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Biomedical subjects

G Holm

Publications and source records attributed to G Holm.

At least 181 records · Page 10Linked to original sources
PubMed1983

Renal degradation of insulin in patients with renal hypertension.

Renal processing of insulin was studied over plasma insulin levels of 5-80 mU/l by renal vein catheterization in 14 patients. Kidneys of patients with a normal GFR removed around 30% of the insulin from arterial plasma. In 6 patients having unilateral renal artery stenosis but only moderately impaired renal blood flow and unchanged PAH-extraction, a higher or unchanged fractional insulin extraction was seen in all but one, compared with the contralateral kidney. Due to the high fractional extraction of insulin by the kidneys with renal artery stenosis, a preserved total insulin uptake by these kidneys was seen. In 4 patients with renal hypoplasia (2 of them had renal artery stenosis) low values for insulin extraction and insulin uptake were seen on the affected side. One patient with chronic pyelonephritis and uremia had an extremely low renal insulin extraction and uptake. The results suggest that estimation of renal insulin extraction may be an important renal functional test in renovascular patients.

Adult↗
PubMed1983

Mitogen induced blood lymphocyte DNA synthesis as a prognostic indicator in patients with non-Hodgkin's lymphomas in clinical remission.

Monocyte depleted blood lymphocytes were analyzed in 28 patients with non-Hodgkin's lymphoma in early unmaintained complete clinical remission, in 8 long-term complete remission patients, and in 31 age-matched healthy controls, by SRBC rosetting and DNA synthesis induced by concanavalin A, pokeweed mitogen and PPD antigen. The median observation time from testing was 22 months (range 10-49 months). Early complete remission patients with a normal mitogen induced lymphocyte stimulation remained free of relapses. In contrast, patients who relapsed during the observation period had lymphocytopenia (p less than 0.05), reduced lymphocyte responses to mitogen (p less than 0.001) and to PPD antigen (p less than 0.05) as compared with healthy controls. Long-term complete remission patients did not differ from healthy controls with respect to lymphocyte counts and response to mitogen stimulation.

Adult↗
PubMed1983

Neutrophil-mediated antibody-dependent cellular cytotoxicity against erythrocytes. Mechanisms of target cell destruction.

Human neutrophils were cytotoxic to IgG coated ox erythrocytes as determined by a 51Cr release assay. Target cell phagocytosis was found to take place during the cytotoxic reaction, suggesting that cytolysis occurs as a post-phagocytic event. Studies, performed with neutrophils from patients with chronic granulomatous disease, demonstrated that these cells had an impaired cytotoxic activity, despite their ability to normally ingest target cells. Thus the cytotoxicity of human neutrophils against sensitized ox erythrocytes depends mainly on oxidative mechanisms. Oxygen radical scavengers failed to prevent the target cell lysis, possibly because of their inability to gain access into the killing sites. However, when cytotoxicity was carried out in presence of latex particles, pre-incubated with oxygen radical scavengers, a significant inhibition of target cell lysis by superoxide dismutase and cytochrome c was obtained. As well, in these experimental conditions, catalase had no effect. Furthermore, cytotoxicity was unaffected by hemeprotein inhibitors, cyanide and azide. Together, these results indicate that superoxide anion plays a key role in the neutrophil-mediated cytotoxicity against ox erythrocytes, whereas hydrogen peroxide alone or in combination with myeloperoxidase is unoperative under the experimental conditions employed.

Animals↗
PubMed1983

Platelet associated immunoglobulins and complement in idiopathic thrombocytopenic purpura.

A double antibody sandwich enzyme linked immunosorbent assay (ELISA) was applied to quantitate platelet associated (PA) immunoglobulins G, A and M and complement factors C3c and C4. Fifteen patients with acute and 29 patients with chronic idiopathic thrombocytopenic purpura (ITP) were studied as well as 35 normal controls. Forty-three out of 44 (98%) patients had elevated platelet associated immunoglobulins. PAIgG was elevated in 95%, PAIgA in 82% and PAIgM in 74% of the patients. PAC3 was increased in 86% and PAC4 in 57% of the patients. There was strong correlation between PAC3 and PAIgG but not between PAC4 and PAIgG in acute ITP. In chronic ITP, however, PAC4 correlated strongly and even better than PAC3 with PAIgG. This strengthens the conjecture that the pathogenesis of ITP in many acute cases differs from that of chronic ITP.

