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RENAL SCARRING AND NON-ATTACHING ESCHERICHIA COLI
1341 concentrations of acetaldehyde found in the plasma of alcoholics. The specificity of these antibodies seems to be independent of the nature of the carrier protein and is directed towards the acetaldehyde moiety. The potential conversion of all serum proteins into neoantigens could therefore lead to widespread manifestations of autoimmune disease and may explain the variability in the incidence of cirrhosis, diabetes, and other complications of chronic excessive alcohol consumption. Acetaldehyde haptenisation could allow the application of a simple assay for antibody levels and thus provide a true history of recent alcohol intake. In cases of chronic alcohol consumption, although acetaldehyde adducts would be cleared from the plasma with time, immunological memory in the form of B-cell clones might be retained. The resulting high antibody levels might be associated with complications should alcohol consumption be resumed.
pathophysiological
St John’s College, Cambridge CB2 1TP
A.
WHYTE
1. Stevens VJ, Fantl WJ, Newman CB, Cecami A, Peterson CM. Acetaldehydè adducts with hemoglobin. J Clin Invest 1981; 67: 361-69. 2. Israel Y, Hurwitz E, Niemela O, Arnon R. Monoclonal and polyclonal antibodies
against acetaldehyde-containing epitopes Natl Acad Sci USA 1986; 83: 7923-27.
in
acetaldehyde-protein
adducts. Proc
RENAL SCARRING AND NON-ATTACHING ESCHERICHIA COLI
SiR,—The virulence of uropathogenic Escherichia coli has been defined by the severity of acute urinary tract infection (UTI) produced by the bacteria rather than by the ability to cause renal scarring.E coli causing first-time acute pyelonephritis often belong to a limited number of O:K:H serotypes with the ability to resist the bactericidal effect of serum, produce haemolysin, and attach to uroepithelial cells. Indeed, adhesive capacity seems to be the marker most frequently associated with the pyelonephritogenic phenotype.2 Most attaching strains specifically bind to the Galoti-4Galp moiety of the globo-series glycolipid receptors. Since renal scarring is one severe end-point of UTI, it has been assumed that such damage results from infection with the most virulent bacteria. We have evaluated the frequency of attaching bacteria in patients with recurrent acute pyelonephritis in relation to the development of renal scarring. 77 girls were selected for study because of recurrent episodes of acute pyelonephritis, diagnosed by bacteriuria, fever, loin pain, and two of three laboratory criteria (raised C-reactive protein, increased sedimentation rate, or reduced renal concentrating capacity’). Renal scarring was defmed at urography as calyceal deformity combined with parenchymal reductionand vesicoureteral reflux was diagnosed by voiding cystourethrography.6 35 patients had renal scarring and 42 did not, and the average follow-up was 10 and 7 years, respectively. The ages at the first detected episodes of acute pyelonephritis were similar in the groups. Those with reflux were younger (median 2-2, range 0-3-6-5) than those without reflux (median 5-5, range 0-5-12) at the first pyelonephritic episodes. The median number of urographies was four (range two to nine) in the scarred and three (range two to five) in the non-scarred group. 142 isolates were available from the episodes of acute pyelonephritis. The analysis of bacterial determinants of scarring is complicated by the time lapse between the infection and radiological detection of the scar. During this time additional UTI episodes may occur. We included only the 58 isolates from infections before the detection of scarring. 60% of the scarred patients had had negative urography before the detection of scarring. The patients with renal scarring had a significantly higher frequency of non-E coli. The E coli strains were analysed for adhesive capacity, by haemagglutination and specific binding to latex beads coated with globotetraosylceramide .7 The frequency of positive reactions is shown in the table. The patients with scarring had a significantly lower frequency of E coli with adhesins specific for globo-series of glycolipid receptors than those without scarring. These results demonstrate significant differences between bacteria causing recurrent pyelonephritis in patients with and
FREQUENCY OF ATTACHING ESCHERICHIA COLI
IN PATIENTS WITH
AND WITHOUT RENAL SCARRING
*Measured
as specific bindmg to the globo-senes of glycolipids, for E coli strains. tFor frequency in non-scarred versus frequency in scarred group.
