Biomedical subjects

M Lishner

Publications and source records attributed to M Lishner.

At least 55 records · Page 3Linked to original sources

PubMed1998

Pleural effusion in patients with non-Hodgkin's lymphoma: a case-controlled study.

BACKGROUND: Pleural effusion is reported in up to 20% of patients with non-Hodgkin's lymphoma (NHL), most often at presentation. However, the prognostic implications of such findings are not clear. The majority of the information in the literature is based on minor observational studies or case reports. Therefore, a case-controlled study was performed to verify the clinical significance of pleural effusion in NHL. METHODS: Seventeen patients with pleural effusion at the time of presentation of NHL were identified. They were categorized by grade of NHL (based on the Working Formulation). Twenty-nine control patients with similar histopathologic characteristics who had Stage III/IV NHL without pleural effusion were matched to these cases by age, time of diagnosis, and treatment. RESULTS: Ten patients with intermediate grade NHL were matched with 23 controls. No statistically significant difference in complete remission or survival rates between these groups was found (P=0.69 and P=0.7, respectively). The remission and survival rates also were similar in the subgroup of patients and controls who were treated with aggressive chemotherapy. Similarly, no difference was found in these parameters between four cases and six matched controls with low grade lymphoma. No matched controls were found for the patients with high grade lymphoma, but these patients had an unfavorable outcome. Fourteen of the 17 studied patients had an exudative type of pleural effusion. Thoracentesis yielded a positive cytologic finding in every case. CONCLUSIONS: The presence of pleural effusion at the time of presentation of NHL does not adversely affect complete remission or survival rates.

Adult↗

PubMed1998

Temporal differences in replication timing of homologous loci in malignant cells derived from CML and lymphoma patients.

A close association usually exists between replication timing of a given locus and its transcriptional activity: expressed loci replicate early whereas silent ones replicate late. Accordingly, alleles that show concomitant expression replicate synchronously, while those displaying an allele-specific mode of expression show temporal differences in their replication timing, i.e., they replicate asynchronously. We aimed in our study to see whether the cancer phenotype is accompanied by a relaxation in the temporal control of allelic replication. Fluorescence in situ hybridization (FISH) was used to determine the level of synchronization in replication timing of four pairs of homologous loci in samples of malignant cells derived from patients with chronic myeloid leukemia (CML) and lymphoma and in samples from healthy individuals. Four loci, HER2 mapped to 17q11.2-q12, a locus at 21q22, TP53 mapped to 17q13.1, and MYC mapped to 8q24 were studied. In each sample we analyzed two chromosomal regions, either 17q11.2-q12 and 21q22 or 17p13.1 and 8q24. The results showed distinct differences between healthy individuals and CML/lymphoma patients: all samples derived from noncancerous subjects showed high levels of synchrony in replication timing of alleles, whereas those of cancer patients displayed a large temporal difference in replication timing, indicating early and late replicating alleles. Thus, as judged by four unrelated loci, malignancy is associated with changes in the replication pattern of homologous loci.

Alleles↗

PubMed1998

Leukocyte function in chronic myeloproliferative disorders.

The myeloproliferative disorders (MPD) are clonal diseases that originate from a transformed stem cell and involve all myeloid lineage. The affected cells have both proliferative and functional impairment. Therefore, we evaluated and compared neutrophil function in 31 patients with polycythemia vera (PV), idiopathic myelofibrosis (MF), chronic myeloid leukemia (CML), and essential thrombocytosis (ET). Neutrophil chemotaxis, random migration, bactericidal activity and superoxide anion release in these patients were simultaneously compared to those of 31 healthy controls. In this study, chemotactic activity was significantly impaired in patients with PV and CML as compared to controls (M+/-SE: 42 +/- 6 vs. 69+/- 5 cells/field; p<0.005 and 47+/-7 vs. 68+/- 5; p<0.05, respectively). The assessment of the bactericidal activity of neutrophils showed no impairment in most of the patients. In the CML group, the serum had a very strong "lytic" effect on bacteria, possibly due to the high levels of serum lysozyme (22 +/- 2 microgram/ml). The superoxide anion release was found to be normal in most of the patients. Nevertheless, in 25% of PV patients the superoxide production was impaired (less than 60% of the simultaneous controls). In ET most patients had normal neutrophil function. Regarding the effect of treatment, neutrophil chemotactic activity was found to be significantly reduced in the hydrea-treated patients, as compared to the non- treated patients (p<0.001) or healthy controls (<0.0001). We conclude that disturbances in neutrophil function are present in patients with various MPDs, except ET. This probably reflects abnormal maturation of ancessors of the damaged stem cells. Nevertheless, we should keep in mind that therapy itself could affect neutrophil functions. This matter should be studied more extensively. Although infections are not common in MPD disorders, they occasionally occur. It is possible that impairment in the phagocytic function contribute to the development of infections in patients with myeloproliferative disorders.

