Comparison of the comet assay and the oxygen microelectrode for measuring tumor oxygenation in head-and-neck cancer patients . PURPOSE To compare the Eppendorf PO2 histograph and the alkaline comet assay as methods of measuring tumor hypoxia in patients with head-and-neck squamous cell carcinomas . MATERIALS AND METHODS As part of a larger clinical trial , 65 patients with head-and-neck squamous cell carcinoma nodal metastasis underwent tumor oxygenation measurements with Eppendorf PO2 histographs and comet assays , performed on fine-needle aspirates at 1 and 2 min after 5 Gy . Fifty-four patients had sufficient tumor cells for comet analysis at 1 min and 26 at both 1 and 2 min . Individual cells were examined for DNA single-strand breaks by alkaline gel electrophoresis , and the distribution of values was quantified using median tail moment ( MTM ) . Nonirradiated tumor cells from pretreatment fine-needle aspirates received 5 Gy in vitro to establish the oxygenated response . RESULTS There was a significant correlation between the 1- and 2-min MTM ( slope = 0.77 +/- 0.03 ) . There was no relationship between DNA damage in tumor cells irradiated in vitro and in vivo . No correlation was found between Eppendorf PO2 measurements and comet MTM . There was a statistically significant correlation between the treatment response in the node studied and comet MTMs , whereas no correlation was observed between treatment response and Eppendorf measurements . CONCLUSIONS Comet assays are reproducible , as shown by biopsies at 1 and 2 min . Intertumor variation in the MTM is not a result of intrinsic radiosensitivity but of tumor hypoxia . There was no correlation between Eppendorf PO2 measurements and comet MTM . Comet assays were better than Eppendorf in predicting treatment response as an end point for short-term outcome . Longer follow-up is needed to determine the role of the comet assay as a predictor for locoregional tumor control and survivals .

Eppendorf PO2 histograph

alkaline comet assay

tumor oxygenation measurements with

Eppendorf PO2 histographs

and

comet assays

5 Gy in vitro

tumor oxygenation

tumor hypoxia

DNA damage in tumor cells

head-and-neck cancer

head-and-neck squamous cell carcinomas

65 patients

head-and-neck squamous cell carcinoma

Fifty-four patients


The utility of laparoscopy in the diagnosis of acute appendicitis in women of reproductive age . AIM To see whether laparoscopy improves the accuracy of a clinical diagnosis of acute appendicitis in women of reproductive age , and to determine what the long-term sequelae are of not removing an appendix deemed at laparoscopy to be normal . METHOD The initial part of the study was undertaken during 1991-1992 . Female patients between 16 and 45 years were eligible for inclusion once a clinical decision had been made to perform an appendicectomy for suspected acute appendicitis . Following consent , patients were randomized into two groups . One group had open appendicectomy , as planned . The other group had laparoscopy , followed by open appendicectomy only if the appendix was seen to be inflamed or was not visualized . The end points for the study were the clinical outcomes of all patients , and the results of histology , where appropriate . An attempt was made to contact all patients at 10 years to determine whether they had had a subsequent appendicectomy , or had been diagnosed with another abdominal condition that might be relevant to the initial presentation in 1991-1992 . RESULTS Laparoscopic assessment was correct in all cases in which the appendix was visualized . Diagnostic accuracy was improved from 75 % to 97 % . Laparoscopy was associated with no added complications , no increase in hospital stay in patients who went on to appendicectomy , and a reduction in hospital stay for those who underwent laparoscopy alone . No patients developed a problem over the 10-year follow-up period from having a normal-looking appendix not removed at laparoscopy . CONCLUSION Laparoscopic assessment of the appendix is reliable , and to leave a normal-looking appendix at laparoscopy does not appear to cause any long-term problems .

laparoscopy

open appendicectomy

laparoscopy

open appendicectomy

histology

Diagnostic accuracy

no added complications

no increase in hospital stay

reduction in hospital stay


Efficacy of second versus third generation oral contraceptives in the treatment of hirsutism . OBJECTIVE To compare second versus third generation combination oral contraceptives ( OCs ) in the treatment of hirsutism . METHODS Women with hirsutism , as defined by a minimum Ferriman-Gallwey score of 10 , were randomized in a double-blind fashion to receive an OC containing either ethinyl estradiol/desogestrel or ethinyl estradiol/levonorgestrel for 9 months of treatment . Ferriman-Gallwey scores , androgen levels and sex hormone-binding globulin were measured at baseline and every 3 months for the duration of the study . Hormones were measured in duplicate by radioimmunoassay . RESULTS Of the 47 women enrolled , 24 were randomized to ethinyl estradiol/desogestrel and 23 were randomized to ethinyl estradiol/levonorgestrel . Mean sex hormone-binding globulin increased significantly in subjects using the desogestrel-containing contraceptive compared with the levonorgestrel-containing contraceptive . Ten subjects completed the 9 months of treatment in the levonorgestrel group and 11 completed the study in the desogestrel group . Mean free testosterone and 3alpha-androstanediol glucuronide decreased significantly in the group receiving ethinyl estradiol/desogestrel but not in the ethinyl estradiol/levonorgestrel group . Mean Ferriman-Gallwey scores decreased significantly in both treatment groups . Improvement in mean Ferriman-Gallwey score was 35.7 +/- 38.1 % ( p < 0.001 ) for the ethinyl estradiol/desogestrel arm and 33.4 +/- 27.3 % ( p < 0.001 ) for the ethinyl estradiol/levonorgestrel arm . There were no statistically significant differences found in the improvement of Ferriman-Gallwey scores between the two treatment arms , although the power to detect a difference was limited by the small sample size . CONCLUSIONS Treatment of hirsute women with third generation OCs containing desogestrel results in a significant increase in sex hormone-binding globulin and decrease in free testosterone and 3alpha-androstanediol glucuronide . Both second and third generation OCs were clinically effective in treating hirsutism .

oral contraceptives

ethinyl estradiol/desogestrel

ethinyl estradiol/levonorgestrel

ethinyl estradiol/desogestrel

ethinyl estradiol/levonorgestrel .

desogestrel-containing contraceptive

levonorgestrel

desogestrel

ethinyl estradiol/desogestrel

ethinyl estradiol/levonorgestrel

ethinyl estradiol/desogestrel

ethinyl estradiol/levonorgestrel

third generation

OCs

desogestrel

OCs

Ferriman-Gallwey scores

androgen levels

sex hormone-binding globulin

Hormones

Mean sex hormone-binding globulin

Mean free testosterone

3alpha-androstanediol glucuronide

Mean Ferriman-Gallwey scores

Ferriman-Gallwey score

Ferriman-Gallwey scores

sex hormone-binding globulin

free testosterone

3alpha-androstanediol glucuronide


Phase III trial comparing whole-pelvic versus prostate-only radiotherapy and neoadjuvant versus adjuvant combined androgen suppression : Radiation Therapy Oncology Group 9413 . PURPOSE This trial tested the hypothesis that combined androgen suppression ( CAS ) and whole-pelvic ( WP ) radiotherapy ( RT ) followed by a boost to the prostate improves progression-free survival ( PFS ) by 10 % compared with CAS and prostate-only ( PO ) RT . This trial also tested the hypothesis that neoadjuvant and concurrent hormonal therapy ( NCHT ) improves PFS compared with adjuvant hormonal therapy ( AHT ) by 10 % . MATERIALS AND METHODS Eligibility included localized prostate cancer with an elevated prostate-specific antigen ( PSA ) < or = 100 ng/mL and an estimated risk of lymph node ( LN ) involvement of 15 % . Between April 1 , 1995 , and June 1 , 1999 , 1,323 patients were accrued . Patients were randomly assigned to WP + NCHT , PO + NCHT , WP + AHT , or PO + AHT . Failure for PFS was defined as the first occurrence of local , regional , or distant disease ; PSA failure ; or death for any cause . RESULTS With a median follow-up of 59.5 months , WP RT was associated with a 4-year PFS of 54 % compared with 47 % in patients treated with PO RT ( P =.022 ) . Patients treated with NCHT experienced a 4-year PFS of 52 % versus 49 % for AHT ( P =.56 ) . When comparing all four arms , there was a progression-free difference among WP RT + NCHT , PO RT + NCHT , WP RT + AHT , and PO RT + AHT ( 60 % v 44 % v 49 % v 50 % , respectively ; P =.008 ) . No survival advantage has yet been seen . CONCLUSION WP RT + NCHT improves PFS compared with PO RT and NCHT or PO RT and AHT , and compared with WP RT + AHT in patients with a risk of LN involvement of 15 % .

radiotherapy

adjuvant hormonal therapy ( AHT )

NCHT

AHT

PO RT + AHT

WP RT + NCHT

PO RT

NCHT

PO RT

AHT

WP RT + AHT

progression-free survival ( PFS )

Failure for PFS

death

4-year PFS

4-year PFS

progression-free difference

survival advantage

PFS


Systematic approach to benign paroxysmal positional vertigo in the elderly . OBJECTIVE We evaluated the effectiveness of a management approach that combines the canalith repositioning maneuver ( CRM ) and vestibular rehabilitation ( VR ) in the treatment of benign positional paroxysmal vertigo ( BPPV ) in elderly persons . STUDY DESIGN AND SETTING Forty-seven patients ( > /=70 years old ) with the diagnosis of unilateral posterior semicircular canal BPPV formed the study population . This study has 2 parts . In the first part , patients were randomly assigned to 1 of 2 groups : the CRM and avoidance ( no treatment ) . Patients were evaluated 1 month after the first visit . Those patients not responding to treatment were enrolled in the second part of the study , treated with an individualized combination of CRM and VR , and then reevaluated 3 months later . RESULTS Statistically significant improvement of vertigo and provoked nystagmus in 64 % of patients in the CRM group compared with the no-treatment group . After the addition of VR , 77 % of all patients improved . CONCLUSION A combination of CRM and VR improves BPPV in the elderly . SIGNIFICANCE These findings suggest that although CRM is more effective than no treatment , VR can be added to improve the results in the treatment of BPPV .

