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Biomedical subjects

P Philip

Publications and source records attributed to P Philip.

At least 73 records · Page 4Linked to original sources
PubMed1992

Polygraphic investigation of respiration during sleep in infants and children.

Controls of respiration have different settings during sleep than during wakefulness. Respiration will also be influenced by sleep state organization and circadian rhythm. Polygraphic monitorings in infants and children must take into account the timing of the longest sleep and longest wakeful periods and the distribution of sleep states. Attention must be given not only to "apneas" and blood gas changes monitored noninvasively but also to breathing frequency, upper airway resistance, and the impact of respiratory changes on the cardiovascular system and sleep continuity. Respiratory efforts and upper airway resistance are responsible for important mechanical intrathoracic changes, which must be evaluated, since they have clinical consequences. For example, infants with an apparent life-threatening event may have an unrecognized increase in upper airway resistance long before having a mixed or obstructive sleep apnea. Muscle disorders in young children require regular sleep monitoring whose results will strongly influence therapeutic approaches. Therapy may change over time, depending on the prominence of the inspiratory muscle weakness or the importance of the mandibular abnormalities induced by the muscle disorder and its impact on upper airway resistance during sleep. At times, it is difficult to avoid sleep disturbances with aggressive investigation of breathing during sleep, and several successive days of monitoring may be needed to determine sleep-related pathology.

Airway Resistance↗
PubMed1992

Acute monocytic or myelomonocytic leukemia with balanced chromosome translocations to band 11q23 after therapy with 4-epi-doxorubicin and cisplatin or cyclophosphamide for breast cancer.

PURPOSE: To report five cases of acute monocytic or myelomonocytic leukemia after chemotherapy with 4-epidoxorubicin for breast cancer and to evaluate the risk of leukemia after the use of this drug. PATIENTS AND METHODS: One hundred fifty-seven patients with advanced breast cancer were randomized to either 4-epi-doxorubicin plus cisplatin or 4-epi-doxorubicin alone. An additional 203 patients were treated prospectively with 4-epi-doxorubicin alone. All were observed closely for leukemic complications. RESULTS: Three patients from the randomized study developed leukemia; all were in the subgroup of 74 patients who received 4-epi-doxorubicin plus cisplatin, whereas no leukemia was observed among the remaining 83 patients in the randomized study or among the additional 203 patients who were treated prospectively with 4-epi-doxorubicin alone (P = .023, log-rank test). In the subgroup of 74 patients who were treated with 4-epi-doxorubicin plus cisplatin, the cumulative risk of leukemia was 16.0% +/- 9.9% (mean +/- SE) 33 months after the start of therapy; the relative risk was 668 (95% confidence interval [Cl], 138 to 1,953). Two other cases of acute monocytic and myelomonocytic leukemia were observed after 4-epi-doxorubicin plus alkylating agents were administered for breast cancer. Three of five cases of leukemia presented balanced translocations to chromosome band 11q23 and two, loss of a whole chromosome no. 7 or its long arm. CONCLUSIONS: 4-epi-doxorubicin is leukemogenic, and the leukemias are often acute monocytic or myelomonocytic with balanced chromosome translocations to band 11q23, such as in the leukemias after therapy with the epipodophyllotoxins. Furthermore, our results suggest a synergistic effect in leukemogenesis between 4-epi-doxorubicin targeting DNA-topoisomerase II and directly genotoxic drugs such as cisplatin or alkylating agents.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Increased risk of myelodysplasia and leukaemia after etoposide, cisplatin, and bleomycin for germ-cell tumours.

Among the cytostatic drugs only the alkylating agents have been firmly established as being leukaemogenic. This report describes 4 cases of acute myeloid leukaemia and 1 of myelodysplasia occurring in a cohort of 212 patients with germ-cell tumours treated with etoposide, cisplatin, and bleomycin. The mean cumulative risk of leukaemic complications was 4.7% (SE 2.3) 5.7 years after start of etoposide-containing chemotherapy, and, compared with the risk in the general population, the relative risk of overt leukaemia was 336 (95% CI 92-861). No leukaemias were detected in a previous cohort of 127 patients with germ-cell tumours treated with cisplatin, bleomycin, and vinblastine. The increased risk of leukaemia was most probably due to etoposide alone or in combination with cisplatin or bleomycin, since other published work has also not revealed an excess of leukaemias among patients with germ-cell tumours treated with only cisplatin, bleomycin, and vinblastine. The risk of leukaemia was dose related since all 5 patients with leukaemic complications were among the 82 who had received a cumulative dose of more than 2000 mg/m2 etoposide, whereas no leukaemias were observed among 130 patients who had received up to 2000 mg/m2 (p = 0.004). 3 of the leukaemic patients had balanced chromosome translocations affecting bands 11q23 and 21q22. These translocations, and perhaps also other balanced aberrations, seem to be characteristic of myelodysplasia and acute leukaemia occurring after therapy with cytostatic agents acting on DNA-topoisomerase II.

