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Biomedical subjects

J Mattsson

Publications and source records attributed to J Mattsson.

At least 55 records · Page 3Linked to original sources

An exceptional group-I intron-like insertion in the SSU rDNA of lichen mycobionts.

An exceptional group-I intron-like insertion at position 940 of the nuclear small subunit rDNA is found in lichen mycobionts of the families Parmeliaceae and Lecanoraceae. This shared insertion site is exceptional as it follows a G. Although several features of the self-splicing Tetrahymena intron are missing, the conserved structure of the presumed core region indicates that the new intron-like insertion, which is missing in mature transcripts, is not part of a silenced ribosomal repeat. It is unlikely that the new insertion is horizontally transferred from the adjacent position 943. A phylogenetic analysis indicates congruence with lichen phylogeny and suggests that the insertion has been vertically inherited.

Base Sequence↗

Improved survival after bone marrow transplantation for early leukemia using busulfan-cyclophosphamide and individualized prophylaxis against graft-versus-host disease: a long-term follow-up.

To minimize immunosuppression, allow a graft-versus-leukemia (GVL) effect, and reduce relapse incidence, 73 leukemic recipients of human leukocyte antigens-identical sibling marrow were given graft-versus-host disease (GVHD) prophylaxis based on the estimated risk of GVHD development. Methotrexate (MTX) monotherapy was given to patients with an estimated low risk of developing GVHD, whereas MTX + cyclosporine (CsA) was given to 'high-risk' patients. After engraftment, CsA was discontinued, and weekly MTX was reinstituted and given until 3 months post-bone marrow transplant. Conditioning consisted of busulfan (BU) + cyclophosphamide (CY) (n = 35) or CY + total body irradiation (TBI) (n = 38). Retrospective controls were given CY + TBI and MTX + CsA (n = 39). The median observation time was 5 yr 11 months. Chronic GVHD increased to 53% in the individual BU + CY group and 46% in the individual CY + TBI group, compared to 25% in the control group (p = 0.05). This increase was restricted to the limited form. The actuarial relapse incidence decreased to 20% in the individual BU + CY group, compared to 52% in the control group, p = 0.03. In the individual CY + TBI group, the relapse incidence was 44% (n.s. versus controls, p = 0.04 versus individual BU + CY). The 5-yr relapse-free survival (RFS) in the individual BU + CY group was 66%, in the control group, 41% (p = 0.07), and in the individual CY + TBI group, 45% (p = 0.1 versus individual BU + CY). Patients with early leukemia in the individual BU + CY group had a RFS of 83%, compared to 44% in the control group (p = 0.02) and 42% in the individual CY + TBI group (p = 0.01). In the multivariate analysis, advanced leukemia beyond first complete remission and first chronic phase and conditioning with CY + TBI were correlated to poor RFS. In summary, the individualized prophylaxis itself did not reduce the relapse incidence. However, in patients with early leukemia conditioning with BU + CY, our method of individualizing the GVHD prophylaxis might be of value, since this group had the best RFS in this study.

Aged↗

Unrelated donor stem cell transplantation after autologous transplantation: experience of a single center.

Patients who do not respond to autologous stem cell transplantation (ASCT) have a poor prognosis. Concerns about toxicity limit the use of unrelated donor stem cell transplantation (UDSCT), but the knowledge about outcome after UDSCT post-ASCT is limited. We carried out a retrospective analysis of the outcome in seven consecutive patients with leukemia (n = 5), myeloma (n = 1) and graft failure (n = 1) who underwent UDSCT after ASCT. Donors were matched for HLA-A, -B and -DR (n = 6) or had one class I antigen mismatch (n = 1). Tissue typing was performed by a high-resolution genomic technique for class II. Median patient age was 34 (11-54) years and time from ASCT to UDSCT was 16 (3-22) months. Patients with malignant diseases were given TBI and a CY preparatory regimen. In addition, all patients received T cell antibodies prior to UDSCT. Grade I acute GVHD developed in all seven patients, but there was no sign of more severe acute GVHD. Two of four evaluable patients developed limited chronic GVHD. Three died of transplant-related toxicity, all due to pulmonary complications. Four patients are alive at 1.1, 1.5, 3.1 and 4.9 years post-UDSCT. A closely matched UDSCT could be considered for selected patients who are not cured by an ASCT.

