Long-term deficiency of circulating and hippocampal insulin-like growth factor I induces depressive behavior in adult mice: a potential model of geriatric depression.

Numerous studies support the hypothesis that deficiency of insulin-like growth factor I (IGF-1) in adults contributes to depression, but direct evidence is limited. Many psychological and pro-cognitive effects have been attributed to IGF-1, but appropriate animal models of adult-onset IGF-1 deficiency are lacking. In this study, we use a viral-mediated Cre-loxP system to knockout the Igf1 gene in either the liver, neurons of the CA1 region of the hippocampus, or both. Knockout of liver Igf1 reduced serum IGF-1 levels by 40% and hippocampal IGF-1 levels by 26%. Knockout of Igf1 in CA1 reduced hippocampal IGF-1 levels by 13%. The most severe reduction in hippocampal IGF-1 occurred in the group with knockouts in both liver and CA1 (36% reduction), and was associated with a 3.5-fold increase in immobility in the forced swim test. Reduction of either circulating or hippocampal IGF-1 levels did not alter anxiety measured in an open field and elevated plus maze, nor locomotion in the open field. Furthermore, local compensation for deficiencies in circulating IGF-1 did not occur in the hippocampus, nor were serum levels of IGF-1 upregulated in response to the moderate decline of hippocampal IGF-1 caused by the knockouts in CA1. We conclude that adult-onset IGF-1 deficiency alone is sufficient to induce a depressive phenotype in mice. Furthermore, our results suggest that individuals with low brain levels of IGF-1 are at increased risk for depression and these behavioral effects are not ameliorated by increased local IGF-1 production or transport. Our study supports the hypothesis that the natural IGF-1 decline in aging humans may contribute to geriatric depression.

Basal and hypercapnia-altered cerebrovascular perfusion predict mild cognitive impairment in aging rodents.

With increasing age, a subset of otherwise healthy individuals undergoes impairments in learning and memory that have been termed mild cognitive impairment (MCI). The enhanced neuronal activity associated with learning and memory requires increased cerebral blood flow (CBF) to specific brain regions. However, the interactions between cerebral blood flow and MCI remain unclear. In this study, we address whether baseline or hypercapnia-induced (increased blood CO(2) levels) changes in CBF are modified with age, and whether these measures are predictive of cognitive status in rodents. Adult and aged rats were evaluated using a hippocampally-dependent task in a water maze. Aged rats were classified as memory-impaired or memory-intact based on performance comparisons with adult rats. Cerebral blood flow was assessed using flow-alternating inversion recovery (FAIR) magnetic resonance imaging (MRI), before and after breathing 10% CO(2). The transition period between CO(2) concentrations was examined with blood oxygen level dependent (BOLD) MRI. Separation of aged animals into memory-intact and impaired categories revealed increased basal perfusion in the dorsal hippocampus of memory-impaired versus memory-intact aged animals. Linear regression revealed that higher hippocampal perfusion was correlated with impaired memory in aged animals, and a logistic regression indicated that hippocampal perfusion predicted spatial memory ability. Several brain regions of aged rats demonstrated an attenuation of the perfusion increase normally observed in adult rats under hypercapnia. Memory-impaired animals were the primary contributor to this effect, as their perfusion response to hypercapnia was significantly reduced compared to adult animals. Aged, memory-intact animals were not significantly different from adults. BOLD MRI demonstrated a reduced response in aged animals to hypercapnia, with impaired animals being the primary contributor to the effect. A logistic regression model based on basal and hypercapnia perfusion correctly predicted cognitive status in 83.3% of animals tested. Our results indicate that age-related changes in vascular reactivity and perfusion are important contributing factors in memory impairment.

Use of transabdominal ultrasonography to determine the location of cryptorchid testes in the horse.

REASONS FOR PERFORMING STUDY: Transrectal ultrasonography is a reliable technique to identify intra-abdominal testes, but can be hazardous or impractical in fractious, juvenile or small equids. The transabdominal approach therefore requires validation. OBJECTIVES: To evaluate the sensitivity and specificity of transabdominal ultrasonography to localise cryptorchid testes. METHODS: Thirty-eight horses admitted for cryptorchidism underwent transabdominal ultrasonography to locate errant testes. Location of the testes was confirmed during surgery (n = 37) or necropsy (n = 1). RESULTS: Horses weighed 175-760 kg. Twenty-two testes were located within the abdomen, 19 in the inguinal space and 3 in a subcutaneous location. In 2 horses, a thick winter coat prevented adequate contact between the probe and the skin, and visualisation of their inguinal testis and one abdominal testis was missed during transabdominal ultrasonography. Excluding the 2 horses with excessive hair, the sensitivity of transabdominal ultrasonography to locate errant testes was 97.6% (93.2% when all horses were included), and its specificity 100%. CONCLUSIONS: Transabdominal ultrasonography is a reliable, safe and immediate technique to diagnose cryptorchidism precisely in horses of all ages, sizes and temperaments. POTENTIAL RELEVANCE: Transabdominal ultrasonography provides an immediate definitive diagnosis of adominal cryptorchidism and should enhance selection of an appropriate surgical approach for their removal.

The use of clinical practice guidelines (CPGs) to evaluate practice and control costs in ventriculoperitoneal shunt management.

BACKGROUND: As a step toward maximizing the quality and cost-effectiveness of neurosurgical care, we designed clinical practice guidelines (CPGs) for the management of VP shunt malfunctions and infections at a tertiary care pediatric teaching institution. The detailed CPGs determine the use of radiographic studies, laboratory tests, and invasive procedures in the management of this problem. One purpose of the CPGs is to provide clear clinical guidelines for the medical trainee, thereby reducing variability in care and unnecessary utilization of resources. METHODS: The CPGs were developed in stages over a 2-year period. The practice patterns in our institution for the management of shunt malfunctions and infections were articulated. They were compared with those published in the neurosurgical literature, and areas of clinical decision-making variability were identified. Preliminary guidelines were formulated, and data regarding patient care were prospectively collected. Based on this data, final CPGs were formulated and implemented. Total and itemized hospital charges for patients managed according to the CPGs were compared with those for patients in the 3 years before CPG implementation. RESULTS: CPG-managed patients had generally lower total and itemized charges as compared with control patients. Decreased charges per hospital day and charges for shunt films in the CPG group were statistically significant. CONCLUSIONS: The process by which the CPGs were developed and implemented, as well as the CPGs themselves, are described. We also present the clinical, demographic, and financial data that were prospectively collected for all patients managed within the CPGs over an initial 1-year period and compare it with data obtained for control groups of shunt malfunction patients admitted during the 3 years before implementation of the CPGs. We find a trend toward reduction of charges after implementation of the CPG.

Iatrogenic developmental effects of pediatric intensive care.

Critically ill children in the pediatric intensive care environment are at particular risk for experiencing health care interventions that hinder them from progressing through their normal developmental milestones. Knowledge of the factors that influence iatrogenic developmental insults can help the nurse develop the skills and sensitivity to meet the complex needs of these children and their families.

The comatose child: analysis of factors affecting intracranial pressure.

The child with a head injury is a critical care nursing challenge. Care objectives include decreasing the physical and emotional effects of brain trauma and assisting the child to return to the highest possible level of functioning.