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Biomedical subjects

G N Morris

Publications and source records attributed to G N Morris.

At least 19 recordsLinked to original sources

Regulation of the endogenous NO pathway by prolonged inhaled NO in rats.

Nitric oxide (NO) modulates the endogenous NO-cGMP pathway. We determined whether prolonged inhaled NO downregulates the NO-cGMP pathway, which may explain clinically observed rebound pulmonary hypertension. Rats were placed in a normoxic (N; 21% O2) or hypoxic (H; 10% O2) environment with and without inhaled NO (20 parts/million) for 1 or 3 wk. Subsequently, nitric oxide synthase (NOS) and soluble guanylate cyclase (GC) activity and endothelial NOS (eNOS) protein levels were measured. Perfusate cGMP levels and endothelium-dependent and -independent vasodilation were determined in isolated lungs. eNOS protein levels and NOS activity were not altered by inhaled NO in N or H rats. GC activity was decreased by 60 +/- 10 and 55 +/- 11% in N and H rats, respectively, after 1 wk of inhaled NO but was not affected after 3 wk. Inhaled NO had no effect on perfusate cGMP in N lungs. Inhaled NO attenuated the increase in cGMP levels caused by 3 wk of H by 57 +/- 11%, but there was no rebound in cGMP after 24 h of recovery. Endothelium-dependent vasodilation was not altered, and endothelium-independent vasodilation was not altered (N) or slightly increased (H, 10 +/- 3%) by prolonged inhaled NO. In conclusion, inhaled NO did not alter the endogenous NO-cGMP pathway as determined by eNOS protein levels, NOS activity, or endothelium-dependent vasodilation under N and H conditions. GC activity was decreased after 1 wk; however, GC activity was not altered by 3 wk of inhaled NO and endothelium-independent vasodilation was not decreased.

Administration, Inhalation↗

Farnesylation of Batten disease CLN3 protein.

The carboxyl terminal of the predicted amino acid sequence of the Batten disease CLN3 gene protein is CQLS. This motif is expected to be a site for farnesylation at the cysteine residue. In order to determine whether this is indeed farnesylated we have carried out the in-vitro prenylation of tetrapeptides CVLS, CAIL and CQLS using a farnesyl transferase preparation from bovine brain. The data shows that the CQLS is a good acceptor of a farnesyl group similar to CVLS while it is a poor acceptor of a geranylgeranyl group unlike CAIL, which is a good acceptor of a geranylgeranyl group. This suggests that the CLN3 gene product may be a farnesylated protein.

Adolescent↗

Inhaled nitric oxide as a selective pulmonary vasodilator in clinical anesthesia.

Inhaled nitric oxide (NO) is a selective pulmonary vasodilator in adult and pediatric patients. Inhaled NO diffuses into the pulmonary vascular smooth muscle where it results in vasodilation via stimulation of guanylyl cyclase. Systemic hemodynamics are not altered because inhaled NO is rapidly inactivated by hemoglobin. Oxygenation is also increased in certain patients as inhaled NO only vasodilates those segments of the pulmonary vasculature which are ventilated. There is growing evidence that inhaled NO may be a useful therapeutic agent in the treatment of pulmonary hypertension and hypoxemia from a variety of causes. Areas of greatest interest to anesthesia and critical care personnel may involve treatment of persistent pulmonary hypertension of the newborn (PPHN), adult respiratory distress syndrome (ARDS), and postoperative pulmonary hypertension secondary to cardiac disease. The potential toxicity of inhaled NO, particularly on immature and developing lungs, must be considered. While inhaled NO exerts acute beneficial effects, it is unclear if there are long-term benefits. Multicenter trials are currently underway to determine if inhaled NO decreases mortality from PPHN or decreases morbidity associated with ARDS.

Administration, Inhalation↗

Laryngeal mask airway performance: effect of cuff deflation during anaesthesia.

We studied the effect of deflating the laryngeal mask airway (LMA) cuff in situ on recorded respiratory tidal ventilation in 30 spontaneously breathing anaesthetized patients. Another 26 patients were studied in whom the LMA cuff was undisturbed. Deflation of the cuff to a pressure of 22 mm Hg (below an estimated arteriolar perfusion pressure of the pharyngeal mucosa), by removing approximately 50% of the recommended cuff injection volume, had a minimal effect on tidal ventilation (P = 0.9). This manoeuvre may have a role in minimizing transmitted cuff pressure on the adjacent pharyngeal mucosa. Complete cuff deflation, however, resulted in a 17% decrease in mean tidal ventilation (P < 0.05), with two patients (6%) demonstrating a substantial leak around the cuff and airway obstruction. The practice of complete cuff deflation during the recovery period from anaesthesia cannot be recommended.

