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Biomedical subjects

M Lishner

Publications and source records attributed to M Lishner.

At least 37 records · Page 2Linked to original sources
PubMed2001

Pregnancy and radiation.

The risk of foetal irradiation during pregnancy is discussed. It seems that, due to the low level of X-ray exposure to the foetus, neither diagnostic radiography nor nuclear diagnostic examination justifies termination of pregnancy. Radiotherapy for breast cancer, Hodgkin's disease and cervical cancer in pregnant women is reviewed. Radiation therapy for breast cancer is not an absolute contraindication for pregnancy and the risk-benefit assessment should be discussed with the mother. The risk to the foetus during radiotherapy for supradiaphragmatic Hodgkin's disease appears to be minimal, provided special attention is paid to the treatment techniques and the foetus is adequately shielded. Radiotherapy for the treatment of cervical cancer may be necessary during pregnancy, but the timing should be adjusted taking into consideration gestational age. Offspring of cancer patients who were treated by radiotherapy appear to be at little risk of childhood cancer or birth defects. Cancer patients should not be discouraged from having children and can expect a good outcome of pregnancy. However, in the non-pregnant woman, to further reduce any risk it is advisable to delay pregnancy for 12 months following completion of radiation therapy.

Breast Neoplasms↗
PubMed2001

Effect of simvastatin alone and in combination with cytosine arabinoside on the proliferation of myeloid leukemia cell lines.

BACKGROUND: Cholesterol biosynthesis is regulated by the activity of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. Cholesterol and its derivatives are required in high concentrations by neoplastic proliferating cells for both DNA synthesis and cell growth. Thus, inhibition of HMG-CoA reductase could effect cell cycle progression and proliferation. Therefore, we examined the effect of an HMG-CoA reductase inhibitor (simvastatin) alone and in combination with cytosine arabinoside (ARA-C) on the proliferation of two AML cell lines. METHODS: AML blasts derived from two cell lines (HL-60 and AML-2) were incubated with increasing concentrations of either simvastatin alone or simvastatin alone for 24 hours with ARA-C added thereafter. The effect of the drugs on cell proliferation in liquid culture (3H thymidine uptake) and on clonogenic assay was analyzed. RESULTS: We found that the number of proliferating AML blasts (suspension cultures) and colony formations (agar cultures) of both cell lines declined significantly after incubation with simvastatin. Preincubation of both cell lines with simvastatin by the addition of increasing concentrations of ARA-C produced a degree of growth inhibition that was significantly greater than that of the individual compounds. This antigrowth interaction was additive rather than synergistic. CONCLUSIONS: We conclude that simvastatin has a major antiproliferative effect on AML blasts in vitro. Also, the combination of simvastatin and ARA-C significantly enhanced the antiproliferative effect of each drug. These findings may open new avenues in both the laboratory and clinical research of the treatment of leukemia.

Anticholesteremic Agents↗
PubMed2001

Cancer chemotherapy during pregnancy. Consortium of cancer in pregnancy evidence.

QUESTION: I have an 8-weeks' pregnant patient who was diagnosed with stage III Hodgkin's disease last week. The oncologist suggests delaying chemotherapy until the second trimester. What are the effects of chemotherapy on a fetus after the first trimester? Where can I find reliable information on the subject? ANSWER: Available data suggest that exposure to chemotherapy during the first trimester of pregnancy is associated with increased risk of major malformations. Exposure during the second and third trimesters does not result in major malformations, but could have nonteratogenic effects, such as low birth weight. The brain develops throughout pregnancy, and it could be affected later in pregnancy.

Abnormalities, Drug-Induced↗
PubMed2000

Bcl-2 rearrangement in patients with chronic hepatitis C associated with essential mixed cryoglobulinemia type II.

Hepatitis C virus (HCV) infection is found in 80% to 90% of patients with essential mixed cryoglobulinemia (EMC) type II, which is associated with monoclonal IgMk produced by monoclonal B cells. It was investigated whether bcl-2 rearrangement is associated with the clonal B-cell proliferation of EMC induced by hepatitis C. The study groups were composed of 15 patients with HCV and EMC, 12 patients with HCV without EMC, and 7 patients with chronic liver disease (CLD) unrelated to HCV. Fluorescence in situ hybridization with probes was applied to JH and to bcl-2 to study whether JH/bcl-2 translocation was present in these patients. Thirteen of 15 (86%) of patients with HCV-related EMC had the JH/bcl-2 translocation, a significantly higher rate than in HCV patients without EMC (16%; P < .001). Bcl-2 rearrangement was not detected in the patients with CLD not related to HCV. The JH/bcl-2 translocation may constitute a pathogenetic link for the development of NHL in patients with HCV infection. (Blood. 2000;96:2910-2912)

Adult↗
PubMed2000

Extension of transplantation free time by lamivudine in patients with hepatitis B-induced decompensated cirrhosis.

