Effects of canola meal source on the standardized ileal digestible amino acids and apparent metabolizable energy contents for broiler chickens.

Two studies were conducted to determine the effect of canola meal source on the standardized ileal digestible amino acids (AA) and nitrogen-corrected apparent metabolizable energy (AMEn) contents of canola meal (CM) from 6 processing plants in Canada. Two plants provided CM in both mash and pellet forms, while the other 4 provided CM in mash form only, giving a total of 8 samples. In the standardized ileal digestibility (SID) assay, 280 birds were housed 7 per cage and fed a commercial starter diet from 1 to 14 d of age followed by the test diets from 15 to 21 d. Diets were formulated to contain CM as the only source of protein. Chromic oxide was included in all diets as an indigestible marker. Diets were randomly assigned to 5 cages of 7 birds. On d 21, birds were euthanized by CO2 asphyxiation and digesta samples were collected from the terminal ileum for SID of AA. The SID values were calculated using ileal endogenous AA losses determination. In the AMEn assay, 330 birds were housed 6 per cage and fed a commercial starter diet from 1 to 14 d of age followed by the experimental diets from 15 to 19 d. The 8 experimental diets contained 30% of CM and 70% of a corn-soybean meal-based diet. There were differences (P < 0.05) among CM samples in the standardized ileal digestible content of all AA. Standardized ileal digestible contents of Arg, Lys, Met, and Thr averaged 2.17, 1.74, 0.53, and 1.03%, respectively. Pelleting reduced (P < 0.05) the standardized ileal digestible content of all AA in CM from one of the plants. There were differences (P<0.05) among CM samples in the AMEn contents with values ranging from 1,590 to 2,041 kcal/kg DM. In conclusion, there was effect of CM source on the standardized ileal digestible AA and AMEn contents. Regression equations for predicting standardized ileal digestible contents of selected AA from a simple measure of acid detergent fiber (ADF) were developed.

Standardized ileal digestible amino acid contents of canola meal from Canadian crushing plants for growing pigs.

Studies have shown that there are variations in the chemical and nutritive composition of canola meal (CM) produced in Canada, some of which may result from differences among the canola seed crushing plants. Therefore, it is necessary to determine the variability in the nutritive value of CM as its end users desire increased meal consistency and more information on any potential variability in AA digestibility. Thus, 18 ileal cannulated barrows (average initial BW = 23.3 kg) were used to determine the apparent (AID) and standardized (SID) ileal digestibility of N and AA and standardized ileal digestible N and AA contents in CM from 6 processing plants in Canada. Two processing plants provided CM in both mash and pellet forms, whereas the other 4 provided it only in mash form, giving a total of 8 CM samples. The barrows were fed 9 cornstarch-based diets. The first 8 diets were formulated to contain the CM samples as the only source of AA. The ninth diet was a casein-cornstarch diet to determine ileal endogenous AA losses. All diets contained 0.3% titanium dioxide as an indigestible marker. Pigs were housed individually in pens and were fed the 9 diets in a completely randomized design for 3 periods to give 6 pigs per diet. Each experimental period lasted for 7 d, consisting of 5 d of adaptation and 2 d of ileal digesta collection at 2-h intervals from 0800 to 2000 h on d 6 and 7. There was an effect ( < 0.05) of CM source on 1) the AID of N, Met, Cys, Thr, Val, Gly, and Ser; 2) the SID of N, Met, and Cys; and 3) the standardized ileal digestible content of all AA. Pelleting reduced ( < 0.05) the standardized ileal digestible content of Arg, Ile, Glu, and Gly in 1 of the CM samples tested and of all AA except His in the other CM sample. The SID values for Arg, Lys, Met, and Thr averaged 87.2%, 78.2%, 84.5%, and 74.1%, respectively. The standardized ileal digestible contents of Arg, Lys, Met, and Thr averaged 2.10%, 1.71%, 0.50%, and 1.01%, respectively. In conclusion, there were variations in the AID, SID, and standardized ileal digestible AA contents of CM among crushing plants in Canada.

