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Biomedical subjects

G Holm

Publications and source records attributed to G Holm.

At least 109 records · Page 6Linked to original sources

Increased blood clearance rate of indium-111 oxine-labeled autologous CD4+ blood cells in untreated patients with Hodgkin's disease.

Untreated patients with Hodgkin's disease (HD) have a blood T-lymphocytopenia mainly caused by a reduction of the CD4+ subset. Indirect support for a sequestration of T cells in the spleen and tumor-involved lymphoid tissue has accumulated. To test the hypothesis that the blood CD4 T-lymphocytopenia in patients with HD is caused by an altered lymphocyte traffic, 12 untreated HD patients and five in complete clinical remission (CCR) were studied. Blood lymphocytes were collected by leukapheresis and gradient centrifugation, and were further purified by an adherence step. The cells were labeled with indium-111 oxine and reinfused intravenously into the patient. The radioactivity of CD4+ and CD8+ blood lymphocytes separated by immunoabsorption was measured from serial blood samples. CD4+ cells were eliminated more rapidly in untreated patients than patients in CCR. Repeated gamma camera imaging after autotransfusion of indium-111 oxine labeled cells demonstrated an accumulation of radioactivity in tumor-involved tissue of untreated patients. These findings support the concept of an enhanced elimination of CD4+ cells in patients with active HD that may contribute to the observed blood T-lymphocytopenia and may reflect a biologic response to the tumor.

Adolescent↗

Increased muscle dynamic endurance associated with weight reduction on a very-low-calorie diet.

To assess muscle function after a period of negative energy balance, 32 obese women were placed on a 544-kcal/d, high-protein diet for 4 wk. Weight loss was associated with a decrease in the waist-to-hip-circumference ratio (WHR) and significantly higher emptying of abdominal than gluteal fat cells. The low-calorie regimen was associated with a significant increase in isokinetic muscle endurance, a decrease in glycogen concentration, and an increase in glycogen synthase (GS) activity and its fractional velocity (FV). The GS activity and its FV were negatively correlated with the WHR before treatment whereas their subsequent increase was correlated with the decrease in WHR. Dietary treatment produced a decrease in the isokinetic muscle strength, which was correlated with the reduction in lean body mass. The improvement in dynamic endurance observed after energy restriction parallels not only the increase in GS activity in muscle but also the decrease in glycogen stores and glucose oxidation, and most probably depends on the increased utilization of fatty acids.

Adipose Tissue↗

The incidence of cancer among blood donors.

This study presents data on cancer incidence among 37,795 blood donors in an attempt to test the hypothesis that blood donation might be associated with cancer development. At a median follow-up time of nine years (range 5-13 years) a total of 1152 cancer cases have been diagnosed. The expected number of cancer cases derived from an age-matched population was 1459 giving a relative risk ratio (RR) of 0.79 (p less than 0.001). Calculations were made with and without latency periods between first blood donation and the diagnosis of cancer (0, 5, 10, 15 years). Overall, significantly decreased cancer incidence was observed (p less than 0.001) though the number of observed cases of haematological malignancies was not significantly different from that expected. For polycythaemia vera, however, the O/E ratio was 1.81 possibly indicating an association with blood donation. A more likely explanation is that this reflects increased diagnosis of polycythaemia vera in the blood donor population.

Blood Donors↗

Increased insulin resistance and fat cell lipolysis in obese but not lean women with a high waist/hip ratio.

Increased lipolysis in abdominal adipocytes has been suggested to be of importance for the insulin resistance typical for abdominal obesity. In order to differentiate between fat distribution, measured as waist/hip ratio (WHR), and amount of body fat, glucose disposal during a euglycaemic clamp as well as lipolysis in isolated cells from abdominal and gluteo-femoral regions were studied in 20 obese and 20 lean postmenopausal women with a high (n = 10) and low (n = 10) WHR, respectively. The lipolytic response was increased in cells from obese women irrespective of region. Furthermore, lipolysis was enhanced in abdominal compared with the gluteo-femoral cells in obese women with a high WHR. Fasting blood glucose and insulin were increased in both groups of obese women while the degree of insulin resistance was most pronounced in the obese women with a high WHR. It is concluded that increased body fat is associated with both insulin resistance and increased lipolysis, and that this relationship is stronger in the presence of a high WHR. A high WHR may increase the expression of obesity as a risk for insulin resistance and this may be mediated through an increased lipolytic rate.

Adipose Tissue↗

A longitudinal study of class and subclass antibody response to pneumococcal vaccination in splenectomized individuals with special reference to patients with Hodgkin's disease.

