[Surgical method in treatment of total kyphosis in ankylosing spondylitis]. / Operationsmethoden zur Behandlung der Totalkyphose bei der Spondylitis ankylosans.

In spite of extensive, conservative methods for treating spondylitis, more or less distinct kyphotic deformities are common. Pain usually plays a minor role as an indication for surgery either as local instability or as impairment of the large hip or knee joints. Much more common are the loss of social contact and the lack of visual contact with the surroundings, both of which the patients find unacceptable. The monosegmental, lumbar correction method as used at an early stage implicated a high rate of complications. The implant supported methods, and in particular those that allow the potential for dorsal transpediculated fixation, allowed, in the early 1980s, dorsal lordotic measures in the form of a multilocus method and, in the mid-1980s, a modified monosegmentary method as well. Both of these methods are widely accepted because of their good long-term results. The possible complications no longer include the disturbance of the spinal cord but are rather to be found in the poor general condition of the patient. The restoration of a largely normal equilibrium of the backbone relieves the musculature and is therefore a definitive pain therapy for muscle tension problems. Straightening the backbone also relieves the hip joints and therefore it is possible in many cases to delay the implantation of a hip prosthesis.

[Treatment of scoliosis and scoliokyphosis in Recklinghausen neurofibromatosis]. / Behandlung der Skoliose und Skoliokyphose bei Neurofibromatosis Recklinghausen (NF).

Spine deformities are a frequent symptom of neurofibromatosis Recklinghausen. Especially NF1 shows next to numerous alterations in the skeleton in some cases massive scoliosis and kyphosis. There are different theories for the development of the spine deformities, one of them is that specific alterations of the vertebra are caused by an elevated intraspinal pressure on the osteoporotic bone. A classification from a clinical point of view discriminates 3 types of severity. Type 1 shows instead of the in x-rays inconspicuous findings neurofibromatosistypical alterations in other diagnostic procedures (e.g. MRI). Extreme variations like short curved scoliokyphosis with massive destruction and severe spine imbalance are described as type 3. Operative treatment is dependent on the severity of the deformity. Intraspinal tumors have to be removed. Because of the elevated neurological risk the proceeding has to be very careful, sometimes there is a temporary Halo-extension necessary. Anterior substance defects are filled with bone or cages. The posterior instrumentation (in most of the cases a 2-rod-stabilization) is performed by transpedicular screws. Frequently there is a concave chest wall plastic (CTP) indicated. To prevent neurological complications early surgical procedure is sometimes necessary. Complications can be reduced by careful proceeding, exact preoperative diagnostic and classification. But next to operative experience a qualified anaesthesiological and intensive care units are absolutely necessary.

Lepirudin (recombinant hirudin) for parenteral anticoagulation in patients with heparin-induced thrombocytopenia. Heparin-Associated Thrombocytopenia Study (HAT) investigators.

BACKGROUND: We prospectively investigated lepirudin for further parenteral anticoagulation in patients with heparin-induced thrombocytopenia (HIT). METHODS AND RESULTS: Patients with confirmed HIT (n=112) received lepirudin according to need for 2 to 10 days (longer if necessary): A1, treatment: 0.4 mg/kg IV bolus, followed by 0.15 mg. kg(-1). h(-1) intravenous infusion, n=65; A2, treatment in conjunction with thrombolysis: 0.2 mg/kg, followed by 0.10 mg. kg(-1). h(-1), n=4; and B, prophylaxis: 0.10 mg. kg(-1). h(-1), n=43. Outcomes from 95 eligible lepirudin-treated patients were compared with those of historical control patients (n=120). Complete laboratory response (activated partial thromboplastin time ratio >1.5 with /=1 outcome (cumulative incidence 30.9% versus 52.1%; relative risk [RR] 0.71; P=0.12, log-rank test). Bleeding events were more frequent in the lepirudin group than the historical control group (cumulative incidence at 35 days, 44.6% versus 27.2%; RR 2.57; P=0.0001, log-rank test). No difference was observed in bleeding events requiring transfusion (cumulative incidence at 35 days, 12.9% versus 9.1%; RR 1.66; P=0.23, log-rank test); no intracranial bleeding was observed in the lepirudin group. CONCLUSIONS: Lepirudin effectively prevents death, limb amputations, and new thromboembolic complications and has an acceptable safety profile in HIT patients. Treatment should be initiated as soon as possible if HIT is suspected.

Recombinant hirudin (lepirudin) provides safe and effective anticoagulation in patients with heparin-induced thrombocytopenia: a prospective study.

