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A Platz

Publications and source records attributed to A Platz.

At least 19 recordsLinked to original sources
PubMed2001

Cytoplasmic and nuclear accumulation of beta-catenin is rarely caused by CTNNB1 exon 3 mutations in cutaneous malignant melanoma.

Beta-catenin plays an important role in the Wnt signaling pathway by activating T-cell factor (Tcf)/lymphoid enhancer factor (Lef)-regulated gene transcription. The level of beta-catenin is regulated through GSK-3beta phosphorylation of specific serine and threonine residues, all of which are encoded for in exon 3 of the beta-catenin gene (CTNNB1). Mutations altering the GSK-3beta phosphorylation sites lead to cellular accumulation of beta-catenin and constitutive transcription of Tcf/Lef target genes. Such mutations have previously been found in melanoma cell lines. In our study, primary melanomas and their corresponding metastases were screened for CTNNB1 exon 3 mutations using single-strand conformation polymorphism and nucleotide sequence analysis. One of 31 primary tumors and 1 of 37 metastases, both originating from the same patient, had a TCT to TTT mutation at codon 45, changing serine to phenylalanine. Immunohistochemical analysis revealed membranous localization of beta-catenin in a majority of the samples. The mutated primary tumor and metastasis, however, displayed widespread cytoplasmic and nuclear expression of beta-catenin. An additional 30% of the primary tumors showed focal cytoplasmic and nuclear staining. Thus, beta-catenin exon 3 mutations are rare in primary as well as metastatic melanomas and do not explain the abnormal cytoplasmic and nuclear localization of beta-catenin found in a relatively large fraction of primary melanomas.

Cell Nucleus↗
PubMed2001

Haplotype analysis and age estimation of the 113insR CDKN2A founder mutation in Swedish melanoma families.

Germline mutations in the CDKN2A tumor suppressor gene located on 9p21 have been linked to development of melanomas in some families. A germline 3-bp insertion in exon 2 of CDKN2A, leading to an extra arginine at codon 113 (113insR), has been identified in 17 Swedish melanoma families. Analysis of 10 microsatellite markers, spanning approximately 1 Mbp in the 9p21 region, showed that all families share a common allele for at least one of the markers closest to the CDKN2A gene, suggesting that the 113insR mutation is an ancestral founder mutation. Differences in the segregating haplotypes, due to meiotic recombinations and/or mutations in the short-tandem-repeat markers, were analyzed further to estimate the age of the mutation. Statistical analysis using a maximum likelihood approach indicated that the mutation arose 98 generations (90% confidence interval: 52-167 generations), or approximately 2,000 years, ago. Thus, 113insR would be expected to have a more widespread geographic distribution in European and North American regions with ancestral connections to Sweden. Alternatively, CDKN2A may lie in a recombination hot spot region, as suggested by the many meiotic recombinations in this narrow approximately 1-cM region on 9p21.

Alleles↗
PubMed2001

[Experiences with using a potentially temporary vena cava filter in multiple trauma patients].

INTRODUCTION: In Europe, there is little experience in the application of temporary cava filters in patients with multiple injuries. Especially patients with pelvic injuries, fractures of the spine, and the lower extremities are at high risk for thromboembolic events like thrombosis or pulmonary emboli. Moreover, in patients with severe head injuries, anticoagulation is contraindicated. METHOD: We present in this paper our experience with 24 consecutive patients with multiple injuries who were treated with a temporary cava filter. The insertion site was either the femoral (n = 20) or the jugular (n = 4) vein. The 24 patients revealed a mean ISS of 35.1 +/- 2.01 points. Nineteen patients had pelvic injuries and 17 patients suffered from severe head injury. In 17 patients the insertion of the filter was prophylactic, in 4 patients a thrombosis was present and in 3 patients a non-fatal pulmonary emboli was diagnosed before the application of a cava filter. RESULTS: No complication occurred due to insertion of the filter. In one patient a thrombosis of the cava was observed as the only overall complication (1 of 24 = 4.2%). CONCLUSION: The insertion of a cava filter in patients with multiple injuries with contraindication for anticoagulation is a safe and effective procedure to prevent fatal pulmonary emboli.

Adult↗
PubMed2001

[Abdominal impalement injuries].

Impalement is an uncommon and spectacular injury, which combines aspects of both blunt and penetrating trauma. With reference to our own seven patients we discuss the initial management and the operative treatment of this rare injury. Further we demonstrate the imminent problems after impalement injuries such as removal of the impaled object, treatment of colon- and other abdominal organ injuries, and management of vascular injuries.

