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.

Influence of pathogens causing clinical mastitis on reproductive variables of dairy cows.

In dairy cattle, mastitis is a disease of the mammary gland caused by pathogens such as bacteria, viruses, fungi, and algae. Mastitis causes economic losses to dairy farms as well as public health concerns. The reproductive efficiency of commercial dairy herds has important implications for the economic success of dairy operations and is strongly associated with the health status of cows. Mastitis has previously been linked with decreased fertility of dairy cows, but the effect of specific pathogens on the severity of fertility reduction is still unclear. In this study, cows diagnosed with mastitis caused by major pathogens (Staphylococcus aureus, Streptococcus agalactiae, Escherichia coli, Klebsiella spp., Mycoplasma spp., and environmental Streptococcus) needed more artificial inseminations (AI) than did cows with mastitis caused by minor pathogens (coagulase-negative Staphylococcus and Corynebacterium spp.) and healthy cows. Cows diagnosed with mastitis, independent of what pathogen was causing mastitis, had more days open compared with nonmastitic cows. The percentage of cows that successfully established pregnancy at first AI was greater for the control group than for the major pathogens group but not significantly different from the minor pathogens group. Pregnancy loss was lower in the control group than in the major pathogens group; however, there was no difference compared with the minor pathogen group. Mastitis caused by gram-negative bacteria decreased the percentage of pregnancy per first AI and increased days open and pregnancy loss compared with the control group. Cows with mastitis caused by gram-positive bacteria also had increased days open compared with control cows. This study shows that different mastitis-causing bacteria can affect the fertility of cows differently. Mastitis events caused by major pathogens and gram-negative bacteria were associated with the greatest decrease in reproductive efficiency.

Hybrid female mate choice as a species isolating mechanism: environment matters.

A fundamental goal of biology is to understand how new species arise and are maintained. Female mate choice is potentially critical to the speciation process: mate choice can prevent hybridization and thereby generate reproductive isolation between potentially interbreeding groups. Yet, in systems where hybridization occurs, mate choice by hybrid females might also play a key role in reproductive isolation by affecting hybrid fitness and contributing to patterns of gene flow between species. We evaluated whether hybrid mate choice behaviour could serve as such an isolating mechanism using spadefoot toad hybrids of Spea multiplicata and Spea bombifrons. We assessed the mate preferences of female hybrid spadefoot toads for sterile hybrid males vs. pure-species males in two alternative habitat types in which spadefoots breed: deep or shallow water. We found that, in deep water, hybrid females preferred the calls of sterile hybrid males to those of S. multiplicata males. Thus, maladaptive hybrid mate preferences could serve as an isolating mechanism. However, in shallow water, the preference for hybrid male calls was not expressed. Moreover, hybrid females did not prefer hybrid calls to those of S. bombifrons in either environment. Because hybrid female mate choice was context-dependent, its efficacy as a reproductive isolating mechanism will depend on both the environment in which females choose their mates as well as the relative frequencies of males in a given population. Thus, reproductive isolation between species, as well as habitat specific patterns of gene flow between species, might depend critically on the nature of hybrid mate preferences and the way in which they vary across environments.

Impact of the serum- and glucocorticoid-inducible kinase 1 on platelet dense granule biogenesis and secretion.

BACKGROUND: Platelet secretion is critical to development of acute thrombotic occlusion. Platelet dense granules contain a variety of important hemostatically active substances. Nevertheless, biogenesis of platelet granules is poorly understood. OBJECTIVES: Serum- and glucocorticoid-inducible kinase 1 (SGK1) has been shown to be highly expressed in platelets and megakaryocytes, but its role in the regulation of platelet granule biogenesis and its impact on thrombosis has not been investigated so far. METHODS AND RESULTS: Electron microscopy analysis of the platelet ultrastructure revealed a significant reduction in the number and packing of dense granules in platelets lacking SGK1 (sgk1(-/-) ). In sgk1(-/-) platelets serotonin content was significantly reduced and activation-dependent secretion of ATP, serotonin and CD63 significantly impaired. In vivo adhesion after carotis ligation was significantly decreased in platelets lacking SGK1 and occlusive thrombus formation after FeCl3 -induced vascular injury was significantly diminished in sgk1(-/-) mice. Transcript levels and protein abundance of dense granule biogenesis regulating GTPase Rab27b were significantly reduced in sgk1(-/-) platelets without affecting Rab27b mRNA stability. In MEG-01 cells transfection with constitutively active (S422) (D) SGK1 but not with inactive (K127) (N) SGK1 significantly enhanced Rab27b mRNA levels. Sgk1(-/-) megakaryocytes show significantly reduced expression of Rab27b and serotonin/CD63 levels compared with sgk1(+/+) megakaryocytes. Proteome analysis identified nine further vesicular transport proteins regulated by SGK1, which may have an impact on impaired platelet granule biogenesis in sgk1(-/-) platelets independent of Rab27b. CONCLUSIONS: The present observations identify SGK1 as a novel powerful regulator of platelet dense granule biogenesis, platelet secretion and thrombus formation. SGK1 is at least partially effective because it regulates transcription of Rab27b in megakaryocytes.

