PubMed Health⌕ Search

Biomedical subjects

T Klingebiel

Publications and source records attributed to T Klingebiel.

At least 163 records · Page 9Linked to original sources
PubMed1987

[Radiation absorption and proton relaxation times of the liver in vitro following carbon tetrachloride poisoning].

In 57 rats the radiation absorption or proton relaxation times were determined in vitro after single carbon tetrachloride poisoning. The inflammatory changes induced by CCl4 result in marked water absorption and moderate of fat. Histologically, there are cell necroses, toxic swellings of cells, regenerating cells rich in water content, and fatty vacuoles. These phenomena result in a reduction of radiation absorption due to the increased water and fat accumulation. Prolongation of both relaxation times is mainly due to water absorption.

Animals↗
PubMed1986

[Bone marrow transplantation in acute leukemia, chronic myeloid leukemia, severe aplastic anemia and stage IV neuroblastoma. Effect of antiviral prevention with anti-CMV-hyperimmunoglobulin and acyclovir].

Bone marrow transplantation was performed between IV/82 and X/85 in 64 patients with acute leukemia (n = 36), chronic myelogenous leukemia (CML; n = 13), severe aplastic anemia (n = 12), and neuroblastoma stage IV (n = 3). Of these patients 57 received allogeneic marrow from HLA-ABCDR identical, MLC-negative sibling donors. Six transplants were performed with syngenic marrow and one with autologous marrow. Of the 64 patients 48 survived 40-1,250 days after transplantation, resulting in a survival rate (SR) of 75% and a survival probability (SP) of 71%. Of the 36 patients suffering from acute leukemia (SR = 64%, SP = 51%), patients with acute myelogenous leukemia (AML) in first complete remission (n = 11; SR = 81%, SP = 76%), as well as patients with acute lymphatic leukemia (ALL) in 1st to 4th complete remission at the time of transplantation (n = 14; SR = 81%, SP = 76%) show a favorable prognosis. A poor survival rate was seen for patients with AML when transplanted in second or partial remission (1/5; SR = 20%), as well as for patients suffering from ALL and transplanted during relapse or partial remission (1/6; SR = 16%). Of 13 patients suffering from CML 12 survived the transplantation free of relapse (SR = 93%, SP = 92%), and one patient died from varicella zoster pneumonia. Of the transplanted patients with severe aplastic anemia, 12 of 13 are surviving with complete hematologic reconstitution; one patient, however, died on day 10 from a sepsis. In our patient group, the SR as well as the SP has been improved through changes in the irradiation protocol concomitant with prophylactic application of anti-CMV hypergammaglobulin, as well as through additional oral medication of Azyklovir. The 41 patients (BMT No. 7-47) with total body irradiation at one time show an SR of 44% and an SP of 41%. The following 46 patients (BMT No. 48-93) have reached an SR of 83% and an SP of 74% under the regimen of fractionated total body irradiation, plus prophylaxis with anti-CMV hypergammaglobulin and Azyklovir. Within this group, no fatal CMV pneumonia was encountered as opposed to six patients lost from CMV pneumonia in the first group.

Acyclovir↗
PubMed1986

[Bone marrow transplantation in chronic myeloid leukemia. Influence of gnotobiotic measures, especially antiviral prophylaxis].

Bone marrow from HLA-identical siblings was transplanted in 14 patients with chronic myeloid leukaemia (CML), including one patient in acceleration phase and one in chronic phase following 2 blast crises. Restoration of the bone-marrow occurred in all cases and Philadelphia chromosome could not be detected in any of the patients after the transplantation. Two patients died due to lung complications. Twelve patients who received antiviral prophylaxis (aciclovir per os, anti-CMV-hyperimmunoglobulin) after the transplantation are in very good condition with 140 to 790 days complete clinical and cytogenetic remission. Bone-marrow transplantation, as a curative measure for patients with CML up to the age of 45 (50), should be included in therapy schemes when an HLA-identical sibling is available.

Acyclovir↗
PubMed1986

Clinical experiences in the treatment of neuroblastoma with 131I-metaiodobenzylguanidine.

