Progressive aortic valve inflammation occurring despite apparent remission of relapsing polychondritis

We describe a patient with relapsing polychondritis in whom aortic valve inflammation developed 3 years after diagnosis, when the polychondritis had been in apparent remission for an extended period of time. Infection and cardiac involvement can be significant complications of relapsing polychondritis. Recommendations for monitoring and treatment of patients with this disease are discussed.     

High- and low-affinity receptors regulate platelet responses to phorbol diesters and teleocidin

We examined binding of ³H-phorbol dibutyrate (³H-PDBu) to gel filtered human platelets (GFP) and discovered that GFP possess two classes of receptors for phorbol diesters (PDE). High-affinity (HA) receptors, approximately 5000/GFP, bound ³H-PDBu with an apparent dissociation constant (K_D) of approximately 12 nM. Low-affinity receptors were approximately 5 times more numerous (2.4 × 10⁴/GFP) and had a 10-fold lower affinity for ³H-PDBu (apparent K_D = 115 nM). The potencies of phorbol myristate acetate (PMA) and PDBu paralleled their binding affinities to the PDE receptors. Teleocidin (Tel), although structurally distinct from PDE, competed with ³H-PDBu for its HA-receptors (K_I Tel = 1.9 nM). Binding of PDE to HA- or LA- receptors was rapid, reversible, saturable and stereospecific. The HA- and LA-receptors modulated different platelet responses. HA-receptors regulated the secretion of β-thromboglobulin from -granules and the release of N-acetyl-β-D-hexosaminidases from lysosomes. LA-receptors mediated both platelet aggregation and the release of serotonin from dense granules. This is the first demonstration of two physiologically active classes of PDE/Tel receptors in human platelets, and demonstrates that particular platelet responses may be directed by distinct classes of receptors for specific agonists.     

Morphological and GABA-immunoreactive development of the embryonic chick telencephalon

The development of neurons utilizing γ-aminobutyric acid (GABAergic neurons) in prosencephalon and telencephalon from chicken embryonic days 4–14 (E4–E14) was studied by means of immunohistochemistry. Furthermore, routine histology and transmission electron microscopy, respectively, were performed in order to study the morphological development in the designated area. The main finding is that development of GABAergic neurons in the chick telencephalon is rapid; the GABA neurons are appearing in bulk at day 8, being “overexpressed” at days 10–11, decreasing in numbers thereafter and achieving mature morphology on day 14, which is considerably faster than in the rodent.Morphological analysis revealed that the prosencephalon mainly consisted of a thin layer of undifferentiated neuroblasts in the E4 embryo. By E6, the prosencephalon had increased in thickness and occasional cells outside the neuroepithelium showed a more mature morphology with a few cells weakly staining positive for GABA. At E8, the prospective granular and subventricular layers had developed. At E14, the appearance of the telencephalon is approximating that of the adult since both ependymal cells and morphologically mature neurons can be seen.     

Parental stress and burden following traumatic brain injury amongst children and adolescents

Primary objectives: To assess parental stress following paediatric traumatic brain injury (TBI), and examine the relationship between self-reported problems, parental stress and general health.

Research design: Parents of 97 children admitted with a TBI (49 mild, 19 moderate, 29 severe) to North Staffordshire National Health Service Trust, and parents of 31 uninjured children were interviewed and assessed.

Methods and procedures: Structured interviews were carried out with families, and parents assessed on the Parenting Stress Index (PSI/SF) and General Health Questionnaire (GHQ-12) at recruitment, and repeated 12 months later.

Main outcomes and results: Forty parents (41.2%) of children with TBI exhibited clinically significant stress. Regardless of injury severity, parents of injured children suffered greater stress than control parents as measured by the PSI/SF (p = 0.001). There was a highly significant relationship between number of problems reported and level of parental stress (p = 0.001). Financial burden was related to severity of TBI. At follow-up, one third of parents of children with severe TBI scored ≥18 on the GHQ-12, signifying poor psychological health.

Conclusions: The parents of a child with serious TBI should be screened for abnormal levels of stress. Parental stress and family burden may be alleviated by improved information, follow-up and support.     

