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Biomedical subjects

M Alcalay

Publications and source records attributed to M Alcalay.

At least 55 records · Page 3Linked to original sources
PubMed1994

[Treatment of Takayasu's disease with low-dose methotrexate. Apropos of a case].

Persistent evidence of inflammation at the occlusive phase of Takayasu's arteritis is of adverse prognostic significance. Low-dose weekly methotrexate therapy given in combination with a corticosteroid may be effective in such patients. We report a personal case which supports the data obtained by Fauci and coworkers, as well as the conclusions of the other two similar case-reports in the literature.

Drug Therapy, Combination↗
PubMed1994

[Chemonucleolysis of disk herniation with low back pain as the single symptom: 20 cases].

Disk herniation can manifest as isolated low back pain, which is usually intermittent and accompanied with stiffness of the lumbar spine. There is almost general agreement that neither neurosurgical treatment nor chemonucleolysis is appropriate in patients with this clinical pattern. We used chemonucleolysis in 19 patients with recurrent episodes of isolated low back pain and one patient with severe permanent isolated low back pain dating back to a conservatively-treated episode of sciatica. All 20 patients had disk herniation documented by imaging studies. A very good or satisfactory outcome was recorded in ten patients after three months, 11 after six months and 12 in March 1993 after a mean follow-up of 72 months. The treatment was well tolerated, even in those patients who were not improved; a single patient developed an episode of acute low back pain that required surgical treatment. In patients with low back pain and disk herniation, there is currently no means of determining whether a causal relationship links these two abnormalities. Nevertheless, we believe that chemonucleolysis can be proposed in severe forms, provided the patients are apprised of current success rates.

Adult↗
PubMed1994

Fetal biophysical profile score in triplet pregnancies.

Assessment of the last fetal biophysical profile score (BPS) (excluding nonstress test) prior to delivery was carried out in 35 triplet pregnancies. A normal BPS was found to be reliable in predicting nondistressed fetuses in triplets (specificity, 94.9%), while an equivocal BPS (6/8) had low sensitivity (14.3%) in predicting distressed fetuses. Two stillbirths were not detected by ultrasound prior to delivery. No correlation was found between the BPS and either neonatal morbidity or perinatal mortality. The BPS could not differentiate between distressed and nondistressed fetuses in the same pregnancy. These results suggest that an equivocal BPS has limited value in predicting fetal distress in triplet pregnancies, but a normal one could be used to predict nondistressed fetuses.

Adult↗
PubMed1994

Exacerbation of Wegener's granulomatosis during pregnancy: report of a case with tracheal stenosis and literature review.

Wegener's granulomatosis (WG) is a rare multisystem disease of unknown etiology. We describe a woman with WG who relapsed twice during 2 pregnancies with appearance of tracheal stenosis. During the first pregnancy which ended with a delivery of a healthy baby, the subglottic stenosis responded to laser radiation and glucocorticosteroid therapy. An uneventful therapeutic abortion was performed during the 2nd pregnancy. Our case brings to 15 the number of pregnancies which were recorded in 10 women with WG. Diagnosis of WG was done during pregnancy in 4 cases, and at the postpartum period in 3 cases. Eight pregnancies occurred in women with known WG, relapse occurred in 5 pregnancies. Two cases ended with maternal death. It seems therefore that pregnancy may have a significant contribution both to the relapse of WG and to its appearance.

Adult↗
PubMed1994

Hepatitis A in French hemophiliacs.

The prevalence of serum antibodies to hepatitis A virus (HAV) in 793 hemophilia A (HA) and 89 hemophilia B (HB) patients coming from 10 French Hemophilia Centers and treated since 1986-1987 with solvent/detergent (SD)-treated products is reported. The results indicated seropositivity to HAV of 29.9% in HA and 40.4% in HB patients. There was no difference among the patients according to severity of the disease, HIV serology or administration of factor VIII during the last 12 months. Seropositivity increased with age from 5.2% in HA children to 42.4% in adults (in HB the respective prevalences in the same groups were 7.7% and 56.1%). When compared to normal controls (n = 585), the prevalence of HAV seropositivity was not excessive in HA patients (n = 206). 19/20 children exclusively treated with a very-high-purity SD-factor VIII concentrate (Centre régional de transfusion sanguine, Lille) remained HAV seronegative. Six cases of HAV contamination were reported in patients with severe HA, probably reflecting the level of HAV endemy in the normal population in France. No special risk of HAV transmission linked to the SD products used in France since 1986 had thus been identified.