Systematic approach

CRM and avoidance ( no treatment )

vertigo

provoked nystagmus

VR

BPPV


Preservative-free ocular hydrating agents in symptomatic contact lens wearers : saline versus PVP solution . PURPOSE To compare two preservative-free hydrating agents , in multidose ( ABAK ) bottles , in contact lens wearers experiencing symptoms of ocular dryness . METHODS The endpoint of this 4-week multicenter , randomized , double-blind , parallel-group study comparing a 2 % polyvinylpyrrolidone ( PVP ) solution with a 0.9 % NaCl solution was to assess ocular discomfort using a visual analog scale . A biomicroscopic examination and a test of tolerability on instillation were also performed , and adverse events were recorded . RESULTS Thirty-nine subjects were enrolled ( 23 PVP ; 16 NaCl ) . The average age was 30 ; subjects were predominantly female , and mostly wore frequent-replacement contact lenses . They were all exposed to environmental factors such as routine use of video monitors or air conditioning . The two groups were similar at baseline ( D0 ) . Both PVP and NaCl improved the comfort of contact lens wear ( P = 0.0003 ) , with no difference between them ( P = 0.25 ) . The mean daily duration of lens wear and the daily number of instillations to relieve discomfort ( 4.2 +/- 2.0 for PVP ABAK ; 4.6 +/- 1.9 for NaCl ABAK ) were comparable . However , PVP use led to more favorable evolution of fluorescein-staining corneal punctuations ( P = 0.028 ) . Safety was good , with minimal adverse events considered unrelated to the products . Lens wettability was excellent , and there were no clinically relevant deposits . Most subjects also found the ABAK bottles convenient . CONCLUSIONS Ocular hydration improves comfort in contact lens wearers . NaCl is an appropriate first-line treatment , but for subjects with fluorescein-staining punctuations , lubrication with PVP is preferable .

saline

PVP solution

preservative-free hydrating agents

0.9 % NaCl solution

PVP

NaCl

PVP

NaCl

PVP

NaCl

PVP

ocular dryness

comfort of contact lens wear

Safety

adverse events

Lens wettability

symptomatic contact lens wearers

contact lens wearers

ocular dryness

Thirty-nine

female


Short-term effects of prednisolone and dexamethasone on circulating concentrations of leptin and sex hormone-binding globulin in children being treated for acute lymphoblastic leukaemia . OBJECTIVE Disturbances in body weight regulation are often encountered during glucocorticoid treatment and are associated with increased insulin resistance and truncal fat accumulation . Children were investigated who were receiving glucocorticoid treatment for acute lymphoblastic leukaemia ( ALL ) . They were randomized to receive either prednisolone or dexamethasone as part of induction of remission . This randomization process provided a suitable opportunity to compare the effects of these two administered steroid on surrogate markers of adipocyte activity ( leptin ) and hyperinsulinaemia/insulin resistance ( SHBG ) . DESIGN AND PATIENTS Prospective study over 16 weeks of children randomized to receive prednisolone ( 40 mg/m2 ) or dexamethasone ( 6.5 mg/m2 ) as part of the MRC-ALL97/99 induction chemotherapy for ALL . Nineteen children ( 8 male , 11 female ) with a median age 5.9 years ( range 2.6-13 years ) were recruited into the study . Main outcome measures were body mass index ( BMI ) , serum leptin and sex hormone binding globulin ( SHBG ) . RESULTS Glucocorticoid administration for 5 weeks resulted in significant ( P < 0.05 ) increases in BMI , leptin ( corrected for BMI ) and the leptin : SHBG ratio and lowering of SHBG . Dose for dose , dexamethasone was significantly more potent than prednisolone in altering these parameters . CONCLUSIONS Short-term glucocorticoid treatment has significant effects on BMI , leptin and SHBG . The leptin : SHBG ratio increase indicates that this may be a novel and sensitive biochemical marker of metabolic change . Our results suggest that glucocorticoid treatment regimens should be kept as short as possible to avoid possible detrimental effects associated with increased adiposity and insulin resistance .

prednisolone

dexamethasone

glucocorticoid

glucocorticoid

prednisolone

dexamethasone

prednisolone

dexamethasone

induction chemotherapy

dexamethasone

prednisolone

glucocorticoid

body mass index ( BMI )

BMI

children

acute lymphoblastic leukaemia

Children

acute lymphoblastic leukaemia ( ALL )

children

Nineteen

children

male

female

5.9 years


Changing Childbirth : a pilot project . OBJECTIVE To compare the outcomes of an adapted pilot Changing Childbirth initiative providing continuity of care by a group of known midwives with traditional maternity care . DESIGN Between-groups trial to compare levels of satisfaction and clinical outcomes for two groups of women , cared for either under this Changing Childbirth scheme or the traditional model of care . METHOD Of the 200 women who agreed to participate in the project , 100 were randomly allocated to the pilot scheme and 100 to the traditional care package . During the postpartum period , information was collected via a questionnaire about participants ' levels of satisfaction with a variety of aspects of care provided during the antenatal , delivery and postpartum periods . Data about clinical outcomes for the two groups were also obtained . RESULTS Women in the pilot group had significantly more continuity of care throughout each of the three periods , were generally more satisfied with their care , felt that they had more choice over a variety of aspects of care and experienced no compromise in clinical outcomes ( P = 0.05 or less in each case ) . IMPLICATIONS FOR PRACTICE Many previous attempts to introduce the Changing Childbirth initiative have revealed significant problems , particularly with regard to the continuity of carer requirement . Taking account of local health care needs and existing provision , the present study adapted this concept to continuity of care . This did not apparently affect any of the guiding principles contained in the original document , and yet enhanced satisfaction . It would appear that the Changing Childbirth agenda can be adapted and integrated with local health care situations without sacrificing any of the overarching principles .

pilot scheme

traditional care package

continuity of care

satisfied

more choice

variety of aspects of care

compromise


Stapled mucosectomy for acute thrombosed circumferentially prolapsed piles : a prospective randomized comparison with conventional haemorrhoidectomy . OBJECTIVE Stapled mucosectomy has been developed as an alternative to conventional haemorrhoidectomy for the elective treatment of haemorrhoids , but has not been assessed in the emergency setting . The aim of this study was to compare this technique with a conventional procedure for acute thrombosed circumferential prolapsed haemorrhoids . PATIENTS AND METHODS A prospective randomized comparison of conventional Milligan-Morgan haemorrhoidectomy and stapled mucosectomy was carried out on 35 consecutive patients presenting with acute thrombosed circumferential prolapsed haemorrhoids . Operative data , postoperative stay , pain assessment and persistent symptoms were compared at discharge and at 2 week and 6 week review . Additionally at 6 week review the time to return to work was recorded and an endoanal ultrasound was carried out . RESULTS Thirty patients were randomized and followed up for six weeks . Although postoperative stay and in-hospital analgesia were the same , patients from the stapled group reported significantly more pain at discharge . However , by 2 weeks the conventional group reported significantly higher pain scores particularly on passing stool . By this stage over half the stapled group patients reported no pain at all . More patients in the conventional group complained of persistent symptoms of pain , bleeding and discharge at 2 week and 6 week review with 20 % requiring readmission compared with none in the stapled group . The median return to work was significantly shorter for the stapled group ( 14 days vs 28 days , P < 0.05 ) . Although all patients claimed to be continent , two patients from each group had ultrasonic evidence of internal sphincter damage . CONCLUSION Stapled mucosectomy for acute thrombosed circumferential piles is feasible and may result in less pain , a more rapid resolution of symptoms and an earlier return to work compared with a conventional procedure .

Stapled mucosectomy

conventional haemorrhoidectomy

conventional procedure

endoanal ultrasound

conventional group

Operative data

postoperative stay

pain assessment

persistent symptoms

endoanal ultrasound

postoperative stay

in-hospital analgesia

higher pain scores

no pain

persistent symptoms of pain

bleeding

discharge

internal sphincter damage

less pain

Thirty

stapled group

conventional group


An exposure prevention rating method for intervention needs assessment and effectiveness evaluation . This article describes a new method for ( 1 ) systematically prioritizing needs for intervention on hazardous substance exposures in manufacturing work sites , and ( 2 ) evaluating intervention effectiveness . We developed a checklist containing six unique sets of yes/no variables organized in a 2 x 3 matrix of exposure potential versus protection ( two columns ) at the levels of materials , processes , and human interface ( three rows ) . The three levels correspond to a simplified hierarchy of controls . Each of the six sets of indicator variables was reduced to a high/moderate/low rating . Ratings from the matrix were then combined to generate a single overall exposure prevention rating for each area . Reflecting the hierarchy of controls , material factors were weighted highest , followed by process , and then human interface . The checklist was filled out by an industrial hygienist while conducting a walk-through inspection ( N = 131 manufacturing processes/areas in 17 large work sites ) . One area or process per manufacturing department was assessed and rated . Based on the resulting Exposure Prevention ratings , we concluded that exposures were well controlled in the majority of areas assessed ( 64 % with rating of 1 or 2 on a 6-point scale ) , that there is some room for improvement in 26 percent of areas ( rating of 3 or 4 ) , and that roughly 10 percent of the areas assessed are urgently in need of intervention ( rated as 5 or 6 ) . A second hygienist independently assessed a subset of areas to evaluate inter-rater reliability . The reliability of the overall exposure prevention ratings was excellent ( weighted kappa = 0.84 ) . The rating scheme has good discriminatory power and reliability and shows promise as a broadly applicable and inexpensive tool for intervention needs assessment and effectiveness evaluation . Validation studies are needed as a next step . This assessment method complements quantitative exposure assessment with an upstream prevention focus .

exposure prevention rating method

checklist

Exposure Prevention ratings

inter-rater reliability .


A randomized trial of the canalith repositioning procedure . OBJECTIVE To compare the effectiveness and complications of our adaptation of the canalith repositioning procedure ( CRP ) with the expectation treatment for benign paroxysmal positional vertigo . STUDY DESIGN A randomized , controlled trial in the setting of a neurotological clinic in Thailand . METHODS Fifty-eight patients with posterior benign paroxysmal positional vertigo were randomly assigned to treatment and control groups using a block of four . The treatment group was treated with the modified CRP technique until the nystagmus disappeared . A mastoid oscillator was not used , nor were any instructions given for patients after the maneuver . Both groups recorded the daily grading of symptoms and the amount of anti-vertiginous drugs ( cinnarizine ) taken . Objective and subjective assessments were made weekly until the nystagmus disappeared or until 4 weeks had passed since treatment began . RESULTS The rates of effectiveness of CRP treatment and the control treatment for benign paroxysmal positional vertigo were 75.9 % and 48.2 % , respectively . There was a significant difference in the treatment outcomes of the CRP and control groups ( P =.03 ) . The CRP group used significantly fewer drugs than the control group ( P =.001 ) . Complications in the CRP group , such as lateral canalithiasis and fainting , were observed in 13.8 % of the patients . CONCLUSIONS The CRP was more effective than the expectation treatment for benign paroxysmal positional vertigo insofar as it provided faster recovery and required less dependence on medication . Complications of CRP were limited to 13.8 % of patients .

canalith repositioning procedure

modified CRP technique

cinnarizine

CRP treatment

CRP

CRP

CRP

CRP

CRP

daily grading of symptoms

Objective and subjective assessments

nystagmus

rates of effectiveness of CRP treatment

used significantly fewer drugs

lateral canalithiasis and fainting

recovery

dependence on medication .

