Search PubMed⌕ Search

Biomedical subjects

P Philip

Publications and source records attributed to P Philip.

At least 55 records · Page 3Linked to original sources
PubMed1996

Tiredness and somnolence despite initial treatment of obstructive sleep apnea syndrome (what to do when an OSAS patient stays hypersomnolent despite treatment).

From a database of 4,129 patients with sleep-disordered breathing (SDB), we found 207 subjects (43 women) that still complained of daytime tiredness, fatigue, and/or sleepiness despite treatment. In 25 subjects the sleepiness developed 1 to 36 months following treatment and was related to noncompliance (8 subjects), significant weight increase and/or inappropriate treatment (10 subjects), or development of new medical problems (7 subjects). In the remaining 182 subjects, sleepiness was noted within 1 month after what was judged appropriate treatment for SDB. In this group, the reason for persistent complaint was divided into four categories: 1) inappropriate treatment as a result of not using the measurement of esophageal pressure (Pes) in the initial diagnosis (41 subjects), 2) nonfunctional treatment (3 subjects), 3) associated narcolepsy-like syndrome (2 subjects), and 4) emergence of obesity and/or periodic leg movements as significant factors (135 subjects). The 135 subjects in this last category could be subdivided into three subgroups: 1) younger subjects, severely overweight with lower mean nocturnal saturated arterial oxygen (SaO2) values; 2) older subjects, of normal weight, with high numbers of periodic leg movements (PLM); and 3) moderately overweight subjects, with a combination of PLM and lower mean SaO2 values than expected. Treatments were aimed at eliminating the identified problems; they included standard medications for PLM and nasal bilevel positive airway pressure (BiPAP) for low SaO2 measurements. These treatments were not effective in specific cases, and stimulant medications had to be prescribed.

Adult↗
PubMed1996

Health-related quality of life in patients with insomnia treated with zopiclone.

Insomnia can cause impaired productivity and absenteeism from work, increased risk of accidents, and impaired quality of family and social life. Thus, it can compromise quality of life in affected individuals and result in costs to society as a whole. The nonbenzodiazepine hypnotic zopiclone is effective and well tolerated in the treatment of insomnia. Importantly, it also has minimal effects on next-day performance and psychological function. 458 patients treated with zopiclone for 14 days showed significantly greater improvement compared with placebo recipients in sleep evaluation questions and scores for activity, social and professional quality-of-life aspects. After 8 weeks, the improvement in scores for sleep, activity and social questions remained significantly higher in patients who had received zopiclone compared with placebo recipients. No significant differences were observed between 167 patients who had been taking zopiclone for at least 12 months and a control group of 381 persons with no sleep problems in virtually all of the 5 aspects of the quality-of-life questionnaire. Some important aspects such as relationships and professional life were not modified by zopiclone. When insomnia is treated appropriately, compared with no treatment, patients' feelings about their quality of life are improved and, furthermore, do not appear to differ significantly from perceptions of quality of life in those without sleep-related problems.

Azabicyclo Compounds↗
PubMed1996

Clonal chromosome aberrations in myeloid leukemia after styrene exposure.

OBJECTIVES: The purpose of the study was to determine the risk of myeloid leukemia subclassified according to clonal chromosome aberrations in styrene-exposed workers. METHODS: A nested case-referent study was carried out on 19 myeloid leukemia patients, of which 12 showed clonal chromosome aberrations, and 57 referents ascertained within the Danish reinforced plastics industry and similar industries with no styrene exposure. RESULTS: A 2.5-fold increased risk for myeloid leukemia with clonal chromosome aberrations (95% confidence interval 0.2-25.0) was found among workers of companies with styrene exposure. CONCLUSIONS: The results suggest that styrene may cause leukemia through a clastogenic effect. But similar findings could also have been found if the exposure was associated with a specific subtype of leukemia prone to develop the chromosome aberrations in question. Due to the few observations and the lack of detailed exposure data, additional studies are needed to corroborate or refute the present suggestive findings.

