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Biomedical subjects

D Wolff

Publications and source records attributed to D Wolff.

At least 19 recordsLinked to original sources
PubMed2006

Replacement of calcineurin inhibitors with daclizumab in patients with transplantation-associated microangiopathy or renal insufficiency associated with graft-versus-host disease.

Transplantation-associated microangiopathy (TAM) or renal insufficiency (RI) after allogeneic hematopoietic stem cell transplantation is associated with a high mortality. As calcineurin inhibitors (CI) may contribute to TAM or RI, we evaluated the efficacy of replacing CI by daclizumab in patients with graft-versus-host disease (GVHD). Thirteen patients with GVHD-associated TAM and five patients with RI were treated with daclizumab 1 mg/kg intravenous (i.v.)/week, discontinuation of the CI and continuation of the remaining GVHD treatment. All patients had acute GVHD (steroid-sensitive (n=4), steroid-refractory (n=10)) or chronic GVHD (n=4) and were treated with CI before the start of daclizumab. Nine of 13 patients with TAM treated with daclizumab and discontinuation of CI achieved complete remission of TAM, two had stable disease, and one patient did not respond. Patients receiving daclizumab for RI without TAM showed stabilization (2/5) or improvement (3/5) of renal function. Four of 14 patients with acute GVHD achieved CR, two partial remission, eight patients did not respond and 11/14 died at a median of 39 days after start of the daclizumab. Our data demonstrate that replacement of CI by daclizumab can improve TAM and RI. However, mortality remains high in patients with acute GVHD.

Acute Disease↗
PubMed2006

Redefining the risks of prenatally ascertained supernumerary marker chromosomes: a collaborative study.

BACKGROUND: A marker chromosome is defined as a structurally abnormal chromosome that cannot be identified by routine cytogenetics. The risk for phenotypic abnormalities associated with a marker chromosome depends on several factors, including inheritance, mode of ascertainment, chromosomal origin, and the morphology, content, and structure of the marker. METHODS: to understand the karyotype-phenotype relationship of prenatally ascertained supernumerary de novo marker chromosomes, we combined data from prenatal cases obtained from 12 laboratories with those from studies in the literature. We were able to obtain cytogenetic and phenotypic data from 108 prenatally ascertained supernumerary de novo marker chromosomes to refine the phenotypic risk associated with these markers. Because of the growing number of cases and because more techniques are available to delineate marker morphology, we have been able to group risk estimates into subcategories, such as by marker type and whether there are ultrasound abnormalities. RESULTS: If a de novo supernumerary marker chromosome is found prenatally, our data suggest there is a 26% risk for phenotypic abnormality when there is no other information defining the marker (such as chromosomal origin or information about the existing phenotype). However, if high resolution ultrasound studies are normal, this risk reduces to 18%. CONCLUSIONS: Our findings strongly support the value of additional genetic studies for more precisely defining the risk in individual cases involving marker chromosomes.

Chromosome Aberrations↗
PubMed2005

[Allogeneic blood stem cell transplantation in high-risk patients after conditioning with treosulfan and fludarabine].

BACKGROUND AND OBJECTIVE: Allogeneic transplantation can not be offered to many patients due to potential side-effects of conventional conditioning. Dose-reduced conditioning approaches improve tolerability, however, treatment efficacy may be reduced as well. We have, therefore, developed a dose intense but toxicity reduced conditioning regimen based on treosulfan and fludarabine and report first results. PATIENTS AND METHODS: 65 patients with a median age of 50 years were transplanted from related (n = 21) or unrelated donors (n = 44) after conditioning with treosulfan (3 x 10, 3 x 12 or 3 x 14 g/m(2) i. v.) and fludarabine (5 x 30 mg/m(2) i. v.). 21 patients were in complete remission (CR) and 44 patients had not reached a CR at the time of transplantation. 59 of 65 patients were considered unfit for a conventional conditioning regimen. RESULTS: The actuarial overall survival after 3 years is 59.2 %, the event-free survival 40.1 %. Patients with a related donor or transplantation in CR had a better overall (85.4 resp. 74.2 %) and event-free survival (52.2 % resp. 61.9 %). The cumulative incidence of relapse at 3 years was 26.2 %. Non-relapse mortality at day 100 is 17.4 % (cumulative incidence). In stepwise Cox regression analyses for overall survival, event-free survival and non-relapse mortality the covariables transplantation in CR vs. not in CR and the donor status were shown to be influential. CONCLUSIONS: These results with a conditioning therapy of treosulfan and fludarabine indicate that patients despite higher age, concomitant disease or after intensive pretreatment can be successfully transplanted without increased treatment-related mortality.