Synapsin II gene expression in the dorsolateral prefrontal cortex of brain specimens from patients with schizophrenia and bipolar disorder: effect of lifetime intake of antipsychotic drugs.

Synapsins are neuronal phosphoproteins crucial to regulating the processes required for normal neurotransmitter release. Synapsin II, in particular, has been implied as a candidate gene for schizophrenia. This study investigated synapsin II mRNA expression, using real-time reverse transcriptase-PCR, in coded dorsolateral prefrontal cortical samples provided by the Stanley Foundation Neuropathology Consortium. Synapsin IIa was decreased in patients with schizophrenia when compared with both healthy subjects and patients with bipolar disorder, whereas synapsin IIb was only significantly reduced in patients with schizophrenia when compared with healthy subjects but not in patients with bipolar disorder. Furthermore, lifetime antipsychotic drug use was positively associated with synapsin IIa expression in patients with schizophrenia. Results suggest that impairment of synaptic transmission by synapsin II reduction may contribute to dysregulated convergent molecular mechanisms, which result in aberrant neural circuits that characterize schizophrenia, while implicating involvement of synapsin II in therapeutic mechanisms of currently prescribed antipsychotic drugs.

Starch source and content in postpartum dairy cow diets: effects on plasma metabolites and reproductive processes.

The objective of this study was to examine the effects of dietary starch source and content in the immediate postpartum period on plasma metabolites and hormones and ovarian follicular development. One of 3 diets was fed in a randomized block design to 40 cows from calving until 70 d in milk. The diets contained 45% alfalfa silage (AS), 45% barley silage (BS), or 41% barley silage and 4% supplemental starch (SS) on a dry matter basis. All diets contained 45% barley-based concentrate and 10% alfalfa hay. Resulting starch levels were 25.2, 23.3, and 26.7% for AS, BS, and SS, respectively. Body condition was scored every other week and dry matter intake and milk yield were recorded daily. Milk samples were obtained weekly and blood samples were taken at calving and then every other week to determine concentrations of glucose, insulin, insulin-like growth factor-1, ß-hydroxybutyrate, and nonesterified fatty acids. Transrectal ultrasonography was performed twice per week from 7 d after calving until first ovulation or 62 d in milk in all cows. For a subset of 7 AS-, 8 BS-, and 9 SS-fed cows, a complete estrous cycle was monitored for ovarian dynamics, and blood samples were collected every second day for progesterone and estradiol. Luteinizing hormone pulsatility was also determined (5 cows/treatment) approximately 15 d postcalving. Treatment had no effect on body condition score, dry matter intake, blood metabolites, milk yield, or milk fat and protein contents, but BS-fed cows had significantly higher levels of milk urea nitrogen compared with SS cows. Cows fed SS (31 d) tended to have a shorter interval from calving to first ovulation than cows fed AS (43 d) or BS (38 d). The incidence of double first ovulations was higher in cows fed SS (46%) compared with those fed BS (0%). Treatment had no effect on LH pulse frequency or amplitude, ovarian dynamics, or progesterone and estradiol concentrations during the observed estrous cycle. Energy balance did not differ among cows fed the 3 diets. Overall, dietary starch source and concentration had little effect on productivity or metabolic status of postpartum cows.

Translocation of AIF in the human and rat striatum following protracted haloperidol, but not clozapine treatment.

Loss of mitochondrial membrane integrity and consequent release of apoptogenic factors may be involved in mediating striatal neurodegeneration after prolonged treatment with the typical antipsychotic drug haloperidol. Apoptosis-inducing factor (AIF), an intramitochondrial protein, may have a large influence on mediating haloperidol-induced striatal neuron destruction. Translocation of this protein from mitochondria to the nucleus promotes cell death independently of the caspase cascade. To examine how AIF may contribute to haloperidol-induced apoptosis, AIF translocation was observed in three haloperidol treatment paradigms. SH-SY5Y cells were treated with both haloperidol and clozapine and examined for AIF immunofluorescence. Immunohistochemistry was also performed on human striatal sections obtained from the Stanley Foundation Neuropathology Consortium and on rat brain sections following 28 days of antipsychotic drug treatment. In the cellular model haloperidol, but not clozapine treatment increased the nuclear AIF immunofluorescent signal and decreased cell viability. Corollary to these findings, striatal sections from patients who had taken haloperidol and rats who were administered haloperidol both had an elevated nuclear AIF signal. The results provide novel evidence implicating the involvement of AIF in haloperidol-associated apoptosis and its relevance to the development of typical antipsychotic drug-related adverse effects such as tardive dyskinesia.

