Upsala J Med Sci 84: 7 5 - 8 2 , 1979 The Effect of Short-term High-dose Treatment with Methenamine Hippurate of Urinary Infection in Geriatric Patients with Indwelling Catheters 11. Evaluation by m e a n s of a quantified urine sediment Astrid Norberg, Bo Norberg, Ulf Parkhede, Hans Gippert and Rolf Ekman The School Of'Nursing and Drparfmenfs oJ'Education, I n f e r n a l Medicine and Clinical Clirmistry, University of L u n d , S\r,eden. 3 M Riker Ltrborafories. Shurholmen, Sw'eden ABSTRACT The u r i n e s e d i m e n t of 12 g e r i a t r i c p a t i e n t s w i t h i n d w e l l i n g c a t h e t e r s was quan- t i f i e d by t h e glutaraldehyde-cytocentrifuge method p r i o r t o , d u r i n g and a f t e r a c l i n i c a l t r i a l of methenamine h i p p u r a t e ( M H ) , 2 g x 3 d a i l y g i v e n f o r 34 days as t h e s o l e t h e r a p e u t i c a g e n t f o r u r i n a r y t r a c t i n f e c t i o n . c o n c e n t r a t i o n i n t h e u r i n e of t h e s e p a t i e n t s w a s 100 c e l l s / p l ( Q , - Q 3 5 0 - 3 5 0 ) , i . e . t e n f o l d h i g h e r t h a n t h e u p p e r normal l i m i t s r e p o r t e d i n h e a l t h y p r o b a n d s . The median b a c t e r i u r i a i n t h e c o n t r o l p e r i o d was 1 2 x l o 5 b a c t e r i a / m l u r i n e , i n t e r q u a r t i l e r a n g e 10-60 x 10 500 x 10 b a c t e r i a / m l . n o t p r o m i n e n t and c o u l d n o t b e c o r r e l a t e d w i t h MH t r e a t m e n t , n o r w i t h c a t h e t e r changes. The r e p o r t e d o b s e r v a t i o n s s u g g e s t t h a t s h o r t - t e r m h i g h - d o s e t r e a t m e n t w i t h MH as s o l e t h e r a p e u t i c a g e n t r e d u c e d p y r u r i a and b a c t e r i u r i a i n t h e group of p a t i e n t s s t u d i e d . The median l e u k o c y t e 5 b a c t e r i a / m l and e x t r e m e i n d i v i d u a l v a l u e s 300- 5 H e m a t u r i a , d e f i n e d a s '> 24 e r y t h r o c y t e s / p l u r i n e , w a s I N T R O D U C T I O N The c l i n i c a l r e l e v a n c e of b a c t e r i u r i a and p y u r i a i n p a t i e n t s w i t h i n d w e l l i n g c a t h e t e r s i s complex. These p a t i e n t s r e g u l a r l y a c q u i r e b a c t e r i u r i a due t o t h e a s c e n s i o n of g u t m i c r o b e s a l o n g t h e mucous l a y e r s u r r o u n d i n g t h e c a t h e t e r ( 2 , 6 , 7 , 8 ) . The b a c t e r i u r i a i s t h o u g h t t o r e f l e c t t h e sum of b a c t e r i a l i n f e c t i o n s of t h e u r i n a r y t r a c t and b a c t e r i a l growth i n t h e u r i n e ( c f . 1 0 ) . T h r e e f a c t o r s a r e thought t o c o n t r i b u t e t o t h e p y u r i a of p a t i e n t s w i t h indwel- l i n g c a t h e t e r : 4 , 1 5 ) , t h e b a c t e r i a - i n d u c e d i n f l a m m a t i o n of t h e u r i n a r y t r a c t ( 1 1 ) and o t h e r chemical o r p h y s i c a l i r r i t a n t s . The u r i n e becomes c l o u d y and f o u l - s m e l l i n g due t o b a c t e r i u r i a , p y u r i a , mucous s e c r e t i o n s , b a c t e r i a l p r o d u c t s and s a l t p r e c i p i - t a t i o n . t h e r e a c t i o n of t h e u r