Title
 Systematic detection and multidisciplinary care of delirium in older medical inpatients : a randomized trial .

 ABSTRACT BACKGROUND
 Delirium is common and often goes undetected in older patients admitted to medical services . It is associated with poor outcomes . We conducted a randomized clinical trial to determine whether systematic detection and multidisciplinary care of delirium in older patients admitted to a general medical service could reduce time to improvement in cognitive status .

 ABSTRACT METHODS
 Consecutive patients aged 65 or more who were newly admitted to 5 general medical units between Mar. 15 , 1996 , and Jan. 31 , 1999 , were screened with the Confusion Assessment Method within 24 hours after admission to detect prevalent delirium and rescreened within a week to detect incident cases . Patients with delirium were randomly allocated to receive the intervention or usual care . Subjects in the intervention group were seen by a geriatric specialist consultant and followed in hospital for up to 8 weeks by an intervention nurse who liaised with the consultant , attending physicians , family and the primary care nurses . Subjects in the usual care group received standard hospital services but could consult geriatric specialists as needed . A research assistant , blinded as to treatment allocation , administered within 24 hours after enrolment the MiniMental Status Exam ( MMSE ) , Delirium Index ( measuring the severity of the delirium ) and Barthel Index ( measuring independence of personal care ) . Improvement was defined as an increase in the MMSE score of 2 or more points , with no decrease below baseline plus 2 points , or no decrease below a baseline MMSE score of 27 . A short form of the Informant Questionnaire on Cognitive Decline in the Elderly was completed to identify patients with possible dementia . Subjects were assessed 3 times during the first week and weekly thereafter for up to 8 weeks in hospital or until discharge . Data on clinical severity of illness , length of stay and living arrangements after discharge were also collected . The primary outcome measure was time to improvement in MMSE score .

 ABSTRACT RESULTS
 Of the 1925 patients who met the inclusion criteria and were screened , 227 had prevalent or incident delirium and consented to participate ( 113 in intervention group and 114 in usual care group ) . There were no clinically significant differences between the intervention and usual care groups except for sex ( female 58.4 % v. 50.0 % ) and marital status ( married 34.8 % v. 41.2 % ) . Overall , 48 % of the patients in the intervention group and 45 % of those in the usual care group met the predetermined criteria for improvement . The Cox proportional hazards ratio ( HR ) for a shorter time to improvement with the intervention versus usual care , adjusted for age , sex and marital status , was 1.10 ( 95 % confidence interval [ CI ] 0.74-1.63 ) . There were no significant differences within 8 weeks after enrolment between the 2 groups in time to and rate of improvement of the Delirium Index , the Barthel Index , length of stay , rate of discharge to the community , living arrangements after discharge or survival . Outcomes between the 2 groups did not differ statistically significantly for patients without dementia ( HR 1.54 , 95 % CI 0.80-2.97 ) , for those who had less co-morbidity ( HR 1.36 , 95 % CI 0.75-2.46 ) or for those with prevalent delirium ( HR 1.15 , 95 % CI 0.48-2.79 ) .

 ABSTRACT CONCLUSIONS
 Systematic detection and multidisciplinary care of delirium does not appear to be more beneficial than usual care for older patients admitted to medical services .

Title

Systematic

detection

and

multidisciplinary

care

of

delirium

in

older

medical

inpatients

a

randomized

trial

ABSTRACT BACKGROUND

Delirium

is

common

and

often

goes

undetected

in

older

patients

admitted

to

medical

services

It

is

associated

with

poor

outcomes

We

conducted

a

randomized

clinical

trial

to

determine

whether

systematic

detection

and

multidisciplinary

care

of

delirium

in

older

patients

admitted

to

a

general

medical

service

could

reduce

time

to

improvement

in

cognitive

status

ABSTRACT METHODS

Consecutive

patients

aged

or

more

who

were

newly

admitted

to

general

medical

units

between

Mar.

and

Jan.

were

screened

with

the

Confusion

Assessment

Method

within

hours

after

admission

to

detect

prevalent

delirium

and

rescreened

within

a

week

to

detect

incident

cases

Patients

with

delirium

were

randomly

allocated

to

receive

the

intervention

or

usual

care

Subjects

in

the

intervention

group

were

seen

by

a

geriatric

specialist

consultant

and

followed

in

hospital

for

up

to

weeks

by

an

intervention

nurse

who

liaised

with

the

consultant

attending

physicians

family

and

the

primary

care

nurses

Subjects

in

the

usual

care

group

received

standard

hospital

services

but

could

consult

geriatric

specialists

as

needed

A

research

assistant

blinded

as

to

treatment

allocation

administered

within

hours

after

enrolment

the

MiniMental

Status

Exam

MMSE

Delirium

Index

measuring

the

severity

of

the

delirium

and

Barthel

Index

measuring

independence

of

personal

care

Improvement

was

defined

as

an

increase

in

the

MMSE

score

of

or

more

points

with

no

decrease

below

baseline

plus

points

or

no

decrease

below

a

baseline

MMSE

score

of

A

short

form

of

the

Informant

Questionnaire

on

Cognitive

Decline

in

the

Elderly

was

completed

to

identify

patients

with

possible

dementia

Subjects

were

assessed

times

during

the

first

week

and

weekly

thereafter

for

up

to

weeks

in

hospital

or

until

discharge

Data

on

clinical

severity

of

illness

length

of

stay

and

living

arrangements

after

discharge

were

also

collected

The

primary

outcome

measure

was

time

to

improvement

in

MMSE

score

ABSTRACT RESULTS

Of

the

patients

who

met

the

inclusion

criteria

and

were

screened

had

prevalent

or

incident

delirium

and

consented

to

participate

in

intervention

group

and

in

usual

care

group

There

were

no

clinically

significant

differences

between

the

intervention

and

usual

care

groups

except

for

sex

female

v.

and

marital

status

married

v.

Overall

of

the

patients

in

the

intervention

group

and

of

those

in

the

usual

care

group

met

the

predetermined

criteria

for

improvement

The

Cox

proportional

hazards

ratio

HR

for

a

shorter

time

to

improvement

with

the

intervention

versus

usual

care

adjusted

for

age

sex

and

marital

status

was

confidence

interval

CI

There

were

no

significant

differences

within

weeks

after

enrolment

between

the

groups

in

time

to

and

rate

of

improvement

of

the

Delirium

Index

the

Barthel

Index

length

of

stay

rate

of

discharge

to

the

community

living

arrangements

after

discharge

or

survival

Outcomes

between

the

groups

did

not

differ

statistically

significantly

for

patients

without

dementia

HR

CI

for

those

who

had

less

co-morbidity

HR

CI

or

for

those

with

prevalent

delirium

HR

CI

ABSTRACT CONCLUSIONS

Systematic

detection

and

multidisciplinary

care

of

delirium

does

not

appear

to

be

more

beneficial

than

usual

care

for

older

patients

admitted

to

medical

services


Title
 [ Diagnostic methods and prophylaxis of purulent inflammation in postsurgical wounds ] .

Title

Diagnostic

methods

and

prophylaxis

of

purulent

inflammation

in

postsurgical

wounds


Title
 Trial of unsaturated-fat diet .

Title

Trial

of

unsaturated-fat

diet


Title
 Preliminary effects of progressive muscle relaxation on cigarette craving and withdrawal symptoms in experienced smokers in acute cigarette abstinence : a randomized controlled trial .

 ABSTRACT BACKGROUND
 Cigarette craving usually occurs in conjunction with unpleasant feelings , including stress , as part of a withdrawal syndrome . Progressive muscle relaxation ( PMR ) , a behavioral technique used to reduce stress by concentrating on achieving muscle relaxation , may reduce levels of cigarette craving and other substance-related negative feelings and withdrawal symptoms .

 ABSTRACT METHODS
 Demographic and cigarette use data were collected from 32 experienced smokers at the King Chulalongkorn Memorial Hospital , Bangkok , Thailand using the Semi-Structured Assessment for Drug Dependence and Alcoholism . Participants were asked to refrain from smoking for at least 3 hours before the visit ( acute abstinence ) and were randomly allocated to a 1-session PMR group ( n = 16 ) or a control activity group ( e.g. , reading newspaper , n = 16 ) . The intervention group was instructed to practice PMR individually in a quiet , private , air-conditioned room for about 20minutes . Craving , other substance-related feelings , and autonomic nervous responses ( e.g. , blood pressure and pulse rate ) were assessed immediately before and after the 1-session intervention .

 ABSTRACT RESULTS
 There were no differences in demographics , cigarette use/dependence , and baseline craving characteristics between the PMR and control groups . However , the control group had higher levels of high and paranoia feeling , and pulse rate than the PMR group at baseline . After practicing PMR , but not after a control activity , smokers undergoing acute abstinence had significantly lower levels of cigarette craving , withdrawal symptoms , and systolic blood pressure than at baseline . After controlling for baseline differences , abstaining smokers using PMR had lower levels of cigarette craving , withdrawal symptoms , and systolic blood pressure than smokers who undertook a control activity .

 ABSTRACT CONCLUSIONS
 PMR significantly reduces cigarette craving , withdrawal symptoms , and blood pressure in smokers undergoing acute abstinence . PMR may be used as an adjunct to cigarette dependency treatments .

Title

Preliminary

effects

of

progressive

muscle

relaxation

on

cigarette

craving

and

withdrawal

symptoms

in

experienced

smokers

in

acute

cigarette

abstinence

a

randomized

controlled

trial

ABSTRACT BACKGROUND

Cigarette

craving

usually

occurs

in

conjunction

with

unpleasant

feelings

including

stress

as

part

of

a

withdrawal

syndrome

Progressive

muscle

relaxation

PMR

a

behavioral

technique

used

to

reduce

stress

by

concentrating

on

achieving

muscle

relaxation

may

reduce

levels

of

cigarette

craving

and

other

substance-related

negative

feelings

and

withdrawal

symptoms

ABSTRACT METHODS

Demographic

and

cigarette

use

data

were

collected

from

experienced

smokers

at

the

King

Chulalongkorn

Memorial

Hospital

Bangkok

Thailand

using

the

Semi-Structured

Assessment

for

Drug

Dependence

and

Alcoholism

Participants

were

asked

to

refrain

from

smoking

for

at

least

hours

before

the

visit

acute

abstinence

and

were

randomly

allocated

to

a

PMR

group

n

or

a

control

activity

group

e.g.

reading

newspaper

n

The

intervention

group

was

instructed

to

practice

PMR

individually

in

a

quiet

private

air-conditioned

room

for

about

Craving

other

substance-related

feelings

and

autonomic

nervous

responses

e.g.

blood

pressure

and

pulse

rate

were

assessed

immediately

before

and

after

the

intervention

ABSTRACT RESULTS

There

were

no

differences

in

demographics

cigarette

use/dependence

and

baseline

craving

characteristics

between

the

PMR

and

control

groups

However

the

control

group

had

higher

levels

of

high

and

paranoia

feeling

and

pulse

rate

than

the

PMR

group

at

baseline

After

practicing

PMR

but

not

after

a

control

activity

smokers

undergoing

acute

abstinence

had

significantly

lower

levels

of

cigarette

craving

withdrawal

symptoms

and

systolic

blood

pressure

than

at

baseline

After

controlling

for

baseline

differences

abstaining

smokers

using

PMR

had

lower

levels

of

cigarette

craving

withdrawal

symptoms

and

systolic

blood

pressure

than

smokers

who

undertook

a

control

activity

ABSTRACT CONCLUSIONS

PMR

significantly

reduces

cigarette

craving

withdrawal

symptoms

and

blood

pressure

in

smokers

undergoing

acute

abstinence

PMR

may

be

used

as

an

adjunct

to

cigarette

dependency

treatments


Title
 Autologous stem-cell transplantation after second-line brentuximab vedotin in relapsed or refractory Hodgkin lymphoma .

