Alpha-1 and alpha-2 adrenoceptor binding in cerebral cortex: Competition studies with [3H]prazosin and [3H]idazoxan

Summary The tritiated adrenergic antagonists prazosin ([³H]PRZ) and idazoxan ([³H]IDA, or RX-781094) bind specifically and with high affinity in membrane preparations from cerebral cortex to alpha-1- and alpha-2-adrenoceptors respectively. Saturation experiments, performed to determine the density of receptors (B_max; maximum binding capacity) and the dissociation constant (K_d 25 °C), were analyzed by the methods of Eadie and Hofstee, iterative modelling, and the procedure of Hill. The pharmacologic properties and specificity of the labelling was verified by displacement experiments using alpha-adrenergic antagonists and agonists. The antagonist drugs showed the following order of potency to displace [³H]prazosin: prazosin phentolamine corynanthine > pyrextramine yohimbine piperoxan > benextramine > idazoxan; for the agonists: clonidine (–)-noradrenaline (–)-adrenaline phenylephrine, while other drugs, such as (–)-propranolol, dopamine, (–)-isoproterenol and serotonin only competed with the alpha-1-ligand at concentrations above 20 M. The alpha₂-sites labelled by [³H]idazoxan were characterized by the antagonist displacement sequence idazoxan phentolamine > yohimbine = > piperoxan pyrextramine benextramine prazosin corynanthine. The agonists order of potency to compete with [³H]idazoxan was clonidine phenylephrine = > (–)-adrenaline > (–)-noradrenaline, and for other related drugs it was (–)-propranolol dopamine serotonin > (–)-isoproterenol. These competition experiments clearly showed two pharmacologically distinct sites, but question the relative specificity of some of the adrenergic drugs.Abreviations [³H]PRZ [³H]prazosin - [³H]IDA [³H]idazoxan - B_max maximum binding capacity - K_d dissociation constant - IC 50 inhibitory concentration that reduces binding by 50% - K_i inhibition-dissociation constant - nH Hill coefficient - CMC coefficient of multiple correlation - fmol/mg p fentomoles per mg of protein - nM nanomolar Recipient of a F.R.S.Q. Studentship.     

Biochemical Changes after Vertical Banded Gastroplasty for Morbid Obesity

A prospective study of biochemical changes after vertical banded gastroplasty for morbid obesity, in 94 patients (10 males and 84 females, ages ranging from 18 to 59 years) has been carried out. Liver function tests and electrolyte estimations were performed preoperatively, during hospitalisation for surgery, at 6 weeks and at 6 months postoperatively, and demonstrated no significant changes in liver function in these patients 6 months after surgery. The study concludes that there is no increase in the risk of liver damage or electrolyte disturbance after vertical gastroplasty, but that there may be subtle hepatic changes present as gall bladder disease developed in 18 patients postoperation (19%).     

Autoradiography of glutamate receptor binding in adult Lurcher mutant mice

The mutation Lurcher, resulting from a gain of malfunction of the delta2 glutamate receptor expressed specifically by cerebellar Purkinje cells, causes a primary total loss of these neurons of the cerebellar cortex, as well as the secondary degeneration of cerebellar granule and inferior olive neurons. The distributions of glutamate receptors sensitive to amino-methylisoxazole-propionic acid (AMPA), to kainic acid (KA), and to N-methyl-D-aspartic acid (NMDA) as well as metabotropic sites (MET1 and MET2) were examined in wild type and Lurcher mice by quantitative autoradiography. This study was undertaken to determine the gene effect on the distribution of the various glutamate receptor subtypes, as well as how the cerebellar lesion affects the glutamatergic system in other brain regions. In cerebellum, there were postsynaptic AMPA and metabotropic receptors on Purkinje cells, postsynaptic NMDA receptors on granule cells, as well as KA receptors on granule cells or on parallel fibers. Taking into account surface areas, binding to all receptor subtypes was lower in the cerebellar cortex of Lurcher mutants than in wild type mice, while in the deep cerebellar nuclei only KA receptors were diminished. In other brain regions, the alterations followed always the same pattern characterized by a decrease of NMDA and KA receptors but with an increase of AMPA sites; these reciprocal changes were seen in thalamus. neostriatum, limbic regions, and motor cerebral cortical regions. Comparisons of glutamate receptor distribution in Lurcher mutants and in human autosomal cerebellar ataxia may permit further understanding of the role of glutamate-induced toxicity on neuronal death in these heredo-degenerative diseases.     

Acute appendicitis presenting with a testicular mass: ultrasound appearances

Acute appendicitis presenting with scrotal symptoms is a rare event, occurring when a patent processus vaginalis persists. We present a case where ultrasound demonstrated an inflamed appendix and a scrotal abscess, allowing the correct surgical management in a difficult clinical situation. In a child presenting with scrotal signs and vague lower abdominal symptoms, an ultrasound assessment of the right iliac fossa should always be performed.     

