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Biomedical subjects

K E Robertson

Publications and source records attributed to K E Robertson.

15 recordsLinked to original sources
PubMed2001

The impact of pioglitazone on glycemic control and atherogenic dyslipidemia in patients with type 2 diabetes mellitus.

BACKGROUND: To evaluate the glycemic control, lipid effects, and safety of pioglitazone in patients with type 2 diabetes mellitus. DESIGN AND METHODS: Patients (n = 197) with type 2 diabetes mellitus, a hemoglobin A1c (HbA1c) > or = 8.0%, fasting plasma glucose (FPG) > 7.7 mmol/l (140 mg/dl), and C-peptide > 0.331 nmol/l (1 ng/ml) were enrolled in this 23-week multi-center (27 sites), double-blind clinical trial and randomized to receive either a placebo or pioglitazone HCl 30 mg (pioglitazone), administered once daily, as monotherapy. Patients were required to discontinue all anti-diabetic medications 6 weeks before receiving study treatment. Efficacy parameters included HbA1c fasting plasma glucose (FPG), serum C-peptide, insulin, triglycerides (Tg), and cholesterol (total cholesterol [TC], high-density lipoprotein-cholesterol [HDL-C], low-density lipoprotein-cholesterol [LDL-C]). Adverse event rates, serum chemistry, and physical examinations were recorded. RESULTS: Compared with placebo, pioglitazone significantly (P= 0.0001) reduced HbA1c (-1.37% points), FPG (-3.19 mmol/l; -57.5 mg/dl), fasting C-peptide (-0.076+/-0.022 nmol/l), and fasting insulin (-11.88+/-4.70 pmol/l). Pioglitazone significantly (P < 0.001) decreased insulin resistance (HOMA-IR; -12.4+/-7.46%) and improved beta-cell function (Homeostasis Model Assessment (HOMA-BCF); +47.7+/-11.58%). Compared with placebo, fasting serum Tg concentrations decreased (-16.6%; P = 0.0178) and HDL-C concentrations increased (+12.6%; P= 0.0065) with pioglitazone as monotherapy. Total cholesterol and LDL-C changes were not different from placebo. The overall adverse event profile of pioglitazone was similar to that of placebo, with no evidence of drug-induced elevations of serum alanine transaminase (ALT) concentrations or hepatotoxicity. CONCLUSIONS: Pioglitazone improved insulin resistance and glycemic control, as well as Tg and HDL-C - which suggests that pioglitazone may reduce cardiovascular risk for patients with type 2 diabetes.

Adult↗
PubMed2000

Therapy focused on lowering postprandial glucose, not fasting glucose, may be superior for lowering HbA1c. IOEZ Study Group.

OBJECTIVE: To compare the overall efficacy of combination therapies focused on fasting or postprandial blood glucose in patients with type 2 diabetes not adequately controlled with oral sulfonylurea agents alone. RESEARCH DESIGN AND METHODS: A total of 135 patients were randomly assigned for 3 months to 1 of 3 combination regimens with glyburide (G) that addressed postprandial blood glucose with insulin lispro (L+G), premeal blood glucose with metformin (M+G), or fasting blood glucose (FBG) with bedtime NPH insulin (NPH+G). RESULTS: At end point, HbA1c was significantly lower with all therapies (P = 0.001) and was significantly lower for L+G (7.68+/-0.88%) compared with either NPH+G (8.51+/-1.38%, P = 0.003) or M+G (8.31+/-1.31%, P = 0.025). FBG at end point was significantly lower for NPH+G (8.49+/-2.36 mmol/l) compared with either L+G (10.57+/-1.97 mmol/l, P = 0.001) or M+G (9.69+/-2.89 mmol/l, P = 0.029). The mean 2-h postprandial glucose after a test meal was significantly lower for L+G (10.87+/-2.88 mmol/l) versus NPH+G (12.21+/-3.12 mmol/, P = 0.052) or versus M+G (12.72+/-3.26 mmol/l, P = 0.009). The overall rate of hypoglycemia (episodes per 30 days) was low and not statistically significant between groups (P = 0.156). CONCLUSIONS: Adding a second antihyperglycemic agent, regardless of its timing of action, lowers HbA1c and glucose values. However, when insulin lispro was used to focus on postprandial blood glucose, there was a greater impact on overall metabolic control. These data support the importance of lowering postprandial blood glucose to optimize overall glycemic control and thus improve long-term outcomes.

