621
unsuitable for the detection of the
rarer
mosaic forms of Down’s
syndrome. More significantly, we acknowledge that predictive accuracy will also be dependent on the degree of maternal contamination that can be tolerated. The best technique for separating fetal cells from maternal blood5,6 will need to be followed by a larger study, in which the availability of a simple PCR-based method for DNA measurement in Down’s syndrome should prove valuable. Unit of Pathology, University of Leeds,
Leeds LS2 9JT, UK, Unit of Obstetrics and Gynaecology, St James’s University Hospital, Leeds, and Institute of Epidemiology and Health Services Research, University of Leeds
D. MILLER P.-Z. TANG R. S. V. CARTMILL M. D. GRIFFITH-JONES R. J. LILFORD H. S. CUCKLE
1. Admolfi M. On a non-invasive approach to prenatal diagnosis based on the detection of fetal nucleated cells in maternal blood. Prenat Diagn 1991; 11: 799-804. 2. Lichter P, Boyle AL, Cremer T, Ward DC. Analysis of genes by nonisotopic in situ hybridisation. Genet Anal 1991; 8: 24-35. 3 Salbaum JM, Weidemann A, Lemaire H-G, Masters CL, Beyreuther K. The promoter of Alzheimer’s disease amyloid A4 precursor gene. EMBO J 1988; 7: 2807-13. 4 Lench N, Stanier P, Williamson R Simple non-invasive method to obtain DNA for gene analysis. Lancet 1988; i: 1356-58. 5 Bruch JF, Metezeas P, Garcia-Fonknechten N, et al. Trophoblast like cells sorted from maternal blood using flow cytometry. A multiparametric study involving transmission electron microscopy and fetal DNA amplification. Prenat Diagn 1991; 11: 787-98. 6 Mueller UW, Hawed CS, Wright AE. Isolation of fetal trophoblast cells from penpheral blood of pregnant women. Lancet 1990; 336: 197-201.
Molecular analysis of nosocomial infection by oxacillin-resistant Staphylococcus aureus lacking protein A and clumping factor SIR,—An outbreak ot oxacillm-resistant Staphylococcus
aureus
’ORSA) in 45 patients occurred in an 1800-bed university-affiliated hospital in south Germany in November, 1991. The strains were clumping-factor and protein-A negative by usual agglutination tests. No clumping-factor-negative ORSA had been recorded in the hospital during the 6 months before the identification of the epidemic strains. The outbreak started in the intensive-care unit of the department of surgery, and spread to the intensive-care unit of the department of anaesthesiology and to nearly all surgical wards in the hospital. 4 patients had septicaemia, 1 of whom died with acute endocarditis. Another 2 patients had pneumonia and 1 died. This ORSA caused wound infection in 28 patients, urinary-tract
infections in another 3 patients. 7 patients had the strain in tracheal secretion without signs of pneumonia or other infection. In 1 case an outbreak strain was found at necropsy in ethmoidal cells without signs of staphylococcal infection. All the patients had the typical risk criteria described by Brumfitt et al:1 old age and/or surgical wounds, venous access sites, and/or serious illness such as carcinoma. The 58 nursing and medical staff involved were examined repeatedly for nasal carriage. Only 2 harboured the outbreak strain. This low frequency concurs with Brumfitt et al.l Tube coagulase-test and biochemical analysis of the isolates with the API-System (Bio Merieux) resulted in definitive identification (99-9%) of S aureus. Susceptibility testing proved the ORSA to be sensitive only to novobiocine, tetracycline, co-trimoxazole, vancomycin, rifampicin, and fusidic acid. All 47 ORSA uniformly contained a single plasmid of 32 kb with identical restriction patterns. After digestion of chromosomal DNA with Sma I and separation of the DNA by pulsed-field gel electrophoresis,’ fragment bands of identical size were observed, which indicates clonal identity of the isolates. During the oubreak period, we obtained ORSA suspected to cause smaller outbreaks from three other hospitals in south Germany. DNA fingerprinting showed the same patterns as our strains. The following effective measures were adopted to terminate the series of infections: strict isolation of the infected patients, discharge of carriers as soon as clinically feasible; and treatment of nasal carriers with mupirocin and their exclusion from nursing in intensive-care units until they were shown to be cured. Staphylococci with yellow pigmentation that are negative by slide agglutination tests for clumping factor and protein A should be tested for DNase and free coagulase. Even DNase, clumping-factor, and protein-A negative ORSA have been described in a few sporadic cases.3 In addition to biochemical typing and antibiotic susceptibility patterns, molecular methods for demonstrating clonality are necessary for specifying strains presumed responsible for outbreaks. Institute for Hygiene and Microbiology, University of Wurzburg, D-8700 Wurzburg, Germany, and Department of Surgery,
University Hospital, Wurzburg
ANDREAS SCHWARZKOPF HANNELIESE SCHMIDT-ROTTE HERBERT SCHMIDT ELMAR KUNZ HELGE KARCH JÜRGEN HEESEMANN
Methicillin-presistant Staphylococcus aureus. N Engl J Med 1989; 320: 1188-96. 2. Ichiyama S, Ohta M, Shimokata K, Kato N, Takeuchi J. Genomic DNA fingerprinting by pulsed field gel electrophoresis as an epidemiological marker for study of nosocomial infections caused by methicillin resistant Staphylococcus aureus. J Clin Microbiol 1991; 29: 2690-95. 3. Neville LO, Billington OJ, Kibbler CC, Gillespie SH. Methicillin resistant Staphylococcus aureus without clumping factor, protein A and DNase. Lancet 1991; 1. Brumfitt W, Hamilton-Miller J.
