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T J Anderson

Publications and source records attributed to T J Anderson.

At least 55 records · Page 3Linked to original sources
PubMed2001

Improved endothelial function with metformin in type 2 diabetes mellitus.

OBJECTIVES: This study was designed to assess the effect of metformin on impaired endothelial function in type 2 diabetes mellitus. BACKGROUND: Abnormalities in vascular endothelial function are well recognized among patients with type 2 (insulin-resistant) diabetes mellitus. Insulin resistance itself may be central to the pathogenesis of endothelial dysfunction. The effects of metformin, an antidiabetic agent that improves insulin sensitivity, on endothelial function have not been reported. METHODS: Subjects with diet-treated type 2 diabetes but without the confounding collection of cardiovascular risk factors seen in the metabolic syndrome were treated with metformin 500 mg twice daily (n = 29) or placebo (n = 15) for 12 weeks. Before and after treatment, blood flow responses to intraarterial administration of endothelium-dependent (acetylcholine), endothelium-independent (sodium nitroprusside) and nitrate-independent (verapamil) vasodilators were measured using forearm plethysmography. Whole-body insulin resistance was assessed on both occasions using the homeostasis model (HOMA-IR). RESULTS: Subjects who received metformin demonstrated statistically significant improvement in acetylcholine-stimulated flows compared with those treated with placebo (p = 0.0027 by 2-way analysis of variance), whereas no significant effect was seen on nitroprusside-stimulated (p = 0.27) or verapamil-stimulated (p = 0.40) flows. There was a significant improvement in insulin resistance with metformin (32.5% reduction in HOMA-IR, p = 0.01), and by stepwise multivariate analysis insulin resistance was the sole predictor of endothelium-dependent blood flow following treatment (r = -0.659, p = 0.0012). CONCLUSIONS: Metformin treatment improved both insulin resistance and endothelial function, with a strong statistical link between these variables. This supports the concept of the central role of insulin resistance in the pathogenesis of endothelial dysfunction in type 2 diabetes mellitus. This has important implications for the investigation and treatment of vascular disease in patients with type 2 diabetes mellitus.

Blood Flow Velocity↗
PubMed2001

Biological and clinical effects of aromatase inhibitors in neoadjuvant therapy.

Postmenopausal women with large primary oestrogen receptor-rich (>20 fmol/mg protein or 80 histoscore) breast cancers have been treated neoadjuvantly with either letrozole (2.5 or 10 mg daily n=12 in each case) or anastrozole (1 or 10mg daily n=12 and 11, respectively). Tumour was available for analysis before treatment (wedge biopsy) and 3 months later at definitive surgery (wide local excision or mastectomy). Clinical response to treatment was assessed by sequential measurements of tumour volume based on caliper assessment, ultrasound and mammography. Results showed that in these selected groups of patients a reduction in tumour volume with treatment was observed in 43 of 47 cases (91%). Pathological responses, i.e. clear decrease in tumour cellularity or increased fibrosis was evident in 32 cases (68%). Furthermore, there was a decrease with therapy in immunohistochemical staining for Ki67 in all tumours. Staining for progesterone receptor (PgR) was reduced in all 21 PgR-positive cancers treated with letrozole and in 16 of 17 positive cancers treated with anastrozole. These effects are at least as great as those seen in a non-randomised group of patients treated with tamoxifen over the same time period (additionally tamoxifen treatment was often associated with an increase in PgR staining). The results suggest that potent specific aromatase inhibitors will be valuable in treating hormone-dependent cancers.

Anastrozole↗
PubMed2001

The dangers of using single locus markers in parasite epidemiology: Ascaris as a case study.

Molecular markers are used widely to discriminate between closely related species of parasites, and in many cases a single locus is used for this purpose. This article aims to show how molecular data derived from a single genetic marker or linkage group - in this case mitochondrial DNA - can lead to ambiguous conclusions and to illustrate how a multilocus approach has enhanced our understanding of the epidemiology of two closely related parasites, the nematodes Ascaris suum, which infects pigs, and Ascaris lumbicoides, which infects humans.

