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Biomedical subjects

A Duncan

Publications and source records attributed to A Duncan.

At least 37 records · Page 2Linked to original sources

Homocysteine levels in healthy New Zealanders and those with vascular disease.

AIMS: Levels of plasma homocysteine (tHcy) have been shown to vary between populations. The aim of the present study was to determine tHcy levels in a New Zealand population to facilitate interpretation of international reference ranges. METHODS: Fasting tHcy levels were determined in 431 volunteer men and women, aged between 17 and 83 years, from the greater Otago region. Subjects with self-reported incidences of vascular disease (n=138) were compared with healthy control subjects (n=293). RESULTS: Mean (SD) fasting tHcy level of the entire population was 8.3(3.5) micromol/L and men had significantly higher levels than women (9.0(3.4) and 7.8(3.5) micromol/L, respectively, p<0.05). Levels increased significantly with increasing age (0.5 micromol/L for every ten years). There was a small but non-significant difference in tHcy levels between subjects with and without vascular disease (difference after excluding two outliers and adjusting for age and gender; 0.63, 95% CI, -0.03,1.29). tHcy levels were not significantly correlated with lipid or lipoprotein levels. CONCLUSION: Levels of tHcy in a group of volunteers from the greater Otago region were similar to those reported in other populations at high risk of cardiovascular disease. Reference ranges derived from these populations would appear to be applicable for New Zealanders. tHcy measurements should be made when assessing individuals at high risk of vascular disease and intervention strategies considered.

Adolescent↗

Statistical mechanics of charged polymers in electrolyte solutions: a lattice field theory approach.

The lattice field theory approach to the statistical mechanics of a classical Coulomb gas [R.D. Coalson and A. Duncan, J. Chem. Phys. 97, 5653 (1992)] is generalized to include charged polymer chains. Saddle-point analysis is done on the functional integral representing the partition function of the full system. Mean-field level analysis requires extremization of a real-valued functional which possesses a single minimum, thus guaranteeing a unique solution. The full mean-field equations for such a coupled system are derived, as well as the leading (one-loop) fluctuation corrections. Two different numerical real-space lattice procedures are developed to implement the generalized theory; these are applied to the problem of a charged polymer confined to a spherical cavity in an electrolyte solution. The results provide insight into the physics of confined polyelectrolytes.

Journal Article↗

Scleromyxedema: a complete response to prednisone.

Scleromyxedema is a disorder characterized by a typical rash due to the accumulation of mucin in the dermis. It is always associated with a monoclonal protein in the serum and can have a wide variety of systemic manifestations. We describe a 40-year-old woman who had scleromyxedema associated with a monoclonal G lambda protein. Severe systemic symptoms included fatigue, esophageal dysmotility, and myopathy. Symptoms resolved completely with oral prednisone therapy, and she remained in clinical remission 24 months after use of prednisone was discontinued. Scleromyxedema is commonly treated with alkylating agents, which have been associated with pronounced morbidity and mortality. We suggest that oral corticosteroid therapy may be a reasonable initial choice for treating this disease and that alkylating agents be reserved for corticosteroid-refractory disease.

Adult↗

Cells expressing the NG2 antigen contact nodes of Ranvier in adult CNS white matter.

The NG2 antibody, which recognises an integral membrane chondroitin sulphate, labels a significant population of cells in adult CNS white matter tracts of the rat optic nerve and anterior medullary velum (AMV). Adult NG2+ cells are highly complex with multiple branching processes and we show by EM immunocytochemistry that they extend perinodal processes, which contact nodes of Ranvier. NG2+ cells do not react to conventional immunohistochemical markers for adult glia and so we reservedly term them NG2P cells. In vitro, NG2 labels oligodendrocyte-type-2 astrocyte (O-2A) progenitors that can give rise to oligodendrocytes or type-2 astrocytes, depending on the culture medium. Thus, it is possible that NG2P cells may be derived from the same stem cells as oligodendrocytes. Interestingly, NG2+ cells identified previously in adult CNS displayed phenotypic characteristics of O-2Aadult progenitors and it is possible that, like them, NG2P cells might retain the capacity of generating oligodendrocytes in the adult CNS. This may be an important role of NG2P cells in demyelinating diseases such as multiple sclerosis. It is significant therefore that the perinodal processes of NG2P cells contact the only sites of exposed axolemma in myelinated axons, so that NG2P cells are ideally situated to detect and respond to changes in axonal function during demyelination. A further implication of our finding is that NG2P cells may perform functions at nodes of Ranvier previously attributed to perinodal astrocytes, including the clustering and maintenance of sodium channels in the axon membrane at nodes, during development and following demyelination.

