Radiologic features compared to clinical findings in a prospective study of 153 patients with metastatic spinal cord compression treated by radiotherapy

Summary Plain radiography, myelography and post-myelographic CT-scan are described and related to clinical findings in a prospective study of 153 consecutive patients with myelographic signs of spinal cord compression. The majority of the metastatic tumours arise in the vertebral body or the pedicles. In 80% of the patients with total blockage to the contrast medium on myelography the post-myelographic-CT showed passage of the contrast medium. Ambulatory function at time of diagnosis was correlated to the degree and the localization of the epidural block. In 64 patients who underwent a second myelography, the post-treatment findings of sensory function were correlated to radiological regression.     

Heterogeneity of neocortical cerebral blood flow deficits in dementia of the Alzheimer type: a [99mTc]-d,l-HMPAO SPECT study.

Regional cerebral blood flow (rCBF) was measured with high resolution brain dedicated single photon emission computer tomography (SPECT) and [99mTc]-d,l-hexamethyl-propylene-amine-oxime (HMPAO) in 25 patients with probable Alzheimer's disease and in 25 control subjects, selected according to rigorous inclusion and exclusion criteria. The aim was to analyse the topography of rCBF deficits in individual patients. In the group of patients with Alzheimer's disease as a whole, global CBF was reduced, but a factorial analysis of variance did not show disproportionate reduction of rCBF in any brain region. A parametric analysis of the rCBF data in individual patients was carried out with reference to normal values for internal rCBF ratios and to 13 different abnormal rCBF patterns. These theoretical patterns were predefined by showing significant hypoperfusion in at least one, or in any relevant combination of two, three, or four, of four major brain regions (a left and right frontal and a left and right posterior region). All patients with Alzheimer's disease and none of the control subjects had an abnormal rCBF pattern. Eleven of the 13 different patterns were seen in the patients. Frontal changes were seen in 19 (76%) of the patients, more often than previously reported. No single Alzheimer's disease pattern could be derived from our data. The number of regions with hypoperfusion, but not the presence of frontal changes, correlated significantly with the duration of disease. It is concluded that a clinical diagnosis of probable Alzheimer's disease is associated with heterogeneous patterns of rCBF deficits as measured with SPECT and [99mTc]-d,l-HMPAO. This heterogeneity may reflect different stages of the disease or cognitive subtypes and help explain published discrepancies concerning the topography of hypoperfusion in Alzheimer's disease. An analysis of individual rCBF data may add important information in the investigation of diseases with heterogeneous effects on the brain.     

A -243A-->G polymorphism upstream of the gene encoding GAD65 associates with lower levels of body mass index and glycaemia in a population-based sample of 5857 middle-aged White subjects.

AIMS: The glutamate decarboxylase gene (GAD2) encodes GAD65, an enzyme catalysing the production of the gamma-aminobutyric acid (GABA) which interacts with neuropeptide Y to stimulate food intake. It has been suggested that in pancreatic islets, GABA serves as a functional regulator of pancreatic hormone release. Conflicting results have been reported concerning the potential impact of GAD2 variation on estimates of energy metabolism. The aim of this study was to elucidate potential associations between the GAD2-243A-->G polymorphism and levels of body mass index (BMI) and estimates of glycaemia. METHODS: Using high-throughput chip-based matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, the GAD2-243A-->G (rs2236418) polymorphism was genotyped in a population-based sample (Inter99) of 5857 middle-aged, unrelated Danish White subjects. RESULTS: The G-allele was associated with modestly lower BMI (P = 0.01). In a case-control study of obesity, the G-allele frequency in 2582 participants with BMI < 25 kg/m2 was 19.5% (18.4-20.6) compared with 17.1% (15.5-18.8) in 968 participants having BMI > or = 30 kg/m2 (P = 0.03), odds ratio 0.9 (0.7-1.0). Of the 5857 subjects, GG carriers had lower fasting plasma glucose levels (mmol/l) [AA (n = 3859) 5.6 +/- 0.8; AG (n = 1792) 5.5 +/- 0.8; GG (n = 206) 5.5 +/- 0.8, P = 0.008] and lower 30-min oral glucose tolerance test (OGTT)-related plasma glucose levels (AA 8.7 +/- 1.9; AG 8.6 +/- 1.9; GG 8.6 +/- 2.0, P = 0.04), adjusted for sex, age and BMI. Analysing subjects who were both normoglycaemic and glucose tolerant (n = 4431) GG carriers still had lower fasting plasma glucose concentrations: AA (n = 2895) 5.3 +/- 0.4; AG (n = 1383) 5.3 +/- 0.4; GG (n = 153) 5.2 +/- 0.4 (P = 9.10(-5)). CONCLUSION: The present study suggests that the GAD2-243A-->G polymorphism in a population of middle-aged White people associates with a modest reduction in BMI and fasting and OGTT-related plasma glucose levels.     

Access to primary health care in urban Iceland

The accessibility by telephone of primary health care was studied in Reykjavik and its surrounding municipalities. Comparison was also made between community run health centres and private practices. About 60% of the total population of Iceland live within the study area. The study used medical secretaries as patient substitutes. During the prescribed telephone time, all "patients" were able to make telephone contact with their practice facilities, and 80% reached their doctor within 10 min. The waiting time for non-acute appointments was never more than three days. The study did not detect any difference in accessibility between community run health centres and privately owned GP practices.     

The ubiquitin ligase Rnf6 regulates local LIM kinase 1 levels in axonal growth cones

LIM kinase 1 (LIMK1) controls important cellular functions such as morphogenesis, cell motility, tumor cell metastasis, development of neuronal projections, and growth cone actin dynamics. We have investigated the role of the RING finger protein Rnf6 during neuronal development and detected high Rnf6 protein levels in developing axonal projections of motor and DRG neurons during mouse embryogenesis as well as cultured hippocampal neurons. RNAi-mediated knock-down experiments in primary hippocampal neurons identified Rnf6 as a regulator of axon outgrowth. Consistent with a role in axonal growth, we found that Rnf6 binds to, polyubiquitinates, and targets LIMK1 for proteasomal degradation in growth cones of primary hippocampal neurons. Rnf6 is functionally linked to LIMK1 during the development of axons, as the changes in axon outgrowth induced by up- or down-regulation of Rnf6 levels can be restored by modulation of LIMK1 expression. Thus, these results assign a specific role for Rnf6 in the control of cellular LIMK1 concentrations and indicate a new function for the ubiquitin/proteasome system in regulating local growth cone actin dynamics.