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B A Robinson

Publications and source records attributed to B A Robinson.

At least 19 recordsLinked to original sources
PubMed2005

Inhibition of NF-kappa B activity and cFLIP expression contribute to viral-induced apoptosis.

Virus-induced activation of nuclear factor-kappa B (NF-kappaB) is required for Type 3 (T3) reovirus-induced apoptosis. We now show that NF-kappaB is also activated by the prototypic Type 1 reovirus strain Lang (T1L), which induces significantly less apoptosis than T3 viruses, indicating that NF-kappaB activation alone is not sufficient for apoptosis in reovirus-infected cells. A second phase of virus-induced NF-kappaB regulation, where NF-kappaB activation is inhibited at later times following infection with T3 Abney (T3A), is absent in T1L-infected cells. This suggests that inhibition of NF-kappaB activation at later times post infection also contributes to reovirus-induced apoptosis. Reovirus-induced inhibition of stimulus-induced activation of NF-kappaB is significantly associated with apoptosis following infection of HEK293 cells with reassortant reoviruses and is determined by the T3 S1 gene segment, which is also the primary determinant of reovirus-induced apoptosis. Inhibition of stimulus-induced activation of NF-kappaB also occurs following infection of primary cardiac myocytes with apoptotic (8B) but not non-apoptotic (T1L) reoviruses. Expression levels of the NF-kappaB-regulated cellular FLICE inhibitory protein (cFLIP) reflect NF-kappaB activation in reovirus-infected cells. Further, inhibition of NF-kappaB activity and cFLIP expression promote T1L-induced apoptosis. These results demonstrate that inhibition of stimulus-induced activation of NF-kappaB and the resulting decrease in cFLIP expression promote reovirus-induced apoptosis.

Apoptosis↗
PubMed2004

Expression of vascular endothelial growth factor D is associated with hypoxia inducible factor (HIF-1alpha) and the HIF-1alpha target gene DEC1, but not lymph node metastasis in primary human breast carcinomas.

BACKGROUND: Vascular endothelial growth factor D (VEGF-D) induces angiogenesis and lymphangiogenesis. Nodal metastasis is recognised as a powerful prognostic marker in breast carcinoma, but the molecular mechanisms underlying this process are unknown. Although it has been suggested that VEGF-D may regulate nodal metastasis, this is based largely on animal models, its role in human disease being unclear. AIMS: To measure the pattern and degree of VEGF-D protein expression in normal and neoplastic human breast tissues. METHODS: The pattern and degree of VEGF-D expression was measured in normal tissue and invasive carcinomas, and expression was correlated with clinicopathological parameters, hypoxia markers, and survival. Because other VEGF family members are affected by oestrogen, whether VEGF-D is regulated by oestrogen in breast cancer cell lines was also assessed. RESULTS: VEGF-D was significantly positively associated with hypoxia inducible factor (HIF-1alpha) (p = 0.03) and the HIF-1alpha regulated gene DEC1 (p = 0.001), but not lymph node status, the number of involved lymph nodes, patient age, tumour size, tumour grade, lymphovascular invasion, oestrogen receptor, progesterone receptor, c-erb-B2, or tumour histology (all p>0.05). There was no significant relation between tumour VEGF-D expression and relapse free (p = 0.78) or overall (p = 0.94) survival. VEGF-D expression was enhanced by oestrogen in MCF-7 and T47D breast cancer cells, and was blocked by hydroxytamoxifen. CONCLUSION: These findings support a role for hypoxia and oestrogen induced VEGF-D in human breast cancer and also suggest that tamoxifen and related oestrogen antagonists may exert some of their antitumour effects through the abrogation of VEGF-D induced function.

Breast Neoplasms↗
PubMed2001

Vascular endothelial growth factor-B and vascular endothelial growth factor-C expression in renal cell carcinomas: regulation by the von Hippel-Lindau gene and hypoxia.