cDNA array reveals increased expression of glucose-dependent insulinotropic polypeptide following chronic clozapine treatment: role in atypical antipsychotic drug-induced adverse metabolic effects.

Clozapine is an atypical antipsychotic drug with unique pharmacological and therapeutic properties. Unlike the typical antipsychotic drug, haloperidol, clozapine does not cause extrapyramidal side effects; however, weight gain, dyslipidemia, and type II diabetes are commonly associated with the use of this drug in subjects with schizophrenia. The aim of this study was to profile gene expression in the rat striatum following clozapine treatment. Chronic treatment with clozapine revealed upregulation of several genes including the glucose-dependent insulinotropic polypeptide (GIP) gene by over 200% in the rat striatum. The cDNA array results for the GIP gene were confirmed by real-time RT-PCR as well as by radioimmunoassay. Expression of the GIP gene in the central nervous system is consistent with the results of retinal GIP gene expression as reported by other investigators. Taken together, these findings implicate the possible role of GIP as a neuromodulator in the central nervous system. GIP is an insulinotropic agent with stimulatory effects on insulin synthesis and release from the pancreas. However, changes in brain GIP levels are most likely unrelated to the metabolic adverse effects (dyslipidemia, type II diabetes, weight gain) associated with clozapine treatment. Therefore, we also measured GIP gene expression in the K-cell-rich regions, duodenum and jejunum (small intestine), and plasma GIP levels using radioimmunoassay following chronic treatment with clozapine. GIP mRNA levels in the small intestine and the plasma GIP at the protein level were significantly elevated in clozapine-treated subjects. Furthermore, as observed in humans, chronic clozapine treatment also caused weight gain, and increased levels of insulin, triglycerides and leptin in the plasma. These results suggest that adverse metabolic effects associated with clozapine treatment may be related to its ability to increase intestinal gene expression for GIP.

Total asymmetric synthesis of the putative structure of the cytotoxic diterpenoid (-)-sclerophytin a and of the authentic natural sclerophytins A and B.

An enantioselective synthetic route to the thermodynamically most stable diastereomer of the structure assigned to sclerophytin A (5) has been realized. The required tricyclic ketone 33 was prepared by sequential Tebbe-Claisen rearrangement of lactones 29 and 30, which originated from the Diels-Alder cycloaddition of Danishefsky's diene to (5S)-5-(d-menthyloxy)-2(5H)-furanone (14). An allyl and a cyano group were introduced into the resulting adduct by means of stereocontrolled allylindation under aqueous Barbier-like conditions and by way of cyanotrimethylsilane, respectively. Following stereocontrolled nucleophilic addition of a methyl group to 33, ring A was elaborated by formation of the silyl enol ether, ytterbium triflate-catalyzed condensation with formaldehyde, O-silylation, and Cu(I)-promoted 1,4-addition of isopropylmagnesium chloride. The superfluous ketone carbonyl was subsequently removed and the second ether bridge introduced by means of oxymercuration chemistry. Only then was the exocyclic methylene group unmasked via elimination. An alternative approach to the alpha-carbinol diastereomer proceeds by initial alpha-oxygenation of 37 and ensuing 1,2-carbonyl transposition. Neither this series of steps nor the Wittig olefination to follow induced epimerization at C10. Through deployment of oxymercuration chemistry, it was again possible to elaborate the dual oxygen-bridge network of the target ring system. Oxidation of the organomercurial products with O(2) in the presence of sodium borohydride furnished 72, which was readily separated from its isomer 73 after oxidation to 61. Hydride attack on this ketone proceeded with high selectivity from the beta-direction to deliver (-)-60. Comparison of the high-field (1)H and (13)C NMR properties and polarity of synthetic 5 with natural material required that structural revision be made. Following a complete spectral reassessment of the structural assignments to many sclerophytin diterpenes, a general approach to sclerophytin A, three diastereomers thereof, and of sclerophytin B was devised. The presence of two oxygen bridges as originally formulated was thereby ruled out, and absolute configurations were properly determined. Key elements of the strategy include dihydroxylation of a medium-ring double bond, oxidation of the secondary hydroxyl in the two resulting diols, unmasking of an exocyclic methylene group at C-11, and stereocontrolled 1,2-reduction of the alpha-hydroxy ketone functionality made available earlier.

