Search

Introduction: Critical for advancing a Learning Health System (LHS) in the U.S., a regulatory safe harbor for deidentified data reduces barriers to learning from care at scale while minimizing privacy risks. We examine deidentified data policy as a mechanism for synthesizing the ethical obligations underlying clinical care and human subjects research for an LHS which conceptually and practically integrates care and research, blurring the roles of patient and subject., Methods: First, we discuss respect for persons vis-a-vis the systemic secondary use of data and tissue collected in the fiduciary context of clinical care. We argue that, without traditional informed consent or duty to benefit the individual, deidentification may allow secondary use to supersede the primary purpose of care. Next, we consider the effectiveness of deidentification for minimizing harms via privacy protection and maximizing benefits via promoting learning and translational care. We find that deidentification is unable to fully protect privacy given the vastness of health data and current technology, yet it imposes limitations to learning and barriers for efficient translation. After that, we evaluate the impact of deidentification on distributive justice within an LHS ethical framework in which patients are obligated to contribute to learning and the system has a duty to translate knowledge into better care. Such a system may permit exacerbation of health disparities as it accelerates learning without mechanisms to ensure that individuals' contributions and benefits are fair and balanced., Results: We find that, despite its established advantages, system-wide use of deidentification may be suboptimal for signaling respect, protecting privacy or promoting learning, and satisfying requirements of justice for patients and subjects., Conclusions: Finally, we highlight ethical, socioeconomic, technological and legal challenges and next steps, including a critical appreciation for novel approaches to realize an LHS that maximizes efficient, effective learning and just translation without the compromises of deidentification., Competing Interests: The authors declare no conflicts of interest., (© 2022 The Authors. Learning Health Systems published by Wiley Periodicals LLC on behalf of University of Michigan.)

Background: Although people who smoke cigarettes are overrepresented among hospital inpatients, few are connected with smoking cessation treatment during their hospitalization. Training, accountability for medication use, and monitoring of all patients position pharmacists well to deliver cessation interventions to all hospitalized patients who smoke. Methods: A large Midwestern University hospital implemented a pharmacist-led smoking cessation intervention. A delegation protocol for hospital pharmacy inpatients who smoked cigarettes gave hospital pharmacists the authority to order nicotine replacement therapy (NRT) during hospitalization and upon discharge, and for referral to the Wisconsin Tobacco Quit Line (WTQL) at discharge. Eligible patients received the smoking cessation intervention unless they actively refused (ie, "opt-out"). The program was pilot tested in phases, with pharmacist feedback between phases, and then implemented hospital-wide. Interviews, surveys, and informal mechanisms identified ways to improve implementation and workflows. Results: Feedback from pharmacists led to changes that improved workflow, training and patient education materials, and enhanced adoption and reach. Refining implementation strategies across pilot phases increased the percentage of eligible smokers offered pharmacist-delivered cessation support from 37% to 76%, prescribed NRT from 2% to 44%, and referred to the WTQL from 3% to 32%. Conclusion: Hospitalizations provide an ideal opportunity for patients to make a tobacco quit attempt, and pharmacists can capitalize on this opportunity by integrating smoking cessation treatment into existing inpatient medication reconciliation workflows. Pharmacist-led implementation strategies developed in this study may be applicable in other inpatient settings., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2021.)

Henrietta Lacks' deidentified tissue became HeLa cells (the paradigmatic learning health platform). In this article, we discuss separating research on Ms Lacks' tissue from obligations to promote respect, beneficence, and justice for her as a patient. This case illuminates ethical challenges for the secondary use of biospecimens, which persist in contemporary learning health systems. Deidentification and broad consent seek to maximize the benefits of learning from care by minimizing burdens on patients, but these strategies are insufficient for privacy, transparency, and engagement. The resulting supply chain for human cellular and tissue-based products may therefore recapitulate the harms experienced by the Lacks family. We introduce the potential for blockchain technology to build unprecedented transparency, engagement, and accountability into learning health system architecture without requiring deidentification. The ability of nonfungible tokens to maintain the provenance of inherently unique digital assets may optimize utility, value, and respect for patients who contribute tissue and other clinical data for research. We consider the potential benefits and survey major technical, ethical, socioeconomic, and legal challenges for the successful implementation of the proposed solutions. The potential for nonfungible tokens to promote efficiency, effectiveness, and justice in learning health systems demands further exploration., (©Marielle S Gross, Amelia J Hood, Robert C Miller Jr. Originally published in JMIR Bioinformatics and Biotechnology (https://bioinform.jmir.org), 22.10.2021.)

