Effects of niacin and betaine on bovine mammary and uterine cells exposed to thermal shock in vitro.

The objective of this study was to investigate the direct effects of feed supplements niacin and betaine on the heat shock responses of in vitro cultured cells derived from bovine mammary and uterine tissues. First, we determined the mRNA expression profiles of the niacin receptor (GPR109A) in bovine tissues (liver, skin, uterus, udder, and ovary) and in cells derived from bovine mammary epithelium (mammary alveolar cells, MAC-T; bovine mammary epithelial cells, BMEC) and endometrium (bovine endometrial cells, BEND). We found that GPR109A was distributed in all examined tissues and cells, and the highest expression was in cells from skin and udder. Second, we evaluated the effects of niacin treatment on the mRNA abundance of heat shock proteins 70 and 27 (HSP70 and HSP27) in MAC-T, BMEC, and BEND under thermoneutral conditions and heat stress, and whether these effects were associated with alterations in the mRNA expression of prostaglandin E2 synthesis-related genes, including cyclooxygenase 1 and 2 (COX-1 and COX-2) and microsomal prostaglandin E synthase 1 and 2 (mPGES-1 and mPGES-2). Quantitative PCR data indicated that niacin suppressed HSP70 mRNA expression in BMEC and both HSP70 and HSP27 in BEND under thermoneutral conditions. Only COX-2 expression was downregulated by niacin in BMEC; other prostaglandin E2 synthesis-related genes stayed unaltered in BMEC and BEND. The mRNA abundance of HSP70, COX-1, COX-2, and mPGES-1 were elevated in niacin-treated MAC-T. During heat stress, niacin increased mRNA levels of HSP70 and HSP27 in MAC-T and HSP27 in BEND, but decreased HSP70 in BMEC. Although mPGES-2 was stimulated by niacin in BEND, the mRNA expression of prostaglandin E2 synthesis-related genes were consistent with neither HSP70 nor HSP27 expression patterns in niacin-treated BMEC and MAC-T. These data suggest that the effects of niacin on heat shock protein expression and prostaglandin E2 synthesis were not well coupled in these cells. Finally, we tested the effects of betaine treatment on viability and apoptosis in BMEC. Compared with control cultures, viability was higher in betaine-treated cells at 8 h under thermoneutral conditions and at 16 h in heat stress, and apoptotic rates were lower at 8 h. Our data support a dual role for niacin in regulating heat shock protein expression in normal and heat-shocked cells derived from mammary and uterine tissues, and positive effects of betaine in regulating mammary cell viability during heat stress.

Evaluation of dietary betaine in lactating Holstein cows subjected to heat stress.

Betaine (BET), a natural, organic osmolyte, improves cellular efficiency by acting as a chaperone, refolding denatured proteins. To test if dietary BET reduced the effect of heat stress (HS) in lactating dairy cows, multiparous, lactating Holstein cows (n=24) were blocked by days in milk (101.4±8.6 d) and randomly assigned to 1 of 3 daily intakes of dietary BET: the control (CON) group received no BET, mid intake (MID) received 57mg of BET/kg of body weight, and high dose (HI) received 114mg of BET/kg of body weight. Cows were fed twice daily and BET was top-dressed at each feeding. Cows were milked 2 times/d and milk samples were taken daily for analysis. Milk components, yield, feed intake, and water intake records were taken daily. Rectal temperature and respiration rate were taken 3 times/d at 0600, 1400, and 1800h. Cows were housed in environmentally controlled rooms and were allowed acclimation for 7d at thermoneutral (TN) conditions with a mean temperature-humidity index of 56.6. Cows were then exposed to 7d of TN followed by 7d of HS represented by a temperature-humidity index of 71.5 for 14d. This was followed by a recovery period of 3d at TN. Dietary BET increased milk yield during the TN period. No differences were found between BET and CON in total milk production or milk composition during HS. The increase in water intake during HS was not as great for cows fed BET compared with controls. The cows on CON diets had higher p.m. respiration rate than both MID and HI BET during HS, but lower rectal temperature compared with BET. No difference was found in serum glucose during TN, but cows given HI had elevated glucose levels during HS compared with CON. No differences were found in serum insulin levels between CON and BET but an intake by environment interaction was present with insulin increasing in HI-treated lactating dairy cows during HS. The heat shock response [heat shock protein (HSP) 27 and HSP70] was upregulated in bovine mammary epithelial cells in vitro. Blood leukocyte HSP27 was downregulated at the HI dose under TN conditions and HSP70 was upregulated at the HI dose and this effect was increased by HS. No effect was seen with the MID dose with HSP27 or HSP70. The lack of effect of BET at MID may be associated with uptake across the gut. We conclude that BET increased milk production under TN conditions and was associated with reduced feed and water intake and slightly increased body temperatures during HS of cows fed BET. The effect of BET on milk production was lost during HS with HI BET, whereas serum glucose levels increased during HS.

