Oxaprozin versus diclofenac in NSAID-refractory periarthritis pain of the shoulder . OBJECTIVE To evaluate the efficacy and safety of oxaprozin in comparison with diclofenac in patients with periarthritis pain of the shoulder previously unsuccessfully treated with nonsteroidal anti-inflammatory drugs other than diclofenac and oxaprozin . METHODS In this open , multicentre , randomised , controlled study , eligible patients with periarthritis of the shoulder were randomised to receive either oxaprozin 1200 mg once daily ( n = 49 ) or diclofenac 50 mg three times daily ( n = 47 ) . The treatment period was 15 +/- 1 days . The study was planned on a hypothesis of equivalence between the two study drugs . The primary study endpoint was the change from baseline at day 15 in the patient-assessed shoulder pain score . Secondary efficacy variables included investigator-assessed shoulder function , patient-assessed quality of life on the Short-Form-36 ( SF-36 ) Acute Health Survey and both patients ' and investigators ' overall assessment of efficacy . RESULTS At day 15 , the mean changes in shoulder pain score from baseline in the oxaprozin and diclofenac groups were -5.85 +/- SD 4.62 and -5.54 +/- SD 4.41 , respectively . The difference between the two groups was not statistically significant , confirming the hypothesis of the study that oxaprozin is as effective as diclofenac . Investigator-assessed shoulder function improved in both groups but more so in the oxaprozin group ( p = 0.028 at day 15 ) . Quality of life as measured by SF-36 total score was also improved in both treatment groups , with a trend toward greater improvement in the oxaprozin group . Furthermore , a significantly more favourable effect on the SF-36 'mental health ' item was observed in oxaprozin compared with diclofenac-treated patients at day 15 ( p = 0.0202 ) . As assessed by investigators , the overall efficacy of oxaprozin was superior to that for diclofenac at visit 3 ( 8 +/- 1 days ) ( p = 0.0067 ) . Patients also assessed the overall efficacy of oxaprozin as superior to that of diclofenac at visits 3 ( 8 +/- 1 days ) ( p = 0.0235 ) and 4 ( 15 +/- 1 days ) ( p = 0.0272 ) . Only six adverse events , all of which were mild or moderate in intensity and occurred in four diclofenac recipients , were observed in the study . CONCLUSIONS As expected , once-daily oxaprozin proved to be as effective as diclofenac three times daily in reducing the primary efficacy variable of patient-assessed shoulder pain score in patients with periarthritis of the shoulder refractory to previous treatments with other NSAIDs . Oxaprozin was shown to be superior to diclofenac in improving shoulder function and was considered by investigators and patients to have greater overall efficacy than diclofenac . In addition , oxaprozin showed a trend toward superior results in improving patients ' quality of life compared with diclofenac . A trend towards better tolerability results for oxaprozin compared with diclofenac was also noted .

Oxaprozin

diclofenac

oxaprozin

diclofenac

oxaprozin

diclofenac

oxaprozin

diclofenac

oxaprozin

oxaprozin

diclofenac

oxaprozin

diclofenac

diclofenac

oxaprozin

diclofenac

Oxaprozin

diclofenac

diclofenac

oxaprozin

diclofenac

oxaprozin

diclofenac

efficacy

shoulder pain score

difference

Investigator-assessed shoulder function

effect

SF-36 'mental health ' item

efficacy

adverse events

patient-assessed shoulder pain score

shoulder function

quality of life

tolerability results

periarthritis

shoulder pain

periarthritis


A prospective randomised comparison of sublingual and vaginal misoprostol in second trimester termination of pregnancy . OBJECTIVE To compare the efficacy , side effects and acceptability of sublingual and vaginal misoprostol for second trimester medical abortion . DESIGN Prospective randomised controlled trial . SETTING Tertiary referral unit and a teaching hospital . POPULATION Two hundred and twenty-four women at 12 to 20 weeks of gestation . METHODS The women were randomised to receive either sublingual or vaginal misoprostol 400 microg every 3 hours for a maximum of five doses . The course of misoprostol was repeated if the woman did not abort within 24 hours . MAIN OUTCOME MEASURES The success rate at 48 hours , induction-to-abortion interval and the side effects . RESULTS There was no significant difference in the success rate at 48 hours ( sublingual : 91 % ; vaginal : 95 % ) . However , the success rate at 24 hours was significantly higher in the vaginal group ( 85 % ) compared with the sublingual group ( 64 % ) . There was no difference in the median induction-to-abortion interval ( sublingual : 13.8 hours ; vaginal : 12.0 hours ) . Significantly more women in the sublingual group preferred the route to which they were assigned when compared with the vaginal group . The incidence of fever was also less in the sublingual group . CONCLUSION The use of vaginal misoprostol for second trimester medical abortion resulted in a higher success rate than sublingual misoprostol at 24 hours but the abortion rate was similar at 48 hours . Vaginal misoprostol should be the regimen of choice but sublingual misoprostol is also an effective alternative .

sublingual and vaginal misoprostol

sublingual and vaginal misoprostol

sublingual or vaginal misoprostol

misoprostol

vaginal misoprostol

misoprostol

Vaginal misoprostol

sublingual misoprostol

efficacy

side effects

acceptability

side effects

the success rate at 48 hours

success rate at 24 hours

preferred the route

The incidence of fever

success rate

abortion rate

second trimester medical abortion .

Two hundred and twenty-four women


Comparison of an allograft in an experimental putty carrier and a bovine-derived xenograft used in ridge preservation : a clinical and histologic study in humans . PURPOSE The aim of this randomized , controlled , blinded clinical study was to compare ridge dimensions and histologic characteristics of ridges preserved with 2 different graft materials . MATERIALS AND METHODS Twenty-four subjects , each requiring a nonmolar extraction and delayed implant placement , were randomly selected to receive ridge preservation treatment with either an allograft in an experimental putty carrier plus a calcium sulfate barrier ( PUT ) or a bovine-derived xenograft ( BDX ) plus a collagen membrane . Horizontal and vertical ridge dimensions were determined using a digital caliper and a template . At 4 months postextraction , a trephine core was obtained for histologic analysis . RESULTS The average ridge width decreased by 0.50 mm for both groups ( P < .05 ) . The midbuccal vertical change for the PUT group was a loss of 0.3+/-0.7 mm versus a gain of 0.7+/-1.2 mm for the BDX group , a difference of 1.0 mm ( P > .05 ) . Histologic analysis revealed vital bone in the PUT group of about 61 % +/-9 % versus 26 % +/-20 % for the BDX group ( P < .05 ) . DISCUSSION Greater vital bone fill in the PUT group may be attributable to earlier and greater vascular invasion of the carrier material . The putty material was characterized by ease of handling , simple placement , and enhanced graft particle containment . CONCLUSIONS Allograft mixed with an experimental putty carrier produced significantly more vital bone fill than did the use of a xenograft with no carrier material . Ridge width and height dimensions were similarly preserved with both graft materials .

allograft

graft materials

calcium sulfate barrier

bovine-derived xenograft ( BDX )

BDX

BDX

xenograft

histologic analysis

ridge width

midbuccal vertical change

vital bone

vital bone fill

Ridge width and height dimensions

humans

Twenty-four

nonmolar extraction

delayed implant placement


A double blind randomized trial to compare the effects of eprosartan and enalapril on blood pressure , platelets , and endothelium function in patients with essential hypertension . The renin-angiotensin system is the major contributor to development of hypertension , atherosclerosis , and many other cardiovascular diseases . Angiotensin II , one of the main effectors of this system , contributes to the pathogenesis of hypertension and plays an important role in monocyte , platelet , and endothelium interactions . The effects on platelet and endothelial function , either by angiotensin converting enzyme inhibitors or angiotensin receptor antagonists , are still not well understood . A double-blind , randomized , prospective trial of either enalapril ( 10-20 mg daily ) or eprosartan ( 400-800 mg daily ) over a 10-week period was conducted in 42 patients ( 27 males , 15 females ) . Platelet activation was evaluated by measuring platelet factor 4 ( PF-4 ) , beta-thromboglobulin ( beta-TG ) , the ratio of platelet factor 4 to beta-thromboglobulin , and endothelial function by measuring total plasma nitrate levels , von Willebrand factor ( vWF ) levels , and blood flow using venous occlusive plethysmography . After a 10-week treatment with enalapril or eprosartan , the sitting blood pressure in both the enalapril group ( from 152.2 +/- 18.7 mmHg to 141.9 +/- 23.5 mmHg , P < 0.05 ) and eprosartan group ( from 151 +/- 10.0 mmHg to 142.3 +/- 12.9 mmHg , P < 0.05 ) was significantly reduced . Significant diastolic blood pressure ( DPB ) reduction ( from 94 +/- 8.7 to 84.5 +/- 9.6 mmHg , P < 0.05 ) and a greater DBP reduction response were found in the eprosartan group ( 63 % in eprosartan versus 25 % in enalapril ) . Additionally , dose-dependent reductions in the indices of platelet activation and endothelial dysfunction were observed in patients administered high dose treatments of eprosartan and enalapril , and the beneficial effects of these agents were not correlated with the reduction of blood pressure using both agents . Eprosartan is effective and well-tolerated in the treatment of mid-to-moderate hypertension , and the DBP response reduction to eprosartin was better than that to enalapril . A high dose of either eprosartan or enalapril significantly decreased the indices of platelet activation and endothelial dysfunction in hypertensive patients . The benefits of both agents can not be explained solely by their antihypertensive effects and possibly may be mediated through their unique effect on angiotensin blockade .

eprosartan and enalapril

enalapril

eprosartan

enalapril or eprosartan

enalapril

eprosartan

eprosartan

eprosartan

enalapril

eprosartan and enalapril

Eprosartan

eprosartin

enalapril

eprosartan or enalapril

blood pressure

platelets

endothelium function

platelet and endothelial function

von Willebrand factor ( vWF ) levels

sitting blood pressure

diastolic blood pressure ( DPB )

DBP

platelet activation

endothelial dysfunction

blood pressure

effective

well-tolerated

DBP

platelet activation

essential hypertension

males

females

hypertensive


Flutamide-metformin plus ethinylestradiol-drospirenone for lipolysis and antiatherogenesis in young women with ovarian hyperandrogenism : the key role of early , low-dose flutamide . A low-dose combination of flutamide-metformin and ethinylestradiol-drospirenone was recently found to reduce the excess of total and abdominal fat , to diminish the deficit in lean mass , and to attenuate the dysadipocytokinemia of young women with ovarian hyperandrogenism , a variant of polycystic ovary syndrome . We questioned the need to give flutamide , an androgen receptor blocker , together with an oral contraceptive that contains drospirenone , a progestin claimed to have antiandrogen properties . The additive effects of low-dose flutamide ( 62.5 mg/d ) were assessed over 3 months in young patients with hyperinsulinemic ovarian hyperandrogenism ( n = 40 ; age , approximately 17 yr ; body mass index , approximately 22 kg/m ( 2 ) ) ; all participants started on metformin ( 850 mg/d ) and a fourth-generation contraceptive ( ethinylestradiol 30 microg plus drospirenone 3 mg , 21 d/month ) , and they were randomized to receive flutamide in addition ( n = 20 ) or not ( n = 20 ) . Fasting blood glucose , serum insulin , lipid profile , testosterone , adiponectin , and IL-6 were determined at baseline and after 3 months , together with body composition ( by dual x-ray absorptiometry ) and with Doppler assessment of ovarian arterial resistance . At start , the pulsatility and resistance indices of ovarian arteries were elevated . By comparison of 3-month changes between randomized subgroups , the addition of low-dose flutamide was found to have consistently ( more ) normalizing effects on low-density lipoprotein cholesterol , IL-6 , and adiponectin , lean body mass , total and abdominal fat mass , and arterial flow in the ovaries . In conclusion , low-dose flutamide is herewith identified as a pivotal component within a first contraceptive combination therapy that has been shown to attenuate the hypoadiponectinemia , ovarian vascular hyperresistance , lean mass deficit , and central adiposity of young women with polycystic ovary syndrome . Finally , these data challenge any claim that drospirenone , as currently used in a contraceptive , is a clinically significant antiandrogen .

