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Biomedical subjects

P J Maguire

Publications and source records attributed to P J Maguire.

13 recordsLinked to original sources

Effects of diet on pharmacokinetics of phenobarbital in healthy dogs.

OBJECTIVE: To determine effects of various diets on the pharmacokinetics of phenobarbital and the interactive effects of changes in body composition and metabolic rate. DESIGN: Prospective study. ANIMALS: 27 healthy sexually intact adult female Beagles. PROCEDURE: Pharmacokinetic studies of phenobarbital were performed before and 2 months after dogs were fed 1 of 3 diets (group 1, maintenance diet; group 2, protein-restricted diet; group 3, fat- and protein-restricted diet) and treated with phenobarbital (approx 3 mg/kg [1.4 mg/lb] of body weight, p.o., q 12 h). Pharmacokinetic studies involved administering phenobarbital (15 mg/kg [6.8 mg/lb], i.v.) and collecting blood samples at specific intervals for 240 hours. Effects of diet and time were determined by repeated-measures ANOVA. RESULTS: Volume of distribution, mean residence time, and half-life (t1/2) of phenobarbital significantly decreased, whereas clearance rate and elimination rate significantly increased with time in all groups. Dietary protein or fat restriction induced significantly greater changes: t1/2 (hours) was lower in groups 2 (mean +/- SD; 25.9 +/- 6.10 hours) and 3 (24.0 +/- 4.70) than in group 1 (32.9 +/- 5.20). Phenobarbital clearance rate (ml/kg/min) was significantly higher in group 3 (0.22 +/- 0.05 ml/kg/min) than in groups 1 (0.17 +/- 0.03) or 2 (0.18 +/- 0.03). Induction of serum alkaline phosphatase activity (U/L) was greater in groups 2 (192.4 +/- 47.5 U/L) and 3 (202.0 +/- 98.2) than in group 1 (125.0 +/- 47.5). CONCLUSIONS AND CLINICAL RELEVANCE: Clinically important differences between diet groups were observed regarding pharmacokinetics of phenobarbital, changes in CBC and serum biochemical variables, and body composition. Drug dosage must be reevaluated if a dog's diet, body weight, or body composition changes during treatment. Changes in blood variables that may indicate liver toxicosis caused by phenobarbital may be amplified by diet-drug interactions.

Alkaline Phosphatase↗

Bioartificial organ support for hepatic, renal, and hematologic failure.

The current strategy to the treatment of SIRS and MODS uses a multidisciplinary approach that emphasizes supportive therapy. Herein, we have presented a futuristic approach that focuses on replacing the function of failed organs using bioartificial technology (Table 1). Bioartificial organ technology may allow the intensivist to provide physiologic organ replacement either as a bridge to transplantation or as a "time-buying" element until native organs that have become acutely dysfunctional or nonfunctional in a variety of clinical settings, can recover their function or regenerate their mass. As bioartificial organ technology matures, it is conceivable as an ultimate goal that non-immunogenic bioartificial organs would be miniaturized or redesigned and acutely placed within the intracorporeal space as replacement organs.

Bioartificial Organs↗

Quo vadis?

There is an explosion of DNA and genetic research today. The dignity of life dictates caution be urged in the use of preembryos and fetal parts for these studies.

Ethics, Medical↗

Two-colour immunoenzymatic technique using sequential staining by APAAP to evaluate two cell antigens.

AIMS: To extend the alkaline phosphatase-antialkaline phosphatase (APAAP) immunoenzyme single stain method to a more generally applicable double stain technique. This will allow two primary antibodies of the same isotype of IgG and specifically the nuclear antigen bromodeoxyuridine (BRdU) to be evaluated with a cell surface antigen identifier. METHOD: Sequential applications of the APAAP method showed two antigen sites by different dye couplings to a common alkaline phosphatase substrate, producing blue and red reaction products on the same slide. Antigens on different cell populations as well as those in different compartments of the same cell were analysed. The method allowed a surface antigen monoclonal to be revealed first, using an optimal fixative, before alcohol/gluteraldehyde fixation was used to start the second (BRdU) staining sequence. RESULTS: An analysis of double staining of T lymphocyte subsets (CD4 and CD8) showed no significant difference in the order of application of the primaries (n = 10) and no significant difference from their corresponding single stain results (n = 50), confirming the validity of the technique where antigens are exclusively distributed. Other examples, including antigens distributed in different compartments of the same cell, displayed discrete staining which implied validity. CONCLUSION: Double staining by APAAP with this technique seems to be applicable to those cases where antigens are exclusively distributed and includes cases where different compartments of the same cell are stained. It is especially useful in revealing antigens that require different fixation and preparation--that is DNA incorporated BRdU with a surface antigen. But it does seem to have a limited ability to produce a dual colour at a common site.

Antibodies, Monoclonal↗

Hypocalcemia associated with a calcitonin-producing hepatocellular carcinoma.

We report a case of symptomatic hypocalcemia with a calcitonin-producing tumor. This case is unusual for two reasons. First, the primary tumor was a hepatocellular carcinoma that was producing large amounts of calcitonin. To our knowledge, well-defined cases of calcitonin-secreting hepatoma have not been previously reported. Second, the patient's hypercalcemia was shown to be secondary to hypomagnesemic inhibition of parathyroid function and not related to hypercalcitonemia.

Aged↗

Pharmacokinetics and protein binding of cis-dichlorodiammine platinum (II) administered as a one hour or as a twenty hour infusion.

The pharmacokinetics of cis-dichlorodiam-minoplatinum (II) (cisplatin) have been studied in seven patients, of whom four received the drug as a one hour infusion and three received it as a 20 h infusion. The patients receiving the drug over one hour exhibited biphasic clearance of total platinum with a rapid initial phase (8.7-22.5 min) and a prolonged second phase (30.5-106 h). Free (ultrafilterable) cisplatin was readily detectable in this group and was rapidly cleared (half-life about 22 min). The volume of distribution of the drug was 50.3-65.6 liters and it was 26.6-50% excreted in the urine in 48 h. In the patients receiving the 20 h infusion, a more complex plasma elimination curve was seen, with the appearance of a secondary peak. Free drug was not detectable in these patients and they showed less urinary excretion (21.4-25.9% at 48 h) than the one hour group. Cisplatin was bound to several plasma proteins, including albumin, transferrin, and gamma-globulin. The data indicate that cisplatin is retained in the body more extensively after a 20 h infusion than after a one hour infusion.

Biological Availability↗