Ventilatory stimulation by dopamine-receptor antagonists in the mouse.

Ventilation was measured by a plethysmographic method in awake mice before and after intraperitoneal injection of neuroleptic drugs to test the hypothesis that dopaminergic mechanisms modulate control of breathing in this species. Dose-dependent augmentation of ventilation at rest and during hypoxia, and reduced ventilation during hypercapnia was demonstrated for haloperidol, droperidol, prochlorperazine and chlorpromazine (P less than 0.05 or less for each drug). Doses of drugs causing maximal increase of the ventilatory response to hypoxia were linearly related (r = 0.98, P less than 0.001) to in vitro affinity of the drugs for dopamine receptors. Despite presumed equal dopamine-receptor blockade, the drugs had unequal effects on the ventilatory response to hypoxia. Droperidol augmented hypoxic ventilation to 290% of the control value, chlorpromazine to 250% control, prochlorperazine to 190% control and haloperidol to 120% control. These differences in efficacy were in the same order as the affinities of the drugs for alpha-adrenoceptors. The effect of combined haloperidol (90 nmol kg-1) and varying doses of phentolamine (175-900 nmol kg-1) was assessed to test the hypothesis that alpha-antagonism was a factor in determining the increase in ventilation following dopamine blockade. Phentolamine caused dose-dependent augmentation of the ventilatory effects of haloperidol (P less than 0.01) but had no ventilatory effect when given alone. Carotid body resection in anaesthetized mice abolished the stimulation of hypoxic ventilation caused by droperidol. It is concluded that dopaminergic mechanisms in the carotid body modulate ventilatory control in the awake mouse. The drugs most effective in augmenting hypoxic ventilation are those that block both dopamine and alpha-adrenoceptors.     

Myocardial infarction in sickle cell anemia

A review of the electrocardiograms (ECG) of 108 patients with sickle cell anemia found only 3 with patterns consistent with myocardial infarction. Two of the 3 patients with ECG infarct patterns had postmortem examination confirmation of the infarction. These two patients had no significant coronary atherosclerosis nor did the other six autopsied patients in the present series. Literature reports of postmortem examinations on patients with sickle cell anemia confirm the scarcity of coronary atherosclerosis and myocardial infarction in these patients. Forty of the 108 ECGs showed signs of left ventricular hypertrophy and 20 others had nondiagnostic ST and T wave abnormalities. Nine showed first degree AV block and four right bundle branch block.     

In vitro effects of bleomycin on a carcinoma of the oesophagus cell line.

A dose of 10 microgram/ml bleomycin inhibited the growth of oesophageal carcinoma cells and non-squamous cells in vitro. Drug concentration, density of cells and the time of exposure to the drug were important variables. The oesophagus cancer cells increased in volume by 2,5 +/- 0,2% per hour until the onset of lysis at 96 hours. The effects of the drug were irreversible even when the exposure time was only 24 hours. A certain proportion of the cell population was resistant to bleomycin and these cells remained resistant when the drug was removed for 48 hours and then replaced. No drug inactivation or uptake could be detected with the use of microbiological assay after 4 days of incubation with 3 cell types. There is poor correlation between in vitro and in vivo results.     

Mixed malignant tumour of the lung.

A mixed malignant tumour of the lung intermediate in type between pulmonary blastoma and carcinosarcoma is described. The epithelial component consisted of squamous carcinoma, undifferentiated carcinoma, and clefts lined by bland epithelial cells. The supporting stroma was composed of pleomorphic sarcoma, fibrosarcoma, chondrosarcoma, osteosarcoma, and indeterminate mesenchymal tissue. The tumour was removed surgically, but the patient died postoperatively with rapidly developing multiple bony and soft tissue metastases. Subcutaneous metastases showed the appearnce of poorly differentiated pleomorphic sarcoma. Published reports of mixed malignant lung tumours are reviewed.