[Abdominal compartment syndrome. Töns C, Schachtrupp A, Trau, M, Mumme T, Schuplelick V (2000). Abdominal compartment syndrome: prevention and treatment. Chirurg 71: 918-926].
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Abdomen↗
Biomedical subjects
M Engelhardt
Publications and source records attributed to M Engelhardt.
[Radiation and burn trauma (combined injury). Considerations in surgical treatment].
Combined injury syndrome (CIS) is defined as mechanical and/or thermal trauma associated with radiation injury. Each of these injuries is characterized by several systemic reactions, influencing especially the immune system and fluid balance. Experiences gained during World War II, the clinical observations after radiation accidents and experimental studies demonstrate that CIS can be considered as an own entity of disease characterized by increased mortality due to additive effects of the combined injuries. Up to now, our knowledge concerning the pathomechanisms of combined injuries is not sufficient. Nevertheless, there is a growing body of evidence that two basically different effects compromise organ function: (i) resembling or identical reactions of each trauma type simply added up to an increased systemic damage and (ii) posttraumatic alterations, where the effect of one kind of trauma synergistically increases the totally different effect of the other. Due to the associated acute radiation syndrome and the special pathophysiology of CIS, surgical treatment has to be considerably different from that of conventional multiple injured patients. Initial surgical procedures must be completed during the short time period of 48-72 h before onset of radiation-induced neutropenia and thrombocytopenia. This includes primary wound closure, management of all the abdominal, thoracical and vascular injuries as well as definite osteosynthesis. Later, all invasive procedures must be avoided due to the high risk of opportunistic infections and possible massive hemorrhage. When hematopoietic recovery begins, subsequent steps of surgical treatment can be taken into consideration. However, it is important, that as in conventional trauma, resuscitation and emergency care have priority and should be performed independent of the degree of radiation injury.
Burns↗
[Pott triad and Schmorl nodules. A historical overview of kyphosis with special reference to tuberculous spondylitis and Scheuermann disease].
This report provides an overview of the history of the different types of kyphosis (arcuated and angulated forms). Especially tuberculous spondylitis and Scheuermann's disease are pointed out from among the large group of kyphotic diseases. Therefore, Beckhterew's disease, the combination of rickets and kyphosis as well as the dysraphic diseases and constitutional kyphosis caused by faulty posture are only mentioned. These two special types of kyphosis (Scheuermann's disease and tuberculous spondylitis) are presented from the first description with diagnostic findings, the ideas of pathogenesis and aspects of treatment through to the different periods of medical history. This article describes the way of thinking and discussing of opinion leaders at the beginning of the century and the influence of new techniques and developments (asepsis, antisepsis, anesthesia, bacteriology, X-ray, antibiotics) on the differential diagnosis and therapy. It is impossible to give a complete overview of all aspects during the centuries concerning tuberculous spondylitis or arcuated kyphosis. The authors of this article have focussed their studies on developments from the first descriptions until World War II, based mainly on literature from German journals and historical books from the library of the German Museum for Orthopedic History and Science.
Eponyms↗
[Historical development of sports orthopedics].
The history of German sports medicine was decisively influenced by the surgeon August Bier at the beginning of the twentieth century. Initially, general medical and physiological problems were emphasized. Individual treatment of injured athletes played an increasing role at the end of last century. Operative treatment of injured athletes and earlier rehabilitation has changed therapeutic standards of orthopedic treatment. During critical discussion of the historical development of the treatment of ruptured anterior cruciate ligaments and meniscal tears, it becomes evident that treatment methods once rejected may now prove to be useful and correct.
Germany↗
Analysis of stem cell apheresis products using intermediate-dose filgrastim plus large volume apheresis for allogeneic transplantation.