e t h r a l mucosa t o a l a r g e f o r e i g n body ( 3 , 75 It i s r e a s o n a b l e t o assume t h a t t h e u r i n e s e d i m e n t r e f l e c t s t h e t o t a l e f f e c t of f o r e i g n body, mucosal l e s i o n s , b a c t e r i a l i n v a s i o n and l e u k o c y t e e m i g r a t i o n . I n a p r e v i o u s s t u d y ( 1 3 ) , w e r e p o r t e d a s i m p l e and r a p i d method of s a m p l i n g , f i x i n g , s t a i n i n g and q u a n t i f y i n g t h e c e l l s and b a c t e r i a of t h e u r i n e from g e r i - a t r i c p a t i e n t s w i t h an i n d w e l l i n g c a t h e t e r . The aim of t h e p r e s e n t s t u d y was t o e l u c i d a t e t h e problems of q u a n t i f y i n g t h e p r e v i o u s l y d e s c r i b e d g l u t a r a l d e - h y d e - c y t o c e n t r i f u g e s e d i m e n t and a p p l y t h i s u r i n e s e d i m e n t t o t h e e v a l u a t i o n o f s h o r t - t e r m high-dose t h e r a p y w i t h methenamine h i p p u r a t e (MH) as t h e s o l e t r e a t - ment of u r i n a r y i n f e c t i o n i n p a t i e n t s w i t h i n d w e l l i n g c a t h e t e r s . MATERIAL AND METHODS The s t u d y i n v o l v e d 14 i n p a t i e n t s a t t h e s o m a t o g e r i a t r i c wards of S a i n t Lars H o s p i t a l , Lund. t o s e v e r a l y e a r s b e f o r e t h e y e n t e r e d t h e s t u d y ( 1 4 ) . a week d u r i n g t h e p r e - t r e a t m e n t c o n t r o l - p e r i o d , days 10-17, d u r i n g t r e a t m e n t w i t h methenamine h i p p u r a t e (MH, H i p r e x R , R i k e r L a b o r a t o r i e s , Loughborough, L e i c e s t e r . E u g l a n d ) , 2 g x 3 , d a i l y from day 18-52 and d u r i n g t h e p o s t - t r e a t - m e n t c o n t r o l p e r i o d , d a y s 66-73, as d e s c r i b e d i n t h e c l i n i c a l r e p o r t ( 1 4 ) . During days 1-9 d i f f e r e n t c y t o c e n t r i f u g e p r e p a r a t i o n s of t h e g l u t a r a l d e h y d e - suspended l e u k o c y t e s and b a c t e r i a were e v a l u a t e d ( 1 3 ) . Two p a t i e n t s were exc- l u d e d due t o f r e q u e n t b l o c k a g e of t h e c a t h e t e r s a f t e r p r e - s a m p l i n g p l u g g i n g , see below. They h a d a l l had i n d w e l l i n g c a t h e t e r s f o r a p e r i o d of 6 months U r i n e w a s sampled t w i c e The c a t h e t e r w a s p l u g g e d i m m e d i a t e l y a f t e r b r e a k f a s t , 15-30 m i n u t e s b e f o r e s a m p l i n g . I n p a t i e n t s no. 1, 3 , 4 u r i n e w a s o b t a i n e d a f t e r p l u g g i n g f o r 2 h r s b e f o r e b r e a k f a s t . The u r i n e , a p p r o x i m a t e l y 1 5 m l , w a s c o l l e c t e d i n a s t e r i l e t u b e and t h o r o u g h l y s h a k e n i n o r d e r t o d i s p e r s e t h e s o l i d s . The u r i n e ( 0 . 1 ml) w a s t h e n immediately t r a n s f e r r e d t o 0 . 9 m l 2% g l u t a r a l d e h y d e (Taab L a b o r a t o r i e s , Reading. England) i n p h o s p h a t e b u f f e r , 0 . 1 3 5 M , pH 7.4. The g l u t a r a l d e h y d e - suspended c e l l s and b a c t e r i a , 0 . 