without renal scarring. The scarred patients were usually infected with poorly attaching bacteria. In the others scarring did not develop despite recurrent infections with attaching E coli. The strains causing renal scarring may have special virulence determinants (eg, mannose-specific adhesins8) but we favour the conclusion that development of renal scarring is associated with increased host susceptibility and that repeated infections with attaching bacteria may be insufficient to induce renal scarring in the resistant host. Department of Clinical Immunology, University of Goteborg, S-413 46 Goteborg, Sweden; and Departments of Paediatric Radiology and Division of Nephrology, Department of Paediatrics, East Hospital, Goteborg 1.
Svanborg-Edén C, Hagberg L, Adhesion of Escherichia coli
Hanson m
HELENA LOMBERG MIKAEL HELLSTRÖM
ULF JODAL CATHARINA SVANBORG EDÉN
LÅ,
urinary
T, Leffler H, Olling S. infection. In: Adhesion and 80) London Pitmans Medical,
Korhonen tract
microorganism pathogenicity (Ciba Found Symp 1980: 161-87.
2. Vaisanen-Rhen V, Elo J, Vaisanen E, et al P-fimbnated clones among uropathogenic Escherichia coli strains. Infect Immun 1984; 43: 149-55. 3. Leffler H, Svanborg-Edén C. Chemical identification of a glycosphingolipid receptor for Escherichia coli attaching to human urinary epithelial cells and agglutinating human erythrocytes FEMS Microbiol Lett 1980; 8: 127-34. 4. Jodal U, Lmdberg U, Lincoln K. Level diagnosis of symptomatic urinary tract infections in childhood Acta Paediatr Scand 1975, 64: 201-08. 5. Hodson C, Wilson S. Natural history of chronic pyelonephritic scarring. Br Med J 1965; ii: 191-94. 6 International reflux study report. Medical versus surgical treatment of primary vesicoureteral reflux: a prospective international reflux study in children. J Urol
1981, 125: 277-83. 7.
8
Lomberg H, Cedergren B, Leffler H, Nilsson B, Carlstrom A-S, Svanborg-Edén C. Influence of blood group on the availability of receptors for attachment of uropathogenic Escherichia coli. Infect Immun 1986; 51: 919-26 Harber MJ, Topley N, Jenner DE, et al. Virulence factors of urinary pathogens in relation to kidney scarring. In: Asscher AW, Brumfitt W, eds. Microbial diseases in nephrology. Chichester: John Wiley & Sons, 1986: 69-82
HALOPERIDOL-INDUCED DYSTONIA IN COCAINE ADDICTS
SIR,-Dystonic reactions are among the most severe adverse of neuroleptic drugs.1 3-10 % of patients have at least one dystonic reaction during the first few weeks of treatment,l,2 although for higher potency neuroleptic rates above 30 % have been reported.3,4 In one study 12 healthy volunteers were given a single 0 125 mg/kg intravenous dose of haloperidol and 4 experienced a dystonic reaction.4 As part of our studies on dopaminergic mechanisms of cocaine action we gave 7 male research volunteers aged 21-38 8 mg intramuscular doses of haloperidol on two consecutive days. Written consent, the volunteers being told about the possibility of dystonic reactions, was obtained. All were heavy cocaine users on a closed research ward; they had been free of drugs other than cocaine for at least 10 days. All patients had received intravenous cocaine within 72 h of the administration of haloperidol, both drugs were given under research conditions. None of the patients had any major psychiatric disorder, and only 1 reported any prior neuroleptic use. Of the 7 participating patients, 6 experienced acute dystonic reactions. In 4 the onset of dystonia was about 22 h after the first dose; in 2 patients the reaction was within 3 h of the second dose. In 4 patients the dystonia was characterised by torticollis; in 1 case this was accompanied by an oculogyric crisis, in 2 cases by buccolingual reactions
symptoms, and in 1 case by truncal musculature involvement. In both remaining cases of dystonia the dominant features were buccolingual, accompanied by mild oculogyric symptoms in 1. Extrapyramidal symptoms other than dystonia were much less
pathophysiological
St John’s College, Cambridge CB2 1TP
A.
