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Biomedical subjects

A Platz

Publications and source records attributed to A Platz.

At least 19 recordsLinked to original sources

Immunohistochemical analysis of the N-ras p21 and the p53 proteins in naevi, primary tumours and metastases of human cutaneous malignant melanoma: increased immunopositivity in hereditary melanoma.

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)

Dysplastic Nevus Syndrome

Glutathione transferase P1-1 expression in human melanoma metastases: correlation to N-RAS mutations and expression.

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.

Biomarkers, Tumor

[Determination of serum lead levels following shotgun injury].

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.

Adult

[Chylothorax after blunt thoracic trauma].

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.

Adult

Melanoma metastases from patients with hereditary cutaneous malignant melanoma contain a high frequency of N-ras activating mutations.

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.

Alleles

[Management of the compartment syndrome in hemophilic patients].

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.

Adult

[Prevention of thromboembolism in hip fracture: unfractionated heparin versus low molecular weight heparin ( a prospective, randomized study)].

In a prospective, randomized study in patients with hip fracture we discuss whether a single dose of low-molecular-heparin (Sandoparin) has the same effect as a tripple dose of standard-heparin (Liquemin: 3 x 5000 I.E.) The first dose of low-molecular-heparin respectively standard-heparin is given in the emergency room before the operation. Between 4th and 6th day following operation the patients were screened for deep vein thrombosis: Clinical examination, Liquid Crystal Contact Thermography (LCCT), colour coded ultrasound examination and with phlebography. 33 patients have been treated with standard-heparin and 35 with low-molecular-heparin. In the group of standard-heparin 30% of all the patients showed a deep vein thrombosis, whereas only 17% deep vein thrombosis were found in the group treated with low-molecular-heparin. But to reach statistical significance in both groups 60 patients are needed. Postoperative haemorrhagic complications were seen in 6.1% in the group of standard-heparin and in 8% in the group of low-molecular-heparin. The LCCT and the ultrasound examination were compared with the phlebography. The LCCT had a sensitivity of 92% and a specificity of 85%. The ultrasound examination had a sensitivity of only 15%! Therefore the ultrasound examination is an unsuitable screening method to detect deep vein thrombosis in patients with fractures of the proximal end of the femur.

Aged

[Computerized tomography follow-up in the acute phase after craniocerebral trauma].

Because of methodological reasons, within the first day after a head trauma, CT scan often does not demonstrate all the pathological consequences of brain injury. Additionally, secondary sequelae are frequent events. In our series of 129 patients the findings on subsequent CT scans done during the posttraumatic course were worse compared to the initial CT in 45% of patients. This deterioration on the CT scan was seen irrespective of the initial GCS score and the initial diagnosis of circumscribed or diffuse injury. The event observed most often was bleeding into a preexisting contusion or even bleeding into a region which had looked normal on the first CT scan. In the vast majority of cases, this happened within the first 2 weeks after the initial trauma. We conclude that an initially pathological CT should be repeated early in the posttraumatic period even in patients with mild to moderate head injury. In particular, we recommend that patients having sustained diffuse brain injuries should be transferred to neurotraumatology units for specialised management, even when there may not be immediately obvious indications for surgical intervention.

Adolescent

[Management of patient data in an intensive care unit with Macintosh and Filemaker Pro--extra effort or facilitation of routine care with improved information flow?].

A documentation system for patients in ICU is presented. The programming is based on Filemaker Pro from Claris. Two files have been created: the first "1 Eintritt" contains all the patients data like name, address, the patients history, diagnosis, therapies as the planned procedures. All these data can be imported into the second file "2 KG Unfallchirurgie" with a personal identification number. Complications, new results or further procedures can be added. Different layouts allow the user to print summaries or duty reports. The experience with 300 patients showed, that this system is easy to learn and to use, that it has a good compliance with the medical staff and that is gains a lot of time writing summaries or reports used for transferring patients to other units.

Attitude of Health Personnel

[Retroperitoneal rectum perforation during barium enema].