Treatment of neuroblastoma is an unsolved problem of pediatric oncology. In spite of highly intensified chemotherapy, the long-term survival rate of children with a metastatic neuroblastoma is below 10%. We therefore used 131I-metaiodobenzylguanidine (MIBG) for the first time to treat children with a neuroblastoma in relapse or primary unresponsiveness to chemotherapy. We had previously demonstrated that MIBG is useful for the scintigraphic imaging of neuroblastoma lesions and had investigated the cytotoxicity and uptake of MIBG in various neuroblastoma cell lines. We treated 6 children with neuroblastoma in a total of 19 courses. Three of the children suffered from a relapse of neuroblastoma; 3 had never gained a remission. Four of the 6 children lost their bone pain and fever during the first 3 days. In 5 of the 6 children the solid tumor as well as the bone marrow infiltration responded to MIBG treatment, with responses ranging from transitory decrease of the tumor mass to complete disappearance of abdominal tumors. We also witnessed a stabilization of osteolytic lesions, a decrease in elevated serum catecholamines, and a decrease in bone marrow infiltration. Five of the 6 children died of tumor progression 55-249 days after the first MIBG treatment.

3-Iodobenzylguanidine↗
PubMed1985

Creatinine clearance and renal interstitium in diffuse endocapillary proliferative glomerulonephritis.

Morphometric investigations of the renal cortex on biopsies obtained from patients with diffuse proliferative endocapillary glomerulonephritis (EPGN) were compared to biopsies without pathological changes, both groups having a normal serum creatinine concentration at the time of biopsy. Our findings are as follows: In both groups a statistically significant correlation exists between the decrease of the endogenous creatinine clearance and the broadening of the interstitium. The mean endogenous creatinine clearance value in EPGN is 107.6 +/- 40.6 ml/min/1.73 qm, the mean endogenous creatinine clearance in normal kidneys is 108.2 +/- 28.5 ml/min/1.73 qm; the mean interstitial volume in EPGN is 14.5 +/- 2.9 vol.%, that in normal kidneys 9.5 +/- 2.9 vol.%, the difference is statistically significant. Comparing the run of the two curves (relationship between endogenous creatinine clearance and interstitial volume) of the investigated groups, one finds that they run a nearly parallel course, the curve of the EPGN being shifted statistically significant to the right. The mean values of number, single- and total area of the peri- and intertubular capillaries are identical in the cases of EPGN and in those biopsies without pathological findings. Furthermore no correlations could be established between the above mentioned measuring values and the endogenous creatinine clearance in the both investigated groups. Consequently in these cases with normal serum creatinine concentration the reduction of the glomerular filtration rate (gfr) accompanied by interstitial broadening cannot be explained by an impairment of the postglomerular blood flow. Perhaps a tubular functional disturbance, the cause or the consequence of the interstitial broadening impairs glomerular function by the tubular-glomerular feedback-mechanism and/or by an elevation of the intratubular hydrostatic pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1983

A contribution to the morphology and pathogenesis of thyroid-like lesions in the kidney.

The morphological variations of thyroid-like lesions in the kidney in 15 cases with chronic destructive interstitial nephritis as the basic alteration were examined with light microscopy and immunohistological methods. Reflux pyelonephritis was present in some cases. Thyroid-like lesions can develop at any age. "Mature" thyroid-like lesions possess large follicular structures and solid tubular epithelial cell complexes, whereas the follicular structures in "young" thyroid-like lesions are small. The hyaline casts are Tamm-Horsfall protein positive in between one- and two-thirds of the follicles. IgA is present in all follicular lumina. The thyroid-like lesions are the result of a regenerative process. They develop after subtotal parenchymal destruction of remaining tubular epithelial cells from the ascending limb of the loop of Henle, the distal convoluted tubules and the collecting ducts. They are pathognomonic for healed destructive bacterial interstitial nephritis, but can also be observed in analgesic nephropathy, hydronephrosis, and nephronophthisis when these basic diseases are preceded by pyelonephritis.

Adolescent↗
PubMed1983

Morphometric studies on acute renal failure in humans during the oligoanuric and polyuric phases.

