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Bovine bone morphogenetic protein (bBMP) fraction-induced repair of craniotomy defects in the rhesus monkey (Macaca speciosa).

Large cranial defects do not always heal spontaneously, especially in humans; often they have to be obturated with metallic or acrylic fillers. Bilateral cranial trephine defects, measuring 14-20 mm in diameter, were created in three Rhesus monkeys, providing a typical primate model system for investigations in comparative physiology of bone regeneration. Each skull had one control and one experimental trephine defect. Control defects were implanted with bovine serum albumin (BSA). Experimental defects were implanted with 100-200 mg of a partially purified fraction of bovine bone morphogenetic protein (bBMP) in two monkeys. In one monkey, the BMP was incorporated in a 1:1 poly(lactic) poly(glycollic) acid copolymer, high-viscosity formula. The animals were killed at eight weeks, ten weeks, and 16 weeks after implantation. The tissue responses were analyzed by computed histomorphometry and routine histologic examination. At each time interval, the BMP implanted defects produced more complete regeneration than the control implants. The morphogenetic response occurred in the following sequences: mesenchymal cell proliferation, chondrogenesis, and increased bone formation. BMP-induced osteogenesis may initiate the regenerative process. The copolymer releases BMP but may constitute a barrier to the end stages of replacement by new bone, and would be more useful in a low-viscosity rapidly biodegradable form.

Animals↗

Our experience in diagnosing and surgical treatment of traumatic intracranial hematomas. Analysis of 610 patients.

610 patients with traumatic intracranial hematomas treated in the Clinic of Neurosurgery in Plovdiv University of Medicine from 1975 to 1990 were studied. The study aimed at analyzing the most common clinical symptoms and paraclinical indicators leading to correct diagnosis and showing the possibilities of approximate determination of the hematoma location in accordance with the shift of the brain midline and the trauma biomechanics. It also recommends the most effective surgical method which yields the least number of hematoma recurrences. In the study the most common clinical symptom is shown to be the lucid interval. The most common paraclinical indicator is the shift of the brain midline caused by the pathological process. Visualization of the brain midline used in conjunction with the data from the biomechanics of the injury could guide the surgeons for the first burr hole in the exploratory trephination of the skull. It is recommended that, if possible, osteoplastic trephination of the skull on a four-burr-hole bone flap should be applied in the acute period of the craniocerebral trauma. This surgical method assures achievement of the best hemostasis, complete evacuation of the hematoma and the least percentage of recurrences of hematoma after surgery.

Brain Injuries↗

Lymphosarcoma of the frontal sinus and nasal passage in a cow.

A 5-year-old cow was evaluated because of a 2-week history of ataxia and other vague neurologic signs. Previous treatments included intravenous and orally administered calcium, but improvement was not seen. Bilateral mucoserous nasal discharge and a pair of firm, smooth masses caudodorsal to the eyes were found on the frontal bones on physical examination. The cow's condition deteriorated rapidly within 48 hours; head pressing and inability to rise were observed. The frontal sinuses were radiographically normal. Trephination of the frontal sinuses revealed a space-occupying mass that was interpreted on histologic examination to be lymphosarcoma. Other evidence of neoplasia was not discovered on gross necropsy or histologic examination. Primary lymphosarcoma has not been described at this location in cows. Clinically it resembles chronic frontal sinusitis, and trephination may be necessary to differentiate the 2 diseases.

Animals↗

Endothelial lamellar keratoplasty using an artificial anterior chamber and a microkeratome.

