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Biomedical subjects

C Urban

Publications and source records attributed to C Urban.

At least 109 records · Page 6Linked to original sources

Treatment of infant leukemia with busulfan, cyclophosphamide +/- etoposide and bone marrow transplantation.

Infants with acute leukemia have a poor chance of being cured by conventional chemotherapy. We therefore treated cases of infant leukemia with high dose chemotherapy followed by bone marrow transplantation (BMT). Six suffered from acute leukemia and one from refractory anemia with excess of blasts (RAEB-t). The conditioning regimen consisted of busulfan (BU) and cyclophosphamide (CY), and was intensified by adding etoposide (VP) in four cases. At the time of BMT the children were 4, 5, 12, 13, 13, 14, and 20 months old. Three children were autografted, three received HLA-identical marrow from a sibling donor, and one child received matched unrelated donor marrow. All five children who were grafted in complete (CR) or partial remission (PR) are alive and well in CR 7, 13, 24, 37, and 46 months after allogeneic (two patients) or autologous (three patients) BMT, and 13, 17, 29, 42, and 53 months after initial diagnosis. The child with RAEB-t and the one transplanted in second chemotherapy-resistant relapse of acute non-lymphoblastic leukemia relapsed at 7 and 17 months respectively. The chemotherapy regimen was well tolerated. BU-CY-VP is a promising alternative treatment to regimens including total body irradiation for very young children suffering from acute leukemia.

Bone Marrow Transplantation↗

Acute megakaryocytic leukemia in children. Clinical, immunologic, and cytogenetic findings in two patients.

An unusual presentation of acute megakaryocytic leukemia (AMKL) is reported in two young children. The first child had a 10-day history of ptosis of the right eyelid as the initial manifestation of AMKL, a clinical picture not previously described in this variant of leukemia. Computed tomographic scanning showed multiple intracranial mass lesions, and the diagnosis of AMKL was confirmed by immunophenotyping of bone marrow blasts. The second child had Down syndrome and received alkylating agents and radiation therapy for treatment of metastatic rhabdomyosarcoma of the orbit. She had AMKL as second malignancy. Both patients had acquired chromosome 21 anomalies in their leukemic blasts. The first patient, constitutionally normal, had an i(21q) in his leukemic blasts; the patient with constitutional trisomy 21 had tetrasomy 21 and additional chromosomal changes. The clinical symptoms and the results of morphologic, immunologic, and cytogenetic studies are discussed.

Blepharoptosis↗

Effect of a beta-lactamase inhibitor, tazobactam, on growth and penicillin-binding proteins of Borrelia burgdorferi.

The effects of tazobactam, a relatively new beta-lactamase inhibitor, were investigated on growth and penicillin-binding proteins (PBPs) of Borrellia burgdorferi. A previous communication from our group demonstrated several proteins capable of binding labelled penicillin in this organism. Of these proteins, 94-kDa and 57-kDa PBPs possessed the highest affinity for penicillin and were assumed to be essential proteins involved in cell-wall synthesis. In these experiments, tazobactam was used in competition binding experiments as well as on whole spirochetes. Only the 94-kDa and 57-kDa PBPs were affected by increasing amounts of tazobactam during competition-binding experiments and growth of B. burgdorferi was also inhibited. These results may explain the in vitro activity of beta-lactamase inhibitors in general and suggest a utility for these compounds when examining PBPs with hydrolysing activity and/or organisms with beta-lactamases.

Bacterial Proteins↗

Role of candida in pathogenesis of antibiotic-associated diarrhoea in elderly inpatients.

