Biomedical subjects
Publications and source records attributed to G Holm.
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The digital skin microcirculation was studied by vital capillaroscopy in 32 consecutive patients with Raynaud's phenomenon. A detailed classification (stages 0-6) of the capillary abnormalities based upon observations of the capillaries in many different sites of the fingers was used. Associated diseases were searched for by an extensive clinical and immunological investigation. Seventeen (53%) of the patients had distinct structural changes in the capillaries but only 6 of them showed a restricted total digital circulation. Fifteen (88%) of these 17 patients displayed an underlying disease and/or immunological abnormalities. The corresponding figure for patients with mild or no capillary changes was 40% (p less than 0.01). Thus, the presence of marked (greater than or equal to stage 3) skin capillary abnormalities seems to be a good indicator of an associated systemic disease. The majority of patients in this category improved their capillary status during successful treatment of the underlying disease. We conclude that the form of capillaroscopy used in this study is a sensitive method for evaluating disturbances of the skin microcirculation in patients with Raynaud's phenomenon. The method may also contribute to the clinical evaluation of patients with this syndrome by identifying those with an underlying systemic disease.
Total lymphocyte counts were determined on an average 13.4 years before establishment of the diagnosis in 20 of 95 consecutive patients with chronic lymphocytic leukemia (CLL). The reasons for performing the white blood cell and differential counts did not include diabetes, autoimmune diseases or verified viral infections which are conditions well known to be associated with lymphocytopenia or lymphocytosis. The mean total lymphocyte count in the patient group was 2.6 X 10(9)/l and did not differ from that of an age-matched control group. There was no significant association between the pretreatment lymphocyte count and the time between test and diagnosis. We conclude that patients with CLL have not a lymphocytopenic state antedating the diagnosis of CLL.
Ten severely obese women were subjected to physical training for three months on ad libitum diet. Under metabolic ward conditions oral glucose tolerance test was performed before and after the training period with the same energy intake quantitatively and qualitatively, and glucose, insulin, connecting (C)-peptide, gastric inhibitory polypeptide (GIP) and pancreatic polypeptide (PP) were determined. In confirmation of previous work, physical training caused no decrease in body fat in these severely obese subjects, and no change in body cell mass or glucose tolerance, while insulin and blood pressure decreased. The control of dietary conditions demonstrated that the latter phenomena were not due to quantitative or qualitative changes in the diet. C-peptide concentrations decreased also, indicating effects of physical training in obesity on insulin production. GIP is believed to be a gastrointestinal factor facilitating insulin secretion (Incretin). Previous work has indicated that gastrointestinal factor(s) are involved in the insulin lowering effect seen after physical training. It is possible that GIP is contributing to this phenomenon.
In a randomized clinical trial intermittent high-dose melphalan/prednisone (MP) treatment has been compared with human leukocyte interferon (IFN) administration. Three to 6 X 10(6) IU of IFN was given im daily. Therapy was continued to progression of the disease. Fifty-five patients were randomized to receive MP and 75 were randomized to receive IFN. Forty-four percent of the patients receiving MP responded to therapy as opposed to only 14% of the patients receiving IFN (P less than 0.001). This difference was mainly due to a low response rate in IFN-treated IgG myelomas, while the response rate for IgA and Bence Jones myelomas did not differ significantly between the two treatment groups. Median duration of response was shorter for IFN-responding patients (23 months) as compared to patients in the MP group (35 months). During follow-up, second-line therapy was given more frequently in the IFN group (91%) than in the MP group (59%). Time on initial treatment was significantly shorter in the IFN group (3 months) than in the MP group (19 months). Since more patients responded to second-line therapy in the IFN group than in the MP group, total survival did not differ significantly between the two groups.
Sera from 296 unselected and untreated patients with non-Hodgkin lymphoma (NHL) classified according to the Rappaport and the Kiel systems were analyzed for antibodies to Epstein-Barr virus (EBV). The aim of the study was to determine whether antibody spectra and titers to EBV-coded antigens correlated to clinical and immunological variables and whether the titers were of any prognostic significance. Increased antibody titers to EB viral capsid antigen (VCA) and slightly raised titers to early antigens (EA) of the diffuse (D) and restricted (R) types were noted frequently. Anti-VCA antibody titers correlated to clinical stage and age of the patients but not to histological subgroups according to the Rappaport or the Kiel classification systems. However, anti-VCA titers greater than or equal to 1:2560 were seen only in diffuse lymphomas according to the Rappaport and in non-follicle cell-derived lymphomas according to the Kiel classifications. Patients with complement-receptor-positive diffuse lymphomas had higher anti-VCA titers than complement-receptor-positive nodular cases. Anti-VCA titers also correlated positively to serum IgG levels (p less than 0.01). Total number of lymphocytes separated from peripheral blood and mitogen induced (ConA, PWM) DNA synthesis were recorded before treatment in 56 of the patients. The patients exhibited a significant lymphocytopenia as well as a significantly reduced lymphocyte response to mitogens (p less than 0.001) compared to healthy controls. Elevated anti-VCA titers and anti-EA titers correlated to a good mitogen-induced lymphocyte response (p less than 0.05). Only anti-D 1:40 at diagnosis predicted a poor prognosis.
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Explore the source record for details and available documents.
