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Biomedical subjects

G Holm

Publications and source records attributed to G Holm.

At least 127 records · Page 7Linked to original sources

Clinical features of Hodgkin's disease in Cuba and Sweden.

A clinical study of 182 Swedish and 164 Cuban consecutive adult patients with Hodgkin's disease was performed comparing age, sex, histopathology, clinical stage, symptoms, and various laboratory tests. A bimodal age distribution was observed which was more pronounced in the Swedish series. A male/female ratio 1.8/1.0 in both samples was observed. Nodular sclerosis and Stage IA and IIA were more common in Swedish patients while in the Cuban, mixed cellularity and Stage IIIB and IVB dominated in patients below fifty years of age. The Swedish patients exhibited an age distribution similar to that found in other industrialized Western countries, while the Cuban patients had an age distribution pattern typical for countries with an intermediate epidemiological pattern.

Adolescent↗

Stimulation of bronchoalveolar lavage (BAL) and blood lymphocytes by Kveim antigen, tuberculin and concanavalin A in sarcoidosis.

BAL and blood mononuclear cells and their reactivity to Kveim antigen, tuberculin and concanavalin A (Con A) were studied in nine patients with different clinical stages of sarcoidosis. After separation by plastic adherence, non-adherent cells (mainly lymphocytes) were admixed with 10% autologous adherent cells (monocytes/macrophages). After 3 and 6 days' culture with Kveim antigen (1, 10, 100 micrograms/ml), PPD tuberculin (2.5 micrograms/ml) and Con A (10, 20, 40 micrograms/ml) stimulation was measured as incorporation of 14C-thymidine into DNA. Except for occasional reactions the study did not show any unitary significant increase in lymphocyte response to the different concentrations of Kveim antigen in either BAL or blood. For Con A there was a weaker response by BAL-mononuclear cells with no difference between 3 and 6 days, compared with blood where there was an early peak. The lymphocyte reaction to PPD was weak with no difference between blood and BAL.

Adult↗

Studies on calcium exchange in platelets in human diabetes.

Calcium has a key role in platelet aggregation. In order to assess the role of calcium metabolism in the platelet in diabetes mellitus, calcium exchange into and out of the cytosol was investigated in platelets from eight patients with insulin-treated diabetes with a mean duration of 10 years without any clinical complications. Their mean HbAIc (glycosylated haemoglobin) was 9% (normal range 3.4-5.4%). Influx rate of 45Ca2+ was significantly increased by 35% in diabetic platelets compared with controls. The efflux rate was significantly reduced during the first 15 min but total efflux measured over 2 h was equal in diabetic and control platelets. Access to sequestered non-mitochondrial calcium in the dense tubular system was gained by permeabilization of the cells with saponin. Into cells loaded with 45Ca2+, Inositol 1, 4, 5 triphosphate (IP3) was introduced and release of the sequestered ion would be determined. In control platelets calcium release was prompt and amounted to 43%. In diabetic platelets the response to IP3 was blunted and was only 17%. The nutritional and hormonal status influenced the response to IP3 in diabetes and, to a lesser extent, in controls. In the fasting state and without insulin the release was reduced but in the fed state and after insulin the release of calcium from diabetic platelets was equal to those of controls. It is concluded that abnormalities exist in platelet calcium handling in diabetes that can be influenced by insulin and the nutritional status.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

High doses of natural alpha-interferon (alpha-IFN) in the treatment of multiple myeloma--a pilot study from the Myeloma Group of Central Sweden (MGCS).

alpha-interferon (alpha-IFN) is a biological response modifier with a dose-dependent activity. The present study on the treatment of patients with multiple myeloma with high doses of natural alpha-IFN was designed to meet this dose-dependent concept. 50 previously untreated patients with IgA and BJ myelomas and a s-Creatinine less than or equal to 200 mumol/l entered the study. Various treatment schedules were tested. The initial plan was to give the patients 30 X 10(6) U alpha-IFN daily. This dosage, however, gave unacceptable toxicity. Step-by-step decreasing dose schedules were given to the patients, 10 X 10(6) U of alpha-IFN daily for 7 consecutive d repeated every 3rd week was found to be the maximal tolerable dose that could be given to most patients. 36% (95% confidence levels: 22%-50%) of the patients responded: 41% of the IgA myelomas and 23% of BJ myelomas. Median time to response was 1.5 months and median response duration was 20 months. Impaired general condition and central nervous system and gastrointestinal-related toxicity were the main adverse reactions. Hematological side-effects were mild.

Aged↗

Delayed skin hypersensitivity in man. The effect of repeated tests with low-dose antigen.