Adult↗
PubMed1983

Lymphocyte counts and functions in arterial and venous splenic blood of patients with Hodgkin's disease. Evidence for elimination of spontaneously DNA synthesizing cells in the spleen.

Lymphocyte counts and functional competence of lymphocytes from arterial and venous splenic blood were studied in six patients with Hodgkin's disease subjected to splenectomy. One patient was untreated, four were tested after mantle field treatment and a sixth patient had a splenic relapse after total nodal radiotherapy. The percentage of E binding cells in splenic venous blood was lower than that of arterial blood though no significant differences were found in total lymphocyte or E binding cell counts. The spontaneous lymphocyte DNA synthesis was lower in venous than in arterial splenic lymphocytes in all patients. Pokeweed mitogen (PWM)-induced DNA synthesis was much lower in lymphocytes from splenic venous blood than in those from arterial blood in two patients and marginally decreased in another two. The pattern of concanavalin A response was similar to that of PWM. The elimination of lymphocytes over the spleen could not be related to the presence of lymphocytotoxic serum factors or to splenic weight or histologically verified tumour involvement. The results support the notion that some facets of the blood lymphocyte abnormalities in Hodgkin's disease may be explained by removal of functionally active lymphocyte subpopulations in the spleen. It is also concluded that spontaneously activated lymphoid cells are detained in the spleen.

Adult↗
PubMed1982

Lymphocytotoxic serum factors and lymphocyte functions in untreated Hodgkin's disease.

The prevalence of complement dependent, cold-reactive lymphocytotoxic serum factors (LT) was studied in 80 untreated patients with Hodgkin's disease by a microcytotoxicity assay. Sera from 24 patients (30%) contained LT as judged from at least 50% lysis of lymphocytes from 16 to 23 randomly selected normal donors. The spontaneous incorporation of 14C-thymidine into blood lymphocytes from patients with LT was significantly higher than that of lymphocytes from LT-negative patients and from healthy controls. Total lymphocyte and T-cell counts, Concanavalin A, and pokeweed mitogen-induced lymphocyte DNA synthesis were lower in patients with LT. Lymphocytotoxic sera were more frequently encountered in patients with B symptoms, advanced disease, or nodular sclerosis/lymphocyte predominance histopathologic characteristics. LT were often found in patients with large and tumor-involved spleens. The ability of patient's serum to inhibit control lymphocyte response to Concanavalin A stimulation did not differ between LT-positive and LT-negative patients. We conclude that the presence of LT is associated with a quantitative and qualitative impairment of blood T-lymphocytes in untreated patients with Hodgkin's disease.

Adolescent↗
PubMed1982

Cyclic autoimmune hemolytic anemia as a presenting manifestation of splenic Hodgkin's disease.

The case report of a 52-year-old woman with an eight-year history of cyclic autoimmune hemolytic anemia and progressive splenic enlargement is presented. At laparotomy the enlarged spleen and splenic hilar lymph nodes showed lymphocyte-predominant Hodgkin's disease. No specific antitumor treatment was given and three years following splenectomy the patient is in excellent health and has not experienced any new hemolytic episodes. The patient illustrates the association between Hodgkin's disease and autoimmune hemolytic anemia as well as the extreme variation in the clinical picture of the disease.

Anemia, Hemolytic, Autoimmune↗
PubMed1982

Prednimustine and vincristine compared with cytosine arabinoside and thioguanine for treatment of elderly patients with acute nonlymphoblastic leukemia.

Sixty-seven patients with acute nonlymphoblastic leukemia (ANLL) and above the age of 60 years were randomly allocated to treatment with either prednimustine + vincristine or cycles with cytosine arabinoside and thioguanine. Of the 67 patients, 13 (19%) entered a complete remission and four a partial remission. Of 33 patients randomized to prednimustine and vincristine (15 adequately treated), three entered a complete remission and one a partial remission. Four further patients went into complete remission after a switch to other treatment modalities. Of 34 patients randomized to cycles of ARA-C and thioguanine (22 adequately treated), four entered a complete remission and three a partial remission with the correct program. One patient entered a remission with intermittent cytosine arabinoside + thioguanine (wrong program) and one further patient entered a complete remission after a switch to prednimustine and vincristine. Prednimustine + vincristine did not appear to be superior to treatment with cytosine arabinoside thioguanine cycles for elderly patients with ANLL.

Acute Disease↗
PubMed1982

Effect of a modified guar gum preparation on glucose and lipid levels in diabetics and healthy volunteers.

