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Biomedical subjects

K Federlin

Publications and source records attributed to K Federlin.

At least 19 recordsLinked to original sources
PubMed1992

Production of mitogen-contamination free alginates with variable ratios of mannuronic acid to guluronic acid by free flow electrophoresis.

Commercial alginates consisting of variable homopolymeric regions of beta-D-mannuronic acid and alpha-L-guluronic acid, interspaced with regions of alternating blocks, are potent stimulators of macrophages and lymphocytes. Therefore, inflammatory reactions and fibrotic overgrowth of the beads result if Langerhans islets are encapsulated in raw alginate hydrogel beads (cross-linked with divalent cations). The result is random failure of the islets some time after transplantation. Analysis of raw alginates by using free flow electrophoresis demonstrated that commercial alginates contained at least 10-20 fractions (characterized by different electrophoretic mobilities) which showed mitogenic activity. These fractions could be quantitatively separated from the alginic acids by free flow electrophoresis on a preparative scale. The purified alginates cross-linked with Ca2+ ions exhibited no mitogenic reactions as proved by an in vitro assay. In addition, examination of purified Ba2+ alginate beads implanted intraperitoneally in rats or mice for three weeks showed no fibrotic overgrowth in contrast to implants made from unpurified alginate.

Alginates↗
PubMed1992

Disappearance of a pituitary tumor after 15 months of treatment with CV 205-502, a new dopamine agonist.

We report the case of a 27-year-old woman with a prolactin-secreting macroadenoma of the pituitary gland who was under treatment with a new dopamine agonist, Sandoz CV 205-502. Immediately after diagnosis of a 12 x 10 mm intrasellar prolactinoma, treatment with CV 205-502 was begun at a daily dose of 0.075 mg. Under this low dose, prolactin in the serum normalized after 4 weeks, the initial hormone value being 189.9 ng/ml. After 6 months of therapy there was still a 6 x 6 mm tumor, and after 15 months of treatment the pathological process could no longer be observed with magnetic resonance imaging. In the 20th month of therapy the patient became pregnant. An ovulatory menstrual cycle had been present for a few months.

Adult↗
PubMed1992

Antibodies to the M(r) 64,000 (64K) protein in islet cell antibody positive non-diabetic individuals indicate high risk for impaired beta-cell function.

A prospective study of a normal childhood population identified 44 islet cell antibody positive individuals. These subjects were typed for HLA DR and DQ alleles and investigated for the presence of antibodies to the M(r) 64,000 (64K) islet cell antigen, complement-fixing islet cell antibodies and radiobinding insulin autoantibodies to determine their potency in detecting subjects with impaired Beta-cell function. At initial testing 64K antibodies were found in six of 44 islet cell antibody positive subjects (13.6%). The same sera were also positive for complement-fixing islet cell antibodies and five of them had insulin autoantibodies. During the follow-up at 18 months, islet cell antibodies remained detectable in 50% of the subjects studied. In all six cases who were originally positive, 64K antibodies were persistently detectable, whereas complement-fixing islet cell antibodies became negative in two of six and insulin autoantibodies in one of five individuals. HLA DR4 (p less than 0.005) and absence of asparic acid (Asp) at position 57 of the HLA DQ beta chain (p less than 0.05) were significantly increased in subjects with 64K antibodies compared with control subjects. Of 40 individuals tested in the intravenous glucose tolerance test, three had a first phase insulin response below the first percentile of normal control subjects. Two children developed Type 1 (insulin-dependent) diabetes mellitus after 18 and 26 months, respectively. Each of these subjects was non-Asp homozygous and had persistent islet cell and 64K antibodies.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Alginate coating of islets of Langerhans: in vitro studies on a new method for microencapsulation for immuno-isolated transplantation.

Immuno-isolated transplantation offers the attractive prospect of being able to transplant xenogeneic islets without immunosuppression. This study introduces a completely new method of coating single islets using a homogeneous alginate membrane approximately 10 microns thick. During glucose challenge (perifusion and static incubation) encapsulated islets show the same pattern and quantity of insulin release as non-encapsulated controls. This encapsulation method markedly reduces the amount of transplanted material by reducing the size of the capsule. It is suggested that encapsulated islets may be transplanted into sites such as the renal capsule or omentum or even by intraportal injection into the liver.

