Biomedical subjects
Publications and source records attributed to R Bartl.
This is a report of a rare case of an avulsion of the apophysis of anterior inferior iliac spine by a 14-year-old football player. Origin, diagnosis, differential diagnosis, and treatment are evaluated and described.
OBJECTIVE: To quantify gadolinium-related enhancement in the bone marrow of the spine in normals and in patients with homogeneous diffuse malignant bone marrow infiltration. DESIGN AND PATIENTS: The patients consisted of two groups: group 1 comprised 94 healthy adults (18-86 years) without bone marrow disease and group 2 comprised 30 patients with homogeneous diffuse malignant bone marrow infiltration due to myeloma (n = 20) or breast carcinoma (n = 10). All patients received intravenous gadopentetate dimeglumine (Gd-DTPA), 0.1 mmol/kg body weight. Pre- and postcontrast signal intensity (SI) on T1-weighted spin-echo (SE) images (TR/TE: 572 ms/15 ms) was measured over a region of interest (ROI) and the percentage SI increase was calculated. The results were confirmed by bone marrow biopsy (n = 20) and clinical parameters (n = 10). Dynamic contrast-enhanced studies using a spoiled gradient-recalled-echo (GRE) sequence (TR/TE/alpha: 68 ms/6 ms 75 degrees) were performed in 10 controls with normal bone marrow. RESULTS AND CONCLUSION: Contrast material enhancement in healthy persons can vary greatly (range 3-59%, mean 21%, SD 11%). With increasing age there is a significant decrease in contrast enhancement (Pearson's correlation, P < 0.01). The percentage SI increase in patients with intermediate-grade (biopsy 20-50 vol%) and high-grade (biopsy > 50 vol%) diffuse malignant bone marrow infiltration was significantly higher than in normals (mean 67%, SD 34%, P < 0.001). Low-grade (biopsy < 20 vol%) diffuse malignant bone marrow infiltration can not be assessed by non-enhanced T1-weighted SE images or Gd-DTPA application. In conclusion, contrast material enhancement in healthy persons can vary greatly and is dependent on age, while intermediate-grade and high-grade diffuse malignant bone marrow infiltration can be objectively assessed with SI measurements.
Sacral insufficiency fractures develop over a period of time and show time-dependent changes. We report on 15 CT examinations of 5 patients with early-stage insufficiency fractures of the sacrum. In 4 patients only irregular sclerosis without distinct fracture lines was present in 7 of 8 fractures. Of these 4 patients; 3 exhibited intraosseous gas inclusions in a ventral part of a lateral mass; 5 of 8 fractures disclosed a ventral cortical break. When distinct fracture lines had developed in 1 patient, intraosseous vacuum phenomenon had disappeared. Fracture lines evolve over weeks to months and show central bone absorption. The fractures can heal as demonstrated in 4 of 6 fractures in 3 patients, can persist over 1 year without significant changes or can progress to pseudoarthrosis with bone destruction similar to neuropathic joint disease. Intraosseous vacuum phenomena can persist to this stage. Intraosseous vacuum phenomenon is recognized as a potential finding in the early stage of sacral insufficiency fracture, which also is true for irregular sclerosis and ventral cortical disruption.
PURPOSE: To define the different infiltration patterns in the spine in multiple myeloma, in correlation with histological and clinical findings. Quantitative signal evaluation with contrast media (Gd-DTPA). To compare the results in MRI with X-ray films. MATERIAL AND METHODS: 61 patients with proven multiple myeloma and 50 controls were examined (1.0 Tesla, T1-w SE, opposed phase GE images). RESULTS: Five infiltration patterns with different clinical stages were detected: normal bone marrow (11%) in cases of low interstitial marrow infiltration (biopsy), pure diffuse infiltration (25%), focal involvement (33%), combined diffuse/focal infiltration (23%) and a "salt-and pepper" pattern (8%). In diffuse plasmacytoma the 40% signal intensity increase was modification of diffuse infiltration. MRI proved to be more sensitive than radiography. CONCLUSION: MRI is able to show the type and the extension of bone marrow infiltration in multiple myeloma. Diffuse involvement can be objective with gadopentetate dimeglumine.
