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N Duncan

Publications and source records attributed to N Duncan.

At least 19 recordsLinked to original sources
PubMed2006

Optimizing the use of cyclosporin in allogeneic stem cell transplantation.

Cyclosporin remains the most widely used immunosuppressive agent in patients undergoing allogeneic stem cell transplantation (SCT). The increased awareness of the impact of the intensity of post-transplant immunosuppression on determining outcome after allogeneic SCT has resulted in a re-examination of whether cyclosporin is currently being optimally used in this population of patients. Recent studies in solid organ transplantation have questioned whether the use of trough levels provides the most accurate reflection of the immunosuppressive actions of cyclosporin and alternative strategies to monitor cyclosporin dosage after liver and kidney transplantation are increasingly being used. As a result there is now interest in examining whether there is scope for translating these advances into the arena of haematopoietic transplantation. In this paper, we will review the rationale underlying the current schedules for dosing and monitoring cyclosporin after allogeneic SCT and identify specific areas in which the use of cyclosporin requires re-evaluation. These include evaluation of whether patient outcome would be improved by using peak cyclosporin levels to determine dosing schedules, analysis of optimal cyclosporin dosing schedules in patients undergoing reduced intensity allografts and investigation of surrogate markers of cyclosporin's immunosuppressive activity.

Cyclosporine↗
PubMed2005

Rituximab is effective in the management of refractory autoimmune cytopenias occurring after allogeneic stem cell transplantation.

Autoimmune haemolytic anaemia (AIHA), immune thrombocytopenia (ITP) and autoimmune neutropenia (AIN) are well-recognised complications of allogeneic stem cell transplantation (SCT), but have previously only been reported in the context of myeloablative conditioning regimens. Management of AIHA, ITP or AIN occurring after allogeneic SCT is unsatisfactory since they frequently prove refractory to conventional therapies including splenectomy. As a consequence, autoimmune cytopenias occurring after allogeneic SCT are associated with substantial morbidity and mortality. We report four patients who developed AIHA or ITP after allogeneic transplantation -- three of which occurred after a reduced-intensity conditioning (RIC) regimen. All patients demonstrated a complete response to Rituximab, having failed to respond to conventional treatment including high-dose prednisolone and intravenous immunoglobulin (IVIg). We conclude that Rituximab can be a valuable agent in the management of autoimmune cytopenias occurring after allogeneic SCT and that autoimmune cytopenias may be a hitherto unrecognised complication of RIC regimens.

Adult↗
PubMed2005

Post-anaesthetic myelomalacia in a horse.

This article describes a rare neurological complication of anaesthesia in a 2 year-old Clydesdale colt undergoing castration. Anaesthesia was induced with glyceryl guaiacol ether and ketamine and maintained with halothane. Following an uneventful anaesthetic of 40 minutes, the horse recovered from anaesthesia in a padded recovery stall. After approximately 70 minutes in the recovery stall, the horse attempted to stand and adopted a dog sitting position. One hundred and fifty minutes later, the horse became distressed and was sedated with xylazine. Clinical examination of the horse did not reveal any evidence of myositis or fractures. A neurological examination revealed an intact anal reflex, deep pain response in the hind legs, tail tone and voluntary movement of the hind legs was possible. The horse deteriorated neurologically over the next 24 hours and was euthanased on humane grounds. The horse was submitted for necropsy. Gross pathology was unremarkable except for a small amount of haemorrhage around the right kidney. Histopathology revealed no abnormalities in any muscle groups or peripheral nerves. Congestion and axonal swelling of the spinal cord was evident from T16 to S1. Ischaemic neurons were evident from L 1 to L 6. The most prominent lesions were at L4 and L5. A diagnosis of myelomalacia was made. This is a rare complication of anaesthesia in horses with 9 case studies appearing in the literature since 1979. This is the 1st case to be reported in South Africa. The speculated pathophysiology and risk factors for this complication are discussed.

Anesthesia, General↗
PubMed2004

Phylogeographical patterns in the American Pacific Northwest: lessons from the arionid slug Prophysaon coeruleum.

Some of the earliest studies of phylogenetic concordance involve native plants from the Pacific Northwest where many taxa showed clear genetic breaks between southern and northern populations. To test whether similar breaks also occur in invertebrate species with low dispersal capacities, genetic data from two mitochondrial genes are assembled for individuals of the arionid slug Prophysaon coeruleum throughout the species' range. Bayesian inference revealed three major clades and a total of eight subclades. It is argued that the demographic and genealogical past of P. coeruleum has resulted in a deep and shallow phylogeographical structure. The deep structure is at least 2.6-5.9 million years old and therefore clearly predates the Pleistocene period. Superimposed on this structure is a shallow structure that is most likely less than 2 million years old and probably the result of Pleistocene perturbations. Molecular analyses revealed that the three known colour traits in P. coeruleum do not represent monophyletic groups and that they do not match the patterns of genetic structure found. It is argued that the colour traits are perhaps a response to different levels of UV-radiation. The study adds to the increasing evidence that the phylogeographical structure of some taxa is more complex than previously thought. Moreover, it shows that genealogical concordance should not be deduced from phylogeographical patterns alone but should be based on an understanding of timing and causes of historical processes that lead to those patterns.