flutamide-metformin

ethinylestradiol-drospirenone

drospirenone

low-dose flutamide

metformin

flutamide

flutamide

drospirenone

lipolysis and antiatherogenesis

excess of total and abdominal fat

lean mass

dysadipocytokinemia

Fasting blood glucose

serum insulin

lipid profile

testosterone

adiponectin

pulsatility

resistance indices

adiponectin , lean body mass

total and abdominal fat mass

arterial flow in the ovaries

hypoadiponectinemia

ovarian vascular hyperresistance

lean mass deficit

central adiposity

young

women

ovarian hyperandrogenism

young

women

ovarian hyperandrogenism

variant of polycystic ovary syndrome

17 yr


Low-dose oral etoposide-based induction regimen for children with acute lymphoblastic leukemia in first bone marrow relapse . We evaluated the clinical response to low-dose etoposide in relapsed acute lymphoblastic leukemia ( ALL ) . Of the 45 patients with ALL in first bone marrow relapse enrolled on the ALL R15 protocol , 44 had received epipodophyllotoxins during frontline therapy . In the first week of remission induction therapy , patients received etoposide ( 50 mg/m ( 2 ) per day ) administered orally as a single agent once or twice daily . On Day 8 , patients started to receive dexamethasone , vincristine , and L-asparaginase . Etoposide was administered until Day 22 . Two courses of consolidation therapy were followed by continuation therapy or hematopoietic stem cell transplantation . After 7 days of single-agent etoposide treatment , peripheral blast cell counts ( P=0.013 ) and percentages of bone marrow blasts ( P=0.016 ) were significantly reduced . In all , 38 ( 84.4 % ) attained second remission . Only time to relapse was significantly associated with outcome ( P=0.025 ) : the 5-year event-free survival estimates ( +/-se ) were 52.0+/-9.6 % for those with late relapse and 20.0+/-8.0 % for those with early relapse . We conclude that low-dose etoposide administered orally has a cytoreductive effect in relapsed ALL .

Low-dose oral etoposide-based

low-dose etoposide

etoposide

Etoposide

continuation therapy

hematopoietic stem cell transplantation

low-dose etoposide

clinical response

peripheral blast cell counts

percentages of bone marrow blasts

second remission .

time to relapse

5-year event-free survival

children

acute lymphoblastic leukemia

acute lymphoblastic leukemia

ALL


Estradiol and the addition of progesterone increase the sensitivity to a neurosteroid in postmenopausal women . The aim of this study was to compare the pharmacodynamic response to a neuroactive steroid , pregnanolone , before and during different hormonal settings of postmenopausal hormone replacement therapy ( HRT ) , using natural progesterone . A second aim was to investigate whether the response to pregnanolone was associated with cyclicity in negative mood symptoms during treatment . Twenty six postmenopausal women with climacteric symptoms were administered HRT in a randomized , double blinded , placebo-controlled , crossover study . The women received 2 mg oral estradiol ( E ( 2 ) ) continuously during two 28-day cycles and 800 mg of vaginal progesterone or placebo sequentially for the last 14 days of each treatment cycle . Pharmacodynamic response to pregnanolone was assessed before treatment , and during the last week of each treatment cycle , by comparing the effects of intravenous pregnanolone ( 3alpha-hydroxy-5beta-pregnan-20-one ) on saccadic eye velocity ( SEV ) , saccade acceleration , saccade latency and self-rated sedation . Throughout the study daily symptom rating scales were kept . According to the daily symptom rating scales , patients were divided into two groups ; one group who displayed a significant variance in negative mood symptoms during HRT ( cyclicity ) and one group with no cyclical changes in negative mood symptoms during treatment . During treatment with either E ( 2 ) alone or E ( 2 ) +progesterone the response in saccadic eye movement parameters and in self-rated sedation to pregnanolone was enhanced compared to pretreatment values . The SEV , saccade acceleration and sedation responses to pregnanolone was also increased in women expressing cyclicity in negative mood symptoms compared to women with no cyclical changes in negative mood during HRT . In conclusion , during treatment with either E ( 2 ) alone , or E ( 2 ) +progesterone , pregnanolone sensitivity was increased . Women expressing cyclicity in negative mood symptoms were more sensitive to pregnanolone than women without symptom cyclicity during HRT .

Estradiol

progesterone

neuroactive steroid , pregnanolone

natural progesterone

pregnanolone

HRT

oral estradiol ( E ( 2 ) )

vaginal progesterone

placebo

HRT

E ( 2 ) alone

E ( 2 ) +progesterone

pregnanolone

HRT

E ( 2 )

E ( 2 ) +progesterone

pregnanolone

HRT

negative mood symptoms

Pharmacodynamic response

daily symptom rating scales

daily symptom rating scales

negative mood symptoms

saccadic eye movement parameters

self-rated sedation

negative mood symptoms

pregnanolone sensitivity

postmenopausal

women

Twenty six

postmenopausal

women

climacteric symptoms

negative mood symptoms

negative mood symptoms

negative mood symptoms


Peripheral arterial disease : therapeutic confidence of CT versus digital subtraction angiography and effects on additional imaging recommendations . PURPOSE To compare multi-detector row computed tomographic ( CT ) angiography and digital subtraction angiography ( DSA ) prior to revascularization in patients with symptomatic peripheral arterial disease for the purpose of assessing recommendations for additional imaging and physician confidence ratings for chosen therapy . MATERIALS AND METHODS In a randomized controlled trial , 73 patients were assigned to CT angiography , and 72 were assigned to DSA . Physician confidence in the treatment decision was measured as a continuous outcome on a scale of 0-10 ( uncertain to certain ) and as a dichotomous outcome ( further imaging recommended , yes or no ) . Mean confidence scores and additional imaging recommendations were compared between CT and DSA groups in an intention-to-diagnose-and-treat analysis . To detect trends in confidence , confidence scores were plotted over time , and multiple linear regression analysis was performed . To detect trends in additional imaging recommendations , logistic regression analysis was used . Data from eligible nonrandomized patients were analyzed separately . RESULTS No statistically significant difference in baseline characteristics between randomized groups was found . CT had a lower confidence score than did DSA ( 7.2 vs 8.2 , P < .001 ) . Further imaging was recommended more often after CT ( 25 of 71 patients , 35 % ) than after DSA ( nine of 66 patients , 14 % ; P = .003 ) . Analysis of trends demonstrated increasing ( but not statistically significant ) confidence in CT and stable confidence in DSA . No significant difference was found in baseline characteristics between randomized and nonrandomized patients . Among nonrandomized patients , no significant difference in mean confidence score ( 8.2 vs 8.3 , P = .26 ) was found between CT ( n = 24 ) and DSA ( n = 26 ) . CONCLUSION With CT angiography , physician confidence decreases with an associated increase in additional imaging prior to revascularization in patients with symptomatic peripheral arterial disease . Given that CT is less invasive than DSA , results suggest that CT may replace DSA in selected cases .

CT

digital subtraction angiography

digital subtraction angiography ( DSA )

revascularization

CT angiography

DSA

CT

DSA

CT

DSA

CT

DSA

CT

DSA

CT

DSA

CT angiography

CT

DSA

CT

DSA

Mean confidence scores

additional imaging recommendations

additional imaging recommendations

lower confidence score

confidence

confidence

No significant difference

mean confidence score

73 patients

were assigned to CT angiography , and

were assigned to DSA


Parent management training and Asperger syndrome : a randomized controlled trial to evaluate a parent based intervention . This controlled trial of a parent management intervention aimed to increase parental competence in management of problem behaviours associated with Asperger syndrome . The intervention compared two formats , a 1 day workshop and six individual sessions . Measures were taken on three occasions : pre-intervention , at 4 weeks , and at 3 month follow-up . Variables of interest were number and intensity of problem behaviours , and parent evaluation of social interaction skills . Results showed parents reporting fewer and lower intensity of problem behaviours and increased social interactions at 4 weeks and 3 months . Results held across formats and suggest that parent management training can provide an effective intervention for parents of a child with Asperger syndrome . Group differences on outcome measures and in the use of strategies are discussed along with limitations of the study .

Parent management training

parent based intervention

parent management intervention

parent based intervention

intensity of problem behaviours

increased social interactions

parent based

Asperger syndrome

child

Asperger syndrome


Differential response of seven subjects with autistic disorder to clomipramine and desipramine . OBJECTIVE Clomipramine , a serotonin reuptake blocker that has unique antiobsessional properties , was hypothesized to have a different effect from that of desipramine , a tricyclic antidepressant with selective adrenergic effects , for the stereotyped , repetitive behaviors in autism . METHOD Seven subjects , ages 6-18 years , with autistic disorder completed a 10-week double-blind , crossover trial of clomipramine and desipramine following a 2-week single-blind , placebo phase . RESULTS Clomipramine was superior to desipramine and placebo , as indicated by standardized ratings of autism and anger as well as ratings of repetitive and compulsive behaviors . Clomipramine and desipramine were equally superior to placebo for ratings of hyperactivity . Parents of all seven subjects elected to have their children continue to take clomipramine after the study . CONCLUSIONS Clomipramine and desipramine are differentially effective in treating the obsessive-compulsive and core symptoms in autistic disorder . Biological links between compulsions and stereotyped , repetitive behaviors in autistic disorder should be explored .