Adult↗

A prospective randomized trial of Filgrastim (r-metHuG-CSF) given at different times after unrelated bone marrow transplantation.

A study was done to compare treatment with Filgrastim (r-metHuG-CSF) given at three different times after unrelated bone marrow transplantation (BMT). Sixty-nine patients grafted with HLA-A, -B and -DR-compatible unrelated bone marrow were randomized to Filgrastim (5 microg/kg/day) starting on day 0 (n = 23), day +5 (n = 23) or day +10 (n = 23) after BMT. No significant differences were detected in hematological recovery, days with fever, days on antibiotics, incidence of bacteremia or need for erythrocyte, platelet and granulocyte transfusions between the three groups. Patients given Filgrastim starting on day 0, day +5 or day +10, respectively, reached an absolute neutrophil count (ANC) >0.5 x 109/l on a median of 17, 16 and 16 days after BMT. Starting Filgrastim treatment on day +10, rather than on day 0, reduced the costs of Filgrastim by $1060, with no significant change in the median number of days-to-hospital discharge in the three Filgrastim-treated groups. The incidences of acute and chronic GVHD, transplantation-related mortality, relapse, leukemia-free survival and patient survival (PS) were similar in all groups.

Adolescent↗

Bilateral subdural haematomas following lumbar puncture in three haematopoietic stem cell transplant recipients.

Between 1990 and 1996, three patients (1.1%), all with CML, among 272 patients with haematological malignancies, developed bilateral subdural haematomas (SDH) after treatment with i.t. MTX before HSCT in our unit. Since October 1996, we have given i.t. MTX only to patients at increased risk of CNS leukaemia such as ALL and AML M4 or M5. We suggest that intrathecal treatment before HSCT should only be given to patients at increased risk of CNS leukaemia.

Adult↗

Isolated hepatic perfusion with extracorporeal oxygenation using hyperthermia, tumour necrosis factor alpha and melphalan.

AIMS: To determine the toxicity and efficacy of isolated hepatic perfusion with tumour necrosis factor alpha (TNF-alpha) and melphalan (Alkeran) under mild hyperthermic conditions. METHODS: A phase I trial was performed. Eleven patients with unresectable metastatic malignancies in the liver were pre-treated with 3 x 10(6) U leukocyte IFN daily 2 days before the perfusion. The liver was isolated and inflow catheters inserted in the hepatic artery and the portal vein. The hepatic veins were drained via a catheter in the retrohepatic caval vein. The venous blood flow from the lower extremities and the splanchnic circulation was bypassed to the axillar vein. The liver circuit was perfused with oxygenated blood and 30-200 microg TNF-alpha was added. At 39 degrees C in the liver circuit 0.5 mg/kg melphalan was added and the perfusion was continued for 1 h. RESULTS: Six patients underwent re-operation due to post-operative bleeding. Two patients died of coagulopathy or multiple organ failure within the first post-operative month. Three of six patients with liver metastases from malignant melanoma or leiomyosarcoma showed a partial response while no patients with liver metastases from colorectal cancer showed any response. The mean survival time was 20 months, which is within the same range as seen in previous isolated hepatic perfusion (IHP) studies. CONCLUSIONS: IHP with this drug regimen is a method with a considerable toxicity, though it is hard to distinguish between toxicity from TNF-alpha and that from the perfusion procedure itself. The method was not effective in patients with colorectal liver metastasis, but the results in melanoma and leiomyosarcoma patients warrant further studies.

Adult↗

Responses of plant vascular systems to auxin transport inhibition.

