Psychosocial impact of Von Hippel–Lindau disease: levels and sources of distress

Lammens CRM, Bleiker EMA, Verhoef S, Hes FJ, Ausems MGEM, Majoor‐Krakauer D, Sijmons RH, Luijt van der RB, Ouweland van den AMW, Van Os Tam, Hoogerbrugge N, Gomez‐Garcia EB, Dommering CJ, Gundy CM, Aaronson NK. Psychosocial impact of von Hippel–Lindau disease: levels and sources of distress. Von Hippel–Lindau disease (VHL) is a hereditary tumor susceptibility syndrome, characterized by an increased risk of developing multiple benign and malignant tumors at various sites and ages with limited preventive options. This study evaluates the prevalence of distress among VHL family members and factors associated significantly with such distress. Forty‐eight families with a VHL mutation were identified via the nine family cancer clinics in the Netherlands. In total, 171 family members (carriers, 50% at‐risk, non‐carriers) were approached, of whom 123 (72%) completed a self‐report questionnaire. Approximately 40% of the VHL family members reported clinically relevant levels of distress, approaching 50% among the carriers and, possibly even more striking, 36% among the non‐carriers. Having lost a first degree relative due to VHL during adolescence (OR 11.2; 95% CI 1.4–86.9) was related significantly to heightened levels of distress. Approximately, only one‐third of those who reported heightened levels of distress had received professional psychosocial support. A substantial percentage of family members experience clinically relevant levels of distress. We would recommend the introduction of a procedure for screening for distress in this vulnerable population. Special attention should be paid to those individuals who have lost a close relative due to VHL during adolescence.     

Improved preoperative evaluation of cerebral cavernomas by high-field, high-resolution susceptibility-weighted magnetic resonance imaging at 3 Tesla: comparison with standard (1.5 T) magnetic resonance imaging and correlation with histopathological findings--preliminary results

OBJECTIVES: To compare high-field, high-resolution, susceptibility-weighted magnetic resonance imaging (3 Tesla [T] HR-SW-MRI) and standard (1.5 Tesla [T]) MRI for the detection of cerebral cavernomas. To evaluate the ability of 3 T HR-SW-MRI to visualize intralesional structures compared with standard (1.5 T) MRI, in correlation with histopathologic findings. MATERIALS AND METHODS: Seventeen patients with cerebral cavernomas underwent both standard (1.5 T) MRI (T1-SE, T2-TSE, T2*-GRE) and 3 T HR-SW-MRI (TR/TE 43.3/9.1 millisecond; 512 x 384 x 48 matrix; FOV 250 mm; SI 72 mm) at our institution. All MR images were evaluated by 3 radiologists in consensus for detectability, size (1 cm), and conspicuity (good, acceptable, poor) of the lesions at both field strengths, and for the presence of hypointense intralesional tubular structures. In 7 patients, MR findings were correlated with histopathologic findings. RESULTS: Both 3 T HR-SW-MRI and standard (1.5 T) MRI detected 22 lesions in 17 patients; 3 T HR-SW-MRI detected an additional 7 lesions in 6 patients. On average, 3 T HR-SW-MRI detected 1.706 +/- 0.92 (median = 1) lesions per patient, whereas standard (1.5 T) MRI detected 1.235 +/- 0.664 lesions per patient (P = 0.016). Lesion conspicuity was good in all 3 T HR-SW-MR images and good in 68.2% and acceptable in 31.8% of standard (1.5 T) MR images (P = 0.016). In 22 lesions detected at both field strengths, 3 T HR-SW-MRI demonstrated intralesional tubular structures in 72.7% and standard (1.5 T) MRI demonstrated these structures in 31.8% (P = 0.001). Intralesional tubular structure correlated to conglomerates of cavernous vessel, as verified by histopathology. CONCLUSION: Compared with standard (1.5 T) MRI, 3 T HR-SW-MRI allows superior detection and characterization of cerebral cavernomas. Despite increased susceptibility effects, ie, signal loss at higher magnetic field strengths, the visualization of intralesional tubular structures is feasible. This may be helpful in the diagnosis, presurgical planning, and noninvasive follow-up after gamma-knife radiosurgery.     

Rapid and preferential distribution of blood-borne alphaCD3epsilonAb to the liver is followed by local stimulation of T cells and natural killer T cells

Dissemination of soluble molecules or antigens via the blood stream is considered to lead to a uniform distribution in the various organs of the body, but organ-specific microarchitecture and vascularization may influence this. Following intravenous injection of alphaCD3epsilon antibody (alphaCD3epsilonAb) we observed clear differences in antibody binding to Fcgamma receptor (FcgammaR)(+) antigen-presenting cells (APCs) or T lymphocytes in different organs. Significant binding of blood-borne alphaCD3epsilonAb was only detected in the spleen and liver and not in the thymus or lymph node. In the spleen, only 10% of dendritic cells/macrophages and 40% of T-cell receptor (TCR)-beta(+) cells were positive for alphaCD3epsilonAb, and, dependent on FcgammaR-mediated cross-linking of alphaCD3epsilonAb, a similar percentage of splenic TCR-beta(+) cells were stimulated and became CD69(+). Stimulation of TCR-beta(+) cells in the liver was at least as efficient as in the spleen, but almost all T cells and all scavenger liver sinusoidal endothelial cells bound alphaCD3epsilonAb. In contrast to CD69 up-regulation, only CD4(+) natural killer T (NKT) cells and CD11a(high) CD8(+) T cells were activated by alphaCD3epsilonAb and expressed interferon (IFN)-gamma. Again, IFN-gamma release from NKT/T cells was at least as efficient in the liver as in the spleen. Taken together, our results support the notion that the combination of extensive hepatic vascularization and very high scavenger activity allows the liver to fulfill its metabolic tasks and to promote stimulation of the large but widely distributed hepatic population of NKT/T cells.     

Stress perception and commuting

This paper analyzes the determinants of the perceived stress level of workers with a special focus on the effects of commuting, while controlling for personal and work-related characteristics. Using ordered logistic regression we find that several dimensions of the commuting situation, such as impedance, control and predictability of commuting, significantly influence the perceived stress level. Therefore, stress and stress-related health problems should be taken into consideration when analyzing the economic costs of commuting.     

Deep white matter infarction: correlation of MR imaging and histopathologic findings

Focal and confluent areas of periventricular hyperintensity have been reported on magnetic resonance (MR) images in 30% of patients over 60 years of age. In order to better understand the pathologic basis of these lesions, the authors studied 14 formalin-fixed brains with MR imaging. Multiple focal areas of hyperintensity were identified in the periventricular white matter in three of the 14 brains studied (21%). Subsequent gross and microscopic pathologic examination of both hyperintense and normal-intensity areas was performed on 87 tissue sections. The larger lesions were characterized centrally by necrosis, axonal loss, and demyelination and therefore represent true infarcts. Reactive astrocytes oriented along the degenerated axons were identified at distances of up to several centimeters from the central infarct. This is called isomorphic gliosis and is associated with increased intensity on T2-weighted images that increases the apparent size of the central lesion.     

The Course of Geriatric Syndromes in Acutely Hospitalized Older Adults: The Hospital-ADL Study

Objectives

To establish the prevalence and course of geriatric syndromes from hospital admission up to 3 months postdischarge and to determine the probability to retain geriatric syndromes over the period from discharge until 3 months postdischarge, once they are present at admission.