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Biomedical subjects

M Zimmer

Publications and source records attributed to M Zimmer.

At least 73 records · Page 4Linked to original sources
PubMed1995

NONMEM analysis in determining the tri-exponential disposition of cefotaxime: a method of evaluating serum and urinary phase I data.

The time above the minimum inhibitory concentration (MIC) is an important surrogate parameter for the efficacy of cephalosporines. In clinical practice cefotaxime (CTX) is usually administered every 8 h or 12 h. Unfortunately the limit of quantification (LOQ) of the available assay is not low enough to detect CTX concentrations in serum later than 6 h after a 2 g i.v. dose. Consequently the time above MIC has to be estimated by extrapolation of the available serum data. Due to the concentrating properties of the kidney, concentrations in urine following a 2 g dose however remain above the LOQ for up to 16 h. It is therefore possible to follow the pharmacokinetics of CTX in urine within a 12 h dosing interval. Due to the linear pharmacokinetics of CTX, serum concentrations, and accordingly the time above MIC, can be estimated by using the measured urinary excretion and the calculated renal clearance. The pharmacokinetics of cefotaxime were studied in 12 healthy subjects who received a single 2 g i.v. dose administered as a short infusion. Blood and fractional urine were collected up to 24 h after dosing. For the characterization of the true terminal half-life only sparse and unbalanced serum and urinary data was available. In such situations, the population approach is the method of choice for estimating the kinetic parameters. The combined analysis of serum and urinary data using NONMEM shows the superiority of a tri-exponential compared to a bi-exponential pharmacokinetics model. As a result, the predicted serum trough levels of cefotaxime following twice daily dosing are about 30-fold higher than those extrapolated from the bi-exponential model. Consequently, the concentrations of CTX- and its metabolite desacetyl-CTX--are above the MIC of many therapeutically relevant pathogens for a longer period of time than previously assumed. In conclusion, a twice daily dosing regimen for cefotaxime is adequate for a number of clinically relevant pathogens. This is supported by the positive outcome in previous clinical trials following this dosing regimen.

Body Weight↗
PubMed1994

Construction of a human MluI YAC library.

We describe a cloning strategy for the construction of a human genomic library in yeast artificial chromosomes (YACs) based on complete digestion of high-molecular-weight DNA with the infrequently cutting restriction enzyme MluI. Cloning of MluI fragments in the vector pYAC-RC and one subsequent size fractionation by preparative pulsed-field gel electrophoresis yielded a library with average insert sizes of 600 kb. Ninety-seven percent of the colonies were recombinant. An additional size fractionation of MluI fragments prior to ligation had no significant influence on the size of the YACs. The library currently consists of 5000 clones, which is the equivalent of one human genome. Nineteen percent of the YACs were larger than 1.2 Mb. Since smaller MluI fragments are lost during sizing, we also performed cloning without size fractionation. Only 20% of the colonies were recombinant, probably due to unligated vector fragments that were present during the transformation.

Bacterial Proteins↗
PubMed1994

Expression of the NMDA R1 receptor in selected human brain regions.

The distribution of the N-methyl-D-aspartate R1 receptor was investigated in human hippocampus, cerebellum and frontal cortex by means of in situ hybridization and immunocytochemistry. Expression of N-methyl-D-aspartate R1 receptors was observed in layers II-VI of the frontal cortex with the highest density of positive neurones in layer IV, V and VIa. The entire human hippocampus was labelled, with marked differences in intensity between the CA 1 and CA 2/3 region. Furthermore we found marked differences in the intracellular localization of the protein between granule and pyramidal cells. In the cerebellum granule and Purkinje cells stained positive, as revealed by both in situ hybridization and immunocytochemistry. These findings suggest that the receptor has a less restricted cell specific expression than previously thought, although the distribution is largely in accordance with the expression of N-methyl-D-aspartate R1 mRNA in the rat.

Adult↗
PubMed1994

The human Met-ase gene (GZMM): structure, sequence, and close physical linkage to the serine protease gene cluster on 19p13.3.

Cosmid clones containing the genes for the human and murine natural killer cell serine protease Met-ase (gene symbol GZMM; granzyme M) were identified by screening human and murine cosmid libraries with rat Met-ase (RNK-Met-1) cDNA. The human gene has a size of 7.5 kb and an exon-intron structure identical to that of serine protease genes located on human chromosomes 5q11-q12, 14q11.2, and 19p13.3 that are expressed by lymphocytes, mast cells, or myelomonocyte precursors. Using cosmid DNA as a probe for fluorescence in situ hybridization, we identified the chromosomal position of human Met-ase as 19p13.3. Interphase studies with two differentially labeled probes for Met-ase and the azurocidin (AZU1), proteinase 3 (PRTN3), and neutrophil elastase (ELA2) gene cluster revealed that the distance of Met-ase from this gene cluster is in the range of 200 to 500 kb. Using differentially labeled mouse cosmid probes, we also mapped the murine gene for Met-ase to chromosomal band 10C, close to the gene for lamin B2. Thus, the Met-ase, AZU1, PRTN3, and ELA2 genes fall into an established region of homology between mouse chromosomal band 10C and human 19p13.3.

