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Biomedical subjects

D J Wilkinson

Publications and source records attributed to D J Wilkinson.

At least 55 records · Page 3Linked to original sources

Cholinergic modulation of apical Na+ channels in turtle colon: analysis of CDPC-induced fluctuations.

Current fluctuation analysis was used to investigate the properties of apical Na+ channels during muscarinic inhibition of active Na+ absorption. A reversible Na+ channel blocker, 6-chloro-3,5-diaminopyrazine-2-carboxamide (CDPC), was used to induce fluctuations in the short-circuit current (I(sc)). Power density spectra of the CDPC-induced fluctuations exhibited a clearly discernible Lorentzian component, characterized by a corner frequency that was linearly related to CDPC concentration between 20 and 100 microM. The on (k'on) and off (k(off)) rate coefficients for the CDPC blocking reaction were k'on = 11.1 +/- 0.8 rad.s-1.microM-1 and k(off) = 744 +/- 53 rad/s, and the microscopic inhibition constant was 67 microM (n = 11). CDPC blocking kinetics were not significantly different after inhibition of Isc by 5 microM serosal carbachol. Single-channel Na+ current (iNa) and the density of open and blocked Na+ channels (N(ob)) were estimated from the fluctuations induced by 40 microM CDPC. Under control conditions, iNa was 0.43 +/- 0.05 pA and N(ob) was 251 +/- 42 X 10(6)/cm2 (n = 10). After exposure to serosal carbachol (2-10 microM) for 60 min, Na+ current and N(ob) were reduced by approximately 50%, but iNa was not changed significantly. These results indicate that muscarinic inhibition of electrogenic Na+ absorption was associated with a reduction in the number of open Na+ channels in the apical membrane. They also suggest that this downregulation of transport involved a coordinated decrease in both apical and basolateral membrane conductances.

Amiloride↗

Intra-articular and subcutaneous prilocaine with adrenaline for pain relief in day case arthroscopy of the knee joint.

A randomised, double-blind study was conducted to assess the influence of intra-articular and subcutaneous prilocaine with adrenaline on postoperative pain in day case arthroscopy of the knee. The time to first dose of oral analgesia postoperatively was significantly prolonged in those patients receiving prilocaine but no significant difference in analgesic effect was demonstrated at 4, 8, and 12 h after operation between the two groups.

Ambulatory Surgical Procedures↗

Plasma lignocaine levels during transurethral prostatectomy.

It has been reported that transurethral absorption of lignocaine may cause systemic toxicity when associated with mucosal damage within the urethra. We measured the serum levels of lignocaine in 30 patients after the transurethral administration of 400 mg lignocaine gel just before transurethral prostatectomy. In 11 patients additional lignocaine was given as part of the anaesthetic induction (Group A). In 19 patients no additional lignocaine was given (Group B). Two patients in Group A and three patients in Group B also underwent Otis urethrotomy. The mean peak plasma lignocaine concentration as measured by sequential venous samples was 1424 ng/ml in Group A and 72 ng/ml in Group B. We conclude that 400 mg lignocaine gel applied endourethrally before transurethral resection of the prostate results in plasma concentrations well below the toxic levels.

Aged↗

A radioimmunoassay method for the determination of nedocromil sodium in plasma and urine.

A radioimmunoassay method for the determination of nedocromil sodium (FPL 59002 disodium salt) in human plasma and urine is described. The method employs a primary antiserum raised in a sheep, and a mono-tyramide derivative of nedocromil sodium labelled with iodine-125 as a heterogeneous radioligand. Free and bound radioligand are separated using a secondary anti-sheep IgG antiserum. All three reagents are added simultaneously to samples containing nedocromil sodium prior to an overnight incubation. The method has a limit of detection of 0.25 ng ml(-1), when plasma sample volumes of 100 microl are analysed, and is accurate and precise. Inter-assay relative standard deviations (N = 18) of 15.1, 5.0 and 5.6% were found at concentrations in plasma of 0.5, 2.0 and 6.0 ng ml(-1) respectively. The method is specific as indicated by negligible cross-reaction of the anti-nedocromil sodium antiserum with a range of drugs. The method is applicable to the analysis of samples from subjects who have inhaled nedocromil sodium from a pressurised aerosol.

Journal Article↗

A double-blind study of the respiratory effects of nalbuphine hydrochloride in spontaneously breathing anesthetized patients.

Nalbuphine hydrochloride 0.2 mg/kg was compared with meperidine 0.5 mg/kg in a double-blind study in 20 patients undergoing elective inguinal hernia repair while breathing spontaneously under general anesthesia. The respiratory effects of the two drugs studied were continuously and accurately recorded with a wet wedge spirometer throughout the procedure. The acute respiratory effects of these analgesic drugs could therefore be assessed. The measurements recorded before any surgical stimulation showed that both nalbuphine and meperidine produce a similar degree of respiratory depression. These results are at variance with earlier studies that drew conclusions from measurements that were neither continuous nor accurate. Nalbuphine was found to be a satisfactory analgesic adjuvant in this anesthetic technique.

