Hyperpipecolic acidaemia: a diagnostic tool for peroxisomal disorders

Peroxisomal disorders include a complex spectrum of diseases, characterized by a high heterogeneity from both the clinical and the biochemical points of view. Specific assays are required for the study of peroxisome metabolism. Among these, pipecolic acid evaluation is considered as a supplementary test. We have established the diagnostic role of pipecolic acid in 30 patients affected by a peroxisomal defect (5 Zellweger syndromes, 10 Infantile Refsum diseases, 1 neonatal adrenoleukodystrophy, 6 patients affected by a peroxisomal biogenesis disorder with unclassified phenotype, 1 case of rhizomelic chondrodysplasia punctata (RCDP), 2 acyl-CoA oxidase deficiencies, 2 bifunctional enzyme deficiencies, 2 Refsum diseases, and 1 beta-oxidation deficiency). Pipecolic acid was increased in all generalized peroxisomal disorders, while normal pipecolic acid with abnormal very long chain fatty acid concentrations was strong evidence for a single peroxisomal enzyme deficiency. Unexpectedly, hyperpipecolic acidaemia was found also in a child affected by RCDP and in two patients with Refsum disease. In six patients the suggestion of a peroxisomal disorder was raised by the fortuitous finding of a pipecolic acid peak in amino acid chromatography, routinely performed as a general metabolic screening. For all patients, pipecolic acid proved to be a useful parameter in the biochemical classification of peroxisomal disorders.     

Identification of high risk patients with severe, but asymptomatic aortic stenosis

Whether asymptomatic patients with severe aortic stenosis benefit from surgery remains unclear. We report our data recently published in the New England Journal of Medicine on the natural history of this disease and predictors of outcome.     

Functional Cluster Analysis of CT Perfusion Maps: A New Tool for Diagnosis of Acute Stroke?

CT perfusion imaging constitutes an important contribution to the early diagnosis of acute stroke. Cerebral blood flow (CBF), cerebral blood volume (CBV) and time-to-peak (TTP) maps are used to estimate the severity of cerebral damage after acute ischemia. We introduce functional cluster analysis as a new tool to evaluate CT perfusion in order to identify normal brain, ischemic tissue and large vessels. CBF, CBV and TTP maps represent the basis for cluster analysis applying a partitioning (k-means) and density-based (density-based spatial clustering of applications with noise, DBSCAN) paradigm. In patients with transient ischemic attack and stroke, cluster analysis identified brain areas with distinct hemodynamic properties (gray and white matter) and segmented territorial ischemia. CBF, CBV and TTP values of each detected cluster were displayed. Our preliminary results indicate that functional cluster analysis of CT perfusion maps may become a helpful tool for the interpretation of perfusion maps and provide a rapid means for the segmentation of ischemic tissue.     

Spatial analysis of the distribution of Ixodes dammini (Acari: Ixodidae) on white-tailed deer in Ogle County, Illinois.

The pattern of infestations of Ixodes dammini on white-tailed deer in Ogle County in Illinois was studied through examinations of hunted deer from 1988 to 1990. The Illinois Geographic Information System mapped the spatial distribution of tick infestations on deer and related it to a known endemic focus for I. dammini and Borrelia burgdorferi (Castle Rock State Park), and to a major waterway (Rock River). Second-order neighborhood analysis was used to analyze the spatial distribution of deer around Castle Rock State Park. More than 25% of deer were infested. All deer were clustered around CRSP, but the clustering resulted mostly from clustering of infested deer around CRSP. CRSP is apparently the only important source of tick infestations in Ogle County. Clustering of infested deer did not change during the 3-yr study period. The dispersion pattern of ticks on deer was aggregated, with twice and three times as many ticks collected from bucks as from does and from fawns, respectively. More male ticks than female ticks were collected from infested deer. Of 59 ticks removed from harvested deer in 1990, 5.1% tested positive for B. burgdorferi.     

Numerical and structural chromosomal abnormalities detected in human sperm with a combination of multicolor FISH assays