The relationship between two cellular prognostic parameters of multiple myeloma, the plasma cell labeling index (LI%) and bone marrow histology was studied. The LI% as the percentage of monoclonal plasma cells in the S-phase was measured by bromodeoxyuridine incorporation using the anti-bromodeoxyuridine antibody BU-1. The histologic classification was based on six plasma cell types that allow prognostic grading as the Marschalko, small cell, cleaved, polymorphous, asynchronous, and blastic types. The biopsies also were used for estimating the degree of infiltration. Beta 2-microglobulin (IMx assay, Abbott, North Chicago, IL), the most significant serum parameter for myeloma also was measured for comparison. Bone marrow specimens and sera were obtained from 50 myeloma patients. Fourteen patients with smoldering myeloma were characterized by well-differentiated Marschalko or small cell type cells, a low LI% and a low beta 2-microglobulin concentration. Considering all myeloma patients, plasma cell type and degree of infiltration showed a significant correlation with LI% and beta 2-microglobulin concentration. Patients with plasma cells that were not mature cells of the Marschalko or small cell type revealed a high LI% or high beta 2-microglobulin level in 16 of 19 cases. However, a high LI% or high beta 2-microglobulin level could be detected in only 8 of 31 patients with plasma cells of the Marschalko or small cell type. Three of 21 stage I patients did not show the typical finding of a low LI%, low beta 2-microglobulin level, and a favorable grade. Stage II patients were not uniformly characterized by LI%, beta 2-microglobulin and plasma cell morphology. The percentage of nucleolated plasma cells was not associated with the LI%. Bone marrow histology, LI%, and beta 2-microglobulin concentration appear to be supplementary prognostic factors. If LI% and beta 2-microglobulin levels are not measured, a higher risk could be overlooked in cases with mature plasma cells.
OBJECTIVE: This study describes infiltration patterns of multiple myeloma in spinal MR imaging and correlates the findings with biopsies, survival rates, and signal intensity measurements in unenhanced and enhanced studies. MATERIALS AND METHODS: Fifty-three patients with multiple myeloma and 53 age-matched controls underwent MR imaging of the spine. Twenty-nine patients underwent sagittal T1-weighted spin-echo enhanced imaging and all patients underwent sagittal T1-weighted spin-echo unenhanced and opposed-phase gradient-recalled echo images, and signal intensity measurements were taken. MR imaging was correlated to marrow specimens (n = 40) and a clinical staging system. The probability of survival was also calculated. Finally, we performed qualitative visual evaluation (infiltration pattern, degree of tumor involvement) and a quantitative evaluation (marrow signal intensity ratios, contrast enhancement). RESULTS: Five infiltration patterns were found: normal-appearing marrow with low-grade interstitial infiltration (n = 5), focal (n = 18), diffuse (n = 12), focal and diffuse (n = 13), and salt-and-pepper (n = 5). Infiltration pattern correlated with clinical staging; all patients with normal-appearing and salt-and-pepper patterns were clinically stage I. Diffuse marrow infiltration was assessed by marrow ratios: low-grade infiltration, greater than 2.0; intermediate, 1.0-2.0; highgrade, less than 1.0. Contrast enhancement with a signal intensity increase greater than 40% indicated diffuse infiltration. In the control group, all of whom had no marrow disease, enhancement varied (mean +/- SD, 16% +/- 8.9%) but did not exceed 40%. Marrow involvement on MR images correlated significantly with clinical staging and survival (p < or = .001). CONCLUSION: MR imaging with opposed gradient-recalled echo sequences and contrast enhancement provided data that allowed us to classify infiltration patterns and to quantify diffuse marrow involvement in multiple myeloma, both of which correlated to clinical staging and biopsy. Also, the MR data was of prognostic value. Therefore, like laboratory parameters, biopsies, and radiographs, MR imaging can be a supporting pillar in staging and planning treatment of patients with multiple myeloma.
We implanted in case of hip-near fractures of the femur after DHS the anti-rotation screw with help of a special parallel drill guide. It was possible to position the anti-rotation screw in a parallel fashion in all patients so that the dynamic effect of the DHS was not impaired and a faulty penetration of the screw into the hip by a badly positioned anti-rotation screw could be avoided. The radiological follow up shows us no sign of impaired healing.
