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Biomedical subjects

G Holm

Publications and source records attributed to G Holm.

At least 145 records · Page 8Linked to original sources

Clinical findings and prognostic factors in chronic myeloid leukemias.

Ninety-one previously untreated patients with chronic myeloid leukemia admitted to three Stockholm hospitals 1973-1978 were studied. There were 49 men and 42 women with a mean age of 56 years (range 15-93). Sixty-five patients were Philadelphia chromosome (Ph1) positive and 17 were Ph1 negative (mean age 51 and 70 years, respectively). After a mean observation time of 5.2 years, 64 patients had deceased, 45 of them in blast transformation. A low hemoglobin value and a high total blast cell count at diagnosis were associated with a poor prognosis in the Ph1 positive group. Other routine clinical and laboratory variables were of subordinate prognostic importance. Early splenectomy in 15 Ph1 positive patients did not improve survival. Median survival from diagnosis was 38 months for Ph1 positive patients as compared to 12 months for the Ph1 negative group.

Adolescent↗

Prognostic influence of early diagnostic splenectomy in Hodgkin's disease. A long-term follow-up.

The influence of early laparotomy with splenectomy on prognosis in patients with Hodgkin's disease who were regarded as having uncertain prognostic indices (all patients except those with lymphocytic predominance and nodular sclerosis stages IA and IIA with right-sided presentation, stage IV disease, splenomegaly or age greater than 65 years) was evaluated in a randomized trial initiated in Jan. 1973. The patients were treated with total nodal irradiation (excluding the splenic and hepatic areas) and 33 of 69 patients were randomized to laparotomy with splenectomy. No significant difference in relapse-free or overall survival was found between the two groups after a median observation time of 85 months. Progressive or recurrent disease was as common in splenectomized as in non-splenectomized patients. Splenectomized patients with splenic tumour involvement fared worse than those without. It is concluded that diagnostic laparotomy with splenectomy is of no benefit in this clinical setting.

Adolescent↗

Antipyretic effect of indomethacin in malignant lymphoma.

Fifteen patients with lymphoid malignancies and tumour-related fever (greater than 38.0 degrees C) were given 50 mg indomethacin (IM) orally. This resulted in a reduction of body temperature in all cases (mean +/- SD 3.4 +/- 2.0 degrees C). In one patient with untreated Hodgkin's disease, temperature fell from 40.6 degrees C to 30.6 degrees C within 12 hours without any cardiovascular or respiratory distress. The lytic effect of IM on fever was more pronounced and more rapid in the 15 patients with lymphoma than in a group of 10 patients with acute myocardial infarction. IM therapy has a clear value in relieving tumour-associated fever in patients with malignant lymphoma. There may be a qualitative difference between the IM response of tumour-related fever and fever related to non-malignant diseases.

Adult↗

Acetylcholine receptor antibodies and anti-idiotypic antibodies produced in blood lymphocyte cultures from patients with myasthenia gravis.

The production of acetylcholine receptor antibody idiotypes and of antibodies directed against receptor antibody idiotopes were studied in cultures of blood mononuclear cells from 11 patients with myasthenia gravis and 11 healthy donors. The antibody specificities were defined by their reaction with monoclonal anti-receptor and anti-idiotypic antibodies. Cells from eight patients but no controls produced both kinds of antibodies. These antibodies were less frequently found in patients' sera. In no patient were antibody specificities present in serum not detected in cell cultures. It is concluded that the B-cell repertoire of specific autoantibodies is more completely disclosed by analysis of blood cell cultures than by serum antibody determinations. The results suggest an idiotype-anti-idiotype regulation of anti-acetylcholine receptor autoimmunity in myasthenia gravis.

Antibodies↗

Muscle adaptations and glucose control after physical training in insulin-dependent diabetes mellitus.

Six men and three women with insulin-dependent diabetes (without complications) participated in physical training three times a week for 20 weeks. Physical training did not change the concentration of fasting blood-glucose, glucose excretion in urine or glucosylated haemoglobin (HbA1). However, the glucose disposal rate during euglycaemic clamp increased after training. In two patients a minor reduction of insulin dosage was necessary to alleviate slight hypoglycaemic episodes. The training resulted in significant increases in quadriceps isometric and dynamic strength and endurance. Maximal oxygen uptake increased by 8%, the activity of glycolytic enzymes in vastus lateralis muscle by 47% for hexokinase, and 30% for tri-osephosphate dehydrogenase and 25% for lactic dehydrogenase, the activity of oxidative enzymes by 42% for citrate synthase and 46% for 3-hydroxy-acyl-CoA-dehydrogenase. The glycogen concentration in the vastus lateralis muscle did not change significantly. Lipoprotein lipase activity did not change in muscle, nor in adipose tissue. The mean muscle fibre area increased by 25% and the area of FTa fibres by 30%. The new formation of capillaries around different muscle fibres was significant for FTb fibres (26%). The proliferation of capillaries, however, appeared to be insufficient to cope with the increased area of muscle fibres. As a result, the mean area of muscle fibre supplied by one capillary (a measure of diffusion distance) significantly increased after training for FTa fibres. It is concluded that with the exception of deficient proliferation of capillaries, patients with insulin-dependent diabetes mellitus show a normal central and peripheral adaptation to physical training. Physical training does not apparently improve blood glucose control in most cases, despite an increased insulin sensitivity.

