68
basal chloride secretion.’ We have also detected significantly reduced secretory response to intraluminal pilocarpine in 10 obligate CF heterozygotes.8 Of the 99 patients attending the CF clinic in Sheffield 67% were dF508 homozygotes, 30% were heterozygous, and 3% had other undefined mutations. The secretory responses of small-bowel biopsy tissue from 12 &Dgr;F508 homozygotes has been compared with 8 CF patients who were heterozygous for &Dgr;F508. 2 of these patients expressed the F553X mutation; the others were all negative for the six non-dF508 mutations G542X, 621 + IC > A, R506T, G551D, Y563N, and I7I7-1G >A. Basal short circuit currents (SCC) were lower in dF 508 homozygotes than in heterozygotes and peak SCC responses with 1 mmol/1 acetylcholine stimulation were lower too: SCC (µA/cm2) Basal No Stimulated Genotype 508508 508/other Non-CF control
12 8 28
11.3 (5.4)* 35-3 (11 1)*
52-5(34)
-0-3(0-3) 2-1 (1’5) 27-1(0-3)
with the scale of Hunt and Hess. A neurological examination will always depend on the experience of the investigator, whereas blood glucose measurement offers an objective, rapid, and cheap route to early prognostic information. Hyperglycaemia seems to reflect increased activity of the
comparable
sympathetic nervous system.2,3
Department of Neurology, University Hospital Innsbruck, A-6020 Innsbruck, Austria
KLAUS BEREK STEFAN KIECHL BETTINA PFAUSLER ANDREA AUCKENTHALER ERICH SCHMUTZHARD
1 Hunt
WE, Hess RM. Surgical risk as related to time of intervention in the repair of intracranial aneurysms. J Neurosurg 1968; 28: 14-20. 2. Benedict CR, Phil D, Loach AB. Sympathetic nervous system activity in patients with subarachnoid hemorrage. Stroke 1978; 9: 237-44 3. Spitzer K, Thie A, Kunze K. Haufigkeit und Prognose internistischer Komplikationen bei spontanen intrakraniellen Hamatomen. Nervenarzt 1988; 59: 647-53
*p = 0-04 (Mann-Whitney, one-tailed)
the numbers are small and although the genetically group is likely to have included patients with a mutation of similar severity to dF 508 the data suggest a tend towards higher basal chloride secretion and better response to cholinergic stimulation in CF dF5o8 heterozygotes. This would be compatible with the finding that patients with pancreatic sufficiency generally present later, have lower sweat chloride levels, milder respiratory disease, normal growth, and a better overall prognosis.9
Although
heterogeneous
Departments of Paediatrics and Biomedical Science, University of Sheffield. Children’s Hospital, Sheffield S10 2TH, UK
C. J. TAYLOR H. HUGHES P. T. HARDCASTLE J. HARDCASTLE
B-S, Rommens J, Buchanan DM, et al. Identification of the cystic fibrosis gene genetic analysis Science 1989, 245: 1073-80 Kerem B-S, Buchanan JA, Dune P, et al DNA marker haplotype association with pancreatic sufficiency in cystic fibrosis Am J Hum Genet 1989; 44: 827-34 Kan YW, Lee M, Furberra A, Angius A, Cao N. Polymorphism of DNA sequence in the &bgr;-globin gene region. Application to prenatal diagnosis of &bgr;° thalassemia in Sardinia. N Engl J Med 1980; 302: 185-88. Kerem E, Corey M, Kerem B-S, et al. The relationship between genotype and phenotype in cystic fibrosis—analysis of the most common mutation (&Dgr;F508). N Engl J Med 1990, 323: 1517-22 European Working Group on CF Genetics Hum Genet 1990; 85: 436-45 Johansen HK, Nir M, Holby N, Koch C, Schwartz M. Severity of cystic fibrosis in patients homozygous and heterozygous for &Dgr;F508 mutation Lancet 1991, 337: 631-34. Taylor CJ, Baxter PS, Hardcastle J, Hardcastle PT Failure to induce secretion in jejunal biopsy samples from children with cystic fibrosis Gut 1988; 29: 957-62 Baxter PS. MD thesis, Cambridge University, 1991. Gaskin K, Gurwitz D, Dune P, Corey M, Levinson H, Forstner G. Improved respiratory prognosis in patients with cystic fibrosis with normal fat absorption. J Pediatr 1982, 100: 857-62
1 Kerem
2 3
4
5.
6
7.