Highly purified blood lymphocytes from healthy individuals were obtained from samples collected before and after a standardized bicycle ergometer test. In accordance with previous findings physical work resulted in a marked increase of circulating lymphocytes, with a proportionate decrease of T lymphocytes and increase of non-T lymphocytes including B cells. The decrease of T lymphocytes was accounted for by a reduction of cells reactive with the monoclonal OKT4 serum (helper/inducer), whereas the proportion of OKT8-positive cells (suppressor/cytotoxic) remained unchanged. The lymphocyte production of IgG, IgM, and IgA after 7 days culture with pokeweed mitogen and the lymphocyte DNA synthesis after activation by allogeneic cells was reduced during work. It is concluded that nonspecific stress changes the composition of T-lymphocyte subsets with depression of T-cell stimulation and T-cell-dependent immunoglobulin production.
The study comprises 26 patients with non-Hodgkin's lymphoma who entered complete remission. Lymphocyte subsets and spontaneous and mitogen (ConA, PWM)-induced DNA synthesis were recorded in purified blood lymphocytes harvested before treatment, in remission and in relapse. The T and B lymphocytopenia noted in untreated patients persisted in complete remission. At diagnosis the spontaneous DNA synthesis was increased and the response to mitogen was decreased as compared to controls. Both functions became normalised during complete remission in most patients under 60 yr. The lymphocyte abnormalities reappeared during relapse. A low response to mitogen (ConA) in complete remission seemed to predict early relapse in patients younger than 60 yr. It is concluded that functional abnormalities of blood lymphocytes in non-Hodgkin's lymphoma are closely related to the presence of active disease.
Patients with newly diagnosed multiple myeloma were randomly allotted to an intermittent high-dose melphalan/prednisone (MP) treatment (120 patients) or a continuous low-dose melphalan (M) regimen (99 patients). The median observation time was 59 months (range 33-84). Response to therapy was obtained in 45% of the MP group and 31% of the M group (P less than 0.05). No significant difference in response with regard to clinical stage was noted. Median survival was 36 months in the MP group and 29 months in the M group. Survival was longer in stage I and II myeloma than in the stage III cases, at least in the MP group. The median and 5-yr survival rates in stages I and II were significantly better in the MP than in the M group. Response to therapy was associated with length of survival, median survival being 62 months in responding patients and 20 months in non-responders. The MP and M groups did not differ in this respect.
Insulin release is influenced by the autonomic nervous system. In the periphery the regulation occurs via both alpha-adrenergic and beta-adrenergic receptors. The parasympathetic nervous system is important in the central regulation of insulin secretion. Nevertheless, adrenergic mechanisms are also concerned. This review discusses the mechanisms for the adrenergic regulation of insulin release and some clinical conditions where these mechanisms are concerned.
Metabolic effects of physical exercise in type I diabetes are reviewed. Physical training leads to an increased insulin sensitivity but does not seem to influence the metabolic control. However, the metabolic control is of importance for the exercise results. Patients in a good control do not differ from normal individuals concerning working capacity, recovery after hypoglycemia and hormonal balance. Furthermore, abnormalities in the blood glucose homeostasis during exercise in type I diabetes are discussed as well as potential beneficial effects of physical training in the prevention of cardiovascular disease.
The effects of delayed cutaneous hypersensitivity (DCH) testing (Multitest, Institute Mérieux) on lymphocyte counts and functions were studied in seven healthy women. All had normal DCH responses and lymphocyte functions. No influence of the DCH testing on subsequent tests for lymphocyte subpopulations and mitogen- and antigen-induced DNA synthesis was observed. The PPD skin test did not boost or otherwise alter the in vitro lymphocyte response to PPD. It may be concluded that Multitest is a simple way of assessing DCH and that this test does not interfere with repeated in vitro tests of lymphocyte capacity.
Human neutrophils activated by phorbol myristate acetate were cytotoxic to ox erythrocytes, as determined by the 51Cr release method. Maximal cytolysis was obtained with a phorbol myristate acetate concentration of 5 ng/ml and with an effector to target cell ratio of 1:4. An intact neutrophil metabolic burst and production of oxygen-derived-free radicals were essential for the cytotoxic event, since neutrophils from patients with chronic granulomatous disease failed to exhibit any ox erythrocyte lysis. The target cell destruction was completely prevented by catalase, was unaffected by superoxide dismutase, and was reduced approximately to one-third by azide and cyanide. These data suggest that, under our experimental conditions, the ox erythrocyte killing by phorbol myristate acetate-activated neutrophils mainly depends on myeloperoxidase and hydrogen peroxide.
Blood and lymph node T-lymphocyte subpopulations have been studied in untreated non-Hodgkin lymphoma (NHL) patients and healthy controls. T-lymphocytes were determined by the E-rosette technique and by OKT3/LEU4 monoclonal antibodies; OKT4/LEU3 and OKT8/LEU2 monoclonal antibodies were used to identify T-cell subsets with helper/inducer and suppressor/cytotoxic activity, respectively. OKT4+ T-cells were low in patients, while OKT8+ T-cell numbers were normal. The OKT4+/OKT8+ blood lymphocyte ratio was below the normal range in about 50% of the patients. The ratio was higher in lymph nodes than in blood of patients and controls. The results may suggest that untreated NHL patients have a reduced pool of T-cells with phenotypic markers of OKT4/LEU3. Monoclonal blood B-lymphocytes were found in 45% of the cases. The presence of such cells in blood was frequently associated with a low OKT4+/OKT8+ ratio.
4 children with idiopathic thrombocytopenic purpura were treated with high dose i.v. IgG. Platelet associated immunoproteins were determined with an Elisa technique. Platelet counts increased in all patients, while simultaneously platelet associated IgG, IgA, IgM, C3 and C4 decreased. Serum antiplatelet antibody increased during treatment suggesting that administration of high doses of IgG interferes with the binding of antiplatelet antibody.