A pair of multicolor FISH assays (X-Y-21 and A-M-16) was developed for human sperm to simultaneously measure sex ratios; aneuploidies involving chromosomes 1, 16, 21, X, and Y; meiotic diploidies; and structural aberrations involving chromosome 1p. Sex ratios in sperm were not significantly different from unity among healthy men. Baseline frequencies of disomic sperm for chromosomes 1, 8, and 21 were similar (6.7 per 10(4) sperm, 95% CI of 5.6-8.1), suggesting that among these three chromosomes, chromosome 21 was not especially prone to nondisjunction. Frequencies of disomy 16 sperm were significantly lower, however (3.5 per 10(4) sperm, 95% CI of 2.0-6.2; P < 0.02). The baseline frequencies of sperm disomy by FISH for chromosomes 16 and 21 were validated against aneuploidy data obtained by the hamster-egg technique for human sperm cytogenetics. The frequencies of X-X, Y-Y, X-Y ("Klinefelter") sperm and sex-null ("Turner") sperm were 5.5, 5.1, 5.5, and 7.8 per 10(4) sperm, respectively. For chromosomes 16 and 21, the frequencies of nullisomic and disomic sperm were similar, suggesting that gain and loss events occurred symmetrically. However, more gain than loss was reported for chromosomes 1, X, and Y. The frequency of MI and MII diploid sperm (with flagella) was approximately 12 per 10(4) (range 8.3-16.7 per 10(4) sperm). Based on flagella data, the frequency of somatic cells in the semen was estimated to be approximately 1.8 per 10(4) sperm. Loss or gain of a portion of chromosome-arm 1p occurred in 5.5 per 10(4) sperm, and the percentage of sperm carrying structural aberrations within the haploid genome as calculated from FISH (1.4%), was similar to that obtained with the hamster-egg technique. These complementary sperm FISH assays have promising applications in studies of chromosomally abnormal sperm after exposure to occupational, medical, and environmental toxicants.     

Neuromagnetic investigation of somatotopy of human hand somatosensory cortex

Summary In order to investigate functional topography of human hand somatosensory cortex we recorded somatosensory evoked fields (SEFs) on MEG during the first 40 ms after stimulation of median nerve, ulnar nerve, and the 5 digits. We applied dipole modeling to determine the three-dimensional cortial representations of different peripheral receptive fields. Median nerve and ulnar nerve SEFs exhibited the previously described N20 and P30 components with a magnetic field pattern emerging from the head superior and re-entering the head inferior for the N20 component; the magnetic field pattern of the P30 component was of reversed orientation. Reversals of field direction were oriented along the anterior-posterior axis. SEFs during digit stimulation showed analogous N22 and P32 components and similar magnetic field patterns. Reversals of field direction showed a shift from lateral inferior to medial superior for thumb to little finger. Dipole modeling yielded good fits at these peak latencies accounting for an average of 83% of the data variance. The cortical digit representations were arranged in an orderly somatotopic way from lateral inferior to medial superior in the sequence thumb, index finger, middle finger, ring finger, and little finger. Median nerve cortical representation was lateral inferior to that of ulnar nerve. Isofield maps and dipole locations for these components are consistent with neuronal activity in the posterior bank of central fissure corresponding to area 3b. We conclude that SEFs recorded on MEG in conjunction with source localization techniques are useful to investigate functional topography of human hand somatosensory cortex non-invasively.     

Skeletal muscle mitochondrial function and lean body mass in healthy exercising elderly

BACKGROUND: The decline in muscle mass (sarcopenia) with aging may be related to a decline in mitochondrial function. However, investigators have yet to reach a consensus as to whether a decline in mitochondrial function can be attenuated by physical activity has yet to reach a consensus. METHODS: Using dynamic 31PMRS to measure mitochondrial function, we measured baseline Phosphocreatine (PCr), inorganic phosphate (Pi), phosphodiester (PDE), [ADP], pH and recovery times (t(1/2)) for PCr and [ADP] following exercise, in 45 older (73+/-4 years, SD), and 20 younger subjects (25+/-4 years, SD) who were matched for body mass across high and low activity levels and within age and sex groupings. RESULTS: Baseline PCr, and Pi, were lower, and PDE higher in the older subjects compared to younger subjects (all P<0.01). The t(1/2)(ADP) was longer in older subjects (P<0.001) controlling for age and sex in the low activity group (P=0.02). In the older low activity groups, t(1/2)(PCr) was longer than high activity groups. Higher PDE levels were positively correlated with longer t(1/2)(PCr) in the older low activity females (both P<0.05). CONCLUSIONS: Our data suggests that mitochondrial function declines with age in healthy, exercising elderly adults and that the decline appears to be influenced by the level of physical activity.     

Serial dexamethasone suppression tests in psychiatric illness: Part II. A study in major depressive disorder

Weekly dexamethasone suppression tests (DSTs) were performed in 35 patients with major depressive disorder until clinical response. At initial evaluation, 65% of the patients showed nonsuppression, and 85.7% showed nonsuppression at least once during the treatment period. Normalization of the DST results usually coincided with or occurred before clinical recovery, although isolated "peaks" of DST nonsuppression occurred in 45.7% of the patients, irrespective of the clinical course. The test was not useful as a predictor of clinical recovery or relapse. Moderately ill depressed patients had significantly higher nonsuppression rates than schizophrenic or manic patients with corresponding severity scores, indicating that different factors might be associated with nonsuppression in different diagnoses. However, many abnormal DST results could neither be related to the course of the depression nor to the severity of illness; thus other factors must also be responsible for DST nonsuppression.