245
this equal prevalence and the prevalence of type 2 diabetes being ten times that of type 1, one can conclude that a patient with type 2 diabetes has a ten-fold less chance of progressing to severe microangiopathy. This is explained by the fact that severe late microangiopathic complications are related to diabetes duration irrespective of the type of diabetes,3 and some patients are too old at onset of NIDDM to live long enough for microvascular complications to develop. Our results for NIDDM are more likely to be underestimates than overestimates because of our criteria for classification and because few type 2 diabetics in France are referred
university centres. Some of our findings do not accord with those of a study in which maculopathy proved uncommon in IDDM.’ Conversely, in that study, proliferative retinopathy was believed to be much less common in NIDDM than in IDDM.4 In our study 42-3% of to
patients with macular oedema had type 1 diabetes and more than 40% with preproliferative or proliferative retinopathy had type 2 disease. Thus for an individual patient, NIDDM is less likely than IDDM to lead to severe late microangiopathic complications, especially when onset is late in life. However, the number of patients with these complications is equally distributed among the two types of diabetes. Department of Diabetes, Hôtel-Dieu Hospital, 75004 Paris, France
G. SLAMA
A. PENFORNIS
M. J. HAARDT J. J. ALTMAN A. BESSE
1. Cowie CC, Port FK, Wolfe RA, Savage PJ, Moll PP, Hawthorne VM. Disparities in incidence of diabetic end-stage renal disease according to race and type of diabetes. N Engl J Med 1989; 321: 1074-79. 2. Klein R, Klein BEK, Moss SE, Davis MD, DeMets DL. The Wisconsm Epidemiologic Study of Diabetic Retinopathy, III. prevalence and risk of diabetic retinopathy when age at diagnosis is 30 or more years Arch Ophthalmol 1984; 102: 527-32. 3. Watkins PJ, Grenfell A, Edmonds M. Diabetic complications of non-insulindependent diabetes. Diabetes Med 1987; 4: 293-96. 4 Frank RN. Diabetic retinopathy: current concepts of evaluation and treatment. Clin Endocrinol Metab 1986; 15: 933-69.
Amyloid &bgr;-protein deposition in skin of patients with dementia SIR,-Amorphous deposits of amyloid p-protein ([iA4), with or without neuritic plaques and neurofibrillary tangles, have been demonstrated in the brains of patients with Alzheimer’s disease (AD), and one report suggested that this protein can be detected immunohistochemically in the skin and intestines of AD and Down’s syndrome patients and in some healthy elderly people.’ Such observations might provide clues to the causes of AD and could prove useful in confirming the clinical diagnosis. To study &bgr;A4 and its precursor protein (APP 695) in the skin of elderly individuals and those with dementia we did 4 mm punch biopsies on the medial side of the upper arm in 35 patients (32 women, 3 men; mean age 81 [10 SD] years) with probable AD, in 15 patients with multi-infarct dementia (MID) (12 women, 3 men; 81 [7] y), and from 19 non-demented controls (17 women, 2 men; 82 [7]). The study was approved by the local ethical committee. All participants or a near relative gave informed consent. All were given a clinical neurological investigation and cognitive status was assessed by mini-mental-status (MMS) examinationactivities of daily living,3 and ischaemic score.4 All patients were long-term inpatients and most were severely demented; MMS scores were 3 (5) for AD, 6 (6) for MID, and 25 (4) for the controls. Skin samples were fixed in 10% neutral formalin. We used a polyclonal antibody at a dilution of 1 in 4000 raised