clomipramine

desipramine

clomipramine

desipramine

placebo

ratings of autism and anger

ratings of hyperactivity

obsessive-compulsive

core symptoms

seven

subjects with autistic disorder

Seven

ages 6-18 years

autistic disorder

seven


Further evaluation of docosahexaenoic acid in patients with retinitis pigmentosa receiving vitamin A treatment : subgroup analyses . OBJECTIVE To determine whether docosahexaenoic acid will slow the course of retinal degeneration in subgroups of patients with retinitis pigmentosa who are receiving vitamin A . DESIGN A cohort of 208 patients with retinitis pigmentosa , aged 18 to 55 years , were randomly assigned to 1200 mg of docosahexaenoic acid plus 15 000 IU/d of vitamin A given as retinyl palmitate ( DHA + A group ) or control fatty acid plus 15 000 IU/d of vitamin A ( control + A group ) and followed up over 4 years . Seventy percent of the patients in each group were taking vitamin A , 15 000 IU/d , prior to entry . We compared rates of decline in ocular function in the DHA + A vs control + A groups among the subgroups defined by use or nonuse of vitamin A prior to entry . We also determined whether decline in ocular function was related to red blood cell phosphatidylethanolamine docosahexaenoic acid level , dietary omega-3 fatty acid intake , or duration of vitamin A use . Main outcome measures were Humphrey Field Analyzer visual field sensitivity , 30-Hz electroretinogram amplitude , and visual acuity . RESULTS Among patients not taking vitamin A prior to entry , those in the DHA + A group had a slower decline in field sensitivity and electroretinogram amplitude than those in the control + A group over the first 2 years ( P =.01 and P =.03 , respectively ) ; these differences were not observed in years 3 and 4 of follow-up or among patients taking vitamin A prior to entry . In the entire cohort , red blood cell phosphatidylethanolamine docosahexaenoic acid level was inversely related to rate of decline in total field sensitivity over 4 years ( test for trend , P =.05 ) . This was particularly evident over the first 2 years among those not on vitamin A prior to entry ( test for trend , P =.003 ) . In the entire control + A group , dietary omega-3 fatty acid intake was inversely related to loss of total field sensitivity over 4 years ( intake , < 0.20 vs > or =0.20 g/d ; P =.02 ) . The duration of vitamin A supplementation prior to entry was inversely related to rate of decline in electroretinogram amplitude ( P =.008 ) . CONCLUSIONS For patients with retinitis pigmentosa beginning vitamin A therapy , addition of docosahexaenoic acid , 1200 mg/d , slowed the course of disease for 2 years . Among patients on vitamin A for at least 2 years , a diet rich in omega-3 fatty acids ( > or =0.20 g/d ) slowed the decline in visual field sensitivity .

docosahexaenoic acid

vitamin A

docosahexaenoic acid

vitamin A

vitamin A

DHA + A

control + A

vitamin A

not taking vitamin A

DHA + A

control + A

vitamin A

docosahexaenoic acid

not on vitamin A

dietary omega-3 fatty acid

vitamin A supplementation

vitamin A therapy

docosahexaenoic acid

vitamin A

omega-3 fatty acids

30-Hz electroretinogram amplitude

visual acuity

field sensitivity

electroretinogram amplitude

total field sensitivity

total field sensitivity

duration of vitamin A supplementation

retinitis pigmentosa

retinitis pigmentosa

retinitis pigmentosa

18 to 55 years

retinitis pigmentosa


Association of race with complications and prognosis following acute coronary syndromes . The baseline characteristics , complications , and survival of 489 black and 6,890 non-black patients with acute coronary syndromes were studied . Important racial differences were observed in demographic features , atherosclerosis risk factors , and treatment strategies ; however , despite these differences , no independent difference was observed in clinical outcomes according to race . The 1-year mortality rate was 2.9 % for black patients and 2.5 % for non-black patients ( p = 0.93 ) .

race

treatment strategies

characteristics

complications

survival

racial differences

atherosclerosis risk factors

treatment strategies

mortality rate

coronary syndromes


Treatment of severe aplastic anemia with antilymphocyte globulin , cyclosporine and two different granulocyte colony-stimulating factor regimens : a GITMO prospective randomized study . BACKGROUND AND OBJECTIVES In a previous study we showed that patients with severe aplastic anemia ( SAA ) treated with anti-lymphocyte globulin ( ALG ) , cyclosporin ( CyA ) and granulocyte colony-stimulating factor ( G-CSF ) 5 micro g/kg/day had an encouraging outcome . However , failure to respond , delayed responses , partial responses , relapses and early deaths remain significant problems . The aim of the present study was to test whether a higher dose of G-CSF ( 10 micro g/kg/day ) would reduce these complications . DESIGN AND METHODS This was a multicenter prospective trial in 77 SAA patients treated with horse ALG ( 15 mg/kg/day day1-5 ) and CyA ( 5 mg/kg/day day 1-180 ) . Patients were randomized to receive G-CSF 5 micro g/kg/day ( n=38 , group A ) or 10 micro g/kg/day ( n=39 , group B ) from day +1 to day +30 . All patients then received G-CSF 5 micro g/kg/day from day +31 to day +90 . The primary end point of this study was response at day +120 . Secondary end points were early deaths , blood counts at day +120 , and survival . RESULTS At day +120 responses were classified as absent , partial , and complete in 12 , 22 , and 4 patients in group A and in 23 , 7 , and 9 patients in group B ( p=0.001 ) . At last follow-up these figures were respectively 9 , 12 , and 17 vs 19 , 2 , and 18 ( p=0.004 ) . Thirteen patients ( 5 in group A and 8 in group B ) died before day 120 ( p=0.3 ) . Median peripheral blood counts on day 120 were comparable in the two groups : Hb 10.5 and 9.5 g/dL in group A and B , respectively ( p=0.6 ) , Neutrophil counts were 2.4 vs 1.9x10 ( 9 ) /L in groups A and B ( p=0.4 ) and platelet counts were , respectively , 42 vs 36x10 ( 9 ) /L ( p=0.3 ) . The actuarial survival at 4 years is 72 % in group A and 67 % in group B ( p=0.3 ) . INTERPRETATION AND CONCLUSIONS Increasing the dose of G-CSF does not appear to reduce early deaths , does not improve peripheral blood counts nor survival , and may reduce the response rate in patients with SAA receiving ALG and CyA .

antilymphocyte globulin

cyclosporine

anti-lymphocyte globulin ( ALG

cyclosporin ( CyA )

G-CSF

horse ALG ( 15 mg/kg/day day1-5 )

CyA ( 5 mg/kg/day day 1-180 )

G-CSF 5

G-CSF

ALG

CyA

early deaths

reduce these complications .

response

early deaths ,

blood counts

survival .

responses

absent , partial

complete

died

peripheral blood counts

Neutrophil counts

platelet counts

actuarial survival

reduce early deaths

peripheral blood counts

survival

response rate


Atrial remodeling after mitral valve surgery in patients with permanent atrial fibrillation . BACKGROUND Mitral valve pathology is frequently associated with auricular dilatation and atrial fibrillation . Mitral surgery allows an immediate surgical auricular remodeling and besides in those cases in which sinus rhythm is reached , it is followed by a late remodeling . The aim of this study is to investigate the process of postoperative auricular remodeling in patients with permanent atrial fibrillation undergoing mitral surgery . METHODS In a prospective randomized trial , 50 patients with permanent atrial fibrillation and dilated left atrium , submitted to surgical mitral repair , were divided into two groups : Group I contained 25 patients with left auricular reduction and mitral surgery , and Group II contained 25 patients with isolated valve surgery . Both groups were considered homogeneous in the preoperative assessment . RESULTS After a mean follow-up of 31 months , 46 % of patients included in Group I versus 18 % of patients included in Group II restarted sinus rhythm ( p = 0.06 ) . An auricular remodeling with size regression occurred in those patients who recovered from sinus rhythm , worthy of remark in Group II ( -10.8 % of left auricular volume reduction in Group I compared to -21.5 % in Group II ; p < 0.05 ) . A new atrial enlargement took place in those patients who remained with atrial fibrillation ( +16.8 % left auricular volume in Group I vs. +8.4 % in Group II ; p < 0.05 ) . CONCLUSIONS Mitral surgery produces an atrial postoperative volume that decrease especially when reduction techniques are employed . Late left atrial remodeling depended on the type of atrial rhythm and postoperative surgical volume .

Atrial remodeling

mitral valve surgery

Mitral surgery

mitral surgery

left auricular reduction

mitral surgery

isolated valve surgery

Atrial remodeling

sinus rhythm

new atrial enlargement

atrial rhythm

postoperative surgical volume

permanent atrial fibrillation

permanent atrial fibrillation

permanent atrial fibrillation

dilated left atrium

isolated valve surgery


Absorption of intramuscular phenobarbitone in children with severe falciparum malaria . The absorption of intramuscular phenobarbitone 7 mg.kg-1 was studied in 11 Karen children aged between 1.7 and 11 y with severe falciparum malaria . Eight of the children were comatose . Clinical findings were compared with those in 9 further children with severe malaria of similar age range ( four of whom were unconscious ) , who received an identical placebo . One child , who had received placebo , had repeated convulsions and died 1 h after admission to hospital . The remainder made an uncomplicated recovery . There were no convulsions subsequent to treatment , although the study was too small to assess anticonvulsant efficacy . There was no observable toxicity , but phenobarbitone recipients had a significant tendency to deepen in their level of coma or to become sleepy within the 4 h after drug administration . Phenobarbitone was rapidly absorbed , reaching a mean ( range ) peak concentration of 34.2 [ 29.3-42.6 ] mumol.l-1 in a median ( range ) of 4 ( 2.5-12 ) h. These values are comparable to those previously reported in healthy children and in children with febrile convulsions . Intramuscular phenobarbitone is well absorbed in children with severe malaria ; the optimum prophylactic anticonvulsant dose remains to be determined .

intramuscular phenobarbitone 7 mg.kg-1

identical placebo .

repeated convulsions

uncomplicated recovery .

convulsions

toxicity

level of coma

become sleepy

febrile convulsions

children

falciparum malaria

Karen

between 1.7 and 11 y

falciparum malaria

Eight


Faulty Japanese sentences are judged more grammatical when punctuation is used : negative implications for Chomsky 's principle of Full Interpretation . 88 adult Japanese speakers judged the grammaticality of isolated simple bitransitive sentences involving an uninterpretable extra argument in addition to three legitimate arguments . The sentences thus violated Chomsky 's principle of Full Interpretation which prohibits the structure building of a sentence including uninterpretable elements . The primary variable of interest was the presence or absence of punctuation , i.e. , commas , which enclosed the extra argument . Findings showed that sentences with punctuation were judged more grammatical than the ones without punctuation , with an average score of judged grammaticality exceeding 3 on a 7-point scale ( 1 =least grammatical ; 7=most grammatical ) . This score would not be expected if the speakers possess and judge the sentences in conformity with the principle of Full Interpretation .

grammatical

uninterpretable extra argument

legitimate arguments

grammatical

adult

Japanese


Enhanced induction of apoptosis in lung adenocarcinoma after preoperative chemotherapy with tegafur and uracil ( UFT ) . PURPOSE To determine if the preoperative administration of tegafur and uracil ( UFT ) to patients with lung adenocarcinoma could induce apoptosis . METHODS We conducted a randomized prospective study on 30 patients with lung adenocarcinoma , divided into two groups of 15 patients each . One group received UFT 600 mg/day preoperatively for 7 consecutive days and a control group received no chemotherapy or radiotherapy . The apoptotic index ( AI ) was determined by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate biotin nick end-labeling ( TUNEL ) method . Expression of Ki-67 was examined by immunohistochemical staining . The concentration of 5-fluorouracil ( 5-FU ) in tumor tissue was measured by chemical assay . RESULTS The AI of lung adenocarcinoma cells increased significantly in the UFT-treated group but not in the control group . A significant positive correlation was seen between the AI and the 5-FU concentrations in the tumor tissue . CONCLUSIONS The continuous oral administration of UFT for 7 days preoperatively resulted in enhanced apoptosis and a significant positive correlation between the AI and 5-FU concentrations in lung adenocarcinoma . Therefore , it may be possible to evaluate the effects of adjuvant chemotherapy based on the AI .

tegafur

uracil

tegafur and uracil ( UFT )

no chemotherapy or radiotherapy

induction

apoptotic index ( AI )

