Diabetes mellitus, hypertension and medial temporal lobe atrophy: the LADIS study.

HYPOTHESIS: Based on recent findings on the association between vascular risk factors and hippocampal atrophy, we hypothesized that hypertension and diabetes mellitus (DM) are associated with medial temporal lobe atrophy (MTA) in subjects without disability, independent of the severity of white matter hyperintensities. METHODS: In the Leukoaraiosis And DISability in the elderly (LADIS) study, we investigated the relationships between DM, hypertension, blood pressure and MTA in 582 subjects, stratified by white matter hyperintensity severity, using multinomial logistic regression. MTA was visually scored for the left and right medial temporal lobe (score 0-4), and meaned. RESULTS: Mean age was 73.5 years (sd 5.1), 54% was female. Of the subjects, 15% had DM, and 70% had a history of hypertension. The likelihood of having MTA score 3 was significantly higher in subjects with DM (OR 2.9; 95% CI: 1.1-7.8) compared with an MTA score of 0 (no atrophy). The odds ratio for MTA score 2 was not significantly increased (OR 1.8; CI: 0.9-4). Systolic and diastolic blood pressure and a history of hypertension were not associated with MTA. There was no interaction between DM and hypertension. Stratification on white matter hyperintensities (WMH) did not alter the associations. CONCLUSION: Our study strengthens the observation that MTA is associated with DM, independently of the amount of small vessel disease as reflected by WMH.     

L-Ala-substituted rat galanin analogs distinguish between hypothalamic and jejunal galanin receptor subtypes

In order to explore which amino acids or which blocks of amino acids in the 29 amino acid neuropeptide galanin are important for recognition of the endogenous ligand by galanin receptor subtypes present in the jejunum and in the hypothalamus, respectively, we have carried out L-Ala substitutions of individual amino acids or of blocks of amino acids in the rat galanin sequence and examined the binding of the obtained analogs to the rat hypothalamic and jejunal galanin receptor subtypes. This study reveals that the galanin sequence YLLGPH^9–14 is essential for recognition of galanin by both the rat hypothalamic and jejunal galanin receptor subtypes. Substitution of the N-terminal amino acids, GWTL^1–4, leads to total loss of affinity of galanin for both hypothalamic and jejunal galanin receptors. The α-helical C-terminal amino acid (25–29) part of galanin has no greater influence on the affinity of galanin to the hypothalamic galanin receptor subtype. L-Ala substitution of the C-terminal amino acids of galanin KHGLT^25–29 shows, however, that this C-terminal motif is essential for the recognition by the jejunal galanin receptor subtype, whereas amino acids in the middle portion of galanin NSAG^5–8 are of importance for binding to the hypothalamic but not to the jejunal receptor. [Ala^5–8] Galanin thus has a more than 100-fold higher affinity to jejunal receptor than to the hypothalamic receptor, while [Ala^25–29] galanin has a more than 100-fold higher affinity for the hypothalamic than for jejunal galanin receptor subtypes. pH dependence of the galanin binding to these receptor subtypes is also different. © Munksgaard 1997.     

Health Experience of Compressed Air Workers during Construction of the Mass Transit Railway in Hong Kong

This paper reports the health experience of compressed air workersduring construction of the Island Line Section of the Mass TransitRailway in Hong Kong. The requirements of CIRIA's Code of Practiceincluding specifications of the Blackpool Tables for decompressionprocedures and the employment of doctors to monitor the healthof exposed workers by regular examination were prescribed bylocal legislation. Over a 3 year period there were 394 716 man-decompressionsfrom pressures between 1 and 3-5 kg/cm² with 2032 cases of acutedecompression sickness giving a bends rate of 0-52 per cent.The epidemiology followed the usual pattern of increase in bendsrate with increase in pressure and length of shift and withage. Most attacks occurred within a short period after decompressionand the majority of limb pains affected the leg. There werealso 10 cases of barotrauma and 22 cases of dysbaric osteonecrosisof which 7 resulted in some disability. The low incidence ofillness was an index of the effectiveness of the Code of Practiceas applied to a large scale compressed air work operation butthe toll of dysbarism, albeit small, underlines the problemthat there are as yet no decompression procedures which willprotect all men at all times and indicates the need for furtherresearch and work-site evaluation. Requests for reprints should be addressed to: W. K. Lo, Occupational Health Division, Labour Department Headquarters, Harbour Building, 38 Pier Road, Central Hong Kong.     

Localized pachydermodactyly in tuberous sclerosis

Pachydermodactyly refers to a rare form of digital fibromatosis involving the proximal portions of the fingers. There are only nine cases reported in the literature, ill idiopathic and occurring in young men. We report a 5-year-old Chinese boy with tuberous sclerosis who presented with localized pachydermodactyly since birth. This congenital form of pachydermodactyly may represent an additional cutaneous sign of tuberous sclerosis.     

