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Biomedical subjects

M Rozman

Publications and source records attributed to M Rozman.

At least 19 recordsLinked to original sources

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↗

Smoldering multiple myeloma: natural history and recognition of an evolving type.

Patients with smoldering multiple myeloma (SMM) meet the diagnostic criteria of multiple myeloma (MM) but are asymptomatic. Between January 1978 and July 2001, 53 patients (median age 63 years) were diagnosed with SMM. The median serum M-protein and proportion of bone marrow plasma cells were 36 g/l and 27% respectively. Two subsets of SMM were identified: (i) evolving SMM (n = 22), characterized by a progressive increase in serum M-protein, a previously recognized monoclonal gammopathy of undetermined significance (MGUS) and a significant higher proportion of IgA type and (ii) non-evolving SMM (n = 26) with stable M-protein that abruptly increases when symptomatic MM develops. Thirty-four patients developed symptomatic MM. The median time to progression in the overall series was 3.2 years and the only feature associated with a shorter time to progression was the evolving versus non-evolving type (1.3 vs. 3.9 years respectively, P = 0.007). The pattern of progression consisted of anaemia, lytic bone lesions or both, without renal failure, hypercalcaemia or extramedullary plasmacytomas. Fifty-seven per cent of patients that required chemotherapy showed no or minimal response. The median survival from diagnosis and from progression was 8.2 and 3.5 years respectively.

Adult↗

Malignant transformation in IgM monoclonal gammopathy of undetermined significance.

Monoclonal gammopathy of undetermined significance (MGUS) is a frequent disorder characterized by the presence of a small serum M-protein in individuals with no evidence of multiple myeloma (MM), Waldenstrom's macroglobulinemia (WM), or primary amyloidosis (AL). Although one fourth of these individuals will develop a malignant disease, there are no well-established predictors of outcome, particularly in the IgM type MGUS. Among 434 patients diagnosed with MGUS from 1970 to 2001 with a minimum follow-up of 1 year, 52 (27 men and 25 women; median age, 67 years) of IgM type were identified. After a median follow-up of 5 years, five patients (9.6%) have developed WM. The risk of transformation was 13.3% (95% confidence interval [CI], 0 to 27) and 27.7% (95% CI, 0.3 to 55.1) at 10 and 20 years, respectively. The variables significantly associated with transformation were the proportion of bone marrow plasma cells (BMPC) and the percentage of bone marrow lymphocytes (BML). No significant differences in the risk of transformation were found between IgM MGUS and the remaining MGUS types. Thus, in IgM MGUS the rate of transformation was similar to the risk observed in other MGUS types, the percentage of BMPC and BML being the features significantly associated with evolution into WM.

Aged↗

Multiple cell cycle regulator alterations in Richter's transformation of chronic lymphocytic leukemia.

To investigate the role of the cell cycle regulators p21(Waf1), p27(Kip1), retinoblastoma (Rb), and cyclin D1 in Richter's transformation of chronic lymphocytic leukemia (CLL), we analyzed 19 CLL and eight Richter's syndrome (RS) tumors, previously characterized for p53 and ARF/INK4a abnormalities. p21(Waf1)immunohistochemical expression was negative in 12 of 15 CLL (80%), whereas it was moderate or strong in three of seven RS (43%). p21(Waf1) gene was in germline configuration in all the tumors analyzed. Four immunohistochemical patterns of p53 and p21(Waf1) expression were observed: (1) p53-/p21- in 10 of 15 CLL (67%), but only in two of six RS (33%); (2) p53+/p21+ in three CLL (20%) and two RS (33%); (3) p53-/p21+ in one RS; and (4) p53++/p21- in two CLL and one RS. Two p53+/p21+ CLL evolved into RS. p53 mutations clustered around the p53++/p21- (two CLL and one RS) and p53-/p21- (one CLL and one RS) tumors. While the majority of CLL displayed strong p27 immunoreactivity, RS tumors were constantly p27-negative. p27(Kip1) gene was in germline configuration in all the tumors analyzed. Most CLL cases were negative for Rb expression. In contrast, all RS exhibited strong Rb expression. Cyclin D1 overexpression was only detected in one CLL evolving into RS and one RS. In conclusion, a p53+/p21- immunohistochemical pattern is shown exclusively by p53-mutated CLL/RS. Additionally, our results suggest a possible implication of moderate/strong p21(Waf1) expression, loss of p27 expression, and cyclin D1 overexpression in the Richter's transformation of CLL.