Blood Glucose↗
PubMed1999

Expression of ptc and gli genes in talpid3 suggests bifurcation in Shh pathway.

talpid3 is an embryonic-lethal chicken mutation in a molecularly un-characterised autosomal gene. The recessive, pleiotropic phenotype includes polydactylous limbs with morphologically similar digits. Previous analysis established that hox-D and bmp genes, that are normally expressed posteriorly in the limb bud in response to a localised, posterior source of Sonic Hedgehog (Shh) are expressed symmetrically across the entire anteroposterior axis in talpid3 limb buds. In contrast, Shh expression itself is unaffected. Here we examine expression of patched (ptc), which encodes a component of the Shh receptor, and is probably itself a direct target of Shh signalling, to establish whether talpid3 acts in the Shh pathway. We find that ptc expression is significantly reduced in talpid3 embryos. We also demonstrate that talpid3 function is not required for Shh signal production but is required for normal response to Shh signals, implicating talpid3 in transduction of Shh signals in responding cells. Our analysis of expression of putative components of the Shh pathway, gli1, gli3 and coupTFII shows that genes regulated by Shh are either ectopically expressed or no longer responsive to Shh signals in talpid3 limbs, suggesting possible bifurcation in the Shh pathway. We also describe genetic mapping of gli1, ptc, shh and smoothened in chickens and confirm by co-segregation analysis that none of these genes correspond to talpid3.

Animals↗
PubMed1997

Alterations in Msx 1 and Msx 2 expression correlate with inhibition of outgrowth of chick facial primordia induced by retinoic acid.

Spatially-restricted expression domains of Msx 1 and Msx 2 in the developing chick face suggest that they may play a role in epithelial-mesenchymal interactions governing outgrowth of facial primordia. Retinoid application to developing chick faces reproducibly inhibits upper beak outgrowth but the lower beak is unaffected. In the normal face, high levels of Msx gene transcripts in upper and lower beak primordia correlate with regions of outgrowth. Following retinoid treatment, Msx 1 and Msx 2 transcripts are rapidly down-regulated in upper beak primordia where outgrowth is inhibited, but remain largely unchanged in lower beak primordia, where outgrowth is unaffected. Decreases in gene expression precede retinoid-induced morphological changes in the upper beak, suggesting that Msx gene products are involved in mediating the effect of retinoids on facial development.

Abnormalities, Drug-Induced↗
PubMed1997

Recent molecular advances in understanding vertebrate limb development.

Considerable recent advances have been made in understanding the mechanisms of vertebrate limb development. New information about molecules governing cell interactions in embryonic limbs begins to bridge the gap between the experimental analysis and genetics of congenital limb defects. There are four main stages in vertebrate limb development: initiation, specification of limb pattern, tissue formation accompanied by limb morphogenesis, and growth. Although classical embryology focused on chick embryos and recent molecular analysis centres on limbs of both chickens and mice, most of the fundamental mechanisms that have been uncovered appear to be conserved between vertebrates and are likely to be directly applicable to human limb development.

Animals↗
PubMed1997

Shh, Fgf4 and Hoxd gene expression in the mouse limb mutant hypodactyly.

The semidominant mouse mutation hypodactyly (Hd), caused by a deletion within the Hoxa13 gene, results in reduced digits; heterozygotes lack digit I in the hindlimb and homozygotes have only one digit on each limb. We investigated expression of Shh and Fgf4 signaling molecules involved in digit specification in mutant limb buds. Shh and Fgf4 are expressed in the posterior part of the limb buds as normal but expression may be slightly prolonged. The extent of digit reduction in hypodactyly is much more severe than in the Hoxa13 deficient mouse and resembles that in the Hoxa13(-/-)/Hoxd13(-/-) double mutant mouse. We found that the pattern of Hoxd13 and Hoxd11 transcripts was not markedly different in the mutant compared with the normal limbs even though the mutant limbs are narrower. Therefore Hoxd genes are transcribed as normal in the mutant. This makes it likely that the severe digit reductions in hypodactyly are caused by interference with Hoxd13 function at the protein level. Similar interactions between mutant and normal HOX gene products have been suggested to occur in the human semidominant disorder, synpolydactyly, caused by mutations in HOXD13.

Animals↗
PubMed1996

Uremic pruritus.

Uremic pruritus and its treatment are reviewed. Pruritus affects 50-90% of patients undergoing peritoneal dialysis or hemodialysis; symptoms usually begin about six months after the start of dialysis and range from localized and mild to generalized and severe. The mechanism underlying uremic pruritus is poorly understood; possibilities include secondary hyperparathyroidism and divalent-ion abnormalities; histamine, allergic sensitization, and proliferation of skin mast cells; hypervitaminosis A; iron-deficiency anemia; neuropathy and neurologic changes; or some combination of these. The cornerstone of therapy for uremic pruritus is regular, intensive, efficient dialysis. Other nonpharmacologic measures consist of the use of non-complement-activating dialysis membranes, compliance with dietary restrictions, electric-needle (acupuncture) therapy, and ultraviolet light therapy. Pharmacologic treatments that have been used include activated charcoal, antihistamines, capsaicin, cholestyramine, emollients and topical corticosteroids, epoetin, pizotyline, ketotifen, and nicergoline. Treatment results have been highly variable, and many of the clinical trials have been flawed. Phosphate-binding agents appear to be the most effective. Although enough is known to determine a reasonable set of steps in approaching a patient's uremic pruritus, more research is needed to understand the pathophysiology of this condition and to establish more reliable treatments. Pruritus is a common and sometimes severe complication of chronic renal failure. Efficient dialysis, dietary restrictions, phosphate-binding therapy, and phototherapy are the most effective treatments currently available.

