ) , the subjects received 2x100 microg of salbutamol from a metered dose inhaler with a spacer . The bronchodilator response to salbutamol was expressed as a percentage of initial FEV1 ( deltaFEV1 % init ) . Bronchial challenge with both agonists failed to alter significantly the airway response to salbutamol , with the deltaFEV1 % init mean value ( range ) being 16.9 % ( 9.0-31.9 ) and 17.5 % ( 11.6-31.2 ) on the sham and histamine/methacholine challenge day respectively . It was shown that the degree of bronchodilatation achieved after salbutamol 200 microg is not affected by prior bronchoprovocation testing when enough time is allowed for the airways to recover spontaneously to baseline forced expiratory volume in one second . Thus evaluation of airway responsiveness by both bronchial provocation tests and bronchodilator testing can be assessed reliably within a few hours in asthmatic patients .

salbutamol

salbutamol

histamine

methacholine

sham challenge with normal saline

salbutamol

initial FEV1

airway response

deltaFEV1 % init mean value

asthma

bronchial asthma


Randomised placebo-controlled trial of rhesus-human reassortant rotavirus vaccine for prevention of severe rotavirus gastroenteritis . BACKGROUND Rotavirus is the most common cause of acute childhood gastroenteritis . Vaccination with live oral heterologous rotavirus vaccines may prevent rotavirus gastroenteritis . We assessed the efficacy of rhesus-human reassortant rotavirus tetravalent vaccine ( RRV-TV ) against severe rotavirus gastroenteritis in Finnish children in a randomised placebo-controlled double-blind trial . METHODS Placebo or RRV-TV ( titre 4x10 ( 5 ) plaque-forming units ) was given to infants at ages 2 , 3 , and 5 months . The children were followed up for one or two rotavirus epidemic seasons . The main outcome measure was protection against severe rotavirus gastroenteritis ( score > or =11 on a 20-point severity scale ) . 2398 children were enrolled and received at least one dose of RRV-TV ( n=1191 ) or placebo ( n=1207 ) . The primary efficacy analysis was based on children who received three doses of RRV-TV ( n=1128 ) or placebo ( n=1145 ) . FINDINGS 256 episodes of rotavirus gastroenteritis occurred at any time during the study ; 65 were among 1191 RRV-TV recipients , and 191 among 1207 placebo recipients ( vaccine efficacy 66 % [ 95 % CI 55-74 ] ; intention-to-treat analysis ) . 226 episodes were included in the primary efficacy analysis of fully vaccinated children ( 54 among 1128 RRV-TV recipients , 172 among 1145 placebo recipients ; vaccine efficacy 68 % [ 57-76 ] ) . 100 episodes were severe , eight in RRV-TV recipients and 92 in placebo recipients ( vaccine efficacy 91 % [ 82-96 ] ) . INTERPRETATION RRV-TV vaccine was highly effective against severe rotavirus gastroenteritis in young children . Incorporation of this vaccine into routine immunisation schedules of infants could reduce severe rotavirus gastroenteritis by 90 % and severe gastroenteritis of all causes in young children by 60 % .

placebo-controlled

placebo-controlled

Placebo

RRV-TV

placebo

RRV-TV

placebo

RRV-TV

RRV-TV vaccine

severe rotavirus gastroenteritis

efficacy

severe rotavirus gastroenteritis

efficacy

severe rotavirus gastroenteritis

severe gastroenteritis

children

infants at ages 2 , 3 , and 5 months

children

young children


Randomised trial of laparoscopic versus open cholecystectomy for acute and gangrenous cholecystitis . BACKGROUND Laparoscopic cholecystectomy ( LC ) has become the treatment of choice for elective cholecystectomy , but controversy persists over use of this approach in the treatment of acute cholecystitis . We undertook a randomised comparison of the safety and outcome of LC and open cholecystectomy ( OC ) in patients with acute cholecystitis . METHODS 63 of 68 consecutive patients who met criteria for acute cholecystitis were randomly assigned OC ( 31 patients ) or LC ( 32 patients ) . The primary endpoints were hospital mortality and morbidity , length of hospital stay , and length of sick leave from work . Analysis was by intention to treat . Suspected bile-duct stones were investigated by preoperative endoscopic retrograde cholangiography ( LC group ) or intraoperative cholangiography ( OC group ) . FINDINGS The two randomised groups were similar in demographic , physical , and clinical characteristics . 48 % of the patients in the OC group and 59 % in the LC group were older than 60 years . 13 patients in each group had gangrene or empyema , and one in each group had perforation of the gallbladder causing diffuse peritonitis . Five ( 16 % ) patients in the LC group required conversion to OC , in most because severe inflammation distorted the anatomy of Calot 's triangle . There were no deaths or bile-duct lesions in either group , but the postoperative complication rate was significantly ( p=0.0048 ) higher in the OC than in the LC group : seven ( 23 % ) patients had major and six ( 19 % ) minor complications after OC , whereas only one ( 3 % ) minor complication occurred after LC . The postoperative hospital stay was significantly shorter in the LC than the OC group ( median 4 [ IQR 2-5 ] vs 6 [ 5-8 ] days ; p=0.0063 ) . Mean length of sick leave was shorter in the LC group ( 13.9 vs 30.1 days ; 95 % CI for difference 10.9-21.7 ) . INTERPRETATION Even though LC for acute and gangrenous cholecystitis is technically demanding , in experienced hands it is safe and effective . It does not increase the mortality rate , and the morbidity rate seems to be even lower than that in OC . However , a moderately high conversion rate must be accepted .

laparoscopic

open cholecystectomy

Laparoscopic cholecystectomy

( LC )

elective cholecystectomy

LC

open cholecystectomy ( OC )

