- Email: [email protected]
Malaria prophylaxis dosage
showed afterdrop, arrhythmias, or vascular collapse, and none needed cardiocirculatory support with catecholamines.
remaining patient, who had alcohol intoxication, developed severe bleeding from oesophageal varices during rewarming and died. 6 patients fully recovered and survived to hospital discharge. 2 patients died later in hospital; neither death was related to hypothermia (adult respiratory distress syndrome after prehospital aspiration, irreversible ischaemic brain damage after avalanche accident). Forced hot air rewarming is widely used during and after major surgery, but no data are available on the use of forced hot air rewarming in patients with accidental hypothermia. Our preliminary data indicate that forced hot air rewarming is easy to do, is effective, and does not induce arrhythmias or vascular collapse in patients with a core temperature as low as 24°C. Rewarming rates for forced hot air rewarming are close to those for immersion therapy or warm fluid lavage of body cavities.’ At our institution forced hot air rewarming has replaced alternative methods of active rewarming in hypothermic patients with a perfusing cardiac rhythm.
The
*P Mair, E Kornberger, C Hörmann Department of Anaesthesia and Intensive Care Medicine, University of Innsbruck School of Medicine, A-6020 Innsbruck, Austria 1 Danzl DF, Pozos RS, Auerbach PS, et al. Multicenter hypothermia survey. Ann Emerg Med 1987; 16: 1042-55.
diagnosis of spinal muscular atrophy by gene deletion analysis
Figure: Prenatal diagnosis
results
A=deletion analysis of SMN exons 7 and 8 with single-strand conformation polymorphism. Lane 1 is affected individual showing deletion of telomeric SMN exons 7 and 8 (marked with arrow). Lanes 2 and 3 are parents showing both centromeric and telomeric exons 7 and 8. Lane 4 is affected sibling showing deletions of telomeric exons 7 and 8. Lane 5 is unaffected sibling showing no deletions. Lane 6 is chorionic villus sample showing same pattern as that of affected sibling in lane 4. B=haplotype analysis with flanking DNA markers.
This is especially helpful since new mutations in this disorder have been confirmed in families with no previous family history of the disease.5 The assay will also be applicable to those cases where only small samples from affected individuals are available.
Prenatal
SiR-Childhood-onset spinal muscular atrophy (SMA) is one of the most common autosomal recessive disorders, affecting about 1 in 6000 live births’ and is characterised by symmetrical weakness, atrophy of limb muscles, and degeneration of anterior horn cells. Depending on clinical severity, SMA is classified into types I, II, and 111;2 all 3 types of SMA are localised to chromosome 5ql3. In the past, prenatal diagnosis has depended on flanking linked DNA markers and the availability of samples from a previously affected child, and in some instances linkage to chromosome 5 was uncertain. A candidate gene, the survival motoneuron (SMN) gene, has been shown to be deleted in 98-6% of SMA patients.3 The SMN gene is present in two almost identical copies on chromosome 5 and the deletions associated with the disease occur in the telomeric copy of the gene. A woman who had
previously had a child with type I SMA about genetic counselling for her present pregnancy. Chorionic villi were analysed with linked DNA markers’ to determine whether the fetus had inherited the affected haplotype; the sample was also tested for deletion in the SMN gene. Studies with linked markers had correctly predicted the outcome of a previous pregnancy as normal. The figure shows that the fetus shared the same haplotype as the affected boy and was at high risk of being affected. Deletion analysis of the SMN gene shows that the parents and the unaffected sibling have exons 7 and 8 of both the telomeric and centromeric copies of the SMN gene (lanes 2, 3, and 5). The fetus and the affected sibling have the deletions for the telomeric SMN exons 7 and 8 (lanes 4 and 6). The fetus was therefore predicted to be at very high risk of being affected and the pregnancy was terminated. This direct test will be very useful for the diagnosis of SMA because of its high accuracy (98% of patients have the deletions). Although there is no correlation between the phenotype and the deletions, the test will also be useful to the neurologist for the confirmation of chromosome-5-linked SMA in the many isolated cases that present in the clinic. contacted
Nanda R Rodrigues, Louise Campbell, Nicholas Owen, Charles H Rodeck, *Kay E Davies *Molecular Genetics Group, Institute of Molecular Medicine, John Radcliffe Hospital, Oxford OX3 9DU, UK; and Department of Obstetrics and Gynaecology, University College and Middlesex School of Medicine, University College, London
1 2
3
Peam JH. Principles and practices of medical genetics. Edinburgh: Churchill Livingstone, 1985: 414-25. Munsat TL. International SMA collaboration: workshop report. Neuromuscul Disord 1994; 1: 81. Lefebvre S, Burglen L, Reboullet S, et al. Identification and characterization of a spinal muscular atrophy determining gene. Cell
1995; 80: 155-65. 4
5
Francis MJ, Morrison KE, Campbell L, et al. A contig of nonchimaeric YACs containing the spinal muscular atrophy gene in 5q13. Hum Mol Genet 1993; 2: 1161-67. Rodrigues NR, Owen N, Talbot K, Ignatius J, Dubowitz V, Davies KE. Deletion analysis of the survival motor neuron gene on 5q13 in autosomal recessive spinal muscular atrophy. Hum Mol Genet 1995; 4: 631-34.
