Biomedical subjects
Publications and source records attributed to G Holm.
Four patients with myelomatosis (one IgG-chi-type, two IgA-chi, and one Bence Jones-x) were given human leucocyte interferon as the only treatment for from 3 to 19 months. Remission was complete in two patients and partial in the other two. Normal bone-marrow haematopoiesis was slightly inhibited. The disease has not so far progressed in any of the patients.
Forty-four adult patients under 60 years of age with acute nonlymphoblastic leukemia were randomized for induction treatment with one of the following three regimens: R 1 = courses of daunorubicin on day 1 + ARA-C on days 1--5; R 2 = courses of daunorubicin on days 1 and 2 + ARA-C on days 4--8; R 3 = courses of daunorubicin-DNA complex on days 1--2 + ARA-C on days 4--8. Out of 14 patients, 9 went into remission on R 1, 6 out of 14 on R 2, and 8 out of 16 on R 3. The preliminary results suggest that daunorubicin-DNA complex has the same efficacy for inducing remission as daunorubicin alone, if the same time intervals and dosages are used.
The immunological side-effects under treatment with antihypertensive drugs are mainly limited to autoimmunity and autoimmune disease caused by alpha-methyldopa and hydralazine. Autoimmune hemolytic anemia is more common during treatment with alpha-methyldopa. Hydralazine may induce antinuclear antibodies. Some patients develop a SLE-like syndrome. Its clinical picture is less severe and its prognosis is more favourable than that of spontaneous SLE. During treatment with low doses the disease develops exclusively in patients who are slow acetylators. It may appear also in rapid acetylators during the high dose treatment. The symptoms are usually reversible after withdrawal of the drug.
In order to identify metabolic risk factors other than hypercholesterolaemia, all cases of acute myocardial infarction, diagnosed in males aged under 40 years, were studied over a period of 6 years in Göteborg, Sweden. Twenty out of twenty-four patients who were alive at the time of the study were compared with forty controls matched for serum cholesterol concentration. A previous report has noted lower apolipoprotein A (apoA) and a higher alpha-lipoprotein triglyceride concentration in these young myocardial infarction patients compared with the matched controls. Basal blood glucose, oral glucose tolerance and plasma insulin levels did not differ between the patients and controls, i.e. decreased glucose tolerance and elevated plasma insulin levels were not found to be additional risk factors for myocardial infarction in young males if serum cholesterol concentration was taken into consideration. This finding could be explained by the fact that patients and controls were all high cholesterol individuals and a difference between the patients and the general population is still possible. Low apoA was a risk factor independent of serum cholesterol as well as glucose intolerance and elevated plasma insulin levels.
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The influence of tocopherol in an intramuscular dose of 5 mg/100 g body wt. on the effect of local X-ray irradiation of 2 intramuscularly transplanted tumours in the rat was studied. A significantly enhanced effect of irradiation by tocopherol was found, in contrast to the tumour radioprotecting effect with large doses of tocopherol earlier described in literature.
The blood lymphocytosis in CLL is caused mainly by a rise of immunoglobulin (Ig)-bearing leukemic lymphocytes. Most cells carry Fc-receptors, while the percentage with receptors for human complement is very low with the present technique. The leukemic lymphocytes carry only one of the light chain types, which suggests a monoclonal origin. CLL patients with lymphocytes expressing kappa light chains may have a more benign disease than lambda-CLL. T-lymphocyte levels are high during the early course of the disease but decrease with its progression and are low in patients with "active" disease.