BACKGROUND: Liver transplantation for hepatitis B virus (HBV)-induced cirrhosis carries a high risk of graft reinfection and poor prognosis. Active viral replication is considered a contraindication for transplantation in most centers. Lamivudine, a new nucleoside analog, is a potent inhibitor of HBV replication that has been used safely for pretransplantation suppression of HBV replication. METHODS: We report the pattern of response to lamivudine treatment in three consecutive patients with decompensated cirrhosis due to the replicative phase of chronic HBV infection. RESULTS: In addition to virological and biochemical response, impressive clinical improvement was noted in all three patients, with disappearance of the ascites and marked improvement of synthetic liver function tests. One patient converted to anti-hepatitis B surface and is free of symptoms 20 months after initiation of treatment. The other two patients experienced significant clinical improvement for 8 to 9 months and were removed from the waiting list for transplantation. However, progressive liver disease recurred in both patients--one underwent liver transplantation and the other is a candidate for the procedure. CONCLUSION: The administration of lamivudine for pretransplantation HBV suppression was associated with impressive clinical and biochemical improvement. Lamivudine may extend the transplantation free time in such patients. The mechanism of this desirable effect should be explored.

Adult↗
PubMed2000

The diagnostic significance of polyclonal lymphocytosis in pleural effusions.

AIM: To evaluate the diagnostic contribution and clinical relevance of analysing subpopulations of lymphocytes in pleural effusions. METHODS: Forty patients (age >60 years) with newly diagnosed, polyclonal, lymphocyte-rich pleural effusions were evaluated. The following data were collected: demographic characteristics, associated diseases, fluid type, fluid white blood cells count, differential morphology and immunephenotyping, and final diagnosis. RESULTS: Of the 33 patients for whom biochemical data were available, 18 had exudative effusion, while 15 had transudate. Thirty-three fluids contained mostly T cells and only one was B-cell rich. (The lymphocytes of five patients with malignant epithelial cells in the effusion were not subtyped.) Thirty-two of the 33 T-cell rich fluids contained mainly CD4+ lymphocytes. The most common causes of pleural effusion were congestive heart failure (17 patients) and epithelial malignant diseases (eight patients), while none of the patients had tuberculosis. Since most effusions were CD4+ rich, no correlation could be detected between lymphocyte subtyping and diagnosis or the biochemical type of the fluids. Congestive heart failure was significantly associated with transudates, while malignant diseases correlated with exudates. CONCLUSIONS: Most patients with pleural polyclonal lymphocytosis, especially those with transudates, have congestive heart failure. The presence of exudative, lymphocyte-rich effusion is an indication for further evaluation, since it is most commonly associated with malignancy. The clinical value of lymphocyte subtyping is low and this procedure should not be used routinely.

Aged↗
PubMed2000

Multiple myeloma: monoallelic deletions of the tumor suppressor genes TP53 and RB1 in long-term follow-up.

Recently, a working-model of a stepwise malignant transformation in the molecular pathogenesis of multiple myeloma (MM) was proposed, involving the tumor suppressor gene TP53 and retinoblastoma gene (RB1) as prominent components of cell cycle control. To further define the role of TP53 and RB1 in disease progression, we retrospectively analyzed by fluorescence in situ hybridization (FISH) cytological material from 16 patients who underwent sequential bone marrow biopsies during the course of their disease. For TP53, no deletions were detected at presentation or during follow-up. It is possible that the patients reported here represent a subset with relatively long survival, and therefore did not demonstrate the TP53 deletions that had been reported in patients with a very poor prognosis. For RB1, monoallelic deletion was demonstrated in nine patients. In each case, the deletion appeared already in the first biopsy analyzed. The presence of a deletion did not affect the rate of tumor progression or the length of follow-up, and thus prognosis. Monoallelic deletions of RB1 appear to be a frequent and early event in the pathogenesis of MM, without obvious relevance for disease progression.