Adult↗

PubMed1998

Intermittent dobutamine treatment in patients with chronic refractory congestive heart failure: a randomized, double-blind, placebo-controlled study.

BACKGROUND: Intravenous dobutamine administration improves short-term hemodynamics in patients with severe congestive heart failure (CHF). However, the clinical benefit of periodic administration remains controversial. OBJECTIVE: To evaluate the efficacy of intermittent dobutamine administration in patients with refractory CHF. METHODS: Nineteen patients with New York Heart Association class III/IV, ischemia-induced CHF participated in this double-blind, placebo-controlled study. All patients received intravenous dobutamine or placebo over a 24-hour period every 2 to 3 weeks for 6 months. They were also treated with angiotensin-converting enzyme inhibitors, digoxin, and diuretics. The number of admissions for CHF and mortality rate were compared. RESULTS: Ten patients received dobutamine and nine received placebo. The pretreatment characteristics were similar in both groups. No statistically significant difference was observed between the number of admissions for CHF (p = 0.11). The median survival after enrollment was 7.97 months in the placebo group and 4.6 months in the dobutamine group. The Kaplan-Meier survival curves overlay, with no statistically significant difference between the treatment arms (p = 0.7). CONCLUSION: Intermittent dobutamine infusions in patients with refractory CHF have no effect on the need for hospitalization or on survival.

Adrenergic beta-Agonists↗

PubMed1998

Ascitic fluid to serum bilirubin concentration ratio for the classification of transudates or exudates.

OBJECTIVE: We compared the ascitic fluid to serum bilirubin ratio with three other ways of classifying ascitic fluid to the categories of exudate or transudate: the serum-ascites albumin gradient, the total protein concentration of the fluid, and the adaptation of Light's criteria for the detection of pleural fluid exudate, i.e., fluid to serum protein or LDH ratio or fluid LDH concentration. (Recently it has been reported that the pleural fluid to serum bilirubin ratio is statistically equivalent to Light's criteria.) Also, we evaluated whether the addition of the bilirubin ratio to the other criteria increases their diagnostic accuracy. METHODS: Eighty-one specimens of ascitic fluid from 81 different patients were obtained. They were analyzed prospectively by SMA12, whereas the category of the fluid was determined according to the clinical diagnosis. The diagnostic accuracy of each criterion alone and in combination with the bilirubin ratio, with reference to the contended etiology, were evaluated. RESULTS: The best criterion is the albumin gradient (overall accuracy = 0.84). The bilirubin and LDH ratio criteria had equivalent overall accuracy (0.815 and 0.802, respectively). The addition of the bilirubin ratio to any criterion did not improve its predictive or overall accuracy. CONCLUSIONS: Ascitic fluid to serum bilirubin ratio is an additional marker for the distinction of transudate from exudate. A ratio > 0.6 has a statistically significant association with exudate.

Ascitic Fluid↗

PubMed1998

Breast cancer during pregnancy. Approach to rational management.

QUESTION: A 35-year-old woman attending my clinic in the 20th week of pregnancy had a lump in her breast. Open biopsy revealed ductal carcinoma. Radical mastectomy with axillary lymph node biopsy showed three out of 10 nodes positive. What are the short- and long-term implications of chemotherapy during pregnancy? ANSWER: Patients with breast cancer during pregnancy should be treated using the same criteria as their nonpregnant counterparts, with the modifications required by pregnancy. The benefits of the diagnostic workup and use of chemotherapy, radiotherapy, and surgery have to be weighed carefully against their risk to the unborn baby.

