1275
Health care for elderly patients in Japan
mg/kg daily for 2 weeks followed by the alternate days for 4 weeks. During the course of therapy 2 patients each had one relapse, in 1 of whom steroid dependence later developed. The number of relapses in the year before institution of levamisole (3-3 [0’5]/patients per year) did not differ from that in the year after it was stopped (2-3 [l’3]/patients course
of prednisolone 2
same amount on
SIR,-When governments in many developed countries began to talk of limiting their health expenditures by rationing, Japan
developed a policy for care of elderly people to cover its lack of social welfare. As in other countries the scheme was prompted by the ageing of the population and the rising cost of their care and treatment, accounting for almost 40% of all medical costs. Japan’s good health insurance coverage and moderate health expenditure in respect of gross national product are well recognised, but what is less well known and specific to Japan is that because of the lack of social policy for elderly care, there is strong competition for entry to the few public nursing homes, and its great national wealth does not assure the Japanese public of a good quality of life at home. There is no suitable housing for disabled and handicapped people, no place for sick and old people or family care for them, and home visiting arrangements are far from satisfactory (only public health nurses visit twice a week). Therefore even after recovery from illness, old people have nowhere to go, and admission to hospital for social continues to inflate the medical cost of care for such because without social support hospitals tend to apply medical procedures to maintain their income. The law for health and medical services for the aged was put into effect in 1983 and amended in 1987. Intermediate (between hospital and home) care facilities were set up nationwide, and there are now 431 homes for 34 752 elderly people which will be expanded to serve 230 000 users. Intermediate facilities are funded partly by the user (about k200 per month) and partly by the government (four times as much as the user). These intermediate homes have fewer medical staff than hospitals and fewer care workers than nursing homes. With the restricted admission criteria neither users nor facility managers are satisfied. The maximum stay is 3 months, and users have to return home (or go to a nursing home) as soon as they can manage daily tasks without help, but housing conditions and the social care system remain the same. As for managers, they must provide the necessary medical help while keeping within the limited budget. Compared with the high cost of private nursing homes, these intermediate care facilities seem attractive for convalescent people. However, the funding system is unsatisfactory because there is no upper limit for users’ payments and there are large numbers of bedridden (700 000) or senile dementia patients (1 million) who cannot afford the fees. Although they offer day-care or short-stay (within 2 weeks), without the need for reform of the social system, they will endanger care for elderly people. Different national health service systems should be compared with respect to outcome assessment to see if this type of national scheme for elderly people provides an efficient and cost-effective service. If so, a wealthy nation like Japan should be able to afford full coverage of social health insurance and achieve good health status indices. reasons
patients,
5-6-9-307 Hanazono, Kumamoto,
Japan 860
KYOKO IMAMURA
Levamisole in nephrotic syndrome StR,—The British Association for Pediatric Nephrology (June 29, p 1555) reports the efficacy and safety of levamisole in
maintaining steroid-free remission in children with steroiddependent nephrotic syndrome. None of the 31 patients treated with levamisole had serious side-effects. The researchers refer to the frequency of neutropenia in this and previous studies, with only 3 of 140 patients having a neutrophil count of less than 2 x 109/1. Manna et aP and Mongeau et al2 also reported that treatment with levamisole was effective in frequently relapsing or steroid-dependent nephrotic syndrome, with minimum sideeffects. Reports of agranulocytosis (neutrophil count < 2 x l0"/l) with levamisole are mostly associated with treatment of connective tissue or neoplastic diseases.3 We have examined the effect of a 12-week course of levamisole in 9 boys and 3 girls with frequently relapsing nephrotic syndrome. The mean age at onset of nephrotic syndrome was 2-2 years and that at onset of therapy was 6’ 3 years. Levamisole was given in a dose of 5 mg/kg on alternate days for 12 weeks. The drug was started immediately after remission had been achieved with a 6-week very low
per
year).
Agranulocytosis developed in 1 patient (total white cell count 1.2 x 109/1; lymphocytes 95%, polymorphonuclear cells 2%, eosinophils 2%, and monocytes 1%) 4 weeks after start of treatment.