Angiogenesis is essential for tumor growth and metastasis. It is regulated by numerous angiogenic factors, one of the most important being vascular endothelial growth factor (VEGF). Recently VEGF-B and VEGF-C, two new VEGF family members, have been identified that bind to the tyrosine kinase receptors flt-1 (VEGFR1), KDR (VEGFR2), and flt-4 (VEGFR3). Although the importance of VEGF-A has been shown in renal carcinomas, the contribution of these new ligands in kidney tumors is not clear. We have, therefore, measured the mRNA level of VEGF-B and VEGF-C together with their receptors by RNase protection assay (RPA) in 26 normal kidney samples and 45 renal cell cancers. We observed a significant up-regulation of VEGF-B (P = 0.002) but not VEGF-C (P = 0.3) in neoplastic kidney compared with normal tissues. In addition, although VEGF receptors were higher in tumors than normal kidney, there was a significant up-regulation of only flt-1 (P = 0.003) but not KDR (P = 0.12) or flt-4 (P = 0.09). There was also a significant correlation between VEGF-C and both of its receptors flt-4 (P = 0.006) and KDR (P = 0.03) but no association between VEGF-B and its receptor flt-1 (P = 0.23). A significant increase was observed in flt-1 (P < 0.001), KDR (P = 0.02), and flt-4 (P = 0.01) but not VEGF-B (P = 0.82) or VEGF-C (P = 0.52) expression in clear cell compared with chromophil (papillary) carcinomas. No significant association was demonstrated between VEGF-B, VEGF-C, flt-1, KDR, and flt-4 with patient sex, patient age, or tumor size (P > 0.05). The effect of von Hippel-Lindau (VHL) gene and hypoxia on VEGF-B and VEGF-C expression in the renal carcinoma cell line 786-0 transfected with wild-type and mutant VHL was determined by growing cells under 21% O2- and 0.1% O2. In wild-type VHL cells, whereas VEGF-A was significantly up-regulated under hypoxic compared with normoxic conditions (P < 0.001), expression of VEGF-C was reduced (P < 0.002). Nevertheless, the repression of VEGF-C was lost in mutant VHL cell lines under hypoxia. In contrast VEGF-B was not regulated by VHL despite clear up-regulation in vivo. These findings strongly support an enhanced role for this pathway in clear cell carcinomas by regulating angiogenesis and/or lymphangiogenesis. The study shows that clear cell tumors are able to up-regulate angiogenic growth factor receptors more efficiently than chromophil (papillary), that clear cell tumors can use pathways independent of VHL to regulate angiogenesis, and that this combined regulation may account for their more aggressive phenotype, which suggests that targeting VEGFR1 (flt-l) may be particularly effective in these tumor types.

Adenocarcinoma, Clear Cell↗
PubMed2001

VEGF-B expression in human primary breast cancers is associated with lymph node metastasis but not angiogenesis.

Angiogenesis is essential for tumour growth and metastasis. It is regulated by numerous angiogenic factors, one of the most important being vascular endothelial growth factor (VEGF). Recently VEGF-B, a new VEGF family member that binds to the tyrosine kinase receptor flt-1, has been identified. Although the importance of VEGF has been shown in many human tumour types, the contribution of VEGF-B to tumour neovascularization is unknown in any tumour type. This study therefore measured the mRNA level of VEGF-B and its receptor flt-1 by ribonuclease protection assay and the pattern of VEGF-B expression by immunohistochemistry in 13 normal breast samples and 68 invasive breast cancers. Flt-1 expression was significantly higher in tumours than in normal breast (p=0.02) but no significant difference was seen in VEGF-B between normal and neoplastic breast (p=0.3). There was a significant association between VEGF-B and node status (p=0.02) and the number of involved nodes (p=0.01), but not with age (p=0.7), size (p=0.6), oestrogen receptor (ER) (p=0.2), grade (p=0.5) or vascular invasion (p=0.16). No significant relationship was present between VEGF-B and flt-1 (p=0.2) or tumour vascularity (p=0.4). VEGF-B was expressed mostly in the cytoplasm of tumour cells, although occasional stromal components including fibroblasts and endothelial cells were also positive. No difference in VEGF-B expression was observed adjacent to regions of necrosis, in keeping with this VEGF family member not being hypoxically regulated. These findings suggest that VEGF-B may contribute to tumour progression by a non-angiogenic mechanism, possibly by increasing plasminogen activators and hence metastasis, as has been described in vitro. Measurement of VEGF-B together with other angiogenic factors may identify a poor prognostic patient group, which may benefit from anti-VEGF receptor therapy targeted to flt-1 (VEGFR1) as well as kdr (VEGFR2).

Adult↗
PubMed2001

Angiopoietin-1 is inversely related to thymidine phosphorylase expression in human breast cancer, indicating a role in vascular remodeling.

