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Biomedical subjects

C Aul

Publications and source records attributed to C Aul.

At least 109 records · Page 6Linked to original sources
PubMed1994

[Prophylaxis against mycoses in neutropenic patients].

During the last years, the proportion of cancer patients who develop systemic fungal infections has increased steadily. These infections are characterised by high mortality, especially in patients with persistent granulocytopenia and in those receiving allogeneic bone marrow transplants. The most important pathogens in neutropenic patients are Candida and Aspergillus spp. Usually, Candida infections arise from overgrowth in the gastrointestinal tract, while Aspergillus infections are acquired by inhalation of spores. Prophylaxis of systemic fungal infections seems mandatory since optimal strategies for diagnosis and treatment of these infections are lacking. Treatment with the non-absorbable polyenes nystatin and amphotericin B is useful for prophylaxis of superficial fungal infections, provided that compliance of the patients is optimal. The imidazoles ketoconazole and miconazole can reduce the incidence of superficial fungal infections, but there are conflicting data regarding their value for prevention of systemic mycoses. There are several studies indicating that prophylactic use of fluconazole reduces the incidence of mucosal and systemic fungal infections, especially in patients receiving allogeneic bone marrow transplants. Fluconazole shows reduced activity against several Non-albicans spp. and is not active against Aspergillus spp. Itraconazole has in vitro and in vivo activity against several Aspergillus spp. but high serum and tissue levels are necessary. However, bioavailability of itraconazole is reduced in patients with raised gastric pH and no i.v. formulation is available. Although there is some evidence for its prophylactic activity against Aspergillus infections in neutropenic patients, more studies are necessary to confirm these findings. Intravenous amphotericin B cannot be recommended for routine prophylactic use because of its toxicity.(ABSTRACT TRUNCATED AT 250 WORDS)

Amphotericin B↗
PubMed1994

Possible transmission of sarcoidosis via allogeneic bone marrow transplantation.

Allogeneic bone marrow transplantation (BMT) was performed in a 34-year-old man for non-Hodgkin's lymphoma. Two years before bone marrow harvest, pulmonary sarcoidosis was diagnosed in the donor. After steroid therapy, disease of the donor was in clinical remission with only minor radiological signs at the time of BMT. On day 90 after BMT, active sarcoidosis was diagnosed in the recipient. Besides radiologic signs and increased angiotensin converting enzyme levels, diagnosis was proved by characteristic histologic changes in lung and liver biopsies. Immunosuppressive therapy was changed from high dose cyclosporine to high dose methylprednisolone and symptoms promptly resolved within 10 weeks. This case indicates the possibility of transmission of sarcoidosis by marrow transplantation.

Adult↗
PubMed1994

Risk assessment in primary myelodysplastic syndromes: validation of the Düsseldorf score.

We have recently proposed a scoring system for risk assessment in primary myelodysplastic syndromes (MDS). In this score, one point is allocated to each of the following four parameters: bone marrow blasts > or = 5%, LDH > 200 U/l, hemoglobulin concentration < or = 9 g/dl, and platelet count < or = 100 x 10(9)/l. In a published series of 235 untreated patients with primary MDS, three prognostic groups (group A, score 0; group B, score 1 or 2; group C, score 3 or 4) were identified which differed significantly in both survival and rates of leukemic transformation. The present study was undertaken to reexamine the usefulness of our scoring system by applying it to an independent population of 263 newly diagnosed MDS patients. Morphological subtypes were RA in 53 (20%), RARS in 32 (12%), pure sideroblastic anemia (PSA) in 41 (16%), RAEB in 60 (23%), RAEB/T in 34 (13%), and CMML in 43 cases (16%). The predictive value of the Düsseldorf score could be assessed in 244 of 263 patients (initial LDH levels or platelet counts lacking in 19 cases). Forty-two patients were assigned to group A (low risk), 132 to group B (intermediate risk), and 70 to group C (high risk). Two-year cumulative survival was 86% in group A, 57% in group B and 14% in group C. Five-year cumulative survival was 53, 26 and 0%, respectively (p < 0.00005). Cumulative risk of AML 2 years after diagnosis was 3% in group A, 12% in group B, and 41% in group C (p < 0.05). Additional validation of the score was provided by extended follow-up of the initial patient population on which the scoring system was based. Survival curves in this patient population developed as predicted by the score. An important advantage of the Düsseldorf score is its ability to identify high-risk patients among the RA and RARS subgroups, even though by definition medullary blasts are less than 5%. The inclusion of LDH levels as a prognostic parameter also qualifies the Düsseldorf score for a correct assessment of CMML patients. In the new study population, LDH was confirmed as an important prognostic factor. After 2 years, actuarial survival for patients with LDH levels < or = 200 U/l was 61%, compared with 34% for patients with LDH > 200 U/l. Five-year cumulative survival was 32 and 14%, respectively (p < 0.00005).(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1993

