Apoptosis of vasopressinergic hypothalamic neurons in chronic diabetes mellitus

The hyperosmolality associated with diabetes mellitus triggers an increase in neuronal activity and vasopressin production within magnocellular neurosecretory cells (MNCs) of the hypothalamic supraoptic nucleus (SON). In this study, we examined the effect of chronic diabetes on the function and survival of these neurons. After 6 months, but not 6 weeks, of streptozotocin (STZ)-induced diabetes, we observed an increase in the appearance of small hyperchromatic neurons and a decrease in SON neuronal density. A subpopulation of neurons within the SON at this time point demonstrated positive staining for cleaved caspase-3 and TUNEL, two markers of apoptosis. In addition, the number of vasopressin-positive neurons was decreased. Markers for apoptosis did not colocalize with vasopressin immunopositivity; this was probably due to a diabetes-induced degenerative process causing downregulation of vasopressin expression or depletion of neuropeptide. Although the phenotypes of the apoptotic neurons were not identified, other SON neurons including oxytocin-producing neurons are unlikely to be affected by chronic hyperglycemia. Microglial hypertrophy and condensation were also observed in the 6-month diabetic SON. Although upregulation of vasopressin production in response to acute hyperosmolality is adaptive, prolonged overstimulation of vasopressin-producing neurons in chronic diabetes results in neurodegeneration and apoptosis.     

Inhibition of erbB receptor family members protects HaCaT keratinocytes from ultraviolet-B-induced apoptosis

In the human epidermis, the cells most at risk for the development of cancer due to sunlight exposure are the keratinocytes. In animal models, ultraviolet-B is a complete carcinogen, capable of inducing and promoting the development of malignant cells. A key element of ultraviolet-B-induced carcinogenesis is the ability of ultraviolet-B to induce the expression of a number of cellular proteins and activate growth factor receptor tyrosine kinases, including the erbB receptor family. Keratinocytes express the erbB1 (also called EGF-R, HER1), the erbB2 (also known as neu or HER2), and the erbB3 (HER3) subtypes. In general, activation of the erbB receptor family leads to a cellular proliferative response. In certain instances, however, activation of an erbB receptor can induce differentiation, cell cycle arrest, and even apoptosis. The inhibition of tyrosine kinase activity in rodent models and human skin has been shown to inhibit some ultraviolet-B response pathways. We have shown that the inhibition of erbB receptors, by both pharmaceutical and immunologic means, will inhibit ultraviolet-B-induced apoptosis in the HaCaT human keratinocyte cell line. This inhibition was specific for the erbB receptor family and specific for ultraviolet-B-induced apoptosis. These results suggest that, in certain instances, ultraviolet-B-induced apoptotic signaling requires erbB family receptor activity.     

Paraspinal abscess complicated by endocarditis following a facet joint injection⋆

Infectious complications secondary to lumbar facet injections are exceedingly rare, follow an indolent course, and local sequelae include abscess spread or infections of the central nervous system. We present the case of the development of a facet abscess and infective endocarditis, which developed shortly after a lumbar facet injection. With the increase in interventional pain procedures, physicians must be aware of potential infectious complications.     

Implementation,reliability testing,and compliance monitoring of the Confusion Assessment Method for the Intensive Care Unit in trauma patients

OBJECTIVE: To implement delirium monitoring, test reliability, and monitor compliance of performing the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) in trauma patients. DESIGN AND SETTING: Prospective, observational study in a level 1 trauma unit of a tertiary care, university-based medical center. PATIENTS: Acutely injured patients admitted to the trauma unit between 1 February 2006 and 16 April 2006. MEASUREMENTS AND RESULTS: Following web-based teaching modules and group in-services, bedside nurses evaluated patients daily for depth of sedation with the Richmond Agitation-Sedation Scale (RASS) and for the presence of delirium with the CAM-ICU. On randomly assigned days over a 10-week period, evaluations by nursing staff were followed by evaluations by an expert evaluator of the RASS and the CAM-ICU to assess compliance and reliability of the CAM-ICU in trauma patients. Following the audit period the nurses completed a postimplementation survey. The expert evaluator performed 1,011 random CAM-ICU assessments within 1[Symbol: see text]h of the bedside nurse's assessments. Nurses completed the CAM-ICU assessments in 84% of evaluations. Overall agreement (kappa) between nurses and expert evaluator was 0.77 (0.721-0.822; p[Symbol: see text]<[Symbol: see text]0.0001), in TBI patients 0.75 (0.667-0.829; p[Symbol: see text]<[Symbol: see text]0.0001) and in mechanically ventilated patients 0.62 (0.534-0.704; p[Symbol: see text]<[Symbol: see text]0.0001). The survey revealed that nurses were confident in performing the CAM-ICU, realized the importance of delirium, and were satisfied with the training that they received. It also acknowledged obstacles to implementation including nursing time and failure of physicians/surgeons to address treatment approaches for delirium. CONCLUSIONS: The CAM-ICU can be successfully implemented in a university-based trauma unit with high compliance and reliability. Quality improvement projects seeking to implement delirium monitoring would be wise to address potential pitfalls including time complaints and the negative impact of physician indifference regarding this form of organ dysfunction.     

From intrusive thoughts to obsessions: The role of perceptions of responsibility, salience, and thought suppression

Salkovskis [1985. Obsessional-compulsive problems: A cognitive-behavioural analysis. Behaviour Research and Therapy, 23, 571–583.] hypothesized that intrusive thoughts are more likely to occur if the thought is salient for the individual, triggers feelings of responsibility and if the individual attempts to suppress the thought. The relationship between these three factors (responsibility, salience, thought suppression) and frequency of intrusive thoughts as well as anxiety were examined in the present study. One hundred female college students were led to believe that a snake had escaped from the cage in which it was housed. Half of the participants were led to believe that they were responsible for the snake's escape and half were not (Responsibility/No Responsibility). Half of the participants in each Responsibility condition were instructed to suppress thoughts of snakes during a stream of consciousness exercise and half were not (Thought Suppression vs. No Thought Suppression). All participants then completed a second stream of consciousness without suppression instructions. Salience groups were determined by a median split on a measure of snake fearfulness. Participants for whom the snake was a salient stimulus and who believed that they were responsible for the snake's escape had the highest frequency of snake thoughts during the second stream of consciousness task and also experienced the highest levels of state anxiety. Findings are discussed with respect to Salkovskis' model.