Expression of Ki-67

immunohistochemical staining

AI of lung adenocarcinoma cells

AI

the 5-FU concentrations

apoptosis

AI

lung adenocarcinoma

patients with lung adenocarcinoma


Position of anterior capsulorhexis and posterior capsule opacification . PURPOSE To evaluate whether the position of the anterior continuous curvilinear capsulorhexis influences the rate of posterior capsule opacification ( PCO ) . METHODS A total of 119 patients , aged 61-86 years , underwent cataract surgery with phacoemulsification performed by a single surgeon . The patients were randomized to implantation with either a silicone intraocular lens ( IOL ) ( SI40NB , Allergan ) or an AcrySof IOL ( MA60BM , Alcon ) . Three years after surgery , the rate of PCO was analysed using the evaluation of posterior capsule opacification computer software ( EPCO ) . The results were related to the capsulorhexis position , which was assessed with a retroillumination photograph . RESULTS If the capsulorhexis was located partially or completely off the optics of the IOL , compared to totally on the IOL , significantly more PCO was found ( p = 0.0014 ) . When comparing within each IOL type , patients with AcrySof IOLs were found to have significantly less PCO when the capsulorhexis was totally on the optic ( p = 0.0048 ) . This difference was also significant in the silicone group ( p = 0.041 ) . CONCLUSION A relatively small and central capsulorhexis allowing for the complete covering of the IOL optics by the rhexis edges seems to protect against PCO in cataract surgery , with both round-edged silicone IOLs and sharp-edged hydrophobic acrylic IOLs .

silicone intraocular lens ( IOL )

SI40NB , Allergan

AcrySof IOL

IOL optics

acrylic IOLs

rate of PCO

capsulorhexis

optics of the IOL

totally on the IOL

PCO

PCO

PCO

61-86 years


Creon 10,000 Minimicrospheres vs. Creon 8,000 microspheres -- an open randomised crossover preference study . Creon 10,000 Minimicrospherestrade mark ( Creon ) 10,000 MMS ) is a pancreatic enzyme formulation that contains smaller spheres of pancreatin in a 50 % smaller capsule than conventional microspheres ( Creon ) 8,000 ) . This three-centre study investigated the preference of cystic fibrosis ( CF ) patients for these products . In one centre , 72 h stool fat excretion and coefficient of fat absorption ( CFA ) were also compared . Fifty-nine patients with a mean age 10 years ( range 3-17 ) took Creon 8,000 ms for 14 days and were then randomised to 28 days of Creon 8,000 ms followed by 28 days of Creon 10,000 MMS , or vice versa . Dosing was lipase for lipase according to the labelled declaration . At the end of the second treatment period , 51 of 54 patients who completed the study expressed a preference , with a statistically significant preference in favour of Creon 10,000 MMS ( 47/51 ; 87 % ) vs. Creon 8,000 ms ( 4/51 ; 7.4 % ; P < 0.0001 ) . Stool fat ( g/day ) and CFA ( % ) were measured in 24 patients at the end of each treatment period : the products were therapeutically equivalent ( Creon 10,000 : 8.4 g/day , 91.3 % CFA ; Creon 8,000 : 6.7 g/day , 93.5 % CFA ) . Both products were well tolerated . In conclusion , in CF children we found a clear preference for Creon 10,000 MMS compared with Creon 8,000 ms with no difference in fat absorption between the two products . Creon 10,000s smaller capsules are easier to take and should aid patient compliance .

Creon 10,000 Minimicrospheres

Creon 8,000 microspheres

microspheres ( Creon ) 8,000 )

Creon 8,000 ms

Creon 10,000 MMS

Creon

Creon

preference

stool fat excretion

coefficient of fat absorption ( CFA )

statistically significant preference

Stool fat ( g/day )

CFA ( % )

fat absorption

cystic fibrosis ( CF )

Fifty-nine

mean age 10 years ( range 3-17 )

51 of 54

CF

children


Effects of finasteride on the morphology of polycystic ovaries .

finasteride

morphology of polycystic ovaries .

polycystic ovaries .


In-hospital costs of self-expanding nitinol stent implantation versus balloon angioplasty in the femoropopliteal artery ( the VascuCoil Trial ) . PURPOSE Although several prospective studies have examined the safety and efficacy of stent placement for femoropopliteal arterial disease , the current cost of these procedures is unknown . To estimate and compare hospital costs associated with conventional balloon angioplasty ( percutaneous transluminal angioplasty [ PTA ] ) and stent placement for patients with symptomatic peripheral arterial disease , the authors performed a prospective economic evaluation in conjunction with the Intracoil Femoropopliteal Stent Trial ( VascuCoil ) . MATERIALS AND METHODS Between May 1997 and December 1999 , 266 patients with stenotic or occluded superficial femoral or popliteal arteries were prospectively randomized to treatment with the IntraCoil stent or PTA . Detailed resource use and cost data for each patient 's initial revascularization procedure and ensuing hospitalization were collected and analyzed on an intention-to-treat basis . RESULTS Compared with conventional balloon angioplasty , stent placement did not improve clinical outcomes but increased procedure duration , equipment costs , and physician services . As a result , initial hospital costs were approximately 3,500 dollars higher for patients randomized to the IntraCoil stent , compared with PTA ( 8,435 dollars vs 4,980 dollars ; P < .001 ) . CONCLUSIONS As performed in the VascuCoil trial , primary stent placement for femoropopliteal disease did not improve clinical outcomes but increased initial treatment costs by more than 3,000 dollars . Because there were no substantial differences in subsequent clinical outcomes between the two treatments , it is unlikely that these increased initial costs would be offset by savings in follow-up costs . These findings suggest that a strategy of routine stent implantation for patients undergoing femoropopliteal PTA is not optimal on economic grounds and that PTA with provisional stent implantation is preferred .

balloon angioplasty

stent placement

stent placement

IntraCoil stent

PTA

conventional balloon angioplasty

stent placement

IntraCoil stent

PTA

stent

PTA

PTA

provisional stent implantation

In-hospital costs

safety

efficacy

hospital costs

resource use

cost data

clinical outcomes

initial hospital costs

clinical outcomes

initial treatment costs

clinical outcomes

initial costs

follow-up costs .

femoropopliteal arterial disease

patients undergoing femoropopliteal PTA


Equivalence study of a topical diclofenac solution ( pennsaid ) compared with oral diclofenac in symptomatic treatment of osteoarthritis of the knee : a randomized controlled trial . OBJECTIVE . To compare the safety and efficacy of a topical diclofenac solution versus oral diclofenac in relieving the symptoms of primary osteoarthritis ( OA ) of the knee , in a randomized , double-blind , double-dummy equivalence trial . METHODS A total of 622 men and women with radiological evidence of primary knee OA and mild to severe symptoms were randomly assigned to treatment with a topical diclofenac solution plus placebo oral capsules , or placebo topical solution plus oral diclofenac ( 50 mg ) capsules . Patients applied 50 drops of study solution and took 1 study capsule 3 times daily for 12 weeks . Efficacy variables were pain and physical function , measured by the Western Ontario and McMaster Universities ( WOMAC ) VA 3.1 OA Index , and patient global assessment ( PGA ) . Equivalence in the per-protocol group was based on previously defined ranges of clinically significant difference . Safety was assessed by evaluation of adverse events , vital signs , and laboratory data . RESULTS The difference in mean ( 95 % CI ) change scores ( final minus baseline ) between treatments was 13.3 mm ( -8.6 to 35.2 ) for pain ( total scale 500 mm ) , 71.0 mm ( -2.4 to 144.5 ) for physical function ( total scale 1700 mm ) , and 4.3 mm ( -1.2 to 9.8 ) for PGA ( total scale 100 mm ) . The CI for each efficacy variable fell within the predefined equivalence ranges ( pain , +/- 75 mm ; physical function , +/- 255 mm ; PGA , +/- 20 mm ) , indicating that no clinically relevant difference was found between the 2 treatment arms . Safety analyses of patients applying topical diclofenac solution revealed some minor skin irritation at the application site -- mostly skin dryness in 83/311 ( 27 % ) patients -- but a significantly reduced incidence , relative to oral diclofenac , of total and severe gastrointestinal ( GI ) adverse events , including dyspepsia , abdominal pain , diarrhea , and nausea . The number of patients developing abnormal liver function tests ( including clinically significant elevation ) , hemoglobin , and creatinine clearance was significantly higher in the oral diclofenac group . CONCLUSION Application of this topical diclofenac solution to the knee of patients with OA produced relief of symptoms equivalent to oral diclofenac , with minor local skin irritation , but significantly reduced incidence of diclofenac-related GI complaints and abnormal laboratory values .

oral diclofenac

topical diclofenac solution

oral diclofenac

topical diclofenac solution

placebo oral capsules

placebo topical solution

oral diclofenac

diclofenac solution

oral diclofenac

topical diclofenac solution

oral diclofenac

safety and efficacy

Safety analyses

dyspepsia

abdominal pain

diarrhea

nausea

relief of symptoms

incidence of

diclofenac-related GI complaints

abnormal laboratory values

osteoarthritis of the knee :

patients with OA


The effect of calcium supplementation on bone density in premenarcheal females : a co-twin approach . The age and developmental stage at which calcium supplementation produces the greatest bone effects remain controversial . We tested the hypothesis that calcium supplementation may improve bone accrual in premenarcheal females . Fifty-one pairs of premenarcheal female twins ( 27 monozygotic and 24 dizygotic ; mean +/- sd age , 10.3 +/- 1.5 yr ) participated in a randomized , single-blind , placebo-controlled trial with one twin of each pair receiving a 1200-mg calcium carbonate ( Caltrate ) supplement . Areal bone mineral density ( aBMD ) was measured at baseline and 6 , 12 , 18 and 24 months . There were no within-pair differences in height , weight , or calcium intake at baseline . Calcium supplementation was associated ( P < 0.05 ) with increased aBMD compared with placebo , adjusted for age , height , and weight at the following time points from baseline : total hip , 6 months ( 1.9 % ) , 12 months ( 1.6 % ) , and 18 months ( 2.4 % ) ; lumbar spine , 12 months ( 1.0 % ) ; femoral neck , 6 months ( 1.9 % ) . Adjusted total body bone mineral content was higher in the calcium group at 6 months ( 2.0 % ) , 12 months ( 2.5 % ) , 18 months ( 4.6 % ) , and 24 months ( 3.7 % ) , respectively ( all P < 0.001 ) . Calcium supplementation was effective in increasing aBMD at regional sites over the first 12-18 months , but these gains were not maintained to 24 months .

calcium supplementation

calcium supplementation

calcium supplementation

placebo-controlled

Calcium supplementation

bone accrual

Areal bone mineral density ( aBMD )

aBMD

aBMD

premenarcheal females :


Endoscopic sphincterotomy by using pure-cut electrosurgical current and the risk of post-ERCP pancreatitis : a prospective randomized trial . BACKGROUND It has been suggested that the use of pure-cut electrosurgical current for endoscopic sphincterotomy may reduce the risk of post-ERCP pancreatitis . The aim of this study was to determine whether pure-cut current reduces the risk of pancreatitis compared with blend current . METHODS Patients were randomly assigned to undergo sphincterotomy over a non-conductive guidewire with 30 W/sec pure-cut current or 30 W/sec blend-2 current by a blinded endoscopist . Serum amylase and lipase levels were determined 1 day before and within 24 hours after ERCP . Post-ERCP pancreatitis was the primary outcome of interest . Secondary outcomes were as follows : severity of immediate bleeding , as graded by a 3-point scale from 1 ( no bleeding ) to 3 ( injection or balloon tamponade therapy required to stop bleeding ) and evidence of delayed bleeding 24 hours after ERCP . Analyses were performed in intention-to-treat fashion . RESULTS A total of 246 patients were randomized ( 116 pure-cut current , 130 blend current ) . There were no differences in baseline characteristics between the groups . The overall frequency of post-ERCP pancreatitis was 6.9 % , with no significant difference in frequency between treatment arms ( pure cut , 7.8 % vs. blend , 6.1 % ; p = 0.62 ) . The difference in rates of pancreatitis between the two groups was 1.7 % : 95 % CI [ -4.8 % , 8.2 % ] . Six patients ( 2.4 % ) had delayed bleeding after ERCP , of which two required transfusion . There was a significant increase in minor bleeding episodes ( grade 2 ) in the pure-cut group ( p < 0.0001 ) . Delayed episodes of bleeding were equal ( n = 3 ) in each arm . CONCLUSIONS The type of current used when performing endoscopic sphincterotomy does not appear to alter the risk of post-ERCP pancreatitis . The selection of electrosurgical current for biliary endoscopic sphincterotomy should be based on endoscopist preference .

