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Biomedical subjects

K Tiedemann

Publications and source records attributed to K Tiedemann.

At least 37 records · Page 2Linked to original sources

Use of granulocyte-macrophage colony-stimulating factor in two children treated with cord blood transplantation.

Cord blood contains stem cells in amounts similar to or slightly less than those present in a bone marrow collection to be used for bone marrow transplantation (BMT). Too few cord blood transplants (CBT) have yet been performed to define the ability to achieve engraftment and the rate of engraftment. Two cord blood transplants have been performed using granulocyte-macrophage colony stimulating factor (GM-CSF) to hasten engraftment. Two children, aged 5 and 6 years received a CBT using HLA-identical stem cells collected at the birth of a sibling. One child had X-linked lymphoproliferative disease (XLP), and the other, acute lymphoblastic leukemia in second complete remission. One had an ABO and one an Rh blood group mismatch. Conditioning therapy consisted of cyclophosphamide, melphalan, and antithymocyte globulin or busulphan and cyclophosphamide. Graft-versus-host disease prophylaxis was methotrexate and cyclosporine or cyclosporine. Both children were given GM-CSF at 5 micrograms/kg/day from day 1 until the absolute neutrophil count (ANC) reached 1.0 x 10(9)/L for 3 consecutive days. If this level was not reached by day 14, the dose of GM-CSF was doubled. Both children engrafted rapidly, with ANCs reaching 0.5 x 10(9)/L in 12 and 16 days. Engraftment was confirmed by blood group in both and sex chromosome typing in one. Both children developed mild GVHD localized to skin, which resolved with steroid therapy. The child with XLP was cured and has survived for 34 months; the second child has survived 27 months with normal marrow function but has had a relapse of leukemia.(ABSTRACT TRUNCATED AT 250 WORDS)

ABO Blood-Group System↗

Results of intensive therapy in childhood acute myeloid leukemia, incorporating high-dose melphalan and autologous bone marrow transplantation in first complete remission.

Childhood acute myeloid leukemia (AML) has a poor prognosis with standard chemotherapy. Allogeneic bone marrow transplantation (BMT) in remission improves the outlook only for the one third of patients with sibling donors. Autologous BMT with a lower morbidity and mortality is available to all. In this study, maximum cytoreduction was achieved by intensive early chemotherapy. Final intensification, with autologous BMT was offered to all those remaining in first complete remission (CR). Patients received two induction and two consolidation courses of intensively scheduled chemotherapy. Cytoreduction was assessed on day 14 and remission was assessed after courses 2 and 4. Bone marrow was harvested after recovery from the second consolidation course or after the first maintenance course and separated on a discontinuous percoll gradient before cryopreservation. Twenty-eight of 31 consecutively enrolled patients achieved CR. Three relapsed early and, of the 25 eligible, 24 underwent autologous BMT. Twenty-three patients received high-dose melphalan and 1 received busulphan and cyclophosphamide before autologous BMT at a median of 113 days (range, 86 to 301) after initial CR. Trilineage engraftment occurred in all. Neutrophil recovery to greater than 0.5 x 10(9)/L occurred at a median of 46 days (range, 13 to 92) after autologous BMT. Platelet recovery was delayed, with a median time to achieve greater than 20 x 10(9)/L of 42 days (range, 18 to 215). With a minimum follow up of 25 months following autologous BMT only 3 children have relapsed. The 5-year event-free survival rate (EFS) from diagnosis is 68% (95% confidence interval, 46% to 90%). Five-year EFS following autologous BMT is 87% (95% confidence interval, 67% to 100%). Autologous BMT with high-dose melphalan administration after intensive chemotherapy has produced EFS equivalent to allogeneic BMT and is associated with a strikingly low relapse rate. High-dose melphalan appears to be a valuable agent for conditioning therapy in AML.

Acute Disease↗

Effective multi-agent chemotherapy for advanced abdominal lymphoma and FAB L3 leukemia of childhood.

Between June 1981 and May 1988, 51 children with diffuse undifferentiated, advanced (Murphy Stage III and IV) intra-abdominal non-Hodgkin's lymphoma were treated on an intensive multi-drug chemotherapy protocol without irradiation to the primary tumour. Therapy was completed for Stage III disease at one year, but Stage IV patients continued with a further year of therapy until January 1986, when it was reduced to one year. Central nervous system (CNS) prophylaxis consisted of eight doses of intrathecal MTX for all children, and 24 Gy cranial irradiation for Stage IV patients only. There were 42 patients with Stage III disease (III A n = 29 and III B n = 13) and nine patients with Stage IV disease, of whom eight had extensive bone marrow and extramedullary disease (FAB L3 ALL). No patient had CNS disease at presentation. Forty-eight of 51 children (94%) achieved a complete remission. Two children died during remission induction therapy and eleven children relapsed, mostly within eight months of diagnosis. All patients have completed therapy. Failure free survival is 76% for Stage III and 67% for Stage IV patients, with a median followup of 90 and 64 months, respectively. Subdividing Stage III patients into Stage III A and III B did not show significantly different survival (P = 0.9), but the number of patients in Stage III B is small. These results compare favourably with the most effective published protocols, and toxicity has been manageable.