Characterization of a toxin A-negative, toxin B-positive strain of Clostridium difficile responsible for a nosocomial outbreak of Clostridium difficile-associated diarrhea.

Clostridium difficile-associated diarrhea (CAD) is a very common nosocomial infection that contributes significantly to patient morbidity and mortality as well as to the cost of hospitalization. Previously, strains of toxin A-negative, toxin B-positive C. difficile were not thought to be associated with clinically significant disease. This study reports the characterization of a toxin A-negative, toxin B-positive strain of C. difficile that was responsible for a recently described nosocomial outbreak of CAD. Analysis of the seven patient isolates from the outbreak by pulsed-field gel electrophoresis indicated that this outbreak was due to transmission of a single strain of C. difficile. Our characterization of this strain (HSC98) has demonstrated that the toxin A gene lacks 1.8 kb from the carboxy repetitive oligopeptide (CROP) region but apparently has no other major deletions from other regions of the toxin A or toxin B gene. The remaining 1.3-kb fragment of the toxin A CROP region from strain HSC98 showed 98% sequence homology with strain 1470, previously reported by M. Weidmann in 1997 (GenBank accession number Y12616), suggesting that HSC98 is toxinotype VIII. The HSC98 strain infecting patients involved in this outbreak produced the full spectrum of clinical illness usually associated with C. difficile-associated disease. This pathogenic spectrum was manifest despite the inability of this strain to alter tight junctions as determined by using in vitro tissue culture testing, which suggested that no functional toxin A was produced by this strain.

Regional dissemination and control of epidemic methicillin-resistant Staphylococcus aureus. Manitoba Chapter of CHICA-Canada.

A methicillin-resistant Staphylococcus aureus (MRSA) strain introduced into the largest tertiary-care teaching hospital in Manitoba in 1993 led to a sustained outbreak with secondary outbreaks at one community hospital, two large long-term-care facilities, and nosocomial transmission at a second teaching hospital. Control measures were consistent at each institution and were coordinated on a province-wide basis. MRSA is not currently endemic in any facility in the province.

Diabetes update with a cardiac perspective.

Diabetes is a chronic illness that affects 6% of the U.S. population. In daily practice, nurses have the opportunity to share with patients and colleagues recent advances in the management of diabetes to improve outcomes. Given the prevalence of heart disease in this population, nurses in the cardiovascular field have the unique opportunity to initiate risk-reduction strategies and collaborate with diabetes team members to optimize qualify of life for patients with diabetes.

Nosocomial pneumonia on general medical and surgical wards in a tertiary-care hospital.