2 m l , were spun down on a s l i d e 2-4 h r s a f t e r s a m p l i n g by means of a c y t o c e n t r i f u g e ( S h a n d o n - E l l i o t C y t o s p i n ) a t 1 , 0 0 0 r . p . m . , 10 m i n . , u s i n g t w i n p r e p a r a t i o n s from each specimen. w a s always s t a i n e d w i t h t h e May-Griinwald-Giemsa s t a i n (MGG) and t h e o t h e r w i t h h a e m a t o x y l i n - e o s i n , p e r i o d i c a c i d S c h i f f o r P a p a n i c o l a o u s t a i n , as p r e v i o u s l y d e s c r i b e d ( 1 3 ) . One of t h e p r e p a r a t i o n s It i s e v i d e n t from t h e above d e s c r i p t i o n of t h e p r e p a r a t i o n of t h e u r i n e s e d i m e n t t h a t t h e c e l l number on t h e s l i d e s h o u l d be l i n e a r l y c o r r e l a t e d t o t h e number of c e l l s i n t h e o r i g i n a l u r i n e sample: 1. g l u t a r a l d e h y d e ) . 2. 20 ul u r i n e w a s spun down on e a c h s l i d e (200 u l of a 10% u r i n e s u s p e n s i o n i n The r e l a t i o n between t h e a r e a of a high-power v i s u a l f i e l d of t h e Z&ss 76 p h o t o m i c r o s c o p e u s e d ( r = 7 5 um) and t h e a r e a of t h e c e l l p r e p a r a t i o n on t h e s l i d e ( ~ = 3 , 0 0 0 um) w a s d e f i n e d by: 1 2 2 r 7 1 - R IT 1 , 6 0 0 - - The whole s l i d e p r e p a r a t i o n w a s scanned u n d e r t h e x10 l e n s . The a r e a w i t h t h e h i g h e s t c e l l d e n s i t y w a s f u r t h e r e v a l u a t e d u n d e r t h e xl00 l e n s , t o t a l mag- n i f i c a t i o n ~ 1 , 0 0 0 . and t h e a v e r a g e c e l l number was t a k e n t o r e p r e s e n t t h e c e l l u l a r i t y of t h e p r e - p a r a t i o n e x c e p t when t h e lower number w a s z e r o . Then one t h i r d of t h e h i g h e s t c e l l number w a s a p p r o x i m a t e d t o r e p r e s e n t t h e c e l l d e n s i t y as a c o r r e c t i o n f o r t h e h e t e r o g e n o u s d i s p e r s i o n of c e l l s . When t w i n specimens d i f f e r e d i n c e l l den- s i t y , t h e one w i t h t h e h i g h e r c e l l d e n s i t y was r e c o r d e d , s i n c e l o s s of c e l l s d u r i n g p r e p a r a t i o n a p p e a r e d t o b e more l i k e l y t h a n p r o d u c t i o n of excess c e l l s ( 1 3 ) . The extreme r a n g e s of c e l l s p e r high-power f i e l d were n o t e d S t a t i s t i c s . The r e s u l t s were s u b j e c t e d t o n o n - p a r a m e t r i c a n a l y s e s a c c o r d i n g t o S i e g e 1 1956 ( 1 7 ) . RESULTS The t r a n s f o r m a t i o n c u r v e between c e l l s p e r high-power f i e l d and c e l l s p e r p 1 u r i n e i s shown i n F i g u r e 1 t o g e t h e r w i t h t h e normal l i m i t s f o r l e u k o c y t e concen- t r a t i o n and e r y t h r o c y t e c o n c e n t r a t i o n r e p o r t e d by L i t t l e 1964 (11). The median l e u k o c y t e c o n c e n t r a t i o n of t h e p r e s e n t p a t i e n t s w a s 100 ( Q , - Q3 50 - 350) l e u k o c y t e s / p l u r i n e d u r i n g t h e p r e - t r e a t m e n t c o n t r o l p e r i o d ( T a b l e 1 1 , i . e . a t e n f o l d h i g h e r l e u k o c y t e c o n c e n t r a t i o n t h a n t h e u p p e r l i m i t s of l e u k o c y t e c o n c e n t r a t i o n i n h e a l t h y probands r e p o r t e d by L i t t l e 1964 (11). The r a n k sums s u g g e s t e d a r e l a t i v e r e d u c t i o n i n p y u r i a d u r i n g t h e l a t e p e r i o d of MH t r e a t m e n t (Table l), b u t t h i s t e n d e n c y w a s n o t s i g n i f i c a n t ( 0 . 