[Retrospective analysis of the clinical course of 12 children given the diagnosis essential thrombocythemia]. / Retrospektive Analyse des klinischen Verlaufs bei 12 Kindern mit der Verdachtsdiagnose einer essenziellen Thrombozythämie.

BACKGROUND: Essential Thrombocythemia (ET) is an acquired myeloproliferative disorder (MPD) characterized by excessive production of platelets. The disorder is usually affecting adults and is rarely diagnosed in children. PATIENTS AND METHODS: In this retrospective study we describe 12 children aged 5-16 years in whom ET was presumed. RESULTS: Median follow-up was 59 months (range 10-72). At diagnosis 7 patients had clinical symptoms (syncope, poor concentration, fatigue, abdominal pain and mild bleeding), 5 patients were diagnosed accidentally (operation, allergy, enuresis, pneumonia, routine examination). Median platelet count at diagnosis was 1 325 x 10 (9)/L (range 600-3 050). In 11 cases bone marrow morphology was consistent with ET, one patient had chronic idiopathic myelofibrosis. Cytogenetics were normal in all studied cases. Within 6 months after the initial presentation one patient who was diagnosed accidentally developed thrombosis, another patient had mild bleeding. 8 patients were treated with acetylsalicylic acid (in addition, 1 patient received hydroxyurea, 2 patients received anagrelide). On last follow-up all patients were alive, none had developed leukemia. 5 patients experienced hematological remission. 2 of these children had not received any therapy. CONCLUSIONS: Many patients had symptoms attributable to ET. The clinical course is heterogeneous with complete normalization of platelets in the absence of cytoreductive therapy in some children. Due to the low incidence of ET in children indications for therapy are unclear and can only be deduced from findings obtained from studies in adults.

The International Prognostic Scoring System (IPSS) for childhood myelodysplastic syndrome (MDS) and juvenile myelomonocytic leukemia (JMML).

The International Prognostic Scoring System (IPSS) for myelodysplastic syndrome (MDS) is based upon weighted data on bone marrow (BM) blast percentage, cytopenia, and cytogenetics, separating patients into four prognostic groups. We analyzed the value of the IPSS in 142 children with de novo MDS and 166 children with juvenile myelomonocytic leukemia (JMML) enrolled in retro- and prospective studies of the European Working Group on childhood MDS (EWOG-MDS). Survivals in MDS and JMML were analyzed separately. Among the criteria considered by the IPSS score, only BM blasts <5% and platelets >100 x 10(9)/l were significantly associated with a superior survival in MDS. In JMML, better survival was associated with platelets >40 x 10(9)/l, but not with any other IPSS factors including cytogenetics. In conclusion, the IPSS is of limited value in both pediatric MDS and JMML. The results reflect the differences between myelodysplastic and myeloproliferative diseases in children and adults.

Facilitated synthesis of inulin esters by transesterification.

Inulin, the polydisperse polyfructose, extracted from chicory, has been modified via transesterification, using fatty acid methyl esters (FAME). The grafting of an alkyl chain onto the inulin backbone under different conditions for the development of potential tensio-active derivatives is described. The modification of the biopolymer was performed in polar organic solvents, such as dimethyl sulfoxide (DMSO) and N-methylpyrrolidinone (NMP). Depending on the type of solvent, different catalytic systems, such as DMSO-Na+, NaH, and NaOMe, were used and compared in reaction efficiency and reproducibility. Therefore the synthesized derivatives were characterized by 1H- and 13C NMR. The methods using NaH had a mean reaction efficiency of 80%, whereas the one using NaOMe showed a slight decrease in reaction efficiency to 75%. However, the method using NaOMe in NMP proved to be the preferred way to graft the inulin backbone with FAME on a bigger scale. The methods using DMSO as a solvent were not attractive since the end products had a specific bad smell.

Comparison of the biomechanics of hydroxyapatite and polymethylmethacrylate vertebroplasty in a cadaveric spinal compression fracture model.

OBJECT: Polymethylmethacrylate (PMMA) has long been used in the stabilization and reconstruction of traumatic and pathological fractures of the spine. Recently, hydroxyapatite (HA), an osteoconductive, biocompatible cement, has been used as an alternative to PMMA. In this study the authors compare the stabilizing effects of the HA product, BoneSource, with PMMA in an experimental compression fracture of L-1. METHODS: Twenty T9-L3 cadaveric spine specimens were mounted individually on a testing frame. Light-emitting diodes were placed on the neural arches as well as the base. Motion was tracked by two video cameras in response to applied loads of 0 to 6 Nm. The weight-drop technique was used to induce a reproducible compression fracture of T-11 after partially coring out the vertebra. Load testing was performed on the intact spine. postfracture, after unilateral transpedicular vertebroplasty with 7 to 10 ml of PMMA or HA, and after flexion-extension fatiguing to 5000 cycles at +/- 3 Nm. No significant difference between the HA- and PMMA cemented-fixated spines was demonstrated in flexion, extension, left lateral bending, or right and left axial rotation. The only difference between the two cements was encountered before and after fatiguing in right lateral bending (p < or = 0.05). CONCLUSIONS: The results of this study suggest that the same angular rigidity can be achieved using either HA or PMMA. This is of particular interest because HA is osteoconductive, undergoes remodeling, and is not exothermic.

