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Biomedical subjects

K M Goebel

Publications and source records attributed to K M Goebel.

At least 37 records · Page 2Linked to original sources

Effect of intra-articular orgotein versus a corticosteroid on rheumatoid arthritis of the knees.

The effects of intra-articular injections of orgotein (4 mg a week for six weeks) and of methylprednisolone acetate (4 mg a week for six weeks) on the knee joints were compared in a random long-term trial. Twenty-eight patients with active, definitive rheumatoid arthritis were studied by double-blind comparison. The first control examination made after six weeks of therapy showed no differences between the joints treated with orgotein or with steroid. However, at the final control examination after 24 weeks, a disparity between both drug regimens became apparent. Clinical response was evaluated in the knees in terms of cumulative rheumatoid activity index based on morning stiffness, range of flexion, pain scores, and 25-foot walking time. After 24 weeks, orgotein was found to be superior to steroid in the major points of the clinical assessment index but equipotent in marked improvement of the rheumatoid activity index after six weeks of treatment. After intrasynovial orgotein injections, synovial fluid enzyme activity fell significantly, concurrently with reduced prostaglandin E2 formation. Synovial fluid leukocyte counts also decreased, but the percentage of polymorphonuclear cells increased simultaneously only in the orgotein-treated group. The results suggest that patients with rheumatoid arthritis of the knee joints who show good response to orgotein during a short course of treatment are likely to continue their positive response and possibly attain increased relief of symptoms over longer periods of treatment, in contrast to those patients receiving steroids.

Adult↗

Biorheological and metabolic dysfunctions of density-fractionated erythrocytes in diabetics with peripheral vascular disease.

Preliminary communications are presented about a serial study of biorheological and metabolic dysfunctions of density-fractionated erythrocytes (RBC) in diabetics with vaso-occlusive disorders. The study aimed at evaluating the influence of metabolic disorder due to diabetes mellitus on RBC substrates, deformability and glycohaemoglobin (HbA1) levels. The peak HbA1 level served to confirm the duration of serum metabolic disorder due to diabetic crisis. The rheological and metabolic changes of RBC were compared with serial estimations repeated on the same patients when asymptomatic concerning diabetes after insulin therapy. RBC deformability was measured optoelectronically by microcomputer-assisted polymicroviscometry (filtrometry) following separation of RBC into old (dense) and young (buoyant) fractions by means of density-layer centrifugation. 15 adult patients with diabetes mellitus typ II associated with macroangiopathy Fontaine II underwent RBC investigations before and after diabetic therapy. Those RBC fractions containing older cells disclosed an impaired metabolism, increased HbA1 levels and markedly altered deformability which significantly differed from values obtained from young RBC. But after insulin-therapy old RBC fractions only revealed persistently an increase of HbA1 levels and metabolic disorder associated with a still altered deformability, in contrast to young RBC which in again showed normal values. The preliminary results suggest an adaptable alteration of RBC metabolism and function in diabetes, predominantly existing in old RBC, but after insulin-therapy still persisting only in old (dense) fractions. Thus, a prolonged pathologic effect of older RBC occurred in diabetes probably resulting in a further persistent maintenance of diabetic vascular disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

[Comparative double blind trial of pirprofen, indomethacin, and placebo in the treatment of rheumatoid arthritis].

One hundred and thirty-four out-patients suffering from active rheumatoid arthritis were treated for 2 weeks by 1200 mg of Pirprofen (400 mg t.i.d.) 150 mg of Indomethacin (50 mg t.i.d.) or a placebo. On all criteria, the anti-inflammatories were more effective than the placebo (p less than 0.05). The overall therapeutic efficacy was satisfactory in 87% of patients on Pirprofen, 77% on Indomethacin and 26% on placebo.

Adult↗

[Rheology, metabolism and oxygen transport in old and young erythrocytes in arterial occlusive disease].

Red blood cell (RBC) rheological and metabolic functions were studied in 10 diabetics with peripheral vascular disease (PAD) following separation of RBC according to cell age by density layer centrifugation. Decreased levels of ADP, ATP, 2,3-DPG and GSH were observed in dense layers of RBC containing older cell fractions. Further, raised lactate/pyruvate ratios were obtained from the same RBC fractions. O2-function was markedly impaired in all patients with PAD. Thus, metabolic disorder of RBC associated with reduced red cell deformity by retarding blood flow through the microcirculation may be important factors in states of peripheral vascular insufficiency in diabetics.

