1171
Common complaints associated with the use of an eyepad included itching, burning, and pain. Comeal epithelial defects after removal of corneal foreign bodies are usually small and, as Hulbert finds, tend to heal within 24-48 h. Larger traumatic epithelial defects cause considerable pain, tearing, photophobia, and blepharospasm, and treatment of these without eyepads is usually impractical. The use of a soft bandage contact lens is especially useful for such defects because it allows visual function to be retained during healing, provides better pain relief, and the abrasion heals more quickly than with the use of an eyepad and bandage.’ Daily review is necessary because infection is a risk. The cost of a bandage contact lens ([,17) has to be taken into account but is probably offset by the need for fewer outpatient visits, with the possibility of sterilisation and re-use of the lens. One of the reasons for pain from eyepads could be difficulty with keeping the eyelids shut under the eyepad, and many ophthalmologists tape the eyelids shut before the application of a double pad and bandage. This may be especially useful in general casualty departments where the use of bandage contact lenses might be impractical. Finally, Hulbert does not mention the use of cycloplegics for any of his patients. These are almost routinely used for the treatment of corneal abrasions and are very useful for the pain caused by ciliary spasm. Moorfields Eye Hospital, London EC1V 2PD, UK
B. C. K. PATEL
1 Acheson
JF, Joseph J, Spalton DJ. Use of soft contact lenses m an eye casualty department for the primary treatment of traumatic corneal abrasions. Br J Ophthalmol 1987; 71: 285-89. 2. Chiapella AP, Rosenthal AR. One year in the eye casualty. Br J Ophthalmol 1985; 69: 865-70.
Nuclear medicine and the
hepatobiliary tract
SIR,-We read your editorial (March 23, p 706) with interest, but feel that the application of newer-generation agents is understated. We have found ’Mebrofenin-HIDA’ valuable with bilirubin concentrations of up to 720 imol/1, and others have used IODIDA at bilirubin concentrations of up to 1300 Eunol/1 z Third generation HIDA agents are more rapidly and selectively excreted, and are indicated in deeply jaundiced patients, in those on intensive care units, for the assessment of biliary obstruction and leaks after surgery, and in undiagnosed jaundice. In these cases, accurate functional information may be obtained with bilirubin concentrations well above 200 Jlffioljl. G. EVANS
Hepatobiliary and Liver Transplantation Unit, Royal Free Hospital and School of Medicine,
A. J. W. HILSON
London NW3 2QG, UK
K. E. F. HOBBS
1. Hilson AJW, Evans G, Hobbs KEF. Tc 99m bromotrimethyl HIDA (mebrofenin): a clinical assessment. Eur J Nucl Med 1985; 11 (suppl 22): A37. 2 Schwarzrock R, Kotzerke J, Hundeshagen H, Bocker K, Ringe B. 99mTc-diethylioda-HIDA (JODIDA): a new hepatobiliary agent in clinical comparison with
99mTc-disopropyl-HIDA (DISIDA) in jaundiced patients. Eur J Nucl Med 1986; 12: 346-50.
S!R,—The reliability of genetic tests for presymptomatic diagnosis of hereditary diseases relies on the precision of the genetic maps which have been established around the disease loci. Such maps provide two pieces of information-the order in which the
along the chromosome
All affected individuals have shown characteristic signs (including over 100 colorectal adenomatous polyps) of adenomatous polyposis. Correct paternity was assessed by genotyping all family members with three highly polymorphic VNTR probes. Blood from deceased patient 13 was not available and haplotype has been reconstructed. For patients 1115 to 11110 the allelic status of the APC gene has not been determined clinically but is inferred from haplotype analysis. Mnl1 polymorphism at EF5.44 locus has been validated by typing over 400 members of pedigrees from the Centre d’Etude du Polymorphisme Humain. Boxes in affected individuals indicate affected haplotype in proximity of the gene. R denotes rare recombination event between APC and EF5.44. CHRPE=congenital hypertrophy of retinal pigment epithelium
between
Reliability of presymptomatic test for adenomatous polyposis coli
informative polymorphisms and the morbidity locus
Rare recombination event between APC and EF5.44.
are
aligned
and the genetic distance between pairs of adjacent loci (expressed as the probability of recombination between them during meiosis). These data are usually generated through multilocus linkage analyses in computer programs and are accompanied by an estimate of their reliability. Occasionally, the exact order of closely linked loci can be determined with confidence from a single rare recombination event. Mr Dunlop and colleagues (Feb 9, p 313) report the use of a genetic test to estimate the risk of inherited familial adenomatous polyposis in 41 at-risk symptom-free individuals. Risks were computed on the assumption that the disease locus APC lies
two polymorphic loci probed by C11P11 and EF5.44. However, systematic genotyping of over 400 members of affected
French families has disclosed one family strongly suggesting that APC may be distal to this region. The affected family (figure) was genotyped at six polymorphic loci. If one excludes EF5-44, these probes can be placed on either side of the APC locus with great confidence.1-4 Except for patient 116, all clinically diagnosed affected patients have inherited an identical haplotype from their affected parent. However, on the evidence of a Mnll restriction fragment length polymorphism at EF5 44, the maternal haplotype of individual 116 was generated by a recombination event between APC and EF5’44. In this patient, the distal region of the recombined haplotype is identical to that of his affected siblings but the CRI-L372 allele in the proximal region is identical to that of his unaffected brother 119. The EF5-44 maternal allele segregates with the proximal part of the haplotype, indicating the order shown in the figure. If we had assumed EF5-44 to be distal to APC, lack of clinical information on patient 116 would have led us to classify misleading
this
patient
and his
very low residual
two sons
risk)
as
erroneously (with
unaffected. In contrast,
a
we
Common complaints associated with the use of an eyepad included itching, burning, and pain. Comeal epithelial defects after removal of corneal foreign bodies are usually small and, as Hulbert finds, tend to heal within 24-48 h. Larger traumatic epithelial defects cause considerable pain, tearing, photophobia, and blepharospasm, and treatment of these without eyepads is usually impractical. The use of a soft bandage contact lens is especially useful for such defects because it allows visual function to be retained during healing, provides better pain relief, and the abrasion heals more quickly than with the use of an eyepad and bandage.’ Daily review is necessary because infection is a risk. The cost of a bandage contact lens ([,17) has to be taken into account but is probably offset by the need for fewer outpatient visits, with the possibility of sterilisation and re-use of the lens. One of the reasons for pain from eyepads could be difficulty with keeping the eyelids shut under the eyepad, and many ophthalmologists tape the eyelids shut before the application of a double pad and bandage. This may be especially useful in general casualty departments where the use of bandage contact lenses might be impractical. Finally, Hulbert does not mention the use of cycloplegics for any of his patients. These are almost routinely used for the treatment of corneal abrasions and are very useful for the pain caused by ciliary spasm. Moorfields Eye Hospital, London EC1V 2PD, UK
B. C. K. PATEL
1 Acheson
JF, Joseph J, Spalton DJ. Use of soft contact lenses m an eye casualty department for the primary treatment of traumatic corneal abrasions. Br J Ophthalmol 1987; 71: 285-89. 2. Chiapella AP, Rosenthal AR. One year in the eye casualty. Br J Ophthalmol 1985; 69: 865-70.