OBJECTIVE: To compare postoperative astigmatic change and graft stability using 2 different donor button diameters in endothelial lamellar keratoplasty to treat corneal endothelial failure. METHODS: A 200- micro m-thick corneal flap keratectomy was performed in human donor corneoscleral rims (n = 20; 10 donors and 10 recipients) using an artificial anterior chamber and a manual microkeratome (ALTK System; Moria USA, Doylestown, Pa). After flap reflection, stromal bed trephination was performed to obtain a disc consisting of posterior stroma, Descemet membrane, and endothelium. Host beds of 7.0 mm and 7.25-mm (n = 5) or 7.50-mm (n = 5) donor buttons were obtained using a freehand trephine. The graft was secured with 8 interrupted sutures (10-0 nylon) in the stromal bed. The flap was sutured with 3 interrupted sutures. Transplanted corneas were submitted to increasing intrachamber pressures to detect graft stability, and preoperative and postoperative videokeratographic data were recorded to assess astigmatic change. RESULTS: The mean (SD) postoperative astigmatic change was 1.14 (3.17) diopters (D) in the 7.25-mm donor button group and 2.27 (1.77) D in the 7.50-mm donor button group (P =.69). Mean (SD) resisted pressures of 75.4 (44.81) mm Hg and 100.4 (46.86) mm Hg were observed in the 7.25-mm and 7.50-mm groups, respectively (P =.54). CONCLUSION: Both donor button sizes exhibited similar graft stability and astigmatic postoperative change in this experimental model. CLINICAL RELEVANCE: As endothelial lamellar keratoplasty becomes further developed as a clinical alternative to penetrating keratoplasty, this laboratory model system should be useful in evaluating different mechanical factors that contribute to graft success.

Adult↗

Radioactive and bioassay of intraocular antibiotics: double-assay technique to compare penicillin G, cefamandole, and gentamicin in ocular tissues in vivo.

We examined the correlation between radioactive assay and trephine-discbioassay of penicillin G sodium, cefamandole nafate, and gentamicin sulfate in ocular tissues of pigmented rabbits after subconjuctival administration of antibiotic. We devised a technique whereby a single sample of tissue could be assayed by both methods. This was achieved by performing the bioassay first, then measuring the resudual radioactivity in the agar and specimens. The results of both methods were generally within 13%. An exception was gentamicin in iris and choroidretina, for which the bioassay result was strikingly less than the radioassay value. No such discrepancy was evident when similar studies were carried out with gentamicin in albino rabbits. This suggests that the phenomenon is due to tight binding of gentamicin by melanin-containing tissues. The trephine-disc bioassay provides an accurate measure of diffusible bioactive antibiotic in ocular tissues.

Animals↗

Refractive variation and donor tissue size in aphakic keratoplasty. A prospective randomized study.

Forty-six patients were examined in a prospective, randomized clinical study to compare the use of the same size trephine on both donor and recipient with the use of a 0.5-mm larger trephine on the donor in aphakic keratoplasty and in keratoplasty combined with lens extraction. The results showed no statistically significant difference in refractive error, either in spherical equivalents or in astigmatism. The larger donor tissue may have some value in reducing high plus-refractive error and in reducing intraocular pressure after surgery.

Aphakia↗

Apoptosis and proliferation (PCNA labelling) in CML--a comparative immunohistological study on bone marrow biopsies following interferon and busulfan therapy.

A comparative morphometric analysis was performed on smears and trephine biopsies of normal bone marrow and in chronic myelogenous leukaemia (CML) to assess the effects of therapy on apoptosis and cell proliferation. The in situ end-labelling (ISEL) technique was used for the demonstration of programmed cell death, in combination with the monoclonal antibody PG-M1 to identify macrophages. Cell proliferation was evaluated by employing the monoclonal antibody PC10 directed against proliferating cell nuclear antigen (PCNA). In CML (48 patients), significantly higher rates of apoptosis were observed than in normal bone marrow (smears, frozen sections, and paraffin-embedded samples) of 15 patients. In contrast, the PCNA labelling index of CML was not different from controls. In bone marrow tissue derived from CML patients, about 36 per cent of apoptotic bodies were ingested with CD68-positive macrophages. Study of the histotopographical distribution of labelled cells revealed that in CML, in contrast to the normal bone marrow, programmed cell death and PCNA activity were concentrated along the paratrabecular generation zone. In 28 patients with CML treated with interferon (IFN), sequential trephine biopsies displayed a significant enhancement of apoptosis which was associated with a decrease in PCNA reactivity. In contrast to this finding, no such alterations could be observed in 24 patients who received busulfan (BU) monotherapy. This study furthers the understanding of cell kinetics in CML. IFN therapy induces apoptosis and suppresses cell proliferation. The rate of programmed cell death prior to therapy and the extent of IFN-triggered apoptosis exert a significant predictive impact on survival. In this study, ISEL-positive (apoptotic) cells and bodies do not correspond to unscheduled cell repair as detected by PCNA immunoreactivity.