Adult↗
PubMed1996

Adult psychophysiologic insomnia and positive history of childhood insomnia.

Sixty-five adults diagnosed with "psychophysiologic chronic insomnia" following the criteria of the Association of Sleep Disorders Centers were investigated. They were subdivided into two groups based on whether onset of the insomnia had occurred in childhood or adulthood. Fifty similar-aged patients with obstructive sleep apnea syndrome (OSAS) were also investigated and served as a contrast group. All subjects were given polygraphic recordings and structured interviews, and all completed sleep questionnaires after reviewing the questions with an investigator. On many indices evaluating subjective daytime alertness and well-being, the psychophysiologic insomnia patients had scores similar to the OSAS patients. There were no significant differences between the childhood-onset and adult-onset psychophysiologic insomnia patients on most of the investigated items. However, the childhood-onset psychophysiologic insomniinacs had moderately but significantly higher reports of nightmares. This group also reported having had longer sleep latencies, significantly more "fear of the dark" and more frequent nightmares during childhood than the adult-onset group. These statistically significant findings reflected only a moderate increase in subjective scores, however, and in general the childhood-onset and adult-onset psychophysiologic insomnia patients were very similar.

Adult↗
PubMed1995

Different genetic pathways in leukemogenesis for patients presenting with therapy-related myelodysplasia and therapy-related acute myeloid leukemia.

Development of myelodysplasia (MDS) with subsequent progression to acute myeloid leukemia (AML) is an example of the multistep process of malignant transformation in which each step often relates to genetic abnormalities that can be directly seen as chromosomal aberrations. Therapy-related MDS and AML (t-MDS and t-AML) may serve as an ideal model for a study of the genetic evolution of MDS and AML because chromosomal abnormalities are observed in most cases and because the disease is often diagnosed early due to a close patient follow-up. The cytogenetic characteristics at diagnosis were studied in 137 consecutive cases of t-MDS and t-AML, including 22 new cases, and correlated with the clinical characteristics and the course of the disease. Balanced translocations to chromosome bands 11q23 and 21q22 represent primary steps in pathways leading directly to overt t-AML. Specific chromosomal deletions or losses, on the other hand, represent primary or secondary events in alternative pathways leading to t-MDS with potential for subsequent transformation to overt t-AML. Loss of a whole chromosome 7 (-7) or deletion of its long arm (7q-) and deletion of the long arm of a chromosome 5 (5q-) were the most frequent primary abnormalities significantly related to t-MDS. Loss of a whole chromosome 5 (-5) was also a primary event, but surprisingly, was observed equally in t-MDS and in t-AML. Deletion of chromosome 13, including bands q13q14, was another less common primary aberration of t-MDS. Except for -7 and del(13q), these primary aberrations were most often observed together with secondary abnormalities. These included balanced aberrations involving band 3q26 and various deletions of chromosome 3, a gain of a whole chromosome 8, deletions of the short arm or loss of chromosomes 12 and 17, loss of a whole chromosome 18, and deletions of the short arm of chromosome 21. Deletions or loss or chromosomes 5 and 7 were significantly associated with previous therapy with alkylating agents (P = .002), and balanced translocations to chromosome bands 3q26, 11q23, and 21q22 were significantly associated with previous therapy with drugs targeting DNA-topoisomerase II (P < .00005). Other characteristic aberrations were not related to any specific type of therapy. The molecular changes believed to contribute to the development of t-MDS and t-AML have been identified for many of these chromosomal abnormalities.

Acute Disease↗
PubMed1994

Translocation (3;21)(q26;q22) in therapy-related myelodysplasia following drugs targeting DNA-topoisomerase II combined with alkylating agents, and in myeloproliferative disorders undergoing spontaneous leukemic transformation.