 ABSTRACT GENERAL
 We previously demonstrated that brentuximab vedotin ( BV ) used as second-line therapy in patients with Hodgkin lymphoma is a tolerable and effective bridge to autologous hematopoietic cell transplantation ( AHCT ) . Here , we report the post-AHCT outcomes of patients treated with second-line standard/fixed-dose BV and an additional cohort of patients where positron-emission tomography adapted dose-escalation of second-line BV was utilized .

 ABSTRACT GENERAL
 Patients on the dose-escalation cohort received 1.8 mg/kg of BV intravenously every 3 weeks for two cycles . Patients in complete remission ( CR ) after two cycles received two additional cycles of BV at 1.8 mg/kg , while patients with stable disease or partial response were escalated to 2.4 mg/kg for two cycles . All patients , regardless of treatment cohort , proceeded directly to AHCT or received additional pre-AHCT therapy at the discretion of the treating physician based on remission status after second-line BV .

 ABSTRACT GENERAL
 Of the 20 patients enrolled to the BV dose-escalation cohort , 8 patients underwent BV dose-escalation . BV escalation was well-tolerated , but no patients who were escalated converted to CR . Of 56 evaluable patients treated across cohorts , the overall response rate ( ORR ) to second-line BV was 75 % with 43 % CR . Twenty-eight ( 50 % ) patients proceeded directly to AHCT without post-BV chemotherapy , and a total of 50 patients proceeded to AHCT . Thirteen patients received consolidative post-AHCT therapy with either radiation , BV , or a PD-1 inhibitor . After AHCT , the 2-year progression-free survival ( PFS ) and overall survival were 67 % and 93 % , respectively . The 2-year PFS among patients in CR at the time of AHCT ( n = 37 ) was 71 % compared with 54 % in patients not in CR ( p = 0.12 ) . The 2-year PFS in patients who proceeded to AHCT directly after receiving BV alone was 77 % .

 ABSTRACT GENERAL
 Second-line BV is an effective bridge to AHCT that produces responses of sufficient depth to provide durable remission in conjunction with AHCT ( clinicaltrials.gov : NCT01393717 ) .

Title

Autologous

stem-cell

transplantation

after

second-line

brentuximab

vedotin

in

relapsed

or

refractory

Hodgkin

lymphoma

ABSTRACT GENERAL

We

previously

demonstrated

that

brentuximab

vedotin

BV

used

as

second-line

therapy

in

patients

with

Hodgkin

lymphoma

is

a

tolerable

and

effective

bridge

to

autologous

hematopoietic

cell

transplantation

AHCT

Here

we

report

the

post-AHCT

outcomes

of

patients

treated

with

second-line

standard/fixed-dose

BV

and

an

additional

cohort

of

patients

where

positron-emission

tomography

adapted

dose-escalation

of

second-line

BV

was

utilized

ABSTRACT GENERAL

Patients

on

the

dose-escalation

cohort

received

mg/kg

of

BV

intravenously

every

weeks

for

two

cycles

Patients

in

complete

remission

CR

after

two

cycles

received

two

additional

cycles

of

BV

at

mg/kg

while

patients

with

stable

disease

or

partial

response

were

escalated

to

mg/kg

for

two

cycles

All

patients

regardless

of

treatment

cohort

proceeded

directly

to

AHCT

or

received

additional

pre-AHCT

therapy

at

the

discretion

of

the

treating

physician

based

on

remission

status

after

second-line

BV

ABSTRACT GENERAL

Of

the

patients

enrolled

to

the

BV

dose-escalation

cohort

patients

underwent

BV

dose-escalation

BV

escalation

was

well-tolerated

but

no

patients

who

were

escalated

converted

to

CR

Of

evaluable

patients

treated

across

cohorts

the

overall

response

rate

ORR

to

second-line

BV

was

with

CR

Twenty-eight

patients

proceeded

directly

to

AHCT

without

post-BV

chemotherapy

and

a

total

of

patients

proceeded

to

AHCT

Thirteen

patients

received

consolidative

post-AHCT

therapy

with

either

radiation

BV

or

a

inhibitor

After

AHCT

the

progression-free

survival

PFS

and

overall

survival

were

and

respectively

The

PFS

among

patients

in

CR

at

the

time

of

AHCT

n

was

compared

with

in

patients

not

in

CR

p

The

PFS

in

patients

who

proceeded

to

AHCT

directly

after

receiving

BV

alone

was

ABSTRACT GENERAL

Second-line

BV

is

an

effective

bridge

to

AHCT

that

produces

responses

of

sufficient

depth

to

provide

durable

remission

in

conjunction

with

AHCT

clinicaltrials.gov


Title
 Inefficiency of randomization methods that balance on stratum margins and improvements with permuted blocks and a sequential method .

 ABSTRACT GENERAL
 Stratified permuted blocks randomization is commonly applied in clinical trials , but other randomization methods that attempt to balance treatment counts marginally for the stratification variables are able to accommodate more stratification variables . When the analysis stratifies on the cells formed by crossing the stratification variables , these other randomization methods yield treatment effect estimates with larger variance than does stratified permuted blocks . When it is truly necessary to balance the randomization on many stratification variables , it is shown how this inefficiency can be improved by using a sequential randomization method where the first level balances on the crossing of the strata used in the analysis and further stratification variables fall lower in the sequential hierarchy .

Title

Inefficiency

of

randomization

methods

that

balance

on

stratum

margins

and

improvements

with

permuted

blocks

and

a

sequential

method

ABSTRACT GENERAL

Stratified

permuted

blocks

randomization

is

commonly

applied

in

clinical

trials

but

other

randomization

methods

that

attempt

to

balance

treatment

counts

marginally

for

the

stratification

variables

are

able

to

accommodate

more

stratification

variables

When

the

analysis

stratifies

on

the

cells

formed

by

crossing

the

stratification

variables

these

other

randomization

methods

yield

treatment

effect

estimates

with

larger

variance

than

does

stratified

permuted

blocks

When

it

is

truly

necessary

to

balance

the

randomization

on

many

stratification

variables

it

is

shown

how

this

inefficiency

can

be

improved

by

using

a

sequential

randomization

method

where

the

first

level

balances

on

the

crossing

of

the

strata

used

in

the

analysis

and

further

stratification

variables

fall

lower

in

the

sequential

hierarchy


Title
 Randomized double-blind study of the Reliefband as an adjunct to standard antiemetics in patients receiving moderately-high to highly emetogenic chemotherapy .

 ABSTRACT OBJECTIVE
 Our goal was to evaluate the efficacy and tolerability of the Reliefband as an adjunct to standard antiemetics in patients receiving moderately-high to highly emetogenic chemotherapy .

 ABSTRACT METHODS
 Forty-nine adult cancer patients receiving moderately-high or highly emetogenic chemotherapy were randomized to receive either the active Reliefband ( n = 26 ) or an inactive device ( n = 23 ) . Patients continued to receive all scheduled and as needed antiemetic agents as prescribed . The device was worn the day of chemotherapy administration for 5 days ( days 1-5 ) . Patients maintained a daily dairy of nausea severity , vomiting and retching episodes , and antiemetic medications taken . Each patient completed a Functional Living Index Emesis ( FLIE ) and a tolerability survey at the conclusion of the study . A Wilcoxon rank sum test was used to compare the number of vomiting episodes , severity of nausea and FLIE scores between the two groups .

 ABSTRACT RESULTS
 Patients wearing the active Relifband experienced less vomiting ( Reliefband 1.9 versus inactive device 4.6 mean episodes ; p = 0.05 ) , retching ( 1.4 versus 3.6 mean episodes ; p = 0.05 ) , and nausea severity ( 0.91 versus 1.65 mean cm/day ; p = 0.01 ) over the 5-day period compared to patients wearing the inactive device . Vomiting was statistically significantly reduced during the delayed period ( 0.42 versus 1 ; p = 0.032 ) , whereas nausea was significantly reduced during the acute ( 0.71 versus 2.3 ; p = 0.028 ) and delayed ( 1.8 versus 3.3 ; p = 0.020 ) periods . FLIE scores did not differ between the two treatment groups ( 91 versus 80 ; p = 0.088 ) .

 ABSTRACT CONCLUSIONS
 This study suggests that patients receiving moderately-high to highly emetogenic chemotherapy who experience nausea and vomiting despite scheduled antiemetics may benefit from the use of the Reliefband as an adjunct to antiemetics . Limitations of this study include differences in risk factors for emesis , chemotherapy , and antiemetic regimens . A larger , better , controlled randomized study is needed to better define optimal use of this device .

Title

Randomized

double-blind

study

of

the

Reliefband

as

an

adjunct

to

standard

antiemetics

in

patients

receiving

moderately-high

to

highly

emetogenic

chemotherapy

ABSTRACT OBJECTIVE

Our

goal

was

to

evaluate

the

efficacy

and

tolerability

of

the

Reliefband

as

an

adjunct

to

standard

antiemetics

in

patients

receiving

moderately-high

to

highly

emetogenic

chemotherapy

ABSTRACT METHODS

Forty-nine

adult

cancer

patients

receiving

moderately-high

or

highly

emetogenic

chemotherapy

were

randomized

to

receive

either

the

active

Reliefband

n

or

an

inactive

device

n

Patients

continued

to

receive

all

scheduled

and

as

needed

antiemetic

agents

as

prescribed

The

device

was

worn

the

day

of

chemotherapy

administration

for

days

days

Patients

maintained

a

daily

dairy

of

nausea

severity

vomiting

and

retching

episodes

and

antiemetic

medications

taken

Each

patient

completed

a

Functional

Living

Index

Emesis

FLIE

and

a

tolerability

survey

at

the

conclusion

of

the

study

A

Wilcoxon

rank

sum

test

was

used

to

compare

the

number

of

vomiting

episodes

severity

of

nausea

and

FLIE

scores

between

the

two

groups

ABSTRACT RESULTS

Patients

wearing

the

active

Relifband

experienced

less

vomiting

Reliefband

versus

inactive

device

mean

episodes

p

retching

versus

mean

episodes

p

and

nausea

severity

versus

mean

cm/day

p

over

the

period

compared

to

patients

wearing

the

inactive

device

Vomiting

was

statistically

significantly

reduced

during

the

delayed

period

versus

p

whereas

nausea

was

significantly

reduced

during

the

acute

versus

p

and

delayed

versus

p

periods

FLIE

scores

did

not

differ

between

the

two

treatment

groups

versus

p

ABSTRACT CONCLUSIONS

This

study

suggests

that

patients

receiving

moderately-high

to

highly

emetogenic

chemotherapy

who

experience

nausea

and

vomiting

despite

scheduled

antiemetics

may

benefit

from

the

use

of

the

Reliefband

as

an

adjunct

to

antiemetics

Limitations

of

this

study

include

differences

in

risk

factors

for

emesis

chemotherapy

and

antiemetic

regimens

A

larger

better

controlled

randomized

study

is

needed

to

better

define

optimal

use

of

this

device


Title
 Periprocedural Management of Oral Anticoagulation .

 ABSTRACT GENERAL
 Decisions surrounding periprocedural anticoagulation management must balance thromboembolic and procedural bleed risk . The interruption of both warfarin and DOACs requires consideration of anticoagulant pharmacokinetics , procedural bleed risk and patient characteristics . There is a diminishing role for periprocedural bridging LMWH overall and no role for bridging LMWH for the procedural interruption of DOACs . A clinical approach to perioperative DOAC management based on operative bleeding risk and renal function is safe and effective , and at present , is preferred over preprocedural DOAC levels testing . Clear communication of the anticoagulation interruption plan to both the patient and the patient 's care team is essential .

Title

Periprocedural

Management

of

Oral

Anticoagulation

ABSTRACT GENERAL

Decisions

surrounding

periprocedural

anticoagulation

management

must

balance

thromboembolic

and

procedural

bleed

risk

The

interruption

of

both

warfarin

and

DOACs

requires

consideration

of

anticoagulant

pharmacokinetics

procedural

bleed

risk

and

patient

characteristics

There

is

a

diminishing

role

for

periprocedural

bridging

LMWH

overall

and

no

role

for

bridging

LMWH

for

the

procedural

interruption

of

DOACs

A

clinical

approach

to

perioperative

DOAC

management

based

on

operative

bleeding

risk

and

renal

function

is

safe

and

effective

and

at

present

is

preferred

over

preprocedural

DOAC

levels

testing

Clear

communication

of

the

anticoagulation

interruption

plan

to

both

the

patient

and

the

patient

's

care

team

is

essential


Title
 [ A new contribution to the experimental study of pregnancy toxemia ] .