TGFß1 and SGK1-sensitive store-operated Ca2+ entry and Orai1 expression in endometrial Ishikawa cells.

The serum-and-glucocorticoid-inducible-kinase-1 (SGK1) is ubiquitously expressed and under genomic control by cell stress, hormones and further mediators. A most powerful stimulator of SGK1 expression is transforming growth factor TGFß1. SGK1 is activated by insulin and growth factors via phosphatidylinositol-3-kinase and the 3-phosphoinositide-dependent kinase PDK1. As shown recently, SGK1 increases the store-operated Ca(2+) entry (SOCE), which is accomplished by the pore-forming ion channel unit Orai. Most recent observations further revealed that SGK1 plays a critical role in the regulation of fertility. SGK1 is up-regulated in the luminal epithelium of women with unexplained infertility but down-regulated in decidualizing stromal cells of patients with recurrent pregnancy loss. The present study explored whether Orai1 is expressed in endometrium and sensitive to regulation by SGK1 and/or TGFß1. To this end, Orai1 protein abundance was determined by western blotting and SOCE by fura-2 fluorescence. As a result, Orai1 was expressed in human endometrium and in human endometrial Ishikawa cells. Orai1 expression and SOCE in Ishikawa cells were increased by transfection with constitutively active (S422D)SGK1 but not by transfection with inactive (K127N)SGK1. The difference of SOCE between (S422D)SGK1 and (K127N)SGK1-transfected cells was virtually abrogated in the presence of Orai1 inhibitor 2-aminoethoxydiphenyl borate (2-APB, 50 µM). Similar to (S422D)SGK1 transfection TGFß1 treatment up-regulated both Orai1 protein abundance and SOCE. In conclusion, Orai1 is expressed in the human endometrium and is up-regulated by SGK1 and TGFß1. The present observations thus uncover a novel element in SGK1-sensitive regulation of endometrial cells.

Lipocalin-2 serum levels are increased in acute hepatic failure.

Lipocalin-2 (LCN-2), which is expressed in immunocytes as well as hepatocytes, is upregulated in cells under stress from infection or inflammation with increase in serum levels. We sought to investigate the relevance of LCN-2 in the setting of acute hepatic failure, particularly when addressed with the molecular adsorbent recirculating system (MARS). We measured serum LCN-2 concentrations with enzyme-linked immunosorbent assay (ELISA) in 8 patients with acute-on-chronic-liver failure (ACLF) and acute liver failure (ALF) who were treated with MARS. The controls were 14 patients with stable chronic hepatic failure (CHF). LCN-2 was determined immediately before and after the first MARS session. Baseline LCN-2 serum concentrations were significantly increased among ACLF and ALF patients as compared with CHF (P = .004 and P = .0086, respectively). There was no significant difference between the ALF and ACLF group. Moreover, serum LCN-2 levels did not change significantly during the MARS treatment. Serum LCN-2 levels, therefore, may be useful to discern acute from chronic hepatic failure and to monitor the course as well as the severity of the disease.

The effect of the molecular adsorbent recirculating system on moxifloxacin and meropenem plasma levels.

BACKGROUND: Adequate plasma antibiotic concentrations are necessary for effective elimination of invading microorganism; however, extracorporeal organ support systems are well known to alter plasma concentrations of antibiotics, requiring dose adjustments to achieve effective minimal inhibitory concentrations in the patient's blood. METHODS: A mock molecular adsorbent recirculating system (MARS) circuit was set using 5000 ml of bovine heparinized whole blood to simulate an 8-h MARS treatment session. After the loading dose of 400 mg of moxifloxacin or 2 g of meropenem had been added, blood was drawn from the different parts of the MARS circuit at various time points and analyzed by high-performance liquid chromatography. The experiments were performed in triplicate. Additionally, meropenem concentrations were determined in the plasma of one patient treated with MARS suffering from acute liver failure due to an idiosyncratic reaction to immunosuppressive medication. RESULTS: In our single-compartment model, a significant decrease in the quasi-systemic concentration of moxifloxacin and meropenem could be detected as early as 15 min after the commencing of the MARS circuit. Moreover, within 60 min the moxifloxacin and meropenem concentrations were less than 50% of the initial value. The activated charcoal removed the majority of moxifloxacin and meropenem in the albumin circuit. In our patient, the meropenem concentrations in the return line after MARS were constantly lower than in the access line, indicating a likely removal of meropenem through MARS. CONCLUSION: Our data provide evidence that moxifloxacin and meropenem are effectively removed from the patient's blood by MARS, leading to low plasma levels. Dose adjustments of both antibiotic compounds may be required.