Previously, a dose-dependent influence of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on CD34+ mobilization was demonstrated. In this single-center prospective analysis, 52 healthy donors were investigated to determine the efficacy of intermediate-dose rhG-CSF 2x8 microg/kg donor body weight (bw) and intermediate large volume apheresis (LVA, median 12 l) to mobilize peripheral blood progenitor cells (PBPC) for allogeneic transplantation. The median number of CD34+ cells in apheresis products was 0.45% and 2.2x10(6)/kg recipient bw per single apheresis. A total of 5.4x10(6)/kg CD34+ cells were collected with two (range: one to three) LVA. In the analysis of donor subgroups, higher peripheral blood (PB) and apheresis results were obtained in male vs female donors; however, donor weight significantly differed in both groups. Heavier donors displayed higher PB and apheresis CD34+ counts; however, when CD34+ cells/kg were adjusted to a constant bw, similar harvest results were calculated in males and females, demonstrating that gender per se does not, whereas bw does affect apheresis results. Younger donors had significantly higher PB CD34+ counts, higher CD34+ numbers per single apheresis, increased CFU, more T, B, and CD61+, comparable NK, and less CD14+ cells. A correlation analysis of donor age and apheresis results displayed an age-related decline of 0.46x10(6)/kg CD34 cells per decade of donor aging. Cell subsets in apheresis products were CD14 (49%), CD3 (22%), CD4 (13%), CD8 (7%), CD61 (20%), CD19 (5%), and CD16/56+ (3%) cells, with increasing CD14+ cells and decreasing CD3, CD4, CD8, CD61, CD19, and CD16/56+ cells on subsequent days of apheresis. Compared to our previous analysis using high- (2x12 microg) and low-dose (1x10 microg) rhG-CSF for allogeneic PBPC mobilization, the intermediate-dose showed a similar CD34+ mobilization potential to 1x10 microg rhG-CSF; however, with use of LVA, two instead of three (p<0.05) aphereses were sufficient to mobilize > or =4x10(6)/kg bw CD34+ cells in most donors. Taken together, our results demonstrate that intermediate-dose rhG-CSF sufficiently mobilizes > or =4x10(6)/kg x bw CD34+ cells with use of LVA and that especially younger donors display increased CD34+ cell numbers.
Adult↗
Hematopoietic recovery of ex vivo perfusion culture expanded bone marrow and unexpanded peripheral blood progenitors after myeloablative chemotherapy.
Ex vivo culture of hematopoietic progenitor cells for autologous transplantation has generated world-wide interest, since it offers the prospect of using a limited cell number, and may allow more efficient gene transfer and passive elimination of contaminating tumor cells. In this study, we expanded bone marrow (BM) cells from 10 breast cancer patients to determine whether small BM aliquots can durably restore hematopoiesis, and whether thrombopoietin (TPO) improves hematopoietic reconstitution after myeloablative chemotherapy. We used the AastromReplicell System (ARS), performing a computer-controlled, stromal-based cell expansion process with frequent medium, cytokine and gas exchange. For the inoculation of 9 x 10(8) MNC, a median BM volume of 97.8 ml (range, 72.4-272) was harvested. We found a median 4.5-fold nucleated cell expansion, an 18-fold CFU-GM expansion, and 69% of input LTC-IC numbers. Nucleated and Lin-/CD34+ cells were infused with a median of 43.5 x 10(6)/kg (range, 34.1-71.7) and 2.8 x 10(5)/kg (range, 0.95-5.9), respectively. Despite tumor cell detection by immunocytochemical staining in 3/10 patients before expansion, tumor cells were not detectable in 9/10, and in one patient 1 log reduced post ARS culture. Following high-dose STAMP V chemotherapy, all patients received 12-day expanded BM cells. The median time to engraftment was 17 days (range, 11-20) for WBC >1000/microl, and 28 days (range, 21-55) for platelets >20,000/microl. A correlation between post-expansion Lin-/CD34+ cells and engraftment for ANC >500/microl, WBC >1000/microl and platelets >20,000/microl was observed. Hematopoiesis has been maintained for a median of 15 (range, 6-24) months. Our results demonstrate that transplantation of ex vivo expanded small BM aliquots allows hematopoietic reconstitution after myeloablative chemotherapy. Ex vivo generated ARS cells can reduce the risk of tumor cell reinoculation with autotransplants and may be valuable in settings in which only small stem cell doses are available, eg when using cord blood transplants or in non-mobilizing patients.
Adult↗
Attenuation of sepsis-related immunoparalysis by continuous veno-venous hemofiltration in experimental porcine pancreatitis.
