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Biomedical subjects

W Friedl

Publications and source records attributed to W Friedl.

At least 73 records · Page 4Linked to original sources
PubMed1997

Microsatellite instability analysis: a multicenter study for reliability and quality control.

The molecular biology section of the Hereditary Non-Polyposis Colorectal Cancer study group-Germany, instituted a multicenter study to test the reliability and quality of microsatellite instability (MSI) analysis. Eight laboratories compared MSI analyses performed on 10 matched pairs of normal and tumor DNA from patients with colorectal carcinomas. A variety of techniques were applied to the detection of microsatellite changes: (a) silver and ethidium bromide staining of polyacrylamide gels; (b) radioactive labeling; and (c) automated fluorescence detection. The identification of highly unstable tumors and tumors without MSI was achieved in high concordance. However, the interpretation of the band patterns resulted in divergent classifications at several microsatellite marker loci for a large fraction of this tumor/normal panel. The data on more than 30 primers per case suggest that the enlargement of the microsatellite panel to more than 10 loci does not influence the results. In this study, cases with MSI in less than 10% of loci were classified as microsatellite stable, whereas MSI was diagnosed in cases with more than 40% of all markers unstable. We propose that a panel of five microsatellite loci consisting of repeats with different lengths should be analyzed in an initial analysis. When less than two marker loci display shifts in the microsatellite bands from tumor DNA, the panel should be enlarged to include an additional set of five marker loci. The number of marker loci analyzed as well as the number of unstable marker loci found should always be identified. These criteria should result in reports of MSI that are more comparable between studies.

Chromosome Deletion↗
PubMed1997

[Biomechanics of combined Kirschner wire osteosynthesis in the human model of unstable dorsal, distal radius fractures (Colles type)].

In an experimental study, the biomechanical qualities of the combined Kirschner wire osteosynthesis (KWO) in the unstable Colles' fracture were analyzed. This type of pin fixation is our preferred osteosynthesis in the treatment of unstable Colles' fracture because it allows immediate functional therapy. It represents a modification of Kapandji's dynamic KWO, compensating for the insufficient volar stability by means of the conventional static KWO. Clinical experience according to the anatomical and functional results, was very encouraging suggesting that a clinical concept based on the biomechanical principles of combined KWO and its single components should be constituted. Simulation of the unstable Colles' fracture was realized by dorsal wedge osteotomy of the distal end of the radius using cadaveric material. This fracture model was subsequently pinned using the different KWO types and tested by a standardized vector energy testing device regarding its stability in the four main loading directions. The combined KWO unifies the advantage of volar stability of the conventional KWO with the high dorsal stability of dynamic KWO. The main functional principle of dynamic KWO with regard to its axial stability consists in the repositioning of the dorsal bone fragmentation zone and hence the reconstitution of cortical load transmission. Besides its good stabilization, dynamic KWO also leads to optimal alignment of the distal metaphyseal fragment. Furthermore, the experiments yielded important information about technical aspects of the surgical procedure, which helps us to avoid anatomical and functional deficiencies. Based on these experimental findings, the surgical technique of combined KWO was standardized.

Biomechanical Phenomena↗
PubMed1997

[The prospects for Kirschner-wire osteosynthesis in the dorsally unstable distal radius fracture (Colles' type)].

The following experimental study was conducted to develop biocompatible methods of osteosynthesis in fractures of the distal radius and to evaluate their stability. A model of dorsal wedge osteotomy in the distal radial metaphysis was used to develop the surgical technique and to test the stability of the alternative methods of osteosynthesis. The concept for this model was based on commercially available materials which were either biodegradable or osteoconductive. Four different forms of biocompatible osteosynthesis were compared to combined Kirschner wire osteosynthesis (KWO), our preferred method of treatment of unstable Colles fracture. Biocompatible osteosynthesis was achieved with an invasivity and stability comparable to that of KWO. In conclusion, injection osteosynthesis exceeded the other biocompatible methods of osteosynthesis in all respects. Regarding the recent developments in injectable materials for osteosynthesis it offers the best perspective for clinical application.

Biocompatible Materials↗
PubMed1997

Loss of the PLA2G2A gene in a sporadic colorectal tumor of a patient with a PLA2G2A germline mutation and absence of PLA2G2A germline alterations in patients with FAP.