Aged↗
PubMed2000

Replication status as a marker for predisposition for lymphoma in patients with chronic hepatitis C with and without cryoglobulinemia.

OBJECTIVE: Essential mixed cryoglobulinemia (EMC) type II is associated with hepatitis C virus (HCV) in 90% of the patients with this disorder. A significant subset of these patients is at risk to develop non-Hodgkin lymphoma (NHL). The objective of this study was to examine whether the presence of EMC, a presumably premalignant step of lymphoproliferation, is associated with changes in the replication state of normal structural genes. MATERIALS AND METHODS: The study group included three subgroups: (1) seven patients with HCV without EMC; (2) eight patients with HCV associated with EMC. 3. Seven patients with follicular lymphoma; and (3) six healthy individuals served as control group. Monocolor fluorescent in situ hybridization (FISH) with probes to p53, RB-1, and 21q22 was applied to leukocytes nuclei for the evaluation of replication timing. RESULTS: Asynchronous replication (SD) rate was similar in patients with NHL and those with HCV associated with EMC and both are significantly higher when compared to patients with HCV without EMC and to normal controls (p < 0.01) for each comparison. This held true for all studied loci (21q22, RB-1, and p53). Patients infected by HCV (but without EMC) had a significantly higher rate of asynchronous pattern in comparison with healthy controls (p < 0.01). CONCLUSIONS: Patients with a "premalignant" clinical condition HCV with EMC already demonstrate asynchronous type of replication which is similar to patients who already have an established malignant disease (i.e., NHL). In the future, replication may be used to assess the risk of malignant transformation in patients with "benign" proliferation.

Adult↗
PubMed2000

Neurological complications of essential thrombocytosis (ET).

OBJECTIVE: To evaluate the prevalence of neurological abnormalities in patients with ET and attempt to identify risk factors for neurological complications. METHOD: Ninety-five patient charts were reviewed from January 1983-July 1999. Seventy patients fulfilled the Polycythemia Vera Study Group criteria for diagnosing ET. RESULTS: Eighteen patients (25.7%) had episodes of neurological impairment, 52 (74.3%) had none. Neurological features-- occlusive cerebrovascular event-9; chronic headache-3 and dizziness-3, mononeuritis multiplex, sinus vein thrombosis and epilepsy-1 each. The interval between diagnosis of ET and occurrence of neurological events ranged from time of presentation (10 patients) to 13 years (1 patient) with a high predominance of females, 88.8% and 55%, respectively. CONCLUSIONS: Neurological complications occurred at presentation or during follow-up in approximately 25% of patients with ET. Our observation suggests that further investigation focusing on the possible mechanisms for neurological deficits in females with ET should be considered.

Adult↗
PubMed1999

Primary antiphospholipid syndrome associated with pernicious anaemia.

AIM: To determine whether there is an association between pernicious anaemia and antiphospholipid antibody syndrome. METHODS: Fifteen patients with pernicious anaemia and 11 patients with iron deficiency anaemia (controls) were evaluated for clinical parameters of thrombosis and/or the presence of antiphospholipid antibodies, antinuclear antibodies or lupus anticoagulant. RESULTS: One asymptomatic patient with pernicious anaemia had laboratory features suggestive of the antiphospholipid syndrome. An additional three patients in each group had slightly elevated antiphospholipid antibody concentrations, within one standard deviation of the normal range. CONCLUSION: The association between pernicious anaemia and antiphospholipid antibody syndrome is rare and evaluation should be guided by clinical indications.

Adult↗
PubMed1999

Deletion of 6q27 in chronic lymphocytic leukemia and multiple myeloma detected by fluorescence in situ hybridization.

Nonrandom deletions of the long arm of chromosome 6 (6q) are associated with various lymphoid malignancies. It has been suggested that deletions of 6q25-27, 6q21, and 6q23 typically occur in intermediate-grade, high-grade, and low-grade lymphomas, respectively. We used fluorescence in situ hybridization (FISH) to evaluate the occurrence of 6q27 deletion in chronic lymphatic leukemia (CLL) and multiple myeloma (MM). 6q27 deletion was detected in 21% of patients with CLL and in 28% of patients with MM. The percentage of cells containing deletions ranged between 25-49. Two patients with MM had progressive disease and the aberration was detected in both. We conclude that FISH is a sensitive method to detect 6q27 deletion in lymphoproliferative disorders. Also, this deletion is not specific to intermediate-grade lymphomas, but occurs also in CLL and MM.