Animals↗
PubMed2001

A phylogenetic analysis of filarial nematodes: comparison with the phylogeny of Wolbachia endosymbionts.

Infection with the endosymbiotic bacteria Wolbachia is widespread in filarial nematodes. Previous studies have suggested concordance between the phylogeny of Wolbachia with that of their nematode hosts. However, there is only one published molecular phylogenetic study of filarial species, based on the 5S rRNA gene spacer. The phylogeny proposed by this study is partially incongruent with previous classifications of filarial nematodes, based on morphological characters. Furthermore, both traditional classifications and molecular phylogenies are, in part, inconsistent with the phylogeny of Wolbachia. Here we report mitochondrial cytochrome oxidase I (COI) gene sequences for 11 species of filaria and for another spirurid nematode which was included as an outgroup. In addition, 16S rRNA, wsp and ftsZ gene sequences were generated for the Wolbachia of several filarial species, in order to complete the available data sets and further resolve the phylogeny of Wolbachia in nematodes. We used these data to evaluate whether nematode and Wolbachia phylogenies are concordant. Some of the possible phylogenetic reconstructions based on COI gene were congruent with the phylogeny of Wolbachia and supported the grouping of the rodent filaria Litomosoides sigmodontis with the lymphatic filariae (i.e. Brugia spp. and Wuchereria spp.) and the sister group relationship of Dirofilaria spp. and Onchocerca spp. However, the placement of the Wolbachia-free filaria Acanthocheilonema viteae is ambiguous and dependent on the phylogenetic methods used.

Animals↗
PubMed2001

Escherichia coli O157:H7 becomes resistant to sodium chlorate in pure culture, but not in mixed culture or in vivo.

AIMS: Chlorate kills Escherichia coli O157:H7 and may be an effective feed additive for use in food animals. This study was designed to determine if development of chlorate-resistant E. coli O157:H7 strains was likely. METHODS AND RESULTS: Escherichia coli O157:H7 was chlorate-sensitive, but became chlorate-resistant in pure batch culture and in sterilized faecal fluid; it was killed in mixed culture and did not become resistant. Addition of chlorate to continuous pure cultures caused chlorate resistance, but chlorate addition to mixed continuous culture eliminated E. coli O157:H7 and no resistance occurred. Piglets challenged with E. coli O157:H7 were treated with chlorate; populations were reduced and colonies were always chlorate-sensitive. CONCLUSION: Chlorate-resistant E. coli O157:H7 can be selected in pure, but not mixed culture, and results suggest that terminal chlorate feeding will not select for chlorate-resistance in vivo. SIGNIFICANCE AND IMPACT OF THE STUDY: Chlorate can reduce food-borne pathogens prior to harvest, but development of resistance does not appear likely in vivo.

Animals↗
PubMed2001

Persistence of a vancomycin-resistant Enterococcus faecium in an anaerobic continuous-flow culture of porcine microflora in the presence of subtherapeutic concentrations of vancomycin.

Recombined porcine continuous-flow culture (RPCF) maintained in a continuous-flow fermentation system is effective in protecting neonatal and weaned pigs against infection by enteropathogens. In the current study, we demonstrate the effect of RPCF on vancomycin-resistant enterococci (VRE) in the presence and absence of subtherapeutic levels of vancomycin. Also examined was the ability of VRE to transfer vancomycin resistance to endogenous Enterococcus faecalis 137.1. When RPCF was challenged with VRE, the rate of VRE clearance was dependent on the method of challenge. In the control experiment, RPCF was challenged with 7.0 log10/CFU/ml VRE. Clearance of VRE from the culture was observed within 7 days at a rate of 1.44 log10/day. RPCF containing 0.001 microg/ml vancomycin cleared VRE at a slightly lower rate of 0.94 log10/day. RPCF containing 0.01 microg/ml or 0.1 microg/ml vancomycin reduced the level of VRE from 7.0 log10/CFU/ml to 2.0 log10/CFU/ml within 9 days, but failed to clear the VRE after 24 days. During the period of decline, the VRE clearance rate for the 0.01 microg/ml and 0.1 microg/ml vancomycin-treated cultures was 0.52 log10/day, and 0.53 log10/day, respectively. E. faecalis 137.1 endogenous to RPCF did not acquire the vancomycin resistance genes throughout the experiment as evidenced by direct selection, ribotyping, and pulsed-field gel electrophoresis.