Acute Disease↗
PubMed1991

Efficiency of transcranial electrostimulation on anxiety and insomnia symptoms during a washout period in depressed patients. A double-blind study.

In order to test the efficacy of cerebral electrostimulation (electrosleep) as an alternative to drug therapy for the treatment of anxiety and insomnia, we conducted a double-blind study in a sample of 21 depressed inpatients submitted to a 5-day period of drug washout on admission to the psychiatric department. During this withdrawal period, anxiety and insomnia were exacerbated in the placebo group, whereas anxiety decreased and sleep duration improved in the active treatment group, with a divergent evolution during the 5-day washout period. The depressive criteria did not respond differentially to treatment, however. Thus, the effects of this drug washout period are markedly attenuated by cerebral electrostimulation, which is of possible interest in the management of psychotropic drug withdrawal.

Adult↗
PubMed1991

Aberrations of chromosome 6 in 193 newly diagnosed untreated cases of chronic lymphocytic leukemia.

Aberrations of chromosome 6 were observed in 11 of 193 cases of chronic lymphocytic leukemia diagnosed January 1, 1984-November 1, 1988 and investigated cytogenetically within 30 days after diagnosis. The 6p was rearranged in 5 cases: 4 balanced and 1 unbalanced translocation. The 6q was involved in 6 cases: 4 deletions and 2 balanced translocations. Three of the del(6q) may be identical: del(6)(q13q27). In two cases there were no additional aberrations. Aberrations of chromosome 6 correlated significantly with an advanced clinical stage, diffuse pattern of bone marrow infiltration, and increased SmIgM-fluorescence intensity. All these factors are associated with poor prognosis. Although the number of cases with 6q aberrations is still too small and the observation period too short to show significant influence on survival, the presence of 6q aberrations at diagnosis may prove useful in delineating a subtype of chronic lymphocytic leukemia with poor prognosis.

Bone Marrow↗
PubMed1991

Two different classes of therapy-related and de-novo acute myeloid leukemia?

Two different classes of therapy-related acute myeloid leukemia (t-AML) seem to emerge. One class follows therapy with alkylating agents, increases in frequency with age, often presents with myelodysplasia (MDS), responds poorly to chemotherapy, and shows monosomy 7(-7), monosomy 5(-5), or loss of various parts of the long arms of these chromosomes (5q- and 7q-). The other class is related to therapy with cytostatic drugs targeting at DNA-topoisomerase II, often presents with overt leukemia, responds more favorably to chemotherapy, and shows balanced chromosome aberrations, primarily translocations involving chromosome bands 11q23 and 21q22. These two classes of t-AML may have their counterparts in de-novo acute myeloid leukemia (de-novo AML).

Acute Disease↗
PubMed1990

Chromosome aberrations and prognostic factors in therapy-related myelodysplasia and acute nonlymphocytic leukemia.

Cytogenetic studies of 91 consecutive patients with therapy-related myelodysplasia or overt acute nonlymphocytic leukemia disclosed characteristic defects of chromosome 7 in 48 cases and of chromosome 5 in 21 cases. The chromosome 5 abnormalities were consistently present in all abnormal mitoses at the time of diagnosis, as were the chromosome 7 abnormalities in 45 of the 48 patients. Various abnormalities, primarily of the short arm of chromosome 17, were observed in 13 cases, abnormalities of the long arm of chromosome 21 were observed in 12 cases, and rearrangements of 11q23 were seen in nine cases. Thirteen patients presented a normal karyotype. Previous therapy with alkylating agents, the presence of an initial myelodysplastic phase, and abnormalities of chromosome 7 or 5 were interdependent. Patients with 11q23 rearrangement typically developed overt leukemia of FAB types M4 or M5a without myelodysplasia and with a short latent period. Evaluated by Cox regression analysis, complete remission of the primary malignancy and a malignant lymphoma as primary tumor were the two most important and independent prognostic factors indicating a longer survival (P = .008). In addition, the platelet count at diagnosis was a significant prognostic factor (P = .01). For the subgroup of 62 patients with myelodysplasia, the number of chromosome aberrations, the percentage of blasts in the bone marrow, and the hemoglobin level were other significant and independent prognostic factors (P = .05, .05, and .004, respectively). The most important predictive factor for a favorable response to intensive antileukemic chemotherapy in overt leukemia was the absence of a preceding myelodysplastic phase (P = .0014).

Adult↗
PubMed1990

High risk of therapy-related leukemia and preleukemia after therapy with prednimustine, methotrexate, 5-fluorouracil, mitoxantrone, and tamoxifen for advanced breast cancer.

