Biomedical subjects
Publications and source records attributed to A Platz.
The incidence of the abdominal compartment syndrome (ACS) after severe abdominal and/or pelvic trauma is 3%. ACS occurs within hours and causes severe organ dysfunction. Decompressive emergency laparotomy restores this impaired organ function.
BACKGROUND: Approximately 10% of human cutaneous melanomas occur in families in which several members are affected. The familial predisposition to this disease is often associated with dysplastic nevus syndrome, a condition in which afflicted family members have multiple dysplastic nevi (atypical moles). The chromosome region 9p21 and markers on chromosomes 1p and 6p have been linked to melanoma susceptibility. The tumor suppressor genes CDKN2A and CDKN2B have been mapped to the 9p21 region, and genetic analyses have revealed the presence of germline CDKN2A alterations in melanoma families. The reported frequencies of such alterations, however, vary among these families. PURPOSE: The present investigation was carried out to determine the frequencies of CDKN2A and CDKN2B germline gene mutations among members in a population-based cohort of Swedish melanoma families (i.e., melanoma kindreds). METHODS: DNA was prepared from blood samples obtained from 181 individuals belonging to 100 melanoma kindreds. The polymerase chain reaction (PCR) technique, followed by single-strand conformation polymorphism (SSCP) and nucleotide sequence analyses, were used to identify the types and frequencies of mutations in exons 1, 1beta, 2, and 3 of the CDKN2A gene and in exons 1 and 2 of the CDKN2B gene. RESULTS: CDKN2A gene aberrations were independently identified by both SSCP and nucleotide-sequence analyses. Nucleotide-sequence analysis identified a single point mutation leading to a substitution of leucine for proline in codon 48 of exon 1 in a family with a history of melanoma and several other cancers. A second abnormality, leading to an insertion of an extra arginine residue at codon number 113 of exon 2, was seen in four separate families. The CDKN2A exon-3 coding region had the wild-type sequence in all samples. No germline mutations were found in the alternative exon 1beta of the CDKN2A gene or in exons 1 and 2 of the CDKN2B gene. CONCLUSIONS: The present investigation demonstrates that CDKN2A germline gene mutations were observed in 7.8% of the 64 Swedish melanoma kindreds that each included at least two first-degree relatives with melanoma and dysplastic nevus syndrome. No CDKN2A exon 1beta or CDKN2B mutations were identified. The critical genes responsible for the inheritance of a susceptibility to develop melanoma among family members in this population have yet to be identified.
Despite improved surgical techniques there is still a risk of mortality in elective general surgery. In a prospective study preoperative data from 3250 patients were collected and compared with postoperative systemic complications, using univariate chi 2 analysis. Highly significant (P < 0.00001) variables were subjected to stepwise logistic regression analysis. The severity of operative procedure, higher American Society of Anesthesiologists (ASA) grade, symptoms of respiratory disease and malignancy were found to be significant risk factors predicting postoperative morbidity (P < 0.05). Using these four variables, a simple preoperative risk scoring system has been defined. Class A (up to 5 points) was defined as a low-risk group (systemic complication rate 5.0 per cent), class B (5-7 points) was intermediate risk (systemic complication rate 17.9 per cent) and class C (8-10 points) was high risk (systemic complication rate 33.3 per cent). Patients at high risk for perioperative and postoperative complications are more likely to be identified by this analysis than by using the ASA classification alone.
The purpose of this study was to evaluate the influence of additional, extracranial injuries and subsequent neurological complications in the intensive care unit on the functional outcome after head injury with extradural haematoma. The retrospective analysis included 139 adult patients with acute extradural haematomas admitted to the intensive care unit. Fifty-seven patients (41 per cent) were multiply injured (Injury Severity Score (ISS) = 36.5), and 82 (59 per cent) had a single head injury (ISS = 24.9). Fifty-four patients (39 per cent) developed neurological complications such as intracranial pressure (ICP) increase alone (N = 16), intracranial bleeding, ischaemic brain lesions or epileptic seizures with an associated ICP increase (N = 24) or without (N = 14). Overall, 77 per cent of the patients had a functional outcome (Glasgow outcome score 4 or 5); 46 per cent had a good recovery, 31 per cent were moderately disabled, 10 per cent were severely disabled, 4 per cent were persistently vegetative, and 9 per cent died. Differences were found between (1) patients with and without complications, (2) patients with extradural haematomas and patients with additional intracranial lesions, and (3) patients with a 'severe' Glasgow Coma Score (GCS) of 3-8 and patients with a GCS of 9-15. The presence of additional intracerebral injuries, and not extracerebral injuries, as well as the management of elevated ICP determines the final outcome in patients with extradural haematomas.