against a synthetic peptide comprising residues 2-43 of the human &bgr;A4 sequence and polyclonal anti-APP695 at 1 in 1500. The antibodies were provided by K. B. Staining was done with the ’Vectastain Elite’ kit (Vector, Burlingame, California). Staining in blood vessels was graded 0 (none) to 3 (intense) and staining in the other regions was recorded as + or - (yes or no). As a negative control the staining was done with omission of primary antibody. No specimens showed immunoreactivity for APP, which accords with a recent report. Positive immunoreactivity for pA4 was seen in small dermal vessels, in the subepithelial region, and in the
epidermal basement membrane area. The staining was often granular. 57% of probable AD patients, 40% of 15 MID patients, and 37% of controls showed pA4 immunoreactivity in dermal blood vessels:
Staining
Controls
All
Probable AD Familial
Sporadic
MID
Immunoreactivity was seen both in the endothelial cells of the vessels and around the vessels. Staining in the basement membrane area was observed in 63%, 60%, and 53% of AD, MID, and controls, respectively. Differences in pA4 immunoreactivity between the three study groups were not significant, even if staining was simply classified as + or -. In 2 AD cases the diagnosis was confirmed at necropsy; these patients’ biopsy samples had not
displayed any pA4 immunoreactivity. A family history was available for 33 probable AD cases. 12 of 14 sporadic cases (86%) and 8 of 19 familial cases (42%) showed endothelial immunoreactivity (p=0’01). Staining in the small dermal vessels did
not
correlate with age, age
at
onset, disease
duration, cognitive performance, activities of daily living, or ischaemic score in AD patients or in controls though the ischaemic score was related to staining in MID patients (r=0-64, n =15, p = 0-0005), and the mean ischaemic score for pA4-negative MID patients was significantly lower than that of positive MID cases 6-0 (2-3) vs 9-0 (2-1); p=0’012. Neither the use of drugs nor
accompanying diseases such as diabetes or arthritis explained pA4 immunoreactivity. pA4 immunoreactivity is thus detectable in the skin of a high proportion of dementia and non-demented individuals. Since some of our controls may be in a preclinical stage of AD (explaining the positive staining) it will be of interest to continue to monitor their cognitive status. HILKKA SOININEN STINA SYRJÄNEN OUTI HEINONEN HEIKKI NEITTAANMÄKI RIITTA MIETTINEN LEO PALJÄRVI KARI SYRJÄNEN
Departments of Neurology, Pathology, and Dermatology, University of Kuopio Centre for Molecular Biology, University of Heidelberg,
Heidelberg, Germany
KONRAD BEYREUTHER
Department of Neurology, University of Kuopio, 70211 Kuopio, Finland
PAAVO RIEKKINEN
1.
Joachim CL, Mon H, Selkoe DJ. Amyloid &bgr;-protein deposition in tissues other than
brain in Alzheimer’s disease. Nature 1989; 341: 226-30. 2. McKhann G, Drachman D, Folstein M, et al. Clinical diagnosis of Alzheimer’s disease: report of NINCDS-ADRDA work group under auspices of Department of Health and Human Services Task Force on Alzheimer’s disease. Neurology 1984; 34: 939-44. 3 American Psychiatric Association. Diagnostic and statistical manual of mental disorders. Washington, DC: APA, 1980. 4. Folstein MF, Folstein SE, McHugh PR. Mini-mental-state. A practical method for
grading cognitive state of patients for the clinician. J Psychiatr Res 1975; 12: 189-98. 5. Arai H, Lee VM-Y, Messinger ML, et al. Expression patterns of &bgr; amyloid precursor protein (&bgr;-APP) in neural and nonneural human tissues from Alzheimer’s disease and centre subjects. Ann Neurol 1991; 30: 686-93.
