Biomedical subjects
Publications and source records attributed to T Kessler.
Avulsion fractures of the tibial tuberosity are rare. In general, juvenile male athletes sustain this fracture. A combination of Ogden type 3A fracture in combination with a posterior fracture of the proximal tibial epiphysis type Salter 2 is described for the first time. The necessity for immediate surgical intervention to prevent secondary soft tissue injury is stressed.
The increasing prevalence of Parkinson syndrome and its cost-intensive modern therapies make for a growing economic burden. Studies on cost to date have limited validity owing to the various methods employed (retrospective, focus on partial expenses, minimal case numbers, etc.). The present study collected data pertaining to direct costs. Seventy-seven patients were followed for 10 months. They had been outpatients when enrolled in the study. Hospitalization or comparable changes during the course of observation were registered accordingly. The most significant result revealed by the study is that expenses for medication by far take up the biggest share of the direct costs. In the early stage of the disease (H and Y I), the monthly costs of drug treatment amount to 397.67 Euros. With advancing ailment, costs rose to 561.56 Euros in H and Y 2, 588.30 Euros in H and Y 3, 604.86 Euros in H and Y 4, and 645.77 Euros in H and Y 5. (Average costs for disease remedies amount to 25.46 Euros.) Inpatient costs were 13.47 Euros (with DBS, 19.04 Euros). Adjuvants aggregated to 3.50 Euros per month, medical technical diagnostic workup to 18.74 Euros (47.60 Euros including DBS), and medical services to 15.73 Euros.
In analogy to solid neoplasms, accumulating data suggest the requirement of angiogenesis also for the development and progression of hematopoietic malignancies including acute myeloid leukemia (AML). Inhibition of increased microvessel density in bone marrow (BM) might be a promising target for pharmacological interventions aimed at reducing disease activity. Among the putative inhibitors of angiogenesis, thalidomide has demonstrated a considerable efficacy in myelodysplastic syndromes (MDS) and AML with overall response rates up to 56% and 25%, respectively. Responders experienced hematologic improvements with increased hemoglobin and platelet counts resulting in temporary transfusion independence. In AML, partial responses--defined as reduction of the leukemic blast cell infiltration of at least 50% in BM--occurred in four of 20 patients after one month of thalidomide administration in a previous phase I/II study. Additionally, we observed a long-term response in one AML patient of more than 20 months, meanwhile fulfilling the criteria of complete remission. The decrease in leukemic blast infiltration in BM of responders was accompanied by a significant reduction of the microvessel density. Overall adverse events caused by the drug consisted mainly of fatigue, constipation, skin rash and polyneuropathy with a tolerable dose of 200-400 mg p.o. per day. In conclusion, thalidomide as a single agent has significant anti-leukemic activity with some evidence for anti-angiogenic effects in BM, although the precise mechanism of action remains to be elucidated.
Imaging guidelines have been proposed by the German Society of Ultrasonography (DEGUM, 1996) for the locomotor apparatus using five standardized sections of the elbow that allow a reproducible presentation of the surrounding soft tissues and cortical landmarks of this joint. Intra-articular fractures form a variable amount of hematoma, which is easily detected by ultrasound using the proposed standardized sectional planes. Ultrasonography is a cost-effective, easy-to-use and radiation-free method to exclude intra-articular fractures of the elbow. Intra-articular effusions and effusions besides the radial head are indirect signs of bony involvement. Suspected radial head injuries in children and adults can easily be examined by ultrasound. Detection of intra-articular effusions may then lead to further investigation with magnetic resonance imaging (MRI) when needed. MRI is unnecessary when ultrasonography shows no effusions in elbow injuries.
