Sean O'Reilly

Ceruloplasmin and 5-hydroxyindole metabolism in pregnancy

Abstract Measurements of whole blood serotonin, serum ceruloplasmin, and urinary 5-hydroxyindole acetic acid during pregnancy, at the time of delivery, in the immediate postpartum period, and in the newborn are reported. The results suggest that though blood 5-HT levels increase during pregnancy there is not a corresponding increase in urinary output of 5-hydroxyindoles. The possible relationship of these findings to the increased serum ceruloplasmin levels during pregnancy is discussed in the light of what is known about the metabolism of 5-HT and the biochemistry of ceruloplasmin. The necessity for further studies is emphasized.

Dopamine and basal ganglia disorders.

THE APPLICATION of biochemical knowledge and techniques has led to greater understanding of the pathogenesis of a variety of disease states. Distribution of a particular substance in the tissues has led investigators to study the metabolism of the molecule in question in patients with diseases that involved such tissues. Thus, no doubt, it was the relatively recent finding that dopamine in the brain had its highest concentration in the basal ganglia’ that led Barbeau and his co-workers2 to measure the urinary output of dopamine in parkinsonism and other disorders of the basal ganglia. The purpose of this paper is to present results of similar investigations in our laboratory which, though somewhat at variance with those reported by Barbeau and his associates, may, when followed up by further studies, lead to confirmation of their findings and to elucidation of the role of dopamine in the physiology and pathophysiology of the basal ganglia.

Iron metabolism in Wilson's disease: Kinetic studies with iron59

THE METAmLIsbi OF IRON in Wilson’s disease has not received much attention, although several reports over the past forty years or more have indicated that an important relationship exists. In 1922, Lowyl reported excess storage of iron in the liver, a finding reiterated in 1958 by Butt and his co-workers.2 Cartwright and co-workers3 and Walshe4 reported the occurrence of hemolysis in patients with Wilson’s disease. Wiseman; found evidence of a relationship between the absorption of copper and iron from the gastrointestinal tract. Goldberg and colleaguess had shown that an excess of copper produced hemolytic anemia in animals, and, perhaps more relevant to Wilson’s disease, Lahey and associates7 had found that copper-deficient animals may develop a severe anemia morphologically similar to anemia of iron deficiency. There is experimental evidence that ceruloplasmin and iron may act in a coupled oxidation sy~tem~.~ and that ceruloplasmin may be involved in oxidation of ferrous iron to ferric iron preparatory to formation of a ferric-transferrin complex.1° Decreased serum iron levels in one of our patients with Wilson’s disease, a finding similar to that reported by Tschabitscher and Schinko,” led to the studies reported here.

Problems in Wilson's disease

IN 1906, GOWERS~ wrote: “These cases were under observation many years ago, and their record has been waiting for the facts that might elucidate their mystery, but waiting in vain.” He was referring to two cases of “tetanoid chorea” associated with cirrhosis of the liver, which he had seen in 1888 and which Kinnier Wilson rightly claimed as examples of the disease bearing his name. Many of the facts for which Gowers waited in vain have come to light during the ensuing sixty years, yet the disease still presents many problems. The purpose of this paper is to review the main problems and to suggest answers to some of them.

Diffuse glioma of the spinal cord with hypoglycorrhachia.

MENINGEAL GLIOMATOSIS secondary to an intramedullary glioma of the spinal cord is acknowledged to be an uncommon occurrence, and only sporadic cases have been reported.132 It is the purpose of this paper to report a case of an intramedullary glioma with diffuse meningeal dissemination and extreme hypoglycorrhachia in order to underline the criteria for premortem diagnosis. The elevation of cerebrospinal fluid (CSF) protein associated with spinal cord gliomas is a consistent though nonspecific finding, but hypoglycorrhachia usually raises the possibility of bacterial meningitis. In a review of the literature, Berg3 found that in 75% of cases of various diffuse neoplastic diseases of the meninges the spinal fluid glucose levels were below 40 mg. percent. Since the diagnosis of these cases antemortem is difficult unless malignant cells are demonstrated in the spinal fluid, we wish to stress the importance of abnormaIly Iow CSF sugar content occurring with diffuse neoplastic involvement of the leptomeninges.

Detection of the carrier of Wilson's disease

SUMMARYWhole-body counting over a three- to four-week period following the intravenous administration of copper 67 in 11 normal volunteers, 2 neurological control patients, 7 control subjects with cirrhosis, and 10 homozygotes and 7 heterozygotes of Wilsons disease showed that whole-body retention of radio-copper was prolonged in the wilsonian subjects, both homozygous and heterozygous, and in cirrhotic patients with ascites or hepatocellular failure or both. If the latter can be excluded, prolonged whole-body retention of radiocopper serves to identify the presence of the abnormal gene or allele of Wilsons disease. Because of overlap, it is not possible to distinguish the heterozygote from the homozygote by whole-body counting alone. External probe counting over the liver and muscle, carried out in 5 control subjects, 8 homozygotes, and 5 heterozygotes, revealed abnormal hepatic uptake with little apparent release of radiocopper and usually evident uptake in muscle in the homozygotes and reasonably normal hepatic uptake with delayed release and no apparent muscle uptake in the heterozygotes, compared with the control subjects. It appears that external monitoring of hepatic and muscle radioactivity, in addition to whole-body turnover measurements after intravenous copper 67, permits more accurate determination of the genetic status of individuals in respect to Wilsons disease.