To assess the role of auxin flows in plant vascular patterning, the development of vascular systems under conditions of inhibited auxin transport was analyzed. In Arabidopsis, nearly identical responses evoked by three auxin transport inhibitor substances revealed an enormous plasticity of the vascular pattern and suggest an involvement of auxin flows in determining the sites of vascular differentiation and in promoting vascular tissue continuity. Organs formed under conditions of reduced auxin transport contained increased numbers of vascular strands and cells within those strands were improperly aligned. In leaves, vascular tissues became progressively confined towards the leaf margin as the concentration of auxin transport inhibitor was increased, suggesting that the leaf vascular system depends on inductive signals from the margin of the leaf. Staged application of auxin transport inhibitor demonstrated that primary, secondary and tertiary veins became unresponsive to further modulations of auxin transport at successive stages of early leaf development. Correlation of these stages to anatomical features in early leaf primordia indicated that the pattern of primary and secondary strands becomes fixed at the onset of lamina expansion. Similar alterations in the leaf vascular responses of alyssum, snapdragon and tobacco plants suggest common functions of auxin flows in vascular patterning in dicots, while two types of vascular pattern alterations in Arabidopsis auxin transport mutants suggest that at least two distinct primary defects can result in impaired auxin flow. We discuss these observations with regard to the relative contributions of auxin transport, auxin sensitivity and the cellular organisation of the developing organ on the vascular pattern.

Arabidopsis↗

Results of different strategies for reducing cytomegalovirus-associated mortality in allogeneic stem cell transplant recipients.

BACKGROUND: Several preventive strategies against cytomegalovirus (CMV) disease have been developed during the last decade. These have frequently been used in combination, and it has been difficult to identify each strategy's contribution. METHODS: Risk factors for CMV disease, death in CMV disease and transplant-related mortality were analyzed in 584 patients, who underwent a total of 594 allogeneic bone marrow transplants. RESULTS: The overall probability of CMV disease was 8.9%. No seronegative patient who had a seronegative marrow donor developed CMV disease. The corresponding probabilities for seronegative patients with seropositive donors, seropositive patients with seronegative donors, and seropositive patients with seropositive donors were 5.4%, 13.7%, and 11.7%, respectively. In multivariate Cox models, the use of preemptive antiviral therapy and being CMV-seronegative reduced the risk for CMV disease, CMV-associated death, and transplant-related mortality (TRM). Patients who received unrelated or mismatched family donor transplants had increased risks for CMV disease, CMV-associated death, and TRM. Older age was a significant risk factor for CMV disease and TRM. A total of 258 patients who were monitored by polymerase chain reaction for CMV DNA were analyzed separately to assess whether addition of another CMV preventive strategy could give benefit. Patients who received mismatched or unrelated donor transplants had increased risk for CMV disease, death in CMV disease, and TRM. High-dose acyclovir prophylaxis or addition of intravenous immune globulin had no influence. CONCLUSIONS: Preemptive therapy based on polymerase chain reaction for CMV DNA was associated with reduced risks for CMV disease, CMV-associated death, and TRM, whereas other prophylactic modalities did not give additional benefit.

Acyclovir↗

Low incidence of acute graft-versus-host disease, using unrelated HLA-A-, HLA-B-, and HLA-DR-compatible donors and conditioning, including anti-T-cell antibodies.