Adolescent↗
PubMed1994

Effect of the acute promyelocytic leukemia PML/RAR alpha protein on differentiation and survival of myeloid precursors.

Acute promyelocytic leukaemia is characterized by an expansion of haematopoietic precursors arrested at the promyelocytic stage (1). The differentiation block can be reversed by retinoic acid, which induces blast differentiation both in vitro (2) and in vivo (3-4). Acute promyelocytic leukaemia is also characterized by a 15;17 chromosome translocation (5) with breakpoints within the retinoic acid alpha receptor (RAR alpha) gene on 17 and within the PML gene, that encodes a putative transcription factor of unknown function (6-7), on 15 (8-10). As a consequence of the translocation a PML/RAR alpha gene is formed. It is transcriptionally active and encodes a PML/RAR alpha fusion protein detectable in all APL cases (11-14). We expressed the PML/RAR alpha protein in U937 myeloid precursor cell line and show that they: 1) lose the capacity to differentiate under the action of different stimuli (vitamin D3, transforming growth factor beta 1); ii) acquire enhanced sensitivity to retinoic acid; iii) exhibit a higher growth rate that is due to a reduction in apoptotic cell death. These results provide the first evidence of biological activity of PML/RAR alpha and recapitulate critical features of the promyelocytic leukemia phenotype.

Cell Differentiation↗
PubMed1993

The acute promyelocytic leukemia-specific PML-RAR alpha fusion protein inhibits differentiation and promotes survival of myeloid precursor cells.

Acute promyelocytic leukemia is a clonal expansion of hematopoietic precursors blocked at the promyelocytic stage. The differentiation block can be reversed by retinoic acid, which induces blast maturation both in vitro and in vivo. Acute promyelocytic leukemia is characterized by a 15;17 chromosome translocation with breakpoints within the retinoic acid alpha receptor (RAR alpha) gene on 17 and the PML gene, which encodes a putative transcription factor, on 15. A PML-RAR alpha fusion protein is formed as a consequence of the translocation. We expressed the PML-RAR alpha protein in U937 myeloid precursor cells and showed that they lost the capacity to differentiate under the action of different stimuli (vitamin D3 and transforming growth factor beta 1), acquired enhanced sensitivity to retinoic acid, and exhibited a higher growth rate consequent to diminished apoptotic cell death. These results provide evidence of biological activity of PML-RAR alpha and recapitulate critical features of the promyelocytic leukemia phenotype.

Animals↗
PubMed1993

The effect of fertility drugs and in vitro methods on the outcome of 106 triplet pregnancies.

OBJECTIVE: To compare the effect of fertility drugs and IVF on the outcome of triplet pregnancies. DESIGN: Prospective clinical study. SETTING: A single university medical center. PATIENTS: One hundred six consecutive triplet pregnancies treated from 1984 through 1992. MAIN OUTCOME MEASURES: The frequency of pregnancy loss, livebirths, and antenatal and neonatal complications was compared in spontaneous, clomiphene citrate (CC), menotropins, and IVF triplet pregnancies. RESULTS: Eighty-one of the 106 (76.4%) triplet pregnancies progressed beyond 25 weeks, comprising 6 of 7 (85.7%) spontaneous pregnancies, 13 of 16 (81.2%) CC induced, 44 of 56 (78.6%) menotropin induced, and 18 of 27 (66.6%) IVF gestations. There were no significant differences in the stillbirth and neonatal mortality rates according to the mode of conception. The mean gestational ages and the mean birth weights were similar in the four groups. The frequency of premature contractions, premature rupture of membranes, cesarean section, and neonatal complications were similar in the ovulation induction and IVF pregnancies. CONCLUSION: Triplet pregnancies after ovulation induction and IVF have a similar outcome.

Adult↗
PubMed1993

The molecular genetics of acute promyelocytic leukemia.