Effectiveness of patient safety training in equipping medical students to recognise safety hazards and propose robust interventions.

OBJECTIVES: In an effort to improve patient safety attitudes and skills among third-year medical students, two patient safety training sessions were added to their curriculum, complementing a previously implemented second-year curriculum on quality improvement, patient safety and teamwork. METHODS: Safety attitudes and skills were assessed before and after students completed the medicine clerkship training and were compared with historical controls. Students identified and reported on observed safety events, with their reports matched to event type and harm score with contemporaneous safety reports from University of Missouri's Patient Safety Network (PSN). Comparisons were assessed by five internal safety experts using criteria for report submission "worthiness", blame tone, target of blame and presence/strength of proposed solutions. RESULTS: Students completing the third-year safety booster conferences expressed statistically higher comfort levels with identifying the cause of an error than did the student control group (p<0.05). Medical students proposed safety interventions that were more robust than those suggested by event reporters regarding similar events within our health system (p<0.0001). The worthiness and blame tone of medical student reports were not statistically different than event reports in PSN. CONCLUSIONS: Completion of two 1-h patient safety booster conferences in the third year of medical school led to increased student comfort in safety event analysis. Students documented stronger resolution robustness scores, suggesting similar training should be offered to PSN reporters. Medical students represent an underutilised resource for identifying and proposing solutions for patient safety issues.

The natural history of recovery for the healthcare provider "second victim" after adverse patient events.

BACKGROUND: When patients experience unexpected events, some health professionals become "second victims". These care givers feel as though they have failed the patient, second guessing clinical skills, knowledge base and career choice. Although some information exists, a complete understanding of this phenomenon is essential to design and test supportive interventions that achieve a healthy recovery. METHODS: The purpose of this article is to report interview findings with 31 second victims. After institutional review board approval, second victim volunteers representing different professional groups were solicited for private, hour-long interviews. The semistructured interview covered demographics, participant recount of event, symptoms experienced and recommendations for improving institutional support. After interviews, transcripts were analyzed independently for themes, followed by group deliberation and reflective use with current victims. RESULTS: Participants experienced various symptoms that did not differ by sex or professional group. Our analysis identified six stages that delineate the natural history of the second victim phenomenon. These are (1) chaos and accident response, (2) intrusive reflections, (3) restoring personal integrity, (4) enduring the inquisition, (5) obtaining emotional first aid and (6) moving on. We defined the characteristics and typical questions second victims are desperate to have answered during these stages. Several reported that involvement in improvement work or patient safety advocacy helped them to once again enjoy their work. CONCLUSIONS: We now believe the post-event trajectory is largely predictable. Institutional programs could be developed to successfully screen at-risk professionals immediately after an event, and appropriate support could be deployed to expedite recovery and mitigate adverse career outcomes.

Educational quality improvement report: outcomes from a revised morbidity and mortality format that emphasised patient safety.

