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Biomedical subjects

C August

Publications and source records attributed to C August.

At least 55 records · Page 3Linked to original sources
PubMed1996

Prognostic significance of nuclear DNA content and proliferative activity in renal cell carcinomas. A clinicopathologic study of 58 patients using mitotic count, MIB-1 staining, and DNA cytophotometry.

BACKGROUND: For a variety of human malignancies, static DNA cytophotometry and immunostaining for the Ki-67 antigen using the antibody MIB-1 have provided significant prognostic information. METHODS: Surgical specimens of 58 renal cell carcinomas (RCCs) were investigated by conventional histology, DNA cytophotometry, and MIB-1 immunostaining. RESULTS: The MIB-1 indices and DNA data were found not only to be significantly correlated with various other morphologic parameters, but also to the clinical behavior of RCC. In the course of this study (median observation period: 31 months), 27% of patients died from RCC. None of these patients belonged to the group of 37 patients with RCCs exhibiting diploid or euploid DNA histograms. Lethal outcome occurred in only 16 of the 21 patients (76%) with noneuploid or aneuploid histogram tumors (P < 0.0001). According to their MIB-1 indices and upon choosing different cutoff levels, the 58 RCCs were categorized into 2 groups with either low or high proliferative activity. Using the median and the mean MIB-1 index as cutoffs, none of the patients with tumors showing low proliferative activity had died, whereas 16 of 29 patients (55%) or, respectively, 16 of 25 patients (64%) with tumors exhibiting high proliferative activity, had died from RCC (P < 0.0001). CONCLUSIONS: In addition to tumor grade and stage, both a high MIB-1 index and a noneuploid or aneuploid DNA histogram of a given RCC have the potential to identify tumor patients with an impaired prognosis.

Antigens, Neoplasm↗
PubMed1996

Bone marrow transplantation in pediatric patients with severe aplastic anemia: cyclophosphamide and anti-thymocyte globulin conditioning followed by recombinant human granulocyte-macrophage colony stimulating factor.

PURPOSE: Graft rejection remains a serious problem in patients transplanted for severe aplastic anemia. Although additional immunosuppression with irradiation may decrease graft failure, significant sequelae may ensue. We evaluated a nonirradiation containing conditioning regimen for children with severe aplastic anemia with matched sibling donors utilizing cyclophosphamide and anti-thymocyte globulin (ATG). To accelerate myeloid recovery, GM-CSF was used posttransplant. PATIENTS AND METHODS: Twelve patients, with a median age of 3 years underwent BMT from HLA identical sibling (n = 11) or syngeneic (n = 1) donors. Conditioning was cyclophosphamide 50 mg/kg x 4 days and anti-thymocyte globulin 30 mg/kg x 3 days. GM-CSF was administered at 10 micrograms/kg until a neutrophil count of 1,000 was achieved. Cyclosporine alone was used for graft-versus-host disease prophylaxis. RESULTS: All patients achieved durable engraftment at follow-up of 5-51 + months, with the exception of the identical twin. Median time to neutrophil counts > 200/microliters, 500/microliters, and 1,000/microliters were 12, 13, and 15 days, respectively. Acute GVHD of less than or equal to grade II occurred in four patients; one patient had grade III. This has resolved in all but one. CONCLUSION: The nonradiation conditioning regimen of cyclophosphamide/ATG appears to achieve durable engraftment in transfused children with matched sibling donors. GM-CSF may accelerate myeloid recovery without exacerbating GVHD, but its contribution to allogeneic transplant required further study.

Adolescent↗
PubMed1996

Pilot study of high-dose thiotepa and etoposide with autologous bone marrow rescue in children and young adults with recurrent CNS tumors. The Children's Cancer Group.

PURPOSE: This study was designed to determine the toxicity, radiographic response rate, and outcome following high-dose thiotepa, etoposide, and autologous bone marrow rescue (ABMR) for young patients with recurrent malignant brain tumors. METHODS: Eligibility criteria required adequate renal, hepatic, and pulmonary function, and no bone marrow infiltration. Thiotepa 300 mg/m2 and etoposide 500 mg/ m2 were infused on 3 consecutive days, and autologous bone marrow was infused 72 hours following chemotherapy. RESULTS: Forty-five patients with recurrent high-grade brain tumors, aged 8 months to 36 years (median, 8 years), were treated. Seven patients (16%) died of treatment-related toxicities within 56 days of marrow reinfusion. Delayed platelet engraftment occurred in 44% of patients who survived beyond day 56. Of 35 patients with radiographically measurable disease who survived at least 28 days following ABMR, there were two complete responses (CRs) and six partial responses (PRs), for an overall response (CRs plus PRs) rate of 23% (SE = 7%). Objective responses were observed in four of 14 assessable patients with high-grade glioma and in two of six with primitive neuroectodermal tumors (PNETs)/ medulloblastoma. Survival was significantly improved in patients treated with minimal residual disease (P < .0005). Five of 18 patients (28%) with high-grade gliomas remain free of disease at 39+, 44+, 49+, 52+, and 59+ months post-ABMR. CONCLUSION: The combination of high-dose thiotepa and etoposide has activity against a variety of recurrent childhood brain tumors. These results merit further evaluation in children and young adults with both recurrent and newly diagnosed high-grade brain tumors.

