Labeling the human skeleton with 41Ca to assess changes in bone calcium metabolism.

Bone research is limited by the methods available for detecting changes in bone metabolism. While dual X-ray absorptiometry is rather insensitive, biochemical markers are subject to significant intra-individual variation. In the study presented here, we evaluated the isotopic labeling of bone using 41Ca, a long-lived radiotracer, as an alternative approach. After successful labeling of the skeleton, changes in the systematics of urinary 41Ca excretion are expected to directly reflect changes in bone Ca metabolism. A minute amount of 41Ca (100 nCi) was administered orally to 22 postmenopausal women. Kinetics of tracer excretion were assessed by monitoring changes in urinary 41Ca/40Ca isotope ratios up to 700 days post-dosing using accelerator mass spectrometry and resonance ionization mass spectrometry. Isotopic labeling of the skeleton was evaluated by two different approaches: (i) urinary 41Ca data were fitted to an established function consisting of an exponential term and a power law term for each individual; (ii) 41Ca data were analyzed by population pharmacokinetic (NONMEM) analysis to identify a compartmental model that describes urinary 41Ca tracer kinetics. A linear three-compartment model with a central compartment and two sequential peripheral compartments was found to best fit the 41Ca data. Fits based on the use of the combined exponential/power law function describing urinary tracer excretion showed substantially higher deviations between predicted and measured values than fits based on the compartmental modeling approach. By establishing the urinary 41Ca excretion pattern using data points up to day 500 and extrapolating these curves up to day 700, it was found that the calculated 41Ca/40Ca isotope ratios in urine were significantly lower than the observed 41Ca/40Ca isotope ratios for both techniques. Compartmental analysis can overcome this limitation. By identifying relative changes in transfer rates between compartments in response to an intervention, inaccuracies in the underlying model cancel out. Changes in tracer distribution between compartments were modeled based on identified kinetic parameters. While changes in bone formation and resorption can, in principle, be assessed by monitoring urinary 41Ca excretion over the first few weeks post-dosing, assessment of an intervention effect is more reliable approximately 150 days post-dosing when excreted tracer originates mainly from bone.

[(15)N(2)]arginine as a first potential inhaled diagnostic agent to characterize respiratory diseases.

Conventional diagnosis of the pulmonary tract uses physical methods such as spirometry and oscillometry. However, the inhalation of a chemical diagnostic agent ought to provide novel ways of more specific diagnosis, for instance of inflammatory states of the bronchial and lung mucosa. The stable isotope technique using a (15)N-labeled substrate appears to be a suitable tool for this application. In a pilot study, defined amounts of the amino acid L-[guanidino-(15)N(2)]arginine monohydrochloride (aqueous solution, 20 atom % (15)N) were inhaled as a diagnostic agent by healthy volunteers and pulmonary patients suffering from asthma bronchiale. The amino acid is resorbed and partly metabolized to (15)NO. The exhaled air was collected under defined conditions in 10-L breath bags and analyzed for NO using chemiluminescence. Under standardized test conditions, healthy persons (n = 6) exhaled 0.97 +/- 0.08 micromol NO/m(3) and asthmatic patients (n = 7) 1.17 +/- 0.14 micromol NO/m(3). A better distinction was expected comparing the (15)NO exhalation. The (15)N abundance of NO was determined using a Cryotrap gas chromatography - mass spectrometry set-up. Between 30 and 80 minutes after inhaling 700 mg [(15)N]arginine, a maximum with a plateau of the (15)NO abundance was found in the exhaled air. At this time, healthy and asthmatic subjects exhibited clear differences in their exhaled (15)NO amounts. Under standardized test conditions, the healthy persons (n = 6) exhaled 102.3 +/- 6.7 nmol (15)NO/m(3), whereas asthmatic patients (n = 7) exhaled only 76.1 +/- 10.9 nmol (15)NO/m(3). It is concluded that (15)NO yielded after the inhalation of (15)N-labeled arginine could be a potential marker for demonstrating pathophysiological changes in the lung epithelium. This method could pave a new diagnostic principle of "inhalative breath test."

Psychiatric wills of mental health professionals: a survey of opinions regarding advance directives in psychiatry.

Psychiatric wills are advance directives for an eventual involuntary treatment in psychiatry. We attempted to determine psychiatric professionals' knowledge and opinion about this legal option and obtain their formulations of advance directives for themselves. A total of 101 psychiatric nurses and psychiatrists at the Department of Psychiatry of the University of Vienna responded to a questionnaire about psychiatric wills and anonymously drafted advance directives for themselves concerning psychiatric treatment in case of an acute psychosis. Fifty-four percent knew about this legal option, 55% considered it an appropriate legal possibility, and 29% considered it inappropriate. The study also found that 75% of respondents reject certain methods of therapy, e.g. 30% want to exclude the use of neuroleptic medications, and 46% reject ECT. We conclude that although there is little experience so far with advance directives for psychiatric patients, there is an interest and predominance of positive attitudes towards this legal option among mental health professionals. Concerning their preferences, professionals felt inclined to make very specific statements as to which available treatment strategies they would reject and which they would request for their treatment. This bodes well for the widespread use of advance directives in mental health settings.

["Because it concerns me"--patient-directed discharge letters]. / "Weil es mich betrifft"--direkt an Patientlnnen gerichtete Entlassungsbriefe.

PURPOSE: Evaluation of practicability and acceptance of discharge summaries addressed directly to patients after psychiatric hospitalisation. METHODS: Over a period of 3 months 65 patients got discharge summaries addressed directly to them. Doctors and patients--4 months after discharge--were asked to evaluate this procedure. RESULTS: Both doctors' and patients' acceptance and evaluation was very positive. Argumentations for this view were the need to give and get information and the impression that this procedure can enhance confidence and trust.

The comparative efficacy of carbamazepine low and high serum level and lithium carbonate in the prophylaxis of affective disorders.

The prophylactic efficacy of carbamazepine slow release (CBZ) at ke different blood levels and lithium carbonate slow release (LI) was compared in a retrospective/prospective, randomized, 2-year open trial. 84 patients with a DSM-III-R diagnosis of recurrent affective disorder who had no prophylactic medication in the 2 years preceding the trial (no LI nonresponders), were randomly allocated to three treatment groups: CBZ low (15-25 mumol/l), CBZ high (28-40 mumol/l) and LI (0.6-0.8 mumol/l). Fifty-eight patients completed the full observation period of 2 years, 26 patients dropped out. There were no statistically significant differences in the efficacy of the prophylactic treatment for bipolar patients. For the unipolar patients, the group with a low CBZ serum level showed no reduction in the duration of episodes. The two other treatment groups seem to be equal in attenuation of a unipolar course of an affective disorder.

Computerized documentation for lithium outpatients (routine and research data).

To follow up the status and further outcome of patients with recurrent affective and schizoaffective disorders treated in a lithium/prophylactic treatment outpatient (LOP) clinic the authors have developed a documentation system based on a database, which ASCII files. This system should be useful as a basis for optimal treatment and is helpful for special research purposes regarding prophylactic treatment (lithium salts, carbamazepine, antidepressants, etc.). The documentation system consists of two parts, one for routine documentation system consists of two parts, one for routine monitoring including basic data, global course, and routine form with side-effects, and another one for research purposes with documentation of laboratory findings, EEG, and documentation of every cycle which can be added easily. Moreover, with this documentation system it will be possible to compare results from different research centres.