Anaerobiosis↗
PubMed2001

Endothelin antagonism uncovers insulin-mediated vasorelaxation in vitro and in vivo.

The endothelial actions of insulin remain an area of intense research because they relate to both insulin sensitivity and vascular tone. Physiological doses of insulin evoke endothelium-dependent vasorelaxation in humans; however, this remains a pharmacological phenomenon in rat aortas. Because insulin may stimulate the divergent production of both nitric oxide and endothelin-1, we hypothesized that the lack of insulin-induced vasorelaxation at low/subthreshold concentrations may be due to the concurrent production of endothelin-1, which in turn serves to inhibit nitric oxide-dependent, insulin-mediated dilation. To investigate this, we studied the effects of subthreshold concentrations of insulin (100 mU/L) on norepinephrine-induced contraction in rat aortas following short-term and long-term endothelin blockade. In addition, the effects of tetrahydrobiopterin inhibition (with diaminohydroxyprimidine) on norepinephrine-induced contraction in the presence of insulin and endothelin receptor blockade were investigated. Subthreshold concentrations of insulin failed to evoke vasorelaxation in rat aortas. Strikingly, short-term endothelin A/B receptor blockade with bosentan (10(-2) mmol/L) uncovered insulin-mediated dilation; the percent maximum contraction and sensitivity of aortas to norepinephrine were attenuated (% maximum relaxation: bosentan+insulin 74+/-4%* versus bosentan 92+/-3%, insulin 107+/-5% P:<0.002; pD(2) values: bosentan+insulin 6.87+/-0.14* versus bosentan 7.40+/-0.15, insulin 7.63+/-0.11, *P:<0.002). This effect was mediated through endothelin A receptors because bosentan and BQ-123 (10(-2) mmol/L) attenuated norepinephrine-induced contraction to a similar degree. In addition, insulin evoked vasorelaxation in aortas isolated from rats after long-term bosentan treatment (100 mg. kg(-1). d(-1), 3 weeks). The component of insulin-mediated vasorelaxation uncovered by endothelin receptor blockade was tetrahydrobiopterin-dependent because it was reversed by diaminohydroxyprimidine. These data demonstrate, for the first time, the functional interaction between insulin, endothelin-1, and tetrahydrobiopterin in modulating vascular tone in rat aortas in vitro and in vivo.

Acetylcholine↗
PubMed2001

Dysfluency and involuntary movements: a new look at developmental stuttering.

Studies using modern imaging techniques suggest that, in developmental stuttering, there is dysfunction within the cortical and subcortical areas of the motor control system wider than that pertaining to speech motor control alone. If this is the case, one might expect motor deficits extending beyond and unrelated to the production of speech in people who stutter. This study explored this proposal by investigating the presence and characteristics of involuntary movements accompanying stuttering. Sixteen adults with developmental stuttering and 16 controls matched for age and sex were audio-videotaped during 5 minutes of conversational speech and reading a passage of 350 words. Audio-data were examined for dysfluencies. Movements of the face, head and upper body considered involuntary and not part of normal facial expression or gesture and not part of the mechanics of speech were identified and described from muted video-data. Subjects who stuttered had a higher proportion of classic (within-word) dysfluencies accompanied by involuntary movements (IMs) than controls during speech (24.4% vs. 4.5%, p = .054) and reading (28.6% vs. 4.9%, p = .033). There was no difference in proportion of classic dysfluencies accompanied by IMs between speech and reading for either group. IMs were also seen in both groups during fluent speech, with a similar incidence during free speech (3.9% vs. 3.0%, NS) but a greater incidence in the subjects who stuttered during reading (2.4% vs. 0.8%, p = .03). In contrast, there was no difference between the two groups for IMs accompanying normal (between-word) dysfluencies. This suggests that classic and normal dysfluency and their accompanying IMs have different etiologies. The notion that stuttering and IMs are due to altered function in a motor control system wider than that of speech motor control alone is supported by a higher incidence of IMs in people who stutter during both classic dysfluencies and fluent speech.

