Inpatient computer-based standing orders vs physician reminders to increase influenza and pneumococcal vaccination rates: a randomized trial

Context  Computerized reminder systems increase influenza and pneumococcal vaccination rates, but computerized standing order systems have not been previously described or evaluated. Objective  To determine the effects of computerized physician standing orders compared with physician reminders on inpatient vaccination rates. Design, Setting, and Patients  Randomized trial of 3777 general medicine patients discharged from 1 of 6 study wards during a 14-month period (November 1, 1998, through December 31, 1999) composed of 2 overlapping influenza seasons at an urban public teaching hospital. Interventions  The hospital’s computerized physician order entry system identified inpatients eligible for influenza and pneumococcal vaccination. For patients with standing orders, the system automatically produced vaccine orders directed to nurses at the time of patient discharge. For patients with reminders, the computer system provided reminders to physicians that included vaccine orders during routine order entry sessions. Main Outcome Measure  Vaccine administration. Results  During the approximately 6 months of the influenza season, 50% of all hospitalized patients were identified as eligible for influenza vaccination. Twenty-two percent of patients hospitalized during the entire 14 months of the study were found eligible for pneumococcal vaccination. Patients with standing orders received an influenza vaccine significantly more often (42%) than those patients with reminders (30%) (P <.001). Patients with standing orders received a pneumococcal vaccine significantly more often (51%) than those with reminders (31%) (P <.001). Conclusions  Computerized standing orders were more effective than computerized reminders for increasing both influenza and pneumococcal vaccine administration. Our findings suggest that computerized standing orders should be used more widely for this purpose.      

Cingulotomy for psychiatric disease: microelectrode guidance, a callosal reference system for documenting lesion location, and clinical results

OBJECTIVE: To evaluate magnetic resonance imaging (MRI)- and microelectrode recording-guided cingulotomy for patients with psychiatric disorders and to develop a new method of mapping lesion location in anterior cingulate cortex that takes into account the significant interindividual variability in callosal morphometry. METHODS: MRI and microelectrode recording were used to guide placement of radiofrequency lesions in patients with obsessive-compulsive disorder (n = 21) or affective disorders (n = 5). Postoperative improvement was evaluated with the Yale-Brown Obsessive-Compulsive Scale in 15 of the 21 obsessive-compulsive disorder patients studied. From the postoperative MRI scans, we developed a coordinate system for position in the anterior cingulate cortex. The callosal line passes from the most anterior point of the corpus callosum (c = 0) to the most posterior (c = 100). We reconstructed the lesions onto a sagittal map from the Talairach and Tournoux atlas using the distance along the callosal line and the distance above the upper surface of the corpus callosum. RESULTS: The location of neuronal activity distinguished gray and white matter and was useful in delineating the upper and lower cortical banks of the cingulate gyrus, the cingulate bundle, and the corpus callosum. This information was used to place the lesions. Lesions typically were 6 to 8 mm in diameter on T2-weighted MRI scans. The inferior margins were along the corpus callosum from c = 16 to c = 38. Four of 15 patients with obsessive-compulsive disorder had a documented decrease of more than 35% on the Yale-Brown Obsessive-Compulsive Scale, but only one patient had a sustained benefit for more than 1 year. CONCLUSION: Microelectrode recording is useful for lesion placement. Our system for reporting location in anterior cingulate cortex normalizes for differences in callosal morphometry. These techniques may aid future study.     

Atypical neuroleptics in child and adolescent psychiatry

Atypical neuroleptics have enriched our treatment programmes, especially in childhood and adolescent schizophrenia. This article reviews the use of atypical neuroleptics in children and adolescents with schizophrenic disorder. It considers the receptor binding profile and pharmacological properties, indications, side effects, clinical applications and trials of atypical neuroleptics in comparison to the classical neuroleptic haloperidol in adolescent schizophrenia. Special emphasis is placed on the most common atypical neuroleptics clozapine, olanzapine and risperidone since most studies are carried out with these compounds, especially with clozapine. More clinically controlled trials have to be conducted since only one was performed so far. The place of the atypical neuroleptics is discussed and further studies are necessary in order to differentiate the indications tested so far and to find out if the spectrum of indications can be broadened.     

