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Biomedical subjects

A Ost

Publications and source records attributed to A Ost.

At least 55 records · Page 3Linked to original sources
PubMed1992

DNA aneuploidy in ulcerative colitis: reproducibility, topographic distribution, and relation to dysplasia.

Fifty-nine patients with longstanding, total ulcerative colitis were followed up in a prospective colonoscopic surveillance program. Biopsy specimens were sampled from predetermined locations of the colon and rectum at regular intervals. All specimens were assessed for histological dysplasia and, by flow cytometry, for detection of DNA aneuploidy during 8 years of follow-up. Special emphasis was made to correlate the findings of DNA aneuploidy with findings of dysplasia at colonoscopy or, in case proctocolectomy was performed, in the surgical specimen. Fifteen patients (25.4%) had DNA aneuploidy detected at least once during the follow-up. Eight of 10 patients with repeated findings had consistent ploidy level of the aneuploid peaks from one examination to another. Ten patients had multiple peaks. DNA aneuploidy tended to become more widespread in the bowel during the follow-up but persisted in the same part(s) of the colon and rectum. DNA aneuploidy occurred before development of definite dysplasia in 6 patients, simultaneously with development of dysplasia in 6 patients, and after the development of dysplasia in 1 patient only. In 2 patients, single aneuploid peaks were detected once but could not be found again at subsequent examinations. Dysplasia correlated closely topographically to DNA aneuploidy, but the latter finding was more common without concomitant dysplasia. Only in 1 patient, and at one examination, definite dysplasia was recorded without findings of DNA aneuploidy. Detection of DNA aneuploidy in patients with ulcerative colitis is persistent and reproducible and closely correlated to dysplasia. Widespread changes indicate that the entire colorectal mucosa is at increased risk of malignant transformation. Changes in nuclear DNA content appear to be an earlier phenomenon than dysplasia in the malignant transformation of the colorectal mucosa in ulcerative colitis, and the use of flow cytometry in surveillance programs may be of value for selection of patients at high risk of developing colorectal carcinoma.

Aneuploidy↗
PubMed1992

KBM-3, an in vitro model of human acute myelomonocytic leukemia.

A human acute myelomonocytic leukemia cell line, KBM-3, was developed to study the pathophysiology of human acute myeloid leukemia. This cell line was characterized by morphology, immunophenotype, Giemsa-banding pattern, in vitro proliferation capacity, and tumorigenicity in nude mice. The KBM-3 cell line was established in the presence of exogenous lymphokines (human placenta-conditioned medium, HPCM), but medium for later passages did not contain HPCM. We found high cellular expression of the mRNA message for granulocyte-macrophage colony-stimulating factor (GM-CSF), which we suggest may be important for the immortalization of the cell line. KBM-3 cells have an immature myelomonocytic phenotype. Cytogenetic analysis revealed a pseudodiploid karyotype with five characteristic marker chromosomes and ranging in total number from 45 to 49. In suspension cultures, the cells had a doubling time of 23 h and a cloning efficiency of about 30% in soft agar independent of exogenous lymphokines. Two-thirds of nude mice injected with 1 x 10(4) KBM-3 cells and all animals injected with 1 x 10(5) cells developed S.C. granulocytic sarcomas within 6-8 weeks. These tumors were locally invasive but did not give rise to distant metastases. When transplanted to a new set of nude mice, all tumors formed secondary sarcomas at the site of implant. We conclude that the KBM-3 cell line may have value for studying the molecular events that underlie the neoplastic transformation in human myeloid leukemia.

Adult↗
PubMed1991

Mucosal dysplasia and DNA content in ulcerative colitis patients with ileorectal anastomosis. Follow-up study in a defined patient group.

In a follow-up study of an epidemiologically defined patient group comprising 1,274 patients with ulcerative colitis diagnosed in Stockholm County during 1955-1979, 55 patients had undergone colectomy with ileorectal anastomosis (IRA). Nine of these were found to have Crohn's disease after histopathologic review of the colectomy specimens. Of the 46 patients with ulcerative colitis remaining for evaluation, two died postoperatively. Twenty-five patients were subsequently reoperated with rectal excision owing to intractable inflammatory activity (n = 22, one postoperative death) or owing to dysplasia (n = 3). Of 19 patients with their IRA still intact at time of follow-up, 15 patients (median disease duration 23 years) had a flexible sigmoidoscopy with multiple biopsies performed. The average length of the remaining rectum and sigmoid colon was 26 cm. No patient had findings of dysplasia, carcinoma, or DNA aneuploidy. None of the four remaining patients had developed dysplasia or carcinoma at the time of the latest regular rigid sigmoidoscopy. The risk of malignant transformation in this selected group of patients with ulcerative colitis operated upon with colectomy and IRA derived from an epidemiologically defined population seems to be low.

