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AbstractContextEvery year, approximately 0.4 million women suffer from endometrial cancer (EC) worldwide and it has become the most common gynecological malignancy. Almost 66% of EC cases are diagnosed at an early stage and can be cured by performing surgery while those at an advanced stage turns out to be fatal. Biomarkers of endometrial cancer would be very valuable for screening of women who are at high risk and in detecting the chance of recurrence of disease.ObjectiveThe current article has reviewed studies published on expression of biomarkers and susceptibility to EC.MethodsGoogle Scholar and PubMed were used as searching platforms and we have majorly considered the literature from last 10 years.ResultsPotential biomarkers of EC identified from various studies were summarised.

Antimicrobial resistance [AMR] has emerged as a global and national priority and establishing an effective surveillance system for antimicrobial resistance is an essential prerequisite for generating evidence for informed policymaking at both national and state levels.

Recent studies have indicated a significant decline in the population of the house sparrow (Passer domesticusL.) at the global level. In India also, the house sparrow population is being drastically decreased. Considering the issue, an attempt has been made to monitor the current status of house sparrows across Dehradun City of Uttarakhand from 2017 to 2019. The line transect method was used for bird surveys in the three habitats (high-density urban area, low-density urban area, and suburban area). The results showed that the population of house sparrows was significantly higher in the suburban area (84.19 ± 8.05) as compared to those in high-density (12.75 ± 2.02) and low-density (42.97 ± 4.74) urban areas. Similarly, the number of active nests was also found higher in a suburban area as compared to other areas. Additionally, a total of 87 co-occurring avian species were observed in the study area with maximum avian diversity reported in low-density (H = 2.85) followed by suburban (H = 2.67) and high-density urban areas (H = 2.12) respectively. This study suggested that the regular monitoring of house sparrows and co-occurring avian species is important to understand the population trend of the house sparrow in the study area.

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The preceding papers in this Series have outlined how underuse and overuse of health-care services occur within a complex system of health-care production, with a multiplicity of causes. Because poor care is ubiquitous and has considerable consequences for the health and wellbeing of billions of people around the world, remedying this problem is a morally and politically urgent task. Universal health coverage is a key step towards achieving the right care. Therefore, full consideration of potential levers of change must include an upstream perspective—ie, an understanding of the system-level factors that drive overuse and underuse, as well as the various incentives at work during a clinical encounter. One example of a system-level factor is the allocation of resources (eg, hospital beds and clinicians) to meet the needs of a local population to minimise underuse or overuse. Another example is priority setting using tools such as health technology assessment to guide the optimum diffusion of safe, effective, and cost-effective health-care services. In this Series paper we investigate a range of levers for eliminating medical underuse and overuse. Some levers could operate effectively (and be politically viable) across many different health and political systems (eg, increase patient activation with decision support) whereas other levers must be tailored to local contexts (eg, basing coverage decisions on a particular cost-effectiveness ratio). Ideally, policies must move beyond the purely incremental; that is, policies that merely tinker at the policy edges after underuse or overuse arises. In this regard, efforts to increase public awareness, mobilisation, and empowerment hold promise as universal methods to reset all other contexts and thereby enhance all other efforts to promote the right care.

Overuse, which is defined as the provision of medical services that are more likely to cause harm than good, is a pervasive problem. Direct measurement of overuse through documentation of delivery of inappropriate services is challenging given the difficulty of defining appropriate care for patients with individual preferences and needs; overuse can also be measured indirectly through examination of unwarranted geographical variations in prevalence of procedures and care intensity. Despite the challenges, the high prevalence of overuse is well documented in high-income countries across a wide range of services and is increasingly recognised in low-income countries. Overuse of unneeded services can harm patients physically and psychologically, and can harm health systems by wasting resources and deflecting investments in both public health and social spending, which is known to contribute to health. Although harms from overuse have not been well quantified and trends have not been well described, overuse is likely to be increasing worldwide.

Underuse—the failure to use effective and affordable medical interventions—is common and responsible for substantial suffering, disability, and loss of life worldwide. Underuse occurs at every point along the treatment continuum, from populations lacking access to health care to inadequate supply of medical resources and labour, slow or partial uptake of innovations, and patients not accessing or declining them. The extent of underuse for different interventions varies by country, and is documented in countries of high, middle, and low-income, and across different types of health-care systems, payment models, and health services. Most research into underuse has focused on measuring solutions to the problem, with considerably less attention paid to its global prevalence or its consequences for patients and populations. Although focused effort and resources can overcome specific underuse problems, comparatively little is spent on work to better understand and overcome the barriers to improved uptake of effective interventions, and methods to make them affordable.