Endoscopic sphincterotomy

pure-cut electrosurgical current

sphincterotomy

pure-cut current

sphincterotomy

current

endoscopic sphincterotomy

electrosurgical current

endoscopic sphincterotomy

pancreatitis

Post-ERCP pancreatitis

severity of immediate bleeding ,

balloon

evidence of delayed bleeding

post-ERCP pancreatitis

pancreatitis

delayed bleeding

minor bleeding episodes

Delayed episodes of bleeding


The relationship of changes in EORTC QLQ-C30 scores to ratings on the Subjective Significance Questionnaire in men with localized prostate cancer . PURPOSE To examine the relationship between changes in health-related quality-of-life ( HRQOL ) on the EORTC Quality of Life Questionnaire ( QLQ-C30 ) , and patients ' perceptions of HRQOL changes as measured by the Subjective Significance Questionnaire ( SSQ ) . PATIENTS AND METHODS A total of 101 patients completed the QLQ-C30 on weeks 1 , 4 and 7 of radical external-beam radiation therapy ( RT ) for localized cancer of the prostate . Patients rated their change in physical functioning , emotional functioning , social functioning , and overall/global quality of life ( QOL ) by completing a seven-category SSQ at weeks 4 and 7 . The association between changes in the QLQ-C30 change and the corresponding SSQ ratings were determined by calculation of mean change scores for each SSQ category and by Spearman rank correlation coefficient analysis . RESULTS Patients ' completion of the QLQ-C30 and SSQ exceeded 95 % . Statistically significant changes in fatigue , pain , appetite , diarrhea , and global QOL scores were detected during RT . For patients reporting 'a little ' change in global QOL on the SSQ , absolute mean QLQ-C30 change scores ranged between 0 to 15 points with 12/16 mean change scores between 2.5 and 8.5 points . In the entire study sample , correlations between SSQ patient ratings and QLQ-C30 change scores were lower than previously reported , ranging between 0.15 and 0.24 for the four different domains , but were higher when QOL scores producing ceiling effects were omitted . CONCLUSION The SSQ and QLQ-C30 may measure related concepts that could assist in the interpretation of changes in scores and in the calibration of the QLQ-C30 . However , the nature of this relationship could not be elucidated in this data set because of a lack of variance in HRQOL scores in the study sample . Further investigation should be carried out in study samples with sufficient variance to allow more robust conclusions .

Questionnaire

external-beam radiation therapy ( RT )

SSQ

SSQ

SSQ

SSQ

SSQ

SSQ

SSQ

Subjective Significance Questionnaire

physical functioning

emotional functioning

social functioning

overall/global quality of life ( QOL )

seven-category SSQ

fatigue

pain

appetite

diarrhea

global QOL scores

global QOL

SSQ

QLQ-C30 change scores

QOL scores

men with localized prostate cancer .


Time intervals production in tapping and oscillatory motion . We applied spectral analysis on series of time intervals produced in a synchronization-continuation experiment . In the first condition intervals were produced by finger tapping , and in the second by an oscillatory motion of the hand . Results obtained in tapping were consistent with a discrete , event-based timing model . In the oscillatory condition , the spectra suggested a continuous , dynamic timing mechanism , based on the regulation of effector stiffness . It is concluded that the oscillatory character of movement can offer an important resource for timing control . The use of an event-based timing control such as postulated in the Wing-Kristoffersson model could be restricted to a quite limited class of rhythmic tasks , characterized by the concatenation of discrete events .

spectral analysis

tapping

oscillatory motion

finger tapping

oscillatory motion of the hand

tapping

oscillatory condition

oscillatory character


Neridronate prevents bone loss in patients receiving androgen deprivation therapy for prostate cancer . UNLABELLED Today , androgen deprivation therapy is a cornerstone of treatment for advanced prostate cancer , although it presents important complications such as osteoporosis . Neridronate , a relatively new bisphosphonate , is able to prevent bone loss in patients with prostate cancer during androgen ablation . INTRODUCTION Androgen-deprivation therapy ( ADT ) is a cornerstone of treatment for advanced prostate cancer . This therapy has iatrogenic complications , such as osteoporosis . The aim of our study was to evaluate the efficacy of neridronate , a relatively new bisphosphonate , to prevent bone loss during androgen ablation . MATERIALS AND METHODS Forty-eight osteoporotic patients with prostate cancer , treated with 3-month depot triptorelina , were enrolled and randomly assigned to two different treatment groups : group A ( n = 24 ) was treated with a daily calcium and cholecalciferol supplement ( 500 mg of elemental calcium and 400 IU cholecalciferol ) , and group B ( n = 24 ) received in addition to the same daily calcium and cholecalciferol supplement , 25 mg of neridronate given intramuscularly every month . All patients also received bicalutamide for 4 weeks . Lumbar and femoral BMD was evaluated by DXA at baseline and after 1 year of therapy ; moreover , deoxypyridinoline ( DPD ) and bone alkaline phosphatase ( BALP ) were determined at the beginning , midway through , and at the end of the study . RESULTS After 6 and 12 months , whereas patients treated only with calcium and cholecalciferol ( group A ) showed a marked bone loss , with increased levels of DPD and BALP compared with baseline values , patients treated also with neridronate ( group B ) had substantially unchanged levels of these markers . After 1 year of treatment , lumbar and total hip BMD decreased significantly in patients treated only with calcium and cholecalciferol ( group A ) , whereas it did not change significantly at any skeletal site in patients treated also with neridronate ( group B ) . No relevant side effects were recorded during our study . CONCLUSIONS Neridronate is an effective treatment in preventing bone loss in the hip and lumbar spine in men receiving ADT for prostate cancer .

Neridronate

androgen deprivation therapy

Neridronate

bisphosphonate

triptorelina

bicalutamide

Neridronate

bone loss

osteoporosis

bone loss

efficacy

Lumbar and femoral BMD

marked bone loss

increased levels of DPD and BALP

change significantly

relevant side effects

bone loss

prostate cancer

advanced prostate cancer

prostate cancer

advanced prostate cancer

Forty-eight

prostate cancer

prostate cancer .


Effects of brain-penetrating ACE inhibitors on Alzheimer disease progression .

brain-penetrating ACE inhibitors

Alzheimer disease progression .

brain-penetrating ACE inhibitors

Alzheimer disease


Effect of ibuprofen on cyclooxygenase and nitric oxide synthase of gastric mucosa : correlation with endoscopic lesions and adverse reactions . The aim of this study was to evaluate the effect of ibuprofen on gastric mucosa and enzymes involved in gastroprotection in healthy volunteers . Twenty-four Helicobacter pylori-negative subjects were randomized to treatment with ibuprofen or ibuprofen-arginate ( each 600 mg/6 hr during 3 days ) . Endoscopies were performed 1 week before and after treatment . Biopsies were taken from the gastric antrum and corpus for determination of prostaglandin E2 ( PGE2 ) by ELISA and cyclooxygenase ( COX-1 and COX-2 ) and nitric oxide synthase ( eNOS and iNOS ) by western blot . All subjects had at least one gastric lesion except for two individuals taking ibuprofen-arginate . Ibuprofen-arginate caused a lower rate of clinical adverse reactions than ibuprofen . Subjects with gastric lesions or adverse reactions had lower PGE2 levels . COX-1 , COX-2 , eNOS , and iNOS were detectable in all subjects . The constitutive enzymes ( COX-1 and eNOS ) did not change after treatment . COX-2 was higher in corpus than antrum and it increased after ibuprofen treatment . iNOS tended to increase mildly in the corpus in subjects with adverse reactions or endoscopic lesions . There were no significant differences between ibuprofen and ibuprofen-arginate in PGE2 , or enzymes .

ibuprofen

ibuprofen

ibuprofen

ibuprofen-arginate

Endoscopies

ELISA

endoscopic lesions

adverse reactions

clinical adverse reactions

gastric lesions

COX-1 , COX-2 , eNOS , and iNOS

healthy

Twenty-four

Helicobacter pylori-negative


Transitions during effective treatment for cocaine-abusing homeless persons : establishing abstinence , lapse , and relapse , and reestablishing abstinence . Data are reported on drug use among cocaine-dependent homeless persons who participated in a clinical trial that compared day treatment only ( DT , n = 69 ) with day treatment plus abstinent-contingent housing and work ( DT+ , n = 72 ) . Drug use was measured with multiple weekly urine toxicologies . Compared with DT participants , more DT+ participants established abstinence , maintained abstinence for longer durations , were marginally significantly more likely to lapse , and significantly less likely to relapse . Of all participants who established abstinence and then relapsed , DT+ participants relapsed later and were more likely to reestablish abstinence . These analyses yield information on the processes involved in the manner in which drug use changes as a result of abstinent-contingent housing and work .

day treatment only

day treatment

abstinent-contingent housing and work

abstinence

abstinent-contingent housing and work

lapse

relapse

reestablish abstinence

cocaine-abusing

cocaine-dependent

72 )


A double-blind , placebo-controlled study of the efficacy of transdermal clonidine in autism . BACKGROUND Autistic individuals often exhibit hyperarousal behaviors ( e.g. , stereotyped body movements , self-stimulation , hypervigilance , and hyperactivity ) . Clonidine , an alpha 2-adrenergic receptor agonist , has been shown to be effective in reducing impulsivity , inattention , and hyperactivity associated with attention deficit disorder with hyperactivity . This study investigated the efficacy and safety of transdermal clonidine in reducing hyperarousal behaviors associated with autism . METHOD A double-blind , placebo-crossover study with transdermal clonidine was performed in nine autistic males ( aged 5 to 33 years ) . Subjects received either clonidine ( approximately 0.005 mg/kg/day ) or placebo by a weekly transdermal patch . Each trial lasted 4 weeks with a 2-week washout period between treatment phases . Subjects were evaluated every 2 weeks by clinician raters and weekly by parents . RESULTS The clonidine treatment showed a significant difference from placebo treatment on three subscales of the Ritvo-Freeman Real Life Rating Scale ( i.e. , social relationship to people , affectual responses , and sensory responses ) . The Clinical Global Impressions scale indicated that clonidine produced a significant improvement on severity of illness , global improvement , and efficacy index for therapeutic effect of the drug . A patient global rating scale showed clonidine treatment resulted in significant improvement in comparison with placebo . Adverse effects included sedation and fatigue during the first 2 weeks of clonidine treatment . CONCLUSION Results from this preliminary study show that clonidine was effective in reducing several hyperarousal behaviors and improved social relationships in some autistic subjects . Further studies are needed in a larger autistic population to determine the dose-response relationship of clonidine .

