Urinary excretion of beta-aminoisobutyrate and pseudouridine in acute and chronic myeloid leukemia.

End products of nucleic acid metabolism including beta-aminoisobutyrate (beta-AIB) and pseudouridine (psi-Urd) have been considered as potential biochemical markers for cancer. The urinary excretion of both metabolites was investigated in abnormal hematopoietic conditions including 26 patients with acute myeloid leukemia (AML) and chronic myeloid leukemia (CML) and was compared to that of 25 healthy controls. beta-AIB excretion in CML was directly correlated to the leukocyte count, the indicator of tumor cell mass. beta-AIB excretion was elevated in 27 and 75% of untreated AML and CML cases, respectively. Marrow blast cell content tended to correlate positively with psi-Urd excretion in AML. psi-Urd excretion was elevated in 82 and 87% of untreated AML and CML, respectively. Turnover of hematopoietic cells seemed to be a determinant for beta-AIB excretion, indicating higher cell turnover in CML patients compared to that in AML patients and in controls. With cytostatic treatment, excretion levels of beta-AIB and/or psi-Urd decreased after a transient rise.

Effect of tryptophan and nicotinamide loads on urinary excretion of RNA metabolites by bladder cancer patients.

In a comparative study of tryptophan metabolism and urinary excretion of nucleic acid derivatives (including beta-aminoisobutyric acid, 7-methylguanine, pseudouridine, and urate) in 12 male bladder cancer patients, the excretion of pseudouridine and 7-methylguanine decreased significantly after an oral dose of 2 g L-tryptophan. A similar decrease occurred after an oral nicotinamide load of 50 mg four times a day, which indicated a possible common mode of action of tryptophan and nicotinamide. No definite resolution could be made as to the causal mechanism for the observed descrase in RNA turnover.

[Basal ganglia calcifications demonstrated by CT. Is further investigation necessary when this is found incidentally?]. / CT-påviste forkalkninger i basalganglierne. Kraeves der naermere udredning ved tilfaeldig påvisning?

Calcification in the basal ganglia in the brain is, as a rule, asymptomatic and is therefore observed as an incidental finding at CT examination for other cerebral conditions e.g. tumours or haemorrhage. The question is whether incidental finding of calcification in the basal ganglia indicates the need for further supplementary investigations. Three case histories and study of the literature are quoted to illustrate this. It is concluded that investigation is not indicated in patients over the age of 50 years with limited, bilateral, symmetrical calcifications in the globi pallidi. In patients under 50 years, investigation in the form of detailed history taking, neurological examination and haematological investigation is indicated.

[Prostacyclin inhalation in pulmonary failure following smoke inhalation]. / Prostacyklininhalation ved lungesvigt efter røgforgiftning.

A 42 year-old man was admitted to hospital due to smoke inhalation. Thirty-three hours after admission arterial oxygen saturation was 80-90% with FiO2 = 1.0. Inhalation with prostacyclin was commenced with a dose rate of 7 ng/kg/min with an immediate effect, i.e. SATaO2 increased to 100%. Prostacyclin was terminated after 24 hours, when FiO2 was reduced to 0.5. It is concluded that prostacyclin inhalation therapy may have effect in patients following pulmonary smoke injury.

[Surgical treatment of abdominal aorta aneurysm 1983-1987. A multicenter study. 1266 operations, development and early results]. / Operative behandling af abdominalt aorta-aneurysme 1983-1987. Multicenterundersøgelse. 1,266 operationer, udvikling og tidlige resultater.

During the years 1983-1987, 1,266 operations for abdominal aortic aneurysm (AAA) were carried out in eight surgical departments with vascular surgical function. The activity increased constantly corresponding to 311 patients in 1987 or 50% more than in 1983. During this period the distribution between patients subjected to elective operation and those operated upon as emergencies was very uniform. In the latter group, only a slight increase in the number of AAA patients with rupture was observed. The risk of complications was low with a significant decrease in the need for dialysis. The early mortality was constant for the patients subjected to elective operation remained constant about 5.5%. A marked decrease in the early mortality was observed for the patients operated upon as emergencies with rupture from 63 to 50% and without rupture from 37 to 25%. At the conclusion of the period, ultrasonic scanning became the preoperative investigation of election and introduction of an aortic prosthesis the method of operation of election. Patients with AAA should be recognized so that elective surgery can be offered before a condition endangering life develops.

Bone mass as referent for urinary hydroxyproline excretion: age and sex-related changes in 125 normals and in primary hyperparathyroidism.

