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Biomedical subjects

D Douer

Publications and source records attributed to D Douer.

At least 19 recordsLinked to original sources

High frequency of acute promyelocytic leukemia among Latinos with acute myeloid leukemia.

A high frequency (24%) of acute promyelocytic leukemia (APL) was noted among acute myelocytic leukemia (AML) cases at the Los Angeles County-University of Southern California (LAC-USC) Medical Center, in comparison with the expected frequency of 5% to 15%. Because of the high proportion of Latinos in this center, we questioned if APL is more common in this ethnic group. The proportion of APL among the 80 AML patients of Latino origin was significantly higher (30; 37.5%) when compared with the 62 non-Latinos (4; 6.5%) (P = .00001). In an attempt to verify this finding on a larger group of patients, we analyzed 276 pathologically verified cases of AML in patients aged 30 to 69 years from the entire County of Los Angeles, registered on an ongoing population-based epidemiologic study of AML. APL was more frequent among the 47 Latinos (24.3%) than in the 229 non-Latinos (8.3%) (P = .0075). APL is seen in younger patients with AML, but Latino AML patients also had a higher frequency of APL after accounting for their younger age (age-adjusted odds ratio for APL among Latinos in LAC-USC Medical Center, 9.4 [95% confidence interval (CI) 2.9, 30] P = .0002; among Latinos in the population-based study, 3.0 [95% CI 1.3 to 6.9] P = .01). The different ethnic distribution of AML was found to be due to a higher proportion of APL cases per se, and not to a lower proportion of any other French-American-British subtype (P = .0004). These results, from two different populations of AML patients, indicate that Latinos with AML have a higher likelihood of the APL subtype of disease, which may suggest a genetic predisposition to APL and/or exposure to distinct environmental factor(s).

Adolescent

Increased incidence of central venous catheter-related infections in bone marrow transplant patients.

In view of an apparent increase of central venous catheter-related infections among our bone marrow transplant (BMT) patients, a retrospective study of infectious complications of central venous catheters was conducted. During 1992, 147 central venous catheters were placed in 133 patients. The overall infection rate of all catheters was 3.3 per thousand catheter-days (bacteremia 1.8, site infection 1.5). Patients scheduled for BMT had the highest infection rate of 11.5 (bacteremia 6.7, site infection 4.8). HIV patients had an infection rate of 6.6 per thousand catheter-days (bacteremia 3.8 and site infection 2.8) and patients with other diagnoses had a rate of 2.4 (bacteremia 1.3 and site infection 1.1). The difference of infection risk among the three groups is statistically significant (logrank p < .0001). In analyzing the 11 BMT patients more carefully, 14 catheters were placed. Of these, 9 catheters were removed, 8 (89%) of which were secondary to infection. Multivariate analysis showed that patients under 50 and BMT patients were more likely to develop catheter-related infection. While the cause of this complication is not known at present, the possible association with PBSC harvest is of much concern.

Adult

Comparative study of infectious complications of different types of chronic central venous access devices.

BACKGROUND: Various devices for central venous access are widely used in patients with cancer. The authors studied the incidence of infectious complications affecting these different devices. METHODS: A retrospective study of 111 central venous access devices (VAD) placed in 1992 was conducted. RESULTS: Subcutaneous ports were placed in 42 patients, single lumen Groshong catheters in 45, single lumen Hickman catheters in 15, double lumen Hickman catheters in 5, and double lumen Groshong catheters in 4. Prognostic factors analysis was performed with the log rank test and Cox's multivariate analysis. Different VAD types were compared with the likelihood ratio test. There was no significant difference in the risk of VAD-related infection between Hickman and Groshong catheters. Double lumen catheters were slightly more likely to cause infectious complications than single lumen catheters, although the difference was not statistically significant (P = 0.072 and 0.083 for bacteremia and site infection, respectively). No significant difference was observed in the risk of infection between subcutaneous ports and external catheters. Multivariate analysis using Cox's proportional hazards model demonstrated age younger than 50 years as the only significant risk factor, thus younger patients should be monitored more closely. CONCLUSIONS: No significant difference was observed in the risk of infection between subcutaneous ports and external catheters. There was a slightly higher risk of infection in double lumen catheters than single lumen catheters, although the difference did not reach statistical significance. Considering the small sample size, the results should be confirmed in larger prospective studies.

Adult

Myeloproliferation in long-term plasmacytoma-regressor mice.