OBJECTIVE: To describe the demographic, clinical, and microbiologic characteristics of patients who develop nosocomial pneumonia on general medical and surgical wards of a tertiary-care hospital. DESIGN: A 1-year, prospective, descriptive study. SETTING: A 1,100-bed, tertiary-care, urban hospital. POPULATION: Patients experiencing nosocomial pneumonia were identified through surveillance on general medical and surgical wards, using a standard case definition. RESULTS: 92 pneumonias in 85 patients on general wards were identified. The mean age of patients was 63 +/- 17 years, 55 patients (65%) were male, and 75 cases of pneumonia (81%) were acquired on surgical wards. Bacteremia was identified in 8 (13%) of 62 episodes, and 48 (52%) grew potential pathogens from respiratory specimens. Twenty-six patients (28%) required transfer to the intensive-care unit (ICU), and 20 (22%) received mechanical ventilation. By multivariate analysis, patients with a thoracic surgical procedure or with Staphylococcus aureus isolated from respiratory secretions were more likely to require ICU admission. The overall mortality rate was 20% (17/85), with a directly associated mortality of 14% (12/85). Patients who died were older, more frequently resided on a medical ward, and had a greater mean number of comorbidities. These patients often were treated nonaggressively and were not considered candidates for ICU admission due to advanced age and poor underlying clinical status. CONCLUSIONS: Although the morbidity of nosocomial pneumonia in this population was high, as evidenced by high rates of transfer to ICU, the directly associated mortality was relatively low. Those requiring ICU admission require further study to identify preventive measures that could decrease the morbidity in this group. Interventions to prevent pneumonia or to improve prognosis may not be feasible for the majority of these patients who die from nosocomial pneumonia.

Rapid geographic spread of a methicillin-resistant Staphylococcus aureus strain.

In May 1993, an outbreak of methicillin-resistant Staphylococcus aureus (MRSA) was identified at our tertiary care teaching center. The epidemic MRSA strain was transmitted efficiently in the hospital environment. Subsequent investigations indicated that the strain had been introduced into western Canada by a patient who had recently been hospitalized for 3 months in the Punjab, India, and had been admitted to a hospital in rural British Columbia shortly after his arrival in Canada. Transfer of the patient to a hospital in Vancouver and subsequent transfer of a colonized patient contact to a hospital in Winnipeg, Manitoba, resulted in major outbreaks of MRSA at these two large tertiary care centers within 6 weeks of the arrival of the index case in Canada. Epidemiological typing of the S. aureus coagulase gene with use of a polymerase chain reaction method and pulsed-field gel electrophoresis documented clonality of this strain. These outbreaks again illustrate both the propensity of certain strains of S. aureus to produce epidemic disease, including rapid spread within the institutional setting, and the global nature of problems with antimicrobial resistance.

Molecular epidemiology of Legionella pneumophila infection at a Canadian tertiary care institution.

OBJECTIVE: To characterize the molecular epidemiology of Legionella species infection at one Canadian tertiary care centre. DESIGN: Twenty-eight clinical isolates and 12 environmental isolates obtained over a six-year period were analyzed by restriction fragment length polymorphism (rflp) of chromosomal dna. Isolates included 15 from 12 patients with hospital acquired illness and 13 from nine patients with community acquired infection. RESULTS: One nosocomial strain was Legionella micdadei and one community strain was Legionella pneumophila serotype 6; all others were L pneumophila serotype 1. rflp typing revealed one clone for all cases of a 1985 single-ward outbreak and five of six nonoutbreak L pneumophila nosocomial cases. An rflp pattern identical or highly related to that of the nosocomial clonal type was noted among nine of 12 L pneumophila serotype 1 community isolates. The remaining three isolates had two related rflp patterns distinct from the institutional strain. The nosocomial and community strains were isolated from multiple institutional water samples in the institution. For the environmental isolates, monoclonal antibody typing was more discriminating than rflp typing: seven monoclonal antibody subtypes were distinguished among 12 environmental isolates comprising three distinct rflp patterns. CONCLUSIONS: Despite multiple L pneumophila serotype 1 strains isolated in the authors' institutional water, a single clone of L pneumophila produced most disease. Community acquired disease was caused by a wider variety of strains.

Respiratory interaction after spinal anesthesia and sedation with midazolam.