OC

LC

LC

intraoperative cholangiography

OC

LC

LC

OC

OC

LC

OC

LC

OC

hospital mortality

morbidity

length of hospital stay

length of sick leave from work

Suspected bile-duct stones

gangrene

empyema

severe inflammation

deaths

bile-duct lesions

postoperative complication

minor complications

postoperative hospital stay

Mean length of sick leave

safe

effective

mortality rate

morbidity rate

acute and gangrenous cholecystitis

acute cholecystitis

acute cholecystitis

acute cholecystitis


Effects of formoterol , salmeterol or oxitropium bromide on airway responses to salbutamol in COPD . We examined whether a pretreatment with formoterol , oxitropium bromide , or salmeterol might modify the dose-response curves to inhaled salbutamol in patients with stable and partially reversible chronic obstructive pulmonary disease ( COPD ) . Sixteen outpatients with partially reversible , stable COPD received 24 microg formoterol , 50 microg salmeterol , 200 microg oxitropium bromide , or placebo on four non-consecutive days . Spirometric testing was performed immediately before inhalation of treatment and after 2 h. A dose-response curve to inhaled salbutamol was then constructed using doses of 100 , 100 , 200 microg and 400 microg -- that is , a total cumulative dose of 800 microg . Dose increments were given at 20 min intervals with measurements being made 15 min after each dose . Formoterol , salmeterol , or oxitropium bromide elicited a significant increase in forced expiratory volume in one second ( FEV1 ) compared with placebo ( mean differences ( L ) = placebo 0.05 ; formoterol 0.34 ; salmeterol 0.27 ; oxitropium bromide 0.23 ) . Dose-dependent increases in FEV1 were seen ( mean values ( L ) before salbutamol and after a cumulative dose of 100 , 200 , 400 , and 800 microg = placebo : 1.06 , 1.28 , 1.35 , 1.39 , 1.41 ; formoterol : 1.33 , 1.37 , 1.41 , 1.44 , 1.44 ; salmeterol : 1.30 , 1.33 , 1.36 , 1.39 , 1.42 ; oxitropium bromide : 1.27 , 1.34 , 1.37 , 1.41 , 1.40 ) . Statistical analysis revealed no significant differences in FEV1 and forced vital capacity ( FVC ) responses to salbutamol after therapy with formoterol , salmeterol , or oxitropium bromide compared with placebo . This study clearly shows that a pretreatment with a conventional dose of formoterol , salmeterol , or oxitropium bromide does not preclude the possibility of inducing a further bronchodilation with salbutamol in patients suffering from partially reversible chronic obstructive pulmonary disease .

formoterol

salmeterol

oxitropium bromide

salbutamol

formoterol

oxitropium bromide

salmeterol

salbutamol

24 microg formoterol

50 microg salmeterol

200 microg oxitropium bromide

placebo

Spirometric testing

salbutamol

Formoterol

salmeterol

oxitropium bromide

placebo

placebo

formoterol

salmeterol

oxitropium bromide

placebo

formoterol

salmeterol

oxitropium bromide

formoterol

salmeterol

oxitropium bromide

placebo

formoterol

salmeterol

oxitropium bromide

salbutamol

airway responses to salbutamol

bronchodilation

COPD .

partially reversible

stable COPD


Zolmitriptan ( 311C90 ) does not interact with fluoxetine in healthy volunteers . Zolmitriptan ( Zomig , formerly 311C90 ) is a selective 5-hydroxytryptamine ( 5-HT ) 1B/1D-receptor agonist with central and peripheral activity for the acute treatment of migraine . This randomized , placebo-controlled , crossover study investigated the effects of fluoxetine administration on the pharmacokinetics and pharmacodynamics of zolmitriptan . Twenty volunteers were given single doses of fluoxetine 20 mg or an identical placebo daily for 28 days prior to receiving a single 10 mg oral dose of zolmitriptan . Sixteen volunteers completed the two treatment phases . The pharmacokinetic parameters of zolmitriptan and its metabolites were not significantly affected by fluoxetine pretreatment . The pharmacodynamic effects of zolmitriptan were also unaffected by fluoxetine pretreatment . There were small , clinically insignificant increases in blood pressure following zolmitriptan which were unaltered by fluoxetine . Zolmitriptan was well tolerated when given alone or concomitantly with fluoxetine . These results indicate that there is no contraindication to the use of zolmitriptan in patients treated concurrently with selective serotonin reuptake inhibitors and that no adjustment of the zolmitriptan dose is required in these circumstances .

Zolmitriptan ( 311C90 )

fluoxetine

placebo-controlled

fluoxetine

zolmitriptan

fluoxetine 20 mg

placebo

zolmitriptan

zolmitriptan

fluoxetine

zolmitriptan

fluoxetine

zolmitriptan

fluoxetine

Zolmitriptan

fluoxetine

zolmitriptan

selective serotonin reuptake inhibitors

zolmitriptan

pharmacodynamic effects of zolmitriptan

blood pressure

well tolerated

contraindication

Twenty

Sixteen

serotonin reuptake inhibitors


Diet design for a multicenter controlled feeding trial : the DELTA program . Delta Research Group . OBJECTIVE To describe the process and results of diet standardization , diet validation , and monitoring of diet composition , which were key components of protocol 1 of Dietary Effects on Lipoproteins and Thrombogenic Activity ( DELTA-1 ) , the initial protocol in a program of multicenter human feeding studies designed to evaluate the effects of amount and type of fat on lipoproteins and hemostasis parameters in various demographic groups . DESIGN DELTA-1 was based on a randomized , blinded , crossover experimental design . Three diets were fed for 8 weeks to 103 healthy men and women aged 22 to 67 years at 4 field centers . Diet A , an average American diet , was designed to provide 37 % of energy from fat , 16 % of energy from saturated fatty acids ( SFAs ) ; diet B ( step 1 diet ) was designed to provide 30 % of energy from fat , 9 % of energy from SFA ; and diet C ( low SFA diet ) was designed to provide 26 % of energy from fat , 5 % of energy from SFA . Key features of diet standardization included central procurement of fat-containing foods , inclusion of standard ingredients , precision weighing of foods -- especially sources of fat and cholesterol -- and use of standardized written procedures . SETTING For menu validation , a set of 12 menus for each diet was prepared in duplicate and chemically assayed . For monitoring of diet composition during the study , an 8-day diet cycle ( 6 weekday and 2 weekend menus ) was sampled by every field center twice during each of 3 feeding periods . STATISTICAL ANALYSES Means ( +/- standard error ) were calculated and compared with target nutrient specifications . RESULTS DELTA-1 was able to provide a standardized diet that met nutrient specifications across 4 field centers over 24 weeks of participant feeding spanning a total of 8 months . APPLICATIONS Prestudy chemical validation of menus and continuous sampling and assay of diets throughout the study are essential to standardize experimental diets and to ensure that nutrient target goals are met and maintained throughout a controlled multicenter feeding study .

