Safety and acceptability of practice-nurse-managed care of depression in patients with diabetes or heart disease in the Australian TrueBlue study.

OBJECTIVES: To determine the safety and acceptability of the TrueBlue model of nurse-managed care in the primary healthcare setting. DESIGN: A mixed methods study involving clinical record audit, focus groups and nurse interviews as a companion study investigating the processes used in the TrueBlue randomised trial. SETTING: Australian general practices involved in the TrueBlue trial. PARTICIPANTS: Five practice nurses and five general practitioners (GPs) who had experienced nurse-managed care planning following the TrueBlue model of collaborative care. INTERVENTION: The practice nurse acted as case manager, providing screening and protocol-management of depression and diabetes, coronary heart disease or both. PRIMARY OUTCOME MEASURES: Proportion of patients provided with stepped care when needed, identification and response to suicide risk and acceptability of the model to practice nurses and GPs. RESULTS: Almost half the patients received stepped care when indicated. All patients who indicated suicidal ideations were identified and action taken. Practice nurses and GPs acknowledged the advantages of the TrueBlue care-plan template and protocol-driven care, and the importance of peer support for the nurse in their enhanced role. CONCLUSIONS: Practice nurses were able to identify, assess and manage mental-health risk in patients with diabetes or heart disease.

Functional characterization of CYP2A13 polymorphisms.

CYP2A13 is an efficient catalyst of metabolic activation of the human carcinogens 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and N'-nitrosonornicotine (NNN). This study investigated the functional consequences of CYP2A13 polymorphisms that result in single amino acid substitutions. Five CYP2A13 variants, namely CYP2A13*2 (R257C), CYP2A13*5 (F453Y), CYP2A13*6 (R494C), CYP2A13*8 (D158E), and CYP2A13*9 (V323L), were expressed and evaluated for coumarin binding affinity, coumarin 7-hydroxylation, and -hydroxylation of (S)-NNN and NNK. In addition, the 133_134 Thr deletion variant, coded for by CYP2A13*3, was expressed but was not stable to the protein purification procedure. A 30-42% decrease in coumarin 7-hydroxylation catalytic efficiency was determined for R257C and D158E. No effect on coumarin binding or (S)-NNN metabolism was observed. Three variants, R257C, D158E, and V323L, had two- to threefold decreased catalytic efficiency for NNK -hydroxylation. CYP2A13 polymorphisms resulted in modest changes in coumarin 7-hydroxylation and NNK -hydroxylation activities in vitro. Although these changes are not likely to impact in vivo metabolism, these data should aid in the interpretation and design of future epidemiology studies.

Effect of a meal on human whole blood serotonin.

Levels of whole blood serotonin and tryptophan were measured in 11 human subjects after the consumption of a meal. Blood samples were obtained at 30 and 15 min before the meal and at 15, 30, and 60 min postcibal. One-hour urine specimens were collected for 5 subjects at 0, 60, and 120 min. Whole blood serotonin and tryptophan and urinary 5-hydroxyindoleacetic acid were measured using specific high-performance liquid chromatographic methods. A precibal mean (+/- SEM) serotonin level of 136 +/- 8 ng/ml (n = 22) was observed; means at 15, 30, and 60 min after the meal were 138 +/- 20 ng/ml (n = 9), 145 +/- 18 ng/ml (n = 11), and 138 +/- 16 ng/ml (n = 11), respectively. At no time were postcibal levels of whole blood serotonin significantly higher than baseline levels (paired t-test). Urinary excretion of 5-hydroxyindoleacetic acid also was unchanged; mean hourly rates were 230 +/- 23 micrograms/h before the meal, and 196 +/- 17 micrograms/h and 190 +/- 33 micrograms/h (n = 5) during the first and second hour postcibal, respectively. The absence of a postcibal increase of serotonin in circulating whole blood indicates that serotonin is probably not a human gastrointestinal hormone in the usual sense.

Two-dimensional high-performance liquid chromatographic determination of 5-hydroxyindoleacetic acid and homovanillic acid in urine.

The biomedically and neurochemically important compounds 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) have been simultaneously determined in human urine after reverse-phase two-dimensional high-performance liquid chromatography. A 10-fold-diluted urine sample (20 microliters) is first separated on a C18 column (30 X 0.39 cm) using an 85% pH 6.0 phosphate buffer/15% methanol solvent system. The elution volume containing both 5-HIAA and HVA (Rt approximately 3 min) is collected. Recoveries (mean +/- SD) for this purification step, which is monitored using fluorometric detection, were usually above 90%. After acidification of the approximately 2 ml collected fraction, 100 microliters is reinjected on a C18 column and separated (Rt: 5-HIAA, 4 min; HVA 5.5 min) using an 80% pH 3.5 phosphate buffer/20% methanol mobile phase. The compounds are determined by flow-through amperometry with absolute detection limits of approximately 25 pg. Both 5-HIAA and HVA are well resolved from other electroactive species present and are easily determined at normal and greatly reduced concentrations in human urine.