Pulmonary Deposition of Salbutamol Aerosol Delivered by Metered Dose Inhaler, Jet Nebulizer, and Ultrasonic Nebulizer in Mechanically Ventilated Rabbits

ESPR PULMONARY DEPOSITION OF SALBUTAMDL AEROSOL DELIVERED BY METERED DOSE INHALER (MDI), JET NEBULIZER AND ULTRASONIC NEBULIZER IN MECHANICALLY VENTILATED RABBITS. Tai F.Fok, Mazan M.Al-Essa, S h e l l y Monhan, Myrna B.Dolovich, G e o f f r e y Coates, Barry Bowen, Haresh M. K i r p a l a n i Dept o f P e d i a t r i c s , Medicine & Nuclear Medicine, Mcnaster U n i v e r s i t y , Hamilton, O n t a r i o , Canada Technetium-99m l a b e l l e d Salbutamol was a d m i n i s t e r e d through a (5 tracheostomy t o ventilated r a b b i t s by e i t h e r a n MDI puffs,lOOpg/puff) a i d e d w i t h a s p a c e r (MV15 A e m h a n t b e r , T r u d e l l , Canada) (Groupl, n=7); o r by n e b u l i z a t i o n (10DpgIkg i n 3ml Technetium-9% l a b e l l e d 5% albumin). N e b u l i z a t i o n was c a r r i e d o u t f o r 20 min. w i t h a J e t (Hudson, USA) (Group 2, n = l l ) o r U l t r a s o n i c d e v i c e (Siemens, Sweden) u s i n g e i t h e r a s t a n d a r d (Group 3 , n=6) o r a small Lung d e p o s i t i o n was e s t i m a t e d by g a m a (Group 4, n=7) r e s e r v o i r . c o u n t i n g o f t h e autopsy lung specimens: mean(sd): @ 1 b k of lxnt slulitd Is % of total do*" W I 1 O.iZ(0.II) 0.Z (0.14) 0.g (0.33) 9Q 2 2 394, p4.S 2 11 1.U (0.11) 0.48 (0.11) 0.48 (0.19) "Q 4 , 111 dkr @.@I 3 6 3.9 (1.93) 0.S (0.31) 0.m (0.31) I 1 1.29(2.02) 1.m (1,111 3.s (1.31) Salbutamol was uniformly d i s t r i b u t e d i n t h e l u n g s i n group 1 and 2, b u t showed a p r e d i l e c t i o n f o r t h e r i g h t a n t e r i o r azygous l o b e s and t h e c e n t r a l lung r e g i o n s i n group 3 and 4. Conclusion: i n d e l i v e r i n g Salbutamol t o v e n t i l a t e d r a b b i t s , t h i s U l t r a s o n i c d e v i c e p r o v i d e s g r e a t e r lung d e p o s i t i o n b u t l e s s uniform d i s t r i b u t i o n t h a n e i t h e r J e t o r MDI. Reducing r e s e r v o i r volume enhances its e f f i c i e n c y o f delivery f u r t h e r , but a l s o y i e l d s d i f f e r e n t i a l deposition i n lobes. OUTCOME O F VERY PRETERM SMALL FOR DATE INFANTS. Joke H Kok', S P Verloove-Vanhorick. R Brand. Dept of Neonatology', Academic Medical Centre, Amsterdam. SERUM 'I'RANSFERRIN RECEPTOR ( T f K ) AND ERYTHROPOIETIN ( E p o l AS 1113ZCATORS OF ERYTHRO?OIESTS I N CHILDREN WITH NEWLY DIAGNOSED ACUTE LYMPHOBLASTIC LEUKEMIA ( A L L ) . S a n n a M . K i v i v u o r i , L a s s e V i i n i k k a , M a r t t i A. S i i m e s Children's Hospital, University of Helsinki, Helsinki The i n i t i a l depression of erythropoiesis followed by a r a p i d s t i m u l a t i o n of e r y t h r o p o i e s i s i n c h i l d r e n w i t h newly d i a g n o s e d ALL may s e r v e a s a m o d e l t o s t u d y T f R a n d E p o a s i n d i c a t o r s of erythropoiesis.we s t u d i e d weekly t h e blood h e m o g l o b i n a n d r e t i c u l o c y t e c o u n t s , T f R a n d E p o f r o m 35 c h i l d r e n w i t h n e w l y d i a g n o s e d ALL d u r i n g 1 2 w e e k s f r o m d i a g n o s i s . T h e mean a g e o f t h e p a t i e n t s w a s 6 . 1 y e a r s . T h e p a t i e n t s w e r e t r e a t e d a c c o r d i n g t o t h e S c a n d i n a v i a n ALL p r o t o c o l s . S e r u m TfR a n d Epo c o n c e n t r a t i o n s w e r e m e a s u r e d b y IFMA ( P e d i a t r R e s 1 9 9 3 ; 3 4 : 2 9 7 ) a n d E I A m e t h o d s , r e s p e c t i v e l y . T h e mean w e e k l y TfR c o n c e n t r a t i o n s w e r e 2 . 8 + 0 . 2 m g / l (SEM) a t d i a g n o s i s . T h e y g r a d u a l l y d e c r e a s e d t o 2 . 1 k0.2 mg/l a t 3 weeks. T h i s a f t e r , t h e v a l u e s i n c r e a s e d a n d r e a c h e d t h e maximal l e v e l a t 8 weeks ( 4 . 9 + 0 . 