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Biomedical subjects

A Koch

Publications and source records attributed to A Koch.

At least 199 records · Page 11Linked to original sources
PubMed1997

The 60 minutes myocardial infarction project. Treatment and clinical outcome of patients with acute myocardial infarction in Germany.

AIMS: To describe patient characteristics, pre-hospital delay, treatment, complications and outcome in patients with acute myocardial infarction admitted to hospitals in Germany. METHODS AND RESULTS: The study was of prospective observational multicentre design. Those involved were consecutive patients with acute Q-wave myocardial infarction admitted within 96 h of onset of symptoms to 136 German hospitals between July 1992 and September 1994 (n = 14980, median age 66 (quartiles 57, 74) years, 68% male, 48% anterior wall infarction). Median pre-hospital delay was 170 (90, 475) min, with 17% arriving within the first hour and 61% within 4 h of onset of symptoms. The following patient groups had a short pre-hospital delay: males, those aged less than 65 years, those admitted at night or the weekend, those with a previous myocardial infarction, those in need of cardiopulmonary resuscitation, and those with a diagnostic first ECG. The first ECG was diagnostic in 67.6% of cases. Reperfusion therapy was used in 53%, with thrombolytic therapy in 51.6%. Median time from admission to initiation of treatment was 30 (20, 55) min. Respective rates of treatment with aspirin, nitrates, and beta-blockers were 81%, 83%, and 16%. Major complications were cerebral bleeding (0.4%), bleeding requiring transfusions (0.9%), left ventricular rupture (0.6%) and anaphylactic shock (0.1%). Median hospital stay was 20 (13, 26) days. In-hospital death rate was 17.2%. Increased hospital mortality was observed with female gender, an unknown or long pre-hospital delay, a diagnostic first ECG, anterior wall infarction, trauma or major operation within the last 14 days, renal insufficiency and malignoma. CONCLUSIONS: 'Real-life' hospital mortality is much higher than previously reported in clinical trials. To reduce hospital mortality, the efficacy of thrombolysis should be increased by shortening the pre-hospital delay, and the use of concomitant therapy, especially beta-blockers, should be increased.

Aged↗
PubMed1997

Characterization of neural cell lines derived from SV40 large T-induced primitive neuroectodermal tumors.

We recently reported intriguing properties of neural tumors generated by retrovirus-mediated transfer of the SV40 large T antigen into fetal rat brain transplants. Histopathologically, these neoplasms displayed characteristic features of primitive neuroectodermal tumors (PNET) and exhibited a striking potential for migration into the host brain. In the present study, four cell lines were derived from these PNETs and characterized. Two lines with an immature phenotype expressed the embryonal form of the neural cell adhesion molecule and nestin. They showed spheroid formation and delicate cell processes. The remaining cell lines had a flat, epitheloid appearance and were immunoreactive for synaptophysin, neurofilament proteins and glial fibrillary acidic protein. These cells constitute valuable tools to study the cellular origin(s) and molecular basis of PNETs, differentiation of neural progenitors and tumor cell migration in the brain.

Animals↗
PubMed1997

Isolation and characterization of a pigmentless-conidium mutant of Aspergillus fumigatus with altered conidial surface and reduced virulence.

Aspergillus fumigatus is an important pathogen of immunocompromised hosts, causing pneumonia and invasive disseminated disease with high mortality. The factors contributing to the predominance of A. fumigatus as an opportunistic pathogen are largely unknown. Since the survival of conidia in the host is a prerequisite for establishing disease, we have been attempting to identify factors which are associated with conidia and, simultaneously, important for infection. Therefore, an A. fumigatus mutant strain (white [W]) lacking conidial pigmentation was isolated. Scanning electron microscopy revealed that conidia of the W mutant also differed in their surface morphology from those of the wild type (WT). Mutant (W) and WT conidia were compared with respect to their capacities to stimulate an oxidative response in human phagocytes, their intracellular survival in human monocytes, and virulence in a murine animal model. Luminol-dependent chemiluminescence was 10-fold higher when human neutrophils or monocytes were challenged with W conidia compared with WT conidia. Furthermore, mutant conidia were more susceptible to killing by oxidants in vitro and were more efficiently damaged by human monocytes in vitro than WT conidia. In a murine animal model, the W mutant strain showed reduced virulence compared with the WT. A reversion analysis of the W mutant demonstrated that all phenotypes associated with the W mutant, i.e., altered conidial surface, amount of reactive oxygen species release, susceptibility to hydrogen peroxide, and reduced virulence in an murine animal model, coreverted in revertants which had regained the ability to produce green spores. This finding strongly suggests that the A. fumigatus mutant described here carries a single mutation which caused all of the observed phenotypes. Our results suggest that the conidium pigment or a structural feature related to it contributes to fungal resistance against host defense mechanisms in A. fumigatus infections.

