Biomedical subjects

J Haier

Publications and source records attributed to J Haier.

At least 19 recordsLinked to original sources

PubMed2004

[A multidisciplinary mModule for oncological documentation within a hospital information system].

The follow-up documentation of oncological patients in Germany is inadequate in many cases: it is usually limited to a minimal dataset mandated by the epidemiological tumor registers; it is carried out in a paper-based fashion and rarely in a multi-disciplinary context. Parallel documentation efforts can result in redundant or erroneous data and excess work. The introduction of hospital information systems (HIS) allows the implementation of digital oncological documentation systems integrated in surrounding clinical workflows that can provide access to existing data sources as well as data entry and presentation across departmental boundaries. This concept enables the integration of tumor documentation, quality assurance and process optimization within HIS. Feasibility requirements include a high flexibility and adaptability of the underlying HIS to reach a seamless integration of oncological documentation forms within routine clinical workflows. This paper presents the conceptual design and implementation of a modular oncological documentation system at the Muenster University Hospital that is capable of integrating the documentation requirements of multiple departments within the hospital.

Computer Systems↗

PubMed2004

Role of tumor cell adhesion and migration in organ-specific metastasis formation.

To form clinically evident metastases--the main cause of death in cancer patients--, tumor cells (TC) must complete a highly complex series of steps called the metastatic cascade, including local invasiveness, intravasation, circulation, adhesion and extravasation, survival, proliferation and angiogenesis. Since failure of any one of these steps results in metastatic failure, understanding the metastatic cascade may guide us to new therapeutic concepts. Here we review the role of specific TC adhesion and migration processes for organ-selective metastasis formation. TC adhesion in the microvasculature of host organs is a specific and highly regulated process mainly mediated by selectins for TC/endothelial cell binding and by integrins for TC/extracellular matrix interactions. Defined expression of the adhesion molecules and their corresponding ligands in the host organs and on the TC governs organ-selective non-random TC arrest. TC motility and subsequent chemotactically guided extravasation of adherent cells is the second rate-limiting step in organ-specific metastasis formation. Only if cells have completed adhesion and extravasation the growth of micrometastases and finally clinically evident metastases can occur.

Animals↗

PubMed2003

Multiple co-infections (Mycoplasma, Chlamydia, human herpes virus-6) in blood of chronic fatigue syndrome patients: association with signs and symptoms.

Previously we and others found that a majority of chronic fatigue syndrome (CFS) patients showed evidence of systemic mycoplasmal infections, and their blood tested positive using a polymerase chain reaction assay for at least one of the four following Mycoplasma species: M. fermentans, M. hominis, M. pneumoniae or M. penetrans. Consistent with previous results, patients in the current study (n=200) showed a high prevalence (overall 52%) of mycoplasmal infections. Using forensic polymerase chain reaction we also examined whether these same patients showed evidence of infections with Chlamydia pneumoniae (overall 7.5% positive) and/or active human herpes virus-6 (HHV-6, overall 30.5% positive). Since the presence of one or more infections may predispose patients to other infections, we examined the prevalence of C. pneumoniae and HHV-6 active infections in mycoplasma-positive and -negative patients. Unexpectedly, we found that the incidence of C. pneumoniae or HHV-6 was similar in Mycoplasma-positive and -negative patients, and the converse was also found in active HHV-6-positive and -negative patients. Control subjects (n=100) had low rates of mycoplasmal (6%), active HHV-6 (9%) or chlamydial (1%) infections, and there were no co-infections in control subjects. Differences in bacterial and/or viral infections in CFS patients compared to control subjects were significant. Severity and incidence of patients' signs and symptoms were compared within the above groups. Although there was a tendency for patients with multiple infections to have more severe signs and symptoms (p<0.01), the only significant differences found were in the incidence and severity of certain signs and symptoms in patients with multiple co-infections of any type compared to the other groups (p<0.01). There was no correlation between the type of co-infection and severity of signs and symptoms. The results indicate that a large subset of CFS patients show evidence of bacterial and/or viral infection(s), and these infections may contribute to the severity of signs and symptoms found in these patients.