Humans↗
PubMed1996

Process for preventing or identifying and resolving problems in drug therapy.

A consistent process for preventing or identifying and resolving problems related to drug therapy is described. The process was originally developed to help pharmacy students focus on drug therapy issues during their clinical clerkship rotations. The first version of this approach to quality improvement consisted of lists of questions designed to prompt the student to prevent or identify and correct drug therapy problems. Because the learning style of some students is more visual, the questions were incorporated into flow charts. Students at a community hospital used the flow charts during their rotations through the critical care, medical-surgical, and psychiatric units, and the process appeared to result in improvements in the quality of care and in savings in the cost of care. As a result, a staff development and training project was begun to determine if staff pharmacists who use this process to evaluate drug therapy will begin to provide pharmaceutical care. This sort of transitional model of pharmaceutical care may expedite global implementation of the new practice philosophy. Flow charts encouraging a uniform approach to the prevention or identification and correction of drug therapy problems were developed for use by pharmacy students and generalist pharmacists.

Clinical Clerkship↗
PubMed1996

Cellular analysis of limb development in the mouse mutant hypodactyly.

The limb defect in the mouse Hypodactyly (Hd) affects only the distal structures. Heterozygotes (Hd/+) lack all or part of the distal phalanx and the terminal claw of digit on the hindlimbs; mice homozygous (Hd/Hd) for the mutation have just one digit on each of the four limbs. Early limb development in the mutant appears normal and a change in morphology can only be detected later. Limb buds of Hd/+ and Hd/Hd embryos become reduced in width, with Hd/Hd buds becoming very pointed instead of rounded. This change in bud shape is correlated with an increase in cell death anteriorly in Hd/+ hindlimbs and both anteriorly and posteriorly in Hd/Hd fore- and hindlimb buds. The apical ectodermal ridge is very pronounced in pointed Hd/Hd limb buds. Mesenchyme cells from the Hd/Hd mutant in culture show a cell-autonomous change in behaviour and less cartilage differentiates.

Animals↗
PubMed1995

Expression of genes encoding bone morphogenetic proteins and sonic hedgehog in talpid (ta3) limb buds: their relationships in the signalling cascade involved in limb patterning.

The chicken mutant talpid3 (ta3) has polydactylous limbs with up to 7-8 morphologically similar digits. This lack of antero-posterior polarity in digit pattern is correlated with symmetrical expression of genes of the HoxD complex. We determined the distribution of polarizing activity in limb buds of the chick mutant ta3 by assessing the ability of mesenchyme from various positions along the antero-posterior axis to induce digit duplications when grafted anteriorly into a normal limb. Cells with highest polarizing activity were found at the posterior margin of the wing as in the polarizing region of normal limb buds. However, in contrast to normal limb buds, ta3 anterior mesenchyme also had low polarizing activity. Application of retinoic acid or a polarizing region graft to the anterior of ta3 limb buds changed digit morphology but did not induce digit duplications or digits with any characteristic a-p pattern. To determine which genes are associated with polarizing activity and which are associated with patterning of the digits, we examined expression of the genes Sonic hedgehog (shh), Bmp-2, and Bmp-7, whose expression is normally confined to the posterior margin of the early wing bud and is associated with the polarizing region. In addition, we determined the distribution of Fgf-4 transcripts which in normal limb buds are restricted to the posterior part of the apical ectodermal ridge. In ta3 limb buds, shh expression is restricted to the posterior limb mesenchyme, which has high polarizing activity, but is not expressed in regions which have low polarizing activity. In contrast, Bmp-2 and Bmp-7 are expressed uniformly along the a-p axis. Fgf-4 transcripts are present throughout the apical ectodermal ridge in ta3 limb buds. In the ta3 mutant, there is both an abnormal distribution of signalling activity and response to polarizing signals. In addition, the dissociation between the expression of shh and Bmps suggests distinct roles for the encoded molecules in signalling and response in a-p patterning of limb buds.

Animals↗
PubMedDate not supplied

The latest developments in insulin injection devices.

The next several years promise dramatic changes in the treatment of diabetes, many of which will be driven by rapidly developing technology. Today's patient with diabetes has ready access to more information about the disease and its treatment options. As a result of this increased knowledge base, insulin-treated patients have become more autonomous in the management of their diabetes and may be better prepared to participate in making informed choices regarding insulin delivery devices. As with any insulin regimen, diabetes educators are encouraged to provide ongoing patient education and follow-up to assure optimal use of these new technologies.

Equipment Design↗