Heparin-induced thrombocytopenia (HIT) is a rare adverse drug reaction. The anti-PF4 antibody assay (ELISA) is utilized to assist in the clinical evaluation of HIT due to its high negative predictability and wide-spread availability. However, it also associated with false positive results. The 4T score can assist in predicting an individual's risk for HIT and the need for further laboratory testing. This was a single-center prospective observational cohort study. Orders for HIT testing were sent via page to a clinical pharmacist to calculate a 4T score. If low risk, the pharmacist contacted the ordering prescriber to recommend discontinuation of laboratory testing. During the study, a clinical support tool was implemented to assist prescribers with ordering HIT tests. The study was divided into a pharmacist intervention group and a control group. A total of 303 pages were received. One hundred nine were missed due to unavailability of the pharmacist at time of page. A pharmacist reviewed 194 pages and intervened on 132. One hundred seven were scored as low risk, 70 as intermediate risk and 9 as high risk. Pharmacist intervention resulted in discontinuing 64 ELISA and 11 serotonin release assay tests. The clinical support tool resulted in a yearly decrease of HIT testing by 27%. Laboratory cost savings totaled $11,000 but did not include avoidance of laboratory technician or drug cost. Pharmacist involvement in the clinical assessment of HIT and the use of a support tool resulted in the reduction of HIT tests in low risk patients.

Background: Analysis of safe laparoscopic grasping thresholds for the colon has not been performed. This study aimed to analyse tissue damage thresholds when the colon is grasped laparoscopically, correlating histological changes to mechanical compressive forces., Methods: An instrumented laparoscopic grasper was used to measure the forces applied to porcine colon, with data captured and plotted as a force-time (f-t) curve. Haematoxylin and eosin histochemistry of tissue subjected to 10, 20, 40, 50 and 70 N for 5, 30 and 60 s was performed, and the area of colonic circular and longitudinal muscle was compared in grasped and un-grasped regions. The area under the f-t curve was calculated as a measure of the accumulated force applied, known as the force-time product (FTP)., Results: FTP ranged from 55.7 to 3793 N.s. Significant differences were observed between the muscle area of the grasped and un-grasped regions in both longitudinal and circular muscle at 50 N and above for all grasping times. For the longitudinal muscle, significant differences were observed between grasped and un-grasped areas at 20 N force for 30 s (mean difference = 59 mm 2 , 95% CI 41-77 mm 2 , P = 0.04), 20 N force for 60 s (mean difference = 31 mm 2 , 95% CI 21.5-40.5 mm 2 , P = 0.006) and 40 N force for 30 s (mean difference 37 mm 2 , 95% CI 27-47 mm 2 , P = 0.006). Changes in histology correlated with mechanical forces applied to the longitudinal muscle at a FTP over 300 N s., Conclusions: This study characterizes the grasping forces that result in histological changes to the colon and correlates these with a mechanical measurement of the applied force. The findings will contribute to the development of smart laparoscopic graspers with active constraints to prevent excessive grasping and tissue injury.

Developments in healthcare technology could improve patient care and reduce healthcare costs. There is a need to facilitate communication and increase efficiency in surgical pre-assessment clinics. This study aimed to develop an iPad application to deliver an electronic patient questionnaire, and to evaluate its use in the pre-assessment environment. Software was developed, MyOp, for a standard iPad that mirrored the paper-based pre-assessment system, with features designed for ease of patient use and remote data transfer. A case-control study was conducted, comparing use of MyOp with paper-based practice, to evaluate feasibility and patient preference. Patients were offered the use of MyOp or paper-based system. Outcomes measured included time to complete iPad questionnaire, consultation duration, and a patient preference questionnaire. MyOp cost £3500 to develop. 104 individuals participated in the study, 53 MyOp and 51 controls. MyOp reduced the median consultation duration by 5.00 min. A reduction was seen in all subgroups except those aged over 70 or urology patients. Patients preferred to complete the form independently, using a touchpad or computer but expressed concerns about data security. Use of an electronic patient questionnaire reduces consultation time delivering greater efficiency of pre-assessment nurse time. Preconceived ideas about the use of technology in older age groups are likely inaccurate and less of a barrier than previously thought. Electronic pre-assessments could be used routinely to reduce demands on healthcare facilities, improve patient care, and triage patients prior to clinic attendance.