Analysis of Variance↗
PubMed2003

Stem cell transplantation after salvage therapy with high-dose cytarabine and amsacrine in adults with high-risk leukaemia.

Stem cell transplantation (SCT) may be the only curative option for patients with relapsed or refractory leukaemia, that is, high-risk (HR) leukaemia. Several salvage regimens have been used to cytoreduce disease before SCT, but disease progression or treatment toxicity limits numbers of patients receiving SCT. Here, we report our experience with high-dose cytarabine and amsacrine (Ara-amsa) to salvage patients with HR-leukaemia in the context of SCT. A total of 34 patients with HR-leukaemia (20 AML, 12 ALL, two advanced CML) received 3 g/m(2)/day cytarabine for 5 days and amsacrine 200 mg/m(2)/day for 3 days. Disease response was observed in 62% of patients. Toxicity was limited to neutropenic fever, one patient developed cerebellar toxicity and there was one treatment-related death. A total of 17 patients proceeded to SCT (12 allografts and five autografts). Median survival (OS) of all patients was 10.8 months (95% CI 7.8-21). Patients who were consolidated with SCT after salvage therapy had a superior median OS of 29.4 months (95% CI 12.5-upper limit not reached, n=17) than those who did not receive SCT (6.7 months, CI 1.5-8.6, P<0.0001). Median disease-free survival with SCT (23 months) was higher than after treatment with salvage chemotherapy alone (6.7 months, P=0.0002). Thus Ara-amsa can be used effectively to salvage HR-leukaemia, enabling further consolidation with SCT.

Adolescent↗
PubMed2002

Recovery of renal function after autologous stem cell transplantation in myeloma patients with end-stage renal failure.

The disease-free survival of patients with myeloma and severe renal failure after high-dose melphalan and autologous stem cell rescue is similar to those with normal renal function at the time of the autograft. However, recovery of renal function after intensive treatment is uncommon and patients with end-stage renal failure continue to be dialysis-dependent. We report two patients with myeloma who required regular haemodialysis from diagnosis, but became dialysis-independent after a high-dose melphalan autograft. Thus, in some patients, renal function may be partially salvageable despite the requirement for dialysis at the time of autografting.

Disease-Free Survival↗
PubMed2001

Peracute vanadium toxicity in cattle grazing near a vanadium mine.

Animals may act as bioindicators for potential human health problems associated with mining and refining. Eight cattle died after a vanadium mine dam collapsed close to the area in which they were grazing. Necropsies were conducted on five cattle. Affected animals had shown a watery bloody diarrhea, red urine and listlessness before collapsing. On necropsy (n = 5) there was a moderate bilateral multifocal granulomatous-like conjunctivitis. The most prominent lesions were eosinophillic granulomatous-like inflammation of the thymus, mediastinal and mesenteric lymph nodes, oesophagus, abomasum and colon. There was also marked hyperaemia of the abomasal mucosa with petechiation. Pulmonary and tracheal haemorrhage was also present. Histopathology showed severe inflammatory cell infiltration (mainly eosinophils with lesser numbers of neutrophils and macrophages) of lymphoid tissue associated with the thymus, lymph nodes, esophagus, abomasum, colon and conjunctiva. There were also areas of tissue necrosis, congested blood vessels and haemorrhage. Conjunctival lesions point to a systemic rather than a local effect as the cattle in this case died following ingestion rather than inhalation of vanadium. The causal relationship between intoxication and death is conventionally based on the level of that toxin present in tissues at necropsy. The variability in demonstrating vanadium in biological samples may have been due to the rapid excretion of vanadium by the living animal, or the solubility of the salts, which results in the substance leaching into the fluid portion of the samples. Cross-reactions with colorimetric tests for arsenic should also be noted.

Animals↗
PubMed1997

Balance in children with otitis media with effusion.

To determine the presence of balance disorders in young children who had otitis media with effusion (OME), 25 subjects, aged 13-57 months, diagnosed by pediatric otolaryngologists, were tested on the gross motor subtest of the Peabody Developmental Motor Scales, a standardized test of motor development with established norms. Parents also filled out questionnaires about their children's balance skills. Subjects with unilateral disease did not differ significantly from normals. Subjects with bilateral disease, however, were significantly impaired compared to normals on balance, locomotion and total score and they were significantly impaired compared to unilateral subjects on all scores. Parental perceptions of their children's balance correlated poorly with the test results. These data suggest that young children with bilateral otitis media with effusion are delayed in developing motor skills that require dynamic balance. Therefore, in spite of a negative history for balance problems physicians should consider balance performance when developing a treatment plan. Children with balance impairments might benefit from more aggressive intervention.

Child, Preschool↗
PubMed1997

An economic evaluation of the use of granulocyte colony-stimulating factor after bone marrow transplantation in children.

