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Biomedical subjects

M J Landon

Publications and source records attributed to M J Landon.

At least 19 recordsLinked to original sources

The Ohmeda Rascal II. A new gas analyser for anaesthetic use.

The Ohmeda Rascal II is a multigas analyser and pulse oximeter for dedicated anaesthetic.use. It uses the Raman scattering of laser light to identify and quantify oxygen, nitrogen, carbon dioxide, nitrous oxide and three volatile anaesthetic agents. Its response times equal or better the published response times of infrared or photo-acoustic devices. It is linear within the clinical ranges of all gases and vapours, simple to use, requires no maintenance, holds its calibration well, and is a suitable monitor for clinical and research use.

Alcohols↗

Components of the inspiratory-arterial isoflurane partial pressure difference.

We have measured the partial pressure of isoflurane simultaneously in inspired gas (PIiso), end-expired gas (PE'iso), mixed-expired gas (PEiso), arterial (Paiso) and mixed venous blood (Pviso) in six patients (aged 57-79 yr) anaesthetized with nitrous oxide, oxygen and isoflurane before surgery and after PE'iso had been stable for at least 15 min. We related these changes to the various indices of pulmonary maldistribution to determine if they were sufficient to explain reported differences between PE'iso and Paiso. Alveolar deadspace dilution of end-expired gas was calculated for carbon dioxide and this dilution factor used to calculate the "ideal" alveolar Piso (PAiso) from the observed inspired and end-expired concentrations. Shunt fraction was measured for oxygen and then used to calculate the partial pressure of isoflurane in the pulmonary end-capillary blood (Pc'iso) from the partial pressure in arterial and mixed venous blood. Mean (SE) values were: PIiso 0.69 (0.05) kPa; PE'iso 0.52 (0.04) kPa; PAiso 0.50 (0.04) kPa; Pc'iso 0.38 (0.04) kPa; Paiso 0.35 (0.03) kPa and Pviso 0.22 (0.02) kPa; Paiso: PE'iso 0.66 (0.02) kPa. The mean "ideal" alveolar to pulmonary end-capillary Piso difference was 0.12 (0.01) kPa and highly significant (P < 0.001). Paiso was substantially less than PE'iso but, for isoflurane, the difference was reasonably constant (range 0.14-0.22 kPa). The difference was attributable in part to the effects of shunt and deadspace, but also a failure of equilibration of isoflurane between the alveolar gas and pulmonary end-capillary blood. It is likely to be different for other anaesthetics. We conclude that, while PE'iso may adequately reflect Paiso for isoflurane, it cannot be assumed that the relation between end-expiratory gas and arterial partial pressures is the same for all anaesthetics.

Aged↗

Isoflurane inhibits insulin secretion from isolated rat pancreatic islets of Langerhans.

We have investigated the effects of isoflurane on insulin secretion in vitro from rat isolated islets of Langerhans and found a significant, dose-related and reversible inhibition of insulin secretion. Isoflurane 2% decreased insulin secretion stimulated by glucose 20 mmol litre-1 to basal, nonstimulated values. In other studies to identify the stage in the stimulus secretion pathway for insulin at which the anaesthetic may exert an inhibitory action, we have stimulated insulin release using glyceraldehyde and a phorbol ester. Insulin secretion induced by these secretagogues was also blocked by isoflurane. This suggests that the inhibitory effect of the anaesthetic agent may be at a site distal to stimulation of insulin secretion by glyceraldehyde and phorbol esters.

Anesthesia, Inhalation↗

Influence of vitamin B12 status on the inactivation of methionine synthase by nitrous oxide.