PURPOSE: Angiogenesis is essential for tumor growth and metastasis. It is a complex, dynamic process that is coordinated by several classes of angiogenic factors. One candidate family is the Tie2 tyrosine kinase, whose expression is restricted largely to endothelial cells. Tie2 has three known ligands, angiopoietin (Ang)-1, Ang-2, and Ang-4, that have different functional effects but play a requisite role in embryonic vessel remodeling. Because there are only limited data on the Tie2 pathway in human breast cancer, and our previous data have suggested that breast tumors establish a blood supply by vascular remodeling, we have investigated the expression of Ang-1, Ang-2, Ang-4, and Tie2 in a series of normal and neoplastic human breast tissues. EXPERIMENTAL DESIGN: We examined mRNA expression by reverse transcription-PCR in 6 normal and 52 malignant breast tissues and correlated expression with clinicopathological and angiogenic variables. We also examined the effect of physiological levels of estrogen on Ang expression. RESULTS: Ang-1, Ang-2, Ang-4, and Tie2 were detected in 19%, 52%, 35%, and 65%, respectively, of tumor samples. There was a significant reduction in expression of tumor Ang-1 (P = 0.04), Ang-2 (P = 0.01), Ang-4 (P = 0.004), and Tie2 (P = 0.02) compared with that in normal breast tissues. There was a significant relationship in tumors between all Angs and between each ligand and Tie2. In a multivariate analysis, there were significant positive correlations between Ang-4 and estrogen receptor (P = 0.016) and a significant inverse correlation between Ang-1 and thymidine phosphorylase expression (P = 0.01). No significant associations were observed between the other members of the Ang/Tie2 gene family and patient age, tumor size, lymph node status, tumor grade, vascular invasion, tumor vascularity, vascular maturation, thymidine phosphorylase, or vascular endothelial growth factor A expression (P > 0.05 for all). The potential regulation of Ang-4 by estrogen was further investigated in vitro. Addition of physiological concentrations of 17beta-estradiol (1 nM) to hormone-free media caused no significant change in Ang-4 mRNA abundance (P = 0.75) in the estrogen receptor-positive cell line MCF-7 after either 2 or 18 h, despite demonstrating induction for the estrogen response gene pS2. CONCLUSIONS: These findings suggest that the Ang/Tie2 pathway plays a significant role in human breast tumor angiogenesis but provide no initial evidence for direct regulation of the pathway by estrogen.

Angiopoietin-1↗
PubMed2000

Hemorrhagic lymphadenopathy as a presenting feature of primary al amyloidosis.

Lymphadenopathy associated with hemorrhage as a presenting feature of primary (AL) amyloidosis has not previously been described. We report two such cases one of whom had an acquired factor X and IX deficiency. The clinical presentations were characterized by sudden spontaneous enlargement of lymph nodes followed by partial regression. In both cases significant delay in diagnosis, and hence treatment, occurred due to the mode of presentation. One patient died with rapidly progressive disease but the other has had an excellent response to therapy with high-dose melphalan (HDM, 200 mg/m2) and peripheral blood stem cell rescue. AL amyloid should be considered in all patients presenting with hemorrhagic lymphadenopathy.

Adult↗
PubMed2000

The short form of the alternatively spliced flt-4 but not its ligand vascular endothelial growth factor C is related to lymph node metastasis in human breast cancers.

Angiogenesis is essential for tumor growth and metastasis. It is regulated by numerous angiogenic factors, one of the most important being vascular endothelial growth factor (VEGF). Recently, VEGF-C, a new VEGF family member, has been identified that binds to the tyrosine kinase receptors flt-4 [VEGF receptor (VEGFR) 3] and KDR (VEGFR2). Although the importance of VEGF has been shown in many human tumor types, the contribution of VEGF-C and its primary receptor flt-4 to tumor progression is less well understood. We have therefore measured the level of VEGF-C, flt-4, and KDR mRNA by RNase protection assay and the pattern of VEGF-C expression by immunohistochemistry in 11 normal breast tissue samples and 61 invasive breast cancers. No significant difference in VEGF-C expression was observed between normal and neoplastic breast tissues (P = 0.11). There was a significant correlation between VEGF-C and both flt-4 (P = 0.02) and KDR (P = 0.0002), but no association was seen between VEGF-C and either lymph node status (P = 0.66) or number of involved nodes (P = 0.88), patient age (P = 0.83), tumor size (P = 0.20), estrogen receptor status (P = 0.67), or tumor grade (P = 0.35). No significant relationship was present between VEGF-C and vascular invasion (P = 0.30), tumor vascularity (P = 0.21), VEGF-A (P = 0.62), or thymidine phosphorylase expression (P = 1.00). VEGF-C was expressed predominantly in the cytoplasm of tumor cells, although occasional stromal components including fibroblasts were also positive. We could demonstrate no association between lymph node metastasis and either VEGF-C (P = 0.66) or flt-4 (P = 0.4). However, we did observe a significant loss of the long but not the short isoform of flt-4 in tumors compared with normal tissues (P = 0.02 and P = 0.25, respectively), and this difference was largely accounted for by the reduction of long flt-4 in node-positive tumors. These findings strongly support a role for VEGF-C/flt-4 signaling in tumor growth by enhancement of angiogenesis and/or lymphangiogenesis and suggest that differential regulation of these processes may be controlled via flt-4 isoform transcription. They further suggest that the measurement of flt-4 isoform expression may identify a patient group that is likely to have node-positive disease and therefore benefit from additional treatment and also emphasize an additional ligand interaction that could be exploited by anti-VEGFR therapy.