5 m g / l ) . T h e p a t t e r n o f t h e mean v a l u e s f o r r e t i c u l o c y t e c o u n t s w a s slrnilar; 1 . 3 0 . 2 8 a t d i a g n o s i s , 0.3 +0.05% a t 2 weeks a n d 4 . 7 + 1 . 3 % a t 8 w e e k s . I n c o n t r a s t , Epo l e v e l s w e r e e l e v a t e d a n d b e h a v e d d i f f e r e n t l y . T h e mean v a l u e was 330 IU/L a t diagnosis. A f t e r t h e t h e r a p y s t a r t e d t h e v a l u e s g r a d u a l l y d e c r e a s e d by week 5 a n d remained s t a b l e t h e r e a f t e r (mean v a l u e s 7 9 - 1 1 1 I U / L ) . U n d e r t h e s e c o n d i t i o n s we c o n c l u d e t h a t 1) T f R l e v e l r e f l e c t s t h e r a t e o f e r y t h r o p o i e s i s , a n d 2 ) T f R l e v e l 1s u n d e p e n d e n t o n t h e Epo l e v e l s . THE CHRONIC FORM OF COXSACKIE VIRUS INFECTION OF CHILDREN WITH INSUI.Iii DEPENDENT DIABETES MELLITUS. Tatyana K . Konopleva, Lenaera S. Lozovskaja S c i e n t i f i c Research I n s t i t u t e of P e d i a t r i c s , Russian Academy of Medlcal S c i e n c e , Moscow, R u s s i a . We examined 100 c h i l d r e n with i n s u l i n dependent d i a b e t e s m e l l i t u s (IDDM) and 30 h e a l t h y c h ~ l d r e n by v i r o l o g i c a l method ( r e a c t i o n of i n d i r e c t immunofluorescention). We founded t h a t Coxsackie A and U virrtses a r e d i s c o v e r e d i n sediment u r i n e c e l l s more o f t e n In c h i l d r e n wit11 IDDM a s a t t h e b e g i n n i n g of d i s e a s e ( 7 9 . 3 % ) a s a t longlime d i s e a s e ( 5 2 . 2 % ) i n comparison w i t h c h i l d r e n c o n t r o l group ( 1 6 . 1 % ) . A f t e r t h e r e p e a t e d s e l e c t e d exam s i c k c h i l d r e n d u r i n g t h e i n t e r v a l from 5 t i l l 18 months we founded t h a t 5 c l ~ i l d r e n had t h e p e r s ~ s t e n c r of determined Coxsackie viruses ( A s , A16, 8 2 , 0 3 , B4). The examination of a u t o p s i a m a t e r i a l s of 7 d i e d c h i l d r e n w i t h IDDM shown t h a t Coxsackie v i r u s r s *:is f o u ~ ~ d ridn Llssitcs o f p a n c r e a s , thymus, kidlleys. Tl~er.efr,r.<., t . l ~ l s rlnt.;~ pro\,e t h e p a r t i c i p a t i o n of Coxsackie r l r r l s c s i l l ( l ~ i l d r r ~l n ,D M etiology. A HIGHLY PREVALENT SPLICE SITE MUTATION IN THE CYSTATHIONINEO-SYNTHASE GENE IS ASSOCIATED WITH POOR VITAMIN B 6 RESPONSE IN HOMOCYSTINURIA Hans G. Koch, Kurt Ullrich, Thomas Deufel, and Erik Harms Kinderklinik der Westfalischen Wilhelms-UNversitat Munster, FRG D I O X I N AND POLYCHLORINATED BIPHENYL LEVELS I N WOMEN IN RELATION TO THEIR L I V I N G AREA I N m, Objective: To investigate the effect of intra-uterine growth retardation on mortality and developmental outcome at 5 years of age in a cohort of very preterm infants. Patients and methods: From a national collaborative study of 1338 liveborn infants of < 32 weeks andlor < 1500 grams, 765 infants were selected on gestational age (GA) between 25 and 32 weeks, kaukasian race, and without having congenital malformati-: ons. Infants were classified according to Kloosterman's percentiles. Small for gestatio' nal age (SGA) infants ( < 10th centile) were compared with appropriate for age (AGA) infants (2575th centlle). Results: Neonatal mortality and mortaltty at 5 years of age is significantly higher in SGA compared with AGA after stratifying for C section or vaginal delivery (OR 0.55' (0.32 - 0.95) p=0.02), a simtlar result is found after taken into account GA, sex, multiple pregnancy (MPR) as confounders. Overall outcome at 5 year expressed in handicap rate (WHO definition) is not significantly different (SGA 20% vs AGA 1 3 % ~ (p= 0.17)). However, cerebral palsy is less frequent in SGA infants than in AGA infants (7.2% vs 14.9%). while retardation of gross motor sk~llsis more frequent i" SGA infants (15.7% vs 7.4%). Mental development, languagelspeech development and need for special educat~onseems to be worser in SGA infants, but is not statistically significantly different (OR 0.85) after correctton for confounders GA, sex, and MPR. Conclusion: Mortality in SGA infants is about twice as high as compared to A G d infants in the hrst 5 years. Overall developmental outcome In the SGA survivors at 51 p a n t s . 