Anastomosis, Surgical↗
PubMed1991

Expression of CD15 as predictor of relapse in children with acute lymphoblastic leukemia of the pre-B type.

Pre-B acute lymphoblastic leukemia (ALL) was diagnosed in 37 children morphologically, histochemically, and by immunophenotyping by flow cytometry. In all patients the leukemic blasts expressed HLA-DR and CD19 (Leu-12). In 10 patients 20% or more of the blast cells expressed a myeloid antigen: CD15 (Leu-M1) in seven, CD33 (My9) in two and CD13 (My7) in one patient. All 37 children achieved complete remission, but eight relapsed. Relapse occurred in six of seven patients with CD15-positive blasts, but in only two of 27 patients with CD15-negative blasts (p = 0.0003). Thus, the occurrence of CD15 on the blasts of children with pre-B ALL shows a remarkable association with a high risk of relapse, and these patients should therefore be considered to belong to the high-risk group regardless of other prognostic factors.

Adolescent↗
PubMed1991

Treatment of myelodysplastic syndromes with recombinant human erythropoietin.

12 patients with myelodysplastic syndromes were treated with recombinant human erythropoietin (r-epo). 5 patients had stable anemia, 78-92 g/l, and 7 were transfusion-dependent. In 11 patients, r-epo was given intravenously three times a week, with dose escalation after 4 and 8 wk if hemoglobin did not increase more than 15 g/l. The doses were 600, 1500 and 3000 U/kg bodyweight/wk. The 12th patient was treated subcutaneously with a dose of 560 U/kg/wk. 3 patients showed a significant response with an increase in hemoglobin of greater than or equal to 15 g/l. 2 of these had stable anemia before treatment and increased in hemoglobin from 87 to 116 g/l and from 80 to 99 g/l, respectively. The 3rd patient was transfusion-dependent and rose to a stable hemoglobin level between 76 and 80 g/l without transfusions. 2 patients showed a reduction of their transfusion need. Mean initial serum erythropoietin in the responding group was 366 U/l compared to 1049 among the non-responders (p = 0.367). Response was observed in 5/7 patients without bone marrow sideroblasts and in 0/5 patients with sideroblasts (p = 0.027). Erythropoietin seems to be an effective and well-tolerated treatment for a certain proportion of patients with MDS. A larger patient material might provide a model for predicting responses.

Adult↗
PubMed1991

Incidence in Sweden and clinical features of familial hemophagocytic lymphohistiocytosis.

We retrospectively studied the incidence of familial hemophagocytic lymphohistiocytosis (FHL) in children during the 16-year period 1971-86. First, all departments of pediatrics, pathology, and infectious diseases were enquired for children with FHL or disorders resembling FHL. Secondly, the causes of death of all children who died during the study period in Sweden (n = 19,542) were also investigated. Files and histological specimens were further studied in selected children. By using a set of inclusion/exclusion criteria, we found 32 children with FHL. The incidence was 1.2/1,000,000 children per year. One child per 50,000 live borns developed FHL during this period. The sex ratio was close to 1:1. Prominent early clinical signs were fever (91%), splenomegaly (84%), hepatomegaly (90%), rash (43%), and lymph node enlargement (42%). Neurological symptoms, which developed in 47%, could totally dominate the clinical picture and develop prior to other symptoms and signs. Common laboratory findings were pancytopenia, hypertriglyceridemia, hypofibrinogenemia, elevated serum transaminases, hyperbilirubinemia, hyponatremia, hypoalbuminemia, and a moderate spinal fluid pleocytosis. Chest X-ray often revealed mostly discrete pulmonary infiltrates. FHL is an underdiagnosed disease and in only 11/32 children was diagnosis made during their lifetime. It is important to be aware of the disorder as potential therapy now exists.

Adolescent↗
PubMed1991

Carcinoma and DNA aneuploidy in Crohn's colitis--a histological and flow cytometric study.

Twenty four patients with longstanding colonic Crohn's disease were examined prospectively with colonoscopy and multiple biopsy sampling in order to detect histological dysplasia or abnormal aneuploid DNA content, or both. Biopsy specimens were taken from 10 predetermined locations in the colon and rectum. No patient had definite dysplasia but three displayed DNA aneuploidy (12.5%), and one of these subsequently developed a carcinoma (Dukes' C at operation) in the ascending colon. No concomitant dysplasia was detected but the carcinoma as well as other parts of the mucosa were DNA aneuploid. It is concluded that dysplasia is rare in patients with Crohn's colitis, but findings of DNA aneuploidy warrant vigilance in follow up as this may indicate impending carcinoma. Further prospective studies are needed before the predictive value of DNA aneuploidy can be determined and before general recommendations of colonoscopic surveillance, as in longstanding ulcerative colitis, can be made.

Adult↗
PubMed1990

Long-term results of ileorectal anastomosis in ulcerative colitis in Stockholm County.