OBJECTIVE: To evaluate the influence of plum-, cranberry- and blackcurrant juice on urinary stone risk factors. DESIGN: Investigations were carried out in 12 healthy male subjects aged 18-38 y. All subjects received a standardized diet formulated according to the dietary recommendations of the German Society of Nutrition. The subjects provided 24 h urine collections in a control, three loading phases. In each loading phase a neutral mineral water was substituted for 330 ml of the particular juice. RESULTS: Cranberry juice decreased the urinary pH, whereas the excretion of oxalic acid and the relative supersaturation for uric acid were increased. Blackcurrant juice increased the urinary pH and the excretion of citric acid. The excretion of oxalic acid was increased too. All changes were statistically significant. The plum juice had no significant effect on the urinary composition. CONCLUSION: It is concluded that blackcurrant juice could support the treatment and metaphylaxis of uric acid stone disease because of its alkalizing effect. Since cranberry juice acidifies urine it could be useful in the treatment of brushite and struvite stones as well as urinary tract infection. SPONSORSHIP: Funded by our own Division respectively the University.
Vascular endothelial growth factor (VEGF) and its cellular receptor VEGFR-2 have been implicated as the main endothelial pathway required for tumor neovascularization. However, the importance of the VEGF/VEGFR-2 system for angiogenesis in hematologic malignancies such as AML remains to be elucidated. In 32 patients with newly diagnosed untreated AML, we observed by immunohistochemical analysis of bone marrow biopsies significantly higher levels of VEGF and VEGFR-2 expression than in 10 control patients (P <0.001). In contrast, VEGFR-1 staining levels in AML patients were in the same range as in the controls. Expression of VEGF and VEGFR-2 was significantly higher in patients with a high degree of microvessel density compared to those with a low degree (VEGF: P =0.024; VEGFR-2: P =0.040) and correlated well with bone marrow microvessel density (r(s)=0.566 and 0.609, respectively; P <0.001). Furthermore, in patients who achieved a complete remission following induction chemotherapy VEGFR-2 staining levels decreased into the normal range. In conclusion, our results provide evidence for increased expression of VEGF/VEGFR-2 of leukemic blasts and correlation with angiogenesis in the bone marrow of AML patients. Thus, VEGF/VEGFR-2 might constitute promising targets for antiangiogenic and antileukemic treatment strategies in AML.
OBJECTIVES: Surgery of ruptured abdominal aortic aneurysms is associated with a high mortality rate, mostly related to multi-organ-failure after a prolonged intensive care therapy. In a retrospective study attempts are made to identify individual organ-dysfunction risk profiles influencing the outcome. METHODS: Fifty seven patients (53 men, 4 women, mean age 71.8 +/- 8.8 years) with ruptured abdominal aortic aneurysms underwent graft replacement in a three year period. Fourty eight preoperative, 13 intraoperative and 34 postoperative variables were analyzed. A multi-organ dysfunction (MOD) score was used. RESULTS: The perioperative mortality rate was 31%. Significance of pre-existing risk factors at admission was identified only for cardiovascular diseases. Multiple linear regression analysis indicated that hemoglobin < 90 g/l, systolic blood pressure < 80 mmHg and ECG signs of ischemia at admission are highly significant risk factors. Patients, who died later than 48 hours postoperatively, deceased mainly from MOD (93%) and required intensive care significantly longer than surviving patients (p < 0.0005). All patients with a MOD score > or = 4 died (n = 7). These patients required 26% of all ICU-days and 72% of the ICU-days of the nonsurvivors. CONCLUSION: Patients with ruptured aortic aneurysms should not be excluded from treatment. However, a physiological scoring system after 48 h appears justifiable in order to decide on the appropriateness of continued ICU support.