Fasting urinary hydroxyproline: creatinine ratio (OHPr:Cr) and bone mineral content of the forearm (BMC) were measured in 125 normals, 67 females and 58 males, aged 20-79 years, and in 15 patients with primary hyperparathyroidism. In normals, both variables were significantly correlated to age and sex. The interrelation of OHPr:Cr and BMC was studied in subgroups of normals who were supposedly in metabolic balance, that is, females aged 20-39 years (n = 24) and males aged 20-49 years (n = 29). In both sexes OHPr:Cr and BMC were positively correlated: r = 0.60 and 0.58, respectively (P less than 0.001). On this basis, BMC correction of all OHPr:Cr values was undertaken now revealing a stable increased level of bone resorption per unit of bone mass in postmenopausal females. In males OHPr:Cr per unit of BMC remained unaltered throughout life. In primary hyperparathyroidism, in which increased bone resorption is inherent, the discriminatory power of OHPr:Cr was significantly improved when calculated per unit of BMC (P less than 0.001). These observations suggest that estimation of bone resorption by use of OHPr:Cr requires adjustment for differences in bone mass.

A study on the clinical significance of urinary beta-aminoisobutyric acid in patients with urothelial tumours.

Urinary beta-aminoisobutyric acid (beta-AIB) has been measured in 141 patients with urothelial tumours and 60 controls. Ninetyone of the patients have been followed-up for an average period of about 2 years, which included many determinations of the beta-AIB excretion. Thirtysix patients died during the control periods. Urinary beta-AIB was found to be significantly correlated to the grade of tumour cell dysplasia, but not to the clinical tumour stage. The treatment had no major influence on the excretion. Characteristic changes in the excretion preceding high-grade tumour recurrences are demonstrated. Autopsy findings with tumour tissue in the urinary tract and distant metastases were significantly correlated to a low urinary beta-AIB in the terminal phase of the disease. The results are discussed in relation to the degradation of thymine, the dual origin of beta-AIB and the tumour-host metabolism. It is concluded, that urinary beta-AIB can contribute to the graduation of malignancy, but is not valuable as a general screening procedure for urothelial cancer.

Urinary pseudouridine and beta-aminoisobutyric acid in patients with low grade urothelial tumours. Relations between excretion and tumour recurrence.

The simultaneous 24 hours excretion of pseudouridine and beta-aminoisobutyric acid in the urine from patients treated for low grade urothelial tumours has been determined and related to tumour recurrence inside of 6 months after the determinations. The results of 53 assays in 39 patients without clinical signs of recurrence at the time of the detrmination showed a high excretion of pseudouridine in 53% and of beta-aminoisobutyric acid in 28.5% of the assays. Recurrences appeared more often after a high urinary pseudouridine (53.5%) than after a low, but the difference was not statistically significant (p more than 0.05) and more often after a low urinary beta-aminoisobutyric acid (52.5%) than after a high (p less than 0.01). The highest incidence of recurrence was in patients with a simultaneously high urinary pseudouridine and a low urinary beta-aminoisobutyric acid. Seventy per cent of these excretion patterns were from patients, who developed a recurrence before 6 months (p less than 0.002).

Sodium dodecyl sulfate-stable complexes between serpins and active or inactive proteinases contain the region COOH-terminal to the reactive site loop.

Recently inhibitors of the serpin family were shown to form complexes with dichloroisocoumarine (DCI)-inactivated proteinases under native conditions (Enghild, J. J., Valnickova, Z., Thøgersen I., and Pizzo, S. V. (1994) J. Biol. Chem. 269, 20159-20166). This study demonstrates that serpin-DCI/proteinase complexes resist dissociation when analyzed in reduced SDS-polyacrylamide gel electrophoresis. Previously, SDS-stable serpin-proteinase complexes have been observed only between serpins and catalytically active proteinases. The stability of these complexes is believed to result from an acyl-ester bond between the active site Ser195 of the proteinase and the alpha-carbonyl group of the scissile bond in the reactive site loop. We have further analyzed the structure of the SDS-stable serpin-proteinase and serpin-DCI/proteinase complexes. The results of these studies demonstrate the presence of the COOH-terminal region of the serpin in both complexes. Since (i) modification of Ser195 does not prevent formation of SDS-stable complexes and (ii) COOH-terminal peptides are present in both complexes, the previously described mechanism does not sufficiently explain the formation of SDS-stable complexes.