3 > p > 0 . 2 ) , as e v a l u a t e d by t h e Friedman two-way a n a l y s i s of v a r i a n c e . The c o n c e n t r a t i o n of b a c t e r i a i n t h e u r i n e f o l l o w e d t h e same p a t t e r n a s t h e l e u k o c y t e c o n c e n t r a t i o n a l t h o u g h on a h i g h e r n u m e r i c a l l e v e l ( T a b l e 2 ) . median c o n c e n t r a t i o n d u r i n g t h e p r e - t r e a t m e n t c o n t r o l p e r i o d w a s 1,200 b a c t e r i a / P1 u r i n e , i n t e r q u a r t i l e r a n g e 1,000 - 6,000 b a c t e r i a / p l u r i n e . s u g g e s t a r e l a t i v e r e d u c t i o n i n b a c t e r i a d u r i n g t h e l a t e p e r i o d of MH t r e a t m e n t ( T a b l e 2), b u t t h i s t r e n d was n o t s i g n i f i c a n t ( 0 . 3 > p > 0 . 2 ) , when e v a l u a t e d b y t h e Friedman two-way a n a l y s i s of v a r i a n c e . The The r a n k sums I n c o n t r a s t t o p y u r i a and b a c t e r i u r i a , m i c r o s c o p i c h a e m a t u r i a d e f i n e d as 1 2 4 e r y t h r o c y t e s / p l u r i n e was n o t a p r o m i n e n t f e a t u r e i n t h e p a t i e n t s s t u d i e d ( F i g . 3 2 T a b l e 1. L e u k o c y t e s p e r high-power m i c r o s c o p i c f i e l d ( 1 8 x 10 ,um ) i n t h e $ 1 ~ - t a r a l d e h y d e - f i x e d c y t o c e n t r i f u g e - p r e p a r e d q u a n t i f i e d u r i n e s e d i m e n t s o f g e r i a - t r i c p a t i e n t s w i t h i n d w e l l i n g c a t h e t e r s b e f o r e , d u r i n g and a f t e r t r e a t m e n t w i t h methenamine h i p p u r a t e ( M H ) , 2 g x 3 d a i l y . Median v a l u e s w i t h i n e a c h p e r i o d , b a s e d o n 3-5 m e a s u r e m e n t s o n d i f f e r e n t d a y s w i t h i n t h e p e r i o d ( c f . 1 3 ) . An i n - d i v i d u a l measurement was b a s e d o n d o u b l e p r e p a r a t i o n s f r o m t h e same u r i n e s p e c i - men. MM: m e d i a n o f m e d i a n s . Q, - Q 3 : i n t e r q u a r t i l e r a n g e . R . : t h e r a n k sums o f t h e F r i e d m a n two-way a n a l y s i s o f v a r i a n c e ( 1 7 ) r e f l e c t t h e J e l a t i v e c h a n g e s i n p y u r i a d u r i n g t h e p e r i o d s t u d i e d , d a y s 1-73. P r e - t r e a t m e n t I n i t i a l p e r i o d L a t e p e r i o d P o s t - t r e a t m e n t c o n t r o l p e r i o d o f t r e a t m e n t o f t r e a t m e n t c o n t r o l p e r i o d P a t . Sex Days 10-17 Days 18-35 Days 36-52 Days 66-73 1. f 2 . m 3 . f 4 . f 5 . f 6 . f 7. f 8 . m 9 . f 1 0 . f 11. f 1 2 . f 3 . 0 0 . 3 1 . 0 1 . 3 0 . 7 5 .O 8 . 0 0.7 1 . 3 7 .O 4 . 0 0 . 3 1 . 9 6 .9 75.0 0 . 9 0 . 3 2.5 5 3 . 0 2 . 2 0 . 3 5 . 0 4 . 2 3 . 9 1 . 0 2.2 8 . 0 0 . 7 0 . 0 4 . 0 30.0 1 .o 0 . 7 4 . 0 1 . 7 0 . 7 2 . 0 1 . 7 1 1 . 0 1 . 7 0 . 3 5 . 0 3 0 . 0 0 . 7 0 . 7 9 . 