Adolescent↗

PubMed2001

The role of tumor cell adhesion as an important factor in formation of distant colorectal metastasis.

PURPOSE: The interactions of blood-borne colorectal carcinoma cells with vascular endothelium are important during hematogenous formation of distant metastases. To adhere to the vessel wall, circulating carcinoma cells that come into contact with the microvasculature must resist the attractive forces of the flow of plasma and other circulating cells that tend to detach them from the wall. METHODS: Hydrodynamic adhesion assays have been introduced to mimic the microcirculation and investigate cell adhesion under flow conditions. Different aspects of colorectal cancer cell adhesion during hematogenous formation of distant metastases are summarized and discussed in this review. RESULTS: Adhesion of colorectal carcinoma cells to endothelial cells and extracellular matrix is influenced by the presence of fluid flow. Shear forces alone are able to induce signal transduction events in these cells that result in cell activation and modification of adhesive behavior. CONCLUSIONS: Consideration of fluid dynamics of circulating colorectal cancer cell movement in the microcirculation leads to new knowledge of in vivo processes that are involved in tumor cell adhesion to the vessel wall in host organs. Shear forces have been found to influence adhesive properties of colorectal carcinoma cells to endothelial cells and underlying subendothelial extracellular matrix. Understanding the complex processes involved in tumor cell adhesion may result in the development of novel therapeutic strategies.

Cell Adhesion↗

PubMed2001

Tumor cell adhesion under hydrodynamic conditions of fluid flow.

Current evidence indicates that tumor cell adhesion to the microvasculature in host organs during formation of distant metastases is a complex process involving various types of cell adhesion molecules. Recent results have shown that stabilization of tumor cell adhesion to the microvascular vessel wall is a very important step for successful tumor cell migration and colonization of host organs. We are beginning to understand the influences of fluid flow and local shear forces on these adhesive interactions and cellular responses within the circulation. Mechanosensory molecules or molecular complexes can transform shear forces acting on circulating tumor cells into intracellular signals and modulate cell signaling pathways, gene expression and other cellular functions. Flowing tumor cells can interact with microvascular endothelial cells mediated mainly by selectins, but the strength of these bonds is relatively low and not sufficient for stable cell adhesions. Integrin-mediated tumor cell adhesion and changes in the binding affinity of these adhesion molecules appear to be required for stabilized tumor cell adhesion and subsequent cell migration into the host organ. Failure of the conformational affinity switch in integrins results in breaking of these bonds and recirculation or mechanical damage of the tumor cells. Various cell signaling molecules, such as focal adhesion kinase, pp60src or paxillin, and cytoskeletal components, such as actin or microtubules, appear to be required for tumor cell adhesion and its stabilization under hydrodynamic conditions of fluid flow.

Animals↗

PubMed2000

Tumor cell adhesion of human colon carcinoma cells with different metastatic properties to extracellular matrix under dynamic conditions of laminar flow.

PURPOSE: Shear forces have an important influence on cell adhesion and other cellular functions, and malignant cell lines appear to possess different adhesive properties under static and dynamic conditions. Thus, we analyzed human colon carcinoma cell adhesion under dynamic conditions and examined the interactions of HT-29 colon carcinoma cells of different metastatic properties with various immobilized ECM components. METHODS: Wall shear adhesion threshold (WSAT), dynamic adhesion rate (DAR), and adhesion stabilization rate (ASR) were compared between the cell lines using dynamic conditions in a laminar flow chamber by decreasing the flow (wall shear stress) of cell suspensions. Patterns of cell adhesion under dynamic conditions were compared to adhesive interactions in static microtiterplate assays. RESULTS: Poorly metastatic HT-29P cells adhered six times more than highly metastatic cells to type I collagen under laminar fluid flow, whereas only highly metastatic HT-29LMM showed adhesive interactions with fibronectin under static and dynamic conditions. High rates of cell adhesion to collagen IV were found under static, but not under dynamic, conditions. CONCLUSIONS: Although poorly and highly metastatic HT-29 cells express similar patterns of integrins, they differ in their adhesive properties to ECM components under static and dynamic conditions. Hydrodynamic shear forces appear to influence adhesive properties of HT-29 cells, and differences between dynamic and static cell adhesion were found.