Nuclear medicine and the
hepatobiliary tract
SIR,-We read your editorial (March 23, p 706) with interest, but feel that the application of newer-generation agents is understated. We have found ’Mebrofenin-HIDA’ valuable with bilirubin concentrations of up to 720 imol/1, and others have used IODIDA at bilirubin concentrations of up to 1300 Eunol/1 z Third generation HIDA agents are more rapidly and selectively excreted, and are indicated in deeply jaundiced patients, in those on intensive care units, for the assessment of biliary obstruction and leaks after surgery, and in undiagnosed jaundice. In these cases, accurate functional information may be obtained with bilirubin concentrations well above 200 Jlffioljl. G. EVANS
Hepatobiliary and Liver Transplantation Unit, Royal Free Hospital and School of Medicine,
A. J. W. HILSON
London NW3 2QG, UK
K. E. F. HOBBS
1. Hilson AJW, Evans G, Hobbs KEF. Tc 99m bromotrimethyl HIDA (mebrofenin): a clinical assessment. Eur J Nucl Med 1985; 11 (suppl 22): A37. 2 Schwarzrock R, Kotzerke J, Hundeshagen H, Bocker K, Ringe B. 99mTc-diethylioda-HIDA (JODIDA): a new hepatobiliary agent in clinical comparison with
99mTc-disopropyl-HIDA (DISIDA) in jaundiced patients. Eur J Nucl Med 1986; 12: 346-50.
S!R,—The reliability of genetic tests for presymptomatic diagnosis of hereditary diseases relies on the precision of the genetic maps which have been established around the disease loci. Such maps provide two pieces of information-the order in which the
along the chromosome
All affected individuals have shown characteristic signs (including over 100 colorectal adenomatous polyps) of adenomatous polyposis. Correct paternity was assessed by genotyping all family members with three highly polymorphic VNTR probes. Blood from deceased patient 13 was not available and haplotype has been reconstructed. For patients 1115 to 11110 the allelic status of the APC gene has not been determined clinically but is inferred from haplotype analysis. Mnl1 polymorphism at EF5.44 locus has been validated by typing over 400 members of pedigrees from the Centre d’Etude du Polymorphisme Humain. Boxes in affected individuals indicate affected haplotype in proximity of the gene. R denotes rare recombination event between APC and EF5.44. CHRPE=congenital hypertrophy of retinal pigment epithelium
between
Reliability of presymptomatic test for adenomatous polyposis coli
informative polymorphisms and the morbidity locus
Rare recombination event between APC and EF5.44.
are
aligned
and the genetic distance between pairs of adjacent loci (expressed as the probability of recombination between them during meiosis). These data are usually generated through multilocus linkage analyses in computer programs and are accompanied by an estimate of their reliability. Occasionally, the exact order of closely linked loci can be determined with confidence from a single rare recombination event. Mr Dunlop and colleagues (Feb 9, p 313) report the use of a genetic test to estimate the risk of inherited familial adenomatous polyposis in 41 at-risk symptom-free individuals. Risks were computed on the assumption that the disease locus APC lies
two polymorphic loci probed by C11P11 and EF5.44. However, systematic genotyping of over 400 members of affected
French families has disclosed one family strongly suggesting that APC may be distal to this region. The affected family (figure) was genotyped at six polymorphic loci. If one excludes EF5-44, these probes can be placed on either side of the APC locus with great confidence.1-4 Except for patient 116, all clinically diagnosed affected patients have inherited an identical haplotype from their affected parent. However, on the evidence of a Mnll restriction fragment length polymorphism at EF5 44, the maternal haplotype of individual 116 was generated by a recombination event between APC and EF5’44. In this patient, the distal region of the recombined haplotype is identical to that of his affected siblings but the CRI-L372 allele in the proximal region is identical to that of his unaffected brother 119. The EF5-44 maternal allele segregates with the proximal part of the haplotype, indicating the order shown in the figure. If we had assumed EF5-44 to be distal to APC, lack of clinical information on patient 116 would have led us to classify misleading
this
patient
and his
very low residual
two sons
risk)
as
erroneously (with
unaffected. In contrast,
a
we