Complications


Service variation in baseline variables and prediction of risk in a randomised controlled trial of psychological treatment in repeated parasuicide : the POPMACT Study . The treatment protocol and baseline characteristics of 480 subjects with a history of repeated parasuicide recruited in five centres to a randomised therapeutic trial of manual assisted cognitive-behaviour therapy ( MACT ) and treatment as usual ( TAU ) are described . Most patients had significant anxiety and depressive disturbance with 42 % having a personality disorder . Variation in service policies influenced recruitment , with earlier assessment centres seeing people with more frequent episodes of self-harm and greater parasuicide risk than later ones . Parasuicide risk was also significantly greater in those with their first parasuicide episode at an earlier age and in those with a more recent latest episode .

psychological treatment

treatment as usual ( TAU )

anxiety

depressive disturbance

episodes of self-harm

parasuicide risk

Parasuicide risk


Safety of an astaxanthin-rich Haematococcus pluvialis algal extract : a randomized clinical trial . A growing body of scientific literature indicates that astaxanthin is a more powerful antioxidant than other carotenoids and vitamin E and may confer numerous health benefits . The purpose of this investigation was to conduct a human safety study with a Haematococcus pluvialis algal extract with high levels of astaxanthin . Thirty-five healthy adults age 35-69 years were enrolled in a randomized , double-blind , placebo-controlled trial of 8 weeks ' duration . All participants took three gelcaps per day , one at each meal . Nineteen participants received gelcaps with an algal extract in safflower oil , containing 2 mg of astaxanthin each ( treatment ) ; 16 participants received gelcaps containing safflower oil only ( placebo ) . Blood pressure and blood chemistry tests , including a comprehensive metabolic panel and cell blood count , were conducted at the beginning of the trial and after 4 and 8 weeks of supplementation . No significant differences were detected between the treatment and the placebo groups after 8 weeks of supplementation with the algal extract in the parameters analyzed , except for serum calcium , total protein , and eosinophils ( P < .01 ) . Although the differences in these three parameters were statistically significant , they were very small and are of no clinical importance . These results reveal that 6 mg of astaxanthin per day from a H. pluvialis algal extract can be safely consumed by healthy adults .

astaxanthin

placebo-controlled

astaxanthin

safely


Treatment of recurrent chronic hyperplastic sinusitis with nasal polyposis . OBJECTIVE To demonstrate the long-term efficacy of intranasal furosemide , an inhibitor of the sodium chloride cotransporter channel at the basolateral surface of the respiratory epithelial cell , vs no therapeutic intervention vs intranasal mometasone furoate , a corticosteroid , in preventing relapses of chronic hyperplastic sinusitis with nasal polyposis . DESIGN Randomized prospective controlled study . Patients were examined every 6 months during follow-up ( range , 1-9 years ) . PATIENTS One hundred seventy patients with bilateral obstructive or minimally obstructive chronic hyperplastic sinusitis with nasal polyposis . INTERVENTION All patients were surgically treated in the ENT Department , University of Siena Medical School . One month after surgery , group 1 patients ( n = 97 ) started treatment with intranasal furosemide , group 2 ( n = 40 ) received no therapeutic treatment , and group 3 ( n = 33 ) were treated with mometasone . MAIN OUTCOME MEASURES Clinical and instrumental evaluation of postoperative outcomes . RESULTS Seventeen ( 17.5 % ) of 97 patients in group 1 , 12 ( 30.0 % ) of 40 patients in group 2 , and 8 ( 24.2 % ) of 33 patients in group 3 experienced nasal polyposis relapses . We noted a prevalence of early-stage relapse in patients treated with furosemide or mometasone , whereas patients who did not receive any treatment experienced more severe grades of chronic hyperplastic sinusitis with nasal polyposis ( P < .005 ) . CONCLUSION Use of intranasal furosemide represents a valid therapeutic treatment in the prevention of chronic hyperplastic sinusitis with nasal polyposis .

furosemide

no therapeutic intervention

mometasone furoate , a corticosteroid

intranasal furosemide

received no therapeutic treatment

mometasone

furosemide

mometasone

furosemide

nasal polyposis relapses .

early-stage relapse


Recombinant human thrombopoietin augments mobilization of peripheral blood progenitor cells for autologous transplantation . This study assessed the ability of various schedules of recombinant human thrombopoietin ( rhTPO ) to enhance mobilization of peripheral blood progenitor cells ( PBPCs ) in 134 patients with cancer undergoing high-dose chemotherapy and autologous PBPC transplantation . Patients received the study drug on days 1 , 3 , and 5 before initiation of granulocyte colony-stimulating factor ( G-CSF ) 10 microg/kg/day on day 5 and pheresis starting on day 9 . Randomly assigned treatments on days 1 , 3 , and 5 were : group 1 ( n=27 ) placebo , placebo , rhTPO 1.5 microg/kg ; group 2 ( n=27 ) rhTPO 1.5 microg/kg , placebo , placebo ; groups 3 ( n=28 ) and 4 ( n=22 ) rhTPO 0.5 microg/kg on all 3 treatment days ; and group 5 ( n=30 ) placebo on all 3 treatment days . After high-dose chemotherapy and PBPC transplantation , groups 1 through 4 received rhTPO 1.5 microg/kg days 0 , +2 , +4 , and +6 with either G-CSF 5 microg/kg/day ( groups 1-3 ) or granulocyte-macrophage colony-stimulating factor 250 microg/m ( 2 ) /day ( group 4 ) . Group 5 received placebo plus G-CSF 5 microg/kg/day . The addition of rhTPO to G-CSF increased median CD34+ cell yield/pheresis in cohorts in which rhTPO was started before day 5 , with higher yields in groups 2 ( 2.67 x 10 ( 6 ) /kg ) and groups 3 and 4 ( 3.10 x 10 ( 6 ) /kg ) than in group 1 ( 1.86 x 10 ( 6 ) /kg ) or group 5 ( 1.65 x 10 ( 6 ) /kg ) ( P=.006 across groups ) . Comparing rhTPO to placebo , higher percentages of patients achieved the minimum yield of CD34+ > or =2 x 10 ( 6 ) /kg ( 92 % v 75 % ; P=.050 ) as well as the target yield of CD34+ > or =5 x 10 ( 6 ) /kg ( 73 % v 46 % ; P= .041 ) . rhTPO-treated patients required fewer phereses to achieve minimum ( P= .011 ) and target ( P= .015 ) CD34+ cell values . rhTPO given after transplantation did not speed platelet recovery . No neutralizing antibodies were observed . We conclude that rhTPO can safely enhance mobilization of PBPC , reduce the number of leukapheresis , and allow more patients to meet minimal cell yield requirements to receive high-dose chemotherapy with PBPC transplantation .

Recombinant human thrombopoietin

placebo , placebo

rhTPO

placebo

rhTPO

rhTPO

rhTPO

placebo

rhTPO-treated

rhTPO

rhTPO

chemotherapy

PBPC transplantation

peripheral blood progenitor cells

median CD34+ cell yield/pheresis

minimum yield of CD34+

CD34+ cell values

platelet recovery

PBPC

leukapheresis

autologous transplantation .

cancer


A proof of concept study to evaluate putative benefits of montelukast in moderate persistent asthmatics . AIMS Whether chronic dosing with montelukast confers benefit in patients with moderate to severe asthma remains to be fully established . A proof of concept study was performed evaluating putative benefits with montelukast in moderate persistent asthmatics who were taken off inhaled corticosteroids ( ICS ) and switched to salmeterol . The latter was done to dissociate the effects of montelukast from ICS . METHODS Twenty moderate to severe persistent asthmatics completed a randomized double-blind crossover study . Subjects received montelukast 10 mg daily or placebo for 2 weeks each . This was preceded by a 2-week run-in when ICS were discontinued and salmeterol started , and used on a regular basis throughout the study . Measurements were made after run-in and after both randomized treatments . RESULTS There were no significant sequence effects for responses as to whether placebo or montelukast were given first or second . Methacholine PD20 values after run-in , first and second placebo were 63 micro g , 60 micro g and 64 micro g , respectively ( corresponding to 2 , 4 and 6 weeks of ICS washout , respectively ) . Lung function deteriorated pre vs post run-in , which was significant ( P < 0.05 ) for FEF25-75 % predicted . Montelukast conferred significant ( P < 0.05 ) improvements as change from post run-in compared with placebo in methacholine PD20 , FEV1 % predicted , FEF25-75 % predicted , diurnal peak expiratory flow , symptoms and salbutamol use . For the primary outcome of methacholine PD20 , this amounted to a 1.6-fold difference ( 95 % CI 1.1 , 2.5 ) . CONCLUSIONS In moderate persistent asthmatics switched from taking ICS to salmeterol alone , adding montelukast conferred significant benefits on all parameters of asthma control . Further studies are indicated to evaluate whether montelukast exhibits additive effects to ICS/long-acting beta2-adrenoceptor agonist combination inhalers upon clinically important outcomes .

montelukast

montelukast

montelukast

salmeterol

montelukast

montelukast 10 mg daily

ICS

salmeterol

placebo

montelukast

placebo

placebo

salmeterol

montelukast

montelukast

putative benefits

sequence effects

Methacholine PD20 values

Lung function deteriorated

diurnal peak expiratory flow

symptoms

salbutamol use

moderate persistent asthmatics

patients with moderate to severe asthma

Twenty


Antiinflammatory effects of the phosphodiesterase-4 inhibitor cilomilast ( Ariflo ) in chronic obstructive pulmonary disease . Cilomilast ( Ariflo ) , a new oral phosphodiesterase-4 selective inhibitor , improves lung function in chronic obstructive pulmonary disease ( COPD ) . We have evaluated its antiinflammatory effects in 59 patients with COPD randomized to receive cilomilast , 15 mg two times a day , or placebo for 12 weeks . Induced sputum differential cell counts were obtained at baseline and at five further visits . Interleukin-8 and neutrophil elastase were measured in sputum supernatant . Bronchial biopsies obtained at baseline and at Week 10 were immunostained and counted for neutrophils , CD8+ and CD4+ T-lymphocyte subsets , and CD68+ macrophages . Cells expressing the genes for interleukin-8 and tumor necrosis factor-alpha were identified by in situ hybridization and quantified . Compared with placebo , analysis of variance ( ANOVA ) of the change from baseline showed that cilomilast did not alter any sputum endpoint or FEV1 . However , bronchial biopsies demonstrated that cilomilast treatment was associated with reductions in CD8+ ( p = 0.001 ; ANOVA ) and CD68+ cells ( p < 0.05 ; ANOVA ) . In addition , by Poisson analysis , comparison of cell counts analyzed as a ratio of active to placebo demonstrated reductions of CD8+ ( 48 % p < 0.01 ) and CD68+ ( 47 % p = 0.001 ) cells . This is the first demonstration of reduction by any agent of airway tissue inflammatory cells characteristic of COPD . Phosphodiesterase-4 inhibitors represent a promising new class of substances for use in antiinflammatory treatment of this disease .