The Min (multiple intestinal neoplasia) mouse with a germline mutation in the adenomatous polyposis coli gene serves as an animal model for familial adenomatous polyposis coli (FAP). The number and age at onset of colorectal adenomas varies in the offspring of Min mice crossed with other strains. The murine gene for the secretory phospholipase A2 (PLA2G2A) was found to be the main candidate for these variations. To test the hypothesis of a correlation between PLA2G2A gene alterations and human tumor development, we screened 14 patients with FAP and 20 patients with sporadic colorectal cancer for germline and somatic PLA2G2A gene mutations. None of the individuals with FAP showed PLA2G2A germline alterations. However, a germline mutation was observed in one patient with an apparently sporadic colorectal tumor; the wildtype allele was somatically lost in the tumor of this patient.

Adenomatous Polyposis Coli↗
PubMed1997

Hereditary nonpolyposis colorectal cancer: causative role of a germline missense mutation in the hMLH1 gene confirmed by the independent occurrence of the same somatic mutation in tumour tissue.

Evaluation of the causative role of germline mutations in DNA mismatch repair genes in hereditary nonpolyposis colorectal cancer (HNPCC) families can be difficult. Whereas nonsense, frameshift or splice-site mutations are presumed to lead to dysfunctional gene products and thus are generally considered to be causative, the evaluation of missense mutations often remains uncertain. We observed a novel germline mutation in the hMLH1 gene (His-->Pro at codon 329) in an HNPCC family. The same missense mutation also occurred as a somatic event in the colonic tumours of two other HNPCC patients who had germline mutations at different sites of the hMLH1 gene. Thus, the H329P mutation present in the germline can be considered as having an aetiological role in this HNPCC family.

Adaptor Proteins, Signal Transducing↗
PubMed1997

Muir-Torre syndrome: clinical features and molecular genetic analysis.

We report a 62-year-old man with rectal cancer, two keratoacanthomas and multiple sebaceous adenomas, epitheliomas and sebaceous hyperplasia. His brother and father died from colorectal cancer. A subgroup of patients with the Muir-Torre syndrome (MTS) is allelic to the cancer family syndrome. This genetic disorder is caused by an autosomal dominant inherited germline mutation in one of the DNA mismatch repair genes. It is thought that a somatic mutation of the other allele leads to a genomic instability responsible for tumorigenesis. In the patient presented here the instability was detected in two characteristic skin lesions; sebaceous adenoma and epithelioma. The search for a causal germline mutation revealed a frameshift mutation in the mismatch repair gene hMSH2 leading to a truncated protein. A presymptomatic molecular diagnosis can be offered to the children of the patient.

Carcinoma↗
PubMed1997

Identification of APC exon 15 mutations in families suspected of familial adenomatous polyposis (FAP).

Patients with familial adenomatous polyposis coli (FAP) reveal numerous colorectal adenomas as well as benign and malignant extracolonic lesions. Adenomatous polyposis coli (APC) gene mutations are the crucial genetic defect in FAP. The APC mutation molecular analysis of 20 FAP families was performed using the novel and effective method of the heteroduplex analysis (HDA). All of these families were screened for mutations in APC exon 15. APC mutations were identified in 4 individuals of two families. These two families were also screened by the protein truncation test (PTT). The PTT results confirmed previous findings obtained by HDA. The results of molecular analysis were correlated with the clinical manifestations of extracolonic lesions and congenital hypertrophy of retinal pigment epithelium (CHRPE). Positive correlation of all clinical examinations and mutations of APC gene was observed in all 4 FAP patients.

Adenomatous Polyposis Coli↗
PubMed1996

Technetium-99m human immunoglobulin (HIG): a new substance for scintigraphic detection of bone and joint infections.

Technetium (99m-Tc)-labelled, polyclonal human immunoglobulin (HIG) has been described as a new agent to detect local infection and inflammation. In this study, we tested 99m-Tc HIG in 55 patients with suspected chronic (n = 42) and acute (n = 13) skeletal infection. Diagnosis was proven operatively (n = 44) and clinically (n = 11), including microbiological culture tests (n = 46). A gamma camera scan was performed 4 and 24 hours after I.v. injection of 500 MBq 99m-Tc-HIG. 99m-Tc-HIG scanning achieved a sensitivity of 91% and a specificity of 93%. We found one false negative and five false positive scintigraphic results in 55 patients. No clinical or biochemical side effects were encountered after 99m-Tc-HIG injection. We recommend this technique especially for localisation of low-grade, chronic osteomyelitis. The mechanisms and kinetics of 99m-Tc-HIG, however, are worth investigating more extensively.

Acute Disease↗
PubMed1996

Familial adenomatous polyposis: a submicroscopic deletion at the APC locus in a family with mentally normal patients.