Title

A

new

contribution

to

the

experimental

study

of

pregnancy

toxemia


Title
 Oral immunotherapy with type V collagen in idiopathic pulmonary fibrosis .

 ABSTRACT GENERAL
 Idiopathic pulmonary fibrosis ( IPF ) is a progressive lung disease with poor prognosis . IPF appears to be heterogeneous in pathobiology with ∼ 40 % of IPF patients found to have elevated levels of circulating antibodies to the autoantigen type V collagen ( col ( V ) ) . Following a targeted , precision medicine approach , we conducted a phase 1 study to test the safety and explore potential efficacy of IW001 , a col ( V ) oral immunotherapeutic developed to treat antibody-positive IPF patients . We divided 30 antibody-positive IPF patients into three cohorts for daily dosing over a 24-week period . All patients completed treatment without serious adverse events , acute exacerbations or IPF-related hospitalisations . A decline in lung function occurred in the lowest-dose cohort that was comparable to that reported in placebo arms of published IPF trials . In contrast , the highest-dose cohort showed a trend toward stabilisation of forced vital capacity and matrix metalloproteinase 7 , and a reduction in binding of C1q to anti-col ( V ) antibodies . IW001 may modulate the immune response to col ( V ) and may represent a new therapeutic for col ( V ) - reactive IPF patients .

Title

Oral

immunotherapy

with

type

V

collagen

in

idiopathic

pulmonary

fibrosis

ABSTRACT GENERAL

Idiopathic

pulmonary

fibrosis

IPF

is

a

progressive

lung

disease

with

poor

prognosis

IPF

appears

to

be

heterogeneous

in

pathobiology

with

of

IPF

patients

found

to

have

elevated

levels

of

circulating

antibodies

to

the

autoantigen

type

V

collagen

col

V

Following

a

targeted

precision

medicine

approach

we

conducted

a

phase

study

to

test

the

safety

and

explore

potential

efficacy

of

a

col

V

oral

immunotherapeutic

developed

to

treat

antibody-positive

IPF

patients

We

divided

antibody-positive

IPF

patients

into

three

cohorts

for

daily

dosing

over

a

period

All

patients

completed

treatment

without

serious

adverse

events

acute

exacerbations

or

IPF-related

hospitalisations

A

decline

in

lung

function

occurred

in

the

lowest-dose

cohort

that

was

comparable

to

that

reported

in

placebo

arms

of

published

IPF

trials

In

contrast

the

highest-dose

cohort

showed

a

trend

toward

stabilisation

of

forced

vital

capacity

and

matrix

metalloproteinase

and

a

reduction

in

binding

of

to

anti-col

V

antibodies

may

modulate

the

immune

response

to

col

V

and

may

represent

a

new

therapeutic

for

col

V

reactive

IPF

patients


Title
 Is Na + modeling necessary in high flux dialysis ?

 ABSTRACT GENERAL
 One important pathogenic factor in dialysis hypotension is the drop in plasma osmolality . Increasing the dialysate Na + concentration decreases hypotensive episodes . The authors studied 39 patients being treated with high flux dialysis . During a 9 week period , the patients were on a standard Na + dialysate ( Na + = 140 meq/L ) basal period ( B ) ; 9 % ( Na + = 149 meq/L ) linear ( L ) ; step drop ( S ) ; and exponential drop ( E ) . The Na + program was changed weekly at random . The results obtained with the three Na + modeling programs were similar . We compared the periods with and without Na + modeling : no differences were found in weight gained interdialysis , mean blood pressure predialysis and postdialysis , and hemoconcentration . Serum Na + levels were significantly higher predialysis and postdialysis for those patients on Na + modeling . Hypotensive episodes and cramps decreased 50 % with Na + modeling . The amount of hypertonic and normal saline given during dialysis was markedly reduced . Na + modeling should always be used in patients being maintained on high flux dialysis .

Title

Is

modeling

necessary

in

high

flux

dialysis

ABSTRACT GENERAL

One

important

pathogenic

factor

in

dialysis

hypotension

is

the

drop

in

plasma

osmolality

Increasing

the

dialysate

concentration

decreases

hypotensive

episodes

The

authors

studied

patients

being

treated

with

high

flux

dialysis

During

a

week

period

the

patients

were

on

a

standard

dialysate

meq/L

basal

period

B

meq/L

linear

L

step

drop

S

and

exponential

drop

E

The

program

was

changed

weekly

at

random

The

results

obtained

with

the

three

modeling

programs

were

similar

We

compared

the

periods

with

and

without

modeling

no

differences

were

found

in

weight

gained

interdialysis

mean

blood

pressure

predialysis

and

postdialysis

and

hemoconcentration

Serum

levels

were

significantly

higher

predialysis

and

postdialysis

for

those

patients

on

modeling

Hypotensive

episodes

and

cramps

decreased

with

modeling

The

amount

of

hypertonic

and

normal

saline

given

during

dialysis

was

markedly

reduced

modeling

should

always

be

used

in

patients

being

maintained

on

high

flux

dialysis


Title
 [ Comparative study of the efficacy and tolerability of 2 modalities of intravenous cibenzoline administration in the reduction of recent spontaneous atrial arrhythmia ] .

 ABSTRACT GENERAL
 This multicentre , single blind , parallel group study compared the efficacy and clinical and electrocardiographic tolerance of a 2 minute intravenous administration of cibenzoline at a dose of 1.2 mg.kg-1 with that of a 10 minute 1.75 mg.kg-1 infusion in patients presenting with spontaneous atrial fibrillation ( AF ) for less than 6 weeks . Sixty-two patients ( 40 men and 22 women ) with an average age of 62 years and presenting with sustained AF for at least 30 minutes with a ventricular rate greater than or equal to 80 bpm were randomly assigned to groups and received via the intravenous route either one of the two treatments . Efficacy ( return to sinus rhythm ) was assessed by an ECG recording every 5 minutes and at 45 and 60 minutes thereafter . Sixty-one of the 62 randomised patients were assessed for efficacy . Cibenzoline , administered in the form of a bolus or infusion , proved effective within one hour in 4 patients in each group ( 13 % ) and arrhythmia persisted with ventricular rate of less than 80 bpm in 10 ( 33 % ) and 5 ( 16 % ) of the patients respectively . In patients in whom sinus rhythm was not restored , ventricular rate was significantly reduced by cibenzoline . The patients in whom normal rhythm was restored under one of these treatment regimens were significantly younger . Patients in whom rhythm returned to normal following the administration of the bolus had AF of significantly more recent onset than that of the patients in whom abnormal rhythm persisted , whilst the history of the AF did not differ significantly between these two types of response after the infusion . ( ABSTRACT TRUNCATED AT 250 WORDS )

Title

Comparative

study

of

the

efficacy

and

tolerability

of

modalities

of

intravenous

cibenzoline

administration

in

the

reduction

of

recent

spontaneous

atrial

arrhythmia

ABSTRACT GENERAL

This

multicentre

single

blind

parallel

group

study

compared

the

efficacy

and

clinical

and

electrocardiographic

tolerance

of

a

minute

intravenous

administration

of

cibenzoline

at

a

dose

of

with

that

of

a

minute

infusion

in

patients

presenting

with

spontaneous

atrial

fibrillation

AF

for

less

than

weeks

Sixty-two

patients

men

and

women

with

an

average

age

of

years

and

presenting

with

sustained

AF

for

at

least

minutes

with

a

ventricular

rate

greater

than

or

equal

to

bpm

were

randomly

assigned

to

groups

and

received

via

the

intravenous

route

either

one

of

the

two

treatments

Efficacy

return

to

sinus

rhythm

was

assessed

by

an

ECG

recording

every

minutes

and

at

and

minutes

thereafter

Sixty-one

of

the

randomised

patients

were

assessed

for

efficacy

Cibenzoline

administered

in

the

form

of

a

bolus

or

infusion

proved

effective

within

one

hour

in

patients

in

each

group

and

arrhythmia

persisted

with

ventricular

rate

of

less

than

bpm

in

and

of

the

patients

respectively

In

patients

in

whom

sinus

rhythm

was

not

restored

ventricular

rate

was

significantly

reduced

by

cibenzoline

The

patients

in

whom

normal

rhythm

was

restored

under

one

of

these

treatment

regimens

were

significantly

younger

Patients

in

whom

rhythm

returned

to

normal

following

the

administration

of

the

bolus

had

AF

of

significantly

more

recent

onset

than

that

of

the

patients

in

whom

abnormal

rhythm

persisted

whilst

the

history

of

the

AF

did

not

differ

significantly

between

these

two

types

of

response

after

the

infusion

ABSTRACT

TRUNCATED

AT

WORDS


Title
 [ Immunological treatment of spontaneous repeated abortions . The value of transfusing the partner 's leukocytes in the third week of gestation ] .

 ABSTRACT GENERAL
 Twenty-two nulli - all primipara who had had previous repeated spontaneous abortions and who did not have anti-HLA antibodies for the partner , received immunological treatment consisting of a single transfusion of the partner 's lymphocytes in the third week of pregnancy , and giving natural progesterone supplements after the kinetic of Beta-HCG in the plasma had been assessed . The number of pregnancies which went to terme ( 94 % success ) was significantly better than those obtained in our first protocol which was to give one to three transfusions of the partner 's lymphocytes before the pregnancy started ( 58 % success rare after 24 treatments ) . Apart from obtaining much better results the second protocol made it possible to avoid giving a significant number of useless transfusions ( 22 % of pre-conceptual transfusions were not followed by a pregnancy at all ) .

Title

Immunological

treatment

of

spontaneous

repeated

abortions

The

value

of

transfusing

the

partner

's

leukocytes

in

the

third

week

of

gestation

ABSTRACT GENERAL

Twenty-two

nulli

all

primipara

who

had

had

previous

repeated

spontaneous

abortions

and

who

did

not

have

anti-HLA

antibodies

for

the

partner

received

immunological

treatment

consisting

of

a

single

transfusion

of

the

partner

's

lymphocytes

in

the

third

week

of

pregnancy

and

giving

natural

progesterone

supplements

after

the

kinetic

of

Beta-HCG

in

the

plasma

had

been

assessed

The

number

of

pregnancies

which

went

to

terme

success

was

significantly

better

than

those

obtained

in

our

first

protocol

which

was

to

give

one

to

three

transfusions

of

the

partner

's

lymphocytes

before

the

pregnancy

started

success

rare

after

treatments

Apart

from

obtaining

much

better

results

the

second

protocol

made

it

possible

to

avoid

giving

a

significant

number

of

useless

transfusions

of

pre-conceptual

transfusions

were

not

followed

by

a

pregnancy

at

all


Title
 Intra-arterial carboplatin chemotherapy for brain tumors : a dose escalation study based on cerebral blood flow .

 ABSTRACT OBJECTIVE
 To perform in intra-arterial dose escalation study of carboplatin based on hemispheric blood-flow estimation in patients with recurrent malignant glioma . The primary purpose was to determine the maximally tolerated intra-arterial dose .

 ABSTRACT METHODS
 Methods included : 1 ) selective intra-arterial delivery performed with modern microcatheters , 2 ) pulsatile infusion , and 3 ) dosage based on local cerebral blood-flow estimation ( middle cerebral artery 60 % , anterior cerebral artery 20 % , posterior cerebral artery 15 % , and anterior choroidal artery 5 % of the hemispheric blood-flow ) . The deliveries were performed above the ophthalmic artery in the anterior circulation , or above the anterior inferior cerebellar arteries in the posterior circulation . The doses were escalated from 200 mg/hemisphere at 50 mg increments . Twenty-one patients were studied ( 14 with glioblastoma multiforme , five anaplastic astrocytoma , one aggressive low-grade glioma , one metastasis ) . Patients had recurrent glioma limited to one hemisphere and Karnofsky score of 50 or greater . Concomitant therapies were allowed .