PROBLEM: Although morbidity and mortality conferences (MMCs) are meant to promote quality care through careful analysis of adverse events, focus on individual actions or the fear of incrimination may interfere with identification of system issues contributing to the adverse outcomes. DESIGN: Participant attitudes before and after the intervention towards patient safety and conference redesign were assessed using an attitudinal survey. A list of contributing factors, recommended solutions and targeted system improvements was maintained with ongoing progress recorded. SETTING: Department of Internal Medicine training programme at University of Missouri-Columbia. PARTICIPANTS: Residents and fellows from the above residency programme. EDUCATIONAL OBJECTIVES: (1) Distinguish between culture of blame/shame and patient safety culture, (2) identify gaps in quality contributing to adverse outcomes (3) identify strategies to close gaps and (4) participate in root cause analysis, demonstrating an ability to review an adverse event and recommend an action plan. STRATEGIES FOR CHANGE: An interdisciplinary team modified the internal medicine MMC to emphasise a better understanding of patient safety principles and system-based practice interventions. For each adverse event analysed, root causes were identified, followed by discussion of system interventions that might prevent future such events. KEY MEASURES FOR IMPROVEMENT: (1) Attitudes of residents and fellows regarding patient safety, as measured on a 20-item, five-point ordinal scale survey, (2) system improvements generated from the patient safety MMC (PSMMC) and (3) attendance at PSMMC. EFFECTS OF CHANGE: Clinical outcomes: 121 system improvement recommendations were made and 39 were pursued on the basis of likelihood of achieving high impact changes. 23 improvements were implemented, 11 were partially implemented or in progress, and 5 were abandoned due to impracticality or redundancy. Educational outcomes: 58 residents and fellows completed surveys before and after modification of conference format. 6/20 survey items showed substantial change with four of these changes occurring in the desired direction. Eleven of the remaining 14 responses changed in the desired direction. Average MMC attendance increased from 41+/-8 to 50+/-10 participants (p<0.03). LESSONS LEARNT: The new PSMMC initiated multiple improvements in the quality of patient care without sacrificing attendance or attitudes of the residents or fellows. The new PSMMC promotes opportunities for participants to improve quality of patient care in a safe and nurturing environment.

Use of the forced oscillating airflow technique to measure the resistance of the equine upper airway: effects of laryngoventriculectomy and laryngoplasty.

Investigations were carried out to determine whether measurements of total respiratory resistance (TRR) made in resting animals could detect changes due to laryngeal hemiplegia. Control values of TRR were obtained in eight ponies and in six of these the measurements were repeated after division of the left recurrent laryngeal nerve in the mid-cervical region; two were retained as controls. A further set of measurements were made before two of the operated animals were subjected to left laryngoventriculectomy (Hobday operation). A laryngoplasty ('tie-back' operation) was performed on another two animals. Measurements of TRR were made at three-monthly intervals on all eight ponies for the next two years. Endoscopic examination of the larynx was carried out at the time of the measurements. All ponies showed a marked, but regular, variation in TRR over the two-year observation period. Nerve section was shown to be associated with an increase in TRR in five ponies. The Hobday operation decreased TRR in one animal and had no marked effect in the second. The tie-back operation was associated with a decreased TRR in one pony and an increase in the second. Autopsies were carried out on all six operated ponies and measurements of TRR and lower respiratory resistance (LRR) were made immediately before the animals were killed. Evidence of regeneration of the recurrent laryngeal nerve was seen in one of the ponies which underwent the Hobday operation. Histological evidence of regeneration was found in another pony.(ABSTRACT TRUNCATED AT 250 WORDS)

A clinical trial of three anaesthetic regimens for the castration of ponies.

After premedication with intravenous xylazine 30 ponies were anaesthetised for castration under field conditions with intravenous ketamine, thiopentone or methohexitone. The duration of anaesthesia was adequate for surgery and the times taken to stand were similar in each group. The recovery of the ponies after ketamine was quieter than after either of the barbiturates and this may be an advantage when skilled assistance is lacking. However, all the anaesthetics appeared to be suitable for performing minor surgery in the field.

Clinical anaesthesia in the horse: comparison of enflurane and halothane.

