Toxicokinetics of the active doxorubicin metabolite, doxorubicinol, in sulphur-crested cockatoos (Cacatua galerita).

The pharmacokinetics of doxorubicinol, a cytotoxic metabolite of the anticancer drug, doxorubicin, were studied in four healthy sulphur-crested cockatoos (Cacatua galerita) after a 20 min intravenous infusion of 2 mg/kg. Plasma doxorubicinol concentrations were measured by HPLC. The pharmacokinetic parameters were estimated using a non-compartmental method. The mean (+/- SD) peak concentration was 8341 +/- 3132 microg/L at 17.5 +/- 5.0 min after the start of the infusion, and doxorubicinol concentrations declined biexponentially to 154.3 +/- 34.5 microg/L, 40 min after the end of the infusion. Systemic clearance was 0.940 +/- 0.473 L/h/kg, mean residence time was 0.165 +/- 0.133 h, and steady-state volume of distribution was 0.123 +/- 0.0526 L/kg. The terminal half-life was 0.660 +/- 0.611 h. Detectible but unquantifiable concentrations of doxorubicinol were present in the plasma ultrafiltrate of two birds during the infusion, indicating very extensive plasma protein binding. Physiological, haematological and biochemical monitoring over 3 weeks showed that doxorubicinol at a single infused dose of 2 mg/kg caused no toxicities of major concern.

Doxorubicin pharmacokinetics following a single-dose infusion to sulphur-crested cockatoos (Cacatua galerita).

OBJECTIVE: To determine the pharmacokinetics of doxorubicin in sulphur-crested cockatoos, so that its use in clinical studies in birds can be considered. DESIGN: A pharmacokinetic study of doxorubicin, following a single intravenous (i.v.) infusion over 20 min, was performed in four healthy sulphur-crested cockatoos (Cacatua galerita). PROCEDURE: Birds were anaesthetised and both jugular veins were cannulated, one for doxorubicin infusion and the other for blood collection. Doxorubicin hydrochloride (2 mg/kg) in normal saline was infused i.v. over 20 min at a constant rate. Serial blood samples were collected for 96 h after initiation of the infusion. Plasma doxorubicin concentrations were assayed using an HPLC method involving ethyl acetate extraction, reverse-phase chromatography and fluorescence detection. The limit of quantification was 20 ng/mL. Established non-parametric methods were used for the analysis of plasma doxorubicin data. RESULTS: During the infusion the mean +/- SD for the Cmax of doxorubicin was 4037 +/- 2577 ng/mL. Plasma concentrations declined biexponentially immediately after the infusion was ceased. There was considerable intersubject variability in all pharmacokinetic variables. The terminal (beta-phase) half-life was 41.4 +/- 18.5 min, the systemic clearance (CI) was 45.7 +/- 18.0 mL/min/kg, the mean residence time (MRT) was 4.8 +/- 1.4 min, and the volume of distribution at steady state (V(SS)) was 238 +/- 131 mL/kg. The extrapolated area under the curve (AUC(0-infinity)) was 950 +/- 677 ng/mL x h. The reduced metabolite, doxorubicinol, was detected in the plasma of all four parrots but could be quantified in only one bird with the profile suggesting formation rate-limited pharmacokinetics of doxorubicinol. CONCLUSIONS AND CLINICAL RELEVANCE: Doxorubicin infusion in sulphur-crested cockatoos produced mild, transient inappetence. The volume of distribution per kilogram and terminal half-life were considerably smaller, but the clearance per kilogram was similar to or larger than reported in the dog, rat and humans. Traces of doxorubicinol, a metabolite of doxorubicin, were detected in the plasma.

A time-resolved fluorescence immunoassay for the determination of a novel respiratory therapeutic agent, AR-C68397XX (Viozan) in human plasma.

A dissociation-enhanced lathanide fluorescence immunoassay (DELFIA) method has been developed for the determination of AR-C68397XX, a novel respiratory therapeutic agent, in human plasma. The method is a 'direct' immunoassay and provides an alternative to the solid phase extraction RIA described in a previous publication, which employs the same specific antiserum. The DELFIA method is suitable for the determination of the analyte at pg ml(-1) concentrations. The non-isotopic label was prepared by complexation of a DTPA derivative of AR-C68397XX with free europium cation (Eu3+). Plasma samples were diluted at least 5-fold prior to analysis to eliminate matrix interference. The calibration range is 10-2000 pg ml(-1), and the LOQ of the method is 50 pg ml(-1) using 50 microl of diluted human plasma sample.