Introduction Analysis of force application in laparoscopic surgery is critical to understanding the nature of the tool-tissue interaction. The aim of this study is to provide real-time data about manipulations to abdominal organs. Methods An instrumented short fenestrated grasper was used in an in vivo porcine model, measuring force at the grasper handle. Grasping force and duration over 5 small bowel manipulation tasks were analyzed. Forces required to retract gallbladder, bladder, small bowel, large bowel, and rectum were measured over 30 seconds. Four parameters were calculated-T(hold), the grasp time; T(close), time taken for the jaws to close; F(max), maximum force reached; and F(rms), root mean square force (representing the average force across the grasp time). Results Mean F(max) to manipulate the small bowel was 20.5 N (±7.2) and F(rms) was 13.7 N (±5.4). Mean T(close) was 0.52 seconds (±0.26) and T(hold) was 3.87 seconds (±1.5). In individual organs, mean F(max) was 49 N (±15) to manipulate the rectum and 59 N (±13.4) for the colon. The mean F(max) for bladder and gallbladder retraction was 28.8 N (±7.4) and 50.7 N (±3.8), respectively. All organs exhibited force relaxation, the F(rms) reduced to below 25 N for all organs except the small bowel, with a mean F(rms) of less than 10 N. Conclusion This study has commenced the process of quantifying tool-tissue interaction. The static measurements discussed here should evolve to include dynamic measurements such as shear, torque, and retraction forces, and be correlated with evidence of histological damage to tissue., (© The Author(s) 2016.)

Study Objectives: Rapid eye movement sleep behavior disorder (RBD) is a condition closely associated with Parkinson disease (PD). RBD is a sleep disturbance that frequently manifests early in the development of PD, likely reflecting disruption in normal functioning of anatomical areas affected by neurodegenerative processes. Although specific neuropathological aspects shared by RBD and PD have yet to be fully documented, further characterization is critical to discovering reliable biomarkers that predict PD onset. In the current study, we tested the hypothesis of altered functional connections of the substantia nigra (SN) in patients in whom RBD was diagnosed., Design: Between-groups, single time point imaging., Setting: UTHSC-H 3 telsa MRI center., Participants: Ten patients with RBD, 11 patients with PD, and 10 age-matched controls., Interventions: NA., Measurements and Results: We measured correlations of SN time series using resting state blood oxygen level-dependent functional magnetic resonance imaging (BOLD-fMRI) in patients with idiopathic RBD who were at risk for developing PD, patients in whom PD was diagnosed, and age-matched controls. Using voxelwise analysis of variance, different correlations (P < 0.01, whole-brain corrected) between left SN and left putamen were found in patients with RBD compared with controls and patients with PD. SN correlations with right cuneus/precuneus and superior occipital gyrus were significantly different for patients with RBD compared with both controls and patients with PD., Conclusions: The results suggest that altered nigrostriatal and nigrocortical connectivity characterizes rapid eye movement sleep behavior disorder before onset of obvious motor impairment. The functional changes are discussed in the context of degeneration in dopaminergic and cognition-related networks.

