Buprenorphine differentially alters breathing among four congenic mouse lines as a function of dose, sex, and leptin status.

The opioid buprenorphine alters breathing and the cytokine leptin stimulates breathing. Obesity increases the risk for respiratory disorders and can lead to leptin resistance. This study tested the hypothesis that buprenorphine causes dose-dependent changes in breathing that vary as a function of obesity, leptin status, and sex. Breathing measures were acquired from four congenic mouse lines: female and male wild type C57BL/6J (B6) mice, obese db/db and ob/ob mice with leptin dysfunction, and male B6 mice with diet-induced obesity. Mice were injected intraperitoneally with saline (control) and five doses of buprenorphine (0.1, 0.3, 1.0, 3.0, 10 mg/kg). Buprenorphine caused dose-dependent decreases in respiratory frequency while increasing tidal volume, minute ventilation, and respiratory duty cycle. The effects of buprenorphine varied significantly with leptin status and sex. Buprenorphine decreased minute ventilation variability in all mice. The present findings highlight leptin status as an important modulator of respiration and encourage future studies aiming to elucidate the mechanisms through which leptin status alters breathing.

Analysis of Medical Error Contributing to Missed Acute Myeloid Leukemia Diagnosis.

Hospitals and physicians attempt to minimize medical error by putting systems checks and balances in place at multiple levels. The effectiveness of these hospital-specific strategies to thwart error is called into question, as medical error remains a leading cause of death in the United States. This case report outlines the course of a 62-year-old man with a history of non-small cell lung cancer and right tongue squamous cell carcinoma, who had been admitted to an outside hospital for possible pneumonia. On initial presentation, the patient was pancytopenic with an absolute neutrophil count of 598. As his counts continued to downtrend and his conditioned worsened, oncology saw the patient and attributed the pancytopenia to "transient myelosuppression from pneumonia". This statement impacted the trajectory of the patient's care, delaying his ultimate diagnosis and treatment for acute myeloid leukemia. This case emphasizes the power of framing and anchoring biases in medical decision making and the need to evolve practice models from the current method of closed-door inquiry towards a more inclusive system of error reporting and analysis.

Buprenorphine Depresses Respiratory Variability in Obese Mice with Altered Leptin Signaling.

BACKGROUND: Opiate-induced respiratory depression is sexually dimorphic and associated with increased risk among the obese. The mechanisms underlying these associations are unknown. The present study evaluated the two-tailed hypothesis that sex, leptin status, and obesity modulate buprenorphine-induced changes in breathing. METHODS: Mice (n = 40 male and 40 female) comprising four congenic lines that differ in leptin signaling and body weight were injected with saline and buprenorphine (0.3 mg/kg). Whole-body plethysmography was used to quantify the effects on minute ventilation. The data were evaluated using three-way analysis of variance, regression, and Poincaré analyses. RESULTS: Relative to B6 mice with normal leptin, buprenorphine decreased minute ventilation in mice with diet-induced obesity (37.2%; P < 0.0001), ob/ob mice that lack leptin (62.6%; P < 0.0001), and db/db mice with dysfunctional leptin receptors (65.9%; P < 0.0001). Poincaré analyses showed that buprenorphine caused a significant (P < 0.0001) collapse in minute ventilation variability that was greatest in mice with leptin dysfunction. There was no significant effect of sex or body weight on minute ventilation. CONCLUSIONS: The results support the interpretation that leptin status but not body weight or sex contributed to the buprenorphine-induced decrease in minute ventilation. Poincaré plots illustrate that the buprenorphine-induced decrease in minute ventilation variability was greatest in mice with impaired leptin signaling. This is relevant because normal respiratory variability is essential for martialing a compensatory response to ventilatory challenges imposed by disease, obesity, and surgical stress.