Visuotopic mapping through a multichannel stimulating implant in primate V1.

We report on our efforts to establish an animal model for the development and testing of a cortical visual prostheses. One-hundred-fifty-two electrodes were implanted in the primary visual cortex of a rhesus monkey. The electrodes were made from iridium with an activated iridium oxide film, which has a large charge capacity for a given surface area, and insulated with parylene-C. One-hundred-fourteen electrodes were functional after implantation. The activity of small (2-3) neuronal clusters was first recorded to map the visually responsive region corresponding to each electrode. The animal was then trained in a memory (delayed) saccade task, first with a visual target, then to a target defined by direct cortical stimulation with coordinates specified by the stimulating electrode's mapped receptive field. The SD of saccade endpoints was approximately 2.5 larger for electrically stimulated versus visual saccades; nevertheless, when trial-to-trial scatter was averaged out, the correlation between saccade end points and receptive field locations was highly significant and approached unity after several months of training. Five electrodes were left unused until the monkey was fully trained; when these were introduced, the receptive field-saccade correlations were high on the first day of use (R = 0.85, P = 0.03 for angle, R = 0.98, P < 0.001 for eccentricity), indicating that the monkey had not learned to perform the task empirically by memorizing reward zones. The results of this experiment suggest the potential for rigorous behavioral testing of cortical visual prostheses in the macaque.

Feasibility of a visual prosthesis for the blind based on intracortical microstimulation of the visual cortex.

The feasibility of producing a visual prosthesis for the blind using intracortical microstimulation (ICMS) of the visual cortex was studied in a 42-year-old woman who had been totally blind for 22 years secondary to glaucoma. Thirty-eight microelectrodes were implanted in the right visual cortex, near the occipital pole, for a period of 4 months. Percepts reported as small spots of light, called phosphenes, were produced with 34 of the 38 implanted microelectrodes. Threshold currents for phosphene generation with trains of biphasic pulses were as low as 1.9 microA, and most of the microelectrodes had thresholds below 25 microA. Phosphene brightness could be modified with stimulus amplitude, frequency and pulse duration. Repeated stimulation over a period of minutes produced a gradual decrease in phosphene brightness. Phosphenes did not flicker. The apparent size of phosphenes ranged from a "pin-point' to a "nickel' (20 mm diameter coin) held at arm's length. Phosphene size usually decreased as stimulation current was increased but increased slightly as the train length (TL) was increased. At levels of stimulation near threshold, the phosphenes were often reported to have colours. As the stimulation level was increased, the phosphenes generally became white, greyish or yellowish. Individual phosphenes appeared at different distances from the subject. When two phosphenes were simultaneously generated, the apparent distances of the individual phosphenes sometimes changed to make them appear to be at about the same distance. When three or more phosphenes were simultaneously generated, they became coplanar. Except for rare occasions, phosphenes extinguished rapidly at the termination of the stimulation train. When stimulation TLs were increased beyond 1 s, phosphenes usually disappeared before the end of the train. The duration of phosphene perception could be increased by interrupting a long stimulation train with brief pauses in stimulation. Intracortical microelectrodes spaced 500 microns apart generated separate phosphenes, but microelectrodes spaced 250 microns typically did not. This two-point resolution was about five times closer than has typically been achieved with surface stimulation. With some individual microelectrodes, a second closely spaced phosphene was sometimes produced by increasing the stimulation current. Phosphenes moved with eye movements. When up to six phosphenes were simultaneously elicited, they all moved with the same relative orientation during eye movements. All phosphenes were located in the left hemi-field with the majority above the horizontal meridian. There was a clustering of most of the phosphenes within a relatively small area of visual space. The potentially greater microelectrode density and lower power requirements of ICMS compared with surface stimulation appears encouraging for a visual prosthesis. However, further studies with blind subjects are required to optimize stimulation parameters and test complex image recognition before the feasibility of a visual prosthesis based on ICMS can be established.

Laser exposure of Parylene-C insulated microelectrodes.

The polymer, Parylene-C, has proven to be a biocompatible insulation for microelectrodes. However, due to its inert nature, the removal of the insulation from the tips of microelectrodes is difficult. This paper describes the use of an ultraviolet laser system to micromachine Parylene-C insulation with photoablation to precisely expose an arbitrary shape recording or stimulating surface.