BACKGROUND: The immunological type of heparin-induced thrombocytopenia (HIT) is the most frequent drug-induced thrombocytopenia. This study evaluated the efficacy of recombinant hirudin (r-hirudin or lepirudin), a potent thrombin inhibitor, for anticoagulation in patients with confirmed HIT. METHODS AND RESULTS: Eighty-two patients in this prospective, multicenter study received 1 of 4 intravenous r-hirudin regimens: A1, HIT patients with thrombosis (n=51), 0.4-mg/kg bolus and then 0.15 mg. kg-1. h-1; A2, HIT patients with thrombosis receiving thrombolysis (n=5), 0. 2-mg/kg bolus and then 0.1 mg. kg-1. h-1; B, HIT patients without thrombosis (n=18), 0.1 mg. kg-1. h-1; and C, during cardiopulmonary bypass surgery (n=8), 0.25-mg/kg bolus and then 5-mg boluses as needed. Response criteria were increase in platelet count by >/=30% to >10(9)/L and activated partial thromboplastin time (aPTT) values 1.5 to 3.0 times baseline values achieved with a maximum of 2 dose increases. No placebo control was used for ethical reasons. Outcomes of a subset of r-hirudin-treated patients who met predefined inclusion criteria (n=71) were compared with those of a historical control group (n=120) for combined and individual incidences of death, amputations, new thromboembolic complications, and incidences of bleeding. Platelet counts increased rapidly in 88.7% of r-hirudin-treated patients with acute HIT. In regimens A1 and A2, the 25% and 75% quartiles of the aPTT were within the target range at all but 1 time point. The incidence of the combined end point (death, amputation, new thromboembolic complications) was significantly reduced in r-hirudin patients compared with historical control patients (P=0.014). During first selected treatment, the adjusted hazard ratio for r-hirudin patients versus historical control was 0.279 (95% CI, 0.112 to 0.699; P=0.003). Bleeding rates were similar in both groups. CONCLUSIONS: r-Hirudin treatment is associated with a rapid and sustained recovery of platelet counts, sufficient aPTT prolongations, and true clinical benefits for patients with HIT.

Physical performance and cardiovascular and metabolic adaptation of elite female wheelchair basketball players in wheelchair ergometry and in competition.

Spinal cord injury leads to a pronounced reduction of cardiovascular, pulmonary, and metabolic ability. Physical activity, up to and including high-performance sports, has obtained importance in the course of rehabilitation and the postclinical phase. Thirteen elite female wheelchair basketball players from the German National Basketball Team and 10 female sedentary spinal cord-injured persons were examined in the study. Heart volume was measured by an echocardiography. All subjects underwent a graded exercise test on a wheelchair ergometer. Additionally, heart rate, lactate, and player points were measured during a competitive basketball game in wheelchair basketball players. Cardiac dimensions were larger for spinal cord-injured wheelchair basketball players (620.3 ml; 9.6 ml x kg(-1)) in comparison with spinal cord-injured persons (477.4 ml; 8.2 ml x kg(-1)) but did not exceed the heart volume of untrained nonhandicapped persons. In contrast, athletes with amputations or those having had poliomyelitis reached training-induced cardiac hypertrophy in relation to body mass (713.7 ml; 13.2 ml x kg(-1)), as observed in nonhandicapped athletes. During graded wheelchair ergometry, wheelchair basketball players showed a higher maximal work rate (59.9 v 45.5 W), maximal oxygen consumption (33.7 v 18.3 ml x min(-1) x kg(-1)), and maximal lactate (9.1 v 5.47 mmol x l(-1)) without a difference in maximal heart rate and workload at AT4 than did spinal cord-injured persons. The average heart rate during the wheelchair basketball game was 151 x min(-1), and the lactate concentration was 1.92 mmol x l(-1). Female athletes with a less severe handicap and higher maximal oxygen consumption during the graded exercise test reached a higher game level in the evaluation. During the competitive basketball game, high cardiovascular stress was observed, indicating a fast aerobic metabolism; the anaerobic lactic acid capacity played a subordinate role. Wheelchair basketball is an effective and suitable sport to enhance physical performance and to induce positive physiological adaptations.

Treatment of the spondylolisthesis. : Operation in situ or reposition spondylodesis.

The indication for operative treatment of spondylolisthesis in children and juvenile patients relies mainly on the progressive slipping of the vertebra, with consecutive deformation, on the other hand on neurological disorders, that may be seen as rigid lumbar extension with contractation of hip and knee joints. In the adult patient the main reason for treatment is the painful instability, often accompanied by root pain caused by degenerative changes as a result of repairment. The treatment consists of comlete reduction of the slipping vertebra, and reconstruction of the physiological lumbar lordosis through a postolateral and anterior interbody fusion. In case of additional compression of neurological structures, an extensive decompression must be performed. Today it is possible to reposition nearly every spondylolisthesis, even ankylosed spondyloloptosis. In some cases it is necessary to performe the reposition step by step in two sessions in order to allow the neurological structures to accomodate. Finally you reach through a complete reposition a physiological curve with correct impact of the biomechanic forces and a harmonic relation between posterior compression and anterior axial force. A complete reposition with an negativ angle in the slipping segment brings the axial force back into physiological position and prevents early degenerative changes in the neighbouring segments. A posterior fusion in situ can not reduce the pathological biomechanics and has to lead to a high rate of pseudarthrosis with an increase of the anterior slipping. Even anterior fusion only is not sufficient, as the posterior interarticular portion remains divided, the disposition or dysplasia of the facett joints increases the segmentmovement. As a result you see resorption and pseudarthrosis of the anterior fusion. Only in case of undamaged discs and ligaments in juvenile patients without anterior slipping a try with a posterior laminoplastic is allowed.

