The Social Epistemology of Clinical Placebos.

Many extant theories of placebo focus on their causal structure wherein placebo effects are those that originate from select features of the therapy (e.g., client expectations or "incidental" features like size and shape). Although such accounts can distinguish placebos from standard medical treatments, they cannot distinguish placebos from everyday occurrences, for example, when positive feedback improves our performance on a task. Providing a social-epistemological account of a treatment context can rule out such occurrences, and furthermore reveal a new way to distinguish clinical placebos from standard medical treatments.

Patient autonomy and withholding information.

Disclosure in clinical practice is aimed at promoting patient autonomy, usually culminating in patient choice (e.g., to consent to an operation or not, or between different medications). In medical ethics, there is an implicit background assumption that knowing more about (X) automatically translates to greater, or more genuine, autonomy with respect to one's choices involving (X). I challenge this assumption by arguing that in rare cases, withholding information can promote a patient's autonomy (understood as the capacity for rational choice in alignment with one's values and goals).

Creation of a chemotherapy-induced nausea/vomiting dashboard to improve outcomes for pediatric cancer patients.

PURPOSE: Two of the most common acute side effects of chemotherapy are nausea and vomiting. Nausea and vomiting impact quality of life, nutritional status, and ability to tolerate further chemotherapy. Parents of pediatric oncology patients rank nausea as one of the most bothersome treatment-related symptoms. METHODS: Utilizing Quality Improvement methodology, we developed a dashboard interface to facilitate extraction of data from the electronic medical record (EMR), which is presented via a visual display that summarizes the type of chemotherapy and antiemetic medications, use of as needed medications, and number of episodes of emesis. RESULTS: This dashboard interface allows for rapid and efficient identification of patients whose antiemetic regimen is mismatched for the emetogenicity of ordered chemotherapy, thus providing a timely opportunity to modify the antiemetic regimen based on published guidelines before administration of chemotherapy drugs. It also allows measurement of the effectiveness of the antiemetic regimen in terms of the number of break through emesis and the need for as needed medications. CONCLUSIONS: A novel CINV dashboard was created, which visually conveys complex information about antiemetics, chemotherapy emetogenicity, as needed medications, and breakthrough vomiting for inpatient pediatric oncology patients.

Successful management of sirolimus toxicity in a hematopoietic stem cell transplant patient using automated red blood cell exchange.

BACKGROUND: Sirolimus is an immunosuppressive agent used in organ rejection prophylaxis in solid-organ transplantation, graft-vs-host disease prophylaxis in hematopoietic stem cell transplantation, and as an immune modulator for patients with lymphangioleiomyomatosis and vascular malformations. Sirolimus has a narrow therapeutic index with potential severe side effects, including hypertension, hepatotoxicity, nephrotoxicity, and neurotoxicity. CASE REPORT: We report a case of a 19-year-old woman with severe sickle cell disease who underwent a matched unrelated hematopoietic stem cell transplantation, whose course was complicated by sirolimus toxicity. This case was challenging because sirolimus has no specific antidote, is largely bound to red blood cells (RBCs), has a high distribution volume, and cannot be removed by dialysis or plasmapheresis. RESULT: Due to the concern for toxicity, we looked into possibilities for rapid sirolimus clearance using automated RBC exchange. The treatment was effective in decreasing blood sirolimus levels within the therapeutic ranges. CONCLUSION: The use of RBC exchange is potentially safe and effective in the management of a case of sirolimus toxicity.

Dystrobrevins in muscle and non-muscle tissues.

The alpha- and beta-dystrobrevins belong to the family of dystrophin-related and dystrophin-associated proteins. As constituents of the dystrophin-associated protein complex, alpha-dystrobrevin was believed to have a role predominantly in muscles and beta-dystrobrevin in non-muscle tissues. Recent reports described novel localisations and molecular characteristics of alpha-dystrobrevin isoforms in non-muscle tissues (developing and adult). While single and double knockout studies have revealed distinct functions of dystrobrevin in some tissues, these also suggested a strong compensatory mechanism, where dystrobrevins displaying overlapping tissue expression pattern and structure/function similarity can substitute each other. No human disease has been unequivocally associated within mutations of dystrobrevin genes. However, some significant exceptions to these overlapping expression patterns, mainly in the brain, suggest that dystrobrevin mutations might underlie some specific motor, behavioural or cognitive defects. Dystrobrevin binding partner DTNBP1 (dysbindin) is a probable susceptibility gene for schizophrenia and bipolar affective disorder in some populations. As dysbindin abnormality is linked to Hermansky-Pudlak syndrome, dystrobrevins and/or their binding partners may also be required for proper function of other non-muscle tissues.

The influence of the rate of pH decline on the rate of ageing for pork. I: interaction with method of suspension.