Translocation (3;21)(q26;q22) has been observed only rarely in de novo myelodysplasia (MDS) and de novo acute myeloid leukemia (AML), but, including the two new cases in the present study, the aberration has now been identified in at least 10 cases of t-MDS or t-AML. All these 10 patients had previously received alkylating agents, in nine patients combined with a drug targeting at DNA-topoisomerase II (doxorubicin in eight cases). Eight of the ten patients presented with t-MDS. A further 20 patients with various myeloproliferative disorders and an identical t(3;21) have been reported. In these cases, t(3;21) was not related to any specific type of previous therapy but was associated with transformation from chronic stage disease to overt AML.

Alkylating Agents↗
PubMed1994

Standardized multicentric quantimetry of differentiation antigens expression. The GEIL's approach in acute lymphoblastic leukemia. Groupe d'Etude Immunologique des Leucémies.

The use of flow cytometry as a common tool has opened the field of quantimetric immunophenotyping. This could help refine the definition of leukemic proliferations, and perhaps provide new prognostic criteria. We investigated whether this approach could be applied to multicentric immunophenotyping. The reproducibility of quantitative measurements on different types of flow cytometers was tested using a single batch of calibrating and "blind" fluorescent beads. Less than 7% CV was obtained between 20 different laboratories. We then explored the variations noted with control or normal lymphocytes, using various CD4 monoclonal antibodies, which were found to be lower than 10%. We finally applied this strategy to acute lymphoblastic leukemias (ALL), performing quantitative measurements of CD10 using one single aliquoted batch of FITC-CD10 in comparison with locally used reagents. PreB-ALL could indeed be further stratified depending on the density of CD10 expression. Use of the same monoclonal antibody is however recommended, since PreB-ALL also seem to display epitopic variations of the CD10 molecule.

CD4 Antigens↗
PubMed1994

Sleep fragmentation in normals: a model for sleepiness associated with upper airway resistance syndrome.

Eight young adults underwent 1 night of auditory sleep fragmentation followed by four naps of the multiple sleep latency test and performance testing the next day. A latin-square design was used to compare results with baseline. Efforts were made to eliminate effects of learning on repeated performance tests. A mean of 303 arousals, lasting a mean of 11 seconds, disrupted nocturnal sleep. This sleep fragmentation was induced to mimic as closely as possible the nocturnal sleep disruption seen in subjects with upper airway resistance syndrome. There was a significant disruption of nocturnal sleep architecture with a significant overall decrease in slow-wave sleep (SWS) and a significant but more moderate decrease in rapid eye movement (REM) sleep during the fragmented night. The most interesting finding related to analysis by thirds of the night, which indicated an important increase over time in arousal threshold during SWS followed by REM sleep. This threshold increase was associated with a parallel increase in dB(A) levels needed to induce an arousal. Stages 1 and 2 nonrapid eye movement (NREM) sleep were less affected by the stimulation, but the amount of stage 1 NREM sleep decreased from the beginning to the end of the night, again indicating an increase in pressure to sleep. Following 1 night of sleep fragmentation, subjects had significantly shorter sleep latencies on the multiple sleep latency test for naps 2, 3 and 4. There was a significant relationship between percent nocturnal SWS and mean sleep latencies. The selected performance tests were not affected by 1 night of sleep fragmentation, despite the obvious sleepiness.

Adult↗
PubMed1993

Rearrangements of the MLL gene in therapy-related acute myeloid leukemia in patients previously treated with agents targeting DNA-topoisomerase II.