The process of new blood vessel growth from existing vasculature, known as angiogenesis, is critical to several pathological conditions, most notably cancer. Both MMP2, which degrades the extracellular matrix (ECM), and integrin alpha(V)beta(3), which contributes to endothelial cell attachment to the ECM, are critically involved in this process. Recent findings have shown that MMP2 is localized in an active form on the surface of invasive endothelial cells based on its ability to directly bind integrin alpha(V)beta(3), suggesting that disrupting this protein--protein interaction may represent a new target for the development of angiogenesis inhibitors. The screening of small molecule libraries led to the identification of compounds which disrupt the MMP2--alpha(V)beta(3) interaction in an in vitro binding assay. A prototypical inhibitor was further found to prevent the degradation of the protein matrix without directly inhibiting MMP2 activity or disrupting the binding of alpha(V)beta(3) to its classical ECM ligand, vitronectin. The synthesis and screening of analogues and substructures of this lead compound allowed the identification of requisite structural features for inhibition of MMP2 binding to alpha(V)beta(3). This led to the synthesis of a more water-soluble derivative which maintains the in vitro biological properties and has potent antiangiogenic and antitumor activity in vivo, validating the target as one useful for therapeutic intervention.
Matrix metalloproteinase 2 (MMP2) can associate with integrin alpha(v)beta3 on the surface of endothelial cells, thereby promoting vascular invasion. Here, we describe an organic molecule (TSRI265) selected for its ability to bind to integrin alphav(v)beta3 and block alpha(v)beta3 interaction with MMP2. Although disrupting alpha(v)beta3/MMP2 complex formation, TSRI265 has no effect on alpha(v)beta3 binding to its extracellular matrix ligand vitronectin and does not influence MMP2 activation or catalytic activity directly. However, TSRI265 acts as a potent antiangiogenic agent and thereby blocks tumor growth in vivo. These findings suggest that activated MMP2 does not facilitate vascular invasion during angiogenesis unless it forms a complex with alpha(v)beta(3) on the endothelial cell surface. By disrupting endothelial cell invasion without broadly suppressing cell adhesion or MMP function, the use of compounds such as TSRI265 may provide a novel therapeutic approach for diseases associated with uncontrolled angiogenesis.
Viral vectors based on lentiviruses, such as the human immunodeficiency virus, are able to transduce a broad spectrum of nondividing cells in vivo. This ability of lentiviral vectors makes them an attractive vehicle for gene transfer into the liver. In order to determine the requirements for efficient lentiviral gene transfer, we used a fluorescence imaging system, which allows the detection of cells and tissues that express fluorescent reporter genes (e.g., green fluorescence protein) in the living animal. We show that the latest generation of lentiviral vectors efficiently transduces the murine liver. Further analysis demonstrated that neither cell-cycle activation nor division of liver cells is a prerequisite for lentiviral gene transfer in vivo.
Angiogenesis in Patients with Hematologic Malignancies The importance of angiogenesis for the progressive growth and viability of solid tumors is well established. Emerging data suggest an involvement of angiogenesis in the pathophysiology of hematologic malignancies as well. Recently, we and others have reported increased angiogenesis in the bone marrow of patients with acute myeloid leukemia (AML) and normalization of bone marrow microvessel density when patients achieved a complete remission (CR) after induction chemotherapy. Tumor angiogenesis depends on the expression of specific mediators that initiate a cascade of events leading to the formation of new microvessels. Among these, VEGF (vascular endothelial growth factor), FGF (fibroblast growth factor) and angiopoietins play a pivotal role in the induction of neovascularization in solid tumors. These cytokines stimulate migration and proliferation of endothelial cells and induce angiogenesis in vivo. Recent data suggest an important role for these mediators in hematologic malignancies as well. Isolated AML blasts overexpress VEGF and VEGF receptor 2. Thus, the VEGF/VEGFR-2 pathway can promote the growth of leukemic blasts in an autocrine and paracrine manner. Therefore, neovascularization and angiogenic mediators/receptors may be promising targets for anti-angiogenic and anti-leukemic treatment strategies. The immunomodulatory drug thalidomide inhibits angiogenesis in animal models. Moreover, it has significant activity in refractory multiple myeloma. In a current phase II study for patients with primary refractory or relapsed multiple myeloma using a combination of thalidomide with hyperfractionated cyclophosphamide and dexamethasone (Hyper-CDT), we observed a partial remission in 12 of 14 evaluable patients (86%). Thus, this combination seems to be very potent. Furthermore, we evaluated the safety and efficacy of thalidomide in patients with AML not qualifying for intensive cytotoxic chemotherapy. 