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Biomedical subjects

A Schirmer

Publications and source records attributed to A Schirmer.

At least 19 recordsLinked to original sources

Influence of the angiotensin converting enzyme inhibitor ramipril on high-sensitivity C-reactive protein (hs-CRP) in patients with documented atherosclerosis.

UNLABELLED: Some medications have been shown to produce reductions in hs-CRP levels after initiating therapy. Whereas the role of the renin-angiotensin system in the inflammatory process has been documented in more detail during the last few years, the impact of an ACE-inhibitor therapy on this process has not been fully understood so far. The aim of this study was to investigate the effect of a therapy with the angiotensin-converting enzyme (ACE) inhibitor ramipril on hs-CRP plasma concentrations in patients with atherosclerosis. METHODS AND RESULTS: A total of 24 patients were enrolled in this prospective, uncontrolled, open-label multicenter study. Inclusion criteria were documented atherosclerosis, baseline high-sensitivity C-reactive protein between 3 and 12 mg/l, LDL-Cholesterol < or =150 mg/dl and no previous treatment with ACE inhibitors or angiotensin receptor blockers. Ten patients, pretreated with statins, and 10 patients not previously treated with statins were eligible for statistical analysis. Baseline high-sensitivity C-reactive protein was significantly decreased from 3.99+/-1.61 mg/l (mean+/-SD) to 2.72+/-1.19 mg/l (-32%) after 3 months treatment with 10 mg ramipril daily (p=0.0002). The decrease was more pronounced in patients who had not been treated with statins previously (-1.50 mg/l+/-1.44 mg/l) compared to those who were pretreated (-0.90 mg/l+/-0.93 mg/l). CONCLUSIONS: The ACE inhibitor ramipril administered in a daily dose of 10 mg to patients with atherosclerosis reduces the high-sensitivity C-reactive protein concentration. This effect may contribute to cardiovascular risk reduction mediated by ramipril aside from the blood pressure lowering effect.

Adult↗

[Cardiovascular risk stratification in general practice].

CONCLUSION: The ESC risk charts are helpful to identify high risk patients in general practice who are candidates for preventive treatment. The use of the ESC charts is one important step to initiate "evidence based medicine" in the daily practice of preventive cardiology.Cardiovascular diseases are the most important causes of premature disability and death in Germany. High risk patients however are frequently not recognized. A systematic risk stratification in general practice could identify high risk persons and allow a cost effective treatment approach. The goal of the CAD-scoring week was to identify high risk persons with the use of the ESC risk charts and to evaluate the treatment resulting from risk stratification. In addition the feasibility of the risk charts in daily office routine was to be evaluated. A total of 1122 of 20 000 (5.6%) contacted general physicians agreed to participate in the screening procedure. More than 27 000 patients (> 50 yrs) were evaluated using the ESC risk charts. 21.6% of women (n = 15 018) vs 22.2%* of men (n = 12 361) had markedly elevated blood pressure (> 150 mmHg), 29 vs. 24%* had a total cholesterol > 250 mg/dl (6.5 mmol/l), 25.5 vs 29.9%* smoked and 28.4 vs. 31.9%* had diabetes (*female vs male: p < 0.0003). Altogether 19.4% of women vs. 53% of men were newly identified as high risk patients (risk > 20% in 10 years). More than 40% of these high risk patients received drug treatment for prevention (ASA, lipid lowering drugs or ACE inhibitors). More than 70% of the participating physicians judged the risk charts to be helpful in patient management.

Adult↗

[Complication rate in the treatment of inter- and subtrochanteric femur fractures with two intramedullary osteosyntheses. Comparison of a conventional nailing system and a rotation stable fixation of the head-neck-fragment, gammanail and glidingnail].