 ABSTRACT RESULTS
 Carboplatin was escalated to a dose of 1400 mg/hemisphere . One patient had a permanent neuromotor decline . The predominant toxicity was hematopoietic . The median time to tumor progression was 22 weeks , median survival 39 weeks , and the response rate 70 % ( 50 % SD and 20 % PR ) of 19 patients .

 ABSTRACT CONCLUSIONS
 Hemispheric blood-flow estimation allowed us to escalate the dose of intra-arterial carboplatin to twice what was previously considered safe . Responses compared favorably to previous studies . Further studies are needed to determine if this method will provide improved and durable responses .

Title

Intra-arterial

carboplatin

chemotherapy

for

brain

tumors

a

dose

escalation

study

based

on

cerebral

blood

flow

ABSTRACT OBJECTIVE

To

perform

in

intra-arterial

dose

escalation

study

of

carboplatin

based

on

hemispheric

blood-flow

estimation

in

patients

with

recurrent

malignant

glioma

The

primary

purpose

was

to

determine

the

maximally

tolerated

intra-arterial

dose

ABSTRACT METHODS

Methods

included

selective

intra-arterial

delivery

performed

with

modern

microcatheters

pulsatile

infusion

and

dosage

based

on

local

cerebral

blood-flow

estimation

middle

cerebral

artery

anterior

cerebral

artery

posterior

cerebral

artery

and

anterior

choroidal

artery

of

the

hemispheric

blood-flow

The

deliveries

were

performed

above

the

ophthalmic

artery

in

the

anterior

circulation

or

above

the

anterior

inferior

cerebellar

arteries

in

the

posterior

circulation

The

doses

were

escalated

from

mg/hemisphere

at

mg

increments

Twenty-one

patients

were

studied

with

glioblastoma

multiforme

five

anaplastic

astrocytoma

one

aggressive

low-grade

glioma

one

metastasis

Patients

had

recurrent

glioma

limited

to

one

hemisphere

and

Karnofsky

score

of

or

greater

Concomitant

therapies

were

allowed

ABSTRACT RESULTS

Carboplatin

was

escalated

to

a

dose

of

mg/hemisphere

One

patient

had

a

permanent

neuromotor

decline

The

predominant

toxicity

was

hematopoietic

The

median

time

to

tumor

progression

was

weeks

median

survival

weeks

and

the

response

rate

SD

and

PR

of

patients

ABSTRACT CONCLUSIONS

Hemispheric

blood-flow

estimation

allowed

us

to

escalate

the

dose

of

intra-arterial

carboplatin

to

twice

what

was

previously

considered

safe

Responses

compared

favorably

to

previous

studies

Further

studies

are

needed

to

determine

if

this

method

will

provide

improved

and

durable

responses


Title
 Commentary on hepatoblastoma minisymposium .

Title

Commentary

on

hepatoblastoma

minisymposium


Title
 Fenretinide ( 4-HPR ) in chemoprevention of oral leukoplakia .

 ABSTRACT GENERAL
 A controlled clinical trial has been underway at the Istituto Nazionale Tumori ( INT ) of Milan since 1988 . The goal of the trial is to evaluate the effectiveness of fenretinide ( 4-HPR ) in preventing relapses , new localizations , and carcinomas in patients with benign postoperative diagnoses who have been surgically treated for oral leukoplakias . This paper presents the design and the preliminary results of this study . To date , 137 patients have been randomized , following surgical excision of oral leukoplakia , to receive either 200 mg 4-HPR daily for 52 weeks or no intervention . Twenty local relapses or new localizations have occurred so far in the control group and 9 in the 4-HPR group . Seven patients have interrupted the intervention because of toxicity . No impaired dark adaptation has been observed . We conclude that 4-HPR is well-tolerated and appears to be effective in preventing relapses and new localizations during the treatment period .

Title

Fenretinide

in

chemoprevention

of

oral

leukoplakia

ABSTRACT GENERAL

A

controlled

clinical

trial

has

been

underway

at

the

Istituto

Nazionale

Tumori

INT

of

Milan

since

The

goal

of

the

trial

is

to

evaluate

the

effectiveness

of

fenretinide

in

preventing

relapses

new

localizations

and

carcinomas

in

patients

with

benign

postoperative

diagnoses

who

have

been

surgically

treated

for

oral

leukoplakias

This

paper

presents

the

design

and

the

preliminary

results

of

this

study

To

date

patients

have

been

randomized

following

surgical

excision

of

oral

leukoplakia

to

receive

either

mg

daily

for

weeks

or

no

intervention

Twenty

local

relapses

or

new

localizations

have

occurred

so

far

in

the

control

group

and

in

the

group

Seven

patients

have

interrupted

the

intervention

because

of

toxicity

No

impaired

dark

adaptation

has

been

observed

We

conclude

that

is

well-tolerated

and

appears

to

be

effective

in

preventing

relapses

and

new

localizations

during

the

treatment

period


Title
 Additional hippocampectomy in the surgical management of intractable temporal lobe epilepsy associated with glioneuronal tumor .

 ABSTRACT GENERAL
 In surgery for epileptogenic glioneuronal tumor in the temporal lobe , whether additional hippocampectomy is needed remains in dispute . We retrospectively analysed clinical profile and seizure outcome in a consecutive series of six patients , paying special attention to pathophysiologic conditions in the ipsilateral hippocampus . Long-term video electroencephalography ( EEG ) monitoring showed attenuation of background activity , followed by ictal discharges in the ipsilateral temporal region in five cases . ( 18 ) Fluorodeoxyglucose-positron emission tomography ( FDG-PET ) in five cases showed hypometabolism in the ipsilateral medial temporal lobe . Intraoperative electrocorticography ( ECoG ) after removal of the tumor revealed frequent paroxysmal activity or electrographic seizure activity on the hippocampus in five cases . A high incidence of hippocampal pathology , such as hippocampal sclerosis in four cases and dysgenesis in one case , was demonstrated . Five patients who underwent additional hippocampectomy along with resection of the tumor became completely seizure-free . Our findings indicated a proclivity for the epileptogenic zone to encompass the medial structures and for hippocampal pathology to be present even when no direct medial tumor involvement was identified . Thus , it is conceivable that removal of the hippocampus with the guidance of pre - and intraoperative multimodal examinations , in addition to resection of the tumor , may be recommended to achieve ' complete ' freedom from seizures .

Title

Additional

hippocampectomy

in

the

surgical

management

of

intractable

temporal

lobe

epilepsy

associated

with

glioneuronal

tumor

ABSTRACT GENERAL

In

surgery

for

epileptogenic

glioneuronal

tumor

in

the

temporal

lobe

whether

additional

hippocampectomy

is

needed

remains

in

dispute

We

retrospectively

analysed

clinical

profile

and

seizure

outcome

in

a

consecutive

series

of

six

patients

paying

special

attention

to

pathophysiologic

conditions

in

the

ipsilateral

hippocampus

Long-term

video

electroencephalography

EEG

monitoring

showed

attenuation

of

background

activity

followed

by

ictal

discharges

in

the

ipsilateral

temporal

region

in

five

cases

Fluorodeoxyglucose-positron

emission

tomography

FDG-PET

in

five

cases

showed

hypometabolism

in

the

ipsilateral

medial

temporal

lobe

Intraoperative

electrocorticography

ECoG

after

removal

of

the

tumor

revealed

frequent

paroxysmal

activity

or

electrographic

seizure

activity

on

the

hippocampus

in

five

cases

A

high

incidence

of

hippocampal

pathology

such

as

hippocampal

sclerosis

in

four

cases

and

dysgenesis

in

one

case

was

demonstrated

Five

patients

who

underwent

additional

hippocampectomy

along

with

resection

of

the

tumor

became

completely

seizure-free

Our

findings

indicated

a

proclivity

for

the

epileptogenic

zone

to

encompass

the

medial

structures

and

for

hippocampal

pathology

to

be

present

even

when

no

direct

medial

tumor

involvement

was

identified

Thus

it

is

conceivable

that

removal

of

the

hippocampus

with

the

guidance

of

pre

and

intraoperative

multimodal

examinations

in

addition

to

resection

of

the

tumor

may

be

recommended

to

achieve

complete

freedom

from

seizures


Title
 The diagnostic significance of the minimal erythema dose .

Title

The

diagnostic

significance

of

the

minimal

erythema

dose


Title
 Pegaptanib : in exudative age-related macular degeneration .

 ABSTRACT GENERAL
 Pegaptanib , an aptamer , is an antagonist of vascular endothelial growth factor that has shown efficacy in the treatment of patients with exudative age-related macular degeneration ( AMD ) . In two randomised , double-masked trials in patients with exudative AMD ( n = 1208 ) , the proportion of responders ( those losing < 15 letters of visual acuity ) at 54 weeks was significantly higher in intravitreous pegaptanib 0.3 mg recipients than in those receiving sham injections ( 70 % vs 55 % ; p < 0.001 ) . These trials were conducted concurrently and analysed as a single study ; the treatments were given every 6 weeks for 48 weeks . The improvement in visual acuity with pegaptanib was maintained in a 1-year extension of these trials . Similar favourable results with pegaptanib 0.3 mg were seen in terms of the secondary efficacy endpoints ( e.g. proportion of patients experiencing severe loss of visual acuity or legal blindness in the study eye ) . These vision-improving effects of pegaptanib were associated with beneficial angiographic effects . Intravitreous pegaptanib 0.3-3 mg was well tolerated with most ocular adverse events being mild-to-moderate and transient . Serious injection-related adverse events occurred in < or = 1.3 % of patients treated with pegaptanib . There were no systemic adverse events that could be definitely attributed to pegaptanib .

Title

Pegaptanib

in

exudative

age-related

macular

degeneration

ABSTRACT GENERAL

Pegaptanib

an

aptamer

is

an

antagonist

of

vascular

endothelial

growth

factor

that

has

shown

efficacy

in

the

treatment

of

patients

with

exudative

age-related

macular

degeneration

AMD

In

two

randomised

double-masked

trials

in

patients

with

exudative

AMD

n

the

proportion

of

responders

those

losing

letters

of

visual

acuity

at

weeks

was

significantly

higher

in

intravitreous

pegaptanib

mg

recipients

than

in

those

receiving

sham

injections

vs

p

These

trials

were

conducted

concurrently

and

analysed

as

a

single

study

the

treatments

were

given

every

weeks

for

weeks

The

improvement

in

visual

acuity

with

pegaptanib

was

maintained

in

a

extension

of

these

trials

Similar

favourable

results

with

pegaptanib

mg

were

seen

in

terms

of

the

secondary

efficacy

endpoints

e.g.

proportion

of

patients

experiencing

severe

loss

of

visual

acuity

or

legal

blindness

in

the

study

eye

These

vision-improving

effects

of

pegaptanib

were

associated

with

beneficial

angiographic

effects

Intravitreous

pegaptanib

mg

was

well

tolerated

with

most

ocular

adverse

events

being

mild-to-moderate

and

transient

Serious

injection-related

adverse

events

occurred

in

or

of

patients

treated

with

pegaptanib

There

were

no

systemic

adverse

events

that

could

be

definitely

attributed

to

pegaptanib


Title
 [ Clinical study of the action of a new antibiotic ( doxycycline ) in oto-rhino-laryngological infections ] .

Title

Clinical

study

of

the

action

of

a

new

antibiotic

doxycycline

in

oto-rhino-laryngological

infections


Title
 Slow-wave sleep and waking cognitive performance II : Findings among middle-aged adults with and without insomnia complaints .