Cytogenetically visible deletions that include the adenomatosis polyposis coli (APC) locus have repeatedly been reported in mentally handicapped polyposis patients. We report on a family with a submicroscopic deletion of about 200 kb including more than the 3' half of the APC gene and the adjacent DP1 gene. The deletion was detected by linkage analysis with flanking and intragenic markers and proven by in situ hybridisation with intragenic cosmid clones. All the familial adenomatous polyposis (FAP) patients and persons at risk in the family show normal behaviour and intelligence. Thus, it is conceivable that at least some of the FAP patients in whom mutations could not be identified by routine methods may have large but submicroscopic deletions.

Adenomatous Polyposis Coli↗
PubMed1996

Attenuated familial adenomatous polyposis due to a mutation in the 3' part of the APC gene. A clue for understanding the function of the APC protein.

The identification of germline mutations in a large number of clinically well-characterised patients with familial adenomatous polyposis (FAP) has allowed the unravelling of several genotype-phenotype relationships that can now be interpreted in the light of the structure and functional domains of the adenomatous polyposis coli (APC) protein. An attenuated phenotype has been found to be associated with mutations at the 5' end of the gene, while a severe clinical expression was found in patients with the most common mutation at codon 1309. So far, only few mutations in the 3' half of the gene have been published. We report on two families with a rather mild phenotype due to a frameshift mutation at codon 1597. These families may represent a clue for defining a 5' border for the occurrence of a second region of attenuated FAP that is localised in the 3' part of the APC gene. We propose a model to explain the relationship between the severity of the disease and the size of the mutant APC protein.

Adenomatous Polyposis Coli↗
PubMed1996

[Craniocerebral trauma in acute surgical management. Primary care in a general community hospital].

Head traumas frequently occur in polytrauma patients but are also found as isolated injuries. In our hospital trauma center without a neurosurgical department, in a 21-month period, 489 patients with head/brain trauma were treated. This represents 6.5% of all patients treated in the trauma and reconstructive surgery clinic. In commotio cerebri (CC = 89.5% of the patients) constant conservative management and an uneventful course were observed; in 69 patients with contusio cerebri, 18 craniotomy operations had to be performed. In contrast, in only two cases was reoperation because of recurrent hematoma necessary. In four cases with complex and/or additional injuries, transfer to a neurosurgical center took place, and in two cases photophone consultation with that center was used. The mortality was 14.5%. The diagnostic and therapeutic regimens for the different types of injury and the requirements for the management of head/brain trauma in trauma centers without neurosurgical departments are presented: emergency service and medical staff, emergency room management, intensive care management, qualified neurological examination, X-ray imaging, including CT scan, OP-room equipment and trained surgeons. If these requirements are not available in a given hospital, early transfer of all patients for whom surgical management could be necessary to a neurosurgical department should be attempted. Only in patients with severe bleeding must immediate craniotomy be performed even in hospitals which do not have all the above mentioned facilities. In patients with intracerebral bleeding, bleeding in the dorsal fossa, injury of brain nerves, carotid artery or sinus cavernosus injuries, frontobasal injuries with liquor fistula or pneumonencephalon, transfer of the patients to specialized neurosurgical centers is indicated. With this selection, we obtained the same results in a trauma center without a neurosurgical department as reported in the literature. This avoids overloading neurosurgical centers with head/brain injury patients.

Brain Concussion↗
PubMed1996

Is the mismatch repair deficient type of Muir-Torre syndrome confined to mutations in the hMSH2 gene?

The Muir-Torre syndrome (MTS) is a rare autosomal-dominant condition characterized by the occurrence of sebaceous skin lesions and internal tumours in a patient. It has been demonstrated that at least a subgroup of MTS exhibits clinical and molecular genetic features of hereditary nonpolyposis colorectal cancer, including microsatellite instability in skin and visceral tumours, because of mutations in DNA mismatch repair genes. We have identified germline mutations in the hMSH2 gene in two unrelated MTS patients ascertained because of their skin tumours. Our results, together with published MTS cases, support the hypothesis that MTS with its characteristic skin lesions is confined to mutations in the hMSH2 gene.

Adult↗
PubMed1996

Insertion/deletion polymorphism in the angiotensin-converting-enzyme gene and blood pressure during ergometry in normal males.

A sample of 66 healthy, unrelated males with normal blood pressure were studied for a possible association between an insertion/deletion polymorphism in the gene coding for the angiotensin converting enzyme and blood pressure response to physical exercise. No association was found between the polymorphism and systolic blood pressure at rest and during stress. Statistically significant associations between the polymorphism and diastolic blood pressure were observed during exercise and post-stress. At maximal workload, among homozygotes for the deletion, the mean diastolic blood pressure was 93 (+/- 10) mmHg, among homozygotes for the insertion it was 82 (+/- 8) mmHg, among heterozygotes it was 85 (+/- 10) mmHg. The difference was still statistically significant 3 minutes post-stress. The angiotensin converting enzyme polymorphism may be a marker for genetically determined differences in the response of the cardiovascular system to physical stress.