The combined use of midazolam and spinal anesthesia is common in clinical practice. Despite the known potential for each to alter ventilation, the effect of their interaction has not been examined. Nineteen healthy volunteers were studied to assess the impact of intravenous midazolam (0.05 or 0.075 mg/kg), spinal anesthesia (T3-T8; mean level, T6), and their combination on resting ventilation and ventilatory responses to progressive hyperoxic hypercapnia. Resting ventilatory pattern was altered significantly by each condition. Midazolam caused a 29% decrease in resting tidal volume and a 24% decrease in mean inspiratory flow rate, while respiratory frequency increased by 14% and minute ventilation remained unchanged. By contrast, spinal anesthesia alone caused a 32% increase in tidal volume, a 24% increase in mean inspiratory flow rate, and a 13% increase in minute ventilation accompanied by a 14% decrease in respiratory frequency. The combination of midazolam and spinal anesthesia caused a significant decrease in minute ventilation (19%), tidal volume (28%), and mean inspiratory flow rate (27%), all of which were significantly more than the predicted sum of the individual interventions. Midazolam and spinal anesthesia each produced a significant decrease in hypercapnic ventilatory response slope, whereas their combination provoked no net change in hypercapnic ventilatory response slope. Interpretation of the hypercapnic ventilatory response data was complicated by shifts in the position of the ventilatory response curve, particularly under the spinal anesthesia condition. It is concluded that intravenous midazolam depresses resting ventilation, spinal anesthesia stimulates resting ventilation, and their combination has a modest synergistic effect of depressing resting ventilation.

Nosocomial pneumonia in a Canadian tertiary care center: a prospective surveillance study.

OBJECTIVE: To determine the contribution of etiologic agents, including Legionella pneumophila and respiratory viruses to nosocomial pneumonia at a tertiary care center. DESIGN: Prospective surveillance of nosocomial pneumonia with standardized laboratory investigations. SETTING: A 1,100-bed tertiary care center. PATIENTS: All adult inpatients. RESULTS: One hundred and thirty-five Nosocomial pneumonias (5.7/1,000 discharges) were identified. Four (3.0%) were L pneumophila serogroup 1 infections (0.17/1,000 discharges). Legionellosis occurred in non-high-risk patients, and three cases would not have been identified without active surveillance. Viral seroconversion was identified in seven (19%) of 36 cases with specimens available (0.59/1,000 discharges): five influenza B, one influenza A, and one respiratory syncytial virus. IgM serology was positive in one case each for Mycoplasma pneumoniae and Chlamydia species. No geographical clustering was observed for viral infections, and these would not have been identified without active surveillance. Mortality for all nosocomial pneumonia was 25%. Patient factors significantly associated with a poorer outcome included older age, underlying disease, low serum albumin, renal insufficiency, lower platelet count, endotracheal intubation, respiratory failure, bacteremia, and use of antacids. CONCLUSIONS: This prospective surveillance suggested that L pneumophila and viral agents were uncommon causes of nosocomial pneumonia at our institution during this surveillance period.

Age-related cognitive recovery after general anesthesia.

This study was designed to quantify the rate of mental recovery in elderly and young patients after general anesthesia for intraabdominal surgery (cholecystectomy). Forty patients (25-83 yr) were given four tests assessing neuropsychological function once preoperatively and on five occasions postoperatively. Two of the four neuropsychological tests showed impairment in scores in the elderly patients on the first postoperative day (Symbol Digit Modalities Test, P less than 0.004; The Trail Making Test, P less than 0.03). In addition, one of the tests (Symbol Digit Modalities Test) showed a deterioration in the younger patients (P less than 0.05). The changes that did occur in these tests on the first postoperative day reverted to baseline levels thereafter. There were no significant changes in the remaining two tests, the Mini Mental State Test or the Digit Span Test, at any time in either group. We conclude that postoperative mental deterioration is no greater in elderly than in young patients.

A randomized comparison of midazolam and diazepam injectable emulsion in cataract surgery.

The purpose of this study was to compare the psychomotor recovery of patients sedated with either midazolam or Diazemuls using the digit symbol substitution test and the Trieger test. Sixty patients were allocated in random double-blind fashion to receive either midazolam or diazepam in oil emulsion (Diazemuls) as intravenous sedation for cataract surgery. Both groups received fentanyl 0.5 micrograms.kg-1 IV. Tests of cognition were performed by the patients prior to sedation and at half-hourly intervals for three hours after cataract surgery. In a dose ratio of 1:4, midazolam was found to produce better sedation but more prolonged recovery than Diazemuls. Anterograde amnesia was comparable in the two groups, while more patients in the Diazemuls group developed episodes of apnoea and venous irritation.