GH/GHRH axis in HIV lipodystrophy.

Approximately half of patients with HIV-infection develop abnormal body fat distribution, characterized by increased abdominal, breast, and dorsocervical adiposity and decreased fat in the limbs and face in association with antiretroviral therapy. Changes in fat distribution are associated with dyslipidemia, insulin resistance, and increased cardiovascular risk in patients with HIV lipodystrophy. Growth hormone secretion is reduced and responses to standardized stimulation testing altered, suggesting relative growth hormone deficiency in this population.

A tribute to Dr. Paul A. J. Janssen: entrepreneur extraordinaire, innovative scientist, and significant contributor to anesthesiology.

Dr. Paul Janssen was the founder of Janssen Pharmaceutica and the developer of over 80 pharmaceutical compounds that proved useful in human, botanical, and veterinary medicine. He and his coworkers synthesized the fentanyl family of drugs, many other potent analgesics, droperidol, etomidate, and numerous other important medicines that were extremely useful in psychiatry, parasitology, gastroenterology, cardiology, virology, and immunology.

Polycystic ovary syndrome in obese adolescents.

Purpose Of Review: As the prevalence of pediatric obesity escalates, polycystic ovary syndrome is an increasingly common morbidity for adolescent females. This review describes recent insights into the pathophysiology and treatment of polycystic ovary syndrome, with special attention given to the relationship between polycystic ovary syndrome and obesity.

Recent Findings: Recent research has elucidated three key concepts in our understanding of polycystic ovary syndrome.

Identification and characterization of a selective peroxisome proliferator-activated receptor beta/delta (NR1C2) antagonist.

The identification of small molecule ligands for the peroxisome proliferator-activated receptors (PPARs) has been instrumental in elucidating their biological roles. In particular, agonists have been the focus of much of the research in the field with relatively few antagonists being described and all of those being selective for PPARalpha or PPARgamma. The comparison of these agonist and antagonist ligands in cellular and animal systems has often led to surprising results and new insights into the biology of the PPARs.

The nuclear receptor-coactivator interaction surface as a target for peptide antagonists of the peroxisome proliferator-activated receptors.

The peroxisome proliferator-activated receptors (PPARalpha, PPARdelta, and PPARgamma) constitute a family of nuclear receptors that regulates metabolic processes involved in lipid and glucose homeostasis. Although generally considered to function as ligand-regulated receptors, all three PPARs exhibit a high level of constitutive activity that may result from their stimulation by intracellularly produced endogenous ligands. Consequently, complete inhibition of PPAR signaling requires the development of inverse agonists.

Modulation of androgen receptor activation function 2 by testosterone and dihydrotestosterone.

The androgen receptor (AR) is transcriptionally activated by high affinity binding of testosterone (T) or its 5alpha-reduced metabolite, dihydrotestosterone (DHT), a more potent androgen required for male reproductive tract development. The molecular basis for the weaker activity of T was investigated by determining T-bound ligand binding domain crystal structures of wild-type AR and a prostate cancer somatic mutant complexed with the AR FXXLF or coactivator LXXLL peptide. Nearly identical interactions of T and DHT in the AR ligand binding pocket correlate with similar rates of dissociation from an AR fragment containing the ligand binding domain.

Atypical mycobacterial infection in patients with cystic fibrosis: update on clinical microbiology methods.

While patients with cystic fibrosis (CF) have had dramatic improvement in their survival rates, this has been accompanied by the emergence of more virulent pathogens such as Pseudomonas aeruginosa and Burkholderia cepacia complex organisms. In addition, there has been emergence of organisms of increasing clinical significance such as the nontuberculous mycobacterial (NTM). Although TB infection in patients with CF is extremely uncommon, there is growing concern with regard to atypical Mycobacterium spp, in particular Mycobacterium abscessus.

A structural and in vitro characterization of asoprisnil: a selective progesterone receptor modulator.

Selective progesterone receptor modulators (SPRMs) have been suggested as therapeutic agents for treatment of gynecological disorders. One such SPRM, asoprisnil, was recently in clinical trials for treatment of uterine fibroids and endometriosis. We present the crystal structures of progesterone receptor (PR) ligand binding domain complexed with asoprisnil and the corepressors nuclear receptor corepressor (NCoR) and SMRT.

The spectrum of SCN1A-related infantile epileptic encephalopathies.

The relationship between severe myoclonic epilepsy of infancy (SMEI or Dravet syndrome) and the related syndrome SMEI-borderland (SMEB) with mutations in the sodium channel alpha 1 subunit gene SCN1A is well established. To explore the phenotypic variability associated with SCN1A mutations, 188 patients with a range of epileptic encephalopathies were examined for SCN1A sequence variations by denaturing high performance liquid chromatography and sequencing. All patients had seizure onset within the first 2 years of life.

Toddler drowning prevention: teaching parents about water safety in conjunction with their child's in-water lessons.