Six healthy volunteers and 17 diabetics (6 insulin-dependent and 11 diet- and tablet-treated) were treated with a special processed, palatable guar gum (10 g b.i.d. immediately before meals) for periods of one or three weeks or, in some cases, up to 13 weeks. A standardized test meal was given to study the effect of the fiber on postprandial glucose levels. Ten g guar was stirred in water and taken immediately before the test meal. The postprandial blood glucose levels were similar in the healthy volunteers but significantly lower in the diabetics following treatment with guar for one and three weeks, respectively. Furthermore, the fasting blood glucose levels were significantly lower in the diabetics after three, but not one, weeks of treatment. The lower postprandial glucose levels were coupled with attenuated and delayed insulin levels in accordance with an effect of guar gum on the rate of carbohydrate absorption. The cholesterol levels were on average reduced with 14% in the diabetics following three weeks' treatment with guar. The higher the initial cholesterol level, the greater the reduction in cholesterol; 26% reduction was achieved in four patients with initial levels above 7 mM. The alpha-lipoprotein cholesterol levels were not significantly changed, thus an increase in the alpha-lipoprotein cholesterol/total serum cholesterol ratio was obtained. Neither plasma triglycerides nor body weights altered during treatment. The reported side-effects were as expected and were usually mild and transient (e.g. increased flatulence). The data show that guar gum also reduces postprandial glucose levels on a long-term basis and may improve the diabetic control. Additionally, treatment with this fiber leads to a concentration-dependent decrease in cholesterol levels.

Adult↗
PubMed1982

Effect of physical training on insulin uptake by the perfused rat liver.

Hepatic uptake of insulin by the in situ perfused rat liver has been measured in rats subjected for 9 wk to physical training (T rats) on a treadmill. Three sedentary groups, one food-restricted (FR) to have the same weight as T rats, one freely-eating (FE), and one sucrose-fed (SF) were also studied. Each liver was cyclically perfused for 30 min with three different insulin concentrations in the medium (approximately 80, approximately 500, and approximately 2000 microunits/ml). Plasma insulin concentrations in T rats were 50 and 17, in FR 55 and 20, in FE 71 and 30 and in SF 84 and 42 microunits/ml in portal and peripheral venous plasma, respectively. Insulin decay curves followed first order kinetics. Taking FE rats as controls physical training enhanced hepatic clearance (expressed in ml/g/min) by 37%-60% whereas sucrose feeding reduced it by 15%-31% during the three perfusion periods. Food restriction in the FR rats caused only minor changes. Similar results were obtained with respect to hepatic extraction ratio and insulin removal. There was a significant negative correlation between portal insulin concentration and hepatic clearance rate. The results indicate that the hepatic extraction of insulin depends on portal insulin concentration. The mean net insulin uptake of the liver was similar in the groups, utilizing portal insulin concentrations and the hepatic clearance rate for calculations. As previously shown, the low peripheral plasma insulin levels after physical training are due mainly to a decreased insulin secretion from the pancreas. This is thus magnified by the efficient trapping of insulin in the liver.

Animals↗
PubMed1982

Lymphocyte function in untreated Hodgkin's disease: an important predictor of prognosis.

One hundred and twenty seven consecutive and previously untreated patients with Hodgkin's disease (HD) (mean age 47 years) from the Stockholm area admitted to Radiumhemmet, Karolinska Hospital, were studied. The age-matched control group consisted of 167 healthy adults. Incorporation of [14C]-dT was measured on Day 1 in unstimulated monocyte-depleted lymphocyte cultures, and on Day 3 in cultures activated by PWM, ConA and PPD, T and B cells were enumerated by surface markers. The patients had significantly decreased relative and total T-cell counts, and the lymphocyte DNA synthesis induced by mitogens and PPD was severely impaired, whilst the spontaneous DNA synthesis was significantly greater than in controls. At follow-up (mean 4 years) 40 patients have died. Deceased patients showed greater spontaneous lymphocyte activation and less response to mitogen and antigen stimulation than the survivors. The 5-year survival of patients with severe lymphocyte impairment was 20%, compared to 80% for the remainder. The lymphocyte tests added prognostic information to that from clinical staging. Disregarding the lack of knowledge of the mechanisms underlying the lymphocyte impairment, we suggest that these relatively simple immunological tests should be included in the clinical evaluation of HD patients and would guide the choice of therapy.

Adolescent↗
PubMed1982

In vitro production of monoclonal and polyclonal immunoglobulins by peripheral blood mononuclear cells in human plasma cell myeloma.