Adaptation, Physiological↗

The effects of physical training on insulin secretion and effectiveness and on glucose metabolism in obesity and type 2 (non-insulin-dependent) diabetes mellitus.

Obese subjects with normal glucose tolerance (n = 55), and, in another study, a group of patients with Type 2 (non-insulin-dependent) diabetes (n = 33), and controls (n = 13) matched for body weight and age but with normal glucose tolerance, participated in an individualized physical training program for 3 months. Under controlled dietary conditions, metabolic studies were performed before and in steady state after the last exercise session after training in the subjects showing signs of physical training in VO2 max and heart rate measurements. No changes occurred in body weight, body cell mass, body fat or adipose tissue cellularity. Oral glucose tolerance was improved in the patients with diabetes mellitus only. In both diabetic and control subjects initially elevated C-peptide concentrations decreased, while low C-peptide values increased and which was particularly pronounced in diabetic subjects with subnormal values. Peripheral insulin values did not change. Glucose disposal rate measured with the glucose clamp technique was similar in diabetic patients and control subjects. An improvement was seen at both submaximal and maximal insulin levels in both groups, correlating with improvement in glucose tolerance in the diabetic subjects. No changes were found in adipocytes in insulin binding or the antilipolytic effect of insulin at submaximal insulin levels, but there was a normalization of a decreased glucose incorporation into triglycerides. These results indicate that both insulin secretion and effectiveness are altered by physical training in different ways in different clinical entities. They suggest that in insulin resistant conditions with high insulin secretion (as indicated by high C-peptide concentrations) the increased peripheral insulin sensitivity is followed by a decreased insulin secretion. This is not associated with an improvement of glucose tolerance. In Type 2 diabetes with low insulin secretion, an increased insulin secretion results from physical training, perhaps due to accompanying sensitization of the autonomic nervous system. Peripheral insulin concentrations are not altered, suggesting that the extra insulin produced is captured by the liver. This mechanism, as well as the improved peripheral insulin responsiveness seen in the whole body and also seen at the cellular level, probably both contribute to an improvement in glucose tolerance.

Adipose Tissue↗

Characterization of chronic lymphocytic leukemia (CLL) cells with low density of surface membrane bound immunoglobulins (smIg).

The study consists of 6 CLL patients with leukemic blood lymphocytes lacking T-cell characteristics and with smIg on only a very small fraction of the cells detected by microscopy or FACS analysis after direct immunofluorescence (IFL) staining. Using B-cell specific monoclonal antibodies all leukemias were found to be of the B-cell type. SmIg, mainly of IgD-class and the monotypic light chain, was detected on a large number of cells in all cases when using direct IFL. No lymphocyte clone was judged to be of the pre-B-cell type or represented fully differentiated terminal B-cells. CLL cells from the individual cases probably represent intermediate B-cell maturation steps. The results lend no support to the suggestion that this subtype of CLL necessarily belongs to an early stage of differentiation just beyond the pre-B-cell level.

Antibodies, Monoclonal↗

Use of dodecyl sulfate as an esterase inhibitor before gas-chromatographic determination of labile beta-adrenoceptor blocking drugs.

Sodium dodecyl sulfate (SDS) was introduced as an esterase inhibitor in the determination of two extremely labile, ultrashort-acting beta-blockers-esmolol and flumolol--in whole blood. SDS was much more efficient than previously used agents in preventing hydrolysis. The assay comprises solvent extraction, perfluoroacylation, and capillary gas-chromatography with electron-capture detection. The limit of detection (the concentration at which the coefficient of variation is 10-15%) for the drugs is 5 nmol/L of whole blood.

Adrenergic beta-Antagonists↗

Non-response of muscle capillary density and lipoprotein-lipase activity to regular training in diabetic patients.

Ten obese women with normal glucose tolerance, 10 obese patients with sulphonylurea-treated non-insulin-dependent diabetes (NIDD) and 11 patients with insulin-dependent diabetes (IDD; treated for 3-31 yr) took part in a 10-week programme of physical training in 50-min sessions, 2-3 times a week. As a result of training, maximal oxygen uptake increased significantly by about 18, 13 and 8% in the 3 groups, respectively, and citrate synthase in muscle increased significantly by 27-42%. The lipoprotein-lipase activity in muscle tissue (sampled by a needle-biopsy technique from the lateral vastus muscle) did not change. The number of capillaries/fibre in muscle tissue increased. This was accompanied by an increase in muscle fibre area, resulting in an unchanged number of capillaries/mm2. This may explain why the lipoprotein-lipase activity was unaltered. The latter activity in the group with IDD was lower than was predicted from the number of capillaries/mm2. This number was in fact larger than in the obese and NIDD groups. These results indicate that the increase in capillary density and lipoprotein-lipase activity that occurs in healthy young individuals as an effect of endurance training does not take place in obese, NIDD and IDD patients.