WHYTE
1. Stevens VJ, Fantl WJ, Newman CB, Cecami A, Peterson CM. Acetaldehydè adducts with hemoglobin. J Clin Invest 1981; 67: 361-69. 2. Israel Y, Hurwitz E, Niemela O, Arnon R. Monoclonal and polyclonal antibodies
against acetaldehyde-containing epitopes Natl Acad Sci USA 1986; 83: 7923-27.
in
acetaldehyde-protein
adducts. Proc
RENAL SCARRING AND NON-ATTACHING ESCHERICHIA COLI
SiR,—The virulence of uropathogenic Escherichia coli has been defined by the severity of acute urinary tract infection (UTI) produced by the bacteria rather than by the ability to cause renal scarring.E coli causing first-time acute pyelonephritis often belong to a limited number of O:K:H serotypes with the ability to resist the bactericidal effect of serum, produce haemolysin, and attach to uroepithelial cells. Indeed, adhesive capacity seems to be the marker most frequently associated with the pyelonephritogenic phenotype.2 Most attaching strains specifically bind to the Galoti-4Galp moiety of the globo-series glycolipid receptors. Since renal scarring is one severe end-point of UTI, it has been assumed that such damage results from infection with the most virulent bacteria. We have evaluated the frequency of attaching bacteria in patients with recurrent acute pyelonephritis in relation to the development of renal scarring. 77 girls were selected for study because of recurrent episodes of acute pyelonephritis, diagnosed by bacteriuria, fever, loin pain, and two of three laboratory criteria (raised C-reactive protein, increased sedimentation rate, or reduced renal concentrating capacity’). Renal scarring was defmed at urography as calyceal deformity combined with parenchymal reductionand vesicoureteral reflux was diagnosed by voiding cystourethrography.6 35 patients had renal scarring and 42 did not, and the average follow-up was 10 and 7 years, respectively. The ages at the first detected episodes of acute pyelonephritis were similar in the groups. Those with reflux were younger (median 2-2, range 0-3-6-5) than those without reflux (median 5-5, range 0-5-12) at the first pyelonephritic episodes. The median number of urographies was four (range two to nine) in the scarred and three (range two to five) in the non-scarred group. 142 isolates were available from the episodes of acute pyelonephritis. The analysis of bacterial determinants of scarring is complicated by the time lapse between the infection and radiological detection of the scar. During this time additional UTI episodes may occur. We included only the 58 isolates from infections before the detection of scarring. 60% of the scarred patients had had negative urography before the detection of scarring. The patients with renal scarring had a significantly higher frequency of non-E coli. The E coli strains were analysed for adhesive capacity, by haemagglutination and specific binding to latex beads coated with globotetraosylceramide .7 The frequency of positive reactions is shown in the table. The patients with scarring had a significantly lower frequency of E coli with adhesins specific for globo-series of glycolipid receptors than those without scarring. These results demonstrate significant differences between bacteria causing recurrent pyelonephritis in patients with and
FREQUENCY OF ATTACHING ESCHERICHIA COLI
IN PATIENTS WITH
AND WITHOUT RENAL SCARRING
*Measured
as specific bindmg to the globo-senes of glycolipids, for E coli strains. tFor frequency in non-scarred versus frequency in scarred group.
without renal scarring. The scarred patients were usually infected with poorly attaching bacteria. In the others scarring did not develop despite recurrent infections with attaching E coli. The strains causing renal scarring may have special virulence determinants (eg, mannose-specific adhesins8) but we favour the conclusion that development of renal scarring is associated with increased host susceptibility and that repeated infections with attaching bacteria may be insufficient to induce renal scarring in the resistant host. Department of Clinical Immunology, University of Goteborg, S-413 46 Goteborg, Sweden; and Departments of Paediatric Radiology and Division of Nephrology, Department of Paediatrics, East Hospital, Goteborg 1.