Alternative Splicing↗
PubMed1998

Identification of a novel PTEN mutation (L139X) in a patient with Cowden disease and Sjögren's syndrome.

Cowden disease is an autosomal dominant disorder associated with an increased risk of breast, thyroid, and skin cancer in which germline mutations in a candidate tumour suppressor gene (PTEN) have been identified previously. Sjögren's syndrome is a chronic inflammatory and autoimmune disorder of exocrine glands for which the genetic basis is unknown. This report describes a novel PTEN mutation (L139X) in a patient with Cowden disease and Sjögren's syndrome. This observation raises the possibility of a link between mutations in the PTEN gene and Sjögren's syndrome.

Adult↗
PubMed1997

A sequential Bayesian algorithm for dose individualisation of carboplatin.

Carboplatin is associated with significantly less nephrotoxicity and neurotoxicity than is cisplatin. The dose-limiting toxicity of carboplatin is myelotoxicity. A number of dosing methods have been described that allow a value for the area under the concentration-time curve to be targeted on the basis of the patient's renal function. Recently a formalised analysis of the pharmacodynamic response to carboplatin revealed a therapeutic window in which the response rate was maximal and toxicity, tolerable. Optimal therapy would result from targeting this window in the individual patient. The aim of this study was to develop a Bayesian dose-individualisation method for carboplatin. The method involved (1) development of a high-performance liquid chromatography (HPLC) method to measure serum concentrations of carboplatin; (2) a pharmacokinetic study in 12 women receiving carboplatin for ovarian cancer to estimate the population pharmacokinetic values for this group of patients; (3) development of population models to describe the concentration-time course of carboplatin in serum along with associated errors; and (4) development of an algorithm that uses a sequential Bayesian design, which enables estimation of future doses of carboplatin on the basis of feedback from serum concentrations. The results of each of the stages were (1) the coefficient of variation of the assay was 6.3% within day and 8.4% between days (r2 = 0.9993), and the limit of detection was 0.25 mg/l; (2) Patients' ages ranged from 49 to 68 years, their weights varied from 46 to 85 kg, and their glomerular filtration rate ranged from 3.2 to 7.4 l/h. A geometric mean clearance (Cl) of 6.8 L/h and a steady-state volume of distribution (Vss) of 221 were estimated, which are similar to previously published data; (3) and a two-compartment model best described the data. Two error models were developed, the first describing the error associated with the assay and the second, the error of the two-compartment model, i.e. error due to individual variation in pharmacokinetics and error due to model mis-specification. Finally, (4) the development of a sequential Bayesian dose-individualisation method for carboplatin is described. To our knowledge, this is the first sequential design that has been used for dose individualisation of chemotherapy. The program is specific for carboplatin and operates independently of commercially available Bayesian software. Doses predicted by this program are being tested prospectively against conventional dosing methods.

Aged↗
PubMed1997

Hodgkin's cells express CD83, a dendritic cell lineage associated antigen.