All-trans retinoic acid in patients with myelodysplastic syndromes: results of a pilot study.

Considering the beneficial effect of all-trans retinoic acid (ATRA) in acute promyelocytic leukemia (APL), it has been speculated that ATRA might also be useful for treating other hematologic malignancies. To test this hypothesis, we performed a dose-escalating 3-month-trial of ATRA in 15 patients with primary or secondary myelodysplastic syndromes (MDS). Morphologic diagnoses were refractory anemia (RA) in 4, RA with ring sideroblasts (RARS) in 2, RA with excess blasts (RAEB) in 7, and RAEB in transformation (RAEB/T) in 2 cases. Patients included were required to have one or more of the following criteria: transfusion-dependent anemia, pronounced neutropenia (< or = 0.5 x 10(9)/L) or thrombocytopenia (< or = 20 x 10(9)/L), or increasing blast cells in the peripheral blood or bone marrow. Therapy was started at an ATRA dose of 30 mg/m2/d, administered orally as two doses of 15 mg/m2 every 12 hours. The retinoid dose was increased to 60 mg/m2/d after 4 weeks and to 90 mg/m2/d after 8 weeks. Among 14 patients assessable for response, none obtained a complete or partial remission. Three patients had a minor response, manifested by either reduction in transfusion requirements (2 patients) or increase in neutrophil and platelet counts (1 patient). During the study period, 5 patients progressed to more advanced stages of MDS or overt leukemia. Three patients with chromosomal abnormalities receiving ATRA for a period of 10 to 12 weeks retained their cytogenetic marker after completion of treatment. Side effects of ATRA primarily affected the skin and mucous membranes, with 13 of 15 patients having at least low-grade dermatologic toxicity. In 2 cases, treatment had to be prematurely stopped because of intolerable conjunctivitis or progressive neurologic symptoms. These data suggest that ATRA has little effect on MDS. The lack of response of MDS patients, as compared with those with APL, may be attributed to the absence of the t(15;17) translocation that seems to be a prerequisite for clinical efficacy of ATRA.

Adult↗
PubMed1993

High-dose versus intermediate dose cytosine arabinoside combined with mitoxantrone for the treatment of relapsed and refractory acute myeloid leukemia: results of an age adjusted randomized comparison.

193 patients with relapsed or refractory acute myeloid leukemia (AML) were entered into a prospective randomized comparison of high-dose versus intermediate dose cytosine arabinoside (AraC) both combined with mitoxantrone (mitox) according to the previously established sequential HD-AraC/mitox regimen (S-HAM). AraC was administered by 3 hr inf. q 12 hrs on days 1, 2, and 8, 9 at randomly assigned doses of either 3.0 versus 1.0 g/m2 in pts. < 60 years of age or 1.0 versus 0.5 g/m2 in older pts. Mitox was given to all cases at a dose of 10 mg/m2/d on days 3, 4, and 10, 11. Randomization was stratified for primary refractoriness against induction therapy and the length of first remission in relapsed cases (< 6 mths., 6-18 mths., > 18 mths.). From 151 presently evaluable cases 72 pts (48%) achieved a complete remission (CR), 38 cases (25%) were non-responders (NR) and 41 pts. (27%) died within the first 6 weeks after the start of treatment (early death = ED). No significant differences were found in CR rates being 52% and 44% for the 3.0 versus 1.0 g/m2 AraC regimens in pts. < 60 years and 48% and 45% after 1.0 versus 0.5 g/m2 AraC in older pts. No differences between the respective regimens emerged either for the time to CR (median 46 days) nor remission duration (median 4.5 mths). Analysis of treatment failures, however, demonstrated a significantly higher rate of NR after the lower dose regimens in both age groups of 41% and 32% versus 11% and 14% in pts. receiving AraC at higher doses (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

[Myelodysplastic syndromes. The epidemiological and etiological aspects].