Animals↗
PubMed1997

Characterization of the aes gene of Escherichia coli encoding an enzyme with esterase activity.

malQ mutants of Escherichia coli lacking amylomaltase cannot grow on maltose. They express the maltose system constitutively and are sensitive to maltose when grown on another carbon source. In an attempt to isolate a multicopy suppressor that would result in growth on maltose, we transformed a malQ mutant with a gene bank of E. coli DNA which had been digested with Sau3a and cloned in pBR322. We screened the transformants on MacConkey maltose plates. A colony was isolated that appeared to be resistant to maltose and was pink on these plates, but it was still unable to grow on minimal medium with maltose as the carbon source. The plasmid was isolated, and the gene causing this phenotype was characterized. The deduced amino acid sequence of the encoded protein shows homology to that of lipases and esterases. We termed the gene aes, for acetyl esterase. Extracts of cells harboring plasmid-encoded aes under its own promoter exhibit a fivefold higher capacity to hydrolyze p-nitrophenyl acetate than do extracts of cells of plasmid-free strains. Similarly, strains harboring plasmid-encoded aes are able to grow on triacetyl glycerol (triacetin) whereas the plasmid-free strains are not. The expression of plasmid-encoded aes resulted in strong repression of the maltose transport genes in malT+ strains (10-fold reduction), but not in a malT(Con) strain which is independent of the inducer. Also, overproduction of MalT counteracted the Aes-dependent repression, indicating a direct interaction between MalT and Aes.

Acetylesterase↗
PubMed1997

Molecular characterization of the Bacillus stearothermophilus PV72 S-layer gene sbsB induced by oxidative stress.

S-layer protein variation from a hexagonally ordered (SbsA; 130 kDa) to a obliquely ordered (SbsB; 98 kDa) protein in Bacillus stearothermophilus PV72 is mediated by an increased oxygen supply. To elucidate the molecular basis of S-layer protein variation in B. stearothermophilus PV72, the sbsB gene, coding for the 98-kDa protein, was cloned by means of inverse PCR technology and sequenced. The sbsB coding region cloned in pUC18 was expressed in Escherichia coli, without its own regulatory upstream sequences but with its putative transcriptional terminator. The reading frame of sbsB (2,760 nucleotides) is predicted to encode a protein of 920 amino acids, including the signal sequence. Amino acid sequence comparison of SbsA and SbsB did not reveal any significant homology. The expression of sbsB in E. coli resulted in an accumulation of SbsB self-assembly products in the cytoplasm.

Amino Acid Sequence↗
PubMed1997

Insulin-like growth factor-I and its binding protein-3 in serum: are they good screening properties for the diagnosis of growth hormone deficiency?

Serum insulin-like growth factor-I and insulin-like growth factor binding protein-3 are simply-determined screening analytes if growth hormone deficiency is suspected. The analysis of growth hormone secretion using standardised stimulation tests and secretion profiles is complicated and expensive in comparison. In retrospect, we have examined the value of insulin-like growth factor-I and its binding protein-3 for the diagnostic clarification of patients with short stature (n = 117). In 39/117 patients growth hormone secretion was investigated as ward patients. Growth hormone deficiency was diagnosed in 10 patients, for 16 patients the diagnosis was neurosecretory dysfunction. For all patients (n = 7) with lowered insulin-like growth factor binding protein-3 and insulin-like growth factor-I values (insulin-like growth factor binding protein-3 < 5th percentile, insulin-like growth factor-I < 10th percentile) a growth hormone disorder was proven. Conversely, however, only 3/10 patients with classical growth hormone deficiency (n = 3) showed a lowering of both analytes. 8/10 patients with classical growth hormone deficiency and 8/16 patients with neurosecretory dysfunction had at least one lowered value. Two patients showed normal values for insulin-like growth factor-I and insulin-like growth factor binding protein-3 despite biochemically proven growth hormone deficiency. The combined determination of insulin-like growth factor-I and insulin-like growth factor binding protein-3 can provide valuable help during preliminary diagnosis of patients of short stature, indicating a disturbance of the growth hormone secretion if the values are lowered. Normal values do not, however, exclude the possibility of a growth hormone deficiency. Inpatient endocrinological testing is indispensible if growth hormone deficiency is suspected.

Adolescent↗
PubMed1997

[Value of polymerase chain reaction (PCR) in diagnosis of tuberculosis and mycobacterium infections caused by ubiquitous mycobacteria].

