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Biomedical subjects

L J Dusci

Publications and source records attributed to L J Dusci.

At least 19 recordsLinked to original sources
PubMed1992

Comparison of cyclosporine measurement in whole blood by high-performance liquid chromatography, monoclonal fluorescence polarization immunoassay, and monoclonal enzyme-multiplied immunoassay.

Monitoring of cyclosporine concentrations in whole blood is used routinely as a guide to adjusting dose so as to achieve optimal therapeutic benefit with minimal adverse effects. In the present study, we have compared a specific high-performance liquid chromatography (HPLC) assay with a fluorescence polarization immunoassay (TDx) and an enzyme-multiplied immunoassay (Emit). Both Emit and TDx assays employ a monoclonal antibody to cyclosporin A and therefore have the potential for a high degree of specificity. Blood specimens (EDTA as anticoagulant) were obtained from 113 patients (71 renal transplants, 17 liver transplants, and 25 other categories) taking cyclosporine and analysed by all three methods. There were significant correlations between results for HPLC and Emit (Emit = 10.54 + 1.07 x HPLC; r2 = 0.82, p less than 0.001) and between results for HPLC and TDx (TDx = 9.16 + 1.42 x HPLC; r2 = 0.82, p less than 0.001). Compared to HPLC analysis, 74% and 96%, respectively, of Emit and TDx results were to the left of the line of identity. The TDx monoclonal antibody appears to have a lesser degree of specificity than that used in the Emit assay. Mean concentrations of cyclosporine measured by Emit and TDx were 17% and 51% higher, respectively, than those measured by HPLC. Because of this overestimation, we suggest that both Emit and TDx methods may find their most appropriate use in routine therapeutic monitoring of renal transplant patients in whom metabolite concentrations are less variable over time.

Antibodies, Monoclonal↗
PubMed1992

The excretion of dothiepin and its primary metabolites in breast milk.

1. The excretion of dothiepin, nordothiepin, dothiepin-S-oxide and nordothiepin-S-oxide into breast milk was studied in eight women. Exposure to drug was measured in five of their infants, and possible drug-related effects were assessed in all eight infants. 2. Using pre-feed milk samples mean (+/- s.e. mean) milk:plasma (M:P) ratios were 0.78 +/- 0.12, 0.85 +/- 0.16, 1.18 +/- 0.29 and 1.86 +/- 0.29 for dothiepin, nordothiepin, dothiepin-S-oxide and nordothiepin-S-oxide, respectively. In post-feed milk samples, the mean M:P ratio for dothiepin (1.59 +/- 0.32) was significantly greater (P less than 0.05) but M:P ratios for the metabolites were similar. 3. Mean total calculated infant daily doses, (in dothiepin equivalents and as a percent of the maternal dose) were 0.58% for dothiepin, 0.23% for nordothiepin, 2.47% for dothiepin-S-oxide, and 1.17% for nordothiepin-S-oxide. 4. Plasma samples were obtained from five infants. In one, both dothiepin and nordothiepin were below their minimum quantifiable levels (2 micrograms l-1) while in four others both dothiepin-S-oxide and nordothiepin-S-oxide were below their minimum quantifiable levels (10 micrograms l-1). No adverse effects were found in any of the eight infants. 5. Use of dothiepin by depressed mothers is unlikely to be a significant hazard to their breast-feeding infants.

Adult↗
PubMed1991

Intravenous regional administration of methylprednisolone in rheumatoid arthritis.

Intravenous regional administration of corticosteroid (IVRAS) in the treatment of rheumatoid arthritis of the hand has not been reported previously. The method is based on a modification of Bier's block, with substitution of corticosteroid for local anaesthetic. Twenty-two patients were assessed in this double-blind, placebo-controlled study. The technique was safe and effective in improving grip strength, with a group mean improvement of more than 50%. Because suppression of endogenous cortisol production 24 h after treatment was commensurate with the dose of methylprednisolone used (40 mg), we could not exclude that the response may have been due to systemic steroid. Further studies are required to define the real value of IVRAS as it may offer alternative treatment of the joints and tendons within the hand and wrist in some patients rather than more prolonged oral therapy or individual, multiple joint or sheath injections.

Arthritis, Rheumatoid↗
PubMed1991

Disposition of dothiepin after overdose: effects of repeated-dose activated charcoal.

Although the tricyclic antidepressant dothiepin is often encountered in deliberate self-poisonings, there are no published studies of its disposition in overdose. In the present study, we have documented the plasma disposition of dothiepin and its major metabolites in eight overdose patients. All had high initial levels of dothiepin (819-3,851 micrograms/L), dothiepin-S-oxide (655-2,162 micrograms/L), nordothiepin (88-422 micrograms/L), and nordothiepin-S-oxide (176-530 micrograms/L) that were considerably above steady-state therapeutic concentrations. In three patients who received treatment with repeated-dose activated charcoal, dothiepin half-lives were 10.6, 12.5, and 13.1 h compared with the literature range of 18.5-24 h. All patients survived and none experienced any significant cardiovascular event despite exhibiting clinical signs of tricyclic antidepressant overdose. We suggest that repeated-dose activated charcoal treatment may decrease the dothiepin half-life after overdose.

