[Peroral selenium therapy in growth pain in children].
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Biomedical subjects
Publications and source records attributed to J Waldenström.
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Two unusual, and perhaps causally related, clinical and cytogenetic features in a patient with Waldenström's macroglobulinemia are presented. Firstly, during the progression of the primary macroglobulinemia bone destruction and hypercalcemia occurred. Secondly, a t(1;3)(p36;q21) was found as the sole clonal chromosomal abnormality. This translocation is characteristic of acute myeloid leukemia (AML) and myelodysplastic syndromes with a high propensity for progressing to AML. The t(1;3) has previously never been reported in a lymphoproliferative disorder. Since the abnormality is associated with acute transformation of cells of the myelopoietic lineages, it is possible that the t(1;3), found in cells of lymphoid origin in the present case, not only induced the neoplastic process as such but also brought about the unusually malignant tumor progression.
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Among a cohort of 348 women aged 50 on entering a 12-year prospective study, the incidence of diabetes was increased (17.1%) during follow-up in those who initially had fasting glucose concentration above the upper quintile, a fasting serum insulin concentration above the upper quintile (14.9%), a disappearance rate of glucose below the lowest quintile in an IV glucose tolerance test (12.7%), or early insulin response below the lowest quintile (17.1%). The incidence in all women was 4.9%. By multivariate analysis, the highest risk was for high fasting serum insulin concentration. Obesity and treatment with antihypertensive drugs further increased the risk. An initial low early insulin response was not however a prerequisite for the development of manifest diabetes. Determination of fasting insulin concentration, especially in overweight hypertensive subjects, is of value in order to find out which subjects are at high risk of developing diabetes.
The effect of 60 min of ischaemia on glomerular and tubular functions (osmolar clearance, fractional Na+ excretion, K+ clearance, concentrating ability) after different periods of time was studied in New Zealand White rabbits. Pronounced changes in both glomerular and tubular functions were observed immediately on reperfusion and after 48 h. One week after ischaemia the functions appeared to be normalized. Mannitol is routinely used in clinical kidney transplantation due to its hyperosmolar effects and its ability to scavenge the hydroxyl radical. In the present study the possible additive protective effect against ischaemia-reperfusion damage of a combined pretreatment with mannitol and oxygen free radical scavengers or mannitol and a xanthine oxidase inhibitor was examined. Oxypurinol was chosen as the xanthine oxidase inhibitor due to its direct inhibitory effect. Concerning glomerular function, no protective effect of the combined pretreatment compared with mannitol alone was observed. However, concerning the tubular function tests combined pretreatment with either mannitol-superoxide dismutase-catalase or mannitol-oxypurinol turned out to be superior compared with that of mannitol alone.
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One of the secondary objectives of the MIAMI Trial which evaluated the role of the beta-1-selective blocker metoprolol in suspected acute myocardial infarction was to further assess whether early intervention with beta-blockade can limit infarct size. A total of 5,778 patients from 104 worldwide centres were randomized into the trial. Various enzymes such as aspartate aminotransferase (ASAT), creatine kinase (CK), CK MB, CK B, lactate dehydrogenase (LD) and LD isoenzyme I were analysed. All enzymes were used according to the clinical routine of the respective hospital, except ASAT which was analysed once daily for 3 days in the majority of cases and LD I which was analysed every 12 h for 72 h in a subsample. A consistent observation was the lower serum enzyme activity among patients receiving metoprolol and randomized early after onset of symptoms, whereas no difference between metoprolol and placebo was observed in patients treated later in the course. The results of the MIAMI Trial support previous observations that early institution of metoprolol therapy limits infarct size, as indicated by the maximum serum enzyme activity.
We determined the catalytic concentration of gamma-glutamyltransferase in serum from a population sample of 1408 women in seven age strata between 26 and 72 years. The range in healthy individuals for the different age groups was found to increase with age with a maximum of the central 0.95 fractile interval at 58 years (0.17-1.68 microk/l). The serum gamma-glutamyltransferase activity correlated with body mass index, blood pressure and concentrations of blood glucose and serum ferritin, triglycerides and cholesterol. During follow-up of women with gamma-glutamyltransferase activity greater than 1.20 microk/l, no woman developed any disease possibly related to the original finding of raised serum gamma-glutamyltransferase activity, several individuals being apparently healthy. Apparently, the serum gamma-glutamyltransferase assay is an unspecific indicator of several metabolic abnormalities. High values may be found in individuals in whom all commonly done investigations have given results within the health-associated reference interval.