Intrauterine and
intrapartum transmission of HIV
SiR,—Three letters in The Lancet (Sept 7, p 631; Sept 28, p 829) comment upon our article on HIV viraemia in pregnant women and
their offspring.’1 Dr Johnstone and colleagues claim that we falsely compared newborn babies with 6-month-old children. This was not done because all children were not tested on both occasions. The statistical analysis we did compared viraemia in individual motherchild pairs. This revealed that placental transmission of HIV across the placenta during maternal viraemia was not consistent. Dr Roques and co-workers report that among 30 prospectively studied
this equal prevalence and the prevalence of type 2 diabetes being ten times that of type 1, one can conclude that a patient with type 2 diabetes has a ten-fold less chance of progressing to severe microangiopathy. This is explained by the fact that severe late microangiopathic complications are related to diabetes duration irrespective of the type of diabetes,3 and some patients are too old at onset of NIDDM to live long enough for microvascular complications to develop. Our results for NIDDM are more likely to be underestimates than overestimates because of our criteria for classification and because few type 2 diabetics in France are referred
university centres. Some of our findings do not accord with those of a study in which maculopathy proved uncommon in IDDM.’ Conversely, in that study, proliferative retinopathy was believed to be much less common in NIDDM than in IDDM.4 In our study 42-3% of to
patients with macular oedema had type 1 diabetes and more than 40% with preproliferative or proliferative retinopathy had type 2 disease. Thus for an individual patient, NIDDM is less likely than IDDM to lead to severe late microangiopathic complications, especially when onset is late in life. However, the number of patients with these complications is equally distributed among the two types of diabetes. Department of Diabetes, Hôtel-Dieu Hospital, 75004 Paris, France
G. SLAMA
A. PENFORNIS
M. J. HAARDT J. J. ALTMAN A. BESSE
1. Cowie CC, Port FK, Wolfe RA, Savage PJ, Moll PP, Hawthorne VM. Disparities in incidence of diabetic end-stage renal disease according to race and type of diabetes. N Engl J Med 1989; 321: 1074-79. 2. Klein R, Klein BEK, Moss SE, Davis MD, DeMets DL. The Wisconsm Epidemiologic Study of Diabetic Retinopathy, III. prevalence and risk of diabetic retinopathy when age at diagnosis is 30 or more years Arch Ophthalmol 1984; 102: 527-32. 3. Watkins PJ, Grenfell A, Edmonds M. Diabetic complications of non-insulindependent diabetes. Diabetes Med 1987; 4: 293-96. 4 Frank RN. Diabetic retinopathy: current concepts of evaluation and treatment. Clin Endocrinol Metab 1986; 15: 933-69.
Amyloid &bgr;-protein deposition in skin of patients with dementia SIR,-Amorphous deposits of amyloid p-protein ([iA4), with or without neuritic plaques and neurofibrillary tangles, have been demonstrated in the brains of patients with Alzheimer’s disease (AD), and one report suggested that this protein can be detected immunohistochemically in the skin and intestines of AD and Down’s syndrome patients and in some healthy elderly people.’ Such observations might provide clues to the causes of AD and could prove useful in confirming the clinical diagnosis. To study &bgr;A4 and its precursor protein (APP 695) in the skin of elderly individuals and those with dementia we did 4 mm punch biopsies on the medial side of the upper arm in 35 patients (32 women, 3 men; mean age 81 [10 SD] years) with probable AD, in 15 patients with multi-infarct dementia (MID) (12 women, 3 men; 81 [7] y), and from 19 non-demented controls (17 women, 2 men; 82 [7]). The study was approved by the local ethical committee. All participants or a near relative gave informed consent. All were given a clinical neurological investigation and cognitive status was assessed by mini-mental-status (MMS) examinationactivities of daily living,3 and ischaemic score.4 All patients were long-term inpatients and most were severely demented; MMS scores were 3 (5) for AD, 6 (6) for MID, and 25 (4) for the controls. Skin samples were fixed in 10% neutral formalin. We used a polyclonal antibody at a dilution of 1 in 4000 raised