Arterial Occlusive Diseases↗

Intrasynovial orgotein therapy in rheumatoid arthritis.

30 patients with active classical rheumatoid arthritis affecting the knee took part in a 12-week double-blind trial in which intra-articular injections of orgotein (4 mg/week for 6 weeks) were compared with intra-articular aspirin 4 mg/week for 6 weeks. After 12 weeks clinical and biochemical assessments showed that orgotein was superior to aspirin. Clinical response was measured in terms of the cumulative rheumatoid activity index (RAI) which was based on scores for morning stiffness, range of flexion, pain and 25-foot (7.5 m) walking time. Treatment with orgotein resulted in significant improvement of the RAI; the improvement correlated with findings on knee-joint scanning which showed reduced mean uptake of 99mTc-pyrophosphate. After intra-articular orgotein injections, synovial fluid IgM and IgG rheumatoid factor levels fell significantly; so did prostaglandin E2 formation and lactate dehydrogenase activity. The changes in the synovial fluid suggest that the anti-inflammatory properties of orgotein may lie in its effect on proliferating synovia.

Anti-Inflammatory Agents↗

Neuromyopathy and vitamin E deficiency in man.

A 12-year-old boy, born of a consanguineous marriage, had ataxia, sensory neuropathy, generalized muscle hypotrophy and a lower serum vitamin E level. Two of his relatives had died of a clinically similar disorder in their late adolescence. Morphologically, his striated muscle fibers and Schwann cells of his sural nerve contained numerous autofluorescent acid phosphatase-positive lipopigments which, by electron microscopy, consisted of a finely granular matrix surrounded by a trilaminar membrane. These lysosomal lipopigments were similar to those observed in muscle fibers of a patient afflicted with abeta-lipoproteinemia. They probably represent the morphological sequelae of long-standing vitamin E deficiency in this child, the extract origin of which has not been fully elucidated.

Child↗

Erythrocyte membrane fluidity, lipid peroxidation and lysis in alcoholic liver disease.

The still unexplained occurrence of hemolytic anemia in cases of alcoholic liver disease prompted us to study the toxic effect of ethanol on the membrane and metabolic properties of erythrocytes (RBC) in chronic alcoholics (n = 7). Raised susceptibility of RBC to hydrogen peroxide with significantly increased fluidity of membrane lipids were obtained signaling an oxidative metabolic stress. A twofold reduction of ATP and GSH initiated an oxidation of cellular sulfhydryl groups thus impairing enzyme kinetics of pyruvate kinase (PK). Yet heat stability of PK was markedly reduced only in those fractions containing older RBC. Further results indicate that ethanol-induced acquired PK instability may be triggered by a dialyzable and hence non-protein-bound compound, not detectable by experimental procedures owing to its low molecular weight. Thus it is conceivable that the hemolytic implication of ethanol in alcoholic liver disease may be due to abnormal membrane fluidity and metabolic disorder finally involving PK-control mechanism.

Adenine Nucleotides↗

[Disorders of erythropoiesis in alcoholic ketoacidosis in patients with chronic liver diseases].

To evaluate the toxic effect of ethanol on erythropoiesis in alcoholic ketoacidosis (AK), 6 male patients were studied in the acute and remittent phase of AK. Episodes of metabolic acidosis in nondiabetic chronic alcoholics were associated with protracted vomiting and prolonged intestinal symptoms. AK was associated with elevated beta-hydroxybutyrate, acetoacetate and lactate/pyruvate plasma levels. Analysis of plasma lipids showed raised HDL cholesterol, fatty acids and phospholipids resulting in a concomitant disorder of lipid metabolism in red cell ghosts. A red cell metabolic disorder with reduced ATP and glutathione levels was also observed in patients suffering from mild hemolytic anemia. On admission, miscellaneous toxic effects on erythropoiesis were detected when bone marrow was aspirated. This study lends further support to the hypothesis that there is a linkage of different factors producing serious but transient hematologic and oncologic implications of ethanol in patients with AK.