Adult↗

Assessment of cellular expression of parathyroid hormone-related protein mRNA and protein in multiple myeloma.

The capacity of multiple myeloma cells to generate parathyroid hormone-related protein (PTHrP) has been examined by in situ assessment of PTHrP mRNA and PTHrP protein in myeloma cells of patients in whom the disease was associated with the development of hypercalcaemia. The presence of PTHrP mRNA was evaluated by in situ hybridization using an antisense riboprobe, and PTHrP by immunohistochemistry using a monoclonal antibody, in archival bone marrow trephine specimens from 17 patients. PTHrP mRNA was detected in myeloma cells in 16 of the 17 patients, indicating a high frequency of PTHrP gene expression in myeloma cells in these subjects. PTHrP protein was, on the other hand, detected in the myeloma cells of only five of these patients. The impact of the mercury-based fixation and decalcification procedure used for processing the bone marrow trephine specimens was assessed to determine the influence of this process on the outcome of the immunohistochemical assay for PTHrP. It was shown that this preparative procedure resulted in a marked reduction of immunohistochemically detectable PTHrP, which provides a possible explanation for the lower frequency of positivity for PTHrP in myeloma cells in the bone marrow specimens. The present findings are consistent with the view that PTHrP can be generated in myeloma cells in vivo, and could contribute to osteolysis and hypercalcaemia, as in patients with cancer.

Aged↗

Lung biopsy in immunocompromised patients: one institution's experience and an approach to management of pulmonary disease in the compromised host.

The authors report on their institution's experience with 53 lung biopsies, including 26 open, 22 transbronchial, and five trephine air drill biopsies, performed in immunocompromised patients with roentgenographic pulmonary infiltrates. Open biopsy was far more likely to provide a specific etiologic diagnosis (81%, P less than 0.001) than transbronchial biopsy (32%), or trephine biopsy (20%). Infection (17 biopsies), neoplastic disease, (7) or drug-related pneumonitis (2) were identified most frequently. Patients with myeloproliferative disease, granulocytopenia, or those who had not received prior immunosuppressive therapy were most likely to have a nondiagnostic biopsy (P less than 0.05 for each factor). The overall complication rate of biopsy procedures was 15% and was comparable with all three methods. Survival in this series was not significantly lower if a specific etiologic diagnosis could not be established, but correlated with the respiratory rate (less than 20 per minute), pO2 (greater than 60 torr), and the roentgenographic pattern (other than bilateral diffuse disease) at the time of biopsy (P less than 0.05 for each factor). There were 18 cases (34%) in which a clearcut etiologic diagnosis would not be established at the time of biopsy; based on serologic tests performed ex post facto, 2 of 12 of these cases (17%) were Legionnaire's disease. Lung biopsies were helpful in the management of the majority of the cases, although nondiagnostic biopsies continue to be a problem. The authors propose an approach to the management of compromised patients with pulmonary infiltrates.

Biopsy↗

Bone marrow involvement in histiocytosis X.

