[Admission and discharge decisions in psychiatric hospitals : The 7-day cycle: analysis based on the VIPP database]. / Aufnahme- und Entlassentscheidungen in der Psychiatrie : Der 7-Tage-Zyklus: Analyse auf Grundlage der VIPP-Datenbank.

BACKGROUND: The legislation requires all scientific societies in the field of inpatient psychiatric and psychosomatic healthcare to survey and assess the effects and financial incentives of the new flat rate day-based remuneration system in psychiatric and psychosomatic facilities (PEPP system). As day-based remuneration systems may be an incentive to extend treatment, it is necessary to measure and analyze the future development of the number of cases and the duration of treatment. OBJECTIVES: This article surveys admission and discharge decisions of psychiatric and psychosomatic facilities. The distribution of admissions and discharges throughout the days of the week were analyzed to search for evidence of a systematic extension of treatment over the weekend. MATERIAL AND METHODS: The analysis is based on data from the Versorgungsrelevante Indikatoren in der Psychiatrie und Psychosomatik (VIPP, treatment-relevant indicators in psychiatry and psychosomatics) project database, which contains routine data from psychiatric and psychosomatic facilities. On this basis the distributions of admissions and discharges throughout the days of the week were analyzed on aggregate and diagnosis-specific levels. RESULTS: Patients were mostly admitted to hospitals within the first 3 weekdays. The discharge mostly took place on Fridays and not as a financial incentive on Mondays. Regarding the patient length of stay a 7-day cycle can be observed, which may indicate the importance of medical and organizational factors in discharge decisions. CONCLUSION: The results do not show evidence for a systematic extension of treatment over the weekend. Over the next years it will be important to observe the development of the duration of treatment and the number of cases to assess the influence of the economic incentives of the PEPP system on the utilization of psychiatric and psychosomatic healthcare.

Investigation of volatile metabolites during growth of Escherichia coli and Pseudomonas aeruginosa by needle trap-GC-MS.

A new method for the growth-dependent headspace analysis of bacterial cultures by needle trap (NT)-gas chromatography-mass spectrometry (GC-MS) was established. NTs were used for the first time as enrichment technique for volatile organic compounds (VOCs) in the headspace of laboratory cultures. Reference strains of Escherichia coli and Pseudomonas aeruginosa were grown in different liquid culture media for 48 h at 36 °C. In the course of growth, bacterial culture headspace was analysed by NT-GC-MS. In parallel, the abiotic release of volatile organic compounds (VOC) from nutrient media was investigated by the same method. By examination of microbial headspace samples in comparison with those of uninoculated media, it could be clearly differentiated between products and compounds which serve as substrates. Specific microbial metabolites were detected and quantified during the stationary growth phase. P. aeruginosa produced dimethyl sulfide (max. 125 µg L(-1) < limits of quantification (LOQ)), 1-undecene (max. 164 µg L(-1)) and 2-nonanone (max. 200 µg L(-1)), whereas E. coli produced carbon disulfide, butanal and indole (max. 149 mg L(-1)). Both organisms produced isoprene.

[The new payment system in psychiatry - do elderly people belong to the losers? An analysis on the basis of the VIPP1 data base]. / Das neue Entgeltsystem in der Psychiatrie - gehören ältere Patienten zu den Verlierern? Eine Analyse auf der Grundlage der VIPP-Datenbank.

The development of the lump-sum reimbursement System in psychiatry and psychosomatics (PEPP) (Klimke et al., 2014) is being negatively considered - also in gerontopsychiatry.Thus it is reasonable to make a timely analysis of the effects of PEPP on health-care structures. For this two analyses have been carried out. On the one hand the day mix index of elderly patients (> 64 years) was compared with that of younger ones (> 17 years, < 65 years). On the other hand younger and older were included in the analysis with regard to the available treatment minutes in exact daily classifications according to the PsychPV. It is seen that evaluation of the individual day was markedly higher for gerontopsychiatric patients not only in inpatient (difference > 0.1) but also in outpatient (difference > 0.07) setting. The exact daily classifications according to PsychPV, however, were markedly poorer for the elderly patients. Thus, on the basis of routine data of VIPP projects, a clear change can be seen in favour of the elderly patient under PEPP conditions as compared to financing according to PsychPV. However, concern remains that the ageing population and modernisation of therapy are not being sufficiently taken into account. The new reimbursement system merely regulates the distribution of available resources; if these resources are too low nothing will change by the PEPP-System.

Dietary flavonoids do not affect vitamin E status in growing rats.