Serum uric concentration was determined in a series of 1462 women, aged 38-60 when first examined in 1968-69, as the first phase of a longitudinal population study in Gothenburg, Sweden. Serum uric acid concentration was positively correlated to the 12-year overall mortality in univariate analysis. No relationship was observed between initial serum uric acid values and incidence of myocardial infarction, angina pectoris, ECG changes indicating ischaemic heart disease or stroke. The association between serum uric acid concentration and mortality was independent of age, body mass index, systolic blood pressure, adipose tissue distribution, smoking habits, serum cholesterol concentration, serum triglyceride concentration, serum creatinine concentration, serum calcium concentration, use of diuretics, and haematological disease. The increased mortality could not be explained by any increase in malignant neoplastic disease.
The formation of FdUMP and the inhibition of TS were studied in a subcutaneously growing transplantable rat colon carcinoma and in regenerating rat liver following bolus administration of 5-FU, with or without HPP pretreatment. In tumor, peak levels of FdUMP at 30 min following bolus 5-FU, 100 mg/kg, averaged 4931 +/- 587 pmol/g. Pretreatment with HPP, 50 mg/kg, 24 h and 1 h before 5-FU, reduced the peak FdUMP level to 2085 +/- 387 pmol/g. The inhibition of TS by 5-FU treatment was greater than 95% by 30 min, and after 48 h residual enzyme inhibition averaged 40%. No effect on TS inhibition by 5-FU treatment could be observed as a result of HPP pretreatment. The levels of TStot increased linearly after 5-FU treatment and doubled within 48 h. In regenerating rat liver, neither FdUMP levels nor TS inhibition, studied at 1 h after bolus 5-FU, were affected by HPP pretreatment.
In 727 patients with acute myocardial infarction, different enzyme variables reflecting infarct size were related to the 5-year mortality rate. The maximum activity of serum heat-stable lactate dehydrogenase (LD), analyzed every 12 hours for 48 to 108 hours, was significantly associated with the 5-year mortality rate when patients with a first myocardial infarction were evaluated (p less than 0.001), and similarly (p less than 0.001) when patients with a previous myocardial infarction were included in the analyses. Very similar results were found when the maximum activity of aspartate aminotransferase (ASAT) analyzed once daily for 3 days was related to the mortality rate over 5 years, whereas the maximum activity of creatine kinase (CK) and CK subunit B analyzed every 6 hours for 48 hours in a subset of patients did not predict the outcome to the same extent. The results from LD and ASAT analyses clearly indicated that the association between infarct size and 5-year mortality rate was caused by the much higher mortality rate in patients with larger infarcts during the first year after onset of infarction, whereas after the first year, incidence of death appeared to be independent of the original infarct size. Thus we conclude that although a highly significant relationship between infarct size and overall 5-year survival was found, the mortality rate seemed to be higher in patients with larger infarcts, particularly during the first year after infarction.
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Renal function and morphology were studied before and after 60 min of renal ischaemia and contralateral nephrectomy in five groups of rabbits. The animals were pretreated with superoxide dismutase, catalase, allopurinol or mannitol. One group was not pretreated and served as a control. A moderate transient increase in serum creatinine concentration was observed in the control rabbits, while a significantly less pronounced increase was noted after pretreatment with superoxide dismutase, catalase and mannitol. Pretreatment with allopurinol did not significantly reduce the postoperative increase in serum creatinine and sodium excretion, but the urine osmolality returned to normal more rapidly than in the control group. The appearance under the light microscope of kidney tissue taken from surviving rabbits was found to be normal irrespective of pretreatment. Severe tubular necrosis was observed in the kidneys from rabbits that died during the observation period.
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In 585 patients with a first myocardial infarction the enzymatically estimated infarct size was related to the clinical course during a 2-year follow-up. Infarct size was estimated from maximum heat-stable lactate dehydrogenase activity. A higher maximum serum activity was associated with a higher mortality rate, more treatment with diuretics, digitalis and antiarrhythmics and a lower frequency of return to work. Patients with smaller infarcts according to maximum serum activity, however, had a higher incidence of angina pectoris and a higher reinfarction rate. We conclude that although there is a strong association between serum enzyme activity and mortality during a 2-year follow-up, the relation with morbidity appears to be more complex.