against a synthetic peptide comprising residues 2-43 of the human &bgr;A4 sequence and polyclonal anti-APP695 at 1 in 1500. The antibodies were provided by K. B. Staining was done with the ’Vectastain Elite’ kit (Vector, Burlingame, California). Staining in blood vessels was graded 0 (none) to 3 (intense) and staining in the other regions was recorded as + or - (yes or no). As a negative control the staining was done with omission of primary antibody. No specimens showed immunoreactivity for APP, which accords with a recent report. Positive immunoreactivity for pA4 was seen in small dermal vessels, in the subepithelial region, and in the
epidermal basement membrane area. The staining was often granular. 57% of probable AD patients, 40% of 15 MID patients, and 37% of controls showed pA4 immunoreactivity in dermal blood vessels:
Staining
Controls
All
Probable AD Familial
Sporadic
MID
Immunoreactivity was seen both in the endothelial cells of the vessels and around the vessels. Staining in the basement membrane area was observed in 63%, 60%, and 53% of AD, MID, and controls, respectively. Differences in pA4 immunoreactivity between the three study groups were not significant, even if staining was simply classified as + or -. In 2 AD cases the diagnosis was confirmed at necropsy; these patients’ biopsy samples had not
displayed any pA4 immunoreactivity. A family history was available for 33 probable AD cases. 12 of 14 sporadic cases (86%) and 8 of 19 familial cases (42%) showed endothelial immunoreactivity (p=0’01). Staining in the small dermal vessels did
not
correlate with age, age
at
onset, disease
duration, cognitive performance, activities of daily living, or ischaemic score in AD patients or in controls though the ischaemic score was related to staining in MID patients (r=0-64, n =15, p = 0-0005), and the mean ischaemic score for pA4-negative MID patients was significantly lower than that of positive MID cases 6-0 (2-3) vs 9-0 (2-1); p=0’012. Neither the use of drugs nor
accompanying diseases such as diabetes or arthritis explained pA4 immunoreactivity. pA4 immunoreactivity is thus detectable in the skin of a high proportion of dementia and non-demented individuals. Since some of our controls may be in a preclinical stage of AD (explaining the positive staining) it will be of interest to continue to monitor their cognitive status. HILKKA SOININEN STINA SYRJÄNEN OUTI HEINONEN HEIKKI NEITTAANMÄKI RIITTA MIETTINEN LEO PALJÄRVI KARI SYRJÄNEN
Departments of Neurology, Pathology, and Dermatology, University of Kuopio Centre for Molecular Biology, University of Heidelberg,
Heidelberg, Germany
KONRAD BEYREUTHER
Department of Neurology, University of Kuopio, 70211 Kuopio, Finland
PAAVO RIEKKINEN
1.
Joachim CL, Mon H, Selkoe DJ. Amyloid &bgr;-protein deposition in tissues other than
brain in Alzheimer’s disease. Nature 1989; 341: 226-30. 2. McKhann G, Drachman D, Folstein M, et al. Clinical diagnosis of Alzheimer’s disease: report of NINCDS-ADRDA work group under auspices of Department of Health and Human Services Task Force on Alzheimer’s disease. Neurology 1984; 34: 939-44. 3 American Psychiatric Association. Diagnostic and statistical manual of mental disorders. Washington, DC: APA, 1980. 4. Folstein MF, Folstein SE, McHugh PR. Mini-mental-state. A practical method for
grading cognitive state of patients for the clinician. J Psychiatr Res 1975; 12: 189-98. 5. Arai H, Lee VM-Y, Messinger ML, et al. Expression patterns of &bgr; amyloid precursor protein (&bgr;-APP) in neural and nonneural human tissues from Alzheimer’s disease and centre subjects. Ann Neurol 1991; 30: 686-93.
Intrauterine and
intrapartum transmission of HIV
SiR,—Three letters in The Lancet (Sept 7, p 631; Sept 28, p 829) comment upon our article on HIV viraemia in pregnant women and
their offspring.’1 Dr Johnstone and colleagues claim that we falsely compared newborn babies with 6-month-old children. This was not done because all children were not tested on both occasions. The statistical analysis we did compared viraemia in individual motherchild pairs. This revealed that placental transmission of HIV across the placenta during maternal viraemia was not consistent. Dr Roques and co-workers report that among 30 prospectively studied
