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Biomedical subjects

T Kearney

Publications and source records attributed to T Kearney.

17 recordsLinked to original sources

Integrating decision tools for the sustainable management of land contamination.

The approach to taking decisions on the management of land contamination has changed markedly over 30 years. Change has been rapid with policy makers and regulators, practitioners and researchers having to keep pace with new technologies, assessment criteria and diagnostic methods for their measurement, techniques for risk analysis and the frameworks that support decision-makers in their efforts to regenerate historically contaminated land. Having progressed from simple hazard assessment through to 'sustainability appraisal' we might now consider piecing together the experience of decision-making for managing land contamination. Here, we critically review recent developments with a view to considering how better decisions can be made by integrating the decision tools available. We are concerned with the practicality of approach and the issues that arise for practitioners as decision criteria are broadened.

Conservation of Natural Resources↗

Fibrin sealant reduces the duration and amount of fluid drainage after axillary dissection: a randomized prospective clinical trial.

BACKGROUND: Patients who have axillary dissections during lumpectomy or modified radical mastectomy for breast carcinoma accumulate serosanguinous fluid, potentially resulting in a seroma. Currently accepted practice includes insertion of one or more drains for fluid evacuation. This multicenter, randomized, controlled, phase II study was undertaken to evaluate whether a virally inactivated, investigational fibrin sealant is safe and effective when used as a sealing agent to reduce the duration and volume of serosanguinous fluid drainage and to determine the dose response of this effect. STUDY DESIGN: Patients undergoing lumpectomy or modified radical mastectomy were randomized to treatment with 4, 8, or 16 mL of fibrin sealant or control (no agent) at the axillary dissections site. Patients undergoing modified radical mastectomy also received an additional 4 or 8 mL of fibrin sealant at the skin flap site. Efficacy was evaluated by the number of days required for wound drainage and the volume of fluid drainage compared with control. Safety was confirmed by clinical course, the absence of viral seroconversion, and no major complications attributable to the sealant. RESULTS: The 4-mL axillary dissection dose of fibrin sealant significantly reduced the duration and quantity of fluid drainage from the axilla following lumpectomy (p < or = 0.05). In the modified radical mastectomy patients, a 16-mL axillary dissection dose combined with an 8-mL skin flap dose was significantly effective in reducing the number of days to drain removal (p < or = 0.05) and fluid drainage (p < or = 0.01). There were no fibrin sealant patient viral seroconversions and no major complications attributable to the sealant. A number of wound infections were noted, although this may represent a center-specific effect. CONCLUSIONS: Application of fibrin sealant following axillary dissection at the time of lumpectomy or modified radical mastectomy can significantly decrease the duration and quantity of serosanguinous drainage. The viral safety of the product was also supported.

Axilla↗

Hypopituitarsim is associated with triglyceride enrichment of very low-density lipoprotein.

The dyslipidemia associated with hypopituitarism may contribute to increased vascular mortality. The atherogenic potential of lipoproteins is determined not only by concentration but also by their composition. We therefore studied very low-density lipoprotein composition and apolipoprotein B kinetics in 16 hypopituitary subjects and 16 controls. Hypopituitarism was associated with reduced high-density lipoprotein cholesterol (0.98[0.82-1.18] vs. 1.35[1.15-1.41] mmol/liter, P < 0.001) and increased triglyceride concentrations (1.64[1.09-2.77] vs. 1.12[0.66-1.67] mmol/liter, P = 0.01). Total (P = 0.76) and low-density lipoprotein cholesterol (P = 0.56) concentrations were similar. Very low-density lipoprotein- triglyceride was significantly increased (1.48[1.02-2.55] vs. 0.9[0.31-2.30] mmol/liter, P = 0.004), but very low-density lipoprotein cholesterol levels were similar (P = 0.93). The molar ratios of very low-density lipoprotein-triglyceride:apolipoprotein B (6193[4283-9566] vs. 3599[3188-6854], P = 0.005) and very low-density lipoprotein-triglyceride:cholesterol (2.8[1.98-3.78] vs. 1.6[1.44-2.80], P < 0.003) were significantly increased; very low-density lipoprotein-cholesterol:apolipoprotein B molar ratios (P = 0.93) were similar. Very low-density lipoprotein apolipoprotein B fractional synthetic rate (a measure of apolipoprotein B catabolism, P = 0.42) and pool size (P = 0.63) were similar. The very low-density lipoprotein apolipoprotein B absolute synthetic rate (a measure of apolipoprotein B synthesis) tended to be higher in hypopituitarism (17.7[2.91-19.50] vs. 26.6[19.64-28.05] mg/kg per day, P = 0.24) but failed to reach statistical significance. The absolute synthetic rate, and hence very low-density lipoprotein production, correlated with very low-density lipoprotein triglyceride:apolipoprotein B ratio (P = 0.02, Rs = 0.63), suggesting that triglyceride enrichment of very low-density lipoprotein is important in the mechanism underlying very low-density lipoprotein overproduction in hypopituitarism. Because triglyceride-enriched lipoproteins are proatherogenic, this may contribute to the vascular mortality observed in hypopituitarism. The reasons for these observations are unknown; GH deficiency or routine endocrine replacement may be important.