Adult↗

Simultaneous diagnosis of hairy cell leukemia and chronic lymphocytic leukemia/small lymphocytic lymphoma: a frequent association?

The association of hairy cell leukemia (HCL) with other neoplasms, mainly non-Hodgkin's lymphomas, is well known. However, the simultaneous diagnosis of HCL and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is rare, with only few cases of such an association having been reported. We describe three patients with a well-characterized HCL in whom a CLL/SLL population was detected. Of note, these cases represent a significant proportion (11.5%; 95% CI: 0% to 24%) of the total number of HCL cases diagnosed in our institution during the same period of time. All three patients were treated with deoxycoformycin. They achieved a complete response of the HCL, whereas the CLL/SLL population persisted in all cases. The immunoglobulin gene rearrangement analysis, in two informative cases, suggested that the HCL and CLL/SLL populations arose from different B cell clones. This study indicates that the association of HCL and CLL/SLL might be much more frequent than previously recognized. Therefore, a large panel of monoclonal antibodies, including those necessary to detect CLL/SLL, should be employed when studying patients with HCL.

Antimetabolites, Antineoplastic↗

HTLV-1 and HTLV-2 infections in HIV-infected individuals from Santos, Brazil: seroprevalence and risk factors.

Because HTLV-I, HTLV-2, and HIV share identical modes of transmission, simultaneous or subsequent infections with these retroviruses are to be expected. The population of Santos, the largest port in Latin America, includes large numbers of female commercial sex workers and intravenous drug users, presumably having been exposed to retroviral infection. To evaluate the seroprevalence of HTLV infection and their associated risk factors, a cross-sectional survey was carried out in 499 HIV-infected individuals from Santos, Brazil. HTLV testing consisted of enzyme immunoassays for serologic screening and confirmatory Western blot testing. Overall HTLV-I and HTLV-2 seroprevalences were 6.0% (95% confidence interval [CI], 3.9-8.1) and 7.4% (95% CI, 5.1-9.7), respectively. Multivariate logistic regression for statistical analysis revealed HTLV-I infection to be independently associated with: intravenous drug use (IDU) (odds ratio [OR]. 2.99; 95% CI, 1.09-8.20), seropositivity to hepatitis C virus (HCV) (OR, 3.03; 95% CI, 1.02-9.01) and < 3 years of education (OR, 4.73; 95% CI, 1.56-14.41). HTLV-2 infection was associated with: IDU (OR, 3.22; 95% CI, 1.33-7.84), HCV seropositivity (OR, 5.40; 95% CI, 1.86-15.66) and nonwhite race (OR, 3.32; 95% CI, 1.58-7.00). Results indicate that HIV-infected individuals living in Santos are at similarly high risk of being exposed to HTLV-1 and HTLV-2. IDU constitutes the main risk factor for HTLV acquisition in this population, and there is no significant risk associated with sexual practice.

Adolescent↗

The glycaemic index values of Vietnamese foods.

OBJECTIVE: To determine and compare the glycaemic index (GI) values of a range of Vietnamese foods in two racial groups. DESIGN AND SUBJECTS: Twelve healthy subjects (six Asian and six Caucasian) consumed 50 g carbohydrate portions of a reference food (glucose sugar) and nine Vietnamese foods (three rices, three noodle products and three sweet foods) in random order after an overnight fast. The reference food was tested on two separate occasions, and the Vietnamese foods were each tested once. Capillary blood samples were taken at time 0 (fasting), 15, 30, 45, 60, 90 and 120 min from the start of each meal. Samples were analysed for plasma glucose and the incremental areas under the plasma glucose curves (AUC) were used to calculate the GI values of the test foods, using glucose as the reference food (ie GI value of glucose=100). The mean GI value of each food was calculated for the entire group of subjects (n=12) and for both racial groups (n=6). RESULTS: The three rices had surprisingly high GI values (86-109), whereas the noodle products had relatively low GI values (39-61). The sugar-rich foods produced intermediate GI values (54-79). The GI values for the nine foods calculated separately for the two racial groups were not significantly different from each other (P=0.26). CONCLUSIONS: The GI values derived from Caucasian subjects are likely to be applicable to Asian populations. Varieties of imported rice from Thailand were found to have high GI values. Alternative low-GI staples, such as rice noodles, may be preferable for Asian/Vietnamese people with diabetes. SPONSORSHIP: This study was funded by the University of Sydney.