Background: Huntington disease (HD) is a genetic, neurodegenerative disorder characterized by chorea, behavioral co-morbidities, cognitive deficits, and eye movement abnormalities. We sought to evaluate whether reflexive and voluntary orienting prove useful as biomarkers of disease severity in HD., Methods: Eleven HD subjects were evaluated with the motor subscale of the Unified Huntington Disease Rating Scale (UHDRS) and the Montreal Cognitive Assessment. Using an infrared eye tracker, we also measured latency and error rates of horizontal and vertical saccades using prosaccade and antisaccade eye movement tasks. We calculated simple and age-controlled correlations between eye movement and clinical parameters., Results: Prosaccade latency correlated with total chorea score. HD patients with greater clinical severity were significantly slower in the prosaccade task. Antisaccade error rate also correlated with UHDRS motor score and total chorea score. HD patients with greater clinical severity as measured by either measure made significantly more errors in the antisaccade task. All these correlations remained significant even when age was taken into account., Conclusions: The results of the present age-controlled study show for the first time that both reflexive and voluntary eye motor control in HD patients decrease with increase in disease severity suggesting declines in both motor and cognitive function. Thus, relatively simple eye movement parameters (latency and error rate) obtained from simple tasks (prosaccade and antisaccade) may serve as quantitative biomarkers of sub-cortical and cortical disease severity in HD and could aid in predicting onset, distinguishing subtypes, or evaluating disease progression and novel therapies., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Schizophrenic patients are heterogeneous with respect to voluntary eye movement performance, with some showing impairment (e.g., high antisaccade error rates) and others having intact performance. To investigate how this heterogeneity may correlate with different cognitive outcomes after treatment, we used a prosaccade and antisaccade task to investigate the effects of haloperidol in schizophrenic subjects at three time points: baseline (before medication), 3-5 days post-medication, and 12-14 days post-medication. We also investigated changes on the Stroop Task and the Positive and Negative Syndrome Scale (PANSS) in these same subjects. Results were compared to matched controls. When considered as a single patient group, haloperidol had no effects across sessions on reflexive and voluntary saccadic eye movements of schizophrenic patients. In contrast, the performance of the Control group improved slightly but significantly across sessions on the voluntary eye movement task. When each subject was considered separately, interestingly, for schizophrenic patients change in voluntary eye movement performance across sessions depended on the baseline performance in a non-monotonic manner. That is, there was maximal worsening of voluntary eye movement performance at an intermediate level of baseline performance and the worsening decreased on either side of this intermediate baseline level. When patients were divided into categorical subgroups (nonimpaired and impaired), consistent with the non-monotonic relationship, haloperidol worsened voluntary eye movement performance in the nonimpaired patients and improved performance in the impaired patients. These results were only partially reflected in the Stroop Test. Both patient subgroups showed clinically significant improvement over time as measured by the PANSS. These findings suggest that haloperidol has different effects on cognitive performance in impaired and nonimpaired schizophrenic patients that are not evident in clinical ratings based on the PANSS. Given that good cognitive function is important for long-term prognosis and that there is heterogeneity in schizophrenia, these findings are critical for optimal evaluation and treatment of schizophrenic patients., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objective: The purpose of this study was to quantify volumes of specific subcortical gray matter nuclei implicated in Parkinson's disease (PD) as a preliminary step for identifying a non-invasive clinical biomarker for PD. We hypothesized that REM sleep behavior disorder (RBD) patients, at risk for developing PD, will demonstrate a pattern of neuronal degeneration reflected in reduced striatal volumes on T1-weighted MRI., Methods: We compared measures of RBD patients confirmed by polysomnography (PSG) with groups of age/gender-matched Control subjects and early PD (EPD) patients (Hoehn & Yahr < 2). Clinical measurements included the Unified Parkinson's disease Rating Scales (UPDRS), timed gait and finger tapping tasks, the Parkinson's Disease Questionnaire (PDQ-39), and a time-synchronized video recorded single-night PSG. Volumetric measurements were derived from high-resolution T1-weighted 3 T MRI images., Results: The matched Control and EPD groups were statistically similar to the RBD group in age, gender, handedness, and total brain volumes. The RBD group had smaller bilateral putamen volumes (both raw and normalized by brain tissue volume), in addition to some clinical impairment on the UPDRS and PDQ-39., Conclusions: Reduced putamen volumes may be a structural marker for RBD and reflect a pattern of neurodegeneration that predicts the development of PD., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Rationale: Differences in 5-hydroxytryptamine (5-HT) function have been the subject of extensive research in psychiatric studies. Many studies have manipulated L -tryptophan (Trp) levels to temporarily decrease (depletion) or increase (loading) 5-HT synthesis. While most researchers have used a 100-g formulation, there has been ongoing interest in using smaller-sized formulations., Objectives: This study examined the time course of multiple plasma indicators of brain 5-HT synthesis after a 50-g depletion and loading as a comparison to the corresponding 100-g formulations that are typically used., Materials and Methods: Plasma was collected from 112 healthy adults at seven hourly intervals after consumption of either a 50- or 100-g depletion or loading. Self-ratings of mood and somatic symptoms were completed before and after Trp manipulations., Results: The primary findings were that (1) the 50- and 100-g formulations produced the expected changes in plasma indicators after both depletion (-89% and -96%, respectively) and loading (+570% and +372%, respectively); (2) the 100-g depletion showed more robust effects at the 4, 5, and 6 h measurements than the 50-g depletion; (3) there was significant attrition after both the 100-g depletion and loading, but not after either of the 50-g formulations; and (4) both the 50- and 100-g depletions produced increases in negative self-ratings of mood and somatic symptoms, while loading significantly increased negative ratings after the 100 g only., Conclusions: There are important considerations when choosing among formulation sizes for use in Trp manipulation studies, and the complete 7-h time-course data set of the typical plasma Trp measures presented here may help researchers decide which methodology best suits their needs.