After cessation of treatment,
counts
returned
to
normal
days. Further treatment with levamisole was not given. Erythematous pruritic rash developed 4 weeks after the start of therapy in another patient. The drug was stopped and the rash subsided in one month. The drug was reintroduced after another 4 within 10
weeks without recurrence of the rash. Our preliminary results indicate that the effect of treatment with a 12-week course of levamisole is not sustained, and most cases relapse after withdrawal of treatment. A long course of therapy may be effective in maintaining steroid-free remission.1,2 Since the occurrence of agranulocytosis is not dose dependent and cannot be predicted, regular blood counts are necessary. Department of Paediatrics, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110029, India
R. N. SRIVASTAVA A. S. VASUDEV A. BAGGA
AL, Polito C, Gado RD, Foglia AC. Levamisole in children’s idiopathic nephrotic syndrome. Child Nephrol Urol 1988-89; 9: 200-02. 2. Mongeau JG, Robitaille PO, Roy F Clinical efficacy of levamisole in the treatment of primary nephrosis in children Pediatr Nephrol 1988; 2: 398-401. 3. Symoens J, Veys E, Mielanis M. Adverse reactions to levamisole. Cancer Treat Rep 1978; 62: 1721-30. 1 Manna
Safety of transcranial magnetic stimulation in patients with abdominally implanted electronic devices SiR,—Magnetic transcranial stimulation (MTCS) has become a valuable tool in the assessment of descending motor pathways." However, safety in patients with implanted devices remains a concern, and the application of MTCS in patients with implanted cardiac pacemakers and ferromagnetic implants, such as aneurysm clips, is not recommended.4 Patients on spinal cord stimulation (SCS) for the control of pain or spasticity5-7 are also likely to have repeated neurophysiological evaluation, so we decided to investigate in 4 patients the influence of MTCS on internally powered, magnetically controlled (Medtronic) or externally powered, radiofrequency-coupled (Neuromed) SCS pulse generators implanted in the lower abdomen. Since magnetic field strength falls off as the cube of axial distance, we were concerned not so much about displacement of the epidural electrode or damage to the pulse generator as with interactions of the field with the electronic control of the stimulators that affect the on-off mode, amplitude, pulse width, rate, and cathode-anode combination. Patient 1 (65, M; 9-year history of progressive spastic paraparesis) had a Medtronic ’ITREL II’ model 7424 implantable pulse generator connected to a Medtronic ’Pisces Quad’ (four electrode) lead placed epidurally at Til. Patient 2 (48, F; 25-year history of multiple sclerosis) had an identical SCS system with a T11 electrode for control of spasticity. Patient 3 (24, M; spastic tetraparesis due to traumatic brain injury) had a Neuromed MNT-94 pulse generator connected to a Neuromed 1994JF lead at C3. Patient 4 (49, F; chronic pain and spasticity secondary to spinal cord injury) had the same SCS system as patient 3 with a Neuromed 1980JF lead at T12. She also had a drug-delivery system (Medtronic ’Synchromed 8611H’) connected to an intrathecal catheter. These electronic devices were implanted in the lower abdomen in all 4 patients. An estimated peak magnetic flux density of 001 T, determined from measurements made in air using a 1 cm diameter sensing coil, was present at the lead tip in patient 3. All other leads and pulse generators were exposed to less than 0.001 T. In patients 1 and 2 the implanted SCS was turned off before MTCS with a Cadwell MES-10 magnetic stimulator using a 9-5 cm
1276
SUMMARY DATA FROM FISH STUDIES WITH D15Z1
diameter coil placed over the vertex. MTCS was started at 20% output intensity and augmented in increments of 20% up to 100%, corresponding to 2 T. After each increase, the implanted SCS system was checked with a radiofrequency link. MTCS neither turned on the SCS system nor caused any change in control settings. Patients 3 and 4 had MTCS studies with the systems turned on and off. No electrode displacement was noted and no SCS controls (or drug-delivery indices in patient 4) were altered. Normal operation of the implants was noted at the end of the study in all patients. MTCS at the vertex with a Cadwell MES-10 magnetic stimulator seems not to affect adversely the implants used in our study. Our findings allow further investigation of how neuroaugmentative interventions might alter the function of descending motor pathways. Extrapolation to other systems should be done cautiously.
