Effect of testosterone on medial preoptic/anterior hypothalamic neurone responses to stimulation of the lateral septum

Electrophysiological recordings were made from medial preoptic/anterior hypothalamic (MPOAH) neurones which could be orthodromically excited from the lateral septum (LS) in gonadally intact and castrated male rats. Castration significantly reduced the mean percentage of MPOAH neurones which responded reliably to 0.6 Hz stimulation (from 81.1% to 54.1%) and this could be reversed by testosterone propionate (from 52.5% to 90.1%). Both in the gonadally intact (58.1%) and castrated (53.8%) groups these MPOAH neurones with LS inputs also had inputs from the contralateral fimbria (CFIMB). A further experiment investigated whether these MPOAH neurones responding to LS stimulation had connections with the arcuate/median eminence (ARC/ME) region or the medial forebrain bundle (MFB). Altogether, 23.2% projected directly into the MFB and 9.5% into the ARC/ME. A further 28.4% and 31.6% of these MPOAH neurones received inputs from these respective brain regions. A small population of MPOAH neurones were also found which could be driven antidromically both from the LS and the MFB.Results show that testosterone alters the responsiveness of MPOAH neurones to stimulation of the LS. Since subpopulations of these neurones project to the MFB/and ARC/ME the effects of castration on them may reflect both changes in sexual behavior and, for example, gonadotropin release.     

New insight into the pathophysiology of severe hypothyroidism in an infant with multiple hepatic hemangiomas

We report on an infant with severe acquired hypothyroidism resulting from both increased activity of type 3 iodothyronine deiodinase and increased production of TSH-like hormone from hepatic hemangiomas. The combination of these two mechanisms in a patient with hepatic hemangiomas has not been reported previously.     

Somatostatin induces striatal dopamine release and contralateral turning behaviour in the mouse

Application of somatostatin to the striatum of the anaesthetized rat has previously been shown to elicit large increases in extracellular levels of dopamine and GABA via a glutamate-dependent mechanism. These actions have been ascribed to the SSTR2 receptor. Here we describe experiments designed to investigate whether these effects occur in C57Bl6 mice and if they elicit rotational behaviours associated with increased dopamine in the striatum. Application of somatostatin resulted in increased concentrations of dopamine in striatum, hippocampus and amygdala of anaesthetized mice. Unilateral striatal infusions of the peptide by retrodialysis increased locomotion. Application of N-methyl-D-aspartate and AMPA to the freely-moving mouse striatum resulted in increased dopamine release; however, only AMPA caused increased locomotion. These results further confirm that somatostatin can play a role in the control of locomotor function by modulating striatal dopamine release.     

The effects of nitric oxide on striatal serotoninergic transmission involve multiple targets: an in vivo microdialysis study in the awake rat

The role of endogenous nitric oxide (NO) in N-methyl-D-aspartate (NMDA)-induced modulation of serotonin (5-HT) release in the striatum of freely moving rats has been studied using microdialysis technique. NMDA-induced increase in 5-HT release was significantly inhibited by selective nitric oxide synthase (nNOS) inhibitor S-methylthiocitrulline (S-Me-TC), ONOO- scavenger L-cysteine (L-cys), and guanylate cyclase (GC) inhibitor 1H[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ). These data suggest that modulation of 5-HT levels is linked to the formation of NO produced by NMDA receptor activation and that endogenously produced NO increases 5-HT concentrations both by stimulating formation of 3'-5'-cyclic monophosphate (cGMP) and conversion of ONOO-.     

Community provision for informal live-in carers of stroke patients

Stroke is common and disabling. Most stroke patients are cared for at home by informal carers. This study of informal carers of stroke patients measured service provision and satisfaction with different aspects of community care received by these carers. Dissatisfaction was expressed with training and information provision for carers, communication between carers and community services, speed of response and coordination of community services, and perceived support. Problems of information provision were most marked for those patients with most disability and/or older carers.     