placebo-controlled

transdermal clonidine

Clonidine

clonidine

placebo-crossover

clonidine

clonidine

placebo

clonidine

placebo

clonidine

clonidine

placebo .

clonidine

clonidine

clonidine .

efficacy and safety

social relationship to people

affectual responses

Clinical Global Impressions scale

severity of illness

global improvement

efficacy index

patient global rating scale

several hyperarousal behaviors

social relationships

autism

Autistic

hyperarousal behaviors

hyperarousal

autism

nine

autistic

autistic

autistic


A new social communication intervention for children with autism : pilot randomised controlled treatment study suggesting effectiveness . BACKGROUND Psychosocial treatments are the mainstay of management of autism in the UK but there is a notable lack of a systematic evidence base for their effectiveness . Randomised controlled trial ( RCT ) studies in this area have been rare but are essential because of the developmental heterogeneity of the disorder . We aimed to test a new theoretically based social communication intervention targeting parental communication in a randomised design against routine care alone . METHODS The intervention was given in addition to existing care and involved regular monthly therapist contact for 6 months with a further 6 months of 2-monthly consolidation sessions . It aimed to educate parents and train them in adapted communication tailored to their child 's individual competencies . Twenty-eight children with autism were randomised between this treatment and routine care alone , stratified for age and baseline severity . Outcome was measured at 12 months from commencement of intervention , using standardised instruments . RESULTS All cases studied met full Autism Diagnostic Interview ( ADI ) criteria for classical autism . Treatment and controls had similar routine care during the study period and there were no study dropouts after treatment had started . The active treatment group showed significant improvement compared with controls on the primary outcome measure -- Autism Diagnostic Observation Schedule ( ADOS ) total score , particularly in reciprocal social interaction -- and on secondary measures of expressive language , communicative initiation and parent-child interaction . Suggestive but non-significant results were found in Vineland Adaptive Behaviour Scales ( Communication Sub-domain ) and ADOS stereotyped and restricted behaviour domain . CONCLUSIONS A Randomised Treatment Trial design of this kind in classical autism is feasible and acceptable to patients . This pilot study suggests significant additional treatment benefits following a targeted ( but relatively non-intensive ) dyadic social communication treatment , when compared with routine care . The study needs replication on larger and independent samples . It should encourage further RCT designs in this area .

social communication intervention

routine care alone .

intervention

existing care

regular monthly therapist contact

treatment

routine care alone

children with autism :


Skin manifestations of inhaled corticosteroids in COPD patients : results from Lung Health Study II . OBJECTIVE To define the relationship between skin bruising ( as well as other cutaneous manifestations ) and inhaled corticosteroid ( ICS ) therapy vs placebo in subjects with COPD who were participating in a clinical trial . To explore the relationship between easy skin bruising and other systemic effects of ICS therapy , including adrenal suppression and loss of bone mineral density ( BMD ) . DESIGN Double-blind , randomized , placebo-controlled clinical trial of triamcinolone acetonide ( 1200 microg daily ) vs placebo in participants with mild-to-moderate COPD . SETTING Lung Health Study II , a clinical trial to assess the effect of ICS compared to placebo in 1,116 participants in 10 centers over > 3.5 to 4.5 years . PARTICIPANTS A total of 1,116 smokers or recent ex-smokers with mild-to-moderate COPD ( age range , 40 to 69 years ; mean age , 56.3 years ; 37.2 % female ) . MEASUREMENTS AND RESULTS Every 6 months , a structured questionnaire was administered to elicit reports of any bruising and/or skin rashes , slow healing of cuts or sores , or other skin changes . Compliance with inhaler use was assessed by canister weighing . A significantly higher proportion of ICS than placebo participants who complied with using their inhaler reported easy bruising ( 11.2 % vs 3.5 % , respectively ) and the slow healing of skin cuts or sores ( 2.4 % vs 0.5 % , respectively ) . Older men in the ICS group with good inhaler compliance appeared to be at the greatest risk of bruising . In those participants undergoing serial measurements of adrenal function and BMD , no association was noted between skin bruising and either the suppression of adrenal function or the loss of BMD as systemic complications of ICS use . CONCLUSION These findings indicate that moderate-to-high doses of ICSs result in an increased incidence of easy bruising and impairment in skin healing in middle-aged to elderly persons with COPD . No association was noted between skin bruising and other markers of systemic toxicity from the use of ICSs .

corticosteroids

corticosteroid ( ICS )

triamcinolone acetonide

placebo

ICS

ICS

ICS

skin bruising

cutaneous manifestations

adrenal suppression

and

loss of bone mineral density ( BMD

skin changes

easy bruising

slow healing of skin cuts or sores

risk of bruising

skin bruising

suppression of adrenal function

loss of BMD

easy bruising

impairment in skin healing

skin bruising

systemic toxicity

COPD patients :

subjects with COPD


[ Long-term effects of 7-year growth hormone substitution on bone metabolism , bone density , and bone quality in growth hormone-deficient adults ] . BACKGROUND AND PURPOSE Subnormal bone mineral density ( BMD ) and increased fracture risk are described in patients with growth hormone deficiency ( GHD ) . Growth hormone ( GH ) has been reported to have beneficial effects on bone in GHD . The aim of this study was to investigate the long-term effects of GH replacement therapy on bone metabolism , BMD , and bone quality in patients with GHD . PATIENTS AND METHODS 20 adult patients with GHD ( eleven male , nine female , mean age 42.5 years ) were included in the study and randomized to either GH or placebo in a dose of 0.25 U/kg body weight/week . After 6 months all patients received GH . After a 1-year double-blind , placebo-controlled study the patients were followed for another 72 months in an open study . The patients were compared to 20 age- und sex-matched healthy controls . Bone turnover was determined by ICTP ( type I collagen carboxyterminal cross-linked telopeptide ) as parameter of bone resorption and PICP ( carboxyterminal propeptide of type I procollagen ) as marker of bone formation . BMD was measured at the lumbar spine by dual-photon absorptiometry ( DPA ) and at the forearm by single-photon absorptiometry ( SPA ) . Apparent phalangeal ultrasound transmission velocity ( APU ) was assessed as parameter of bone quality independent of BMD . RESULTS At the beginning of the study BMD at both measuring sites was lower in patients with GHD than in healthy controls . During the 1st year of GH replacement therapy BMD decreased , followed by a continuous increase in BMD ( about 12 % ) up to 60 months which remained unchanged thereafter , building up a plateau . After 72 months no significant difference between the patients and the healthy controls could be detected . Concerning parameters of bone turnover , first ICTP as marker of bone resorption showed a significant increase , later on the marker of bone formation increased as well . APU decreased during the first 6 months of treatment , but had returned to its baseline value after 24 months and remained unchanged throughout the rest of the study . CONCLUSION BMD is subnormal in adults with GHD . GH replacement therapy stimulates bone turnover in patients with GHD and in the long term such stimulation results in an increased BMD . Thereby , GH shows a triphasic action on BMD : an initial decrease in BMD during the 1st year , followed by a continuous increase in BMD with buildup of a stable plateau after 60 months . The newly formed bone seems to have normal bone elasticity .

growth hormone substitution

Growth hormone ( GH )

GH replacement therapy

GH

placebo

GH

placebo-controlled

GH

GH

bone metabolism

bone density

bone quality

Subnormal bone mineral density ( BMD )

increased fracture risk

effects on bone

bone metabolism

BMD

bone quality

Bone turnover

BMD

BMD

BMD

BMD

bone turnover

first ICTP

bone resorption

marker of bone formation

APU

BMD

bone turnover

BMD

BMD

BMD

BMD

normal bone elasticity

growth hormone-deficient

adults

growth hormone deficiency ( GHD )

GHD

adult

GHD

eleven

nine

42.5 years )


Effects of bifidobacterium breve supplementation on intestinal flora of low birth weight infants . BACKGROUND It is known that the bifidobacteria flora play important roles in mucosal host defense and can prevent infectious diseases . Because bacterial populations develop during the first day of life , the authors examined whether the early administration of bifidobacteria has a positive effect on the health of low birth weight infants . METHODS The effects of oral administration of Bifidobacterium breve ( B. breve ) supplements were studied in a controlled trial with low birth weight infants ( average birth weight 1489 g ) . The infants were divided into three groups : Group A and B received a dose of 1.6 x 10 ( 8 ) cells of B. breve supplement twice a day , commencing either from several hours after birth ( group A ) or 24 h after birth ( group B ) . Group C , the control group , received no supplement . RESULTS There were no significant differences in birth weight , treatment with antibiotics , and the starting time of breast-feeding among the three groups . A Bifidobacterium-predominant flora was formed at an average of 2 weeks after birth in group A and at an average of 4 weeks after birth in group B , while no Bifidobacterium was isolated in eight out of 10 infants in group C during the observation period of 7 weeks . In comparison between group A and B , Bifidobacterium was detected significantly earlier in group A , and the number of Enterobacteriaceae present in the infants at 2 weeks after birth was significantly lower in group A . CONCLUSION The results of the present study suggest that very early administration of B. breve to low birth weight infants is useful in promoting the colonization of the Bifidobacterium and the formation of a normal intestinal flora .

bifidobacterium breve

cells of

B.

breve supplement

control

no supplement

effect on the health

birth weight

treatment with antibiotics

starting time of breast-feeding

Bifidobacterium-predominant flora

Bifidobacterium

Bifidobacterium

low birth weight

infants


Risperidone in the treatment of disruptive behavioral symptoms in children with autistic and other pervasive developmental disorders . OBJECTIVE To investigate the efficacy and safety of risperidone for the treatment of disruptive behavioral symptoms in children with autism and other pervasive developmental disorders ( PDD ) . METHODS In this 8-week , randomized , double-blind , placebo-controlled trial , risperidone/placebo solution ( 0.01-0.06 mg/kg/day ) was administered to 79 children who were aged 5 to 12 years and had PDD . Behavioral symptoms were assessed using the Aberrant Behavior Checklist ( ABC ) , Nisonger Child Behavior Rating Form , and Clinical Global Impression-Change . Safety assessments included vital signs , electrocardiogram , extrapyramidal symptoms , adverse events , and laboratory tests . RESULTS Subjects who were taking risperidone ( mean dosage : 0.04 mg/kg/day ; 1.17 mg/day ) experienced a significantly greater mean decrease on the irritability subscale of the ABC ( primary endpoint ) compared with those who were taking placebo . By study endpoint , risperidone-treated subjects exhibited a 64 % improvement over baseline in the irritability score almost double that of placebo-treated subjects ( 31 % ) . Risperidone-treated subjects also exhibited significantly greater decreases on the other 4 subscales of the ABC ; on the conduct problem , insecure/anxious , hyperactive , and overly sensitive subscales of the Nisonger Child Behavior Rating Form ( parent version ) ; and on the Visual Analog Scale of the most troublesome symptom . More risperidone-treated subjects ( 87 % ) showed global improvement in their condition compared with the placebo group ( 40 % ) . Somnolence , the most frequently reported adverse event , was noted in 72.5 % versus 7.7 % of subjects ( risperidone vs placebo ) and seemed manageable with dose/dose-schedule modification . Risperidone-treated subjects experienced statistically significantly greater increases in weight ( 2.7 vs 1.0 kg ) , pulse rate , and systolic blood pressure . Extrapyramidal symptoms scores were comparable between groups . CONCLUSIONS Risperidone was well tolerated and efficacious in treating behavioral symptoms associated with PDD in children .

