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Biomedical subjects

A C Thompson

Publications and source records attributed to A C Thompson.

At least 19 recordsLinked to original sources
PubMed2001

Modulation of pre- and postsynaptic dopamine D2 receptor function by the selective kappa-opioid receptor agonist U69593.

The repeated administration of selective kappa-opioid receptor agonists prevents the locomotor activation produced by acute cocaine administration and the development of cocaine-induced behavioral sensitization. Previous studies have shown that dopamine (DA) D2 autoreceptors modulate the synthesis and release of DA in the striatum. Evidence that kappa agonist treatment downregulates DA D2 receptors in this same brain region has recently been obtained. Accordingly, the present studies were undertaken to examine the influence of repeated kappa-opioid receptor agonist administration on pre- and postsynaptic DA D2 receptor function in the dorsal striatum using pre- and postsynaptic receptor-selective doses of quinpirole. Rats were injected once daily with the selective kappa-opioid receptor agonist U69593 (0.16-0.32 mg/kg s.c.) or vehicle for 3 days. Microdialysis studies assessing basal and quinpirole-evoked (0.05 mg/kg s.c.) DA levels were conducted 2 days later. Basal and quinpirole-stimulated locomotor activity were assessed in a parallel group of animals. The no-net flux method of quantitative microdialysis revealed no effect of U69593 on basal DA dynamics, in that extracellular DA concentration and extraction fraction did not differ in control and U69593-treated animals. Acute administration of quinpirole significantly decreased striatal DA levels in control animals, but in animals treated with U69593, the inhibitory effects of quinpirole were significantly reduced. Quinpirole produced a dose-related increase in locomotor activity in control animals, and this effect was significantly attenuated in U69593-treated animals. These data reveal that prior repeated administration of a selective kappa-opioid receptor agonist attenuates quinpirole-induced alterations in DA neurotransmission and locomotor activity. These results suggest that both pre- and postsynaptic striatal DA D2 receptors may be downregulated following repeated kappa-opioid receptor agonist administration. Synapse 39:343-350, 2001. Published 2001 Wiley-Liss, Inc.

Animals↗
PubMed2001

Increased patient satisfaction from transrectal ultrasonography and biopsy under sedation.

OBJECTIVE: To determine the acceptability and patient satisfaction of transrectal biopsy undertaken with the patient under sedation. Patients and methods A retrospective questionnaire was sent to 100 patients who had undergone transrectal biopsy between January and August 1998. Levels of patient acceptability and satisfaction were assessed using visual analogue scales (VAS, with a maximum score of 10 being the least satisfactory or acceptable) and direct questions about the side-effects of the procedure. A subsequent prospective study was undertaken on 130 patients undergoing transrectal biopsy with sedation between January 1999 and January 2000. RESULTS: The mean score for patient discomfort with sedation was 1.5, compared with 3.5 with no sedation. The overall satisfaction score improved from 3.1 to 0.9 with sedation. Complication rates were comparable, although slightly higher overall in the prospective group. Conclusion Sedation can significantly reduce patient discomfort and make the transrectal biopsy a more satisfactory experience for the patient. This is particularly important in the proportion of men who need to be considered for repeat biopsies.

Biopsy↗
PubMed2001

Analgesic efficacy of orally administered buprenorphine in rats.

The analgesic effect of orally administered buprenorphine was compared with that induced by a standard therapeutic injected dose (0.05 mg/kg of body weight, s.c.) in male Long-Evans rats. Analgesia was assessed by measuring pain threshold, using the hot-water tail-flick assay before and after administration of buprenorphine. The results suggest that a commonly used formula for oral buprenorphine in flavored gelatin, at a dose of 0.5 mg/kg, does not increase pain threshold in rats. Instead, oral buprenorphine doses of 5 and 10 mg/kg were necessary to induce significant increases in pain threshold. However, these doses had to be administered by orogastric infusion because the rats would not voluntarily eat flavored gelatin containing this much buprenorphine. The depth of analgesia induced by these infused doses was comparable to that induced by the clinically effective s.c. treatment (0.05 mg/kg).

Administration, Oral↗
PubMed2000

Kappa-opioid receptor activation modifies dopamine uptake in the nucleus accumbens and opposes the effects of cocaine.

