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Biomedical subjects

K Federlin

Publications and source records attributed to K Federlin.

At least 127 records · Page 7Linked to original sources
PubMed1993

Osteoporosis and bone metabolic parameters in dependence upon calcium intake through milk and milk products.

The bone mineral content of young adults as well as of osteoporotic patients and age-matched controls without bone disease was measured by single-photon absorptiometry. A retrospective nutrition survey was additionally made to study the relationship between bone mineral content and calcium intake in different periods of life. The bone mineral content and bone mineral density of young adults is directly related to the calcium intake through milk and dairy products. The osteoporotics had a significantly lower bone mineral content than the controls. Calcium intake through milk and milk products in childhood and adolescence had been significantly lower in the patients than in the controls, whereas in the later periods of life (20-30 years prior to the study and at the time of the study) there were no significant differences between the calcium intakes of the two groups. It was also found that an adequate intake of calcium protected against increased bone resorption, as evidenced in particular by the reduced levels of serum osteocalcin, a parameter of bone turnover. In conclusion it can be stated that the data support the hypothesis that adequate calcium intake through milk and milk products in childhood and adolescence is a decisive marker for obtaining a maximum bone mass (peak adult bone mass) and for the prevention of osteoporosis. Furthermore, it can be stated that increased calcium intake in the later years may not reduce the accelerated risk of osteoporosis resulting from inadequate calcium intake during childhood and adolescence.

Absorptiometry, Photon↗
PubMed1993

[Increased activation of CD8-positive lymphocytes in patients with Crohn's disease].

CD8+ (suppressor/cytotoxic) T lymphocyte subpopulations were studied in the peripheral blood of patients with Crohn's disease by flow cytometry analysis. Consistent with earlier reports, increased numbers of CD8+CD57+ cells were observed as compared with controls. However, expanded CD8+CD57+ cells were not found to be present in a distinct clinical subset of patients. A substantial number of patients had enhanced numbers of DR+ and CD45RO CD8+ cells. In addition, high numbers of CD8+ cells which were CD57CD45RO double positive, and a correlation between numbers of CD8+CD57+ and CD8+DR+ lymphocytes were detected. By use of an enzyme immunoassay, significantly elevated levels of soluble CD8 antigen were demonstrated in patients' sera, and results were associated with ESR values. Taken together, the data suggest increased activation of CD8+ lymphocytes which might result from systemic disease activity. Disturbances within CD8+ lymphocytes do not seem to be specific to Crohn's disease since similar alterations could be observed in patients with another inflammatory condition, rheumatoid arthritis.

Adolescent↗
PubMed1993

[Impaired function of polymorphonuclear neutrophilic granulocytes in rheumatoid arthritis].

The aim of this study was to investigate the PMN functions ingestion (I), bacterial killing (BK) as well as the chemiluminescence response to phorbol esters (PMACL) as a measure of PMN respiratory burst activity in RA compared to osteoarthritis and controls. Our findings demonstrated a significant reduction of I and BK in RA compared to OA and controls (p < 0.01 resp.) but an enhanced PMACL (p < 0.01). There was no significant difference of I, BK and PMACL in OA and control subjects. These data clearly demonstrated impaired PMN ingestion and bacterial killing yet enhanced PMACL in RA, thus contributing at least in part to altered host defense in these patients.

Arthritis, Rheumatoid↗
PubMed1993

Transplantation of free and microencapsulated islets in rats: evidence for the requirement of an increased islet mass for transplantation into the peritoneal site.

Microencapsulation of islets of Langerhans may avoid the necessity of a permanent immunosuppressive drug therapy and opens up new perspectives for xenotransplantation in the treatment of insulin dependent diabetes. In a mouse model we recently showed long-term normoglycemia after microencapsulated xenotransplantation. Since the acceptance of mice to any kind of foreign material is quite high we assume that the rat model better reflects the situation of higher mammalians or even humans. Due to the volume of the transplanted material (i.e. islets+alginate-capsule) only the peritoneal cavity can be used up to now. The quantity of islets necessary to normalize the non-fasting blood glucose level was much higher than expected and free transplants needed even a higher amount of islets than encapsulated ones (3000 encapsulated vs. 2 x 3000 non-encapsulated). Transplantation beneath the kidney capsule was successful with only 1200-1500 islets per rat proving the metabolic potency of the islets. Implantation of empty capsules did not alter the diabetic state. We conclude that the alginate matrix may act as a "spacer" creating a distance between the consuments of a lacking substrate esp. oxygen in an unfavourable environment and perhaps protect it from unspecific mediators released during the postoperative period. Our findings underline the necessity for smaller capsules that would enable us to use other transplantation sites.

