Cyclic hematopoiesis: effects of lithium on colony-forming cells and colony-stimulating activity in grey collie dogs

The cycling of blood cell counts in grey collie dogs with cyclic hematopoiesis can be eliminated by treatment with oral lithium carbonate. To explore the mechanism by which lithium alters this stem cell disorder, studies of bone marrow granulocyte-macrophage progenitor cells (CFU-C), neutrophil colony-forming cells (neutrophilic CFU-C), and colony-stimulating activity (CSA) were performed. In untreated dogs, the proportions of CFU-C were found to fluctuate cyclically, but the cyclic fluctuations in neutrophil colony-forming cells were even more marked, with numbers decreasing to undetectable levels during each period of neutrophilia. Dogs on lithium, however, did not cycle the numbers of total or neutrophilic CFU-C. Tritiated thymidine suicide rates were not altered by treatment with lithium. Serum CSA levels and bone marrow cell elaboration of CSA were not increased by lithium. These studies suggest that lithium corrects cyclic neutropenia by a direct effect on the differentiation and proliferation of CFU-C; normalization of the proportion of CFU-C that enter neutrophilopoiesis appears to be an important effect of the lithium therapy.     

The Treatment of Porphyria Cutanea Tarda by Venesection

The effect of treatment on 21 patients with porphyria cutaneatarda is described. Before treatment the exposed skin showed blistering and fragility,milia, hirsutes, and changes in pigmentation, with pseudosclerodermain some. A history of a heavy alcohol consumption either atpresentation or in the past was obtained from approximately50 per cent of the patients whilst 30 per cent admitted to onlya moderate intake of alcohol. No evidence of excess alcoholcould be obtained from the remaining 20 per cent. Plasma ironwas raised in 70 per cent of patients and serial determinationsshowed that this persisted in 30 per cent. Porphyrin excretion showed a gross excess of urinary uroporphyrinin all patients and increased urinary coproporphyrin in 80 percent. The changes in faecal porphyrins were less marked andin nearly 60 per cent were normal. Liver iron was increased in all patients biopsied. Thirty percent showed cirrhosis, the remainder lesser hepatocellular damage.Only one patient showed completely normal liver-function tests. Sensitivity of the skin to 400 nm radiation was tested in allbut one of the patients and abnormal reactions obtained in nearly80 per cent. Treatment was by repeated venesections in 16 patients and allsave one showed an excellent response. Urinary uroporphyrinslowly fell to normal or near normal and this was followed byimprovement in the skin. Spontaneous blistering was the firstclinical sign to disappear, closely followed by cessation ofabnormal fragility. Other cutaneous signs regressed slowly andin most patients the skin returned almost to normal. One manceased consumption of alcohol and this was followed by a completebiochemical and clinical remission. One patient died of cardiacfailure which developed a few months after venesections werestopped. Two patients have shown biochemical relapse with a marked risein urinary uroporphyrin excretion but with no deteriorationin the skin. A second course of venesections has returned urinaryuroporphyrin excretion to near normal levels in each case. The way in which venesection produces this excellent therapeuticresponse is unknown but several hypotheses are discussed, e.g.depletion of iron in the hepatic cell. It is suggested that venesection is the treatment of choicefor porphyria cutanea tarda. ¹Dr. Ramsay is in receipt of a grant from The Medical ResearchCouncil.