Abdominal Neoplasms↗

Prevention of cyclophosphamide/cytarabine-induced emesis with ondansetron in children with leukemia.

Ondansetron, a 5HT3 antagonist, was given to 20 children aged 4 to 18 years who were undergoing treatment with the Australian and New Zealand Childhood Cancer Study Group Acute Lymphocytic Leukaemia (ALL) Study V Protocol. The study was open, dose ranging, and noncomparative, and designed to evaluate safety and efficacy of ondansetron in preventing nausea and vomiting caused by cyclophosphamide intravenous (IV) 1,000 mg/m2 day 1, and cytarabine IV subcutaneously (SC) 75 mg/m2 on days 2 to 5. Ten patients were given ondansetron 5 mg/m2 IV (group A) and subsequently another 10 patients were given ondansetron 3 mg/m2 IV (group B). Oral ondansetron was given for 14 doses, at the same dosage for both groups, commencing simultaneously with the IV infusion and continuing at 8 hourly intervals, ie, until day 5. The oral dose was based on surface area with the following schedule: 0.3 to 0.6 m2, 2 mg; 0.6 to 1 m2, 3 mg; and greater than 1 m2, 4 mg. Vomiting on the first day of chemotherapy was reported in group A by one patient and by one patient in group B. Vomiting during days 2 to 5 was reported by two group-A patients and by three group-B patients. Nausea was recorded on day 1 by one patient in group A, and two in group B, and on days 2 to 5 by three patients in group A, and by seven in group B. All patients were alert during treatment with ondansetron and there was no dystonia. There were no changes in renal function or hematology values that could be ascribed to the study drug. Transient elevations in bilirubin and liver enzymes were observed. We conclude that our results indicate that ondansetron is a safe and extremely effective single-agent antiemetic with minimal side effects, when administered both IV and orally.

Administration, Oral↗

Precocious puberty associated with malignant thoracic teratoma and malignant histiocytosis in a child with Klinefelter's syndrome.

A 10-year-old boy with precocious puberty of 2 1/2 years' duration presented with a malignant thoracic teratoma with elevated levels of beta human chorionic gonadotropin (beta-HCG) and alpha fetoprotein (alpha FP). The mediastinal tumor was completely excised and adjuvant chemotherapy commenced. Within 3 weeks of commencing chemotherapy he developed hematologic abnormalities that, with the subsequent clinical illness, led to a diagnosis of malignant histiocytosis. Death occurred a few days after start of therapy for malignant histiocytosis. Cytogenic studies showed the somatic karyotype to be that of Klinefelter's syndrome, while the malignant cells in marrow and lymph node carried an additional marker chromosome. This case, with others reported, suggest that the XXY karyotype may influence the development of mediastinal germ cell tumors, which in themselves appear to be associated with the early onset of a malignancy of the hemopoietic system.

Child↗

The current potential of plastination.

This review surveys the potential of plastination, a technique of tissue preservation introduced eight years ago. In this process, water and lipids in biological tissues are replaced by curable polymer which are subsequently hardened, resulting in dry, odorless and durable specimens. The procedure consists of the following steps - fixation, dehydration, forced impregnation in a vacuum, and hardening. The properties of the finished specimen are determined by the class of polymer used. Silicone yields flexible, resilient specimens, allows the broadest range of application, and provides satisfactory results with minimum equipment. Specimens plastinated with an epoxy-silicone copolymer are rigid enough to be polished, but are not unbreakable. This resin is used for thick, opaque body slices and showcase specimens. Epoxy resins are used for thin (2.5 mm), transparent body or organ slices. They are cast between polyester foils or glass plates and can be used for histological investigations. Polyester resin is used for the production of opaque brain slices, which gives excellent differentiation between grey and white matter. The application of plastination in research and the production of teaching specimens is discussed with special regard to the equipment required, cost, and feasibility of the processing.

Anatomy↗

Structural and functional comparison of mesonephric and metanephric proximal tubules.

