Mapping brain size and cortical gray matter changes in elderly depression.

BACKGROUND: In elderly depression, volumetric brain imaging findings suggest abnormalities of the frontal lobe, particularly the orbitofrontal cortex, and the hippocampus. No studies to date have mapped cortical abnormalities over the entire brain surface in major depression. Here, we conducted detailed spatial analyses of brain size and gray matter within the cortical mantle in elderly patients with major depression. METHODS: High-resolution, three-dimensional, structural magnetic resonance imaging data and cortical pattern matching methods were used in 24 depressed elderly patients and 19 group-matched controls to measure local brain size and proportions of gray matter at thousands of homologous cortical surface locations. RESULTS: Prominent brain size reductions were observed in the depressed subjects in the orbitofrontal cortex bilaterally. Cortical gray matter measurements revealed significant gray matter increases in the orbitofrontal cortex, adjacent to focal trend level significant decreases of gray matter in the same region. Depressed patients also exhibited significant gray matter increases in parietal cortices, as well as the left temporal cortex. CONCLUSIONS: Complex cortical changes may contribute to the brain size reduction of the orbitofrontal cortex and to the gray matter abnormalities detected in orbitofrontal cortex and temporoparietal cortices, thereby providing a potentially new window into the pathophysiology of elderly depression.     

Androgen receptor YAC transgenic mice carrying CAG 45 alleles show trinucleotide repeat instability

X-linked spinal and bulbar muscular atrophy (SBMA) is caused by a CAG repeat expansion in the first exon of the androgen receptor (AR) gene. Disease-associated alleles (37-66 CAGs) change in length when transmitted from parents to offspring, with a significantly greater tendency to shift size when inherited paternally. As transgenic mice carrying human AR cDNAs with 45 and 66 CAG repeats do not display repeat instability, we attempted to model trinucleotide repeat instability by generating transgenic mice with yeast artificial chromosomes (YACs) carrying AR CAG repeat expansions in their genomic context. Studies of independent lines of AR YAC transgenic mice with CAG 45 alleles reveal intergenerational instability at an overall rate of approximately 10%. We also find that the 45 CAG repeat tracts are significantly more unstable with maternal transmission and as the transmitting mother ages. Of all the CAG/CTG repeat transgenic mice produced to date the AR YAC CAG 45 mice are unstable with the smallest trinucleotide repeat mutations, suggesting that the length threshold for repeat instability in the mouse may be lowered by including the appropriate flanking human DNA sequences. By sequence-tagged site content analysis and long range mapping we determined that one unstable transgenic line has integrated an approximately 70 kb segment of the AR locus due to fragmentation of the AR YAC. Identification of the cis - acting elements that permit CAG tract instability and the trans -acting factors that modulate repeat instability in the AR YAC CAG 45 mice may provide insights into the molecular basis of trinucleotide repeat instability in humans.      

Cryopreservation of human oocytes: a review of current problems and perspectives

It is well recognized that the ability to cryopreserve unfertilizedhuman oocytes would make a significant contribution to infertilitytreatment. However, despite considerable interest, very fewsuccessful pregnancies have arisen from cryopreserved oocytesafter thawing, insemination and transfer of the subsequent embryo.The reasons for this lack of progress may well result from adearth of information on how the various biophysical changesduring a cryopreservation regimen affect human oocyte function.Recently, fundamental studies on the effects of cooling, membranepermeability, cryoprotectant addition and ice formation havebeen performed on human oocytes by a number of groups, and theseform the basis of the current review. It is likely that successfulhuman oocyte cryopreservation will only follow once these factorsare fully understood, but the existing base of knowledge shouldprovide a platform for further improvements in the techniquescurrently employed.     

Initial evaluation of a continuous speech recognition program for radiology

The aims of this work were to measure the accuracy of one continuous speech recognition product and dependence on the speaker's gender and status as a native or nonnative English speaker, and evaluate the product's potential for routine use in transcribing radiology reports. IBM MedSpeak/Radiology software, version 1.1 was evaluated by 6 speakers. Two were nonnative English speakers, and 3 were men. Each speaker dictated a set of 12 reports. The reports included neurologic and body imaging examinations performed with 6 different modalities. The dictated and original report texts were compared, and error rates for overall, significant, and subtle significant errors were computed. Error rate dependence on modality, native English speaker status, and gender were evaluated by performing ttests. The overall error rate was 10.3 +/- 3.3%. No difference in accuracy between men and women was found; however, significant differences were seen for overall and significant errors when comparing native and nonnative English speakers (P = .009 and P = .008, respectively). The speech recognition software is approximately 90% accurate, and while practical implementation issues (rather than accuracy) currently limit routine use of this product throughout a radiology practice, application in niche areas such as the emergency room currently is being pursued. This methodology provides a convenient way to compare the initial accuracy of different speech recognition products, and changes in accuracy over time, in a detailed and sensitive manner.     