O6-methylguanine-DNA methyltransferase (MGMT) is a DNA repair protein, which removes alkyl groups from the O6 atom of guanine residues. Tumour cells which lack MGMT are sensitive to cytostatic drugs such as dacarbazine (DTIC), whose active species bind to this site. To explore whether analyses of MGMT expression can be used as a predictive test for clinical sensitivity to DTIC in melanomas, we developed a method to assay MGMT mRNA levels in cells obtained by fine needle aspiration biopsies of metastases. cDNA was synthesised from mRNA prepared from biopsy material. Polymerase chain reaction was performed using primers complementary to MGMT cDNA and to beta-actin, which served as an internal control. Analyses of 44 biopsies from 35 patients showed a considerable variation in MGMT mRNA, with 15 samples (34%) lacking detectable mRNA. In 6 out of 8 patients in whom more than one tumour was analysed, separate metastases had different levels of MGMT mRNA. There was no correlation between MGTM activity studied by a biochemical assay and MGMT mRNA levels when these were compared in 10 surgical biopsies.
A common characteristic of cancer cells is unrestrained cell division. This may be caused by mutational changes in genes coding for components of cell cycle-controlling networks. Alterations in genes involved in G1 checkpoint control have been registered in many human tumours, and investigations from several laboratories show that such alterations, taken together, are the most frequent changes detected in cancer cells. The present paper describes mutational analysis by polymerase chain reaction-single-strand conformation polymorphism (PCR/SSCP) and nucleotide sequence analysis of the genes coding for the p15, p53 and N-ras proteins in 26 metastases from 25 melanoma patients. The registered mutation frequencies add together with previously registered mutations in p16 in the same patient samples to a substantial total frequency of 44% of patients with mutation in at least one of the investigated genes. These results show the occurrence of heterogeneous defects among components of the cell cycle controlling machinery in a human melanoma tumour sample collection and demonstrate that the total frequency of detected alterations increases with the number of cell cycle controlling genes included in the screening panel.
We analysed 26 metastases from 25 patients with sporadic cutaneous malignant melanoma for alterations in the CDKN2 gene by a combined polymerase chain reaction/single-strand conformation polymorphism (PCR/SSCP)/nucleotide sequencing approach. Eleven alterations (one in exon 1, five in exon 2 and five in the 3' non-coding sequence of the exon 3 region) were concordantly and independently detected by both SSCP and nucleotide sequence analysis. Two of the exon 2 changes and the five changes in the non-coding exon 3 region are likely to represent natural polymorphism. Four (15%) of 26 metastases thus had CDKN2 mutations and belonged to 3 (12%) of 25 patients. Semi-quantitative PCR furthermore revealed no sign of homozygous deletions of the CDKN2 exon 2 region. The results support an involvement of the CDKN2 product in the development of a subgroup of sporadic melanomas and encourage the search for alterations in additional genes of the 9p21 region.
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INTRODUCTION: In 1985 Ciaglia [2] introduced percutaneous tracheostomy as a minimal invasive procedure. Since October 1991 percutaneous tracheostomy has been performed in 40 patients at the University Hospital in Zürich. This paper compares our complication rate using the Cook-system with the conventional open technique in the literature. MATERIALS AND METHODS: 40 patients, mean 53.6 years of age, 26 male, 14 female. Indications were: inability to perform sufficient bronchial suction, recurrent atelectasis, long term ventilation, difficult or prolonged weaning (i.e. neurotrauma). The tracheal tube is introduced following stepwise dilatation after making skin incision, according to the Seldinger technique. RESULTS: In all patients tracheostomy was carried out as an elective procedure in the Intensive Care Unit. Time between primary intubation and tracheostomy varied between O and 51 days, mean 15.9 days. Complications occurred in 5/40 cases (12.5%), with only one serious complication: the tracheostoma was misplaced, requiring intubation. Beside that we have seen 2 minor hematomas, 1 bradycardia and 1 subcutaneous emphysema. CONCLUSIONS: Percutaneous tracheostomy can be safely performed at bedside in the ICU. The method is simple and has a lower complication rate compared to the conventional open technique as reported by Hazard [7] and Griggs [8].
