T. K. I. Larmi

Comparison of activities of drug‐metabolizing enzymes in human fetal and adult livers

The in vitro capacity of human fetal liver to metabolize 3,4‐benzpyrene, aniline, aminopyrine, and hexobarbital was lower than that of human adult liver from patients with uncomplicated cholelithiasis. Fetal liver drug‐metabolizing capacity, expressed as percentages of adult values, was 2.4, 27.8, 32.0, and 36.1 per cent, respectively, for the four substrates studied. Cytochrome P‐450 content and nicotinamide adenine dinucleotide phosphate (NADPH)—cytochrome c reductase activity in fetal liver microsomes also reflected the lower drug‐metabolizing activity, being 27.4 and 49.2 per cent, respectively, of adult values. Microsomal protein content was about 26 mg per gram wet weight in fetal liver and about 35 mg per gram in adult liver. Recovery of microsomes was 40% to 60% in both fetal and adult livers. All parameters studied exhibited considerable variation, which ranged from three‐ to elevenfold. Fetal drug metabolism, although generally lower than in the adult, may, in some cases, be higher than maternal drug metabolism.

Cytochrome P-450-linked monooxygenase system and drug-induced spectral interactions in human liver microsomes

Summary Human liver microsomes isolated from operation biopsy samples from patients with cholelithiasis or a malignant disease, were studied with respect to a drug-oxidizing monooxygenase system. The human liver contained about 30-40 mg of microsomal protein per gram of wet weight and about 50% of that was recovered in the microsomal fraction. The mean levels of cytochrome P-450, NADPH-cytochrome c reductase and cytochrome b5 in the livers of cholelithiatic patients were essentially similar to those in the livers of rat and guinea pig and only slightly lower than those in the rabbit liver. The cytochrome P-450-carbon monoxide difference spectrum exhibited a peak at 450 nm and, in microsomes from several smokers, no peak shift to 448 nm was evident. Studies with ethyl isocyanide as a ligand revealed a typical difference spectrum with a peak ratio at pH 7.4 of 455/430 nm of 0.46 and a pH intercept of at about 7.9. There was no correlation between cigarette smoking and a peak ratio. Drug-induced interactions of type I (SKF 525A, bromobenzene), type II (aniline, n-octylamine, KCN) and reverse type I (phenacetin, n-butanol) variety were detected in liver samples studied. Hexobarbital and aminopyrine gave either type I or reverse type I spectral changes. The spectral dissociation constant for aniline was of the same order of magnitude as in rat liver microsomes. These studies seem to indicate that although qualitative differences between hepatic monooxygenase systems in man and laboratory animals may exist, available evidence suggests that many essential differences are only quantitative in nature.

A comparison between serum ferritin concentration and the amount of bone marrow stainable iron

There was good parallelism between serum ferritin levels and the amount of bone marrow stainable iron in 123 patients with gastritis, gastric ulcer and duodenal ulcer. A serum ferritin concentration of about 20-25 micrograms/l is the approximate level below which stainable iron cannot be demonstrated in the bone marrow.

Anaesthesia Induction and Lower Oesophageal Sphincter Pressure

The effects of some drugs generally used in premedication for and induction of anaesthesia on the lower oesophageal sphincter (LOS) pressure were investigated in 30 dogs, using the modern oesophageal manometric technique. In thiopental‐induced anaesthesia, a distinct pressure gradient was noted between the LOS and gastric pressure. Atropine eliminated this pressure gradient almost completely. Metoclopramide increased the LOS pressure significantly, and subsequent atropine administration was unable to bring it down. Metoclopramide administered after atropine was unable to elevate the LOS pressure reduced by atropine. Succinylcholine had no observable lasting effect on the LOS pressure.

Cerebrospinal fluid and serum transaminases and lactic dehydrogenase after head injury.

It is well known that central nervous tissue contains much glutamic oxaloacetic transaminase (G.O.T.), less lactic dehydrogenase (L.D.H.) and only little glutamic pyruvic transaminase (G.P.T.) (Cohen 1951, Wroblewski h LaDue 1955). Experimental cerebral infarction in laboratory animals has been demonstrated to increase serum and cerebrospinal fluid G.O.T. activity (Wakim et al. 1956). Clinical observations also show that serum and cerebrospinal fluid G.O.T. and L.D.H. activities increase in some neurological diseases and cerebral infarctions (Fleisher et al. 1957, Green et al. 1957, Mellick h Bassett 1964). The purpose of the present study was to determine whether there are any changes in cerebrospinal fluid and sernm G.O.T., G.P.T. and L.D.H. activities after traumatic head injuries.

