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M Ravid

Publications and source records attributed to M Ravid.

At least 37 records · Page 2Linked to original sources

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↗

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↗

ACE inhibitors in elderly patients with hypertension. Special considerations.

Angiotensin converting enzyme (ACE) inhibitors have emerged as the class of antihypertensive and vasodilatatory agents of first choice in the treatment of elderly patients with hypertension. Normotensive patients with congestive heart failure, post-anterior myocardial infarction, or diabetes mellitus with evidence of microangiopathy will also benefit from continuous ACE inhibition. The long term use of ACE inhibitors is associated with improved survival and reduced cardiovascular, cerebral and renal morbidity in these patients. In elderly atherosclerotic patients, these agents provide good control of systolic and diastolic blood pressure and peripheral resistance, with remarkable preservation of vital organ perfusion and infrequent adverse effects. Used as monotherapy, the effectiveness of ACE inhibitors is limited. However, there are advantages for using them in combination with other drugs, notably thiazide diuretics, nitrates and calcium antagonists. Renal function is thus preserved and left heart hypertrophy is prevented. There are no major differences between the various ACE inhibitors, and the choice of drug is largely a matter of personal preference.

Adrenergic beta-Antagonists↗

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↗

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↗

Fluorescence in situ hybridization (FISH) for retrospective detection of trisomies 3 and 7 in multiple myeloma.

The malignant plasma cells of multiple myeloma (MM) have a low proliferative activity and therefore cytogenetic studies of the disease have been severely limited. We evaluated the role of fluorescence in situ hybridization (FISH) in the detection of numerical chromosomal abnormalities in early stages of myeloma and the applicability of the method to stored archival slides. Old air-dried bone marrow smears from 15 myeloma patients obtained at presentation were probed with alpha satellite DNA sequences to chromosomes 3 and 7. Numerical chromosome aberrations were found in eight (53%) of the patients, including six (of 12) with trisomy 7, and two (of eight) with trisomy 3. This study demonstrates that FISH is a sensitive method for the detection of numerical aberrations in myeloma and for the study of old slides for retrospective analysis.

Aged↗

The BCL-1, BCL-2, and BCL-3 oncogenes are involved in chronic lymphocytic leukemia. Detection by fluorescence in situ hybridization.

The putative oncogenes BCL-1, BCL-2, and BCL-3 are commonly rearranged by translocations to the immunoglobulin genes in B-cell malignancies. However, Southern blotting rarely detected their involvement in chronic lymphocytic leukemia (CLL). This discrepancy could stem from some unique features of the oncogenesis of CLL or be due to shortcomings of Southern blotting. We have therefore evaluated the role of fluorescence in situ hybridization (FISH) in the detection of these oncogenes in CLL. Twenty consecutive CLL patients were studied by FISH for the detection of BCL-1, BCL-2, or BCL-3 rearrangement and for the presence of trisomy 12. Selected patients were also evaluated by classical cytogenetic techniques and by Southern blot analysis. Juxtaposition of JH and BCL-1 was demonstrated in 10 (50%), BCL-2 in three (15%), and BCL-3 in four (20%) of the patients. Trisomy 12 was detected by FISH in 11 (55%) patients. The coexistence of trisomy 12 and translocation of the BCL-1 oncogene was common. Three of the patients had chromosomal aberrations compatible with those detected by FISH. In contrast, in none of the five patients selected by their positive FISH findings was a rearrangement demonstrated by Southern blotting. We conclude that FISH is a sensitive method for the detection of oncogene involvement in CLL. Mainly BCL-1, but also BCL-2 and BCL-3, are commonly translocated to the immunoglobulin heavy chain locus on chromosome 14. These translocations are often associated with trisomy 12. These findings indicate that the BCL oncogenes are commonly involved in CLL and lend support to the multi-hit theory of cancer development.

Aged↗

Plasma lipids and the progression of nephropathy in diabetes mellitus type II: effect of ACE inhibitors.

Ninety-four normotensive type II diabetics with normal renal function and microalbuminuria were randomized to receive enalapril 10 mg/day or placebo and were followed for five years. In the patients treated by enalapril plasma creatinine values and albuminuria remained stable throughout the observation period. Their plasma total cholesterol decreased from an initial value of 245 +/- 27 mg/dl to mean study value of 236 +/- 29 mg/dl, and to a fifth year value of 232 +/- 27 mg/dl (P < 0.001). The changes in HDL cholesterol and triglyceride values were nonsignificant. In the placebo group there was a significant increase in albuminuria and a mean decline of 13% in reciprocal creatinine values during the five years. Plasma total cholesterol increased from an initial mean value of 246 +/- 24 to a mean study value of 252 +/- 25 mg/dl, and to a fifth year mean value of 259 +/- 32 mg/dl (P < 0.001). There was a significant correlation between both initial and mean plasma total cholesterol values, and the decline in renal function and the rise in albuminuria in the placebo treated patients. This correlation persisted after stratification for blood pressure. Treatment with enalapril did not eliminate these correlations. Cholesterol may be an additional risk factor for diabetic nephropathy. ACE inhibitors may have a modest cholesterol lowering effect in diabetic patients mediated, in part, through the decline in albuminuria.

Adult↗

Sequential levels of ceftriaxone in intervertebral disc removed as part of scoliosis surgery.

A single intravenous loading dose of 1 g ceftriaxone was injected at different intervals before surgery for correction of spinal scoliosis. Serum and concomitant disc samples were obtained and assay was performed using high-pressure liquid chromatography. Data showed that the antibiotic levels in intervertebral disc space reached 3.5 mcg/mg, which is above the minimum inhibitory concentration for most of the relevant pathogens, as early as 1 hour after intravenous administration. These therapeutic levels were maintained for more than 5 hours, an accepted period for most spinal surgical procedures.