Adult↗

Influence of patient position on withdrawal forces during removal of lumbar extradural catheters.

We have investigated the force required to remove lumbar extradural catheters from 88 parturients to determine the effects of patient positioning at removal, relative to the position at insertion. Parturients were allocated randomly to one of four groups: LS (lateral insertion, sitting withdrawal), LL (lateral insertion, flexed lateral withdrawal), SL (sitting insertion, lateral withdrawal) or SS (sitting insertion, sitting withdrawal). In both positions, the lumbar spine was kept maximally flexed. The force required to remove the catheter was measured at withdrawal. We found that the withdrawal force was influenced by the relationship between the position at removal and that at insertion, and we recommend that for ease of removal, patients should be placed in the same position as they were at the time of insertion. Compared with all other groups, the withdrawal force in patients in group LS was significantly greater (P < 0.05).

Adolescent↗

The response to varying concentrations of inhaled nitric oxide in patients with acute respiratory distress syndrome.

We investigated the response to varying concentrations of inhaled nitric oxide (NO) in 18 patients with acute respiratory distress syndrome (ARDS). The study was divided into two parts. In Part 1, 5-40 ppm of inhaled NO was evaluated in 10 patients with ARDS. In Part 2, 0.1-10 ppm of inhaled NO was evaluated in eight patients with ARDS. Inhaled NO significantly (P < 0.05) decreased the mean pulmonary artery pressure (MPAP) and pulmonary vascular resistance index (PVRI), and increased the arterial oxygenation (PaO2) at concentrations of 0.1 to 40 ppm. No dose response was detectable for the pulmonary artery pressure (PAP) or PVRI over this dose range. The increase in PaO2 at 10 ppm of NO was significantly greater than that at 0.1 ppm but not 1 ppm. The decrease in PVRI and the increase in PaO2 were both significantly correlated with the baseline PVRI. While the maximum hemodynamic and oxygenation responses to inhaled NO are achieved at approximately 1 ppm, it appears that the maximum hemodynamic response is observed at lower concentrations (0.1 ppm) of inhaled NO than the improvement in oxygenation (1-10 ppm). Higher concentrations of NO do not produce any further change in these variables. It appears that the baseline PVRI may be the best marker predicting a beneficial response to NO.

Administration, Inhalation↗

Feasibility of day case laparoscopic cholecystectomy in unselected patients.

The feasibility of day case laparoscopic cholecystectomy was assessed in unselected patients using a standard anaesthetic protocol. Postoperative pain and nausea were assessed at 6 and 24 h postoperatively (visual analogue scale, range 0-10). Thirty-two patients were studied (23 female, 9 male, mean age 49.6 years). The mean duration of surgery was 68 min. At 6 h after surgery, 10 patients (31%) had no pain at rest. For the group as a whole, the median pain score was 3 at rest (range 0-6), 4 on movement (0-9), and 5 on coughing (0-9) and eight patients (25%) were nauseated. At 24 h, 15 (46.9%) had no pain at rest. For the group as a whole, the median pain score was 1 at rest (0-7), 3 (0-6) on movement and 3 on coughing (0-9). The same eight patients were nauseated. Ten patients (31.3%) were judged fit for discharge at 6 h, and 28 (87.5%) by 24 h. There was no statistical difference in mean age or duration of surgery in those judged fit for early discharge compared to the study group as a whole. Nausea was an important factor in those unfit for discharge at 24 h. Selection criteria might improve these figures. From the results of our study, 24 h admission is a more realistic goal and will be suitable for most patients requiring laparoscopic cholecystectomy.

Adult↗

Bovine brain gray and white matter exhibit differential protein prenyl transferase activity.

Protein farnesyl transferase and geranylgeranyl transferase-I activities were determined in gray and white matter from various regions of bovine brain. Farnesyl transferase activity was 3-8 times greater than geranylgeranyl transferase-I activity. However, farnesyl transferase activity was about 2 times greater in the white matter than in the gray matter in all regions of the brain. Mixing experiments indicated lack of farnesyl transferase activators in white matter. This difference in farnesyl transferase activity may be due to enzyme content and may have implications in brain cell function.

Alkyl and Aryl Transferases↗