635
Screening for osteoporosis SIR,-We were surprised by Dr Raffle and Dr Cooper’s (July 28, p 242) dismissal of screening for osteoporosis. The National Osteoporosis Society (NOS) is campaigning for improved diagnosis, treatment, and prevention of osteoporosis. Hip fractures due to osteoporosis’ and spinal osteoporosis, which affects a younger age group of women and causes long-term pain and deformity, are growing problems. As part of this campaign the NOS has called for bone density DEXA screening to become more widely available for high-risk women (eg, those with early menopause, early hysterectomy, early oophorectomy, or a strong family history of osteoporosis, and users of high-dose corticosteroids). We agree that hormone replacement therapy (HRT) should be considered for all menopausal women, but those without symptoms are unlikely to comply in the longterm unless low density on a bone scan
shows that such
treatment
is necessary. Most
general
practitioners are unwilling to offer HRT unless these two criteria are met. HRT has proved to reduce the relative risk of hip fracture little as 0.32.2 The NOS is concerned that dismissal of screening will discourage many health authorities from installing diagnostic machines. There are only forty DEXA bone-density screening machines in over two hundred authorities and few of these are available for general practitioner referrals in the National Health Service-most are used for private practice or for research. This facility can thus hardly be described as a "screening juggernaut". The NOS believes in and is raising funds for further research, but Raffle and Cooper seem to want another 10 years of research until the exact answer is found, which is unhelpful to the present generation of menopausal women. The half a million people who have written to us in the past year want the benefit of the best advice we have now, and want either treatment or reassurance that they do not need treatment. We are not advocating long-term HRT for all women but it seems clear that we need to screen this high-risk group. to as
National Osteoporosis Barton Meade House, P0 Box 10, Radstock, Bath BA3 3YB, UK
Society,
ALLAN DIXON, Chairman
LINDA EDWARDS, Director
1 Fractured neck of
femur, prevention and management. London: Royal College of Physicians of London, January, 1989. 2. Kiel DP, Felson DT, Anderson JJ, Wilson PNF, Moskowitz MA. Hip fracture and the use of oestrogens in postmenopausal women: the Framingham study. N Engl J Med 1987; 317: 1169-74.
Gallium-transferrin binding in Alzheimer’s disease SIR,-Dr Farrar and colleagues reported (March 31, p747) a significantly lower gallium-transferrin binding in patients with dementia of the Alzheimer type than in younger healthy controls. Their results were critisised by Dr Spear (June 2, p 1348) for the lack of strict diagnostic criteria and, furthermore, for the possibility that they could be due to age differences between the groups. We have tried to replicate the findings of Farrar et al by investigating 6’Ga binding in patients diagnosed as having probable Alzheimer’s disease according to NINCDS-ADRDA criteria,1 and in healthy age and sex matched controls. Binding of6’Ga to plasma proteins was measured as described by Farrar et al, with the following modifications: (1) only 0-5 ml of plasma was used; (2) the incubation and gel filtration media included 20 mmol/l NaHC03; and (3) bound and free 6’Ga were separated by gel-filtration on ’Sephadex G-25’. Composition of the RESULTS OF GALLIUM-67 BINDING STUDIES
study groups and the percentages of 67Ga binding to plasma proteins are shown in the table. Patients had moderate to severe dementia of the Alzheimer type with mini-mental-state scores (maximum 30) ranging from 0 to 14 (mean 4-1). Gallium binding in the dementia group was significantly lower than in controls (one-tailed t-test; F 9-81; p 0-042). Our results confirm those of Farrar et al. We are exploring the possibility that these findings may relate to the severity of cognitive impairment and the degree of cerebral atrophy as measured by computed tomography. Our preliminary results indicate that this may indeed be the case. =
=
Institute of
Department of Neuroscience, Psychiatry
M. BRAMMER S. RICHMOND
Section of Old Age Psychiatry, Institute of Psychiatry, London SE5 8AF, UK
A. BURNS H. FÖRSTL R. LEVY
1. McKhann G, Drachman D, Folstein M, et al. Clinical diagnosis of Alzheimer’s disease report on the NINCDS-ADRDA work group under the auspices of the Department of Health and Human Services Task Force on Alzheimer’s disease. Neurology 1984; 34: 939-44.