The global ubiquity of overuse and underuse of health-care resources and the gravity of resulting harms necessitate an investigation of drivers to inform potential solutions. We describe the network of influences that contribute to poor care and suggest that it is driven by factors that fall into three domains: money and finance; knowledge, bias, and uncertainty; and power and human relationships. In each domain the drivers operate at the global, national, regional, and individual level, and are modulated by the specific contexts within which they act. We discuss in detail drivers of poor care in each domain.

Background: Diallyl disulfide (DADS), a principal organosulfur component of garlic, is known for its medicinal properties including anti-cancer activity. Prior studies have demonstrated that the compounds containing Diallyl disulfide moieties exhibited diverse therapeutic potential with promising biological activities. In the present study, we have investigated the in vitroanticancer activity of Diallyl disulfide derivatives (5a–5 l and 7e-7m) against human cancer cell lines. Methods: The effect of DADS analogs on different cancer cell lines was measured through MTT assay. Cell cycle progression, apoptosis, DNA fragmentation and levels of ROS were analyzed through FACS and confocal imaging. Results: Bis[3-(3-fluorophenyl)prop-2-ene]disulfide (compound 5b) was the most potent compound among the tested DADS derivatives. FACS analysis revealed that increase in ROS generation by compound 5b was accompanied by cell cycle arrest in the G2/M phase and apoptosis in MIA PaCa-2 cells. Further, the apoptosis was confirmed by TUNEL assay. Western blot analysis showed that compound 5b induces G2/M phase arrest viaROS mediated DNA-damage, which in turn, induces phosphorylation of Chk1/Cdc25c/Cdc2 pathway. Furthermore, altered levels of ROS triggers intrinsic apoptotic cascade, as evidenced by dissipated mitochondrial membrane potential (?), decrease in Bcl-2/Bax ratio, cytochrome c release and cleavage of procaspase-3. Scavenging of ROS by antioxidant N-acetyl-cysteine (NAC) reversed the compound 5b induced augmented intracellular ROS levels and cell death. Conclusion: Taken together, the anti-proliferative effects of compound 5b were attributed to intracellular ROS accumulation, which in turn, triggers apoptosis by mediating DNA damage-induced G2/M phase arrest and evoking mitochondrial apoptotic pathway in MIA PaCa-2 cells.

High intra-abdominal pressure and reverse Trendelenburg position during laparoscopic cholecystectomy (LC) are risk factors for venous stasis in lower extremity. Lower limb venous stasis is one of the major pathophysiological elements involved in the development of peri-operative deep vein thrombosis. Low pressure pneumoperitoneum (7–10 mmHg) has been recommended in patients with limited cardiac, pulmonary or renal reserve. The purpose of this study was to observe the effect of various pneumoperitoneum pressures on femoral vein (FV) hemodynamics during LC. A total of 50 patients undergoing elective LC were enrolled and they were prospectively randomized into two groups containing 25 patients each. In group A high pressure pneumoperitoneum (14 mmHg) and in group B low pressure pneumoperitoneum (8 mmHg) was maintained. Comparison of pre-operative and post-operative coagulation profile was done. Preoperative and intraoperative change in femoral vein diameter (FVD) (AP and LAT), cross-sectional area (CSA) and peak systolic flow (PSF) during varying pneumoperitoneum pressure was recorded in FV by ultrasound Doppler. First measurement (pre-operative) was carried out just after the induction of anesthesia before creation of pneumoperitoneum and second measurement (intra-operative) was taken just before completion of surgery with pneumoperitoneum maintained. Changes in coagulation parameters were less significant at low pressure pneumoperitoneum. There was statistical significant difference in the pre-operative and intra-operative values of FVD, CSA and PSF in both groups when analyzed independently (P= 0.00). There was no significant difference in pre-operative values of FVD, CSA and PSF (P> 0.05) among two groups but when the comparison was made between the intra-operative values, there was significant increase in FVD (AP) (P= 0.016), CSA (P= 0.00) and decrease in PSF (P= 0.00) at high pressure pneumoperitoneum. This study provides evidence of using low pressure pneumoperitoneum during LC as changes in FV hemodynamics and coagulation parameters were less pronounced at low pressure pneumoperitoneum.