Acidosis↗

Long-term treatment of hyperlipoproteinemia with etofibrate: clinical observations.

We investigated the changes in serum lipid concentrations of patients treated with Etofibrate as part of their routine management in the metabolic ambulatory care unit of the Medical Policlinic at the University of Marburg. In our study, 26 patients who had not responded well to prior treatment for Types IIa, IIb, III and IV hyperlipoproteinemia were given a daily dose of 900 mg Etofibrate for up to 48 months. As a result to this treatment, serum total cholesterol levels fell by up to 17,6% and triglyceride levels by up to 47,8%. We observed no tachyphylaxis toward Etofibrate. The results of standard laboratory parameters measured in parallel with drug treatment reflect a good tolerance for Etofibrate. This substance is highly suited as a potent lipid-lowering agent.

Adult↗

[Current aspects of rheumatoid arthritis].

According to recent investigations two factors might play an essential role in the pathogenesis of rheumatoid arthritis (R.A.). Besides genetic components, i.e. the HLA-system and familial aggregation, the immune processes, mediating tissue inflammation and injury, are acknowledged as having established roles in the pathogenesis of R.A. The present report reemphasizes recent data concerning the autoimmunity and the immunologic network with trends of therapy in R.A. In view of the effectiveness of new nonsteroidal antiinflammatory drugs, a double-blind study of suxibuzon vs. indomethacin in 30 patients with active R.A. is described in detail. Both drugs were active and similar in their efficacy at 4 weeks as judged by clinical and laboratory measurements. No serious toxic side-effects were observed in both treatment regimens.

Administration, Oral↗

[Red cell metabolism and function in shock (author's transl)].

In patients with shock the metabolism and O2-function of the erythrocytes were studied following separation according to cell-age by density layer centrifugation using a new supporting medium. Metabolic acidosis in patients with postoperative shock (n=8) and in patients with shock due to severe congestive heart failure (n=12) provoked decreased levels of 2,3-diphosphoglycerate, ADP, ATP and reduced glutathione. Raised lactate/pyruvate ratios were observed also in both groups, whereas the O2-function of the erythrocytes was markedly disturbed in all patients. Patients of both groups received glucocorticoid-infusions resulting in a significant improvement of the extent and pattern of the red cell metabolic disorder.

Adult↗

[Inherited hemolytic anemia due to pyruvate kinase deficiency: II. Density-layer centrifugation of erythrocytes (author's transl)].

Heterogeneous clinical features of inherited hemolytic anemia due to pyruvate kinase (PK) deficiency were observed in three related homozygous patients. Erythrocytes were separated into old and young cells by means of density-layer centrifugation using a new supporting medium: Stractan-Urografin gradients. Those fractions containing older RBC disclosed defective PK which resulted in an impaired metabolism. Following an intake of chloramphenicol the clinical course of one female family member converted to acute monocytic leukemia. Thus, the report of a PK instability trait, in one family member associated with pancytopenia which converted in leukemia, suggests that inherited red cell enzyme deficiency might be also an expression of the vulnerability of the hematopoietic stem cells.

Adult↗

[Glucocorticoid-induced effect of erythropoietin in haemolytic anaemia with uraemia and red cell enzyme deficiency (author's transl)].

The effect of 6-methylprednisolone (GCC) was studied on erythropoietin (ESF) levels and on the metabolic functions of erythrocytes (RBC). GCC (U mg/kg/day for 15 days) was administered to 6 patients with the haemolytic-uraemic syndrome (group B) and to 6 patients with non-spherocytic haemolytic anaemia due to hereditary pyruvate kinase enzyme deficiency (group C). 6 healthy persons served as control (group A). The metabolic functions of RBC were investigated by assaying HMPS activity, GSH/GSSG and lactate/pyruvate ratios, relevant glycolytic intermediates, 2,3-DPG, ATP, and key enzymes. A significant increase in ESF was observed in group B patients after GCC therapy, correlating with an improvement in the haemolytic state, and consequent rectification of the secondary disturbances of RBC metabolism. Group C patients already had raised ESF levels before GCC therapy; no further increase occured in response to treatment and no other clinical or haematological change was recorded. Hence, no harmonal influence of GCC on the disturbed RBC metabolic process was detectable in the cases.

Adult↗