Cilomilast ( Ariflo )

cilomilast

placebo

cilomilast

cilomilast

Phosphodiesterase-4 inhibitors

Antiinflammatory effects

lung function

antiinflammatory effects

Induced sputum differential cell counts

Interleukin-8 and neutrophil elastase

sputum endpoint or FEV1

reductions in CD8+

CD68+ cells

reductions of CD8+

airway tissue inflammatory cells

chronic obstructive pulmonary disease

COPD


Prevention of coronary spasm by nicorandil : comparison with nifedipine . The efficacy of nicorandil was compared with that of nifedipine in 13 patients with vasospastic angina enrolled in a randomized , placebo-controlled , crossover study . All patients had a coronary spasm during coronary arteriography , either spontaneously or ergometrine-induced . During two consecutive periods of 2 days , patients received active drugs or placebo in a randomized order . Each patient received single oral doses of 30 mg nicorandil , 10 mg nifedipine , and , on 2 days , a placebo . One hour after drug intake , patients underwent an ergometrine test with increasing doses of Methergin ( ergometrine ) ( 0.05 , 0.10 , 0.20 , and 0.40 mg every 5 min ) . After placebo , the tests always were positive , and the ECG changes occurred at the same +/- 1 dose of ergometrine in 10 cases , showing good reproducibility . After nicorandil , the tests were negative in nine patients and positive for a higher or lower dose of ergometrine in three and one patient , respectively ( p = 0.0034 vs. placebo ) . After nifedipine , the tests were negative in five patients and positive for a higher or the same dose of ergometrine in four and four patients , respectively ( p = 0.0039 vs. placebo ) . Nifedipine ( 10 mg ) and nicorandil ( 30 mg ) were equally effective in eight patients ; in the remaining five patients , nicorandil had better results ( p = 0.06 ) . Nicorandil ( 30 mg ) prevents ergometrine-induced coronary spasm . This compound may be beneficial in patients with vasospastic angina .

nicorandil :

nifedipine .

nicorandil

nifedipine

placebo-controlled

active drugs

placebo

nicorandil

nifedipine

placebo

Methergin ( ergometrine )

placebo

ergometrine

nicorandil

ergometrine

placebo )

nifedipine

ergometrine

placebo

Nifedipine

nicorandil

Nicorandil

ECG changes

ergometrine-induced coronary spasm

vasospastic angina

coronary spasm

vasospastic angina

coronary spasm

coronary arteriography

vasospastic angina


Evaluation of asthma knowledge and quality of life in Hungarian asthmatics . BACKGROUND The objective was to develop an educational instrument , to assess its impact as an intervention instrument and to examine quality of life ( QoL ) . METHODS 119 asthmatics were randomized ( 64 in the intervention and 55 in the reference group ) . The education instrument was developed based on the EuroPharm-Forum Guidelines and its impact assessed by a self-developed questionnaire . Patients ' QoL , asthma knowledge was assessed twice , once before and after the education seminar , education was only provided for the intervention group . QoL was measured with the St George 's Respiratory Questionnaire ( SGRQ ) and a visual analogue scale ( VAS ) . RESULTS We found significant differences in answers to the asthma questions , by 40 % improvement , but no changes in the control group . In inhaler-use technique , we could not find significant changes neither in the intervention nor in the control group . There were no significant differences between the results of the two visits neither with the VAS nor with the SGRQ on the QoL data . CONCLUSION The results indicate that asthmatics experience lower QoL . As the subjects were regularly controlled asthmatics they had better general knowledge and inhaler-use technique was expected . The results suggest that it is necessary to regularly refresh asthma knowledge , to assess patients ' self-management plans to achieve long-term effectiveness of asthma management .

educational instrument

reference

education instrument

education seminar

QoL

visual analogue scale ( VAS )

VAS

SGRQ

QoL data

QoL

asthmatics


The prevalence of IgE sensitization to formaldehyde in asthmatic children . BACKGROUND Formaldehyde ( FA ) is well documented as a cause of occupational asthma . Recently , attention has been paid to FA as an allergen and a pollutant that enhances allergic sensitization . We have investigated the prevalence of FA-specific IgE in asthmatic children and the correlation between IgE sensitization to FA and the severity of asthma . METHODS One hundred and fifty-five children were investigated , 122 of them asthmatic and 33 nonallergic . Specific IgE against FA was measured by CAP RAST . In addition , the patients answered a questionnaire , containing questions on clinical features of their asthma , their living conditions , and symptoms of mucosal irritation . RESULTS Of all the subjects assessed , FA-specific IgE was detected in only two asthmatics , and their IgE levels of FA were low ( 0.42 and 0.46 UA/ml ) . One of the two patients with FA-specific IgE had severe asthma and frequent symptoms of mucosal irritation , but the other had mild asthma and only rare symptoms of mucosal irritation . CONCLUSIONS The prevalence of IgE sensitization to FA appears very low in Japanese children , whether or not they have asthma . Therefore , it appears likely that FA is not one of the major allergens causing childhood asthma .

Formaldehyde

FA

CAP RAST

questionnaire

occupational asthma .

enhances allergic sensitization .

severity of asthma .

Specific IgE against FA

FA-specific IgE

IgE sensitization

asthmatic

asthmatic


A randomized clinical trial of treatment of clomiphene citrate-resistant anovulation with the use of oral contraceptive pill suppression and repeat clomiphene citrate treatment . OBJECTIVE The purpose of this study was to evaluate the effectiveness and endocrine response of oral contraceptive ovarian suppression followed by clomiphene citrate in patients who previously were clomiphene citrate resistant . STUDY DESIGN Forty-eight patients from a private tertiary infertility clinic were assigned randomly prospectively to either group 1 ( oral contraceptive/clomiphene citrate ) , which received continuous oral contraceptives followed by clomiphene citrate , or to group 2 ( control ) received no treatment in the cycle before clomiphene citrate treatment . On day 3 , 17 beta-estradiol , follicle-stimulating hormone , luteinizing hormone , and androgens were assayed before and after treatment . Follicle growth , ovulation , and pregnancy were evaluated . The Student t test and analysis of variance were used for statistical significance . RESULTS The oral contraceptive/clomiphene citrate group had a significantly higher percentage of patients who ovulated and of ovulatory cycles and pregnancies . Significantly lower levels of 17 beta-estradiol , luteinizing hormone , and androgen levels were seen in the oral contraceptive/clomiphene citrate group , with no significant changes in group 2 . CONCLUSION Suppression of the ovary with oral contraceptives results in excellent rates of ovulation and pregnancy in patients who previously were resistant to clomiphene citrate . The decreases in ovarian androgens , luteinizing hormone , and 17 beta-estradiol may be responsible for the improved response .

oral contraceptive

clomiphene citrate

clomiphene citrate

group 2 ( control ) received

clomiphene citrate

effectiveness

endocrine response

Student t test and analysis of variance

percentage

ovulated

ovulatory cycles and pregnancies .


Clinic visit and waiting : patient education and satisfaction . Patients who were taught about their health problems while waiting in the clinic ( n = 104 ) were significantly more satisfied with the education received during that visit than the control group ( n = 101 ) . The longer patients waited in the clinic to see their providers , the less satisfied they were with the clinic visit .

patient education

control group

patient education

and satisfaction

satisfied with the education

satisfied

health problems


Pethidine versus tramadol for pain relief during labor . OBJECTIVE To evaluate and compare the analgesic efficacy and adverse effects of tramadol and pethidine in labor . METHOD Fifty-nine full term parturients were randomly assigned to one of two groups in active labor . Group 1 received 100 mg pethidine ; group 2 , 100 mg tramadol , intramuscularly . Analgesic efficacy , maternal side effects , changes in the blood pressure , heart rate , and duration of labor were assessed . RESULT At 30 and 60 min after drug administration , pain relief was greater in the pethidine group than in tramadol group . The incidence of nausea and fatigue was higher in the tramadol group . Following drug administration the decrease in systolic and diastolic blood pressure and the increase in heart rate were statistically significant in both groups . No significant difference was found between the groups when compared for duration of labor and Apgar scores . None of the neonates developed respiratory depression . CONCLUSION Pethidine seems to be a better alternative than tramadol in obstetric analgesia because of its superiority in analgesic efficacy and low incidence of maternal side effects .

Pethidine versus tramadol

tramadol

pethidine

pethidine ;

tramadol

pethidine

tramadol

tramadol

Pethidine

tramadol

analgesic efficacy

adverse effects

Analgesic efficacy

maternal side effects

changes in the blood pressure

heart rate

duration of labor

pain relief

nausea and fatigue

heart rate

duration of labor and Apgar scores

respiratory depression

analgesic efficacy

maternal side effects

pain relief during labor .

Fifty-nine

active labor


[ Long term observation in effects of potassium and calcium supplementation on arterial blood pressure and sodium metabolism in adolescents with higher blood pressure ] . OBJECTIVE To investigate the effects of potassium and calcium supplementation in table salt on reduction of arterial blood pressure and sodium metabolism in adolescents with higher blood pressure . METHODS A single blind placebo-controlled trial was carried out for two years in 220 adolescents with higher blood pressure , aged 18 - 22 years , who were randomly divided into supplementary group ( n = 110 ) and control group ( n = 110 ) . Each of the subjects in the supplementary group and their family members was given 10 mmol of potassium and 10 mmol of calcium mixed in their table salt daily for 24 months . RESULTS Night urinary sodium and potassium excretion increased ( urinary Na ( + ) , P < 0.05 ; urinary K ( + ) , P < 0.01 ) and blood pressure lowered by 5.3 mm Hg/1.8 mm Hg in average from the baseline in the supplementary group two years after potassium and calcium supplementation , as compared with that in the control group increased by ( 1.3/1.7 ) mm Hg . CONCLUSIONS Adequate supplement of potassium and calcium in daily table salt intake was an effective way to prevent form hypertension and could promote their urinary sodium excretion and reduction of arterial blood pressure in adolescents with higher blood pressure .

potassium and calcium supplementation

potassium and calcium supplementation

placebo-controlled

potassium and calcium supplementation

supplement of potassium and calcium

arterial blood pressure

sodium metabolism

arterial blood pressure

sodium metabolism

blood pressure lowered

form hypertension

urinary sodium excretion

reduction of arterial blood pressure


Effect of 2 weeks of theophylline on glucose counterregulation in patients with type 1 diabetes and unawareness of hypoglycemia . BACKGROUND AND OBJECTIVE A single dose of theophylline improves hypoglycemia unawareness in type 1 diabetic patients . Prolonged theophylline use is , however , associated with emergence of tolerance . This study investigated whether prolonged use of theophylline retains efficacy for counterregulatory defects in patients with type 1 diabetes and hypoglycemia unawareness . METHODS Experiments were performed with 12 subjects with type 1 diabetes and hypoglycemia unawareness . All subjects participated in a crossover study of 2 randomly scheduled 15-day study periods during which 250 mg theophylline twice daily or matching placebo was used . On the final day of each period , hyperinsulinemic ( 360 pmol x m ( -2 ) x min ( -1 ) ) hypoglycemic ( 5.0 , 3.5 , 2.5 mmol x L ( -1 ) ) glucose clamps were used to assess counterregulatory and cardiovascular responses . RESULTS Under normoglycemic conditions , there were no differences between theophylline and placebo . Under hypoglycemic conditions , theophylline enhanced responses of growth hormone , symptoms , heart rate , and pulse pressure ( all P < .05 ) , induced sweating at higher plasma glucose levels ( P =.039 ) , and reduced exogenous glucose requirements ( P =.018 ) . Hypoglycemia-induced responses of epinephrine , norepinephrine , and cortisol were not enhanced by theophylline . CONCLUSIONS Prolonged use of theophylline has a sustained effect on cardiovascular , metabolic , and symptom responses to hypoglycemia in patients with type 1 diabetes and hypoglycemia unawareness . Whether these results translate into clinical benefit remains to be determined .