A biomechanical comparison between anterior and transverse interbody fusion cages.

STUDY DESIGN: Human cadaveric lumbar spines underwent placement of threaded fusion cages (TFCs) in either an anterior or transverse orientation. Spines underwent load testing and angular rotation measurement in the intact state, after diskectomy, after cage placement, and after fatiguing. Angular rotations were compared between cage orientations and interventions. OBJECTIVE: To determine which cage orientation resulted in greater immediate stability. SUMMARY OF BACKGROUND DATA: There has been extensive biomechanical study of interbody fusion cages. The lateral orientation has been increasingly used for intervertebral fusion, but a direct biomechanical comparison between cages implanted either anteriorly or transversely in human cadaveric spines has not been performed. METHODS: Fourteen spines were randomized into the anterior group (anterior diskectomy and dual anterior cage placement) and the lateral group (lateral diskectomy and single transverse cage placement). Pure bending moments of 1.5, 3.0, 4.5, and 6.0 Nm were applied in flexion, extension, lateral bending, and axial rotation. Load testing was performed while intact, after diskectomy, after cage placement, and after fatiguing. Angular rotation was compared between anterior and lateral groups and, within each group, among the different interventions. RESULTS: Segmental ranges of motion were similar between spines undergoing either anterior or lateral cage implantation. CONCLUSIONS: These results demonstrate few differences between angular rotation after either anterior or lateral TFC implantation. These findings add to data that find few differences between orientation of implanted TFCs. Combined with a decreased risk of adjacent structure injury through a lateral approach, these data support a lateral approach for lumbar interbody fusion.

In vitro biomechanical analysis of three anterior thoracolumbar implants.

OBJECT: The goal of this study was to evaluate the comparative efficacy of three commonly used anterior thoracolumbar implants: the anterior thoracolumbar locking plate (ATLP), the smooth-rod Kaneda (SRK), and the Z-plate. METHODS: In vitro testing was performed using the T9-L3 segments of human cadaver spines. An L-1 corpectomy was performed, and stabilization was achieved using one of three anterior devices: the ATLP in nine spines, the SRK in 10, and the Z-plate in 10. Specimens were load tested with 1.5-, 3-, 4.5-, and 6-Nm in flexion and extension, right and left lateral bending, and right and left axial rotation. Angular motion was monitored using two video cameras that tracked light-emitting diodes attached to the vertebral bodies. Testing was performed in the intact state in spines stabilized with one of the three aforementioned devices after the devices had been fatigued to 5000 cycles at +/- 3 Nm and after bilateral facetectomy. There was no difference in the stability of the intact spines with use of the three devices. There were no differences between the SRK- and Z-plate-instrumented spines in any state. In extension testing, the mean angular rotation (+/- standard deviation) of spines instrumented with the SRK (4.7 +/- 3.2 degrees) and Z-plate devices (3.3 +/- 2.3 degrees) was more rigid than that observed in the ATLP-stabilized spines (9 +/- 4.8 degrees). In flexion testing after induction of fatigue, however, only the SRK (4.2 +/- 3.2 degrees) was stiffer than the ATLP (8.9 +/- 4.9 degrees). Also, in extension postfatigue, only the SRK (2.4 +/- 3.4 degrees) provided more rigid fixation than the ATLP (6.4 +/- 2.9 degrees). All three devices were equally unstable after bilateral facetectomy. The SRK and Z-plate anterior thoracolumbar implants were both more rigid than the ATLP, and of the former two the SRK was stiffer. CONCLUSIONS: The authors' results suggest that in cases in which profile and ease of application are not of paramount importance, the SRK has an advantage over the other two tested implants in achieving rigid fixation immediately postoperatively.

Spinal stability with anterior or posterior ray threaded fusion cages.