The fate of intravenous [3H]glycopyrrolate in man

Glycopyrrolate was labelled in one methyl group with tritium and its fate was studied in six patients with T‐tube drainage by determining serum levels as well as the biliary and urinary excretion of radioactivity after intravenous injection. More than 90 % of the radioactivity had disappeared from serum in 5 min and after 30 min almost no radioactivity could be found. The highest radioactivity in bile was found in samples taken 30 or 60 min after the injection. However, measurable radioactivity was found in most cases after 48 h. The first urine samples (0–3 h) showed the greatest radioactivity, and in 48 h 85% of the total radioactivity was excreted into the urine. Paper chromatography showed that both in bile and in urine over 80% of the radioactivity corresponded to unchanged glycopyrrolate. That appreciable amounts of glycopyrrolate were excreted into the bile suggests that the spasmolysis achieved with glycopyrrolate could be based partly on a local action on the bile ducts.

Effects of ethanol on the cyclic AMP system of the dog gastric mucosa

The effect of ethanol on the cyclic AMP system of the dog fundic mucosa was studied in vitro. The gastric mucosal content of cyclic AMP was increased by 2.5% ethanol, whereas 10 and 20% ethanol decreased the mucosal content of cyclic AMP. The activity of adenylate cyclase was increased by 2.5 and 5% ethanol, whereas 10% ethanol did not significantly affect it. The activity of cyclic AMP phosphodiesterase was inhibited by ethanol in a competitive manner. The increase in the gastric mucosal content of cyclic AMP, induced by low concentrations of ethanol, is apparently due to the stimulation of adenylate cyclase and inhibition of phosphodiesterase. Changes in the phosphodiesterase or adenylate cyclase activites do not explain the decrease of the mucosal content of cyclic AMP by higher concentrations of ethanol. The mechanism of the decrease is discussed.

INFANTILE ANEURYSM OF THE DUCTUS ARTERIOSUS: Diagnosis, Incidence, Pathogenesis, and Prognosis

Abstract. Heikkinen, E. S., Similä, S., Laitinen, J. and Larmi, T. (Departments of Surgery, Paediatrics and Roentgenology, University of Oulu, Oulu, Finland). Infantile aneurysm of the ductus arteriosus. Acta Paediat Scand, 63:241, 1974.–A neoplastic‐like density on X‐ray is not a rare diagnostic problem in infancy. Nevertheless, knowledge about the infantile ductal aneurysm (IDA) producing a characteristic tumour‐like mediastinal shadow on plain chest film is very limited.

Leiomyosarcoma of the vein. Review of the literature and report of a case.

The literature on primary leiomyosarcoma of the vein is reviewed and a new case is presented. The disease is extremely uncommon, and only 40 cases have been published. Of these tumours, 25 were located in the caval vein and 16 in a peripheral vein. Pre-operative diagnosis is very difficult. The symptoms depend on the localisation of the venous obstruction produced by the tumour and on the completeness of the obstruction. Operative therapy should be given priority, and the results especially for peripheral vein tumours are satisfactory, despite the tendency to later metastases. The haemody-namic discomfort caused by radical excision of the tumour is slight, especially if collaterals have had time to develop.

Effect of surgery on liver function in patients with liver cancer.

The effect of hepatic resection, hepatic artery ligation (HAL), and artery ligation combined with regional infusion of 5-fluorouracil (HAL + 5-FU) on liver function was investigated by liver tests including antipyrine in 20 patients with liver cancer. One month after resection the conventional liver tests except serum albumin were normalized, but the rate of antipyrine elimination was still significantly reduced. This suggests that the oral antipyrine test may be a sensitive reflector of the reserve capacity of the liver. Palliative procedures (HAL +/- 5-FU) had a transient effect on conventional liver tests and a negligible effect on functional liver capacity as determined by the antipyrine test or serum albumin concentration. On the basis of our results it remains unknown whether antipyrine determination provides any additional advantage over serum albumin as a measure of functional liver capacity in localized liver diseases, such as liver tumours.