Changes of hepatic and systemic haemodynamics following somatostatin administration in patients with hepatitis B-related cirrhosis

Abstract Somatostatin has been used to effectively control acute variceal haemorrhage, with conjectured mechanisms on portal hypertension. We, therefore, evaluated the effects of somatostatin on hepatic and systemic haemodynamics in 15 patients with hepatitis B-related cirrhosis and portal hypertension. All patients received an intravenous, continuous infusion of somatostatin 250 μg/h, following a bolus injection of 250 μg. In systemic haemodynamics, the mean arterial pressure (MAP) increased ( P < 0.05), associated with a reflex bradycardia within 3 min following bolus injections, compared with basal values. The right atrial pressure, pulmonary capillary wedge pressure, inferior vena cava pressure, cardiac index, and systemic vascular resistance remained unaffected after drug infusion. In hepatic haemodynamics, the wedge hepatic vein pressure remained unchanged after drug administration. However, there was an increase in free hepatic vein pressure (FHVP; P < 0.05), and a trend toward a decrease in the hepatic vein pressure gradient (HVPG; P = 0.063), within 3 min after bolus injection. Furthermore, the hepatic blood flow decreased significantly at 10 and 30 min after somatostatin infusion ( P < 0.05). The effective sinusoidal perfusion assessed by indocyanine green infusion also decreased progressively at 10 min ( P = 0.057) and 30 min ( P < 0.05). We concluded that somatostatin, at the dose used in this study, caused a transient and bolus-related vasoconstrictive effect, resulting in increases in MAP and FHVP, a decrease in heart rate, and a trend toward lower HVPG. In addition, somatostatin reduced the hepatic blood flow and effective sinusoidal perfusion which may be hazardous to cirrhotic patients during variceal haemorrhage.     

Increased frequency of a new polymorphism in the cell division cycle 2 (cdc2) gene in patients with Alzheimer's disease and frontotemporal dementia

Recent studies show linkage between Alzheimer's disease (AD) and two loci on chromosome 10. The cell division cycle 2 (cdc2) gene is located close to one of the chromosome 10 markers, and is a candidate gene for AD since it is involved in the pathogenesis of AD. We sequenced coding exons and flanking intronic sequences and the promoter region on the cdc2 gene and found three new single nucleotide polymorphisms (SNPs). We analyzed 272 Caucasian AD cases, 160 controls and 70 cases with frontotemporal dementia (FTD) for these SNPs. Homozygosity for one of the SNPs (Ex6+7I/D) was more frequent in both AD and FTD cases than in controls. In the combined tauopathy (AD and FTD) group the odds ratio (OR) was 1.77 (95% CI 1.19-2.63) for the Ex6+7II genotype. Our findings suggest that the Ex6+7I allele is associated with tauopathies, both AD and FTD.     

Evaluation of linear registration algorithms for brain SPECT and the errors due to hypoperfusion lesions

The semiquantitative analysis of perfusion single-photon emission computed tomography (SPECT) images requires a reproducible, objective method. Automated spatial standardization (registration) of images is a prerequisite to this goal. A source of registration error is the presence of hypoperfusion defects, which was evaluated in this study with simulated lesions. The brain perfusion images measured by 99mTc-HMPAO SPECT from 21 patients with probable Alzheimer's disease and 35 control subjects were retrospectively analyzed. An automatic segmentation method was developed to remove external activity. Three registration methods, robust least squares, normalized mutual information (NMI), and count difference were implemented and the effects of simulated defects were compared. The tested registration methods required segmentation of the cerebrum from external activity, and the automatic and manual methods differed by a three-dimensional displacement of 1.4+/-1.1 mm. NMI registration proved to be least adversely effected by simulated defects with 3 mm average displacement caused by severe defects. The error in quantifying the patient-template parietal ratio due to misregistration was 2.0% for large defects (70% hypoperfusion) and 0.5% for smaller defects (85% hypoperfusion).     

Tau immunoreactivity detected in human plasma, but no obvious increase in dementia

Tau proteins are central to the neuropathology of Alzheimer's disease and tau levels in cerebrospinal fluid are elevated in affected individuals. In this study, we investigated the presence of tau in plasma from subjects with Alzheimer's disease (n = 16), frontotemporal dementia (n = 10), vascular dementia (n = 16) and from healthy controls (n = 15). By using an ELISA with monoclonal tau antibodies, tau immunoreactivity was detected in approximately 20% of the subjects. However, no difference between the disease and control groups was seen. After gel filtration of tau immunopositive plasma, the peak reactivity was found in the 160-kD fraction, indicating the source to be tau-like molecules of high-molecular-weight or polymers of low-molecular-weight tau isoforms. We conclude that measurements of tau in plasma cannot be utilized diagnostically for Alzheimer's disease or for the other dementias investigated. Copyrightz1999S.KargerAG,Basel