Biomedical subjects
C S Norton
Publications and source records attributed to C S Norton.
Environmental context and drug history modulate amphetamine-induced c-fos mRNA expression in the basal ganglia, central extended amygdala, and associated limbic forebrain.
The context in which amphetamine is administered modulates its ability to induce both behavioral sensitization and immediate early gene expression. When given in a novel test environment amphetamine produces greater levels of c-fos and arc mRNA expression in many brain regions relative to when it is given in the home cage. The purpose of the current study was to determine if environment and drug history interact to influence amphetamine-induced c-fos mRNA expression. Rats with a unilateral 6-hydroxydopamine lesion were treated for 7 days with saline or 0.5 mg/kg of d-amphetamine (i.v.) in a distinct and relatively novel test environment (Novel), or in their home cage (Home). Following a 10-12-day withdrawal period, a challenge injection of either saline or 0.5 mg/kg d-amphetamine was administered. In situ hybridization histochemistry was used to examine c-fos mRNA expression in several regions of the basal ganglia, the central extended amygdala, and limbic forebrain. In most brain regions amphetamine given in the Novel environment produced greater c-fos mRNA expression than when given it was given at Home, and drug history had no effect on amphetamine-induced c-fos mRNA expression. However, within the subthalamic nucleus, substantia nigra reticulata, and central nucleus of the amygdala prior experience with amphetamine in the Novel but not Home environment enhanced the effect of an amphetamine challenge injection on c-fos mRNA expression. In contrast, there was a decrease in c-fos mRNA expression in amphetamine-pretreated animals, regardless of environmental context, in the ventral portion of the far caudal striatum. Reexposure to an environment previously paired with amphetamine produced a conditioned increase in c-fos mRNA expression in portions of the caudate-putamen, the subthalamic nucleus, the nucleus accumbens shell and a conditioned decrease in c-fos mRNA expression in the central nucleus of the amygdala. We conclude that environmental context and drug history interact to alter the basal ganglia and central extended amygdala circuitry engaged by subsequent exposure to amphetamine, or exposure to an environment previously paired with amphetamine.
Injectable silicone biomaterial for faecal incontinence due to internal anal sphincter dysfunction.
BACKGROUND: A weak or disrupted internal anal sphincter can cause passive faecal incontinence. Conservative measures may help some patients but there is no simple surgical solution for those who fail conservative treatment. A successful technique using trans-sphincteric injection of a bulking agent to augment the internal anal sphincter was developed in a previous pilot study. AIM: To determine the clinical results and underlying physiological effects of biomaterial injection. PATIENTS: Six patients (four males, median age 53 years (range 36-65)) with faecal incontinence to solid or liquid stool related to poor internal anal sphincter function, of varied aetiology, were recruited. METHODS: Silicone based biomaterial injections were performed, under local anaesthesia, with antibiotic cover. Three injections were placed circumferentially, trans-sphincterically, entering away from the anal margin and injecting at or just above the dentate line. Anorectal physiological studies, endoanal ultrasound, a bowel symptom diary, a validated incontinence score, and quality of life questionnaires were completed before treatment and on completion of follow up. RESULTS: At a median follow up of 18 months (range 15-19), five of six patients had marked symptom improvement. Faecal incontinence scores improved from a median of 14/24 (range 11-20) before to 8/24 (6-15) after injection. Short form-36 quality of life physical and social function scores improved from a median of 26/100 (5-33) to 79/100 (25-100) and from 10/100 (5-37) to 100/100 (50-100), respectively. There was a corresponding physiological increase in maximum anal resting and squeeze pressures. Ultrasound showed the Bioplastique to be retained in the correct position in the improved patients without migration. There were no complications. CONCLUSION: Trans-sphincteric injection of silicone biomaterial can provide a marked improvement in faecal incontinence related to a weak or disrupted internal anal sphincter. This is associated with improved sphincter function and quality of life.
Social defeat alters the acquisition of cocaine self-administration in rats: role of individual differences in cocaine-taking behavior.