We report the case of a 53-year-old male patient with a colonic obstruction caused by a Bochdalek hernia. We discuss the diagnostic strategy and therapy.
METHOD: Since 1993 we have treated 30 children between 2 and 15 years with 31 unstable tibial and femoral shaft fractures. We perform closed reduction und X-ray control and stabilize the fracture using the monotube-fixator, system Howmedica. The advantages of this system are based on the self-drilling, self-cutting screws and the simple dynamization. DISCUSSION: The treatment of dislocated, instable fractures of the tibial and femoral shaft in children using traction method is related with a long hospital stay in an uncomfortable position. The traction method leads to bone healing, but with a high rate of deformity after reposition. We treat the shaft fractures of the lower extremity using the external fixation. This method allows to reach early weight bearing mobilisation, it is related to a shorter hospital stay. The child is already one day after initial treatment allowed to walk with full weight bearing. The treatment with the external fixation is a modification of the traction method. CONCLUSION: We think to have a good concept of treatment using external fixation in children with unstable fractures of the femur and tibia shaft. The disadvantages namely pin tract infections, general anesthesia for removal and difficulties with the reduction are overruled by the advantages as short hospital stay, early weight bearing mobilisation and early return of the child to his own environment.
Immunohistochemical analysis of the N-ras p21 and the p53 proteins was carried out on formalin-fixed sections of naevi, primary melanomas and metastases from patients with sporadic melanoma (SCMM) and with hereditary melanoma (HCMM)/dysplastic naevus syndrome (DNS). Seven out of 11 (64%) common naevi and three out of nine (33%) dysplastic naevi showed increased cytoplasmic N-ras expression. No p53 immunopositivity could be recognized in any of the naevus samples. However, strong N-ras expression as well as immunopositivity for p53 was recognized among primary melanomas and metastases with significantly higher frequency among samples from patients with HCMM compared with samples from SCMM cases (for N-ras, 40% vs 10%, P < 0.01; and for p53 43% vs 17%, P < 0.05). We have earlier registered N-ras codon 61 mutations among metastases from 59% of patients with HCMM and from 24% of subjects with SCMM. A comparison of the genetic data with the immunohistochemical results showed occurrence of increased N-ras p21 expression in the presence and absence of detectable N-ras mutant alleles. Increased expression of wildtype N-ras p21 may contribute to tumorigenicity in the absence of mutational activation, at least in a subset of melanomas. Altogether, N-ras p21 alterations are registered at earlier stages than p53 alterations in melanoma development and may be of aetiological importance, whereas p53 alterations may be associated with tumour progression in the late stages.(ABSTRACT TRUNCATED AT 250 WORDS)
Expression of the detoxication enzyme glutathione transferase P1-1 (GST P1-1) at elevated levels has been noted in many types of human tumors, including melanomas. The products of the human H-RAS, K-RAS and N-RAS genes play a key role in intracellular signal transduction leading to transcriptional activation of AP-1 (Fos/Jun) responsive genes. The oncogenic mutated forms of the ras proteins are constitutively active and interfere with normal signal transduction. Mutated RAS genes as well as increased expression of wild-type ras proteins are common features in human tumors including melanoma. We have characterized 30 melanoma metastases from 23 melanoma patients with reference to N-RAS expression and mutation as well as to GST P1 expression (immunohistochemistry and genetic analysis). Twenty-three of 30 samples (70%) had high N-Ras p21 and/or N-RAS codon 61 mutations and 18 of these 23 samples also had high GST P1-1 immunoreactivity. Seven of 30 (23%) samples had low N-Ras p21 immunoreactivity and no detectable N-RAS codon 61 mutations. Six of these 7 samples (86%) also had low GST P1-1 immunoreactivity. The results indicate a statistically significant correlation (Spearman correlation coefficient, r = 0.56, p = 0.001, 2-tailed test) and provide, for the first time, indirect evidence for a possible coregulation of N-RAS and GST P1 in human malignant melanoma which should be further evaluated.