Risperidone

risperidone

risperidone/placebo

risperidone

risperidone-treated

placebo-treated

Risperidone-treated

risperidone-treated

placebo

risperidone

placebo

Risperidone-treated

Risperidone

Aberrant Behavior Checklist ( ABC )

irritability score

4 subscales of the ABC

Somnolence

weight

children

children

aged 5 to 12 years

PDD


Single nucleotide polymorphism in the hypoxia-inducible factor-1alpha gene in colorectal carcinoma . Colorectal carcinoma is one of the most common malignancies in the world , and its incidence has increased in recent years . We have reported that expression of hypoxia-inducible factor ( HIF ) -1alpha correlates with expression of vascular endothelial growth factor ( VEGF ) , tumor stage , lymphatic invasion , venous invasion , and liver metastasis . It has also been reported that a single nucleotide polymorphism ( SNP ) in exon 12 of HIF-1alpha gene is present in renal cell carcinoma and head and neck squamous cell carcinoma patients . We investigated the C1772T polymorphism in colorectal cancer patients and healthy control subjects to clarify the mechanism of HIF-1alpha activation in colorectal carcinoma . The exon 12 genotype was not associated with sex or age . The distribution of HIF-1alpha genotypes in controls was 89 C/C ( 89 % ) , 11 C/T ( 11 % ) , and 0 T/T ( 0 % ) . The distribution of HIF-1alpha genotypes in colorectal cancer patients was 100 C/C ( 100 % ) , 0 C/T ( 0 % ) , and 0 T/T ( 0 % ) . The difference in genotype distribution between patients and control subjects was significant ( p < 0.0005 ) . These results suggest that the C1772T polymorphism in HIF-1alpha is not involved in progression or metastasis of colorectal carcinoma .

Single nucleotide polymorphism

single nucleotide polymorphism ( SNP )

C1772T polymorphism

HIF-1alpha activation

control

HIF-1alpha genotypes

HIF-1alpha genotypes

C1772T polymorphism

Colorectal carcinoma

colorectal cancer patients

healthy control subjects

colorectal cancer


Effect of gemfibrozil on change in renal function in men with moderate chronic renal insufficiency and coronary disease . BACKGROUND Limited data suggest that low levels of serum high-density lipoprotein cholesterol ( HDL-C ) and high levels of triglyceride-rich lipoproteins may be associated with more rapid rates of kidney function loss in individuals with chronic renal insufficiency ( CRI ) . Although fibric acid derivatives increase serum HDL-C levels and decrease triglyceride levels , their effects on renal function are largely unknown . We conducted this study to determine whether gemfibrozil reduced rates of renal function loss in people with moderate CRI . METHODS This was a post hoc subgroup analysis in the Veterans Affairs High-Density Lipoprotein Intervention Trial , a randomized double-blind trial of gemfibrozil versus placebo in 2,531 men with coronary disease , HDL-C levels of 40 mg/dL or less ( < or =1.0 mmol/L ) , low-density lipoprotein cholesterol levels of 140 mg/dL or less ( < or =3.6 mmol/L ) , and a range of triglyceride values . Moderate CRI is defined as estimated glomerular filtration rate ( GFR ) of 30 to 59.9 mL/min/1.73 m2 at baseline . Multivariate regression was used to calculate rates of decline in estimated GFR for individuals administered gemfibrozil or placebo , controlling for prospectively determined potential confounders . RESULTS Change in renal function could be calculated in 1,981 individuals , of whom 399 individuals ( 20.2 % ) were eligible for inclusion . Among 399 study subjects , the rate of change in renal function in the gemfibrozil group during a median of 61 months was not significantly different from that in the placebo group ( 0.49 mL/min/1.73 m2/y faster ; 95 % confidence interval , 0.09 slower to 1.09 faster ; P = 0.10 ) . No clinically relevant effect of gemfibrozil on renal function was observed in groups defined by baseline lipid levels , kidney function , diabetic status , or other components of the metabolic syndrome . The incidence of transient ( 10 % versus 4 % ; P = 0.01 ) , but not sustained ( 9 % versus 4 % ; P = 0.07 ) , increases in serum creatinine levels of 0.5 mg/dL or greater ( > or =44 micromol/L ) was significantly greater in the gemfibrozil group . However , in 5 subjects with acute increases in serum creatinine levels , serum creatine kinase levels were significantly elevated as well , suggesting that myocyte toxicity may have been responsible . Even when these individuals were excluded , no clinically significant effect of gemfibrozil on kidney function was observed . CONCLUSION Gemfibrozil does not appear to exert a clinically relevant effect on rates of kidney function loss in individuals with moderate CRI , low HDL-C levels , and concomitant coronary disease .

gemfibrozil

gemfibrozil

gemfibrozil

placebo

gemfibrozil

placebo

gemfibrozil

placebo

gemfibrozil

gemfibrozil

gemfibrozil

Gemfibrozil

renal function

rate of change in renal function

renal function

baseline lipid levels

kidney function

diabetic status

components of the metabolic syndrome

serum creatinine levels

serum creatinine

serum creatine kinase levels

kidney function

kidney function

men

moderate chronic renal insufficiency

coronary disease

chronic renal insufficiency ( CRI )

moderate CRI

men

coronary disease

low-density lipoprotein cholesterol

moderate CRI

low HDL-C levels

coronary disease


[ Rilmenidine sympatholytic activity preserves mental and orthostatic sympathetic response and epinephrine secretion ] . BACKGROUND Heightened central sympathetic nervous outflow is common in essential hypertension , contributing to hypertension development and perhaps also to complications . Acute sympathetic nervous activation is a proven trigger for adverse cardiovascular events . Accordingly , antihypertensive drugs inhibiting sympathetic outflow represent a theoretically attractive therapeutic option . OBJECTIVES To study the sympatholytic and blood pressure lowering activity of the imidazoline binding agent rilmenidine at rest and during reflex sympathetic activation . DESIGN AND METHODS The HERA study ( Hyperium Effect on the sympathetic Reflex activation and Adrenaline ) is a randomised , double-blind , 6-week cross-over trial , with a 1-week placebo run-in period , two 2-week active treatment intervals ( rilmenidine 1 mg bid , placebo ) and intervening one week placebo wash-out . In 15 hypertensive patients , noradrenaline and adrenaline plasma kinetics and intra-arterial blood pressure measurements were performed at rest , after mental stress ( difficult mental arithmetic ) and during head-up tilting , at the end of the 2-week dosing periods . RESULTS The noradrenaline spillover rate , indicative of whole body sympathetic activity , was reduced 35 % by rilmenidine at rest ( p < 0.01 ) and remained significantly lower during mental stress and tilting , although the increases in noradrenaline spillover with both stimuli were preserved . The effects on intraarterial blood pressure ran in parallel , a fall in supine resting pressure , but no reduction in BP rise during mental stress and a lack of fall in BP with tilting . On placebo , adrenaline secretion was 162 +/- 27 ng/min ( mean , SE ) at rest , increased by 77 +/- 42 ng/min with mental stress ( p=0.019 ) and was unchanged with tilting . Rilmenidine left adrenaline secretion untouched under all conditions . CONCLUSIONS This study confirms a sympatholytic effect of rilmenidine during supine rest but demonstrates that sympathetic responses during mental stress and tilting are preserved , the latter underlying a perhaps surprising absence of postural hypotension on the drug . The absence of suppression of reflexive sympathetic responses contrasts with the effects of rilmenidine in experimental animals , and emphasises the previously demonstrated unique importance in humans of suprabulbar noradrenergic neuronal projections from the brainstem , which are inhibited by imidazoline binding agents , in regulating tonic sympathetic activity in essential hypertension . Sympathetic nervous inhibition with rilmenidine contrasted with an absence of suppression of the secretion of adrenaline affirming that here , as elsewhere , sympathetic nervous and adrenal medullary function can be disconnected .

Rilmenidine

rilmenidine

placebo

rilmenidine

placebo

placebo

epinephrine secretion ]

adverse cardiovascular events

noradrenaline spillover

intraarterial blood pressure

BP rise

BP

adrenaline secretion

adrenaline secretion

sympathetic responses

tonic sympathetic activity

sympathetic nervous

and adrenal medullary function

hypertensive patients


Total anthelmintic failure to control nematode parasites of small ruminants on government breeding farms in Sabah , East Malaysia . Government-owned small-ruminant breeding farms in Malaysia provide the source of sheep and goats to smallholder farmers in the country . In the eastern Malaysian state of Sabah , high-level stock losses have been recorded on these farms for several years , frequently accompanied by clinical signs indicating pathogenic levels of infections with the nematode parasite Haemonchus contortus . This suggests that their dependence on chemotherapy to control parasite infections had failed . Accordingly , tests for anthelmintic efficacy using the faecal egg count reduction test ( FECRT ) on the range of drugs used to control nematode parasites were carried out on the five government small-ruminant breeding farms in Sabah . These tests showed a total failure of the benzimidazole , imidothiazole , macrocyclic lactone and salicylanilide groups of anthelmintics to control H. contortus infections of sheep and goats on all farms . Drastic changes in animal management need to be made in an attempt to deal with this situation , for which suggestions are made .

faecal egg count reduction test

salicylanilide

anthelmintic efficacy

H. contortus infections

nematode parasites

nematode parasite Haemonchus contortus


Sustained oral health improvement and use of toothbrushes and dentifrice by previous users of traditional materials in a rural population in Andhra Pradesh , India . AIM To follow-up , one year later , a double-blind , randomised study , which investigated the effect of regular brushing with dentifrices on the oral health of an economically disadvantaged rural population in Andhra Pradesh , India who were primarily users of traditional materials . SUBJECTS 150 of the original study population . METHOD Examination to determine whether the improvements in oral health status and oral health behaviour ( use of toothbrush and dentifrice ) , being unsupported , had been sustained since completion of the original study . RESULTS Data analysis showed sustained , statistically significant improvements in gingival health as measured by gingival bleeding and plaque indices ( GBI and PI ) comparing users and non-users of toothbrushes and dentifrice in the original study ( PI : p = 0.04 ; GBI : p = 0.03 ) and sustained use of toothbrushes and dentifrice by 60 % of the subjects at follow-up one year later . CONCLUSIONS This study shows a beneficial effect on oral hygiene indices following the introduction of toothbrushes and dentifrices to a community using traditional oral hygiene materials and sustainability of use of these materials with motivation and support . It may therefore be concluded that it is feasible to achieve significant use of conventional toothbrushes and toothpastes , with consequent major and sustained improvements in plaque control and gingival health in a disadvantaged population hitherto often considered as not amenable to conventional oral hygiene for cultural or economic reasons .