Adult↗

Surface markers and cytotoxic activity of blood natural killer cells studied at the single cell level in Hodgkin's disease.

Purified peripheral blood lymphocytes (PBL) from nine untreated patients with Hodgkin's disease (HD), two HD patients in complete remission and 17 healthy donors were studied for natural killer (NK) cell activity against the K-562 cell line using a single cell cytotoxic assay, which allowed enumeration of effector cells and characterization of their surface membrane phenotypes after staining with monoclonal antibodies. The frequency of NK cells was significantly lower in HD patients than in controls (mean % +/- s.d., 1.9 +/- 0.9 and 2.8 +/- 1.2, respectively), while the fraction of target binding cells was similar in the two groups. The fraction of cytotoxic lymphocytes increased after pre-treatment of PBL with 500 iu leucocyte interferon in all tested control donors (n = 12) and the two patients in remission but only in four of seven untreated patients. No relation between the impaired NK cell frequency and age, tumour histology and clinical stage could be revealed. Subtyping of the target cell binding NK cells by monoclonal antibodies disclosed a marked heterogeneity of effector cells. NK effector cells reactive with M1 and anti-Ia antibodies were enriched while T3+ and T4+ NK lymphocytes tended to be reduced as compared to PBL. There was no difference between patients and healthy donors with regard to the surface antigen patterns of NK cells. Interferon treatment did not alter significantly the phenotypic characteristics of cytotoxic lymphocytes in patients and controls. It is concluded that the impairment of NK cell activity in HD is partly attributed to a lower frequency of cytotoxic effector cells among a normal number of target binding cells. The defect could not be attributed to a selective defect of effector cell subsets.

Adult↗

Familial longevity and prognosis in Hodgkin's disease.

The authors studied the influence of familial longevity on the prognosis in 98 patients with Hodgkin's disease (HD) followed for a long period of time. The survival of parents and grandparents to patients older than 50 years of age who died from progressive HD was significantly shorter than that of ancestors to survivors in the same age group. The excess death rate among relatives to the deceased patients was mainly caused by tuberculosis, which suggests a T-cell defect. The prognostic information achieved by analyzing duration of life of ancestors was superior to that given by the clinical stage. No association between familial longevity and prognosis was observed in young patients (less than or equal to 50 years of age). These findings are consistent with the hypothesis that HD in the elderly may be a separate clinical entity, and may also have important implications as to the understanding and treatment of HD in the elderly.

Adult↗

Prognostic factors in Hodgkin's disease with special reference to age.

A series of 182 patients with Hodgkin's disease, diagnosed between January 1973 and December 1978 was used to identify prognostic factors with special reference to age. There were 118 men and 64 women (mean age, 47 years; r = 15-92). During the same period 57 elderly patients who were never referred, were reported to the Local Cancer Registry. The diagnosis had been established shortly before death or at autopsy. The 182 patients under study were evenly distributed in Stages I-IV. Nodular sclerosis (38%) and mixed cellularity (38%) were the most common histologic subtypes. The 5-year survival probability estimate was 28% in patients above 50 years as compared to 74% in the remainder. Survival was significantly better in patients with Stage I-II disease and lymphocyte predominance/nodular sclerosis histopathology. Age was the main prognostic factor in the whole series as well as in patients older than 50 years. However, in young patients advanced clinical stage and B-symptoms were related to a poor prognosis. Biologic indicators such as ESR, hemoglobin and albumin were intimately linked to the extent of disease and did not add prognostic information besides that given by the clinical stage. It is concluded that the prognosis in elderly remains poor and appears to be partly unrelated to those factors which determine the prognosis in the young, assumingly reflecting a depressed host-response and/or a decreased tolerance to intensive treatment.

Adult↗

Lack of IgG in a healthy adult: a rare case of dysgammaglobulinemia with undetectable serum IgG, IgA2, and IgE.

No IgG of any subclass could be detected in the serum of a normal healthy male adult (E.E.) who had no recent history of repeated infections. Markedly increased concentrations of both IgM and IgA were present although no IgA2 nor IgE could be demonstrated. No anti-immunoglobulin antibodies were present in the serum; when used as supplement in in vitro cultures, the serum supported differentiation of IgG-producing cells to an equal extent as that of normal serum. No cells with surface or intracellular IgG were found in the peripheral blood although low numbers of IgG-secreting cells could be induced in vitro after mitogen stimulation. No increase in suppressor cell activity was found in cocultivation experiments. T-Cell-enriched populations from E.E. were poor inducers of immunoglobulin synthesis in allogeneic B cells, and B-cell-enriched populations from E.E. could not be triggered to synthesize IgG with the aid of allogeneic T cells. Thus, it seems that lack of IgG does not necessarily lead to a highly increased susceptibility to bacterial infections.

Aged↗