Biomedical subjects
W Kullich
Publications and source records attributed to W Kullich.
[Circulating immune complexes and complement fragment iC3b in chronic polyarthritis during 12 months therapy with oral enzymes in comparison with oral gold].
In the course of a double-blind randomized study lasting 1 year 19 patients suffering from ensured rheumatoid arthritis (ARA criteria) were treated with oral hydrolytic enzymes or oral gold salts. The effects of these therapies were examined in regard to changes in serum concentrations of circulating immune complexes (CIC) and the complement component iC3b. After 12 months treatment with oral enzymes we determined a therapeutically wanted significant decrease of CIC whereas CIC increased up to 6 months. The best but not significant result under therapy with oral gold salts concerning CIC was a decrease in 6 out of 9 patients after 9 months. The complement component iC3b diminished with either therapy during the first 6 months and increased afterwards. As well as the reduction of circulating immune complexes, the intensified inactivation of C3b into iC3b during the second half-year with both treatments indicates that there might be a slight improvement of the pathologically changed immunoreactions after 6 months only. Concerning the examined laboratory parameters, no significant difference was found between both therapies.
[Changes in the serum pepsinogen level during therapy with acemtacin retard as a measure of gastroduodenal tolerance].
Early indications of the development of gastroduodenal lesions can be obtained with the radioimmunological determination of pepsinogen I in serum. The influence of the non-steroidal anti-inflammatory drug Acemetacin in depot form on the course of the pepsinogen levels in serum was examined during 14 day therapy. Mean and median of pepsinogen I in the whole group of 26 patients did not increase significantly. Likewise no increases of the single pepsinogen levels in serum were seen in 85%. Only 4 patients showed increases of about 20 to 27% compared with the initial values. These results indicate that Acemetacin with prolonged action is well tolerated and has only mean influence on the integrity of the mucosa.
Influence of lornoxicam on serum pepsinogen levels.
Serum pepsinogen I was determined radioimmunologically in 18 patients suffering from lumbar backache syndromes. These patients were then treated with lornoxicam 4 mg twice daily over a period of 2 weeks. No significant increase in the serum pepsinogen I level was found in 17 (94.4%) of cases. Using the serum pepsinogen I as a parameter for the integrity of the gastric mucosa, this suggests good gastric tolerance of lornoxicam.
Elevated procollagen-III-peptide in myositis ossificans progressiva.
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[Changes in uric acid and blood lipids in patients with asymptomatic hyperuricemia treated with diet therapy in a rehabilitation procedure].
More than 300 patients with asymptomatic hyperuricaemia had been included in lipometabolic analysis performed before and after 4 weeks of a special low-cholesterol, low-triglyceride and low-purine dietetic regimen. Remarkable in almost the entire hyperuricaemic population (96.7%) had been the presence of serum cholesterol levels of more than 200 mg/dl. Lipoprotein analysis showed that 87% of the patients had increased LDL- and 69% increased VLDL-levels; HDL-levels were pathologically lowered to below 40mg/dl in 41% of the group. After a four-week rehabilitation programme, all lipometabolic parameters and serum urate concentrations were found to have been significantly reduced by the special diet. The results therefore are impressive proof of the major health benefits of purposive nutritional behaviour.
[Sports and coronary heart disease].
The effectivity of an endurance physical training must not be ignored any longer as it is known that physical activity as well in the job as in the leisure time diminishes the risk of coronary artery disease and their consequences. The training should be put through according to the vigorous exercise training with 70 to 80% of the maximal work load in a dynamic work continuously for at least 10 minutes. The optimum duration appears to be about 30 to 40 minutes a day, repeated 3 to 4 times weekly. The best sports for coronary patients are jogging, cycling or bicycle ergometry, country cross skiing, walking in the mountains as well as at diminished performance capacity, gymnastic, walking, golf and with some restrictions swimming.
[Hyperlipoproteinemia in primary gout and asymptomatic hyperuricemia].
More than 800 patients suffering from primary gout or asymptomatic hyperuricemia were examined for the values of total cholesterol and triglycerides and the pattern of lipoproteins. The values for HDL (high-density-lipoprotein = alpha-lipoprotein), LDL (low-density-lipoprotein = beta-lipoprotein) and VLDL (very-low-density-lipoprotein = pre-beta-lipoprotein), found in lipid electrophoresis, were significant abnormal as well in the group of patients with gout (n = 147) as in the group of patients with asymptomatic hyperuricemia (n = 700) versus the healthy controls. It was remarkable, that the values of lipoproteins in asymptomatic hyperuricemia almost were abnormal just as often as in primary gout. Approximately 80% of both groups showed an increased LDL, around 35% a decreased HDL, and an increased VLDL was found in 72% of patients with gout and in 54% of asymptomatic hyperuricemia. Pathological changes of all lipoproteins (HDL, LDL and VLDL) appeared in 23% of patients with gout and in 20% of patients with asymptomatic hyperuricemia. Only 2.7% of patients with gout and 4.8% with hyperuricemia showed a normal lipometabolism.