The long-term results of ileorectal anastomosis in patients with ulcerative colitis in Stockholm County over a 30-year period, 1955 to 1984, were investigated. During this time, 486 patients underwent colectomy and ileorectal anastomosis was performed in 60 of those patients (12 percent). A retrospective histologic examination of the slides of the operative specimens in the latter group revealed that nine patients had Crohn's disease. Of the 51 remaining patients with ulcerative colitis, the colectomy and ileorectal anastomosis was performed as an elective procedure in 44 cases (86 percent) and as a one-stage procedure in 48 patients (94 percent). Complications occurred in 7 of 43 patients (16 percent) undergoing an elective, one-stage procedure. There were two postoperative deaths (4 percent). There were 22 patients (43 percent) who had their ileorectal anastomosis in function at the time of follow-up, with a mean time of observation of 13 years. The cumulative probability of having the ileorectal anastomosis in function at 10 years was 51 percent. The causes of total excision were recurrent inflammation in the retained rectum (N = 23), dysplasia (N = 3), and postoperative complications (N = 3). No rectal carcinoma occurred. Patients with preoperative mild rectal disease had a better outcome (ileorectal anastomosis in function at time of follow-up) compared with patients with moderate rectal disease (P less than 0.001). The functional outcome of ileorectal anastomosis was, if anything, better than what is stated in the literature following pelvic pouch procedure.

Adolescent↗
PubMed1990

Colonoscopic surveillance in long-standing total ulcerative colitis--a 15-year follow-up study.

In a 15-year surveillance program composed of 72 patients with total ulcerative colitis, 12 patients developed definite dysplasia. At endoscopy, low-grade dysplasia was detected in seven patients, high-grade in four, and a carcinoma (Dukes' stage A at operation) in one. One of the patients with high-grade dysplasia and macroscopical lesions at colonoscopy had a carcinoma (Dukes' A) detected at operation. A sequential development of dysplasia was found in seven patients. The cumulative risk of developing at least low-grade dysplasia was 14% after 25 years of disease duration. Using flow cytometric analyses, abnormal, aneuploid DNA content was detected in biopsies of 12 of 59 patients (20.3%); this correlated significantly with low-grade and high-grade dysplasia. Aneuploidy preceded dysplasia in two patients and was also detected in two dysplasia-free patients. The long-term use of colonoscopic surveillance in ulcerative colitis is a reliable way to select patients, in whom dysplasia is developing, for prophylactic surgery. Additionally, flow cytometric DNA analyses may help in the selection. The risk of missing a carcinoma until it becomes incurable appears to be low.

Adolescent↗
PubMed1990

Acetazolamide-associated aplastic anaemia.

Eleven cases of acetazolamide-associated aplastic anaemia were reported in Sweden during a 17-year period. There were six women and five men with a median age of 71 years (range 63-85 years). The median dose of acetazolamide was 500 mg, and the median duration of treatment was 3 months (range 2-71 months). Ten of the eleven patients died, all within 8 weeks after detection of their aplastic anaemia. The relative risk of developing aplastic anaemia when taking acetazolamide was 13.3 (95% confidence limits (CL); 6.8-25.3). The estimated incidence of reported acetazolamide-associated aplastic anaemia is approximately one in 18,000 patient years. The results strongly indicate that acetazolamide treatment is associated with a substantial increase in the risk of developing aplastic anaemia.

Acetazolamide↗
PubMed1990

Reversal of myelofibrosis by hydroxyurea.

Bone marrow morphology in 39 symptomatic patients with myeloproliferative disorders (polycythaemia vera 15, essential thrombocythaemia 14, idiopathic myelofibrosis 9, myeloproliferative syndrome 1) and elevated platelet counts was studied before and after a median of 18 months of continuous treatment with hydroxyurea. We found a significant reduction of bone marrow fibrosis, believed to be mediated by suppression of thrombopoiesis by hydroxyurea.

Bone Marrow↗
PubMed1990

Diagnoses in patients with severe pancytopenia suspected of having aplastic anemia.

There were 100 patients with pancytopenia notified to the Swedish part of an international study of aplastic anemia (Aa) (1983-1986). Aa was the cause in 16 patients and 50 patients had different conditions explaining their pancytopenia, whereas in 34 patients no obvious explanation was found at the time of discovery of their pancytopenia. A follow-up study in 1987 comprised the patients with Aa (n = 16) and the patients with uncharacterized pancytopenia (n = 34.3 additional patients had then been diagnosed as having Aa whereas 3 patients had a diagnosis of a low-grade NHL and 8 patients a diagnosis of MDS. No (or an inadequate) bone marrow sample had been taken in 9 of the 34 patients. This study shows that pancytopenia may be found in many serious conditions. Patients with pancytopenia should be carefully followed as Aa can develop slowly and as the MDS diagnosis can be difficult to establish at an early stage.

Anemia, Aplastic↗