Adenoma↗

Therapy of estrogen receptor-positive micrometastases in the peritoneal cavity with Auger electron-emitting estrogens--theoretical and practical considerations.

Previous studies have demonstrated that Auger electron-emitting estrogens, when associated with the estrogen receptor (ER), can effect breaks in DNA and ER-dependent radiotoxicity. To evaluate the potential of [123I]-iodoestrogens, ([123I]-IE) to treat ER-positive human cancer cells, we have studied the effect of incubation of [123I]-IE with ER-positive MCF-7 breast cancer cells on cell survival in vitro and found that subnanomolar concentrations of [123I]-IE effectively reduce survival, with a mean lethal dose of about 800 decays per cell. MCF-7 cells incubated 30 min with 2 nM [123I]-IE (13 MBq/ml) showed a 2 log reduction in the ability to form tumors in immunodeficient mice. Evaluation of a mathematical model for [123I]-IE therapy for intraperitoneal micrometases in vivo in the mouse, based on variables related to the (a) specific activity of [123I]-IE; (b) its affinity for ER; (c) the characteristics of the uptake and retention of [123I]-IE by the target cells; (d) the concentration of ER in the tumor cells and (e) the tumor weight suggest that such therapy may be feasible.

Animals↗

Isolated corticotropin deficiency in chronic alcoholism.

Three patients who chronically abused alcohol were found to be hyponatraemic with normal plasma potassium. The first had been admitted with confusion and weight loss, the second with hypotension and sepsis, and the third with confusion and hypoglycaemia-induced seizures. All three patients had a subnormal cortisol response in the short synacthen test; however, the plasma cortisol after three days of tetracosactrin administration was greater than 550 nmol/L. Baseline corticotropin levels were less than 10 pg/mL in all three. No structural lesions of the hypothalamo-pituitary tract were found and there was no evidence of other endocrinopathies. Glucocorticoid replacement therapy led to the resolution of hyponatraemia and hypoglycaemia, where present, and to clinical improvement. The two surviving patients remained hypocortisolaemic in the long term, without recurrence of hyponatraemia or hypoglycaemia. The features of isolated corticotropin deficiency are easily confused with other effects of chronic alcohol abuse. In alcoholic patients with unexplained hyponatraemia, hypoglycaemia or haemodynamic instability, a short tetracosactrin test is advisable.

Adrenocorticotropic Hormone↗

Radiotoxicity of Auger electron-emitting estrogens in MCF-7 spheroids: a potential treatment for estrogen receptor-positive tumors.

To approach treatment of micrometastases of steroid receptor-rich cancers using estrogen receptor-directed therapy with Auger electrons, multicellular spheroids of the estrogen receptor-rich human breast cancer cell line, MCF-7, were prepared and exposed to a range of concentrations of an Auger electron-emitting estrogen, E-17alpha-[123I]-iodovinyl-11beta-methoxyestradiol, [123I]IVME2, in vitro. After washing, the treated spheroids were dissociated to single cells and plated for assay of colony survival, whereby we observed a dose-dependent reduction in survival that was inhibited by inclusion of an excess of unlabeled estradiol in the initial incubation with [123I]IVME2. Spheroids of a range of sizes from 40 to 280 microm showed similar sensitivity to the Auger electron-emitting estrogen. The mean lethal dose was approximately 700 decays per cell and corresponded to an initial [123I]IVME2 concentration of less than 0.5 nM. If the control and treated spheroids were not trypsinized but rather were allowed to grow intact, there was not only a significant reduction in the growth of the treated spheroids, but in 18 days nearly half became necrotic, while few control spheroids were necrotic. Considering the low concentrations of Auger electron-emitting estrogen required for a significant reduction in survival, we believe this approach has merit to pursue in vivo, especially in cases where it may be possible to target the steroid receptor-rich micrometastases directly, such as ovarian cancer.