BACKGROUND: Using unrelated bone marrow, there is an increased risk of graft-versus-host disease (GVHD). METHODS: HLA-A-, HLA-B-, and HLA-DR-compatible unrelated bone marrow was given to 132 patients. The diagnoses included chronic myeloid leukemia (n=43), acute lymphoblastic leukemia (n=29), acute myeloid leukemia (n=27), myelodysplastic syndrome (n=4), lymphoma (n=3), myeloma (n=1), myelofibrosis (n=1), severe aplastic anemia (n=12), and metabolic disorders (n=12). The median age was 25 years (range 1-55 years). HLA class I was typed serologically, and class II was typed by polymerase chain reaction using sequence-specific primer pairs. Immunosuppression consisted of antithymocyte globulin or OKT3 for 5 days before transplantation and methotrexate combined with cyclosporine. RESULTS: Engraftment was seen in 127 of 132 patients (96%). Bacteremia occurred in 47%, cytomegalovirus (CMV) infection in 49%, and CMV disease in 8%. The cumulative incidences of acute GVHD > or = grade II and of chronic GVHD were 23% and 50%, respectively. The 5-year transplant-related mortality rate was 39%. The overall 5-year patient survival rate was 49%; in patients with metabolic disorders and severe aplastic anemia, it was 61% and 48%, respectively. The disease-free survival rate was 47% in patients with hematological malignancies in first remission or first chronic phase and 38% in patients with more advanced disease (P=0.04). Acute GVHD was associated with early engraftment of white blood count (P=0.02). Poor outcome in multivariate analysis was associated with acute myeloid leukemia (P=0.01) and CMV disease (P=0.04). CONCLUSION: Using HLA-A-, HLA-B-, and HLA-DR-compatible unrelated bone marrow and immunosuppression with antithymocyte globulin, methotrexate, and cyclosporine, the probability of GVHD was low and survival was favorable.

Adolescent↗

Dacarbazine-vindesine versus dacarbazine-vindesine-cisplatin in disseminated malignant melanoma. A randomised phase III trial.

In a multicentre phase III study of disseminated malignant melanoma performed in Sweden and Norway, 326 patients were randomised to receive treatment with the combination dacarbazine [DTIC] (D) and vindesine (V) with or without the addition of cisplatin (P). D was given intravenously (i.v.) at a dose of 250 mg/m2 days 1-5 every 4 weeks and V was given i.v. at a dose of 3.0 mg/m2 day 1 weekly. P was given i.v. at a dose of 100 mg/m2 day 1 every 4 weeks. There was no statistically significant difference in overall survival between the treatment arms (P = 0.22). Increased toxicity was observed in the treatment arm containing P of which leucopenia, alopecia and nausea/vomiting were the most pronounced. The median time to progression was significantly longer in patients treated with DVP (4.2 versus 2.2 months, P = 0.007). In conclusion, adding P to DV did not change overall survival but did significantly increase toxicity.

Adolescent↗

Transplantation with unrelated bone marrow in leukaemic patients above 40 years of age.

Twenty-seven patients above 40 years of age (range 40-55) with leukaemia underwent transplantation with haematopoietic stem cells from HLA-A, -B and -DR identical unrelated donors. They were compared to 69 younger patients, median age 23. In the older group, the diagnoses were acute myeloid leukaemia (AML) five, acute lymphoblastic leukaemia (ALL) three and chronic myeloid leukaemia (CML) 19. The corresponding figures in the younger patients were 21, 27 and 21, respectively. Conditioning consisted of cyclophosphamide (120 mg/kg) combined with 10 Gy total body irradiation. Immunosuppression was ATG or OKT3 for 5 days before transplantation and methotrexate combined with cyclosporin A. The probabilities of grades II-IV acute graft-versus-host disease (GVHD) were 23 and 21%, and the cumulative incidences of chronic GVHD were 64 and 50% in the older and younger patient cohorts, respectively. Overall, 3-year transplant-related mortality rates were 46% in patients > or =40 years of age and 32% in patients <40 years of age (P = 0.16). Three-year patient survival rates were 54 and 46% in the two groups, respectively. In patients with chronic phase CML, the corresponding figures were 67 and 68%, respectively. We conclude that patients above 40 years of age should be considered for transplantation with marrow from unrelated donors.

Adult↗

Risk factors for chronic graft-versus-host disease after bone marrow transplantation: a retrospective single centre analysis.