Adolescent↗
PubMed2001

Augmentation of endothelial function by endothelin antagonism in human saphenous vein conduits.

OBJECT: Cerebral revascularization with saphenous vein (SV) conduits is used in the management of hard-to-treat lesions that require deliberate arterial occlusion and in selected patients with occlusive vascular disease. Endothelial dysfunction is thought to contribute to acute perioperative vasospasm and chronic graft atherosclerosis. In the present study the authors examined the contribution of the potent vasoconstrictor endothelin-1 (ET-1) to endothelial dysfunction in human SVs. METHODS: The effects of an ET(A/B) receptor antagonist (bosentan), an ET(A) receptor antagonist (BQ-123), and an ET(B) receptor antagonist (BQ-788) on in vitro endothelium-dependent and -independent responses were studied in human SVs. Vascular segments were obtained in 34 patients who had undergone revascularization procedures, and isometric dose-response curves (DRCs) were constructed using the isolated tissue bath procedure as follows: 1) cumulative DRCs to norepinephrine; and 2) DRCs to acetylcholine (ACh) and sodium nitroprusside in the absence and presence of bosentan, BQ-123, or BQ-788. Maximal vasodilatory responses and sensitivity were compared between groups. In the presence of bosentan (Experiment 1) and BQ-123 or BQ-788 (Experiment 2), ACh responses were significantly augmented (percent maximum relaxation values: 7+/-2 [control] compared with 17+/-3 [bosentan], p < 0.002 [Experiment 1]; and 12+/-2 [control] compared with 29+/-2 [BQ-123] and 25+/-2 [BQ-788], p < 0.003 and p < 0.002, respectively [Experiment 2]). The sensitivity of SVs to ACh was unaffected by treatment. These beneficial effects were specific for the endothelium. CONCLUSIONS: Blockade of ET receptors significantly improves endothelial function in SVs. Furthermore, these effects appear to be independently and maximally mediated by antagonism of either ET(A) or ET(B) receptors. Interventions aimed at improving endothelial function may serve to counter perioperative vasospasm and impede atherosclerosis in SVs used for revascularization procedures.

Aged↗
PubMed2001

Drought associated poisoning of cattle in South Texas by the high quality forage legume Leucaena leucocephala.

Approximately 80 head of yearling cattle grazing on 680 acres exhibited signs of Leucaena leucocephala toxicosis, which was confirmed in 3 animals by detection of 3-hydroxy-4 (IH)-pyridone, the metabolite of the poisonous principle mimosine, in their urine. The animals had grazed leucaena almost exclusively due to lack of alternative forage resulting from drought conditions. Toxicosis from this otherwise high quality forage would likely not have occurred had animals consumed lower amounts of leucaena and could probably have been prevented, as it has been elsewhere, had the animals been colonized with Synergistes jonesii, a beneficial ruminal bacterium capable of degrading the toxic metabolites.

Animal Feed↗
PubMed2000

Randomized comparison of elective stent implantation and coronary balloon angioplasty guided by online quantitative angiography and intracoronary Doppler. DESTINI Study Group (Doppler Endpoint STenting INternational Investigation).