Chromosome band 11q23 is frequently involved in acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) de novo, as well as in myelodysplastic syndromes (MDS) and lymphoma. Five percent to 15% of patients treated with chemotherapy for a primary neoplasm develop therapy-related AML (t-AML) that may show rearrangements, usually translocations involving band 11q23 or, less often, 21q22. These leukemias develop after a relatively short latent period and often follow the use of drugs that inhibit the activity of DNA-topoisomerase II (topo II). We previously identified a gene, MLL (myeloid-lymphoid leukemia or mixed-lineage leukemia), at 11q23 that is involved in the de novo leukemias. We have studied 17 patients with t-MDS/t-AML, 12 of whom had cytogenetically detectable 11q23 rearrangements. Ten of the 12 t-AML patients had received topo II inhibitors and 9 of these, all with balanced translocations of 11q23, had MLL rearrangements on Southern blot analysis. None of the patients who had not received topo II inhibitors showed an MLL rearrangement. Of the 5 patients lacking 11q23 rearrangements, some of whom had monoblastic features, none had an MLL rearrangement, although 4 had received topo II inhibitors. Our study indicates that the MLL gene rearrangements are similar both in AML that develops de novo and in t-AML. The association of exposure to topo II-reactive chemotherapy with 11q23 rearrangements involving the MLL gene in t-AML suggests that topo II may play a role in the aberrant recombination events that occur in this region both in AML de novo and in t-AML.

Adult↗
PubMed1993

Therapy-related myelodysplasia and acute myeloid leukemia. Cytogenetic characteristics of 115 consecutive cases and risk in seven cohorts of patients treated intensively for malignant diseases in the Copenhagen series.

Therapy-related acute myeloid leukemia (t-AML), often presenting as myelodysplasia (t-MDS), has become the most serious long-term complication of cancer therapy and offers a unique opportunity to study chemical leukemogenesis. Seven cohorts of patients treated for six different types of primary tumor have been followed closely for leukemic complications, and 115 consecutive patients with t-MDS or t-AML, including 45 cases from the cohorts, have been investigated cytogenetically at our institutions during the past 16 years. In patients primarily treated with alkylating agents, the risk of t-MDS and t-AML increased by approximately 1% per year from 2 to at least 8 years after start of treatment. In most cases, the disease presented as t-MDS with loss of a whole chromosome 5 or 7, or various parts of their long arms, and the leukemias were of FAB-subtypes M1, M2, or M4. In patients treated with drugs targeting at DNA-topoisomerase II, such as etoposide, doxorubicin, 4-epidoxorubicin, or mitoxantrone combined with drugs reacting directly with DNA, such as cisplatin or alkylating agents, the risk of leukemia increased much more steeply from only one year after start of therapy. These early onset cases often presented as overt leukemia of FAB-subtypes M4 or M5 with balanced translocations to chromosome bands 11q23 and 21q22, whereas later onset cases often shared characteristics with cases observed after therapy with alkylating agents alone. Both alkylation of DNA and poisoning of DNA-topoisomerase II may result in development of t-AML with different clinical and cytogenetic characteristics. There may be a synergistic leukemogenic effect between the two types of drug, and in patients with germ cell tumors treated with etoposide, cisplatin and bleomycin, reassessment suggested the risk of leukemia to increase exponentially with increasing doses of cisplatin and etoposide.

Adult↗
PubMed1993

Short-term liquid marrow cultures are supported by a mixture of haematopoietic cytokines but do not purge for acute myeloid or lymphoid leukemic marrow cells.

Short-term liquid marrow culture (STLMC) is a potential source for autografting in leukemia. In a preclinical setting, including candidates for autologous marrow transplantation, we have studied STLMC supported by a selected mixture of clinical available recombinant human haematopoietic growth factors. STLMC of leukemic marrow cells were prospectively performed to evaluate the purging effect. Bone marrow cells cultured and supported by the selected mixture of rhIL-3/rhGM-CSF/rhEpo revealed an increased number of day 10-12 cultured cells, parallelled by an increased proliferation rate when compared to unstimulated cultures. The median number of myeloid progenitors recognized as day 7 and day 14 granulocyte-macrophage colony-forming units (day 7/14 GM-CFU) was significantly increased in the supported STLMC to 145/305 from 105/115 per ml culture (n = 7, p < 0.01). Further addition of rhKL did not enhance the numbers of day 7 or day 14 GM-CFUs per ml culture. In no instance was the number of clonogenic cells at the end of culture greater than the input day 0, except in cultures of purified CD34-positive marrow progenitors which resulted in an expansion of late myeloid progenitors. Cytokine-supported cultures of leukemic marrow cells from acute myeloid (n = 14) and lymphoblastic (n = 7) leukemia patients were established at the time of diagnosis. In the supported cultures, the cell number increased for myeloblast but was unchanged for lymphoblast leukemic marrow cells compared to non-supported cultures. Immunophenotypic and cytogenetic studies of selected leukemic cell samples identified unchanged myeloid or slightly reduced frequencies of lymphoblastic leukemic cells at the end of culture. This preclinical study supports the idea that the addition of a mixture of clinical available haemopoietic cytokines to STLMC increases the recovery of detectable myeloid progenitors which may enhance myeloid regeneration after autografting. No substantial selective loss of myeloid leukemic cells was found in the cytokine-supported short-term culture system.