Among 551 consecutive recipients of allogeneic bone marrow transplants, 451 survived more than 3 months and were evaluated for chronic graft-versus-host disease (GVHD). Most of the donors were HLA-identical siblings or parents (n = 334). Patients with HLA-mismatched donors (n = 30) and matched unrelated donors (MUD) (n = 87) were also included in the study. In the analysis of all patients, the 5-year cumulative incidence of chronic GVHD was 45%. We analysed 34 risk factors. High recipient age was the single most important risk factor (P < 0.001). Other significant risk factors in multivariate analysis were: acute GVHD grades I-IV (P < 0.001), immune female donor to male recipient (P = 0.006) and chronic myelogenous leukaemia (CML), compared with all other diagnoses (P = 0.014). The cumulative 5-year incidence of chronic GVHD, with no significant risk factors present, was 9%, 29% with one risk factor, 53% with two, 68% with three and 75% with all four risk factors present. In patients with HLA-identical sibling donors and GVHD prophylaxis consisting of a combination of methotrexate (MTX) and cyclosporin A (CsA) (n = 208), increasing recipient age (P < 0.001) and CML (P = 0.007), were found to be significant risk factors for chronic GVHD. Finally, a multivariate analysis in recipients of bone marrow from unrelated donors (n = 89) showed recipient age alone (P = 0.006) to be significantly associated with chronic GVHD.

Adolescent↗

Engraftment and chimerism, particularly of T- and B-cells, in children undergoing allogeneic bone marrow transplantation.

The spectrum of pediatric bone marrow transplantation has changed in recent years. Mismatched and unrelated donor transplants are common, demanding an increased vigilance to detect incipient graft failure, secondary lymphoma as well as relapse and other problems, which now are potentially treatable. To diagnose these complications it may be important to know whether blood and marrow cells are of recipient or donor origin. To evaluate the role of mixed donor-recipient chimerism in relation to clinical problems we adapted a polymerase chain-reaction technique, using fluorescent primers analyzing DNA fragment length polymorphisms, to follow prospectively 17 bone marrow grafted children. To increase the precision of chimerism analysis, immunomagnetically isolated leukocyte populations were assayed in selected cases. Five patients encountered clinical problems related to chimerism. One infant with adenosine deaminase deficiency failed to engraft stem cells, yet succumbed to graft-versus-host disease, mediated by mature donor T-cells. Three children developed significant mixed chimerism. One of these three patients died in relapse of leukemia, while the two other patients who had received T-cell depleted grafts had persistent recipient T-cells, in spite of engraftment. After 5 months, these were displaced by donor T-cells in one of the patients. In the fifth patient, also after T-cell depleted BMT, a fatal donor cell lymphoma occurred. Twelve children had stable full chimerism or in one case a low grade mixed chimerism and remain disease-free throughout follow up (median 9 months). In conclusion, the analysis of chimerism, particularly of separated leukocyte populations, offers an almost indispensable insight and a basis for therapeutic decisions in complicated situations such as grafting involving unrelated or mismatched donors, graft manipulation, adoptive immunotherapy and in immunodeficiency patients.

B-Lymphocytes↗

Risk factors in bone marrow transplant recipients with leukaemia. Increased relapse risk in patients treated with ciprofloxacin for gut decontamination.