Spontaneous recurrent seizures and neuropathology in the chronic phase of the pilocarpine and picrotoxin model epilepsy

In a recent publication, we have shown a potent interaction between the cholinergic and GABAergic systems in regard to seizure generation and developed the pilocarpine(pilo)/picrotoxin(PTX) model, in which combined injections of these agents have induced status epilepticus (SE) in rats. Here we report on the chronic features of this new animal model of epilepsy. Adult male Wistar rats were systemically injected with solutions containing 150/0.5 mg kg-1, 75/1.5 mg kg-1 and 50/2.0 mg kg-1 (pilo dose/PTX dose). Six epileptic and six control animals were observed for 120-131 days for the occurrence of spontaneous recurrent seizures (SRS). Electroencephalographic, neuropathologic and behavioral analyses were subsequently performed. Following SE, the animals went through a latent period and, subsequently, towards a state of 'chronic' epilepsy, characterized by the emergence of SRS. Animals that received 150/0.5 mg kg-1 presented a relatively short latent period, partial events as their most common initial seizure manifestations and a considerable subsequent progression towards generalization. The group injected with 75/1.5 mg kg-1 presented an extensive period during which the majority of the animals exclusively developed partial seizures (50 days). Animals injected with 50/2.0 mg kg-1 presented an average latent period of over 100 days. Only few animals within this group developed SRS. Our EEG, neuropathological and ictal behavioral findings, in conjunction with the fact that SE was required for the posterior development of SRS, suggest that our model parallels a human TLE condition. Even though diverse TLE models have been described, the pilo/PTX model has as a major feature the intriguing occurrence of disparities among these three groups in the chronic period, although no differences could be observed during SE induction. Future experiments conducted in this sense, might lead to important results in regard to the elucidation of mechanisms of epileptogenesis.     

All-trans retinoic acid prevents apoptosis of human marrow CD34+ cells deprived of haematopoietic growth factors

The regulation of apoptosis plays a key role in haematopoiesis. It has been demonstrated that haematopoietic progenitor cells progressively undergo apoptotic cell death in the absence of appropriate growth factors. We studied the effects of pharmacological doses of all-transretinoic acid (ATRA) on the apoptosis of human adult marrow CD34+ progenitor cells cultured for 7 d in a serum-free medium. We quantified CD34+ cells, clonogenic progenitors and 5 week colony-forming cells (CFC) before and after ATRA exposure. Moreover, we defined the apoptotic status of the CD34+ cell fraction by analysis of phosphatidylserine externalization (using annexin V), the relative membrane permeability to 7-aminoactinomycin D (7AAD) and the mitochondrial membrane potential [using 3,3'-dihexyloxacarbocyanine iodide, DiOC6(3)]. In the drastic experimental conditions used, a decrease in viable CD34+ cells, granulocyte-macrophage colony-forming units (CFU-GM), erythroid burst-forming units (BFU-E) and 5 week CFC were observed. Exposure to ATRA partially prevented the decrease in viable CD34+, without a concomitant effect on the clonogenic and more immature progenitors. ATRA-treated CD34+ cells displayed changes in apoptotic status compared with control cultures, particularly in lower annexin V-binding. These results were confirmed using 7AAD and DiOC6(3). Our results demonstrate that ATRA exerts a protective effect on CD34+ cells exposed to such apoptotic stress.     

Noxious activation of spinal or vagal afferents evokes distinct patterns of fos-like immunoreactivity in the ventrolateral periaqueductal gray of unanaesthetised rats

The purpose of this study was to determine if differences exist between the effects of acute treadmill running and restraint stress on corticotropin-releasing hormone (CRH) release within the amygdala of rats. Extracellular CRH immunoreactivity (CRH-IR) was measured in microdialysate collected from the central nucleus of the amygdala (CeA) during exposure to an inactivated treadmill (TC), during 1 h treadmill running to exhaustion (RUN), and 1 h restraint (RES). Extracellular CRH-IR increased from control levels during the first 20-min period for TC, RUN, and RES, with the largest increase during RES. During the second 20-min period, only RES maintained levels higher than control values. CRH release was higher than control during the third 20-min period of RES and RUN. A second experiment consisted of four groups of either cage controls (CC), TC, RUN, or RES. Immediately following the 60-min treatment, brains were removed and trunk blood collected for analysis of tissue CRH-IR and plasma corticosterone. While amygdala tissue CRH-IR was not different in the CC, TC and RUN rats, these groups had significantly lower levels than the RES animals. Hypothalamic tissue CRH-IR was not different between the CC and TC rats, but the levels were significantly higher in the RES and RUN rats than in the two control groups. Plasma corticosterone levels were elevated only in RES and RUN rats. Results from tissue analysis indicate that increased tissue CRH-IR in the amygdala and hypothalamus can be elicited by RES, while only the hypothalamus shows an increase following RUN. Further, extracellular CRH release in the CeA is increased throughout the period of RES, when rats are placed on the treadmill, and when the animals are approaching physical exhaustion. No increase is observed during the running period between placement on the treadmill and intense exertion. Overall, the data suggest that amygdala CRH release is regulated differently during treadmill running and restraint.     