Adult↗
PubMed2005

Treatment of steroid-resistant acute graft-versus-host disease with daclizumab and etanercept.

Steroid-resistant acute GVHD (aGVHD) following allogeneic hematopoietic stem cell transplantation (alloHSCT) continues to be associated with a high mortality. We report the results of a phase II study of treatment of steroid-resistant aGVHD with the IL-2 receptor antibody daclizumab combined with the TNF-receptor fusion protein etanercept. Treatment consisted of daclizumab 1 mg/kg given i.v. on days 1, 4, 8, 15, 22 and etanercept 16 mg/m(2) s.c. on days 1, 5, 9, 13, 17. A total of 21 patients (age 15-61 years) with steroid-resistant aGVHD after alloHSCT were included in the study. Donor types were HLA-matched related (n=6), HLA-matched unrelated (n=14), and HLA-mismatched unrelated (n=1). Eight patients achieved complete, and six showed partial remission of aGVHD. Seven patients did not respond. Four of 21 patients are currently alive with a median follow-up of 586 (185-1155) days. Three patients died due to relapsed malignancy. Treatment-related mortality was due to infectious complications (n=11) or organ failure due to aGVHD (n=3). In total, 12 patients developed subsequent chronic GVHD. In conclusion, the data demonstrate an acceptable response rate of the combination of daclizumab and etanercept in the treatment of steroid-resistant aGVHD. Nevertheless, long-term mortality due to infectious complications and chronic GVHD remains high.

Acute Disease↗
PubMed2005

[The MacIntosh extra-articular knee stabilisation procedure -- an alternative after failed ACL reconstruction?].

Chronic knee instability after loss of the ACL and failed ACL reconstruction is a great problem for the patient and a complex treatment challenge. Minimizing the feeling of instability is the most important issue for the patient. In case of lack of autologous material for reconstruction and lesions of the knee joint because of performed intra-articular procedures, extra-articular techniques are an alternative. In the modified MacIntosh procedure, we tie a strip of iliotibial tractus around the LCL and attach it to the ventrolateral tibial head by screw. Postoperatively, we begin physiotherapy under full weight bearing. Range of motion is limited to 0/0/90 degrees for six weeks. Between 1996 and 2000, nine patients who underwent surgery using the modified Macintosh technique, were evaluated prospectively. The mean follow-up was 11.4 months (6-36 months). We evaluated changes concerning pivot-shift and Lachman-test and documented Lysholm- and Tegner-activity-score pre- and postoperatively. We also registered sporting ability. The pivot shift remained positive, while the anterior drawer, documented by Lachman-test, could be reduced surgically. Lysholm- and Tegner-scores improved significantly. Preoperatively, the mean Tegner-score was 1.44 (0-3), mean Lysholm-score 55.55 points (14-88), respectively. At follow-up examination, scores had improved to 3.55 (3-4) and 82.44 points (69-95), respectively, resulting in a p-value of .007 for the Tegner-, and p = 0.008 for the Lysholm-score. Our surgical treatment could reduce the subjective feeling of instability in all cases. All patients could participate in sports activities at time of follow-up. Our results show, that extra-articular surgical procedures are adequate alternative methods of treatment in cases of persistent knee instability after recurrent failure of ACL reconstruction. The modified MacIntosh procedure described in this study shows encouraging results at medium-term follow-up. The technique is easy to perform and less traumatising for the knee joint.

Adolescent↗
PubMed2005

Multivariate analyses of prognostic factors in acute myeloid leukemia: relevance of cytogenetic abnormalities and CD34 expression.