OBJECTIVE: Insufficiency fractures of the sacrum are found in women who have undergone radiation therapy to the lower abdomen as well as those suffering from osteoporosis of postmenopausal, steroid-induced, or primary biliary cirrhosis-related origin. Increased uptake in bone scintigraphy and osteolytic changes in these fractures can be misinterpreted as bone metastases, leading to unnecessary biopsies and other procedures in the ensuing search for non-existent primary tumor. PATIENTS: In eight female patients averaging 69.4 years of age, insufficiency fracture of the sacrum was diagnosed by computed tomography (CT) and bone scintigraphy. Three underwent a total of five MRI examinations. Malignancy was excluded by histology in two patients and follow-up of at least 6 months in the remainder. Retrospective analysis of CT scans of 13 patients with metastases in the sacrum revealed no vacuum phenomena. RESULTS: In seven of eight patients with insufficiency fracture of the sacrum, vacuum phenomena were shown on CT examination. The gas was localized centrally within the ventral part of the fracture in three patients; gas was located in ten adjacent sacro-iliac joints of six patients. CONCLUSIONS: The vacuum phenomenon may be an incidental finding in osteoarthritis of the sacro-iliac joint, but it has not been previously recognized in IFS. The presence of intra-articular vacuum phenomena in the sacro-iliac joints in combination with a sacral fracture and vacuum phenomena located within the sacral fracture supports a diagnosis of insufficiency fracture or may indeed be the clue by which this diagnosis is established.
406 untreated multiple myeloma patients of stage I (n = 54), II (n = 148) and III (n = 204) were enrolled in the trial. 51/54 stage I and 60/148 stage II patients were asymptomatic and followed without treatment until disease progression (progression free survival: 60% after 4 years for stage I versus 50% after 1 year for stage II). Symptomatic patients of stage I (n = 3/54) and II (n = 88/148) presenting with tumour progression, received melphalan 15 mg/m2 intravenously (i.v.) and prednisone 60 mg/m2 oral days 1-4 (MP). Stage II disease remission rate was 59%, and 50% tumour related survival (TRS) was 59 months. Stage III patients were randomised to receive MP or VBAMDex (vincristine/BCNU/doxorubicin/melphalan/dexamethasone) treatment. 43% of MP treated patients responded compared with 64% of the VBAMDex group. 50% TRS was 36 months in both groups without a detectable difference. 117 responders of stage II and III with stable disease were randomised to receive either IFN-alpha (5 x 10(6) IU, subcutaneous (S.C.) 3 times per week) or no maintenance treatment. The relapse rate in both groups was 50% after 13 months. No survival benefit for IFN alpha treated patients was observed (50% TRS: 45 months).
In vitro data have demonstrated autologous T-lymphocytes with anti-tumour activity in multiple myeloma (MM). Therefore a phase I/II trial was conducted to study the feasibility, the effect on several immunological parameters, and the tumour response induction of low-dose recombinant interleukin-2 (rIL-2) in MM patients. 18 MM patients of advanced stages in progress, who had failed on standard chemotherapy received 9 x 10(6) IU/m2 rIL-2 twice daily on days 1 and 2 and 0.9 x 10(6) IU/m2 twice daily for 5 subsequent days per week subcutaneously from days 3 to 56 (repeated every 12 weeks until progression). Patients were treated for between 8 and 1086 + d (mean 241 d) without serious side-effects. 6/17 patients experienced tumour response (2/17 objective tumour mass reduction, 4/17 long-lasting stable disease following tumour progression before initiation of rIL-2 treatment). During therapy the number of eosinophils increased 15-fold, CD4+ T lymphocytes were activated as demonstrated by enhanced CD25 antigen expression, and CD56+ NK cells expanded in the peripheral blood. Furthermore, a diminished pre-treatment ratio of CD4+/CD8+ lymphocytes was normalized during rIL-2 treatment. NK cell activity and lymphokine activated killer (LAK) cell activity was significantly enhanced. Endogenous IL-2 production and elevated soluble IL-2 receptor serum concentrations were induced. Low-dose rIL-2 can stimulate immune enhancement in MM despite the characteristic tumour-induced immunodeficiency. The treatment has proven though limited efficacy in advanced MM. Because most of the responders experienced termination of tumour progression rather than tumour regression, rIL-2 maintenance of chemotherapy-induced remissions should be investigated.
AIMS: The labelling index as defined by the percentage of bone marrow plasma cells doubling their DNA in the S phase is a useful prognostic factor in multiple myeloma. The aim of this study was to examine the specificity and sensitivity of a new flow cytometric method for measuring the labelling index. METHODS: Bone marrow specimens from five patients with monoclonal gammopathy of undetermined significance and 61 patients with multiple myeloma were investigated. The labelling index (LI%) was determined by means of a microscopic and flow cytometric method using the antibromodeoxyuridine antibody BU-1. Serum thymidine kinase, another index of proliferation, was measured by radioimmunoassay. RESULTS: Good comparability (r = 0.83) and nearly equal imprecision (CV < 20%) were found with microscopic and flow cytometric methods of LI% measurement. However, 1000 or more cells had to be counted by microscopy around the cutoff value to avoid an unacceptable imprecision. Plasma cells with increased S phase (LI% > 1%) were characterised by their reduced light chain fluorescence intensity ratio between plasma cells and nonspecifically stained cells (7.9 v 14.8, p < 0.002), that is, by their generally lowered cytoplasmic immunoglobulin content. There was a moderate correlation between thymidine kinase and labelling index (r = 0.56, p < 0.001). At 100% specificity, myelomas with proliferating plasma cells were more sensitively detected by the labelling index than by serum thymidine kinase (55% v 32% sensitivity). CONCLUSIONS: The labelling index represents a more specific and sensitive proliferation marker than serum thymidine kinase. Flow cytometry does not result in greater precision.