Twelve biopsies from patients in the oligoanuric phase and 17 from patients in the polyuric phase of acute renal failure (ARF) were studied and compared morphometrically with 39 control biopsies. Measurements were taken on silvered semi-thin sections, which were classified according to each of three divisions of the renal cortex. All alterations observed were equally prominent in these three cortical zones. The number of peri- and intertubular capillaries was reduced in both phases of ARF (P less than 0.001), their mean surface area was increased (P less than 0.001), while their total surface area per visual field remained constant. The tubular epithelial tissue was distended in both ARF phases and the tubular lumina were simultaneously widened, as were Bowman's capsular spaces. The causes of these alterations are discussed. The findings are in accord with a concept of the pathogenesis of ARF, which ascribes a central role to damage of individual tubular cells.

Acute Kidney Injury↗
PubMed1982

Acute renal failure--an integrative discussion of morphologic and functional findings.

The ultrastructural alterations at the nephron established in animal experiments, were also confirmed, by means of an electron-microscopic examination, in eight cases of human acute renal failure (ARF). Special consideration was given in this study to single cell alterations, particularly in proximal tubular cells, with emphasis being placed on alterations due to single cell damage in the region of the renal fluid compartments. The ultrastructural alterations of the tubular cells in ARF, suggest serious impairment of the cellular capacity for electrolyte transport and metabolic processes. The shunt paths between the tubular fluid compartment and the functional interstitium, arising from necrosis of the tubular cells or dissolution of the gap or tight junctions, were discussed in terms of their significance for the directional, active transport processes of the tubular cells for sodium chloride and the passive water flow. The morphologic findings were reviewed in light of recent findings on cellular membrane processes and electrolyte transport. A reinterpretation of the morphologic and functional findings in ARF is suggested. This takes into consideration single cell function and the integrity of the renal fluid compartments.

Acute Kidney Injury↗
PubMed1981

Effects of catecholestrogens on luteinizing hormone levels in long tem ovariectomized adult rats.

The long term ovariectomized adult rat was used to test the effects of exogenous estradiol, 4-hydroxyestradiol, and 2-hydroxyestradiol on LH secretion. To this end, different doses of estradiol 3-benzoate, 4-hydroxyestradiol 3,4-dibenzoate, and 2-hydroxyestradiol 2,3-dibenzoate were injected daily at 0800 h, and the LH serum levels were measured on 4 experimental days. At a dose of 1 micrograms/day, estradiol benzoate lowered LH secretion, beginning 48 h after the first injection (morning of day 2), and induced a characteristic LH surge 10 h later. 4-Hydroxyestradiol dibenzoate at the same dose produced less suppression of LH on the morning of day 3, but caused a comparable and highly significant surge on the same evening. Higher doses (3 and 10 micrograms/day) resulted in the same pattern seen with estradiol benzoate. 2-Hydroxyestradiol dibenzoate at comparable doses had no effect. Only extremely high doses (129 micrograms/day) caused slight suppression of tonic LH secretion 72 h after the first injection, and inconsistent LH elevations occurred on the same evening. It is concluded that in this model, catecholestrogens act as estrogens with respect to LH suppression and release, with 4-hydroxyestradiol being a potent estrogen and 2-hydroxyestradiol a weak estrogen.

Animals↗
PubMedDate not supplied

Costal BCG osteomyelitis presenting as a tumor.

We present the case of an 11-month-old male infant who had been BCG vaccinated as a neonate. At the age of nine months, he developed a localized tumor above his right mamilla. The tumor destroyed the fourth rib and infiltrated the surrounding soft tissue. X-ray and CT scan suggested a malignant neoplasm. Histology, however, showed the typical picture of tuberculosis and Mycobacterium bovis (BCG strain) was isolated from the lesion. Thus, the tumor was caused by an unusual presentation of a costal BCG osteomyelitis which was associated with negative findings in the bone scan.

BCG Vaccine↗
PubMedDate not supplied

[Current state of cord blood transplantation in childhood].

