PubMed HealthSearch

Biomedical subjects

G H Mayor

Publications and source records attributed to G H Mayor.

At least 19 recordsLinked to original sources

A study in normal human volunteers to compare the rate and extent of levothyroxine absorption from Synthroid and Levoxine.

Numerous branded and generic formulations of levothyroxine (LT4) sodium tablets are currently available. Results from previous studies attempting to examine the comparative bioavailability of these formulations are difficult to interpret because of subject heterogeneity, single time-point blood sampling, varying degrees of hypothyroidism, and other factors. This study was devised to compare the rate and extent of absorption of LT4 from different LT4 sodium tablet formulations, in a simple model using a single-dose two-way single-blind, randomized cross-over design in 30 normal, healthy, nonpregnant, female subjects. This design controlled for many factors that limited previous LT4 bioavailability studies. Subjects were given a single 600 micrograms dose of LT4 as either Synthroid (Boots Pharmaceuticals, Inc., Lincolnshire, IL) tablets (formulation A) or Levoxine tablets (Daniels Pharmaceuticals, St. Petersburg, FL; formulation B). Measurements of baseline-corrected total T4 serum concentrations determined at multiple time points demonstrated statistically significant differences between the two formulations at the 1.00, 3.00, 5.00, and 18.00 hour sampling times. Statistically significant differences for area under the curve (AUC) (0 to 48 hours) (formulation A, 159.9 +/- 9.4 micrograms-hour/dL; formulation B, 193.4 +/- 10.1 micrograms-hour/dL) and maximum peak plasma concentration (Cmax) (formulation A, 5.91 +/- .34; formulation B, 7.12 +/- .32) also were demonstrated. Furthermore, the ratio of the baseline-corrected total T4 concentrations (B/A x 100) were 120.9% for AUC and 120.5% for Cmax. These data demonstrate that the administration of Synthroid and Levoxine result in a significantly different rate and extent of absorption of LT4, and therefore these two formulations cannot be considered bioequivalent.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

NSAIDs: an overview.

Explore the source record for details and available documents.

Anti-Inflammatory Agents, Non-Steroidal

Evaluation of bidirectional aluminum transfer across hollow fiber dialyzers.

The ultrafiltrable fraction of plasma aluminum (UFAl) determined utilizing the hollow fiber dialyzer is variable and ranges from 10% to 50%. This extreme variability in UFAl led us to examine the possibility of Al binding to the hollow fiber dialyzer. Ultrafiltrate of aqueous Al solutions was obtained by applying a negative pressure of 250 mm Hg to a hollow fiber dialyzer (TriEx-1). In the first of three experimental protocols, Al was measured before and after recirculation of solutions containing 344 to 9244 micrograms/L Al through a hollow fiber dialyzer until the entire volume was collected as ultrafiltrate. UFAl ranged from 0.9% to 37.6% and did not correlate with the initial Al concentration. Total Al binding ranged from 42 micrograms to 1.3 mg. In the second, 16 L of aqueous AlCl3 solution (n = 3), containing from 205 to 411 micrograms/L Al were passed through the blood compartment of a hollow fiber dialyzer. The percentage of UFAl ranged from 4.1% to 17.3% during the first 20 minutes and 79.3% to 81.8% at 120 minutes. Finally, to investigate Al transfer from dialysate, 16 L of deionized distilled water were passed through the blood compartment while 16 L of AlCl3 solutions of 330 micrograms/L and 398 micrograms/L AI passed through the dialysate compartment. Samples were collected from blood and dialysate outflow ports every 20 minutes for 120 minutes. The transfer of Al from dialysate to blood compartment increased with time. However the concentration of Al at the blood outflow port never reached that at the dialysate outflow port.(ABSTRACT TRUNCATED AT 250 WORDS)

Aluminum

The metabolism of aluminum and aluminum-related encephalopathy.

The dialysis encephalopathy syndrome is at once the most widely recognized and most severe manifestation of aluminum toxicity. Evidence linking this syndrome and aluminum intoxication is virtually incontrovertible. The syndrome is characterized by speech and motor difficulties, dementia, and seizures. Less widely recognized symptoms include subtle changes in cognition and personality and directional disorientation. Since the widespread use of water treatment, aluminum exposure in the dialysis population has been primarily via intravenous (IV) medications and oral aluminum-containing, phosphate-binding antacid gels. In addition to the encephalopathy syndrome, aluminum has been linked to toxicity in bone, parathyroid gland, RBC, and kidney. These organ toxicities seem to be the result of specific protein enzyme inhibition. Currently identified factors that affect aluminum accumulation and modulate aluminum balance include uremia, renal function, parathyroid hormone withdrawal and suppression, 1,25-dihydroxycholecalciferol, and serum aluminum binding. Impaired renal function is not a prerequisite for increased tissue aluminum burdens. It is likely that aluminum-related disease will be increasingly observed in populations other than those with chronic renal failure.