250 mg theophylline twice daily

matching placebo

glucose counterregulation

counterregulatory defects

reduced exogenous glucose requirements

type 1 diabetic patients

type 1 diabetes

hypoglycemia unawareness

12 subjects

subjects


The effects of enterostatin intake on food intake and energy expenditure . Enterostatin ( ENT ) has been found to inhibit food intake and selectively inhibit fat intake in rats . Both peripheral and central mechanisms have been proposed . It also has been suggested that ENT may increase thermogenesis . The present study investigated the effects of oral ENT administration on food intake , energy expenditure and body weight in subjects with a preference for a high-fat diet . In a double-blind , placebo-controlled , randomized and crossover design , nine female and three male healthy subjects ( age 34 ( sd 11 ) years , BMI 24.5 ( sd 2.5 ) kg/m ( 2 ) ) with a preference for a high-fat diet ingested ENT ( 3 x 15 mg/d ) or placebo ( PLA ) while consuming a high-fat diet ad libitum for 4 d. Eight subjects ended each intervention with a 36 h stay in the respiration chamber , continuing the diet and treatment . Body-weight loss was significant ( ENT 0.8 ( se 0.3 ) kg , P < 0.05 ; PLA 1.3 ( se 0.3 ) kg , P < 0.001 ) , but not different between treatments . There was no difference between treatments in total energy intake ( ENT 37.1 ( se 2.6 ) , PLA 35.9 ( se 3.2 ) MJ ) , macronutrient composition , hunger , satiety and hedonic scores during the 4 d high-fat diet . Energy expenditure ( 24 h ) ( ENT 9.6 ( se 0.4 ) , PLA 9.5 ( se 0.4 ) MJ ) , sleeping and resting metabolic rate , diet-induced thermogenesis , activity-induced energy expenditure and 24 h RQ ( ENT 0.77 ( se 0.01 ) , PLA 0.77 ( se 0.01 ) ) were similar for both treatments . We conclude that oral ENT administration did not affect food intake , energy expenditure or body weight in subjects with a preference for a high-fat diet experiencing a negative energy and fat balance .

enterostatin intake

Enterostatin ( ENT )

ENT

ENT

placebo-controlled

high-fat diet ingested ENT

placebo ( PLA )

consuming a high-fat diet ad libitum

ENT

PLA

ENT

PLA

ENT

PLA

ENT

PLA

ENT

food intake and energy expenditure .

food intake

energy expenditure

body weight

Body-weight loss

total energy intake

Energy expenditure

food intake

energy expenditure

body weight

fat intake

rats

nine

female

three

male

age 34 ( sd 11 )


Alendronate daily , weekly in conventional tablets and weekly in enteric tablets : preliminary study on the effects in bone turnover markers and incidence of side effects . Bisphosphonates are now in the vanguard of osteoporosis treatment . Frequently , gastro-oesophageal symptoms are associated with these drugs . The objective of this study was to compare side effects and bone turnover markers in postmenopausal women who had received alendronate daily or weekly in tablets with or without enteric coating . We conducted a randomised , double-blind , 3-month trial . The trial involved 75 volunteers , aged 45-58 with moderate to severe osteopenia ( T-score lower than -2 SD ) assessed by quantitative ultrasound . Women were assigned randomly to receive : ( a ) alendronate 10mg/day : ( b ) alendronate 70 mg once a week : or ( c ) enteric alendronate 70 mg per week . We recorded side effects , C-telopeptide , osteocalcin and urine hydroxyproline at the start of the study and at 3 months . After 3 months , pyrosis ( heartburn ) was noted by seven women in group A ( 28 % ) , three in group B ( 12 % ) and two in group C ( 8 % ) ; nausea : by one woman in group B ; and headache by one patient in each group . C-telopeptide ( A : 40.7 % ; B : 34.1 % and C : 38.5 % ) ; hydroxyproline ( A : 31.1 % ; B : 25.3 % and C : 31.5 % ) and osteocalcin ( A : 27.0 % ; B : 25.4 % and C : 25.1 % ) decreased similarly in the three groups . Weekly intake of alendronate , whether conventional or enteric-coated ; is associated with less heartburn and nausea . Enteric alendronate has a similar action to the conventional tablets on biochemical markers .

Alendronate

Bisphosphonates

alendronate

alendronate 10mg/day

alendronate 70 mg once a week :

enteric alendronate 70 mg per week

alendronate

Enteric alendronate

bone turnover markers

incidence of side effects

side effects

C-telopeptide

osteocalcin

urine hydroxyproline

pyrosis ( heartburn )

nausea

headache

C-telopeptide

hydroxyproline

osteocalcin

heartburn and nausea

biochemical markers

75 volunteers

aged 45-58


Virtual reality intervention for older women with breast cancer . This study examined the effects of a virtual reality distraction intervention on chemotherapy-related symptom distress levels in 16 women aged 50 and older . A cross-over design was used to answer the following research questions : ( 1 ) Is virtual reality an effective distraction intervention for reducing chemotherapy-related symptom distress levels in older women with breast cancer ? ( 2 ) Does virtual reality have a lasting effect ? Chemotherapy treatments are intensive and difficult to endure . One way to cope with chemotherapy-related symptom distress is through the use of distraction . For this study , a head-mounted display ( Sony PC Glasstron PLM - S700 ) was used to display encompassing images and block competing stimuli during chemotherapy infusions . The Symptom Distress Scale ( SDS ) , Revised Piper Fatigue Scale ( PFS ) , and the State Anxiety Inventory ( SAI ) were used to measure symptom distress . For two matched chemotherapy treatments , one pre-test and two post-test measures were employed . Participants were randomly assigned to receive the VR distraction intervention during one chemotherapy treatment and received no distraction intervention ( control condition ) during an alternate chemotherapy treatment . Analysis using paired t-tests demonstrated a significant decrease in the SAI ( p = 0.10 ) scores immediately following chemotherapy treatments when participants used VR . No significant changes were found in SDS or PFS values . There was a consistent trend toward improved symptoms on all measures 48 h following completion of chemotherapy . Evaluation of the intervention indicated that women thought the head mounted device was easy to use , they experienced no cybersickness , and 100 % would use VR again .

Virtual reality intervention

virtual reality

symptom distress

Symptom Distress Scale ( SDS )

Revised Piper Fatigue Scale ( PFS ) ,

State Anxiety Inventory ( SAI

decrease

SAI

SDS

PFS

improved symptoms

cybersickness

older

women

breast cancer

women

50 and older

older

women

breast cancer


A comparative study of a new food supplement , ViviScal , with fish extract for the treatment of hereditary androgenic alopecia in young males . A controlled , randomized , double-blind , parallel-group study compared the effects of ViviScal ( a new food supplement incorporating special marine extracts and a silica compound ) with those of a fish extract in the treatment of young males with hereditary androgenic alopecia . The pretreatment histological diagnosis was alopecia with a mild to moderate perifollicular inflammation zone . The study consisted of 20 subjects who received two tablets of ViviScal once daily and 20 who received two tablets of fish extract once daily for 6 months . The mean patient age and mean duration and severity of baldness compared well between the two groups . Most patients had been treated with long-term topical 2 % minoxidil for 1 year or more prior to the study . At baseline and after 6 months ' treatment , a biopsy was taken for histological examination . A non-vellus hair count was performed at baseline and after 2 , 4 and 6 months . In the fish extract treatment group three patients withdrew from the study before the fourth month due to lack of therapeutic effect . After 6 months ' treatment , patients receiving ViviScal showed a mean increase in non-vellus hair of 38 % compared with a 2 % increase in the fish extract treatment group ( P < 0.0001 ) . In the ViviScal group , 19 ( 95 % ) subjects showed both clinical and histological cure , whereas none treated with fish extract showed any clinical or histological difference after 6 months ' treatment ( P < 0.0001 ) . In both groups , a minimal decrease in the erythemal index was observed . In conclusion , ViviScal appears to be the first highly active treatment for androgenic alopecia in young males .

ViviScal , with fish extract

fish extract

two tablets of ViviScal once daily

two tablets of fish extract once daily

minoxidil

fish extract

ViviScal

fish extract

ViviScal

ViviScal

non-vellus hair count

lack of therapeutic effect

mean increase in non-vellus hair

both clinical and histological cure

erythemal index

hereditary androgenic alopecia

young

males

young

males

androgenic alopecia

alopecia

three


A prospective randomized trial of two different endoscopic resection techniques for early stage cancer of the esophagus . BACKGROUND A variety of different endoscopic resection techniques for early stage cancer of the upper GI tract have been described that are more effective than strip biopsy . However , there is no report of a prospective randomized comparison of different techniques . METHODS In a prospective randomized study , 100 consecutive endoscopic resections were performed in 72 patients with early stage esophageal cancer . Fifty endoscopic resections were performed with a " suck-and-ligate " device without prior submucosa injection and 50 with the cap technique with prior submucosa injection of a dilute saline solution of epinephrine . The main assessment criteria were maximum diameter of the resection specimen and of the resection area , and the complication rate . RESULTS No significant differences were observed between the two groups with regard to the maximum diameters and calculated area of the resected specimens ( ligation group : 16.4 [ 4.0 ] x 11 [ 3.1 ] mm/185 [ 84 ] mm ( 2 ) vs. cap group : 15.5 [ 4.1 ] x 10.7 [ 2.7 ] mm/168 [ 83 ] mm ( 2 ) ) , or the maximum diameters and calculated area of the endoscopic resection ulcers after 24 hours ( ligation group : 20.6 [ 4.8 ] x 14.3 [ 4.5 ] mm/314 [ 160 ] mm ( 2 ) vs. cap group : 18.9 [ 5.1 ] x 12.9 [ 3.8 ] mm/260 [ 145 ] mm ( 2 ) ) . There was only a slight advantage ( greater diameter of resection specimens ) for the ligation group in patients who had prior endoscopic treatment . There was one minor episode of bleeding in each group ; there was no severe complication . In 41 of 72 patients ( 57 % ) , further endoscopic therapy after endoscopic resection was necessary because of residual neoplasia at the first follow-up endoscopy after resection ( 61 of 100 resection specimens [ 61 % ] had lateral margins that could not be evaluated because of coagulation artifact or contained malignancy but with the base of the lesion free of tumor ) . CONCLUSIONS The cap technique with submucosa injection and the ligation technique without submucosa injection are similar with respect to efficacy and safety for endoscopic resection of early stage esophageal cancers .

endoscopic resection techniques

endoscopic resection techniques

endoscopic resections

Fifty endoscopic resections

suck-and-ligate " device without prior

submucosa injection

and

cap technique

ligation technique

complication rate

maximum diameters

area of the resected specimens

bleeding

residual neoplasia

72 patients

early stage esophageal cancer


Children with autistic spectrum disorders . I : comparison of placebo and single dose of human synthetic secretin . AIMS To examine the effect of a single dose of human synthetic secretin ( HSS ) on behaviour and communication in children with autism spectrum disorder ( ASD ) using an objective measure of communication and social reciprocity and standardised rating scales . METHODS Randomised , crossover , double blind , and placebo controlled trial of a single intravenous dose of human synthetic secretin ( HSS ) 2 CU/kg . The 62 subjects ( 3-8 years ) were assigned to group 1 ( saline placebo/HSS ) or group 2 ( HSS/saline placebo ) . Diagnosis was confirmed by ADI-R ( Autism Diagnostic Interview-Revised ) algorithm . Severity of symptoms was rated using the CARS ( Childhood Autism Rating Scale ) . Outcome measures included Communication and Symbolic Behavior Scale ( CSBS ) , Ritvo Real-life Rating Scale , weekly Global Rating Scale ( GBRS ) by parents and teachers , and daily log of gastrointestinal symptoms . The communication subscale of the CSBS , specifying communication function , reciprocity , and social-affective signalling was videotaped and scored by a blinded , trained observer . RESULTS Sixty one children completed the study . After randomisation , there were no significant differences in gender , race , age , and parent and teacher GBRS and Ritvo Scale between the two groups . Compared with placebo , secretin treatment was not associated with significant improvement of CSBS standard scores from baseline to 2 or 4 weeks post-infusion . Five children showed clinical improvement in standard scores : two after HSS and three after placebo . There were no significant changes in gastrointestinal symptoms after HSS or saline placebo . CONCLUSIONS A single dose of intravenous human secretin is not effective in changing behaviour and communication in children with ASD when compared to placebo .

