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Biomedical subjects

A N James

Publications and source records attributed to A N James.

At least 19 recordsLinked to original sources

Effects of the selective serotonin reuptake inhibitor, fluoxetine, on regional gastric contractility.

UNLABELLED: Selective serotonin reuptake inhibitors (SSRIs) are increasingly used to treat a variety of disorders but have gastrointestinal side-effects. AIM: To determine the effects of the SSRI, fluoxetine, on gastric smooth muscle contractility. METHODS: Fundic, antral, and pyloric circular muscle contractility of guinea pig muscle strips were measured in vitro. Fluoxetine was added in concentrations from 0.1 nmol L(-1) to 100 mumol L(-1). Receptor antagonists were used to determine the neural pathways involved. RESULTS: Fluoxetine caused concentration dependent contractions, which were greatest in fundus compared with the antrum or pylorus. The contractile effects of fluoxetine in the antrum were reduced by tetrodotoxin, atropine, phentolamine, and the 5-HT(4) receptor antagonist GR 113808. The contractile effects of fluoxetine in the fundus were reduced by atropine, phentolamine, and GR 113808. CONCLUSIONS: Fluoxetine affects gastric contractility with regional variability - contracting the fundus more than the antrum or pylorus. The fluoxetine contractile effect is reduced by tetrodotoxin, atropine, phentolamine, and a 5-HT(4) receptor antagonist. These results suggest fluoxetine interacts with muscarinic, alpha-adrenergic, and serotoninergic receptors and/or ongoing reuptake/release of serotonin in the stomach.

Adrenergic alpha-Antagonists↗

Effects of clonidine and tricyclic antidepressants on gastric smooth muscle contractility.

To determine if and how clonidine and tricyclic antidepressants affect gastric contractility. Guinea pig fundic and antral circular muscle strips were studied in vitro. The effects of clonidine or amitriptyline added in graded concentrations on contractions to electric field stimulation (EFS), acetylcholine (ACh), and SP in the presence of N(epsilon)-nitro-l-arginine methyl ester (l-NAME) were studied. EFS produced frequency dependent contractions of fundic and antral muscle that were abolished by atropine or tetrodotoxin (TTX). ACh contractions were abolished by atropine but not TTX. Clonidine reduced contractile response to EFS but had no effect on ACh contractions. The threshold concentration of clonidine to inhibit EFS contractions was lower in the fundus than in the antrum. Amitriptyline reduced contractions to both EFS and ACh but not to SP. The threshold concentration of amitriptyline to inhibit EFS contractions was lower in the antrum than in the fundus. Both clonidine and amitriptyline affect gastric contractility. At threshold concentrations, clonidine affects fundic contractility whereas amitriptyline affects antral contractility. Clonidine affects gastric contractility in response to EFS but not to ACh, suggesting alpha-2 receptors on cholinergic nerves that reduce ACh release. Amitriptyline inhibits gastric contractility to EFS and ACh suggesting an inhibitory muscle effect.

Acetylcholine↗

Effect of indomethacin on gallbladder inflammation and contractility during acute cholecystitis.

OBJECTIVE: The aim of this study was to determine whether the prostaglandin synthase inhibitor indomethacin reverses the inflammation and abnormal gallbladder contractility that occur after common bile duct ligation (CBDL), a model of acute cholecystitis. METHODS: Gallbladder muscle contractility was studied in vitro in normal, CBDL, and sham-operated guinea pigs. Animals were treated with saline or indomethacin in vivo. Acetylcholine (ACh) was used to directly contract the muscle and electric field stimulation (EFS) to activate intrinsic nerves. Hematoxylin and eosin-stained slides of muscle strips were scored for inflammation. RESULTS: CBDL in saline-treated animals increased the inflammation score and decreased gallbladder muscle contractility to ACh and EFS. Indomethacin decreased the inflammation score and partly reversed the smooth muscle contractile response to ACh 6 and 24 h after CBDL, but not at 48 h. Indomethacin did not reverse the CBDL-induced decrease in nerve-evoked contractions. CONCLUSION: Gallbladder inflammation and contractile dysfunction after CBDL are partly reversed with indomethacin at 6 and 24 h, but not at 48 h. This suggests that, early in the course of CBDL, the inflammation and contractile dysfunction are, in part, prostaglandin-mediated.

Acute Disease↗

Cloned transgenic offspring resulting from somatic cell nuclear transfer in the goat: oocytes derived from both follicle-stimulating hormone-stimulated and nonstimulated abattoir-derived ovaries.