Aim of the study was to evaluate typical complications in osteosynthesis of inter- and subtrochanteric femur fractures with intramedullary nailing systems. In the literature screw perforation of the femoral head into the acetabulum, postoperative fracture of the femur shaft, intraoperative shaft fracture, problems in placing of distal locking screws and deep infections are mostly described. In a retrospective study the complication rate of 100 consecutive gammanail osteosyntheses (GAN) and 96 glidingnail osteosyntheses (GLN) was analysed. 93 % of GAN and 89.3 % of GLN were followed up. Cutting out rate of GAN/GLN was 7.0 %/3.1 %, postoperative shaft fractures occurred in 1.0 %/0 %, intraoperative shaft fractures in 1.0 %/2.1 %, problems with distal locking in 2.0 %/1.0 % and deep infections in 3.0 %/1.0 %. In an analysis of internationally published data on 2 241 GAN and 365 GLN the cut-out rate was 2.3 %/0.5 %, postoperative shaft fracture 2.2 %/1.4 %, intraoperative shaft fracture 1.2 %/0.3 % and deep infection 1.2 %/2.2 %. GLN shows lower complication rates with regard to femoral head perforation and late shaft fracture than GAN.

Aged↗

Genetically engineered analogs of ascomycin for nerve regeneration.

The polyketides FK506 (tacrolimus) and FK520 (ascomycin) are potent immunosuppressants that function by inhibiting calcineurin phosphatase through formation of an FKBP12-FK506/520-calcineurin ternary complex. They also have calcineurin-independent neuroregenerative properties in cell culture and animal models of nervous system disorders. Based on the crystal structure of the FKBP12-FK506-calcineurin complex, we deduced that the 13- and 15-methoxy groups of FK506 or FK520 are important for inhibition of calcineurin phosphatase but not for binding to FKBP12. By genetic modification of the FK520 gene cluster, we generated 13- and 15-desmethoxy analogs of FK520 that contain hydrogen, methyl, or ethyl instead of methoxy at one or both of these positions. These analogs bind FKBP12 tightly, have decreased calcineurin phosphatase inhibition and immunosuppressive properties, and enhance neurite outgrowth in cell cultures. A representative compound was also shown to accelerate nerve regeneration and functional recovery in the rat sciatic nerve crush model.

Acetyltransferases↗

Lateralization of prosody during language production: a lesion study.

To examine brain lateralization of prosody during speech, the sentence production of six right-hemisphere-lesion patients and five left-hemisphere-lesion patients was compared to that of seven normal controls using a question-answer paradigm. The task required the prosodic realization of two different syntactic structures under conditions of wide and narrow focus. Acoustical analyses were carried out on F0 and time structure. These analyses revealed a preserved ability in patients to express differences in syntactic structure via prosody. However, there were deficits in distinguishing narrow focus from wide focus. Whereas both right- and left-hemisphere lesions caused impairments in the realization of F0, time structure was mainly impaired in left-hemisphere patients. Therefore, the present results from language production support functional as well as cue-dependent hypotheses of the lateralization of prosodic processing in the brain.

Adult↗

Biodegradation of polyhydroxyalkanoic acids.

Stimulated by the commercial availability of bacteriologically produced polyesters such as poly[(R)-3-hydroxybutyric acid], and encouraged by the discovery of new constituents of polyhydroxyalkanoic acids (PHA), a considerable body of knowledge on the metabolism of PHA in microorganisms has accumulated. The objective of this essay is to give an overview on the biodegradation of PHA. The following topics are discussed: (i) general considerations of PHA degradation, (ii) methods for identification and isolation of PHA-degrading microorganisms, (iii) characterization of PHA-degrading microorganisms, (iv) biochemical properties of PHA depolymerases, (v) mechanisms of PHA hydrolysis, (vi) regulation of PHA depolymerase synthesis, (vii) molecular biology of PHA depolymerases, (viii) influence of the physicochemical properties of PHA on its biodegradability, (ix) degradation of polyesters related to PHA, (x) biotechnological aspects of PHA and PHA depolymerases.

Amino Acid Sequence↗

Isolation and identification of poly(3-hydroxyvalerate)-degrading strains of Pseudomonas lemoignei.