Background: The integrity of frontal systems responsible for voluntary control and their interaction with subcortical regions involved in reflexive responses were studied in patients with Parkinson's disease (PD). Previous studies have shown that patients with PD have impaired executive function, including deficits in attention, motor planning and decision making., Methods: Executive function was measured through eye movements: reflexive (stimulus driven) prosaccades and voluntary (internally guided) antisaccades. Patients with advanced idiopathic PD, off and on their optimal levodopa therapy, were tested on a prosaccade and an antisaccade task and compared with matched controls., Results: Levodopa significantly increased response time for reflexive prosaccades and reduced error rate for voluntary antisaccades., Conclusions: Consistent with our proposed model, patients with PD in the medicated state are better able to plan and execute voluntary eye movements. These findings suggest levodopa improves function of the voluntary frontostriatal system, which is deficient in PD.

In an attempt to distinguish and define the altered cognitive processes associated with Parkinson's disease (PD), we examine and try to dissociate the components of an effective voluntary saccade: (1) the planning and execution of a voluntary saccade; (2) the suppression of reflexive eye movements; and (3) the working memory processes required. We tested 14 PD patients (off their medications) and 11 control subjects on antisaccade (AS), delayed antisaccade (DAS), and remembered antisaccade (RAS) paradigms. The three tasks required identical responses, each task only differing in a single manipulation for direct comparison--a delay period was added in the DAS, and the target was removed during the delay period of the RAS--allowing us to study the specific cognitive processes involved in the execution of a voluntary saccade. Voluntary saccade response times were longer in the PD group compared to controls on all three tasks, suggesting difficulties in voluntary saccade execution. Furthermore, PD patients showed difficulty suppressing reflexive saccades (increased number of errors in the AS task and increased number of disinhibitions in the DAS task). Finally, our study did not show significant differences in either response time or error rate between the RAS and the DAS tasks for either control subjects or PD patients. In sum, we report evidence for voluntary saccade execution deficits together with problems inhibiting reflexive saccades in Parkinson's disease patients. These findings were correlated with each other and disease severity, suggesting that eye movement measurement may be a useful tool for studying higher cognitive function.

High-throughput methods for generating aptamer microarrays are described. As a proof-of-principle, the microarrays were used to screen the affinity and specificity of a pool of robotically selected antilysozyme RNA aptamers. Aptamers were transcribed in vitro in reactions supplemented with biotinyl-guanosine 5'-monophosphate, which led to the specific addition of a 5' biotin moiety, and then spotted on streptavidin-coated microarray slides. The aptamers captured target protein in a dose-dependent manner, with linear signal response ranges that covered seven orders of magnitude and a lower limit of detection of 1 pg/mL (70 fM). Aptamers on the microarray retained their specificity for target protein in the presence of a 10,000-fold (w/w) excess of T-4 cell lysate protein. The RNA aptamer microarrays performed comparably to current antibody microarrays and within the clinically relevant ranges of many disease biomarkers. These methods should also prove useful for generating other functional RNA microarrays, including arrays for genomic noncoding RNAs that bind proteins. Integrating RNA aptamer microarray production with the maturing technology for automated in vitro selection of antiprotein aptamers should result in the high-throughput production of proteome chips.

1. The metabolic fate of N,N-dimethylcarbamoylmethyl 4-(4-guanidino[14C]benzoyloxy)phenylacetate methanesulphonate (14C-camostat mesylate) was investigated after i.v. administration to man (12-h infusion), and to rat and dog (bolus injection). 2. Renal excretion (mainly in 24 h) accounted for at least 80% dose in all three species, and the only two important metabolites were identified as 4-(4-guanidinobenzoyloxy)phenylacetic acid (GBPA) and 4-guanidinobenzoic acid (GBA). 3. Parent drug was not detected in human plasma either during or after infusion of 14C-camostat mesylate owing to rapid hydrolysis of the side-chain ester group (t1/2 < 1 min). Steady-state levels of both GBPA and GBA in plasma were apparently attained by the end of the infusion period. Mean terminal half-life, systemic clearance and apparent volume of distribution at steady-state of GBPA in man were 1.0 h, 6.4 ml/min per kg and 0.38 l/kg, respectively, and the corresponding values for GBA were 2.4 h, 4.7 ml/min per kg and 1.01/kg respectively. 4. Radioactivity was rapidly distributed to most tissues after bolus i.v. doses of 14C-camostat mesylate to rats and dogs, with highest levels being associated with the liver and kidney, the two main organs of drug elimination. Concentrations in the pancreas, a possible site for drug action, were generally lower than those in plasma.