Challenges for the millennium.

Health sciences librarians will face many new challenges in the new millennium. Some we can predict and some we cannot. The Hospital Information Services columns will explore some of these challenges in this and subsequent issues.

Latanoprost and herpes simplex keratitis.

PURPOSE: To report three cases in which herpes simplex keratitis developed after initiation of latanoprost therapy. METHODS: Case report. RESULTS: One patient with a history of herpes simplex keratitis had recurrence of herpes simplex keratitis with latanoprost treatment, resolution when latanoprost was stopped, and another recurrence when rechallenged with latanoprost. A second patient with a history of herpes simplex keratitis had bilateral recurrence with initiation of latanoprost; antiviral therapy could not eradicate herpes simplex keratitis until the latanoprost was discontinued. The third patient with latanoprost-associated herpes simplex keratitis cleared with the discontinuation of latanoprost and start of antiviral therapy; reinstitution of latanoprost with prophylactic antiviral medication kept the cornea clear, but as soon as the antiviral suppression was discontinued, herpes simplex keratitis reappeared. CONCLUSION: Latanoprost, among its diverse pharmacologic effects, may mediate inflammation in the eye. Prostaglandins may be a final common pathway for stimulating recurrence of herpes simplex keratitis. Clinicians should be aware of this possible association.

Nonoperative management of blunt hepatic trauma.

Abdominal CT scanning makes nonoperative management of liver injury possible. We reviewed medical records of 56 blunt trauma patients with hepatic injury who received initial abdominal CT scan. We examined: 1) Indications for delayed surgery; 2) Disposition or cause of death; 3) Results of follow up CT scans; 4) Long term complications. Over a 53 month period, 1597 patients were admitted for blunt trauma, of which 76 patients were found to have hepatic injury. Twenty patients presented either clinically unstable or with an acute abdomen and underwent diagnostic peritoneal lavage or immediate laparotomy without a CT scan. Abdominal CT scan was performed on 56 patients, 19 of whom had hepatic injury or associated major abdominal injury and underwent laparotomy. One patient died of cardiac arrhythmias following CT scanning. The remaining 36 patients received initial nonoperative management of their hepatic injury. Three patients in this group underwent delayed abdominal surgery. Two developed an acute abdomen. One had a planned nephrectomy. No patient required surgical treatment of their liver injury at the time of laparotomy. Four deaths occurred in the 36 patients managed nonoperatively, all due to associated extra-abdominal injuries. Nineteen patients had 27 CT scans taken as follow up examination at intervals of 1 to 94 days postinjury. All of the CT scans showed stabilization or improvement of hepatic injury. Three patients who had CT scans taken at 3 months postdischarge were asymptomatic, with radiologic resolution of their hepatic injury. Nineteen patients were followed for an average of 61.8 days (range 7-203 days) after discharge with no complications from liver injury.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of online literature searching on length of stay and patient care costs.

PURPOSE: To examine the associations between (1) the economic indicators of hospital costs, charges, and length of stay (LOS) for inpatient cases and (2) the use of MEDLINE searches for such cases. METHOD: An outcome-based, objective, prospective study with an economic evaluation was conducted from September 1989 to September 1990 at three metropolitan Detroit teaching hospitals representing both allopathic and osteopathic care. The study consisted of (1) 192 test cases, derived from a consecutive sample of inpatients of all ages for whom MEDLINE searches were requested at the participating medical libraries, and (2) 10,409 control cases, which were of the same diagnosis-related groups (DRGs) as the test cases but did not involve identified MEDLINE searches. Statistical analysis included the use of multivariate analyses of variance and correlation coefficients. Comparisons of cases were made on case-by-case and DRG bases regarding total patient costs, charges, and lengths of stay for cases with or without MEDLINE searches. RESULTS: The test cases were found to have a higher severity of illness. Among test cases, statistically significant relationships existed between (1) hospital expenses and LOS and (2) hospital expenses and the timing of the search during hospitalization when controlling for LOS. When cases were matched for DRG and LOS, the cases with early searches (i.e., conducted during the first half of hospitalization) had significantly lower expenses. CONCLUSION: Of the test-case patients (for whom MEDLINE searches were conducted during hospitalization), those whose searches were conducted earlier had statistically significantly lower costs, charges, and lengths of stay than those whose searches were conducted later.