Adult↗

Delta-T-lymphocytosis in a patient with thymoma.

BACKGROUND: Malignant thymoma is composed of neoplastic epithelial cells and small lymphocytes. Rarely, patients also may have peripheral T-lymphocytosis. These lymphocytes have been considered nonneoplastic because of their microscopic appearance and immunophenotype, as well as gene rearrangement studies. METHODS: A 42-year-old man developed lymphocytosis 3 years after the completion of intensive combined chemoradiotherapy protocol for lymphocytic thymoma. These peripheral blood lymphocytes were evaluated phenotypically and genotypically. RESULTS: Immunophenotyping established that the cells were CD3 positive, CD4 negative, CD8 negative, T-cell receptor (TCR)-alpha/beta negative, and TCR-gamma/delta positive. Gene rearrangement studies with TCR-delta probe confirmed the monoclonality of these cells. Chromosome analysis showed deletion of chromosome Y. The clinical course was progressive and had the features of malignant lymphoma. CONCLUSIONS: To the authors' knowledge, this is the first report of a patient with thymoma in whom monoclonal proliferation of T-gamma/delta peripheral blood lymphocytes was confirmed immunophenotypically and genotypically. These monoclonal TCR-gamma/delta lymphocytes may belong to the malignant clone of the thymoma; however, the possibility that they represent an evolution of a second lymphatic malignancy cannot be excluded.

Adult↗

Angiotensin-converting enzyme inhibitors and cough: a prospective evaluation in hypertension and in congestive heart failure.

Angiotensin-converting enzyme inhibitors (ACE-I) have become the mainstem of antihypertensive therapy and first-choice agents for vasodilatation in congestive heart failure (CHF). A typical dry cough is the main cause for discontinuation of ACE-I therapy. Data about the incidence, course, and clinical significance of this side effect are conflicting. This study determined the incidence of cough in ACE-I treated patients with hypertension and with CHF and to appreciate its clinical significance; 268 ACE-I treated patients, 164 with hypertension and 104 with CHF were prospectively followed for at least 1 year and specifically questioned about cough and other side effects. In those in whom cough developed, a second and then a third ACE-I were tried. Cough developed in 50 (18.6%) of the 268 patients; 23 patients with hypertension (14%) had coughs 24.7 +/- 17.1 (SD) weeks after initiation of therapy; 27 patients with CHF (26%) had coughs 12.3 +/- 12 (SD) weeks after the start of ACE-I therapy (P = 0.005). All but three patients had coughs also on the second and third ACE-I. The time from the beginning of therapy to the onset of cough was significantly shorter with the second than the first drug. ACE-I agents had to be discontinued in 50% of the patients in whom coughs developed, most of them in the CHF group. In the others, cough was well tolerated or disappeared during subsequent months. The incidence of cough, which necessitated discontinuation of ACE-I treatment, was 4% among patients with hypertension and 18% among patients with CHF (P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Determination of amyloid type by ELISA using milligram amounts of tissue.

A new procedure was developed for isolation and immunochemical identification of amyloid proteins. This procedure involves extraction of amyloid proteins from tissues with aqueous acidic acetonitrile, their purification by HPLC and identification by ELISA. In this way the type of amyloid proteins was defined in amyloid-containing tissues obtained from 15 patients. The technique is simple, rapid and enables typing of amyloid proteins using only milligram amounts of tissue. This is in contrast to the conventional amyloid isolation and chemical identification technique which is laborious, time consuming and requires gram amounts of tissues. The procedure may enable the identification of the type of amyloid in biopsy specimens and thus help in evaluation of prognosis and determination of the therapeutic policy.

Amyloid↗

Detection of bcl rearrangements in B-CLL by fluorescence in situ hybridization.

Data concerning oncogene activation in CLL are very limited. When studied by Southern blot, rearrangements of bcl-1, bcl-2, and bcl-3 have been only infrequently reported. We evaluated the role of fluorescence in situ hybridization (FISH) in the detection of gene rearrangements in two CLL patients. We used multiple DNA probes, including those of chromosome 12, immunoglobulin heavy and light chains, and the oncogenes bcl-1, bcl-2, and bcl-3. Additionally, routine cytogenetic study was performed. In one patient, trisomy 12 and bcl-2 translocation were demonstrated by both methods, while trisomy 12 and bcl-1 translocation were seen in the second patient, who had a normal karyotype. Larger studies should evaluate the role of FISH in the detection of oncogene involvement in CLL and compare it with other molecular methods.

Aged↗

Fibrosing alveolitis associated with primary antiphospholipid syndrome.

The spectrum of the primary antiphospholipid syndrome has expanded in recent years. It has been associated with a number of non-thrombotic syndromes such as pulmonary hypertension, adrenal insufficiency, chorea and avascular necrosis of bone. Yet, it has not been described in association with inflammatory pulmonary disease. We describe a young male with definite primary antiphospholipid syndrome who developed insidious diffuse pulmonary infiltrates. The histopathologic examination of the involved lung demonstrated alveolitis and fibrosis. We suggest that this pulmonary involvement may represent another manifestation of the primary antiphospholipid syndrome.

Adult↗

Aplastic anemia induced by cyclohexylchloroethylnitrousurea.

We report a patient who developed aplastic anemia after three courses of cyclohexylchloroethylnitrousurea (CCNU), procarbazine and oncovine administered after craniotomy and irradiation for brain astrocytoma. To the best of our knowledge, aplastic anemia following CCNU has not been reported previously. The unique course of the disease and implications of this complication are discussed.

Adult↗