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Biomedical subjects

K Klemm

Publications and source records attributed to K Klemm.

At least 19 recordsLinked to original sources

Primary structure differences of human surfactant-associated proteins isolated from normal and proteinosis lung.

The primary structures of human pulmonary surfactant-associated proteins SP-A, SP-B and SP-C isolated from lung lavage of patients with alveolar proteinosis exhibit significant differences from lung surfactant proteins isolated from lungs of healthy individuals. In contrast to SP-A from normal lungs, proteinosis SP-A was shown by SDS gel electrophoresis to contain large amounts of unreducibly cross-linked beta chains. Specific primary structure modifications of SP-C and SP-B proteins were established by direct molecular weight and structural analysis, using [252Cf]plasma desorption mass spectrometry (PD/MS) as the principal method. In comparison to normal lung surfactant SP-B, proteinosis SP-B showed a significantly increased molecular weight by approx. 500 Da for the unreduced protein dimer. SP-C proteins from normal lungs were identified to possess a bis-cysteinyl-5,6-(thioester)palmitoylated structure, and to contain a frayed N-terminus resulting in two sequences of 34 and 35 amino acid residues. In contrast, SP-C from proteinosis patients was modified by (i) partial or even complete removal of palmitate residues and (ii) additional N-terminal proteolytic degradation. These results indicate the presence of pathophysiological structure modifications, which are likely to occur in the alveolar space, and may lead to a reduced surfactant function.

Amino Acid Sequence

(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

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

[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

[In vitro method for estimation of enteral absorption of clanobutin and other drugs].

Two models have been developed for the determination of in vitro absorption of 4-[4-chloro-N-(4-methoxyphenyl)-benzamidol]-butyric acid (clanobutin) and other agents. Permeability coefficients PM are obtained on artificial phospholipid collodion membranes which permit calculation of absorption coefficients k1 for anticipated human enteral absorption with consideration of physiological parameters. At a pH of 7--8 (small intestine) in particular, k1 shows good agreement with in vitro absorption determined in swine intestine and absorption constant ka derived from pharmacological studies in man. The kinetic absorption model simulates gastro-intestinal transport of the substance as well as local changes in pH. It allows calculation of anticipated human gastric (pH 3) and intestinal (pH 7.5) absorption rates with k1 for different gastric filling volumes. The calculated invasion curves are held against invasion curves calculated from pharmacokinetic studies in man. The comparison shows that all invasion curves calculated according to the kinetic absorption model for gastric filling volumes of 125--1000 ml are within the 95% confidence range; very good agreement exists above all with filling volumes of 125--250 ml. The prognostic value of permeation studies on artificial phospholipid collodion membranes and of the use of the kinetic absorption model in drug design is demonstrated by corresponding studies with chenodesoxycholic acid, indometacin, and clofibrinic acid.

Absorption

[Gentamicin-PMMA-beads in treating bone and soft tissue infections (author's transl)].

Temporary implantation of gentamicin-PMMA-beads and -chains provides a most-effective local antibiotic therapy as supplementary and consecutive treatment after surgical procedures executed in bone and soft tissue infections. The broad spectrum antibiotic gentamicin is gradually released from the PMMA beads in high doses, thus ensuring local concentrations of the antibiotic which never can be achieved by systemic application of the same antibiotic. Operative technique and advantages of this new way of local antibiotic therapy are explained. 128 patients were treated for different manifestations of chronic osteomyelitis in 1976. The chronic bone infections subsided completely in 91,4% of the patients, but 11 reinfections were observed within 6 to 24 months after termination of treatment. In 6 of those 11 cases this re-infection was caused by sequestered bone particles which had been overlooked.

Abscess

[The results of experimental and clinical use of Gentamycin PMMA balls (author's transl)].

Authors describe a new method of treatment for bone and soft tissue infections using polymethyl methacrylate balls containing Gentamycin. Advantages of this method can be summarized in 3 points: 1. From the patients point of view saving the rinsing-sucking drainage, early mobilisation etc. 2. From nursing point of view a significant facilitation of the patient's care. 3. From the hospital management's point of view: improved hygienic conditions by eliminating the possible infections related to a rinsing-sucking wet system. Cutting down hospital expences both by abbreviation of the time of hospitalization and saving on expensive antibiotics.

Administration, Topical

[Osteosynthesis for infected femoral pseudarthroses using the interlocking nail. 31 case reports (author's transl)].

31 cases of infected pseudarthrosis of the femur were re-osteosynthesized with the interlocking nail. Bony consolidation was obtained in 26 patients, in all cases the chronic osteomyelitic infection subsided with removal of the nail. Pseudarthrosis persisted in 3 cases, after removal of the nail the patients could walk with a walking splint. In one of this group bony consolidation was obtained after repeated interlocking nailing. Persisting pseudarthrosis and infection was the indication for amputation in 2 cases.

Adolescent