Alginates↗
PubMed1992

A comparative study of antigen expression by skin and pancreas in the prediabetic and diabetic state of the BB rat.

Type 1, insulin-dependent diabetes mellitus is an autoimmune disease with destruction of beta-cells in islets of Langerhans by activated (antigen-positive) infiltrating mononuclear cells accompanied by serological immune phenomena. The pathological mechanism has not yet been clarified in detail, and some inversion in the proportion of epidermal antigen expression has recently been described in spontaneous diabetes. The BB rat is one of the animal models most closely resembling human type 1 diabetes of autoimmune origin. We compared the class I and class II antigen expression in the islets of Langerhans and in the skin of spontaneously diabetic (BBD) and normoglycaemic (BBND) BB rats in the prediabetic, diabetic and non-diabetic states. Class I and class II antigen expression increased significantly in the islets of BBD rats from prediabetes to diabetes and compared with non-diabetic controls. In the same period, the dermal antigen expression (class I and class II) did not decrease and was not lower in BBD than in BBND animals. These results do not support a loss of activated (antigen-positive) dermal cells at the onset of diabetes in the BB rat and do not show a clear correlation with the antigen expression in infiltrated islets of Langerhans.

Aging↗
PubMed1992

Prevention of recurrent autoimmune diabetes in the BB rat by islet transplantation under the renal capsule.

Pancreatic islet grafts transplanted into subjects with spontaneous autoimmune diabetes are threatened by two immune responses, allograft rejection and the recurrence of autoimmune insulitis. To examine the recurrent autoimmune response to transplanted islets it is necessary to exclude islet allograft rejection. The BB rat is a unique model of spontaneous diabetes with clinical and pathological characteristics identical or similar to those found in human insulin dependent diabetes mellitus (IDDM). In this study we demonstrate permanent acceptance of histocompatible islet grafts in chemically induced diabetes and a lack of intracolony tissue antigen rejection in our BB rat colony. Therefore the vigorous destruction of transplanted BB islets in the liver of spontaneously diabetic BB rats is due to recurrence of diabetes. This recurrence can be prevented by transplantation of islets under the renal capsule. This may be important for clinical application in IDDM, particularly with regard to host and donor tissue matching.

Animals↗
PubMed1992

Imbalance of CD4+ lymphocyte subsets in patients with mixed connective tissue disease.

CD4+ (helper/inducer) T lymphocyte subsets were studied in the peripheral blood from patients with mixed connective tissue disease (MCTD) by double-labelling immunofluorescence. The proportion of CD4+CD45RA+ cells was higher (P less than 0.01) when compared with controls, whereas CD4+CD29+ cells were markedly diminished (P less than 0.001). CD4+CD29+ cells were lower than in patients with progressive systemic sclerosis who were studied in parallel. Upon stimulation with phytohaemagglutinin, CD4+ cells from MCTD patients showed a strong reactivity to acquire the CD29+ phenotype. Expression of high levels of CD29 and other adhesion molecules might lead to facilitated localization of CD4+ cells to inflamed tissue. It is suggested that an increased responsiveness of CD4+ cells to activation signals in vivo and accumulation of CD4+CD29+ cells at tissue sites could result in depletion of this cell subset in the peripheral blood of patients with MCTD.

Adult↗
PubMed1992

Mexiletine in the treatment of diabetic neuropathy.

OBJECTIVE: To prove the efficacy of mexiletine in painful diabetic neuropathy. RESEARCH DESIGN AND METHODS: Treatment was provided in three dosages. For pain measurements, a VAS and McGill's verbal rating scale were chosen. Ninety-five patients were included in the study. RESULTS: A global assessment of the VAS among patients showed no differences between mexiletine treatment and placebo. The total evaluation (PRIT) of the McGill scale fell just below the level of significance. More specific exploratory evaluations of subclasses of the McGill scale, representing different degrees of pain, gave remarkable differences between mexiletine and placebo in sensory and miscellaneous items. In special subgroups, which were formed according to types and courses of complaints compiled at the beginning of this evaluation, the substantial advantages of the mexiletine treatment were shown with both the VAS and the McGill scale. CONCLUSIONS: Evidence strongly indicates that, in particular, those patients with stabbing or burning pain, heat sensations, or formication will benefit most by mexiletine therapy. Concerning the dosage, a medium regimen of 450 mg/day seems to be appropriate. With an increase in the antiarryhthmic dosage level, the efficacy does not rise proportionally. Mexiletine proved to be a safe therapy with negligible side effects at the medium dose range, even less than placebo; and remarkably, no cardiovascular side effects were noted. Further studies should avoid global assessments and pay more attention to the variety of complaints and quality of life.