Three diets

Diet A ,

an average American diet

nutrient specifications

men

women


Improved survival with early intensification : combined results from the Medical Research Council childhood ALL randomised trials , UKALL X and UKALL XI . Medical Research Council Working Party on Childhood Leukaemia . The Medical Research Council ( MRC ) United Kingdom trial for childhood acute lymphoblastic leukaemia ( UKALL X ) randomised patients aged 0-14 years inclusive with an initial white blood count of less than 100 x 10 ( 9 ) /l to receive an early intensification block , a late intensification block , both , or neither . The next trial , UKALL XI , for children aged 1-14 years , randomised between different central nervous system ( CNS ) directed therapies . At the beginning of the trial , all patients were also randomised between late intensification alone and both early plus late blocks . The effects of both the early and the late block in UKALL X alone have been reported previously . This paper examines the effect of the addition of the early intensification block to treatment which included late intensification , combining the data from UKALL X and the first part of UKALL XI . Early intensification was associated with fewer bone marrow relapses and a reduction in the odds of death of 0.63 ( 95 % confidence interval : 0.46-0.87 ) . Survival was significantly improved with an increase at 5 years of 8 % , from 79 to 87 % . Following this demonstration that early intensification improves survival , the effect of a third intensification block is under investigation .

early intensification

an early intensification block

late intensification block

late intensification alone

both early plus late blocks

bone marrow relapses

death

Survival

randomised trials


Effect of pravastatin on cardiovascular events in women after myocardial infarction : the cholesterol and recurrent events ( CARE ) trial . OBJECTIVES We sought to determine the effect of pravastatin on recurrent cardiovascular events in women with average cholesterol levels after myocardial infarction ( MI ) . BACKGROUND Little information is available on the effectiveness of lipid lowering in secondary prevention of coronary heart disease ( CHD ) in women ; in particular , those with CHD and average cholesterol levels . METHODS In the Cholesterol and Recurrent Events ( CARE ) trial , 576 postmenopausal women , between 3 and 20 months after MI , with a total cholesterol level < 240 mg/dl and a low density lipoprotein cholesterol level 115 to 174 mg/dl , were randomized to receive pravastatin 40 mg/day or matching placebo for a median follow-up period of 5 years . The main outcome measures were combined coronary events ( coronary death , nonfatal MI , percutaneous transluminal coronary angioplasty [ PTCA ] or coronary artery bypass graft surgery [ CABG ] ) , the primary trial end point ( coronary death or nonfatal MI ) and stroke . RESULTS Women treated with pravastatin had a risk reduction of 43 % for the primary end point ( p = 0.035 ) , 46 % for combined coronary events ( p = 0.001 ) , 48 % for PTCA ( p = 0.025 ) , 40 % for CABG ( p = 0.14 ) and 56 % for stroke ( p = 0.07 ) . The 3,583 men in the CARE trial also showed a reduction in risk , but the magnitude tended to be less . Pravastatin improved plasma lipids similarly in men and women . There were no differences in risk of coronary events in the placebo group between men and women . Minor differences between men and women were present in baseline characteristics and treatment for MI , in general , conferring a higher risk status and a lower incidence of CABG in the women . CONCLUSIONS Pravastatin led to significant early reduction of a wide range of cardiovascular events in post-MI women with average cholesterol levels .

pravastatin

pravastatin

pravastatin 40 mg/day

placebo

Pravastatin

Pravastatin

cardiovascular events

recurrent cardiovascular events

risk reduction

risk

plasma lipids

risk of coronary events

women after myocardial infarction :


Glucosamine in serum of patients after myocardial infarction subjected to rehabilitation training . This paper presents results of 3 weeks physical training on glucosamine level in serum of male patients after myocardial infarction ( MI ) aged between 38 and 61 . Patients were randomised in two groups : the training group ( n = 21 ) , staying in Cardiac Rehabilitation Department and the control group ( n = 11 ) , discharged home for 3 weeks . Each group received identical dietary instructions . The training group performed exercises every day : on bicycle ergometer during 30 minutes ( 5 times a week ) , overall-conditioning exercises for 30 minutes daily and 30 to 60 minutes of walking each day . Before administering of the therapy and 3 weeks later all MI patients performed the bicycle ergometer exercise test until the ventilatory threshold was reached . Before that test and 3 minutes after its termination capillary and venous blood samples were drawn . In the capillary blood samples indices of acid-base balance , lactate level , and glucose level were determined . In venous blood samples the serum levels of immunoreactive insulin , C-peptide and glucosamine were determined as well as binding of 125I-insulin to erythrocyte receptors . Obtained results show that administered therapy increased physical fitness and decreased of glucosamine concentration , insulinaemia and insulin resistance .

