Systematic Review and UK‐Based Study of PARK2 (parkin), PINK1, PARK7 (DJ‐1) and LRRK2 in early‐onset Parkinson's disease

Approximately 3.6% of patients with Parkinson's disease develop symptoms before age 45. Early‐onset Parkinson's disease (EOPD) patients have a higher familial recurrence risk than late‐onset patients, and 3 main recessive EOPD genes have been described. We aimed to establish the prevalence of mutations in these genes in a UK cohort and in previous studies. We screened 136 EOPD probands from a high‐ascertainment regional and community‐based prevalence study for pathogenic mutations in PARK2 (parkin), PINK1, PARK7 (DJ‐1), and exon 41 of LRRK2. We also carried out a systematic review, calculating the proportion of cases with pathogenic mutations in previously reported studies. We identified 5 patients with pathogenic PARK2, 1 patient with PINK1, and 1 with LRRK2 mutations. The rate of mutations overall was 5.1%. Mutations were more common in patients with age at onset (AAO) < 40 (9.5%), an affected first‐degree relative (6.9%), an affected sibling (28.6%), or parental consanguinity (50%). In our study EOPD mutation carriers were more likely to present with rigidity and dystonia, and 6 of 7 mutation carriers had lower limb symptoms at onset. Our systematic review included information from >5800 unique cases. Overall, the weighted mean proportion of cases with PARK2 (parkin), PINK1, and PARK7 (DJ‐1) mutations was 8.6%, 3.7%, and 0.4%, respectively. PINK1 mutations were more common in Asian subjects. The overall frequency of mutations in known EOPD genes was lower than previously estimated. Our study shows an increased likelihood of mutations in patients with lower AAO, family history, or parental consanguinity. © 2012 Movement Disorder Society.     

Some ultrastructural features of the cell surface after SV40 transformation and somatic hybridization with normal untransformed cells.

We have studied the surface properties of four cell lines: normal human fibroblasts (GM-177), SV40 transformed Lesch-Nyhan fibroblasts (LN-SV), mouse macrophages, and somatic cell hybrids between mouse macrophages and human SV40-transformed fibroblasts (LN-SV). The concanavalin A (Con A)-peroxidase method was used to visualize the localization of the Con A binding sites by means of electron microscopy. The mean thickness of the reaction product was calculated and the distribution pattern was visualized by drawing "glycograms," from which the ratio of covered to uncovered areas was measured. Ruthenium red technique was used to study the ability of the cell surface to retain ruthenium red-positive materials after rinsing in phosphate-buffered saline. Before rinsing, there were no differences between thicknesses of the ruthenium red-positive surface layers of normal and virus-transformed Lesch-Nyhan fibroblasts. After rinsing, however, significant differences in the ability to retain ruthenium red-positive material were seen in favor of the SV40-transformed Lesch-Nyhan fibroblasts (54% over 35%). Before rinsing, significant differences in the thickness of the ruthenium red-positive material were found between mouse macrophages and the hybrids between mouse macrophages and SV40-transformed human fibroblasts, with the hybrids expressing a thicker ruthenium red-positive layer than did the parental mouse macrophages. After washing, however, the ability to retain this material was greater in mouse macrophages than in hybrids. The hybrid cell surface resembles that of SV40-transformed human Lesch-Nyhan fibroblasts. The Con A-peroxidase method shows a different distribution of the reaction product. In general, in all four cases the central portions of the cells had less continuous labeling patterns than did their peripheries, while the marginal portions were very often devoid of the reaction product. Normal human fibroblasts had the most continuous surface reaction product, the thickest reaction product, and the greatest Con A:gap ratio. In all four of these measurements, the hybrid cell line expressed great similarity to the parental cell lines, especially to the mouse macrophages.     

Pancreatic acinar cell carcinoma with subcutaneous and intraosseous fat necrosis

On rare occasions, excessive lipase production by functioning pancreatic acinar cell carcinoma results in subcutaneous and intraosseous fat necrosis. A patient with subcutaneous nodules and osteolytic lesions from metastatic fat necrosis associated with this malignancy is reported. Prompt recognition of the syndrome led to complete resection of the otherwise asymptomatic neoplasm of the exocrine pancreas.     

Construction of an odds model of coronary heart disease using published information: the Cardiovascular Health Improvement Model (CHIME)

Background  

There is a need for a new cardiovascular disease model that includes a wider range of relevant risk factors, in particular lifestyle factors, to aid targeting of interventions and improve population models of the impact of cardiovascular disease and preventive strategies. The model needs to be applicable to a wider population including different ethnic groups, different countries and to those with and without cardiovascular disease. This paper describes the construction of the Cardiovascular Health Improvement Model that aims to meet these requirements.     

Rathke cleft cysts: CT, MR imaging, and pathologic features

The authors retrospectively reviewed the clinical, computed tomography (CT), and magnetic resonance (MR) imaging findings in seven patients with pathologically proved Rathke cleft cysts. All the cysts were located in the anterior sella turcica or the anterior suprasellar cistern. Five cysts had both intra- and suprasellar components, one was entirely intrasellar, and the other was predominantly suprasellar in location. The size of the cysts ranged from 8 to 20 mm. CT scans demonstrated low-density homogeneous lesions in four cases. On MR images of three of these four cases, the cysts had the same intensity as cerebrospinal fluid on T1- and T2-weighted images, while in the fourth case, the cyst was hyperintense on the T1-weighted images. In the remaining three cases, CT showed slight hyperdensity relative to brain parenchyma, suggestive of contrast enhancement. MR showed signal heterogeneity of these lesions with focal components of diminished signal intensity of T2-weighted images. These same foci appeared iso- to slightly hyperintense on T1-weighted images.     

CUTANEOUS VASOCONSTRICTION WITH ALERTING STIMULI IN RABBITS REFLECTS A PATTERNED REDISTRIBUTION OF CARDIAC OUTPUT

1. In conscious rabbits, when alerting stimuli elicit vasoconstriction in the ear vascular bed, there is little or no associated change in cardiac output (CO), as measured by chronically implanted Doppler ultrasonic probes. 2. Local anaesthetic injected around the base of the ear substantially diminished the degree of the vasoconstriction elicited during responses. 3. Our results emphasize that selective cutaneous vasoconstriction, an integral part of the response to alerting stimuli in conscious animals, is part of a patterned redistribution of the CO, organized by the brain.     

Work in progress: hybrid temporal-energy subtraction in digital fluoroscopy

Initial clinical results using a digital fluoroscopic implementation of the combined time-energy ("hybrid") subtraction technique are described, with emphasis on carotid and renal imaging. Where patient motion artifacts are due to soft-tissue motion alone, hybrid subtraction can remove them. Due to the need for a finite separation time between high- and low-energy pairs, however, the present implementation of the hybrid technique is not completely immune to soft-tissue motion. The intrinsic signal-to-noise ratio of hybrid imaging is less than that of conventional temporal subtraction. However, since the low-energy temporal subtraction images are included in the hybrid data set, the diagnostic quality of the examination is not compromised.