Mesonephric kidneys of the mid-gestation fetus and metanephric kidneys of the adult are known to differ in many gross features but to be qualitatively similar in their cellular morphology. In the present studies, quantitative morphometric and in vitro microperfusion procedures were used to examine further the physical and transport properties of mesonephric and metanephric (S2) proximal tubule segments from rabbit. In perfused mesonephric proximal tubules the volume transport rate was 0.91 +/- 0.08 nl/min per mm tubule length, 2.7 +/- 0.2 nl/min per mm2 basement membrane (outer tubule) surface area, and 0.19 +/- 0.03 nl/min per mm2 basolateral cell membrane surface areas. For comparison, the S2 portion of metanephric proximal tubules is reported to transport 0.33 +/- 0.02 to 0.53 +/- 0.01 nl/min per mm length or, based on the present findings, 2.8 +/- 0.2 to 4.4 +/- 0.8 nl/min per mm2 basement membrane area and 0.16 +/- 0.02 to 0.25 +/- 0.07 nl/min per mm2 basolateral membrane area. Thus, proximal mesonephric and S2 metanephric segments exhibit approximately the same transport per unit area of basement membrane and per unit area of the basolateral cell membranes across which active transport presumably occurs.

Animals↗

Sacrococcygeal teratoma: has chemotherapy improved survival?

Case records of 57 patients (50 female, 7 male) with sacrococcygeal teratoma who were treated at the Royal Children's Hospital in Melbourne between 1948 and 1986 were reviewed. There were 40 benign and 19 malignant tumors; two patients had malignant recurrence following excision of a benign tumor. The majority of the benign lesions were readily excised; 80% of these patients presented under the age of 6 months. In contrast, 16 of the 19 patients with malignant disease presented after 6 months of age and 12 of these died. Before 1975, malignant lesions were treated with surgery or irradiation, and in a few patients, single-agent chemotherapy. No patients survived. In 1970, intensive multiagent chemotherapy was introduced, with planned delayed surgical resection, with or without postoperative irradiation. Three of five patients treated between 1976 and 1980 survive disease-free and are almost certainly cured. Modern therapy is with cisplatin-containing regimens, and while initial responses in six patients with extensive disease are impressive, it is too early to evaluate the impact of these newer programs on cure.

Antineoplastic Combined Chemotherapy Protocols↗

Oral methotrexate is as effective as intramuscular in maintenance therapy of acute lymphoblastic leukaemia.

It has been postulated that variations in methotrexate absorption may influence the outcome of treatment in lymphoblastic leukaemia. One hundred and forty four children with acute lymphoblastic leukaemia not of the T cell type were randomised to receive continuing treatment with daily 6-mercaptopurine, vincristine, and prednisolone six weekly and methotrexate once weekly, either as a single oral dose or an intramuscular injection. Analysis of results with a minimum follow up of three and a half years has shown that the route of administration of methotrexate has had no influence on relapse at any site, but more children receiving intramuscular methotrexate died in remission. These results indicate that oral methotrexate is as effective as intramuscular methotrexate in continuing treatment of lymphoblastic leukaemia.

Administration, Oral↗

[Thin-section computerized tomography of the skull base].

High-resolution CT images of the skull base are depicted and anatomical structures are described. A large variety of osseous and soft tissue structures can be differentiated in the temporal bone, nasopharynx and orbita. Knowledge of the anatomical structures is essential for the recognition of pathological changes and also plays an essential role for the radiologist involved in diagnosis.

Ear, Inner↗

An inhibitor to factor VIII:C in a patient with possible combined haemophilia A and von Willebrand's disease.

A factor VIII inhibitor has been found in a patient with an unusual combination of factor VIII-related properties. The inhibitor is directed specifically against the clotting activity (VIII:C) of the factor VIII complex. It behaves in a similar fashion to high responding inhibitors of factor VIII seen in haemophilia A patients and it was characterised as an immunoglobulin of the IgG class. Laboratory results from the patient and his family show considerable variation of factor VIII-related properties between various individuals. Overall, the data suggests the co-existence of haemophilia A and von Willebrand's disease in the family and the presence of both diseases in the patient.

Child, Preschool↗

Marrow function reconstitution by fraction 3 of Percoll-density-gradient-separated cells.

Eight children with advanced tumors or acute myeloid leukemia were treated either with very-high-dose multi-agent chemotherapy (4) or marrow ablative high-dose melphalan (4) followed by autologous marrow rescue, using only fraction 3 from a Percoll-discontinuous density gradient separation of bone marrow buffy coats. Each patient received less than 20% of the number of cells usually reinfused from the buffy coat. The yield of CFU-c in Percoll gradient 3 was similar to the yield obtained from whole buffy coats of bone marrow. Reconstitution of marrow function with a neutrophil count greater than 0.5 X 10(9)/L and platelet count greater than 50 X 10(9)/L occurred in 7 patients in a medium time of 15 and 16 days, respectively--a time comparable to that following infusion of whole buffy coat in 20 other patients. In one patient, hemopoietic recovery was considerably delayed, suggesting that fraction 3 from the Percoll gradient had been relatively ineffective in marrow reconstitution. We conclude that fraction 3 from marrow separated on Percoll gradients has the advantages of small volume and good recovery of marrow stem cells and can promptly reconstitute marrow function in the majority of children treated with very-high-dose chemotherapy or marrow ablative doses of melphalan.