Carcinoma↗

PubMed2000

Cell biology and clinical implications of adhesion molecules in colorectal diseases: colorectal cancers, infections and inflammatory bowel diseases.

Adhesion molecules are transmembrane proteins that can anchor cytoskeletal proteins on the cytoplasmic side of the cell membrane, while also connecting extracellular structures on the outer surface of the cell membrane. In addition to physical linkages between the extracellular environment and the cytoskeleton, adhesive complexes participate in important signal transduction systems as modulators or receptors. Their functions in cell signaling are probably at least as important as their cytoskeletal and cell attachment properties. Understanding these regulatory functions appears to be of importance in determining of pathological characteristic of numerous diseases. Expression and functional activity of various adhesion molecules have been found in different diseases affecting the colorectum. In this review we summarize recent advantages about the cell biology these diseases and clinical implications.

Biology↗

PubMed2000

Cell surface molecules and their prognostic values in assessing colorectal carcinomas.

OBJECTIVE: Carcinomas of the colon and rectum are the third leading cause of cancer-related deaths. Although advances in the surgical treatment of primary colorectal cancers have lead to improvements in patient survival at early tumor stages, treatment of more progressive cancers has not resulted in dramatic improvements in patient survival. However, the selection of patient subgroups based on their prognosis and other characteristics could result in improved outcomes from adjuvant therapies in patients with Dukes B and C carcinomas. METHODS: The authors reviewed the available data on the value of cell surface molecules in assessing the prognosis of colorectal carcinomas, paying specific attention to the evaluation of statistical analysis and multivariate procedures. RESULTS: Cell surface molecules have been identified on colorectal carcinoma cells whose expression appears to be related to malignant transformation, tumor progression, or patient prognosis. Among these cell surface molecules, various cell adhesion molecules, growth factor receptors, proteinases, and their receptors and inhibitors have been identified as potentially useful prognostic markers. CONCLUSIONS: Although data exist on the prognostic values of certain cell surface markers, the use of multivariate analysis for the identification of valuable prognostic factors remains uncommon. Using reproducible and standardized multivariate analysis procedures, new tumor markers should be carefully examined for their biologic and prognostic relevance before being considered as potentially useful in the management of colorectal cancers.

Biomarkers, Tumor↗

PubMed1999

Influence of phosphotyrosine kinase inhibitors on adhesive properties of highly and poorly metastatic HT-29 colon carcinoma cells to collagen.

Organ-specific sites of metastastic lesions are determined in part by integrin-mediated adhesion to extracellular matrix (ECM) components. Using poorly (HT-29P) and highly liver-metastatic (HT-29LMM) colon carcinoma cells we previously found different integrin-mediated adhesion to various ECM components, but similar integrin expression of both cell lines. These HT-29 cell lines were used to study adhesion to collagen I (C I) and possible intracellular signaling mechanisms that could explain different adhesive properties. HT-29LMM cells had significantly poorer rates of adhesion to C I (P < 0.05) than HT-29P cells. For examination of the integrin subunits involved in adhesion to C I, cells were treated with various anti-integrin antibodies. These results demonstrated that adhesion of HT-29 cells to C I is mediated in part by the alpha 2 beta 1 integrin. Using immunoprecipitation and Western blotting, both cell lines expressed similar patterns of integrins (alpha 2, alpha 3, alpha 6, and beta 1). Weaker signals were found for the expression of alpha v and beta 5 integrins. Although poorly and highly metastatic cells possessed different patterns of adhesion to C I, these differences were not caused by different expression of integrin subunits. For investigation of the involvement of phosphotyrosine kinases in adhesion, cells were pretreated with the Erbstatin analog, Genistein, or Herbimycin A. Genistein transiently stimulated the adhesive properties of both cell lines. In contrast, Herbimycin A had biphasic effects. At lower concentrations of Herbimycin A stimulation of adhesion was found after 30 and 90 min. However, higher concentrations inhibited adhesive properties. The stimulatory effect was more pronounced in poorly metastatic HT-29P cells. The Erbstatin analog had no effect, probably because of the lack of epidermal growth factor receptor expression in both cell lines. The results suggest that adhesion of tumor cells to ECM components may be dependent on signal transduction into the cell, and tyrosine phosphorylation appears to be involved.