MOPC-315 plasmacytoma-bearing BALB/c mice were treated with high doses of melphalan, causing a permanent and complete regression of the tumor. In the present study we analyzed plasmacytoma-regressor mice (PRM) 3-6 months after plasmacytoma regression. A second group of otherwise untreated normal mice was treated with melphalan (M--control group). A third group of mice remained untreated and served as an age- and sex-matched control group. PRM were cachectic and had an increased mortality rate compared to the M and the C control groups. Histopathological examination indicated that the spleen of PRM showed pronounced abnormalities, primarily in the red pulp. These abnormalities consisted of extramedullary hematopoiesis and myeloid-granulocytic hyperplasia. Spleens of M mice showed similar abnormalities but to a much lesser extent. Flow cytometric analysis of cellular surface markers of PRM splenocytes indicated a high number of large MAC-I- and GR-I-positive cells compared to splenocytes of M or C controls. These large cells also expressed Fc tau receptors (Fc tau RII), stained positively with non-specific esterase and adhered to plastic dishes; a certain percentage expressed MAC-2 and MAC-3 antigens. A quantitative suppression of CD4+ T cells and of B cells was also shown. Circulating levels of TNF were higher in PRM than in M or C mice. The capacity of splenocytes from PRM to secrete factors that stimulated CFU-GM colony formation in soft agar by bone-marrow cells from normal mice was significantly up-regulated compared to that of splenocytes from M or C mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Localization of amplified MYC gene sequences to double minute chromosomes in acute myelogenous leukemia.

Cytogenetic and molecular studies were performed on two dmin-bearing acute myelogenous leukemia (FAB-M2) samples. Both cases were characterized by complex karyotypes containing interstitial deletions of the long arm of chromosome 8 altering band 8q24.1, aberrations affecting the short arm of chromosome 17, and multiple double minute chromosomes (dmin). Using a 1.4 kb cDNA probe coding for the third exon of the MYC oncogene, DNA slot blots indicated MYC gene sequences were amplified in both samples. Fluorescence in situ hybridization using a 9.0 kb genomic probe for MYC was performed in one case and localized the amplified MYC gene sequences to the dmin. Neither patient achieved a complete remission using traditional induction chemotherapy. The complex karyology with amplification of MYC gene sequences appears to represent a poor prognostic subgroup of acute myelogenous leukemia.

Aged

Acute myeloid leukemia subtypes and response to treatment among ethnic minorities in a large US urban hospital.

From January 1, 1987, to August 30, 1991, 86 consecutive new cases of AML diagnosed at the LAC-USC Medical Center were analyzed. A significant difference in the FAB subtypes of AML was observed among different racial groups, with AML-M3 more common in Latinos (40%) and AML-M2 in Orientals (52%). Sixty-seven patients received induction chemotherapy with TAD (thioguanine-cytosine arabinoside-daunorubicin) or like regimens. Median follow-up time of all patients was 16 months. Forty-three patients (64%) achieved complete remission. The median overall survival of those who received induction was 10.5 months. The complete remission rates and overall survival were similar among patients of different ethnic backgrounds.

Acute Disease

Biphenotypic M0 acute myeloid leukemia with trisomy-4.

We report here a rare case of biphenotypic M0 acute myeloid leukemia (AML) associated with trisomy 4. The literature of trisomy 4 in acute leukemia was reviewed. M2 and M4 AML are the most common FAB subtypes associated with trisomy 4. The clinical course of this entity is generally comparable with other non-trisomy 4 cases of AML. Despite the speculation made when first described, no specific environmental toxin has been found to be associated with this entity. C-kit oncogene has been mapped to chromosome 4 recently, and the role of this proto-oncogene in leukemogenesis of trisomy 4 associated leukemia should be further investigated.

Acute Disease

Cardiac arrhythmia after infusion of cryopreserved stem cells.

A retrospective study of the cardiovascular side-effects of 17 patients during and after receiving unpurged cryopreserved autologous bone marrow and/or peripheral blood stem cells was performed. Fourteen (82%) patients developed cardiac arrhythmia, of which 11 (65%) developed sinus bradycardia, four (24%) second degree heart block and one patient had complete heart block. The onset of sinus bradycardia occurred at 15-513 (median 56) min and the onset of heart block ranged from 30 to 680 (median 234) min after starting the stem cell infusion. Hypertension was noted in seven patients (41%) and usually occurred within 2 hours of infusion. There was no mortality or symptoms associated with these findings. Since some of these arrhythmias could be quite severe as assessed electrophysiologically, continuous cardiac monitoring should be considered during and after the infusion of cryopreserved stem cells.

Adolescent

Aplastic anemia in neonatal lupus erythematosus.

OBJECTIVE: To describe an infant with neonatal lupus erythematosus associated with aplastic anemia. SETTING: The pediatric department in a tertiary-care hospital. INTERVENTIONS: Packed red blood cell transfusions and a 3-week course of high-dose steroid therapy. MEASUREMENTS/MAIN RESULTS: The patient presented with severe anemia and a circumscribed, reticular, macular rash on the face and neck at 5 months of age. Skin lesion biopsy revealed epidermic hyperkeratosis, hydropic degeneration of the basal layer, and deposition of immunoglobulins and granular C1q at the dermoepidermal junction. Ro/SS-A antibodies were present in the infant. BFU-E (erythroid progenitor burst-forming unit) colonies in bone marrow increased by about tenfold when suppressor CD8+ T lymphocytes were removed, indicating immune suppression of hematopoiesis. High-dose steroid therapy failed. The infant subsequently developed gram-negative sepsis, severe metabolic acidosis, and consumptive coagulopathy and died. CONCLUSIONS: Neonatal lupus erythematosus may present as part of a spectrum. The disease may range from mild and transient to a severe, life-threatening condition requiring immediate intervention, as in the case reported here. This is the first report of neonatal lupus associated with aplastic anemia due to immune-mediated suppression of hematopoiesis.