 ABSTRACT GENERAL
 Previous studies showing a relationship between nocturnal slow-wave sleep ( SWS ) and subsequent diurnal performance among young normal sleepers and older insomnia sufferers have provided limited support for the notion that this sleep stage serves a restorative role for neurocognitive functioning . The current study , which examined the relationship between SWS and reaction time performance among middle-aged adults with and without insomnia complaints , was conducted to further explore this possibility . A sample of 31 noncomplaining middle-aged ( ages 40 to 59 years ) normal sleepers and a like-aged sample of 27 insomnia sufferers , provided data for the current investigation . All participants underwent nocturnal sleep monitoring immediately prior to undergoing a battery of daytime tests that measured simple reaction time , vigilance/signal detection , and complex reaction time . Results showed relationships between reaction time performances on some tasks and some SWS measures among both the normal sleepers and insomnia sufferers . Findings supported our prediction that the presence of sleep pathology ( e.g. , insomnia ) alters the SWS-performance relationship observed , but the results failed to show a consistent relationship between SWS and subsequent performance within either sample . The findings suggest that the specific performance demands of the task in question as well as physiological parameters other than SWS may determine performance as well . Findings for this and previous studies do provide some support for the contention that the neurocognitive restorative value of SWS may change across the lifespan . Possible implications of the study 's findings are discussed and directions for future research are considered .

Title

Slow-wave

sleep

and

waking

cognitive

performance

II

Findings

among

middle-aged

adults

with

and

without

insomnia

complaints

ABSTRACT GENERAL

Previous

studies

showing

a

relationship

between

nocturnal

slow-wave

sleep

SWS

and

subsequent

diurnal

performance

among

young

normal

sleepers

and

older

insomnia

sufferers

have

provided

limited

support

for

the

notion

that

this

sleep

stage

serves

a

restorative

role

for

neurocognitive

functioning

The

current

study

which

examined

the

relationship

between

SWS

and

reaction

time

performance

among

middle-aged

adults

with

and

without

insomnia

complaints

was

conducted

to

further

explore

this

possibility

A

sample

of

noncomplaining

middle-aged

ages

to

years

normal

sleepers

and

a

like-aged

sample

of

insomnia

sufferers

provided

data

for

the

current

investigation

All

participants

underwent

nocturnal

sleep

monitoring

immediately

prior

to

undergoing

a

battery

of

daytime

tests

that

measured

simple

reaction

time

vigilance/signal

detection

and

complex

reaction

time

Results

showed

relationships

between

reaction

time

performances

on

some

tasks

and

some

SWS

measures

among

both

the

normal

sleepers

and

insomnia

sufferers

Findings

supported

our

prediction

that

the

presence

of

sleep

pathology

e.g.

insomnia

alters

the

SWS-performance

relationship

observed

but

the

results

failed

to

show

a

consistent

relationship

between

SWS

and

subsequent

performance

within

either

sample

The

findings

suggest

that

the

specific

performance

demands

of

the

task

in

question

as

well

as

physiological

parameters

other

than

SWS

may

determine

performance

as

well

Findings

for

this

and

previous

studies

do

provide

some

support

for

the

contention

that

the

neurocognitive

restorative

value

of

SWS

may

change

across

the

lifespan

Possible

implications

of

the

study

's

findings

are

discussed

and

directions

for

future

research

are

considered


Title
 [ Benzoyl superoxide in the treatment of crural ulcers ] .

Title

Benzoyl

superoxide

in

the

treatment

of

crural

ulcers


Title
 Fixed , Fiber-Reinforced Resin Bridges on 5.0-mm Implants in Severely Atrophic Mandibles : Up to 5 Years ' Follow-Up of a Prospective Cohort Study .

 ABSTRACT OBJECTIVE
 The aim of this study was to evaluate the midterm outcomes of fixed , full-arch , fiber-reinforced resin bridges on ultrashort implants in terms of marginal bone loss and overall implant survival .

 ABSTRACT METHODS
 Patients with severely atrophic mandibles , corresponding to Cawood and Howell class V and class VI , were included in this prospective temporal cohort study . Mesial and distal peri-implant bone levels were measured on panoramic radiographs taken at the time of implant insertion ( baseline ) and at follow-up visits .

 ABSTRACT RESULTS
 A total of 17 patients with atrophic mandibular jaws with an average follow-up period of 2.9 ± 1.5 years were included . The cumulative 1 - , 3 - , and 5-year patient-based implant survival rates were 94.1 % , and the cumulative implant survival rates were 98.5 % . The marginal bone level ( MBL ) of the mesial implants was 0.0 ± 0.3 mm at the time of loading ( n = 33 ) , -0.1 ± 0.3 mm ( n = 20 ) after 1 year , -0.4 ± 0.5 mm ( n = 10 ) after 3 years , and -1.5 ± 1.0 mm ( n = 4 ) after 5 years . The mesial bone level depended significantly on time and insertion depth . The MBL of the distal implants was -0.4 ± 0.4 mm ( n = 34 ) at the time of implantation , -0.4 ± 0.6 mm ( n = 20 ) after 1 year , -0.5 ± 0.5 mm ( n = 10 ) after 3 years , and -2.2 ± 1.7 mm ( n = 4 ) after 5 years . The distal bone level depended significantly on time and insertion depth .

 ABSTRACT CONCLUSIONS
 Fixed , full-arch , fiber-reinforced resin bridges retained by 4 ultrashort implants provide a comparatively cost-effective , safe , stable alternative for prosthetic restoration of the severely atrophic mandible . The overall implant survival rate and the MBL after 5 years are equivalent to those of threaded implants of conventional lengths .

Title

Fixed

Fiber-Reinforced

Resin

Bridges

on

Implants

in

Severely

Atrophic

Mandibles

Up

to

Years

Follow-Up

of

a

Prospective

Cohort

Study

ABSTRACT OBJECTIVE

The

aim

of

this

study

was

to

evaluate

the

midterm

outcomes

of

fixed

full-arch

fiber-reinforced

resin

bridges

on

ultrashort

implants

in

terms

of

marginal

bone

loss

and

overall

implant

survival

ABSTRACT METHODS

Patients

with

severely

atrophic

mandibles

corresponding

to

Cawood

and

Howell

class

V

and

class

VI

were

included

in

this

prospective

temporal

cohort

study

Mesial

and

distal

peri-implant

bone

levels

were

measured

on

panoramic

radiographs

taken

at

the

time

of

implant

insertion

baseline

and

at

follow-up

visits

ABSTRACT RESULTS

A

total

of

patients

with

atrophic

mandibular

jaws

with

an

average

follow-up

period

of

years

were

included

The

cumulative

and

patient-based

implant

survival

rates

were

and

the

cumulative

implant

survival

rates

were

The

marginal

bone

level

MBL

of

the

mesial

implants

was

mm

at

the

time

of

loading

n

mm

n

after

year

mm

n

after

years

and

mm

n

after

years

The

mesial

bone

level

depended

significantly

on

time

and

insertion

depth

The

MBL

of

the

distal

implants

was

mm

n

at

the

time

of

implantation

mm

n

after

year

mm

n

after

years

and

mm

n

after

years

The

distal

bone

level

depended

significantly

on

time

and

insertion

depth

ABSTRACT CONCLUSIONS

Fixed

full-arch

fiber-reinforced

resin

bridges

retained

by

ultrashort

implants

provide

a

comparatively

cost-effective

safe

stable

alternative

for

prosthetic

restoration

of

the

severely

atrophic

mandible

The

overall

implant

survival

rate

and

the

MBL

after

years

are

equivalent

to

those

of

threaded

implants

of

conventional

lengths


Title
 Parenteral influenza vaccination influences mucosal and systemic T cell-mediated immunity in healthy adults .

 ABSTRACT GENERAL
 We sought to determine whether palatine tonsils ( PTs ) harbor naturally acquired influenza-specific T cell immunity and whether routine parenteral immunization with influenza vaccine influences mucosal and systemic T cell reactivity . We demonstrate that tonsillar and peripheral blood mononuclear cells ( PBMCs ) proliferate strongly to influenza antigens , suggesting that naturally acquired immunity exists within both the mucosal and systemic compartments . Influenza vaccination induced significantly stronger T cell responses in both PTs and blood , in addition to increasing titers of anti-influenza antibodies in serum and saliva . More-rapid proliferative responses of PTs after vaccination were associated with a shift from a response involving both CD45RA + and CD45RO + T cells to an entirely CD45RO + - dependent response . Interestingly , the ratio of interferon - gamma to interleukin-5 was dramatically higher in cultures of PT T cells responding to influenza than in PBMCs . Our data indicate that parenteral influenza vaccination influences both mucosal and systemic naturally acquired T cell immunity .

Title

Parenteral

influenza

vaccination

influences

mucosal

and

systemic

T

cell-mediated

immunity

in

healthy

adults

ABSTRACT GENERAL

We

sought

to

determine

whether

palatine

tonsils

PTs

harbor

naturally

acquired

influenza-specific

T

cell

immunity

and

whether

routine

parenteral

immunization

with

influenza

vaccine

influences

mucosal

and

systemic

T

cell

reactivity

We

demonstrate

that

tonsillar

and

peripheral

blood

mononuclear

cells

PBMCs

proliferate

strongly

to

influenza

antigens

suggesting

that

naturally

acquired

immunity

exists

within

both

the

mucosal

and

systemic

compartments

Influenza

vaccination

induced

significantly

stronger

T

cell

responses

in

both

PTs

and

blood

in

addition

to

increasing

titers

of

anti-influenza

antibodies

in

serum

and

saliva

More-rapid

proliferative

responses

of

PTs

after

vaccination

were

associated

with

a

shift

from

a

response

involving

both

and

T

cells

to

an

entirely

dependent

response

Interestingly

the

ratio

of

interferon

gamma

to

was

dramatically

higher

in

cultures

of

PT

T

cells

responding

to

influenza

than

in

PBMCs

Our

data

indicate

that

parenteral

influenza

vaccination

influences

both

mucosal

and

systemic

naturally

acquired

T

cell

immunity


Title
 Vitamin E supplementation restores glutathione and malondialdehyde to normal concentrations in erythrocytes of type 1 diabetic children .

 ABSTRACT OBJECTIVE
 This study examined the relationship between cellular glutathione and vitamin E concentrations and the effect of vitamin E ( alpha-tocopherol ) supplementation on glutathione and lipid peroxidation product concentrations in the erythrocytes of type 1 diabetic patients .

 ABSTRACT METHODS
 We obtained written informed consent to participate in this study from diabetic patients ( n = 29 ) and their age-matched nondiabetic siblings ( n = 21 ) according to the guidelines of the Institutional Review Board on Human Experimentation . Diabetic patients were supplemented with a DL-alpha-tocopherol ( vitamin E ) capsule ( 100 IU/orally ) or placebo for 3 months in a double-blind clinical trial . Fasting blood samples were collected from each diabetic patient before the start of and after the 3 months of vitamin E or placebo supplementation . Glutathione , malondialdehyde ( which is a product of lipid peroxidation ) , and alpha-tocopherol were determined using high-performance liquid chromatography A total of 5 diabetic patients were excluded after randomization from the data analyses . Data were analyzed statistically using a paired Students t test to compare 12 diabetic patients taking vitamin E with 12 diabetic patients receiving placebo supplementation and to compare diabetic patients with healthy nondiabetic subjects .

 ABSTRACT RESULTS
 Erythrocytes of diabetic patients had 21 % higher ( P < 0.001 ) malondialdehyde and 15 % lower ( P < 0.05 ) glutathione concentrations than healthy subjects . Vitamin E in erythrocytes had a significant correlation with the glutathione concentrations in the erythrocytes ( r = 0.46 , P < 0.02 ) . Vitamin E supplementation increased glutathione concentrations by 9 % ( P < 0.01 ) and lowered concentrations of malondialdehyde by 23 % ( P < 0.001 ) and of HbA1c by 16 % ( P < 0.02 ) in erythrocytes of diabetic patients . No differences were evident in these parameters before versus after placebo supplementation .

 ABSTRACT CONCLUSIONS
 Glutathione level is significantly related to vitamin E level , and supplementation with vitamin E ( 100 IU/day ) significantly increases glutathione and lowers lipid peroxidation and HbA1c concentrations in the erythrocytes of type 1 diabetic patients .