placebo

human synthetic secretin

human synthetic secretin ( HSS )

placebo

human synthetic secretin ( HSS )

( saline placebo/HSS )

HSS/saline placebo

placebo

secretin treatment

HSS

placebo

HSS

saline placebo

human secretin

placebo

Ritvo Real-life Rating Scale

weekly Global Rating Scale ( GBRS )

GBRS

CSBS standard scores

gastrointestinal symptoms


Children with autistic spectrum disorders . II : parents are unable to distinguish secretin from placebo under double-blind conditions . BACKGROUND Standardised measures of behaviour have failed to detect short term improvement in children with autism following treatment with secretin . However , it is possible that standardised measures are insensitive to dimensions of child behaviour that are nonetheless detectable by parents . AIM To determine the ability of parents of children with autism to guess , under double blind conditions , whether their child had received secretin or placebo . METHODS 2x2 crossover randomised blinded study , comparing the effect of synthetic human secretin 2 U/kg to placebo ( saline ) . Sixty two children with autism ( aged 43-103 months ) were randomly allocated to two groups : group 1 received placebo , followed six weeks later by secretin , and group 2 received secretin followed by placebo . At the conclusion of the study , parents were asked to guess their child 's group assignment . RESULTS Twenty seven families guessed their child 's group assignment correctly and 27 guessed incorrectly . In 48 instances , parents based their guess on perceived improvement ; in six cases , parents based their guess on perceived deterioration . Six families saw no difference after either infusion , and offered no guess . One family dropped out after the first infusion , and one family was lost to follow up after the second infusion . CONCLUSION In a controlled setting , parents of young children with autism are unable to distinguish the short term behavioural effects of secretin from placebo .

secretin

secretin

placebo

synthetic human secretin

placebo ( saline )

secretin followed by placebo

secretin

placebo

Standardised measures of behaviour

short term improvement

deterioration

short term behavioural effects

parents


Cisplatin , epirubicin , leucovorin and 5-fluorouracil ( PELF ) is more active than 5-fluorouracil , doxorubicin and methotrexate ( FAMTX ) in advanced gastric carcinoma . BACKGROUND 5-Fluorouracil ( 5-FU ) , doxorubicin and methotrexate ( FAMTX ) and cisplatin , epirubicin , leucovorin and 5-FU ( PELF ) have both been reported to be superior to the combination 5-FU , doxorubicin and mitomycin C ( FAM ) in advanced gastric carcinoma . On the basis of the presence and dose intensity of the included agents , we hypothesised that PELF would be superior to FAMTX . PATIENTS AND METHODS Two hundred patients with untreated advanced gastric carcinoma were randomised to receive PELF or FAMTX for a maximum of six cycles or until disease progression . RESULTS The complete response ( CR ) rates to PELF and FAMTX were , respectively , 13 % [ 95 % confidence intervals ( CI ) 6 % to 20 % ] and 2 % ( 95 % CI 0 % to 5 % ; P = 0.003 ) , and the objective response rates [ CR plus partial response ( PR ) rates ] 39 % ( 95 % CI 29 % to 49 % ) and 22 % ( 95 % CI 13 % to 30 % ; P = 0.009 ) , thus significantly favouring the PELF combination . The survival rates after 12 months ( 30.8 % versus 22.4 % ) and 24 months ( 15.7 % versus 9.5 % ) were also higher among patients receiving PELF , but these differences were not statistically significant . The toxicities were qualitatively different but quantitatively similar . Both regimens seem to be feasible provided that careful patient monitoring is assured . CONCLUSIONS PELF is significantly more active than FAMTX and deserves further research in the adjuvant setting .

FAMTX

PELF

FAMTX

FAMTX

PELF

FAMTX

complete response ( CR ) rates

objective response rates

partial response

survival rates

toxicities

advanced gastric carcinoma

advanced gastric carcinoma

Two hundred

untreated advanced gastric carcinoma


Phonophoresis versus topical application of ketoprofen : comparison between tissue and plasma levels . BACKGROUND AND PURPOSE Over the last few decades , application of ultrasound has been attempted to enhance transdermal transport of several drugs , a method referred to as " phonophoresis . " The purposes of this study were to examine the influence of ultrasound on the transdermal delivery of ketoprofen in humans and to compare the concentrations found after continuous and pulsed application . SUBJECTS AND METHODS Twenty-six patients with knee disorders requiring arthroscopy were randomly assigned to 1 of 3 groups . Just before surgery , phonophoresis of a ketoprofen gel ( Fastum gel ) was given to group A using continuous ultrasound ( 1 MHz , 1.5 W/cm2 , for 5 minutes ) . Group B received the same treatment but with pulsed ultrasound ( 100 Hz , 20 % duty cycle ) . Group C received 5 minutes of sham ultrasound with the ketoprofen gel . The ultrasound head was moved over a 10-cm2 area using small , continuous , circular movements . Biopsies of adipose tissue and synovial tissue were taken during surgery to evaluate the local penetration of the drug . Blood samples also were collected to determine whether ketoprofen entered the systemic circulation . RESULTS The concentration of ketoprofen in plasma was negligible in all 3 groups . The concentration of ketoprofen in synovial tissue differed from that in fat tissue . A difference in concentration of ketoprofen in synovial tissue was found between group C and groups A and B . The concentration of ketoprofen in fat tissue and synovial tissue was consistently higher in group B than in group A . DISCUSSION AND CONCLUSION This study confirms that phonophoresis of ketoprofen allows the attainment of higher local concentrations , whereas systemic exposure is lower . The results indicate that , in contrast to sham phonopheresis , ultrasound can increase the transdermal delivery of ketoprofen .

Phonophoresis

ketoprofen

phonophoresis of a ketoprofen gel

continuous ultrasound

pulsed ultrasound

sham ultrasound with the ketoprofen gel

concentration of ketoprofen

concentration of ketoprofen

concentration of ketoprofen

Twenty-six

knee disorders requiring arthroscopy


Randomized comparison of interferon alpha and hydroxyurea with hydroxyurea monotherapy in chronic myeloid leukemia ( CML-study II ) : prolongation of survival by the combination of interferon alpha and hydroxyurea . The optimum treatment conditions of interferon ( IFN ) alpha therapy in chronic myeloid leukemia ( CML ) are still controversial . To evaluate the role of hydroxyurea ( HU ) for the outcome of IFN therapy , we conducted a randomized trial to compare the combination of IFN and HU vs HU monotherapy ( CML-study II ) . From February 1991 to December 1994 , 376 patients with newly diagnosed CML in chronic phase were randomized . In all , 340 patients were Ph/BCR-ABL positive and evaluable . Randomization was unbalanced 1:2 in favor of the combination therapy , since study conditions were identical to the previous CML-study I and it had been planned in advance to add the HU patients of study I ( n=194 ) to the HU control group . Therefore , a total of 534 patients were evaluable ( 226 patients with IFN/HU and 308 patients with HU ) . Analyses were according to intention-to-treat . Median observation time of nontransplanted living patients was 7.6 years ( 7.9 years for IFN/HU and 7.3 years for HU ) . The risk profile ( new CML score ) was available for 532 patients : 200 patients ( 38 % ) were low , 239 patients ( 45 % ) intermediate , and 93 patients ( 17 % ) high risk . Complete hematologic response rates were higher in IFN/HU-treated patients ( 59 vs 32 % ) . Of 169 evaluable IFN/HU-treated patients ( 75 % ) , 104 patients ( 62 % ) achieved a cytogenetic response that was complete in 12 % ( n=21 ) , major in 14 % ( n=24 ) , and at least minimal in 35 % ( n=59 ) . Of the 534 patients , 105 ( 20 % ) underwent allogeneic stem cell transplantation in first chronic phase . In the low-risk group , 65 of 200 patients were transplanted ( 33 % ) , 30 ( 13 % ) in the intermediate-risk group , and nine ( 10 % ) in the high-risk group . Duration of chronic phase was 55 months for IFN/HU and 41 months for HU ( P < 0.0001 ) . Median survival was 64 months for IFN/HU and 53 months for HU-treated patients ( P=0.0063 ) . We conclude that IFN in combination with HU achieves a significant long-term survival advantage over HU monotherapy . In view of the data of CML-study I , these results suggest that IFN/HU is also superior to IFN alone . HU should be combined with IFN in IFN-based therapies and for comparisons with new therapies .

interferon alpha and hydroxyurea

interferon ( IFN ) alpha therapy

hydroxyurea ( HU )

IFN therapy

compare the combination of IFN

and

HU

HU monotherapy

Complete hematologic response rates

cytogenetic response

Duration of chronic phase

Median survival

newly diagnosed CML in chronic phase

Ph/BCR-ABL

534 patients

226 patients with IFN/HU

308 patients with HU


Left ventricular mass regression in elderly hypertensives . It is now recognized that left ventricular hypertrophy ( LVH ) , often associated with hypertension , is itself a risk factor for coronary disease in the elderly . Although many agents are capable of controlling blood pressure , the ability of these agents to induce regression of left ventricular ( LV ) mass , and the effect of regression on diastolic relaxation and contractile indices in the elderly are less well known . Our study compared the ability of the calcium blocker , verapamil , and the beta-blocker , atenolol , to both control blood pressure ( BP ) and to induce regression of LV mass in older hypertensives . In addition , the influence of regression on resting diastolic filling and on cardiac output and ejection fraction during rest and mild upright bicycle exercise were determined . Forty-two hypertensives 60 years of age or above , without evidence of ischemic disease underwent 2-D echocardiographic evaluation of LV mass and gated blood pool scan determination of early diastolic filling , cardiac output and ejection fraction . They were then randomized to receive verapamil or atenolol during a four-week titration period so as to achieve a BP of less than 160/90 mm Hg . If BP was not controlled with either agent , chlorthalidone was added . Individuals whose BP was controlled continued on the protocol for six months . At that time , the echocardiographic and gated blood pool studies were repeated both on and after subsequent withdrawal of the study medications . Twenty-one patients were randomized to receive verapamil and 21 patients to receive atenolol . Blood pressure control was achieved with verapamil alone in 18 patients , but with atenolol alone in only 8 patients ( p < 0.01 ) . ( ABSTRACT TRUNCATED AT 250 WORDS )

calcium blocker , verapamil

beta-blocker , atenolol

2-D echocardiographic evaluation

verapamil

atenolol

verapamil

atenolol

blood pressure ( BP )