Objective Pulse-Synchronous "Essential" Tinnitus due to Narrowing of the Transverse Dural Venous Sinus

Subjective tinnitus is a common problem with many etiologies. Objective tinnitus, in which the sound is perceived by both the patient and the examiner, is less common. Objective tinnitus of the vascular type, in which a pulse synchronous bruit is heard by an independent observer, is frequently related to an underlying arterial or arteriovenous malformation, most commonly a dural arteriovenous fistula (DAVF) involving the transverse and sigmoid sinuses. The remaining cases are usually termed "essential" vascular tinnitus, and are presumed to have a venous etiology. In these cases, the audible noise is generally assumed to be produced within the sino-jugular connection, or within an enlarged jugular bulb. We present four documented cases of objective pulse synchronous tinnitus due to focal narrowing (acquired and developmental) of the mid-portion of the transverse dural sinus. In all cases, a bruit was audible directly over a focal constriction in the sinus, demonstrated by cerebral angiography or direct catheter venography. In one case, selective venography revealed a distensible sinus narrowing, associated with a jet of contrast marking fast flow within a developmental sinus segmentation. In another case, a loud pulse synchronous bruit was heard directly over a focal transverse sinus stenosis, which was detected by angiography at the site of a vascular surgical clip. In this case, magnetic resonance (MR) falsely predicted sinus occlusion. In two other cases, an audible bruit was also heard directly overlying a narrowed transverse sinus, seen in the venous phase of angiography. Transverse sinus stenosis is an unappreciated cause of objective pulsatile tinnitus, and we believe that this mechanism may underlie many cases of "essential" or venous etiology tinnitus not otherwise anatomically explained. Non-invasive testing, computed tomography (CT) and MR and non-directed angiography may overlook it. Conventional catheter arteriography or venography should be performed in such cases, with attention to the dural sinuses, if other tests fail to define the anatomic basis of the audible bruit.     

Actigraphically recorded motor activity and immobility across sleep cycles and stages in healthy male subjects

The aim of this study was to compare the extent to which activity and immobility measures are related to sleep stages and sleep cycles in order to improve the informative value of actigraphic assessment of sleep. We therefore performed simultaneous ambulatory polysomnography and wrist-activity monitoring (AM) in 14 healthy male subjects without sleep complaints. In this context, a simple method for transforming raw motor activity data into a time-series reflecting onset and duration of activity and immobility clusters is introduced. Our results demonstrate that nocturnal AM measures were significantly affected by sleep stage. Low activity levels and particularly prolonged episodes of uninterrupted immobility were associated with increasing sleep depth. On the other hand, high activity levels and prolonged episodes of activity were related to intermittent wakefulness during sleep. Our results suggest that measures reflecting the occurrence and duration of activity and immobility clusters provide a better approach in studying the relationship between activity/immobility and sleep stages. Except for the duration of uninterrupted immobility episodes, which showed a significant decrease in the fourth cycle, none of the AM measures showed a significant cycle-to-cycle variation. Consequently, mean nocturnal motor activity measures provide an accurate reflection of the total sleep period. However, none of the AM-derived measures seems useful in evaluating the cycle structure during sleep.     

Involvement of deprivation and environmental lead in neural tube defects: a matched case-control study

OBJECTIVE: To analyse the prevalence of neural tube defects in small geographical areas and seek to explain any spatial variations with reference to environmental lead and deprivation. SETTING: The Fylde of Lancashire in the north west of England. DESIGN: Cases were ascertained as part of a prospective survey of major congenital malformations in babies born in the Fylde to residents there between 1957 and 1981. A matched case-control analysis used infants with cardiovascular system, alimentary tract, and urinary system malformations as controls. Conditional logistic regression was used to assess the effects of more than 10 micrograms/l lead in drinking water and the Townsend deprivation score. RESULTS: The prevalence of neural tube defects in 1957-73 was higher in Blackpool, Fleetwood, and North Fylde, whereas the three control groups showed no significant spatial variation. In 1957-81 mothers living in electoral wards with either a higher proportion of houses with more than 10 micrograms/l lead in the water or a higher deprivation score had a greater risk of having a baby with a neural tube defect. For spina bifida and cranium bifidum alone, this was also true. For anencephaly, deprivation was less important although the effect of lead was still seen. In some neural tube defects, lead may act independently of other possible factors associated with deprivation. It seemed unlikely that lead levels changed significantly during the survey. The percentage of houses with 10 micrograms/l or more of lead in the water in 1984-5 was similar to that found in Great Britain 10 years previously. CONCLUSION: There is evidence to suggest that lead is one cause of neural tube defects, especially anencephaly. This could link the known preventive actions of hard water and folic acid. Calcium is a toxicological antagonist of lead. One cause of a deficiency of folic acid is impaired absorption secondary to zinc deficiency, which may be produced or exacerbated by lead.