rehabilitation training

physical training

discharged home

Glucosamine in serum

glucosamine level in serum

ventilatory threshold

physical fitness

after myocardial infarction

aged between 38 and 61

training group

control group ( n = 11


A double-blind , placebo-controlled study of risperidone in adults with autistic disorder and other pervasive developmental disorders . BACKGROUND Neurobiological research has implicated the dopamine and serotonin systems in the pathogenesis of autism . Open-label reports suggest that the serotonin2A-dopamine D2 antagonist risperidone may be safe and effective in reducing the interfering symptoms of patients with autism . METHODS Thirty-one adults ( age [ mean+/-SD ] , 28.1+/-7.3 years ) with autistic disorder ( n=17 ) or pervasive developmental disorder not otherwise specified ( n=14 ) participated in a 12-week double-blind , placebo-controlled trial of risperidone . Patients treated with placebo subsequently received a 12-week open-label trial of risperidone . RESULTS For persons completing the study , 8 ( 57 % ) of 14 patients treated with risperidone were categorized as responders ( daily dose [ mean+/-SD ] , 2.9+/-1.4 mg ) compared with none of 16 in the placebo group ( P < .002 ) . Risperidone was superior to placebo in reducing repetitive behavior ( P < .001 ) , aggression ( P < .001 ) , anxiety or nervousness ( P < .02 ) , depression ( P < .03 ) , irritability ( P < .01 ) , and the overall behavioral symptoms of autism ( P < .02 ) . Objective , measurable change in social behavior and language did not occur . Nine ( 60 % ) of 15 patients who received treatment with open-label risperidone following the double-blind placebo phase responded . Other than mild , transient sedation , risperidone was well tolerated , with no evidence of extrapyramidal effects , cardiac events , or seizures . CONCLUSION Risperidone is more effective than placebo in the short-term treatment of symptoms of autism in adults .

risperidone

placebo-controlled

risperidone

risperidone

risperidone

placebo

Risperidone

placebo

placebo

Risperidone

placebo

repetitive behavior

aggression

behavioral symptoms of autism

social behavior and language

mild , transient sedation

tolerated

extrapyramidal effects

cardiac events

seizures

autistic disorder

autism .

autism

Thirty-one

adults

autistic disorder

autism

adults


[ Pharmacokinetics of theophylline in sustained-release formulation in young asthmatics ] . Pharmacokinetics of two theophylline ( CAS 58-55-9 ) sustained release preparations ( T : Bronchoretard Capsules/R : Capsule formulation from the US market ) were investigated in an open randomised two-way crossover design . The capsules of the test formulation were opened and administered on a tablespoonful of apple sauce . Nineteen asthmatics aged 6 to 12 years participated in this study . Following individual dosing of 100-300 mg theophylline twice a day , a pharmacokinetic profile for 24 h was derived after seven days of multiple dosing . All relevant parameters for rate ( Cmax ss , Cmin ss , Cav ss , plateau time , peak-trough fluctuation , nocturnal excess , tmax ss ) and extent of absorption ( AUCss ) were calculated for both formulations . With long plateau times ( T : 17.3 h ) and small peak-trough fluctuations ( T : 49.0 % ) , established quality criteria for high quality theophylline preparations were fulfilled by the test formulation . Furthermore , symmetrical peaks resulted after morning and evening administration of the test formulation . In conclusion , smooth and predictable concentration/time profiles were achieved , enabling an efficacious and safe therapy of asthma . This individual mode of administration allows not only a perfect dose titration in young asthmatics , but is also helpful to patients who have difficulty in swallowing large dosage forms .

extent of absorption

plateau times

small peak-trough fluctuations

symmetrical peaks

concentration/time profiles

young asthmatics ]

Nineteen asthmatics aged 6 to 12 years


A prospective randomized study of transurethral resection of the prostate and transurethral vaporization of the prostate as a therapeutic alternative in the management of men with BPH . OBJECTIVE The common goals of new surgical treatment for benign prostatic hyperplasia ( BPH ) are to improve subjective and objective symptoms , to decrease the risk of postoperative complications and short hospitalization . Transurethral electrovaporization of the prostate ( TUVP ) is a new , minimally invasive and a promising alternative to standard transurethral resection of the prostate ( TURP ) in the treatment of BPH . The aim of this study is to compare the efficacy and safety of these two treatment alternatives . METHODS A prospective randomized trial of 60 patients with symptomatic BPH was performed . Preoperative and postoperative International Prostate Symptom Score ( IPSS ) , maximum flow rates ( Qmax ) and complications were recorded in each patient . The volume of the prostate was measured preoperatively and postoperatively using transrectal ultrasound . RESULTS Of the 30 patients who underwent TURP , mean hospital stay was 4.5 days . The Foley catheter was removed on postoperative day 4 following surgery . IPSS decreased from 21.6 to 5.2 , Qmax increased from 9.2 to 19.2 ml/s at 3 months . Mean prostatic volume at 3 months decreased from 51.7 to 26.2 g , a 49.3 % reduction . Of 30 patients undergoing TUVP , mean hospital stay was 2.5 days and the catheter was removed within 2 days following surgery . Postoperative urinary retention did not occur in any patient . IPSS decreased from 19.4 to 4.1 and Qmax increased from 7.9 to 17.7 ml/s at 3 months . Mean prostatic volume decreased from 48.9 to 27.8 g , a 43.1 % reduction at 3 months . In the TUVP group , none of the patients required blood transfusions or developed clinical transurethral resection syndrome . There were no major complications . Sphincteric incontinence , urethral strictures or bladder neck contractures were not recorded . At 3 months postoperatively , 13 patients in the TURP group and 7 patients in the TUVP group had retrograde ejaculation . CONCLUSION Our initial experience of TUVP suggests advantages over conventional TURP through reduced blood loss and shorter hospital stay . It appears to be an effective treatment for BPH ; however , long-term results should be evaluated .

benign prostatic hyperplasia

postoperative complications

efficacy and safety

complications

transrectal ultrasound

Foley catheter

IPSS

Mean prostatic volume

Postoperative urinary retention

IPSS

Mean prostatic volume

blood transfusions

no major complications

Sphincteric incontinence

urethral strictures

bladder neck contractures

retrograde ejaculation

reduced blood loss

shorter hospital stay

men with BPH .