Anaesthesia was induced in 24 horses with xylazine and ketamine and maintained with halothane (12 cases) or enflurane (12 cases) in oxygen. Pulse rate, arterial blood pressure, arterial blood gas values, respiratory rate and tidal volume were measured at regular intervals during anaesthesia. Serial venous blood samples were taken for assay of glucose, urea, haemoglobin, packed cell volume, gamma glutamyl transpeptidase, aspartate aminotransferase, alanine aminotransferase and creatine kinase. Operating conditions and the horses' behaviour in the recovery period were also recorded. In the case of the group of horses receiving enflurane, difficulty was experienced maintaining anaesthesia deep enough for surgery. This group also displayed greater respiratory depression. There were no significant differences between arterial blood pressure values, or any of the haematological or biochemical parameters recorded in each group. Recovery from anaesthesia was significantly faster in horses receiving enflurane but less smooth. It was concluded that, although enflurane appeared to be safe in the horse, the respiratory depression and the unpleasant recovery did not make it a desirable alternative to halothane.

Clinical trial of xylazine with ketamine in equine anaesthesia.

One hundred anaesthetics were administered in a clinical trial to 95 equine patients, ranging in age from nine months to 19 years and in weight from 140 to 1270 kg, undergoing a variety of surgical procedures. Acepromazine maleate premedication (0.01 to 0.03 mg per kg intramuscularly) was given to seven animals, the remainder were not premedicated. Xylazine (1.1 mg per kg) was injected intravenously over a two minute period and after a pause of two minutes ketamine (2.2 mg per kg) was injected rapidly by the same route. For 30 procedures no other anaesthetic was given but in 59 cases anaesthesia was prolonged with halothane-oxygen while in 11 additional intravenous agents were administered. Recumbency followed one-and-a-half to two minutes after completion of the ketamine injection and limb movements occurring immediately after the animal lay down gradually subsided over the next 30 to 60 seconds. On 26 occasions when no other agent was given satisfactory operating conditions were produced for a mean (+/- sd) of 20 +/- 7 minutes and on four occasions when absence of complete muscle relaxation was observed surgery was still possible. When no other agent was given the onset of recovery was abrupt but recovery was always extremely quiet; the animals stood 33 +/- 10 minutes after induction of anaesthesia and showed a remarkable absence of ataxia. A similar recovery was seen in the 56 animals receiving halothane-oxygen and all stood 28 +/- 14 minutes after disconnection from the anaesthetic system. Heart block was observed during induction of anaesthesia bu otherwise cardiovascular and respiratory parameters were well maintained. It was concluded that the xylazine-ketamine combination had advantages over other current techniques of inducing anaesthesia in horses.

Papers and articles measurement of central venous pressure in horses.

Central venous pressure measurements were made in 74 horses and ponies free from clinical evidence of cardiopulmonary disease. Using the sternal manubrium as the zero reference point, the mean value obtained was 12 cm H2O (S.D. +/- 6). There was a significant correlation with body weight (r=0.6, p less than 0.001) but there was none with age, sex, breed or type. During halothane anaesthesia, using the same reference point, the mean value was 24.5 cm H2O (S.D. +/- 6) in 28 animals in right lateral recumbency, 29 cm H2O (S.D. +/- 8) in 17 animals in left lateral recumbency and -6 cm H20 (S.D. +/- 4) IN 27 supine animals. The use of the sternal manubrium as zero reference point did not allow comparison of values in standing and recumbent animals and it was considered that serial measurements were of more value than isolated determinations in assessing the circulatory state of an animal.

Further studies of porcine malignant hyperthermia.

A non-lethal procedure for identifying pigs apt to develop malignant hyperthermia is described. Susceptible animals were exposed to a variety of anaesthetic and other agents and it was shown that thiopentone sodium and CT 1341 (Glaxo) afforded a measure of protection against the development of the syndrome. Pretreatment with procaine did not prevent the onset of the condition and the administration of procaine when muscle rigidity was present failed to prevent a fatal outcome. The syndrome was induced in susceptible animals by halothane, chloroform, and a combination of halothane with suxamethonium. The effects of cyclopropane in susceptible pigs could not be predicted, and other tests showed that suxamethonium alone would not induce muscle contracture. Pretreatment with lignocaine failed to prevent induction of the syndrome by halothane.We believe that the porcine syndrome may result from more than one defect and that in one particular type the most effective treatment is immediate cooling coupled with the administration of sodium bicarbonate.