The effects of repeated applications of low doses of antigen on subsequent delayed cutaneous hypersensitivity (DCH) responses induced by the same antigen were evaluated. Fourteen healthy individuals were tested with seven different antigens given intracutaneously with the Multitest system device (Institute Mérieux). The procedure was repeated on four occasions at 2-week intervals. At the first test, 11 and 13 participants displayed DCH to tetanus and tuberculin, respectively. Neither the proportion of responding individuals nor the mean diameter of the reactions was changed in subsequent tests. However, the DCH pattern varied significantly between subjects (p less than 0.001; variance analysis). There was also a significant variation between the test occasion and skin reactivity. It is concluded that repeated applications of low-dose antigen by Multitest do not boost the DCH response. However, because of the low frequency of response to certain antigens and the low reproducibility of the test, the usefulness of this test system to evaluate DCH reactivity is limited.

Adult↗

Blood clonal B cell excess (CBE) at diagnosis in patients with non-Hodgkin lymphoma (NHL). Relation to clinical stage, histopathology and response to treatment.

Untreated non-leukemic (lymphocytes less than or equal to 4.0 X 10(9)/l) patients with non-Hodgkin lymphoma (NHL) of B cell type often show an excess of B cells in peripheral blood bearing the same light chain isotype as the lymph node tumor cells which may indicate a leukemic spread of the disease. The ratio between kappa- and lambda-bearing lymphocytes (normal range 1.0-3.3) was studied to evaluate the prognostic significance of clonal B cell excess (CBE) at diagnosis in 110 NHL patients. In total 43% had a CBE in peripheral blood. Fifty-two per cent of the patients in clinically advanced stages had CBE and 30% of the patients in stages I and II. CBE was detected in 49% of all patients with low-grade malignant lymphoma and in 32% with high-grade malignancy. Patients with a normal kappa:lambda ratio at diagnosis entered complete remission more often than those with CBE (P less than 0.01). In patients with high-grade but not with low-grade malignant lymphomas remission duration was longer for those with normal kappa:lambda distribution than for the patients with an abnormal ratio (P less than 0.01). Survival was not statistically significantly influenced.

Adult↗

Effects of graded insulin infusions on plasma levels of free fatty acids, adrenaline and noradrenaline directly after open heart surgery.

A four-hour insulin "clamp" technique was used to study the dose-response relationship between a wide range of plasma concentrations of insulin (5.0-7000 mU/l), free fatty acids, adrenaline and noradrenaline in 28 patients directly after open heart surgery. The influence of beta-blockers is discussed. All patients had elevated levels of free fatty acids at the beginning of the study (1020 +/- 77 mumol/l). After 4 hours the decline in free fatty acids was significant in all insulin-treated patients and most pronounced in the groups with insulin concentrations of more than approximately 350 mU/l, i.e. when insulin was infused with 0.3 units/kg bw/hour or more. No significant decrease in free fatty acids was observed in the control group. Adrenaline and noradrenaline in plasma were markedly increased throughout the study and were unaffected by the insulin infusions in all groups.

Adult↗

Cellular production of antibodies related to the acetylcholine receptor in myasthenia gravis: correlation with clinical stage.

Spontaneous and pokeweed mitogen-induced production of specific autoantibodies were studied in cultures of peripheral blood mononuclear cells from patients with different clinical stages of myasthenia gravis. Receptor antibody-related idiotypes and anti-idiotypic antibodies were defined by binding to mouse monoclonal anti-idiotypic and anti-receptor antibodies, respectively. Patients with severe disease had a more complete spectrum of idiotypes in serum, and cells from such patients spontaneously produced more antibody species and higher concentration of both idiotypes and anti-idiotypes than patients with mild disease. The frequencies of antibody specificities in tissue culture supernatants more closely reflected disease activity than those in serum. Tissue culture for the study of different species of autoantibodies has proved to be a useful tool for monitoring the disease and the effects of treatment.

Adult↗

Idiotypic network in myasthenia gravis demonstrated by human monoclonal B-cell lines.

Human monoclonal anti-receptor and anti-idiotypic antibodies were obtained from Epstein-Barr virus-transformed lymphoblastoid cells of patients with myasthenia gravis. The majority of antibodies (85/117) were IgM, and all IgM antibodies had lambda light chains. A marked restriction to one recurrent idiotype was found, despite the additional presence of other idiotypes in the serum from all patients. The presence of idiotypes and anti-idiotypes in the same patient was verified by the demonstration of specific complex formation between an anti-receptor antibody and an anti-idiotypic antibody produced by two different clones. Studies of human monoclonal antibodies produced by lymphoblastoid cell lines provide important information about the B-cell repertoire in myasthenia gravis and demonstrate a basis for a functional antibody network in this disease.