Aluminum

1,25-Dihydroxyvitamin D3 increases serum and tissue accumulation of aluminum in rats.

We examined the effect of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) in both hypercalcemic and hypocalcemic rat models and the effect of exogenous 25-hydroxyvitamin D3 (25(OH)D3) on serum and tissue aluminum (Al) burdens. Rats fed a 0.2% Al diet received daily subcutaneous injections of either 1,25(OH)2D3 (80.9 ng/kg, n = 5 and 809 ng/kg, n = 8), 25 (OH)D3 (809 ng/kg, n = 4, and 8090 ng/kg, n = 8) or propylene glycol vehicle for 18 days. Rats given 809 ng/kg of 1,25(OH)2D3 were hypercalcemic and when compared with pair-fed controls had higher serum (33.1 vs. 14.3 micrograms/L, P less than 0.01), bone (21.2 vs. 13.2 micrograms/gm, P less than 0.01), and kidney (6.5 vs. 2.0 micrograms/gm, P less than 0.01) but not brain (1.2 vs. 1.5 micrograms/gm) or liver (0.9 vs. 0.8 micrograms/gm dry tissue) Al concentration. The lower dose of 1,25(OH)2D3 had no effect on serum or tissue Al. Treatment with 25(OH)D3 did not increase serum Ca and Al or tissue Al concentration. To dissociate a specific effect of exogenous 1,25(OH)2D3 from the concurrent hypercalcemia, endogenous production of 1,25(OH)2D3 was stimulated. Animals were fed a low Ca diet until hypocalcemia developed and were then divided into four groups: one given low Ca (n = 7) for 21 days, one given low Ca plus 0.2% Al (n = 7) for 21 days, one returned to a normal Ca diet (n = 4) for 30 days, and one returned to a normal Ca diet for 9 days and continued with a normal diet plus 0.2% Al (n = 5) for 21 days. Hypocalcemic rats fed the Al diet, when compared with hypocalcemic controls, had higher serum (143.6 vs. 31.8 micrograms/L, P less than 0.01), bone (16.0 vs. 2.9 micrograms/gm, P less than 0.01), and kidney (8.2 vs. 2.8 micrograms/gm, P less than 0.005) but not brain (3.4 vs. 2.3 micrograms/gm) or liver (3.8 vs. 2.3 micrograms/gm) Al concentrations. Serum, bone, and kidney Al concentration was also significantly higher than that in normocalcemic rats fed the Al diet. These results indicate that pharmacologic doses of 1,25(OH)2D3 and dietary hypocalcemia enhance gastrointestinal Al absorption and serum, kidney, and bone Al concentration.

Aluminum

Encephalopathy in chronic renal failure responsive to deferoxamine therapy. Another manifestation of aluminum neurotoxicity.

We describe a patient undergoing chronic hemodialysis who developed a neurologic syndrome consisting of seizures, progressive myoclonus, and mild dementia and who responded to chelation therapy with deferoxamine mesylate. Neither her serum nor bone aluminum concentrations indicated aluminum toxicity. However, the presence of a positive deferoxamine-infusion test was suggestive of an elevated body burden of aluminum. Treatment with deferoxamine resulted in marked clinical improvement in her neurologic status within two months. The utility of using the deferoxamine-infusion test rather than serum aluminum levels in evaluating aluminum toxicity in chronic renal failure is suggested.

Aluminum

Effect of aluminum on the renal handling of phosphate in the rat.

The effects of aluminum (Al) on the renal handling of phosphate (Pi) were studied by clearance techniques in the presence and absence of endogenous parathyroid hormone (PTH) and after Pi infusion. In all groups, a 1-h control period was followed by three 1-h experimental periods in which controls continued to receive saline and experimental animals received Al. Glomerular filtration rate, urine flow rate, and plasma sodium (Na) were not significantly changed between periods in any group. In the presence of endogenous PTH, the fractional excretion of phosphate (FEPi) increased significantly after 3 h of Al infusion (6.1 +/- 0.9 to 15.0 +/- 1.8%, P less than 0.05, n = 8), but not in controls (n = 7), while plasma calcium and Pi decreased, suggesting a PTH effect. However, in acutely thyroparathyroidectomized (TPTX) rats the FEPi also increased significantly after 3 h of Al infusion (4.3 +/- 3.0 to 10.6 +/- 4.2%, P less than 0.05, n = 7), but not in controls (n = 6). In TPTX rats infused with Pi where plasma Pi was increased to 10 mg/dl, FEPi increased significantly after 2 and 3 h of Al (7.0 +/- 1.4 to 15.5 +/- 2.1 to 16.9 +/- 2.2%, P less than 0.01, n = 15), but not in controls (n = 8). In this group, changes in FEPi were accompanied by a small but significant increase in FENa but not urinary cAMP. Blood pH was not significantly different between saline and Al-infused rats. These studies indicate that Al infusion inhibits renal Pi reabsorption by a mechanism independent of PTH, blood pH, or cAMP.