0 1 . 7 1 . 7 MM 1 . 3 3 . 2 1 . 4 1 . 7 3 0 . 0 3 2 . 5 2 3 . 5 3 4 . 0 R 0.7-4.5 1.4-6 .O 0 . 7 - 4 . 0 1 . 2 - 7 .O Ql - Q3 j 2 ) . No e v i d e n c e was f o u n d t h a t e i t h e r s h o r t - t e r m t r e a t m e n t w i t h h i g h - d o s e M H , 2 g x 3 d a i l y , o r c a t h e t e r c h a n g e s i n c r e a s e d t h e i n c i d e n c e o f h a e m a t u r i a i n p a t i e n t s w i t h i n d w e l l i n g c a t h e t e r s . D u r i n g 20 c o n t r o l d a y s w i t h o u t MH, haemat- u r i a was n o t e d i n 1 3 o u t o f 72 u r i n e s e d i m e n t s (18%). D u r i n g MH t r e a t m e n t f o r 34 d a y s , h a e m a t u r i a w a s n o t e d i n 27 o u t o f 1 0 6 u r i n e s e d i m e n t s ( 2 5 % ) . T h i s d i f f e r e n c e was n o t s i g n i f i c a n t ( 0 . 3 > p ; O . 2 ) , a s e v a l u a t e d by t h e x'-test f o r two i n d e p e n d e n t s a m p l e s . Nor d i d t h e number o f c a t h e t e r c h a n g e s i n a n i n d i - v i d u a l p a t i e n t c o r r e l a t e w i t h t h e number o f e p i s o d e s of h a e m a t u r i a ( N = l l , S p e a r m a n ' s r h o = +0.20). DISCUSSION The q u a n t i f i c a t i o n o f b a c t e r i a and c e l l s i n t h e u r i n e o f p a t i e n t s w i t h i n d w e l l i n g c a t h e t e r s i s d i f f i c u l t . One b a s i c c o n d i t i o n i s t h a t t h e c o n c e n t r a t i o n o f b a c t e r i a a n d l e u k o c y t e s a p p e a r s t o b e d e p e n d e n t o n u r i n e p r o d u c t i o n , i . e . e x c r e t i o n o v e r t i m e p r o v i d e s a b e t t e r e s t i m a t i o n t h a n p a r t i c l e c o n c e n t r a t i o n 78 3 2 T a b l e 2 . B a c t e r i a p e r high-power m i c r o s c o p i c f i e l d ( 1 8 x 10 vm ) i n t h e g l u - t a r a l d e h y d e - f i x e d c y t o c e n t r i f u g e - p r e p a r e d q u a n t i f i e d u r i n e s e d i m e n t s of g e r i a - t r i c p a t i e n t s w i t h i n d w e l l i n g c a t h e t e r s b e f o r e , d u r i n g and a f t e r t r e a t m e n t w i t h ,,,&henmine h i p p u r a t e ( M H ) , 2 g x 3 d a i l y . b a s e d on 3-5 measurements on d i f f e r e n t days w i t h i n t h e p e r i o d ( c f . 1 3 ) . An i n d i v i d u a l measurement w a s b a s e d on d o u b l e p r e p a r a t i o n s from t h e same u r i n e specimen. MM: median of medians. Q - Q3: i n t e r q u a r t i l e r a n g e . R . : t h e rank sums of t h e Friedman two-way a n a l y s i s of v a r i a n c e (17) r e f l e c t t d e r e l a t i v e changes i n p y u r i a d u r i n g t h e p e r i o d s t u d i e d , days 10-73. Median v a l u e s w i t h i n e a c h p e r i o d , P r e - t r e a t m e n t I n i t i a l p e r i o d L a t e p e r i o d P o s t - t r e a t m e n t c o n t r o l p e r i o d of t r e a t m e n t of t r e a t m e n t c o n t r o l p e r i o d p a t . Sex Days 10-17 Days 18-35 Days 36-52 Days 66-73 1. f 2 . m 3: f 4 . f 5. f 6 . f 7 . f 8. m 9. f 10. f 11. f 1 2 . f 15 150 1 5 125 15 8 20 10 15 7 150 1 5 9 105 23 30 60 12 19 3 5 1 7 7 1 8 9 40 1 2 100 2 15 8 15 8 15 8 6 a 1 3 105 30 1 5 33 55 10 1 3 40 35 35 55 MM 15 1 9 10 34 13-73 11-33 7-15 14-48 30.5 31.0 23.0 35.5 i1 - 9 3 j (11, 1 6 ) . Under t h e e x p e r i m e n t a l c o n d i t i o n s of t h e p r e s e n t s t u d y , t h e c e l l con- c e n t r a t i o n p e r p l u r i n e w a s e x p e c t e d t o p r o v i d e a c l o s e a p p r o x i m a t i o n o f e x c r e - t i o n p e r u n i t t i m e ( c f . 