Adult↗
PubMed1992

Impairment of polymorphonuclear leukocyte function and metabolic control of diabetes.

OBJECTIVE: In this study, ingestion of Staphylococcus aureus and "bacteria killing" (BK) were measured to evaluate polymorphonuclear leukocyte (PMN) phagocytic functions and chemiluminescence response (CL) to phorbol-myristic acetate (PMA) as respiratory burst activity with regard to metabolic control parameters in diabetic patients. RESEARCH DESIGN AND METHODS: PMN phagocytic functions were assessed in 40 diabetic patients, all receiving insulin and in poor metabolic control, with 3H-thymidine-labeled Staphylococcus aureus in a modified radiometric assay. Bacteria killing was determined by pure-plate counting of surviving bacteria (colony-forming units [cfu]) and luminol-enhanced CL in response to PMA as a measure of respiratory burst. PMN function data were correlated to HbA1 as parameter of recent metabolic control. RESULTS: PMN of diabetic patients showed a significant reduction in Staphylococcus aureus (50.7 +/- 4.1%) and BK (29.4 +/- 4.2%) compared with healthy nondiabetic control subjects (76.6 +/- 4.6% and 16.3 +/- 3.1%, respectively, P less than 0.001), and PMN CL response was markedly reduced in diabetic patients also. Linear regression analysis showed a highly significant negative correlation of HbA1 versus Staphylococcus aureus (r = -0.67, P = 0.001) and a positive correlation for BK (r = 0.73, P less than 0.001). This was also true for CL, although this did not reach statistical significance (P = 0.06). CONCLUSIONS: The data obtained demonstrate impaired PMN phagocytic functions and CL response in diabetic patients. These findings suggest inhibitory effects of elevated glucose concentrations on PMNs, a possible role of protein glycosylation for impairing PMN function, thus contributing in part to altered host defense.

Adult↗
PubMed1992

[Expression of low-affinity Fc epsilon receptors on circulating monocytes in patients with inflammatory rheumatic diseases].

In patients with scleroderma, high proportions of circulating CD23+ monocytes could be detected by FACS analysis as compared with controls. Supernatants obtained from lymphocytes yielded high amounts of interleukin-4-(IL-4-)like activity. The results suggest that IL-4 contributes to monocyte activation in scleroderma. There were no correlations with serum IgE, or numbers of naive and memory-CD4+ lymphocytes.

Antigens, Differentiation, B-Lymphocyte↗
PubMed1992

Surgery, dopamine agonist therapy of combined treatment--results in prolactinoma patients after a 12 month follow-up.

In a non-randomized retrospective study n = 36 prolactinoma patients (n = 7 micro- and n = 29 macroadenomas) were evaluated before (E0), 4 (E1) and 52 weeks (E2) after applying 3 different treatment modalities: A dopamine agonist (DA) therapy (n = 14), B surgery as initial procedure (n = 12) and oral DA therapy, C DA preinjection, subsequent surgery (n = 10) and oral DA medication. T0 outline the effect of the 3 regimens upon serum prolactin (PRL) and tumour size reduction, clinical signs and symptoms, anterior/posterior pituitary lobe function and MRI/CT findings were evaluated in each patient at E0, E1 and E2. In group A, PRL normalization was achieved in n = 10 patients (71%), although the frequency of an empty sella was only one out of 12 macroprolactinoma patients (less than 10%). Patients of group C showed the lowest PRLE2 levels (32 +/- 11 ng/ml, normalization rate 60%), although not statistically significant when compared with the other groups (A: 41 +/- 28 ng/ml, B: 114 +/- 33 ng/ml, normalization rate 31%). According to MRI studies in groups B and C total removal was achieved in 33% and 50% of macroprolactinomas, respectively. The most favourable ratio of the leading pre/posttreatment signs and symptoms was observed in patients of group C. It was concluded that no superiority of either treatment regimen exists for prolactinoma patients. Each mode of therapy has its own benefits which may be applied to the different biological behaviour of a prolactinoma in the respective patient.