In 1989 E. Gluckman reported the successful cord blood transplantation in a boy with Fanconi anemia. Since then more than 1500 allogeneic cord blood transplantations have been performed worldwide. This has been possible because non-profit cord blood banks have been established that provide cryopreserved cord blood products from unrelated donors. However, cord blood transplantation is associated with specific risks that have sofar limited its more widespread use. Its main problem is the limited stem cell dose that is associated with a long aplasia and a high rate of engraftment failure. Therefore, cord blood is used as the stem cell source in only about 1 - 2 % of stem cell transplantations in childhood. The main advantage of cord blood transplantation lies in its low risk for graft-versus-host-disease (GvHD), one of the major causes for posttransplant morbidity and mortality particularly with unrelated stem cell donors. The low risk for GvHD is attributed to the low number of transplanted T cells and their functional immaturity. Another advantage of cord blood transplantation lies in the immediate availability of the cord blood units. Based on the experiences with allogeneic cord blood transplantation the indications for cord blood donation will be discussed.

Blood Donors↗
PubMedDate not supplied

[Relapse of childhood ALL, AML and MDS after allogeneic stem cell transplantation can be prevented by donor lymphocyte infusion in a critical stage of increasing mixed chimerism].

BACKGROUND: Mortality in children with acute leukemias or MDS after allogeneic stem cell transplantation (allo-SCT) is mostly determined by relapses. It was recently shown by us that patients who develop increasing quantities of autologous hematopoietic cells in peripheral blood (increasing mixed chimerism, in-MC) after allo-SCT do significantly more often relapse (P < 0.0001) than patients with a complete chimerism (CC). In a small series of patients with in-MC, the relapse rate could be significantly reduced by administration of donor lymphocytes (DLI). METHODOLOGY: A prospective multicenter study was initiated under the question whether number of relapses can be significantly reduced either by withdrawal of post-transplant immunosuppression and/or by DLI in the critical stage of in-MC. RESULTS: Highly repetitive determination of the genetic status of 114 children with acute leukemias or MDS (ALL: n = 41, AML: n = 39, MDS: n = 34) revealed 55 cases with CC and 43 with in-MC. Relapses occurred significantly (P < 0.0001) more often in patients with in-MC (25/43) than in patients with CC (12/55). In-MC-patients showed a significantly (P < 0.01) enhanced event free survival rate (11/24) when DLI was given and/or post-transplant immunosuppression was stopped compared to patients which did not receive such an interventional regimen (1/19). Two in-MC-patients developed fatal GVHD after immunological intervention. CONCLUSION: These data substantiate that prophylactic immunotherapy on the basis of in-MC is a powerful treatment approach to suppress relapses of acute leukemias and MDS after allo-SCT.

Cause of Death↗
PubMedDate not supplied

Ex vivo expansion of highly purified NK cells for immunotherapy after haploidentical stem cell transplantation in children.

BACKGROUND: Allogeneic natural killer (NK) cells are known to show medium to high cytotoxic activity against HLA-nonidentical leukemia or tumor cells. For a possible benefit of post transplant treatment with NK cells after haploidentical stem cell transplantation (haplo-SCT) we developed a clinical scale procedure for NK cell processing observing Good Manufacturing Practice (GMP). METHODS: Allogeneic donor NK cells were selected from 15 unstimulated leukaphereses using two rounds of immunomagnetic T cell depletion, followed by an NK cell enrichment step. CD56 (+)CD3 (-) NK cells were stimulated and expanded in vitro according to GMP. Quality control of NK cell purity, residual T cells and cytotoxic activity was done by multi-coloured flow cytometric analyses. RESULTS: Purification led to an absolute number of 234-1 237 x 10 (6) CD56 (+)CD3 (-) NK cells from leukapheresis harvests with a median purity of 95 % and a 4 to 6(1/2) log depletion of T cells. After two weeks stimulation with IL-2 a five-fold expansion of NK cells with a T cell contamination below 0.1 % was reached. Median cell viability was 95 % after purification and 99 % after expansion. The IL-2 stimulated NK cells showed a highly increased lytic activity against the MHC-I deficient K562 cells compared to freshly isolated NK cells and a medium cytotoxicity against patients' leukemic cells. CONCLUSIONS: Clinical scale enrichment and activation of allogeneic donor NK cells is feasible. High dose NK cell application may be a new treatment option for pediatric patients with leukemia or solid tumors in case of minimal residual disease or unbalanced chimerism post haplo-SCT as we could show for the first three patients .