Svanborg-Edén C, Hagberg L, Adhesion of Escherichia coli
Hanson m
HELENA LOMBERG MIKAEL HELLSTRÖM
ULF JODAL CATHARINA SVANBORG EDÉN
LÅ,
urinary
T, Leffler H, Olling S. infection. In: Adhesion and 80) London Pitmans Medical,
Korhonen tract
microorganism pathogenicity (Ciba Found Symp 1980: 161-87.
2. Vaisanen-Rhen V, Elo J, Vaisanen E, et al P-fimbnated clones among uropathogenic Escherichia coli strains. Infect Immun 1984; 43: 149-55. 3. Leffler H, Svanborg-Edén C. Chemical identification of a glycosphingolipid receptor for Escherichia coli attaching to human urinary epithelial cells and agglutinating human erythrocytes FEMS Microbiol Lett 1980; 8: 127-34. 4. Jodal U, Lmdberg U, Lincoln K. Level diagnosis of symptomatic urinary tract infections in childhood Acta Paediatr Scand 1975, 64: 201-08. 5. Hodson C, Wilson S. Natural history of chronic pyelonephritic scarring. Br Med J 1965; ii: 191-94. 6 International reflux study report. Medical versus surgical treatment of primary vesicoureteral reflux: a prospective international reflux study in children. J Urol
1981, 125: 277-83. 7.
8
Lomberg H, Cedergren B, Leffler H, Nilsson B, Carlstrom A-S, Svanborg-Edén C. Influence of blood group on the availability of receptors for attachment of uropathogenic Escherichia coli. Infect Immun 1986; 51: 919-26 Harber MJ, Topley N, Jenner DE, et al. Virulence factors of urinary pathogens in relation to kidney scarring. In: Asscher AW, Brumfitt W, eds. Microbial diseases in nephrology. Chichester: John Wiley & Sons, 1986: 69-82
HALOPERIDOL-INDUCED DYSTONIA IN COCAINE ADDICTS
SIR,-Dystonic reactions are among the most severe adverse of neuroleptic drugs.1 3-10 % of patients have at least one dystonic reaction during the first few weeks of treatment,l,2 although for higher potency neuroleptic rates above 30 % have been reported.3,4 In one study 12 healthy volunteers were given a single 0 125 mg/kg intravenous dose of haloperidol and 4 experienced a dystonic reaction.4 As part of our studies on dopaminergic mechanisms of cocaine action we gave 7 male research volunteers aged 21-38 8 mg intramuscular doses of haloperidol on two consecutive days. Written consent, the volunteers being told about the possibility of dystonic reactions, was obtained. All were heavy cocaine users on a closed research ward; they had been free of drugs other than cocaine for at least 10 days. All patients had received intravenous cocaine within 72 h of the administration of haloperidol, both drugs were given under research conditions. None of the patients had any major psychiatric disorder, and only 1 reported any prior neuroleptic use. Of the 7 participating patients, 6 experienced acute dystonic reactions. In 4 the onset of dystonia was about 22 h after the first dose; in 2 patients the reaction was within 3 h of the second dose. In 4 patients the dystonia was characterised by torticollis; in 1 case this was accompanied by an oculogyric crisis, in 2 cases by buccolingual reactions
symptoms, and in 1 case by truncal musculature involvement. In both remaining cases of dystonia the dominant features were buccolingual, accompanied by mild oculogyric symptoms in 1. Extrapyramidal symptoms other than dystonia were much less