Abdominal Injuries↗
PubMed2000

CDKN2A germ-line mutations in individuals with multiple cutaneous melanomas.

Germ-line CDKN2A mutations are present in some kindreds with hereditary cutaneous melanoma, and in Sweden a founder mutation with an extra arginine in codon 113 (113insR) has been identified. We screened 80 individuals with at least two primary cutaneous melanomas, who were identified mainly by a search of a regional cancer registry, for germ-line CDKN2A mutations. In nine patients, CDKN2A alterations that may contribute to melanoma predisposition were detected. In six individuals with a family history of melanoma, the 113insR founder mutation was present. One patient, who also had a family history of melanoma, had a 24-bp deletion that included codons 62-69. An in vitro binding assay established that the resulting mutant p16 protein was unable to bind cyclin-dependent kinase 4 and cyclin-dependent kinase 6. Two patients without a family history of melanoma had CDKN2A alterations: (a) one had a mutation in the 5' noncoding sequence (-14C/T); and (b) the other had an insertion of an extra T in codon 28, which results in a stop signal in codon 43. The median age at diagnosis of the first melanoma was significantly lower, the number of primary melanomas was significantly higher, and the presence of a family history of melanoma was significantly more common in patients with CDKN2A mutations than in those without germ-line mutations. The proportion of CDKN2A mutation carriers was significantly higher among patients treated for three or more primary melanomas compared with those with two tumors only. We conclude that mutation screening of individuals with multiple primary melanomas is a useful strategy to identify new melanoma kindreds with CDKN2A germ-line mutations.

Adolescent↗
PubMed2000

Malignant melanoma in patients with multiple endocrine neoplasia type 1 and involvement of the MEN1 gene in sporadic melanoma.

Multiple endocrine neoplasia type 1 (MEN 1) is a familial cancer syndrome associated primarily with endocrine tumors of the parathyroids, enteropancreas and anterior pituitary. However, tumors of mesenchymal origin such as angiofibroma and collagenoma of the skin have also been associated with the syndrome. This highlights the possibility of an association between MEN 1 and some other types of tumors. Here we report 7 cases of primary malignant melanoma occurring in 7 MEN 1 families, all patients exhibiting classic features of MEN 1. Based on these findings and the previous implication of multiple melanoma tumor suppressor(s) in 11q, including the MEN1 region, we have investigated the involvement of the MEN1 gene in melanoma tumorigenesis. Mutation analysis was performed on a panel of 39 sporadic metastatic melanomas, 13 melanoma cell lines and 20 melanoma families without CDKN2A or CDK4 germline mutations. In addition, 19 sporadic metastatic tumors were screened for loss of heterozygosity (LOH) in 11q13. LOH was detected in 6 tumors (32%), and in 4 of the tumors the pattern of LOH suggested that the deletion included the MEN1 gene locus. A novel somatic nonsense mutation in exon 7 (Q349X) was identified in 1 sporadic tumor which also showed loss of the wild-type allele. We conclude that the MEN1 gene plays a role in the tumorigenesis of a small subgroup of melanoma.

Adult↗
PubMed2000

Hereditary cutaneous melanoma.

Members of some kindreds have a hereditary predisposition for development of cutaneous melanoma. Cytogenetic and linkage studies implicated chromosomes 1p and 9p as possible locations for genetic alterations predisposing for melanoma. Germline mutations in the CDKN2A gene on chromosome 9p21 have been identified in hereditary melanoma, but are present in only approximately 40% of kindreds with linkage to 9p21, indicating that changes in other gene(s) at this location may also predispose to melanoma. In a few families, germline mutations in the CDK4 gene are present. The genetic alterations underlying disease predisposition in a large proportion of melanoma families remain unknown.

Chromosome Mapping↗
PubMed2000

[Traumatic dislocation of the tibialis posterior tendon].

Traumatic dislocations of the tibialis posterior tendon are a rare entity compared to other injuries of the ankle joint. It should be considered if the patient presents with the mechanism of an ankle sprain in combination with severe pain in the region of the internal malleolus. We report of two cases of a traumatic dislocation of the tibialis posterior tendon and discuss the clinical image and the operative treatment.

Adult↗
PubMed2000

[A typical snowboarding injury--fracture of the processus lateralis tali].