20 patients aged 58-85 (median 69) years were recruited to this phase I/II study and were treated with a dose of 200-400 mg per os daily for a duration of 1-40 (median 6) weeks, dependent on the individual tolerability of the drug. In 4 patients we observed a partial response (PR - defined as more than 50% reduction in leukemic blast infiltration in the bone marrow). This was accompanied by an increase in platelet counts and hemoglobin values. One additional patient showed a significant improvement of peripheral blood counts without fulfilling the criteria of a PR. In parallel, we observed a significant decrease in microvessel density in these 5 patients during treatment with thalidomide. In conclusion, thalidomide seems to have anti-angiogenic as well as anti-leukemic activity in AML. The VEGF/VEGFR-2 pathway seems to play an important role in AML. Therefore, receptor tyrosine kinase inhibitors like SU5416 or SU6668 are currently evaluated in the context of phase II studies in AML. We could recently induce a stable remission in a patient with second relapse of her AML refractory towards chemotherapy by administration of SU5416 (compassionate use), a tyrosine kinase inhibitor of VEGFR-2 and ckit. Current and future studies will clarify the role of anti-angiogenic treatment strategies in AML and other hematologic malignancies.
Exertional rhabdomyolysis is a potentially dangerous condition that involves release of intracellular contents from skeletal muscle in concentrations that may cause renal or other systemic complications. The purpose of the two case reports presented is to assist clinicians in recognizing this condition and in considering its predisposing factors. This paper describes two patients who, in the presence of several predisposing risk factors, developed exertional rhabdomyolysis. After diagnoses of rhabdomyolysis were reached, both patients were admitted to a local hospital for several days of monitoring and treatment. After 1 to 2 months of activity modification, both patients successfully resumed full physical activity and military duty.
Recategorization at a higher level reduces tensions between groups. However, recategorization may cause conflicts between the common in-group and a new out-group. Additionally, determinants of conflict between subgroups may enhance conflict at the higher categorization level. In the context of German unification, the authors explored these suggestions with an East German 3-wave longitudinal study and a West German control group. Results show that a salient East German versus West German categorization enhances conflict between subgroups, whereas categorization as German enhances conflict at the common in-group level. Determinants of subgroup conflict also influence conflict at the inclusive level (Germans and foreigners). Thus, recategorization is a 2-edged instrument: Although it reduces conflict at the subgroup level, it may initiate conflict at the common in-group level.
Modulation of the balance between pro- and antiangiogenic factors holds great promise for the treatment of a broad spectrum of human disease ranging from ischemic heart disease to cancer. This requires both the identification of angiogenic regulators and their efficient delivery to target organs. Here, we demonstrate the use of a noncatalytic fragment of matrix metalloproteinase 2 (termed PEX) delivered by lentiviral vectors in different angiogenesis models. Transduction of human endothelial cells with PEX virus suppressed endothelial invasion and formation of capillary-like structures without affecting chemotaxis in vitro. Lentiviral delivery of PEX blocked basic fibroblast growth factor-induced matrix metalloproteinase 2 activation and angiogenesis on chicken chorioallantoic membranes. PEX expression also inhibited tumor-induced angiogenesis and tumor growth in a nude mouse model. Thus, our study shows that lentiviral vectors can deliver sufficient quantities of antiangiogenic substances to achieve therapeutic effects in vivo.