toothbrushes and dentifrice

regular brushing with dentifrices

toothbrush and dentifrice

oral health improvement

effect

beneficial effect on oral hygiene

oral health improvement

oral health


Impact of angiotensin-converting enzyme gene polymorphism on neurohormonal responses to high- versus low-dose enalapril in advanced heart failure . BACKGROUND The impact of angiotensin-converting enzyme ( ACE ) gene polymorphism on neurohormonal dose response to ACE inhibitor therapy is unclear . METHODS ACE Insertion ( I ) or Deletion ( D ) genotype was determined in 74 patients with chronic heart failure who were randomly assigned to receive either high-dose or low-dose enalapril over a period of 6 months . Monthly pre-enalapril and post-enalapril neurohormone levels ( serum ACE activity ( sACE ) , plasma angiotensin II ( A-II ) , plasma renin activity ( PRA ) , and serum aldosterone ( ALDO ) were compared between genotype subgroups and between patients who received high- or low-dose enalapril within each genotype subgroup . RESULTS At baseline , predose/postdose sACE and postdose PRA were significantly higher in the DD genotype . At 6-month follow-up , postdose sACE was reduced in a dose-dependent fashion in all three genotypes ( P < .05 ) . However , predose and postdose ALDO and A-II levels did not differ between each genotype subgroup at baseline or by enalapril dose within each genotype subgroup . ALDO escape and A-II reactivation were not affected by ACE genotype or enalapril dosage . CONCLUSIONS Predose sACE were consistently higher in the DD genotype when compared with ID or II subgroups . Despite a dose-dependent suppression of sACE , there were no observed statistically significant differences in ALDO and A-II suppression or escape with escalating doses of enalapril within each subgroup .

ACE

enalapril

neurohormonal responses

serum aldosterone ( ALDO

predose/postdose sACE and postdose PRA

postdose sACE

predose and postdose ALDO

A-II levels

ALDO escape

A-II reactivation

Predose sACE

suppression of sACE

ALDO

A-II suppression

advanced heart failure .

74 patients

chronic heart failure


A randomized multicenter trial comparing resection and radiochemotherapy for resectable locally invasive pancreatic cancer . BACKGROUND Though the outcome of resection for locally invasive pancreatic cancer is still poor , it has gradually improved in Japan , and the 5-year survival is now about 10 % . However , the advantage of resection over radiochemotherapy has not yet been confirmed by a randomized trial . We conducted this study to compare surgical resection alone versus radiochemotherapy without resection for locally invasive pancreatic cancer using a multicenter randomized design . METHODS Patients with pancreatic cancer who met our preoperative criteria for inclusion ( pancreatic cancer invading the pancreatic capsule without involvement of the superior mesenteric artery or the common hepatic artery , or without distant metastasis ) underwent laparotomy . Patients with operative findings consistent with our criteria were randomized into a radical resection group and a radiochemotherapy group ( 200 mg/m ( 2 ) /day of intravenous 5-fluorouracil and 5040 cGy of radiotherapy ) without resection . The 2 groups were compared for mean survival , hazard ratio , 1-year survival , quality of life scores , and hematologic and blood chemical data . RESULTS Twenty patients were assigned to the resection group and 22 to the radiochemotherapy group . There was 1 operative death . The surgical resection group had better results than the radiochemotherapy group as measured by 1-year survival ( 62 % vs 32 % , P=.05 ) , mean survival time ( > 17 vs 11 months , P < .03 ) , and hazard ratio ( 0.46 , P=.04 ) . There were no differences in the quality of life score or laboratory data apart from increased diarrhea after surgical resection . CONCLUSIONS Locally invasive pancreatic cancer without distant metastases and major arterial invasion appears to be best treated by surgical resection .

resection and radiochemotherapy

resection

radiochemotherapy

surgical resection

radiochemotherapy

radical resection group

radiochemotherapy group

radiochemotherapy

5-year survival

mean survival

hazard ratio

1-year survival

quality of life scores

operative death .

1-year survival

mean survival time

hazard ratio

quality of life score

laboratory data

diarrhea

Japan

Twenty


Low-intensity exercise and reduction of the risk for falls among at-risk elders . BACKGROUND Among elderly persons , falls account for 87 % of all fractures and are contributing factors in many nursing home admissions . This study evaluated the effect of an easily implemented , low-intensity exercise program on the incidence of falls and the time to first fall among a clinically defined population of elderly men and women . METHODS This community-based , randomized trial compared the exercise intervention with a no-intervention control . The participants were 294 men and women , aged 60 years or older , who had either a hospital admission or bed rest for 2 days or more within the previous month . Exercise participants were scheduled to attend exercise sessions lasting 45 minutes , including warm-up and cool-down , 3 times a week for 8 weeks ( 24 sessions ) . Assessments included gait and balance measures , self-reported physical function , the number of medications being taking at baseline , participant age , sex , and history of falling . Falls were tracked for 1 year after each participant 's baseline assessment . RESULTS 29 % of the study participants reported a fall during the study period . The effect of exercise in preventing falls varied significantly by baseline physical function level ( p < or =.002 ) . The risk for falls decreased for exercise participants with low baseline physical functioning ( hazard ratio , .51 ) but increased for exercise participants with high baseline physical functioning ( hazard ratio , 3.51 ) . CONCLUSIONS This easily implemented , low-intensity exercise program appears to reduce the risk for falls among elderly men and women recovering from recent hospitalizations , bed rest , or both who have low levels of physical functioning .

Low-intensity exercise

low-intensity exercise program

exercise intervention

no-intervention control .

Exercise

exercise sessions

exercise

low-intensity exercise program

risk for falls

falls

incidence of falls

time to first fall

gait and balance measures

self-reported physical function

history of falling

Falls

fall

preventing falls

risk for falls

risk for falls

elderly persons


Acid resistance of enamel subsurface lesions remineralized by a sugar-free chewing gum containing casein phosphopeptide-amorphous calcium phosphate . The aim of this clinical study was to investigate the acid resistance of enamel lesions remineralized in situ by a sugar-free chewing gum containing casein phosphopeptide-amorphous calcium phosphate nanocomplexes ( CPP-ACP : Recaldent ) . The study utilized a double-blind , randomized , crossover design with two treatments : ( i ) sugar-free gum containing 18.8 mg of CPP-ACP , and ( ii ) sugar-free gum not containing CPP-ACP as control . Subjects wore removable palatal appliances with insets of human enamel containing demineralized subsurface lesions and chewed the gum for 20 min 4 times per day for 14 days . After each treatment the enamel slabs were removed and half of each lesion challenged with acid in vitro for 8 or 16 h. The level of remineralization was determined using microradiography . The gum containing CPP-ACP produced approximately twice the level of remineralization as the control sugar-free gum . The 8- and 16-hour acid challenge of the lesions remineralized with the control gum resulted in 65.4 and 88.0 % reductions , respectively , of deposited mineral , while for the CPP-ACP-remineralized lesions the corresponding reductions were 30.5 and 41.8 % . The acid challenge after in situ remineralization for both control and CPP-ACP-treated lesions resulted in demineralization underneath the remineralized zone , indicating that the remineralized mineral was more resistant to subsequent acid challenge . The results show that sugar-free gum containing CPP-ACP is superior to an equivalent gum not containing CPP-ACP in remineralization of enamel subsurface lesions in situ with mineral that is more resistant to subsequent acid challenge .

sugar-free chewing gum

sugar-free gum

CPP-ACP

sugar-free gum not containing CPP-ACP

gum for

gum containing CPP-ACP

control gum

sugar-free gum containing CPP-ACP

gum

Acid resistance

acid resistance

challenged with acid

in vitro

level of remineralization

microradiography

level of remineralization

lesions remineralized

demineralization

more resistant

enamel subsurface lesions

enamel lesions

subsurface lesions


Influenza and pneumococcal vaccination as a model to assess C-reactive protein response to mild inflammation . This study was set up to examine whether an influenza vaccine or an influenza vaccine in combination with pneumococcal vaccine can be used as a model to study responses to mild stimulation of the inflammatory system . In this study , 19 subjects received the influenza vaccine , 20 subjects the combination of influenza and pneumococcal vaccine . CRP and prothrombin fragment 1 and 2 ( F1+2 ) were measured at baseline , and two times after vaccination . Influenza vaccination increased CRP by 0.20 mg/L , and influenza in combination with pneumococcal vaccine increased CRP by 0.60 mg/L . F1+2 increased 0.15 nmol/L after the combined vaccination ; an increase in response to the influenza vaccination was not statistically significant . Our findings show that the influenza vaccine alone as well as the combination of the influenza and pneumococcal vaccine increases CRP-levels with a peak 2 days after vaccination .

vaccination

influenza vaccine

influenza and pneumococcal vaccine

Influenza vaccination

pneumococcal vaccine

influenza vaccination

influenza vaccine

influenza and pneumococcal vaccine

CRP

prothrombin fragment 1 and 2 ( F1+2 )

CRP

CRP

response to the influenza vaccination

CRP-levels

mild inflammation .


Use of Interceed ( TC7 ) absorbable adhesion barrier to reduce postoperative adhesion reformation in infertility and endometriosis surgery . The Obstetrics and Gynecology Adhesion Prevention Committee . Interceed ( TC7 ) is a fabric composed of oxidized , regenerated cellulose that was designed to reduce the formation of postsurgical adhesions . We evaluated Interceed ( TC7 ) in a randomized , multicenter clinical study . Sixty-three infertility patients had bilateral pelvic sidewall adhesions removed at laparotomy . One pelvic sidewall was covered by Interceed ( TC7 ) and the other was left uncovered . The deperitonealized areas ( N = 205 ) of all sidewalls were divided into three groups : less than 100 mm2 , N = 72 ; 100-1000 mm2 , N = 95 ; and more than 1000 mm2 , N = 38 . The effectiveness of Interceed ( TC7 ) was evaluated at laparoscopy 10-98 days after laparotomy . Significantly more adhesions were observed at laparoscopy on the control pelvic sidewalls ( 48 of 63 , 76 % ) than on the treated sides ( 26 of 63 , 41 % ) ( P less than .0001 ) . The Interceed ( TC7 ) -treated sidewalls also had significantly less area involved with adhesions at laparoscopy ( P less than .05 , P less than .001 , and P less than .001 in the three groups , respectively ) . Twenty-eight women with severe endometriosis also had significantly more adhesions on the control side ( 23 of 28 , 82 % ) than on the treated side ( 14 of 28 , 50 % ) ( P less than .05 ) . We conclude that Interceed ( TC7 ) effectively reduced the incidence and extent of postoperative adhesions , even in patients with severe endometriosis .

Interceed ( TC7 )

Interceed ( TC7

Interceed ( TC7 )

other was left uncovered

Interceed ( TC7 )

laparotomy

Interceed ( TC7 )

Interceed ( TC7 )

postoperative adhesion reformation

effectiveness of Interceed ( TC7 )

adhesions

area involved with adhesions

adhesions

postoperative adhesions

infertility

endometriosis

Sixty-three

infertility