Surface immunoglobulins (sIg) on human blood lymphocytes were identified by immunofluorescence (IFL) after staining with conjugated F(ab'2) fragments of the anti-Ig antibodies. A large fraction (approximately 20%) of freshly isolated lymphocytes was found to carry sIgG. Polyclocal IgG, which was present on Fc-receptor-bearing lymphocytes, could be removed by incubation and repeated washings only at 37 degrees C. Lymphocytes treated at 37 degrees C expressed the same percentage of sIg+ cells in direct IFL when F(ab')2 fragments of the antibody was used as when undigested aggregate-free IgG antibody was used. Indirect IFL using F(ab')2 fragments in both steps yielded similar sIg+ values. However, much higher percentage of cells carried sIg when undigested antibody was included in one of the steps. The results suggest that incubation and washing at 37 degrees C and the use of F(ab')2 fragments of the antibodies are important to eliminate absorbed sIgG and to avoid absorption of IgG during the staining procedure, thus preventing overestimation of the number of sIg+ B lymphocytes identified by IFL.
27 consanguineous and non-consanguineous relatives to 12 patients with Hodgkin's disease (HD) have been studied. The lymphocyte DNA synthesis induced by concanavalin (ConA) was depressed in 6 patients. 7 out of 15 tested relatives (3 first degree relatives and 4 spouses) showed a profound impairment in lymphocyte response to ConA stimulation. None out of 12 relatives to ConA normal patients was defect in this respect. In relatives to ConA hyporesponsive patients there was a small but statistically significant decrease in lymphocyte response to pokeweed mitogen (PWM) and PPD in vitro. No differences in lymphocyte subpopulations were seen. The findings strongly support an exogenous factory (probably a virus) causing the depressed mitogen response in relatives to immunodeficient patients with HD. A possible linkage between the immunodeficiency and the pathogenesis of HD is discussed.
To elucidate early metabolic adaptations of physical training obese and nonobese subjects were studied before and at different intervals after 1 h of bicycle exercise at 70% of maximal working capacity. Four h after exercise intravenous glucose tolerance (IVGT) and plasma level of alanine were decreased. Compared to the diurnal variation plasma concentration of cortisol was increased. Twenty-four hours after exercise plasma concentrations of cortisol and trihlycerides were decreased. Furthermore, plasma insulin during IVGT test was decreased and blood glycerol increased in the obese subjects. There were no changes in basal insulin, IVGT, or plasma levels of amino acids which were elevated in the obese subjects (valine, isoleucine, leucine, tyrosine, phenylalanine). Forty-eight hours after exercise plasma insulin during IVGT test and plasma triglycerides remained decreased in the obese subjects. Low cortisol levels 24 h after exercise might result in increased insulin effect leading to low plasma insulin levels seen in physically trained subjects. Elevated glycerol levels in the obese subjects might be the first sign of diminishing fat stores secondary to increased lipolysis.
Postabsorptive plasma amino acid and insulin concentrations were determined in subjects with hyperplastic obesity and in nonobese controls before and after a 6-wk period of physical training. After the training period the plasma concentrations of insulin and leucine decreased and the concentration of alanine increased in the obese subjects. No changes were noticed in the controls. The obese subjects had elevated plasma levels of valine, isoleucine, leucine, tyrosine, and phenylalanine before as well as after physical training. The concentrations of these amino acids were correlated to the plasma insulin level and to lean body mass before but only to lean body mass after physical training. It is suggested that the lean body mass, whick is higher in hyperplastic obesity, contributes to the elevated concentrations of amino acids, and it is unlikely that the insulin decreases in the obese subjects after physical training is mediated through an effect of amino acids on insulin secretion.
Purified blood lymphocytes from 81 consecutive and previously untreated patients with Hodgkin's disease were studied in vitro. The patients were evaluated 23 to 52 months after institution of therapy and were divided into two prognostic groups: 1. Complete remission with or without previous relapse/relapses. 2. Uncontrolled relapse or decreased from Hodgkin's disease. Lymphocyte activation by concanavalin A, pokeweed mitogen or phytohaemagglutinin was impaired and spontaneous DNA synthesis was high in patients with poor prognosis as compared to the good prognosis group. The prognostic information increased if the four lymphocyte tests were combined in a score (range 0-8). All 8 patients with pronounced lymphocyte defects (score 7-8), died, while all patients with score 0 and 1 were in complete remission. In contrast, total lymphocyte and T-lymphocyte counts and lymphocyte stimulation by PPD were of no prognostic value. The ability of certain lymphocyte functions to predict prognosis was equal or better than that of age and better than clinical staging, histopathology and symptoms.