Between January 1994 and August 1998, 12 patients with 13 chronic infections after resection arthroplasty were treated successfully with vastus lateralis muscleflap. One patient was suffering from chronic infection on both sides. In all cases we found the infected cavity to be the origin of the persistent infection. The average duration of infection was 8.3 months. The patients had undergone an average of 3.8 operations. Up to now there was no recurrent infection, controlled by clinical investigation, ultrasound and laboratory findings in all 13 cases. Follow up investigation occurred 2.5 years (1.5-4.7) after flap transfer. The flap is easy to harvest. He has a very constant pattern of vascular pedicle and a wide arc of rotation. The functional deficits of donor side morbidity are minimal. That vastus lateralis flap seems to be an ideal procedure to stop draining infections due to infected cavities in the hip region.
In contrast to motivational accounts of the personal-group discrepancy, results from this article suggest that the discrepancy is explained by aggregating different sets of comparison outcomes for either personal or group ratings. Results from a longitudinal study with East German (the minority group) and West German (the majority group) samples confirm the personal-group discrepancy and support our approach. First, social comparisons influenced evaluations of economic situation at both group and personal levels. Second, ratings of group versus personal economic situation were based on different sets of comparisons. Third, the mean structure of both sets of comparison outcomes mirrored the personal-group discrepancy. Fourth, an interaction between personal-group discrepancy and group status supported the authors' suggestions-concerning the direction of the discrepancy.
OBJECTIVES: in a retrospective study, attempts have been made to identify individual organ-dysfunction risk profiles influencing the outcome after surgery for ruptured abdominal aortic aneurysms. METHODS: out of 235 patients undergoing graft replacement for abdominal aortic aneurysms, 57 (53 men, four women, mean age 72 years [s.d. 8.8]) were treated for ruptured aneurysms in a 3-year period. Forty-eight preoperative, 13 intraoperative and 34 postoperative variables were evaluated statistically. A simple multi-organ dysfunction (MOD) score was adopted. RESULTS: the perioperative mortality was 32%. Three patients died intraoperatively, four within 48 h and 11 died later. A significant influence for pre-existing risk factors was identified only for cardiovascular diseases. Multiple linear-regression analysis indicated that a haemoglobin <90 g/l, systolic blood pressure <80 mmHg and ECG signs of ischaemia at admission were highly significant risk factors. The cause of death for patients, who died more than 48 h postoperatively, was mainly MOD. All patients with a MOD score >/=4 died (n=7). These patients required 27% of the intensive-care unit (ICU) days of all patients and 72% of the ICU days of the non-survivors. CONCLUSION: patients with ruptured aortic aneurysms from treatment should not be excluded. However, a physiological scoring system after 48 h appears justifiable in order to decide on the appropriateness of continual ICU support.
Urine volume is the greatest risk factor for nephrolithiasis. High fluid intake is the first general advice given to stone-forming patients for the prevention of their recurrence. The aim of the present study was to evaluate the influence of bicarbonate-rich mineral water (1715 mg bicarbonate/l) on urinary-stone risk factors in comparison with sodium potassium citrate, a well-established treatment for urinary stones. The mineral water and sodium potassium citrate were administered in equimolar concentrations, with respect to the alkali load. All investigations were carried out in healthy male subjects aged 23-38 years. The study followed a cross-over design. All subjects received a standardized diet during the cross-over phase, which was formulated according to the dietary recommendations of the German Society of Nutrition (Deutsche Gesellschaft für Ernährung, 1996). On the loading day of the cross-over phase, fruit tea was substituted for either mineral water or sodium potassium citrate dissolved in fruit tea. The treatment offered during the second part of the cross-over phase was continued for a 4-week follow-up under normal dietary conditions. During the cross-over phase, there was a significant increase in urinary pH (p < 0.001). There was also a significant increase in the excretion of citric acid (P < 0.01), a decrease in the excretion of oxalic acid, and therefore a decrease in the relative supersaturations for calcium oxalate and uric acid. In the follow-up phase also, the relative supersaturations decreased and there were beneficial effects on the other urinary variables. The effect of the bicarbonate-rich mineral water was similar to that of the sodium potassium citrate, which suggests that it could be useful in the prevention of the recurrence of calcium oxalate and uric acid stones.