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Biomedical subjects

M H Depledge

Publications and source records attributed to M H Depledge.

11 recordsLinked to original sources

Respiration and lung function in the mouse, Mus musculus (with a note on mass exponents and respiratory variables).

Ventilatory ability, the diffusing capacity of the lung and oxygen uptake have been investigated in mice of different sizes. Breathing frequency decreased with body weight although minute ventilation (V) increased (V alpha W 1.725). Weight-specific diffusing capacity for carbon monoxide showed little variation with size. Oxygen consumption (VO2) rose with weight according to VO2 alpha W0.41. In older, larger mice this resulted in increased ventilatory requirements (V/VO2).

Animals

Disruption of circulatory and respiratory activity in shore crabs (Carcinus maenas (L)) exposed to heavy metal pollution.

Cardiac and respiratory activity of the shore crab, Carcinus maenas (L.), were disrupted following exposure to heavy metal ions. Exposure to 3 mg l-1 copper ions induced continuous, uninterrupted heart beat in quiescent, undisturbed crabs. Copper ions (10 mg l-1) suppressed cardiac activity and oxygen consumption within 2 hr. Alternating periods of bradycardia and tachycardia were observed together with marked changes in impedance cardiograph trace height. Similar, but more pronounced changes were seen following exposure to 1 mg l-1 mercury ions. Median perfusion index was 100 ml blood ml O2(-1) (range 58-114 ml blood ml O2(-1)) prior to pollution, but increased to peak values within the range 90-220 ml O2(-1) following exposure to copper or mercury. The effects of exposure to copper were transient and largely reversible. Exposure to mercury resulted in 100% mortality 24-48 hr after initial contamination. Death was apparently associated with loss of the osmoregulatory ability of these crabs.

Animals

Changes in cardiac activity, oxygen uptake and perfusion indices in Carcinus maenas (L.) exposed to crude oil and dispersant.

Cardiac activity and oxygen consumption increased when C. maenas were exposed to a 20% solution of the water-soluble fraction of Fortes crude oil, a 10% solution of the dispersant BP1100WD or a combination of both. Normal feeding behaviour was disrupted. Perfusion indices (Q/VO2) decreased as locomotor activity increased following exposure to crude oil. However, exposure to dispersant or dispersant + crude oil resulted in elevation of perfusion index despite crabs becoming active. All test animals survived for at least 6 weeks following exposure to the pollutants. The acute, sublethal effects of dispersant and dispersant + crude oil were more severe than the effects of crude oil alone.

Animals

Dose-independence of early, cyclophosphamide-induced lung damage in mice.

Administration of cyclophosphamide to mice resulted in lung damage which was assessed by measuring breathing rate and lung compliance. Above a threshold dose (approximately 50-100 mg/kg b.w.) the time of onset and severity of early, acute pulmonary dysfunction was dose-independent in the range 100-400 mg/kg. At doses up to 200 mg/kg lung damage was reversible but above this second threshold level, pulmonary fibrosis invariably developed. The severity of late damage (approximately day 40) was dose-related. These findings may help in the interpretation of clinical lung damage associated with cyclophosphamide therapy.

Animals

Mismatched family donors for bone-marrow transplantation as treatment for acute leukaemia.

35 patients were treated for acute myeloid leukaemia or acute lymphoblastic leukaemia with allogeneic bone-marrow grafts from a parent, child, or sibling who was mismatched at the major histocompatibility complex (MHC). 11 of these patients are alive at least 6 months after grafting, 5 of them after more than 2 years. Of the 15 patients aged under 20 at the time of the graft, 8 are alive and well 6 months to 3 years later. Cyclosporin A was given to all patients after grafting. 1 patient died of acute graft-versus-host disease and in 2 other cases this was a major factor in their death. Graft failure caused the death of 2 patients. 4 patients died of recurrent leukaemia. A fatal complication in 12 patients was pulmonary oedema, often associated with convulsions, intravascular haemolysis, and renal failure. Some of these patients had viral or bacterial infections, but in the majority the syndrome was not associated with demonstrable infection. This syndrome, in which the essential lesion appears to be vascular, was much more common in recipients of mismatched than matched grafts. 3 others died from lung disease in which infection was a factor.

Acute Disease

Lung function after bone marrow grafting.

Results of a prospective lung function study are presented for 48 patients with acute myeloid leukemia (AML) treated with total body irradiation (TBI) and bone marrow transplantation (BMT) at the Royal Marsden Hospital between 1978 and 1980. Patients with active disease or who were in remission following cytoreductive chemotherapy had mildly impaired gas exchange prior to grafting. After TBI and BMT all patients studied developed progressive deterioration of lung function during the first 100 days, although these changes were subclinical. Infection and graft-versus-host disease (GvHD) were associated with further worsening of restrictive ventilatory defects and diffusing capacity (DLCO). Beyond 100 days, ventilatory ability returned to normal and gas transfer improved, although it failed to reach pre-transplant levels. There was no evidence of progressive pulmonary fibrosis during the first year after grafting.

Adolescent

Interstitial pneumonitis following bone marrow transplantation after low dose rate total body irradiation.

Idiopathic and infective interstitial pneumonitis (IPn) is a common complication after bone marrow transplantation (BMT) in many centers and carries a high mortality. We report here a series of 107 patients with acute leukemia grafted at the Royal Marsden Hospital in which only 11 (10.3%) developed IPn and only 5 died (5%). Only one case of idiopathic IPn was seen. Factors which may account for this low incidence are discussed. Sixty of 107 patients were transplanted in first remission of acute myeloid leukemia (AML) and were therefore in good general condition. Lung radiation doses were carefully monitored and doses of 10.5 Gy were not exceeded except in a group of 16 patients in whom a study of escalating doses of TBI (up to 13 Gy) was undertaken. The dose rate used for total body irradiation (TBI) was lower than that used in other centers and as demonstrated elsewhere by ourselves and others, reduction of dose rate to less than 0.05 Gy/min may be expected to lead to substantial reduction in lung damage. Threshold doses of approximately 8 Gy for IPn have been reported, but within the dose range of 8 to 10.5 Gy we suggest that dose rate may significantly affect the incidence. Data so far available suggest a true improvement in therapeutic ratio for low dose rate single fraction TBI compared with high dose rate.

Acute Disease

Histopathology of the lung after bone marrow transplantation.

The histopathological changes in the lungs of 32 patients who died after bone marrow transplantation for leukaemia have been studied and compared with those found in 21 patients treated by conventional chemotherapy. The transplanted patients exhibited a higher incidence of interstitial pneumonitis, vascular lesions and viral infections, particularly cytomegalovirus (CMV), although bacterial and fungal diseases were commoner in the non-grafted subjects. The pathogenesis of interstitial pneumonitis is discussed with specific reference to the possible roles of irradiation, chemotherapy, viruses and the immunosuppressive drug cyclosporin A. Ten patients died of a syndrome characterised clinically by fever, skin rash, fluid retention, uraemia, low serum albumin concentrations, low central venous pressure and acute pulmonary oedema. These patients exhibited intra-alveolar haemorrhagic fibrinous exudation with or without interstitial changes. The aetiology of this syndrome is not known but it occurs more frequently in recipients of mismatched grafts and evidence is presented suggesting that viruses may play a significant causative role. No lesion was identified that could be directly attributed to Graft-versus-Host disease.

Adolescent