Division of Restorative Neurology and Human Neurobiology, Baylor College of Medicine, Houston, Texas 77030, USA
MARKUS KOFLER A. ARTURO LEIS ARTHUR M. SHERWOOD J. SCOTT DELAPASSE JOHN A. HALTER *,tFlrst cousms
Freeston IL. Non-invasive motor cortex. Lancet 1985; i: 1106-07.
1. Barker AT,
Jalinous R,
magnetic stimulation of human
2. Claus D, Waddy HM, Harding AE, Murray NMF, Thomas PK. Hereditary motor and sensory neuropathies and hereditary spastic paraplegia: a magnetic stimulation study. Ann Neurol 1990; 28: 43-49. 3. Brouwer B, Ashby P. Altered corticospinal projection to lower limb motoneurons in subjects with cerebral palsy Brain 1991; 114: 1395-1407. 4. Cracco RQ. Evaluation of conduction in central motor pathways: techniques, pathophysiology, and clinical interpretation. Neurosurgery 1987; 20: 199-203. 5. Dimitrijevic MM, Dimitrijevic MR, Illis LS, Nakajima K, Sharkey PC, Sherwood AM. Spinal cord stimulation for the control of spasticity in patients with chronic spinal cord injury I. clinical observations. CNS Trauma 1986; 3: 129-44. 6. Dimitrijevic MR, Illis LS, Nakajima K, Sharkey PC, Sherwood AM. Spinal cord stimulation for the control of spasticity in patients with chronic spinal cord injury II neurophysiologic observations. CNS Trauma 1986; 3: 145-52. 7. Spiegelmann R, Friedman WA. Spinal cord stimulation a contemporary series Neurosurgery 1991; 28: 65-71.
Molecular
cytogenetics of Prader-Willi and Angelman syndromes
SIR,-We read with interest Professor Hulten and colleagues’ (Sept 7, p 638) on genomic imprinting in an Angelman syndrome (AS) and Prader-Willi syndrome (PWS) translocation family. The two syndromes differ phenotypically but have similar chromosome 15q deletions, inherited from the father in PWSl and letter
mother in AS.2 Hulten et al report an unbalanced 15;22 translocation in index children which was overlooked at first, the children being classified as having the 15q11-13 deletion typical of most patients with PWS and AS. The translocation was detected only after application of specialised cytogenetic techniques, including fluorescent in-situ hybridisation (FISH). Genomic imprinting for PWS and AS has important implications for counselling, and FISH with chromosome 15 probes should be undertaken on apparently sporadic PWS and AS patients to rule out subtle translocations of this chromosome involving the
pericentromeric region. We have seen a second instance of genomic imprinting for PWS and AS, and report our experience with FISH with a pericentromeric chromosome 15 probe in this family and in several sporadic PWS and AS cases. During an evaluation for behaviour and schooling difficulties, a 10-year-old girl was diagnosed as having PWS, on the basis of physical features and history. High-resolution chromosome analysis was normal. Review of the family history revealed that an 11 -year-old male paternal cousin had been diagnosed at 4 years of age with AS. His chromosome analysis revealed the typical 15q deletion seen in AS, and G-banded chromosome 15 polymorphisms showed the deletion to be of maternal origin. Paternal high-resolution cytogenetic studies were normal. These cousins are related in a fashion consistent with the imprinting hypothesis-ie, the father of the PWS child and the mother of the AS child are brother and sister. Our molecular cytogenetic study was extended to 4 males and 7 females with PWS (9 with del [15q] and 2 with normal
ND = no detectable difference
chromosomes),1 female and 2 males with AS (all del [15q]), and the parents of the cousin with AS. We used D15Z1, a satellite non-isotopic probe localised to the pericentromeric area of chromosome 15 (Oncor). By FISH at least 20 cells were analysed; several metaphases were photographed from each case and the presence and size of the fluorescent area on each chromosome 15 was recorded. When possible, the size of the fluorescent body from the deleted chromosome 15 and the normal chromosome was compared (table). Our results indicate a difference in the size of the fluorescent area detected by FISH in 9 of 14 PWS or AS patients, but the smaller fluorescent area did not consistently correlate with the deleted chromosome previously identified by short-arm and stalk-length polymorphisms. A size difference was observed in 1 parent; thus, the technique may be useful for identification of chromosome 15 pericentromeric polymorphisms for parental origin studies. We did not identify any previously undetected translocations involving this region in either the PWS or AS patients or the parents of one of the AS patients. Our study indicates that previously undetectable translocations involving the pericentromeric region of chromosome 15 are rare as a cause of the 15q deletion in PWS or AS patients-but FISH may be a useful technique identifying chromosome 15 polymorphisms so that parental origin can be determined. We thank Pamela Grimm for secretarial help and Lora Miller for technical assistance. Supported by March of Dimes Birth Defects Foundation and Tennessee Department of Mental Health and Mental Retardation.
Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee 37237, USA
MERLIN G. BUTLER
Department of Pediatrics, University of Connecticut and St Francis Hospital and Medical Center, Hartford, Connecticut
MARK A. GREENSTEIN
MG, Palmer CG. Parental origin of chromosome 15 deletion in Prader-Willi syndrome Lancet 1983; ii: 1285-86. 2. Knoll JHM, Nicholls RD, Magenis RE, Graham JM, Lalande M, Latt SA. Angelman and Prader-Willi syndrome share a common chromosome 15 deletion, but differ in parental origin of the deletion. Am J Med Genet 1989; 32: 285-90. 1. Butler
Thrombelastography in pregnant patients on low-dose aspirin SIR,-Dr Mallett and Dr Platt (Sept 21, p 765) report a lack of change on thrombelastography (TEG) after 14 days of daily aspirin 150 mg in 7 female and 18 male healthy volunteers. They also emphasise the many advantages of TEG, a bedside test that evaluates all phases of coagulation. Its variables have been reported to correlate well with the clinical setting. We have been using TEG in our delivery suite for several months to monitor coagulation
Health care for elderly patients in Japan
mg/kg daily for 2 weeks followed by the alternate days for 4 weeks. During the course of therapy 2 patients each had one relapse, in 1 of whom steroid dependence later developed. The number of relapses in the year before institution of levamisole (3-3 [0’5]/patients per year) did not differ from that in the year after it was stopped (2-3 [l’3]/patients course
of prednisolone 2
same amount on
SIR,-When governments in many developed countries began to talk of limiting their health expenditures by rationing, Japan
developed a policy for care of elderly people to cover its lack of social welfare. As in other countries the scheme was prompted by the ageing of the population and the rising cost of their care and treatment, accounting for almost 40% of all medical costs. Japan’s good health insurance coverage and moderate health expenditure in respect of gross national product are well recognised, but what is less well known and specific to Japan is that because of the lack of social policy for elderly care, there is strong competition for entry to the few public nursing homes, and its great national wealth does not assure the Japanese public of a good quality of life at home. There is no suitable housing for disabled and handicapped people, no place for sick and old people or family care for them, and home visiting arrangements are far from satisfactory (only public health nurses visit twice a week). Therefore even after recovery from illness, old people have nowhere to go, and admission to hospital for social continues to inflate the medical cost of care for such because without social support hospitals tend to apply medical procedures to maintain their income. The law for health and medical services for the aged was put into effect in 1983 and amended in 1987. Intermediate (between hospital and home) care facilities were set up nationwide, and there are now 431 homes for 34 752 elderly people which will be expanded to serve 230 000 users. Intermediate facilities are funded partly by the user (about k200 per month) and partly by the government (four times as much as the user). These intermediate homes have fewer medical staff than hospitals and fewer care workers than nursing homes. With the restricted admission criteria neither users nor facility managers are satisfied. The maximum stay is 3 months, and users have to return home (or go to a nursing home) as soon as they can manage daily tasks without help, but housing conditions and the social care system remain the same. As for managers, they must provide the necessary medical help while keeping within the limited budget. Compared with the high cost of private nursing homes, these intermediate care facilities seem attractive for convalescent people. However, the funding system is unsatisfactory because there is no upper limit for users’ payments and there are large numbers of bedridden (700 000) or senile dementia patients (1 million) who cannot afford the fees. Although they offer day-care or short-stay (within 2 weeks), without the need for reform of the social system, they will endanger care for elderly people. Different national health service systems should be compared with respect to outcome assessment to see if this type of national scheme for elderly people provides an efficient and cost-effective service. If so, a wealthy nation like Japan should be able to afford full coverage of social health insurance and achieve good health status indices. reasons