This study aimed at investigating potential effects of the flavonoids genistein, quercetin and catechin and the role of co-ingested dietary fat on vitamin E concentrations in rats. In experiment 1, genistein, quercetin and catechin were fed to rats, incorporated into semisynthetic diets at concentrations of 2 g/kg, either as individual compounds or in combination to investigate their individual and possible synergistic actions towards alpha-tocopherol in plasma and selected tissues. For experiments 2 and 3, quercetin was selected as a representative model flavonoid to study the effects of the quantity (5% vs. 10%) and type of dietary fat (coconut fat plus corn oil vs. rapeseed oil; experiment 2) and the role of cholesterol (experiment 3) on potential flavonoid-vitamin E interactions. The concentrations of alpha-tocopherol and gamma-tocopherol in the plasma, liver, lung and cortex of flavonoid-fed rats were not significantly different from the concentrations measured in control rats in all three experiments. However, increasing the amount of coconut fat plus corn oil from 5 to 10% resulted in lower alpha-tocopherol concentrations in plasma and tissue. The alpha-tocopherol concentrations in the rats fed rapeseed oil were significantly higher than in rats fed coconut fat plus corn oil. The addition of 0.2% cholesterol to the diet did not influence the tocopherol concentrations in plasma and tissue in both quercetin-supplemented and control rats. Additionally, the mRNA levels of alpha-TTP, CYP3A4, CYP4F and Mdr2, which are integral proteins involved in vitamin E homeostasis were measured. Only genistein reduced the Mdr2 mRNA level, but none of the other transcripts. All other flavonoids were without effect. In conclusion, co-ingested dietary fat appears to influence vitamin E concentrations in rats, but does not seem to be an important determinant of flavonoid-vitamin E interactions.

Determination of the functional domain organization of the importin alpha nuclear import factor.

Although importin alpha (Imp alpha) has been shown to act as the receptor for basic nuclear localization signals (NLSs) and to mediate their recruitment to the importin beta nuclear import factor, little is known about the functional domains present in Imp alpha, with the exception that importin beta binding is known to map close to the Imp alpha NH2 terminus. Here, we demonstrate that sequences essential for binding to the CAS nuclear export factor are located near the Imp alpha COOH terminus and include a critical acidic motif. Although point mutations introduced into this acidic motif inactivated both CAS binding and Imp alpha nuclear export, a putative leucine-rich nuclear export signal proved to be neither necessary nor sufficient for Imp alpha nuclear export. Analysis of sequences within Imp alpha that bind to the SV-40 T antigen NLS or to the similar LEF-1 NLS revealed that both NLSs interact with a subset of the eight degenerate armadillo (Arm) repeats that form the central part of Imp alpha. However, these two NLS-binding sites showed only minimal overlap, thus suggesting that the degeneracy of the Arm repeat region of Imp alpha may serve to facilitate binding to similar but nonidentical basic NLSs. Importantly, the SV-40 T NLS proved able to specifically inhibit the interaction of Imp alpha with CAS in vitro, thus explaining why the SV-40 T NLS is unable to also function as a nuclear export signal.

The intron enhancer of the immunoglobulin kappa gene activates c-myc but does not induce the Burkitt-specific promoter shift.

In Burkitt's lymphoma cells the c-myc gene locus is consistently fused to the constant region of one of the immunoglobulin genes by chromosomal translocation. The translocated c-myc gene is transcriptionally activated and preferentially transcribed from the P1 promoter whenever the exon-intron structure of c-myc remains intact. In order to define elements involved in this promoter shift we have cloned the translocated c-myc allele from Burkitt's lymphoma cell line BL60, which is characterized by several point mutations. The mutated c-myc allele of BL60 was stably introduced into baby hamster kidney and Burkitt's lymphoma cells. S1 nuclease and RNAase protection mapping experiments demonstrated that the mutated c-myc allele was expressed at a low level and with a normal promoter usage (P2 greater than P1) in Burkitt's lymphoma and baby hamster kidney cells. Furthermore, we have studied the expression of a construct consisting of the mutated c-myc allele, part of the bvr1 (Burkitt's variant rearranging region 1) locus, the human immunoglobulin kappa constant region, and the kappa intron enhancer after stable transfection into Burkitt's lymphoma cells. Although c-myc expression was about fivefold increased, the transcripts still initiated predominantly at promoter P2. This indicates that 5 kb of the constant kappa light-chain locus including the kappa intron enhancer is not sufficient to induce the Burkitt's lymphoma-specific promoter shift.

FTY720 pharmacokinetics in mild to moderate hepatic impairment.