Studies that have assessed the use of granulocyte colony-stimulating factor (G-CSF) following bone marrow transplantation have shown a significantly reduced time to neutrophil recovery with the use of this agent, which may translate into a reduced duration of antimicrobial therapy and hospitalisation. We performed a pharmacoeconomic study evaluating the elective use of G-CSF after bone marrow transplantation in children. 22 consecutive children who underwent bone marrow transplantation and received G-CSF 5 micrograms/kg/day were compared with 18 such children (control group) who did not receive G-CSF. Despite a significant reduction in time to recovery of the absolute neutrophil count (ANC) to > 0.5 x 10(9)/L in G-CSF recipients compared with the control group (14 days vs 20.9 days; p < 0.0001), there was only a trend towards a reduction in the duration of intravenous antimicrobial therapy (14.5 days vs 18.6 days; p = 0.15), and there was no significant difference in the duration of hospitalisation (25.3 days vs 29.8 days). Reasons for prolonged hospitalisation beyond ANC recovery included continued use of total parenteral nutrition, treatment of graft-versus-host disease and treatment of ongoing infection. Overall, the mean total cost for patients receiving G-CSF was Pounds 15001, compared with Pounds 15482 for the control group (1995 values). In conclusion, while there appears to be no benefit in financial terms, the release of a child from strict isolation as a result of early ANC recovery must be taken into consideration.

Bone Marrow Transplantation↗
PubMed1996

Antimicrobial practice. Development of guidelines for gentamicin dosing.

The performance of dosage guidelines for starting gentamicin therapy was evaluated prospectively in 50 patients with suspected or proven Gram-negative septicaemia and the results were compared with results from similar group of 50 patients for whom the guidelines were not followed. Peak concentrations were significantly higher when the guidelines were followed (7.2 (+/- 1.9) mg/L vs 5.7 (+/- 1.8) mg/L) but there was no difference in trough concentrations. Fifty-eight per cent of patients had both peak and trough concentrations within the target range (peak > 5 mg/L, trough < 2 mg/L) when doses were decided empirically; this increased to 96% when the guidelines were followed. However, use of the guidelines achieved peaks of > 7 mg/L in only 56% of patients. A revised protocol with higher doses given less frequently was therefore developed and a prospective assessment of its performance indicated that satisfactory concentrations were obtained in 96% of patients.

Anti-Bacterial Agents↗
PubMed1996

An economic evaluation of peripheral blood stem cell transplantation as an alternative to autologous bone marrow transplantation in multiple myeloma.

Autologous peripheral blood stem cell transplantation (PBSCT) is increasingly being utilised as an alternative to autologous bone marrow transplantation (ABMT) in the treatment of malignant diseases. We have performed a pharmacoeconomic study using cost-minimisation analysis to evaluate the two techniques in a population of multiple myeloma patients undergoing PBSCT (n = 37) or ABMT (n = 14). In the PBSCT group, the time to > 0.5 x 10(9)/l neutrophils was significantly shorter (16 vs 22 days; P = 0.0019) as was the time to > 50 x 10(9)/l platelets (19 vs 27 days; P = 0.0019). The faster haematopoietic recovery resulted in a reduced period of intravenous antibiotic therapy (12 vs 19 days; P < 0.0001), reduced requirements for platelet transfusions (12 vs 31.5 units; P = 0.0005), and ultimately, a significant reduction in duration of hospitalisation (19 vs 27.5 days; P < 0.0001). These clinical benefits translated into economic benefits such that the total cost in the PBSCT group was 27.5% less than in the ABMT group (< Pounds 7995 vs < Pounds 11026; P = 0.0001). We conclude that the use of PBSCT as an alternative to ABMT in patients with multiple myeloma is associated with demonstrable economic advantages in addition to clinical benefits.

Adult↗
PubMed1995

C-9 and N-substituted analogs of cis-(3aR)-(-)-2,3,3a,4,5,9b-hexahydro-3- propyl-1H-benz[e]indole-9-carboxamide: 5-HT1A receptor agonists with various degrees of metabolic stability.

Closely related analogs of the 5-HT1A receptor agonist cis-(3aR)-(-)-2,3,3a,4,5,9b-hexahydro-3-propyl-1H-benz[e]indole-9- carboxamide (1, U93385) were synthesized and pharmacologically evaluated. 9-Carboxamide analogs with varied nitrogen substitution (R2) were synthesized, and their serotonergic activity was evaluated in vitro and in vivo. Many of these compounds were incubated in the presence of rat hepatocytes, and the metabolic stability in vitro was compared to that of compound 1. Only the N-methyl and N-ethyl analogs ((-)-5a and (-)-5b) were more stable than compound 1, indicating that N-dealkylation is a major route of metabolism in this series. In addition, these analogs were found to be partial 5-HT1A receptor agonists in vivo. Modifications were also made to the carboxamide functionality of compound 1 (R1 in 2) to yield substituted amides or ketones. Among these analogs, the methyl ketone (-)-15a was found to be a 5-HT1A agonist with full intrinsic activity in vivo and was approximately 20 times more potent than compound 1 and 5 times more potent than 8-OH-DPAT.

Animals↗