The chromosome breakpoints of the acute promyelocytic leukemia (APL)-specific 15;17 translocation have recently been isolated. They are localized on a previously unknown gene, PML, on chromosome 15 and in the gene that encodes the alpha retinoic acid receptor (RAR alpha) on 17. The translocation, which is balanced and reciprocal, leads to the formation of two fusion genes, PML/RAR alpha and RAR alpha/PML. Both are expressed in APL. The PML/RAR alpha gene codes for two abnormal proteins: the PML/RAR alpha fusion protein and an abnormal PML protein, the RAR alpha/PML gene encodes the RAR alpha/PML fusion protein. Experiments to investigate the biological activity of the abnormal translocation products are in progress. Preliminary results suggest that the PML/RAR alpha fusion protein is responsible for two important properties of the APL phenotype: the differentiation block characteristic of the leukemic blasts and the high sensitivity of the blasts to the differentiative action of retinoic acid (RA) both in vivo and in vitro. The mechanism through which PML/RAR alpha exerts its biological function remains unknown. However, there is accumulating evidence that it acts by interfering with normal endogenous pathways of both RAR alpha and PML. The RAR alpha receptor is implicated in regulating the myeloid differentiation induced by RA. Although the physiological function of PML is not known, it is probably a transcription factor. Definition of the molecular architecture of the t(15;17) has furnished further tools for: (1) molecular diagnosis of APL and (2) highly sensitive evaluation of the neoplastic clone during antileukaemic therapy. The molecular identification of residual APL disease after anti-leukaemia therapy allows patients at risk of relapse to be identified.

Carrier Proteins↗
PubMed1993

Immunoreactive endothelins in human follicular fluid.

Endothelin levels were measured by means of [125I]endothelin-1,2,3 radioimmunoassay in the follicular fluids of 22 mature ovarian follicles of 11 patients, obtained during ovum pickup. In all but 1 of the follicles, endothelin levels were detectable and ranged between 0.2 and 3.6 pg/ml (mean 1.47 +/- 0.99). In this preliminary study, no correlation was found between follicular endothelin levels and oocyte fertilization or the hormonal ovarian response during the follicular phase.

Endothelins↗
PubMed1993

[Association of rheumatoid arthritis and Kaposi disease. Apropos of a case arising after intraarticular corticotherapy].

A 66 year old Corsican HLA A2 and DR5-positive male with moderately active seropositive destructive rheumatoid arthritis developed Kaposi's sarcoma after intraarticular administration of corticosteroids. He had no history of oral corticosteroid therapy, organ transplantation, AIDS, or cancer. Chlorambucil proved ineffective but the outcome was spontaneously favorable following discontinuation of oral corticosteroid therapy initiated after the development of the skin lesions. Six previous reports of concomitant rheumatoid arthritis and Kaposi's sarcoma were found. All six cases occurred following systemic corticosteroid therapy. The high incidence of rheumatoid arthritis and the small number of patients with rheumatoid arthritis and Kaposi's sarcoma suggest that concomitant occurrence of the two conditions may be fortuitous. However, the responsibility of corticosteroid therapy, which preceded development of Kaposi's sarcoma in every case, cannot be ruled out.

Aged↗
PubMed1992

[Unsatisfactory results of intradiscal injection of triamcinolone hexacetonide in the treatment of sciatica caused by intervertebral disk herniation].

Sciatica caused by intervertebral disc herniation can be treated with intradiscal injection of chymopapain. A search for a cheaper and less allergizing product led to triamcinolone hexacetonide, this procedure being known as "nucleorthesis". The first results at 6 months were encouraging. In 3 centres where triamcinolone hexacetonide was tested with a more than 2 years' follow-up 92 patients could be evaluated. The results obtained were considered satisfactory in 34 patients (36.9 percent), but they were poor in 19 patients (20.6 percent), and 39 patients (42 percent) had to be operated upon within 2 years. Return to surgery took place within the 6 months following nucleorthesis in 18 patients (19.56 percent) and beyond this period in 17 patients (22.8 percent) with degradation of the results. Moreover, calcifications were found in 19 out of 38 patients; they were of varying size, sometimes detected only at computerized tomography, and some of them appeared to produce symptoms. All considered, the failure rates, the number of patients who required surgery and the occurrence of large and sometimes symptomatic calcifications make triamcinolone nucleorthesis unacceptable compared with the recognized percentages of success with papain nucleolysis and surgical operations. For these reasons, we consider that this treatment should be abandoned.