Identification of additional prognostic factors besides karyotype is important for the improvement of the risk adapted treatment strategies in acute myeloid leukemia (AML). The aim of this study was to investigate whether other factors besides karyotype could be used as a prognostic tool in newly diagnosed AML. Biological and disease related established and potential prognostic factors were retrospectively analysed in 124 consecutive AML patients treated between 1993 and 2002 at the University hospital Rostock (Germany). One hundred patients received a potential curative intensive chemotherapy (81%), of whom 28 received an allogeneic HSCT at some point of their treatment course, 17 patients (14%) received palliative therapies and 7 patients (5%) received supportive care only. In patients that received potential curative therapies LDH >or=2000 U/l, WBC >50 GPT/l, CD34 surface expression on the AML blasts, secondary AML, unfavorable karyotype and no allogeneic HSCT at some point of treatment course were associated with unfavorable prognosis. However, in the multivariate risk factor analyses only unfavorable karyotype (p=0.012), CD34 positivity of AML blasts (p=0.046), no allogeneic HSCT (p=0.008) and first diagnosis after 1997 (p=0.025) were independent unfavourable prognostic factors. In conclusion, karyotype and CD34 expression are independent prognostic markers in newly diagnosed AML. Furthermore, receiving an allogeneic HSCT at some point of the treatment course seems to be of benefit for AML patients.

Acute Disease↗
PubMed2004

Oral PUVA and topical steroids for treatment of oral manifestations of chronic graft-vs.-host disease.

BACKGROUND: Oral manifestations of chronic graft-vs.-host disease (cGVHD) can significantly affect the quality of life and severity often does not correlate with systemic manifestations. We evaluated the use of topical corticosteroids and the intraoral application of psoralen-UVA (PUVA) for treatment of oral manifestations of cGVHD. METHODS: Overall, 18 patients with oral manifestations of cGVHD were treated with either intraoral PUVA (n=7) or with topical corticosteroids (n=16). Four patients received intraoral PUVA after failure of topical steroids and one patient was treated with topical corticosteroids after failing treatment with intraoral PUVA. A glass fiber extension of an UVA source was used for manual intraoral application. Treatment with topical corticosteroids consisted of 0.1 mg/ml dexamethasone mouth wash four times a day in combination with antifungal prophylaxis. RESULTS: Four patients showed complete local response (CR) due to intraoral PUVA, two improved and one did not respond. Topical corticosteroids resulted in nine patients in CR, two improved and five did not respond. CONCLUSION: Intraoral PUVA as well as topical corticosteroids are effective in treatment of oral manifestations of oral GVHD with few side-effects and improve quality of life in patients with cGVHD.

Administration, Topical↗
PubMed2003

External copper inhibits the activity of the large-conductance calcium- and voltage-sensitive potassium channel from skeletal muscle.

We have characterized the effect of external copper on the gating properties of the large-conductance calcium- and voltage-sensitive potassium channel from skeletal muscle, incorporated into artificial bilayers. The effect of Cu2+ was evaluated as changes in the gating kinetic properties of the channel after the addition of this ion. We found that, from concentrations of 20 microM and up, copper induced a concentration- and time-dependent decrease in channel open probability. The inhibition of channel activity by Cu2+ could not be reversed by washing or by addition of the copper chelator, bathocuproinedisulfonic acid. However, channel activity was appreciably restored by the sulfhydryl reducing agent dithiothreitol. The effect of copper was specific since other transition metal divalent cations such as Ni2+, Zn2+ or Cd2+ did not affect BK(Ca) channel activity in the same concentration range. These results suggest that external Cu2+-induced inhibition of channel activity was due to direct or indirect oxidation of key amino-acid sulfhydryl groups that might have a role in channel gating.

Animals↗
PubMed2002

Treatment of peripheral T-cell lymphomas (PTCL) with high-dose chemotherapy and autologous or allogeneic hematopoietic transplantation.