Before the development of the snowboard sport, the fracture of the lateral process of the talus was a very rare injury. Since the increasing popularity of snowboarding, starting in Europe at about 1980, these fractures occurred more frequently. The largest epidemiological serie from Kirkpatrick in 1998 reports an incidence of 2.3% of all snowboarding injuries representing 15% of all snowboarding ankle injuries [1]. The common mechanism for fracture is dorsiflexion of the ankle and inversion of the hindfoot. Early diagnosis is emphasized in all series reviewed in the literature to prevent long-term complications [4]. Because routine radiographs failed to determine either the size or comminution of the fractured process, CT imaging was used to accurately assess the size, displacement, and comminution of the fractured process. CT scans also showed the extent of subtalar joint involvement, any associated tendon pathology, or additional fractures [5]. Many of these fractures are not visible on plain radiographs and require computed tomography imaging to be diagnosed. Diagnosis of this fracture pattern is paramount; the physician should be very suspicious of anterolateral ankle pain in the snowboarder, where subtle fractures that may require surgical intervention can be confused with anterior talofibular ligament sprains [1]. Most authors agree, that nondisplaced fractures are best treated with cast immobilization and that displaced fractures require a surgical treatment: Single large displaced fragments are reduced and internally fixed, small displaced or comminuted fragments may need surgical excision. After two to three days bedrest with elevated leg, ambulation is started under partial weight bearing of 10-15 kg for 6 weeks. Physicians caring for snowboarders should look specifically for fracture of the lateral process of the talus in a snowboarder with a lateral ankle or foot injury [3]. This fracture can mimic a lateral ankle sprain, yet the fracture is easily missed on plain radiographs of the ankle. Because displaced or comminuted fractures can cause long-term disability, primary care physicians and specialists alike need to be aware of the association of this fracture with snowboarding [3].

Athletic Injuries↗
PubMed2000

Incidence and clinical pattern of the abdominal compartment syndrome after "damage-control" laparotomy in 311 patients with severe abdominal and/or pelvic trauma.

OBJECTIVE: To investigate the incidence, main physiologic effects, and therapeutic management of the abdominal compartment syndrome (ACS) after severe abdominal and/or pelvic trauma. DESIGN: Retrospective analysis from January 1991 to December 1996; prospective study from January 1997 to August 1998. SETTING: Level I trauma center, intensive care unit. PATIENTS: A total of 311 patients with severe abdominal and/or pelvic trauma and "damage-control" laparotomy on day of admission. INTERVENTIONS: The ACS was defined as the development of significant respiratory compromise, including elevated inspiratory pressure of >35 mbar, a decreased Horowitz quotient (<150 torr [<20 kPa]), renal dysfunction (urine output, <30 mL/hr), hemodynamic instability necessitating catecholamines, and a rigid or tense abdomen. Beginning with January 1997, urinary bladder pressure as an additional variable for the diagnosis of ACS was continuously measured in patients (n = 12) at risk. Bladder pressures of >25 mm Hg indicated ACS. MEASUREMENTS AND MAIN RESULTS: Seventeen patients (5.5%) developed ACS because of persistent intra-abdominal/retroperitoneal bleeding (n = 12; 70.6%) or visceral edema (n = 5; 29.4%). All patients with ACS underwent primary fascial closure. In eight of these patients (47%), abdominal and/or pelvic packing for hemostasis was performed. All patients with ACS required decompressive emergency laparotomies because of physiologic derangements. The time between primary laparotomy and decompressive laparotomy was 12.9 +/- 2.0 hrs. Emergency decompression of the abdomen resulted in a significant increase in the cardiac index (+146%), tidal volume (+133%), Horowitz quotient (+156%), and urine output (+1557%), whereas bladder pressure (-63%), heart rate (-19%), central venous pressure (-30%), pulmonary artery occlusion pressure (-43%), peak airway pressure (-31%), partial pressure arterial carbon dioxide (-30%), and lactate (-40%) markedly (p < .05) decreased. In two multiply injured patients with additional head trauma, ACS caused a critical increase of the intracranial pressure, which markedly dropped after the release of abdominal tension. CONCLUSIONS: Risk factors for the occurrence of ACS are severe abdominal and/or pelvic trauma, which require laparotomy and packing for the control of hemorrhage. The ACS occurs within hours and causes life-threatening physiologic derangements and a critical rise in intracranial pressure in patients with combined abdominal/pelvic and head trauma. Decompressive laparotomy immediately restores impaired organ functions. In patients at risk, the continuous measurement of urinary bladder pressure as a simple, noninvasive, and less expensive diagnostic tool for early detection of elevated intra-abdominal pressure is mandatory.