Anemia, Aplastic

[Tonsillar lymphoma].

3 patients with tonsillar lymphoma are described (a man of 68 and women of 62 and 57 years, respectively). The first had intermediate grade lymphoma localized in the tonsil and was treated by tonsillectomy and combined systemic chemotherapy. The second had low-grade lymphoma of the tonsil and widespread involvement of lymphoid tissue in the liver, spleen, mediastinum and retroperitoneum for which chemotherapy was given. The last had intermediate grade lymphoma, but had been misdiagnosed 4 years before as an undifferentiated carcinoma of the tonsil and was irradiated. After the malignant process had extended to the stomach, the correct diagnosis of diffuse large-cell lymphoma was made. Subtotal gastrectomy was followed by combined systemic chemotherapy. All patients responded well to treatment.

Aged

[Treatment of acute myeloid leukemia in a special hematology unit].

Since 1984, 47 patients with untreated acute myeloid leukemia (AML) were hospitalized in a special hematology unit for aggressive chemotherapy. Complete remission was obtained in 68%, 15% died of complications of treatment (infections and bleeding) and 15% had refractory leukemia. The actuarial survival after 3 years for patients in remission was 43%. No patients with refractory leukemia lived more than 1 year. The actuarial remission at 3 years of 21 patients who received additional courses of aggressive chemotherapy (consolidation treatment) was 42%, as opposed to 11% in 11 patients who received maintenance treatment. The 47 patients received 108 courses of aggressive chemotherapy including 47 for induction of remission. During 86 courses (80%) the patients developed fever and in 33 blood cultures were positive; during 16 courses a fungal infection developed. The most common bacterial infection was by E. coli. During the first induction treatment 5 patients died of sepsis and 1 of cerebral hemorrhage. None died during consolidation therapy. During the year preceding the opening of the unit, 12 AML patients were treated on regular medical wards, and five (42%) achieved a complete remission, while 6 died of complications during the first course of induction chemotherapy. Our findings are in line with those of similar units, which indicates the importance of special nursing units for the treatment of acute leukemia.

Adolescent

Tranexamic acid therapy in acute myeloid leukemia: possible reduction of platelet transfusions.

We studied the clinical efficacy and safety of the antifibrinolytic drug tranexamic acid (TA) in patients undergoing chemotherapy for acute leukemia. 54 newley diagnosed AML patients were treated with 1 g of TA every 6 hours until the platelet count rose to above 20 x 10(9)/l. Platelet transfusions were given, irrespective of the count, only when oral, mucosal or significant skin bleeding manifestations were observed. During induction, the average number of days with thrombocytopenia below 20 x 10(9)/l was 14.4 +/- 7.4 and 4.6 +/- 4.1 transfusions were given in each course. During consolidation, the average number of thrombocytopenic days was 8.4 +/- 8.5 and only 1.7 +/- 1.8 transfusions were administered. In 11.5% of the induction and 32.1% of the consolidation courses, no platelet support was required. TA was tolerated very well and no side effects or thromboembolic complications were observed. Only in 6 of the 78 induction courses did a major bleeding event occur and there were none in any of the 53 consolidation courses. Thus it seems that TA therapy allowed a significant reduction in the use of platelet transfusions without submitting the patients to greater bleeding risks.

Acute Disease

Effect in vivo of recombinant GM-CSF on neutropenia and survival in mice treated by high-dose melphalan.

High doses of melphalan cause severe neutropenia and may irreversibly damage hematopoietic stem cells. Treatment of mice with recombinant murine GM-CSF (GM-CSF) for 5 days immediately after 400 micrograms of melphalan did not prevent the severe neutropenia. However, GM-CSF accelerated the neutrophil recovery and reduced the mortality rate during the neutropenic period compared to melphalan-only treated mice. CFU-GM levels measured 6 d after melphalan treatment without GM-CSF were markedly reduced in the bone marrow while being elevated in the spleen. In comparison, GM-CSF further reduced the total CFU-GM population in melphalan-treated mice including the levels in the bone marrow and in the spleen. On d 14 after melphalan, the spleen regained its active CFU-GM production. By d 90, the number of circulating neutrophils, the number of bone marrow CFU-GM and splenic CFU-GM were the same in GM-CSF-treated and -untreated mice. The results suggest that GM-CSF could be used to shorten the neutropenic period and reduce mortality caused by a high dose of melphalan. Though this effect could be at the expense of a temporary reduction in CFU-GM population, GM-CSF did not induce more long-term damage to myelopoiesis than that already caused by melphalan alone.

Agranulocytosis