Antibodies, Monoclonal↗

Blood clonal B cell excess at diagnosis in multiple myeloma: relation to prognosis.

112 patients with multiple myeloma have been studied at diagnosis for the presence of blood clonal B-cell excess (CBE), defined as a ratio between kappa+ and lambda+ lymphocytes outside the normal range (0.9-3.5). 48 patients (43%) had CBE. The increase in light chain-bearing lymphocytes was always that of the M component light chain isotype. The proportions of patients exhibiting CBE were the same in different stages. The response frequency was not influenced by the presence of CBE. However, patients with CBE had a shorter remission duration time (p less than 0.001) and total survival (p less than 0.05) than those without CBE. This was also noticed when each clinical stage was analyzed separately. Moreover, survival was shorter in patients with a large fraction of CBE than in those with a small one. Cox regression analysis revealed that CBE was a much stronger predictor of remission duration than age, clinical stage and renal dysfunction. CBE and response to initial treatment independently were the best factors to indicate survival. It is suggested that analysis of CBE should be included in the clinical characterization of untreated patients with multiple myeloma.

Adult↗

T lymphocyte subpopulations in chronic lymphocytic leukemia of B cell type in relation to immunoglobulin isotype(s) on the leukemic clone and to clinical features.

Total blood T lymphocytes and subpopulations (OKT4+ and OKT8+ cells) were studied in 59 patients with B cell chronic lymphocytic leukemia (B-CLL). In 48 previously untreated patients, total T lymphocytes were higher as compared to healthy controls (p less than 0.001). T-cells and OKT8+ cells were significantly increased in patients in advanced clinical stage and with progressive disease in comparison to patients with low stage and indolent disease. High numbers of OKT8+ lymphocytes were also seen in patients with a dominance of mu heavy chains on the leukemic clone. Moreover, in this patient group the OKT8+ subpopulation correlated with total B cells (r = 0.68, p less than 0.001) while in patients with a mu delta phenotype no such correlation was seen. After successful cytostatic therapy there was a reduction in total numbers of both OKT4+ and OKT8+ cells, in particular, with a concomitant increase in OKT4/OKT8 ratios.

Adult↗

S-phase lymphocytes in chronic lymphocytic leukemia (CLL) in relation to immunoglobulin isotypes on the leukemic clone and to disease activity.

The fraction of blood S-phase (S+) lymphocytes from 41 patients with chronic lymphocytic leukemia of B cell type was determined by flow cytometry. The patients were grouped according to the smig isotype pattern of the leukemic cells. Patients with IgM as the predominant smig had higher numbers of S+ lymphocytes than patients with a leukemic clone co-expressing IgM and IgD (p less than 0.001). High relative as well as total numbers of S+ lymphocytes were associated with short therapy-free and overall survival. T cell proliferation was low although significantly higher in active than in indolent disease.

B-Lymphocytes↗

Antibodies to cardiolipin in young survivors of myocardial infarction: an association with recurrent cardiovascular events.

Antibodies to cardiolipin were measured in 62 survivors of myocardial infarction under age 45 at 3, 12, and 36 months after the acute event. 13 patients (21%) had raised anticardiolipin antibody levels on at least two of the three sampling occasions. Risk-factor profiles and coronary angiographic findings did not differ between the anticardiolipin-positive group and the rest of the patients. No correlation was found between cardiolipin and anti-DNA antibody levels. 8 of the 13 patients with raised anticardiolipin antibody levels experienced additional cardiovascular events during a follow-up of 36-64 months after the first myocardial infarction: cerebral infarction developed in 2, arterial occlusion of the lower limb in 2, new myocardial infarction in 3, pulmonary emboli in 1, and deep-vein thrombosis in 1. These 8 patients had cardiolipin antibody titres of 5 times the mean for voluntary blood donors. Antibodies to cardiolipin are common in young post-infarction patients and should be interpreted as markers of high risk for recurrent cardiovascular events.

Adult↗

Thermogenic effect of food in physically well-trained elderly men.

Basal metabolic rate (BMR) and the thermogenic effect of food (TEF) after a liquid mixed meal of 2092 kJ (500 kcal) were examined in physically well-trained, elderly men in comparison with sedentary weight- and age-matched controls. BMR tended to be higher and TEF was significantly higher in the physically well-trained men than in the controls. No certain differences were found in plasma thyroid hormones or catecholamines. BMR correlated with whole body potassium while TEF did not. The tendency to elevated BMR in the well-trained men might therefore be due to their greater muscle mass. The elevated TEF, however, probably has other causes and might be associated with the elevated catecholamine sensitivity associated with the physically trained condition.

Aged↗