OBJECTIVES: In light of evidence suggesting that hemofiltration favorably influences septic diseases by removing sepsis mediators, the impact of different modalities of continuous veno-venous hemofiltration (CVVH) on outcome and immunologic derangements in porcine pancreatogenic sepsis was evaluated. DESIGN: Randomized, controlled intervention trial. SUBJECTS: Forty-eight minipigs of either sex. INTERVENTIONS: Pancreatitis was induced by intraductal injection of sodium taurocholate (4%, 1 mL/kg body weight [BW]) and enterokinase (2 U/kg BW). Animals were allocated either to untreated controls-group 1-or to one of three treatment groups-group 2: low-volume CVVH (20 mL/kg BW), no change of hemofilters; group 3: low-volume CVVH, filters changed every 12 hrs; and group 4: high-volume CVVH (100 mL/kg BW), filters changed every 12 hrs. Survival represented the major parameter of the study. Serum cytokine levels, sepsis-related down-regulation of major histocompatibility complex II and CD14 expression on leukocytes, bacterial translocation, and endotoxemia were further parameters evaluated in the study. MEASUREMENTS AND MAIN RESULTS: High-volume CVVH combined with periodic filter change was significantly superior compared with less intensive treatment modalities (low-volume CVVH, no filter change) in sepsis protection. Long-term survival (>60 hrs) was found in 67% of group 4 and 33% of group 3 animals (p <.05), whereas in controls and group 2 no animal survived. CVVH ameliorated the initial serum tumor necrosis factor-alpha response and prevented sepsis-induced in vitro endotoxin hyporesponsiveness. Down-regulation of major histocompatibility complex II and CD14 expression on monocytes was significantly improved by CVVH. Improved oxidative burst and phagocytosis capacity in polymorphonuclear leukocytes suggested that leukocyte function was stabilized by CVVH. Also, CVVH significantly reduced bacterial translocation and endotoxemia. CONCLUSIONS: Hemofiltration reversed sepsis-induced immunoparalysis in a porcine model of bile acid-induced pancreatitis. Implications for human pancreatitis must be validated in prospective, clinical protocols.
Acute Disease↗
Telomerase activity and telomere length in acute and chronic leukemia, pre- and post-ex vivo culture.
We studied telomerase regulation and telomere length in hematopoietic progenitor cells from peripheral blood and bone marrow from patients with acute and chronic leukemia and myeloproliferative diseases. CD34+ cells from a total of 93 patients with either acute myeloid leukemia (AML; n = 25), chronic myeloid leukemia (CML; n = 21), chronic lymphocytic leukemia (CLL; n = 18), polycythemia vera (PV; n = 16), or myelodysplastic syndromes (MDS; n = 13) were analyzed before and in 19 patients after ex vivo expansion in the presence of multiple cytokines (kit ligand, interleukin-3, interleukin-6, and granulocyte colony-stimulating factor plus erythropoietin). Compared with hematopoietic progenitor cells from normal donors (n = 108), telomerase activity (TA) was increased 2- to 5-fold in chronic phase (CP)-CML, CLL, PV, and MDS. In AML, accelerated phase (AP) and blastic phase (BP)-CML, basal TA was 10- to 50-fold higher than normal. TA of CP-CML CD34+ cells was up-regulated within 72 h of ex vivo culture, peaked after 1 week, and decreased below detection after 2 weeks. In contrast, TA in AP/BP-CML and AML CD34+ cells was down-regulated after 1 week of culture and decreased further thereafter. The expansion potential of CD34+ cells from patients with leukemia was considerably decreased compared with CD34+ cells from normal donors. The average expansion of cells from leukemic individuals was 6.5-, 2.3-, 0.6-, and 0.2-fold in weeks 1, 2, 3, and 4, respectively, whereas expansion of normal cells was 5- to 15-fold higher. In serial expansion culture, a median telomeric loss of 0.7 kbp was observed during 3-4 weeks of expansion. Our results demonstrate that up-regulation of telomerase is similar in CD34+ cells from CP-CML, CLL, PV, and MDS patients and in normal hematopoietic cells during the first week of culture, whereas in AML and AP/BP-CML, telomerase is high at baseline and down-regulated during expansion culture. High levels of telomerase in leukemic progenitors at baseline may be a feature of both the malignant phenotype and rapid cycling. Telomerase down-regulation during culture of leukemic cells may be due to the decreased expansion potential or repression of normal hematopoiesis, or in AML it may be due to the partial differentiation of AML cells, shown previously to be associated with loss of TA. Telomere shortening during ex vivo expansion correlated with low levels of TA, particularly in chronic leukemic and MDS progenitors where telomerase was insufficient to protect against telomere bp loss during intense proliferation.
Adolescent↗
The effect of exercise on pharmacokinetics and pharmacodynamics of levodopa.