Twenty-eight patients with histiocytosis X (HX) who had bone marrow aspirates and/or trephine biopsies taken at diagnosis were studied. Five of the 28 patients (18%) had bone marrow specimens with clusters of benign histiocytes characteristic of histiocytosis X. Several statistically significant clinical and laboratory differences were found between those patients with positive marrows versus those with uninvolved bone marrows. Presence of HX in the bone marrow was more frequently associated with fever (P less than 0.01), splenomegaly (P less than 0.01), rash (P = 0.04), diabetes insipidus (P = 0.09), and platelet counts less than 175 X 10(9)/L(P = 0.01). Two of the five patients with bone marrow involvement died, whereas there were no deaths due to HX in the other 23 patients. From this review, it is suggested that bone marrow involvement at diagnosis may be associated with more extensive and potentially fatal disease. HX of the marrow was more easily diagnosed from trephine biopsy sections than aspiration smears.

Adolescent↗

In vitro transplantation of fetal human retinal pigment epithelial cells onto human cadaver Bruch's membrane.

Retinal pigment epithelium transplantation has been proposed as adjunctive treatment for age-related macular degeneration following surgical excision of choroidal neovascular membranes. The goal of this study was to develop a model to evaluate retinal pigment epithelium transplantation onto human Bruch's membrane in vitro. We investigated the ability of cultured fetal human retinal pigment epithelium to colonize human cadaver Bruch's membrane, determined the incubation time needed to form a monolayer and to exhibit apical microvilli and tight junctions, and assessed the production of basement membrane. Freshly enucleated (less than 48 hours old) human eyes were cut through the pars plana, and the anterior segment, vitreous, and retina were removed. The native retinal pigment epithelium was debrided with a surgical sponge. Bruch's membrane and choroid at the macula were trephined with a 7.0 mm diameter trephine and then incubated with 1/2 ml of Dulbecco's modified Eagle's medium +15% fetal calf serum+basic fibroblast growth factor (1 ng ml-1), and fetal human retinal pigment epithelium at a concentration of 242,000 cells ml-1. Specimens were incubated for 1, 4, 6, 8, 12, or 24 hours. The specimens were fixed in half strength Karnovsky's fixative, processed, and analysed with scanning and transmission electron microscopy. The retinal pigment epithelium covered the debrided macular specimens to different degrees at different incubation times. After 1 hour, the cells started to attach and flatten (median percent coverage: 78%). The extent of Bruch's membrane coverage by fetal retinal pigment epithelium varied greatly between specimens. After 4-6 hours, the cells covered the entire debrided surface in a monolayer (median percent coverage: 97.2% at 4 hours, 99.8% at 6 hours). Tight junctions were observed, and the cells had few apical microvilli. The lateral cell borders were obliquely oriented with respect to Bruch's membrane, and the nuclei were elongated, exhibited prominent nucleoli, and were oriented parallel to Bruch's membrane. After 6-8 hours, cells started to become hexagonal (median percent coverage at 8 hours: 99.97%). Cells attached to the inner collagenous layer tended to be flatter than cells attached to residual native basement membrane. At 12 and 24 hours, expression of hexagonal shape, tight junctions, and apical microvilli were observed more frequently (median percent coverage: 99.87% at 12 and 100% at 24 hours). No newly formed basement membrane was observed at these time points. In separate experiments comparing attachment in the presence and absence of native RPE basement membrane, the presence of native retinal pigment epithelial basement membrane promoted the early attachment of the cells and more rapid expression of normal morphology. This in vitro system provides a reproducible way to study the adherence of retinal pigment epithelium to normal and diseased human Bruch's membrane.

Aged↗

Intrascleral concentration vs depth profile of mitomycin-C after episcleral application: impact of irrigation.