We have studied the influence of maternal serum B12 concentration on the inactivation of placental methionine synthase activity by nitrous oxide in an obstetric population. This group was known to include patients with a wide range of B12 values. Over 70% of patients were given nitrous oxide either for analgesia during labour or for delivery by Caesarean section, for periods ranging from a few minutes to 11 h. Patients undergoing normal delivery and Caesarean section under extradural anaesthesia served as controls. There was a highly significant relation between placental methionine synthase activity and duration of exposure to nitrous oxide. Inactivation was slower than that described for the liver, which may reflect the intermittent use. There was also a significant relation between maternal B12 and placental methionine synthase activity, but there was a wide scatter of results and the data were not thought to be predictive. There was evidence that inactivation by nitrous oxide was more rapid in patients with small concentrations of B12. We conclude that some patients with reduced serum concentrations of B12 may be at a disadvantage with nitrous oxide anaesthesia.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗

Absorption of isoflurane by silica gel.

We have studied the capacity of the drying agent silica gel (SG) to absorb isoflurane from gas samples. When dry, SG was able to absorb 31 times its own volume of isoflurane vapour, which could be recovered almost completely from the SG by displacement with water vapour. However, we were unable to demonstrate any significant absorption of isoflurane by wet SG. Care must be taken, therefore, when using SG as a drying agent in the sampling line of an analyser during research involving volatile anaesthetic agents.

Anesthesiology↗

Permeability of the human placenta in vivo to four non-metabolized hydrophilic molecules.

1. Permeability of the human placenta to four permeants of different molecular size was measured at Caesarean section in seven normal full-term pregnancies. 2. Placental clearance for mannitol was 8.7 +/- 1.1 ml min-1 (mean +/- S.E.M.), lactulose 6.3 +/- 0.8, chromium ethylenediaminetetraacetic acid (CrEDTA) 3.7 +/- 0.5, and inulin 0.98 +/- 0.1. 3. The permeability data were analysed in terms of restricted diffusion through 'notional' water-filled pores and found to be incompatible with a single population of uniform pores.

Adult↗

Degradation of radiolabelled arginine vasopressin (125I-AVP) by the human placenta perfused in vitro.

The capacity of the human placenta to degrade 125I-labelled arginine vasopressin (125I-AVP) was studied in vitro using a dual circuit perfused lobule preparation. Seven placentas were perfused with the perfusate on the maternal side of the lobule containing 125I-AVP at the upper limit of the physiological range. On average, over a 30-min period, 48% of the 125I-AVP appeared to have been metabolized. With one exception, a patient whose labour was augmented with intravenous oxytocin, no 125I-AVP apparently crossed the placental lobule to the fetal circulation. These data indicate that the human placenta has a considerable capacity to degrade AVP.

Adult↗

In vivo permeability of the human placenta to inulin and mannitol.

1. Permeability of the term human placenta to inulin and mannitol was measured in six normal pregnancies. 2. Bolus and continuous infusion of inulin and mannitol to the mother for 1-2 h before delivery by Caesarean section achieved steady-state maternal serum concentrations. Net accumulation of inulin and mannitol in the fetus was measured by the subsequent neonatal urinary excretion. 3. Transplacental clearance was calculated by dividing the net flux by the time-averaged transplacental concentration gradient. Clearance for inulin was 0.86 +/- 0.1 ml min-1 (mean +/- S.E.M.) and for mannitol 7.3 +/- 0.8 ml min-1 (n = 6 in both cases).

Female↗

The transfer and metabolism of 7-ethoxycoumarin and androstenedione during the in vitro perfusion of the human placental lobule.

1. The in vitro metabolism of 7-ethoxycoumarin in the perfused placental lobule has been investigated and compared with that of androstenedione. 2. Perfusion studies showed that the placental lobule was capable of sustaining the metabolism of 7-ethoxycoumarin to 7-hydroxycoumarin for at least one hour but at a considerably lower rate than that for the conversion of androstenedione to oestrone under the same conditions. 3. Following perfusion with androstendione disproportionately large amounts of oestrone were found in the maternal outflow and ostradiol in the foetal outflow. 4. Appreciably more testosterone was formed when the foetal side of the lobule was perfused with androstenedione than when the maternal side was perfused. 5. The data indicate that the human placenta has only a limited capacity for the metabolism of xenobiotics.