The use of nuclear transfer (NT) techniques to create transgenic offspring capable of producing valuable proteins may have a major impact on the pharmaceutical market. Our objective was to compare the in vivo developmental potential of NT embryos produced from the fusion of transgenic donor cells with cytoplasts prepared from either FSH-stimulated ovaries or nonstimulated abattoir-derived ovaries. Donor cells were prepared from a transgenic fetus carrying the gene for human antithrombin III as a marker and used within four to eight subpassages. Cells were serum deprived for 4 days prior to cytoplast transfer. Oocytes were enucleated by removing the metaphase plate using a DNA stain and epifluorescent illumination. Donor cells were fused to enucleated oocytes by electric pulse and then chemically activated. There was no difference in the number of transferable embryos produced from cytoplasts of FSH-stimulated ovaries or from the fusion of cytoplasts from abattoir ovaries, nor was there a difference in the number of pregnancies established per recipient with either treatment. All pregnancies from both groups culminated in the births of healthy female kids (five total). To our knowledge, this is the first report of cloned goats produced from NT using cytoplasts derived from abattoir ovaries.

Animals↗

Effect of acalculous cholecystitis on gallbladder neuromuscular transmission and contractility.

BACKGROUND: Impaired smooth muscle contractility is important in the pathophysiology of acalculous cholecystitis. Common bile duct ligation (CBDL) is a model of acalculous cholecystitis, producing acute inflammatory changes and decrease in gallbladder smooth muscle contractility. The aim of this study was to determine whether there is coexistent dysfunction of neural efferent motor pathways of the gallbladder after CBDL. MATERIALS AND METHODS: Gallbladder muscle contractility was studied in vitro in normal, CBDL, and sham-operated guinea pigs. Electric field stimulation (EFS; 2-16 Hz) was used to activate intrinsic nerves and exogenous acetylcholine (ACh) was used to directly stimulate the muscle. H&E-stained slides of muscle strips were scored for inflammatory changes. RESULTS: After CBDL, there was a progressive increase in the inflammation score and decrease in gallbladder muscle contractility to ACh. There was also a progressive decline in EFS-induced contractility when expressed as absolute force or normalized to the maximal muscle contractile response to ACh. The nitric oxide synthase inhibitor l-NNA (10 microM) increased EFS-induced contractions by 50 +/- 25% (P = 0.05) in CBDL animals but had no effect in sham surgical controls. CONCLUSIONS: CBDL with its acute gallbladder inflammation affects gallbladder contractility by two mechanisms: (1) decreased smooth muscle contractility, and (2) decreased neurally mediated contractions. The neurally mediated alterations result from dysfunction of cholinergic excitatory nerves and upregulation of nitric-oxide-mediated inhibition of smooth muscle contractility.

Acetylcholine↗

The contractile action of platelet-activating factor on gallbladder smooth muscle.

Platelet-activating factor (PAF) may be a mediator of some sequelae of cholecystitis, a disorder with gallbladder motor dysfunction. The aims of this study were to determine the effect and mechanism of PAF on gallbladder muscle. Exogenous administration of PAF-16 or PAF-18 caused dose-dependent contractions of gallbladder muscle strips in vitro with threshold doses of 1 ng/ml and 10 ng/ml, respectively. The PAF-induced contractions were not significantly reduced by TTX, atropine, or hexamethonium but were significantly inhibited with the PAF receptor antagonists ginkolide B and CV-3988. The PAF-induced contraction was reduced by indomethacin. Preventing influx of extracellular calcium with a calcium-free solution nearly abolished the PAF contractile response. Nifedipine inhibited the PAF contractile response, whereas ryanodine had no effect. Pertussis toxin reduced the PAF contractile response. In conclusion, PAF causes gallbladder contraction through specific PAF receptors on gallbladder muscle. These PAF receptors appear to be linked to a prostaglandin-mediated mechanism and to pertussis toxin-sensitive G proteins. The contractile response is largely mediated through the utilization of extracellular calcium influx through voltage-dependent calcium channels.

Acetylcholine↗

Health-related quality of life in Australian men remaining disease-free after radical prostatectomy.

OBJECTIVE: To determine the health-related quality of life (HRQOL) of Australian men after radical prostatectomy. DESIGN: Cross-sectional study. SETTING: Private and public practices of three urologists in south-east Queensland, July 1989 to June 1995. PARTICIPANTS: 140 men with no evidence of disease recurrence 1 to 6 years after radical prostatectomy. MAIN OUTCOME MEASURES: Voiding and erectile potency and HRQOL. Recall of preoperative status and status at survey were established by an independently administered multi-item questionnaire. RESULTS: 112 men (80%) completed the study questionnaire. Difficulty with bladder control before the operation was reported by 25 (22%; 95% confidence interval [CI], 15%-31.2%), and the incontinence rate after treatment was 22/112 (20%; 95% CI, 12.7%-28.2%). Men with incontinence after operation were more likely to recall preoperative urinary symptoms. Eighty-four (75%) men were happy or coping with their sexual function after radical prostatectomy despite an erectile potency rate of only 12% (95% CI, 7%-20%). Twenty-eight (25%) had tried penile injections and three have had penile prostheses since their operation. Impotence was reported more frequently (40%) as the treatment-related problem most affecting life, followed by "concern about cancer" (12%) and incontinence (8%). Impotence was also the most common cause given for diminished HRQOL. CONCLUSIONS: Loss of sexual function after radical prostatectomy is more commonly perceived as a major problem and is more likely than urinary incontinence to adversely affect HRQOL. Loss of sexual function and its effect on HRQOL needs to be given greater emphasis in counselling before radical prostatectomy.