Mitomycin-C has been reported to cause toxic effects on the ciliary body after episcleral application during glaucoma surgery. We investigated the intrascleral diffusion of mitomycin-C in an experimental model. The episcleral sides of scleral quadrants of 14 human donor eyes were exposed for 5 min to sponges (corneal light shield, Merocel corp., Mystic, CT, U.S.A.) soaked with 200 microg ml(-1)mitomycin-C. After the exposure one of four quadrants was not irrigated and the episcleral sides of three quadrants were irrigated with 40, 100 and 200 ml saline. A 9 mm scleral disk was punched out with a trephine and frozen on a kryotome plate 2 min after the end of mitomycin-C exposure. An 8 mm diameter scleral disk was then cut with a trephine, again frozen on a kryotome plate and then horizontally dissected with a kryotome. For analysis purposes seven cuts of 20 microm thickness were combined to one layer of 140 microm. Six layers could be reproduced and were analysed. The mitomycin-C concentrations of these layers were analysed by high-performance liquid chromatography. A concentration vs depth profile was calculated for each group, and the half-width of concentration was calculated by log-linear regression. The mitomycin-C concentration of layer 1 was 24.51 microg g(-1)(+/-7.52) without irrigation, 13.15 microg g(-1)(+/-4.38) after 40 ml irrigation, 10.29 (+/-3.53) after 100 ml irrigation and 8.4 microg g(-1)(+/-1.62) after 200 ml irrigation. In layers 1-3 the concentration of mitomycin-C was significantly reduced by irrigation (ANOVA). In the deeper intrascleral layers irrigation had no effect on the mitomycin-C concentrations. Between layers 2 and 6 the half-width of the mitomycin-C concentration was 101 microm (no-irrigation group), 141 microm (40 ml irrigation group), 153 microm (100 ml irrigation group), and 164 microm (200 ml irrigation group). Irrigation reduced the mitomycin-C concentration only down to half of the scleral thickness, leaving the deep intrascleral concentrations unchanged.

Antibiotics, Antineoplastic↗

[Demonstration of aqueous outflow patterns of normal and glaucomatous human eyes through the injection of fluorescein solution in the anterior chamber (author's transl)].

After partially injecting the anterior chamber with a 0.2% fluorescein-Ringer solution we examined using a blue filter slitlamp normal eyes, eyes with open-angle glaucoma, and eyes following iridectomy, iridencleisis, Elliot's trephination, and trabeculectomy. In normal eyes at physiological intraocular pressure, 1--9 aqueous veins were found with a mean of 4.6. The distribution of these veins was usually irregular, being more numerous and of largest caliber in the lower nasal quadrant. With only a few exceptions the aqueous veins originated 1--2 1/2 mm peripheral from the limbus and joined the episcleral veins after a short course. The venae recipientes were characterized by a straight and deep course. In eyes with an open-angle glaucoma the average number of aqueous veins was found to be increased compared to the number found in healthy eyes. However, the caliber of these veins was smaller and distribution mor uniform. Eyes having undergone iridectomy do not differ from normal eyes in the mechanism of aqueous humor outflow. After iridencleisis and after trephination the transport of aqueous humor from the anterior chamber is achieved through a filtration bleb: (1) transconjunctival, (2) by bulk-flow through lymphatic vessels, (3) diffusely through lymphatic vessels or veins. In most cases the different transport mechanisms were combined and pure types were seldom found. There was a very definite relationship found between the size of the filtration bleb and the development of draining lymphatic vessels. After trabeculectomy the following drainage mechanisms of the aqueous humor were observed: 1. Subconjunctival outflow of aqueous humor. The further drainage in this case was achieved as in the old types of fistula building operations i.e., primarily through the lymphatic vessels. 2. Direct transport of aqueous humor into the surgical area through newly incorporated veins and lymphatic vessels. 3. Drainage of aqueous humor through still functioning aqueous veins.

Adult↗

Reticulin fibre content of bone marrow infiltrates of malignant non-Hodgkin's lymphomas (B-cell type, low malignancy)--a morphometric evaluation before and after therapy.