OBJECT: The authors conducted a study to determine if the rigidity supplied to the spine by posterior placement of the Ray threaded fusion cage (TFC) is further enhanced by the placement of pedicle screws and, additionally, if bilateral anteriorly placed TFCs render the spine more rigid than a single anteriorly placed TFC. METHODS: Ten human cadaveric spinal specimens (L2-S1) were affixed within a testing frame. Loads of 1.5, 3, 4.5, and 6 Nm were applied to the spine in six degrees of freedom: flexion-extension, right and left lateral bending, and right and left axial rotation. Motion in an x, y, and z cartesian axis system was tracked using dual video cameras following light-emitting diodes attached to the spine and base plate. Load testing of the spines was performed in the intact mode, following which the spinal segments were randomized to receive anterior or posterior instrumentation. In five spine specimens we performed posterior discectomy, posterior lumbar interbody fusion (PLIF) with placement of femoral rings and pedicle screws, PLIF with bilateral TFCs, and bilateral TFCs with pedicle screws. Five other spines underwent anterior-approach discectomy, followed by implantation of a unilateral cage and bilateral cages. Load testing was performed after each step. CONCLUSION: Spines in which PLIF with pedicle screws and TFCs with pedicle screws were placed were more rigid than after discectomy in all directions of motion except flexion. Anterior discectomy provided significantly (p < or = 0.05) less stability in left and right axial rotation than the intact spines and following posterior discectomy. Following anterior implantation of bilateral TFCs, spines were significantly more rigid than after discectomy in all directions except extension.

Biomechanical studies of a dynamized anterior thoracolumbar implant.

STUDY DESIGN: An in vitro investigation into the biomechanical properties of a dynamized anterolateral compression implant that allows controlled subsidence. OBJECTIVES: To determine the extent to which both modes of the anterolateral compression implant (controlled collapsing and rigid) are able to reestablish the stability of the lumbar spine after L4 corpectomy. SUMMARY OF BACKGROUND DATA: Over time, anterior and posterior spinal implants have been associated with progressive angulation, and occasionally implant failure and breakage. To circumvent this occurrence and provide better graft loading, dynamized or collapsing devices for clinical use have been developed. METHODS: Eight fresh calf spines (L1-L6) were placed in a biomechanical testing frame. Pure moments of 6 Nm were loaded onto the intact spine in six directions: flexion, extension, right and left lateral bending, and right and left axial rotation. A total L4 corpectomy then was performed, and the defect grafted with a wooden dowel. Loading was repeated after the specimens were stabilized using the two modes of the anterolateral compression implant in succession. RESULTS: The results showed that both modes of the implant (the rigid mode in particular) restore the stiffness of the unstable spine to normal levels of flexion, extension, and right and left lateral bending, even to levels exceeding normal. These devices, however, fall short of achieving normal stability in right and left axial rotation. CONCLUSION: In the cadaveric calf spine after L4 corpectomy, restoration of stability with a dynamized anterior spinal implant is possible in flexion, extension, and right and left lateral bending, but not in axial rotation.

Biomechanical studies on two anterior thoracolumbar implants in cadaveric spines.

STUDY DESIGN: A biomechanical comparison of two commonly used anterior spinal devices: the Smooth Rod Kaneda and the Synthes Anterior Thoracolumbar Spinal Plate. OBJECTIVES: To compare the stability imparted to the human cadaveric spine by the Smooth Rod Kaneda and Synthes Anterior Spinal Plate, and to assess how well these devices withstand fatigue and uni- and bilateral facetectomy. SUMMARY OF BACKGROUND DATA: Biomechanical studies on the aforementioned and similar devices have been performed using synthetic, porcine, calf, or dog spines. As of the time of this writing, studies comparing anterior spinal implants using human cadaveric spines are scarce. METHODS: An L1 corpectomy was performed on 19 spines. Stabilization was accomplished by an interbody wooden graft and the application of the Smooth Rod Kaneda in 10 spines and the Synthes Anterior Spinal Plate in the remaining 9. Biomechanical testing of the spines was performed in six degrees of freedom before and after stabilization, and after fatiguing to 5000 cycles of +/- 3 Nm of flexion and extension. Testing was repeated after uni- and bilateral facetectomy. RESULTS: After stabilization, the Smooth Rod Kaneda was significantly more rigid than the anterior thoracolumbar bar spinal plate in extension. After fatigue, the Smooth Rod Kaneda was significantly stiffer than the anterior thoracolumbar spinal plate in flexion, extension, right lateral bending, left lateral bending, and right axial rotation. A significant decrease in stiffness was noted with the Synthes device in flexion after bilateral facetectomy compared with the stabilized spine. CONCLUSIONS: The smooth Rod Kaneda device tends to be stiffer than the anterior thoracolumbar spinal plate, particularly in extension, exceeding the anterior thoracolumbar spinal plate in fatigue tolerance. The spine stabilized with the anterior thoracolumbar spinal plate is more susceptible to the destabilizing effect of bilateral facetectomy than than that stabilized with the Smooth Rod Kaneda. The additional rigidity encountered with the Smooth Rod Kaneda must be weighed against the simplicity of anterior thoracolumbar spinal plate application.

