NMDA receptor regulation by amyloid-beta does not account for its inhibition of LTP in rat hippocampus.

Accumulation of amyloid-beta peptide (Abeta) is widely believed to play a critical role in the pathogenesis of Alzheimer's disease. Although amyloid-containing plaques are a key neuropathological feature of AD, soluble forms of Abeta can interfere with synaptic plasticity in the brain, suggesting that this form of the peptide may be responsible for much of the memory deficit seen early in the disease. Here, we investigate the mechanism underlying the effects of Abeta on long-term potentiation (LTP) in area CA1 of rat hippocampus.

Longer-term primary prevention for alcohol misuse in young people: a systematic review.

Objective: To identify and summarize rigorous evaluations of psychosocial and educational interventions aimed at the primary prevention of alcohol misuse by young people aged up to 25 years, especially over the longer term (>3 years).

Methods: Cochrane Collaboration Systematic Review.

Data Sources: A comprehensive search of 22 databases and recursive checking of bibliographies for randomized and non-randomized controlled trials and interrupted time-series studies.

The effects of estrogen on osteoprotegerin, RANKL, and estrogen receptor expression in human osteoblasts.

Estrogen is essential for bone growth and development and for the maintenance of bone health in adulthood. The cellular responses of osteoblasts and osteoclasts to estrogen are initiated via two high-affinity receptors (ERs). Osteoblasts synthesize RANKL (receptor activator of NF-kappaB ligand), necessary for osteoclast formation and function, and osteoprotegerin (OPG), its decoy receptor.

Primary prevention for alcohol misuse in young people.

Background: Alcohol misuse is a cause of concern for health services, policy makers, prevention workers, the criminal justice system, youth workers, teachers and parents.

Objectives: 1. To identify and summarize rigorous evaluations of psychosocial and educational interventions aimed at the primary prevention of alcohol misuse by young people.

Toxicity assessment of sediments from the Grand Calumet River and Indiana Harbor Canal in Northwestern Indiana, USA.

The objective of this study was to evaluate the toxicity of sediments from the Grand Calumet River and Indiana Harbor Canal located in northwestern Indiana, USA. Toxicity tests used in this assessment included 10-day sediment exposures with the amphipod Hyalella azteca, 31-day sediment exposures with the oligochaete Lumbriculus variegatus, and the Microtox Solid-Phase Sediment Toxicity Test. A total of 30 sampling stations were selected in locations that had limited historic matching toxicity and chemistry data.

Effects of estrogen on collagen synthesis by cultured human osteoblasts depend on the rate of cellular differentiation.

Estrogen is known to act on osteoblasts according to their stage of differentiation and estrogen receptor (ER) isoform expression. The aim of this study was to determine when type I collagen (COL1) synthesis by cultured low-passage, human bone-derived osteoblasts (hOBs) is upregulated in response to estrogen. Cell lines from female donors aged 1 and 66 years were cultured for 11 days on collagen in growth medium supplemented with human serum, hydrocortisone, and beta-glycerophosphate.

Group I mGluRs increase excitability of hippocampal CA1 pyramidal neurons by a PLC-independent mechanism.

Previous studies have implicated phospholipase C (PLC)-linked Group I metabotropic glutamate receptors (mGluRs) in regulating the excitability of hippocampal CA1 pyramidal neurons. We used intracellular recordings from rat hippocampal slices and specific antagonists to examine in more detail the mGluR receptor subtypes and signal transduction mechanisms underlying this effect. Application of the Group I mGluR agonist (RS)-3,5-dihydroxyphenylglycine (DHPG) suppressed slow- and medium-duration afterhyperpolarizations (s- and mAHP) and caused a consequent increase in cell excitability as well as a depolarization of the membrane and an increase in input resistance.

Innate immune responses in viral encephalitis.

The innate immune system is multifaceted, comprised of preformed factors, cells, and many proteins and lipid mediators produced by those cells. In the CNS these are critical in initiation and amplification of the inflammatory response and in the subsequent elicitation of the specific T cell response to viral encephalitis. Cells that are resident in brain parenchyma and peripheral cells that are recruited both play key roles in the hosts's responses.

Pediatric legalities.

Health care practitioners must be cognizant of medical malpractice and the criteria that encompass professional liability. The 4 separate but related criteria of professional liability are discussed and explanations given on their importance. Emphasis is placed on pediatric legalities, although there are many aspects of medical malpractice applicable to both the adult and pediatric patient.

Distal scaphoid excision after radioscaphoid arthrodesis.

Radioscaphoid and radioscapholunate arthrodeses are effective surgical procedures for the treatment of nonsalvageable and isolated radiocarpal arthritis. These procedures, however, limit wrist motion significantly as the immobile scaphoid bridges the remaining midcarpal joint. A cadaver study of radioscaphoid arthrodesis followed by distal scaphoid excision was undertaken.

Mechanisms by which high-dose estrogen therapy produces anabolic skeletal effects in postmenopausal women: role of locally produced growth factors.