Benzoquinones↗

PubMed1999

Multiple mycoplasmal infections detected in blood of patients with chronic fatigue syndrome and/or fibromyalgia syndrome.

The aim of this study was to investigate the presence of different mycoplasmal species in blood samples from patients with chronic fatigue syndrome and/or fibromyalgia syndrome. Previously, more than 60% of patients with chronic fatigue syndrome/fibromyalgia syndrome were found to have mycoplasmal blood infections, such as Mycoplasma fermentans infection. In this study, patients with chronic fatigue syndrome/fibromyalgia syndrome were examined for multiple mycoplasmal infections in their blood. A total of 91 patients diagnosed with chronic fatigue syndrome/fibromyalgia syndrome and with a positive test for any mycoplasmal infection were investigated for the presence of Mycoplasma fermentans, Mycoplasma pneumoniae, Mycoplasma hominis and Mycoplasma penetrans in blood using forensic polymerase chain reaction. Among these mycoplasma-positive patients, infections were detected with Mycoplasma pneumoniae (54/91), Mycoplasma fermentans (44/91), Mycoplasma hominis (28/91) and Mycoplasma penetrans (18/91). Multiple mycoplasmal infections were found in 48 of 91 patients, with double infections being detected in 30.8% and triple infections in 22%, but only when one of the species was Mycoplasma pneumoniae or Mycoplasma fermentans. Patients infected with more than one mycoplasmal species generally had a longer history of illness, suggesting that they may have contracted additional mycoplasmal infections with time.

Adult↗

PubMed1999

Beta1-integrin-mediated dynamic adhesion of colon carcinoma cells to extracellular matrix under laminar flow.

To resist substantial wall shear stress exerted by blood flow metastasizing colon carcinoma cells have to form adhesive contacts with endothelial cells and subendothelial extracellular matrix (ECM). At secondary sites tumor cells have to stabilize these initial adhesive interactions to prevent detachment and recirculation. Previously we found that adhesion of colon carcinoma cells to ECM components under static conditions is mediated, in part, by various beta1-integrins. Since other malignant cells possess adhesive properties that are different under static and dynamic conditions, we analyzed human colon carcinoma cell adhesion under flow by decreasing the flow (wall shear stress, WSS) of cell suspensions and allowing cells to interact with collagen-coated surfaces in a laminar flow chamber. HT-29 colon carcinoma cells were used to study wall shear adhesion threshold (WSAT), dynamic adhesion rate (DAR) and adhesion stabilization rate (ASR). DAR was determined after a low flow period using a WSS set at 50% of WSAT. ASR was calculated 60 sec after reestablishment of high WSS. Glass slides were coated with collagen I (C I) or bovine serum albumin (BSA, negative control). In some experiments cells were pretreated with function-blocking anti-beta1 or nonspecific IgG. Rolling of cells occurred on C I- and BSA-coated surfaces at high WSS. By decreasing WSS cell sticking without definite adhesion was found, and cells stuck to BSA at WSS lower than that found for C I. Further decreasing WSS below WSAT enabled stable cell adhesion to C I, but only a few cells adhered to BSA. ASR was found to be 73% of primarily adherent cells (to C I). Pretreatment with anti-beta1 did not affect cell rolling but did inhibit cell sticking and adhesion completely, whereas nonspecific IgG was without effect. Activation of PKC using phorbol ester resulted in an increase of adhesive interactions under dynamic and static conditions, whereas its inhibition reduced adhesion. Adhesive interactions of HT-29 colon carcinoma cells with ECM-coated surfaces under laminar flow conditions occurred in various steps: (1) rolling, (2) sticking or initial adhesion, and (3) stabilization of adhesion. Under shear flow rolling of tumor cells on ECM-coated surfaces appeared to be mediated mainly by physical/mechanical and nonspecific surface-cell membrane interactions, whereas stabilized adhesion to ECM was specifically mediated by beta1-integrin binding to ECM components. PKC seems to be involved in the regulation of adhesion stabilization under static and flow conditions.