The influence of the rate of pH decline post slaughter on the rate of ageing of pork was investigated. The rate of pH decline on 24 finisher pigs was manipulated by altering the method of stunning (carbon dioxide or electrical head to heart) and by the use of electrical stimulation (none or low voltage electrical stimulation (LVES) at 4 min post slaughter). To investigate the effect of pH decline rate on ageing rate independently of the effect on possible muscle shortening, sides were suspended by either the pelvis (to minimize shortening) or conventionally by the Achilles tendon. The data indicated that the rate of pH decline did not influence the rate of ageing but the use of LVES did improve tenderness at 1, 2 and 10 days post slaughter due to the prevention of muscle shortening. Electrical stunning improved tenderness at 1 and 2 days post-slaughter but had a detrimental effect on drip loss. Pelvic suspension improved tenderness at rigor, 1, 2 and 6 days post slaughter due to prevention of muscle shortening. The conditions employed however were not severe enough to induce protein denaturation.

The influence of the rate of pH decline on the rate of ageing for pork. II: Interaction with chilling temperature.

The influence of the rate of pH decline post slaughter on the rate of ageing of pork m. longissimus thoracis et lomborum was investigated. The rate of pH decline on 24 finisher pigs was manipulated by altering the method of stunning (carbon dioxide or electrical head to heart) and by the use of electrical stimulation (none or low voltage electrical stimulation (LVES) at 4 min post slaughter for either 15 s or 60 s). The rate of temperature decline was altered by chilling at 2 or 14 °C until rigor. The pH and temperature decline rates generated were designed to induce cold shortening at one extreme and protein denaturation at the other. The research results showed that the rate of pH decline was increased by electrical stimulation which in turn reduced cold shortening and improved tenderness. Chilling at 14 °C reduced the time to reach rigor by 1.3 h and resulted in a faster aging rate as indicated by a larger percentage change in WBSF from rigor to 4 days postmortem relative to carcases chilled at 2 °C. The greater tenderising effect appeared to be due to a combination of prevention of cold shortening and increased proteolysis. However, chilling slowly at 14 °C or the use of LVES for 60 s or any combination of these treatments did not induce protein denaturation.

Tenderness, ageing rate and meat quality of pork M. longissimus thoracis et lumborum after accelerated boning.

The impact of accelerated boning on tenderness, ageing rate and meat quality of pork longissimus muscle was investigated. Accelerated boning of eight Large White×Landrace pork carcasses at 30 min post-mortem followed by chilling at 0°C resulted in tougher pork with higher drip loss and a darker surface lightness relative to conventional boning at 24 h post-mortem. The increased toughness was still observed at 4 days post-mortem, a time by which 80% of ageing generally had occurred as seen in experiment 2. The increased toughness could be attributed to cold shortening and a reduction in proteolysis.

Effect of calcium infusion on tenderness and ageing rate of pork m. longissimus thoracis et lumborum after accelerated boning.

The effect of calcium chloride infusion at either 0.5 or 6 h post slaughter on tenderness, ageing rate and meat quality of pork longissimus muscle that had been boned at rigor or had undergone accelerated processing and conditioning at either 0 °C or 14 °C was investigated. The time of calcium infusion had no effect on the initial WBSF values or the aging rate. However, calcium infusion overall resulted in lower WBSF initially (1-day post-mortem) and also after 6 days ageing at 2 °C regardless of the processing procedures used. Calcium infusion did not, however, increase the ageing rate compared to comparable treatments that had not been calcium infused. Based on this observation and the myofibrillar fragmentation index results, it was concluded that the increased tenderness due to calcium infusion was not due to increased proteolysis as has been previously postulated, but was due to either a direct effect of calcium on tenderness, or an indirect effect of calcium via increased post-mortem glycolysis and pH decline rate resulting in reduced cold shortening. Calcium infusion had detrimental effects on drip loss and meat colour.

Tenderness of pork m. longissimus thoracis et lumborum after accelerated boning. Part I. Effect of temperature conditioning.

This research investigated the effect on tenderness and meat quality of temperature conditioning at 0, 7, 14 or 21 °C of pork longissimus muscle after accelerated boning (removal from the carcass within 30 min post slaughter). The conditioning temperature had no effect (P>0.05) on tenderness at the end of the conditioning period (i.e. at the onset of rigor) but had a significant effect (P<0.05) after the muscles were aged for four days at 2 °C. After aging, the muscles conditioned at 14 °C were more tender than muscles conditioned at the other three temperatures; the muscles conditioned at 0 °C were tougher than the muscles conditioned at the higher three temperatures. Conditioning at 14 °C produced muscles that had lighter surface colour and lower drip loss due to prevention of cold toughening which occurred at lower temperatures or protein denaturation at the higher temperatures.

Tenderness of pork m. longissimus thoracis et lumborum after accelerated boning. Part II. Effect of post-slaughter ageing.

This research investigated the effect of ageing time (0-10 days) at 2 °C on tenderness of pork longissimus muscle after either rigor boning (RB) or accelerated boning (removal from carcass within 30 min post slaughter) and temperature conditioning at either 0 or 14 °C. Ageing occurred most rapidly in muscles conditioned at 14 °C- maximum tenderization occurred by 4 days post-mortem. RB muscles and muscles conditioned at 0 °C aged more slowly and took 8 and 10 days, respectively, to reach a comparable level of tenderness. Temperature conditioning at 14 °C, produced muscles which had lower drip loss and lighter surface colour.