Amino Acid Sequence↗
PubMed1994

Bone formation in coralline hydroxyapatite. Effects of pore size studied in rabbits.

We analyzed osseous reactions in the rabbit femoral condyle to coralline hydroxyapatite bone substitutes of various pore sizes by radiology and histology. The results were compared to bone repair of empty cavities and to integration of allografts. Spontaneous bone repair of the empty cavities took approximately 12 weeks, while integration of the cryopreserved allografts occurred after 9 weeks. However, no signs of new bone formation were found with the 200 microns pore size hydroxyapatite. In contrast, there was substantial production of bone within the 500 microns pore size implants at 12 and 26 weeks. Our results indicate that the pore size of the coralline hydroxyapatite influenced the development of bone in the implants in the cancellous bone bed of the rabbit femoral condyle. The results also show that spontaneous bone repair should be taken into consideration when the integration of implants is evaluated.

Animals↗
PubMed1994

[Evaluation of the effect of oxytocin use for labor induction on frequency of occurrence and severity of neonatal jaundice].

Authors conducted analysis of effect of method used (which consisted of use of oxytocin, vit B, oestradiol) for labour induction on frequency of occurrence and severity of neonatal jaundice on 3rd day of neonatal life. Analysed material consisted of 1154 deliveries between the years 1990 to 1992 in IInd Department of Obstetrics AM Wrocław. Only completely physiological pregnancies qualified for analysis. The above mentioned sum of analysed deliveries was divided into 2 groups. Ist group consisted of 801 normal deliveries without any oxytocin use 2nd group consisted of 353 normal deliveries during which i.v. oxytocin drip was used either for induction of labour or to intensify uterine contraction during labour. Evaluation of the above data do not show significant increase in cases with hyperbilirubinemia in group with labour induction (7%) in comparison with deliveries without oxytocin use (5%). Moreover eliminating from the analysis cases of jaundice with normal bilirubin level (12 mg%), I degree jaundice, the actual count of cases of hyperbilirubinemia in group without oxytocin use in 26 (3.24%) and in group with oxytocin use is 13 (3.67%) cases (Tab. IV) which is not a significant difference and does not permit us to conclude that oxytocin use for labour induction is responsible for increased frequency of neonatal hyperbilirubinemia.

Female↗
PubMed1994

[Results of surgical treatment of posterior knee instability].

A retrospective study was performed to evaluate the outcome of operative treatment of posterior cruciate ligament (PCL) lesions in 115 patients operated on between 1980 and 1989. Follow-up was possible in 89 patients at 18-124 months postoperatively (average 76 months). In 65 re-examination was possible, while 24 patients returned a questionnaire. The results of patients who were operated on in the acute state were superior to those with chronic instabilities (Lysholm 79.9 +/- 18.5 vs 64.3 +/- 22.1; Tegner 5.7 +/- 2.3 vs 4.2 +/- 2.2; instrumented posterior drawer 5.3 +/- 3.5 mm vs 5.9 +/- 3.8 mm). On the other hand, the preoperative scores of symptomatic patients with chronic instabilities (Lysholm 38.8 +/- 22.0; Tegner 2.1 +/- 1.7) were clearly lower. Extraarticular procedures (Hughston) slightly improved symptoms in posterolateral instabilities. Olecranization of the patella had no influence on the results. Interpretation of the data is difficult as there was no matched group of patients with nonoperative treatment. A reviews of the literature suggests that isolated PCL tears are best treated with conservative management. Only in cases where associated ligamentous injuries require operative treatment should PCL reconstruction be performed. Chronic posterior instabilities should be treated operatively only if the patients are severely symptomatic. However, complete restoration of knee stability was usually not achieved with the techniques presented in this paper.

Adolescent↗
PubMed1993

Human clusterin (CLI) maps to 8p21 in proximity to the lipoprotein lipase (LPL) gene.