Pancreatic fistula is a major cause of morbidity and mortality after pancreaticoduodenectomy. External drainage of pancreaticojejunostomy anastomosis with a stent is used to reduce the rate of pancreatic fistula. This study compares the rates of pancreatic fistula between external stent drainage versus no-stent drainage for pancreaticojejunal anastomosis following pancreaticoduodenectomy. A total of 53 patients undergoing pancreaticoduodenectomy for various benign and malignant pathologies were included in the study. An external stent was inserted across the anastomosis to drain the pancreatic duct in 26 patients and 27 patients received no stent. The primary end point was pancreatic fistula. All surgeries were done by a single surgeon with expertise in hepatobiliary pancreatic surgery at a single institute. The two groups were comparable in demographic data, underlying pathologies, presenting complaints, presence of comorbid illnesses and proportion of patients with preoperative biliary drainage, pancreatic consistency and duct diameter. The pancreatic fistula rates were similar in both the groups (11.5 vs. 14.8 %, P= 0.725). The morbidity and surgical re-exploration rate were statistically not significant between the two groups (65.4 vs. 51.9 %, P= 0.318 and 11.5 vs. 7.4 %, P= 0.60). Postoperative stay was also similar with a mean of 14 days in both the groups (P= 0.66). The mortality rate was statistically not significant in the two groups (3.8 vs. 7.4 %, P= 0.575). External drainage of pancreaticojejunostomy anastomosis and the pancreatic duct with a stent does not decrease the rate of postoperative pancreatic fistula after pancreaticoduodenectomy.Pancreatic fistula is a major cause of morbidity and mortality after pancreaticoduodenectomy. External drainage of pancreaticojejunostomy anastomosis with a stent is used to reduce the rate of pancreatic fistula. This study compares the rates of pancreatic fistula between external stent drainage versus no-stent drainage for pancreaticojejunal anastomosis following pancreaticoduodenectomy. A total of 53 patients undergoing pancreaticoduodenectomy for various benign and malignant pathologies were included in the study. An external stent was inserted across the anastomosis to drain the pancreatic duct in 26 patients and 27 patients received no stent. The primary end point was pancreatic fistula. All surgeries were done by a single surgeon with expertise in hepatobiliary pancreatic surgery at a single institute. The two groups were comparable in demographic data, underlying pathologies, presenting complaints, presence of comorbid illnesses and proportion of patients with preoperative biliary drainage, pancreatic consistency and duct diameter. The pancreatic fistula rates were similar in both the groups (11.5 vs. 14.8 %, P= 0.725). The morbidity and surgical re-exploration rate were statistically not significant between the two groups (65.4 vs. 51.9 %, P= 0.318 and 11.5 vs. 7.4 %, P= 0.60). Postoperative stay was also similar with a mean of 14 days in both the groups (P= 0.66). The mortality rate was statistically not significant in the two groups (3.8 vs. 7.4 %, P= 0.575). External drainage of pancreaticojejunostomy anastomosis and the pancreatic duct with a stent does not decrease the rate of postoperative pancreatic fistula after pancreaticoduodenectomy.

The purpose of this study was to determine whether 26S proteasome is detectable in human bronchoalveolar lavage fluid (BALF) and whether burn and inhalation injury is accompanied by changes in BALF proteasome content or activity. BALF was obtained on hospital admission from 28 patients with burn and inhalation injury (controls: 10 healthy volunteers). Proteasome concentrations were quantified by enzyme-linked immonosorbent assay, and their native molecular mass was assessed by gel filtration. Proteasome peptidase activity was measured using a chymotryptic-like peptide substrate in combination with epoxomicin (specific proteasome inhibitor). BALF protein was increased in patients (P< .001) and correlated positively with the degree of inhalation injury. The 20S/26S proteasomes were detectable in all BALF by enzyme-linked immonosorbent assay. Gel filtration confirmed the presence of intact 20S and 26S proteasome that was stable without soluble ATP/Mg2+. In all BALF chymotryptic-like activity was detectable and could be inhibited with epoxomicin by 60 to 70% (P< .01). Absolute amounts of 20S/26S proteasomes and proteasome activity were increased in patients (P< .001 for all). The relative BALF composition after injury was characterized by increased concentrations of 20S proteasome/mg protein (P= .0034 vs volunteers), decreased concentrations of 26S proteasome/mg protein (P= .041 vs volunteers), and reduced specific proteasome activity (P= .044 vs volunteers). The 26S proteasome per milligram and specific proteasome activity were even further reduced in patients who developed ventilator-associated pneumonia (P= .045 and P= .03 vs patients without ventilator-associated pneumonia). This study supports the novel concept that extracellular proteasomes could play a pathophysiological role in the injured lung and suggests that insufficient proteasome function may increase susceptibility for pulmonary complications.

