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Biomedical subjects

S O'Reilly

Publications and source records attributed to S O'Reilly.

At least 91 records · Page 5Linked to original sources

Determination of the pKa of ionizable enzyme groups by nonlinear regression using a second degree equation.

A second degree equation fitted by nonlinear regression for the analysis of the pH effect on enzyme activity is proposed for diprotic enzyme systems. This method allows the calculation of two molecular dissociation constants (KE1 and KE2 for the free enzyme, KES1 and KES2 for the ES complex) and the pH independent parameters (Vmax and Vmax/Km). The method is validated by bibliographic (alpha-chymotrypsin) and experimental data (almond beta-D-glucosidase). No significant differences were found between present data and those previously reported in the literature using similar experimental conditions. This method works using comparatively few [H+] concentration values within a narrow pH range, preferentially around the optimum, being adequate for diprotic systems with close pKa values.

Computer Simulation↗

Anaplastic carcinoma of the thyroid following radio-iodine therapy.

We describe a 79 year old lady who presented with a cytologically confirmed anaplastic carcinoma of the thyroid gland eleven years after administration of radio-iodine for thyrotoxicosis. This is, we believe, the first such occurrence documented in the Irish literature.

Aged↗

Effect of daily etidronate on the osteolysis of multiple myeloma.

Progressive bone disease in multiple myeloma frequently leads to osteolysis, bone resorption, pathologic fractures, vertebral compression, and hypercalcemia. We conducted a double-blind study in 173 newly diagnosed multiple myeloma patients of etidronate disodium (EHDP), a diphosphonate compound that reduces bone resorption by inhibiting osteoclastic activity. The patients were randomly assigned to receive oral EHDP 5 mg/kg/d or placebo until death or discontinuation due to intolerance or refusal. The extent of vertebral deformity was measured by a vertebral index as well as height. The frequency of pathologic fractures, hypercalcemia, and bone pain was regularly assessed, as well as size and number of osteolytic lesions. All patients received melphalan and prednisone daily for 4 days every 4 weeks as the primary chemotherapy for their disease. Although the repeated measures analysis showed a significant height loss, there was no difference between treatment arms (P = .98). There was no significant difference in bone pain, episodes of hypercalcemia, or development of pathologic fractures. Patients on EHDP showed less deterioration in their vertebral index, but this difference only approached statistical significance (P = .07). We conclude that EHDP therapy used in this dosage schedule does not have a clinically significant impact in multiple myeloma.

Aged↗

Carboplatin dosage: prospective evaluation of a simple formula based on renal function.

A dosage formula has been derived from a retrospective analysis of carboplatin pharmacokinetics in 18 patients with pretreatment glomerular filtration rates (GFR) in the range of 33 to 136 mL/min. Carboplatin plasma clearance was linearly related to GFR (r = 0.85, P less than .00001) and rearrangements of the equation describing the correlation gave the dosage formula dose (mg) = target area under the free carboplatin plasma concentration versus time curve (AUC) x (1.2 x GFR + 20). In a prospective clinical and pharmacokinetic study the formula was used to determine the dose required to treat 31 patients (GFR range, 33 to 135 mL/min) with 40 courses of carboplatin. The target AUC was escalated from 3 to 8 mg carboplatin/mL/min. Over this AUC range the formula accurately predicted the observed AUC (observed/predicted ratio 1.24 +/- 0.11, r = 0.886) and using these additional data, the formula was refined. Dose (mg) = target AUC x (GFR + 25) is now the recommended formula. AUC values of 4 to 6 and 6 to 8 mg/mL. min gave rise to manageable hematological toxicity in previously treated and untreated patients, respectively, and hence target AUC values of 5 and 7 mg/mL min are recommended for single-agent carboplatin in these patient groups. Pharmacokinetic modeling demonstrated that the formula was reasonably accurate regardless of whether a one- or two-compartment model most accurately described carboplatin pharmacokinetics, assuming that body size did not influence nonrenal clearance. The validity of this assumption was demonstrated in 13 patients where no correlation between surface area and nonrenal clearance was found (r = .31, P = .30). Therefore, the formula provides a simple and consistent method of determining carboplatin dose in adults. Since the measure of carboplatin exposure in the formula is AUC, and not toxicity, it will not be influenced by previous or concurrent myelosuppressive therapy or supportive measures. The formula is therefore applicable to combination and high-dose studies as well as conventional single-agent therapy, although the target AUC for carboplatin will need to be redefined for combination chemotherapy.

Antineoplastic Agents↗

Brain death--an opposing viewpoint.

Recent and proposed legislation to establish "brain-related" criteria of death has uniformly confounded irreversible cessation of total brain function with the death of the human person. Much of the confusion comes from widespread misunderstanding of how the word "death" is used and what it means. Cessation of total brain function, whether irreversible or not, is not necessarily linked to total destruction of the brain or to the death of the person. Further, to take vital organs or to otherwise treat people as though they were dead already on the basis of these recent criteria is morally unacceptable to most Orthodox Jews and Christians.

Brain↗

Pigment binding of copper in human bile.

The copper profile of human bile was studied using a Cu-free preparative polyacrylamide gel system. 85 percent and 91 percent of the Cu in the bile of two subjects was found in a leading pigmented band with no additional detectable copper in the remainder of the gel in either subject. The content of the pigmented band was recovered from the gel by an intermediate electrophoretic technique. Subsequent n-butanol extraction removed contaminating bile salts with the formation of a Cu containing pigmented precipitate. Using thin-layer cellulose chromatography this precipitate was separated into two pigments which on the basis of color and diazotization reaction were believed to be conjugated bilirubins. Addition of Cu transformed the pigments into biochemically different species. 64Cu verified copper binding by the altered pigments.

Bile↗

Kinky hair disease. Study of copper metabolism with use of 67Cu.

Metabolism of labeled Cu (67Cu) was studied in three patients with kinky hair disease (KHD). Labeled Cu was administered first intravenously and, later, orally. We determined oral absorption, excretion, and internal kinetics of this metal. Patients with KHD absorbed 11% to 13% of Cu given orally, compared to 46% by unaffected controls. Total excretion of Cu given intravenously during the first seven days after administration was greatly reduced in patients with KHD. The biological half-life of 67Cu in patients with KHD was increased by a factor of 2 to 3 over the normal control. Most of the labeled Cu was retained by the patient's liver, while in the control subject there was more rapid movement to the Cu to circulation (ceruloplasmin). Red blood cells of patients with KHD incorporated orally administered Cu preferentially, which was sufficient to prevent anemia.

Age Factors↗