Androstenedione↗

Effect of nitrous oxide on placental methionine synthase activity.

Methionine synthase activity was measured in 11 placentae after Caesarean section during which nitrous oxide had been used as an anaesthetic agent, and compared with that from 20 placentae after normal vaginal delivery with no exposure to nitrous oxide. There was no significant difference in enzyme activity between the two series.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗

Long-term culture of human trophoblast cells.

A technique is presented for the preparation of cultures of replicating human trophoblast cells from term placentas. The adherent cells obtained were very slow growing (doubling time 12.5 days) as measured by the rate of increase in cell protein, [14C]-leucine uptake and cell number. Cells from individual placentas have been maintained in continuous culture for up to 1 year (10-12 passages) and have been successfully recultured after storage in liquid nitrogen. Cultured cells showed positive immunofluorescent staining for human placental lactogen, human chorionic gonadotrophin, transferrin and type IV collagen. The adenine nucleotide content indicated that energetically the cells were in balance even after prolonged culture.

Cell Division↗

Metabolism of diphenylhydantoin (phenytoin) during pregnancy.

Plasma levels of diphenylhydantoin (DPH) and the 24 hour urinary excretion of both DPH and its major metabolite 5-(p-hydroxyphenyl)-phenylhydantoin (HPPH) were measured serially during pregnancy in a group of five unselected epileptic patients. Plasma DPH levels fell and on average were some 40 per cent lower at term than they had been in early pregnancy. With one exception, the patients were well controlled during pregnancy but two patients who regularly had plasma DPH levels below 10 microgram/ml both suffered seizures in the puerperium. There was no convincing change in the excretion of either DPH or HPPH which together accounted for less than half the administered dose. Gestational length exceeded 41 weeks in 4 of the 5 patients studied but all were delivered of normal healthy infants, of average birthweight, with no congenital defects or clotting disorders.

Adolescent↗

Clinical relevance of coagulation and renal changes in pre-eclampsia.

Changes in coagulation tests (fibrin/fibrinogen degradation products, factor-VIII activity, and platelet-count) and in renal function (creatinine clearance and serum concentration, clearance, and fractional reabsorption of urate) were measured in late pregnancy. 10 patients with severe preeclampsia showed changes in both coagulation and renal function when compared with 13 normotensive controls. 18 patients with mild pre-eclampsia had changes in renal function only. Results from 5 patients with essential hypertension did not differ from those of the normotensive group. When results from the patients with severe pre-eclampsia were arranged in order of decreasing protein excretion, only renal-function tests correlated significantly with this ranking. It is suggested that, in the management of patients with established preeclampsia, assessment of renal function may be of greater practical value than measurement of the degree of coagulopathy.

Adult↗

Effect of anticonvulsant drugs on urinary excretion of gamma-glutamyl transferase in women.

Excretion of gamma-glutamyl transferase was found to be significantly higher in a group of epileptic patients on long-term anticonvulsant therapy than in normal subjects. The losses, which may reflect renal enzyme induction, were unrelated to drug dose or duration of therapy and were significantly lower than those found in normal healthy pregnant women at term.

Anticonvulsants↗

The excretion of gamma-glutamyl transferase in pregnancy.

A cross-sectional study of gamma-glutamyl transferase (gamma-GT) excretion in 316 healthy pregnant women showed the enzyme excretion (mU per mmol creatinine) was significantly higher than that of a non-pregnant control group. The increase was apparent before the end of the first trimester and continued therafter. These changes may be indicative of hypertrophy and/or hyperplasia of the nephron and be part of the overall renal adaptation to normal pregnancy. Even higher levels were recorded in three obstetric patients in whom renal complications were to be expected and this may indicate a specific type of renal damage.

Creatinine↗