patients,
5-6-9-307 Hanazono, Kumamoto,
Japan 860
KYOKO IMAMURA
Levamisole in nephrotic syndrome StR,—The British Association for Pediatric Nephrology (June 29, p 1555) reports the efficacy and safety of levamisole in
maintaining steroid-free remission in children with steroiddependent nephrotic syndrome. None of the 31 patients treated with levamisole had serious side-effects. The researchers refer to the frequency of neutropenia in this and previous studies, with only 3 of 140 patients having a neutrophil count of less than 2 x 109/1. Manna et aP and Mongeau et al2 also reported that treatment with levamisole was effective in frequently relapsing or steroid-dependent nephrotic syndrome, with minimum sideeffects. Reports of agranulocytosis (neutrophil count < 2 x l0"/l) with levamisole are mostly associated with treatment of connective tissue or neoplastic diseases.3 We have examined the effect of a 12-week course of levamisole in 9 boys and 3 girls with frequently relapsing nephrotic syndrome. The mean age at onset of nephrotic syndrome was 2-2 years and that at onset of therapy was 6’ 3 years. Levamisole was given in a dose of 5 mg/kg on alternate days for 12 weeks. The drug was started immediately after remission had been achieved with a 6-week very low
per
year).
Agranulocytosis developed in 1 patient (total white cell count 1.2 x 109/1; lymphocytes 95%, polymorphonuclear cells 2%, eosinophils 2%, and monocytes 1%) 4 weeks after start of treatment.
After cessation of treatment,
counts
returned
to
normal
days. Further treatment with levamisole was not given. Erythematous pruritic rash developed 4 weeks after the start of therapy in another patient. The drug was stopped and the rash subsided in one month. The drug was reintroduced after another 4 within 10
weeks without recurrence of the rash. Our preliminary results indicate that the effect of treatment with a 12-week course of levamisole is not sustained, and most cases relapse after withdrawal of treatment. A long course of therapy may be effective in maintaining steroid-free remission.1,2 Since the occurrence of agranulocytosis is not dose dependent and cannot be predicted, regular blood counts are necessary. Department of Paediatrics, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110029, India
R. N. SRIVASTAVA A. S. VASUDEV A. BAGGA
AL, Polito C, Gado RD, Foglia AC. Levamisole in children’s idiopathic nephrotic syndrome. Child Nephrol Urol 1988-89; 9: 200-02. 2. Mongeau JG, Robitaille PO, Roy F Clinical efficacy of levamisole in the treatment of primary nephrosis in children Pediatr Nephrol 1988; 2: 398-401. 3. Symoens J, Veys E, Mielanis M. Adverse reactions to levamisole. Cancer Treat Rep 1978; 62: 1721-30. 1 Manna
Safety of transcranial magnetic stimulation in patients with abdominally implanted electronic devices SiR,—Magnetic transcranial stimulation (MTCS) has become a valuable tool in the assessment of descending motor pathways." However, safety in patients with implanted devices remains a concern, and the application of MTCS in patients with implanted cardiac pacemakers and ferromagnetic implants, such as aneurysm clips, is not recommended.4 Patients on spinal cord stimulation (SCS) for the control of pain or spasticity5-7 are also likely to have repeated neurophysiological evaluation, so we decided to investigate in 4 patients the influence of MTCS on internally powered, magnetically controlled (Medtronic) or externally powered, radiofrequency-coupled (Neuromed) SCS pulse generators implanted in the lower abdomen. Since magnetic field strength falls off as the cube of axial distance, we were concerned not so much about displacement of the epidural electrode or damage to the pulse generator as with interactions of the field with the electronic control of the stimulators that affect the on-off mode, amplitude, pulse width, rate, and cathode-anode combination. Patient 1 (65, M; 9-year history of progressive spastic paraparesis) had a Medtronic ’ITREL II’ model 7424 implantable pulse generator connected to a Medtronic ’Pisces Quad’ (four electrode) lead placed epidurally at Til. Patient 2 (48, F; 25-year history of multiple sclerosis) had an identical SCS system with a T11 electrode for control of spasticity. Patient 3 (24, M; spastic tetraparesis due to traumatic brain injury) had a Neuromed MNT-94 pulse generator connected to a Neuromed 1994JF lead at C3. Patient 4 (49, F; chronic pain and spasticity secondary to spinal cord injury) had the same SCS system as patient 3 with a Neuromed 1980JF lead at T12. She also had a drug-delivery system (Medtronic ’Synchromed 8611H’) connected to an intrathecal catheter. These electronic devices were implanted in the lower abdomen in all 4 patients. An estimated peak magnetic flux density of 001 T, determined from measurements made in air using a 1 cm diameter sensing coil, was present at the lead tip in patient 3. All other leads and pulse generators were exposed to less than 0.001 T. In patients 1 and 2 the implanted SCS was turned off before MTCS with a Cadwell MES-10 magnetic stimulator using a 9-5 cm
1276
SUMMARY DATA FROM FISH STUDIES WITH D15Z1
diameter coil placed over the vertex. MTCS was started at 20% output intensity and augmented in increments of 20% up to 100%, corresponding to 2 T. After each increase, the implanted SCS system was checked with a radiofrequency link. MTCS neither turned on the SCS system nor caused any change in control settings. Patients 3 and 4 had MTCS studies with the systems turned on and off. No electrode displacement was noted and no SCS controls (or drug-delivery indices in patient 4) were altered. Normal operation of the implants was noted at the end of the study in all patients. MTCS at the vertex with a Cadwell MES-10 magnetic stimulator seems not to affect adversely the implants used in our study. Our findings allow further investigation of how neuroaugmentative interventions might alter the function of descending motor pathways. Extrapolation to other systems should be done cautiously.
Division of Restorative Neurology and Human Neurobiology, Baylor College of Medicine, Houston, Texas 77030, USA
MARKUS KOFLER A. ARTURO LEIS ARTHUR M. SHERWOOD J. SCOTT DELAPASSE JOHN A. HALTER *,tFlrst cousms
Freeston IL. Non-invasive motor cortex. Lancet 1985; i: 1106-07.
1. Barker AT,
Jalinous R,
magnetic stimulation of human
2. Claus D, Waddy HM, Harding AE, Murray NMF, Thomas PK. Hereditary motor and sensory neuropathies and hereditary spastic paraplegia: a magnetic stimulation study. Ann Neurol 1990; 28: 43-49. 3. Brouwer B, Ashby P. Altered corticospinal projection to lower limb motoneurons in subjects with cerebral palsy Brain 1991; 114: 1395-1407. 4. Cracco RQ. Evaluation of conduction in central motor pathways: techniques, pathophysiology, and clinical interpretation. Neurosurgery 1987; 20: 199-203. 5. Dimitrijevic MM, Dimitrijevic MR, Illis LS, Nakajima K, Sharkey PC, Sherwood AM. Spinal cord stimulation for the control of spasticity in patients with chronic spinal cord injury I. clinical observations. CNS Trauma 1986; 3: 129-44. 6. Dimitrijevic MR, Illis LS, Nakajima K, Sharkey PC, Sherwood AM. Spinal cord stimulation for the control of spasticity in patients with chronic spinal cord injury II neurophysiologic observations. CNS Trauma 1986; 3: 145-52. 7. Spiegelmann R, Friedman WA. Spinal cord stimulation a contemporary series Neurosurgery 1991; 28: 65-71.