Antibody class and subclass response to pneumococcal vaccination was monitored in 173 splenectomized individuals. The distribution according to indication for splenectomy was Hodgkin's disease (HD; n = 41), non-Hodgkin lymphoma (NHL; n = 25), autoimmune hemolytic anemia or idiopathic thrombocytopenic purpura (n = 17), accidental splenectomy during abdominal surgery for malignant (AMA; n = 15) and benign (ABE; n = 42) disease and splenectomy due to splenic rupture caused by trauma (TRAUMA; n = 33). Pre-vaccination total IgG pneumococcal antibody values (i.e. against the whole antigen = the vaccine) in the NHL patients were lower than in the ABE and TRAUMA groups (p less than 0.05). The response to vaccination in HD and NHL patients did not differ from that in the other patient groups. Furthermore, pre-vaccination values did not differ between HD patients vaccinated before splenectomy and treatment and those vaccinated after, although the former group showed a better response to vaccination (p less than 0.05). HD and TRAUMA patients were followed by serial serum sampling. The antibody values declined to pre-treatment levels after 3 years but no differences either between HD and TRAUMA patients or between HD patients vaccinated before or after splenectomy and treatment were observed with regard to antibody decrease. It is concluded that pneumococcal antibody levels increased in all splenectomized patient groups following vaccination. The pattern of the antibody decline motivates revaccination studies in patients 2 yr post-immunization.

Adult↗

Natural killer cell activity in monoclonal gammopathies: relation to disease activity.

Natural killer (NK) activity and NK-related cell surface markers (CD16, CD56, CD57) of peripheral blood lymphocytes were studied in patients with multiple myeloma and MGUS (monoclonal gammopathy of undetermined significance). A strong correlation (p less than 0.0001) was found between the numbers of cells positive for the different NK cell surface markers. The proportion of CD16+ cells correlated highly to the lytic capability (lytic units/10(6) cells) of K562 cells (p less than 0.0001). High NK activity and high numbers of cells with NK-related cell surface markers were found in patients with a low tumor burden compared to controls, whereas low values were seen in patients with an advanced disease. The results indicate that NK cells might be involved in the disease process in monoclonal gammopathies, perhaps by exerting a regulatory function on the proliferating B-cell clone.

Adult↗

Epidemiological study of Hodgkin's disease in Cuba and Sweden.

In this register study the epidemiologic features of Hodgkin's disease (HD) in Cuba and Sweden during 1964-1981 are compared. HD in the adult (greater than or equal to 15 years of age) is more common in Sweden than in Cuba (age-standardized incidence rate 3.6 X 10(5) vs. 3.1 X 10(5) but for childhood HD the opposite is true (2.1 X 10(5) vs. 3.0 X 10(5). In both countries a male predominance is found. A decrease in the incidence of HD is noted only in the Swedish population after 1973. The study reveals a stable bimodal age incidence pattern in Sweden but a shift from a linear increasing to a bimodal incidence pattern in Cuba, which parallels the Cuban development from an agricultural to an industrialized country.

Adolescent↗

Higher T-cell imbalance and growth factor receptor expression in B-cell chronic lymphocytic leukemia (B-CLL) as compared to monoclonal B-cell lymphocytosis of undetermined significance (B-MLUS).

The surface marker phenotype of lymphocytes derived from 12 patients with B-CLL was compared to that of lymphocytes from 10 patients with an other monoclonal but clinical benign form of B-cell proliferative disorder termed monoclonal B-cell lymphocytosis of undetermined significance (B-MLUS). A panel of well characterized monoclonal antibodies was used for the surface marker determinations. The mean total number of B cells (CD20) was 8.5 x 10(9)/1 in B-MLUS as compared to 44 x 10(9)/1 in B-CLL (p less than 0.001). B-CLL had a greater imbalance in T-cell subpopulations than B-MLUS and healthy controls. Total numbers of CD3+, CD8+ cells as well as cells expressing the NK-related antigens (CD16, Leu-7) and IL-2 receptor (CD25) bearing lymphocytes were statistically significant higher in B-CLL than in B-MLUS. Analyses of B-cell enriched populations showed that B-CLL represented B cells of an early maturation stage, whereas B cells from B-MLUS were more mature as judged by the loss of the CD21 surface marker. A larger fraction of B cells in B-CLL compared to B-MLUS exhibited a higher activation stage as revealed by the expression of the CD21, CD25 and CD35 structures as well as the FMC7 antigen.