[Assessment of the genotoxic risk caused by the gyrase inhibitor ofloxacin using sister chromatid exchange rate analysis].
Ofloxacin (Tarivid) is a 4-quinolone of the latest generation. Its mechanism of action is the inhibition of the enzyme gyrase which plays a central role in the bacterial DNA-metabolisms. Thus Ofloxacin blocks the reading of the chromosomes and impairs the cell's function and ability to reduplicate leading to eradication of the pathogens. The genotoxicity of Ofloxacin was assessed by analyses of SCE (sister-chromatid-exchange-rates), which is a sensitive and qualitative parameter indicating chromosomal damages. In vitro no change of the SCE-frequencies could be demonstrated in human lymphocytes; in vivo, however, a slight influence not be excluded, which is also true for eventual additive on synergistic effect with other mutagenic factors.
Investigations of the influence of nonsteroidal antirheumatic drugs on the rates of sister-chromatid exchange.
For detection of possible damage to genetic material due to nonsteroidal antirheumatic drugs, a technique was used to determine sister-chromatid exchange rates. The SCE rates before and after therapeutic application of several nonsteroidal antirheumatic drugs (diclofenac, flurbiprofen, ibuprofen, indomethacin, isoxicam, ketoprofen, piroxicam, pirprofen, tiaprofenic acid) were determined in human lymphocytes in vivo. The cytogenetic investigations of these nonsteroidal antirheumatic agents did not reveal any genetic effects during a treatment period of two weeks.
Nuclear medical determination of left ventricular diastolic function in coronary heart disease.
In 64 patients with coronary heart disease, the left ventricular diastolic function was determined by means of a new nuclear medical method (nuclear stethoscope). The investigations revealed an abnormal diastolic filling in 85.9% of the cases on the basis of the parameters peak filling rate and time to peak filling rate as manifestation of a disturbed ventricular function.
[Blood levels and therapeutic effectiveness of piroxicam as affected by the time of administration].
The nonsteroidal antirheumatic preparation hydroxy-2-methyl-N-(2-pyridyl)-2H-1.2-benzothiazine-3-carboxamide 1,1-dioxide (piroxicam, Feldene) from the oxicam group is administered as a single dose of 20 mg/d. The question hence arose as to whether the therapeutic efficacy and the blood level curve (steady state) depend on the time of application. The investigation was carried out in 30 patients with arthroses of peripheral joints receiving the daily dose of piroxicam in the morning, at noon or in the evening. The results showed that irrespective of the time of administration the single dose of 20 mg/d led to a steady-state plasma level with the concentration required for efficacy. The result of therapy attained clinically also proved to be independent of the time of administration.
[Lipoprotein Lp(a) as a risk factor for heart infarct--a family study].
Lp(a) concentrations, apolipoprotein A-I and B, and various lipid parameters were measured from members of 3 families in which myocardial infarction frequently occurred. No correlation could be found between Lp(a) concentration and other lipoprotein parameters. It has been demonstrated that myocardial infarction and atherosclerotic diseases occur only in patients with Lp(a) concentrations higher than 70 mg/dl. An unfavourable Apo B/Apo A-I relation or LDL/HDL relation, associated with high Lp(a) concentration seems to play a decisive role in the development of atherosclerosis or myocardial infarction. The study suggests that subjects with Lp(a) values higher than 100 mg/dl could suffer from a special form of hyperlipoproteinemia ("Hyper-Lp(a)").
[Helicobacter pylori associated gastrointestinal mucosal lesions: is there an increased risk during therapy with nonsteroidal antirheumatic agents?].
ENDPOINTS: Are there connections between Helicobacter pylori-induced and NSAID-induced gastrointestinal mucosal lesions leading to an increased risk? Are there any diagnostic or therapeutic consequences? METHODS: Evaluation of H.P. infection, NSAID medication and mucosal lesions in 303 patients with rheumatic diseases. RESULTS: The prevalence of H.P. infection was 67.7%. Positive H.P. antibodies were found in 96.2% of patients with mucosal lesions, confirmed by endoscopy. There was no statistically significant increase of mucosal lesions in patients with both H.P.-infection and NSAID therapy. CONCLUSIONS: The main cause for gastrointestinal mucosal lesions is H.P. infection (> 90%). A general mucoprotective therapy in patients with H.P. infection and NSAID therapy cannot be supported. It may be supposed that a part of mucosal lesions connected to NSAID-therapy in recent decades probably was the consequence of H.P. infections. Eradication of H.P. might be of higher importance in the future.
Efficacy and tolerance of an oral enzyme combination in painful osteoarthritis of the hip. A double-blind, randomised study comparing oral enzymes with non-steroidal anti-inflammatory drugs.