Animals↗
PubMed1993

Islet transplantation inhibits diabetic retinopathy in the sucrose-fed diabetic Cohen rat.

PURPOSE: To study the effect of islet transplantation on the development of diabetic retinopathy in the sucrose-fed diabetic Cohen rat, a useful experimental model of accelerated microvascular disease. METHODS: Syngeneic transplantation of collagenase-ficoll isolated islets by intraportal injection was performed either after 6 weeks or after 12 weeks of diabetes, i.e., before or after the first morphologic retinal changes, respectively. Retinal digest preparations were examined using quantitative morphologic parameters. RESULTS: After 26 weeks of diabetes, characteristic features of background retinopathy such as a 5% increase in capillary endothelial cells, a 27% pericyte dropout, acellular occluded vessels and, occasionally, microaneurysms developed in untreated animals. Islet transplantation performed after 6 weeks of diabetes completely prevented endothelial cell proliferation and diminished pericyte loss (2950 +/- 140 vs 2390 +/- 40 in diabetic controls, P < 0.01). A significant increase in acellular occluded capillaries persisted (31 +/- 14 vs 8 +/- 2 in NC; P < 0.01). Islet transplantation after 12 weeks of diabetes, i.e., after established pericyte loss, only partially restored capillary cell composition and did not prevent retinal vessel occlusion. These findings indicate that the beneficial effect of islet transplantation on diabetic retinopathy is limited to a time very early in the evolution of this process. CONCLUSIONS: These data suggest that irreversible changes induced by antecedent hyperglycemia play a central role in the progressive development of diabetic retinopathy.

Animals↗
PubMed1993

[Use of intravenous immunoglobulins for immunomodulating therapy of inflammatory rheumatic diseases].

The use of immunosuppressive and long-acting antirheumatic drugs in the treatment of rheumatic diseases is often limited by their side effects. Therefore, it is urgent to search for drugs which are better tolerated and which are at least as effective. Several studies have been performed using intravenously administered immunoglobulins in rheumatoid arthritis patients and in small groups of patients suffering from other connective tissue diseases. The results demonstrate a rapid onset of clinical improvement in patients who respond to this treatment. The tolerance has been excellent so far. This therapy is immunomodulating, since it induces changes in B- and T-lymphocyte function, especially in immunoregulatory T-cell subpopulations. Future work should focus on the establishment of treatment schedules and on the definition of patient subgroups which might benefit most from intravenous immunoglobulin therapy.

Arthritis, Rheumatoid↗
PubMed1993

[Diagnosis and therapy of diabetic polyneuropathy].

Distinction is made between peripheral and autonomic neuropathy. The former is usually painful, while the latter is especially associated with cardiovascular, gastrointestinal and urogenital disturbances. In the diagnosis of peripheral neuropathy, a basic neurological examination (reflex status, vibratory sense) takes precedence over measuring the velocity of nerve conduction and determining the temperature and pain thresholds. The diagnostic approach to the autonomic disturbances is organ-specific (testing of cardiovascular reflexes, sonographic and scintigraphic determination of gastric emptying, infusion urography and uroflowmetry). Early diagnosis and optimal diabetes control are the therapeutic consequences. Symptomatic treatment includes the administration of analgesics, antidepressants and carbamazepine. A newer drug being currently tried is mexiletine. High doses of alpha-liponic acid as well as the fat-soluble B vitamins are used for causal therapy. Clinical trials with aldose reductase inhibitors and gamma-linolenic acid are under way.

Autonomic Nervous System↗
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↗