The part that candida plays in antibiotic-associated diarrhoea was investigated in 24 elderly inpatients (mean age 74 years) who tested negative for Clostridium difficile toxin and other intestinal pathogens. 7 had intestinal overgrowth of Candida species (greater than or equal to 10(5) cfu/ml). None of the 24 matched, antibiotic-treated controls without diarrhoea had candida overgrowth. All 5 patients with diarrhoea and candida overgrowth treated with oral nystatin responded with resolution of diarrhoea and lowering of faecal counts to less than 10(4) cfu/ml within 7 days of start of antifungal therapy despite continuation of antibacterial therapy. In the other 2 patients with candida overgrowth, the diarrhoea subsided spontaneously and faecal candida counts returned to normal (less than 10(4) cfu/ml) after antibacterial agents were withdrawn. In patients without candida overgrowth, diarrhoea persisted until antibiotics were withdrawn, at a mean of 16 days after study entry.

Aged↗

Multiple mechanisms of methicillin resistance and improved methods for detection in clinical isolates of Staphylococcus aureus.

The mec gene of a number of clinical methicillin-resistant Staphylococcus aureus isolates exhibiting a variety of heterogeneous expression modes was selectively inactivated by allelic replacement mutagenesis. While the resistance level of each of the transformants was reduced, the methicillin MIC for these transformants was well above the MIC for susceptible laboratory strains of S. aureus and was similar to the methicillin MIC for many contemporary clinical isolates which did not react with the mec-specific DNA probe but which showed a low or borderline level of resistance to methicillin. A number of those strains had no detectable beta-lactamase, and for about half of the isolates that did carry plasmid-borne beta-lactamase, elimination of the plasmid caused only partial reduction of the methicillin MIC or no reduction at all. The findings suggest that many contemporary strains of staphylococci harbor a combination of at least three distinct beta-lactam resistance mechanisms: (i) the mechanism related to the acquisition of the foreign mec gene and (ii) a beta-lactamase-dependent and (iii) a beta-lactamase-independent mechanism, each one of which can provide a certain degree of resistance against penicillinase-resistant beta-lactam antibiotics.

Clavulanic Acid↗

[Oligosymptomatic Bourneville-Pringle tuberous sclerosis of the brain with giant cell astrocytoma].

We report on a 9-year-old boy who developed subependymal giant-cell astrocytoma associated with tuberous sclerosis. Apart from a few hypopigmented skin patches, the boy's clinical picture was completely unremarkable until the onset of diplopia and vertigo reflecting increased intracranial pressure. Magnetic resonance imaging of the brain revealed subcortical hamartomas in addition to the intraventricular tumour. Seizures and mental retardation were absent. The boy's mother had suffered from seizures during childhood and presented with typical skin lesions. The importance of thorough examination and regular follow-up even in patients with oligosymptomatic variants of tuberous sclerosis is emphasized.

Adult↗

[Endocrinologic function following cranial irradiation in acute lymphoblastic leukemia in childhood].

Endocrinological function was evaluated in 31 children after successful treatment of acute lymphoblastic leukaemia. All patients had received combination chemotherapy and 12-24Gy of cranial irradiation according to the German therapy protocols BFM-81, BFM-83 and BFM-86. Height, weight, bone age and pubertal development, as well as hypothalamic-pituitary function were measured. Long-term linear growth was unaffected in all patients. However, 9 patients showed subnormal serum growth hormone levels in response to pharmacological stimulation of the pituitary. All patients had normal levels of T3 and T4, but one patient showed an increased response of thyrotropin to thyrotropin releasing hormone. All prepubertal and postpubertal children demonstrated appropriate secretion of follicle-stimulation hormone (FSH) and luteinizing hormone (LH) after stimulation with LH-releasing hormone (LH-RH). 3 pubertal girls showed adequate oestradiol levels, but abnormally high levels of gonadotropins in response to LH-RH. Sexual development was normal in two of them, but the third had a late menarche and irregular menses. The significance of these findings is discussed in the context of recommendations possibly to further reduce or completely delete prophylactic cranial irradiation.

Adolescent↗

[Infections in the neutropenic phase following bone marrow transplantation: comparison of laminar airflow isolation with conventional isolation].

