Blood naltrexone levels over time following naltrexone implant.

AIMS: Oral naltrexone is used in the management of both heroin and alcohol dependence. However, poor compliance has limited its clinical utility. The study's objective was to determine the period of therapeutic coverage (>or=2 ng/ml) provided by a 3.3 g naltrexone subcutaneous implant compared with existing data on 1.1 g and 2.2 g implants. METHODS: We assessed free blood naltrexone levels following treatment with a 3.3 g naltrexone implant in heroin dependent patients (n=50) in Perth, Western Australia. Results were compared with previously collated data for patients treated with either a 1.1 g (n=10) or 2.2 g (n=24) implant. RESULTS: Following 3.3 g naltrexone implant treatment, free blood naltrexone levels remained above 2 ng/ml for 145 days (95% CI 125-167). In comparison, 1.1 g or 2.2 g implant treatment resulted in 95 days (95% CI 69-121) and 136 days (95% CI 114-158) coverage, respectively. CONCLUSIONS: The 3.3 g implant provides longer therapeutic coverage than the 1.1 g implant but not significantly longer than the 2.2 g implant.

Achieving long-term continuous blood naltrexone and 6-beta-naltrexol coverage following sequential naltrexone implants.

The aim of this study was to assess blood free naltrexone and 6-beta-naltrexol levels with time following treatment with sequential sustained-release naltrexone preparations. Data were collected from blood samples analysed independently for naltrexone and 6-beta-naltrexol and from clinical record review at a community heroin treatment clinic in Perth, Western Australia. Five patients received sequential 3.4 g (3.49+/-0.01 g and 3.36+/-0.05 g, respectively) naltrexone implants. The second implant was received on average within 131.2+/-15.67 days of the first implant. The mean length of follow-up was 307.2+/-18.28 days of the first implant. Blood naltrexone levels have the potential to remain above 2 and 1 ng/ml for a total of 390 and 524 days, respectively, and blood 6-beta-naltrexol was maintained above 10 ng/ml for a total of 222 days following insertion of these implants. No patient relapsed to dependent heroin use during the implant coverage period while blood naltrexone concentrations were above 2 ng/ml. Results indicate that blood naltrexone and 6-beta-naltrexol levels can be maintained above therapeutic levels for prolonged periods following use of sequential 3.4 g naltrexone implants. These extended periods of coverage will offer significant benefits for managing the heroin-dependent patient.

Blood naltrexone and 6-beta-naltrexol levels following naltrexone implant: comparing two naltrexone implants.

The aim of this study was to profile and compare blood naltrexone and 6-beta-naltrexol levels with time following treatment with two sustained-release naltrexone preparations produced by GoMedical Industries, Australia at a community heroin treatment clinic in Perth, Western Australia. A sample of 10 patients who each received a 1.7 g naltrexone implant were compared to 24 patients who each received a 3.4 g naltrexone implant as treatment for heroin dependence. Blood naltrexone levels following treatment with the 1.7 g naltrexone implant remained above 2 and 1 ng/ml for approximately 90 and 136 days, respectively. Use of the 3.4 g naltrexone implant extended the period of coverage to approximately 297 (1 ng/ml) or 188 (2 ng/ml) days. Blood 6-beta-naltrexol levels remained above 10 ng/ml for approximately 18 and 83 days, respectively, following use of the 1.7 g and 3.4 g naltrexone implants. The current study data indicate that blood naltrexone and 6-beta-naltrexol levels following treatment with either the 1.7 g or 3.4 g naltrexone implant are greater than those reported in other published data on other sustained-release naltrexone preparations. Furthermore, duration of blood naltrexone and 6-beta-naltrexol levels achieved following use of the 3.4 g implant were superior to those achieved with the 1.7 g naltrexone implant, with naltrexone blood levels maintained above 2 ng/ml for a period of approximately 6.3 months compared to 3 months, respectively. The implications of this in managing the heroin-dependent patient, especially those who find it difficult to shift away from dependent use patterns, are discussed.

Headspace/solid-phase microextraction/gas chromatography-mass spectrometry: a screening technique for the recovery and identification of volatile organic compounds (VOC's) in postmortem blood and viscera samples.

