Critical role for GALR1 galanin receptor in galanin regulation of neuroendocrine function and seizure activity

The GALR1 galanin receptor is expressed at high levels within the central nervous system. To determine which specific actions of galanin are mediated by GALR1, we have developed mice with an insertional inactivating mutation within the gene encoding GALR1 (Galr1). Homozygous Galr1-/- mice are viable and capable of breeding. They exhibit no significant difference in growth rate relative to Galr1+/+ controls but have reduced circulating levels of insulin-like growth factor-I (IGF-I) and exhibit spontaneous tonic-clonic seizures. The phenotype of these mice identifies a critical role for GALR1 in neuroendocrine regulation and in mediating the anti-seizure activity of galanin.     

Bone anchored sling for the treatment of post-prostatectomy incontinence

PURPOSE: This ongoing study evaluates the safety and efficacy of a new minimally invasive sling procedure for treating post-prostatectomy incontinence. MATERIALS AND METHODS: A total of 16 men 56 to 74 years old (mean age 67) underwent the procedure using the Straight-In bone anchoring system. Time after prostatectomy was 1.5 to 5 years (mean 2.5). Of the 16 patients 14 had urodynamically confirmed stress urinary incontinence, while 2 had mixed incontinence with stress incontinence and detrusor instability. The procedure is performed with the patient in the lithotomy position using a perineal approach. Four miniature bone screws with pre-attached pairs of No. 1 polypropylene sutures are placed directly into the medial aspect of the inferior rami of the pubic bone. A pair of bone anchors is placed just below the symphysis on each side, and the second pair is inserted 3 to 4 cm. lower. To support the bulbar urethra a gelatin coated polyethylene terephthalate trapezoid shaped sling or cadaveric fascia lata is tied to the pubic bone using the 4 pairs of sutures attached to the bone anchors. Urethral resistance is increased to 30 to 50 cm. water above baseline pressure. RESULTS: Followup was 4 to 20 months (mean 12.2). Of the 14 men with the preoperative urodynamic diagnosis of genuine stress incontinence 12 were cured of incontinence, defined as subjectively dry with no or only 1 pad used daily for security without any episode of leakage, while 2 were improved subjectively with a decrease of 50% or more in pads daily. Two other patients with the preoperative diagnosis of mixed urinary incontinence were improved. Postoperatively urodynamic study in these patients revealed resolved stress incontinence but persistent urge urinary incontinence. They responded to anticholinergics and are completely dry. Intraoperative and postoperative complications were minimal with no erosion, infection or osseous complications. CONCLUSIONS: This new minimally invasive male sling procedure is safe and efficacious. Adjusting sling tension by measuring urethral resistance results in a low rate of over correction and failure. Further experience is needed to establish this procedure as treatment for post-prostatectomy incontinence.     

Determination of the glycoforms of human chorionic gonadotropin beta-core fragment by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry

BACKGROUND: Metabolism of human chorionic gonadotropin (hCG) in the serum and kidney yields the terminal urinary product hCG beta-core fragment (hCGbetacf), comprising two disulfide-linked peptides (beta6-beta40 and beta55-beta92) of which one (beta6-beta40) retains truncated N-linked sugars. Hyperglycosylated hCGbetacf may indicate choriocarcinoma or Down syndrome, but the glycosylation profile of hCGbetacf has not been thoroughly evaluated. METHODS: hCGbetacf, purified from pregnancy urine, was reduced by "on-target" dithiothreitol (DTT) reduction and analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). The mass ([M+H](+)) of the primary sequence of the glycosylated peptide beta6-beta40 was subtracted from the m/z values of the discrete peaks observed to give the masses of the carbohydrate moieties. Carbohydrate structure was predicted by sequentially subtracting the masses of the monosaccharide residues corresponding to N-linked carbohydrates of the hCG beta-subunit reported in the literature. RESULTS: Mass spectra of hCGbetacf revealed a broad triple peak at m/z 8700-11300. After reduction, the triple peak was replaced by a discrete set of peaks between m/z 4156 and 6354. A peak at m/z 4156.8 corresponded to the nonglycosylated peptide (beta55-beta92). The remaining nine peaks indicated that urinary hCGbetacf comprises a set of glycoforms smaller and larger than the trimannosyl core. CONCLUSIONS: hCGbetacf comprises a wider set of glycoforms than reported previously. Peaks of highest mass indicate evidence of hyperglycosylated carbohydrate moieties. The data support previous reports that hCGbetacf oligosaccharides lack sialic acid and galactose residues. No indication was found of a beta6-beta40 peptide that was entirely devoid of carbohydrate.     