Sibling incest: a descriptive study of family dynamics.

This study investigates the characteristics of families in which a member was identified as a victim of sibling incest. Four agencies in a southeastern city provided a convenience sample of 14 family case records from November 1986 through April 1988 for review. Sixteen children were identified as victims of sibling incest, including three boys and 13 girls between the ages of 2 and 10 years (mean = 6.75 years). Perpetrators included 1 girl and 14 boys between the ages of 13 and 17 years (mean = 15.06 years). The incestuous relationship had a major impact on families, especially the children. Many offenders and victims, in addition to experiencing emotional, school, and legal problems, were removed from their homes.

Sibling incest.

Child sexual abuse has gained national attention within the last decade. The most reported and studied form of intrafamilial child sexual abuse is father-daughter incest. However, it is believed that sibling incest may be a more widespread form of intrafamilial sexual abuse. Yet, it has received the least amount of documentation and study. The purpose of this article is to describe sibling incest, including family dynamics. Implications for nursing intervention and research are proposed.

Characteristics of the cellular response of the rat conjunctiva to topically applied leukotriene B4.

Cellular events in the rat conjunctiva were studied at 1, 6 and 24 h following the topical application of leukotriene B4. A significant increase was noted in the number of eosinophils (p less than 0.01) and neutrophils (p less than 0.05) at 1 h and only in eosinophils at 6 h after leukotriene B4 application at the 2-micrograms dose. At the 200-ng dose, the eosinophil count was significantly elevated at 1 h only, and the number of neutrophils was not significantly changed at any time point. No significant increase in cell counts was observed at the 20-ng dose. In conclusion, certain doses of topically applied leukotriene B4 significantly increased the number of eosinophils and neutrophils in the rat conjunctiva.

Sexual abuse and group therapy.

This article described the formation of a structured, open-ended, time-limited, repeatable group for sexually abused girls. The sexually abused pre-adolescent and young adolescent must address developmental tasks while attempting to cope with tremendous guilt, shame, and loss of self-esteem. The value of group therapy as a support to sexually abused children was explored and a format was devised to help them deal with their issues. Discussion questions and topics designated for each session helped meet their specific needs. The group members evaluated the group as being helpful overall. In conclusion, the expansion of psychotherapeutic services to sexually abused children through a structured group format has been proposed. If others are encouraged to engage in such work, then the purpose of this article has been achieved.

Sustained reduction of intraocular pressure in humans with the calcium channel blocker verapamil.

We investigated the effect of the calcium channel blocker verapamil on intraocular pressure in human volunteers. In the initial trial, 15 subjects with untreated ocular hypertension were tested. After a baseline measurement was obtained with applanation tonometry, a 40-microliter drop of verapamil, 1.25 mg/ml, was instilled in one eye. After 30 minutes, a second reading was taken. In a subsequent trial of 12 untreated ocular hypertensive subjects, the duration of action was determined using the same dose and method of delivery. Results showed that verapamil elicited a mean +/- S.E.M. change in intraocular pressure of -3.8 +/- 0.900 mm Hg in the treated eye, and -1.6 +/- 0.400 mm Hg in the untreated eye. This reduction was statistically different in both eyes (treated eye, P = .0007; untreated eye, P = .005). This decrease in intraocular pressure remained statistically significant when compared to predrug baseline values for up to ten hours.

A radioimmunoassay method for the determination of nedocromil sodium in plasma and urine.

A radioimmunoassay method for the determination of nedocromil sodium (FPL 59002 disodium salt) in human plasma and urine is described. The method employs a primary antiserum raised in a sheep, and a mono-tyramide derivative of nedocromil sodium labelled with iodine-125 as a heterogeneous radioligand. Free and bound radioligand are separated using a secondary anti-sheep IgG antiserum. All three reagents are added simultaneously to samples containing nedocromil sodium prior to an overnight incubation. The method has a limit of detection of 0.25 ng ml(-1), when plasma sample volumes of 100 microl are analysed, and is accurate and precise. Inter-assay relative standard deviations (N = 18) of 15.1, 5.0 and 5.6% were found at concentrations in plasma of 0.5, 2.0 and 6.0 ng ml(-1) respectively. The method is specific as indicated by negligible cross-reaction of the anti-nedocromil sodium antiserum with a range of drugs. The method is applicable to the analysis of samples from subjects who have inhaled nedocromil sodium from a pressurised aerosol.