Molecular
cytogenetics of Prader-Willi and Angelman syndromes
SIR,-We read with interest Professor Hulten and colleagues’ (Sept 7, p 638) on genomic imprinting in an Angelman syndrome (AS) and Prader-Willi syndrome (PWS) translocation family. The two syndromes differ phenotypically but have similar chromosome 15q deletions, inherited from the father in PWSl and letter
mother in AS.2 Hulten et al report an unbalanced 15;22 translocation in index children which was overlooked at first, the children being classified as having the 15q11-13 deletion typical of most patients with PWS and AS. The translocation was detected only after application of specialised cytogenetic techniques, including fluorescent in-situ hybridisation (FISH). Genomic imprinting for PWS and AS has important implications for counselling, and FISH with chromosome 15 probes should be undertaken on apparently sporadic PWS and AS patients to rule out subtle translocations of this chromosome involving the
pericentromeric region. We have seen a second instance of genomic imprinting for PWS and AS, and report our experience with FISH with a pericentromeric chromosome 15 probe in this family and in several sporadic PWS and AS cases. During an evaluation for behaviour and schooling difficulties, a 10-year-old girl was diagnosed as having PWS, on the basis of physical features and history. High-resolution chromosome analysis was normal. Review of the family history revealed that an 11 -year-old male paternal cousin had been diagnosed at 4 years of age with AS. His chromosome analysis revealed the typical 15q deletion seen in AS, and G-banded chromosome 15 polymorphisms showed the deletion to be of maternal origin. Paternal high-resolution cytogenetic studies were normal. These cousins are related in a fashion consistent with the imprinting hypothesis-ie, the father of the PWS child and the mother of the AS child are brother and sister. Our molecular cytogenetic study was extended to 4 males and 7 females with PWS (9 with del [15q] and 2 with normal
ND = no detectable difference
chromosomes),1 female and 2 males with AS (all del [15q]), and the parents of the cousin with AS. We used D15Z1, a satellite non-isotopic probe localised to the pericentromeric area of chromosome 15 (Oncor). By FISH at least 20 cells were analysed; several metaphases were photographed from each case and the presence and size of the fluorescent area on each chromosome 15 was recorded. When possible, the size of the fluorescent body from the deleted chromosome 15 and the normal chromosome was compared (table). Our results indicate a difference in the size of the fluorescent area detected by FISH in 9 of 14 PWS or AS patients, but the smaller fluorescent area did not consistently correlate with the deleted chromosome previously identified by short-arm and stalk-length polymorphisms. A size difference was observed in 1 parent; thus, the technique may be useful for identification of chromosome 15 pericentromeric polymorphisms for parental origin studies. We did not identify any previously undetected translocations involving this region in either the PWS or AS patients or the parents of one of the AS patients. Our study indicates that previously undetectable translocations involving the pericentromeric region of chromosome 15 are rare as a cause of the 15q deletion in PWS or AS patients-but FISH may be a useful technique identifying chromosome 15 polymorphisms so that parental origin can be determined. We thank Pamela Grimm for secretarial help and Lora Miller for technical assistance. Supported by March of Dimes Birth Defects Foundation and Tennessee Department of Mental Health and Mental Retardation.
Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee 37237, USA
MERLIN G. BUTLER
Department of Pediatrics, University of Connecticut and St Francis Hospital and Medical Center, Hartford, Connecticut
MARK A. GREENSTEIN
MG, Palmer CG. Parental origin of chromosome 15 deletion in Prader-Willi syndrome Lancet 1983; ii: 1285-86. 2. Knoll JHM, Nicholls RD, Magenis RE, Graham JM, Lalande M, Latt SA. Angelman and Prader-Willi syndrome share a common chromosome 15 deletion, but differ in parental origin of the deletion. Am J Med Genet 1989; 32: 285-90. 1. Butler
Thrombelastography in pregnant patients on low-dose aspirin SIR,-Dr Mallett and Dr Platt (Sept 21, p 765) report a lack of change on thrombelastography (TEG) after 14 days of daily aspirin 150 mg in 7 female and 18 male healthy volunteers. They also emphasise the many advantages of TEG, a bedside test that evaluates all phases of coagulation. Its variables have been reported to correlate well with the clinical setting. We have been using TEG in our delivery suite for several months to monitor coagulation