Clusterin (gene symbol: CLI) is a post-translationally nicked, two-chain plasma and tissue glycoprotein of 80 kDa. It forms high-density lipoprotein complexes with apolipoprotein A-I in plasma, functions as an inhibitor of the cytolytic reaction of the terminal complement proteins C5 to C9, and is secreted by Sertoli cells in large amounts into the seminal fluid. By isolating and characterizing three partially overlapping cosmid clones, we have established the complete physical map of the clusterin gene which spans about 20 kb. The subchromosomal position of the clusterin gene (CLI) and the order of CLI and the lipoprotein lipase (LPL) gene were determined by fluorescence in situ hybridization. We show that CLI, previously assigned to chromosome 8, is located on 8p21 proximal to the LPL locus. Based on this localization we consider clusterin as a novel candidate gene determining susceptibility to atherosclerosis.

Arteriosclerosis↗
PubMed1993

The human granzyme A (HFSP, CTLA3) gene maps to 5q11-q12 and defines a new locus of the serine protease superfamily.

Human granzyme A (HFSP, Hanukah factor serine protease; CTLA3, cytotoxic T-lymphocyte-associated serine esterase-3), a homodimeric, trypsin-like serine protease of 60 kDa found in granules of cytolytic T cells and natural killer cells, is implicated in lymphocyte-mediated target cell lysis. It contributes to DNA fragmentation in perforin (PRF1)-lysed target cells through an unknown mechanism. We have isolated a cosmid clone for the functional gene of human granzyme A and established its complete exon-intron map of 10 kb. Using an 11-kb subfragment of the cloned genomic DNA as a probe, we have identified the chromosomal position of human granzyme A on 5q11-q12. Thus, the human granzyme A gene falls into a region of homology between human chromosome 5 and mouse chromosome 13, band D, where the mouse granzyme A gene has been located previously. The granzyme A gene is not linked to known members of the large superfamily of serine proteases.

Animals↗
PubMed1993

Stress transfer at the femoral bone/bone cement interface as a function of the cement thickness.

When a cement canal prosthesis is used as the femoral component in total hip replacement (THR), the penetration depth of the bone cement can be varied according to the cement implantation pressure. Using experimental data which give a relation between the pressure applied to the cement at implantation and the resulting shape of the cement layer, a three-dimensional finite element study was performed to calculate the stress distribution at the bone/bone cement interface. The calculations show that the interface stresses increase with increasing depth of penetration by the cement layer. The explanation of this effect is that as the bone cement penetrates further into the cancellous bone, the cancellous bone is stiffened and can no longer act as a soft interposition between cortical bone and bone cement. From these results and from the clinical requirement that as little bone as possible be destroyed in any kind of allo-arthroplasty, we conclude that the penetration depth of bone cement into cancellous bone in THR should be minimized to the depth necessary in order to achieve sufficient initial stability of the implant. The results show that a cement-canal prosthesis meets these requirements if a cement implantation pressure of 1.0 bar is used.

Bone Cements↗
PubMed1993

Investigations on mechanism of Salter-1-fractures of the greater trochanter.

This study aims at clarifying why the apophysis of the greater trochanter very rarely separates, in contrast to other apophyses of the hip region. The inclination and area measurement of the greater trochanteric growth plate and the mode of insertion of the muscles on the apophysis were analyzed on the basis of 16 anatomic femoral specimens from newborn to children of 14 years of age. The physiological muscle cross section Q of the muscles inserting at the greater trochanter was determined on 6 specimens. In a cross-sectional radiological study, carried out on 1350 hip joints of healthy children, the inclination of the greater trochanter growth plate was measured. The anatomical and radiological findings show that the nearly plane-shaped greater trochanter growth plate remains inclined at a 50 degree angle to the horizontal body line and is loaded from a diagonally craniolateral direction throughout the total growth period. The lateral surface of the apophysis is covered by a fibrous connection which joins the insertion areas of the gluteus medius, minimus and vastus lateralis muscles. The vastus lateralis muscle is intimately bound to the vastus intermedius muscle by fibrous tissue. According to the results of the physiological muscle cross sections these four muscle groups can form a counteracting muscle sling, which transforms the traction forces at the surface of the greater trochanter into pressure forces in line with a tension band effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Empirical force field analysis of the revised structure of coenzyme F430. Epimerization and geometry of the corphinoid tetrapyrrole.

We undertook an empirical force field analysis of the conformational changes that accompany the diepimerization of coenzyme F430. The crystal structure of 12,13-diepi F430M was used as a test of the parameter set and as the basis for the calculations. The individual pyrrole rings in 13-epi and 12,13-diepi F430 adopt alternating half chair conformations leading to a ruffled macrocycle, native F430 is also ruffled but the individual pyrroles are planar. The 12,13 di-dehydro F430 and native F430 conformations are extremely similar, this accounts for the experimental observation that reduction of 12,13 di-dehydro-F430 forms native F430 and not 12,13-diepi F430. Native F430 can easily accommodate both square planar and, by bending, trigonal bipyramidal coordination geometries about nickel. We suggest that bent trigonal bipyramidal form is the conformer bound to the protein and that direct binding of the amino acid side chains to nickel is probably not important.

