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Biomedical subjects

M A Baxter

Publications and source records attributed to M A Baxter.

At least 19 recordsLinked to original sources

Antioxidant status in patients with uncomplicated insulin-dependent and non-insulin-dependent diabetes mellitus.

Oxidative damage by free radicals has been implicated in the pathogenesis of vascular disease in diabetes. We compared the radical-scavenging antioxidant activity of serum from 28 patients with insulin-dependent diabetes mellitus and 24 patients with non-insulin-dependent diabetes mellitus uncomplicated by vascular disease with age-matched non-diabetic control subjects. Patients with insulin-dependent diabetes had significantly reduced total antioxidant activity (320.2 +/- 11.3 vs. 427.5 +/- 19.2 mumol L-1; P < 0.001). This was attributable to lower urate (209.4 +/- 10.4 vs. 297.1 +/- 16.7 mumol L-1; P < 0.001) and vitamin C levels (63.6 +/- 6.0 vs. 87.5 +/- 4.9 mumol L-1; P < 0.01). Patients with non-insulin-dependent diabetes had lower total antioxidant activity than age-matched control subjects (433.8 +/- 25.4 vs. 473.9 +/- 30.2 mumol L-1; NS), reflecting lower urate (299.5 +/- 19.4 vs. 324.8 +/- 21.4 mumol L-1; NS) and vitamin C levels (38.6 +/- 5.7 vs. 58.5 +/- 5.3 mumol L-1; P < 0.05). Multiple regression analysis showed that urate, vitamin C and vitamin E were the major contributors to serum total antioxidant activity. These results show that diabetic patients have significant defects of antioxidant protection, which may increase vulnerability to oxidative damage and the development of diabetic complications.

Adult↗

Poor glycaemic control is associated with reduced serum free radical scavenging (antioxidant) activity in non-insulin-dependent diabetes mellitus.

The diabetic patient is at significantly increased risk of developing vascular disease. Its aetiology may involve oxidative damage by free radicals and protection against such damage can be offered by radical-scavenging antioxidants. We investigated whether there was a relationship between glycaemic control as assessed by measurement of glycated haemoglobin (HbA1c) and serum antioxidant status in a population of 118 diabetic outpatients with either insulin-dependent or non-insulin-dependent diabetes. Amongst patients with non-insulin-dependent diabetes mellitus there was a significant inverse correlation between levels of glycated haemoglobin and total free radical scavenging activity (r = -0.456, P < 0.0001). This association resulted primarily because of a similar correlation with uric acid (r = -0.421, P = 0.0003). There was also a weak inverse correlation with vitamin A but no significant association with vitamin C or vitamin E levels. There were no significant associations found amongst the patients with insulin-dependent diabetes. These results indicate that poor diabetic control is associated with reduced serum free radical scavenging (antioxidant) activity in non-insulin-dependent diabetes mellitus. By implication improved glycaemic control may preserve serum antioxidant status in diabetes.

Adult↗

Use of near-infrared spectroscopy to evaluate an active in a film coated tablet.

PURPOSE: To provide a method to rapidly screen tablets in the development of new coating technology. METHODS: Near-Infrared (NIR) reflectance spectroscopy was used to quantitatively analyze tablets which were composed of a drug active encasing an active drug core. Diffuse reflectance NIR scans of 240 individual tablets over the range of 1100-2500 nm were obtained. High Performance Liquid Chromatography (HPLC) was used as the reference method. RESULTS: Both qualitative, Principal Component Analysis, and quantitative results showed a strong agreement between the NIR and HPLC methods. The NIR analysis was non-invasive and allowed subsequent testing of the tablets. The contents of the drug active contained in a drug coating was determined to +/- 4% of the target value using NIR analysis. Over 400 samples were analyzed in less than a month utilizing this technique which allowed the optimization of a new coating technology. CONCLUSIONS: NIR analysis allowed the evaluation of the efficiency of a new drug film coating manufacturing process more quickly and inexpensively. Because the Near-Infrared method was non-invasive the tablets were available for further analysis unlike the chromatography method.

Calibration↗

Regulation of myo-inositol transport during the growth and differentiation of thyrocytes: a link with thyroid-stimulating hormone-induced phospholipase A2 activity.