By using selective enrichment of polyhydroxyalkanoate-degrading bacteria and poly(3-hydroxyvalerate)-containing granules from Chromobacterium violaceum as the carbon source, 10 new Pseudomonas lemoignei strains were isolated; these strains were able to degrade poly(3-hydroxyvalerate), as well as poly(3-hydroxybutyrate), in vitro. The new isolates were characterized and identified by comparing them with P. lemoignei LMG 2207(T) (T = type strain). Like P. lemoignei LMG 2207(T) cells, the cells of the 10 new isolates contained mainly hexadecenoic, hexadecanoic, octadecenoic, and dodecanoic acids, as well as hydroxylated fatty acids, and exhibited respiration in the presence of methylpyruvate, 3-hydroxybutyrate, and 4-hydroxybutyrate, but not in the presence of the 92 other carbon sources included in Biolog GN microplates. The protein patterns of the new isolates were almost identical to each other and very similar to the protein pattern of P. lemoignei LMG 2207(T). Some of the new isolates, but not P. lemoignei LMG 2207(T), contained megaplasmids that were about 200 kbp long. The 16S ribosomal DNA genes of strain A62, a representative of the 10 new isolates, and of P. lemoignei LMG 2207(T) exhibited more than 0.99 sequence similarity. The DNA-DNA reassociation value for two representative strains was 100%, and the levels of DNA-DNA reassociation between these strains and the type strain were 60 and 61%. The taxonomy of P. lemoignei is briefly discussed.

Bacterial Proteins↗

Substrate specificities of poly(hydroxyalkanoate)-degrading bacteria and active site studies on the extracellular poly(3-hydroxyoctanoic acid) depolymerase of Pseudomonas fluorescens GK13.

The isolation of poly(3-hydroxyoctanoic acid)- and poly(6-hydroxyhexanoic acid)-degrading bacteria yielded 28 strains with abilities to degrade various polymers. The most versatile strains hydrolyzed five different polyesters comprising short chain length and medium chain length poly(hydroxyalkanoates). The new isolates together with previously isolated poly(hydroxyalkanoate)-degrading bacteria were classified into 11 groups with respect to their polymer-degrading specificities. All PHA depolymerases studied so far have been characterized by the lipase consensus sequence Gly-X-Ser-X-Gly in their amino acid sequence, which is a known sequence for serine hydrolases. When we replaced the central residue, Ser-172, in the corresponding sequence Gly-Ile-Ser-Ser-Gly of the extracellular poly(3-hydroxyoctanoic acid) depolymerase of Pseudomonas fluorescens GK13, with alanine the enzyme lost its activity completely. This result of the mutational experiment indicates that the poly(3-hydroxyoctanoic acid) depolymerase belongs to the family of serine hydrolases.

Amino Acid Sequence↗

Molecular characterization of the extracellular poly(3-hydroxyoctanoic acid) [P(3HO)] depolymerase gene of Pseudomonas fluorescens GK13 and of its gene product.

phaZPfi, the gene encoding the extracellular poly(3-hydroxyoctanoic acid) depolymerase of Pseudomonas fluorescens GK13, was cloned, sequenced, and characterized. It comprises 837 bp and is transcribed as a monocistronic message of about 950 bp from a putative sigma 70-like promoter 32 bp upstream of the ATG start codon. The deduced protein of 278 amino acids reveals a typical leader peptide at its N terminus. When expressed in Escherichia coli, the mature depolymerase started with Ala-23, whereas the mature enzyme purified from P. fluorescens GK13 started with both Leu-34 and Arg-35 determining proteins of 26,687 and 26,573 Da, respectively. The depolymerase is a strongly hydrophobic protein and includes the lipase consensus sequence Gly-X-Ser-X-Gly, which is known for serine hydrolases. Replacement of the central residue, Ser-172, in the corresponding sequence (Gly-Ile-Ser-Ser-Gly) of PhaZPfl with alanine resulted in complete loss of enzyme activity, indicating that the poly(3-hydroxyoctanoic acid) depolymerase belongs to the family of serine hydrolases.

Amino Acid Sequence↗

Functional studies on platelets of a patient with an acquired disorder of platelet function associated with autoantibodies against membrane glycoprotein IIB/IIIA complex.