Hodgkin's cells (HC) are considered to be the malignant cells of Hodgkin's disease (HD), but despite extensive studies, no conclusive evidence has emerged regarding their non-malignant counterpart and the ontogeny of these cells remains controversial. The analysis of a possible dendritic cell (DC) origin of HC has been hampered to date by the lack of a DC lineage specific marker. The expression of the two DC-associated antigens CD83 and CMRF-44, the B lymphocyte restricted molecule CD79, and the costimulator molecule CD86, was examined in lymph nodes from 23 HD patients using immunohistological techniques. The majority of HC expressed the CD83 (22/23) and CD86 antigens (20/23), whereas expression of the CMRF-44 antigen was variable (10/23) and usually only a subpopulation of HC stained. In contrast, the CD79 antigen was absent from most HC (17/23). The presence of the CD83 antigen on HC in the absence of the CD79 antigen supports a possible DC lineage origin for some HC. Regardless of its role in lineage assignment, CD83 may become a useful immunohistological marker for HD as the CD83 antigen was present on most HC.

Antibodies, Monoclonal↗
PubMed1997

Clinical pharmacokinetics and dose optimisation of carboplatin.

Carboplatin shares some of the therapeutic advantages of cisplatin, but without a significant incidence of the dose-limiting neurotoxicity and nephrotoxicity which is experienced with cisplatin. However, its use is associated with dose-limiting bone marrow suppression. Carboplatin is present in the blood as 3 distinct species. These are total platinum and 2 unbound species, carboplatin itself and a decarboxylated platinum-containing degradation product. The 2 main methods used to assay the unbound species are flameless atomic absorption spectrophotometry and high performance liquid chromatography. The first of these methods assays both unbound platinum species, the second is specific for carboplatin. Both unbound species have similar pharmacokinetic profiles for the first 12 hours post-dose. Carboplatin appears to have a linear pharmacokinetic profile over the doses used clinically and does not interact significantly with drugs that are used commonly in combination chemotherapy. The pharmacokinetics of carboplatin are adequately described by an open 2-compartment model with elimination from the central compartment. Its clearance is proportional to the glomerular filtration rate and the volume of distribution of the central compartment appears to correlate with extracellular fluid volume. The elimination half-life varies with renal function and is typically between 2 and 6 hours in patients with a normal glomerular filtration rate and may be as long as 18 hours in patients with impaired renal function. Relationships between systemic exposure to carboplatin, described as the area under the concentration-time curve (AUC), and both toxicity and response have been described. For toxicity the strongest evidence exists for a relationship between AUC and thrombocytopenia. To a lesser extent the relationship between AUC and neutropenia has also been described. Patients already treated with platinum analogues have been shown to develop a greater degree of myelosuppression from any given AUC. In addition, some evidence suggests a relationship between the shape of the concentration-time curve and myelotoxicity, where constant infusions appear less likely to cause myelosuppression on a mg/m2 dose administration basis. The relationship between AUC and response rate is not as clear, this may be related to the lack of studies describing both the dose and AUC of carboplatin. There appears to be a more clearly defined AUC-response relationship for ovarian cancer than for other malignancies, with an AUC of between 5 and 7 mg/ml.min being associated with the maximal response rate [located at the plateau on an AUC-response curve]. However, new data suggest that higher AUCs may lead to greater response rates. Data from testicular cancer also strongly supports an AUC-response relationship with an increased number of treatment failures with carboplatin AUCs < 5 to 6 mg/ml.min. Given the AUC-effect relationships described above a number of studies have been performed to develop models to describe the relationship between both dose and AUC and dose and platelet nadir. In adults, perhaps the most common method is that of Calvert which describes the relationship between dose and AUC. Paediatric formulas have also been described. More recently a number of limited sampling strategies have been proposed as well as Bayesian dose individualisation techniques.

Adult↗
PubMed1995

Quarantine requirements for the importation of black rhinoceros from Zimbabwe into Australia.

The proposal by the Zoological Parks Board of New South Wales to import 10 southern black rhinoceros (Diceros bicornis) from Zimbabwe as part of an international project for conservation of the species presented the Australian Quarantine and Inspection Service (AQIS) with a unique challenge. This importation is, at least in the modern era, the first importation of live herbivores from the African continent. Many of the serious animal diseases in the world are endemic in parts of Africa. Knowledge of which of these diseases infect wild species and may be transmitted from the wild species to domesticated species, is limited. This paper describes the strategies adopted by AQIS to facilitate the importation of rhinoceros while maintaining protection of Australian consumers, rural industries, domestic livestock and fauna against the entry and spread of unwanted pests and diseases.

African Horse Sickness↗
PubMed1994

Second malignant neoplasms in patients with Hodgkin's disease.

