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Biomedical subjects

J F Nunn

Publications and source records attributed to J F Nunn.

At least 91 records · Page 5Linked to original sources

The effect of nitrous oxide inactivation of vitamin B12 on rat hepatic folate. Implications for the methylfolate-trap hypothesis.

Rats exposed to N20 show a decrease in liver folate to about 25% of the initial value after 10 days. There is a transient increase in the amount of 5-methylterrahydropteroylpolyglutamate in the first 24 h, but thereafter the content decreases. The level of 5-methyltetrahydropterolymonoglutamate declines without any transitory increase. The transient accumulation of 5-methyltetrahydropteroylpolyglutamate is due to failure of methionine synthetase. Thereafter the decrease in the amount of methylfolate makes it improbable that trapping of methylfolate is the explanation for failure of folate metabolism in vitamin B12 deficiency.

Animals↗

Effects of oxygen on pulmonary macrophages and alveolar epithelial type II cells in culture.

Cultures of Chinese hamster lung fibroblasts and explants of 20-day-old rat lungs were exposed to 95% oxygen with 5% CO2 in vitro. The Chinese hamster cells had stopped dividing after 17 hours exposure and cell death occurred at a mean time of 67 hours (s.d. 15 hours). The rat lung explants showed macrophages moving over a monolayer of alveolar type II epithelial cells. Both cell types appeared to function normally for 24 hours but cell division in the type II cells was about 50% of control between 12 and 24 hours of exposure and virtually ceased after 26 hours. Cell death commenced after 4 days and was complete in 9 days. Macrophages divided freely in the control cultures but only one division was seen during exposure to oxygen and that occurred during the first 24 hours. Motility was reduced by 50% during the second day of exposure and stopped during the 3rd day. No live macrophages were seen after 4 days exposure. These culture systems appear very suitable for screening drugs for their protective effect against oxygen toxicity.

Animals↗

Posterior intercostal nerve block for pain relief after cholecystectomy. Anatomical basis and efficacy.

The human intercostal space has been studied by excision of the posterior part of the rib cage at autopsy, followed by fixation, decalcification, section and staining. Injection of India ink was used to simulate local anaesthetic. At a point 7 cm from the midline, the distance from the posterior aspect of the rib to the pleura averaged 8 mm. The intercostal nerve usually comprises a number of small bundles without any enclosing fascial sheath. The bundles lie in a triangular space bounded by the rib, the posterior intercostal membrane and the intercostalis intima muscle. The first two appear impervious to the spread of an injected solution, but the last permits spread of the injection round the internal aspect of the rib to gain access to the intercostal spaces above and below that into which the injection has been made. An injection of 3 ml will also spread medially to enter the paravertebral space and surround the sympathetic chain. A small clinical study gave excellent analgesia after operation for a mean duration of 12.3 h following unilateral intercostal block with 3 ml of bupivacaine 0.5% (with adrenaline) into each of the intercostal spaces T5-11, before cholecystectomy through a subcostal incision. There were no complications in the series.

Cholecystectomy↗

Survival of patients ventilated in an intensive therapy unit.

The survival of patients who were artificially ventilated in an intensive therapy unit (ITU) of a district general hospital was studied. The first 100 such patients admitted were followed up for at least four years. Of these, 67 survived treatment in the ITU, 47 were discharged from hospital, and 30 survived four years. (Survival in the ITU of patients who did not require ventilation was 89%.) The effects of age, duration of ventilation, and disease were studied, and a higher survival was found in children, in patients ventilated for under 24 hours, and in patients admitted with drug overdosage. Survival was poor in patients aged over 75 and in those who required ventilation after cardiac arrest or myocardial infarction or for chronic obstructive lung disease. The cost of a bed in an ITUs to be used to the greatest effect it is important to define those patients who are most likely to benefit from the facilities they offer.

Adolescent↗

Halothane does not inhibit human neutrophil function in vitro.

Various indices of function of neutrophils from normal healthy volunteers have been examined after in vitro exposure to halothane. Random free movement on glass was unaffected, but random migration through millipore filters was slightly increased. There was no significant change in migration in response to casein chemotaxis. Phagocytosis, degranulation and the enhanced non-mitochondrial respiration associated with phagocytosis were unaffected. Electron-microscopic appearance at 30 s after exposure to latex particles was normal in all respects.

Cell Movement↗

Cytotoxic effects of procaine, lignocaine and bupivacaine.

Cytotoxic effects of procaine, lignocaine and bupivacaine were investigated on cultures of Chinese hamster lung fibroblasts. Cell growth was inhibited over 24 h exposures with an ED50 of 0.17% for procaine, 0.07% for lignocaine and 0.02% for bupivacaine. Cell survival (measured as colony-forming ability) was reduced over 24 h exposure with an ED50 of 0.21% for procaine, 0.09% for lignocaine and 0.06% for bupivacaine. Morphological changes included vacuolation, cell rounding and retraction from the surface on which the cells were growing. Motility was reduced to about 50% of control by lignocaine 0.1%. On removal of the local anaesthetics, cell growth was resumed after about 15 h without evidence of chromosome damage. Corresponding changes induced by inhalation anaesthetics are only seen at two to three times the minimal alveolar concentration required for anaesthesia.

Animals↗

Anesthesia and the leucocyte.

Effective inhibition of cell division by anesthetics occurs only when cells are exposed to concentrations more than twice those required for anesthesia. Neutropenia following prolonged inhalation of nitrous oxide seems to be caused by a different mechanism, in which the cobalt in B12 is oxidised to the trivalent form by chemical reaction with nitrous oxide. B12 is thereby inactivated and this interferes with folate metabolism and thymidine synthesis: the effect may be detected after only a few hours in vivo exposure of mammals to 50% nitrous oxide. Unlike lymphocytes, the random motility of human neutrophils is not decreased by in vitro exposure to concentrations of halothane required for anesthesia. Similarly there is no effect on chemotaxis to casein and phagocytosis with exposure up to 2% halothane.

Anemia, Megaloblastic↗

Selective inactivation of vitamin B12 in rats by nitrous oxide.

Exposure of rats to nitrous oxide rapidly inactivated the cytosol enzyme, methionine synthetase, but the mitochondrial enzyme, methylmalonyl CoA mutase, seemed to be unaffected, although both enzymes require vitamin B12.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗

Pressure enhancement of the depressant effect of halothane on cilial beat.

In order to test the applicability of the critical volume hypothesis of anaesthetic action to the side effects of anaesthesia, we have studied the pressure-anaesthetic interactions on cilial beat. The swimming speed of Tetrahymena pyriformis was determined at one and 137 atmospheres with 0 to 4 per cent halothane. The pressure and anaesthetic effects were synergistic with the halothane dose-response curve being shifted to the left and increased in slope at the high pressure, although high pressure alone had no significant effect. These results are contrary to the predictions of the critical volume hypothesis and appear to demarcate the narcotic effect of anaesthetics from the type of molecular interaction which is concerned in the effect on cilial beat.

Cilia↗