This paper describes the application of Headspace/Solid-Phase Microextraction/Gas Chromatography-Mass Spectrometry (HS/SPME/GC-MS) to the recovery and identification of volatile organic compounds in blood and viscera samples from deceased persons. The technique is used as a screening procedure to rapidly obtain information relating to toxicological investigations. The technique is suitable for the detection of volatiles (of wide boiling range) including butane, halothane, toluene, xylenes, and petrol residues in blood and viscera (lung, brain, and body fat).

Cloning and expression of a pig liver taurochenodeoxycholic acid 6alpha-hydroxylase (CYP4A21): a novel member of the CYP4A subfamily.

A cytochrome P450 expressed in pig liver was cloned by polymerase chain reaction using oligonucleotide primers based on amino acid sequences of the purified taurochenodeoxycholic acid 6alpha-hydroxylase. This enzyme catalyzes a 6alpha-hydroxylation of chenodeoxycholic acid, and the product hyocholic acid is considered to be a primary bile acid specific for the pig. The cDNA encodes a protein of 504 amino acids. The primary structure of the porcine taurochenodeoxycholic acid 6alpha-hydroxylase, designated CYP4A21, shows about 75% identity with known members of the CYP4A subfamily in rabbit and man. Transfection of the cDNA for CYP4A21 into COS cells resulted in the synthesis of an enzyme that was recognized by antibodies raised against the purified pig liver enzyme and catalyzed 6alpha-hydroxylation of taurochenodeoxycholic acid. The hitherto known CYP4A enzymes catalyze hydroxylation of fatty acids and prostaglandins and have frequently been referred to as fatty acid hydroxylases. A change in substrate specificity from fatty acids or prostaglandins to a steroid nucleus among CYP4A enzymes is notable. The results of mutagenesis experiments indicate that three amino acid substitutions in a region around position 315 which is highly conserved in all previously known CYP4A and CYP4B enzymes could be involved in the altered catalytic activity of CYP4A21.

Determination of salbutamol and detection of other beta-agonists in human postmortem whole blood and urine by GC-MS-SIM.

This paper details a sensitive and quantitative method for the determination of salbutamol and the detection of terbutaline, clenbuterol, fenoterol, and isoprenaline in postmortem human whole blood and urine. It describes solid-phase extraction using a XtrackT XRDAH515 column, formation of trimethylsilyl derivatives, and analysis by gas chromatography-mass spectrometry-selective ion monitoring.

Rapid determination of bacterial abundance, biovolume, morphology, and growth by neural network-based image analysis

Annual bacterial plankton dynamics at several depths and locations in the Baltic Sea were studied by image analysis. Individual bacteria were classified by using an artificial neural network which also effectively identified nonbacterial objects. Cell counts and frequencies of dividing cells were determined, and the data obtained agreed well with visual observations and previously published values. Cell volumes were measured accurately by comparison with bead standards. The survey included 690 images from a total of 138 samples. Each image contained approximately 200 bacteria. The images were analyzed automatically at a rate of 100 images per h. Bacterial abundance exhibited coherent patterns with time and depth, and there were distinct subsurface peaks in the summer months. Four distinct morphological classes were resolved by the image analyzer, and the dynamics of each could be visualized. The bacterial growth rates estimated from frequencies of dividing cells were different from the bacterial growth rates estimated by the thymidine incorporation method. With minor modifications, the image analysis technique described here can be used to analyze other planktonic classes.

Solid-phase extraction and derivatisation methods for beta-blockers in human post mortem whole blood, urine and equine urine.

This paper details various rapid and sensitive methods for the extraction and derivatisation of propranolol, metoprolol, sotalol, atenolol, pindolol, timolol, oxprenolol, alprenolol and penbutolol in equine urine and in human post mortem whole blood and urine. Three solid-phase extraction methods are described involving the use of either XtrackT XRDAH515, Bond Elut Certify or Sep-Pak C18 cartridges. Two derivatisation methods are also described involving the formation of cyclised silyl or pentafluoropropionate derivatives with either chloromethyldimethylchlorosilane or pentafluoropropionic anhydride, respectively. Gas chromatographic-mass spectrometry analysis was carried out in select-ion monitoring mode. All these methods were evaluated using drug-free human post mortem blood, urine and equine urine fortified at various levels with the beta-blockers mentioned above. The application of some of these methods on a forensic case study is also presented. This work does not include samples from equine administration trials of beta-blockers.