Platelet functions have been studied of a 63 year old woman with a severe acquired thrombopathy. The platelets did not adhere to siliconized glass. Aggregation could not be induced by either ADP (1 microM) nor collagen (2 micrograms/ml), no release of serotonin was found under these conditions. Thrombin caused only a weak aggregation response. Quantitative analysis of platelet actin revealed a very low total actin content (473 micrograms/10(9) platelets) and an extremely low F-actin value (3% of total actin). Stimulation of platelets with 0.1 U/ml thrombin for 3 min resulted in an increase of only 5% F-actin, whereas ADP and collagen did not induce any actin polymerization. Ca2+ movement in the patient's platelets is severely impaired after ADP and collagen stimulation, whereas a normal Ca2+ movement was obtained by 0.1 U/ml thrombin. The inhibition of the functions of normal platelets (aggregation and actin polymerization) by addition of patient's serum (5-10% final concentration) points to receptor blockade by platelet autoantibodies in the patient's serum. The antibody was purified by adsorption on Protein-A-Sepharose. Addition of IgG-suspension (5% final concentration) to washed control platelets resulted in similar effects on aggregation and actin polymerization compared to the effects of patient's serum.

Actins↗

Degradation of poly(3-hydroxyoctanoic acid) [P(3HO)] by bacteria: purification and properties of a P(3HO) depolymerase from Pseudomonas fluorescens GK13.

Twenty-five gram-negative bacteria and one gram-positive bacterium capable of growing on poly(3-hydroxyoctanoic acid) [P(3HO)] as the sole source of carbon and energy were isolated from various soils, lake water, and activated sludge. Most of the isolates degraded only P(3HO) and copolymers of medium-chain-length (MCL) hydroxyalkanoic acids (HA). Except for the gram-positive strain, which was able to hydrolyze P(3HO) and poly(3-hydroxybutyric acid) [P(3HB)], no isolate was able to degrade polymers of short-chain-length HA, such as P(3HB) or poly(3-hydroxyvalerate) [P(3HV)]. All strains utilized a large variety of monomeric substrates for growth. All gram-negative strains, but not the gram-positive strain, accumulated poly(hydroxyalkanoic acids) (PHA), consisting of MCL HA, if they were cultivated under accumulation conditions. One strain, which was identified as Pseudomonas fluorescens GK13 (biovar V), was selected and the extracellular P(3HO) depolymerase of this strain was purified from the culture medium of P(3HO)-grown cells by chromatography with Octyl-Sepharose CL4B and by gel filtration with Superose 12. The relative molecular weights of the native and sodium dodecyl sulfate-treated enzymes were 48,000 and 25,000, respectively. The purified enzyme hydrolyzed P(3HO), copolymers of MCL HA, and para-nitrophenyl esters of fatty acids. P(3HB), P(3HV), and characteristic substrates for lipases, such as Tween 80 or triolein, were not hydrolyzed. The P(3HO) depolymerase of P. fluorescens GK13 was insensitive to phenylmethylsulfonyl fluoride and dithioerythritol, unlike other PHA depolymerases. The dimeric ester of 3-hydroxyoctanoic acid was identified as the main product of enzymatic hydrolysis of P(3HO).(ABSTRACT TRUNCATED AT 250 WORDS)

Biodegradation, Environmental↗

Acquired disorder of platelet function associated with autoantibodies against membrane glycoprotein IIb-IIIa complex--1. Glycoprotein analysis.

A patient with idiopathic thrombocytopenic purpura developed after splenectomy a thrombasthenia-like severe haemorrhagic diathesis characterized by a normal or subnormal platelet count, prolonged bleeding time, strongly reduced platelet adhesion to glass and defective platelet aggregation in response to ADP and collagen. In contrast to hereditary thrombasthenia membrane glycoproteins (GP) IIb and IIIa were normally present in the patient's platelets. Immunoelectrophoretic analysis revealed an abnormal behaviour of the patient's GP IIb-IIIa complex. Autoantibodies against GP IIb-IIIa were detected in Triton-extracted washed platelets. Incubation of normal platelets with plasma from the patient resulted in a similar immunoelectrophoretic abnormality of the GP IIb-IIIa complex indicating that bound autoantibodies (IgG) are responsible for the abnormal immunoelectrophoretic behaviour of the patient's GP IIb-IIIa complex. Platelet fibrinogen was severely reduced similar to classical thrombasthenia suggesting that the GP IIb-IIIa complex is involved in platelet fibrinogen storage.

Autoantibodies↗

[Efficacy of adjuvant chemotherapy in metastasizing cervix carcinoma. A pilot study].