The aim of our study was to evaluate the influence of low-intensity exercise on levodopa absorption and levodopa motor effect. We studied the pharmacokinetics and pharmacodynamics of levodopa under resting conditions and under a workload of 50 watts for 2 hours on a cycle ergometer in 12 parkinsonian patients with predictable fluctuations of motor disability. The patients attended the hospital on both days in a provoked off state. After a baseline assessment of motor disability using the Columbia University rating scale (CURS scale) and a blood test for measurement of the baseline levodopa concentration in the plasma, 100 mg levodopa and 25 mg benserazide were administered as a single dose orally. Blood samples for measurement of the levodopa concentration in the plasma were taken, and motor assessments were conducted at 15-minute intervals for 240 minutes and at 30-minute intervals from 240 to 360 minutes. All patients were able to perform the exercise program. The baseline Columbia University rating scale score did not differ significantly between both days. The mean levodopa concentration in plasma at half-maximal motor effect tended to be higher during exercise and indicated that the patients needed a higher levodopa concentration in plasma to achieve the half-maximal motor effect. The maximal levodopa concentration in plasma tended to be higher with exercise. Both trends did not reach statistical significance. In summary, there was not a negative or a positive net effect of exercise on pharmacokinetics and pharmacodynamics of levodopa. However, there were two counteracting trends: a trend toward better levodopa absorption and a trend toward a deteriorated concentration-effect correlation.
Administration, Oral↗
Production of stem-cell transplants according to good manufacturing practice.
Peripheral blood stem cells (PBSCs) are used for transplantation to reconstitute the hematopoietic system after high-dose chemotherapy. They are harvested from peripheral blood after mobilization by cytokines and/or chemotherapy. Further ex vivo manipulation steps (e.g., selection of CD34+ PBSCs, purging, expansion, and differentiation or gene transfer) can be performed. In 1997, more than 12,000 PBSC preparations were transplanted in Europe and the total number is steadily increasing [1]. To ensure quality and safety of the final cell products intended for clinical use, national and international guidelines and regulations have been issued. The implementation of a quality assurance (QA) program including the principles of good manufacturing practice (GMP) and a quality control system is a major requirement. GMP regulations apply to all phases of cell collection, processing, and storage, and to documentation, training of personnel, and equipment of the cell processing laboratory. They have to be followed by pharmaceutical companies and medical doctors who are involved in PBSC processing at academic institutions. The complicated regulatory network for the manufacturing of cell products will help to standardize these procedures and ensure consistent quality and safety in the long term. This will be in the interest of patients and reduce risks of application of individual cell preparations.
Clinical Laboratory Techniques↗
Rapid achievement of complete donor chimerism and low regimen-related toxicity after reduced conditioning with fludarabine, carmustine, melphalan and allogeneic transplantation.
Between August 1998 and July 1999, 21 patients received a novel protocol of reduced conditioning with fludarabine, carmustine and melphalan (FBM) followed by matched-related allogeneic peripheral blood stem cell transplantation (PBSCT) in a prospective multi-center phase I/II study. Cyclosporin A and 'mini-methotrexate' were used for GVHD prophylaxis. Patients were included because of age, advanced disease, previous transplantation or co-morbidity. Hematopoietic engraftment after allogeneic transplantation was rapid with a median white blood count (WBC) >1 x 10(9)/l on day +11 (range 10-17) and a median platelet count >20 x 10(9)/l on day +13 (range 9-36). Donor chimerism was complete in 16/21 (76%) patients at all time points during follow-up and mixed at least on one occasion in 5/21 (24%) patients. The conditioning regimen was well tolerated with low toxicity even in previously transplanted patients. Thirteen patients (62%) developed acute GVHD grades II-IV. Nineteen out of 21 patients achieved complete (CR, n = 15) or partial remission (PR, n = 4) with a median patient follow-up of 354+ days (range 258-577) for patients alive. The reduced intensity protocol FBM is feasible with rapid engraftment, early achievement of complete donor chimerism, low toxicity, especially in heavily pretreated patients, and good response rates in advanced disease patients.
Adult↗
Measurement of telomere length in haematopoietic cells using in situ hybridization techniques.
The DNA of human chromosomes terminates in several kilobases of telomere repeats that are gradually lost with; age and with replication in vitro. Defective telomere maintenance has been shown to be causally linked to cell cycle exit and apoptosis. In order to overcome the limitations imposed by Southern blotting, we have established a quantitative fluorescence in situ hybridization (Q-FISH) technique. This technique allows estimation of telomere length in specific chromosome arms from metaphase cell preparations. Furthermore, we have extended quantitative in situ hybridization to flow cytometry (flow FISH) in order to obtain information on the mean telomere repeat content in suspended cells. Telomere length in granulocytes, monocytes, CD8 and CD4 T lymphocytes and natural killer cells was found to differ slightly in the peripheral blood of adults. However, strikingly longer telomeres were observed in B lymphocytes (approximately 1.3 kb longer), suggesting a functional role for telomere maintenance in this cell subset. In summary, Q-FISH and flow FISH represent new methods for measuring telomere length in single cells and allow studies of telomere dynamics in haematopoietic subpopulations at various stages of normal and abnormal antigen responses.