Abdomen↗
PubMed1999

Endocytosis of heparin-binding protein (CAP37) is essential for the enhancement of lipopolysaccharide-induced TNF-alpha production in human monocytes.

Heparin-binding protein (HBP), also known as CAP37, is a proteolytically inactive serine protease homologue that is released from activated granulocytes. However, HBP is not a biologically inactive molecule but rather a multifunctional protein with properties that include the enhancement of LPS-induced TNF-alpha production from monocytes. We have previously demonstrated that HBP is internalized in monocytes. In the current study, we hypothesize that HBP is internalized in monocytes via endocytosis, and this internalization is an important mechanism by which HBP enhances LPS-induced TNF-alpha release. Using whole blood from healthy donors and flow cytometry, we found that colchicine (0.1-10 mM), cytochalasin D (1000 microM), NH4Cl (10-50 mM), and bafilomycin A1 (0.1-3 microM) significantly reduced the affinity of FITC-HBP for CD14-positive monocytes. Using isolated human monocytes and ELISA, we found that colchicine (0.1 mM), cytochalasin D (30 and 300 microM), NH4Cl (30 mM), and bafilomycin A1 (1 microM) significantly reduced the effect of HBP (10 microg/ml) to enhance LPS (10 ng/ml)-induced TNF-alpha release after 24 h. These findings demonstrate that internalization of HBP in monocytes is essential for the enhancement of LPS-induced TNF-alpha release. Transport of HBP to an activating compartment depends on intact F-actin polymerization and endosomal acidification, an important mechanism for endosomal protein sorting and trafficking.

Adjuvants, Immunologic↗
PubMed1999

[Combined surgery for fractures of the thoraco-lumbar junction using the inlay-span method].

The combined intervention of thoracolumbar fractures using the graft inlay technique. Instable fractures of the thoracolumbar junction must be reduced in an open or closed fashion and fixed internally. Clearance of the spinal channel in case of obstruction is mandatory followed by reconstruction of the anterior part of the spine. Using the combined interventions of transpedicular screw techniques and antero-lateral approaches (transthoracal or retroperitoneal) instable fractures of the thoracolumbar junction can be fixed in comparison to the dorsal intervention the anterior approach is very demanding. The proximity of the big vessels as well as thoracal and abdominal organs and the available space to place the implants need exact preoperative planning. The indications for reconstruction of the anterior part of the spine are influenced by the fracture types and localisations as well as biomechanical considerations. One of the many possibilities to reconstruct the anterior part of the spine is the graft inlay technique, which can be used for mono- or bisegmental spondylodesis. Despite the biological advantages in terms of fusion rates substantial complications can occur using this method for anterior reconstruction of the spine.

Bone Plates↗
PubMed1999

[Duodenal injuries in abdominal trauma].

BACKGROUND: We retrospectively reviewed our patients between 1988 and 1996 with duodenal injuries to demonstrate the diagnostic and therapeutic management. MATERIAL AND METHODS: The charts of six patients treated in the Division of Traumatology of the University Hospital of Zurich between 1988 and 1996 have been retrospectively reviewed. The mean age was 25 years. In four patients a blunt trauma and in two patients a two gunshot caused the duodenal injury. The injury was classified with the "Duodenum Organ Injury Scale". RESULTS: The primary repair was successful in three patients, twice a Roux-en-Y duodenojejunostomy with repair of the biliary tract was performed and once a conservative treatment was chosen. No surgery related complications occurred. Two patients died postoperatively because of associated injuries. CONCLUSIONS: Duodenal injuries are rare and therefore correct diagnosis and treatment is difficult. In case of penetrating trauma or hemodynamic instable patients following blunt trauma the emergent laparotomy is mandatory. CT scan is recommended in cases of hemodynamic stable patients after blunt trauma. Primary repair is the treatment of choice in the majority of duodenal injuries.

Abdominal Injuries↗
PubMed1999

Heparin and enoxaparin enhance endotoxin-induced tumor necrosis factor-alpha production in human monocytes.