Animals↗

Effects of variations in live weight gain on bone growth and composition and on markers of bone turnover in lambs.

Growing lambs were fed the same diet at intakes supporting mean live weight gains of 0.1, 0.2 and 0.3 kg day-1, representing slow, intermediate and fast growth groups, respectively. The effects on bone growth and composition, and on blood and urinary bone marker concentrations or excretion rates were monitored. Compared with the slow-growing lambs, the higher intake group grew twice as fast, had higher rates of bone growth (indicated by external metatarsal length), and larger and heavier bones at slaughter. Bones from fast-growing animals had higher collagen and deoxypyridinoline concentrations, and lower Ca:collagen, Ca :P and pyridinoline : deoxypyridinoline ratios, indicating a less mature bone compared with the slow-growing lambs. Bone growth rate had no effect on plasma osteocalcin, bone-specific alkaline phosphatase or growth hormone concentrations, nor on the urinary excretion of pyridinoline and deoxypyridinoline. The results for plasma markers may be explained by an increase in blood volume linked with increased body weight.

Alkaline Phosphatase↗

Axon-glial relations during regeneration of axons in the adult rat anterior medullary velum.

The anterior medullary velum (AMV) of adult Wistar rats was lesioned in the midsagittal plane, transecting all decussating axons including those of the central projection of the IVth nerve. At selected times up to 200 days after transection, the degenerative and regenerative responses of axons and glia were analyzed using transmission and scanning electron microscopy and immunohistochemistry. In particular, both the capacity of oligodendrocytes to remyelinate regenerated fibers and the stability of the CNS/PNS junctional zone of the IVth nerve rootlet were documented. Transected central AMV axons exhibited four patterns of fiber regeneration in which fibers grew: rostrocaudally in the reactive paralesion neuropil (Group 1); randomly within the AMV (Group 2); into the ipsilateral IVth nerve rootlet, after turning at the lesion edge and growing recurrently through the old degenerated contralateral central trochlear nerve trajectory (Group 3); and ectopically through paralesion tears in the ependyma onto the surface of the IVth ventricle (Group 4). Group 1-3 axons regenerated unperturbed through degenerating central myelin, reactive astrocytes, oligodendrocytes, microglia, and large accumulations of hematogenous macrophages. Only Group 3 axons survived long term in significant numbers, and all became myelinated by oligodendrocytes, ultimately establishing thin sheaths with relatively normal nodal gaps and intersegmental myelin sheath lengths. Schwann cells at the CNS/PNS junction of the IVth nerve rootlet did not invade the CNS, but astrocyte processes grew across the junction into the PNS portion of the IVth nerve. The basal lamina of the junctional glia limitans remained stable throughout the experimental period.

Animals↗

A diet rich in walnuts favourably influences plasma fatty acid profile in moderately hyperlipidaemic subjects.