The effects of cooling supplementary motor area and midline cerebral cortex on neuronal responses in area 4 of monkeys.

It has been postulated that the supplementary motor area (SMA) is involved in the initiation of movement and in gating of afferent input to motor cortex (MI) from peripheral receptors. We studied the responses of 119 neurons in MI to imposed disturbances of wrist-movement performance generated by the introduction of torque pulses before, during and after localized cooling of the SMA in conscious monkeys. The cooling of SMA did not prevent monkeys from making these simple movements. Eighty-two neurons responded to the wrist perturbations. Only 7 of these neurons changed their responsiveness with unilateral or bilateral cooling of SMA. From the data we have obtained on MI neuronal firing patterns, the SMA does not appear to modulate the long-latency trans-cortical stretch reflex during the periods in a task that we have investigated. Nor does it prevent animals from performing these simple movements to a visual target.

Microstimulation mapping of precentral cortex during trained movements.

1. The precentral cortex of three Macaca mulatta monkeys were mapped with intracortical microstimulation (ICMS) while the monkeys performed alternating wrist flexion and extension movements. A forearm cocontraction task was also employed with one monkey. Electromyogram (EMG) recordings from forearm muscles were used to evaluate the results of ICMS. 2. We have found that the results of ICMS can be misleading if EMG activity is not recorded from the responding muscle. Inhibition can be interpreted as excitation if muscle palpation or joint movement are the only response criteria. 3. Movement of the stimulating electrode by as little as 200 microns in a single radial column sometimes changed EMG responses from inhibition to excitation or vice versa, indicating that cortical inhibitory areas for a muscle can be located very close to excitatory zones. 4. Both excitation and inhibition of muscles could be produced with ICMS of precentral cortex when the animal was performing a task involving the muscles being mapped. EMG responses to ICMS were stable, provided that the stimulation was applied at the same time during a repetitive task such that the motoneurons were at a given level of excitability. 5. Zones where ICMS produced inhibition of a particular forearm muscle were interspersed among zones that produced excitation for that muscle. 6. Regions exist in precentral cortex where ICMS activates antagonistic wrist muscles producing cocontraction. 7. The extensive cortical region from which any individual muscle can be activated or suppressed with ICMS and the various combinations of muscles that are activated from within this region suggest that different types of movements involving a single muscle are represented at different locations within this region. 8. At a few locations in precentral cortex, the EMG responses to ICMS were not just a function of the level of excitation of the motoneuron pool at the time of stimulation but were also dependent on the specific task the monkey was performing at the time of stimulation.

HIV infected hospital patients in New York State. The development of longitudinal information from a hospital discharge data system.

Abstracted records of all patients discharged from New York State acute care hospitals from January 1, 1983, through October 1, 1987, containing a diagnosis of HIV infection (N = 36,664) were linked into a longitudinal file of 20,005 patient-specific case histories. A validation study utilizing Medicaid patient-specific discharge information for calendar year 1985 showed that, on the average, each case history of the longitudinal file contained 85% (+/- 5%) of the expected discharges. The number of patients present in the longitudinal file was 10% (+/- 4%)--too large a percentage, due to a failure to link all the discharges to the appropriate case histories. The number of patients with a diagnosis of Pneumocystis carinii pneumonia (PCP) found in the longitudinal file was found to be consistent with the number reported to the New York State AIDS Registry. The longitudinal file appears to be sufficiently accurate and complete to use in evaluating HIV-related acute care in hospitals.

Fiber type composition of monkey forearm muscle.

Histochemical staining methods were applied to selected superficial forearm muscles of Macaca mulatta monkeys. The muscles were analyzed with regard to relative percentage distribution of different fiber types. In extensor carpi radialis brevis, extensor carpi radialis longus, and palmaris longus there was an even dispersion of each fiber type from the superficial to the deep part of the muscle. Extensor digiti communis showed a slightly higher percentage of type I fibers and correspondingly lower percentage of type II fibers in its central as compared to its superficial area. Three muscles, bracioradialis, extensor carpi ulnaris, and flexor carpi radialis, displayed marked differences between their superficial and deep areas. All of them contained a higher proportion of type I fibers (and correspondingly lower percentage of type II fibers) in their deep parts than in their superficial areas. Flexor carpi ulnaris (FCU) differed from the other muscles studied in that it showed distinctly different fiber proportions on either side of a central tendon. While the ulnar head of FCU was dominated by type II fibers (71% compared to 27% type I fibers), the humeral head contained a larger proportion of type I fibers (58% vs. 40% type II fibers). This difference in fiber type distribution suggests different functional demands for the two heads of FCU, with the possibility of more sustained activity in the humeral head.