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Biomedical subjects

K Klemm

Publications and source records attributed to K Klemm.

At least 37 records · Page 2Linked to original sources
PubMed1992

(H+,K+)-ATPase inhibiting 2-[(2-pyridylmethyl)sulfinyl]benzimidazoles. 4. A novel series of dimethoxypyridyl-substituted inhibitors with enhanced selectivity. The selection of pantoprazole as a clinical candidate.

[(Pyridylmethyl)sulfinyl]benzimidazoles 1 (PSBs) are a class of highly potent antisecretory (H+,K+)-ATPase inhibitors which need to be activated by acid to form their active principle, the cyclic sulfenamide 4. Selective inhibitors of the (H+,K+)-ATPase in vivo give rise to the nonselective thiophile 4 solely at low pH, thus avoiding interaction with other thiol groups in the body. The propensity to undergo the acid-catalyzed transformation is dependent on the nucleophilic/electrophilic properties of the functional groups involved in the formation of 2 since this step is both rate-determining and pH-dependent. The aim of this study was to identify compounds with high (H+,K+)-ATPase inhibitory activity in stimulated gastric glands possessing acidic pH, but low reactivity (high chemical stability) at neutral pH as reflected by in vitro (Na+,K+)-ATPase inhibitory activity. The critical influence of substituents flanking the pyridine 4-methoxy substituent present in all derivatives was carefully studied. The introduction of a 3-methoxy group gave inhibitors possessing a combination of high potency, similar to omeprazole and lansoprazole, but increased stability. As a result of these studies, compound 1a (INN pantoprazole) was selected as a candidate drug and is currently undergoing phase III clinical studies.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1992

The use of gentamicin-PMMA chains in the treatment of infected tibial nonunion.

Local antibiotic therapy with gentamicin-PMMA chains and external fixation permit effective simultaneous therapy of both components of infected tibial pseudarthroses: sequestering osteomyelitis and pseudarthrosis. The local concentrations of gentamicin which can be achieved by implantation of gentamicin-PMMA chains are far above the MIC of most common pathogens. This form of local antibiotic therapy is superior to any form of systemic antibiotic therapy. The gentamicin-PMMA chains serve as well as space holders for the bone graft to promote bone consolidation in the absence of infection. The results can be improved by successful management of the soft tissue damage often associated with tibial pseudarthrosis. Pedicled or free muscle graft with microvascular anastomosis is the method of choice.

Drug Therapy, Combination↗
PubMed1990

[Intraoperative staining of tissues].

Possibilities of vital dyeing to determine blood supplied from non blood supplied tissues are subject of many years' investigations. They may play an important role in traumatology, reconstructive and septic surgery. In acute traumatic changes one of the methods known is the so called immediate surgical treatment with delayed operation. In chronic and septic pathological changes there exists a great difficulty distinguishing necrotic parts of bone or soft tissues, which are the cause of long lasting inflammation and external fistulas. This process can last for months or even years if not treated by a proper and precise surgical procedure. Very helpful may be vital dying of tissues which was introduced by K. Klemm in 1970 for the surgical treatment of septic bone necrosis using the Disulphine Blue, produced by Imperial Chemical Industries Limited, Pharmaceuticals, Division, Macclesfield Cheshire, G. B. The tissue dyes are used widely for subcutaneous injections in lymphography, i.e. in about 30,000 patients in USA yearly. Disulphine Blue is a water soluble and partly spirit soluble powder giving a blue solution, which can be sterilized in autoclave. After an intravenous application of 0.25-0.5 ml/kg body of 6.2% solution a green colour of skin and conjunctivas appears in 5 minutes. The dye can appear in bile, bronchial tree, feces and in intestine secretions. It is evacuated with urine. Green colour of the skin disappear after 36 hours in children and after 48 hours in adults. This dye has been used as a direct visual test to investigate normal blood-supplied and necrotic soft and bone tissues. This phenomenon can have a special significance for defining the vitality in inflammation of bone tissue, in burns and in necrosis of soft tissues a.a. of the Achilles tendon. A demonstrative case report. Patient K. J., 32 years old, a worker and sportsman was hospitalized in our clinic because of chronic inflammation and purulent fistulas 10 weeks after two operations in one of hospitals because of traumatic right Achilles tendon rupture. During the first operation the tendon was sutured and the leg immobilized for a period of 6 weeks. After that time the plaster dressing was removed and during the rehabilitation was stated a secondary Achilles tendon rupture. The tendon was resutured. The course after the operation was complicated with haematoma and purulent fistulas. Antibiotics were used but without effect. In our Clinic 10 weeks after the primary injury and unsuccessful local treatment we performed a subsequent operation after slow intravenous injection of 10 ml Disulphine Blue.(ABSTRACT TRUNCATED AT 400 WORDS)

Achilles Tendon↗
PubMed1987

[Closure of soft tissue defects in bone infections using free and pedicled muscle flaps].

Over the period of three years 33 free latissimus dorsi-flaps and 23 pedicled myoplasties of various types for the coverage of large tissue and bone defects are performed. The operative technique of the free muscle transfer with microvascular anastomosis are described in detail. The postoperative management is outlined. The results of the free and pedicled muscle flaps are reported. In free transplantations the success-rate was 88% and in pedicled flaps 65% There is good evidence that bone consolidation and healing of the chronic bone infection can be improved by healthy vital soft tissue coverage. The indications for both procedures and the advantages and disadvantages of free and pedicled flaps are discussed.