OBJECTIVE: To compare two low fat diets one rich in walnuts on parameters of lipid metabolism in a group of hyperlipidaemic subjects. DESIGN: A randomised cross over study. SETTING: Department of Human Nutrition, University of Otago, Dunedin, New Zealand SUBJECTS: Twenty one men with mean (s.d.) levels of total and LDL cholesterol of 6.58 (0.60) and 4.63 (0.58) respectively. INTERVENTIONS: For two periods of four weeks subjects were asked to consume two low fat diets (fat 30% total energy), one containing, on average, 78 g/d walnuts. Walnuts obtained through Lincoln University and the Walnut Growers Group (South Canterbury). RESULTS: Participants reported a higher total fat intake on the walnut diet (38% compared with 30% on the low fat diet P < 0.01) The most consistent change in fatty acid profile of triacylglycerol, phospholipid and cholesterol ester on the walnut diet was a significant (P < 0.01) increase in linoleic acid. Triacylglycerol linolenate also increased significantly (P < 0.01). Total and LDL cholesterol were lower on both experimental diets than at baseline, 0.25 mmol/l and 0.36 mmol/l respectively on the walnut diet and 0.13 mmol/l and 0.20 mmol/l respectively on the low fat diet. High density lipoprotein cholesterol was higher on both the walnut and low fat diets when compared to baseline (0.15 mmol/l and 0.12 mmol/l, respectively). When comparing the walnut and low fat diets only apo B was significantly lower (P < 0.05) on the walnut diet. CONCLUSIONS: Despite an unintended increase in the total fat intake on the walnut diet, fatty acid profile of the major lipid fractions showed changes which might be expected to reduce risk of cardiovascular disease. The reduction of apolipoprotein B suggests a reduction in lipoprotein mediated risk, the relatively low myristic acid content of both diets perhaps explaining the absence of more extensive differences in lipoprotein levels on the two diets.

Adult↗

Clonidine poisoning--an emerging problem: epidemiology, clinical features, management and preventative strategies.

OBJECTIVE: To ascertain whether the incidence of clonidine poisoning in children has increased given the probable increase in clonidine use for treatment of childhood behavioural disorders. METHODS: Cases of clonidine poisoning requiring hospital admission between 1985-95 inclusive were reviewed and demographic data pertinent to each admission were recorded. A literature review was also performed, with particular emphasis on incidence, clinical presentation and management of clonidine poisoning. RESULTS: There were 14 cases of clonidine poisoning during the specified period eight cases presenting in the last 2 years. These eight children or their siblings had been prescribed clonidine for behavioural disorders. The most common signs at presentation were alteration of conscious state (71%) and bradycardia (50%). Nine children were given activated charcoal while seven cases underwent gastric lavage or induced emesis. Although six children were admitted to intensive care, length of hospital stay was less than 24 h in all cases and all had a favourable outcome. CONCLUSION: We concluded that the incidence of clonidine poisoning had increased over the specified period and that, based on our results, this was likely to be due to an increase in clonidine use in childhood behavioural disorders. Based on our data and that from literature review it was evident that there are inconsistencies in the management of clonidine poisoning and that safety measures, namely packaging and education, are inadequate given the increasing profile of clonidine use.

Attention Deficit Disorder with Hyperactivity↗

Effects of variations in dietary calcium and phosphorus supply on plasma and bone osteocalcin concentrations and bone mineralization in growing pigs.

Growing pigs were fed diets supplying 45% (low), 70% (intermediate) and 100% (high) recommended dietary allowances of calcium (the Ca:P ratio was kept constant), but otherwise adequate in nutrients. The effects of varying calcium and phosphorus intakes on bone and plasma osteocalcin were monitored. Mineral content of the diet did not affect feed conversion and live weight gain. Plasma phosphorus concentrations decreased significantly in pigs fed a low mineral diet compared with those fed the high mineral diet, but there were no changes in plasma calcium and osteocalcin concentrations. Bones from the low mineral group had marked reductions in dry matter, calcium and phosphorus contents, as well as increased collagen, pyridinoline and deoxypyridinoline concentrations: osteocalcin concentrations in bone were unaffected by treatment. The results showed no direct link between osteocalcin and the degree of bone mineralization.

Animals↗

A UK survey of laboratory-based gastrointestinal investigations.

A survey of hospital laboratory services has demonstrated marked deficiencies in the performance of gastrointestinal function tests. The repertoire of gastrointestinal investigations available varies widely between laboratories and, in general, analyses are performed infrequently. Most laboratories do not perform internal quality control, and inter-laboratory reproducibility of some analytes is very poor. A wide variety of protocols and reference ranges are in use, many of which are unevaluated. Some analytical methods and protocols in current use are outdated, with published improvements not being applied.

Diagnostic Techniques, Digestive System↗

Randomized trial to evaluate the clinical benefits of serum alpha-glutathione S-transferase concentration monitoring after liver transplantation.