From a total of 18,416 bone-marrow biopsy reports entered into the Düsseldorf Bone Marrow Registry between 1975 and 1990 those of patients diagnosed as having preleukaemia, myeloid dysplasia, panmyelopathy with hypercellular bone marrow, refractory anaemia, sideroblastic anaemia or smoldering leukaemia were reanalyzed together with patient-data. If the diagnosis of myelodysplastic syndrome (MDS) was confirmed, the original blood and bone-marrow smear was re-examined and classified, 584 cases in all (3.2%). During the same period acute myeloid leukaemia had been diagnosed in 506 patients (2.8%). The average annual incidence of MDS in the Düsseldorf area was 3.65 per 100,000 inhabitants. Over 80% of cases occurred from the age of 60 years, while 7% were younger than 50 years. The sex ratio was the same in all subgroups of MDS, except chronic myelomonocytic leukaemia (male:female ratio 1:1.57). 31 patients (5.3%) had received ionizing radiation and/or cytostatic or immunosuppressive treatment for various underlying diseases before MDS had been diagnosed (secondary MDS). Preceding occupational contact with organic solvents could not be excluded with certainty in 12 patients. These data suggest that MDS is a relatively frequent disease of hematopoiesis among the older age groups. The proportion of secondary (treatment-induced) forms is small and does not explain the recently observed increased incidence.

Age Factors↗
PubMed1992

Comparison of in vitro growth characteristics of blast cell progenitors (CFU-L) in patients with myelodysplastic syndromes and acute myeloid leukemia.

Current knowledge is inadequate to explain the different patterns of blast cell accumulation in myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). We compared the growth patterns of blast cell progenitors (CFU-L) in 23 patients with advanced MDS and 32 patients with de novo AML. Circulating blast progenitors were identified in 74% of MDS and 81% of AML samples. Primary plating efficiencies (PE1) were similar in both disorders, despite marked differences in peripheral blast cell concentrations. By cytological and cytochemical examination, colonies from MDS patients were indistinguishable from those obtained in AML. Cell cycle status was assessed by loss of colony formation following short-term exposure to cytosine arabinoside. CFU-L suicide rates (median, range) were 40% (12% to 77%) in MDS and 60.5% (27% to 98%) in AML. Actively proliferating blast cell progenitors are thus not confined to AML, but are also present in the majority of MDS patients. An important difference between MDS and AML was found when self-renewal capacity of CFU-L was examined by means of secondary plating efficiencies (PE2). Colonies could be successfully replated in 74% of AML cases. PE2 showed marked heterogeneity (2 to 730 colonies/10(5) mononuclear cells), with some values indicating excessive self-renewal capacity of CFU-L. In contrast, 62% of the MDS specimens failed to produce any secondary colony growth, and PE2 in the remaining cases was low (5 to 99/10(5) MNC). We conclude that a different balance between self-renewal and determination could be responsible for a slower pace of clonal expansion in MDS, even if the proliferative activity of clonogenic cells is similar to that in AML.

Acute Disease↗
PubMed1992

[Embolizing aortic valve endocarditis in the differential diagnosis of thrombotic thrombocytopenic purpura].