Aged↗

Anti-idiotypic B-cell lines from a patient with monoclonal gammopathy of undetermined significance.

The B-cell repertoire in a patient with benign monoclonal gammopathy of unknown significance was studied using Epstein-Barr virus transformation of peripheral lymphocytes. The presence of anti-idiotypic B cells producing monoclonal antibodies that reacted with idiotypic determinants on the monoclonal immunoglobulin was verified. The two monoclonal anti-idiotypic antibodies studied were of the IgM-kappa type. Such anti-idiotypic antibodies may be part of an idiotypic network regulation of the monoclonal B-cell population.

Antibodies, Anti-Idiotypic↗

Characterization of acetylcholine receptor antibodies in a patient with primary biliary cirrhosis.

Antibodies against the acetylcholine receptor were found in a patient with primary biliary cirrhosis. The patient had no clinical or electrophysiological evidence of disturbed neuromuscular function. The antibodies were of both IgG and IgM isotype. Following passive transfer, these antibodies showed the same capacity to bind in vivo to mouse muscle receptors as immunoglobulins from patients with myasthenia gravis. The affinity of the antibodies was high and comparable to that found in myasthenia gravis patients.

Aged↗

Tumour imaging of indium-111 oxine-labelled autologous lymphocytes as a staging method in Hodgkin's disease.

Following indium-111 oxine-labelled autologous lymphocyte infusion, 39 lymphocyte scintigraphies were performed in 35 patients with Hodgkin's disease (HD). Lymphocytes were obtained after leukapheresis and Lymphoprep gradient centrifugation and were further purified by an adherence step to eliminate monocytes. A median of 1.2 (0.2-3.7) X 10(9) cells were labelled with 6.7 (range 1.9-16.6) Mbq indium-111 oxine and reinfused to the patients. Gamma camera imaging was performed with a GE 400 AT. An accumulation of radioactivity was seen at 54 of 61 sites with enlarged lymph nodes. Increased radioactivity was also seen at 16 sites with no previous clinical evidence of tumour involvement. These data seem very promising and with further methodological improvement lymphoscintigraphy may prove to be an important complement in the staging procedure and follow-up of patients with HD.

Adolescent↗

Type-specific anti-pneumococcal antibody subclass response to vaccination after splenectomy with special reference to lymphoma patients.

The IgG and IgA antibody subclass responses to pneumococcal polysaccharide antigens type 6A and 19F were studied after immunization with a 14-valent vaccine (Pneumovax, MSD), in 53 splenectomized patients (11 Hodgkin's disease, 13 nonHodgkin's lymphoma (NHL), 9 immune haemolytic anaemia or idiopathic thrombocytopenia purpura and 20 posttraumatic splenectomized patients) and 18 non-splenectomized controls. The antibodies were mainly restricted to the IgG2 and IgA2 subclasses. NHL patients had lower pre-vaccination values to the studied antigens and lower antibody response to vaccination than the other patient groups in which the antibody responses did not differ from those of controls. 1 vaccinated NHL patient experienced two episodes of pneumococcal septicaemia, both occurring after chemotherapy which abolished the previously normal IgG2 antibody levels to the pneumococcal antigens. It is concluded that the antibody response to 6A and 19F antigens after pneumococcal vaccination is not reduced in splenectomized patients but is impaired in immunodeficiency states associated with B-cell lymphoma and treatment with cytostatic drugs.

Adolescent↗

Clonal cell surface structures related to differentiation, activation and homing in B-cell chronic lymphocytic leukemia and monoclonal lymphocytosis of undetermined significance.

Cell surface structures related to differentiation, activation and "homing" were identified on the leukemic cell clone in blood of 64 patients with a monoclonal B-cell lymphoproliferative disorder. Patients were selected with regard to clinical signs and symptoms of the disease. 39 patients had progressive chronic lymphocytic leukemia of B-cell type (B-CLL): 16 with lymph node enlargement and 14 with progressive lymphocytosis as the most prominent symptom, respectively. 1 patient had an isolated splenomegaly and 8 had symptoms from enlarged lymph nodes, lymphocytosis and/or splenomegaly. 25 patients had an isolated monoclonal B-cell lymphocytosis in blood and bone-marrow but no other signs or symptoms of the disease. The lymphocytosis in these patients was considered to be of "undetermined significance" and the term B-cell lymphocytosis of undetermined significance (B-MLUS) was used. Patients with a prominent lymphadenopathy and/or splenomegaly had CD22+ leukemic cells while in patients with a progressive lymphocytosis the B-cell clone expressed Leu-8. Thus, CD22 might be related to the homing capacity of B lymphocytes for lymphnodes and spleen, while Leu-8 might define a circulating B-cell subset. In B-MLUS about 50% of the monoclonal B cells co-expressed Leu8 which is consistent with a more differentiated phenotype compared to B-CLL with progressive lymphocytosis. The CD22 expression was mostly low in B-MLUS although a few patients showed high values. The expression of receptors for growth factors (CD23, CD25, CD71) was higher in B-CLL compared to B-MLUS patients (p less than 0.001), which is consistent with a difference in lymphocyte activation stage and/or response to growth factors.