regression of LV mass

BP

BP

BP

elderly

hypertensives

Forty-two

hypertensives

60 years of age or above

without evidence of ischemic disease


Pre-medication with pronase reduces artefacts during endoscopic ultrasonography . BACKGROUND Gastric mucus usually induces artefacts during endoscopic ultrasonography . AIM To investigate the effectiveness of pre-medication with the proteolytic enzyme , pronase , before endoscopic ultrasonography . METHODS Out-patients scheduled for endoscopic ultrasonography were randomly assigned to oral pre-medication with the anti-foam agent , dimethylpolysiloxane , alone ( treatment A ; n = 29 ) , with dimethylpolysiloxane plus sodium bicarbonate ( treatment B ; n = 29 ) or with dimethylpolysiloxane , sodium bicarbonate and pronase ( treatment C ; n = 29 ) . All drinks were given about 10 min before the start of the procedure . After insertion of the endoscope , endoscopists recorded visibility scores before the procedure , imaging scores at endoscopic ultrasonography and the numbers of high-echo spots in the gastric cavity and on the gastric wall surface after the procedure . RESULTS Pre-medication with pronase ( treatment C ) significantly reduced ( both at P < 0.05 ) the visibility score ( score 4 , 46 % ) in comparison with that obtained for pre-medication without pronase ( 10 % for both treatments A and B ) . Treatment with pronase significantly reduced ( both at P < 0.05 ) the endoscopic ultrasonography score in the gastric cavity ( score 4 , 34 % ) in comparison with that found for treatments A ( 7 % ) and B ( 0 % ) . It also significantly reduced ( P < 0.05 ) the endoscopic ultrasonography score on the gastric wall surface ( score 4 , 14 % ) in comparison with that observed for treatment A ( 3 % ) . The numbers of high-echo spots in the gastric cavity and on the gastric wall surface were significantly less ( both at P < 0.001 ) for pre-medication with pronase ( treatment C ) than for pre-medication with treatments A and B . There were no complications associated with the solutions . CONCLUSIONS Pre-treatment with pronase reduced the artefacts during endoscopic ultrasonography .

pronase

ultrasonography

proteolytic enzyme

pronase

endoscopic ultrasonography

anti-foam agent

dimethylpolysiloxane , alone

pronase

pronase

pronase

pronase

pronase

artefacts

artefacts

visibility score

the endoscopic ultrasonography score

endoscopic ultrasonography score

no complications

artefacts


Effects of pentoxifylline administration on urinary N-acetyl-beta-glucosaminidase excretion in type 2 diabetic patients : a short-term , prospective , randomized study . BACKGROUND Tubulointerstitial injury is a major feature of diabetic nephropathy and an important predictor of renal dysfunction . In 45 patients with type 2 diabetes mellitus ( DM ) , we prospectively analyzed urinary excretion of N-acetyl-beta-glucosaminidase ( NAG ) , a marker of tubular renal damage ; the potential relationship with urinary protein excretion ; and effects of pentoxifylline ( PTF ) administration . METHODS Forty-five patients with type 2 DM initially were compared with 15 healthy controls matched for age and sex . After randomization , PTF ( 1,200 mg/d ) was administered for 4 months to 30 patients and results were compared with data from a control group ( n = 15 ) . RESULTS Proteinuria and urinary NAG excretion were significantly greater in patients with DM with respect to healthy controls . Before PTF administration , baseline parameters were similar in both groups of patients with DM . At the end of the study , urinary protein excretion and NAG-creatinine ratios decreased in the active group from 920 +/- 522 mg/d and 14.3 +/- 16.9 U/g to 803 +/- 523 mg/d ( P < 0.001 ) and 10.5 +/- 9.3 U/g ( P < 0.05 ) , respectively . Conversely , proteinuria and urinary NAG excretion did not change in the control group . Regression analysis showed that urinary NAG excretion was significantly associated with duration of DM ( r = 0.61 ; P < 0.001 ) and proteinuria ( r = 0.51 ; P < 0.001 ) . CONCLUSION Urinary NAG excretion is elevated in patients with type 2 DM compared with healthy individuals and increases as nephropathy progresses . PTF administration is effective in reducing proteinuria and urinary NAG excretion in these patients . These findings suggest that PTF may have beneficial effects on tubulointerstitial damage in diabetic kidney disease .

pentoxifylline

pentoxifylline ( PTF )

PTF

control

PTF

PTF

Proteinuria and urinary NAG excretion

proteinuria and urinary NAG excretion

urinary NAG excretion

proteinuria

Urinary NAG excretion

proteinuria and urinary NAG excretion

type 2 diabetic patients :


An in vitro comparative analysis : scanning electron microscopy of dentin/restoration interfaces . One hundred maxillary premolar teeth were randomly allocated to ten groups . Each group was restored with one of ten different restorative techniques . The teeth were stored in deionized water for 7d prior to longitudinal sectioning in a mesio-distal plane . Following sectioning , ten specimens from each group were chosen at random from the 20 available sections . The sectioned surfaces were polished using 600-grit SiC abrasive paper and etched for 10 s with 50 % phosphoric acid to remove the smear layer produced by sectioning . Five tooth sections from the dentin bonding resin groups were allowed to dry at 20 degrees C for 24h . The glass ionomer-based groups were reimmersed in deionized water during this period . The remaining five sections from each group were replicated using an addition-cure vinyl polysiloxane impression material and an epoxy resin . A comparison was made of the sections and the replicas . All tooth specimens were sputter-coated with gold for 4 min and examined using a scanning electron microscope . Replicas were gold-coated for 3 min . Different tooth/restoration interfaces , associated with different materials , were observed . A marked difference between the replicas and tooth sections was observed for glass ionomer-based restorations but not for resin-based bonding systems . Representative samples of replicas and specimens are shown , and the significance of the observed differences is discussed .

ten different restorative techniques

600-grit SiC abrasive paper

epoxy resin

sputter-coated with gold

glass ionomer-based restorations

resin-based bonding

One hundred


A comparison of magnesium sulfate and nimodipine for the prevention of eclampsia .

magnesium sulfate and nimodipine

prevention of eclampsia .

prevention of eclampsia


Reduction of isoflurane MAC by fentanyl or remifentanil in rats . OBJECTIVE The main objective of the study was to determine the effects of three different infusion rates of fentanyl and remifentanil on the minimum alveolar concentration ( MAC ) of isoflurane in the rat . A secondary objective was to assess the cardiovascular and respiratory effects of the two opioid drugs . ANIMAL POPULATION Thirty-seven male Wistar rats were randomly allocated to one of six treatment groups . MATERIAL AND METHODS For all treatment groups anaesthesia was induced with 5 % isoflurane in oxygen using an induction chamber . A 14-gauge catheter was used for endotracheal intubation , and anaesthesia was maintained with isoflurane delivered in oxygen via a T-piece breathing system . A baseline determination of the minimum alveolar concentration of isoflurane ( MACISO ) was made for each animal . Fentanyl ( 15 , 30 , 60 micro g kg-1 hour-1 ) or remifentanil ( 60 , 120 , 240 micro g kg-1 hour-1 ) were infused intravenously into a previously cannulated tail vein . Thirty minutes after the infusion started , a second MACISO ( MACISO+drug ) was determined . The carotid artery was cannulated to monitor the arterial pressure and to take samples for arterial gas measurements . Cardiovascular ( heart rate and arterial pressure ) and respiratory ( respiratory rate and presence/absence of apnoea ) effects after opioid infusion were also recorded . RESULTS Fentanyl ( 15 , 30 , 60 micro g kg-1 hour-1 ) and remifentanil ( 60 , 120 , 240 micro g kg-1 hour-1 ) similarly reduced isoflurane MAC in a dose-dependent fashion : by 10 % at lower doses , 25 % at medium doses and by 60 % at higher doses of both the drugs . Both opioids reduced the respiratory rate in a similar way for all doses tested . No episodes of apnoea were recorded in the remifentanil groups , while administration of fentanyl resulted in apnoea in three animals ( one at each dose level ) . The effects on the cardiovascular system were similar with both drugs . CONCLUSIONS We conclude that the intraoperative use of remifentanil in the rat reduces the MAC of isoflurane , and that this anaesthetic sparing effect is dose-dependent and similar to that produced by fentanyl at the doses tested . CLINICAL RELEVANCE The use of remifentanil during inhalant anaesthesia in the rat can be considered an intravenous alternative to fentanyl , providing similar reduction in isoflurane requirements . Due to its rapid offset , it is recommended that alternative pain relief be instituted before it is discontinued .

fentanyl

remifentanil

fentanyl

remifentanil

isoflurane in oxygen

Fentanyl

remifentanil

Fentanyl

remifentanil

remifentanil

remifentanil

remifentanil

fentanyl

arterial pressure

Thirty-seven

male


Evaluation of the effect of acetazolamide on cystoid macular oedema in patients with Behcet 's disease . AIM To study the effect of acetazolamide on cystoid macular oedema ( CMO ) in patients with Behcet 's disease . PATIENTS AND METHODS A total of 67 eyes of 35 Behcet 's patients with chronic , but well-controlled uveitis , and CMO were randomised into a double-masked , crossover trial comparing the effect of acetazolamide vs placebo . The patients received an initial 4-week course of either 250 mg acetazolamide twice daily ( b.i.d . ) or placebo , followed by a 4-week washout period . They then received a 4-week course of the reverse study medication . An improvement in visual acuity and fundus fluorescein angiographic findings was assessed . RESULTS In total , 29 patients ( 55 eyes ) completed the trial and were available for analysis . Of the 29 , 16 men and 13 were women . The age range was 13-50 years ( mean 33.6 years ) . Patients on acetazolamide showed a slightly better improvement of angiographic signs ( at least by one grade improvement ) over that of placebo ( 12 vs five eyes ) . They also had less deterioration of angiographic signs over that of placebo ( three vs seven eyes ) . However , these findings were not statistically significant ( P=0.99 ) . Acetazolamide had no statistically significant effect ( P=0.53 ) on the improvement of visual acuity of patients over that of placebo ( 13 vs eight eyes ) , nor on the deterioration of visual acuity ( three vs 11 eyes ) . CONCLUSION Despite seemingly favourable results , the 4-week course of acetazolamide ( 250 mg b.i.d . ) has no statistically significant effect on the improvement of the visual acuity and the fluorescein angiographic findings in Behcet 's patients with CMO .

acetazolamide

acetazolamide

acetazolamide

acetazolamide

placebo

acetazolamide

placebo

placebo

Acetazolamide

placebo

acetazolamide

visual acuity

angiographic signs

deterioration of angiographic signs

visual acuity

visual acuity

fluorescein angiographic findings

cystoid macular oedema

Behcet 's disease

Behcet 's disease

67 eyes of 35 Behcet 's patients

men

women

13-50 years

Behcet 's


Advice or exercise for chronic whiplash disorders ? Design of a randomized controlled trial . BACKGROUND Whiplash-associated disorder ( or " whiplash " ) is a common condition incurring considerable expense in social and economic terms . A lack of research on effective therapy for patients with chronic whiplash associated disorders prompted the design of the current study . The primary aim of this randomised controlled trial is to determine the effects of a physical activity program for people with chronic ( symptoms of > 3 months duration ) whiplash . A secondary aim is to determine if pain severity , level of disability and fear of movement/ ( re ) injury predict response to a physical activity program . METHODS/DESIGN This paper presents the rationale and design of a randomised controlled trial examining the effects of advice and individualized sub-maximal exercise programs in the treatment of whiplash associated disorders . DISCUSSION This paper highlights the design , methods and operational aspects of a significant clinical trial in the area of whiplash and chronic pain .