From May 1978 to September 1989 45 patients underwent 25 allogeneic and 21 autologous bone marrow transplantations (BMT) and 1 peripheral stem cell transplantation for the following indications: severe aplastic anemia (n = 4), hematological malignancies (n = 28), malignant solid tumours (n = 12) and sideroblastic anemia (n = 1). The first group of 20 patients was isolated in a conventional hospital room, while management of the aplastic phase in the second group of 25 patients was performed in a laminar air flow (LAF) unit. All patients received total decontamination. In a retrospective analysis the number of positive blood cultures during the neutropenic period was 85% in the first group, as compared with 40% in the second group, and the number of febrile episodes was 85% versus 64%, respectively. Despite the fact that the septic morbidity was lower in the LAF group, mortality during the neutropenic period (15% in group I versus 16% in group II) was unaffected and survival rate (45% in group I versus 36% in group II) did not improve. We conclude that LAF protection will only have a positive impact on survival rate if the incidence of non-infectious complications of BMT, such as organ toxicity or graft-versus-host disease, is likewise reduced.

Adolescent↗

[Oligosymptomatic variant of tuberous sclerosis with subependymal giant cell astrocytoma].

We report on a 9-year-old boy who developed subependymal giant-cell astrocytoma associated with tuberous sclerosis. Remarkably, the boy was not mentally retarded and never had suffered from seizures. Apart from white skin patches symptoms of increased intracranial pressure were the presenting symptoms. The boy's mother, who was present at the boy's admission, presented with skin lesions typical of tuberous sclerosis. The importance of thorough examination of apparently asymptomatic relatives of patients with tuberous sclerosis is emphasized.

Astrocytoma↗

Purification and properties of a kinase from Escherichia coli K-12 that phosphorylates two periplasmic transport proteins.

The phosphorylation in vivo and in vitro of the arginine-ornithine and the lysine-arginine-ornithine (LAO) periplasmic transport proteins of Escherichia coli K-12 was previously reported (Celis, R. T. F. (1984) Eur. J. Biochem. 145, 403-411). The phosphorylative reaction required ATP (as a direct energy donor), Mg2+, and a kinase that can be released by osmotic shock treatment of the cells. The enzyme was purified to electrophoretic homogeneity. The enzyme exhibited an ATPase activity and a kinase activity. Polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate gave an apparent molecular weight of 43,000 for the enzyme. The native protein showed the same molecular weight, suggesting that the protein is a monomer. The protein showed an apparent isoelectric point of 4.8 on isoelectric focusing. The two enzymatic reactions required a divalent cation and the apparent Km value for Mg2+ for the kinase activity was 0.5 mM. Mn2+ and Co2+ served as well as Mg2+, whereas Zn2+ and Ca2+ did not support activity. The ATPase activity of the enzyme yielded an apparent Km value for ATP of 50 microM. A similar value, Km of 100 microM, was calculated for the kinase activity with different concentrations of ATP. The enzyme showed a pH optimum of 7.3.

Adenosine Triphosphate↗

Childhood acute lymphoblastic leukemia: results of the Austrian Cooperative Study Group with the ALL A 84 protocol.

We prospectively treated 127 children with ALL with a risk-adapted regimen. All patients received the identical induction-consolidation therapy. The early maintenance included intermediate dose methotrexate in patients with standard risk (n = 79) and medium risk (n = 39). In addition patients with high risk (n = 6) received high dose ARA-C followed by L-asparaginase. Intensification treatment and prophylactic cranial irradiation was also tailored according to the risk group. Treatment duration was 2 years. Complete remission was achieved in 97.6% of all patients. Treatment-related toxicity accounted for one death in complete remission. The probability of event-free survival (pEFS) for the combined group was 72% at a median follow-up of 42 months. The pEFS was higher in patients with standard risk (SR) than in patients with medium risk (MR) (80% versus 65%; p less than 0.05) at 30 months, but attenuated in the follow-up evaluation at 42 months (76% versus 63%; p less than 0.1). The number of high-risk patients was too small for statistical evaluation. Relapse within the first 18 months after diagnosis indicated a poor prognosis and was more common in patients with MR than in patients with SR. The immunophenotype of the leukemic cells was not found to constitute an independent risk factor after treatment has been risk-adapted. Patients with an initial white blood cell count of more than 50 X 10(9)/l had a worse prognosis than patients with a lower white blood cell count (p less than 0.01).