Conventional hormone replacement therapy acts primarily by preserving bone, but cannot restore lost bone in women with established osteoporosis. Studies in rodents have shown that high doses of estrogens have anabolic skeletal effects, and recent observations in a group of women treated long term with high doses of estrogen indicated that similar effects occur in humans. This study examines the hypothesis that locally produced growth factors, including transforming growth factor-beta (TGF-beta) and platelet-derived growth factors (PDGFs), are involved in mediating the anabolic effects of high-dose estrogen.

Colocalization of glucocorticoid and mineralocorticoid receptors in human bone.

Osteoporosis is a poorly understood but common complication of glucocorticoid therapy. The actions of glucocorticoids are mediated via glucocorticoid receptors (GRs), but in vitro, glucocorticoids also can bind to mineralocorticoid receptors (MRs). It is not known if MR protein is present in human bone and little is known of GR isoform expression (GRalpha and GRbeta).

Multiple changes in gene expression in chronic human Achilles tendinopathy.

Atlas cDNA cell interaction arrays (CLONTECH) were used to examine degenerate tissue from four patients with Achilles tendon disorders, in order to identify changes in expression of genes important in cell-cell and cell-matrix interactions. The greatest difference between normal (post-mortem) and degenerate tissue samples was in the level of MMP-3 (stromelysin) mRNA, which was down-regulated in all the degenerate samples. Quantitative RT-PCR assay of RNA extracted from paired 'normal' and degenerate Achilles tendon tissue samples taken from tendons during surgery mirrored the results of the arrays.

The role of interleukin-18 in vesicular stomatitis virus infection of the CNS.

Intranasal application of vesicular stomatitis virus (VSV) results in the initial infection of the olfactory receptor neurons and a rapid progression of the virus through the mouse central nervous system (CNS). Interleukin-18 (IL-18) is an 18.3-kd cytokine that induces interferon gamma (IFN-gamma) production in mice.

A pharmacokinetic and pharmacodynamic comparison of desmopressin administered as whole, chewed and crushed tablets, and as an oral solution.

Purpose: We performed a crossover study to determine the relative pharmacokinetic bioavailability and antidiuretic activity of desmopressin in 16 orally hydrated, healthy human subjects.

Materials And Methods: The investigation included 5 study periods with 1 period used to establish baseline diuresis in the absence of desmopressin and the remaining 4 randomized to a single 0.6 mg.

Surgical management of advanced ovarian cancer.

Surgery is an essential part of the management of patients presenting with ovarian cancer. Diagnosis, staging, and therapy can be carried out at the time of laparotomy. Unfortunately, the disease often presents at an advanced stage and the outlook for patients is poor with an overall 5-year survival rate of 23%.

Platelet-derived endothelial cell growth factor expression and angiogenesis in cervical intraepithelial neoplasia and squamous cell carcinoma of the cervix.

Growth and metastatic spread of invasive carcinoma depends on angiogenesis, the formation of new blood vessels. Platelet-derived endothelial cell growth factor (PD-ECGF) is an angiogenic growth factor for a number of solid tumors, including lung, bladder, colorectal, and renal cell cancer. Cervical intraepithelial neoplasia (CIN) is the precursor to squamous cell cervical carcinoma (SCC).

Does histological incomplete excision of cervical intraepithelial neoplasia following large loop excision of transformation zone increase recurrence rates? A six year cytological follow up.

Objective: To determine the risk of recurrent cervical intraepithelial neoplasia (CIN) in women with complete or incomplete excision of cervical intraepithelial neoplasia treated by large loop excision of transformation zone (LLETZ).

Design: A retrospective study

Setting: One consultant-led colposcopy clinic at Leicester Royal Infirmary

Population: Three hundred and ninety-four women referred consecutively to the colposcopy clinic between 1991 and 1992.

Main Outcome Measures: The histological recurrence rate of CIN, length of cytological follow up following treatment related to degree of completeness of excision at initial treatment.

Tyrosine phosphorylation-dependent inhibition of hippocampal synaptic plasticity.

We examined the effects of two protein tyrosine phosphatase inhibitors on the induction of synaptic plasticity in CA1 slices of rat hippocampus. Field potential recordings were made in stratum radiatum in response to stimulation of the Schaffer collateral afferents. Bath application of the tyrosine phosphatase inhibitors sodium orthovanadate or phenylarsine oxide for 30 min had little effect on basal synaptic transmission but blocked the induction of both long-term potentiation (LTP) and homosynaptic long-term depression (LTD).

Cervical disease in women referred to colposcopy following inadequate smears.

The aim of this audit was to determine if inadequate cervical smears are associated with significant cervical pathology. Case records for 52 women with three consecutive inadequate smears referred for colposcopy to the Leicester Royal Infirmary (LRI) were retrieved. Sixteen women underwent large loop excision of the transformation zone (LLETZ) and cervical intraepithelial neoplasia (CIN) was identified in six cases.

Preferential formation of strong synapses during re-innervation of guinea-pig sympathetic ganglia.

1. Re-innervation of partially denervated sympathetic ganglion cells was investigated using intracellular recording in guinea-pig lumbar paravertebral ganglia in vitro. The question addressed was whether the pattern of innervation by strong (suprathreshold) and weak (subthreshold) inputs seen normally was restored during re-innervation.