The influence of mild and moderate hepatic impairment on FTY720 pharmacokinetics was assessed. The authors enrolled 32 subjects consisting of 8 with mild and 8 with moderate hepatic impairment based on Child-Pugh criteria and 16 demographically matched control subjects. A single 1-mg oral dose of FTY720 was administered under fasting conditions. Blood, plasma, and urine samples were obtained over a 14-day period for measurement of FTY720 and metabolite concentrations and protein binding. Total blood lymphocyte counts and heart rate were serially monitored to assess pharmacologic responses to FTY720. Peak FTY720 blood concentrations were similar across groups. Oral clearance (CL/F) was reduced 10% in mild hepatic impairment (P = .493) and 31% in moderate hepatic impairment (P = .034). There were no significant differences in blood exposure to the hexanoic or butanoic acid metabolites among groups. The effect of FTY720 on blood lymphocytes was similar across groups, with a mean decrease of 44% from the predose value. Like-wise, the effect of FTY720 on supine heart rate was similar across groups, with a mean 13% decrease from the predose rate occurring 2 to 4 hours postdose and recovering within 1 to 2 days. Although hepatic impairment elicited changes in the disposition of FTY720, the magnitude of these changes suggests that the FTY720 dose does not need to be adjusted in mild or moderate hepatic-impaired patients.

Effects of tetrandrine on calcium channel currents of bovine chromaffin cells.

Calcium channel currents of bovine chromaffin cells are blocked by the bis-benzyl-isoquinoline alkaloid tetrandrine, which is isolated from the roots of the chinese medical herb Stephania tetrandra. The half-maximal inhibition (IC50) occurred at a concentration of about 10 microM. Bovine chromaffin cells possess no low-voltage-activated, but different types of high-voltage activated calcium channel currents. Tetrandrine blocks omega-conotoxin-sensitive N-type, dihydropyridine-sensitive L-type and omega-conotoxin- and dihydropyridine-insensitive calcium channel currents of chromaffin cells. The I/V relationship in not shifted by tetrandrine, indicating that the block is not voltage-dependent. After tetrandrine application the currents become transient in a depolarization- and a concentration-dependent manner. Tetrandrine blocks open calcium channels and the block is use-dependent. When the holding potential returns to resting levels, the channels are unblocked in about 1 sec.

Scintimetric evaluation of remodeling after bone fractures in man.

In a review of bone scans of 2000 post-trauma patients, the following rules of bone remodeling after fracture were found: different bones behave differently; lesions in the vicinity of joints show an early and high accumulation of the tracer within the first days after the trauma, whereas fractures of the axial skeleton and shafts of long bones sometimes need up to 12 days to appear on scan; all except skull fractures demonstrate a steady rise of accumulation intensity compared to normal bone for 2-5 wk; the steepness of increase and time of maximum differ significantly for different fracture sites. Calculating a ratio 24:4 hours after injection helps differentiate fractures from soft tissue lesions since fresh fractures show a ratio > 1:1. We found no clinically relevant dependence on sex and age. The scintigraphic/scintimetric behavior of fractures is reproducible and predictable, adding specificity to the well-known high sensitivity of bone scans.

Inhalation pharmacokinetics of isoprene in rats and mice.

Studies on inhalation pharmacokinetics of isoprene were conducted in rats (Wistar) and mice (B6C3F1) to investigate possible species differences in metabolism of this compound. Pharmacokinetic analysis of isoprene inhaled by rats and mice revealed saturation kinetics of isoprene metabolism in both species. For rats and mice, linear pharmacokinetics apply at exposure concentrations below 300 ppm isoprene. Saturation of isoprene metabolism is practically complete at atmospheric concentrations of about 1000 ppm in rats and about 2000 ppm in mice. In the lower concentration range where first-order metabolism applies, metabolic clearance (related to the concentration in the atmosphere) of inhaled isoprene per kilogram body weight was 6200 mL/hr for rats and 12,000 mL/hr for mice. The estimated maximal metabolic elimination rates were 130 mumole/hr/kg for rats and 400 mumole/hr/kg for mice. This shows that the rate of isoprene metabolism in mice is about two or three times that in rats. When the untreated animals are kept in a closed all-glass exposure system, the exhalation of isoprene into the system can be measured. This shows that the isoprene endogenously produced by the animals is systemically available within the animal organism. From such experiments the endogenous production rate of isoprene was calculated to be 1.9 mumole/hr/kg for rats and 0.4 mumole/hr/kg for mice. Our data indicate that the endogenous production of isoprene should be accounted for when discussing a possible carcinogenic or mutagenic risk of this compound.