Diagnosis of hepatic encephalopathy by proton magnetic resonance spectroscopy SIR,-We have applied the non-invasive technique of proton magnetic resonance spectroscopy (lH-MRS) to identify increased cerebral glutamine concentrations in a 66-year-old woman with chronic hepatic encephalopathy, grade 1. A second and unexpected abnormality was observed in this patient and in two others with proven, but milder hepatic encephalopathy (grade 0), which led to the proposition that ’H-MRS may provide information for both diagnosis and prognosis. Besides 10 age- and sex-matched normal control subjects, 7 other patients were examined: 4 with well-compensated liver disease (one with diabetes mellitus); 2 with elevated blood urea; and 1 with stroke. We used a General Electric 1.5 T MR scanner with the standard imaging head coil. Localisation of the investigated voxels (14-27 ml in the parietal cortex) was achieved by use of a modified stimulated echo sequence1,2 with presaturation of the water signal (TE 30 ms, TM 13-7 ms, TR 15 s, 256-512 scans, 50 min total examination
time). The spectrum in the patient with grade 1 encephalopathy shows three principal abnormalities (figure). Spectra obtained on four separate occasions showed the same differences: (1) The peak urea between 2 0and 2-5ppm is significantly altered (A), the changes being compatible with an increase in glutamine (&bgr;, y proton) with respect to the concentration of N-acetyl aspartate
(NAA). (2) The peak at 3-78 ppm is increased, which is in agreement with an increase of the triplet due to the a-proton of glutamine. The spectra of the patients with grade 0 encephalopathy showed similar but less striking changes. (3) A peak at 3-58 ppm, which was prominent in all 17 controls was reduced to 40% of normal in all 3 patients with hepatic encephalopathy (14 spectra). The main portion of this peak is usually attributed to inositol containing compounds. However, glycine may contribute up to 15%.3 The demonstration of an increased glutamine concentration by 1H-MRS offers a unique non-invasive biochemical diagnosis in chronic hepatic encephalopathy. The additional finding concerns the more than 60% reduction in cerebral inositol (especially myoinositol, we suggest). This was observed in all three patients, and might therefore be dissociated from the increased glutamine content. By comparing spectra of controls and of myoinositol phantoms we estimate the normal human cerebral myoinositol content to be equal to that of NAA (5-5 mmol/1’*). This figure is similar to that found chemically for myoinositol in the rat brain (5 -7 mmol/1),s supporting the view that the metabolite depleted from the brain in hepatic encephalopathy is myoinositol. We propose myoinositol as a marker of chronic hepatic encephalopathy, since its concentration is unchanged in patients
Screening for osteoporosis SIR,-We were surprised by Dr Raffle and Dr Cooper’s (July 28, p 242) dismissal of screening for osteoporosis. The National Osteoporosis Society (NOS) is campaigning for improved diagnosis, treatment, and prevention of osteoporosis. Hip fractures due to osteoporosis’ and spinal osteoporosis, which affects a younger age group of women and causes long-term pain and deformity, are growing problems. As part of this campaign the NOS has called for bone density DEXA screening to become more widely available for high-risk women (eg, those with early menopause, early hysterectomy, early oophorectomy, or a strong family history of osteoporosis, and users of high-dose corticosteroids). We agree that hormone replacement therapy (HRT) should be considered for all menopausal women, but those without symptoms are unlikely to comply in the longterm unless low density on a bone scan
shows that such
treatment
is necessary. Most
general
practitioners are unwilling to offer HRT unless these two criteria are met. HRT has proved to reduce the relative risk of hip fracture little as 0.32.2 The NOS is concerned that dismissal of screening will discourage many health authorities from installing diagnostic machines. There are only forty DEXA bone-density screening machines in over two hundred authorities and few of these are available for general practitioner referrals in the National Health Service-most are used for private practice or for research. This facility can thus hardly be described as a "screening juggernaut". The NOS believes in and is raising funds for further research, but Raffle and Cooper seem to want another 10 years of research until the exact answer is found, which is unhelpful to the present generation of menopausal women. The half a million people who have written to us in the past year want the benefit of the best advice we have now, and want either treatment or reassurance that they do not need treatment. We are not advocating long-term HRT for all women but it seems clear that we need to screen this high-risk group. to as
National Osteoporosis Barton Meade House, P0 Box 10, Radstock, Bath BA3 3YB, UK
Society,
ALLAN DIXON, Chairman
LINDA EDWARDS, Director
1 Fractured neck of
femur, prevention and management. London: Royal College of Physicians of London, January, 1989. 2. Kiel DP, Felson DT, Anderson JJ, Wilson PNF, Moskowitz MA. Hip fracture and the use of oestrogens in postmenopausal women: the Framingham study. N Engl J Med 1987; 317: 1169-74.