8. 9
Prognostic
indices in subarachnoid
haemorrhage SIR,-We agree with Dr Rinkel and colleagues (Oct 19, p 964) that subarachnoid blood distribution in patients with negative angiography is of prognostic relevance. However, we are not convinced that it adds much to the clinical rating scale of Hunt and Hess.’ We studied 70 patients (31 male, 39 female, mean age 48-5years, range 19-83) with subarachnoid haemorrhage who had been admitted to our neurological intensive care unit between September, 1990, and August, 1991. 22 patients (31 %) died, all of them having presented as Hunt and Hess IV or V. All the survivors were Hunt and Hess I-III on admission. Blood glucose was used as an additional prognostic indicator. All 13 patients with a blood glucose above 200 mg/ dl died. 4 out of 10 patients with a blood glucose of 150-200 mg,dl died and 3 survivors had severe neurological deficits such as chronic vegetative state or hemiparesis. 41 (89%) of the 46 patients with normal blood glucose levels recovered completely. 5 of them died later, 3 after a fatal re-bleeding. 1 known diabetic patient was excluded from this analysis. The initial blood glucose seems to be in subarachnoid haemorrhage
outcome
significant predictor of (p
basal chloride secretion.’ We have also detected significantly reduced secretory response to intraluminal pilocarpine in 10 obligate CF heterozygotes.8 Of the 99 patients attending the CF clinic in Sheffield 67% were dF508 homozygotes, 30% were heterozygous, and 3% had other undefined mutations. The secretory responses of small-bowel biopsy tissue from 12 &Dgr;F508 homozygotes has been compared with 8 CF patients who were heterozygous for &Dgr;F508. 2 of these patients expressed the F553X mutation; the others were all negative for the six non-dF508 mutations G542X, 621 + IC > A, R506T, G551D, Y563N, and I7I7-1G >A. Basal short circuit currents (SCC) were lower in dF 508 homozygotes than in heterozygotes and peak SCC responses with 1 mmol/1 acetylcholine stimulation were lower too: SCC (µA/cm2) Basal No Stimulated Genotype 508508 508/other Non-CF control
12 8 28
11.3 (5.4)* 35-3 (11 1)*
52-5(34)
-0-3(0-3) 2-1 (1’5) 27-1(0-3)
with the scale of Hunt and Hess. A neurological examination will always depend on the experience of the investigator, whereas blood glucose measurement offers an objective, rapid, and cheap route to early prognostic information. Hyperglycaemia seems to reflect increased activity of the
comparable
sympathetic nervous system.2,3
Department of Neurology, University Hospital Innsbruck, A-6020 Innsbruck, Austria
KLAUS BEREK STEFAN KIECHL BETTINA PFAUSLER ANDREA AUCKENTHALER ERICH SCHMUTZHARD
1 Hunt
WE, Hess RM. Surgical risk as related to time of intervention in the repair of intracranial aneurysms. J Neurosurg 1968; 28: 14-20. 2. Benedict CR, Phil D, Loach AB. Sympathetic nervous system activity in patients with subarachnoid hemorrage. Stroke 1978; 9: 237-44 3. Spitzer K, Thie A, Kunze K. Haufigkeit und Prognose internistischer Komplikationen bei spontanen intrakraniellen Hamatomen. Nervenarzt 1988; 59: 647-53
*p = 0-04 (Mann-Whitney, one-tailed)
the numbers are small and although the genetically group is likely to have included patients with a mutation of similar severity to dF 508 the data suggest a tend towards higher basal chloride secretion and better response to cholinergic stimulation in CF dF5o8 heterozygotes. This would be compatible with the finding that patients with pancreatic sufficiency generally present later, have lower sweat chloride levels, milder respiratory disease, normal growth, and a better overall prognosis.9
Although
heterogeneous
Departments of Paediatrics and Biomedical Science, University of Sheffield. Children’s Hospital, Sheffield S10 2TH, UK
C. J. TAYLOR H. HUGHES P. T. HARDCASTLE J. HARDCASTLE
B-S, Rommens J, Buchanan DM, et al. Identification of the cystic fibrosis gene genetic analysis Science 1989, 245: 1073-80 Kerem B-S, Buchanan JA, Dune P, et al DNA marker haplotype association with pancreatic sufficiency in cystic fibrosis Am J Hum Genet 1989; 44: 827-34 Kan YW, Lee M, Furberra A, Angius A, Cao N. Polymorphism of DNA sequence in the &bgr;-globin gene region. Application to prenatal diagnosis of &bgr;° thalassemia in Sardinia. N Engl J Med 1980; 302: 185-88. Kerem E, Corey M, Kerem B-S, et al. The relationship between genotype and phenotype in cystic fibrosis—analysis of the most common mutation (&Dgr;F508). N Engl J Med 1990, 323: 1517-22 European Working Group on CF Genetics Hum Genet 1990; 85: 436-45 Johansen HK, Nir M, Holby N, Koch C, Schwartz M. Severity of cystic fibrosis in patients homozygous and heterozygous for &Dgr;F508 mutation Lancet 1991, 337: 631-34. Taylor CJ, Baxter PS, Hardcastle J, Hardcastle PT Failure to induce secretion in jejunal biopsy samples from children with cystic fibrosis Gut 1988; 29: 957-62 Baxter PS. MD thesis, Cambridge University, 1991. Gaskin K, Gurwitz D, Dune P, Corey M, Levinson H, Forstner G. Improved respiratory prognosis in patients with cystic fibrosis with normal fat absorption. J Pediatr 1982, 100: 857-62
1 Kerem
2 3
4
5.
6
7.
8. 9
Prognostic
indices in subarachnoid
haemorrhage SIR,-We agree with Dr Rinkel and colleagues (Oct 19, p 964) that subarachnoid blood distribution in patients with negative angiography is of prognostic relevance. However, we are not convinced that it adds much to the clinical rating scale of Hunt and Hess.’ We studied 70 patients (31 male, 39 female, mean age 48-5years, range 19-83) with subarachnoid haemorrhage who had been admitted to our neurological intensive care unit between September, 1990, and August, 1991. 22 patients (31 %) died, all of them having presented as Hunt and Hess IV or V. All the survivors were Hunt and Hess I-III on admission. Blood glucose was used as an additional prognostic indicator. All 13 patients with a blood glucose above 200 mg/ dl died. 4 out of 10 patients with a blood glucose of 150-200 mg,dl died and 3 survivors had severe neurological deficits such as chronic vegetative state or hemiparesis. 41 (89%) of the 46 patients with normal blood glucose levels recovered completely. 5 of them died later, 3 after a fatal re-bleeding. 1 known diabetic patient was excluded from this analysis. The initial blood glucose seems to be in subarachnoid haemorrhage
outcome
significant predictor of (p