Canine ileal motor activity after a model of jejunoileal autotransplantation

OBJECTIVE: To determine mechanisms by which extrinsic innervation to the jejunoileum controls ileal motility. SUMMARY BACKGROUND DATA: Small bowel transplantation is complicated by diarrhea and delayed gastric emptying, possibly secondary to altered motility. Ileal motility after small bowel transplantation is poorly characterized. METHODS: Motor activity was recorded from four dogs during fasting and after feeding small (64 Kcal) or large (256 Kcal) meals. Short-chain fatty acids known to induce unique ileal motor patterns were administered into the distal ileum during fasting. Dogs were studied before and after jejunoileal denervation simulating autotransplantation. RESULTS: After jejunoileal denervation, the ileal migrating motor complex (MMC) persisted but was no longer temporally coordinated with duodenal MMCs. Spontaneous giant migrating contractions occurred more frequently after denervation and more commonly originated proximally in the jejunum, but the velocity of migration did not differ. In contrast, the incidence and characteristics of spontaneous discrete clustered contractions (DCCs) did not differ. Short-chain fatty acids reproducibly initiated giant migrating contractions and discrete clustered contractions in the distal ileum without differences before and after denervation. Large but not small meals inhibited the ileal MMC after denervation. CONCLUSIONS: Extrinsic innervation and/or intrinsic neural continuity with the duodenum and/or colon control temporal coordination of ileal motility with the duodenum and modulate postprandial inhibition of fasting motility and presence of giant migrating contractions. These changes in motility patterns may prove important in mediating enteric dysfunction after small bowel transplantation.     

A prospective trial of bupropion SR augmentation of partial and non-responders to serotonergic antidepressants

Many patients fail to achieve an adequate response to a given antidepressant trial. The best-studied augmentation agents, lithium and thyroid supplementation are less commonly used. Augmenting antidepressants with bupropion has become an increasingly common strategy in the treatment of resistant depression. Several case reports and 2 open label studies suggest efficacy of this strategy. The purpose of this study is to further examine the utility of bupropion sustained release (SR) augmentation in patients with inadequate response to selective serotonin reuptake inhibitors. Patients who met DSM-IV criteria for major depression and had failed to achieve adequate response to an SSRI were considered for this study. Eligible patients were required to have a score of 16 on the 24-item Hamilton Depression Rating Scale (HDRS). Patients were treated openly for 6 weeks with bupropion SR added to their existing antidepressant. The dose range of bupropion was 150 to 300 mg per day. At each visit, patients were assessed using the Beck Depression Inventory (BDI), the Hamilton Depression Ratings Scale (HDRS), and the Clinical Global Impression (CGI). Twenty-eight patients (12 men, 16 women) entered the study. Twenty-five patients completed the six-week trial. With respect to the clinical benefit of bupropion SR augmentation, 15 out of 28, or 54% of patients, were classified as responders, showing a decrease in their HDRS or BDI scores of 50% or more between baseline and Week 6. This prospective, open-label trial supports the use of bupropion SR in the augmentation of SSRIs and venlafaxine. Placebo controlled trials should be completed to further evaluate the efficacy of this strategy.     

Home oximetry studies for diagnosis of sleep apnea/hypopnea syndrome: limitation of memory storage capabilities

BACKGROUND: Memory oximeters enable diagnostic studies for sleep apnea hypopnea syndrome (SAHS) to be performed in the home. However, memory capabilities may be limited. Study Objectives: To compare a pulse oximeter used at home with an 8-h memory, storing data every 12 s, and in the laboratory, with on-line recording every 2 s. DESIGN: Prospective cohort study. SETTING: Patients' homes and a sleep laboratory. PATIENTS: One hundred patients with suspected SAHS. MEASUREMENTS: Home oximetry and a laboratory full polysomnography. The number of >/= 4% dips in pulse oximetric saturation (SpO(2)) was calculated for each study. Daytime sleepiness was assessed by the Epworth Sleepiness Scale (ESS) score. RESULTS: The mean dips per hour were 5.3/h (range, 0 to 53/h) for home studies and 13.4/h (range, 0 to 106/h) for laboratory studies; the relationship between home and laboratory studies was as follows: home = (0.4 x laboratory) - 0.01 +/- 11.2; r(2) = 0.64. Mean difference was 8.4/h (- 2.5 to + 77.9/h), which correlated with the mean of the measurements. At a cutoff point of 10/h, 52 studies were both negative and 13 studies were both positive. Nineteen home studies were false-negatives. Sensitivity was 0.41, and specificity was 1.0. In these 19 studies, 7 patients had an ESS score > 10 and 4 patients had an ESS score > 14. To confirm that differences were due to different sampling rates, 16 additional patients had on-line data and stored data collected simultaneously in the laboratory. Mean dips per hour were 3.2/h (range, 0.1 to 18.3/h) for the stored data and 8.34/h (0.2 to 22.8/h) for on-line data; the relationship being stored was as follows: 0.5 on-line - 1.17 +/- 2.6; r(2) = 0.69. Mean difference was 5.2/h (0.04 to 15.4 h), which correlated with the mean of the measurements. CONCLUSION: Home studies using a memory storage pulse oximeter may underestimate the number of hypoxic dips, probably due to sampling rates. Clinically significant hypoxic SAHS may therefore be missed.