AIM: To determine the incidence of second malignant neoplasms in patients treated for Hodgkin's disease. METHODS: The records were reviewed of all patients receiving primary treatment for Hodgkin's disease at the Oncology Service, Christchurch Hospital from 1969 to 1992. Second malignant neoplasms presenting at least six months after the diagnosis of Hodgkin's disease were noted and the cumulative risk estimated. RESULTS: Twenty-two second malignant neoplasms developed in 20 of the 209 patients. The risk was 5.6 +/- 3.8% (CI) at five years, 11.4 +/- 6.2% at ten years, and 21.7 +/- 11.2% at 15 years and continued to increase thereafter. Thirteen patients have died of their second malignancy, including two of a third malignancy, while four have been followed for less than one year. Three leukaemias (CML, 1; acute non lymphocytic leukaemia, 2), three lymphomas and 16 solid tumours developed. The risk was greater after six or more cycles of MOPP-like chemotherapy and after radiation doses exceeding 30 Gray. The risk was less after laparotomy and splenectomy (p = 0.0205). CONCLUSIONS: In view of the significant risk of a second neoplasm in survivors of Hodgkin's disease follow up should continue beyond ten years, after which time second malignancies were more likely than recurrence. Efforts should continue to minimise the carcinogenicity of therapy while preserving efficacy.

Adolescent↗
PubMed1993

Interactions of human immunodeficiency virus infection and pregnancy.

OBJECTIVE: To assess the influence of human immunodeficiency virus (HIV) infection on pregnancy outcome and the effect of pregnancy on the short-term course of HIV infection. METHODS: Pregnant women with identified risk factors for HIV infection but without AIDS were tested serologically for HIV antibodies. Seropositive women were compared to seronegative patients with similar risk factors and demographic characteristics at enrollment, at delivery, and 6-8 weeks postpartum. One hundred one seropositive and 97 seronegative subjects were evaluated for symptoms or physical manifestations of HIV infection; evidence of immune dysfunction; historical, physical, or laboratory evidence of related infections; and maternal and neonatal outcome. Both groups were compared to the entire obstetric population delivering at the University of Maryland Hospital during 1 year. RESULTS: There was a significant reduction in reported risk behaviors in both groups during pregnancy as compared to the period before pregnancy (P < .001). The majority of women in both groups were asymptomatic, but seropositive women were more likely to have a history or physical evidence of condylomata (13 versus 4%; P < .05) and higher temperatures on admission to the labor suite (98.6 +/- 1.0 versus 98.3 +/- 0.8F; P = .02). Seropositive women were not at greater risk for antepartum medical complications. Only one woman developed an AIDS-defining opportunistic infection. Although hematologic indices in seropositive women were abnormal, these did not progress over the course of pregnancy. At delivery, seropositive women were more likely to receive antibiotics (25 versus 10%; P = .006) and less likely to have an episiotomy (25 versus 40%; P = .03), but obstetric outcome was unaffected. Neonatal status was independent of antibody status. CONCLUSION: Our findings support a growing body of evidence that pregnancy has no discernible effect on the early progression of HIV disease in asymptomatic women, and infection does not influence perinatal outcome.

Adult↗
PubMed1992

Ondansetron antiemetic therapy for chemotherapy and radiotherapy induced vomiting in children.

AIM: To evaluate ondansetron as the sole antiemetic in children treated with emetogenic chemotherapy and irradiation. METHODS: Fifteen children aged 3-11 years were studied. Seven had acute lymphoblastic leukaemia, two acute myeloid leukaemia, two lymphoma and four had other tumours. Ondansetron 5 mg/m2 IV or 4 mg by mouth was given immediately before chemotherapy or radiation treatment and continued eight hourly for 24 hours. Nausea and vomiting was assessed during treatment and for the next 48 hours, and graded using WHO criteria. RESULTS: Thirty-eight courses of chemotherapy were assessed, 27 severely emetogenic and 11 moderately emetogenic. Two included total body irradiation. The most severe nausea and vomiting was grade 2 (transient vomiting) reported in six children. Nausea and vomiting was abolished on subsequent courses in four of these children by increasing the ondansetron dose frequency to six hourly. The remaining children experienced no nausea or vomiting (n = 7) or only nausea (n = 2). Nausea and vomiting were each completely controlled in 27 courses. CONCLUSIONS: Ondansetron is a cost effective and safe antiemetic in children receiving chemotherapy and total body irradiation, minimises weight loss on treatment and enables outpatient chemotherapy in some cases.

Child↗