Animals↗

PubMed1999

Role of the cytoskeleton in adhesion stabilization of human colorectal carcinoma cells to extracellular matrix components under dynamic conditions of laminar flow.

Adhesion stabilization of malignant cells in the microcirculation is necessary for successful metastasis formation. The adhesion of colon carcinoma cells to microcirculation extracellular matrix (ECM) components is mediated, in part, by integrins that can be intracellularly linked to cytoskeletal proteins. Thus the functional status of at least certain integrins can be regulated by complex interactions with cytosolic, cytoskeletal and membrane-bound proteins. Wall shear stress caused by fluid flow also influences cellular functions, such as cell morphology, cytoskeletal arrangements and cell signaling. Using a parallel plate laminar flow chamber dynamic adhesion of human HT-29 colon carcinoma cells to collagen was investigated and compared with cell adhesion under static conditions. Cells were pretreated with cytochalasin D, nocodazole, colchicine or acrylamide to disrupt actin filaments, microtubules or intermediate filaments. Disruption of actin filaments completely inhibited all types of adhesive interactions. In contrast, impairment of tubulin polymerization or disruption of intermediate filaments resulted in different effects on static and dynamic adhesion. Treatment with acrylamide did not interfere with dynamic cell adhesion, whereas under static conditions it partially reduced adhesion rates. Under dynamic conditions increased initial adhesive interactions between HT-29 cells and collagen were found after disruption of microtubules, and the adherent cells demonstrated extensive crawling on collagen surfaces. In contrast, under static adhesion disrupting microtubules did not affect cell adhesion rates. Cytochalasin D and acrylamide were found to inhibit Tyr-phosphorylation of FAK and paxillin, whereas microtubule disrupting agents at low but not high concentrations increased phosphorylation of these focal adhesion proteins. Our results revealed that cytoskeletal components appear to be involved in adhesion stabilization of HT-29 cells to ECM components, and hydrodynamic shear forces modulate this involvement. Tyr-phosphorylation of focal adhesion proteins, such as paxillin and FAK, appears to be a part of this cytoskeleton-mediated process.

Acrylamide↗

PubMed1999

Different adhesion properties of highly and poorly metastatic HT-29 colon carcinoma cells with extracellular matrix components: role of integrin expression and cytoskeletal components.

Integrin-mediated tumour cell adhesion to extracellular matrix (ECM) components is an important step in the development of metastatic lesions. Thus, integrin expression and integrin-mediated adhesion of colon carcinoma cells to various ECM components was examined. Poorly (HT-29P) and highly (HT-29LMM) liver-metastatic colon carcinoma cells were used to study the rates of adhesion to collagen I (C I), collagen IV (C IV), laminin (LN), fibronectin (FN), or vitronectin (VN) in a static adhesion assay (10-120 min). Cells were untreated or treated with oligopeptides (RGD, GRGDS, YIGSR, RGES), anti-integrin antibodies, or colchicine, nocodazole, cycloheximide, acrylamide or cytochalasin D (to disrupt cytoskeletal structures). Both cell lines expressed similar patterns of integrin expression (alpha2, alpha3, ,alpha6, alphav, beta1, beta4, and beta5) by immunocytochemistry and immunoprecipitation. HT-29LMM cells showed significantly higher rates of adhesion to LN (P < 0.001) and FN (P < 0.001), but significantly poorer rates of adhesion to C I (P < 0.05) and C IV (P < 0.001) than HT-29P cells, respectively, adhesion to VN was insignificant. RGD and GRGDS inhibited HT-29LMM cell adhesion to FN only. Pretreatment with anti-beta, or anti-alpha2 integrin subunits suppressed adhesion to C I and C IV, and adhesion to LN was inhibited with anti-beta1 or anti-alpha6 integrin. Anti-beta1 or anti-alphav blocked adhesion to FN. Pretreatment of cells with cytochalasin D, cycloheximide or acrylamide inhibited adhesive interactions of both cell lines to the ECM components. In contrast, colchicine and nocodazole had no effect. The results demonstrate that adhesion of HT-29 cells to ECM is mediated, in part, by different integrins, depending on the substrate. Poorly and highly metastatic HT-29 cells possessed different patterns of adhesion to the various ECM substrates, but these differences were not due to different expression of integrin subunits. The results also suggested that the initial adhesion of poorly or highly metastatic HT-29 cells to ECM components requires, in part, the presence of native action and intermediate filaments, but not of microtubules. Thus the adhesion of tumour cells to ECM components may be dependent on signal transduction and assembly of microfilaments.