In multiple myeloma, correlations between cytogenetic and morphologic findings are hampered by the relatively scarce chromosomal data and the lack of a widely accepted morphologic classification. The aim of the analysis, comprising 111 patients with multiple myeloma, was to study possible correlations between karyotype and a morphologic classification proposed by Bartl et al. Grade of plasma cell infiltration, predominant cell types (Marschalko, small, cleaved, polymorphous, asynchronous, blastic) and grade of malignancy are the basis of this classification. A pathologic karyotype was found in the bone marrow of 39/111 patients (35%). The incidence of chromosomal anomalies closely correlated with the grade of infiltration, plasma cell type and grade of malignancy. Chromosomal anomalies were rarely detected in patients with low infiltration (16%), but they were frequently found in high-grade infiltration (69%). A low incidence was found in Marschalko (25%) or small cell type (15%); the incidence was much higher in cleaved (75%), asynchronous (65%) and basic cell types (71%). An abnormal karyotype was more frequently found in high (71%) than in intermediate (53%) or low (23%)-grade malignant multiple myeloma. The most consistent structural chromosomal aberration found in five patients was translocation t(11;14)(q13;q32). In four of the five patients small, often cleaved plasma cells were the predominant cell types. These reported correlations between morphological and cytogenetic findings must be confirmed by future studies.
P-glycoprotein (P-gp) expression in mononuclear bone marrow cells was analyzed in 119 patients, including 60 with chronic myelogenous leukemia (CML), 48 with myelodysplastic syndromes (MDS), and 11 with acute myelogenous leukemia (AML). For P-gp measurement an immunocytological method using monoclonal antibodies C219, 4E3, and MRK 16 and the reverse transcription-polymerase chain reaction technique were applied. According to our results obtained in healthy volunteers using the immunocytological method, the limit for P-gp overexpression was set at > or = 10% P-gp-positive mononuclear bone marrow cells and at > or = 30% P-gp-positive mononuclear peripheral blood cells. All 42 CML patients in chronic phase had normal P-gp expression. P-gp overexpression was demonstrated in four of six patients in accelerated myelogenous blast cell phase and in four of 12 CML-BC patients. Of eight CML patients in blast crisis (BC) with normal P-gp expression, partial remission was achieved in three and minor response in five after prednisone/vindesine therapy. All four of the 12 CML-BC patients with P-gp overexpression did not respond to this therapy. Normal P-gp expression was seen in 41 (85.4%) of 48 untreated MDS patients. While P-gp overexpression did not develop during therapy in any of the myelodysplastic syndrome patients treated with low-dose ara-C alone, four of eight treated with low-dose ara-C plus GM-CSF and four of 11 treated with low-dose ara-C and IL-3 developed P-gp overexpression after therapy. Furthermore, 11 AML patients at primary diagnosis, including five AML patients with P-gp overexpression, who were treated with idarubicin, vepesid, and cytarabine V (ara-C) showed a complete remission. Additionally, one daunorubicin-cytarabine-pretreated refractory AML patient was treated with the oral form of the P-gp modulator drug dexniguldipine and achieved complete remission for a duration of 7 months. Our results suggest that in CML patients in BC, P-gp expression influences outcome after therapy. Further more, studies in a larger series of patients are necessary to prove the efficacy and toxicity of idarubicin/vepesid and cytardbine--or dexniguldipine-containing--therapy in relation to P-gp expression of AML patients.
We analyzed osseous reactions in the rabbit femoral condyle to coralline hydroxyapatite bone substitutes of various pore sizes by radiology and histology. The results were compared to bone repair of empty cavities and to integration of allografts. Spontaneous bone repair of the empty cavities took approximately 12 weeks, while integration of the cryopreserved allografts occurred after 9 weeks. However, no signs of new bone formation were found with the 200 microns pore size hydroxyapatite. In contrast, there was substantial production of bone within the 500 microns pore size implants at 12 and 26 weeks. Our results indicate that the pore size of the coralline hydroxyapatite influenced the development of bone in the implants in the cancellous bone bed of the rabbit femoral condyle. The results also show that spontaneous bone repair should be taken into consideration when the integration of implants is evaluated.