Aged↗

Effect of isoproterenol on the plasma C-peptide and insulin levels in humans.

There are conflicting reports on the effect of stimulation of the beta-adrenergic receptors on insulin removal by the liver. It was, therefore, the aim of the present study to clarify that problem. Four experiments have been carried out on a group of 8 healthy female volunteers: (1) isoproterenol was infused intravenously, (2) glucose was infused intravenously, (3) isoproterenol was infused with glucose, and (4) infusion of isoproterenol and glucose was preceded by administration of propranolol (the beta-adrenergic blocking agent). The concentration of C-peptide and insulin was determined in plasma from the antecubital vein. It has been found that stimulation of the beta-adrenergic receptors with isoproterenol reduces insulin removal by the human liver. This effect of isoproterenol is prevented by blockade of the beta-adrenergic receptors with propranolol.

Adrenergic beta-Agonists↗

Differences in blood T and NK cell populations between chronic lymphocytic leukemia of B cell type (B-CLL) and monoclonal B-lymphocytosis of undetermined significance (B-MLUS).

T and NK cell blood subpopulations were determined in 33 patients with B-CLL and in 14 patients with B-MLUS by two-color immunofluorescence. CLL patients had significantly higher total numbers of Leu-7+ and CD8+ cells and lower numbers of CD16+/Leu-7- cells as well as a higher Leu-7/CD16 ratio and a lower CD4/CD8 ratio than MLUS patients and control donors. Moreover, MLUS patients exhibited a significantly lower Leu-7/CD16 ratio as well as a higher frequency of CD16+/Leu-7- cells than healthy donors. These results suggest that B-CLL patients have higher numbers of circulating immature NK cells compared to B-MLUS, while B-MLUS patients have a larger proportion of NK cells with a high lytic capability as compared to both CLL and normal controls. The imbalance between CD4+ and CD8+ cells was prominent in CLL with a low CD4/CD8 ratio, but within the upper normal range in MLUS. Differences in immunoregulatory cell subpopulations between B-CLL and B-MLUS might therefore contribute to the different clinical behavior of these two disorders.

Adult↗

Effects of medetomidine in dogs with mitral regurgitation.

Thirteen small breed dogs with heart murmurs due to mitral regurgitation of varying severity received medetomidine as a sedative drug for teeth cleaning procedures. The dose was 30 micrograms/kg as an intramuscular injection. The drug caused a considerable reduction of the body temperatures and the heart rates over the 6 hrs of monitoring. The respiratory rates increased over the first 30 min and later decreased below control values. Systolic arterial blood pressures did not change significantly. Arterial oxygen tensions were significantly lower at 30 min after drug administration, but the arteriovenous oxygen differences and the carbon dioxide tensions changed very little. On electrocardiograms, sinus bradycardia, marked sinus arrhythmia with sinus pauses, AV-blocks 1st. and rarely 2nd. degree, supraventricular premature contractions (4 dogs) and paroxysmal tachycardia (1 dog) were observed. Echocardiograms showed an insignificant reduction of the shortening fraction and an increase of the left ventricular enlargement ratio as well as the left atrial to aortic root ratio at 30 min after drug administration. All measured parameters had returned to normal values (pre-drug levels) at 24 hrs after sedation. One dog had delayed cardiovascular complications at 3 hrs after drug administration, (period of prolonged asystole), necessitating the use of the antidote MPV 1248, which successfully reversed the abnormality. Two dogs collapsed briefly, at 4 and 5 hrs respectively, after excitement and struggling against physical restraint. In conclusion, medetomidine will have a safe clinical use for sedation of dogs with murmurs from compensated mitral regurgitation as soon as the antidote MPV 1248 (atipamezole) is licensed for clinical use. This will allow the reversion of the cardiopulmonary effects before the time of expected complications.

Adrenergic alpha-Agonists↗