The in vitro monoclonal and polyclonal immunoglobulin (Ig) production of peripheral blood mononuclear cells was studied in human multiple myeloma (four IgG myelomas, one IgA myeloma) and in one patient with benign monoclonal gammopathy. Using an enzyme-linked immunosorbent assay with anti-class-specific antisera and antisera against idiotypic structures on the myeloma protein, it was possible to quantitate separately monoclonal and polyclonal Ig of the same class in cell culture supernatants. After stimulation with pokeweed mitogen (PWM) patients' cells produced lower amounts of polyclonal Ig than cells from healthy adults. In contrast, production of monoclonal Ig could not be enhanced by PWM. Moreover, the kinetics of monoclonal Ig production was different from that of polyclonal Ig. Myeloma cells contained large amounts of monoclonal Ig while their content of polyclonal Ig was low. A rapid release of preformed monoclonal Ig during the first day of culture was not inhibited by puromycin. A later phase of release was partly suppressed by puromycin and was probably caused by active protein synthesis.

Adult↗
PubMed1982

T cells in monoclonal gammopathies.

Subpopulations of human T lymphocytes were analysed by monoclonal antibodies (OKT3, OKT4, OKT8) in healthy controls and in patients with multiple myeloma (MM), Waldenström's macroglobulinemia (WM) and benign monoclonal gammopathy (BMG). Lymphocytes forming rosettes with SRBC correlated well with T cells staining in indirect immunofluorescence by OKT3 monoclonal antibodies. The relative and absolute numbers of OKT4+ T cells were significantly lower in patients than in controls. Though, the percentage of OKT8+ T cells was increased in patients, the total OKT8+ cell counts were normal in all patient groups. The ratio between OKT4+ and OKT8+ lymphocytes was low in the groups of treated MM and of WM patients compared to controls (P less than 0.001). Moreover, the ratio was lower than the normal range in 27% of BMG and 38% of untreated MM patients. The imbalance between OKT4+ and OKT8+ T cells in untreated MM was more pronounced in clinical stage III patients than in stage I and II patients. The most pronounced changes were noted in treated MM patients. The significance of the altered T cell subsets in monoclonal gammopathies with regard to polyclonal and tumor B cell regulation remains to be established.

Adult↗
PubMed1982

Blood T-lymphocyte functions in healthy adults in relation to age.

Blood T-lymphocyte functions were studied in 167 healthy adults (age range 19-91 years). Lymphocyte DNA synthesis induced by concanavalin A, pokeweed mitogen and PPD antigen declined with age while the spontaneous DNA synthesis remained essentially unchanged. Relative and total T-cell counts but not total lymphocyte counts were moderately decreased in elderly persons. The lymphocyte response to mitogens correlated with the PPD-induced activation in vitro. Lymphocyte and T-cell counts did not show any association with the response to mitogens and antigen. A few subjects were tested on several occasions during 2-7 years confirming a good reproducibility of the techniques employed. Thus ageing is associated with diminished number of T-cells and impairment of lymphocyte activation by T-cell mitogens and PPD antigen. The clinical importance of this general age-related T-cell deficiency remains largely unresolved.

Adult↗
PubMed1982

Insulin sensitivity and glucose uptake in the course of surgical treatment for valvular aortic stenosis.

The dose-response relationship between plasma insulin and systemic glucose uptake was studied before, one hour after and 6 months after valvular surgery in 11 patients with valvular aortic stenosis. The immediate effect of valvular surgery was a dramatic rightward shift of the dose-response curve and a decrease in glucose uptake at peak insulin activity. From a comparison between the preoperative and the 6-month postoperative dose-response curves it is concluded that the patients had adapted metabolically to the preoperative haemodynamic situation with increased insulin sensitivity.

Aortic Valve Stenosis↗
PubMed1982

Effect of valvular aortic stenosis on insulin sensitivity.

18 patients with valvular aortic stenosis were given an i.v. glucose tolerance test and an i.v. insulin tolerance test before and 4-36 months after valve replacement. Insulin and C-peptide response to the glucose challenge was smaller preoperatively whereas the glucose response was the same pre- and postoperatively. The effect on blood glucose of the i.v. insulin challenge was more pronounced preoperatively. It is concluded that insulin sensitivity was increased preoperatively and it is suggested that this was a metabolic adaptation to the haemodynamic situation in aortic stenosis, which may have implications for preoperative glucose-insulin-potassium treatment.

Aged↗