Co-factors affecting substance abuse among homosexual men: an investigation within a midwestern gay community

In an effort to begin formation of an empirically based model of gay substance abuse, this study examined the effects of three psychosocial factors, homosexual identity formation, self-esteem and a familial history of substance abuse in the evolution of this phenomenon among homosexual men, a group that appears to manifest appreciably higher rates and concomitantly greater associated problems than the general population. Data were obtained by voluntary subject return of a self-report instrument that was distributed widely over a 6 month period in the metropolitan Cleveland area, resulting in a moderately sized sample. Although the sampling method limited the generalizibility of the results, diminished self-esteem and a familial history of substance abuse had significant associations with both alcohol and drug abuse and were confirmed to be salient predictors, together accounting for almost half the variance in alcohol abuse and over one-third the variance in drug abuse. Moreover, both had the ability to significantly discern between alcohol and drug use groups versus groups found to be alcohol and drug abusive. Levels of a gay identity were not meaningfully associated with substance abuse. Finally, recommendations for further research were explicated.     

Empirically tested psychotherapies for youth internalizing and externalizing problems and disorders

This article is a review of specific psychotherapies that have been supported in clinical trials. Treatments that showed significant effects in studies published over a period of 4 decades were identified, with the goal of complementing the overall picture of treatment benefit provided in narrative reviews and meta-analyses with a detailing of the specific interventions that have shown significant effects. The article focuses on treatments for four broad clusters of problems and disorders that account for a very large proportion of youth mental health referrals: anxiety, depression, attention-deficit/hyperactivity, and conduct.     

Subclinical atherosclerotic calcification and cognitive functioning in middle-aged adults: The CARDIA study

Objective

Cardiovascular risk factors in middle-age are associated with cognitive impairment and dementia in older age. Less is known about the burden of calcified subclinical atherosclerosis and cognition, especially in midlife. We examined the association of coronary artery and abdominal aortic calcified plaque (CAC and AAC, respectively) with cognitive functioning in middle-aged adults.

Methods

This cross-sectional study included 2510 black and white adults (age: 43–55 years) without heart disease or stroke who completed a year 25 follow-up exam (2010–11) as part of the Coronary Artery Risk Development in Young Adults Study. CAC and AAC were measured with non-contrast computed tomography. Cognition was assessed with the Digit Symbol Substitution Test (DSST) (psychomotor speed), Stroop Test (executive function), and Rey Auditory Verbal Learning Test (RAVLT) (verbal memory).

Results

A greater amount of CAC and AAC was associated with worse performance on each test of cognitive function after adjustment for age, sex, race, education, and study center. Associations were attenuated, but remained significant for the DSST and RAVLT following additional adjustment for vascular risk factors, including adiposity, smoking, alcohol use, dyslipidemia, hypertension, and diabetes. Compared to participants without CAC or AAC, those with both CAC and AAC, but not CAC or AAC alone was associated with lower DSST scores (p < 0.05).

Conclusions

In this community-based sample, greater subclinical atherosclerotic calcification was associated with worse psychomotor speed and memory in midlife. These findings underscore the importance of a life course approach to the study of cognitive impairment with aging.     

Regulation of hepatocyte activator inhibitor-1 expression by androgen and oncogenic transformation in the prostate

Hepatocyte activator inhibitor-1 (HAI-1) is a transmembrane serine protease inhibitor that regulates the conversion of latent to active hepatocyte growth factor (HGF). Studies supporting a role for the HGF pathway in prostate carcinogenesis prompted an analysis of HAI-1 expression in the prostate. Here we analyze the regulation of HAI-1 expression by androgen, oncogenic transformation, and cancer progression. Immunohistochemical analysis revealed that HAI-1 expression was restricted to prostate epithelium, where staining occurred primarily in basal and atrophic luminal epithelial cells. Compared to normal glands, HAI-1 expression was significantly increased in localized prostate cancer and was present in most prostate cancer metastases. HAI-1 protein expression levels were sensitive to androgen in normal epithelium but not in cancer. Although androgen did not increase HAI-1 protein expression levels in LNCaP cells, it decreased HAI-1 surface expression, consistent with previous data from our group (Martin DB, Gifford DR, Wright ME, Keller A, Yi E, Goodlett DR, Aebersold R, Nelson PS: Quantitative proteomic analysis of proteins released by neoplastic prostate epithelium. Cancer Res 2004, 64:347-355). HAI-1 overexpression in cancer was predictive of prostate-specific antigen recurrence (relative risk, 1.24). These results suggest that HAI-1 regulates the HGF Met axis on prostate epithelial cells and influences HGF mediated tumor invasion and metastasis.