BACKGROUND: The purpose of this study was to compare long-term outcomes of coronary stenting in all lesions (elective stenting) or only in lesions with inadequate morphological and functional results after balloon angioplasty (guided PTCA). METHODS AND RESULTS: Treatment of multivessel disease, with any lesion length and vessel size, was allowed provided that all lesions were suitable for stent implantation. Patients were randomized to elective stent implantation (n=370) or guided PTCA (n=365). An optimal PTCA result (residual diameter stenosis </=35%, coronary flow reserve measured with a Doppler guidewire >2.0, absence of threatening dissections) was achieved in 166 lesions (43%). The remaining 218 lesions underwent stent implantation (provisional stenting). Final residual diameter stenosis was lower in the elective and provisional stent groups (9.3% and 10.2%) than in the optimal PTCA group (24.8%, P:<0. 00001). On an intention-to-treat analysis, the probability of >/=1 major adverse cardiac event at 12 months was 17.8% in the elective stenting group and 18.9% in the guided PTCA group (20.1% for optimal PTCA and 18.0% for the provisional stenting subgroup, P:=NS). The incidence of repeat target lesion revascularization at 1 year was 14. 9% in the elective stent group and 15.6% in the guided PTCA group (17.6% for optimal PTCA and 14.1% for the provisional stenting subgroup, P:=NS). CONCLUSIONS: When balloon angioplasty is guided by online quantitative angiography and Doppler-derived coronary flow reserve, with provisional stenting reserved for suboptimal results, early and late clinical outcomes are comparable to those achieved by elective stenting of all patients.

Angiography↗
PubMed2000

Central nervous system pathology in 25 dogs with chronic degenerative radiculomyelopathy.

The neuropathology of 20 German shepherd dogs and five German shepherd dog crosses with chronic degenerative radiculomyelopathy were analysed by conventional techniques, immunocytochemistry and electron microscopy. There were previously unrecognised changes in brain nuclei. In the spinal cord, both motor and sensory tracts were involved, principally in their more distal regions. Wallerian degeneration affected the corticorubrospinal pathways in the lateral columns and the ventral funiculi, predominantly in the caudal thoracic and lumbar segments, although more cranial involvement was also observed. The dorsal columns were affected in the caudal lumbar region and the cervical fasciculus gracilis. The regional distribution was variable between cases. Within the brain, abnormalities, including chromatolysis, gliosis and neuronal loss were observed in the red nucleus, lateral vestibular nucleus and, occasionally, in the dentate nucleus. The changes in brain nuclei were compared with those found in dogs at various times after a focal spinal injury. The neuronal changes in the brain may be related to the primary site of damage, and possible aetiological mechanisms are discussed.

Animals↗
PubMed2000

wsp gene sequences from the Wolbachia of filarial nematodes.

Wolbachia endosymbiotic bacteria are widespread in arthropods and are also present in filarial nematodes. Almost all filarial species so far examined have been found to harbor these endosymbionts. The sequences of only three genes have been published for nematode Wolbachia (i.e., the genes coding for the proteins FtsZ and catalase and for 16S rRNA). Here we present the sequences of the genes coding for the Wolbachia surface protein (WSP) from the endosymbionts of eight species of filaria. Complete gene sequences were obtained from the endosymbionts of two different species, Dirofilaria immitis and Brugia malayi. These sequences allowed us to design general primers for amplification of the wsp gene from the Wolbachia of all filarial species examined. For these species, partial WSP sequences (about 600 base pairs) were obtained with these primers. Phylogenetic analysis groups these nematode wsp sequences into a coherent cluster. Within the nematode cluster, wsp-based Wolbachia phylogeny matches a previous phylogeny obtained with ftsZ gene sequences, with a good consistency of the phylogeny of hosts (nematodes) and symbionts (Wolbachia). In addition, different individuals of the same host species (Dirofilaria immitis and Wuchereria bancrofti) show identical wsp gene sequences.

Animals↗