The percutaneous absorption has been investigated in rats of a mixture (3:2, w/w) of N-methyl-2-pyrrolidinone (NMP) and 2-pyrrolidinone (2-P), a combination intended for use as a vehicle in the formulation of an antimycotic drug to enhance skin penetration on dermal application, following co-administration of the two 14C-radiolabelled compounds by the dermal and oral routes. Radioactivity was excreted predominantly in the urine after either route of administration, and comparison of the respective excretion profiles indicated that about three-quarters of the applied dose was absorbed through the skin. Plasma concentrations of each parent compound, as determined by radio-HPLC, reached peak values at 2 hr after oral dosing, and remained relatively uniform during 1-6 hr after application to the skin, suggesting constant percutaneous absorption during this period. NMP appeared to be absorbed through the skin more extensively and at a slightly faster rate than 2-P; total percutaneous absorption tended to be more extensive in female than in male rats. Together, these two 14C-compounds accounted for most of the plasma radioactivity up to 6-8 hr post-administration. However, by 12 hr (when plasma levels were relatively low), most of the radioactivity was associated with unknown polar metabolites. In view of the extensive percutaneous absorption and little first-pass metabolism of the two pyrrolidinones, the oral route was considered to represent a valid alternative to the dermal route for the assessment of the systemic toxicity of the two compounds.

1. Infusions of oleic acid into the colon or the distal part of the ileum in anaesthetized cats inhibits secretion of water and amylase by the pancreas, stimulated by secretin and pancreozymin. Intraileal infusions of other non-water-soluble substances or hypertonic solutions can also inhibit the pancreas. 2. As inhibition can be produced after extrinsic denervation of the pancreas and gut, it must in part be humorally mediated. 3. Pentagastrin-stimulated gastric secretion of acid and pepsin is also inhibited by the intraileal infusions, but the inhibition of acid secretion is less than that of pancreatic secretion. 4. It is suggested that the physiological counterpart of the inhibitory effects induced by the infusion of non-physiological solutions into the colon or ileum is an inhibition of pancreatic secretion brought about by the cessation of intestinal absorption, which marks the completion of the post-prandial digestive process.

Three cases of Norwegian Scabies diagnosed in Glasgow hospitals within 1 year each caused wide-spread outbreaks of papular eruptions amongst the patients and staff, followed later by a few cases of classical scabies. Symptoms and timing suggested that these infections were caused by immature mites derived by personal contact and possibly by contact with infected cuticular fragments which were abundant in the environment of the three patients. To control a ward epidemic, isolation of the Norwegian scabietic should be followed by environmental and then by personal disinfestation.

1. Burimamide (34-1080 muM) caused a concentration-dependent increase in the force and frequency of contraction of kitten isolated atria. 2. Metiamide (467 muM) had no stimulant action on kitten atria and did not modify the effects of burimamide. 3. The atrial stimulation produced by burimamide was reduced by (-)propranolol (34-68 nM) and by cocaine (3 muM). 4. The atrial stimulant effect of burimamide was prevented by pretreatment of kittens with reserpine (1 mg/kg, 24 h before the experiment). 5. It is concluded that burimamide causes atrial stimulation by releasing catecholamines.

1. Pancreotone is a polypeptide material obtained from ileal and colonic mucosa by extraction with alcohol and subsequent precipitation by bile salts. 2. In anaesthetized cats in inhibits the actions of secretin on the pancreas, and of pancreozymin on the pancreas and gall-bladder. 3. Pancreotone has a less powerful inhibitory action on pentagastrin-stimulated gastric secretion. 4. The actions of pancreotone resemble the inhibitory effects on the pancreas and stomach of intraileal and intracolonic infusions of oleic acid and other substances in cats with the vagal and splanchnic nerves cut. Pancreotone may be the humoral mediator of these inhibitory effects. 5. A possible relationship between the actions of pancreotone and somatostatin on the stomach, and of pancreotone and pancreatic polypeptide on the pancreas, is discussed.