338: 518.
Magnesium for hyperventilation syndrome
in Rett’s
SIR,—Rett’s syndrome is characterised by irregular cycles of hyperventilation with hypocapnia alternating with apnoea for up to 120 s with reduced arterial oxygen saturation, cyanosis, and unconsciousness.1,2The hypocapnic alkalaemia and hypoxaemia may impair amine production,3 disturb cerebral perfusion,4 and contribute to progressive neurological impairmentWe gave a girl with Rett’s syndrome and epilepsy magnesium as an anticonvulsant after other anticonvulsants had failed. To our surprise hyperventilation greatly improved. So we studied the effects in six other cases. All seven girls had characteristic stage 2 Rett’s syndrome (intellectual regression, hand stereotypies, microcephaly, hyperventilation with hypocapnic alkalaemia, apnoeic episodes sometimes with loss of consciousness, seizures and autistic features’). Magnesium orotate or citrate, initially 4 mg/kg per day in three doses, was given orally. The dose was gradually increased until diarrhoea occurred (usually at 10 mg/kg per day). Six girls had severe hyperventilation and deep cyanosis during apnoeic episodes. The parents were asked to record these episodes before and 1 month after starting magnesium. The daily episodes of
unsuitable for the detection of the
rarer
mosaic forms of Down’s
syndrome. More significantly, we acknowledge that predictive accuracy will also be dependent on the degree of maternal contamination that can be tolerated. The best technique for separating fetal cells from maternal blood5,6 will need to be followed by a larger study, in which the availability of a simple PCR-based method for DNA measurement in Down’s syndrome should prove valuable. Unit of Pathology, University of Leeds,
Leeds LS2 9JT, UK, Unit of Obstetrics and Gynaecology, St James’s University Hospital, Leeds, and Institute of Epidemiology and Health Services Research, University of Leeds
D. MILLER P.-Z. TANG R. S. V. CARTMILL M. D. GRIFFITH-JONES R. J. LILFORD H. S. CUCKLE
1. Admolfi M. On a non-invasive approach to prenatal diagnosis based on the detection of fetal nucleated cells in maternal blood. Prenat Diagn 1991; 11: 799-804. 2. Lichter P, Boyle AL, Cremer T, Ward DC. Analysis of genes by nonisotopic in situ hybridisation. Genet Anal 1991; 8: 24-35. 3 Salbaum JM, Weidemann A, Lemaire H-G, Masters CL, Beyreuther K. The promoter of Alzheimer’s disease amyloid A4 precursor gene. EMBO J 1988; 7: 2807-13. 4 Lench N, Stanier P, Williamson R Simple non-invasive method to obtain DNA for gene analysis. Lancet 1988; i: 1356-58. 5 Bruch JF, Metezeas P, Garcia-Fonknechten N, et al. Trophoblast like cells sorted from maternal blood using flow cytometry. A multiparametric study involving transmission electron microscopy and fetal DNA amplification. Prenat Diagn 1991; 11: 787-98. 6 Mueller UW, Hawed CS, Wright AE. Isolation of fetal trophoblast cells from penpheral blood of pregnant women. Lancet 1990; 336: 197-201.