us
Malaria
prophylaxis dosage
SiR-Many publications recommend a mg/kg dosage rate of prophylactic antimalarial drugs for children but a fixed amount for adults who may vary from 40 kg to over 100 kg. This is in contrast to treatment schedules in which mg/kg is used for all ages. 3 tourists each weighing 90-100 kg contracted Plasmodium falciparum malaria despite taking 300 mg chloroquine weekly and 200 mg proguanil daily, whereas their normally sized fellow tourists were apparently protected by the same dosage. They travelled in areas with low-level chloroquine resistance. Increasing the dosage to 5 mg/kg chloroquine and 3 mg/kg proguanil might give them better protection but perhaps at greater risk of developing side-effects. If similar findings are confirmed elsewhere 1 suggest that the adult dosage of prophylactic antimalarials should be reviewed. C H Hansford Department of Health and Welfare, Northern Transvaal Province, PO Box 33, Tzaneen 0850, South Africa
1049
remaining patient, who had alcohol intoxication, developed severe bleeding from oesophageal varices during rewarming and died. 6 patients fully recovered and survived to hospital discharge. 2 patients died later in hospital; neither death was related to hypothermia (adult respiratory distress syndrome after prehospital aspiration, irreversible ischaemic brain damage after avalanche accident). Forced hot air rewarming is widely used during and after major surgery, but no data are available on the use of forced hot air rewarming in patients with accidental hypothermia. Our preliminary data indicate that forced hot air rewarming is easy to do, is effective, and does not induce arrhythmias or vascular collapse in patients with a core temperature as low as 24°C. Rewarming rates for forced hot air rewarming are close to those for immersion therapy or warm fluid lavage of body cavities.’ At our institution forced hot air rewarming has replaced alternative methods of active rewarming in hypothermic patients with a perfusing cardiac rhythm.
The
*P Mair, E Kornberger, C Hörmann Department of Anaesthesia and Intensive Care Medicine, University of Innsbruck School of Medicine, A-6020 Innsbruck, Austria 1 Danzl DF, Pozos RS, Auerbach PS, et al. Multicenter hypothermia survey. Ann Emerg Med 1987; 16: 1042-55.
diagnosis of spinal muscular atrophy by gene deletion analysis
Figure: Prenatal diagnosis
results
A=deletion analysis of SMN exons 7 and 8 with single-strand conformation polymorphism. Lane 1 is affected individual showing deletion of telomeric SMN exons 7 and 8 (marked with arrow). Lanes 2 and 3 are parents showing both centromeric and telomeric exons 7 and 8. Lane 4 is affected sibling showing deletions of telomeric exons 7 and 8. Lane 5 is unaffected sibling showing no deletions. Lane 6 is chorionic villus sample showing same pattern as that of affected sibling in lane 4. B=haplotype analysis with flanking DNA markers.
This is especially helpful since new mutations in this disorder have been confirmed in families with no previous family history of the disease.5 The assay will also be applicable to those cases where only small samples from affected individuals are available.