Abnormalities, Drug-Induced↗

PubMed1997

Comparison of enalapril to captopril by 24-hour ambulatory blood pressure monitoring.

The efficacy of a once-daily dose of enalapril was compared with a thrice-daily dose of captopril in an open-label, randomized parallel group study of 27 hypertensive patients. The patients were monitored using conventional measurements of blood pressure and with 24-hour ambulatory blood pressure monitoring at baseline and after 12 weeks of therapy. The end points were 24-hour, daytime, and nighttime mean blood pressure values and the percentage of elevated systolic and diastolic measurements, reflecting the "hypertensive load." Enalapril reduced mean 24-hour systolic blood pressure by 18 mmHg and diastolic blood pressure by 11 mmHg. The comparative values for captopril were 9 mmHg and 2 mmHg, respectively. The mean daytime systolic blood pressure was reduced by 20 mmHg with enalapril versus 7 mmHg with captopril; the diastolic values were lowered by 11 mmHg with enalapril versus 4 mmHg with captopril. The mean nighttime systolic blood pressure was lowered by 16 mmHg with enalapril versus 12 mmHg with captopril; the diastolic values were reduced by 10 mmHg with enalapril and 5 mmHg with captopril. No major side effects were recorded in either group. A single daily 20-mg dose of enalapril, therefore, proved to be equipotent or superior to 75 mg of captopril administered in three divided doses.

Aged↗

PubMed1997

Asynchronous replication of p53 and 21q22 loci in chronic lymphocytic leukemia.

In this study, in order to evaluate the replication pattern and the cell cycle dynamics of normal and malignant cells from patients with chronic lymphocytic leukemia, we applied the FISH technique with the p53 gene. Asynchrony was determined by the presence of one single and one set of double dots in the same cell. The rate of asynchronous replication was significantly higher in malignant cells than in normal cells (a mean of 28 vs 13, respectively, P = 0.023). There were proportionately more cells with two single dots among the normal cells (P = 0.0047). These results probably reflect the changes in gene replication and cell cycle progression that occur in malignant cells.

Cell Cycle↗

PubMed1997

Monoallelic p53 deletion in chronic lymphocytic leukemia detected by interphase cytogenetics.

Chromosomal aberrations can be detected in 50% of patients with chronic lymphocytic leukemia (CLL). A role for tumor suppressor genes in the genesis of lymphoid tumors has been reported. In B-CLL, p53 gene mutations were found in 10-15% of the patients. We used fluorescence in situ hybridization (FISH) to detect p53 deletion in B-CLL. We also correlated the cytogenetic findings with the clinical course. In situ hybridization to interphase nuclei showed monallelic p53 deletion in 6 of 23 patients (26%). The percentage of cells with one p53 signal ranged from 12 to 100. A statistically significant correlation between p53 deletion and progression of CLL was demonstrated. We conclude that FISH is a sensitive and reliable method to detect deletion of specific genes (i.e., p53) in CLL. The finding of p53 deletion is associated with disease progression.

Aged↗

PubMed1997

Induction of apoptosis by chlorodeoxyadenosine and dexamethasone in B-chronic lymphocytic leukemia.

Apoptosis, programmed cell death, occurs in a variety of cellular systems and in response to many different stimuli. In the present study we examined the ability of dexamethasone (Dex) and chlorodeoxyadenosine (2-CdA) to induce apoptosis in lymphocytes of patients with B-chronic lymphocytic leukemia (B-CLL). Lymphocytes of 29 untreated patients and 9 healthy controls were isolated and incubated for 24 hours in the presence or absence of either Dex (2 microM) (n = 15) or 2-CdA (3 microM) (n = 14). Following incubation the cells were harvested and their DNA extracted and analysed for internucleosomal DNA cleavage by UV illumination after electrophoresis on agarose slab gel containing ethidium bromide. In the Dex group, 10 patients showed dexamethasone independent spontaneous apoptosis appearing 24 hours after the start of incubation. These were the only instances of dexamethasone-enhanced apoptosis. Five patients showed no spontaneous or dexamethasone induced apopto sis. Of the 2-CdA group, 5 showed spontaneous apoptosis enhanced by 2-CdA. No spontaneous apoptosis was observed in the cells from 9 other patients, however, 2-CdA induced apoptosis in 8 cases in this group. This study shows that monitoring of apoptosis in CLL may provide important information regarding susceptibility of the cells to drug induced apoptosis.