The Vmax of myo-inositol transport increased 3-fold during epidermal growth factor (EGF)-induced growth and thyroid-stimulating hormone. (TSH)-induced differentiation in primary cultures of sheep and human thyrocytes. The Km remained unaltered. This up-regulation required the presence of insulin. The TSH-induced rise in myo-inositol transport commenced 8 to 16 h after the initial stimulus and achieved a plateau at 24 h. In human thyrocytes the change in Vmax was accompanied by an increase in the steady-state levels of mRNA for the myo-inositol transporter following treatment with either ligand. Examination of the metabolites of myo-inositol showed few significant changes after treatment of sheep thyrocytes with EGF for 24 h. This is consistent with maintenance of the intracellular concentration of myo-inositol as the cells enlarge in preparation for cell division. In TSH-treated cells, however, up-regulation of myo-inositol transport was linked with increased myo-inositol cycling across the cell membrane, increased phospholipase A2-mediated turnover of phosphatidylinositol and a concomitant increase in arachidonic acid turnover. Increased levels of myo-inositol phosphates were also noted 24 h after TSH treatment. These results indicate the initiation of secondary signalling events many hours after the primary stimulus.

Animals↗

Acromegaly and transsphenoidal hypophysectomy: a case report.

Anterior pituitary tumors account for nearly 18% of all intracranial tumors. Pituitary adenomas that cause hypersecretion of growth hormone lead to acromegaly in adults. Patients with acromegaly may present unique problems for the anesthetist because of the overgrowth of airway soft tissues; a difficult mask ventilation and challenging intubation can be expected. A careful preoperative assessment of the patient's airway is essential, and an awake oral or fiberoptic bronchoscopy may be necessary. Postoperatively, these patients are at risk for developing airway problems and diabetes insipidus; therefore, they warrant careful observation. A 42-year-old, 75-kg, ASA physical status III, white male presented 8 months after suffering a head injury in which he was knocked unconscious for approximately 3 minutes. He began experiencing severe headaches, visual changes, and a marked increase in the size of his hands and feet. Four months before admission, he underwent bilateral carpal tunnel repairs. The patient was diagnosed with acromegaly after an extensive endocrine and neurosurgical evaluation. This is a case report of a patient with acromegaly who underwent an elective transsphenoidal hypophysectomy.

Acromegaly↗

Radioiodine therapy for hyperthyroidism in young patients--perception of risk and use.

Although radioiodine is increasingly the treatment of choice in hyperthyroidism, there are regional differences in its use which reflect, in part, concerns regarding safety. We investigated attitudes amongst general practitioners and consultant physicians to the role of radioiodine therapy, and reviewed our own radioiodine prescribing in patients aged less than 40 to elucidate any influence of age and/or sex. We surveyed general practitioners in the former Central Birmingham Health District and consultant physicians in the West Midlands Region to investigate treatment preferences in hyperthyroidism and perceived risk from radioiodine of hypothyroidism, carcinogenesis and infertility. Of 230 general practitioner and 130 consultant physician respondents, less than 1% considered radioiodine the treatment of choice in a 25-year-old female presenting with hyperthyroidism. At relapse after antithyroid drug treatment in a 25-year-old female, only 16.5% of general practitioners and 23.9% of physicians advocated radioiodine, the greatest number preferring partial thyroidectomy. For a 65-year-old at presentation, 49.1% of general practitioners and 62.3% of physicians considered radioiodine the treatment of choice. More than 10% failed to note the risk of hypothyroidism following radioiodine, while 11-34% perceived increased risk of malignancy or infertility. Review of our own practice demonstrated that of 100 patients given radioiodine, 94% were cured of hyperthyroidism when reviewed at a mean of 2.4 years from latest treatment, 70% being hypothyroid. Females given radioiodine were treated less promptly following diagnosis of hyperthyroidism than males (2.2 +/- 0.26 years vs. 1.6 +/- 0.4) and were more likely to have received a preceding course of antithyroid drugs (78% vs. 57%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Inositol lipids and phosphates in the proliferation and differentiation of lymphocytes and myeloid cells.