1 1 ) . The r h e o l o g i c a l p r o p e r t i e s of c a t h e t e r u r i n e a r e a n o t h e r s t u m b l i n g - b l o c k . T h i s u r i n e r e s e m b l e s t h i n g r u e l , t h a t i s n o t a homogenous s u s p e n s i o n . The cor- p u s c l e s t e n d t o c o n c e n t r a t e i n t h e clumps, much l i k e c e l l c o n c e n t r a t i o n w i t h i n a f i b r i n coagulum d u r i n g b l o o d c l o t t i n g . It i s o b v i o u s t h a t t h e p r e s e n c e of a clump i n t h e sample w i l l produce an o v e r - e s t i m a t i o n of t h e c o r p u s c u l a r i t y o f t h e u r i n e and c o n v e r s e l y t h e a b s e n c e of a clump w i l l p r o d u c e a n u n d e r - e s t i m a t i o n . Gram-stained smears of u r i n e c e n t r i f u g a t e s have b e e n r e p o r t e d t o c o r r e l a t e w i t h t h e numbers of v i a b l e o r g a n i s m s c u l t u r e d from t h e same u r i n e specimens ( 9 ) . It i s r e a s o n a b l e t o assume t h a t t h e p r e s e n t c y t o c e n t r i f u g e p r e p a r a t i o n f u r t h e r improved t h e c o r r e l a t i o n between u r i n e organisms and o r g a n i s m s o b s e r v e d on t h e s l i d e . u r i n a r y b a c t e r i a d e r i v e d from t h e s e p a t i e n t s w i t h i n d w e l l i n g c a t h e t e r s ( T a b l e 2) were i n agreement w i t h t h e b a c t e r i a l c o n c e n t r a t i o n s found by p r e v i o u s a u t h o r s by WanS of q u a n t i t a t i v e u r i n e c u l t u r e s (I), i . e . a median p r e - t r e a t m e n t b a c t e r i u r i a c o r r e s p o n d i n g t o 1 2 x l o 5 b a c t e r i a / m l u r i n e , i n t e r q u a r t i l e r a n g e 10 - 60 x 10 T h i s a s s u m p t i o n i s s u p p o r t e d by t h e f a c t t h a t t h e c o n c e n t r a t i o n s of 5 79 F i g . 1. The t r a n s f o r m a t i o n c u r v e bgtweFn c e l l s p e r high-power f i e l d (18 x 1 0 um ) and c e l l s p e r u l u r i n e . The shaded a r e a i n d i c a t e s t h e r e f e r e n c e r a n g e of e r y t h r o - c y t e s and l e u k o c y t e s a c c o r d i n g t o L i t t l e 1964 (11). 0 Number of urine specimens F i g . 2 . I n c i d e n c e and m a g n i t u d e of haema- t u r i a i n 1 2 g e r i a t r i c p a t i e n t s w i t h indwel- l i n g c a t h e t e r s p r i o r t o ( d a y s 10-17), d u r i n g (days 18-52) and a f t e r ( d a y s 66-73) t r e a t - ment w i t h methenamine h i p p u r a t e ( M H ) , 2 g x 3 d a i l y . Erythrocytes /pi urine 0 0.3 0.7 1-2 >2 I I J I , boctcriurio w p y u r i a '""1 M H t reotmcnt 5 4 - F a - t - 1 17 35 52 1 3 D A Y S F i g . 