Adult↗

Contac 400: a possible cause of aspiration under anaesthesia.

Patients often take proprietary medicines which they do not report to their anaesthetist. One such case is reported in which a self administered high dosage of such a medication can be linked with a potentially life threatening anaesthetic complication. Pre-anaesthetic assessment should include specific questioning on over-the-counter medication.

Adult↗

Opioid agonist/antagonists in general anaesthesia.

Pain is a symptom that is universally recognized yet poorly treated. Almost every patient undergoing surgery will experience pain postoperatively. There is increased interest in the control of this pain and many new analgesics have been introduced. One such group of analgesics, the agonist/antagonist opioids, has evoked much interest among anaesthetists.

Analgesics, Opioid↗

Meptazinol--a cause of respiratory depression in general anaesthesia.

The respiratory effects of meptazinol 1 mg kg-1 have been compared with those of pethidine 0.5 mg kg-1 and 1 mg kg-1 in a double-blind trial in 30 patients undergoing arthroscopic meniscectomy under general anaesthesia. Respiratory depression was seen in all treatment groups. Pethidine 1 mg kg-1 produced respiratory depression which was greater than that produced by meptazinol 1 mg kg-1. The least depressant respiratory effects were seen in the group receiving pethidine 0.5 mg kg-1. We submit that the measurement of tidal volume enhances the assessment of the respiratory effects of analgesic drugs during anaesthesia.

Adult↗

Anaesthetic management in Moya-moya disease.

A case of Moya-moya disease requiring anaesthesia for both investigation and attempted surgical correction is presented. The influence of the anaesthetic technique on the abnormal cerebral vasculature, with particular reference to induced hypocapnia, is discussed. Guidelines for a safe method of anaesthesia in this group of patients are suggested.

Anesthesia, General↗

Conjugation of disodium 6-chloro-4-oxo-10-propyl-4H-pyrano[3,2-g]quinoline-2,8-dicarboxy late with glutathione in the rat.

Disodium 6-chloro-4-oxo-10-propyl-4H-pyrano[3,2-g]quinoline- 2,8-dicarboxylate (I) is conjugated with glutathione (GSH) both in vitro and in vivo by nucleophilic replacement of the chlorine substituent in (I). The reaction is catalysed by rat-liver supernatant. The GSH conjugate is the principal excretory product in the rat bile after i.v. administration of (I), accounting for approximately 60% of the dose and 95% of the biliary excretion. Its structure was determined by synthesis and spectroscopic analysis.

Animals↗

Radioimmunoassay of sodium cromoglycate in human plasma.

A sensitive radioimmunoassay method for sodium cromoglycate in human plasma is described. The lowest quantifiable concentration of sodium cromoglycate is 0.93 nmol/l when 0.1 ml plasma samples are analysed. Direct analysis of sodium cromoglycate concentrations in plasma samples collected up to several hours after the administration of single therapeutic doses of the compound is possible. An antiserum raised in a sheep, radioligand heterogeneously labelled with iodine-125, and a second antibody technique for the separation of bound and free radioligand are employed. The inter-assay coefficient of variation is less than 14% (n = 23). The range of the method is limited; both 0.01 and 0.1 ml volumes of plasma must be analysed to encompass the concentration range 0.93-139 nmol/l which may be encountered in plasma samples from patients and human volunteers. The method is specific for sodium cromoglycate as indicated by a low cross-reactivity of the anti-cromoglycate antiserum with a number of drugs.

Animals↗

Cell-specific phosphorylation of H1 histone subtypes among different Chinese hamster cell lines in interphase.

The phosphorylation of H1 histone subtypes was studied in 3 Chinese hamster cell lines (CHO, V79, and CHW). Chromatographic resolution of H1 subtypes showed that all 3 cell lines contained 1 homologous (coeluting) H1 subtype (CHO-1, V79-1, and CHW-1) while V79 and CHW cells contained 2 additional H1 subtypes not found in CHO cells (V79-2,3 and CHW-2,3). N-Bromosuccinimide cleavage of 32P-labeled H1 subtypes demonstrated that all V79 subtypes were phosphorylated in both the NH2- and COOH-terminal regions during interphase while CHO-1 was phosphorylated only in the COOH-terminal region. Tryptic phosphopeptide fractionations, using 2 sequential electrophoretic steps on paper, demonstrated qualitative differences in the 32P-labeled peptides from the 7 H1 subtypes of the 3 cell lines. For example, CHO-1 differed from its V79-1 homologue by 1 phosphopeptide and from its CHW-1 homologue by 3 phosphopeptides. Phosphopeptide differences were also observed among the H1 subtypes of both V79 and CHW cells. The results demonstrate that Chinese hamster cell lines phosphorylated H1 histone subtypes differently during interphase and that there is no rigorous functional connection between the phosphorylation of the NH2-terminal region of 1 or all H1 histone subtypes and the initiation of mitosis in Chinese hamster cells.

Animals↗