[Treatment of spondylolisthesis. Operation in situ or repositioning spondylodesis]. / Behandlung der Spondylolisthese. Operation in situ oder Repositionsspondylodese.

The indication for operative treatment of spondylolisthesis in children and juvenile patients relies mainly on the progressive slipping of the vertebra, with consecutive deformation, on the other hand on neurological disorders, that may be seen as rigid lumbar extension with contractation of hip and knee joints. In the adult patient the main reason for treatment is the painful instability, often accompanied by root pain caused by degenerative changes as a result of repairment. The treatment consists of comlete reduction of the slipping vertebra, and reconstruction of the physiological lumbar lordosis through a postolateral and anterior interbody fusion. In case of additional compression of neurological structures, an extensive decompression must be performed. Today it is possible to reposition nearly ever spondylolisthesis, even ankylosed spondyloloptosis. In some cases it is necessary to performe the reposition step by step in two sessions in order to allow the neurological structures to accomodate. Finally you reach through a complete reposition a physiological curve with correct impact of the biomechanic forces and a harmonic relation between posterior compression and anterior axial force. A complete reposition with an negativ angle in the slipping segment brings the axial force back into physiological position and prevents early degenerative changes in the neighbouring segments. A posterior fusion in situ can not reduce the pathological biomechanics and has to lead to a high rate of pseudarthrosis with an increase of the anterior slipping. Even anterior fusion only is not sufficient, as the posterior inter-articular portion remains divided, the disposition or dysplasia of the facett joints increases the segmentmovement. As a result you see resorption and pseudarthrosis of the anterior fusion. Only in case of undamaged discs and ligaments in juvenile patients without anterior slipping a try with a posterior laminoplastic is allowed.

Biological response modifiers render tumor cells susceptible to autologous effector mechanisms by influencing adhesion receptors.

Adhesion molecules such as CD2 and its ligand CD58 (LFA-3), as well as CD11a/18 (LFA-1) and CD54 (ICAM-1) regulate not only cell to cell attachment but also participate in lymphocyte activation, recirculation, and effector function including cytolytic activity towards tumor cells. We have investigated the role of CD2/CD58 and CD11a/18/CD54 interactions in cellular immune responses directed towards freshly recovered human T cell leukemias. Downregulation of CD54 and CD58 were observed to correlate with enhanced numbers of blasts in circulation and lack of susceptibility to killing by autologous cytotoxic lymphocytes. Furthermore, culturing tumor cells with recombinant TNF-alpha conditioned medium resulted in reinduction of CD54 and CD58 expression and susceptibility to lymphocyte mediated resulted in reinduction of CD54 and CD58 expression and susceptibility to lymphocyte mediated lysis in vitro. Our findings support the view that adhesion molecules play a pivotal role for tumor cell biology in vivo and stress the point that successful immunotherapy of malignant disease may be facilitated by influencing not only the immune response itself but also adhesion molecules on the malignant tumor targets.

Spontaneous responsiveness to cytokines by human T-cell leukemias.

The molecular basis for autonomous growth of malignant forms of human T lymphocytes is not known. It can be investigated by functional responses of malignant cells in comparison with untransformed counterparts. At least two pathways (the CD2 and CD3 pathways) of human T-cell activation have been recently defined on the basis of monoclonal antibody activities in vitro, an experimental model exists which can be used to investigate which pathway of T-cell triggering might be involved in malignant growth. In untransformed T lymphocytes, responses to addition of cytokines are strictly controlled by signals which are mediated through triggering molecules including CD2 and CD3 and we therefore investigated 20 freshly recovered human T leukemias with regard to spontaneous growth in response to interleukins. The majority of cases (16 out of 20) investigated displayed spontaneous responsiveness to cytokines (interleukins 1, 4, and 6), which might be related to activation signals mediated through the CD2 pathway. The functional repertoire of T leukemias did not correlate with expression of differentiation antigens conventionally employed for leukemia typing.

Adhesion molecules on freshly recovered T leukemias promote tumor-directed lympholysis.

Besides facilitating cell to cell adhesion, the molecular interactions between CD2 and its ligand CD58 (lymphocyte function-associated antigen-3 [LFA-3]), as well as between CD11a/18 (LFA-1) and CD54 (intercellular adhesion molecule-1) have recently been recognized to participate in lymphocyte activation, recirculation, and effector function, including cytolytic activity towards tumor cells. We have investigated the role of CD2/CD58 and CD11a/18/CD54 interactions in cellular immune responses directed towards freshly recovered human T-cell leukemias. The data support the notion that downregulation of CD54 and CD58 correlates with enhanced numbers of blasts in circulation and unsusceptibility to killing by autologous cytotoxic lymphocytes. Importantly, after induction of CD54 and CD58 expression on leukemic cells by recombinant cytokines such as tumor necrosis factor-alpha, tumor cells become highly susceptible to lymphocyte-mediated lysis in vitro. Our findings, therefore, stress the point that successful immunotherapy of malignant disease may be facilitated by influencing not only the immune response itself, but also adhesion molecules on the malignant tumor targets.