Norwalk virus binds to histo-blood group antigens present on gastroduodenal epithelial cells of secretor individuals

BACKGROUND & AIMS: Norwalk Virus (NV) is a member of the Caliciviridae family, which causes acute epidemic gastroenteritis in humans of all ages and its cellular receptors have not yet been characterized. Another calicivirus, Rabbit Hemorrhagic Disease Virus, attaches to H type 2 histo-blood group oligosaccharide present on rabbit epithelial cells. Our aim was to test if, by analogy, recombinant NV-like particles (rNV VLPs) use carbohydrates present on human gastroduodenal epithelial cells as ligands. METHODS: Attachment of rNV VLPs was tested on tissue sections of the gastroduodenal junction and on saliva from individuals of known ABO, Lewis, and secretor phenotypes. It was also tested on human Caco-2 cells and on animal cell lines transfected with glycosyltransferases complementary DNA (cDNA). Competition experiments were performed with synthetic oligosaccharides and anticarbohydrate antibodies. Internalization was monitored by confocal microscopy. RESULTS: Attachment of rNV VLPs to surface epithelial cells of the gastroduodenal junction as well as to saliva was detected, yet only from secretor donors. It was abolished by alpha1,2fucosidase treatment, and by competition with the H types 1 and 3 trisaccharides or with anti-H type 1 and anti-H types (3/4) antibodies. Transfection of CHO and TS/A cells with an alpha1,2fucosyltransferase cDNA allowed attachment of VLPs. These transfectants as well as differentiated Caco-2 cells expressing H type 1 structures internalized the bound particles. CONCLUSIONS: rNV VLPs use H type 1 and/or H types (3/4) as ligands on gastroduodenal epithelial cells of secretor individuals.     

Novel paraoxonase (PON1) nonsense and missense mutations predicted by functional genomic assay of PON1 status

Paraoxonase (PON1) has been termed an environmental response enzyme for its function in the detoxification of organophosphate pesticides, nerve agents and pharmaceuticals such as glucocorticoids and statins, as well as its cardioprotective role in breaking down oxidized LDL. PON1(192) genotype can be predicted with high accuracy from an examination of the two-dimensional plot of paraoxon and diazoxon hydrolysis rates [ 1]. Individuals for whom this functional genomic assay failed to predict PON1(192) genotype, or who had a low PON activity relative to others with the same genotype, were predicted to have genetic alterations that explained the inconsistency. Sequencing of the PON1 region of 23 Caucasian individuals detected a nonsense mutation changing amino acid 194 from a Trp to a stop codon (PON1(Trp194stop)). It was predicted that subjects who genotyped as PON1(192QR) but phenotyped as PON1(192QQ) or PON1(192RR) might carry the protein truncation mutation for which the defective product failed to be detected by the phenotyping assay. Screening of the five discordant subjects resulted in the detection of a single Caucasian carrying the stop codon, and determined its phasing on the PON1(192R) allele. Sequencing confirmed the change and revealed an additional subject with a likely deletion of the 5' end of the PON1 gene. Additional sequencing of 25 subjects with low PON1 activities identified two additional previously undescribed PON1 mutations, which may affect PON1 function: PON1(Pro90Leu) associated with the PON1(192Q) allele and PON1(Asp124missplice) associated with the PON1(192R) allele.     

Salmeterol decreases eosinophilic cationic protein and rescue medication in patients inhaling beclomethasone dipropionate: preliminary study in mild and moderate asthma in Trinidad, West Indies

Activated eosinophils play a critical role in asthma pathogenesis, and eosinophil cationic protein (ECP) is a useful indicator of inflammation. Inhaled corticosteroids and long-acting beta2-agonists (LABA) effectively control asthma symptoms and improve airway function. Salmeterol's anti-inflammatory efficacy as add-on therapy to inhaled corticosteroids has not been evaluated in Caribbean populations. We investigated nine non-smoking subjects (three men and six women; mean age: +/- SE, 50.7 +/- 3.82 years) with stable mild and moderate persistent asthma who were inhaling > or = 500 microg beclomethasone dipropionate (BDP) daily. This was a with-in-patient controlled laboratory blind study performed over 8 weeks. Patients received BDP for 2 weeks, add-on salmeterol 100 microg in weeks 3-6 and BDP alone in weeks 7-8. Patients recorded daily morning and night symptoms. Morning peak expiratory flow rate was measured on entry to the study and with sputum ECP at the end of weeks 2, 4, 6 and 8. Salmeterol together with BDP decreased sputum ECP from a pretreatment median value of 897.84 microg/l to 628.38 microg/l after 4 weeks, and ECP continued to decrease even after salmeterol withdrawal. Both drugs decreased the frequency of rescue medication use by approximately 50% and increased the median number of days per week without rescue salbutamol from 0 to 3 days. Salmeterol's bronchoprotective effect was maximal after 4 weeks and was sustained after its withdrawal. In conclusion, this study, performed in Trinidadian asthmatics, used ECP as a surrogate marker of bronchial inflammation and supports the recent Salmeterol Multi-center Asthma Research Trial (SMART) data recommending add-on salmeterol therapy to adequate anti-inflammatory medication such as inhaled corticosteroids for optimal asthma management. Further studies are required to evaluate the anti-inflammatory efficacy and possible tolerance to salmeterol in Caribbean patients.