Adolescent↗

Immunological reconstitution in a patient with severe combined immune deficiency using non-sibling bone marrow depleted of T cells with HuLy-m1.

An infant with severe immune deficiency received bone marrow from an HLA-A, -B, -DR matched, mixed leucocyte reaction non-reactive first cousin. The donor marrow was fractionated on a discontinuous Percoll gradient and before infusion was treated with the anti-human T lymphocyte antibody, HuLy-m1, and rabbit serum as a source of complement. Methotrexate was given during the following two weeks. A rise in the peripheral blood lymphocyte count, indicating engraftment, occurred six weeks after transplantation. There was no clinical evidence of graft versus host disease (GVHD). Engraftment has been sustained for one year and the patient is in normal health and has normal in vitro immunological function. In vitro treatment of human marrow with HuLy-m1 allows stable engraftment and may be useful in attempting to diminish or prevent GVHD.

Animals↗

The pig mesonephros. III. Distal tubule, collecting tubule, and Wolffian duct: SEM- and TEM-studies.

The ultrastructure of the distal and collecting tubules of mature pig mesonephroi (41st gestational day) was studied in perfusion-fixed embryos. In the distal tubule, the three subsegments postulated on the basis of enzyme histochemistry show only minor differences of their luminal surfaces, mostly of cell size. TEM photographs reveal a single cell type with interdigitating basolateral processes, frequently flattened to 30-120 nm lamellae devoid of organelles. Larger interdigitating processes harbor vertically oriented mitochondria in the form of indented plates. The macula densa cells are small, do not interdigitate, and have distended intercellular spaces. The collecting tubule starts with a dorsal convolution, in which intercalated cells (with apical microfolds and numerous mitochondria) occur in addition to interdigitating cells. Further down this segment, the interdigitating cells are gradually replaced by principal cells characterized by interlocking lateral microvilli, basal infoldings, and relatively few organelles. Intercalated cells extend into the Wolffian duct. Although the pig mesonephros has the most differentiated nephron of the mammals studied so far, with metanephros-like cells, its intrinsic urinary concentrating capacity appears to be low in view of its vascularization pattern and nephron architecture.

Animals↗

Vascularization and glomerular ultrastructure in the pig mesonephros.

Vascularization of the pig mesonephros was investigated in embryos 5-8 cm in length. Vascular injections with microfil were cleared and dissected; corrosion casts were studied under the scanning electron microscope (SEM). Perfusion-fixed tissue was used for SEM and transmission electron microscope (TEM) studies, including freeze-fracture specimens. The branches of one mesonephric artery carry up to 15 glomeruli. Several glomeruli occupy the same arterial branch, with very short afferent arterioles proper. The efferent vessels, frequently 2-5, leave the extensive vascular pole opposite the entering arteriole and split into peritubular capillaries radiating towards the superficial veins. These capillaries form vascular regions in the shape of flattened pyramids. Along its course, one nephron is supplied by vessels derived from 4-7 glomeruli. The nephrons have less vascular contact than in the definitive kidney. The ultrastructure of the single mesonephric vessels matches the metanephric counterparts. Epithelioid cells with renin granules are common in afferent arterioles, larger arteries, and efferent vessels. The lobulated glomeruli are up to 750 micron long and flattened, showing the usual features of podocytes, mesangial cells, and an attenuated endothelium with fenestrations between 50 and 250 nm. It partially retains its own basement membrane. There is no proximal mesangium.

Animals↗

Renin immunohistochemistry in the mesonephros and metanephros of the pig embryo.

The occurrence and distribution of renin was investigated in meso- and metanephric kidneys of pig embryos in various gestational stages. The immunohistochemical peroxidase-antiperoxidase-method (PAP) was used on paraffin sections after application of an antiserum against mouse renin which cross reacts with pig renin. Renin immunoreactivity was already found in the mesonephros of 21 day pig embryos (crown-rump(CR)-length 12 mm) with the strongest reaction in the media of the juxtaglomerular afferent arteriole. Efferent vessels, mesonephric arteries, and the aortic wall also contained scattered renin-positive cells. In the definitive kidney, renin was not detected prior to the 25 mm CR-length-stage. In 45 mm embryos, immunocytochemical staining was observed not only in the media of kidney arteries and arterioles, but also in proximal tubules after pinocytic absorption of filtered renin. TEM-studies revealed that the media of both the mesonephric and the developing metanephric arteries and arterioles contains epithelioid cells whose ultrastructure is very similar to that of renin-producing cells in the adult organ. The observed distribution of renin-producing cells along the entire renal arterial tree points to the possibility that the major function of the renin-angiotensin system in the fetal animal is to participate in the stabilization of renal perfusion pressure.

Animals↗