Psychological obstacles to job or career change in late life.

Four studies involving middle-aged and older workers were conducted to (a) explore perceived obstacles to adaptive job or career changes in later-life, and (b) develop an instrument with which to identify older adults who might be more sensitive to such obstacles. A reliable instrument was developed which reflected three broad categories of perceived risk: (a) age-inappropriateness of the change, (b) potential for age-discrimination, and (c) risk of hastened obsolescence. As evidence for the convergent validity of the instrument, the results indicated a heightened sensitivity to job change obstacles among respondents with: (a) age-sensitized concerns about job and financial security, (b) poorer psychological adjustment to a plateaued career, and (c) poorer psychological and social adjustment to their own aging.

Characterisation of taurochenodeoxycholic acid 6 alpha-hydroxylase from pig liver microsomes.

A fraction of cytochrome P-450 catalysing an efficient 6 alpha-hydroxylation of taurine-conjugated 3 alpha,7 alpha-dihydroxy-5 beta- cholanoic acid (taurochenodeoxycholic acid) was partially purified from pig liver microsomes. The specific content of cytochrome P-450 was 6 nmol/mg protein and the preparation showed two major protein bands upon SDS/PAGE. These two bands were isolated after SDS/PAGE and protein blotting. The protein band with a molecular mass of 53 kDa had an N-terminal amino acid sequence and internal sequences resembling that of the cytochrome P-450 4A subfamily (CYP 4A). Polyclonal antibodies raised against this protein were able to, after SDS/PAGE and immunoblotting, detect the protein in microsomal fractions as well as in the purified cytochrome P-450 fraction. Furthermore, addition of these antibodies to a reconstituted system containing the cytochrome P-450 fraction, inhibited 6 alpha-hydroxylation of taurochenodeoxycholic acid by up to 90%. Experiments with irrelevant antibodies did not show inhibition of 6 alpha-hydroxylation. The purified cytochrome P-450 fraction catalysed in addition omega- and omega-1 hydroxylation of lauric acid and 6 alpha-hydroxylation of 3 alpha-hydroxy-5 beta-cholanoic acid (lithocholic acid). However, these hydroxylase activities were rather low compared to 6 beta-hydroxylation of taurochenodexycholic acid. The enzyme fraction did not show hydroxylase activities towards cholesterol and 5 beta-cholestane-3 alpha,7 alpha-diol. These results indicate that 6 alpha-hydroxylation of taurochenodeoxycholic acid is catalysed by a specific species of cytochrome P-450 that, according to N-terminal amino acid sequence as well as catalytic properties, could be a member of the CYP 4A subfamily.

Successful aging at work: an applied study of selection, optimization, and compensation through impression management.

Although many abilities basic to human performance appear to decrease with age, research has shown that job performance does not generally show comparable declines. Baltes and Baltes (1990) have proposed a model of successful aging involving Selection, Optimization, and Compensation (SOC), that may help explain how individuals maintain important competencies despite age-related losses. In the present study, involving a total of 224 working adults ranging in age from 40 to 69 years, occupational measures of Selection, Optimization, and Compensation through impression management (Compensation-IM) were developed. The three measures were factorially distinct and reliable (Cronbach's alpha > .80). Moderated regression analyses indicated that: (1) the relationship between Selection and self-reported ability/performance maintenance increased with age (p < or = .05); and (2) the relationship between both Optimization and Compensation-IM and goal attainment (i.e., importance-weighted ability/performance maintenance) increased with age (p < or = .05). Results suggest that the SOC model of successful aging may be useful in explaining how older workers can maintain important job competencies. Correlational evidence also suggests, however, that characteristics of the job, workplace, and individual may mediate the initiation and effectiveness of SOC behaviors.

Epirubicin and medroxyprogesterone acetate versus estramustine phosphate in hormone-resistant prostatic cancer: a prospective randomized study.

The effect of a medroxyprogesterone acetate (MPA) plus epirubicin combination versus estramustine phosphate was evaluated in 149 prospectively randomized patients with hormone-resistant prostatic cancer. The estimated probability of being free from progression after 1 year was 17% for the patients treated with estramustine and 29% for the MPA-epirubicin group. There is a significant difference between the two groups regarding risk of progression (p = 0.013). However, no difference in survival was recorded (p > 0.30) with about 60% of the patients dead during the first year in both groups. Progression was highly correlated to sedimentation rate (p < 0.001) and to performance index (p = 0.002). Heart failure occurred in a substantial number of patients in both groups which must be considered before starting therapy.