Animals↗

Acceleration in linear growth after splenectomy for hypersplenism in homozygous sickle cell disease.

Chronic hypersplenism in homozygous sickle cell (SS) disease markedly increases haemolysis and the resulting erythropoietic expansion is likely to have a high metabolic cost. Splenectomy for hypersplenism in SS disease is followed by highly significant changes in haematological indices and an increase in height, but not weight, velocity. This pattern is similar to that observed in the trichuris dysentery syndrome after treatment, and differs from the increases in both height and weight velocity that follow nutritional supplementation of severely malnourished children. It is postulated that accelerated linear growth after the reduction in erythropoietic stress may implicate a specific nutrient deficiency in hypersplenic children with SS.

Body Height↗

Osmolar gap with minimal acidosis in combined methanol and methyl ethyl ketone ingestion.

Methyl ethyl ketone is a common solvent but data on overdose in humans are scarce. We report a case of co-ingestion of methyl ethyl ketone together with methanol associated with a hyperosmolar coma without anion gap metabolic acidosis. Blood levels of methyl ethyl ketone and its metabolite, 2-butanol, indicated that this solvent did contribute approximately 20 mosm/L to an observed osmolar gap of 99 mosm/L. At the levels detected, methyl ethyl ketone may have inhibited methanol metabolism, contributing to the low serum formate (1.3 mmol/L) and normal anion gap despite a blood methanol of 67 mmol/L.

Acidosis↗

Continuous intra-arterial oxygen monitoring: accuracy and reliability in the surgical intensive care unit.

The accuracy and reliability of an invasive intra-arterial oxygen sensor catheter was evaluated in 20 critically ill surgical intensive care unit (SICU) patients. All patients required continuous arterial blood pressure monitoring, at least 72 hours of ventilator support, and intermittent arterial blood gas sampling for clinical management. The intra-arterial sensor provided continuous PO2 (PsO2) values on a bedside electronic monitor. PsO2 values were sampled every 60 seconds and automatically stored on a bedside personal computer. Arterial blood gas (ABG) PaO2 values were collected and matched by collection time with corresponding PsO2 values. During 1,238 hours of continuous intra-arterial monitoring, 74,280 PsO2 values and 246 ABG PaO2 values were collected. Of the 246 PaO2 results, 175 (71.3%) had a matching PsO2. Regression of matched PsO2 and PaO2 values yielded a correlation coefficient of 0.58 and standard error of the estimate (SEE) of 33.1 (P < 0.0005). Even though matched PsO2 and PaO2 measurements demonstrated a linear relationship, only 34 per cent of the variation in PsO2 could be attributed to changes in PaO2. Technical sensor or instrument problems affected PsO2 monitoring in 17 of 20 patients and 28 of the 33 sensors tested. The authors conclude that continuous intra-arterial monitoring of PsO2 is a novel idea, but technical issues limit its use in acutely ill, conscious SICU patients.

Adolescent↗

Interpretation of color change in blood with varying degree of methemoglobinemia.

The ability to detect the characteristic "chocolate" brown color of methemoglobin containing blood was tested in a double blind study. We prepared three concentrations of methemoglobin by adding sodium nitrite to 1-2 ml of venous, heparinized blood that was "arterialized" by mixing with room air in vacutainer tubes. House officers (HO) were asked, in a standardized protocol, to make observations ("chocolate", "abnormal" or "normal") about the methemoglobin blood alone (first in Vacutainer, and then on filter paper), and then in comparison with control blood, again in Vacutainer, then filter paper. Each HO assessed only one methemoglobin concentration. Three methemoglobin blood samples were studied with 12-14%, 26-35% and 68% methemoglobin concentrations respectively. We found that the ability to detect visually an abnormal appearance of methemoglobin was significantly improved when the test sample was compared to control blood. The descriptive term "darker than normal" was much more commonly used than "chocolate" to describe the methemoglobin blood.

Blood Specimen Collection↗