Acrylamide↗

PubMed1999

Detection of mycoplasmal infections in blood of patients with rheumatoid arthritis.

OBJECTIVE: Mycoplasmal infections are associated with several acute and chronic illnesses. Some mycoplasmas can enter a variety of tissues and cells, and cause system-wide or systemic signs and symptoms. METHODS: Patients (14 female, 14 male) diagnosed with rheumatoid arthritis (RA) were investigated for mycoplasmal infections in their blood leucocytes using a forensic polymerase chain reaction (PCR) procedure. Amplification was performed with genus- and species-specific primers, and a specific radiolabelled internal probe was used for Southern hybridization with the PCR product. Patients were investigated for the presence of Mycoplasma spp., and positive cases were further tested for infections with the following species: M. fermentans, M. hominis, M. pneumoniae and M. penetrans. RESULTS: The Mycoplasma spp. sequence, which is not entirely specific for mycoplasmas, was amplified from the peripheral blood of 15/28 patients (53.6%) and specific PCR products could not be detected in 13 patients (46.4%). Significant differences (P < 0.001) were found between patients and positive healthy controls in the genus test (3/32) and in the specific tests (0/32). Moreover, the incidence of mycoplasmal infections was similar in female and male patients. Using species-specific primers, we were able to detect infections with M. fermentans (8/28), M. pneumoniae (5/28), M. hominis (6/28) and M. penetrans (1/28) in RA patients. In 36% of the patients, we observed more than one Mycoplasma species in the blood leucocytes. All multiple infections occurred as combinations of M. fermentans with other species. CONCLUSIONS: The results suggest that a high percentage of RA patients have systemic mycoplasmal infections. Systemic mycoplasmal infections may be an important cofactor in the pathogenesis of RA, and their role needs to be explored further.

Adult↗

PubMed1998

Extent of surgery and recurrence rate of hidradenitis suppurativa.

Hidradenitis suppurativa (HS) is a chronic fistula- and abscess-forming disease of the cutis and subcutis of unknown etiology. Disease recurrence is frequent and may cause severe complications. We analyzed patients with HS who underwent surgery between 1976 and 1997. The operative procedures were divided into drainage procedures (n = 6), limited regional (n = 14), and radical wide excisions (n = 11). The extent of surgery was examined in terms of the clinical course and late postoperative sequelae of HS. At a mean follow-up of 72 months, we found developed locoregional recurrent HS in 45% of patients. There was 100% recurrence after drainage, 42.8% after limited, and 27% after radical excision (P < 0.05). HS recurred after a median interval of 3 months for drainage, 11 months for limited excision, and 20 months for radical excision (P < 0.05). The disease-free interval continued up to 35 months. Long-term sequelae included penile amputation and a case of fatal squamous cell carcinoma. Although radical wide excision of the HS-affected cutis is associated with the lowest recurrence rate, it is still considerable and warrants long-term follow-up.