Aluminum

Renal handling of aluminum in the rat: clearance and micropuncture studies.

Previous uncertainty regarding glomerular ultrafilterability (UF) of aluminum has limited the definition of renal Al handling. Glomerular micropuncture was therefore performed in hydropenic Munich-Wistar rats infused with AlCl3 to achieve plasma (P) Al levels between 2 and 10 mg/liter. Glomerular fluid, P, and urine Al concentrations were measured by flameless atomic-absorption spectrophotometry. UFA1 was inversely correlated with PA1 [%UFA1 = 10.3 - 8.4 (log PA1), r = -0.90, P less than 0.01]. When this equation was used to calculate the filtered load (FLA1), A1 excretion (UA1V, ng/min) in simultaneously collected samples was found to be a direct function of FLA1 [UA1V = 5.7 + 0.37 (FLA1), r = 0.93, P less than 0.01]. Fractional excretion (FE) of A1 was 39.4 +/- 4.2% in these hydropenic experiments (FENa = 0.3 +/- 0.1%). We next evaluated the tubular handling of A1 (using these UF data) during step-wise extracellular fluid volume expansion with isotonic saline (2.5, 5.0, 7.0, and 7.0% body wt) and during the infusion of increasing doses (2.7, 5.3, 8.0, and 8.0 mg X kg-1 X h-1) of furosemide as urinary losses were quantitatively replaced. The natriuresis produced by volume expansion (FENa = 1.0, 3.0, 8.4, and 7.9%) and furosemide (FENa = 4.2, 6.0, 6.6, and 6.7%) were comparable. At similar FLA1, 7% volume expansion but not furosemide (at any dose) increased UA1V (240 and 95 ng/min, respectively, vs. 116 ng/min in hydropenia) and FEA1 (84.5 and 29.4 vs. 37.4%, respectively). These data indicate that at pharmacological PA1 levels, less than 8.4% of PA1 is ultrafilterable, suggesting extensive plasma protein binding.(ABSTRACT TRUNCATED AT 250 WORDS)

Aluminum

Parenthood after renal transplantation.

Parenthood in renal allograft recipients is no longer rare. Rational guidelines are needed since there are no absolute medical contraindications to parenthood in recipients of either sex. This report by the patient and her physician describes the clinical course of the recipient of a cadaveric renal allograft, including a normal pregnancy and delivery. Urine protein excretion increased during pregnancy, but later returned to normal. There were no complications to mother or fetus, despite continued immunosuppressive therapy. The problems of parenthood in allograft recipients are discussed from the patient viewpoint, rational guidelines for patient counseling are offered, and the world's literature is reviewed. The possible complications to parent and fetus are discussed, including the complications of pregnancy and immunosuppressive drug therapy. We conclude that parenthood should be the choice of the allograft recipient.

Adult

Prevalence of hepatitis B in 27 Michigan hemodialysis centers.

A large epidemiological survey of inhospital chronic hemodialysis patients was conducted in 27 (93%) of the 29 dialysis centers in Michigan. Serum was collected from 699 patients on chronic maintenance hemodialysis for periods from one month to eight years. Hepatitis B surface antigen (HBsAg) was determined in all patients by radioimmunoassay and positive samples were confirmed by specific neutralization. Antibody against HBsAg (anti-HBs) was determined by radioimmunoassay in 110 HBsAg negative patients from six dialysis units with a high prevalence of hepatitis B. HBsAg was detected in 80 (11.4%) patients distributed among 21 (78%) of 27 dialysis units and anti-HBs in 34 (31%) patients from the selected dialysis units. The prevalence of HBsAg was related to duration of dialysis, number of blood transfusions, and to a history of bilateral nephrectomy, but not to age, sex, race, nor the underlying renal disease. Twenty-one (26%) of the 80 HBsAg positive patients had not been previously identified by the clinical laboratories of their institutions. Since preventive measures were not taken in the care of these inapparent carriers of HBsAg, they represent an unrecognized risk.

Blood Transfusion

Noninvasive measurement of bone mineral mass in the unanesthetized rabbit.

Direct photon absorptiometry was used for the in vivo measurement of bone mineral mass in the rabbit tibia. Bone mineral mass in 124 male and female rabbits was correlated (p less than 0.001) with age to 26 weeks and weight to 5.5 kg. Examining reproducibility and repositioning error, three rabbits were measured 12 times each. Bone mineral mass in the three rabbits was: 0.432 +/- 0.020 g/cm2, 0.414 +/- 0.010 g/cm2 and 0.487 +/- 0.037 g/cm2. The greatest coefficients of variance observed for measurements without repositioning and measurements with repositioning were 4.8% and 7.6%, respectively. The technique provided sensitive, reproducible and noninvasive measurement of bone mineral mass without anesthesia or undue restraint.

Age Factors