Adult↗
PubMed1996

Natriuretic peptides and cyclic guanosine 3',5'-monophosphate in asymptomatic and symptomatic left ventricular dysfunction.

BACKGROUND: Screening for patients with asymptomatic left ventricular dysfunction is of considerable importance because they may benefit from early treatment with angiotensin converting enzyme inhibitors. It has been suggested that atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and cyclic guanosine 3',5'-monophosphate (cGMP) might be useful markers for screening. OBJECTIVE: To compare directly the power of the three immunoreactive forms of ANP (CT-ANP, beta-ANP, NT-ANP) and BNP and cGMP to detect asymptomatic left ventricular dysfunction. METHODS AND RESULTS: Radionuclide ventriculography was used to study left ventricular ejection fraction in 37 patients with asymptomatic left ventricular dysfunction, 32 patients with mild to moderate congestive heart failure, and 38 controls. CT-ANP, NT-ANP, beta-ANP, BNP, and cGMP were measured at rest and 3 minutes after exercise. Plasma BNP was the most sensitive marker for patients with asymptomatic left ventricular dysfunction but it reached only a sensitivity of 58% and a specificity of 76% at rest and a sensitivity of 65% and a specificity of 84% after exercise. Combined measurements of all natriuretic peptides and cGMP did not improve the power to detect asymptomatic left ventricular function above that of a single BNP measurement. CONCLUSIONS: Although natriuretic peptides and cGMP measured at rest and three minutes after ergometry may be useful for monitoring left ventricular dysfunction they are unlikely to be suitable for more general routine screening for completely asymptomatic left ventricular dysfunction.

Adult↗
PubMed1996

Estimation of the mutation frequencies in Charcot-Marie-Tooth disease type 1 and hereditary neuropathy with liability to pressure palsies: a European collaborative study.

A European collaboration on Charcot-Marie-Tooth type 1 (CMT1) disease and hereditary neuropathy with liability to pressure palsies (HNPP) was established to estimate the duplication and deletion frequency, respectively, on chromosome 17p11.2 and to make an inventory of mutations in the myelin genes, peripheral myelin protein 22 (PMP22), myelin protein zero (MPZ) and connexin 32 (Cx32) located on chromosomes 17p11.2, 1q21-q23 and Xq13.1, respectively. In 70.7% of 819 unrelated CMT1 patients, the 17p11.2 duplication was present. In 84.0% of 156 unrelated HNPP patients, the 17p11.2 deletion was present. In the nonduplicated CMT1 patients, several different mutations were identified in the myelin genes PMP22, MPZ and Cx32.

Charcot-Marie-Tooth Disease↗
PubMed1996

[Postoperative MRI morphology of the anterior cruciate ligament after primary ligament suture or ligament-plasty. A prospective study of 50 patients].

AIM: Identification of typical postoperative change after anterior cruciate ligament reconstruction (sutures, tendon grafts) and comparison with clinical tests and ultrasound. PATIENTS AND METHODS: 50 patients with anterior cruciate ligament ruptures were examinated with MRI (1.0 T, surface coil, sagittal T1-3DFT-Fast and sagittal spin-echo), US and clinical function tests (Lachmann, pivot-shift, anterior drawer test). RESULTS: In 19 of 21 patients with continuous low-intensity ligament structures in the MRI, knee stability was very good or good in the clinical tests and US. In 17 of 20 patients with a diagnosis of partial rupture at MRI, we also found a stable knee. 5 of 7 patients with the MRI-signs of ligament rupture showed knee stability at US and clinical tests. Furthermore, at MRI we found minor effusions in 10 patients, meniscus tears in 8 patients and ligament impingement in 2 patients. CONCLUSION: MRI is a valuable method for evaluating and assessing anterior ligament reconstructions. We found a good correlation between the continuous low-intensity ligaments at MRI and knee-stability. In contrast there is a bad correlation between discontinuous ligament structures at MRI and clinical stability of the knee. MRI seems to provide more information than US and clinical tests (for example: minor effusion, meniscus tears, ligament impingement, bone lesions).

Anterior Cruciate Ligament↗
PubMed1996

[The gliding nail. A new implant for complication-free primary load-bearing management of per- and subtrochanteric femoral fractures].

Intramedullary locked nail systems have significant biomechanical advantages in the therapy of per- and subtrochanteric fractures. The rate of intraoperative complications for the gamma nail was very high (42.2%-17.2%); the rate for the gliding nail was 2.7%. The rate of postoperative complications was 13.8%-6% for the gamma nail and 3.9% for the gliding nail.

Activities of Daily Living↗