Molecular analysis of nosocomial infection by oxacillin-resistant Staphylococcus aureus lacking protein A and clumping factor SIR,—An outbreak ot oxacillm-resistant Staphylococcus
aureus
’ORSA) in 45 patients occurred in an 1800-bed university-affiliated hospital in south Germany in November, 1991. The strains were clumping-factor and protein-A negative by usual agglutination tests. No clumping-factor-negative ORSA had been recorded in the hospital during the 6 months before the identification of the epidemic strains. The outbreak started in the intensive-care unit of the department of surgery, and spread to the intensive-care unit of the department of anaesthesiology and to nearly all surgical wards in the hospital. 4 patients had septicaemia, 1 of whom died with acute endocarditis. Another 2 patients had pneumonia and 1 died. This ORSA caused wound infection in 28 patients, urinary-tract
infections in another 3 patients. 7 patients had the strain in tracheal secretion without signs of pneumonia or other infection. In 1 case an outbreak strain was found at necropsy in ethmoidal cells without signs of staphylococcal infection. All the patients had the typical risk criteria described by Brumfitt et al:1 old age and/or surgical wounds, venous access sites, and/or serious illness such as carcinoma. The 58 nursing and medical staff involved were examined repeatedly for nasal carriage. Only 2 harboured the outbreak strain. This low frequency concurs with Brumfitt et al.l Tube coagulase-test and biochemical analysis of the isolates with the API-System (Bio Merieux) resulted in definitive identification (99-9%) of S aureus. Susceptibility testing proved the ORSA to be sensitive only to novobiocine, tetracycline, co-trimoxazole, vancomycin, rifampicin, and fusidic acid. All 47 ORSA uniformly contained a single plasmid of 32 kb with identical restriction patterns. After digestion of chromosomal DNA with Sma I and separation of the DNA by pulsed-field gel electrophoresis,’ fragment bands of identical size were observed, which indicates clonal identity of the isolates. During the oubreak period, we obtained ORSA suspected to cause smaller outbreaks from three other hospitals in south Germany. DNA fingerprinting showed the same patterns as our strains. The following effective measures were adopted to terminate the series of infections: strict isolation of the infected patients, discharge of carriers as soon as clinically feasible; and treatment of nasal carriers with mupirocin and their exclusion from nursing in intensive-care units until they were shown to be cured. Staphylococci with yellow pigmentation that are negative by slide agglutination tests for clumping factor and protein A should be tested for DNase and free coagulase. Even DNase, clumping-factor, and protein-A negative ORSA have been described in a few sporadic cases.3 In addition to biochemical typing and antibiotic susceptibility patterns, molecular methods for demonstrating clonality are necessary for specifying strains presumed responsible for outbreaks. Institute for Hygiene and Microbiology, University of Wurzburg, D-8700 Wurzburg, Germany, and Department of Surgery,
University Hospital, Wurzburg
ANDREAS SCHWARZKOPF HANNELIESE SCHMIDT-ROTTE HERBERT SCHMIDT ELMAR KUNZ HELGE KARCH JÜRGEN HEESEMANN
Methicillin-presistant Staphylococcus aureus. N Engl J Med 1989; 320: 1188-96. 2. Ichiyama S, Ohta M, Shimokata K, Kato N, Takeuchi J. Genomic DNA fingerprinting by pulsed field gel electrophoresis as an epidemiological marker for study of nosocomial infections caused by methicillin resistant Staphylococcus aureus. J Clin Microbiol 1991; 29: 2690-95. 3. Neville LO, Billington OJ, Kibbler CC, Gillespie SH. Methicillin resistant Staphylococcus aureus without clumping factor, protein A and DNase. Lancet 1991; 1. Brumfitt W, Hamilton-Miller J.
338: 518.
Magnesium for hyperventilation syndrome
in Rett’s
SIR,—Rett’s syndrome is characterised by irregular cycles of hyperventilation with hypocapnia alternating with apnoea for up to 120 s with reduced arterial oxygen saturation, cyanosis, and unconsciousness.1,2The hypocapnic alkalaemia and hypoxaemia may impair amine production,3 disturb cerebral perfusion,4 and contribute to progressive neurological impairmentWe gave a girl with Rett’s syndrome and epilepsy magnesium as an anticonvulsant after other anticonvulsants had failed. To our surprise hyperventilation greatly improved. So we studied the effects in six other cases. All seven girls had characteristic stage 2 Rett’s syndrome (intellectual regression, hand stereotypies, microcephaly, hyperventilation with hypocapnic alkalaemia, apnoeic episodes sometimes with loss of consciousness, seizures and autistic features’). Magnesium orotate or citrate, initially 4 mg/kg per day in three doses, was given orally. The dose was gradually increased until diarrhoea occurred (usually at 10 mg/kg per day). Six girls had severe hyperventilation and deep cyanosis during apnoeic episodes. The parents were asked to record these episodes before and 1 month after starting magnesium. The daily episodes of