The primary objective of the study was to develop a parent education programme that addressed parental misconceptions of toddler water safety previously identified by the authors. Parents (n = 106) of 2-4-year-old toddlers enrolled in swim school lessons completed a self-directed questionnaire before and after a 10-week poolside water safety programme. Differences in pre- and post-programme knowledge and beliefs were measured by frequency and chi-square tested to identify significant changes in parental comprehension of toddler water safety after the programme.

Can the ministry collaborate to form the "next generation" of sponsors?

In looking to the future of sponsored ministry of Catholic institutions, the formation of future sponsors--both religious and lay alike--is an important issue. As this ministry continues to evolve, and sponsoring groups determine how best to prepare new sponsors, might it not be time to think about how to pool the ministry's collective wisdom on formation? Sponsors act not only in the name of the health care institution (or other ministry) but on behalf of the faith community engaged in continuing the compassionate healing ministry of Jesus. In Catholic ministry, and particularly health care ministry, sponsors carry out their responsibilities through a multiplicity of organizational relationships.

Instrumentation-related complications of multilevel fusions for adult spinal deformity patients over age 65: surgical considerations and treatment options in patients with poor bone quality.

Study Design: Retrospective follow-up of patients over the age of 65 with a minimum of five-level fusions.

Objective: To determine the effect on outcomes of long constructs in patients with poor bone stock, and to review surgical techniques used in patients with poor bone stock.

Summary Of Background Data: Scoliotic deformities in patients with poor bone stock require alterations in both the surgical technique and preoperative planning.

Parental perceptions of toddler water safety, swimming ability and swimming lessons.

The primary objective of the study was to examine parental perceptions on the role of toddler swimming ability and pre-school swimming lessons in drowning prevention. A self-administered questionnaire was used to obtain information on toddler water safety from parents (n = 882) whose 2 - 4-year-old toddlers were either attending early childhood centres (n = 327) or who were enrolled in swim schools (n = 555). Differences in attitudes between two groups of parents were measured by frequency, with Mann-Whitney U tests used to discern significant differences between groups.

Is the effect of probiotics on atopic dermatitis confined to food sensitized children?

Background: Probiotics have previously been shown to reduce the severity of atopic dermatitis (AD) in infants and children.

Objective: To examine the effect of two probiotics (Lactobacillus rhamnosus and Bifidobacteria lactis) on established AD in children.

Subjects And Methods: Atopic children with current dermatitis received 2 x 10(10) colony forming units/g of probiotic (n=29) or placebo (n=30).

Severe holocarboxylase synthetase deficiency with incomplete biotin responsiveness resulting in antenatal insult in samoan neonates.

We describe 7 Polynesian babies with a unique severe form of holocarboxylase synthetase deficiency characterized by antenatal growth retardation, subependymal cysts, only partial response to biotin, and a poor outcome.

A ligand-mediated hydrogen bond network required for the activation of the mineralocorticoid receptor.

Ligand binding is the first step in hormone regulation of mineralocorticoid receptor (MR) activity. Here, we report multiple crystal structures of MR (NR3C2) bound to both agonist and antagonists. These structures combined with mutagenesis studies reveal that maximal receptor activation involves an intricate ligand-mediated hydrogen bond network with Asn770 which serves dual roles: stabilization of the loop preceding the C-terminal activation function-2 helix and direct contact with the hormone ligand.

Neonatal death after hypoxic ischaemic encephalopathy: does a postmortem add to the final diagnoses?

Background: Case review after fatal perinatal asphyxia may have medicolegal implications. Accurate diagnosis of cause of death is therefore essential.

Objective: To determine consent rate and utility of autopsy after fatal grade III hypoxic ischaemic encephalopathy (HIE) presumed to be secondary to birth asphyxia.

Fentanyl.

Fentanyl, a potent lipid-soluble opioid which was first synthesized more than 40 years ago, is still the most popular opioid used in the perioperative period throughout the world. Fentanyl's introduction, versatility, and popularity have resulted in its use in many acute and chronic pain conditions and a multitude of novel delivery systems in the last two decades. In spite of the development of more potent, safer, faster onset, and both shorter and longer lasting alternative opioids, fentanyl remains the mainstay of anesthesiologists and Certified Registered Nurse Anesthetists in the perioperative period, and for many pain physicians throughout the world.

Detection of mycobacterial DNA from sputum of patients with cystic fibrosis.

Background: Patients with cystic fibrosis (CF) are at high risk from atypical mycobacterial infections. There have been few attempts to delineate the intensity of mycobacterial infection in CF patients in Ireland.

Aims: To examine the incidence of mycobacterial DNA in an archived collection of genomic DNA extracted from the sputa of CF patients within the Northern Ireland population.

Structural basis for androgen receptor interdomain and coactivator interactions suggests a transition in nuclear receptor activation function dominance.

The androgen receptor (AR) is required for male sex development and contributes to prostate cancer cell survival. In contrast to other nuclear receptors that bind the LXXLL motifs of coactivators, the AR ligand binding domain is preferentially engaged in an interdomain interaction with the AR FXXLF motif. Reported here are crystal structures of the ligand-activated AR ligand binding domain with and without bound FXXLF and LXXLL peptides.