The chronic myeloproliferative disorders (MPD) comprise polycythemia vera (PV), idiopathic thrombocythemia (IT), chronic myeloid leukemia (CML) and myelofibrosis/osteomyelosclerosis (MF/OMS). Bone marrow biopsies of 3500 patients with known or suspected MPD were studied, and the clinical and morphologic variables registered were utilized for multivariate data analysis by selected BMD computer programs. The histologic criteria and the histologic subdivisions, as well as the evolution and prognosis of disease are outlined for each of the clinical entities. The results show that a bone marrow biopsy provides independent diagnostic and prognostic data in this group of hematologic malignancies and therefore constitutes an additional parameter in the diagnostic investigation of patients with suspected or established MPD.
A 17-year old-male presented with a 6-week history of weight loss, lassitude and calf pains. On examination he was very pale. Laboratory tests showed a very high erythrocyte sedimentation rate (155 mm in the first hour), anaemia (haemoglobin 10.1 g/dl), and a raised serum creatinine of 1.54 mg/dl. Microhaematuria (5-10 erythrocytes/microliter) and pronounced pyuria (500 leucocytes/microliter) were present, but the urine was sterile and there was no increase in albumin excretion. The serum IgG was raised to 75.7 g/l, suggesting an autoimmune disorder. Anti-nuclear antibodies (titre 1 : 1920) and anti-double-stranded DNA antibodies (31 U/ml) were present, while the serum complement C4 was decreased to 0.11 g/l. Renal histology showed an interstitial nephritis without glomerular involvement, while the bone marrow showed vasculitis accompanied by a prominent plasma-cell infiltrate. A diagnosis of interstitial nephritis associated with systemic lupus erythematosus was made, with asymptomatic cardiac and hepatic involvement. Renal function recovered rapidly with prednisolone therapy (initial dose 2 mg/kg.d). While glomerulonephritis is the most common lupus-associated renal disorder, isolated interstitial nephritis may occur in some cases, often with an absence of proteinuria.
The use of bone allografts is often essential in orthopedic surgery. Strict donor screening, including HIV testing 3 months postoperatively, is mandatory before a transplant may be used. Yet these measures do not definitely rule out the possibility of HIV transmission, as there is a window period before infection is revealed by blood testing. Accordingly, there is a need for virus inactivation methods that can be used on bone allografts. As radiation treatment and chemical methods have a number of disadvantages, we chose a moderate heat treatment of 65 degrees C for a series of animal experiments. In 12 rabbit femoral condyles, moderate-heat-treated bone allografts were implanted into 6-mm drill holes. Twelve normal allografts and 12 empty drill holes served as controls. Radiologic and histological evaluation up to 12 weeks postoperatively revealed slow spontaneous bone remodeling from the rim to the center of the empty cavities. Normal deep frozen allografts were quickly intergrated after a short period of osteoclast reaction around the transplant, with occasional bone bridges between host and allograft. The examination of heat-treated allografts showed no differences to the controls, including morphologic aspects and the time course of osteointegration. Five zones of bone repair and osteointegration were distinguished. We conclude that thermal treatment of bone allografts has adverse effects on osteointegration in the rabbit femoral condyle. Thus, it may contribute to improving safety in human bone transplantation.
Plasma cells obtained from bone marrow samples of 45 patients with MM, eight patients with MGUS, eight patients with Waldenström's macroglobulinaemia (WM), one patient with immunocytoma, and 12 controls were characterized by immunophenotyping, estimation of DNA content, and labeling index, as well as by morphological analysis. Plasma cells from 37/45 myeloma and 5/8 MGUS patients expressed CD38 and CD56 (N-CAM) on their surface but were negative for other NK cell-associated antigens such as CD16 (Fc gamma RIII) or CD2. All tumor cells of less-differentiated cell type (WM, immunocytoma) and normal polyclonal plasma cells were negative for CD56. CD56-specific mRNA was demonstrated in myeloma cells by northern blot analysis. Another adhesion molecule, ICAM-1 (CD54), was found on plasma cells from all patients and controls examined. Coexpression of CD19 (1/45), CD20 (9/45), or CD33 (3/45) was rare and CD10 with CD14 was expressed by a small tumor cell subpopulation of only one myeloma patient. The individual pattern of surface marker expression was not associated with a special-type myeloma protein isotype, stage or status of disease, LI or histological classification; however, a correlation between CD56 expression or histological classification and DNA content of the tumor cells was found.