It is established that receptor-stimulated hydrolysis of phosphatidylinositol 4,5-bisphosphate is an essential signalling reaction in the responses of many haemopoietic cells to stimuli: examples include platelet activation, antigen-driven initiation of cell proliferation in mature B and T lymphocytes and histamine release by mast cells, and chemotaxis and oxygen radical generation by neutrophils. However, the roles of inositol lipids and phosphates in the development of haemopoietic and immune cells are less well understood. This paper discusses three such situations: the sequential employment of phosphatidylinositol 4,5-bisphosphate hydrolysis and cyclic AMP accumulation as two signals essential to the action of the B lymphocyte-stimulatory cytokine interleukin 4; the involvement of antigen receptor-triggered inositol lipid hydrolysis in apoptotic elimination of immature anti-self T lymphocytes in the fetal mouse thymus; and the possible role of changes in the levels of abundant inositol polyphosphates in the differentiation of HL-60 promyelocytic cells and of normal human myeloid blast cells.

Bone Marrow Cells↗

Phaeochromocytomas as a cause of hypotension.

A patient presented with apparent septicaemic shock. Full invasive cardiovascular monitoring revealed systemic hypotension, high normal cardiac output, and a low systemic vascular resistance. Maintenance of systemic vascular resistance and blood pressure was shown to be highly dependent on noradrenaline. Subsequent investigation revealed the presence of a phaeochromocytoma producing adrenaline. The mechanisms by which phaeochromocytomas may produce hypotension are discussed.

Adrenal Gland Neoplasms↗

Effect of Mg2+ on Na(+)-dependent inositol transport. Role for Mg2+ in etiology of diabetic complications.

Diabetes mellitus is associated with a significant reduction in the serum concentration of Mg2+. Several studies have suggested that hypomagnesemia may be implicated in the etiology of diabetic complications; however, no mechanism has been proposed. This study demonstrates that Mg2+ is a positive effector of inositol transport and is capable of promoting a 2.5-fold increase in the affinity of the transporter for inositol. Analysis of the kinetics of inositol transport shows that, at physiological concentrations of inositol, the reductions in Mg2+ concentrations that occur in diabetic patients would result in a significant decline in the rate of inositol transport (1.5- to 2-fold). We suggest that hypomagnesemia may be linked to the development of diabetic complications via reduction in the rate of inositol transport and subsequent intracellular inositol depletion. This assertion allows hypomagnesemia and the polyol theory to be unified into one mechanistic model for the development of diabetic complications.

Biological Transport↗

Changes in the kinetics of inositol transport during TPA-induced differentiation of HL60 cells towards monocytes.

When exposed to the phorbol ester TPA, HL60 cells undergo growth arrest and differentiate towards monocytes. During TPA-induced differentiation there was a 2.6-fold increase in the rate of inositol transport (Vmax), a 2.1-fold increase in intracellular inositol and a 1.5-fold increase in inositol lipid. An increase in the Vmax of inositol transport did not occur when the variant cell line HL60Ast3 was exposed to TPA, which has been shown in this cell line to induce growth arrest but not differentiation. This observation suggests that the change in inositol transport during HL60 monocyte differentiation is specifically associated with the process of cell differentiation as opposed to growth arrest.

Biological Transport↗

Changes in inositol transport during DMSO-induced differentiation of HL60 cells towards neutrophils.

[3H]Inositol uptake by HL60 cells was measured during DMSO-induced differentiation towards neutrophils. The values for Km (53.2 microM) and Vmax (5.3 pmol/min per 10(6) cells) obtained for control HL60 cells are in good agreement with previously published figures for this cell line. Inositol transport into HL60 cells was an active, saturable and specific process which was unaffected by extracellular glucose concentrations. Inositol transport rates changed during DMSO-induced differentiation of HL60 cells towards neutrophils. An increase in inositol transport rates occurred during the first 4 days of exposure to 0.9% DMSO and was concommitant with the period leading to growth arrest and prior to the acquisition of the differentiated phenotype. These changes preceded the rise in intracellular inositol concentration from 10.9 to 132.7 microM seen between day 1 and day 5. After 4 days exposure to DMSO the rate of inositol transport fell to a value of 3.2 +/- 0.3 pmol/min per 10(6) cells at day 7, this was accompanied by a small reduction in intracellular inositol from a peak value of 132.7 to 112 microM. The inositol transport rate, thus, appears to closely accompany changes in the intracellular concentration of inositol. Inositol transport in human peripheral blood neutrophils was an order of magnitude slower than the value for uninduced HL60 cells, but the Km for inositol transport was similar in both cell types and was unchanged during HL60 differentiation. This suggests that changes in inositol transport rate are achieved by the modulation of a commonly expressed inositol transporter, one consequence of which is the alteration of intracellular inositol concentrations.

Biological Transport, Active↗

Endocrinology.

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Adult↗