Animals↗

Usefulness and reproducibility of cytomorphologic evaluations to differentiate myeloma from monoclonal gammopathies of unknown significance.

We attempted to differentiate monoclonal gammopathies of unknown significance (MGUS) and multiple myeloma (MM) on morphologic grounds and to determine interobserver reproducibility of the differentiation. Cytologists blindly evaluated bone marrow smears from 154 patients with bone marrow plasmacytosis for the proportion of plasma cells with predefined cellular atypias. The single morphologic characteristic that most strongly differentiated MM from MGUS was the presence of nucleoli. The percentage of plasma cells, cytoplasmic contour irregularities, and anisocytosis also predicted a diagnosis of myeloma in multivariate analysis. Six cytologists independently evaluated 68 consecutive cases to determine sensitivity and specificity of these cytomorphologic features. The interobserver coefficient of variation for the plasma cell count was 33%. On consideration of the diagnosis, 36 of 41 MGUS cases and all 24 cases of myeloma were classified correctly. The use of a predesigned score system did not present such a bias, although it did not improve overall efficiency. The plasma cell count is the most predictive characteristic of myeloma from a cytologic viewpoint, but the interobserver variability is high. Interobserver variability is also high in the assessment of morphologic atypia, and atypical traits are not uncommon in plasma cells in MGUS.

Blood Cell Count↗

Complete remission of idiopathic myelofibrosis following donor lymphocyte infusion after failure of allogeneic transplantation: demonstration of a graft-versus-myelofibrosis effect.

A patient with idiopathic myelofibrosis (IM) in the osteosclerotic phase received an allogeneic stem cell transplant. Hemopoietic engraftment was rapid, and full donor chimerism was observed on day +70. However, a few months later, replacement of donor hemopoiesis by the patient's 20q- cell clone was observed, followed by reappearance of the blood IM features, marrow fibrosis and osteosclerosis. At 8 months from transplant donor lymphocytes were infused, which induced chronic GVHD. This resulted in normalization of the blood, with disappearance of the fibrosis and osteosclerosis, effects which persisted 20 months later. This case provides evidence for a graft-versus-disease effect in IM.

Female↗

Rapid diagnosis of acute promyelocytic leukemia by analyzing the immunocytochemical pattern of the PML protein with the monoclonal antibody PG-M3.

The fusion protein, promyelocytic leukemia-retinoic acid receptor (PML-RAR)alpha, generated by the t(15;17) translocation has an abnormal cellular distribution with colocalization of RARalpha and PML proteins. We analyzed the immunostaining pattern of PML protein using the PG-M3 monoclonal antibody directed against the amino terminal portion of PML (retained in wild-type PML and PML-RARalpha fusion protein) in the diagnosis of acute promyelocytic leukemia (APL). In addition, we compared this test with other methods for detecting the PML-RARalpha fusion gene. A normal immunostaining pattern was observed in nonmyeloid disorders and in 78 of 111 acute myeloid leukemias (AMLs). A microgranular pattern was observed in 25 AMLs, all corresponding to APL. These results were concordant with the reverse transcriptase-polymerase chain reaction results for PML-RARalpha fusion gene. Only 1 case positive for the PML-RARalpha transcript showed a normal protein pattern by immunocytochemistry. PML immunostaining was helpful to rapidly differentiate 7 cases with borderline characteristics and to obtain the diagnosis in 2 cases with scarce material. The effectiveness and low cost of this technique support its routine use as a first-line procedure in the differential diagnosis of AML.

Antibodies, Monoclonal↗

Correlation between HIV and HCV in Brazilian prisoners: evidence for parenteral transmission inside prison.