Adolescent↗
PubMed1995

[Fatal vacuolar cardiomyopathy in chronic chloroquine drug treatment].

Clinical and morphological findings recorded in an 81-year-old woman patient with a 45-year history of rheumatoid arthritis treated with long-term chloroquine therapy are reported. The cause of death was low cardiac output syndrome, which upon autopsy and postmortem toxicological analyses was classified as vacuolar chloroquine-induced cardiomyopathy. The pathogenesis and the morphological and clinical characteristics of cardiotoxic effects of chloroquine are reviewed.

Aged↗
PubMed1994

[Plexiform fibrohistiocytic tumor. Histology, immunohistology and ultrastructure].

An example of a plexiform fibrohistiocytic tumour (PFT) is presented for the first time in the German-language literature. The diagnostic criteria for this rare soft-tissue neoplasm of childhood and young adulthood, which is mostly subcutaneous in location and has a tendency to recur, include the plexiform structure which gives it its name, extensive siderin deposits and numerous osteoclast-like giant cells. The development of the tumour described here, which occurred in the field of radiation of a malignant haemangiopericytoma excised 7 years previously, indicates the possibility of induction of PFT by radiation.

Adipose Tissue↗
PubMed1994

[Primary hemorrhagic spindle cell tumor of the lymph node with amianthoid structures. Case report and review of the literature].

An example of a benign haemorrhagic spindle cell tumour of the lymph node (synonym: intranodal myofibroblastoma) is presented, which was first described 5 years ago and has not as yet been documented in the German literature. This rare benign mesenchymal neoplasm of the lymph node occurs almost exclusively in the inguinal region. Diagnostic criteria include its composition of myofibroblastic cells (with immunoreactivity for vimentin and actin), which may show nuclear palisading, the presence of peripheral haemorrhage zones and the occurrence of characteristic amianthoid structures, which have the ultrastructural appearance of dense meshworks of collagen fibers. Knowledge of this tumour entity is important for differential diagnosis of primary and secondary malignant mesenchymal neoplasias of the lymph node.

Actin Cytoskeleton↗
PubMed1993

T-cell-depleted maternal bone marrow transplantation for siblings with X-linked severe combined immunodeficiency.

Prenatal diagnosis of X-linked severe combined immunodeficiency in a male fetus made possible elective neonatal bone marrow transplantation before onset of symptoms. Bone marrow transplantation was performed by using T-cell-depleted maternal marrow that had been cryopreserved 2 years earlier, at the time that his older affected brother underwent transplantation. The second patient had less morbidity and more rapid reconstitution of his immune function.

Alleles↗
PubMed1993

Use of cytosine arabinoside and total body irradiation as conditioning for allogeneic marrow transplantation in patients with acute lymphoblastic leukemia: a multicenter survey.

We report the experience of 14 centers which have used the combination of cytosine arabinoside (ara-C; 24-36 g/m2) and total body irradiation (TBI) to prepare 213 patients with acute lymphoblastic leukemia (ALL) for allogeneic BMT. The overall 3-year disease-free survival (DFS) probability is 38% (95% CI: 31-45%); 75 patients died of complications and 51 relapsed. Multivariate analysis identified three factors independently associated with outcome: age, remission/relapse status and patient-donor relationship. The 3-year DFS probability is 52% (41-63%) for the 106 patients aged 0-11 and 25% (16-33%) for the 104 aged 11+ years; the DFS probability was 54% (34-74%), 41% (32-49%) and 19% (5-33%) for those in first remission, later remissions and relapse respectively. Older patients suffered both more toxic deaths and more relapses than young ones. No other covariate was found to predict for outcome. The results using ara-C-TBI are similar to those achieved using cyclophosphamide plus TBI to prepare ALL patients for BMT, perhaps because a seemingly lower relapse rate is offset by more toxic deaths particularly in older patients. Therapeutic trials should focus on reducing toxicity while maximizing antileukemic efficacy, and should stratify for patient and disease-related factors.

Adolescent↗
PubMed1991

Demonstration of glomerular DPP IV activity in kidney diseases.