Lead concentration of pellets is over 95%. Four patients who had sustained shotgun injury with retained shotgun bullets in the body are described. In 3 of 4 patients the blood level of lead was increased, as well as the concentration of Delta-ALA in the urine. In all four patients symptoms due to lead intoxication were absent. Usually the surgical goal is limited to a proper debridement of large wounds in the soft tissue. Therefore it is mandatory to assess the lead level in the blood and the concentration of Delta-ALA in the urine. Thus asymptomatic lead intoxication can be recognized and treated.
The diagnosis of chylothorax following blunt chest trauma is rare, only few cases have been reported. We describe three patients with chylothorax following blunt chest trauma. Conservative treatment consists of drainage, in severe cases mechanical ventilation with PEEP and total parenteral nutrition. In case of persisting and/or increasing chylus production, thoracotomy and ligation of the thoracic duct may be required. In all of our patients thoracostomy was the definite therapeutic modality, no thoracotomy was necessary.
Gunshot wounds to the head have a high morbidity and mortality [1, 2, 3, 4, 5]. In our areas this kind of injury is rarely seen, being mostly due to attempted suicide [6]. To help determine the optimal management of patients with penetrating GSW to the head, retrospective experience with 47 patients from 1986 to 1993 is presented. Due to our experiences we provide the following treatment of patients with craniocerebral gunshot wounds: After a short neurological examination and the stabilization of the vital parameters, we do further examination with skull X-ray and a CT. With these informations we decide about the further treatment: We operate patients with stable vital signs, with GCS higher than 3, as long the ventricular system is not involved. 18 patients survived the injury. The currently living 16 patients were examined and checked concerning outcome after GSW to the head. 11 of 16 patients had a GOS 4 or 5. The remaining 5 patients are dependent on permanent help.
Mutations in N-ras exon 2 codon 61 were studied in formalin-fixed human melanoma metastases. DNA fragments including codon 61 were amplified by polymerase chain reaction (PCR) and mutational analysis was performed by oligonucleotide hybridization (ODN), allele specific PCR and PCR combined with single strand conformation polymorphism analysis (SSCP). Thirty metastases from 25 patients with 'spontaneous' cutaneous melanoma were compared with 35 metastases from 17 patients with 'hereditary' cutaneous melanoma. The frequency of mutations as measured by PCR/ODN was significantly higher in patients with hereditary melanoma (mutations in 24% versus 59%, p < 0.05). The most frequent mutations were C/A transversions to lysine (AAA). The occurrence of lysine mutations was, in addition, studied by allele specific polymerase chain reaction. Again, the mutation frequency was significantly higher in metastases from patients with hereditary melanoma. PCR/SSCP finally enabled the isolation of lysine mutant alleles and nucleotide sequence analysis which confirmed the presence of the mutated codon 61. The relatively higher frequency of N-ras mutations in tumours from patients with hereditary melanoma may be related to the hypermutability described in hereditary melanoma and dysplastic naevus syndrome. The results support an involvement of N-ras mutations in the molecular pathogenesis of melanoma.
Diffuse bleeding in the muscles or localized hematomas are illness-specific factors increasing the possibility of a posttraumatic compartment syndrome in hemophiliac patients. Sufficient substitution of coagulation factor is the first step after trauma. The main principals of surgical treatment are:--a generous fasciotomy with a sufficient skin incision to allow adequate hemostasis under direct visualization. Localized hematomas should be evacuated;--fractures must be definitively stabilized as soon as possible. Therefore, internal fixation should be performed primarily whenever possible;--primary skin grafting of all skin defects to insure early wound closure. Intraoperatively, the underlying exposed surfaces of split thickness skin grafts and donor areas are sealed with fibrin glue. All surgery must be done under sufficient coagulation factor substitution, which has to be continued during wound healing and mobilization.