White coat effect detected using self-monitoring of blood pressure at home : comparison with ambulatory blood pressure . The objective of the study was to investigate whether home blood pressure ( HBP ) is a reliable alternative to ambulatory blood pressure ( ABP ) for the detection of the white coat effect ( WCE ) . Hypertensive patients were randomized to measure HBP for 2 weeks or ABP for 24 h. The alternative measurement was then performed . Clinic blood pressure ( CBP ) was measured in the beginning and end of the study . Subjects with a difference of > or = 20 mm Hg systolic or > or = 10 mm Hg diastolic BP between CBP and awake ABP or CBP and HBP , were classified as clinic reactors . A total of 189 patients completed the study ( 79 on stable antihypertensive treatment ) . There was no difference in the magnitude of WCE assessed using the ABP or the HBP method ( mean discrepancy , systolic BP : -1.5 +/- 11.7 mm Hg , 95 % CI -3.2 , 0.2 ; diastolic BP : 0.9 +/- 7.0 , 95 % CI -0.1 , 1.9 ) . A strong association existed between WCE calculated using the HBP or the ABP method ( r = 0.64/0.59 systolic/diastolic , P < .001 ) . The proportion of patients classified as clinic reactors was identical using the HBP or the ABP method ( 25.9 % ) . Agreement between methods in the classification of clinic reactors was found in 147 patients ( 78 % ) . The sensitivity and specificity of the HBP method to classify correctly clinic reactors ( ABP method used as the standard ) were 57 % and 85 % , respectively , whereas its positive and negative predictive value were 57 % and 85 % . These results indicate that HBP is not appropriate as an alternative to ABP diagnostic testing in the detection of WCE . Nevertheless , HBP appears useful as a screening test for the detection of this phenomenon .

home blood pressure

blood pressure

Clinic blood pressure ( CBP )

WCE

ABP

HBP

systolic BP :

diastolic BP :

WCE

HBP

ABP

clinic reactors

clinic reactors

HBP

HBP

Hypertensive


The effect of quality and amount of dietary fat on the susceptibility of low density lipoprotein to oxidation in subjects with impaired glucose tolerance . OBJECTIVES We examined the effects of a high fat diet rich in monounsaturated fat ( MUFA-diet ) and a moderate fat diet rich in polyunsaturated fat ( PUFA-diet ) on the susceptibility of LDL to oxidation . SUBJECTS 29 subjects with impaired glucose tolerance . METHODS After consuming a run-in diet [ 37 % of energy ( E % ) fat , 18 E % saturated fat ] for three weeks , subjects were randomly assigned either to a MUFA-diet ( 40 E % fat , 19 E % monounsaturated fatty acids ) or a PUFA-diet ( 34 E % fat , 10 E % polyunsaturated fat ) for eight weeks . The susceptibility of LDL to oxidation was measured by challenging LDL with hemin and H2O2 and measuring the time for the reaction to reach maximum velocity . Results are expressed as lag time to oxidation in minutes . RESULTS In the PUFA-diet group ( n = 15 ) lag time tended to decrease during the experimental diet ( 97 +/- 28 vs 90 +/- 25 min , mean +/- s.d. , P = 0.073 ) , whereas in the MUFA-diet group ( n = 14 ) there was no significant change ( lag time 96 +/- 24 vs 100 +/- 16 min , P = 0.408 ) . The mean change in lag time was -7 +/- 14 min ( -7.2 % ) in the PUFA-diet group and +4 +/- 16 min ( +4.0 % ) in the MUFA-diet group ( P = 0.029 , PUFA-diet group vs MUFA-diet group ) . The alpha-tocopherol concentration in LDL increased significantly ( P < 0.01 ) in both diet groups relative to the run-in diet period , but LDL particle score did not change in either of the diet groups during the dietary intervention . In subjects with impaired glucose tolerance a PUFA-rich diet with a moderate amount of fat tended to increase the susceptibility of LDL to oxidation as compared to a higher fat diet rich in MUFA . Furthermore , the negative mean change in lag time to oxidation found in the PUFA-diet group differed significantly from the slightly positive mean change found in the MUFA-diet group .

PUFA-rich

MUFA

effect

susceptibility of LDL to oxidation

susceptibility of LDL to oxidation

lag time to oxidation

lag time

mean change in lag time

alpha-tocopherol concentration in LDL

LDL particle score

susceptibility of LDL to oxidation

lag time to oxidation

impaired glucose tolerance


Impact of work site health promotion on stages of dietary change : the Working Well Trial . The stages of change construct has been applied to healthful dietary behavior in cross-sectional studies . This report examines associations of stages of change with diet prospectively and addresses whether ( 1 ) baseline stage of change predicts participation , ( 2 ) forward changes in stage movement were greater in treatment work sites , and ( 3 ) change in stage was associated with adoption of healthful diets , using data from a cohort of 11,237 employees . Findings indicate that persons in later stages of change reported higher participation levels . Employees from intervention work sites who were in preaction stages at baseline were much more likely to shift into action and maintenance stages than controls . Changes in dietary stage of change were associated with decreases in fat intake and increases in fiber , fruit and vegetable intake . Net change in diet due to the intervention was modest . Stage of change appears to be useful for understanding mediators of health promotion intervention effectiveness .

work site health promotion

decreases in fat intake

stages of dietary change

a cohort of 11,237 employees

persons in later stages of change

controls


The Treatment of Lead-exposed Children ( TLC ) trial : design and recruitment for a study of the effect of oral chelation on growth and development in toddlers . Exposure to lead impairs cognitive development in young children , but the benefits of lowering blood lead pharmacologically are not clear . This report describes the design , recruitment , enrolment and baseline results of the Treatment of Lead-Exposed Children ( TLC ) trial , a randomised , multicentre , placebo-controlled , double-blind clinical trial of the effects of treating lead-exposed children with succimer , a drug that enhances urinary excretion of lead , on cognitive , behavioural and physical development . TLC clinical sites were in Baltimore , Cincinnati and Columbus , Newark and Philadelphia . Children were eligible for TLC if they were between 12 and 33 months of age , had a confirmed blood lead concentration between 20 and 44 micrograms/dL and lived in a residence suitable for lead dust reduction . Randomised children received up to three 26-day courses of succimer or placebo , and were then followed for 3 years . The study can detect a three-point difference in full-scale IQ at 3-year follow-up . Statistical power for the other end points is more difficult to estimate . A total of 1854 children were evaluated and 780 children were randomised between August 1994 and January 1997 . The mean age of randomised children was 24 months and mean blood lead level 26 micrograms/dL . Three-quarters were African-American . Most children had poor , single mothers who had completed 12 or fewer years of school and who lived in older , poorly maintained residences .

oral chelation

succimer

succimer

placebo

full-scale IQ

Lead-exposed Children ( TLC )

toddlers .