Therapy-related acute non-lymphocytic leukemia or preleukemia was observed in five of 71 patients with advanced breast cancer treated with combination chemotherapy comprising prednimustine, methotrexate, 5-fluorouracil, mitoxantrone, and tamoxifen. In this closely followed cohort of patients the cumulative risk of leukemic complications was 25.4% +/- 10.3% (+/- SE) 37 months after start of chemotherapy. The relative risk of overt leukemia was 339 (95% CI: 41-1223), as two cases were observed versus 0.0059 cases expected. The very high risk of leukemia and preleukemia observed may partly reflect the advanced age of the patients (mean, 61 years) and partly the diagnostic procedures used, which included cytogenetic screening of all patients developing refractory cytopenia. A particularly high leukemogenic effect of prednimustine or a synergism between prednimustine and other drugs used in this study cannot be excluded. In the light of the above results, the authors caution against the use of intensive combination chemotherapy with alkylating agents as in the current study in potentially curable patients with breast cancer.

Adult↗
PubMed1989

B-cell chronic lymphocytic leukaemia: clonal chromosome abnormalities and prognosis in 89 cases.

The results of cytogenetic studies are reported in 89 patients with B-cell CLL. LPS (E. coli lipopolysaccharide), PWM (pokeweed mitogen), PHA (phytohaemagglutinin), EBV (Epstein-Barr virus), TPA (phorbol 12-myristate 13-acetate), and LA (leucoagglutinin) were used as mitogens. Mitoses were obtained from 78 cases. Clonal aberrations could be demonstrated in 26 cases. Trisomy 12 was the most frequent finding (8 cases) and was sole abnormality in 4 cases. Chromosomes #14, #17, and #11 were involved in structural aberrations in 5, 7, and 7 cases respectively, but a t(11;14)(q13;q32) was the only structural aberration seen more than once. The median observation time was 47 months (range 1-87). The presence of clonal abnormalities did not influence survival significantly, either when calculated from diagnosis or from cytogenetic analysis. Patients with more than one aberration, however, had a significantly shorter survival than patients with normal mitoses only (p less than 0.05). The survival of 8 patients with trisomy 12 (in 4 as sole abnormality) was not different from that of patients with normal mitoses only.

Chromosome Aberrations↗
PubMed1988

Point mutation of the ras protooncogenes and chromosome aberrations in acute nonlymphocytic leukemia and preleukemia related to therapy with alkylating agents.

Nine cases of overt acute nonlymphocytic leukemia and four cases of preleukemia or a myelodysplastic syndrome, all related to intensive treatment with alkylating agents, were studied cytogenetically and investigated using a rapid and sensitive dot blot screening procedure for point mutations in the Ha-ras, Ki-ras, and N-ras protooncogenes within codons 12, 13, and 61. The technique involves a selective amplification of genomic DNA sequences containing the codon sequence of interest, in combination with oligonucleotide hybridization. Examining fractionated mononuclear cells from bone marrow or peripheral blood, an N-ras mutation at position 13 was observed in one patient with overt leukemia, resulting in a base change from GGT to TGT thus converting glycine to cysteine. The other cases exhibited no ras gene mutations. It is surprising that c-ras mutations are only occasionally observed in overt acute nonlymphocytic leukemia related to treatment with alkylating agents, as such abnormalities have often been observed in acute nonlymphocytic leukemia de novo, and as many alkylating agents are known to produce DNA adducts leading to point mutations and substitution of single amino acids. The fact that deletions of varying parts of the long arms of chromosomes 5 and 7 are observed in most cases of therapy-related acute nonlymphocytic leukemia and preleukemia, as confirmed by our own series of 71 patients, suggests that loss of heterozygosity for specific alleles on the two chromosomes, rather than activation of a protooncogene, could be an important step in leukemogenesis.

Acute Disease↗
PubMed1988

Cytogenetic, clinical, and cytologic characteristics of radiotherapy-related leukemias.

From 1978 to 1985, we observed eight cases of acute nonlymphocytic leukemia or preleukemia, three cases of acute lymphoblastic leukemia, and three cases of chronic myeloid leukemia in patients previously treated exclusively with radiotherapy for other tumor types. The latent period from administration of radiotherapy to development of leukemia varied between 12 and 243 months. Clonal chromosome aberrations reported previously as characteristic of acute nonlymphocytic leukemia following therapy with alkylating agents were observed in three of the eight patients with acute nonlymphocytic leukemia (5q- and -7) and in two of the three patients with acute lymphoblastic leukemia (-7 and 12p-). All three patients with radiotherapy-related chronic myeloid leukemia presented a t(9;22)(q34;q11). The results suggest that cytogenetic characteristics may reflect the etiology in radiation-induced acute leukemias, whereas radiation-related chronic myeloid leukemia does not seem to differ chromosomally from de novo cases of the disease.

Acute Disease↗
PubMed1988

Mafosfamide (ASTA-Z-7654) in vitro treatment of bone marrow does not eradicate Philadelphia-positive cells in chronic myeloid leukaemia.

Bone marrow from 9 patients with Ph1+CML was treated in vitro with varying concentrations of Mafosfamide in order to test the hypothesis that selective pharmacological killing of Ph1-positive cells in CML is feasible. A marked difference in sensitivity to Mafosfamide of CFU-GM was observed, but at all concentrations 100% persistence of Ph1+ cells was noticed. We conclude that, in classical cases of Ph1-positive CML, Mafosfamide purging of bone marrow will not be effective.

Adult↗