The rise in both incidence and the number of multi-drug-resistant strains has made tuberculosis an alarming health problem even in some developed countries. Moreover, due to the HIV pandemic an increase in mycobacterial diseases caused by ubiquitous mycobacteria has been observed. The microbiological standard procedures are critical diagnostic tools, and a more rapid detection of mycobacteria by new laboratory techniques would be helpful. We investigated the role of the polymerase chain reaction (PCR) in the detection of M. tuberculosis complex and of ubiquitous mycobacteria. 580 clinical specimens obtained from 525 patients were examined. The majority of sampled material was bronchoalveolar lavage fluid. Based on cultural identification of mycobacteria, the incidence of tuberculosis in our patients was 3.4%. For detection of M. tuberculosis complex the insertion sequence IS 6110 was used. Relative to cultural identification, diagnostic specificity of PCR was 99.5%, and sensitivity was 66.7%, respectively. In 3.0% of the total patient group and in 8.8% of HIV-infected patients an infection by ubiquitous mycobacteria was found. Ubiquitous mycobacteria were detected using the hypervariable region of the 16S-rRNA-gene, and species-identification was done by sequence analysis. For ubiquitous mycobacteria, sensitivity of PCR was 60.0% relative to cultural identification and 62.5% relative to a proven disease. PCR is a useful method in the rapid diagnosis of pulmonary tuberculosis with excellent specificity but lack of sensitivity.

AIDS-Related Opportunistic Infections↗
PubMed1997

Low molecular weight heparin and unfractionated heparin in thrombosis prophylaxis after major surgical intervention: update of previous meta-analyses.

BACKGROUND: Previous meta-analyses comparing low molecular weight heparin (LMWH) and unfractionated heparin for thrombosis prophylaxis after surgical interventions need updating. METHODS: This is a publication-based meta-analysis of 36 double-blind studies including 16583 patients. Main outcome measures are incidence of deep vein thrombosis (efficacy) and wound haematoma (safety). RESULTS: In general surgery there is no increased efficacy in favour of LMWH (odds ratio (OR) 0.88, 95 per cent confidence interval (c.i.) 0.60-1.30) but there exists a higher incidence of bleeding complications (OR 1.47, 95 per cent c.i. 1.07-2.01). Low-dose LMWH is equally efficacious (OR 1.03, 95 per cent c.i. 0.85-1.26) but safer than unfractionated heparin (OR 0.68, 95 per cent c.i. 0.56-0.82). In orthopaedic surgery there is a trend towards an increased efficacy for LMWH (OR 0.83, 95 per cent c.i. 0.68-1.02) with equivalent safety (OR 0.96, 95 per cent c.i. 0.68-1.36). CONCLUSION: A superiority of LMWH is suggested but heterogeneity might make generalizability to future patients questionable. A meta-analysis on individual patient data should be the next step before randomizing additional patients in future trials.

Double-Blind Method↗
PubMed1997

[Endoscopic fusion of the lumbar vertebrae].

For certain indications, anterior fusion of the lumbar spine is a standard operation. The surgeon specializing in operations on the vertebral column needs to learn to utilize the advantages of laparoscopic surgery. However, an absolute must before employing the technique in patients is adequate training in its use in living animals. For this purpose, the pig is a highly suitable model. The surgical team comprises a surgeon experienced in spinal procedures, an abdominal surgeon with skills in laparoscopic surgery and an experienced camera assistant. In the animal model and in clinical trials, a change in position-organ preparation from the cranial direction, a suprasym-physial approach to the vertebrae-has proved expedient. The use of a special instrumentarium for maintaining the pneumo-peritoneum, for protecting the spinal cord and for exact centering, including the application of a special dowel (ESKA-spacer and instruments) is essential. The greater technical effort may be expected to result in shorter hospitalization (2-3 days) in the future.

Animals↗
PubMed1996

Loss of heterozygosity at locus F13B on chromosome 1q in human medulloblastoma.

Medulloblastoma is a primitive neuroectodermal tumor of the cerebellum with poorly understood pathogenesis. Previous studies have reported loss of heterozygosity (LOH) on chromosome arms 17p, 11p and 9q and cytogenetic abnormalities of chromosome 1 in medulloblastoma. We have used the polymerase chain reaction to amplify 10 microsatellites on the short arm and 8 microsatellites on the long arm of chromosome 1 to assess allelic loss in 22 medulloblastomas. Loss of heterozygosity (LOH) on chromosome 1 was found in 9 cases. Eight medulloblastomas (36%) showed an interstitial LOH on chromosome 1q. The common region of overlap was mapped between D1S 1604 and D1S237 and included the locus F13B in the chromosomal region 1q31-q32.1. An additional tumor had LOH in a proximal region of 1p, but did not exhibit LOH on 1q. None of the medulloblastomas exhibited LOH of the telomeric portion of chromosome 1p, which has been associated with several other human malignancies. Our data suggest the presence of a putative tumor suppressor gene located near the locus F13B on chromosome arm 1q that appears to be involved in the pathogenesis of medulloblastoma.

Adolescent↗
PubMed1996

Endoglucanase II (EGII) of Penicillium janthinellum: cDNA sequence, heterologous expression and promotor analysis.