A 50-year-old man complained of lumbar pains, lack of energy, dysarthria and ataxic gait. Investigation revealed progressive anaemia (haemoglobin initially 10.5 g/dl, later 6.8 g/dl) and thrombocytopenia (initially 67,000/microliters, later 25,000/microliters). In addition he had unexplained pyrexia of up to 39.8 degrees C. Lactate dehydrogenase was 780 U/l and fragmented red cells were noted in the blood film. Because of suspicion of thrombotic thrombocytopenic purpura, treatment with fresh plasma by infusion was immediately initiated. On the third day of treatment he developed left ventricular failure; auscultation revealed a blowing early diastolic murmur over Erb's point together with a spindle-shaped early diastolic murmur over the right second intercostal space. Computed tomography of the skull showed recent haemorrhage into the left half of the cerebellum and an older right posterior infarct. The abdominal ultrasound scan suggested a haemorrhagic spleen infarct. In view of these findings the diagnosis was revised to embolizing aortic endocarditis with aortic reflux (confirmed by colour Doppler echo-cardiography). Aortic valve replacement was performed immediately, and the patient was treated with gentamycin 80 mg/d and teicoplanin 400 mg/d for four weeks. Postoperatively he was given 12 units of platelet concentrate and the platelet count remained stable thereafter (greater than 100,000/microliters). Splenectomy became necessary because the splenic haematoma increased in size during oral anticoagulant therapy. After a 6 week hospital stay the patient was discharged in good condition.

Anti-Bacterial Agents↗
PubMed1992

[A lethal course in pseudomembranous enterocolitis during the parenteral administration of vancomycin and imipenem].

A 48-year-old woman required mechanical ventilation after aortic valve replacement for decompensated aortic valve stenosis when bleeding complications developed and rethoracotomy had to be performed. Acute renal failure necessitated haemodialysis. Septic fever of unknown aetiology failed to respond to oxacillin, cefotaxim and tobramycin. The endotracheal cannula and central venous catheter were changed on the 24th postoperative day and the antibiotic treatment altered to 250 mg imipenem and 125 mg vancomycin three times daily intravenously. The fever soon subsided, but recurred on the 32nd postoperative day, accompanied by increasing leucocytosis. The patient was obstipated but had no intraabdominal signs. Four days later ultrasonography demonstrated thickening of the intestinal wall and coloscopy showed typical pseudomembranous colitis. Intestinal contents were positive for Clostridium difficile toxin. Despite immediate rectal and intragastric administration of 250 mg vancomycin four times daily the patient died of pseudomembranous colitis, confirmed at autopsy. The case demonstrates that vancomycin cannot always prevent the development of pseudomembranous colitis.

Colon↗
PubMed1992

Retinoic acid in the treatment of acute promyelocytic leukemia: inefficacy of the 13-cis isomer and induction of complete remission by the all-trans isomer complicated by thromboembolic events.

The clinical course of three patients with acute promyelocytic leukemia receiving all-trans retinoic acid (ATRA) as a single agent is reported. The first two patients were in first and second relapse of their leukemia that had occurred despite maintenance treatment with 13-cis retinoic acid after chemotherapy-induced complete remission (CR). A switch to ATRA was followed by achievement of a CR in two patients. The third patient received ATRA as first-line therapy. Two patients experienced thromboembolic complications during the phase of ATRA-induced leukocytosis. One of them died of pulmonary embolism on day 16 of treatment. The two responding patients who did not receive consolidation chemotherapy relapsed after 6 and 9 months, respectively. Increase of the ATRA dose failed to induce a new remission.

Adult↗
PubMed1992

The role of low-dose chemotherapy in myelodysplastic syndromes.

Aggressive chemotherapy of myelodysplastic syndromes is rarely feasible because these disorders predominantly occur in elderly patients who often have concurrent illnesses. Alternative treatment modalities must therefore be evaluated. This review summarizes the results that have been obtained with low-dose chemotherapy, especially with low-dose cytosine arabinoside (Ara-C). Overall response rates to treatment with low-dose Ara-C are about 40%, with some 20% of patients achieving a complete remission. Transition of MDS to AML does not reduce the probability of response. The therapeutic outcome cannot be reliably predicted by clinical or experimental parameters. Hematological toxicity is substantial, with approximately 10-25% treatment-related deaths. Duration of response is short and rarely exceeds one year. In terms of overall survival, low dose Ara-C does not appear to be superior to supportive care only. Other cytotoxic agents have not been studied in detail, but data available do not suggest an appreciable advantage over Ara-C. Before denying low-dose chemotherapy a helpful role in MDS, randomized studies should concentrate on those patients who can be expected to derive the greatest benefit. Because of their short survival, patients with RAEBt or those transformed to overt leukemia are such candidates.

Antineoplastic Agents↗