Gallium-transferrin binding in Alzheimer’s disease SIR,-Dr Farrar and colleagues reported (March 31, p747) a significantly lower gallium-transferrin binding in patients with dementia of the Alzheimer type than in younger healthy controls. Their results were critisised by Dr Spear (June 2, p 1348) for the lack of strict diagnostic criteria and, furthermore, for the possibility that they could be due to age differences between the groups. We have tried to replicate the findings of Farrar et al by investigating 6’Ga binding in patients diagnosed as having probable Alzheimer’s disease according to NINCDS-ADRDA criteria,1 and in healthy age and sex matched controls. Binding of6’Ga to plasma proteins was measured as described by Farrar et al, with the following modifications: (1) only 0-5 ml of plasma was used; (2) the incubation and gel filtration media included 20 mmol/l NaHC03; and (3) bound and free 6’Ga were separated by gel-filtration on ’Sephadex G-25’. Composition of the RESULTS OF GALLIUM-67 BINDING STUDIES
study groups and the percentages of 67Ga binding to plasma proteins are shown in the table. Patients had moderate to severe dementia of the Alzheimer type with mini-mental-state scores (maximum 30) ranging from 0 to 14 (mean 4-1). Gallium binding in the dementia group was significantly lower than in controls (one-tailed t-test; F 9-81; p 0-042). Our results confirm those of Farrar et al. We are exploring the possibility that these findings may relate to the severity of cognitive impairment and the degree of cerebral atrophy as measured by computed tomography. Our preliminary results indicate that this may indeed be the case. =
=
Institute of
Department of Neuroscience, Psychiatry
M. BRAMMER S. RICHMOND
Section of Old Age Psychiatry, Institute of Psychiatry, London SE5 8AF, UK
A. BURNS H. FÖRSTL R. LEVY
1. McKhann G, Drachman D, Folstein M, et al. Clinical diagnosis of Alzheimer’s disease report on the NINCDS-ADRDA work group under the auspices of the Department of Health and Human Services Task Force on Alzheimer’s disease. Neurology 1984; 34: 939-44.
Diagnosis of hepatic encephalopathy by proton magnetic resonance spectroscopy SIR,-We have applied the non-invasive technique of proton magnetic resonance spectroscopy (lH-MRS) to identify increased cerebral glutamine concentrations in a 66-year-old woman with chronic hepatic encephalopathy, grade 1. A second and unexpected abnormality was observed in this patient and in two others with proven, but milder hepatic encephalopathy (grade 0), which led to the proposition that ’H-MRS may provide information for both diagnosis and prognosis. Besides 10 age- and sex-matched normal control subjects, 7 other patients were examined: 4 with well-compensated liver disease (one with diabetes mellitus); 2 with elevated blood urea; and 1 with stroke. We used a General Electric 1.5 T MR scanner with the standard imaging head coil. Localisation of the investigated voxels (14-27 ml in the parietal cortex) was achieved by use of a modified stimulated echo sequence1,2 with presaturation of the water signal (TE 30 ms, TM 13-7 ms, TR 15 s, 256-512 scans, 50 min total examination
time). The spectrum in the patient with grade 1 encephalopathy shows three principal abnormalities (figure). Spectra obtained on four separate occasions showed the same differences: (1) The peak urea between 2 0and 2-5ppm is significantly altered (A), the changes being compatible with an increase in glutamine (&bgr;, y proton) with respect to the concentration of N-acetyl aspartate
(NAA). (2) The peak at 3-78 ppm is increased, which is in agreement with an increase of the triplet due to the a-proton of glutamine. The spectra of the patients with grade 0 encephalopathy showed similar but less striking changes. (3) A peak at 3-58 ppm, which was prominent in all 17 controls was reduced to 40% of normal in all 3 patients with hepatic encephalopathy (14 spectra). The main portion of this peak is usually attributed to inositol containing compounds. However, glycine may contribute up to 15%.3 The demonstration of an increased glutamine concentration by 1H-MRS offers a unique non-invasive biochemical diagnosis in chronic hepatic encephalopathy. The additional finding concerns the more than 60% reduction in cerebral inositol (especially myoinositol, we suggest). This was observed in all three patients, and might therefore be dissociated from the increased glutamine content. By comparing spectra of controls and of myoinositol phantoms we estimate the normal human cerebral myoinositol content to be equal to that of NAA (5-5 mmol/1’*). This figure is similar to that found chemically for myoinositol in the rat brain (5 -7 mmol/1),s supporting the view that the metabolite depleted from the brain in hepatic encephalopathy is myoinositol. We propose myoinositol as a marker of chronic hepatic encephalopathy, since its concentration is unchanged in patients