3. R e l a t i v e changes i n b a c t e r i u r i a and p y u r i a d u r i n g t r e a t m e n t w i t h methen- amine h i p p u r a t e ( M H ) , 2 g x 3 d a i l y , i n p e r c e n t o f c o n t r o l v a l u e s . Median v a l u e b a s e d o n t h e p e r i o d medians g i v e n i n T a b l e s 1 and 2 . ____ 80 b a c t e r i a / m l , extreme v a l u e s 300 - 500 x 105 b a c t e r i a l m l . The i n c i d e n c e and magnitude of h a e m a t u r i a was m o d e r a t e , c o n s i d e r i n g t h a t a l a r g e f o r e i g n body, t h e c a t h e t e r , was i n c l o s e c o n t a c t w i t h t h e mucosal membrane of t h e u r i n a r y t r a c t and t a k i n g i n t o a c c o u n t t h e p e r s i s t e n t p y u r i a - b a c t e r i u r i a . MH h a s b e e n t h o u g h t t o b e of l i m i t e d v a l u e i n t h e t r e a t m e n t of e s t a b l i s h e d u r i n a r y t r a c t i n f e c t i o n ( 1 2 ) . If i t i s assumed t h a t MH r e d u c e s b a c t e r i a l growth i n t h e u r i n e w i t h o u t a f f e c t i n g i n f e c t i o n of t h e mucosa, MH t r e a t m e n t c o u l d n o t be e x p e c t e d t o r e d u c e b a c t e r i u r i a and p y u r i a p r i o r t o t h e h e a l i n g of t h e p r e - e x i s t i n g mucosal i n f e c t i o n , i . e . a f t e r MH t r e a t m e n t f o r a t l e a s t 1 - 2 weeks. It i s e v i d e n t from T a b l e s 1, 2 and F i g u r e 3 t h a t a r e l a t i v e r e d u c t i o n of bac- t e r i u r i a and p y u r i a o c c u r e d d u r i n g t h e l a t e p e r i o d of MH t r e a t m e n t , i n g l y , t h e v a l u e s from t h e p r e - t r e a t m e n t c o n t r o l p e r i o d and t h e i n i t i a l t r e a t - ment p e r i o d a r e grouped t o g e t h e r a s one e x t e n d e d c o n t r o l p e r i o d ( T a b l e s 1, 2 ) , t h e p y u r i a w a s a l m o s t s i g n i f i c a n t l y r e d u c e d d u r i n g t h e l a t e MH t r e a t m e n t p e r i o d (p=0.014), as e v a l u a t e d by t h e Friedman two-way a n a l y s i s of v a r i a n c e . t i v e r e d u c t i o n of b a c t e r i u r i a was s t i l l n o t s i g n i f i c a n t (p=O.14). I f a c c o r d - The rela- I n view of t h e s i z e of t h e p r e s e n t m a t e r i a l (N=12) and t h e d i s p e r s i o n of i n d i v i d u a l v a l u e s , t h e r i s k of a c c e p t i n g a f a l s e n u l l h y p o t h e s i s ( i . e . no c u r a - t i v e e f f e c t of M H ) seems g r e a t . It i s more r e a s o n a b l e t o assume from t h e cen- t r a l t e n d e n c y d e s c r i b e d by t h e r a n k sums ( T a b l e s 1, 2) and t h e r e l a t i v i z e d medi- ans ( F i g . 3 . 1 , t h a t s h o r t - t e r m high-dose MH t r e a t m e n t r e d u c e d t h e b a c t e r i u r i a and t h e p y u r i a i n p a t i e n t s w i t h i n d w e l l i n g c a t h e t e r s . ACKNOWLEDGEMENTS no. 1. 2. 3 . 4 . 5 . 6. 7 . T h i s work was s u p p o r t e d by t h e Swedish Medical R e s e a r c h C o u n c i l p r o j e c t 2294 and no. 5362 and g r a n t s from t h e Medical F a c u l t y of Lund. 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R e c e i v e d f o r p u b l i c a t i o n 1 4 t h J u l y 1978 and i n r e v i s e d form 1 6 t h O c t o b e r , 1978. - Address f o r r e p r i n t s : Bo N o r b e r g , M . D . Department of I n t e r n a l Medicine U n i v e r s i t y H o s p i t a l of Lund S-221 85 Lund, Sweden 8 2