Coadministration of kappa-opioid receptor agonists (kappa-agonists) with cocaine prevents alterations in dialysate dopamine (DA) concentration in the nucleus accumbens (Acb) that occur during abstinence from repeated cocaine treatment. Quantitative microdialysis was used to determine the mechanism producing these effects. Rats were injected with cocaine (20 mg/kg, i.p.), or saline, and the selective kappa-agonist U-69593 (0.32 mg/kg, s.c.), or vehicle, once daily for 5 d. Extracellular DA concentration (DA(ext)) and extraction fraction (E(d)), an indirect measure of DA uptake, were determined 3 d later. Repeated cocaine treatment increased E(d), whereas repeated U-69593 treatment decreased E(d), relative to controls. Coadministration of both drugs yielded intermediate E(d) values not different from controls. In vitro DA uptake assays confirmed that repeated U-69593 treatment produces a dose-related, region-specific decrease in DA uptake and showed that acute U-69593 administration increases DA uptake in a nor-binaltorphimine reversible manner. Repeated U-69593 also led to a decrease in [(125)I]RTI-55 binding to the DA transporter (DAT), but did not decrease total DAT protein. These results demonstrate that kappa-opioid receptor activation modulates DA uptake in the Acb in a manner opposite to that of cocaine: repeated U-69593 administration decreases the basal rate of DA uptake, and acute U-69593 administration transiently increases DA uptake. kappa-agonist treatment also alters DAT function. The action of kappa-agonists on DA uptake or DAT binding, or both, may be the mechanism(s) mediating the previously reported "cocaine-antagonist" effect of kappa-opioid receptor agonists.

Analysis of Variance↗
PubMed1998

Sensitization to the conditioned rewarding effects of morphine and cocaine: differential effects of the kappa-opioid receptor agonist U69593.

The ability of the kappa-opioid receptor agonist U69593 to attenuate the sensitization and cross-sensitization which develops to the conditioned rewarding effects of morphine and cocaine was examined using an unbiased place-preference conditioning procedure. The influence of U69593 treatment upon sensitization and cross-sensitization to cocaine was also assessed. Doses of morphine (1.0-5.0 mg kg(-1)) which failed to produce a conditioned response in drug-naive rats produced marked preferences for the drug-paired place in animals which had previously received once daily injections of morphine (5.0 mg kg(-1); s.c.) or cocaine (10.0 mg kg(-1); i.p.) for 5 days. Morphine-induced place preferences also occurred in animals which had received morphine in combination with U69593 (0.04-0.32 mg kg(-1); s.c.) on either days 3-5 or 1-5 of the morphine treatment regimen. In contrast, morphine failed to produce significant conditioning in animals which had received U69593 with cocaine for 5 days. Doses of cocaine (1.0-5.0 mg kg(-1)) which did not produce a conditioned response in naive rats produced preferences for the drug-paired place in animals which had received once daily injections of cocaine (10.0 mg kg(-1) day(-1) x 5 days; i.p.) or morphine (5.0 mg kg(-1) day(-1) x 5 days; s.c.). No enhancement of cocaine-induced conditioning occurred in animals which had received U69593 on days 3-5 or on days 1-5 of the five-day cocaine treatment. In animals, however, which had received U69593 with morphine for 5 days, an enhanced response to cocaine was still seen. These findings confirm that sensitization and cross-sensitization develop to the conditioned rewarding effects of cocaine and morphine. They also indicate that the ability of a kappa-opioid receptor agonist to prevent the development of these sensitized responses depends on the sensitizing agent employed. U69593 prevents sensitization and cross-sensitization induced by cocaine, but does not modify morphine-induced sensitization or the cross-sensitization which develops to cocaine after morphine administration.

Analgesics↗
PubMed1996

Opioid stimulation in the ventral tegmental area facilitates the onset of maternal behavior in rats.

This research investigated the effect of an increase or decrease in opioid activity in the ventral tegmental area (VTA) on the onset of maternal behavior in rats. In Experiment 1, the latency to show maternal behavior toward foster rat pups (sensitization latency) was determined in maternally naive female rats given either nothing or a unilateral intra-VTA injection of morphine sulfate (MS) (0.0, 0.01, 0.03, 0.1 or 0.3 microgram), on the first three days of a 10-day period of constant exposure to pups. Rats treated with 0.03 microgram MS had significantly shorter sensitization latencies than did rats treated with 0.0 microgram MS, 0.01 microgram MS, or receiving no treatment (higher doses of morphine produced intermediate results). The facilitating effect of intra-VTA MS on the onset of maternal behavior was blocked by pretreatment with naltrexone hydrochloride and was found to have a specific site of action in the VTA (MS injections dorsal to the VTA were ineffective). In Experiment 2, sensitization latencies were determined in periparturitional rats given a bilateral intra-VTA injection of either the opioid antagonist naltrexone methobromide (quaternary naltrexone), its vehicle, a sham injection, or left untreated 40 min after delivery of the last pup. The mothers' own pups were removed at delivery; mothers were nonmaternal at the time of testing. Quaternary naltrexone treatment produced significantly slower sensitization to foster pups than did control conditions. Total activity and pup-directed activity did not differ significantly with treatment. The results demonstrate that increased opioid activity in the VTA facilitates the onset of maternal behavior in inexperienced nonpregnant female rats, and decreased opioid activity in the VTA disrupts the rapid onset of maternal behavior at parturition.