The cDNA coding for the endoglucanase EGII of P. janthinellum was cloned and sequenced. The open reading frame comprises 1230 nucleotides and the deduced amino-acid sequence shows an overall homology of 63% with the T. reesei egl2. The cellulose-binding domain of EGII represents a typical member of the A family of cellulases. The egl2 gene is only induced by cellulose or cellobiose and not by sophorose. A promotor fragment including 1 kb was cloned and sequenced. Three major transcription startpoints were identified. Five motifs matching the binding site of the carbon-catabolite repressor CREA of A. nidulans were detected. Their potential implication in repression was analyzed by bandshift assays.

Base Sequence↗
PubMed1996

Enhanced sensitivity of the failing human myocardium to cardiac glycosides and Na(+)-channel activators.

Cardiac glycosides and Na+ -channel activators increase intracellular Na+ and thereby enhance the transport rate of the sarcolemmal Na+/Ca2+ exchanger. We tested the hypothesis of whether increased expression of the Na+/Ca2+ exchanger in failing human myocardium is accompanied by enhanced sensitivity of the failing human myocardium toward cardiac glycosides and Na+ -channel activators. We studied the positive inotropic effects of the new Na+ -channel activator BDF and the cardiac glycoside ouabain in human failing (New York Heart Association [NYHA] functional class IV, heart transplants for dilated cardiomyopathy, n = 11) and nonfailing (donor hearts, n = 5) myocardium on electrically driven left ventricular papillary muscle strips (1 Hz, 37 degrees C). The effectiveness of ouabain and BDF to increase force of contraction was similar in human nonfailing and failing myocardium. BDF was more potent to increase force of contraction in failing than in nonfailing tissue (p < 0.05). The time until maximal inotropic effect developed after ouabain was significantly shorter in NYHA IV (mean 150 +/- 16 min) than in nonfailing myocardium (mean 240 +/- 20 min). These results suggest that human failing myocardium exerts and enhanced sensitivity to cardiac glycosides and Na+ -channel activators, possibly because of enhanced expression of the Na+/Ca2+ exchanger or because of an altered intracellular Na+ -homeostasis.

Adolescent↗
PubMed1996

Correlation of histology, cytogenetics and proliferation fraction (Ki-67 and PCNA) quantitated by image analysis in meningiomas.

Sixty meningiomas were classified histologically according to the WHO criteria and analyzed cytogenetically. The Ki-67 and PCNA proliferation fractions (PRFs) were assessed by immunhistochemistry. The staining results were quantified by TV-image analysis (Miamed, Leica, Germany). Within meningiomas of WHO-grade II/III and those with complete or partial deletion of # 1p, we found a significantly higher mean and maximal Ki-67 PRFs than in those of WHO-grade I and those with all other karyotypes. This was not the case for PCNA PRFs. No differences in PRFs were detectable between histological subtypes. Although these results were obtained after measurement of five high power fields (HPFs) only, the heterogeneity of PRF distribution within the tumors was high. Even after the measurement of 100 HPFs, the 95% confidence intervals were in a range of 18% to 34.3% PRF. This finding seems to be responsible for the moderate interobserver reproducibility of image analytical determination of PRF (r = 0.74). Nevertheless, there was a good correlation between subjective and objective image analytical assessment of PRF (r = 0.83). The significance of the maximum Ki-67 PRF per specimen implies the possibility of selecting those areas which show the highest fraction of positively stained nuclei for measurement, avoiding the problem of intraslide heterogeneity. Thus the time needed for image analytical quantification may be reduced.

Biomarkers, Tumor↗
PubMed1996

[Detection of hearing loss in patrons of a discoteque using TEOAE and DPOAE].

BACKGROUND: The aim of the study was to investigate the potential and difference of pure tone audiogram, TEOAE and DPOAE in the detection of temporary threshold shift. METHODS: 46 disco visitors who were exposed to disco music at an average intensity of 105 dB (A) for 1, 1 1/2 and 2 hours respectively underwent audiological examination before and after noise exposure. Audiological measurements performed were an audiogram and measurements of the TEOAE and DPOAE using the system ILO 92 (Otodynamics). RESULTS: The frequency range where the threshold shift occurred was around 4000 Hz in the 1 hour group and spread over all frequencies when the exposure time increased. The average threshold shift over all frequencies and probands was 6.2 dB for the 1 hour group, 7.1 dB for the 1 1/2 hour group and 10.1 dB after 2 hours of noise exposure. TEOAE amplitudes showed significant reduction only at 2000 and 3000 Hz. Even at threshold shifts exceeding 15 dB, however not in all cases, a reduction of TEOAE amplitudes occurred. Similar results were obtained regarding the DPOAE measurements. CONCLUSIONS: We conclude that TEOAE and DPOAE are not ideal instruments in the detection of temporary threshold shift after noise exposure.

Adolescent↗