Adult↗

PubMed1998

[Different integrin-induced adhesion of highly liver metastatic and little metastatic colon carcinoma cells in an extracellular matrix].

Poorly and highly liver metastatic colon carcinoma cell lines have different integrin-mediated adhesion to extracellular matrix. Specific integrin-mediated interactions between tumor cells and extracellular matrix (ECM) in the host organs are important for organ-specific metastasis. In colon carcinoma integrin expression differs depending on the metastatic potential of the tumor. Integrin-mediated adhesion of poorly (HT-29P) and highly liver-metastatic (HT-29LMM) colon carcinoma to extracellular matrix (ECM; Collagen I-C I, Collagen IV-C IV, Laminin LN, Fibronectin FN, Vitronectin VN) was investigated. HT-29LMM showed significant better adhesion to LN (45% vs. 26%; p < 0.001) and FN 20% vs. 1%; p < 0.001). No adhesion was found to VN. RGD-oligopeptides completely inhibited adhesion to FN. Using inhibition with anti-integrin-mAB it was shown, that adhesion to C I and C IV is mediated by alpha 2 beta 1-integrin, adhesion to LN by alpha 6 beta 1 and adhesion to FN by alpha v beta 1. These results have shown that adhesion of HT-29 cells is mediated by different integrins depending on ECM components. Poorly and highly metastatic cells possessed different patterns of adhesion to various substrates.

Cell Adhesion↗

PubMed1997

[Assessment of regional and systemic toxicity of isolated hyperthermic extremity perfusion with tumor necrosis factor-alpha and melphalan].

Following isolated limb perfusion (ILP) with TNF alpha and melphalan the damage to muscle tissue and its systemic consequences in terms of myoglobinemia and myoglobinuria as well as the activation of the cytokine cascade were investigated. We measured the compartmental pressure of the limb during and after perfusion and determined the serum changes of myoglobin, creatine kinase (CK), interleukin (IL)-6, IL-1, s-IL-2-receptor, TNF-receptor, and ICAM-1 levels. The compartmental pressure rose significantly during ILP and decreased after reperfusion. Following its course, the decision whether to perform a fasciotomy or not can be more reliably made. Serum myoglobin levels exceeded 200 times normal values and the increase occurred significantly earlier than that of CK, thus enabling judgement of the risk of renal failure (crush kidney syndrome). The elevation of serum IL-1 and IL-6 values correlated with the frequency of cardiopulmonary problems (hyperdynamic shock) and facilitated counter-maneuvers. Our data, although obtained from ILP with TNF alpha, could be used to monitor toxicity also when other drug regimens are administered.

Adolescent↗

PubMed1997

Rhabdomyolysis and renal function impairment after isolated limb perfusion--comparison between the effects of perfusion with rhTNF alpha and a 'triple-drug' regimen.

The aim of this study was to monitor serum and perfusate levels of myoglobin (MB) and creatine kinase (CK) during isolated limb perfusion (ILP) in order to identify those at risk of renal failure. We investigated the release of MB and CK in 40 patients who underwent ILP for melanoma (n = 15) or sarcoma (n = 25) using rhTNF alpha/melphalan (n = 28) or a triple-drug regimen (n = 12). Serial determinations of CK and MB were performed in both perfusate and systemic circulation during and after ILP and renal function was assessed. A significant increase of MB could be detected in the perfusate during ILP. After ILP, an up to 100-fold increase with a double peak of MB at 4 h and 24 h postoperatively was observed. The maximum elevation of serum activity of CK was at 30 h. The increase for both proteins was highly significant (P < 0.001). ILP with rhTNF alpha/melphalan yielded significantly (P < 0.001) higher serum values of MB and CK and also the impairment of the renal function was more pronounced. The peak values of MB after ILP occur early and allow the patients most at risk of developing renal failure to be identified. Rhabdomyolysis can be detected early by determination of MB from the perfusate. Further measurements twice daily for 2-3 days post ILP from serum samples as well as daily assessment of MB in the urine is helpful for detecting myoglobinuria and imminent renal failure.

Adult↗