Analgesics, Opioid↗
PubMed1996

Carcinoma of the larynx and hypopharynx in the elderly.

The outcome of a series of 68 patients over 75 years old with carcinoma of the larynx, and 33 patients over 75 years old with hypopharyngeal carcinoma managed by a single oncological team during a 10-year period was studied. Sixty-one of the patients with laryngeal carcinoma were treated with curative intent. The actuarial 3-year survival rate of the whole group was 45%. This contrasts with hypopharyngeal carcinoma in which we found a 3-year survival of 11% with only 17 of the 33 patients suitable for treatment with curative intent. In view of the anticipated poor prognosis of hypopharyngeal carcinoma in the elderly we conclude that treatment should be directed towards palliation without radical surgery whenever possible.

Aged↗
PubMed1996

Interstitial cystitis--an update.

Interstitial cystitis is a rare chronic debilitating condition predominantly affecting middle-aged women. The diagnosis, made from the combination of symptoms, cystoscopic findings and bladder biopsies, is often delayed because GPs are often unaware of the condition. The precise aetiology remains obscure and it is clear that there is much research that needs to be undertaken to shed any light on the various current aetiological theories. There is a wide assortment of therapies already available and many more currently under trial. Until there is further progress in the pathogenesis of IC, it seems unlikely that non-operative treatment will consist of anything but palliation. The only potential cures currently available are cystectomy and urinary diversion or surgical replacement of the bladder by enterocystoplasty.

Cystitis, Interstitial↗
PubMed1996

Role of extracellular dopamine in the initiation and long-term expression of behavioral sensitization to cocaine.

Repeated intermittent administration of cocaine has been shown to sensitize animals to the locomotor-activating effects of this agent. The neurobiochemical basis of this phenomenon, however, remains only partially understood. The present study sought to characterize basal dialysate dopamine (DA) concentrations within the nucleus accumbens (NAc), 2, 12 or 22 days after the cessation of either repeated cocaine (20 mg/kg/day x 5 days) or saline (1.0 ml/kg/day x 5 days) treatment. Locomotor activity and dialysate DA levels in response to a subsequent cocaine administration (20 mg/kg i.p.) were assessed at the same time intervals. Cocaine-pretreated animals exhibited an enhanced motor response to a cocaine injection 2 days after cessation of cocaine treatment. The magnitude of this effect increased progressively over time. Basal DA overflow was elevated 2 days after termination of cocaine treatment; at this time, however, a blunted response of DA neurons to the cocaine administration was observed. As the duration of withdrawal increased, basal dialysate DA concentrations gradually declined, whereas the response of DA neurons to cocaine progressively increased. By day 22 of withdrawal, a significant enhancement of cocaine-induced DA overflow was seen. These findings demonstrate that increased DA overflow in response to cocaine cannot account for the short-term expression of behavioral sensitization to cocaine. Rather, an enhanced DA response develops during later stages of the sensitization process and, therefore, may be one of the mechanisms responsible for the long-term expression of cocaine sensitization.

Animals↗
PubMed1995

Quantitative microdialysis of neuropeptide Y.