Antigens, CD19↗
PubMedDate not supplied

A comparison between three graft manipulation methods for haploidentical stem cell transplantation in pediatric patients: preliminary results of a pilot study.

Transplantation of hematopoietic stem cells from mismatched related donors makes a potential donor available for every child in need of stem cell transplantation. Here, we compare three different graft manipulation methods in patients with leukemias and lymphomas: positive selection of stem cells with either CD34 (n = 39) or CD133-coated magnetic microbeads (n = 14) and a new strategy which depletes T- and B-cells through the use of CD3- and CD19-coated microbeads (n = 11). Median purity of stem cells was comparable after CD34 (+)-selection and CD133 (+)-selection, whereas stem cells were only slightly enriched after CD3 (+)/CD19 (+)-depletion (97.5 %, 93.4 % and 1.02 %). Indirect depletion of T-cells by positive selection resulted in 1 x 10 (4) (median) residual CD3 (+)-cells/kg (0.7-3 x 10 (4)). Patients with CD3/CD19-depleted grafts received 3.2 x 10 (4) (median) (0.7-16 x 10 (4)) residual T-cells/kg. Those grafts also comprised NK-cells (median number: 86 x 10 (6)/kg), dendritic cells and monocytes/granulocytes. Primary engraftment of the stem cell products was comparable after CD34- and CD133-selection (85 and 72 %). In the CD3/CD19 group, 91 % had a primary engraftment. After reconditioning, all patients (64/64) were finally engrafted. Patients with CD34-selected or CD133-selected grafts had similar incidences of a GvHD II-IV (3 and 7 %), whereas a GvHD was slightly increased in patients receiving CD3/CD19-depleted cells (27 %). Reconstitution of CD3 (+) T-cells was faster in the CD3/CD19 group than in the CD34 or CD133 group. These preliminary results indicate, that CD3/CD19-selected grafts may be advantageous regarding engraftment and immunoreconstitution. Since effector cell with potential antileukemic activity are cotransfused, such grafts may be suited in particular for patients with insufficient remission.

AC133 Antigen↗
PubMedDate not supplied

Adenoviral infections after transplantation of positive selected stem cells from haploidentical donors in children: an update.

UNLABELLED: We present updated results of stem cell transplantation with highly purified stem cells from haploidentical parental donors and infection with human adenovirus (HAdV) post stem cell transplantation (SCT). Survival post SCT is primarily determined by relapse, infections and far less by GvHD or other transplant related mortality. During the immune reconstitution the host is at significant risk for severe viral infections. HAdV infection is especially in children an important complication post SCT, with significant morbidity and mortality despite new antiviral treatment strategies. Although control of infection seems to require T-cells, the characterization of HAdV-specific T-cells post SCT has not been introduced in surveillance and treatment decisions. METHODS: Therefore we evaluated the impact of HAdV-infections on the survival between 1995 and 2004 (n = 63) and studied the occurrence of adenovirus-specific T-cells in children with (n = 9) and without (n = 9) HAdV-infection post allogeneic SCT and in healthy donors (n = 53). After stimulation ex-vivo with HAdV-antigen IFN-gamma secreting T-cells were analyzed by flowcytometry and defined as HAdV-specific T-cells. RESULTS: Until day 180 post SCT the cumulative incidence of all lethal viral infections (HAdV n = 5, cytomegalovirus n = 3, herpes simplex virus n = 1) was 16 % for the whole cohort of patients. Cumulative incidence of HAdV-associated mortality was 8.5 %. Cumulative incidence of all lethal viral infections could be now reduced from 16 % to 8 % in conjunction with new surveillance- and therapeutic-strategies. Children with HAdV-associated mortality all had no specific T-cells, although reconstitution of absolute lymphocyte counts exceeded 300/microl within 30 days post transplant. Patients who cleared HAdV infection had normal frequencies of HAdV-specific T-cells until day 200 post SCT. CONCLUSION: In summary adenovirus specific T-cell reconstitution should be monitored in patients after SCT to limit the use of anti viral chemotherapy and help to identify those patients that would benefit from new therapeutic strategies like adoptive transfer of virus specific T-cells.

Adenovirus Infections, Human↗