Biomedical subjects

R P Herrmann

Publications and source records attributed to R P Herrmann.

At least 37 records · Page 2Linked to original sources

PubMed1992

Urate metabolism during bone marrow transplantation.

We studied urate metabolism in 36 patients undergoing both allogeneic and autologous bone marrow transplantation (BMT) without allopurinol. Most patients had low tumour burdens. Three different preparative regimens were used; busulphan/cyclophosphamide (BUCY); BCNU, etoposide, ara-C and melphalan (BEAM) and cyclophosphamide/total body irradiation (CY/TBI). Urate excretion rose during each of the regimens but the pattern of excretion varied with each regimen. Urate excretion remained elevated 72 h after completion of BEAM and BUCY, possibly reflecting the prolonged action of some of the agents used, e.g. melphalan, busulphan and etoposide. Urinary urate concentrations were unchanged compared with pre-chemotherapy levels reflecting the adequacy of the hydration protocol. No significant rise in creatinine was seen and no cases of tumour lysis syndrome occurred. Serum uric acid levels were a poor reflection of urate production, falling in most patients, and are an unreliable end-point for decisions regarding prophylaxis. BMT can be safely undertaken in patients with low tumour loads without allopurinol if an adequate urine volume is maintained. In this series, high levels of urate excretion often persisted for 72 h after the completion of conditioning and adequate hydration should be ensured during this period.

Allopurinol↗

PubMed1991

Streptavidin-biotin immunotoxins: a new approach to purging bone marrow.

Immunotoxins have been used both experimentally and clinically to purge bone marrow of tumor cells or T cells before transplantation. We describe the synthesis of a streptavidin-biotin-toxin conjugate using whole ricin. Streptavidin-biotin-ricin (SA-BR) conjugates were synthesized by biotinylation of whole ricin, which was then complexed with streptavidin. Hybrid molecules consisting of a single biotinylated ricin moiety linked to a streptavidin molecule were separated by gel filtration. This SA-BR conjugate was used in an indirect cytotoxicity assay. The assay involved sensitizing of target cells with biotinylated monoclonal antibody (B-MCAB) followed by treatment with dilutions of SA-BR conjugate. The assay demonstrated a specific antibody-directed cytotoxicity. The strength of this SA-BR system is that a single conjugate was able to be used in conjunction with a library of B-MCABs to selectively target phenotypically different cell types. The application of the SA-BR conjugate is thus only restricted by the availability of B-MCABs specific for the desired target cells. The high affinity of avidin for biotin (Kd approximately 10(-15)) and the ability of a single conjugate to target phenotypically different cells through utilization of a library of B-MCABs gives SA-BR conjugates great potential in the selective targeting of individual cell types.

Antibodies, Monoclonal↗

PubMed1989

Australian snake venoms and their in vitro effect on human platelets.

Thrombocytopenia is generally not associated with cases of envenomation by Australian snakes, however the clinical evidence is conflicting. The in vitro effect of these venoms upon platelets had hitherto not been studied. This study systematically examines the effect on human fresh and fixed platelets of twenty Australian snake venoms, nineteen elapid and an hydrophiid; for comparision four crotalid venoms from the Americas and S.E. Asia were also included. Electron micrographs were taken of platelets after exposure to some of the venoms. Results demonstrated that all venoms except the hydrophiid venom caused fresh platelets to irreversibly aggregate directly, and this was associated with degranulation as evidenced by electron microscopy (EM). Response to all venoms by fixed platelets was less marked and also suggests, that metabolically, active platelets are necessary for the venoms to exert their maximal effect. The hydrophiid venom's action on fresh platelets was unique, as a plasma co-factor was required before aggregation could be induced. Crotalid and hydrophiid venoms were more active against platelets than the elapid venoms. Nevertheless, platelet aggregation and degranulation in the presence of elapid venoms suggests that a platelet response in vitro may be a significant factor in the "defibrination syndrome" induced in humans by Australian snakes.

Australia↗

PubMed1987

PER-117: a new human ALL cell line with an immature thymic phenotype.

A new cell line, PER-117, was established from bone marrow cells of an eighteen months old boy with an acute lymphoblastic leukaemia (ALL). The leukaemic origin of cell line PER-117 is indicated by its cytochemical, immunological and cytogenetic similarity to the patient's fresh leukaemic cells. PER-117 carries a marker chromosome which was identified as a translocation between chromosomes 1 and 11. The surface marker analysis revealed that the phenotype of PER-117 is RFB-1+, RFT-1+ (CD5), 3A1+ (CD7), OKT 9+, OKT 10+ and HLA-DR-. Thus, this cell line appears to represent a prothymocyte or stage I thymocyte and preliminary data suggest that it can be induced in vitro to further differentiate.

Antibodies, Monoclonal↗

PubMed1987

Hyperthermia potentiates the activity of immunotoxin conjugates against common acute lymphoblastic leukaemia cells in vitro.