Tetrandrine effects on calcium currents in cultured neurones of foetal mice.

Tetrandrine, a bis-benzyl-isoquinoline alkaloid from the roots of Stefania Tetranda blocks calcium currents in cultured neurones of the spinal cord of foetal mice. The concentration of half-maximal effect (Kd) measured 100 ms after the beginning of a depolarizing pulse (-80 mV-0 mV) is 8 microM. While high- and low-voltage activated (HVA, LVA) currents are both blocked by Tetrandrine, the slowly inactivating HVA currents appear to be a primary target.

Development of calcium currents in cultures of mouse spinal cord and dorsal root ganglion neurones.

Cultured spinal cord (SC) and dorsal root ganglion (DRG) neurones of 11-13 day old foetal mice were investigated electro-physiologically during differentiation in vitro using the whole-cell patch-clamp technique. High-voltage-activated calcium currents (HVA) and low-voltage-activated (LVA) calcium currents were measured using barium ions as charge carrier. During differentiation in vitro the soma diameter of SC-neurones increased with age (0-42 days in vitro) from 10.3 +/- 2.7 microns to 25.1 +/- 5.9 microns. The capacitance of the soma increased from 7.4 +/- 2.3 pF to 34 +/- 6 pF. The inward calcium current amplitudes increased from 200 pA to 3 nA, while the LVA current amplitude increased only from 50 pA to 100-150 pA. The currents per membrane area through HVA calcium channels increased in the investigated time while the currents through LVA channels decreased.

Inhibition by lead of the calcium plateau current at mouse motor nerve endings.

The inhibition by lead of motor terminal calcium plateau signals has been studied using extracellular, perineuronal electrodes applied to the M. triangularis sterni preparation of the mouse. The long-lasting calcium pateau signal induced by 3,4-DAP (250 mumol) and TEA (10 mmol) blockade of presynaptic potassium channels was irreversibly blocked by micromolar lead concentrations in a concentration-dependent manner. These results suggest that lead antagonizes neuronal calcium channels involved in transmitter release from motor nerve terminals.

Detection of sub-miniature endplate potentials by harmonic analysis.

In phrenic nerve-diaphragm preparations from young rats and mice, long-term recordings of miniature endplate potentials (MEPPs) from single synapses were performed. Amplitude histograms obtained from these experiments were analysed with respect to the presence of multiple peaks which are believed to reflect quantal transmitter release. This was accomplished by subjecting MEPP amplitude histograms as well as matched random number histograms to Fourier analysis; harmonics in the MEPP amplitude distribution were considered valid only if they exceeded those of the random number distribution. In 9 out of 11 experiments, substantial evidence for the existence of preferred amplitudes was obtained; in two cases, however, it was completely missing. Applying our method to a series of promising MEPP amplitude histograms selected from the literature, we found a similar relationship between positive and negative results. We also noted a fairly constant relationship between the size of the elementary sub-MEPPs and the mean amplitude of the bell-MEPPs, named so according to the Gaussian shape of their amplitude distribution.

Detection of herpes simplex virus and adenovirus DNA by dot blot hybridization using in vitro synthesized RNA transcripts.

A new diagnostic assay was developed to detect herpes simplex virus (HSV) and adenovirus DNA in clinical specimens using in vitro synthesized radioactively labelled RNA transcripts from virus-specific DNA fragments cloned in transcription vector pSP 64/65. RNA probes derived from HSV-I-Eco-RI-G-DNA fragment show a sensitivity of less than 3 pg of whole plasmid DNA and hybridize only with DNA of HSV I and II, but not with other viral or cellular DNA. The analysis of 15 clinical specimens showed concordance with virus isolation, except for two culture-negative samples of cerebrospinal fluid of patients with suspected HSV encephalitis, which was confirmed by serology as well as by hybridization. Using RNA transcripts from adenovirus-2-Hind-III-D-DNA fragment, we attained a sensitivity of less than 3 pg of whole plasmid DNA. This probe detected different types of adenovirus, but failed to hybridize to other viral, bacterial or cellular DNA. Compared with the cell culture method this assay did not show any false-positive or false-negative results in 16 different clinical specimens. The technique is sensitive, specific and useful for screening clinical specimens and may be helpful in confirming the diagnosis of HSV encephalitis.

Acute lead exposure transiently inhibits hippocampal neuronal activities in vitro.