Prenatal
SiR-Childhood-onset spinal muscular atrophy (SMA) is one of the most common autosomal recessive disorders, affecting about 1 in 6000 live births’ and is characterised by symmetrical weakness, atrophy of limb muscles, and degeneration of anterior horn cells. Depending on clinical severity, SMA is classified into types I, II, and 111;2 all 3 types of SMA are localised to chromosome 5ql3. In the past, prenatal diagnosis has depended on flanking linked DNA markers and the availability of samples from a previously affected child, and in some instances linkage to chromosome 5 was uncertain. A candidate gene, the survival motoneuron (SMN) gene, has been shown to be deleted in 98-6% of SMA patients.3 The SMN gene is present in two almost identical copies on chromosome 5 and the deletions associated with the disease occur in the telomeric copy of the gene. A woman who had
previously had a child with type I SMA about genetic counselling for her present pregnancy. Chorionic villi were analysed with linked DNA markers’ to determine whether the fetus had inherited the affected haplotype; the sample was also tested for deletion in the SMN gene. Studies with linked markers had correctly predicted the outcome of a previous pregnancy as normal. The figure shows that the fetus shared the same haplotype as the affected boy and was at high risk of being affected. Deletion analysis of the SMN gene shows that the parents and the unaffected sibling have exons 7 and 8 of both the telomeric and centromeric copies of the SMN gene (lanes 2, 3, and 5). The fetus and the affected sibling have the deletions for the telomeric SMN exons 7 and 8 (lanes 4 and 6). The fetus was therefore predicted to be at very high risk of being affected and the pregnancy was terminated. This direct test will be very useful for the diagnosis of SMA because of its high accuracy (98% of patients have the deletions). Although there is no correlation between the phenotype and the deletions, the test will also be useful to the neurologist for the confirmation of chromosome-5-linked SMA in the many isolated cases that present in the clinic. contacted
Nanda R Rodrigues, Louise Campbell, Nicholas Owen, Charles H Rodeck, *Kay E Davies *Molecular Genetics Group, Institute of Molecular Medicine, John Radcliffe Hospital, Oxford OX3 9DU, UK; and Department of Obstetrics and Gynaecology, University College and Middlesex School of Medicine, University College, London
1 2
3
Peam JH. Principles and practices of medical genetics. Edinburgh: Churchill Livingstone, 1985: 414-25. Munsat TL. International SMA collaboration: workshop report. Neuromuscul Disord 1994; 1: 81. Lefebvre S, Burglen L, Reboullet S, et al. Identification and characterization of a spinal muscular atrophy determining gene. Cell
1995; 80: 155-65. 4
5
Francis MJ, Morrison KE, Campbell L, et al. A contig of nonchimaeric YACs containing the spinal muscular atrophy gene in 5q13. Hum Mol Genet 1993; 2: 1161-67. Rodrigues NR, Owen N, Talbot K, Ignatius J, Dubowitz V, Davies KE. Deletion analysis of the survival motor neuron gene on 5q13 in autosomal recessive spinal muscular atrophy. Hum Mol Genet 1995; 4: 631-34.
us
Malaria
prophylaxis dosage
SiR-Many publications recommend a mg/kg dosage rate of prophylactic antimalarial drugs for children but a fixed amount for adults who may vary from 40 kg to over 100 kg. This is in contrast to treatment schedules in which mg/kg is used for all ages. 3 tourists each weighing 90-100 kg contracted Plasmodium falciparum malaria despite taking 300 mg chloroquine weekly and 200 mg proguanil daily, whereas their normally sized fellow tourists were apparently protected by the same dosage. They travelled in areas with low-level chloroquine resistance. Increasing the dosage to 5 mg/kg chloroquine and 3 mg/kg proguanil might give them better protection but perhaps at greater risk of developing side-effects. If similar findings are confirmed elsewhere 1 suggest that the adult dosage of prophylactic antimalarials should be reviewed. C H Hansford Department of Health and Welfare, Northern Transvaal Province, PO Box 33, Tzaneen 0850, South Africa
1049