Dipeptidylpeptidase IV (DPP IV) activity has been found in glomeruli of the rat and other previously investigated animal species, but has not been detected in the glomeruli of the normal human kidney. Under pathological conditions, enzyme activity may be registered. Following investigations on 155 human renal biopsies using polyclonal antisera against IgG, IgA, IgM, C3C, Fibrinogen, and DPP IV, we found glomerular enzyme activity in 43 cases of various histological diagnoses, but never in normal renal tissue. Identical results could be found by the Gly-Prol-beta-MNA substrate reaction. The localization of glomerular enzyme activity in capillary walls could not be definitely determined, possibly enzyme activity occurs in podocytes. Correlation of glomerular DPP IV activity to the deposition of immunoglobulins was not found. Nevertheless, the appearance of DPP IV in human glomeruli seems to be in correlation with some clinical findings, e.g. hypertension. The importance of DPP IV activity in pathohistologically changed glomeruli of human kidney is definitely large, but needs further investigation.

Dipeptidyl Peptidase 4↗
PubMed1990

High-dose multi-agent chemotherapy followed by bone marrow 'rescue' for malignant astrocytomas of childhood and adolescence.

Between April 1986 and March 1989, ten patients under 21 years of age with histologically confirmed malignant astrocytoma, received marrow-ablative chemotherapy with either thiotepa and Etoposide (five patients) or thiotepa, Etoposide and BCNU (five patients), followed by bone marrow 'rescue'. Nine patients had glioblastoma multiforme (GBM), and one patient had an intrinsic brain stem anaplastic astrocytoma (AA). Seven patients were treated for recurrent tumor. Two patients who developed GBM as second malignancies were treated directly following surgical resection. One patient had received irradiation only for recently diagnosed cervical spinal cord GBM. Thiotepa was administered at a total dose of 600-900 mg/M2 over three days, Etoposide was administered at a total dose of 1500 mg/M2 over three days, and BCNU was administered at a total dose of 600 mg/M2 over four days. Non-hematopoietic toxicities have been mainly transient, predictable and acceptable, consisting of oropharyngeal mucositis, cutaneous hyperpigmentation, erythema and desquamation. Four patients achieved complete responses (CR), as determined by radiographic evaluation (CT and/or MRI) on day 28 post-marrow infusion. The mean remission duration of those with CR is 290+ days; two patients presently remain in remission. Two patients achieved partial responses (PR, greater than 50% tumor shrinkage) by day 28 post-marrow infusion; both developed disease progression, at day 61 and 94 post-marrow infusion, respectively. One patient, with a brain stem AA, had stable disease maintained for 13 months post-marrow infusion. With a total (CR + PR) response rate of 60%, these regimens merit evaluation in broader categories of recurrent brain tumor patients, as well as in patients with newly-diagnosed GBM.

Adolescent↗
PubMed1990

[Familial juvenile nephronophthisis--a genetically-caused kidney disease].

It is reported on the course of the autosomal recessive transmitted familiar juvenile nephronophthisis in 3 siblings. Direct symptoms are polydipsia and polyuria with terminal course of chronic renal failure which could treated by dialysis and transplantation. Examination of the safe (parents) and possible (healthy siblings) heterozygotes was without particularities.

Adult↗
PubMed1990

[Familial juvenile nephronophthisis. Pathohistology of a rare genetic disease in three siblings].

Reported in this paper are clinical and morphological findings recorded from two sisters and one brother with familial juvenile nephronophthisis. Coherency in the basic course of the disease was not detectable by histological examinations, in the first place, though infancy developments had been almost identical, and clinical patterns were very similar to each other, with the characteristics including polyuria, polydipsia, hyposthenuria, anaemia, retarded growth, azotaemia, and progressing renal insufficiency. Some of the morphological findings were masked by secondary alterations and organ shrinkage. They were incoherently interpreted following preliminary investigations by different examiners. The pathogenesis of the disease has continued to be obscure. A disorder with tubular basal membranes as primary points of attack is discussed. Autosomal-recessive inheritance seems to be beyond any doubt, following genetic analysis of the family.

Adult↗
PubMed1988

The usefulness of open-lung biopsy in the pediatric bone marrow transplant population.

From October 1976 to October 1986, 126 children had bone marrow transplants at the Children's Hospital of Philadelphia. The indications were acute lymphocytic leukemia (ALL) (30), nonlymphocytic leukemia (24), aplastic anemia (15), solid tumors (47), and miscellaneous conditions (10). Of these, 21 (17%) underwent 22 open-lung biopsies. Fourteen of these patients showed no causative microorganism. When a cause was found it was viral (usually cytomegalovirus [CMV]) in three, fungal in one, Pneumocystis carinii alone in two, both viral and pneumocystis in one, and a combination of viral, bacterial, and pneumocystis in one. Thirteen patients died due to continued deterioration after the biopsy. In only two patients was there a significant change in antimicrobial therapy as a result of the biopsy. Both had Pneumocystis (one in combination with virus and bacteria). One patient with chronic infiltrates showed a lymphocytic interstitial pneumonia, which responded well to steroids. Open-lung biopsy is currently of limited value in this patient population. Survival is dismal unless the patient has Pneumocystis. We believe that prospective studies should be set up to compare open-lung biopsy with empiric antimicrobial therapy. A major emphasis must be on prevention.

Adolescent↗