BACKGROUND: An increase in serum alpha-glutathione S-transferase concentration (GST) has been shown to be a more sensitive and specific marker of hepatocellular damage than equivalent increases in transaminase activities. A randomized clinical trial of 60 liver transplants in 49 patients was carried out to assess the clinical benefits of GST monitoring as a supplementary test to routine liver function tests during the first 3 postoperative months after liver transplantation. METHODS: Mortality and morbidity were compared in graft recipients who had their GST reported daily to the ward (reporting group) and graft recipients who did not. RESULTS: The 3-month survival rate was significantly greater in the reporting group (P=0.033) and the risk of graft loss was halved (relative hazard ratio=0.50; P=0.29). The reporting group also had significantly more patients who spent less than 3 weeks in the hospital throughout the follow-up period (P=0.036). In addition, the reporting group experienced a lower frequency of biopsies per graft (P=0.038), less severe rejection (P=0.015), and a lower incidence of infection episodes per graft (P=0.03). GST increased by >50% above the upper limit of the reference range at a median of 1 day before the equivalent change in alanine transaminase in association with allograft rejection in the combined groups (95% confidence interval=1 to 2 days) but was lower on the day of diagnosis of rejection in the reporting group (P=0.02). This is compatible with the earlier diagnosis of rejection in the reporting group. CONCLUSIONS: We conclude that the monitoring of GST may improve patient care, reducing both mortality and morbidity.

Adult↗

Cone-rod dystrophy due to mutations in a novel photoreceptor-specific homeobox gene (CRX) essential for maintenance of the photoreceptor.

Genes associated with inherited retinal degeneration have been found to encode proteins required for phototransduction, metabolism, or structural support of photoreceptors. Here we show that mutations in a novel photoreceptor-specific homeodomain transcription factor gene (CRX) cause an autosomal dominant form of cone-rod dystrophy (adCRD) at the CORD2 locus on chromosome 19q13. In affected members of a CORD2-linked family, the highly conserved glutamic acid at the first position of the recognition helix is replaced by alanine (E80A). In another CRD family, a 1 bp deletion (E168 [delta1 bp]) within a novel sequence, the WSP motif, predicts truncation of the C-terminal 132 residues of CRX. Mutations in the CRX gene cause adCRD either by haploinsufficiency or by a dominant negative effect and demonstrate that CRX is essential for the maintenance of mammalian photoreceptors.

Adult↗

Respiratory function parameters in infants using inductive plethysmography.

A signal processing technique has been developed to determine respiratory function parameters by processing displacement data obtained from the abdomen and the rib cage of infants using respiratory inductive plethysmography. The technique transforms time-variant signals into the frequency domain, where they are filtered to reduce unwanted signal components. The phase relationship between the abdominal displacement and the rib cage displacement is determined from the phases of the filtered signals. Flow-volume loops, which are currently of great interest in respiratory medicine, are obtained from waveforms representing respiratory tidal flow and respiratory tidal volume. The index of respiratory timing is determined from a waveform representing respiratory tidal flow. The technique has been verified by statistical comparison with data simultaneously obtained using pneumotachography in a clinical study involving 49 infants.

Artifacts↗

A patient homozygous for a mutation in the prothrombin gene 3'-untranslated region associated with massive thrombosis.

We describe the first reported case of a thrombophilia patient genetically homozygous for a recently described polymorphism in the 3'-UTR (untranslated region) of the prothrombin gene. It has previously been demonstrated that this genetic variant due to a G to A transition at nucleotide 20210 is common and associated with an almost threefold increased risk of venous thrombosis. This polymorphism was also shown to be associated with elevated plasma prothrombin (factor II) levels, which in itself was found to be a risk factor for venous thrombosis. The patient was a healthy young Mexican male who presented with a myocardial infarction and subsequent ileofemoral venous thrombosis and massive saddle pulmonary embolus. Testing done during his initial hospitalization suggested a congenital protein C deficiency. The patient was found to be homozygous for the prothrombin gene polymorphism as well as a carrier for factor V Leiden. This case strongly implies a clinically significant role for the factor II gene mutation in both arterial and venous thrombosis and demonstrates the need to perform diagnostic clotting based assays after resolution of acute thrombotic events. These findings further support the 'double hit' theory for thrombophilia in young patients.

Adult↗