advice and

response


Observational learning and the formation of classes of reading skills by individuals with autism and other developmental disabilities . We investigated whether individuals with developmental disabilities will demonstrate stimulus classes after observing another individual demonstrate the prerequisite conditional discriminations . In Experiment 1 , participants learned conditional discriminations among dictated words , pictures , and printed words . They also observed a model without disabilities demonstrate conditional discriminations among a different set of dictated words , pictures , and printed words . The classes assigned to each participant belonged to a larger superordinate category , as did the classes assigned to each model . The superordinate categories were different for participants and models . All participants subsequently demonstrated full stimulus classes with the stimuli involved in direct training : They named pictures , read printed words , and matched pictures and words to one another . However , based on observing a model , none of the participants demonstrated full stimulus classes . In Experiment 2 , participants learned conditional discriminations among the stimuli in three sets , and observed a model 's training with the stimuli in three different sets . The classes assigned to each participant belonged to the same larger superordinate category as did those assigned to their respective model . All participants subsequently demonstrated full stimulus classes with the stimuli involved in direct training . They also demonstrated full classes with at least one of their model 's sets of training stimuli . When full stimulus classes did not occur from observing a model , participants named the model 's pictures , read the model 's printed words , or matched the model 's pictures and words . Stimulus class technology , coupled with the opportunity to observe another individual perform a skill , may be an economical and efficient means of teaching persons with developmental disabilities .

Observational learning

superordinate categories

observed a model 's training

Stimulus class technology

observe another individual perform

stimulus classes

stimulus classes .

full stimulus classes

full classes

autism


Randomized , double-blind , multicenter trial comparing two doses of arzoxifene ( LY353381 ) in hormone-sensitive advanced or metastatic breast cancer patients . BACKGROUND This randomized , double-blind , phase II study assessed two doses of the selective estrogen receptor modulator arzoxifene in women with advanced breast cancer . The primary end point was to choose the best of two doses of arzoxifene based on the response rate or the clinical benefit rate ( CBR ) . Pharmacokinetics and toxicities were also assessed . PATIENTS AND METHODS Ninety-two patients with advanced breast cancer received arzoxifene 20 or 50 mg/day . Tumor response was assessed using World Health Organization criteria . Toxicities were graded according to the National Cancer Institute Common Toxicity Criteria ( NCI-CTC ) system . Pharmacokinetic data were analyzed using the NONMEM software program ( GloboMax , Hanover , MD , USA ) . RESULTS Response rates in the 20 mg arm were numerically higher than the 50-mg arm according to the investigator ( 40.5 % versus 36.4 % ) and the independent review panel ( 42.9 % versus 27.3 % ) . CBR was higher in the 20 mg arm according to the investigator ( 64.3 % versus 61.4 % ) and the independent review panel ( 59.5 % versus 47.7 % ) . Arzoxifene was well tolerated . There were no study drug-related deaths . Mean observed steady-state plasma concentrations of arzoxifene were 3.62 and 7.48 ng/ml for the 20 and 50 mg doses , respectively . CONCLUSIONS There were no significant differences in efficacy or safety between 20 and 50 mg of arzoxifene . Accordingly , arzoxifene 20 mg/day was selected for further study in patients with breast cancer .

arzoxifene ( LY353381 )

arzoxifene

arzoxifene 20 or 50 mg/day

World Health Organization criteria

Toxicities were graded according to the

Arzoxifene

arzoxifene

arzoxifene

arzoxifene

Pharmacokinetics

toxicities

Tumor response

Toxicities

Pharmacokinetic data

Response rates

CBR

drug-related deaths .

steady-state plasma concentrations

efficacy

safety

women

with advanced breast cancer

Ninety-two


Investigation of erosion and abrasion on enamel and dentine : a model in situ using toothpastes of different abrasivity . BACKGROUND Studies in vitro suggest that abrasion and erosion may act synergistically to produce wear of enamel and dentine . Methods in situ are recently available to study separately erosion and abrasion of dental tissues . The aim of this study was to combine two in situ protocols to study the interplay between erosion and abrasion of enamel and dentine . METHOD The study was a single-blind , randomised , five-treatment cross-over design involving 15 healthy volunteers . During each 10-day study period , subjects wore from 0900 to 1700 h an upper removable acrylic appliance holding one polished enamel and one polished dentine specimen . The specimen treatment regimens were : 1 . Drinking water and brushing with toothpaste A . 2 . Drinking water and brushing with toothpaste B . 3 . Drinking orange juice . 4 . Drinking orange juice and brushing with toothpaste A . 5 . Drinking orange juice and brushing with toothpaste B . Drinking and brushing times were around 0900 , 1100 , 1300 and 1500 h. Drinks were consumed as 250 ml over 10 min and brushing ex vivo for 1 min to each specimen . Measurement of tissue loss was made on days 5 and 10 of each period using a profilometer . RESULTS All treatments produced increasing tissue loss over time , which was considerably greater for dentine than enamel . For enamel , the data at days 5 and 10 showed a significant effect for erosion ( i.e . orange juice was significantly more erosive than water ) , but no significant effect for abrasion ( i.e . no significant difference between the two toothpaste treatments ) . The combined orange juice and toothpaste effects were directional for synergy but did not reach significance . For dentine at day 10 , many specimens exceeded the 50 microm set limit of the profilometer and only day 5 data were considered . There were significant effects for erosion ( orange juice produced significantly more erosion than water ) and for abrasion ( paste A was significantly more abrasive to dentine than paste B ) . The synergy effect could not be examined for dentine due to the truncation effect as the set limit of the profilometer was exceeded . CONCLUSIONS Erosion increases the susceptibility of enamel to toothpaste abrasion . Dentine is considerably more susceptible than enamel to erosion and abrasion alone or combined . Dentine loss appears to correlate with toothpaste abrasivity ( RDA value ) .

toothpastes

abrasivity

one polished dentine specimen

Drinking water

brushing

toothpaste

orange juice

orange juice

brushing with toothpaste

erosion

abrasion

enamel and dentine

abrasion

erosion

wear of enamel and dentine

erosion

abrasion

dental tissues

erosion

abrasion

enamel

dentine

tissue loss

tissue loss over time

erosion

abrasion

erosion

abrasion

synergy effect

susceptibility of enamel

toothpaste abrasion

erosion

abrasion

Dentine loss


Efficacy and tolerability of donepezil in vascular dementia : positive results of a 24-week , multicenter , international , randomized , placebo-controlled clinical trial . BACKGROUND AND PURPOSE Clinical observations suggest that patients with vascular dementia ( VaD ) may benefit from treatment with cholinesterase inhibitors . This study evaluated the efficacy and safety of donepezil for relieving symptoms of dementia in VaD . METHODS Patients ( n=603 ; mean age , 73.9 years ; 55.2 % men ) with probable ( 70.5 % ) or possible ( 29.5 % ) VaD , according to criteria of the National Institute of Neurological Disorders and Stroke ( NINDS ) and the Association Internationale pour la Recherche et l'Enseignement en Neurosciences ( AIREN ) , were randomized to 24 weeks of treatment with donepezil 5 mg/d ( n=198 ) , donepezil 10 mg/d ( 5 mg/d for first 28 days ; n=206 ) , or placebo ( n=199 ) . Analyses were based on the intent-to-treat population . RESULTS At week 24 , both donepezil groups showed significant improvement in cognition versus placebo on the Alzheimer 's Disease Assessment Scale-cognitive subscale ( mean change from baseline score effect size : donepezil 5 mg/d , -1.90 ; P=0.001 ; donepezil 10 mg/d , -2.33 ; P < 0.001 ) . Significant improvements in patients ' global function were seen versus placebo at week 24 ( observed cases ) , on the Clinician 's Interview-Based Impression of Change-Plus version only for patients on donepezil 5 mg/d ( P=0.014 ) , and on the Sum of the Boxes of the Clinical Dementia Rating only for patients on 10 mg/d ( P=0.007 ) . Donepezil-treated patients showed significant benefits in activities of daily living over placebo on the Alzheimer 's Disease Functional Assessment and Change Scale ( mean change from baseline score effect size at week 24 : donepezil 5 mg/d , -1.31 , P=0.02 ; donepezil 10 mg/d , -1.31 , P=0.02 ) . Donepezil was well tolerated . Withdrawal rates due to adverse events were relatively low ( placebo , 11.1 % ; donepezil 5 mg/d , 11.1 % ; donepezil 10 mg/d , 21.8 % ; P=0.005 versus placebo ) . CONCLUSIONS These data demonstrate that donepezil is an effective and well-tolerated treatment for VaD and show it may have an important place in the management of this condition .

donepezil

placebo-controlled

cholinesterase inhibitors

donepezil

donepezil

donepezil

placebo

donepezil

placebo

donepezil

donepezil

donepezil

placebo

Efficacy

tolerability

efficacy

safety

improvement in cognition

patients ' global function

activities of daily living

Withdrawal rates

adverse events

vascular dementia

mean age , 73.9 years

men


Cirrhosis and bleeding : the need for very early management . BACKGROUND/AIMS Retrospective studies suggest that the prognosis of patients with cirrhosis and variceal hemorrhage has improved in more recent decades . In a prospective cohort study in which the choice of prophylactic therapy was left to each practitioner , we followed cirrhotic patients with medium/large varices to determine factors predictive of bleeding and death . METHODS Three hundred fourteen patients with grades 2 or 3 esophageal varices ( Child A and B/C : 218 and 96 ) were enrolled . One hundred seventy-three patients had no previous history of variceal bleeding . Only 245 patients ( 100 % of patients with prior variceal hemorrhage , 61 % of patients without prior hemorrhage ) were receiving some form of prophylactic therapy . The median follow-up was 18 months . RESULTS There were 76 bleeding events and 14 related deaths ( 18 % ) ; nine of these deaths occurred within 24 h of bleeding onset ( two at home , two during hospital transfer , and five in hospital , a mean of 2.5 h after onset ; six involved Child C patients ) . Twenty-five deaths were not due to bleeding but were closely related to cirrhosis . In a Cox model , the presence of tense ascites ( relative risk 3.4 , 95 % confidence interval , CI 2.5-5.9 ) and a prior history of hemorrhage ( relative risk 4.4 , 95 % CI 2.6-7.5 ) were independent predictors of variceal hemorrhage . In patients without a prior history of bleeding , bleeding risk was higher with more prolonged prothrombin time and lower when patients were receiving propranolol . CONCLUSIONS Despite the advent of effective drugs and endoscopic therapy for variceal bleeding , about a quarter of deaths occur very early after bleeding onset , confirming the need for rapid specific management .

prophylactic therapy

prophylactic therapy

propranolol

endoscopic therapy

bleeding events

related deaths

bleeding

deaths

variceal hemorrhage

bleeding , bleeding risk

deaths

cirrhosis and variceal hemorrhage

cirrhotic

Three hundred fourteen