Absent otoacoustic emissions predict otitis media in young Aboriginal children: A birth cohort study in Aboriginal and non-Aboriginal children in an arid zone of Western Australia

Background  

Otitis media (OM) is the most common paediatric illness for which antibiotics are prescribed. In Australian Aboriginal children OM is frequently asymptomatic and starts at a younger age, is more common and more likely to result in hearing loss than in non-Aboriginal children. Absent transient evoked otoacoustic emissions (TEOAEs) may predict subsequent risk of OM.     

Anesthesia systems. Part 1: Operating principles of fundamental components

This article is the first in a two-part series on the operation of principal components within Narkomed anesthesia systems. Part 1 illustrates the structure and function of various sections of the machine's internal piping, including components of the pneumatic circuit and the oxygen flush valve, and several safety features, such as the oxygen supply pressure alarm, oxygen failure protection device, and oxygen ratio monitor controller. The article progresses to other basic components of the anesthesia system. Topics include the function of the absorber unit and the flow of gas through it, the principle of operation of the positive end-expiratory pressure valve, the function and mechanics of the adjustable pressure limiter valve, and the open reservoir scavenger system. Part 1 is a valuable tool in understanding the function and pneumatics of the primary components of the anesthesia system.All figures are compliments of the Department of Education at North American Dräger, Telford, PA.     

5-HYDROXYTRYPTAMINE-INDUCED CONTRACTION OF THE MARMOSET AORTA IS MEDIATED BY A 5-HT1-LIKE RECEPTOR

1. 5-Hydroxytryptamine (5-HT) exerts both contractile and relaxant effects in the marmoset isolated aorta, actions that are unaffected by the 5-HT₂ antagonist ketanserin. The aim of the present study was to define the receptors mediating the contractile activity of 5-HT in the marmoset aorta.
2. Contractile responses were elicited in aortic rings that were either: (i) precontracted submaximally with the thromboxane A₂ agonist U44069 in order to amplify the responses; or (ii) exposed to N ^ω-nitro- L -arginine (100 μmol/L) plus LY 53857 (0.1 μmol/L; a 5-HT₂ receptor antagonist shown previously to inhibit relaxation). The effect of 5-HT on adenosine 3',5'-cyclic monophosphate (cAMP) formation was also investigated.
3. The effects of agonists and antagonists comprised: (i) agonist potencies in the order 5-carboxamidotryptamine > 5-HT > sumatriptan > 8-hydroxy-2-(di- n -propylamino)tetralin; (ii) inhibition of contractile action of 5-HT by the 5-HT_1D antagonist GR 127935; (iii) a contractile response to methysergide; (iv) a lack of effect of tropisetron, an antagonist of 5-HT₃ and 5-HT₄ receptors; and (v) inhibition of forskolin-stimulated cAMP formation by 5-HT (in the presence of LY 53857), indicative of negative coupling to adenylate cyclase.
4. The above effects fulfil the criteria for a 5-HT₁-like receptor. In view of the previous finding that this contractile response is insensitive to ketanserin, it is concluded that the contractile effects of 5-HT in the marmoset aorta are mediated exclusively by a 5-HT₁-like receptor.     

The Clinical Course of Epilepsy and Its Psychosocial Correlates: Findings from a U.K. Community Study

As part of a large community-based study, we retrospectively examined the clinical course of epilepsy in an unselected population of people who had a recent history of seizures or were receiving antiepileptic drugs (AEDs). Clinical information was collected from medical records, and information about psychosocial functioning was obtained by means of postal questionnaires sent to identified subjects. The response rate to the postal questionnaire was 71%. There were some deficiencies in the recording of clinical data, which is not unusual since data were taken from records held by primary physicians rather than from hospital clinics. Nevertheless, findings regarding the clinical course of epilepsy corresponded to those of earlier studies. Fifty-seven percent of the sample had had at least a 2-year seizure-free period and 46% of subjects were currently in a remission of at least 2-year duration. There was a clear relationship between current seizure frequency and levels of anxiety and depression, perceived impact of epilepsy, perceived stigma, and marital and employment status. The relationship of seizure frequency and other clinical variables to psychosocial function was explored by multivariate analysis techniques. The amount of variation in scores on the various measures of function accounted for by the clinical variables was small. The most important predictor was current seizure activity, which was the first variable to enter the regression analyses for six of the eight measures of psychosocial function considered. Age at epilepsy onset also emerged as a significant predictor for depression, stigma, and marital status. In individuals with epilepsy in remission, there was little evidence that psychosocial functioning was associated with length of remission, a finding which may in part reflect the nature of this study population. The results indicate that there are several more important predictors of psychopathology and social dysfunction in epilepsy and suggest several implications for treatment interventions.