A morphometric study was performed on bone marrow infiltrates of non-Hodgkin's lymphomas (B-cell type, low malignancy) to evaluate the content of argyrophilic (reticulin) fibres in the various subtypes before and after therapy. In congruence with the corresponding lymph node lesions, subtypes consisted of lymphocytic lymphoma--chronic lymphocytic leukaemia (CLL, n = 39), centroblastic-centrocytic lymphoma (CB-CC, n = 35), lymphoplasmacytoid immunocytoma (LPI, n = 22) and finally hairy cell leukaemia (HCL, n = 21). In comparison with control specimens, morphometric measurements on trephine biopsies (initial staging procedure) disclosed a borderline or minimal increase in reticulin in CLL and moderate fibrosis in CB-CC and LPI, whereas HCL had the greatest increase in fibres. The marrow surrounding focal or patchy lymphoma infiltrates of CLL and CB-CC displayed no relevant changes in fibre density with respect to the control samples. Following chemotherapy, repeated trephine biopsies (restaging procedure) were obtainable from 38 patients. There was no significant decrease in the fibre content of CLL, CB-CC and LPI infiltrates. In HCL an incomplete reduction was recorded after interferon treatment. So-called benign lymphoid lesions may be distinguished from focal-patchy infiltrates of CB-CC and LPI not only by showing a central localization, but also by the absence of significant amounts of reticulin. However, considering the density of the reticulin fibres, a clear-cut discrimination of these lymphoid aggregates from an early nodal-central growth pattern of CLL is not feasible in many cases.

B-Lymphocytes↗

[Internal callus distraction in epiphyseal groove defect--a physiologic means of spontaneous correction. Results of a comparative histomorphologic study in a small and large animal experiment].

For this experimental study we removed with a trephine in small (rabbit) and larger (pigs) animals cylinders of 2 mm respectively 8 mm diameter from the central growth plate area of proximal tibia. The direction of burring is in the axial line of the femur proximo-distally; the insertion point of the trephine is chosen on the cheek of the medial femoral condyle. As common reaction to that kind of trauma the defects in growth plates of rabbits become filled with a bone bridge that joins the epiphyseal core to the metaphyseal trabeculae, leading to gross growth disturbances. In pigs a similar solid bridging as first reaction develops, interrupted later by a zone of longitudinal collagen fibre bundles within a non-mineralized matrix. The distending pressure of surrounding intact growth cartilage continuously brakes fracture callus formation and its calcification. Such so-called internal callus distraction leads to unaltered longitudinal bone growth.

Animals↗

The role of morphology, cytochemistry and immunohistochemistry in the diagnosis of lymphoproliferative disorders.

The bone marrow examination is a valuable procedure in the diagnosis and management of patients who have NHL. Posttherapy bone marrow examination is useful for assessing a patient's response to chemotherapy and for monitoring previously treated patients for evidence of recurrent disease. The bone marrow examination should include trephine biosy section, trephine imprints, aspiration smears, clot sections and blood smears and all of these preparations should be studied by the same pathologist. In addition to the morphologic evaluation, the aspirated marrow is the best material for several important supplemental studies for characterization of NHLs, including immunophenotyping by flow cytometry, cytogenetics, most molecular studies, and microbiologic cultures. Flow cytometric immunophenotyping studies to determine lineage, clonality of B-cell processes, and approximate stage of neoplastic infiltrates are the most useful adjuvant to morphologic assessment for NHLs. This review concentrates on the characteristic morphology, cytochemistry, immunohistochemical assessment and immunophenotyping of each clinical entity according to WHO classification. For the differential diagnosis, reactive lymphoid lesions, including lymphocytic aggregates, reactive polymorphous lymphohistiocytic lesions, benign follicles with germinal centers and polyclonal immunoblastic proliferations will be discussed.

Adolescent↗

Successful treatment by selective arterial embolization of severe retroperitoneal hemorrhage secondary to bone marrow biopsy in post-polycythemic myelofibrosis.