Response of spinal cord blood flow to the nitric oxide inhibitor nitroarginine.

OBJECTIVE: The extent to which nitric oxide (NO) is involved in the modulation of spinal cord blood flow (SCBF) in the uninjured and injured cord is unknown. To elucidate these questions, the following experiments in anesthetized rats were conducted. METHODS: Because NO is an unstable free radical with a half-life of seconds, its role can be understood through the study of the NO synthase inhibitor L-NG-nitroarginine (L-NOARG). L-NOARG was administered intravenously for 30 minutes at a dose of 100 or 500 micrograms/kg/min in 12 and 10 uninjured animals, respectively. SCBF fluctuations at C7-T1 were measured using laser doppler flowmetry. In a second set of 12 rats, L-NOARG (500 micrograms/kg/min) was administered 10 minutes before spinal cord injury using a modified aneurysm clip at C7-T1 and continued for 30 minutes thereafter. RESULTS: In the uninjured animals, L-NOARG was associated with a dose-dependent increase in mean arterial pressure of 20 to 80% above baseline (P = 0.0001), together with a dose-related decrease in SCBF (P = 0.0373). In the injured animals, L-NOARG was associated with a 48% increase in mean arterial pressure. With L-NOARG, the changes in SCBF from baseline after injury were similar to those of noninjured controls (n = 25) and significantly less than injury controls (n = 18) or those receiving phenylephrine (n = 8). CONCLUSION: NO synthase inhibitors, by reducing available NO, cause systemic vasoconstriction and a decrease in SCBF in the uninjured spinal cord. In the injured spinal cord, the administration of L-NOARG results in a redistribution of blood flow with an augmentation in posttraumatic SCBF at the injury site.

Transformation of haploid Datura innoxia protoplasts and analysis of the plasmid integration pattern in regenerated transgenic plants.

We developed a highly efficient transformation protocol for the PEG-mediated direct transfer of plasmid DNA into protoplasts of haploid Datura innoxia. Vectors harbouring a neomycin phosphotransferase II gene or a hygromycin B phosphotransferase gene under the control of different promoters were used in the transformation experiments. Various amounts of plasmid DNA were applied without any carrier DNA to show the direct influence of the plasmid DNA concentration on the transformation efficiency. Approximately 95% of the selected calli were regenerated to plants; 20% of them remained haploid. Total DNA of different transgenic plants was analysed with regard to the integration pattern of the plasmid DNA. Plants carrying only one or two copies of the vector DNA were observed as well as individuals with multi-copy integration (up to ten or more copies).

Computer simulation of arterial flow with applications to arterial and aortic stenoses.

A computer model for simulating pressure and flow propagation in the human arterial system is developed. The model is based on the one-dimensional flow equations and includes nonlinearities arising from geometry and material properties. Fifty-five arterial segments, representing the various major arteries, are combined to form the model of the arterial system. Particular attention is paid to the development of peripheral pressure and flow pulses under normal flow conditions and under conditions of arterial and aortic stenoses. Results show that the presence of severe arterial stenoses significantly affects the nature of the distal pressure and flow pulses. Aortic stenoses also have a profound effect on central and peripheral pressure pulse formation. Comparison with the published experimental data suggests that the model is capable of simulating arterial flow under normal flow conditions as well as conditions of stenotic obstructions in a satisfactory manner.

Numerical study of arterial flow during sustained external acceleration.

A computer model of the human arterial tree based upon the one-dimensional flow equations is used to study the effects of sustained acceleration (+Gz) on eye-level arterial pressure and flow. Steady-state physiological compensatory mechanisms are modelled using human centrifuge data found in the literature. Cases investigated include the supine and standing human (+1 Gz), the application of resistive and occlusive anti-G suits, and the occurrence of a stenosis proximal to the carotid bifurcation. Results indicate that the simulated eye-level pressures and flows satisfactorily correspond with those found in the literature.

Numerical study of pressure and flow propagation in arteries.

A computer model for simulating pressure and flow propagation in the human arterial system is developed. The model is based on the one-dimensional flow equations and includes non-linearities arising from geometry and material properties. Fifty five arterial segments, representing the various major arteries, are combined to form the model of the arterial system. Particular attention is paid to the development of peripheral pressure and flow pulses under normal flow conditions and under conditions of arterial disease. Cases investigated include arteriosclerosis and hypertension as well as the presence of single or multiple vascular occlusions. Results demonstrate that the model is capable of simulating arterial flow in a satisfactory manner.