The possible existence of circulating pancreatic type glucagon (immunoreactive glucagon as measured with a highly specific antibody) of extrapancreatic origin was investigated in 20-25 kg pigs after pancreatectomy. In intact conscious animals intravenous arginine infusions stimulated glucagon as well as insulin secretion, while blood glucose remained unaffected. Two weeks after pancreatectomy, and 48 hours after insulin withdrawal, basal glucagon and glucose concentrations were elevated (from 22 +/- 3.7 to 55 +/- 9.5 pmol/1 and 5.8 +/- 0.4 to 16.2 +/- 2.0 mmol/l, respectively), (mean +/- SEM), while insulin concentrations were either undetectable or very low. After pancreatectomy, however, glucagon concentrations no longer increased during arginine infusion. Gut type glucagon levels were not affected by pancreatectomy, and did not change during arginine infusion. When examined by gel filtration, plasma from unoperated pigs contained two components of pancreatic type glucagon, one coeluting with the glucagon marker, the other eluting earlier, probably reflecting larger molecular size. After pancreatectomy only this larger component was found in the plasma. The role of this component in the control of blood glucose is unknown.
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Severly obese subjects and sex- and age-matched controls underwnet physical training during a 6-wk period. Evidence of training was shown in all subjects by increased aerobic power. Before training the obese subjects were characterized by the following abberations: decreased glucose tolerance, hyperinsulinemia, elevated blood glycerol and plasma free fatty acids, and a blunted plasma growth hormone response during glucose tolerance. Noradrenaline output was elevated, a finding of potential interest for the explanation of increased lipolysis, blood pressure, and heart size in obesity. With training the following changes were found:In the controls there was evidence for the beginning of a decrease of adipose tissue mass. In the obese, however, body weight, body fat, or fat cell size did not decrease during training. Plasma insulin decreased, and a corresponding increase of plasma glycerol was seen. Glucose tolerance was not changed, and this, together with decreased plasma insulin, indicated an increase insulin sensitivity of the periphery. Changes in noradrenaline or growth hormone during training could not explain this increased sensitivity. Urinary cortisol output was found to decrease after training in the obese; this might be interpreted as a decrease in cortisol secretion allowing a more effective insulin action on the periphery.
Thirty-two consecutive, previously untreated patients with plasma cell myeloma were treated with 4-day courses of melphalan (0.25 mg/kg/day) and prednisolone (2 mg/kg/day) every sixth week. The observation period ranged from 26 to 75 months and the total median survival time was 29 months. 75% of the patients responded to therapy and their median survival time was 42 months. Sex did not influence either the response rate or the survival time. Most patients were treated in an out-patient clinic and required a minimum of check-ups.
We studied the immunocompetence of 6 healthy twins, whose monozygotic or dizygotic same-sexed twin partner had died from Hodgkin's disease. Lymphocyte DNA synthesis induced by concanavalin A was markedly reduced at 3 different concentrations in all twins compared to an age-matched group of healthy controls. The lymphocyte response to pokeweed mitogen and to phytohaemagglutinin was also impaired. PPD induced lymphocyte DNA synthesis was low in 3 twins and correlated well with their delayed skin hypersensitivity to the antigen. One twin was completely anergic to 3 different skin antigens. The mean total blood lymphocyte count did not differ from that of controls. There was no change in T or B-lymphocyte subpopulations. The presence of a functional lymphocyte deficiency in all twins strongly suggests that the immunodeficiency in Hodgkin's disease is partly caused by genetic and/or environmental factors.