We studied the in-vitro cytotoxic effect of hyperthermia at 42 degrees C, both alone and in combination with ricin-linked immunotoxins, reactive with the common acute lymphoblastic leukaemia cell lines Reh and KM-3. Assessment of cytotoxicity was by incorporation of 3H-leucine and limiting dilutions analysis. The effect of immunotoxins alone and in combination with hyperthermia on normal human marrow progenitor cells was assessed by conventional colony forming units-granulocyte macrophage (CFU-GM) assay. We found that incubation of either of the cell lines with a mixture of the two immunotoxins, RPH-7-ricin and PHM-6-ricin, at 42 degrees C for one hour (h) potentiated the cytotoxic activity of the immunotoxins at 37 degrees C. At a concentration of 10(-8) mol/L, a 2.2-log kill was seen with KM-3 leukaemic cells at 37 degrees C and a 3.3-log kill at 42 degrees C, an increase of approximately 10 fold in cytotoxic activity. Survival of CFU-GM following treatment at 42 degrees C for one h with a similar concentration of immunotoxins was 26.2% (+/- 13.7%) (equivalent to 0.6 log kill) and 76.0% (+/- 1.83%) (0.1 log kill) when normal marrow was incubated with immunotoxins at 37 degrees C. This suggests relative sparing of normal marrow cells compared with the leukaemic cells tested as indicated by the 2.1-log kill difference (approximately 100 fold) between normal and leukaemic cells at 37 degrees C and the 2.7-log kill (approximately 500-fold) difference at 42 degrees C. We conclude that hyperthermia may have a role in addition to immunotoxins in the purging of marrow ex vivo to remove leukaemic cells.

Antibodies, Monoclonal↗

PubMed1987

Monoclonal antibody-ricin conjugate cytotoxic to cells expressing the common acute lymphoblastic leukemia antigen (CALLA).

The monoclonal antibody PHM-6, which is specific for the common acute lymphoblastic leukemia antigen (CALLA), was conjugated to the plant toxin ricin. Binding of the PHM-6-ricin conjugate to cells via the ricin molecule was blocked by the presence of 100 mM lactose. The IC50 (concentration resulting in 50% inhibition) of the PHM-6-ricin conjugate for the CALLA-positive KM-3 cell line was 280-fold greater than for bone marrow stem cells, indicating the potential of this conjugate for immunological purging of autologous remission marrow.

Antibodies, Monoclonal↗

PubMed1987

Oral idarubicin as single-agent treatment of acute nonlymphocytic leukemia in poor-risk patients.

Oral idarubicin was given as single-agent treatment of acute nonlymphocytic leukemia in 18 poor-risk patients. They comprised nine previously untreated elderly patients, age range 69-86, and nine relapsed pretreated patients, age range 41-76. Overall, two patients achieved complete remission (including one with preceding refractory anemia with excess of blasts) and seven achieved partial responses. Dose-limiting toxic effects were diarrhea and sepsis. In this limited study, oral idarubicin at a dose of 20-25 mg/m2/day X 3 was a well-tolerated drug with potent antileukemic effects. The oral formulation deserves more widespread evaluation.

Administration, Oral↗

PubMed1986

Plasma cofactors necessary for Enhydrina schistosa (beaked sea snake) venom to induce platelet aggregation.

A study of the effect of the venom of the beaked sea snake (Enhydrina schistosa) was undertaken on platelet aggregation. It was found that platelet aggregation and the release reaction occurred in the presence of both venom and plasma but, not with the venom alone. No effect was observed with fixed platelets distinguishing the effect of the venom from that of platelet aggregation with ristocetin or botrocetin and indicating metabolic dependence. Studies to elucidate the plasma factor required for platelet aggregation under the release reaction indicated dependence on the presence of both Factor II and calcium ions. This venom may prove to be a useful laboratory reagent in coagulation studies because of the Factor II and calcium dependence.

Animals↗

PubMed1984

Cross-reactivity of bardick snake venom with death adder antivenom.

A case of a young man who was bitten by a bardick snake (Notechis curtus) and who, apart from marked local swelling, had neither signs of coagulopathy nor neurological symptoms, is reported. The bardick snake venom taken from the site of the bite reacted strongly with the death adder antivenom in the snake venom detection kit, but did not react with the Notechis antivenom. This anomalous reactivity was confirmed when dried bardick snake venom was used. In-vitro observations of the bardick snake venom showed that it had anticoagulant properties similar to those of death adder venom, and was not procoagulant as are the venoms of other snakes of the Notechis genus. The clinical importance of these findings is discussed.

Adolescent↗

PubMed1983

Coagulant and anticoagulant actions of Australian snake venoms.

A systematic study was made of the action on the plasma coagulation system of 20 Australian and Papuan Elapid and Hydrophiid snake venoms and compared with 4 Crotalid venoms and 1 Viper. The majority of Australian venoms were shown to be prothrombin activators with variable dependence on the presence of factor V phospholipid and calcium. None of these venoms had strong thrombin like activity in contrast to the Crotalid venoms which were powerfully thrombin like. The Crotalid venoms were also strongly fibrinolytic unlike the Elapid venoms which showed no or minimal evidence of fibrinolytic activity. Four Elapid venoms and 2 Crotalid venoms showed anticoagulant activity which contained neither antithrombin nor fibrinogenolytic activity and may act upon the prothrombin complex.