OBJECTIVE: The objective of this study was to establish the non-inferiority of an oral enzyme therapy (Phlogenzym-(PE)) as compared to the non-steroidal anti-inflammatory drug (NSAID) diclofenac (DC) in patients with osteoarthritis (OA) of the hip. METHODS: Ninety patients presenting with painful episodes of OA of the hip were treated for 6 weeks in one study centre in a phase III, randomised, double blind, parallel group trial. Altogether, 45 patients were treated in the PE group and 45 patients were treated in the DC group. Primary efficacy criteria were: WOMAC dimensions pain, joint stiffness and function, and Lequesne index as multiple endpoint according to O'Brien. The efficacy criteria were analysed applying the test of non-inferiority with regard to mean changes and frequencies, t-test, U test, ANCOVA and descriptive methods. RESULTS: Within the 6 weeks observation period, the adjusted changes from baseline to endpoint of the target parameters worked out as follows (adjusted differences, mean +/- SEM): WOMAC subscale pain (PE -10.3 +/- 1.2, DC -9.5 +/- 1.2), WOMAC subscale joint stiffness (PE -3.9 +/- 0.5, DC -3.6 +/- 0.5), WOMAC subscale physical function (PE -31.7 +/- 3.5, DC -29.7 +/- 3.5), Lequesne's index (PE -2.89 +/- 0.47, DC -2.27 +/- 0.47). Non-inferiority of PE as compared to DC with regard to the O'Brien's global sum of the standardised adjusted changes from baseline to endpoint in pain, stiffness, physical function, and Lequesne's index was established with p = 0.0025. PE was simultaneously non-inferior as compared to DC with regard to the 4 single endpoints: WOMAC subscale pain (p = 0.0033), WOMAC subscale joint stiffness (p = 0.0061), WOMAC subscale physical function (p = 0.0039), Lequesne's index (p = 0.0008) (closed test procedure). The equivalence tests remained insignificant due to comparatively lower effects of DC. For 71.1% of the PE patients and for 61.4% of the DC patients rates of good or very good global investigator assessments of efficacy were calculated (test of non-inferiority: p = 0.0011). In the majority of patients, tolerability was judged in both drug groups as very good or good. CONCLUSION: This trial showed significant non-inferiority from 6 weeks treatment with PE in patients with OA of the hip with regard to the WOMAC dimensions pain, stiffness and physical function, to Lequesne's index, to the investigator and patients assessments of efficacy, and to the responder rates based on pain, physical function, and patient assessment of efficacy. With regard to drug tolerability some tendencies in favour of PE were detected. However, in this study there was no real difference between PE and DC 100 mg/day, implying an equal benefit-risk relation between the substances. PE may well be recommended for the treatment of patients with osteoarthritis of the hip with signs of inflammation as indicated by a high pain level.
[Value of pepsinogen I in serum as a screening method for early detection of gastroduodenal lesions and follow-up in therapy with non-steroidal antirheumatic drugs].
Gastroduodenal lesions of the mucosa are known to be the most frequent side effect during therapy with non-steroidal antiinflammatory drugs (NSAIDs). We investigated the radioimmunological determination of serum-pepsinogen I as an indicator for the quality of the gastroduodenal mucosa. A good correlation was found between the endoscopy findings of 78 patients and contemporary determinations of serum-pepsinogen. Further, a follow-up of pepsinogen I was made during the treatment of 107 patients with degenerative rheumatic diseases with eight different NSAIDs. The results recommend the determination of pepsinogen I as an indicator of gastroduodenal mucosal changes under therapy with NSAIDs; this determination gives a deciding factor for the gastrolesive potency of an NSAID.
[Cytogenetic studies of human lymphocytes under the influence of oxicams].
The influence of the oxicams, a special group of non-steroidal anti-inflammatory drugs, to the sister chromatid exchange (SCE) was determined on human lymphocytes in vitro and in vivo. The analysis of SCE is a sensitive parameter indicating chromosomal damage. The cytogenetic examinations of Lornoxicam, Tenoxicam, and Piroxicam in vitro showed no influence on the SCE frequencies in therapeutic dosages. With addition of mitomycin C (MMC) to the cultures (a method which simulates an additional genotoxic stress) we found significant higher SCE rates in connection with the oxicams than in controls without an oxicam. A 14-day treatment with Tenoxicam and Lornoxicam changed the spontaneous SCE rates in vivo; Piroxicam did not. The raised SCE levels could indicate an antimutagenic effect of the oxicams if the repair of DNA damages is transferred to a more perfect pathway; however by an overloading of the repair, due to additional genotoxic factors (such as cytostatics, cigarette smoking, x-ray exposure) therapy with oxicams could point out a genotoxic risk.
[Studies on the differentiation of chondrocytes in connection with poly ADP ribose synthesis].
Cell differentiation and the behaviour of poly-(ADP-ribose)-synthesis after treatment with methoxybenzamide and procaine was examined in chondrocytes of cell cultures from albino rats. In this study an increase in cell differentiation was connected with a higher level of poly(ADP-ribose)-synthesis. On the basis of an increase in poly(ADP-ribose)-synthesis in chondrocytes an improved scheme of treatment of some rheumatic diseases could be developed.