OBJECTIVE: It is an accepted fact that confinement conditions increase the risk of some infections related to sexual and/or injecting drugs practices. Mathematical techniques were applied to estimate time-dependent incidence densities of HIV infection among inmates. METHODS: A total of 631 prisoners from a Brazilian prison with 4,900 inmates at that time were interviewed and their blood drawn. Risky behavior for HIV infection was analyzed, and serological tests for HIV, hepatitis C and syphilis were performed, intended as surrogates for parenteral and sexual HIV transmission, respectively. Mathematical techniques were used to estimate the incidence density ratio, as related to the time of imprisonment. RESULTS: Prevalence were: HIV - 16%; HCV - 34%; and syphilis - 18%. The main risk behaviors related to HIV infection were HCV prevalence (OR=10.49) and the acknowledged use of injecting drugs (OR=3.36). Incidence density ratio derivation showed that the risk of acquiring HIV infection increases with the time of imprisonment, peaking around three years after incarceration. CONCLUSIONS: The correlation between HIV and HCV seroprevalence and the results of the mathematical analysis suggest that HIV transmission in this population is predominantly due to parenteral exposure by injecting drug, and that it increases with time of imprisonment.

Adult↗

Anaplastic large-cell lymphoma with rapid evolution to leukemic phase.

Anaplastic large-cell lymphoma (ALCL) is a lymphoproliferative disorder that frequently presents with disseminated disease and extranodal involvement. Rare atypical cells have been detected in the peripheral blood in occasional cases. However, the presence of a prominent leukemic phase is extremely rare in these patients. We describe a patient with a small-cell variant of ALCL of T-cell phenotype, ALK-1 positive, who developed a rapid leukemic phase in association with the progression of the disease. Similar to the nodal biopsy, the predominant cells in bone marrow and peripheral blood were small atypical lymphoid cells. The large tumor cells expressed ALK immunoreactivity with a cytoplasmic and nuclear pattern, whereas some of the small cells showed only a nuclear-restricted pattern of staining. An RT-PCR study detected the NPM-ALK chimeric product in the nodal biopsy and in a peripheral blood sample in the early phase of the disease, but it became negative in a peripheral blood sample obtained after completion of the chemotherapy treatment, suggesting that this assay may be useful in the follow-up of these patients. This case indicates that a prominent leukemic phase may develop in ALCL as a manifestation of tumor dissemination and that it may be composed of a predominant small-cell atypical component.

Adult↗

Seroprevalence of HIV, HCV and syphilis in Brazilian prisoners: preponderance of parenteral transmission.

Between November 1993 and April 1994, our physicians' team interviewed and took blood samples of 631 prisoners randomly drawn from the largest prison of South America, which counted about 4700 inmates at that time. The interview consisted of questions related to risk behaviour for HIV infection, and the subjects were asked to provide blood for serological tests for HIV, hepatitis C and syphilis. Our main purpose was to investigate the relationship between HCV and injecting drug use as related to HIV seropositivity. Participation in the study was voluntary and confidentiality was guaranteed. Overall prevalences found were as follows: HIV: 16% (95% confidence interval (CI): 13-19%); HCV: 34% (95% CI: 30-38%), and syphilis: 18% (95% CI: 15-21%). Acknowledged use of ever injecting drug was 22% and no other parenteral risk was reported. Our results, as compared with other studies in the same prison, suggest that HIV prevalence has been stable in recent years, and that the major risk factor for HIV infection in this population is parenteral exposure by injecting drug use.

Adolescent↗

Effects of short-term administration of G-CSF (filgrastim) on bone marrow progenitor cells: analysis of serial marrow samples from normal donors.