Assessing the social components of retirement anxiety.

In 4 studies involving 308 men and 384 women aged 25-76, a reliable instrument, the Social Components of Retirement Anxiety Scale (SCRAS), was developed to assess retirement anxiety. The 23-item SCRAS measures 4 factors:Social Integration and Identity, Social Adjustment/Hardiness, Anticipated Social Exclusion, and Lost Friendships. The scale strongly predicts fear of retirement and negative attitudes toward retirement. However, it seems not to be measuring simply a generalized emotional state, exhibiting only minimal correlations with more general measures of anxiety and depression. Elevated scores were observed particularly in persons for whom major social transitions are quite difficult--for example, those who were shy, lonely, had fewer instrumental or communal traits, or expected to have little personal control over their lives after retirement.

Renal function during reperfusion after warm ischaemia in rabbits: an experimental study on the possible protective effects of pretreatment with oxygen radical scavengers or lidoflazine.

Survival and renal function were studied after 60 min of renal ischaemia and contralateral nephrectomy in four groups of French loop rabbits. One group served as untreated control animals. The other groups were pretreated with superoxide dismutase (SOD) and catalase, lidoflazine or a buffered albumin solution containing mannitol, L-methionine and MgCl2. Six out of nine rabbits died during the 14-day follow-up period in the untreated control group, while the corresponding figure in each of the three treatment groups was one out of nine. Five of the rabbits that died exhibited azotaemia or hyperpotassaemia that could explain the death, while four died of non-renal related causes. In the surviving animals, no differences in serum creatinine, potassium and sodium concentration or urinary output of osmoles was observed between the four groups. The increase in serum creatinine of the French loop rabbits observed after 60 min of ischaemia was considerably less pronounced than the corresponding increase observed in New Zealand White rabbits, indicating that the kidneys of the former strain are more tolerant to ischaemia. A cardiomyodepressant factor could be demonstrated in the venous effluent from previously ischaemic kidneys. This release could not be prevented by pretreatment with SOD and catalase.

Effects of oxygen free radical scavengers, xanthine oxidase inhibition and calcium entry-blockers on leakage of albumin after ischaemia. An experimental study in rabbit kidneys.

The effect of pretreatment with various substances protecting against oxygen free radicals on the leakage of proteins across the vessel walls of rabbit kidneys induced by ischaemia has been studied. The leakage of proteins was estimated from the difference between the 120-min distribution space of [131I]albumin and the 5-min distribution space of [125I]albumin, the latter mainly measuring the intravascular volume. Neither SOD (superoxide dismutase), catalase, allopurinol or two different Ca2+ channel blockers (nifedipine, felodipine) could alone reduce the leakage induced by ischaemia. A combined pretreatment with SOD, catalase and nifedipine reduced the leakage in the cortex, and pretreatment with mannitol alone reduced the leakage in the cortex and outer stripe of the medulla. The results indicate that oxygen free radicals are involved in the leakage of proteins across the vessel walls induced by ischaemia, but that other mechanisms are involved as well.

The dissatisfied medical patient: predictors of intent to change doctors.

A favorable patient-doctor relationship is critical for the maintenance of a stable and productive practice. Most adults are likely to have had experiences in physician's offices that have caused upset or dissatisfaction. Many of these experiences will have resulted in changing doctors. The likelihood of changing doctors is more often related to the physician's behavior than to his or her actual competence or efficacy.

Effects of ischaemia on leakage of albumin in rabbit kidneys.

The effect of ischaemia on the leakage of proteins across the vessel walls in rabbit kidneys was studied. The leakage of proteins was estimated from the distribution space of labelled albumin. Various methods to calculate the vascular volume yielding the true extravascular leakage were tested. The most reliable method appeared to be to use the same tracer (131I-albumin, 125I-albumin) for both estimating the leakage and the intravascular volume. One hour of ischaemia induced a drastic increase in the extravasation of proteins in the cortex and outer zone of the medulla but not in the inner zone.