Adolescent↗

Multiple sclerosis in childhood: contribution of serial MRI to earlier diagnosis.

The authors report six children (five girls, one boy) aged 11 to 13 years, of whom four had clinically definite multiple sclerosis (MS) and two had laboratory-supported definite MS. All had brain white matter abnormalities indicative of MS. In three cases, positive findings on the first MRI contributed significantly to their early diagnosis. Follow-up MRI studies over an average period of five months detected morphological changes in three of the children, although there was no concomitant clinical evidence. This raises the question of whether changes in clinically 'silent' lesions on follow-up MRI are antecedents of the essential MS criterion of dissemination over time, which could lead to earlier diagnosis of childhood MS. With cranial computerized tomography (CT) during the first clinical attack, a large focus with a lamellar structure mimicked a brain tumour in two patients. As CT also misses additional small lesions, it should no longer be used as the primary diagnostic method.

Adolescent↗

Penicillin-binding proteins in Borrelia burgdorferi.

Penicillin-binding proteins were identified in Borrelia burgdorferi membranes. A 94-kilodalton penicillin-binding protein was the first to be labeled with tritiated penicillin and was the first band to disappear in a competition experiment. Its binding ability was destroyed when membranes were preboiled. In addition, several of these penicillin-binding proteins comigrated with bands previously identified as surface proteins.

Bacterial Proteins↗

Imipenem-antibiotic monotherapy in juvenile cancer patients with neutropenia.

From 1984 to 1987 two consecutive groups of juvenile cancer patients (n = 45) with fever and neutropenia corresponding in all criteria were examined. In half of the total of 90 febrile episodes and septicemias, a conventional antibiotic combination therapy (Pseudomonas-active penicillin/cephalosporin of the third generation/aminoglycoside) was instituted. In the remaining half imipenem was used as an antibiotic monoagent. In 66% and 60% of the febrile episodes treated with antibiotic combination therapy and with imipenem, respectively, septicemia was confirmed by positive blood cultures. Nineteen febrile episodes occurred in the myeloaplastic phase after bone marrow transplantation. In a comparative study of imipenem as monotherapy versus an antibiotic combination therapy the results obtained with imipenem were superior in many regards. No resistance developed necessitating change of antibiotic therapy. Coagulase-negative Staphylococci, primarily responsible for catheter-associated septicemia, were susceptible. Duration of fever and thus duration of treatment were shorter. The incidence of side effects and costs were lower. Therefore, imipenem as an antibiotic monotherapy in febrile cancer patients with neutropenia appears to be more efficacious than the conventional combination therapy, even during myeloaplasia following bone marrow transplantation. The results and rationale of this retrospective analysis are discussed.

Adolescent↗

[Primary and secondary inoperable teratoid hepatoblastoma--multidisciplinary management].

Hepatoblastomas are the most frequent malignant liver tumors of childhood. Prognosis mostly depends on their resectability. Unresectable tumors are almost invariably fatal, unless their size can be decreased by chemotherapy and/or irradiation to permit surgical removal. In the present case report we discuss the clinical course of a 15 months old boy, who was admitted with primary inoperable teratoid hepatoblastoma. After alternating intravenous and intraarterial chemotherapy as well as radiation therapy, the tumor could be successfully resected. Specific problems of histological diagnosis and of the therapeutic management are discussed, and an overview of the recent literature in behalf of the histological basis, therapeutic possibilities and prognostic factors of hepatoblastomas is given.

Antineoplastic Combined Chemotherapy Protocols↗