Severe retroperitoneal hemorrhage represents an infrequent and serious complication of bone marrow biopsy. A 53-year-old man, diagnosed with polycythemia vera 12 years earlier, was submitted to a bone marrow biopsy due to the appearance of anemia with clinical and hematological features suggesting myelofibrotic transformation, a diagnosis that was confirmed by the marrow study. At 2 h of a right anterior iliac bone marrow trephine biopsy, the patient suddenly developed severe pain in the area of the biopsy, with antialgic flexion of the right leg. Computed tomographic (CT) scan of the abdomen showed a 5 x 9.5 cm hematoma in the right iliac and psoas muscles. The patient was initially managed with analgesics and transfusional support, but the pain persisted and a continuous fall in the hematocrit was observed in the following days. Angiographic examination of the right external iliac artery showed contrast extravasation arising from the circumflex iliac branch, which was embolized using polivinyl alcohol particles and one coil. Following such procedure, the patient recovered uneventfully and was discharged in good condition a few days later. This case illustrates the effectiveness of an endovascular approach in providing a fast and minimally invasive treatment for this life-threatening complication of bone marrow trephine biopsy.

Adult↗

[Myelodysplastic syndromes (MDS). Aspects of hematopathologic diagnosis].

Myelodysplastic syndromes (MDS) are a heterogenous group of clonal stem cell disorders which generally occur in older adults but may also affect children. Primary MDS should be distinguished from secondary MDS associated with antineoplastic or immunosuppressive therapy (t-MDS), exposure to toxic compounds, or genetic disorders. The establishment of a neoplastic clone is reflected by dysplastic features and impaired function which may affect all three hematopoietic cell lineages. The ineffective hematopoiesis which causes bone marrow failure is accompanied by peripheral blood cytopenia and is considered to result from increased apoptosis, at least in the less advanced MDS stages. The elucidation of the molecular pathogenesis of MDS has provided evidence that chromosomal abnormalities are present in about 50% of patients with primary MDS. They include numerical aberrations such as monosomy 5 or 7, trisomy 8, loss of the Y-chromosome and structural abnormalities such as deletion of the long arm of chromosome 5 (5q-syndrome), 7, or 8. Based on the percentage of blasts (<5%, 5-20%, 20-30%) and the presence of >15% ringed sideroblasts for marrows with <5% blasts, the French-American-British (FAB) classifies MDS into 4 morphologic categories: refractory anemia (RA), refractory anemia with excess of blasts (RAEB), refractory anemia with excess of blasts in transformation (RAEB-t), and refractory anemia with ringed sideroblasts. The fifth morphologic type is chronic myelomonocytic leukemia characterized by peripheral blood monocytosis (>1x10(9)/l). However, a modification of this classification will be proposed by the World Health Organization, with the intention of lowering the threshold for the diagnosis of AML from 30% to 20% blast cells. In patients presenting with cytopenias suggesting impaired hematopoiesis, the initial diagnosis depends mainly on the cytological evaluation of bone marrow and blood smears and the histological findings of trephine bone marrow biopsy. In a retrospective analysis we evaluated the occurrence of the distinct FAB-categories as percentage of the total number of MDS cases diagnosed at the Institute of Pathology of the University of Freiburg. A total of 63% fullfilled the criteria of RA/RARS, 17% of RAEB, 14% of RAEB-t, and 6% of CMML. A fibrotic variant of MDS was observed in 7.67% of all cases, ranging from 2.34% in RA up to 15. 42-15.84% in the categories which did not show significant differences with regard to myelofibrosis. The histologic evaluation of a trephine bone marrow biopsy is of critical importance for the evaluation of fibrotic or hypocellular MDS since these patterns are not reflected by the cytological examination. The combined cytological and histological diagnosis of bone marrow and peripheral blood is a reliable tool for the initial diagnosis of MDS. In addition, cytogenetic and molecular analysis should be performed. Presently, the risk of leukemic transformation is evaluated using the International Prognostic Scoring System for MDS, which is the sum of the scores of bone marrow blasts, karyotypes and cytopenia. In the context of clinical trials therapeutic modalities should be considerd according to the age and the general performance state and the prognostic scores of individual patients.

Adult↗