Anti-Inflammatory Agents↗
PubMed1992

Molecular monitoring of the myl/retinoic acid receptor-alpha fusion gene in acute promyelocytic leukemia by polymerase chain reaction.

The acute promyelocytic leukemia (APL) t(15;17) translocation generates a myl/retinoic acid receptor-alpha (RAR-alpha) chimeric gene that is transcribed as a fusion myl/RAR-alpha messenger RNA. Using primer sets derived from RAR-alpha and myl cDNAs, we were able to amplify the breakpoint sites of the fusion transcripts of all 35 APL RNA samples by reverse polymerase chain reaction (PCR) and nested primer approach of two rounds of amplification. DNA fragments of different size were obtained according to the chromosome 15 breakpoints (intron 3-bcr 3; exon 6-bcr 2; and intron 6-bcr 1). bcr 1 and bcr 3 represent the regions of the myl locus most frequently involved among APL (48.5 and 34.2 of cases, respectively); bcr 3 constitutes 62.5% of cases among M3V as compared with 25.9% of M3 cases. The feasibility of monitoring the APL clone by PCR analysis in five APL patients who received different treatment (chemotherapy, all-trans-retinoic acid or bone marrow transplantation) was evaluated. In five of nine bone marrow samples of patients in complete remission, t(15;17)-positive cells could be detected by PCR analysis. We conclude that PCR amplification of the myl/RAR-alpha junctions represents the easiest and rapid method for diagnosis and monitoring of the APL clone.

Adolescent↗
PubMed1992

Expression pattern of the RAR alpha-PML fusion gene in acute promyelocytic leukemia.

Two chimeric genes, PML-RAR alpha and RAR alpha-PML, are formed as a consequence of the acute promyelocytic leukemia (APL)-specific reciprocal translocation of chromosomes 15 and 17 [t(15;17)]. PML-RAR alpha is expressed as a fusion protein. We investigated the organization and expression pattern of the RAR alpha-PML gene in a series of APL patients representative of the molecular heterogeneity of the t(15;17) and found (i) two types of RAR alpha-PML mRNA junctions (RAR alpha exon 2/PML exon 4 or RAR alpha exon 2/PML exon 7) that maintain the RAR alpha and PML longest open reading frames aligned and are the result of chromosome 15 breaking at two different sites; and (ii) 10 different RAR alpha-PML fusion transcripts that differ for the assembly of their PML coding exons. A RAR alpha-PML transcript was present in most, but not all, APL patients.

Base Sequence↗
PubMed1992

Genomic variability and alternative splicing generate multiple PML/RAR alpha transcripts that encode aberrant PML proteins and PML/RAR alpha isoforms in acute promyelocytic leukaemia.

The acute promyelocytic leukaemia (APL) 15;17 translocation generates a PML/RAR alpha chimeric gene which is transcribed as a fusion PML/RAR alpha mRNA. Molecular studies on a large series of APLs revealed great heterogeneity of the PML/RAR alpha transcripts due to: (i) variable breaking of chromosome 15 within three PML breakpoint cluster regions (bcr1, bcr2 and bcr3), (ii) alternative splicings of the PML portion and (iii) alternative usage of two RAR alpha polyadenylation sites. Nucleotide sequence analysis predicted two types of proteins: multiple PML/RAR alpha and aberrant PML. The PML/RAR alpha proteins varied among bcr1, 2 and 3 APL cases and within single cases. The fusion proteins contained variable portions of the PML N terminus joined to the B-F RAR alpha domains; the only PML region retained was the putative DNA binding domain. The aberrant PML proteins lacked the C terminus, which had been replaced by from two to ten amino acid residues from the RAR alpha sequence. Multiple PML/RAR alpha isoforms and aberrant PML proteins were found to coexist in all APLs. These findings indicate that two potential oncogenic proteins are generated by the t(15;17) and suggest that the PML activation pathway is altered in APLs.

Amino Acid Sequence↗