OBJECTIVE: To determine whether heparin or the low-molecular-weight heparin enoxaparin alter lipopolysaccharide (LPS)-induced monocyte activation. SUMMARY BACKGROUND DATA: Heparin is widely used in clinical practice to inhibit the coagulation cascade. However, heparin also is a naturally occurring glucosaminoglycan and a pleiotropic immunomodulator that binds to a variety of proteins. LPS is a component of gram-negative bacteria and is thought to be responsible for many of the deleterious effects seen in sepsis. The binding of LPS to CD14 induces a signaling cascade that results in the release of many inflammatory mediators, including tumor necrosis factor-alpha (TNF-alpha). METHODS: Monocytes from healthy volunteers were isolated and cultured in the presence of saline, LPS (10 ng/ml), heparin (0.1 to 1000 microg/ml), or enoxaparin (0.1 to 1000 microg/ml). In blocking experiments, cells were pretreated for 60 minutes with the monoclonal anti-CD14 antibody MY4 (10 microg/ml) or with isotype-matched control IgG2 (10 microg/ml). TNF-alpha values were measured with enzyme-linked immunosorbent assay. Significance was assessed with analysis of variance. RESULTS: Heparin (10 to 1000 microg/ml) and enoxaparin (1000 microg/ml) significantly enhanced LPS-induced TNF-alpha release. Heparin (1000 microg/ml) or enoxaparin (1000 microg/ml) did not produce TNF-alpha in the absence of LPS. Blockade of CD14 abrogated both LPS-induced TNF-alpha release and the effect of heparin or enoxaparin to enhance LPS-induced TNF-alpha release. CONCLUSIONS: The effect of heparin to enhance LPS-induced TNF-alpha release is a biologic phenomenon that reveals a novel and potentially important host defense mechanism during endotoxemia and sepsis. Binding of LPS to CD14 is necessary to induce this phenomenon, suggesting that both heparin and enoxaparin induce signaling mechanisms that are downstream from the initial binding of LPS on CD14.

Anticoagulants↗
PubMed1999

Posterior elbow dislocation with associated vascular injury after blunt trauma.

BACKGROUND: Injury of the brachial artery is a rare (5-13%) but serious complication after closed elbow dislocation without associated fractures. METHOD: Retrospective analysis of long-term results (mean, 4.1 years) in four patients. RESULTS: All patients underwent emergency repair of the arterial injury within 2.5 hours. In three patients, a reversed saphenous vein graft was used; in one patient the artery was sutured. This latter patient needed another operation with interposition of a reversed saphenous graft, because the primary anastomosis occluded. The capsule and the collateral ligaments were immediately reconstructed in three patients because of instability. No patient showed claudication of the arm. In three patients, a sensory deficiency of median nerve persisted. Average range of motion was 128 degrees of flexion (120-135 degrees) and an extension deficit of 7.5 degrees (15-0 degrees). CONCLUSION: Primary repair of vascular injury after closed elbow dislocation with vein graft and immediate reconstruction of ligamentous injuries results in good long-term functional outcome.

Adult↗
PubMed1999

Internal fixation of distal radius fractures with dorsal dislocation: pi-plate or two 1/4 tube plates? A prospective randomized study.

BACKGROUND: Severely comminuted distal radius fractures can be treated by different methods. Our routine procedure in dorsal dislocated fractures is the dorsal stabilization with two 1/4 tube plates. The new pi-plate is an other device that matches optimally the anatomy of the distal radius and allows a near half-circumferential dorsal buttress of comminuted intraarticular and extra-articular radial fractures. METHODS: In a prospective randomized study, comminuted distal radius fractures with dorsal displacement were stabilized either with two 1/4 tube plates or with the pi-plate. All patients were reviewed at 1, 3, and 6 months after surgery by thorough clinical examination and standard radiographs of both wrists. Results were analyzed and compared in both groups. RESULTS: Subjective and objective results in the pi-plate group are disappointing. Although optimal anatomic results were achieved, the complication-rate was high (14.3%) and the range of motion was limited. At final review, extension and flexion of the injured wrist had recovered to an average of 67% of the normal, contralateral side. Radial and ulnar deviation were limited to 64%, whereas pronation and supination reached 89% and 87%, respectively. Overall, results were good to excellent only in 56%. In a comparable group of patients with similar fractures and stabilization with two 1/4 tube plates, 82% of patients achieved excellent to good results, wrist motion was significantly better (p < 0.05), and no complications occurred. CONCLUSION: With open reduction, cancellous bone grafting, and internal plate fixation in comminuted distal radial fractures, excellent results can be achieved. In our experience, we cannot recommend the 7pi-plate in its current shape and prefer to stabilize distal radius fractures and dorsal fragment dislocations with two 1/4 tube plates.

Adolescent↗