RATIONALE: It is known that social defeat can modulate cocaine self-administration. However, it is unclear whether this psychosocial stressor affects drug-taking behavior to the same extent across all individual animals, particularly those with differing propensities to self-administer psychostimulants. OBJECTIVE: This study examined the effect of social defeat on cocaine self-administration in animals that differ in novelty-seeking behavior that predicts differences in drug self-administration. METHODS: Male Sprague-Dawley rats were first classified into high-responder (HR) and low-responder (LR) groups. HR and LR rats were categorized based on their locomotor activity in a novel environment, with HR rats exhibiting higher locomotor activity than LR rats. Then, male rats were exposed on four occasions to an aggressive Long Evans male rat over the course of 4 days. Control rats were not exposed to the social defeat. All rats were subsequently implanted with jugular catheters and 3 days later placed into the self-administration box to study the acquisition of cocaine self-administration (0.25 mg per infusion). RESULTS: HR non-defeated animals self-administered more cocaine than the LR non-defeated animals. Following social defeat, the acquisition of cocaine self-administration is significantly delayed in HR rats and enhanced in LR rats. CONCLUSION The unique patterns of responsiveness in the HR and LR animals suggest that social defeat plays a role of equalizer of individual differences in drug-taking behavior.
Internal anal sphincter augmentation for fecal incontinence using injectable silicone biomaterial.
PURPOSE: A disrupted or weak internal anal sphincter can lead to passive fecal incontinence. This muscle is not amenable to direct surgical repair. Previous preliminary attempts to restore functional continuity have included a cutaneous flap to fill an anal canal defect, and injection therapy using polytetrafluoroethylene, collagen, or autologous fat. Urologists have also used injections of collagen or silicone to enhance bladder neck function. This pilot study aimed to assess the efficacy of single or multiple injections of the silicone-based product Bioplastique for the symptoms of passive fecal incontinence caused by an anatomically disrupted or intact but weak internal anal sphincter. PATIENTS AND METHODS: Ten patients (6 females; median age, 64, range, 41-80 years) with passive incontinence secondary to a weak (n = 6) or disrupted (n = 4) internal anal sphincter were injected either circumferentially or at a single site, respectively. Patients were assessed before and six weeks after treatment by clinical assessment, two-week bowel diary card, anorectal physiologic testing, and endoanal ultrasound. Patients failing to show improvement after the first injection were offered a second injection six weeks after the first injection. Clinical assessment was further repeated at six months, and five patients had a further ultrasound examination. RESULTS: At six weeks, six of ten patients showed either marked improvement (n = 3) or complete cessation of leakage (n = 3). A further patient was greatly improved after a second injection. Three patients were not improved. At six months, two of the seven patients had maintained marked improvement, and one patient had maintained minor improvement; all of these three patients had circumferential multiple injections. Maximum resting and squeeze anal pressures did not differ significantly between before vs. six weeks after vs. six months after injection. At six weeks endoanal ultrasound (n = 9) confirmed the presence and correct position of the silicone in all but one patient who had experienced obvious external leakage of the product. At six months the silicone remained in the correct position in the five endosonographically assessed patients. Five of the initial patients experienced pain or minor ulceration at the injection site. CONCLUSIONS: Although clinically effective immediately after injection, the benefit of an injectable biomaterial was maintained in only a minority of patients. This occurred despite the continued presence of material in the correct anatomical site. Patients with diffuse weakness treated by circumferential injection seemed to be the most responsive, but further studies are required to clarify this.
Amphetamine and cocaine induce different patterns of c-fos mRNA expression in the striatum and subthalamic nucleus depending on environmental context.
