An animal model was used to study the effects of early administration of intramuscular corticosteroids on mortality and lung histopathology induced by a component of smoke. Thirty-six rabbits (mean weight, 2.7 kg) were exposed to acrolein vapor for 15 min; 30 min later the animals were divided into 3 treatment groups. One group received saline placebo intramuscularly at 12-h intervals, a second group was treated intramuscularly with 100 mg methylprednisolone at 12-h intervals, and a third group was treated with a single 100-mg dose of methylprednisolone followed by doses of saline at 12-h intervals. The animals were studied for a 72-h period. There was a significantly lower mortality in the 2 steroid-treated groups than in the nontreated group. A scoring system was developed for evaluating observed histologic changes in the lung. No correlation was seen between survival and histologic score or between score and treatment. High scores for particular histologic features did not explain mortality nor did they predominate in untreated animals; "vascular congestion" was found to be greater in the steroid-treated group. The beneficial effects of steroids in reducing mortality after inhalation of a common smoke constituent was not associated with any evidence of attenuation of lung damage.

Chest wall movement, partitioned into rib cage and abdomen/diaphragm contributions, was measured using four mercury-in-rubber strain gauges and an analog computer. The relative volume contribution of the rib cage and the abdomen/diaphragm to tidal volume was measured in 13 subjects before and during anaesthesia with thiopentone and halothane. In awake subjects, movement of the abdomen/diaphragm contributed more than 70% of the tidal volume, the smaller rib cage contribution ranged from 5 to 30%. Manual ventilation during induction of anaesthesia showed that the rib cage was less compliant than the abdomen/diaphragm, but when suxameth-onium was given there was a disproportionate increase in rib cage compliance. In nine out of 12 subjects, halothane anaesthesia resulted in a large decrease in the fractional contribution of the rib cage. In two of these subjects there was paradoxical breathing, the rib cage and the abdomen/ diaphragm movement being 180° out of phase. This effect was produced easily in three other subjects by inserting a resistance (1 kPa litre−1 s) into the anaesthetic circuit. The technique also produced information about changes in volume of the trunk induced by anaesthesia. Eleven subjects showed an increase in end-expiratory abdominal volume (mean increase 120 ml) during halothane anaesthesia while there was a mean reduction in end-expiratory rib cage volume of 29 ml. We concluded that halothane depressed both phasic and tonic postural reflex activity, which affected predominantly the rib cage musculature. This reduced the amplitude of phasic rib cage movement, impaired stability of the rib cage and predisposed to paradoxical ventilation. The results also suggested that the reduction in lung volume during anaesthesia may result from a loss of postural control of the chest wall and a central shift of blood volume.

Exposure of rats to a 50% N2O/oxygen mixture led to a rapid loss of methionine synthase activity in both liver and brain. This enzyme has vitamin B12 as a cofactor. There was impaired conversion of deoxyuridine to deoxythymidine by bone marrow cells and this defect followed loss of methionine synthase activity. There was no homocystinuria. Withdrawal of N2O was followed by a relatively slow recovery of methionine synthase activity over four days. The inactivation of vitamin B12 by N2O promises to be a valuable tool in the study of vitamin B12 metabolism.

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.

s of Papers Presented at a One-Day Scientific Meeting of the British Society for Haematology held in London, 17 November 1978 Hypothermia and Sideroblastic Anaemia H. O’BRIEN, J. A. L. AMESS and D. L. MOLLIN Department of Haematology, S t Bartholornew’s Hospital, London A distinct and previously undescribed haematological picture was noted in two patients with hypothermia; and the observation of similar findings in two other patients with recurrent undiagnosed coma led to the recognition that they had the rare neurological syndrome, episodic hypothermia. During hypothermia there was anaemia with reduced normoblastic erythropoiesis, marked sideroblastic change and thrombocytopenia in the presence of a normal number of megakaryocytes. As the patients’ temperature returned towards normal, these changes slowly reversed. Transient thrombocytopenia was well recognized in induced hypothermia for cardiac surgery prior to cardiopulmonary by-pass. There is also experimental evidence suggesting that temperature can affect the extent of erythropoiesis in the bone marrow. However, qualitative changes in erythropoiesis have not been described in hypothermia; the morphological appearances indicate that haem synthesis is affected by changes in body temperature. Cellular Mechanisms in the Regulation of Iron Absorption by the Human Intestine T. M. Cox and T. J. PETERS Department of Medicine, Royal Postgraduate Medical School, London The small intestine has a unique regulatory role in iron homeostasis: absorption is increased in iron deficiency and returns to normal after repletion. It is not clear, however, how this control is effected by the enterocytes. A new method, using peroral duodenal biopsy specimens, has been devised for investigating in detail the mechanism of iron transfer across the small intestine. Fragments of duodenum are incubated with radio-iron and the kinetics of uptake determined within the physiological range of intraluminal iron concentrations. This process has many of the features of carrier-mediated active transport. In eight patients with iron deficiency anaemia iron uptake by the biopsies was enhanced 2-3-fold and kinetic analysis suggests increased carrier activity in the brush border membrane. There was an inverse relationship between duodenal uptake and serum transferrin saturation. Four patients were studied before and after repletion with oral iron. The uptake at 450 pmol/l fell from 17.1 k3.7 (SEM) to 5.3 k2.1 pmol/mg mucosa/min (P<o.os); mean rate for 15 normal controls was 7.2 k0.8 pmol/mg/min. Two patients were studied after correction of the anaemia with packed cells: this did not reduce iron uptake but after oral iron, uptake fell to normal. The mucosal iron levels were significantly lower in the iron deficient patients but remained low after 6 weeks of oral iron therapy even though uptake of radio-iron had fallen to control values. These experiments indicate that iron deficiency reversibly induces brush border iron carriers and shows that entry into the enterocyte is a major regulatory step in the control of iron balance.

An index of permeability of the alveolar-capillary membrane was derived from the relative extraction from the lung into arterial blood of 2 tracers, 125I-antipyrine and 51Cr-ethylenediaminetetraacetate. The effect on this index of aspirating 2 ml of isotonic saline, distilled water, or 10(-1) M hydrochloric acid per kg of body weight was studied in 3 groups of rabbits. The severity and time course of changes in the permeability index were correlated with changes in lung mechanics, gas exchange, serial chest roentgenograms, ratio of extravascular lung water to dry weight, and histologic findings. Aspiration of saline produced no change in the permeability index; aspiration of water produced a large mean +/- SEM increase in the index, from a baseline of 0.025 +/- 0.002 to 1,050 +/- 0.054 (P less than 0.001), but this value returned to baseline 15 min later. After hydrochloric acid, the permeability index increased from a baseline of 0.027 +/- 0.003 to 1.068 +/- 0.098 (P less than 0.005), with no evidence of resolution after 60 min. Changes in lung mechanics, gas exchange, and roentgenograms were smallest after aspiration of distilled water and greatest after aspiration of hydrochloric acid. The functional changes after aspiration of water and saline recovered at a rate proportional to the known clearance rates of these liquids from the lung. The changes after hydrochloric acid either showed no tendency toward recovery or, in the case of the roentgenograms, worsened with time. There were no detectable histologic abnormalities or an increase in the ratio of extravascular lung water to dry weight after aspiration of water or saline, but there were extensive histologic abnormalities and a 70 per cent increase in lung water after acid. The increase in the permeability index after aspiration of water was too transient to exert a deleterious effect. In contrast, the persistence of the increase in the permeability index after hydrochloric acid was associated with persistent functional changes attributable to the considerable increase in lung water.

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.