Antineoplastic Agents, Hormonal↗

PubMed1996

B-cell non-Hodgkin's lymphoma: evidence for the t (14;18) translocation in all hematopoietic cell lineages.

BACKGROUND: B cells of patients with non-Hodgkin's lymphoma (B-NHL) harbor specific chromosomal translocations, including t(14;18), the most common aberration found in this disease. The translocation involves the immunoglobulin (Ig) heavy-chain joining (JH) region gene on chromosome 14 and the BCL2 gene on chromosome 18, resulting in dysregulated expression of the BCL2 gene. The t(14;18) translocation has been thought to occur in the pre-B-cell stage, during the first event of Ig gene rearrangement. PURPOSE: This study was conducted to investigate the potential involvement of nonlymphoid lineages in B-NHL. METHODS: We studied the t(14;18) translocation and other frequently occurring translocations in total bone marrow aspirates of 10 patients with B-NHL, with the use of the fluorescence in situ hybridization (FISH) technique. We also performed cytogenetic analyses on representative bone marrow aspirates from the patients. Moreover, to define which of the major cell lineages present in the bone marrow carry the t(14;18) translocation, we used a series of monoclonal antibodies together with fluorescence-activated cell sorter (FACS) analyses to purify cells positive for CD3 (T cells), CD19 (B cells), CD10 (CALLA-positive cells), CD41a (megakaryocytic cells), CD13 (myeloid cells), and glycophorin A (erythroid cells). The cells of each subgroup underwent FISH analysis with the use of JH and BCL2 probes to detect the t(14;18) translocation. Bone marrow samples obtained from five healthy donors served as controls. RESULTS: Bone marrow cells from eight of the 10 patients studied carried the t(14;18) translocation. When present, the translocation was observed in many or even all of the cell lineages (lymphoid, myeloid, megakaryocytic, and erythroid) present in the bone marrow, including peripheral blood progenitor stem cells; for seven of the eight patients carrying the translocation, it was found in 96%-100% of the unfractionated bone marrow cells as well as in all of the FACS-purified cell fractions in which it could be detected or studied. Conventional cytogenetic analyses performed on representative bone marrow aspirates confirmed the results obtained by FISH analysis. Cells in control bone marrow samples obtained from the five healthy donors were negative for the t(14;18) translocation by FISH analysis. CONCLUSIONS: Our findings indicate that the t(14;18) translocation most probably occurs in a very early multilineage progenitor stem cell. IMPLICATIONS: Given that the t(14;18) chromosomal translocation was found in all types of bone marrow cells when only the B cells were malignant, our results suggest that this translocation is not sufficient to induce neoplastic transformation. This finding underscores the need for the development of new approaches for the detection and surveillance of B-NHL.

Chromosomes, Human, Pair 14↗

PubMed1996

Long-term renoprotective effect of angiotensin-converting enzyme inhibition in non-insulin-dependent diabetes mellitus. A 7-year follow-up study.