This section provides information on the methodology utilized for the 2020 Best Hospitals for America rankings. Topics discussed include the use of the Lown Institute Hospitals Index to evaluate factors such as quality and value of care in addition to civic leadership, the institutions excluded such as those that specialize in cancer care and federal hospitals, and the use of the American Community Survey data of the U.S. Census Bureau (USCB) to measure inclusivity of hospitals.

Fluid shear stress is a key biomechanical regulatory factor in a several biological systems including bone tissue. Bone cells are also regulated by exogenous acoustic vibration, which has therapeutic benefits. In this study, we determined the effects of shear stress and pulsed ultrasound (US), alone and in series on osteoblast morphology and gene expression. We observed that shear stress (19 dyne/cm2) elongated SaOS-2 cells at 3, 6, 24, and 48 h decreasing their shape index from control values of 0.51 ± 0.01, 0.60 ± 0.05, 0.59 ± 0.04, and 0.45 ± 0.01 to 0.45 ± 0.04, 0.47 ± 0.03, 0.39 ± 0.02, and 0.33 ± 0.01, respectively. This morphological effect was inhibited at 24 and 48 h but not at 3 and 6 h by a 20 min pre-exposure to pulsed US (1.5 MHz, 30 mW/cm2). Shear stress significantly decreased Bone Morphogenetic Protein-4 (BMP-4) mRNA levels at 1, 2, 3, 6, and 24 h by 32.5 ± 1.8%, 30.8 ± 3.5%, 49.6 ± 2.8%, 23.5 ± 5.0%, 24.4 ± 2.3%, respectively. A 20 min pulsed US exposure had no significant effect. However, a 20 min pre-exposure to pulsed US caused significant 39.6 ± 3.0% and 25.6 ± 2.7% decreases in BMP-4 levels in shear stress treated cells at 3 and 24 h, respectively. These results show for the first time that pulsed US alters the mechanotransductive effects of shear stress indicating a more comprehensive understanding of therapeutic US will be obtained when it is studied in conjunction with in vivo, regulatory biomechanical forces.Fluid shear stress is a key biomechanical regulatory factor in a several biological systems including bone tissue. Bone cells are also regulated by exogenous acoustic vibration, which has therapeutic benefits. In this study, we determined the effects of shear stress and pulsed ultrasound (US), alone and in series on osteoblast morphology and gene expression. We observed that shear stress (19 dyne/cm2) elongated SaOS-2 cells at 3, 6, 24, and 48 h decreasing their shape index from control values of 0.51 ± 0.01, 0.60 ± 0.05, 0.59 ± 0.04, and 0.45 ± 0.01 to 0.45 ± 0.04, 0.47 ± 0.03, 0.39 ± 0.02, and 0.33 ± 0.01, respectively. This morphological effect was inhibited at 24 and 48 h but not at 3 and 6 h by a 20 min pre-exposure to pulsed US (1.5 MHz, 30 mW/cm2). Shear stress significantly decreased Bone Morphogenetic Protein-4 (BMP-4) mRNA levels at 1, 2, 3, 6, and 24 h by 32.5 ± 1.8%, 30.8 ± 3.5%, 49.6 ± 2.8%, 23.5 ± 5.0%, 24.4 ± 2.3%, respectively. A 20 min pulsed US exposure had no significant effect. However, a 20 min pre-exposure to pulsed US caused significant 39.6 ± 3.0% and 25.6 ± 2.7% decreases in BMP-4 levels in shear stress treated cells at 3 and 24 h, respectively. These results show for the first time that pulsed US alters the mechanotransductive effects of shear stress indicating a more comprehensive understanding of therapeutic US will be obtained when it is studied in conjunction with in vivo, regulatory biomechanical forces.