Adult↗
Telomerase activity in germ cell cancers and mature teratomas.
BACKGROUND: An inverse relationship has been reported between the presence of telomerase enzymatic activity and the induction of differentiation in human tumor cell lines. Male germ cell tumors represent an attractive clinical model to assess this relationship further because high telomerase activity is present in normal germ cell progenitors and in embryonal carcinomas that can differentiate into mature teratomas. To investigate how telomerase activity and the differentiation state of germ cell tumors are related, telomerase activities and telomere lengths were measured in benign testicular tissues, germ cell cancers, and mature or immature teratomas. METHODS: By use of a modified telomeric repeat amplification protocol (TRAP) assay, telomerase activity was measured in four specimens of benign testicular tissue, in 27 germ cell cancers, in seven mature teratomas, and in one immature teratoma. Telomere lengths were measured in all specimens by restriction digestion of genomic DNA and Southern blot hybridization analysis. Associations between telomerase activity and tissue histopathology were assessed with two-sided Fisher's exact tests. RESULTS: Telomerase activity was detected in all examined germ cell cancers and in the benign testicular tissue specimens. In marked contrast, telomerase activity was not detected in any mature teratoma (P<.0001). Very long telomeres were detected in some mature teratomas, consistent with telomerase repression as a late event in teratoma formation. The immature teratoma, with malignant transformation, had high telomerase activity. CONCLUSION: Telomerase is active in germ cell cancers and repressed in mature teratomas. The absence of telomerase activity may contribute to the limited proliferative capacity of mature teratomas. These findings support the existence of an inverse relationship between telomerase activity and the differentiation state of clinical germ cell tumors.
Blotting, Southern↗
Exercise test in Parkinson's disease.
UNLABELLED: In this study we assessed cardiovascular performance and metabolic response after an exercise test in Parkinsonian patients (PD patients). METHODS: 15 PD patients (10 male, 5 female; mean age:63 +/- 6.17 y; mean weight: 72.2 +/- 9.5 kg) and 15 sex, age (mean: 63.8 +/- 5.38 y), and weight-(mean: 72.2 +/- 8.69 kg) matched controls performed an exercise test using a cycle ergometer and a ramp protocol. All patients and control subjects underwent a heart rate variability test prior to the exercise test. At rest and at the end of each interval blood pressure (BP) and capillary lactate samples were taken. Heart rate was monitored continuously. RESULTS: The heart rate variability tests were abnormal in Parkinson's patients. All patients and control subjects achieved an intensity level of 75 watts, 12/15 PD patients managed 100 watts, and 7/15 PD patients managed 150 watts. 12/15 control subjects performed at an intensity level of 125 Watts and 9/15 at an intensity level of 150 Watts. There was no statistically significant difference in heart rate increase but there was a tendency to lower lactate levels at high intensity levels in PD patients. PD patients had a statistically lower systolic BP at 75, 100, 125, and 150 watts. CONCLUSION: We did not find striking differences in cardiovascular adaptation to physical work in PD patients and we propose, therefore, that it should be possible to improve cardiovascular endurance in PD patients. Previously, reports have suggested respiratory chain impairment in Parkinson's disease and poor endurance performance. However, our results do not support a clinically relevant impairment of the respiratory chain.
Blood Pressure↗
Results of spiral CT in patients with fractures of the craniocervical junction suspected on conventional radiographs.
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Cervical Vertebrae↗
Demonstration of a DNase-sensitive network associated with the nuclear pore complexes in rat liver nuclei.