Reasons for rejecting potential donors from a sperm bank program

Purpose: Recruiting donors to a sperm bank program is difficult and slow because of high dropout rates and high rejection rates. The profile of successful and unsuccessful donors was determined at our sperm bank. Methods: A total of 199 men was screened from 1986 to 1994 in the anonymous sperm bank donor program; 174 (87%) men dropped out or did not meet minimum guidelines. The study included 25 accepted donors and 20 rejected men (of 52 rejected donors, only 20 donors who came for two consecutive semen analyses were selected). Sperm quality variables and demographic data were compared between the groups. Results: Accepted donors had significantly better semen quality in motility, velocity, linearity, and ALH than did rejected donors (P < 0.01). More rejected donors than accepted donors were single (P < 0.01). A higher percentage of accepted donors consumed caffeine (P < 0.001), and they were more likely to have college degrees (P < 0.03). Conclusions: These results indicate that loss of interest and poor semen quality were the major reasons for rejection of donors in our anonymous donor sperm bank program.     

Fatal shoulder dystocia: a review of 56 cases reported to the Confidential Enquiry into Stillbirths and Deaths in Infancy

Objective To use information collected by the Confidential Enquiry into Stillbirths and Deaths in Infancy to help obstetric, midwifery and paediatric practice in the management of shoulder dystocia.
Design Review of casenotes by a multidisciplinary focus group.
Sample All 56 cases reported to the Confidential Enquiry into Stillbirths and Deaths in Infancy from England, Wales and Northern Ireland in 1994 and 1995, where stillbirth or neonatal death was attributed to shoulder dystocia.
Main outcome measures Case notes were reviewed with respect to a range of perinatal variables. Comparisons were made with normative data from other studies when appropriate.
Results Maternal obesity and big babies were over-represented in pregnancies complicated by fatal shoulder dystocia. Fetal compromise was recorded in 26% of labours. The median time interval between delivery of the head and the rest of the body was only five minutes. The lead professional at the time the head was delivered was a midwife in 65% of cases. Middle grade or senior obstetric staff were supervising 47% of cases by the time the body was delivered.
Conclusions Antenatal prediction of shoulder dystocia is imprecise, and the majority of deliveries are attended by midwives. A relatively brief delay in delivery of the shoulders may be associated with a fatal outcome.     

Prolonged pregnancy: evaluating gestation-specific risks of fetal and infant mortality

Objective To evaluate gestation-specific risks of stillbirth, neonatal and post-neonatal mortality.
Design Retrospective analysis of 171,527 notified births (1989–1991) and subsequent infant survival at one year, from community child health records.
Setting Notifications from maternity units in the North East Thames Region, London.
Main outcome measures The incidence of births, stillbirths, neonatal and post-neonatal deaths at each gestation after 28 completed weeks. Mortality rates per 1000 total or live births and per 1000 ongoing pregnancies at each gestation were calculated.
Results The rates of stillbirth at term (2.3 per 1000 total births) and post-term (1.9 per 1000 total births) were similar. When calculated per 1000 ongoing pregnancies, the rate of stillbirth increased six-fold from 0.35 per 1000 ongoing pregnancies at 37 weeks to 2.12 per 1000 ongoing pregnancies at 43 weeks of gestation. Neonatal and post-neonatal mortality rates fell significantly with advancing gestation, from 15 1.4 and 31.7 per 1000 live births at 28 weeks, to reach a nadir at 41 weeks of gestation (0.7 and 1.3 per 1000 live births, respectively), increasing thereafter in prolonged gestation to 1.6 and 2.1 per 1000 live births at 43 weeks of gestation. When calculated per 1000 ongoing pregnancies, the overall risk of pregnancy loss (stillbirth + infant mortality) increased eight-fold from 0.7 per 1000 ongoing pregnancies at 37 weeks to 5.8 per 1000 ongoing pregnancies at 43 weeks of gestation.
Conclusion The risks of prolonged gestation on pregnancy are better reflected by calculating fetal and infant losses per 1000 ongoing pregnancies. There is a significant increase in the risk of stillbirth, neonatal and post-neonatal mortality in prolonged pregnancy. This study provides accurate data on gestation-specific risks of pregnancy loss, enabling pregnant women and their carers to judge the appropriateness of obstetric intervention.     

Antenatal corticosteroid therapy and risk of osteoporosis

Objective To assess the risk of maternal osteoporosis associated with antenatal corticosterioid administration for neonatal respiratory distress syndrome prophylaxis.
Design Prospective longitudinal study.
Setting Maternity unit of Chelsea and Westminster Hospital, London.
Population Fourteen pregnant women who received dexamethasone therapy for fetal lung maturation in anticipation of delivery before 34 completed weeks of gestation.
Methods Blood samples were collected before dexamethasone administration, 24 hours and 48 hours after the course of dexamethasone, and within 24 hours of delivery. Serum levels of carboxy terminal pro-peptide of type I pro-collagen (PICP) were measured to monitor the rate of bone formation, and serum levels of cross-linked carboxy terminal telopeptide (ICTP) were measured as a marker of bone resorption.
Main outcome measures Changes in the markers of bone turnover following dexamethasone administration.
Results Serum PICP levels dropped 24 hours after dexamethasone therapy (   P = 0.001  ), but partially recovered by 48 hours (   P = 0.014  ) to reach higher than pre-therapy levels at delivery (   P = 0.044  ). Although there were no corresponding changes in the serum levels of ICTP after 24 and 48 hours of therapy, levels increased from pretherapy to delivery (   P = 0.006  ).
Conclusion Antenatal corticosteroid therapy leads to a transient suppression of, followed by an increase in, bone formation without any significant alteration in the pattern of bone resorption expected during pregnancy.