BACKGROUND: Diabetic nephropathy is the leading cause of end-stage renal disease in developed countries. Duration of diabetes, blood pressure values, and metabolic status are the major determinants of the course of nephropathy, and microalbuminuria is the hallmark of its onset. Angiotensin-converting enzyme inhibitors offer important renoprotection to hypertensive and normotensive patients with insulin-dependent diabetes mellitus and non-insulin-dependent diabetes mellitus. Our study extends previous observations for duration and the effect of angiotensin-converting enzyme inhibition on advanced nephropathy. METHODS: Double-blinded (first phase) and open (second phase) randomized controlled study of 7 years. Ninety-four normotensive patients with non-insulin-dependent diabetes mellitus whose serum creatinine levels were lower than 123.76 mumol/L (1.4 mg/dL) and who had microalbuminuria (30 to 300 mg/24 h) were given enalapril maleate, 10 mg/d, or placebo, for 5 years. For 2 more years they were followed up openly and given the choice to receive enalapril or no treatment. RESULTS: In the enalapril-treated patients, albuminuria remained stable for 7 years. An increase from (mean +/- SD) 123 +/- 58 to 310 +/- 167 mg/24 h occurred in the untreated group after 5 years, and a further increase to (mean +/- SD) 393 +/- 223 mg/24 h occurred after 7 years. Reciprocal creatinine was unchanged in treated patients for 7 years; in the untreated patients, the mean decline was 13% at 5 years and 16% at 7 years. Treatment with enalapril resulted in an absolute risk reduction of 42% for nephropathy to develop during 7 years (95% confidence interval, 15% to 69%; P < .001, Student's t test). Glycosylated hemoglobin and body mass index remained unchanged. CONCLUSIONS: Angiotensin-converting enzyme inhibition offers long-term protection against the development of nephropathy in normotensive patients with noninsulin-dependent diabetes mellitus who have microalbuminuria, and it stabilizes renal function in previously untreated patients with impaired renal function. Discontinuation of treatment results in renewed progression of nephropathy.

Adult↗

PubMed1996

Trisomies 9 and 8 detected by fluorescence in situ hybridization in patients with systemic mastocytosis.

BACKGROUND: Systemic mastocytosis is a rare disease characterized by proliferation of mast cells in one or more organs. The origin of the mast cells is still debated, although it has been recently shown that they derive from CD34+ hematopoietic progenitors. Some clinical and in vitro studies have suggested a possible link between myeloproliferative disorders and systemic mast cell disease. OBJECTIVE: This study was designed to further evaluate the association between systemic mast cell disease and other hematologic disorders by means of conventional cytogenetic analysis and fluorescent in situ hybridization. METHODS: We used cytogenetic analysis and fluorescent in situ hybridization with probes to chromosomes 8 and 9 in six patients with systemic mast cell disease. RESULTS: Fluorescent in situ hybridization helped to identify five patients with trisomy 9 and one with trisomy 8. In contrast, chromosomal analysis demonstrated an abnormal karyotype (45,XO/46,XY) in only one patient. CONCLUSION: The association between myeloproliferation disorders and systemic mast cell disease may be explained by the finding that trisomy 9 and trisomy 8 are common in both disorders. A trisomy was detected in all of the patients in our small group compared with nearly 40% of previously reported patients with myeloproliferative disorders. FISH is more sensitive than conventional cytogenetics in detecting these aberrations.

Adult↗

PubMed1996

The detection of trisomies 8 and 9 in patients with essential thrombocytosis by fluorescence in situ hybridization.

Essential thrombocytosis (ET) is a clonal, chronic myeloproliferative disorder (MPD) originating from a multipotent stem cell. To date no specific cytogenetic marker has been found in ET. It was recently reported that chromosomal aberrations have been detected by fluorescence in situ hybridization (FISH) in patients with normal karyotypes or nonanalyzable metaphases. Therefore, we evaluated whether trisomies 8 and 9, which are commonly found in MPDs, can be detected in ET by FISH and compared the results with chromosome analysis. Peripheral blood mononuclear cells of patients with essential thrombocytosis were studied by classical chromosome banding and by FISH. We used biotin labeled alpha satellite of chromosome 8 and biotin labeled beta satellite of chromosome 9 as probes for the FISH studies. FISH detected 5 patients with trisomy 8 and 5 with trisomy 9 of the 18 patients evaluated. No trisomy was found by cytogenetic studies. The trisomies were detected by FISH in only a minority of the cells. No correlation was found between the presence of a trisomy and clinical characteristics. FISH is a sensitive method for the detection of trisomies 8 and 9 in patients with ET. The common finding of these chromosomal aberrations in MPD suggests that genes associated with myeloid proliferation are located on these chromosomes. Standardization of interphase cytogenetics is needed before this technique can be accepted for routine use in the clinic.

Adult↗

PubMed1996

A clinical approach to "idiopathic" normocytic-normochromic anemia.