Comparison of prostate-specific antigen corrected for total prostate volume and transition zone volume in a population-based screening study . OBJECTIVES To compare the discriminatory potential between prostate cancer and benign conditions of the prostate in a population-based screening study , of serum prostate-specific antigen levels ( PSA ) and PSA corrected for both the total prostate volume ( PSA-D ) and the transition zone volume ( PSA-T ) . METHODS In a randomized population-based screening study ( Rotterdam section of the European Randomized Study of Screening for Prostate Cancer ) , in which 10,865 men have been screened , the biopsy results of 1202 men with PSA levels of 4 ng/mL or more were evaluated . Planimetric and prolate ellipsoid volumes of the total prostate as well as of the transition zone were measured . The measured volumes were compared with the volumes of 57 radical prostatectomy specimens through Spearman 's rank correlation coefficient and agreement tests . A receiver operating characteristic ( ROC ) curve analysis was done of sensitivity and specificity of biopsy indications through PSA and PSA corrected for the volumes measured with transrectal ultrasound . RESULTS In the 1202 men studied , 361 cases of prostate cancer were diagnosed . Both PSA-D and PSA-T showed a significantly higher area under the ROC curve ( 0.77 and 0.79 , respectively ) than PSA alone ( area 0.65 ) . There was no significant difference between PSA-D and PSA-T . The use of a PSA-D threshold value of 0 . 10 ng/mL/cc would have avoided 28 % of biopsies at the cost of 10 % of detectable cancers . A PSA-D threshold of 0.15 ng/mL/cc would have avoided 73.8 % of biopsies at the cost of not diagnosing 43.8 % of detectable cancers . CONCLUSIONS The planimetrically obtained prostate volume showed a more favorable agreement with the radical prostatectomy volume than the prolate ellipsoid volume . The discriminatory potential of the corrected PSA value is better at predicting the results of needle biopsy of the prostate when compared with PSA alone . The use of the transition zone volume for this correction results in a higher discriminatory potential when compared to the use of the total prostate volume ; however , the observed difference was not statistically significant .

transition zone volume

biopsy

transition zone volume

total prostate volume

area under the ROC curve

PSA value

PSA levels


Pelvic lymphocysts following retroperitoneal lymphadenectomy : retroperitoneal partial " no-closure " for ovarian and endometrial cancers . BACKGROUND AND OBJECTIVES Pelvic lymphocysts have been reported mainly following pelvic lymphadenectomy for cervical cancer . We attempted to assess whether retroperitoneal partial " no-closure " reduces the incidence of lymphocyst formation following retroperitoneal lymphadenectomy . METHODS Sixty-one patients with ovarian cancer or endometrial cancer who underwent retroperitoneal lymph node resection were assigned at random to a retroperitoneal partial " no-closure " group or a " closure " group . The incidence of lymphocysts in the two groups as determined using ultrasonography was compared . RESULTS Lymphocysts appeared in 23/61 patients ( 38 % ) in total . In the " closure " group , the incidence was 52 % ( 16/31 ) , but in the " no-closure " group it was only 23 % ( 7/30 ) ; the incidence in the " no-closure " group was significantly lower ( P < 0.05 ) . The incidence of postoperative fever was 17 % ( 5/30 ) in the " no-closure " group , which was lower than that in the " closure " group ( 42 % , 13/31 ) , but not significantly so ( P < 0.1 ) . No patients in the " no-closure " group required surgical procedures such as needle aspiration or cyst drainage . CONCLUSIONS Retroperitoneal partial " no-closure " appears to be a useful procedure for reducing the incidence of pelvic lymphocysts associated with retroperitoneal lymphadenectomy .

retroperitoneal partial " no-closure "

retroperitoneal partial " no-closure "

a "

closure " group

Retroperitoneal partial " no-closure

lymphocyst formation

lymphocysts

Lymphocysts

postoperative fever

pelvic lymphocysts

Sixty-one

ovarian cancer

endometrial cancer

retroperitoneal lymph node resection


Therapy effect of either paclitaxel or cyclophosphamide combination treatment in patients with epithelial ovarian cancer and relation to TP53 gene status . Cell death after treatment with chemotherapy is exerted by activation of apoptosis , and the p53 protein has been shown to actively participate in this process . This recent focus on TP53 status as a possible determinant of cancer therapy response has raised the question of whether or not mutations in the TP53 gene have an influence on paclitaxel therapy . The TP53 status has been analysed at the DNA level in tumours from 45 ovarian cancer patients randomized to treatment with paclitaxel and cisplatin or cyclophosphamide and cisplatin . Therapy response was obtained for 38 patients with clinically evaluable disease after initial surgery . The positive response rate to the paclitaxel/cisplatin therapy was 85 % vs 61 % for the patients who received the cyclophosphamide/cisplatin regimen . A significant difference in relapse-free survival in favour of paclitaxel/cisplatin chemotherapy was found ( P = 0.001 ) . A total of 33 tumour samples ( 73 % ) had detectable sequence alterations in the TP53 gene . When relapse-free survival was estimated for all patients with TP53 alterations in their tumours , a significant better outcome for the paclitaxel/cisplatin group was found compared with the patient group receiving cyclophosphamide and cisplatin therapy ( P = 0.002 ) . We did not observe an association between TP53 tumour status and prognosis for patients who received paclitaxel/cisplatin combination treatment , indicating that the effect of this therapy is not influenced by this parameter .