113 + Screening for mutations of the cystathio~ne-P-synthase (CBS) gene of homocystinuric patients w e detected a splice site mutation (A1224-2C) which results in skipping o f an entire 135bp exon This mutation was reported recently by Kozich and Kraus (Hum.Mut.1,113-123;1992) and found t o be associated with vitamnin B6responsiveness in a compound heterozygous patient with mild clinical course. W e established a SSCP assay to screen for this distinct splice site mutation o f the CBS gene. So far, w e have detected this mutation on 5 out of 28 (17.8%) affected chromosomes from nonrelated homocystinuric patients Three patients were compound heterozygous One male offspring of non-consanguinous parents of German origin was homozygous In contrast to the patient described by Kozich and Kraus, this patient was clearly nonresponsive even when treated with high dose vitamin B6. H e showed a severe clinical phenotype with early ocular involvement and mental retardation. T w o of the three compound heterozygotes detected were also vitamin B6 n o ~ e s p o n d e r swith severe phenotypes. From this we conclude that the splice site mutation A1224-2C represents a frequent defect of the CBS gene causing homocystinuria which is nonresponsive to vitamin B6 treatment. Only when combined with certain other mutations in compound heterozygotes, this second allel may contribute to a milder phenotype and confer vitamln B6 responsiveness PLASMA AN0 HUMAN M I L K OF THE .NETHERLANOS. C o r i n e Koopman-Esseboom', Marcel Huisman', Nynke Weisglas-Kuperus', Rudy E . Boersma', Maria A . d e Ridder' P i e t e r J . Sauer'. 'Dep o f P a e d i a t r , Div o f N e o n a t o l , ' ~ n ~ ot f Epid and B i o s t , Erasmus Univfsophia C h i l d r e n ' s Hosp, Rotterdam. ' ~ e pof Obst and Gynaec, Univ of Groningen, t h e N e t h e r l a n d s . Dioxins and p o l y c h l o r i n a t e d b ~ p h e n y l s ( P C B s ) a r e u b i q u i t o u s t o x i c compounds i n t h e environment t h a t may have a d v e r s e e f f e c t s on t h e neurodevelopment of i n f a n t s . W e examined i f women l i v i n g i n an indust r i a l i z e d a r e a had h i g h e r d r o x i n o r PCB l e v e l s compared t o women l i v i n g i n a semi-urban a r e a . Pregnant women w e r e r e c r u r t e d i n R o t t e r dam c i t y and ~n s u r r o u n d ~ n g , h r g h l y i n d u s t r i a l i z e d a r e a s i n t h e w e s t e r n p a r t of t h e Netherlands, and i n Gronlngen, a semi-urban a r e a i n t h e n o r t h . PCB l e v e l s were i n v e s t i g a t e d i n plasma. I n human m i l k , PCB as w e l l as d i o x i n l e v e l s were measured. Ln PCB 118 plasma (N=406) Ln Dioxin-TEQ milk (N=171) Variable I? S.E. P I? S.E. Rotterdam* 0.12 0.05 .02 0.15 0.06 P .01 0.23 Industrial* 0.08 ,003 0.19 0.09 .03 * B a s e l i n e a r e a = Groningen. P a r t of t h e m u l t ~ p l er e g r e s s i o n a n a l y s i s : f- a o e r c e n t- a~o e> - of human o t h e r s ~ o n i f i c a n t c o v a r ~ a t e s : a n e of t h e women. ~. - -t m i l k , w e e k s of g ~ v e nb r e a s t - f e e d i n g t o o l d e r c h r l d r e n , smoking. 2~ & - - - - conclude t h a t i n f a n t s born i n t h e western i n d u s t r i a l i z e d a r e a o f t h e N e t h e r l a n d s a r e exposed t o h i g h e r l e v e l s o f d i o x i n s and PCBs i n u t e r o and d u r l n g b r e a s t - f e e d ~ n g , compared t o i n f a n t s born i n a semiurban a r e a ~n t h e n o r t h . Although d r e t 1s e s t i m a t e d a s t h e main s o u r c e o f e x p o s u r e , i n h a l i n g and dermal a b s o r p t i o n might be a d d i t i o n a l r o u t e s o f d i o x i n and P C B exposure. We