OBJECTIVES: Normocytic-normochromic anemia is frequently found in patients with chronic disorders. The pathogenesis, epidemiological and clinical characteristics of normocytic normochromic anemia of unknown cause are not well established. We evaluated the role of bone marrow examination and the clinical course of patients with "idiopathic" normocytic-normochromic anemia. DESIGN: Patients with normocytic-normochromic anemia underwent a noninvasive evaluation according to a predetermined protocol. Bone marrow aspiration and biopsy were performed in those patients in whom no explanation for the anemia was found. They were later followed at 3 to 6 month intervals. RESULTS: Thirty-one patients (23 females and 8 males) with "idiopathic" normocytic-normochromic anemia (mean hemoglobin concentration was 10.0 + 0.6 g/dL) were detected. No patient had symptoms related to the anemia. Twenty-nine bone marrow aspirations and 21 biopsies were performed. Iron deficiency and mild myelofibrosis were found in one patient each. The rest of the bone marrow examinations were normal. During 15.5 +/- 10.3 months of follow-up, the hemoglobin level rose marginally to 10.9 + 1.0 g/dL (P < .0002). No changes in clinical or laboratory variables that could be ascribed to anemia were detected. CONCLUSION: Normocytic-normochromic anemia of unknown cause is encountered infrequently in clinical practice and is found mainly in older patients. The evaluation should be noninvasive to exclude correctable causes of the anemia. Bone marrow examination is only rarely contributive in this setting. The prognosis of these patients is excellent.

Adult↗

PubMed1996

Bone marrow involvement, in intensively treated patients with intermediate grade non-Hodgkin's lymphoma, is a risk factor for granulocytopenia and fever.

Intensive combination chemotherapy administered to patients with non-Hodgkin's lymphoma (NHL) is inevitably associated with neutropenia and fever. However, the subset of patients who are at increased risk for myelotoxicity has not been clearly identified as yet. We evaluated 58 patients with NHL in order to verify whether bone marrow involvement (BMI) at diagnosis is a risk factor for neutropenia and infection following intensive chemotherapy. Patients with bone marrow involvement had significantly lower neutrophil counts both at diagnosis and following chemotherapy. An higher percentage of patients with BMI developed neutropenia (< 1000/mm3) following chemotherapy. Furthermore events of febrile neutropenia were more frequently encountered in patients with BMI. We conclude that BMI in patients with NHL is a risk factor for chemotherapy induced neutropenia and fever. The role of colony stimulating factors, administered in an attempt to prevent this complication, should be explored.

Adult↗

PubMed1996

Fluorescent in situ hybridization (FISH) for the detection of trisomy 8 in acute myeloblastic leukemia.

The karyotype of acute myeloid leukemia (AML) blasts has a major prognostic importance. However conventional cytogenetic studies of AML patients may fail to reveal chromosome abnormalities. Trisomy 8 is a common numerical abnormality in all AML subtypes. We evaluated the role of fluorescent in situ hybridization (FISH) in the detection of trisomy 8 in de-novo AML, and compared the results to chromosome analysis in some patients. Cytogenetic studies were performed in 9 of 12 patients. In three patients no metaphases were obtained. Of the remaining six, trisomy 8 was only detected in the metaphases of 1 patient. In contrast, 4 patients showed +8 with FISH and one had a borderline value. We conclude that FISH is a rapid and sensitive method to detect numerical aberrations in AML. In the future larger prospective studies should explore the biological and clinical application of the FISH method in different hematological malignancies.

Adult↗

PubMed1995

Fluorescence in situ hybridization for the detection of trisomies 8 and 9 in polycythemia vera.

Trisomies 8 and 9 are the most common numerical chromosome abnormalities in polycythemia vera (PCV). Their role in the pathogenesis of the disease is unclear, however, as is their diagnostic or prognostic value. We evaluated fluorescent in situ hybridization as compared to chromosome analysis for the detection of trisomies 8 or 9 in peripheral blood cells of PCV patients. We demonstrated that FISH is a more sensitive method for the detection of the abnormalities. A positive correlation between the duration of the disease and trisomy 9 was found. FISH is a sensitive, convenient, and rapid method for the diagnosis and follow-up of chromosome aberrations in patients with PCV. The application of FISH to a larger cohort of patients may provide valuable information regarding the role of the chromosomal aberrations in the initiation and progression of this disease.

Adolescent↗