Adolescent↗
PubMed1992

Islet transplantation: clinical and experimental.

Experimental diabetes in rodents has been successfully treated by implantation of isolated islets using a syngenic system (Lewis rats). It is possible to reverse all diabetic symptoms of the animals and to prevent late complications in kidney, eye and nervous system. Although isolated islets are highly immunogenic in an allogenic system immuno-alteration techniques have been developed and succeeded in longterm survival after culture at low temperature (24 degrees C), UV-irradiation, cryopreservation, pretreatment with Ia-antibodies etc. Islet transplantation in larger animals and in man up to now has been less successful. Although in a few studies longterm survival of canine islets has been observed, other groups were less successful using dogs and pigs in auto- or allo-transplantation. In man there are reports from various institutions during the last fifteen years using adult or fetal islet material. Only in a few instances the patients came off insulin for some weeks or months. The reasons for this failure are probably manifold: low number of islets, impurity, long ischemia time before isolation, transplantation to inappropriate sites, impairment of engraftment in longterm diabetic recipients and recurrence of autoimmunity in transplanted islets. Further studies are necessary to overcome these barriers. Recent observations using a higher number of islets (> 500,000) and new immunosuppressive drugs (FK506) seem to be promising.

Animals↗
PubMed1992

[Impaired induction of chemiluminescence and function of polymorphonuclear neutrophilic granulocytes in diabetes mellitus].

The aim of this study was to investigate PMN-chemiluminescence response as a measure of respiratory burst activity and the phagocytic PMN function "ingestion" with regard to metabolic control parameters in diabetes mellitus (d.m.) in comparison to healthy controls. Our findings demonstrated a significant reduction of chemiluminescence response and ingestion in diabetic patients compared to controls (p less than 0.01 resp.); further an inverse relation of metabolic control parameters in d.m. and PMN impairment, suggesting inhibitory effects on PMN function, thus leading or contributing at least in part to altered host defense.

Diabetes Mellitus↗
PubMed1992

[Reduced phagocytic capacity of circulating granulocytes in diabetes mellitus].

Impaired PMN function is regarded as a major cause for infectious complications in diabetes mellitus (d.m.). The aim of this study was to investigate the phagocytic PMN functions "ingestion" (IN) and "bacterial killing" (BK) with regard to metabolic control parameters and influences of variable glucose concentrations on these PMN functions in vitro. Our findings demonstrated a significant reduction of IN and BK in diabetic subjects compared to controls (p less than 0.001 resp.). The differences between type I and type II d.m. did not reach statistical significance. Linear regression analysis showed significantly negative correlations for fasting blood-glucose concentrations as well as glycosylated hemoglobin (HbA1) and IN (r = -0.34, p 0.03; r = -0.67, p = 0.001) and a highly positive for BK (r = 0.73, p = 0.0001). In vitro there was a significant decrease in IN and BK both in diabetic subjects and controls for glucose concentrations greater than 27.7 mmol/l (p = 0.01 resp.). These data clearly demonstrated impaired PMN ingestion and bacterial killing in diabetic patients, and the degree of PMN dysfunction is inversely related to the degree of metabolic control of diabetes. These findings suggest inhibitory effects of hyperglycemia on PMN functions, thus contributing at least partly to altered host defense in diabetes mellitus.

Blood Bactericidal Activity↗
PubMed1992

[Circulating CD8 as an indicator of inflammatory rheumatic disease].

An enzyme-linked immunoassay detecting soluble CD8 (s-CD8) was applied to study activation of CD8(+)-(suppressor/cytotoxic) T-cells in patients with rheumatic diseases. Compared with normals, s-CD8 levels were elevated in patients with rheumatoid arthritis, ankylosing spondylitis, and polymyositis. In contrast, low s-CD8 values were observed in patients with progressive systemic sclerosis/scleroderma. In systemic lupus erythematosus (SLE), s-CD8 values were correlated with C-reactive protein. This finding and an association with other parameters of clinical activity were confirmed by longitudinal studies. In summary, our findings support the view that implication of CD8(+)-T-cell activation is different in the pathogenesis of each rheumatic disease. Elevated s-CD8 indicates active disease, and can be used to monitor CD8(+)-T-cell activation in SLE while determination of s-CD8 seems to be of little clinical value in the other rheumatic diseases studied.

Adult↗