A clinical-pharmaceutical medication reconciliation with patient interview for a medication review to identify drug-related problems in elective patients during hospital admission.

Background and aim: Drug-related problems (DRPs), e.g.drug-drug interactions (DDI), can lead to adversedrug reactions (ADRs) and thus complications during hospitalization. For this reason, such DRP, DDI and ADR should be identified and characterized as early as possible during hospital admission. We aimed to perform a clinical-pharmaceutical medication reconciliation in which patient-related information was collected and compared to drug-related information in a medication review. Investigations: During a 24-week-period, we consecutively invited patients electively admitted to Urology, Otolaryngology, Oral and Maxillofacial Surgery, General and Visceral Surgery, and Oncology Departments of a 300-bed hospital. A clinical pharmacist performed a patient interview asking for medication, ADR, and adherence. The medication reconciliation considered packages for a brown-bag analysis, medication lists, and data from the clinical information-system (CIS). In a medication review, we matched patient-related information to drug-related information from the drug label, guidelines, drug-databases and websites to identify DRPs. Results: In the study, 356 patients (median age: 58 years) taking 1,712 drugs participated. Of all patients, 7.3% reported ADR and 10.7% missing adherence. 5.3% brought packages that enabled a brown-bag analysis and 21.1% a medication list. In 76.7% of patients, information from CIS was incomplete or not up-to-date. Among the most frequently identified DRPs were "Medication without diagnosis" (31.2%) and "Inappropriate timing of administration" (11.5%). The proportion of patients affected by severe DDI ranged from 0.8%-16.6%, depending on the drug information source. Conclusions: Incomplete patient data, frequently identified DRPs and inconsistent drug-based information make pharmaceutical involvement in medication reconciliation on admission a necessity.

Mechanisms underlying the stimulation of PTH release by GppNHp in permeabilized bovine parathyroid cells.

We examined changes in cAMP and inositol phosphate metabolism to assess the contribution of the guanine nucleotide regulatory (G) protein(s) regulating adenylate cyclase and phospholipase C in mediating the stimulatory effects of GppNHp on PTH release from permeabilized bovine parathyroid cells. To examine the role of Gs, the G protein stimulating adenylate cyclase, and cAMP on PTH release, permeabilized cells were incubated with either GppNHp or isoproterenol, and the effects of these agents on PTH release and cellular cAMP content were determined by RIA. To study the effects of GppNHp on inositol phosphate accumulation, permeabilized cells prelabeled with [3H]inositol were exposed to GppNHp, and inositol phosphates were measured using ion-exchange chromatography. These studies revealed that isoproterenol produced a dose-dependent increment in cAMP content in permeabilized cells with no significant effect on PTH release. Conversely, GppNHp rapidly and markedly elevated PTH release with a smaller and delayed rise in cAMP content. GppNHp- also promoted a dose-dependent increase in inositol monophosphate (IP), inositol bisphosphate (IP2), and inositol trisphosphate (IP3) accumulation, suggesting activation of phosphoinositide hydrolysis. Addition of dioctanoylglycerol, however, a synthetic diacylglycerol (DG) that activates protein kinase C, produced a much smaller increment in PTH release than GppNHp. Moreover, reducing the free calcium concentration to less than 10(-9) M by adding 10 mM EGTA to the permeabilization medium dissociated the effects of GppNHp and DG on secretion, increasing GppNHp-stimulated PTH release while reducing PTH secretion evoked by DG.(ABSTRACT TRUNCATED AT 250 WORDS)

Permeabilization reveals classical stimulus-secretion coupling in bovine parathyroid cells.