Title

Vitamin

E

supplementation

restores

glutathione

and

malondialdehyde

to

normal

concentrations

in

erythrocytes

of

type

diabetic

children

ABSTRACT OBJECTIVE

This

study

examined

the

relationship

between

cellular

glutathione

and

vitamin

E

concentrations

and

the

effect

of

vitamin

E

alpha-tocopherol

supplementation

on

glutathione

and

lipid

peroxidation

product

concentrations

in

the

erythrocytes

of

type

diabetic

patients

ABSTRACT METHODS

We

obtained

written

informed

consent

to

participate

in

this

study

from

diabetic

patients

n

and

their

age-matched

nondiabetic

siblings

n

according

to

the

guidelines

of

the

Institutional

Review

Board

on

Human

Experimentation

Diabetic

patients

were

supplemented

with

a

DL-alpha-tocopherol

vitamin

E

capsule

IU/orally

or

placebo

for

months

in

a

double-blind

clinical

trial

Fasting

blood

samples

were

collected

from

each

diabetic

patient

before

the

start

of

and

after

the

months

of

vitamin

E

or

placebo

supplementation

Glutathione

malondialdehyde

which

is

a

product

of

lipid

peroxidation

and

alpha-tocopherol

were

determined

using

high-performance

liquid

chromatography

A

total

of

diabetic

patients

were

excluded

after

randomization

from

the

data

analyses

Data

were

analyzed

statistically

using

a

paired

Students

t

test

to

compare

diabetic

patients

taking

vitamin

E

with

diabetic

patients

receiving

placebo

supplementation

and

to

compare

diabetic

patients

with

healthy

nondiabetic

subjects

ABSTRACT RESULTS

Erythrocytes

of

diabetic

patients

had

higher

P

malondialdehyde

and

lower

P

glutathione

concentrations

than

healthy

subjects

Vitamin

E

in

erythrocytes

had

a

significant

correlation

with

the

glutathione

concentrations

in

the

erythrocytes

r

P

Vitamin

E

supplementation

increased

glutathione

concentrations

by

P

and

lowered

concentrations

of

malondialdehyde

by

P

and

of

by

P

in

erythrocytes

of

diabetic

patients

No

differences

were

evident

in

these

parameters

before

versus

after

placebo

supplementation

ABSTRACT CONCLUSIONS

Glutathione

level

is

significantly

related

to

vitamin

E

level

and

supplementation

with

vitamin

E

IU/day

significantly

increases

glutathione

and

lowers

lipid

peroxidation

and

concentrations

in

the

erythrocytes

of

type

diabetic

patients


Title
 A novel formulation of inhaled sodium cromoglicate ( PA101 ) in idiopathic pulmonary fibrosis and chronic cough : a randomised , double-blind , proof-of-concept , phase 2 trial .

 ABSTRACT GENERAL
 Cough can be a debilitating symptom of idiopathic pulmonary fibrosis ( IPF ) and is difficult to treat . PA101 is a novel formulation of sodium cromoglicate delivered via a high-efficiency eFlow nebuliser that achieves significantly higher drug deposition in the lung compared with the existing formulations . We aimed to test the efficacy and safety of inhaled PA101 in patients with IPF and chronic cough and , to explore the antitussive mechanism of PA101 , patients with chronic idiopathic cough ( CIC ) were also studied .

 ABSTRACT GENERAL
 This pilot , proof-of-concept study consisted of a randomised , double-blind , placebo-controlled trial in patients with IPF and chronic cough and a parallel study of similar design in patients with CIC . Participants with IPF and chronic cough recruited from seven centres in the UK and the Netherlands were randomly assigned ( 1:1 , using a computer-generated randomisation schedule ) by site staff to receive PA101 ( 40 mg ) or matching placebo three times a day via oral inhalation for 2 weeks , followed by a 2 week washout , and then crossed over to the other arm . Study participants , investigators , study staff , and the sponsor were masked to group assignment until all participants had completed the study . The primary efficacy endpoint was change from baseline in objective daytime cough frequency ( from 24 h acoustic recording , Leicester Cough Monitor ) . The primary efficacy analysis included all participants who received at least one dose of study drug and had at least one post-baseline efficacy measurement . Safety analysis included all those who took at least one dose of study drug . In the second cohort , participants with CIC were randomly assigned in a study across four centres with similar design and endpoints . The study was registered with ClinicalTrials.gov ( NCT02412020 ) and the EU Clinical Trials Register ( EudraCT Number 2014-004025-40 ) and both cohorts are closed to new participants .

 ABSTRACT GENERAL
 Between Feb 13 , 2015 , and Feb 2 , 2016 , 24 participants with IPF were randomly assigned to treatment groups . 28 participants with CIC were enrolled during the same period and 27 received study treatment . In patients with IPF , PA101 reduced daytime cough frequency by 31 · 1 % at day 14 compared with placebo ; daytime cough frequency decreased from a mean 55 ( SD 55 ) coughs per h at baseline to 39 ( 29 ) coughs per h at day 14 following treatment with PA101 , versus 51 ( 37 ) coughs per h at baseline to 52 ( 40 ) cough per h following placebo treatment ( ratio of least-squares [ LS ] means 0 · 67 , 95 % CI 0 · 48-0 · 94 , p = 0 · 0241 ) . By contrast , no treatment benefit for PA101 was observed in the CIC cohort ; mean reduction of daytime cough frequency at day 14 for PA101 adjusted for placebo was 6 · 2 % ( ratio of LS means 1 · 27 , 0 · 78-2 · 06 , p = 0 · 31 ) . PA101 was well tolerated in both cohorts . The incidence of adverse events was similar between PA101 and placebo treatments , most adverse events were mild in severity , and no severe adverse events or serious adverse events were reported .

 ABSTRACT GENERAL
 This study suggests that the mechanism of cough in IPF might be disease specific . Inhaled PA101 could be a treatment option for chronic cough in patients with IPF and warrants further investigation .

 ABSTRACT GENERAL
 Patara Pharma .

Title

A

novel

formulation

of

inhaled

sodium

cromoglicate

in

idiopathic

pulmonary

fibrosis

and

chronic

cough

a

randomised

double-blind

proof-of-concept

phase

trial

ABSTRACT GENERAL

Cough

can

be

a

debilitating

symptom

of

idiopathic

pulmonary

fibrosis

IPF

and

is

difficult

to

treat

is

a

novel

formulation

of

sodium

cromoglicate

delivered

via

a

high-efficiency

eFlow

nebuliser

that

achieves

significantly

higher

drug

deposition

in

the

lung

compared

with

the

existing

formulations

We

aimed

to

test

the

efficacy

and

safety

of

inhaled

in

patients

with

IPF

and

chronic

cough

and

to

explore

the

antitussive

mechanism

of

patients

with

chronic

idiopathic

cough

CIC

were

also

studied

ABSTRACT GENERAL

This

pilot

proof-of-concept

study

consisted

of

a

randomised

double-blind

placebo-controlled

trial

in

patients

with

IPF

and

chronic

cough

and

a

parallel

study

of

similar

design

in

patients

with

CIC

Participants

with

IPF

and

chronic

cough

recruited

from

seven

centres

in

the

UK

and

the

Netherlands

were

randomly

assigned

using

a

computer-generated

randomisation

schedule

by

site

staff

to

receive

mg

or

matching

placebo

three

times

a

day

via

oral

inhalation

for

weeks

followed

by

a

week

washout

and

then

crossed

over

to

the

other

arm

Study

participants

investigators

study

staff

and

the

sponsor

were

masked

to

group

assignment

until

all

participants

had

completed

the

study

The

primary

efficacy

endpoint

was

change

from

baseline

in

objective

daytime

cough

frequency

from

h

acoustic

recording

Leicester

Cough

Monitor

The

primary

efficacy

analysis

included

all

participants

who

received

at

least

one

dose

of

study

drug

and

had

at

least

one

post-baseline

efficacy

measurement

Safety

analysis

included

all

those

who

took

at

least

one

dose

of

study

drug

In

the

second

cohort

participants

with

CIC

were

randomly

assigned

in

a

study

across

four

centres

with

similar

design

and

endpoints

The

study

was

registered

with

ClinicalTrials.gov

and

the

EU

Clinical

Trials

Register

EudraCT

Number

and

both

cohorts

are

closed

to

new

participants

ABSTRACT GENERAL

Between

Feb

and

Feb

participants

with

IPF

were

randomly

assigned

to

treatment

groups

participants

with

CIC

were

enrolled

during

the

same

period

and

received

study

treatment

In

patients

with

IPF

reduced

daytime

cough

frequency

by

at

day

compared

with

placebo

daytime

cough

frequency

decreased

from

a

mean

SD

coughs

per

h

at

baseline

to

coughs

per

h

at

day

following

treatment

with

versus

coughs

per

h

at

baseline

to

cough

per

h

following

placebo

treatment

ratio

of

least-squares

LS

means

CI

p

By

contrast

no

treatment

benefit

for

was

observed

in

the

CIC

cohort

mean

reduction

of

daytime

cough

frequency

at

day

for

adjusted

for

placebo

was

ratio

of

LS

means

p

was

well

tolerated

in

both

cohorts

The

incidence

of

adverse

events

was

similar

between

and

placebo

treatments

most

adverse

events

were

mild

in

severity

and

no

severe

adverse

events

or

serious

adverse

events

were

reported

ABSTRACT GENERAL

This

study

suggests

that

the

mechanism

of

cough

in

IPF

might

be

disease

specific

Inhaled

could

be

a

treatment

option

for

chronic

cough

in

patients

with

IPF

and

warrants

further

investigation

ABSTRACT GENERAL

Patara

Pharma


Title
 Eliminating the Residual Negative Pressure in the Endoscopic Ultrasound Aspirating Needle Enhances Cytology Yield of Pancreas Masses .

 ABSTRACT BACKGROUND
 Prior to withdrawing the EUS-FNA needle from the lesion , the stopcock of the suction syringe is closed to reduce contamination . Residual negative pressure ( RNP ) may persist in the needle despite closing the stopcock .

 ABSTRACT OBJECTIVE
 To determine whether neutralizing RNP before withdrawing the needle will improve the cytology yield .

 ABSTRACT METHODS
 Bench-top testing was done to confirm the presence of RNP followed by a prospective , randomized , cross-over study on patients with pancreas mass . Ten milliliters of suction was applied to the FNA needle . Before withdrawing the needle from the lesion , the stopcock was closed . Based on randomization , the first pass was done with the stopcock either attached to the needle ( S + ) or disconnected ( S - ) to allow air to enter and neutralize RNP and accordingly the second pass was crossed over to S + or S - . On-site cytopathologist was blinded to S + / S - .

 ABSTRACT RESULTS
 Bench tests confirmed the presence of RNP which was successfully neutralized by disconnecting the syringe ( S - ) from the needle . Sixty patients were enrolled , 120 samples analyzed . S + samples showed significantly greater GI tract contamination compared to S - samples ( 16.7 vs. 6.7 % , p = 0.03 ) . Of the 53 patients confirmed to have pancreas adenocarcinoma , FNA using S - approach was positive in 49 ( 93 % ) compared to 40 using the S + approach ( 76 % , p = 0.02 ) .

 ABSTRACT CONCLUSIONS
 Despite closing the stopcock of the suction syringe , RNP is present in the FNA needle . Neutralizing RNP prior to withdrawing the needle from the target lesion significantly decreased GI tract contamination of the sample thereby improving the FNA cytology yield .

 ABSTRACT BACKGROUND
 NCT01995474 .