To determine the effect of G-CSF administration on both the total number of CD34+ cells and the primitive CD34+ subsets in bone marrow (BM), we have analyzed BM samples serially obtained from 10 normal donors in steady-state and during G-CSF treatment. Filgrastim was administered subcutaneously at a dosage of 10 microg/kg/day (n = 7) or 10 microg/kg/12 h (n = 3) for 4 consecutive days. Peripheral blood sampling and BM aspirates were performed on day 1 (just before G-CSF administration), day 3 (after 2 days of G-CSF), and day 5 (after 4 days of G-CSF). During G-CSF administration, a significant increase in the total number of BM nucleated cells was observed. The percentage (range) of CD34+ cells decreased in BM from a median of 0.88 (0.47-1.44) on day 1 to 0.57 (0.32-1.87), and to 0.42 (0.16-0.87) on days 3 and 5, respectively. We observed a slight increase in the total number of BM CD34+ cells on day 3 (0.66 x 10(9)/l (0.13-0.77)), and a decrease on day 5 (0.23 x 10(9)/l (0.06-1.23)) as compared with steady-state (0.40 x 10(9)/l (0.06-1.68)). The proportion of primitive BM hematopoietic progenitor cells (CD34+CD38-, CD34+HLA-DR-, CD34+CD117-) decreased during G-CSF administration. In parallel, a significant increase in the total number of CD34+ cells in peripheral blood was observed, achieving the maximum value on day 5. These results suggest that in normal subjects the administration of G-CSF for 5 days may reduce the number of progenitor cells in BM, particularly the most primitive ones.

Adult↗

Magnetic resonance imaging in myelofibrosis and essential thrombocythaemia: contribution to differential diagnosis.

To ascertain the value of magnetic resonance (MR) imaging in the differential diagnosis between myelofibrosis (MF) and essential thrombocythaemia (ET), 38 patients were analysed. 20 patients had MF (idiopathic myelofibrosis, 15 cases; post-ET myelofibrosis, four cases; post-polycythaemic MF, one case) and 18 ET. Mean age was 61.5 years (range 30-89) for patients with MF and 60.9 years (range 26-83) for ET patients. MR imaging was performed in the dorsal vertebrae in all cases, and also in both femurs in 2 5 of the patients. In most ET cases the MR signal of the dorsal vertebrae was not modified, whereas it was markedly reduced in MF (P=0.0000001). With regard to femoral marrow, it was usually fatty in ET, with an absent to moderate degree of reconversion seen in the 14 cases analysed, contrasting with the marked degree of reconversion noted in 10/11 patients with MF (P=0.000007). An inverse correlation was demonstrated between the vertebral signal and the degree of femoral reconversion. These differences were due to the fact that in ET the bone marrow adipose tissue is grossly preserved, whereas in MF it is usually markedly decreased or absent. The above results indicate that MR imaging is a useful tool for the differential diagnosis of ET and MF, with the usefulness of this technique increasing when vertebral and femoral bone marrow studies are combined.

Adult↗

Acute myeloblastic leukemia with minimal myeloid differentiation: phenotypical and ultrastructural characteristics.

AML-M0 is an infrequent form of acute myeloblastic leukemia characterized by negative reaction with myeloperoxidase (MPO), Sudan Black and lymphoid antigens and positivity for CD13 or CD33. In the present study we describe the immunophenotypical and ultrastructural characteristics of a group of AML-M0 in adult patients. Nine out 218 AML leukemias (4.1%) fulfilled the AML-M0 criteria. CD13 or CD33 were positive in eight out nine cases, with two or more positive myeloid antigens being present in 82% of the cases. Immunological MPO was positive in 57% of the cases and CD68 in 33%. In no case megakaryocytic and erythroid markers present. Four cases (44%) expressed CD7 and TdT but only two coexpressed both antigens. In none of the cases was CD3 or CD22 cytoplasmic expression found. Ultrastructurally, a low number of granules was seen in all cases whereas ferritin particles or rhopheocytosis were not observed. Ultrastructural MPO was positive in one out of five cases and platelet peroxidase (PPO) was negative in the four cases studied. Two out of six cases showed karyotypic abnormalities (hypotetraploidy and a complex karyotype, respectively). In two out three cases a rearranged pattern for JH gene was observed. TCR (Cbeta and Jgamma) rearrangements were not detected in any case. AML-M0 is an infrequent form of acute myeloblastic leukemia. A large panel of myeloid monoclonal antibodies (MoAb) and the study of the cytoplasmic expression of myeloid antigens is necessary to diagnose this form of leukemia. AML-M0 usually coexpress lymphoid markers. Ultrastructural studies may be of help to discard an immature erythroid proliferation.

Adult↗