Peripheral T-cell lymphomas (PTCL) are a rare entity of non-Hodgkin's lymphomas (NHL). Despite the poor outcome after conventional chemotherapy, the impact of high-dose chemotherapy (HDCT) and autologous or allogeneic stem cell transplantation is not well defined in these patients. In a retrospective study, we evaluated the outcome of 15 patients (9 male, 6 female) with PTCL after HDCT with autologous (10 patients) and allogeneic (5 patients) stem cell transplantation between 1996 and 2001 at our department. At the time of transplantation three patients were in second remission, seven patients were in partial remission (PR), and three patients had refractory disease. Two patients were treated with sequential HDCT (cyclophosphamide, adriamycin, vincristine, etoposide, prednisolone, m-CHOEP). The conditioning regimes were heterogeneous. After HDCT ten patients (67%, autologous 7, allogeneic 3) achieved CR, two patients (13%, autologous 2, allogeneic 0) had refractory disease, and three patients (20%, autologous 1, allogeneic 2) died because of toxic side effects before evaluation of response was performed. The median overall survival (OS) was 12 months. The 1-year probability of survival for the autologous and allogeneic groups was 58% and 40%, respectively. At the time of evaluation, six patients are alive and nine patients have died (four severe infection, one late toxicity, two disease progression, and two relapse). Despite the small number of patients in this study, HDCT with autologous or allogeneic hematopoietic transplantation seems to be an effective treatment option that can achieve CR for patients with PTCL. Because of the poor outcome of these patients after conventional chemotherapy, HDCT seems to be a rational option in first-line therapy. Whether it improves survival in these patients should be further investigated.

Adult↗
PubMed2002

Progressive interstitial fibrosis of the lung in sclerodermoid chronic graft-versus-host disease.

Sclerodermoid chronic graft-versus-host disease (sGVHD) is a well-known complication in patients with a long history of chronic GVHD. Pulmonary involvement in chronic GVHD presents typically as bronchiolitis obliterans (BO). Pulmonary fibrosis after allogeneic hematopoietic stem cell transplantation (HSCT) is presumed to be caused by the long-term toxicity of the conditioning regimen or the result of lung injury elicited predominantly by viral infections or GVHD. We present two patients with late onset pulmonary fibrosis associated with moderate sGVHD of the skin after HSCT. At the initial diagnosis of chronic GVHD both patients presented with symptoms of interstitial pneumonia. Years later both patients developed moderate to severe interstitial pulmonary fibrosis in association with sGVHD. One patient showed additional clinical and histological signs of BO. While one patient responded to increased immunosuppression including total nodal irradiation (1 Gy), the other patient died due to complications related to pulmonary fibrosis.

Adult↗
PubMed2001

Changes in health care providers' knowledge, attitudes, beliefs, and behaviors regarding domestic violence, following a multifaceted intervention.

PURPOSE: To improve domestic violence (DV) identification, management, and referral in a not-for-profit rural health network, training for health care professionals was implemented using a train-the-trainer approach, two one-hour training sessions, and dissemination of a clinical protocol. The multifaceted approach also involved modifications of emergency department medical records, distribution of office enablers, and a local public health campaign. The authors measured the effectiveness of this campaign. METHODS: After implementation of a multifaceted training and public awareness campaign, a questionnaire designed by the Centers for Disease Control to measure knowledge, attitudes, beliefs, and intended behaviors (KABB) of health care providers relative to DV was administered to 380 health care professionals in the fall of 1997, with a follow-up survey completed after the intervention in the fall of 1999. RESULTS: The response rates for the pre- and post-intervention surveys were 67% (n = 380) and 56% (n = 273), respectively. Two scales were correlated in the base-line survey: self-efficacy (related to DV response) and familiarity with referral resources. Reporting of victim identification in the preceding year increased from 36% to 39%. Those with training were more likely to have identified a victim within the year (OR = 2.86; 95% CI, 1.73-4.74). Among the 232 respondents with complete data, multiple analysis of variance demonstrated statistically significant overall improvement across all scales. Nine of the 13 KABB scales revealed significant increases from pre- to posttest and included: screening, workplace resources, making referrals, provider self-efficacy, victim autonomy, victim understanding, legal requirements, staff preparation, and too busy/can't help. CONCLUSION: A comprehensive training program for health care providers can increase their self-efficacy in responding to DV victims.

Adult↗