Objective. The objective of our study was to test the efficacy of the bispectral index (BIS) compared with spectral edge frequency (SEF), relative delta power, median frequency, and a combined univariate power spectral derivative in predicting movement to incision during isoflurane/oxygen anesthesia.Methods. A total of 42 consenting patients were assigned to 3 groups, isoflurane 0.75, 1.0, and 1.25 minimal alveolar concentration (MAC). Anesthesia was induced with thiopental and maintained with the appropriate end-tidal concentration of isoflurane. The electroencephalogram (EEG) was recorded using a microcomputer system, and data were analyzed off-line. The EEG during the 2 min before incision was analyzed. Following skin incision, each patient was carefully observed for 60 sec to detect occurrence of purposeful movement.Results. For all groups combined, there was a statistically significant difference for BIS (p<0.0001) and also for relative delta power (p<0.016) between movers and non-movers. There was a statistically significant difference between movers and nonmovers at 1.25 MAC isoflurane for BIS (p<0.01). There were no other significant differences for any other EEG variable at any concentration of isoflurane. No EEG variable showed a relationship to isoflurane concentration.Conclusions. When bispectral analysis of the EEG was used to develop a retrospectively determined index, there was an association of the index with movement. Thus, it may be a useful predictor of whether patients will move in response to skin incision during anesthesia with isoflurane/oxygen.

We describe a case of a 26-year-old patient wherein a temperature probe introduced through the nose for intra operative temperature monitoring was inadvertently cut during the ongoing surgical procedure. The missing segment of the probe was retrieved from the trachea which formed an unusual site in spite of the presence of a cuffed endotracheal tube. The present case serves as a reminder that cuffed endotracheal tube does not necessarily protect the airway from aspiration of solid foreign bodies from the oral or nasal airway.

Describimos el caso del corte inadvertido de una sonda introducida por la nariz para medir la temperatura intraquirúrgica, en un paciente de 26años. El segmento faltante de la sonda se recuperó de la tráquea, un sitio inusual en vista de la presencia del tubo endotraqueal con balón. Este caso sirve para recordar que el tubo endotraqueal con balón no protege necesariamente a la vía aérea contra la aspiración de cuerpos extraños sólidos provenientes de la vía oral o la vía nasal.

IMPORTANCE: Overuse of health care services exposes patients to unnecessary risk of harm and costs. Distinguishing patterns of overuse among hospitals requires hospital-level measures across multiple services. OBJECTIVE: To describe characteristics of hospitals associated with overuse of health care services in the US. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cross-sectional analysis used Medicare fee-for-service claims data for beneficiaries older than 65 years from January 1, 2015, to December 31, 2017, with a lookback of 1 year. Inpatient and outpatient services were included, and services offered at specialty and federal hospitals were excluded. Patients were from hospitals with the capacity (based on a claims filter developed for this study) to perform at least 7 of 12 investigated services. Statistical analyses were performed from July 1, 2020, to December 20, 2020. MAIN OUTCOMES AND MEASURES: Outcomes of interest were a composite overuse score ranging from 0 (no overuse of services) to 1 (relatively high overuse of services) and characteristics of hospitals clustered by overuse rates. Twelve published low-value service algorithms were applied to the data to find overuse rates for each hospital, normalized and aggregated to a composite score and then compared across 6 hospital characteristics using multivariable regression. A k-means cluster analysis was used on normalized overuse rates to identify hospital clusters. RESULTS: The primary analysis was performed on 2415 cohort A hospitals (ie, hospitals with capacity for 7 or more services), which included 1 263 592 patients (mean [SD] age, 72.4 [14] years; 678 549 women [53.7%]; 1?017?191 White patients [80.5%]). Head imaging for syncope was the highest-volume low-value service (377?745 patients [29.9%]), followed by coronary artery stenting for stable coronary disease (199?579 [15.8%]). The mean (SD) composite overuse score was 0.40 (0.10) points. Southern hospitals had a higher mean score than midwestern (difference in means: 0.06 [95% CI, 0.05-0.07] points; P?&lt;?.001), northeast (0.08 [95% CI, 0.06-0.09] points; P?&lt;?.001), and western hospitals (0.08 [95% CI, 0.07-0.10] points; P?&lt;?.001). Nonprofit hospitals had a lower adjusted mean score than for-profit hospitals (-0.03 [95% CI, -0.04 to -0.02] points; P?&lt;?.001). Major teaching hospitals had significantly lower adjusted mean overuse scores vs minor teaching hospitals (difference in means, -0.07 [95% CI, -0.08 to -0.06] points; P?&lt;?.001) and nonteaching hospitals (-0.10 [95% CI, -0.12 to -0.09] points; P?&lt;?.001). Of the 4 clusters identified, 1 was characterized by its low counts of overuse in all services except for spinal fusion; the majority of major teaching hospitals were in this cluster (164 of 223 major teaching hospitals [73.5%]). CONCLUSIONS AND RELEVANCE: This cross-sectional study used a novel measurement of hospital-associated overuse; results showed that the highest scores in this Medicare population were associated with nonteaching and for-profit hospitals, particularly in the South.