Cross-Sectional Studies↗

Extracorporeal shock wave lithotripsy for ureteric calculi with the Dornier MFL5000 lithotriptor at a multi-user centre.

We have reviewed 241 consecutive cases of ureteric calculi managed with the Dornier MFL5000 lithotriptor. The patients were individually managed by 24 visiting urologists between October 1990 and September 1991. There were 153 cases of upper ureteric calculi, of which 59 were successfully manipulated back to the renal pelvis prior to treatment, and 94 were treated in situ. There were 27 mid-ureteric and 61 lower ureteric cases; in 51% of stones treated in situ ureteric stents were placed prior to extracorporeal shock wave lithotripsy. All stones were radio-opaque and localised with on-line fluoroscopy. The outcome of treatment was assessed at 3 months, with failure defined as residual calculi > or = 4 mm. The follow-up rate was 89%. The overall fragmentation rate after a single treatment was 72%, which increased to 81% with re-treatment. Of the upper ureteric calculi, manipulated stones had a significantly higher fragmentation rate (85%) compared with in situ stones (63%). The fragmentation rate was 89% for mid-ureteric stones and 71% for lower ureteric stones. Factors that significantly influenced fragmentation were retrograde manipulation of stone, number of impulses delivered and age of the patient. Stone size, the presence of a ureteric stent and mode of anaesthesia did not significantly influence fragmentation. These results suggest the Dornier MFL5000 lithotriptor is effective for the management of ureteric calculi in a multi-user setting.

Adolescent↗

The use of thioglycolic acd in hair-bearing skin inlay urethroplasty.

Thioglycolic acid, in commercially available spray, lotion or cream, was used to remove the hair from the scrotum, pubis and perineum in 45 patients, with minimal discomfort in only 11 patients and wound infection in only one. Eighty-five per cent of these patients said they preferred the depilatory cream to the routine pre-operative shave with a razor. In 3 of 4 patients where it was instilled intraurethrally to remove hairs from skin-inlay urethroplasties it was successful in removing hairs; in the fourth patient most of the hairs were removed. None of these patients had anything more than a short-lasting irritation afterwards.

Hair Removal↗

Attachment of Neisseria gonorrhoeae to human sperm. Microscopical study of trypsin and iron.

Pilated Neisseria gonorrhoeae of colony type 1 (T1) and non-pilated bacteria of colony type 4 (T4) were observed by transmission (TEM) and scanning electron microscopy (SEM). No pili were observed on T4 gonogocci, but two types of pili--straight, type a, and bent, type b--were seen on T1 by TEM. When incubated with human sperum and examined by either TEM or SEM, T1 gonococci were seen to attach by individual pili, by several pili wound together as a rope, or by direct contact. Gonococci from T4 colonies attached only by direct contact. Treatment with typsin (1 mg/ml) damaged or removed pili from gonococci. After incubation with trypsin, attachment of pilated gonococci to sperm was decreased significantly, but such treatment did not affect attachment of non-pilated gonococci. Incubation of gonococci from either colony type in 0.1 mmol/l ferric nitrate, followed by incubation with sperm, significantly increased attachment of only T4 bacteria. No pili were seen on T4 gonococci treated with ferric nitrate; thus, it appears that factors other than pili alone are concerned in attachment of these gonococci to sperm.

Attachment Sites, Microbiological↗

Radiolabeling of and macromolecular syntheses in Neisseria gonorrhoeae types 1 and 4.

Type 1 and type 4 cells of Neisseria gonorrhoeae were grown in a liquid medium that maintained colony type for several hours. Organisms from both types of colonies incorporated labeled glucose, as well as nucleic acid and protein precursors, into specific cellular fractions during growth in the medium. Ribonucleic acid and protein were synthesized actively by the bacteria, with incorporation of label chased by the addition of unlabeled precursors. The method can be used to label type 1 and type 4 cells of gonococci with specific isotopes for studies of metabolic and biochemical changes.

Adenine↗