Three hundred and six patients with low- and intermediate-risk leukaemias undergoing allogeneic BMT between 1980 and March 1996 were studied regarding transplantation-related mortality (TRM), relapse, and leukaemia-free survival (LFS). Among the patients were 262 recipients of marrow from HLA-identical siblings and 44 patients receiving marrow from HLA-A, -B, and -DR identical unrelated donors. Between 1986 and 1993, 153 adult patients received ciprofloxacin continuously during Cy conditioning, but since November 1993 ciprofloxacin has not been given until after Cy treatment. TRM at 5 yr showed an incidence of 30%. Significant risk factors in Cox regression multivariate analysis comprised acute GVHD grades II-IV (p < 0.0001), seropositivity for 3-4 herpes viruses prior to BMT (p = 0.002), intermediate risk disease (p = 0.008), female donor to male recipient (p = 0.015), and a donor age over 17 yr (p = 0.025). The risk of relapse was studied from 90 d after BMT, and the overall 5-yr incidence was 32%. Significant risk factors comprised acute leukaemia, as compared to CML (p = 0.003), total body irradiation (TBI) compared to busulphan treatment (p = 0.011), gram-negative prophylaxis with ciprofloxacin during cyclophosphamide (Cy) conditioning (p = 0.024), GVHD prophylaxis using a combination of methotrexate (MTX) and cyclosporine (CSA), compared to monotherapy (p = 0.037) and absence of chronic GVHD (p = 0.050). The 5-yr probability of relapse in patients receiving ciprofloxacin prophylaxis during Cy conditioning was 40%, compared to 24% in patients not receiving this treatment (p = 0.01). Overall, LFS at 5 yr was 49%. LFS was evaluated from day 30 after BMT until relapse or death of the patient. We found no difference in TRM, relapse or LFS between recipients of HLA-identical sibling or unrelated bone marrow, risk factors significantly associated with an inferior LFS included acute GVHD grades II-IV (p = 0.0002), intermediate risk disease (p = 0.003), donor seropositivity for 3-4 herpes viruses (p = 0.046), and TBI conditioning (p = 0.048).

Adult↗

The Gothenburg breast screening trial: first results on mortality, incidence, and mode of detection for women ages 39-49 years at randomization.

BACKGROUND: The effect of mammography screening on breast carcinoma mortality in women ages < 50 years remains unclear. METHODS: A randomized trial of invitation to breast carcinoma screening with mammography was performed in the city of Gothenburg, Sweden. The purpose was to estimate the effect of mammographic screening on breast carcinoma mortality in women ages < 50 years. Randomization was initially by day-of-birth cluster (18% of subjects), and subsequently by individual (82% of subjects). Between September 1983 and April 1984, 11,724 women ages 39-49 years were randomized to the study group. This group was invited to mammographic screening every 18 months. Two-view mammography was used at each screen unless the density of the breast at the previous screen indicated that single view was adequate. Fourteen thousand two hundred and seventeen women in the same age range were randomized to a control group that was not invited to undergo screening until the fifth screen of the study group (between 6 and 7 years after randomization). Women with breast carcinoma diagnosed up to the time immediately after the first screen of the control group were followed for death from breast carcinoma until the end of December 1994. RESULTS: A 45% reduction in mortality from breast carcinoma was observed in the study group compared with the control group (relative risk [RR] = 0.55, P = 0.035, 95% confidence interval [CI], 0.31-0.96). A conservative estimate based on removal of the tumors detected at the first screen of the control group gave a mortality reduction of 44% (RR = 0.56, P = 0.046, 95% CI, 0.31-0.99). In both cases, the effect was statistically significant. CONCLUSIONS: Mammographic screening can reduce mortality from breast carcinoma in women ages < 50 years. The mortality reduction can be substantial if high quality mammography is used and an 18-month interscreening interval is strictly adhered to.

Adult↗

The Gothenburg Breast Cancer Screening Trial: preliminary results on breast cancer mortality for women aged 39-49.

We carried out a randomized trial of invitation to screening mammography in the city of Gothenburg, Sweden, to estimate the effect of screening on breast cancer mortality in women under age 50 years. A total of 11,724 women aged 39-49 were randomized to the study group, which was invited to mammographic screening every 18 months; 14,217 women in the same age range were randomized to a control group, which was not invited to screening until the fifth screen of the study group. Breast cancers diagnosed in both groups between randomization and immediately after the first screen of the control group were followed up for death from breast cancer to the end of December 1994. There was a significant 44% reduction in mortality from breast cancer in the study group compared to the control group (relative risk [RR] = 0.56, P = 0.042, 95% confidence interval [CI]: 0.32-0.98). A conservative estimate based on removal of the cancers detected at the first screen of the control group gave an RR = 0.59 (P = 0.069, 95% CI: 0.33-1.05). The true answer is likely to lie between the two estimates. These data suggest that mammographic screening can reduce breast cancer mortality in women under age 50, particularly if high-quality mammography is used and a short interscreening interval is adhered to.

Adult↗