Unlike most secretory cells, high extracellular Ca2+ inhibits, rather than stimulates, PTH release from parathyroid cells. To gain more direct access to the potentially unique secretory apparatus of this cell type, we developed techniques for permeabilizing parathyroid cells using electroshock. Exposure of dispersed bovine parathyroid cells to five 2-kV discharges results in more than 90% uptake of trypan blue and rapid loss of intracellular 86Rb, documenting permeabilization of the plasma membrane. Unlike intact parathyroid cells, a high Ca2+ concentration increases PTH release 2.8-fold from permeabilized cells, with half-maximal and maximal stimulation at 10(-5) and 4 X 10(-4) M Ca2+, respectively, a pattern similar to classical stimulus-secretion coupling. Moreover, PTH release was low at Ca2+ concentrations equivalent to those in intact cells at low extracellular Ca2+ levels (approximately 2 X 10(-7) M). Cellular mechanisms other than changes in the cytosolic Ca2+ concentration per se, therefore, presumably mediate low Ca2+-stimulated PTH release in the intact cell. Diacylglycerol and protein kinase C may play a role in this process, since dioctanoylglycerol (10(-4) M) and 12-O-tetradecanoyl phorbol 13-acetate (10(-6) M) each enhance PTH release from permeabilized cells 2- to 4-fold at a Ca2+ concentration (approximately 2 X 10(-7) M) equivalent to that present in the intact cell at low extracellular Ca2+ concentrations.

Guanine nucleotides are potent secretagogues in permeabilized parathyroid cells.

We studied the effects of GTP and its' analogues on PTH release in permeabilized parathyroid cells to assess their role in mediating the unusual inverse relationship between Ca2+ and PTH release in intact parathyroid cells. Both 10-5 M GppNHp and GTP gamma S, nonhydrolysable analogues of GTP, produce up to an 8-fold enhancement of PTH release, which is dose-dependent. This effect is specific for GTP analogues as we could not mimic it with other nucleotides. 10(-3) M GDP beta S, a nonhydrolysable GDP analogue, completely abolishes GppNHp-stimulated hormone release, providing further support for mediation of this effect by a guanine-nucleotide regulatory protein. In GppNHp-stimulated cells, PTH release is maximal at free [Ca2+] less than 200 nM and progressively decreases as the free [Ca2+] increases from 300 nM to 100 microM. These results suggest the presence of a guanine-nucleotide binding protein in the parathyroid cell that may play an important role in the regulation of PTH secretion by Ca2+ and perhaps other secretagogues.

Eating in the laboratory: behavioural aspects of the positive energy balance.

A survey is made of a number of experiments conducted in our laboratory over the last six years. Our working hypothesis assumes that positive energy balance, which should not be prematurely defined as the cause of obesity, is itself caused by disturbances in appetite and satiation control which, given certain environmental conditions, can favour the occurrence of obesity. Three points are considered: (1) The hyperphagic reaction as a response to stress. The experimental findings suggest that the hyperphagic reaction is not primarily a biologically determined phenomenon but rather a learned response. The hyperphagic reaction is found more frequently in female and overweight persons. Most children react to stress with a decrease in food consumption. (2) Disturbances of satiation control. The food intake of obese Ss has a linear time function, whilst children and normal weight adults reveal a biological, negatively accelerated satiation curve. (3) Increased responsiveness to external cues. The concept of externality is extended to include the aspect of an internal-external stimulus discrepancy. The findings show that not only manifest obese Ss but also latent obese Ss are characterized by an increased responsiveness to external cues. In three different experiments with the same Ss it could be demonstrated that externality is to a greater or lesser extent independent of the experimental procedure. Finally, methodological aspects are discussed, because in studies on human appetite the possibility exists that experimental procedure, sample composition and laboratory conditions can exert a direct influence on the results.

[The personality of obese persons in psychological tests with special consideration on latent obesity]. / Zur Persönlichkeit Adipöser in psychologischen Tests unter Berücksichtigung latent Fettsüchtiger

The results of psychological tests of the obese are inconsistent and no characteristic personality structure of the obese can be deduced from them. Investigations in childhood obesity failed to establish a general psychogenetic model of obesity. Yet overweight and ideal weight-subjects differ in spontaneous eating behaviour. Appetite and satiety of obese subjects are controlled by external stimuli to a far greater extent than in nonobese. From a behavioural scientific viewpoint it is proposed that learning experiences during childhood socialisation generate the disposition for obesity which can manifest itself later, after interaction with a special environment. At this stage, however, individual reactions to starting overweight are insolved; this process is strongly influenced by individual personality structures: an inadequate conflict management favours obesity; by cognitive control normal weight can be preserved in spite of the acquired disposition for obesity. Taking these "latently obese" as an example the role of personality structure and wrong eating habits is discussed and related to possible therapeutic strategies. A model of the psychogenetic basis of obesity is proposed. In this model eating-related learning experience is attributed a primary role and individual personality structure a secondary role in the psychogenesis of obesity.