In the dorsal striatum, there are two major populations of medium spiny projection neurons. One population is positive for dynorphin mRNA (DYN+), and these cells project preferentially to the substantia nigra, forming the so-called 'direct pathway'. A second population is positive for enkephalin mRNA (ENK+), and these cells influence the substantia nigra indirectly, via the globus pallidus and subthalamic nucleus. Psychostimulant drugs, such as amphetamine and cocaine, are reported to induce immediate early genes (IEGs) in only one subpopulation of dorsal striatal projection neurons, DYN+ cells. However, this apparent selectivity appears to be a function of environmental context. We found that when given in the animal's home cage, amphetamine and cocaine increased expression of the IEG, c-fos, almost exclusively in DYN+ cells. However, when given in a novel environment, amphetamine and cocaine increased c-fos mRNA in both DYN+ and ENK+ cells. Furthermore, amphetamine and cocaine increased c-fos mRNA expression in the subthalamic nucleus when administered in the novel environment, but not when given at home. We conclude that the neural circuitry engaged by psychostimulant drugs, and their ability to induce specific patterns of gene expression, are determined by the environmental context in which they are experienced. This may be related to the ability of environmental novelty to facilitate psychostimulant drug-induced neuroplasticity.
Long-term results of overlapping anterior anal-sphincter repair for obstetric trauma.
BACKGROUND: Anterior structural damage to the anal sphincter occurs in up to a third of women at first vaginal delivery, and of these a third have new bowel symptoms. The standard treatment for such structural damage is anterior overlapping anal-sphincter repair. We aimed to assess the long-term results of this operation. METHODS: We assessed the long-term results in 55 consecutive patients who had had repair a minimum of 5 years (median 77 months [range 60-96]) previously. Questionnaire and telephone interview assessed current bowel function and continence, restriction in activities related to bowel control, and overall satisfaction with the results of surgery. 42 of these patients had been continent of solid and liquid stool at a median of 15 months after the repair. FINDINGS: We were able to contact 47 (86%) of the 55 patients. One of these patients had required a proctectomy and end ileostomy for Crohn's disease. Of the remaining 46 patients, 27 reported improved bowel control without the need for further surgery, and 23 rated their symptom improvement as 50% or greater. Seven patients had undergone further surgery for incontinence and one patient had not had a covering stoma closed. Thus, the long-term functional outcome of the sphincter repair alone could be assessed in 38 patients. Of these patients, none was fully continent to both stool and flatus; only four were totally continent to solid and liquid stool; six had no faecal urgency; and eight had no passive soiling. Of the 38 patients, 20 still wore a pad for incontinence and 25 reported lifestyle restriction. 14 reported the onset of a new evacuation disorder after sphincter repair. 23 of the 46 patients contacted had a successful long-term outcome (defined as no further surgery and urge faecal incontinence monthly or less). INTERPRETATION: The results of overlapping sphincter repair for obstetric anal-sphincter damage seem to deteriorate with time. Preoperative counselling should emphasise that although most patients will improve after the procedure, continence is rarely perfect, many have residual symptoms, and some may develop new evacuation disorders.
Repeated cocaine exposure attenuates the ability of 5-hydroxytryptamine to release striatal dopamine in vivo.
Cocaine was administered repeatedly to rats and striatal microdialysis performed 1, 7, 14, or 21 days after the last cocaine injection. Local perfusion of 10 microM serotonin (5-hydroxytryptamine, 5-HT) increased basal dopamine levels approximately 7-fold (664 +/- 79%, 813 +/- 104% and 669 +/- 22%, n = 6, P < 0.0001) in saline-treated controls, whereas in cocaine-treated animals the effect was significantly attenuated (432 +/- 55%, 465 +/- 61% and 497 +/- 48% n = 6-10, P < 0.03) at 1, 7 and 14 days of withdrawal. The 5-HT effect on dopamine release returned to control levels 21 days after cocaine exposure and was not altered by acute cocaine treatment (30 mg/kg, i.p. 24 h prior). The results suggest that repeated cocaine administration attenuates the effectiveness of 5-HT on striatal dopaminergic activity.
Letter: More on that 350 kVp chest X-ray system.
Explore the source record for details and available documents.
That constant potential circuit.
Explore the source record for details and available documents.