The effects of acute lead exposure on extracellularly recorded evoked responses in the CA1 region of hippocampal slices were investigated. Field potentials in response to paired-pulse stimulation were assessed while perfusing the slices with normal media and media containing lead in concentrations of 0.2 microM to 53 microM. The evoked population excitatory postsynaptic potentials decreased during lead exposure to a lesser extent than the orthodromically evoked population spike, whereas the presynaptic fiber volley remained unchanged. The maximal inhibition of the orthodromically evoked responses depended strongly on the lead concentration. The input-output relations of the orthodromic responses obtained during perfusion with lead significantly differed from those during control conditions. The somatic short-term potentiation obtained by paired-pulse stimulation increased during the lead exposure. Lead seemed to inhibit the evoked activities only transiently: within 20 min after lead onset, the recorded responses had reached the control level again in spite of further lead perfusion. In contrast to the orthodromically evoked responses, the antidromically evoked population spikes remained constant at all concentrations used. It is concluded from these results that lead acts presynaptically in the hippocampal slice preparation. Additionally, lead interferes with non-synaptic processes at the pyramidal neurons in the CA1. Possible influences of lead over different neurotransmitter systems are discussed.

Inhibition by tetrandrine of calcium currents at mouse motor nerve endings.

The inhibition by the bis-benzyl-isoquinoline alkaloid tetrandrine of motor terminal calcium currents has been studied using extracellular, perineuronal electrodes in the M. triangularis preparation of the mouse. The calcium plateau current was irreversibly blocked, whereas the fast calcium current remained unaffected. From these results a calcium antagonism on neuronal calcium channels involved in transmitter release at motor nerve terminals is suggested.

CALCIUM CHANNEL CURRENTS IN CULTURED PARS INTERCEREBRALIS NEUROSECRETORY CELLS OF ADULT LOCUSTA MIGRATORIA

The medial neurosecretory cells (MNSCs) of the pars intercerebralis in the brain of insects release various hormonal factors that control essential physiological and developmental functions such as moulting, reproduction and metabolism (Wigglesworth, 1940; Girardie, 1966; Goldsworthy, 1969), and these cells are therefore of considerable biological significance. A culture system for locust embryonic pars intercerebralis neurosecretory cells has recently been developed (Vanhems et al. 1993), and Rossler and Bickmeyer (1993) have established an in vitro system for growing larval and adult medial neurosecretory cells. Calcium plays an important role in neural physiology: neurosecretion depends on calcium influx into the cells and calcium currents carry the rising phase of action potentials in different types of insect neurones (Orchard, 1976; Pitman, 1979); calcium also mediates other ionic currents (Thomas, 1984). It is therefore of considerable interest to characterize the types of calcium channel currents found in locust neurosecretory neurones.

Chronic prenatal and postnatal Pb2+ exposure increases [3H]MK801 binding sites in adult rat forebrain.

We have measured the binding of [3H]MK801 to the N-methyl-D-aspartate (NMDA) receptor-ion channel in membrane preparations from adult rat forebrain exposed to lead (Pb2+) during gestation, lactation, and postweaning. Our results indicate a 30.9% increase in the number of [3H]MK801 binding sites in Pb2+ exposed animals relative to controls. No significant changes in the affinity constant were observed. The level of blood Pb2+ for which such changes were measured was 13.9 +/- 2.8 micrograms/dl. These results indicate that alterations in the NMDA receptor-ion channel complex are present at blood Pb2+ levels which are environmentally relevant and suggest that chronic Pb2+ exposure during development can influence the NMDA receptor complex in the adult rat brain.

Effects of maternal lead exposure on functional plasticity in the visual cortex and hippocampus of immature rats.

We examined the amount of long-term potentiation (LTP) in slices from the visual cortex and hippocampus of pre- and postnatally lead-exposed rats and controls at postnatal days (PND) 12-20. A dietary lead intake of 750 ppm by the dams resulted in a mean blood lead concentration in the suckling offspring of about 17' micrograms/dl. While high-frequency stimulation (HFS) of the white matter induced LTP of the field potentials in layers II/III in cortical slices of ten out of the 14 control rats, only three of the twelve lead-exposed rats showed a small amount of LTP. However, in slices from seven of the twelve lead-exposed rats a long-term depression was found following HFS. Furthermore, paired-pulse inhibition was weaker in cortical slices from the lead-exposed as compared to the control rats. In the CA1 hippocampal region the amount of LTP was significantly reduced in the lead-exposed group only in slices taken from rats at PND 16-20, while no differences were seen in slices from younger animals. It is concluded that even low level lead exposure impairs functions of the visual cortex in the immature rat. We suggest that the developing hippocampus is able to compensate for lead-induced functional deficits in the 2nd postnatal week, being more vulnerable at older ages.