The feasibility of using the difference method of quantitative microdialysis to measure neuropeptide Y (NPY) was evaluated in vitro and in vivo. The accuracy of this method was tested in vitro under steady-state conditions for 3 test solutions containing known concentrations of NPY. The estimated concentrations of NPY were 1.2 +/- 0.6, 3.7 +/- 0.9, and 15.1 +/- 0.7 pg/microliter (mean +/- SEM) in agreement with the actual concentrations of NPY in the test solutions which were 1.1 +/- 0.8, 4.6 +/- 0.6, and 14.6 +/- 0.5 pg/microliter (mean +/- SEM of solution samples), respectively. The responsiveness of the estimated NPYext measure to changes in the external concentration of NPY was also evaluated in vitro. An accurate estimate of NPYext was obtained within the first sampling period (within 15 min) after a 2-3-fold increase in the test solution concentration of NPY and within 2-3 sampling periods (15-45 min) in response to a 2-3-fold decrease in the test solution concentration of NPY. In vivo, the estimated basal concentration of NPY in dialysis samples from probes in the medial basal hypothalamus of anesthetized female rats (n = 4) was 4.0 +/- 1.6 pg/microliters and increased to 9.5 +/- 0.3 pg/microliter during K+ stimulation. Relative recovery was 22% in vivo under steady-state conditions and ranged from 14% to 30% during dynamic conditions. These results demonstrate that the difference method of quantitative microdialysis accurately estimates picomolar concentrations of NPY in vitro, and is sufficiently sensitive to detect basal and increasing concentrations of NPY in vivo.

Animals↗
PubMed1995

Langerhans cells in normal and pathological vocal cord mucosa.

The Langerhans cells in samples of histologically normal and pathological vocal cord mucosa were counted after identification using S-100 polyclonal antibody. Langerhans cells were commonly seen in vocal cord polyp epithelium but were infrequent in normal cord mucosa. They were also identified in samples of squamous carcinoma, severe dysplasia and chronic inflammation.

Aged↗
PubMed1994

Tumor-associated tissue eosinophilia and long-term prognosis for carcinoma of the larynx.

Tumor-associated tissue eosinophilia (TATE) has been previously reported to be associated with a favorable prognosis for a variety of carcinomas, including head and neck cancer. We have examined this relationship in a series of 104 patients with laryngeal cancer who were observed for 5 years or more. Patients were followed up for a minimum of 5 years or until death. The original laryngeal biopsy histologic slides were examined and graded for TATE. Tumor-associated tissue eosinophilia was absent in 73 of the 104 biopsy specimens, and 25 of these 73 patients died directly of laryngeal carcinoma within 5 years. In all, 31 patients had TATE and only 3 subsequently died of laryngeal carcinoma within 5 years (P = 0.009, chi-square test). It appears, therefore, that TATE is associated with a good long-term prognosis for laryngeal carcinoma.

Adult↗
PubMed1993

Malignant melanoma of the nasal cavity and paranasal sinuses.

Malignant melanoma affecting the nasal cavity and paranasal sinuses is a rare condition with a poor prognosis. The Head and Neck Oncology Clinic at the University Hospital Nottingham has treated 16 patients in an 8-year-period. Twelve patients were treated with primary radical surgery and salvage radiotherapy was used for 7 patients with local recurrence. This resulted in tumour shrinkage in 4 patients. Eight patients treated surgically, have died of systemic spread. Four are currently alive, although 2 have local disease.

Adult↗
PubMed1992

Gastric vagotomy blocks opioid analgesia enhancement produced by placenta ingestion.

Ingestion of amniotic fluid or placenta by rats has been shown to enhance opioid-mediated analgesia induced by morphine injection, footshock, vaginal/cervical stimulation, or late pregnancy. This enhancement by ingestion appears to be specific to the central actions of opioids. The present study was designed to examine the possibility that information traveling via the vagus nerve might be involved in mediating this effect. Rats that had undergone either selective gastric vagotomy or sham vagotomy were injected with either morphine sulfate or vehicle and fed either placenta or a meat control. Enhancement was observed in rats that had undergone sham vagotomy but not in those that had undergone gastric vagotomy. These results support an interpretation of vagal involvement in the enhancement of opioid-mediated analgesia by placenta.

Analgesia↗
PubMed1992

Darier's disease of the external ear.

Darier's disease is a hereditary dermatological condition characterized by crusted papules distributed over the seborrhoeic areas of the trunk and head. A case of Darier's disease presenting to the Otolaryngology department because of severe involvement of the pinna is reported. The typical histological appearances are described and treatment discussed.

Darier Disease↗
PubMed1992

Intra-tympanic injections in the treatment of tinnitus.

Prolonged reduction or abolition of tinnitus has been reported in about two-thirds of patients treated with a single or weekly-repeated injection through the tympanic membrane of either dexamethasone or lignocaine. In a small-scale trial of these treatments, dexamethasone gave 6 patients little benefit but few side-effects. Lignocaine gave 5 patients no lasting benefit but violent vertigo for several hours. A. Axelsson (personal communication) had similar experience with 6 patients treated with intra-tympanic lignocaine. It is concluded that this form of treatment does not seem sufficiently effective to offset its low acceptability.

Adult↗