Rat liver nuclei have been studied by transmission electron microscopy after resuspension in a phosphate-buffered salt solution containing SO2-4 as the quantitatively dominant anion. Owing to the high solubility of chromatin in the presence of SO2-4 instead of Cl- at isotonicity, nuclei are depleted for chromatin by DNase I digestion in this buffer, eliminating the need for high-salt extraction. This shows that at least 75% of the nuclear pore complexes are associated with fibrogranular structures, which ramify as a network throughout the nucleus, interconnecting the nuclear lamina, interchromatin granule clusters and nucleoli. Perichromatin granules are located in this material proximal to the nuclear pore complexes. Most of the chromatin is removed without major impact on the network, but below a level of 25% residual chromatin there is a considerable reduction of this material, and only about 15% of the connections to the nuclear pore complexes are resistant to digestion with DNase I or streptodornase A and B. The percentage of nuclear pore complexes connected to the network is further reduced by salt extraction and RNase treatment. These results suggest that DNA is an integral part of the network, which presumably plays a role in nucleo-cytoplasmic transport of RNA and protein.
Animals↗
Therapeutic value of exercise training in Parkinson's disease.
PURPOSE: The objective of this study was to investigate the influence of an intensive exercise training on motor disability, mood, and subjective well-being in parkinsonian patients. METHODS: The study was designed as an open long-term pilot trial over 20 wk. Sixteen slightly to moderately affected idiopathic parkinsonian patients (PD) were included. An intensive standardized exercise training was performed twice weekly over 14 wk in all patients. Evaluations were performed before the start of the study (exam. 1), after 7 wk (exam 2), 14 wk (exam 3), and 20 wk (exam 4/long-term effect). The test battery included: 1) basic motor test (BMT) [test for muscle strength, flexibility, and coordination]; 2) Unified Parkinson's Disease Rating Scale (UPDRS) and Columbia University Rating Scale (CURS) for PD-specific motor disability; and 3) registration of psychometric data by Mini Mental State (MMS) for dementia and the Adjective Mood Questionnaire of Zeersen (AMQZ) and Sickness Impact Profile (SIP) for subjective well-being. RESULTS: UPDRS sigma score (P < 0.0001), CURS sigma score (P < 0.0001) and BMT 2 score (P < 0.0001) improved significantly by exercise training. Six weeks after termination of the training program, the majority of the patients had lost only minor components of their regained motor skills. There was no significant change in cognitive function during the study. The results of open interviews referring to subjective well-being were confirmed by the AMQZ and SIP. As an unexpected side effect, dyskinesias seemed to be better controlled. CONCLUSION: Motor disability as well as mood and subjective well-being can be clearly improved by intensive sports activities in early to medium stage PD patients. A sustained ongoing benefit outlasting the active training period for at least 6 wk can be achieved but the exact duration of this benefit is open.
Affect↗
Scintigraphy and immunohistology of antimyosin-Fab during graft rejection.
Up to now, the cellular localization pattern of monoclonal antimyosin antibodies (AMA) during acute rejection has not been described. Focused on this the authors made immunohistochemical and scintigraphic studies (AMS) with AMA in an animal transplantation model. Heterotopic cervical heart transplantation was performed in 12 mongrel dogs. Immunosuppression consisted of triple drug therapy. As standard the grafts were examined by daily transmural biopsies and routine histology. Dependent on the daily biopsy results, 0.5 mg of indium 111 ((111)In)-labeled AMA-Fab was injected. Subsequently every 2 hours transmural biopsy cylinders were taken out of the right ventricle and examined in indirect peroxidase staining technique. Forty-eight hours after AMA injection, scintigraphy in single photon emission computed tomography (SPECT) technique (AMS) was carried out and the heart-to-lung ratio (H/L-ratio) was calculated. The immunohistochemical maximum of AMA accumulation could be found 20 to 72 hours after AMA injection. This means that a scintigraphic examination should be done earlier than 20 hours and later than 3 days after injection. Dependent on the grades of bioptic rejection diagnosis a specific morphologic AMA localization was seen (grade I+II intercellular and slightly intracellular detection of AMA, grade III strongly intracellular and in particular perinuclear accumulation of the antibody, p<0.01). Moreover, the authors found a good correlation between scintigraphic H/L-ratio results and the corresponding histologic findings (grade I: H/L = 2.1 +/- 0.2; grade II: H/L = 3.1 +/- 0.2; grade III: H/L = 3.5 +/- 0.3; n = 19; p<0.02). The recently described positive AMS scans even in cases of mild rejection seem to be subject to an intercellular AMA localization. This typical AMA morphology during mild rejection favors the theory of the pore-forming protein allowing the efflux of myosin fragments as effector mechanism of cytotoxic lymphocytes in the early phase of acute rejection. The immunohistochemical AMA examination could explain the present discrepancy between positive AMS results of an intracellular protein in cases of mild or moderate acute rejection when visible cellular damage in the corresponding routine histology is absent.
Animals↗