Adult↗
PubMed1991

Excretion of indomethacin in breast milk.

1. The excretion of indomethacin into breast milk and subsequent exposure of infants was studied in 16 women and seven of their infants. The median milk:plasma ratio in seven patients where there were measurable drug concentrations in both milk and plasma was 0.37. 2. Total infant dose, assuming a daily milk intake of 150 ml kg-1 and 100% absorption, ranged from 0.07% to 0.98% (median = 0.18%) of the weight adjusted maternal dose. 3. Plasma samples were obtained in seven infants. In six of these, indomethacin concentrations were below the sensitivity of the assay (less than 20 micrograms l-1), while one infant had a plasma indomethacin concentration of 47 micrograms l-1. 4. No adverse effects due to indomethacin were reported in the infants.

Adult↗
PubMed1990

Excretion of diazepam and its metabolites in human milk during withdrawal from combination high dose diazepam and oxazepam.

The excretion of diazepam, N-desmethyldiazepam, temazepam and oxazepam in breast milk was studied during withdrawal of a 22-year-old patient from combined high dose diazepam and oxazepam therapy. Concentrations of these benzodiazepines in plasma from both the woman and her nursing infant (1 year old) were also documented. Diazepam, N-desmethyldiazepam, temazepam and oxazepam were found in the maternal plasma and milk with mean milk: plasma ratios of 0.2, 0.13, 0.14 and 0.10 respectively. It was calculated on a mg kg-1 basis that the infant received some 4.7% of the maternal dose. Diazepam could not be detected in the infant's plasma, but low levels of N-desmethyldiazepam (20 and 21 micrograms l-1), temazepam (7 micrograms l-1) and oxazepam (7.5 and 9.6 micrograms l-1) were present. The infant showed no overt physical or mental symptoms of benzodiazepine intoxication.

Adult↗
PubMed1987

Simultaneous determination of clobazam, N-desmethyl clobazam and clonazepam in plasma by high performance liquid chromatography.

A method is described for the simultaneous determination of clobazam, its active metabolite N-desmethylclobazam, and clonazepam in plasma by high performance liquid chromatography. The drugs are extracted with diethyl ether from 1.0 ml plasma adjusted to pH 9.0 and separated on a C18 reverse phase column using a mobile phase of 40% acetonitrile in phosphate buffer pH 3.0. The ultraviolet absorbance is monitored at a wavelength of 313 nm. The method has a coefficient of variation of less than 5% and an overall recovery of greater than 85% and is sufficiently sensitive for the therapeutic monitoring of these drugs.

Anti-Anxiety Agents↗
PubMed1987

High-performance liquid chromatographic method for measurement of pentamidine in plasma and its application in an immunosuppressed patient with renal dysfunction.

A rapid method for the quantitation of pentamidine in plasma by high-performance liquid chromatography is described. Pentamidine was extracted from plasma using a mixed solvent of 40% acetonitrile in chloroform. Reversed-phase chromatography was then performed on a mu Bondapak C-18 column, using a mobile phase of acetonitrile containing 0.1% H3PO4 and 0.1% NaCl (20:80) and the eluting peaks detected by their UV absorbance at 262 nm. The assay had a within-day coefficient of variation of less than 3.8%, an absolute recovery of 92%, and a limit of detection of 15 nmol/L. The method was applied during pentamidine mesylate treatment (4 mg/kg/day) for Pneumocystis carinii pneumonia in an immunosuppressed patient with impaired renal function. Plasma levels rose slowly to a plateau (range 530-880 nmol/L) after 7 days of treatment, suggesting a half-life of around 1.5-2 days.

Amidines↗
PubMed1986

Buprenorphine: a new maintenance opiate?

Heroin-dependent out-patients who had been prescribed buprenorphine by general practitioners took part in a controlled study in which 2 mg or 4 mg of buprenorphine were administered by the sublingual route to assess its acceptability as a maintenance opiate and to determine the effects of its abrupt withdrawal and reintroduction a week later. Subjects who received 4 mg of buprenorphine reported being more intoxicated and having fewer symptoms of opiate withdrawal than did the subjects who received the 2-mg dose. Subjects who received the higher dose also abused opiate and benzodiazepine drugs less frequently. When buprenorphine was ceased abruptly, the subjects reported mild withdrawal discomfort for which many requested symptomatic treatment. The reintroduction of buprenorphine caused their condition to restabilize. The subjects' use of opiate drugs, as shown by urine assay, rose from a prevalence of around 15% of specimens at the beginning to about 50% of specimens at the end of the five-week study period. Sublingual buprenorphine was acceptable to opiate-addicted outpatients as a maintenance treatment. However, daily doses of greater than 4 mg will probably be required to suppress concurrent opiate abuse, and detoxification will need to be undertaken gradually.

Administration, Oral↗