Title

Eliminating

the

Residual

Negative

Pressure

in

the

Endoscopic

Ultrasound

Aspirating

Needle

Enhances

Cytology

Yield

of

Pancreas

Masses

ABSTRACT BACKGROUND

Prior

to

withdrawing

the

EUS-FNA

needle

from

the

lesion

the

stopcock

of

the

suction

syringe

is

closed

to

reduce

contamination

Residual

negative

pressure

RNP

may

persist

in

the

needle

despite

closing

the

stopcock

ABSTRACT OBJECTIVE

To

determine

whether

neutralizing

RNP

before

withdrawing

the

needle

will

improve

the

cytology

yield

ABSTRACT METHODS

Bench-top

testing

was

done

to

confirm

the

presence

of

RNP

followed

by

a

prospective

randomized

cross-over

study

on

patients

with

pancreas

mass

Ten

milliliters

of

suction

was

applied

to

the

FNA

needle

Before

withdrawing

the

needle

from

the

lesion

the

stopcock

was

closed

Based

on

randomization

the

first

pass

was

done

with

the

stopcock

either

attached

to

the

needle

S

or

disconnected

S

to

allow

air

to

enter

and

neutralize

RNP

and

accordingly

the

second

pass

was

crossed

over

to

S

or

S

On-site

cytopathologist

was

blinded

to

S

S

ABSTRACT RESULTS

Bench

tests

confirmed

the

presence

of

RNP

which

was

successfully

neutralized

by

disconnecting

the

syringe

S

from

the

needle

Sixty

patients

were

enrolled

samples

analyzed

S

samples

showed

significantly

greater

GI

tract

contamination

compared

to

S

samples

vs.

p

Of

the

patients

confirmed

to

have

pancreas

adenocarcinoma

FNA

using

S

approach

was

positive

in

compared

to

using

the

S

approach

p

ABSTRACT CONCLUSIONS

Despite

closing

the

stopcock

of

the

suction

syringe

RNP

is

present

in

the

FNA

needle

Neutralizing

RNP

prior

to

withdrawing

the

needle

from

the

target

lesion

significantly

decreased

GI

tract

contamination

of

the

sample

thereby

improving

the

FNA

cytology

yield

ABSTRACT BACKGROUND


Title
 Why less severe degrees of hypertension should be treated .

Title

Why

less

severe

degrees

of

hypertension

should

be

treated


Title
 Cholinergic and neuroleptic induced catalepsy : modification by lesions in the globus pallidus and substantia nigra .

Title

Cholinergic

and

neuroleptic

induced

catalepsy

modification

by

lesions

in

the

globus

pallidus

and

substantia

nigra


Title
 Local analgesic and vascular effects of intradermal ropivacaine and bupivacaine in various concentrations with and without addition of adrenaline in man .

 ABSTRACT GENERAL
 Ropivacaine , a new long-acting amino-amide local anaesthetic agent , and bupivacaine , in various concentrations with or without addition of adrenaline , were tested in a randomized , double-blind study using intradermal wheals . Ten non-smoking , healthy , young male volunteers participated . In series I plain solutions of ropivacaine ( 0.25 % , 0.5 % , 0.75 % and 1 % ) and bupivacaine ( 0.25 % , 0.5 % and 0.75 % ) were injected intradermally and in series II the same concentrations , with the addition of adrenaline 5 ug.ml-1 ( 1:200,000 ) , were used . The same volunteers took part in both series , with an interval of at least three weeks between the experiments . Saline was included as control in both series . Pin-pricking was used to assess the dermal analgesia . Plain solutions of ropivacaine produced significantly longer durations of dermal analgesia than did plain solutions of bupivacaine , in all tested concentrations . A significant increase in duration was seen for both local anaesthetics when adding adrenaline . Local vascular effects at the injected areas were determined by visual inspection ( nil , pink , pale ) . Local blanching ( pale ) was significantly more frequent for plain solutions of ropivacaine , in all tested concentrations . Local redness ( pink ) was significantly more frequent with plain bupivacaine , in a dose-dependent relation . An initial redness was frequently observed for both local anaesthetics containing adrenaline , followed by blanching at most sites .

Title

Local

analgesic

and

vascular

effects

of

intradermal

ropivacaine

and

bupivacaine

in

various

concentrations

with

and

without

addition

of

adrenaline

in

man

ABSTRACT GENERAL

Ropivacaine

a

new

long-acting

amino-amide

local

anaesthetic

agent

and

bupivacaine

in

various

concentrations

with

or

without

addition

of

adrenaline

were

tested

in

a

randomized

double-blind

study

using

intradermal

wheals

Ten

non-smoking

healthy

young

male

volunteers

participated

In

series

I

plain

solutions

of

ropivacaine

and

and

bupivacaine

and

were

injected

intradermally

and

in

series

II

the

same

concentrations

with

the

addition

of

adrenaline

were

used

The

same

volunteers

took

part

in

both

series

with

an

interval

of

at

least

three

weeks

between

the

experiments

Saline

was

included

as

control

in

both

series

Pin-pricking

was

used

to

assess

the

dermal

analgesia

Plain

solutions

of

ropivacaine

produced

significantly

longer

durations

of

dermal

analgesia

than

did

plain

solutions

of

bupivacaine

in

all

tested

concentrations

A

significant

increase

in

duration

was

seen

for

both

local

anaesthetics

when

adding

adrenaline

Local

vascular

effects

at

the

injected

areas

were

determined

by

visual

inspection

pink

pale

Local

blanching

pale

was

significantly

more

frequent

for

plain

solutions

of

ropivacaine

in

all

tested

concentrations

Local

redness

pink

was

significantly

more

frequent

with

plain

bupivacaine

in

a

dose-dependent

relation

An

initial

redness

was

frequently

observed

for

both

local

anaesthetics

containing

adrenaline

followed

by

blanching

at

most

sites


Title
 Sildenafil effects on exercise , neurohormonal activation , and erectile dysfunction in congestive heart failure : a double-blind , placebo-controlled , randomized study followed by a prospective treatment for erectile dysfunction .

 ABSTRACT BACKGROUND
 Erectile dysfunction ( ED ) is common in patients with congestive heart failure ( CHF ) . ED reduces quality of life , and it may affect compliance , thereby impairing the success of CHF treatment .

 ABSTRACT RESULTS
 In the first phase ( fixed-dose double-blind , randomized , placebo-controlled , two-way crossover study ) , we studied in 23 men with CHF the effects of 50 mg sildenafil on exercise and neurohormonal activation . Patients underwent a treadmill 6-minute cardiopulmonary walking ( 6 ' WT ) test followed by a maximal cardiopulmonary exercise test ( ET ) . In the second phase , patients received sildenafil , taken as required for ED . Sildenafil reduced the heart rate ( HR ) ( bpm ) before the 6 ' WT ( from 75 + / -15 to 71 + / -14 , P = 0.02 ) and ET ( from 75 + / -15 to 71 + / -15 , P = 0.02 ) ; the systolic blood pressure ( mm Hg ) before the 6 ' WT ( from 116 + / -18 to 108 + / -18 , P = 0.004 ) and ET ( from 116 + / -15 to 108 + / -17 , P = 0.001 ) ; the diastolic blood pressure before the 6 ' WT ( from 69 + / -9 to 63 + / -11 , P = 0.01 ) and ET ( from 70 + / -8 to 65 + / -10 , P = 0.004 ) ; and the Ve/VCO2 slope during the 6 ' WT ( from 32 + / -7 to 31 + / -6 , P = 0.04 ) and ET ( from 33 + / -8 to 31 + / -5 , P = 0.03 ) . Sildenafil attenuated the HR increment during the 6 ' WT ( P = 0.003 ) and ET ( P = 0.000 ) . Sildenafil increased the peak * O2 from 16.6 + / -3.4 to 17.7 + / -3.4 mL/kg per min ( P = 0.025 ) and the exercise time from 12.3 + / -3.4 to 13.7 + / -3.2 minutes ( P = 0.003 ) . Sildenafil improved most scores of International Index of Erectile Function .

 ABSTRACT CONCLUSIONS
 Sildenafil was tolerated and effective for ED treatment in CHF , and improved the exercise capacity . The reduction of HR during exercise with sildenafil could theoretically decrease the myocardial oxygen consumption during sexual activity .

Title

Sildenafil

effects

on

exercise

neurohormonal

activation

and

erectile

dysfunction

in

congestive

heart

failure

a

double-blind

placebo-controlled

randomized

study

followed

by

a

prospective

treatment

for

erectile

dysfunction

ABSTRACT BACKGROUND

Erectile

dysfunction

ED

is

common

in

patients

with

congestive

heart

failure

CHF

ED

reduces

quality

of

life

and

it

may

affect

compliance

thereby

impairing

the

success

of

CHF

treatment

ABSTRACT RESULTS

In

the

first

phase

fixed-dose

double-blind

randomized

placebo-controlled

two-way

crossover

study

we

studied

in

men

with

CHF

the

effects

of

mg

sildenafil

on

exercise

and

neurohormonal

activation

Patients

underwent

a

treadmill

cardiopulmonary

walking

WT

test

followed

by

a

maximal

cardiopulmonary

exercise

test

ET

In

the

second

phase

patients

received

sildenafil

taken

as

required

for

ED

Sildenafil

reduced

the

heart

rate

HR

bpm

before

the

WT

from

to

P

and

ET

from

to

P

the

systolic

blood

pressure

mm

Hg

before

the

WT

from

to

P

and

ET

from

to

P

the

diastolic

blood

pressure

before

the

WT

from

to

P

and

ET

from

to

P

and

the

slope

during

the

WT

from

to

P

and

ET

from

to

P

Sildenafil

attenuated

the

HR

increment

during

the

WT

P

and

ET

P

Sildenafil

increased

the

peak

from

to

mL/kg

per

min

P

and

the

exercise

time

from

to

minutes

P

Sildenafil

improved

most

scores

of

International

Index

of

Erectile

Function

ABSTRACT CONCLUSIONS

Sildenafil

was

tolerated

and

effective

for

ED

treatment

in

CHF

and

improved

the

exercise

capacity

The

reduction

of

HR

during

exercise

with

sildenafil

could

theoretically

decrease

the

myocardial

oxygen

consumption

during

sexual

activity


Title
 Right ventricular myocardial function in ARF patients . PEEP as a challenge for the right heart .

 ABSTRACT OBJECTIVE
 To examine the hemodynamic effects of external positive end-expiratory pressure ( PEEP ) on right ventricular ( RV ) function in acute respiratory failure ( ARF ) patients .

 ABSTRACT METHODS
 Prospective , with retrospective analysis on the basis of RV volume response to PEEP .

 ABSTRACT METHODS
 General intensive care unit in a university teaching hospital .

 ABSTRACT METHODS
 20 mechanically ventilated ARF patients ( mean lung injury score = 2.6 + / - 0.45 SD ) .

 ABSTRACT METHODS
 Incremental levels of PEEP ( 0-5-10-15 cmH2O ) were applied and RV hemodynamics were studied by means of a Swan-Ganz catheter with a fast-response thermistor for right ventricular ejection fraction ( RVEF ) measurement . According to their response to PEEP 15 , two groups of patients were defined : group A ( 9 patients ) with unchanged or increased RV end-diastolic volume index ( RVEDVI ) and group B ( 11 patients ) with decreased RVEDVI .

 ABSTRACT RESULTS
 At zero PEEP ( ZEEP ) the hemodynamic parameters of the two groups did not differ . In group A , cardiac index ( CI ) and stroke volume index ( SI ) decreased at all PEEP levels ( 5 , 10 , and 15 cmH2O ) , while RVEF started to decrease only at a PEEP of 10 cmH2O ( -10.8 % ) , and RVES ( systolic ) VI increased only at PEEP 15 cmH2O ( +21.5 % ) . RVEDVI was not affected by PEEP . In group B , CI and SI decreased at all PEEP levels ( 5 , 10 , and 15 cmH2O ) . Similarly , RVEDVI started to decrease at PEEP 5 cmH2O , while RVESVI decreased only at PEEP 15 cmH2O ( -21.4 % ) . RVEF was not affected by PEEP in this group . In each patient the slope of the relationship between RVEDVI and right ventricular stroke work index ( RVSWI ) , expressing RV myocardial performance , was studied . This relationship was significant ( no change in RV contractility ) in 8 of 11 patients in group B and in only 2 patients in group A . In 4 patients in group A , PEEP shifted the RVSWI/RVEDVI ratio rightward in the plot , indicating a decrease in RV myocardial performance in these patients .