Animals↗

PubMed1983

A unique T-cell monoclonal antibody with potential uses in autologous bone marrow transplantation.

A monoclonal antibody reactive with an antigen expressed by a T-cell subset has been produced. The antibody designated RPH-1 reacts with a subset of normal T-cells and thymocytes. The antibody was strongly reactive with blast cells from 3 patients with T-acute lymphoblastic leukemia (T-ALL) and also reacted with cells of 2 patients with non-T-ALL. The antibody did not react with leukemic cells from patients with acute myeloid leukemia (AML) or B-chronic lymphocytic leukemia (B-CLL)). RPH-1 reacted with 2 T-cell lines, no B-cell lines and no myeloid cell lines. Absence of toxicity to granulocyte macrophage colony forming units (CFU-GM) by RPH-1 in the presence of complement was demonstrated, and in view of strong reactivity with certain leukemic cells, potential application of RPH-1 as an immunological means of selectively removing tumour cells is indicated.

Adolescent↗

PubMed1982

Chromosomal studies in healthy blood donors with IgA deficiency.

Chromosomal analysis was performed in 70 asymptomatic blood donors found over a 5-year period in a large screening programme to be IgA deficient. No abnormalities were found in any of these individuals in relation to their chromosomal constitution and, in particular, chromosome 18 was normal in all individuals. A further 10 symptomatic individuals with IgA deficiency also showed a normal chromosomal constitution with no abnormalities of chromosome no. 18.

Blood Donors↗

PubMed1982

Technique for human bone marrow harvest.

The usual technique of harvesting bone marrow for allogeneic or autologous transplantation involves passage of the marrow suspension through discs of stainless steel mesh of increasingly small diameter. We describe a sterile technique which is much less messy and produces a single cell suspension. Potter-Elvehjem homogenizers are used to break up the marrow particles. This procedure has been used successfully in 6 patients where allogeneic transplantation was performed and in 6 harvests of autologous marrow. Marrow cryopreserved in this way contains viable committed stem cells and is not subject to agglutination following subsequent thawing.

Bone Marrow Cells↗

PubMed1981

Passovoy factor deficiency in five Western Australian kindreds.

Passovoy factor deficiency, a coagulation abnormality affecting the intrinsic coagulation system, was discovered in 5 Western Australian kindreds. The defect is inherited as an autosomal dominant and is associated with a clinical bleeding tendency characterized by easy bruising and undue blood loss following trauma such as dental extraction and tonsillectomy. Fresh frozen plasma appears to provide effective prophylaxis during surgery. The activated partial thromboplastin time (APTT) shows a prolongation which, in most patients, is of relatively slight degree, and this may be the reason for the paucity of reports in the literature. The discovery of 5 kindreds carrying the defect suggests that it may be relatively common in the Australian community and that care should be taken to identify and follow up minor grades of abnormality of the APTT where individuals suspected of having an inherited bleeding tendency are screened. A sample from one case was distributed, with a clinical history, to participants in the Royal College of Pathologists of Australasia 1980 Quality Assurance Programme in Haematology. Approximately one-third of 175 participants failed to detect the definite abnormality present.

Australia↗

PubMed1979

Plasma thrombin assay using a chromogenic substrate in disseminated intravascular coagulation due to snake bite envenomation.

Using the chromogenic substrate, Tos-Gly-Pro-Arg-pNA-HCl (Chromozym TH, Boehringer Mannheim) plasma thrombin was estimated in six cases of envenomation by Australian elapid snakes. All patients manifested findings characteristic of defibrination due to envenomation by these snakes. Fibrin-fibrinogen degradation products were grossly elevated, as was plasma thrombin in all cases. Following treatment with antivenene, all abnormal coagulation parameters returned rapidly towards normal by 24 hours and plasma thrombin disappeared.

Adult↗

PubMed1977

Angioimmunoblastic lymphadenopathy with dysproteinemia.

Three cases of angioimmunoblastic lymphadenopathy with dysproteinemia are reported which illustrate the characteristic clinico-pathological features. These cases also provide information relating to the ultrastructure of the interstitial acidophil material, the histopathological spectrum, where treatment has been attempted, and an incidence figure for an Australian community. Detailed immunological investigations in one case suggest that the disease is a primary B-lymphocyte abnormality.

Adult↗

PubMed1976

Extensive primary lymphoma of the gastrointestinal tract.

A case of extensive primary lymphocytic lymphoma (lymphosarcoma) of the gastrointestinal tract is reported. At the time of presentation the patient had diffuse involvement of the gastrointestinal tract from the stomach to the ano-rectal junction. Malabsorption was present. Pre-treatment immunologic studies showed elevated serum IgA and IgG, but impaired humoral and cellular immunity. Death occurred 13 months after diagnosis.

Aged↗

PubMed1975

The management of patients with the Kasabach-Merritt syndrome.

The Kasabach-Merritt syndrome comprises consumption coagulation associated with giant haemangioma. A case is reported of disseminated intravascular coagulation complicating dental extraction in a 36-year-old male with this syndrome. The pre-operative management with anticoagulant therapy is discussed and the relevant literature reviewed.

Adult↗