Direct laryngoscopy remains an invaluable and readily available option despite the increasing use of video laryngoscope for securing the airway in different situations, particularly in limited resource and unanticipated difficult airway scenarios. Several variations of the laryngoscope blades are available for various purposes. However, knowledge of the functioning of different blades in a similar controlled environment is required because of the unavailability of all blades in a given setting.

The article discusses the development of the Lown Institute Hospital Index for ranking hospitals in the U.S. Topics explored include the way existing hospital rankings mainly focused on the quality of hospital performance, the examination of various factors ranging from hospital readmissions to patient safety to assess quality of care, and the application of the Risk Stratification Index (RSI) machine learning algorithm in the creation of the Lown Index.

With the aim of better understanding what the public (as opposed to “patients”) wants from health care, this study asked people on the street, “What does the right health care mean to you?” Responses ranged from “Caring about me more than just in the appointment” to “That everyone should see exactly what medical treatment costs.” A qualitative analysis revealed that all responses fell into 2 overarching categories: health care at the interpersonal level and health care at the system level. Approximately 66.7% of responses included system-level factors, whereas 59% of responses included interpersonal-level factors. We conclude that the public is cognizant of and concerned about issues that also concern patients and others working to improve health care and, thus, should be engaged in the process to design care in a way that meets their needs and preferences before they become ill or interact with the delivery system.

Appropriate use criteria (AUC) have been developed for guiding clinical decision-making for coronary revascularization (revasc). We studied a prospective cohort of 693 pts initiated in 1992 and managed with optimal medical therapy (OMT). AUC scores could be calculated using noninvasive test results and coronary angiographic data in 230 pts, which constitute the study group. When non-invasive findings were discordant, patients were put in the higher risk stratum. Revasc status and myocardial infarction (MI) events were ascertained as of June 2005. Mortality status was ascertained as of December 31, 2008. Based on AUC scores, pts were classified as Appropriate (A), Inappropriate (I), or Uncertain (U) for revasc. Decisions to pursue invasive evaluation and revasc were based solely on stability of symptoms, LV function, and exercise duration. Survival analysis and stepwise Cox modeling was used to assess AUC class as a predictor of outcomes.

Fentanyl, a mu selective opioid agonist in wide clinical use, raises the ventricular fibrillation threshold in the normal canine myocardium. We have previously shown that this effect is amplified by haemorrhagic stress. In order to determine if mu receptor activation is antifibrillatory during acute myocardial ischaemia, we compared the effects of two mu selective agents, fentanyl and buprenorphine, in open chest chloralose anaesthetised dogs. Each drug was administered intravenously in two doses 1 h apart (fentanyl 30 μg·kg−1·dose; buprenorphine 0.3 mg·kg−1·dose). Ventricular fibrillation threshold was measured during right ventricular pacing using the single stimulus technique. The threshold was determined before and during a 10 min left anterior descending coronary artery occlusion. Prior to fentanyl administration, ventricular fibrillation threshold decreased from a control value of 19(SEM 2) mA to 12(1) mA during coronary artery occlusion. After the first dose of this drug an attenuation in the ischaemia induced fall in fibrillation threshold from 23(4) mA to 15(2) mA was observed. After the second dose of fentanyl the decline in fibrillation threshold was significantly blunted at 22(4) mA during control and 18(3) mA during occlusion, p<0.05 compared to no drug. In an additional series of experiments atropine sulphate abolished the antifibrillatory action of fentanyl, indicating that vagal efferent activation is responsible for the protective effect of the drug during acute myocardial ischaemia. This is in contrast with its mode of action during haemorrhage, when it enhances vagal afferent inhibition of sympathetic tone, and atropine pretreatment is without effect. Buprenorphine, a partial mu agonist, had no effect on ventricular fibrillation threshold although it caused significant declines in heart rate and arterial blood pressure. These findings indicate that a full mu agonist increases cardiac electrical stability but that a partial mu agonist does not. Furthermore, the mechanisms responsible for the antifibrillatory action of mu agonism may be specific to the physiological stressor involved.