The examination of rectum and colon with barium sulfate is a method which is increasingly replaced by the endoscopy; therefore, the routine of doing this examination is increasingly vanishing. This means that the risk of this method increases. We report a case and discuss the symptomatology as well as the management of a perforation of the rectum during an examination with barium sulfate.

Aged

[Extended surgical indications in combined shoulder girdle fracture].

The combination of an ipsilateral clavicule and scapula fracture causes a double instability of the shoulder. In opposite to an isolated clavicule or scapula fracture this injury should be treated operatively. Diagnosis of the scapula fracture in polytrauma can be difficult. If there is a clinical or radiologic suspicion, the indication for a CT scan is given. Osteosynthesis with plates from separated approaches, first the scapula from dorsal then the calvicule from ventral has proven good. The nervus suprascapularis must be treated carefully and, if necessary, liberated from the fracture. The optimal treatment of this injury is not always possible in polytraumatised patient.

Clavicle

[Who should be hospitalized following mild craniocerebral trauma?].

The frequency of minor closed head injuries is high. These injuries may be complicated by the development of life-threatening intracranial hematomas. A well-defined selection criteria for admission must be proposed to guarantee an efficacious observation. In our series of 489 hospitalized patients with a GCS of 15 when seen in the emergency room: 4 patients required evacuation of an intracranial hematoma, 11 revision of a depressed skull fracture or a compound fracture of base of the anterior fossa. Using the existence of a skull fracture as a selection for admission, a strategy proposed by Jennett and colleagues, it would have been possible to reduce the number of patients hospitalized by 70% without missing a patient who developed an intracranial hematoma. Following these criteria no intracranial hematoma would be missed in our patients with a GCS of 15. We suggest that the use of plain x-rays to identify skull fractures and subsequent hospitalization prevents missing an intracranial hematoma. Those patients with diminished levels of consciousness of focal neurologic deficits require admission irrespective of skull fractures.

Adult

[Surgical management of severe pelvic crush injuries].

Control of hemorrhage and prevention of septic complications are the predominant difficulties associated with severe pelvic crush injuries. According to our experience spontaneous tamponade, external compression (MAST/G-suits), and blind ligation of the hypogastric artery seem to be ineffective, whereas angiography followed by embolization, controlled ligation or vascular reconstruction, packing with scheduled 2nd look reexploration, and rigid fixation of the pelvic ring are recommended to control severe hemorrhage associated with these injuries. Moreover, early repair of bowel and urinary tract lesions, diverting colostomy with rectal wash-out, radical debridement, and open wound care of degloving avulsion injuries appear to be the most important procedures to prevent posttraumatic sepsis. Our pelvic crush trauma protocol is based on 84 consecutive cases treated between 1972 and 1990. In all cases the Injury Severity Score (ISS) was over 40 points, each patient required at least 10 units of whole blood or red cells, the overall mortality rate was 41 out of 84 patients.

Combined Modality Therapy

Early detection and prevention of cutaneous malignant melanoma: emphasis on Swedish activities.

The incidence of cutaneous malignant melanoma has increased more than the incidence of any other malignant tumour disease in Sweden the last three decades. Parallel to the almost 6% annual increase in incidence there has been a 3% annual increase in mortality. The knowledge of significant risk factors for melanoma (intermittent sun exposure and phenotypic traits related to skin pigmentation and propensity for dysplastic nevi) as well as the relationship between thin tumours and a good prognosis has been used to develop strategies for primary and secondary prevention. In this paper the Swedish programs for education of physicians, nurses and the general population are presented. A nationwide program for the identification and follow-up of individuals with dysplastic nevus syndrome has been initiated. The effects of the programs are followed by population-based melanoma registries.

Humans

[Bassini or Shouldice operation?].