 ABSTRACT CONCLUSIONS
 PEEP affects RV function in ARF patients . The decrease in cardiac output is more often associated with a preload decrease and no change in RV contractility . On the other hand , the finding of increased RV volumes with PEEP may be associated with a reduction in RV myocardial performance . Thus , these results suggest that assessment of RV function by PEEP and preload recruitable stroke work may disclose otherwise unpredictable alterations in RV function .

Title

Right

ventricular

myocardial

function

in

ARF

patients

PEEP

as

a

challenge

for

the

right

heart

ABSTRACT OBJECTIVE

To

examine

the

hemodynamic

effects

of

external

positive

end-expiratory

pressure

PEEP

on

right

ventricular

RV

function

in

acute

respiratory

failure

ARF

patients

ABSTRACT METHODS

Prospective

with

retrospective

analysis

on

the

basis

of

RV

volume

response

to

PEEP

ABSTRACT METHODS

General

intensive

care

unit

in

a

university

teaching

hospital

ABSTRACT METHODS

mechanically

ventilated

ARF

patients

mean

lung

injury

score

SD

ABSTRACT METHODS

Incremental

levels

of

PEEP

were

applied

and

RV

hemodynamics

were

studied

by

means

of

a

Swan-Ganz

catheter

with

a

fast-response

thermistor

for

right

ventricular

ejection

fraction

RVEF

measurement

According

to

their

response

to

PEEP

two

groups

of

patients

were

defined

group

A

patients

with

unchanged

or

increased

RV

end-diastolic

volume

index

RVEDVI

and

group

B

patients

with

decreased

RVEDVI

ABSTRACT RESULTS

At

zero

PEEP

ZEEP

the

hemodynamic

parameters

of

the

two

groups

did

not

differ

In

group

A

cardiac

index

CI

and

stroke

volume

index

SI

decreased

at

all

PEEP

levels

and

while

RVEF

started

to

decrease

only

at

a

PEEP

of

and

RVES

systolic

VI

increased

only

at

PEEP

RVEDVI

was

not

affected

by

PEEP

In

group

B

CI

and

SI

decreased

at

all

PEEP

levels

and

Similarly

RVEDVI

started

to

decrease

at

PEEP

while

RVESVI

decreased

only

at

PEEP

RVEF

was

not

affected

by

PEEP

in

this

group

In

each

patient

the

slope

of

the

relationship

between

RVEDVI

and

right

ventricular

stroke

work

index

RVSWI

expressing

RV

myocardial

performance

was

studied

This

relationship

was

significant

no

change

in

RV

contractility

in

of

patients

in

group

B

and

in

only

patients

in

group

A

In

patients

in

group

A

PEEP

shifted

the

RVSWI/RVEDVI

ratio

rightward

in

the

plot

indicating

a

decrease

in

RV

myocardial

performance

in

these

patients

ABSTRACT CONCLUSIONS

PEEP

affects

RV

function

in

ARF

patients

The

decrease

in

cardiac

output

is

more

often

associated

with

a

preload

decrease

and

no

change

in

RV

contractility

On

the

other

hand

the

finding

of

increased

RV

volumes

with

PEEP

may

be

associated

with

a

reduction

in

RV

myocardial

performance

Thus

these

results

suggest

that

assessment

of

RV

function

by

PEEP

and

preload

recruitable

stroke

work

may

disclose

otherwise

unpredictable

alterations

in

RV

function


Title
 How far is real life from COPD therapy guidelines ? An Italian observational study .

 ABSTRACT BACKGROUND
 According to the GOLD international guidelines , the treatment of chronic obstructive pulmonary disease ( COPD ) should be proportional to the severity of airflow obstruction graded according to FEV ( 1 ) % predicted . Regular treatment with long-acting bronchodilators should be prescribed for symptomatic patients with FEV ( 1 ) < 80 % . Inhaled corticosteroids should be added in patients with FEV ( 1 ) < 50 % predicted and frequent exacerbations .

 ABSTRACT OBJECTIVE
 To investigate whether pulmonologists follow the GOLD guidelines when prescribing treatment for COPD .

 ABSTRACT METHODS
 A multicenter , cross-sectional , observational study was carried out in 49 Pulmonary Units evenly distributed throughout the country . For each patient the demographic , clinical data and the current therapies were registered in an electronic database .

 ABSTRACT RESULTS
 4094 patients ( mean age : 70.9 ± 9.4 ; males 72.4 % , female 27.6 % ) were enrolled . Disease severity was classified as : mild ( 745 ) , moderate ( 1722 ) , severe ( 923 ) , very severe ( 704 ) . Irrespective of disease severity , inhaled corticosteroids alone or in combination with long-acting bronchodilators were used in 15.2 % and 66.8 % of patients , respectively . The appropriateness of the pharmacological treatment of the COPD patients was defined in accordance with the GOLD recommendations . The treatment was appropriate in 37.9 % of patients and inappropriate in 62.1 % , p < 0.0001 . The inappropriateness was due to under-prescription in 7.2 % and to over-prescription in 54.9 % of patients . The presence and the number of exacerbations represented an important trigger for over-prescription at stages I and II .

 ABSTRACT CONCLUSIONS
 This study shows that there is a poor relationship between the recommendations of the GOLD international guidelines and current clinical practice , and that exacerbations may play a role in over-prescription .

Title

How

far

is

real

life

from

COPD

therapy

guidelines

An

Italian

observational

study

ABSTRACT BACKGROUND

According

to

the

GOLD

international

guidelines

the

treatment

of

chronic

obstructive

pulmonary

disease

COPD

should

be

proportional

to

the

severity

of

airflow

obstruction

graded

according

to

FEV

predicted

Regular

treatment

with

long-acting

bronchodilators

should

be

prescribed

for

symptomatic

patients

with

FEV

Inhaled

corticosteroids

should

be

added

in

patients

with

FEV

predicted

and

frequent

exacerbations

ABSTRACT OBJECTIVE

To

investigate

whether

pulmonologists

follow

the

GOLD

guidelines

when

prescribing

treatment

for

COPD

ABSTRACT METHODS

A

multicenter

cross-sectional

observational

study

was

carried

out

in

Pulmonary

Units

evenly

distributed

throughout

the

country

For

each

patient

the

demographic

clinical

data

and

the

current

therapies

were

registered

in

an

electronic

database

ABSTRACT RESULTS

patients

mean

age

males

female

were

enrolled

Disease

severity

was

classified

as

mild

moderate

severe

very

severe

Irrespective

of

disease

severity

inhaled

corticosteroids

alone

or

in

combination

with

long-acting

bronchodilators

were

used

in

and

of

patients

respectively

The

appropriateness

of

the

pharmacological

treatment

of

the

COPD

patients

was

defined

in

accordance

with

the

GOLD

recommendations

The

treatment

was

appropriate

in

of

patients

and

inappropriate

in

p

The

inappropriateness

was

due

to

under-prescription

in

and

to

over-prescription

in

of

patients

The

presence

and

the

number

of

exacerbations

represented

an

important

trigger

for

over-prescription

at

stages

I

and

II

ABSTRACT CONCLUSIONS

This

study

shows

that

there

is

a

poor

relationship

between

the

recommendations

of

the

GOLD

international

guidelines

and

current

clinical

practice

and

that

exacerbations

may

play

a

role

in

over-prescription


Title
 EEG brain mapping in gerontopsychopharmacology : on protective properties of pyritinol against hypoxic hypoxidosis .

Title

EEG

brain

mapping

in

gerontopsychopharmacology

on

protective

properties

of

pyritinol

against

hypoxic

hypoxidosis


Title
 Comparison of nifedipine and propranolol used in combination with diuretics for the treatment of hypertension .

 ABSTRACT GENERAL
 One hundred patients participated in a double-blind , randomized study to compare the antihypertensive efficacy of sustained-release nifedipine and propranolol in hypertensive patients whose diastolic blood pressure exceeded 95 mm Hg while receiving diuretic therapy . Nifedipine ( mean dose , 79.6 mg per day ) decreased blood pressure by 11.4 / 10.5 mm Hg ; propranolol ( mean dose , 198.4 mg per day ) decreased blood pressure by 13.5 / 10.3 mm Hg . Reduction of diastolic blood pressure to below 90 mm Hg was achieved in 63 percent of nifedipine-treated patients and in 57 percent of propranolol-treated patients . Nifedipine therapy was associated with an increase in high-density lipoprotein cholesterol levels and a decrease in serum triglyceride levels . In contrast , propranolol therapy was associated with a decrease in high-density lipoprotein cholesterol levels and an increase in serum triglyceride levels . Nifedipine is as effective as propranolol in the treatment of patients with mild to moderate hypertension whose blood pressure is inadequately controlled by diuretic therapy .

Title

Comparison

of

nifedipine

and

propranolol

used

in

combination

with

diuretics

for

the

treatment

of

hypertension

ABSTRACT GENERAL

One

hundred

patients

participated

in

a

double-blind

randomized

study

to

compare

the

antihypertensive

efficacy

of

sustained-release

nifedipine

and

propranolol

in

hypertensive

patients

whose

diastolic

blood

pressure

exceeded

mm

Hg

while

receiving

diuretic

therapy

Nifedipine

mean

dose

mg

per

day

decreased

blood

pressure

by

mm

Hg

propranolol

mean

dose

mg

per

day

decreased

blood

pressure

by

mm

Hg

Reduction

of

diastolic

blood

pressure

to

below

mm

Hg

was

achieved

in

percent

of

nifedipine-treated

patients

and

in

percent

of

propranolol-treated

patients

Nifedipine

therapy

was

associated

with

an

increase

in

high-density

lipoprotein

cholesterol

levels

and

a

decrease

in

serum

triglyceride

levels

In

contrast

propranolol

therapy

was

associated

with

a

decrease

in

high-density

lipoprotein

cholesterol

levels

and

an

increase

in

serum

triglyceride

levels

Nifedipine

is

as

effective

as

propranolol

in

the

treatment

of

patients

with

mild

to

moderate

hypertension

whose

blood

pressure

is

inadequately

controlled

by

diuretic

therapy


Title
 Long-term angiotensin-converting enzyme inhibition with ramipril reduces thrombin generation in human hypertension .

 ABSTRACT GENERAL
 Antihypertensive treatment reduces the risk of thromboembolic events in hypertension . The aim of this study was to examine the influence of angiotensin-converting enzyme inhibition on blood coagulation in subjects with mild-to-moderate essential hypertension . Fibrinogen , thrombin-antithrombin complex ( TAT ) and Factor VII were determined in plasma at rest and after a mental stress test following placebo for 6 weeks , or ramipril for 6 weeks or 6 months . Ramipril reduced resting TAT , and tended to reduce fibrinogen ; Factor VII remained unchanged . Mental stress increased fibrinogen , but did not alter TAT or Factor VII activity . The reduced thrombin generation in patients taking ramipril may explain in part why angiotensin-converting enzyme inhibitors reduce thromboembolic complications in patients with cardiovascular disease .

Title

Long-term

angiotensin-converting

enzyme

inhibition

with

ramipril

reduces

thrombin

generation

in

human

hypertension

ABSTRACT GENERAL

Antihypertensive

treatment

reduces

the

risk

of

thromboembolic

events

in

hypertension

The

aim

of

this

study

was

to

examine

the

influence

of

angiotensin-converting

enzyme

inhibition

on

blood

coagulation

in

subjects

with

mild-to-moderate

essential

hypertension

Fibrinogen

thrombin-antithrombin

complex

TAT

and

Factor

VII

were

determined

in

plasma

at

rest

and

after

a

mental

stress

test

following

placebo

for

weeks

or

ramipril

for

weeks

or

months

Ramipril

reduced

resting

TAT

and

tended

to

reduce

fibrinogen

Factor

VII

remained

unchanged

Mental

stress

increased

fibrinogen

but

did

not

alter

TAT

or

Factor

VII

activity

The

reduced

thrombin

generation

in

patients

taking

ramipril

may

explain

in

part

why

angiotensin-converting

enzyme

inhibitors

reduce

thromboembolic

complications

in

patients

with

cardiovascular

disease