Aged↗
PubMed1999

Replication pattern in cancer: asynchronous replication in multiple myeloma and in monoclonal gammopathy.

In this study we evaluated the replication pattern and cell-cycle dynamics of cells from patients considered to have a premalignant condition (monoclonal gammopathy, or MGUS) and patients with multiple myeloma (MM), as well as healthy controls. We applied the fluorescence in situ hybridization (FISH) technique with the TP53, RB-1 and 21q22 loci on the patient's cells. Asynchrony was determined by the presence of one single and one set of double dots in the same cell. The rate of asynchronic replication was significantly higher in the cells from MM patients, with intermediate value in the cells from MGUS, while the lowest rate was in cells from controls. We suggest that these results may reflect the changes in gene replication and cell-cycle progression that occur in premalignant and malignant cells.

Aged↗
PubMed1999

Deletion 5q31 in patients with stable, melphalan-treated multiple myeloma.

The risk of myelodysplastic syndrome (MDS) or acute myeloblastic leukemia (AML) in patients with multiple myeloma has been estimated to be 10-20% after 10 years. Most myeloma patients develop MDS/AML after 3-4 years of treatment with alkylating agents, mainly melphalan; chromosomes 5 and 7 are most frequently involved. We studied 14 patients with myeloma by fluorescence in situ hybridization (FISH) with a probe to 5q31 (the critical area of deletion on chromosome 5) to verify whether deletion of 5q31 occurs during the course of stable, uncomplicated myeloma, and to assess the clinical importance of this abnormality. We found 2 patients (14%) with deletion of 5q31 in 30-40% of their peripheral white blood cells. One patient with this deletion received a high cumulative amount of melphalan, and the other patient was treated with multiple alkylating agents, including melphalan. In these patients, no clinical or laboratory evidence of transformation occurred 14 and 12 months after the finding of the aberration. These findings suggest that 5q-may occur months prior to the overt development of (t)-MDS/AML, and raise important concerns regarding the management of patients with this and similar aberrations, including modification of treatment and performance of cytogenetic evaluation prior to autologous or PSC transplantation. The clinical and biological implications of these findings should be evaluated in larger clinical and laboratory studies.

Aged↗
PubMed1999

Association between alopecia and response to aggressive chemotherapy in patients with Hodgkin's disease.

The clinical significance and implications of absence of alopecia and/or neutropenia in patients treated with chemotherapy for malignant disease is unknown. We hypothesized that there is a common mechanism of resistance to the effects and the adverse effects of anticancer treatment, which may have clinical implications. To evaluate this hypothesis, we conducted a retrospective analysis of the charts of 17 consecutive patients with Hodgkin's disease who received at least 4 courses of combination chemotherapy (ABVD or MOPP/ABV). Twelve patients underwent complete alopecia while 5 patients retained their hair or had only minimal hair loss. The two groups had similar pretreatment characteristics. Ten (83%) of the patients with alopecia achieved complete remission as compared with 2 (40%) of the patients who retained their hair (P = 0.11). Also, patients without alopecia had fewer episodes of neutropenia (0% vs 33%, P = 0.02), delays of scheduled treatments (0% vs 66%, P = 0.02) or number of courses with dose reductions (20% vs 41%, P = 0.39). These differences shows a clear trend which did not reach statistical significance due to the small number of patients. We suggest that, in intensively treated patients with Hodgkin's disease, the absence of alopecia may predict a poor response to treatment. Also, patients without alopecia probably have fewer episodes of leukopenia, deferral of treatment courses or number of courses with dose reductions. We hypothesize that there is a common mechanism of resistance to cytotoxic agents that may prevent apoptotic death in both normal and malignant cells.

Adult↗
PubMed1999

Seroconversion of hepatitis B during chemotherapy for malignant lymphoma.

We report a patient with chronic hepatitis B infection who developed lymphoma and was treated with concomitant cytotoxic and antiviral therapy. In contrast to the expected life threatening fulminant hepatitis that is often reported in this clinical setting, in our patient normalization of liver function tests with temporary loss of viral replication markers were seen. The implications of this rare clinical and serological course are discussed.

Adult↗