Bone Marrow↗
PubMed1993

Characteristics of pro-T ALL subgroups: comparison with late T-ALL. The Groupe d'Etude Immunologique des Leucémies.

A group of 30 acute lymphoblastic leukemias (ALL) with the early pro-T phenotype CD7+/cCD3+/CD1-/CD3-/CD4-/CD8-were identified among 103 newly diagnosed ALL with T-lineage markers (T-ALL). Pro T-ALL was more often observed in adults, and showed a lower incidence of hyperleukocytosis than more mature T-ALL. Mediastinal masses and polar acid phosphatase positivity in blast cells were however observed with the same frequency in pro T-ALL and late T-ALL, and rearrangements of both T-cell receptor (TCR) beta and gamma genes were observed in half the pro T-ALL cases tested. The expression of CD34, DR, and myeloid (My) markers was significantly more frequent in pro T-ALL than in late T-ALL, and these three features were strongly linked. TCR gene rearrangements were two to three times more frequent in CD34- and My-pro T-ALL. However, both CD34+ and My+ pro T-ALL showed an incidence of mediastinal masses and polar acid phosphatase positivity similar to this observed in CD34- and My- cases. This supports the assumption that both types of ALL indeed are engaged in the T-lineage, and confirms intracytoplasmic cCD3 as the earliest marker for this lineage. Moreover, CD34 appears to persist up to an early stage of T-cell maturation, where the cells retain myeloid potentiality. Loss of CD34 correlates with TCR-beta gene rearrangement and definitive commitment to the T lineage. Event-free survival analysis suggested a poorer outcome for pro T-ALL in adult patients.

Adolescent↗
PubMed1992

High-dose tamoxifen as an enhancer of etoposide cytotoxicity. Clinical effects and in vitro assessment in p-glycoprotein expressing cell lines.

Twenty-six patients with relapsed or drug-resistant cancer were treated with a combination of oral etoposide (300 mg day-1 for 3 days) and high-dose oral tamoxifen as a potential modulator of drug resistance (480 or 720 mg day-1 for 6 days beginning 3 days before etoposide). One patient with relapsed high-grade lymphoma and one with adenocarcinoma of unknown primary site has a partial response. Toxicity consisting of nausea, vomiting and subjective dizziness, unsteadiness of gait and malaise occurred during tamoxifen treatment. Serum levels of tamoxifen averaged 3-3.5 microM on day 4 of all courses of treatment at both 480 and 720 mg day-1. N-desmethyltamoxifen levels were lower than tamoxifen during the first course (2 microM) but increased to equal tamoxifen levels during the second course. Didesmethyltamoxifen levels remained below 1 microM. In vitro, both tamoxifen and the standard modulator of multidrug resistance, verapamil, produced minor enhancement of etoposide cytotoxicity in the MCF-7 wt cell line but produced no enhancement with any other cell line. High, intermittent doses of tamoxifen can be given with acceptable toxicity and produce serum levels that have been shown to modulate drug resistance in vitro. In vitro, however, such levels have no significant effect on etoposide cytotoxicity towards a range of wild-type and MDR cell lines.

ATP Binding Cassette Transporter, Subfamily B, Mem↗