Adolescent↗
PubMed1986

[The social environment and consequences in patients with posttraumatic osteomyelitis].

As soon as the extent of damage--especially in infected nonunion with substantial bone defect--becomes clinically apparent, the patient should be fully informed about the possibilities of treatment, which functional result can be expected in an attempt to salvage the extremity and the implications of long-term hospitalization with the necessity for multiple operations on the patient's social and professional rehabilitation. The patient may then decide for himself that early amputation will give him much better chances in his future life.

Adaptation, Psychological↗
PubMed1986

[Treatment of chronic osteomyelitis with gentamicin PMMA chains].

In the treatment of chronic osteomyelitis radical removal of sequestrated bone fragments is of essential importance. Any antibiotic therapy - whether systemically or locally applied - can only be a supplementary measure. By implantation of gentamicin-PMMA-chains into infected cavities high local concentrations of the antibiotic can be achieved which are far above the minimal bactericidal concentrations of most common pathogens. As result of the very low concentrations of gentamicin in the serum and urine there is no hazard of nephrotoxicity and ototoxicity. Chronic sequestrating osteosyntheses and infected non-unions are the most important indications for the application of gentamicin-PMMA-chains.

Chronic Disease↗
PubMed1986

The sulphoxide moiety of substituted benzimidazoles is essential for inhibition of parietal cell K+/H+-ATPase.

The antisecretory action of the benzimidazole sulphoxide derivative B 823-10, 2[(4-methoxy-3-methyl-2-pyridylmethyl)-sulphinyl]- 5-trifluoromethyl(1H)-benzimidazole, was compared with the effect of the corresponding sulphide B 823-08 in several in vivo and in vitro and in vitro test systems. The sulphide B 823-08 and the sulphoxide B 823-10 were found to be equipotent in the Shay rat. The sulphide was found to inhibit H+ secretion in intact rabbit gastric glands and enriched guinea-pig parietal cells with lower potency than the corresponding sulphoxide. The relative potency in antisecretory activity (sulphide/sulphoxide) decreased in the following rank order: Shay rat: gastric glands: parietal cells. Purified K+/H+-ATPase was not blocked by the sulphide, whereas the sulphoxide inhibited the overall as well as the partial reactions of this enzyme. In all in vitro systems tested, inhibition of H+ secretion and enzyme activity by the sulphoxide, but not by the sulphide, was antagonized by SH-compounds such as dithiothreitol. It is concluded that in vivo sulphoxidation of the sulphide plays an important role in acid inhibition. In vitro an additional inhibitory mechanism of the sulphide has to be considered.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1986

The thiol-proteindisulfide-oxidoreductase--a new marker enzyme of monocytes from peripheral blood.

Monocytes were enumerated by three different methods, cytochemical staining for alpha-naphthyl-acetate esterase-activity, immunofluorescence test using the monoclonal antibody BL-M/G and immunochemical staining for the enzyme thiol-proteindisulfide-oxidoreductase (TPO, EC 1.8.4.2) using a polyclonal rabbit anti-rat TPO immunoglobulin. For the comparison of these methods mononuclear cells from peripheral blood of healthy volunteers, patients with different diseases and adherent cell populations were tested. Statistical analysis showed no differences between the markers within these groups (H-test) and a significant correlation between the numbers of monocytes. TPO was found to be also valid for enumeration of monocytes obtained by adherence methods.

Antibodies, Monoclonal↗
PubMed1985

[Isolation of monocytes by adherence to gelatin-layered surfaces].

The method for purification of monocytes using adherence to gelatin coated glass surfaces described by Chien et al. was optimized by drastic shortening the incubation time and modifying the culture media. After one adherence step we obtained monocytes with a purity of 73-78% and a recovery of 53%. Thiol-protein-disulfide-oxidoreductase (TPO), a new enzyme marker of monocytes, was found to be also valid for monocytes obtained by adherence methods. Comparing the number of TPO-containing monocytes with other markers (alpha-naphthylacetate esterase, peroxidase, phagocytosis of latex particles, acridine orange fluorescence, antigens detected by the monoclonal BL-M/G antibody) almost identical values were found.

Acridine Orange↗
PubMed1984

Dipeptidyl peptidase IV and alpha-naphthylacetate esterase in human T lymphocytes: cytochemical and biochemical investigations.

Dipeptidyl peptidase IV (DP IV) activity of human lymphocytes was measured using biochemical assays of cell suspensions and enzyme cytochemical staining of smears from capillary blood and mononuclear cells (MNC). The hydrolysis rate of Gly-Pro-pNA in suspensions of MNC correlates well with the number of DP IV reactive cells as determined by cytochemical staining. MNC from healthy volunteers were shown to contain 44 +/- 10% lymphocytes reactive for DP IV. Using preparations of T lymphocytes and adherent MNC it was shown that DP IV is specific for T lymphocytes. About 60% of T lymphocytes contain DP IV and 94% of DP IV reactive cells form rosettes with sheep erythrocytes. Parallel staining for DP IV and unspecific acid alpha-naphthylacetate esterase (ANAE) yielded nearly the same figure of cells stained for ANAE in a dot-like pattern (50 +/- 10% MNC) as was observed for DP IV. Correlation of both markers indicates that DP IV expressing lymphocytes presumably represent that subpopulation of TM cells which is characterized by a dot-like reaction pattern of ANAE.

Dipeptidyl Peptidase 4↗