chemotherapy

paclitaxel

paclitaxel

cyclophosphamide

cisplatin

paclitaxel/cisplatin

cyclophosphamide/cisplatin

paclitaxel/cisplatin chemotherapy

paclitaxel/cisplatin

cyclophosphamide

cisplatin

paclitaxel/cisplatin

Therapy effect

TP53 status

TP53 status

Therapy response

positive response rate

relapse-free survival

sequence alterations in the TP53 gene

relapse-free survival

TP53 alterations

TP53 tumour status

epithelial ovarian cancer

ovarian cancer


Postoperative injection of phenylbutazone does not influence fibrinolytic shutdown . Twenty-nine patients undergoing cholecystectomy because of chronic calculous cholecystitis were randomised to receive phenylbutazone 10 mg/kg intramuscularly or a control injection ( vehicle-containing local anaesthetic ) immediately after completion of surgery . Fibrinogen and plasminogen concentrations in plasma , plasminogen activator inhibitor activity in plasma and fibrinolytic activity in concentrated euglobulins were determined before surgery and on the first , third and seventh postoperative days . Phenylbutazone delayed the postoperative rise of fibrinogen concentration and reduced the plasminogen level on the first day after surgery . Fibrinolytic activity in euglobulins was decreased after the operation in both groups . The great dispersion of the results of plasminogen activator inhibitor activity was the plausible cause of the lack of any significant difference in this variable . The postoperative fibrinolytic shutdown , reflected by the decrease of fibrinolytic activity , was unaffected by phenylbutazone . It can be speculated , however , that the decline of plasminogen concentration after surgery in patients receiving this drug was the result of its stimulatory influence on the conversion of plasminogen into plasmin .

phenylbutazone

phenylbutazone 10 mg/kg intramuscularly

control injection

Phenylbutazone

phenylbutazone .

fibrinolytic shutdown

rise of fibrinogen concentration

plasminogen level

Fibrinolytic activity in euglobulins

postoperative fibrinolytic shutdown

fibrinolytic activity

plasminogen concentration

Twenty-nine

chronic calculous cholecystitis


Incidence and time course of cardiovascular side effects during spinal anesthesia after prophylactic administration of intravenous fluids or vasoconstrictors . UNLABELLED We studied the time course of arterial hypotension and/or bradycardia requiring treatment during spinal anesthesia and compared the efficacy of i.v . fluid or vasoconstrictor administration for the prevention of these side effects . Patients ( n = 1066 ) were randomly allocated to either a volume group ( lactated Ringer 's solution 15 mL/kg within 15 min before spinal anesthesia ) , a dihydroergotamine group ( 10 microg/kg i.m . 15 min before anesthesia ) , or a placebo group . All patients breathed O2-enriched air during spinal anesthesia ( 4 mL of plain 0.5 % bupivacaine ) . With the placebo , there were side effects ( mean incidence 22.9 % ) for up to 45 min after the start of anesthesia . Dihydroergotamine reduced the incidence of side effects , preferentially the late ones , more ( mean incidence 11.8 % ) than fluid administration ( mean incidence 16.9 % ) , which was effective only during the first 15 min of anesthesia . Both heart rate and arterial pressure decreased within 15 min before the manifestation of symptoms . In a subgroup of patients , the incidence of side effects ( 8 % ) was greatly reduced by the intraoperative application of both sedatives and opioids . We conclude that cardiovascular side effects may occur at any time during spinal anesthesia . Fluid administration reduced the incidence of early events , but dihydroergotamine the late events . IMPLICATIONS Cardiovascular side effects requiring treatment occurred at any time during spinal anesthesia in our placebo-controlled study , regardless of the prophylactic regimen ( fluid infusions versus dihydroergotamine ) .

spinal anesthesia

intravenous fluids

vasoconstrictors

fluid

vasoconstrictor

lactated Ringer 's solution

dihydroergotamine

anesthesia

placebo group

spinal anesthesia

bupivacaine

placebo

Dihydroergotamine

placebo-controlled

fluid infusions

dihydroergotamine

cardiovascular side effects

side effects

incidence of side effects

incidence of side effects

cardiovascular side effects

incidence of early events

late events .

Cardiovascular side effects

spinal anesthesia


Laser therapy combined with brachytherapy for the palliation of malignant dysphagia . BACKGROUND/AIM OF STUDY Laser therapy is effective in relieving malignant dysphagia , but repeated treatments at 4 to 6 week intervals are usually required . This prospective randomised trial is designed to determine if addition of brachytherapy offers any advantages over laser therapy alone . METHODS Patients with inoperable carcinoma of the oesophagus were randomised to receive either endoscopic Nd : YAG laser therapy alone , or laser followed by brachytherapy . Patients who developed worsening dysphagia during follow-up were offered further treatment as appropriate . RESULTS Fourteen patients were randomised to receive laser only , and 12 to receive laser followed by brachytherapy . Of these 12 , one was lost to follow-up and four did not receive brachytherapy because they were unfit , had extension into the cardia or had mainly extrinsic compression . These 4 are included on an 'intention-to-treat ' basis . The mean therapeutic interval for the brachytherapy group was significantly longer , 83 days compared to 36 days for the laser group ( p = 0.026 ) . There were no differences in the degree of dysphagia relief , number of endoscopic procedures or survival times . CONCLUSION The preliminary results of this trial suggest that brachytherapy in addition to laser therapy prolongs the first therapeutic interval . However , no long-term advantages have been shown .