There are reported preliminary results of a pilot-study in the postoperative adjuvant treatment of cervical carcinoma with involvement of the iliac lymph nodes. It was done a prospective randomized study. There were 3 groups of treatment: adjuvant chemotherapy with a combination of Cisplatin and 5-Fluorouracil over 6 cycles; adjuvant chemotherapy like in the first group over 3 cycles plus Telecobalt-irradiation till the doses of 50 Gy in the small pelvis; and postoperative irradiation with Telecobalt till the doses of 50 Gy in the small pelvis. The fate of 41 patients could be evaluated. There were no statistical differences between the 3 groups in age, histology, staging and follow-up. Also the survival rate and the rate of the disease-free time didn't show a significant difference, but it seems, that the chemotherapy with Cisplatin and 5-Fluorouracil could be able to improve the poor prognosis of the cervical carcinoma with metastases.

Adult↗

[Second-look operation or second-look laparoscopy for evaluating complete remission of ovarian cancer].

Doubtlessly the exploration of the peritoneal cavity is essential for the determination of the efficacy of cis platine chemotherapy in ovarian cancer. Second-look operation and second-look laparoscopy are established as diagnostic methods. In a follow up study containing 92 patients with CR after cis platine chemotherapy it has been evident that the remission time is independent on the kind of invasive diagnostic methods. In contrast to these results the noninvasive diagnostic methods (like CT or X ray in 19 pat.) survival time was 20 months. The difference to both other groups is significant. Therefore it is necessary in cases with complete response to secure the results invasively, but a second-look operation is not compulsary.

Adult↗

[Efficacy of an adjuvant norethisterone acetate therapy (NEA) of endometrial carcinoma treated with primary surgery or irradiation].

UNLABELLED: The efficiency of NEA (norethisteronacetate) as an adjuvant hormone therapy in 196 pat. suffering from endometrial cancer has been evaluated in a prospective randomized trial. Primarily 93 patients had been operated on and 103 ones irradiated. From these 45 patients following surgery and 51 ones following radiation therapy had been treated with NEA. Schedule of adjuvant NEA therapy was for a time 6 ms 50 mg/d followed by 6 ms pause and so on till 5 years post op. 5 years survival in the operation group was 91.7 per cent without and 81.6 per cent with NEA, in the irradiated group 43.1 per cent and 44.8 per cent respectively. Side effect (47.9%) were caused by NEA at least twice higher than in control groups. IN CONCLUSION: the adjuvant hormone treatment without hormone receptor analysis is not recommendable.

Aged↗

[Tumor chemotherapy of ovarian cancer patients in advanced age].

Retrospectively the side effects caused by toxicity of cis-platinum chemotherapy combinations, the prolongation of the intervals in tumour chemotherapy without treatment determined by this, and the interruption of therapy caused by this 23 patients with ovarian cancer at an age of below 55 (average age 49.6 years) were contrasted with those of 25 patients with ovarian cancer, aged above 55. By means of the convergence table no significant differences in toxicity between the two age groups could be discerned at an error probability of 10 per cent. According to our experience the advanced age does not present any essential contra-indication for tumour chemotherapy in patients with ovarian cancer.

Age Factors↗

[Experiences with cisplatin (Platidiam) chemotherapy in secondary resistant ovarian carcinomas].

Experiences with cis Platin therapy in cases of ovarian cancers after previous tumorchemotherapy are reported. 23 patients were treated with 100 mg cis Platin (DDP)/m2 (Lachema, CSSR, Brno) in intervals of four weeks following extensive hyperhydratation. We observed following therapeutic effects: CR 4 of 23 pat., PR 11 of 23 pat., NC 3 of 23 pat. and progression in 5 cases. The average remission-time was the best in cases with CR (8,3 month) and the worst in cases without any therapeutic effect (1 month). Side effects observed: severe vomiting was compulsory in all cases. Twice we observed neuro- and ototoxicity after the 5th respectively 6th cyclus. DDP is an effective but also toxic cytostatic drug for treatment of ovarian cancer in the 2nd or 3rd line. It should be used in cases of secondary resistant tumours.

Adolescent↗