Between October 1988 and March 1990 a controlled, prospective study was conducted comparing the operative methods of Bassini and Shouldice for hernia repair. On 100 patients (11 female, 89 male) the Shouldice-technique was used, on 55 patients (6 female, 49 male) the Bassini-technique. Most patients were operated under local anesthesia. No significant difference was noted between the two groups regarding the postoperative complication rate (hematoma, wound infection). However, patients had a shorter hospital stay after the Shouldice operation. Six patients (10.9%) had recurrent hernia after the Bassini procedure, one patient (1%) after the Shouldice procedure. An increased risk for recurrent disease was found in patients with the Bassini operation who already had recurrent hernia. Because of the significant shorter hospital stay and the significant lower incidence of recurrent hernia, we abandoned the operative method of Bassini in favour of the Shouldice procedure.

Female

[Perforated cecum diverticulum as cause for acute abdomen].

Perforation of a solitary cecal diverticulum is a rare cause of acute abdomen and an uncommon differential diagnosis for acute appendicitis. Nine hundred cases have been described since Potiers first description in 1912, either localized in the cecum or in the ascending colon. A further case and its course are described.

Abdomen, Acute

Differences among human tumor cell lines in the expression of glutathione transferases and other glutathione-linked enzymes.

A large number of human tumor cell lines of various origins have been investigated with respect to expression of glutathione-linked enzymes in the cytosol fraction. The amounts of the different enzymes were estimated by use of activity measurements and by silver staining or immunoblot analysis after electrophoresis of cytosol fractions purified by affinity chromatography on S-hexylglutathione Sepharose. Class Pi glutathione transferase was the most abundant enzyme in most tumor cells; the cell lines HepG2 and Raji were exceptions in not expressing significant amounts of this enzyme. HepG2 cells derive from hepatocytes, which normally do not express the class Pi enzyme, whereas Raji cells originate from B-lymphocytes, which normally do express a class Pi glutathione transferase. The highest level of the class Pi transferase, in terms of protein reacting with antibodies as well as enzyme activity, was noted in the colon carcinoma cell line LS174T. Hu549Pat cells, EBV-transformed B-lymphocytes, also expressed high levels of a protein reacting with antibodies specific for class Pi glutathione transferases, but did not display any significant activity with ethacrynic acid, a substrate characteristic for this class. Class Alpha and class Mu glutathione transferases, in cell lines expressing these isoenzymes, were present in significantly lower concentrations than the class Pi enzyme. Most of the tumor cells contained a class Alpha transferase composed of 27.5 kd subunits, which has the physicochemical and immunological properties of the most basic glutathione transferase found in human skin. In several cell lines, a protein was detected with an apparent subunit Mr value of 30 kd that was tentatively identified as an additional class Alpha glutathione transferase not previously described. In addition, other glutathione-linked enzyme activities, namely glutathione peroxidase, glutathione reductase and glyoxalase I, were assayed with specific substrates in the cytosolic fraction of the tumor cells; glyoxalase I could also be estimated semiquantitatively by silver staining of SDS-PAGE cells after affinity chromatography. Like the glutathione transferases, these enzymes displayed distinctly different levels of expression in the various cell lines. Thus, virtually every cell line was found to have a unique pattern of glutathione-linked enzymes, suggesting that the resistance phenotypes of the cells differ accordingly.

Cell Line

Transthyretin messenger ribonucleic acid expression in the pancreas and in endocrine tumors of the pancreas and gut.

Transthyretin (TTR) cDNA probes were used to determine the presence of TTR mRNA in Northern blots from rat, porcine, and human organs as well as from human endocrine tumors. We also used in vitro translation in our study of the human tissues. In accordance with previous findings, TTR mRNA was found in the choroid plexus and, to a lesser extent, in the liver of all three species. In addition low levels of TTR mRNA were identified in the rat and human pancreas. All of the endocrine pancreatic tumors (two glucagonomas, two insulinomas, and one nonfunctional tumor) and the gut carcinoid also contained TTR mRNA, whereas other endocrine tumors (two pheochromocytomas and one paraganglioma) and one adenocarcinoma of the pancreas were TTR mRNA negative. The level of TTR mRNA expression in most of the endocrine pancreatic tumors exceeded that in the liver. The in vitro translations produced pre-TTR molecules of similar size for all TTR mRNA-positive human organs and tumors.

Animals