Laser therapy

laser therapy

endoscopic Nd : YAG laser therapy

laser

brachytherapy

laser only

brachytherapy

brachytherapy

brachytherapy

malignant dysphagia

mean therapeutic interval

degree of dysphagia relief

number of endoscopic procedures

survival times


Combined modality therapy in advanced Hodgkin 's disease : a report on 218 patients with a median follow-up of eight years . BACKGROUND AND OBJECTIVE This study was designed to evaluate the efficacy and toxicity of monthly alternating ABVD/MOPP compared to ABVD/OPP regimens in patients with advanced stage Hodgkin 's disease ( HD ) , as well as in early stage patients with systemic symptoms and/or bulky disease . DESIGN AND METHODS 218 patients with previously untreated HD entered this study : 106 patients in arm A ( ABVD/MOPP ) and 112 in arm B ( ABVD/OPP ) . Patients received eight courses of one of the two regimens after stratification according to the stage . Patients in complete remission ( CR ) received 20 Gy to the involved field and 40 Gy to the spleen . The actuarial survival curves were performed according to Kaplan and Meier . RESULTS No statistically significant differences were observed between the two arms in terms of CR rate and toxicity . However , analysis of total relapses revealed that patients treated with ABVD/OPP had a significantly higher likelihood of achieving a second CR compared to patients who entered the ABVD/MOPP arm . INTERPRETATION AND CONCLUSIONS Both schemes of chemotherapy followed by radiotherapy produce high percentages of CR , low risk of relapse and an acceptable toxicity .

Combined modality therapy

ABVD/MOPP compared to ABVD/OPP

( ABVD/MOPP )

ABVD/OPP

efficacy and toxicity

actuarial survival curves

CR rate

toxicity

total relapses

second CR

CR

low risk of relapse

acceptable toxicity

HD

106 patients

arm A ( ABVD/MOPP

arm B ( ABVD/OPP ) .

ABVD/MOPP arm


The influence of sequential annual vaccination and of DHEA administration on the efficacy of the immune response to influenza vaccine in the elderly . The present study examined the effect of repeated vaccination and of dehydroepiandrosterone ( DHEA ) treatment on the immune response to influenza vaccine in elderly subjects . Seventy-one elderly volunteers , aged 61-89 years , enrolled in a prospective randomized , double-blind study to receive either DHEA ( 50 mg qd p.o . for 4 consecutive days starting 2 days before immunization ) or placebo . Antibody response against the three strains of vaccine was measured before and 28 days after vaccination , and compared between previously vaccinated and non-vaccinated subjects . DHEA treatment did not enhance established immunity . A significant decrease in attainment of protective antibody titer ( titer of 1:40 or greater ) against A/Texas in subjects with non-protective baseline antibody titer was recorded following DHEA treatment compared to placebo ( 52 vs. 84 % , P < 0.05 ) . Post-immunization titers against influenza A strains were significantly higher in those subjects who were never immunized before . Additionally , post-vaccination protective titers against the A/Johannesburg strain were more prevalent in those subjects who were never vaccinated before . The results were not the same for anti-B/Harbin antibodies-repeated vaccination caused a non-significant increase in HI titer in previously vaccinated subjects .

vaccination

DHEA administration

vaccination

dehydroepiandrosterone ( DHEA )

influenza vaccine

DHEA

placebo .

DHEA treatment

DHEA treatment

established immunity .

protective antibody titer

Post-immunization titers

post-vaccination protective titers

influenza vaccine

elderly

elderly

Seventy-one

elderly

61-89 years


Aspartame : neuropsychologic and neurophysiologic evaluation of acute and chronic effects . BACKGROUND Neurobehavioral symptoms have been reported anecdotally with aspartame . OBJECTIVE This study sought to determine whether aspartame can disrupt cognitive , neurophysiologic , or behavioral functioning in normal individuals . DESIGN Forty-eight healthy volunteers completed a randomized , double-blind , placebo-controlled , crossover study . The first month was aspartame free . Subjects then consumed sodas and capsules with placebo , aspartame , or sucrose for 20 d each . Order was randomized and subjects were assigned to either a high- ( 45 mg x kg body wt ( -1 ) x d ( -1 ) ) or low- ( 15 mg x kg body wt ( -1 ) x d ( -1 ) ) dose aspartame group . Neuropsychologic and laboratory testing was done on day 10 of each treatment period to determine possible acute effects and on day 20 for possible chronic effects . RESULTS Plasma phenylalanine concentrations increased significantly during aspartame treatment . Neuropsychologic results ; adverse experiences ; amino acid , insulin , and glucose values ; and electroencephalograms were compared by sex and by treatment . No significant differences were found for any dependent measure . CONCLUSION Large daily doses of aspartame had no effect on neuropsychologic , neurophysiologic , or behavioral functioning in healthy young adults .

Aspartame

aspartame

aspartame

placebo-controlled

aspartame

sodas and capsules with placebo

aspartame

sucrose

aspartame

aspartame

behavioral functioning

Forty-eight

healthy

young adults


Behavioral changes in autistic individuals as a result of wearing ambient transitional prism lenses . A double-blind crossover design was used to assess the efficacy of wearing ambient lenses to reduce the behavioral symptoms of autism . Eighteen autistic individuals , ranging in age from 7 to 18 years , participated in the study . Behavior , attention , and orientation were evaluated at 1 1/2 months , 2 months , 3 months , and 4 months . Compared to the placebo condition , the results showed a decrease in behavior problems at the 1 1/2 and 2 month assessment periods and a slight loss of these benefits at the 3 and 4 month assessment periods . These findings support the prediction that ambient lenses , worn without engaging in visual-motor exercises , have positive effects on autistic individuals .

ambient transitional prism lenses

wearing ambient lenses

placebo

ambient lenses

Behavioral changes

Behavior , attention , and orientation

behavior problems


Conservative treatment of plantar fasciitis . A prospective study . A randomized , prospective study was conducted to compare the individual effectiveness of three types of conservative therapy in the treatment of plantar fasciitis . One hundred three subjects were randomly assigned to one of three treatment categories : anti-inflammatory , accommodative , or mechanical . Subjects were treated for 3 months , with follow-up visits at 2 , 4 , 6 , and 12 weeks . For the 85 patients who completed the study , a statistically significant difference was noted between groups , with mechanical treatment with taping and orthoses proving to be more effective than either anti-inflammatory or accommodative modalities .

Conservative treatment

conservative therapy

anti-inflammatory

accommodative modalities .

individual effectiveness

plantar fasciitis

One hundred three