Calorimetry↗
PubMed1993

A comparison of efficacy of Tołpa Torf Preparation (TTP) in the treatment of cervicitis with or without surgery.

Tołpa Torf Preparation (TTP) is an immunomodulating drug produced by Torf Corporation, Wrocław and registered for human use in Poland. TTP enhances the process of tissue regeneration. Authors evaluate TTP effectiveness in the treatment of inflammatory states of the cervix, especially cervical erosions and the influence of this preparation of the macroscopic, cytological and bacteriological state of the cervix. TTP was used in 31 patients with the diagnosis of cervical erosion. All patients treated as yet were classified into 3 groups, depending on the treatment of cervical erosion used previously. TTP was administered orally in the dose of 5 mg (in 10 ml of water) daily during 10 days and locally in the form of tampons soaked with 1% TTP solution in the volume of 5 ml also during 10 days. TTP administered this way has beneficial therapeutic effects on the healing of cervical erosion accelerating the process of epithelialization and bringing normalization of the cytological picture. Especially beneficial in the treatment of cervical erosion is combined use of TTP and electrocoagulation or curettage--the healing time can be shortened by half.

Adjuvants, Immunologic↗
PubMed1993

[Blood lamination in bone cement--effect of cementing technique].

The quality of the cement layer influences the long-term survival of cemented endoprostheses. However, blood and fluid laminations within the cement layer, which can form during implantation of endoprostheses, lead to the deterioration of bone cement. Since the bone cement is the weakest part in the construction consisting of prosthesis, bone and bone cement, further weakening of the bone cement should be avoided if possible. By means of in vitro studies, three different cementing techniques were tested, measuring quantitatively the amount of fluid within the cement layer after implantation. The least amount of fluid within the cement layer was found in the cement-canal technique, and the highest amount in anterograde cement injection. Retrograde cement injection led to intermediate values.

Biomechanical Phenomena↗
PubMed1992

Three human elastase-like genes coordinately expressed in the myelomonocyte lineage are organized as a single genetic locus on 19pter.

The human neutrophil and monocyte-derived serine protease homologues neutrophil elastase (NE), proteinase 3 (PR3), and azurocidin (AZU) are involved in a variety of immune defense reactions. NE and PR3 assist in the destruction of phagocytosed microorganisms, cleave the important connective-tissue protein elastin, and generate chemotactic activities by forming alpha 1-proteinase inhibitor complexes and elastin peptides. AZU is cytotoxic to certain microorganisms and chemotactic for monocytes. All three proteins are produced and packaged into azurophil granules in large quantities during neutrophil differentiation. We have isolated several cosmid clones each of which contains the functional genes for AZU, PR3, and NE in this order. The PR3 gene is separated by 8 kilobases from the 3' end of the AZU gene and by 3 kilobases from the 5' end of the NE gene. We report a physical map of the gene cluster, its location on chromosome 19pter, and the exon-intron organization of the AZU and PR3 genes. Our fluorescence in situ hybridization studies disprove the previous chromosomal assignment of the human NE gene to 11q14. The five exons of AZU and PR3 are organized like those of NE and other granule-associated serine proteases of hematopoietic cells. NE, PR3, and AZU are coordinately downregulated in the premonocytic cell line U937 during induced terminal differentiation. The cluster-like physical organization of these genes and concerted regulation during hematopoietic differentiation suggests that they are located in a developmentally activated chromatin domain promoting high-level, cell-specific expression in the monocyte-myelocyte lineage.

Amino Acid Sequence↗
PubMed1992

Bone-cement removal with the excimer laser in revision arthroplasty.

The excimer laser was thought to be an appropriate tool for the removal of bone cement without damaging the bone. However, due to its low ablation rate, its clinical use in total hip revision arthroplasty proved to be impossible. This experimental study was designed to evaluate the maximal ablation rate by adjusting the laser's parameters. Energy density, frequency, pulse duration, radiation area, quantity of pulses, and environmental conditions were varied in the experimental setup. Even with the best set of parameters the excimer laser was about ten times slower than, e.g., the carbon dioxide laser. The removal of 10 g bone cement takes about 1 h. Thus, complete cement removal by means of the excimer laser alone is not possible. However, selective application of the excimer laser in combination with other techniques could be discussed.

Arthroplasty↗