A systematic review of viral transmission risk to healthcare staff comparing laparoscopic and open surgery.

BACKGROUND: Throughout the United Kingdom, there have been sweeping changes to the practice of medicine due to the COVID-19 pandemic. For the surgical speciality, there have been changes to both elective and emergency practice. Concern regarding potential aerosolisation during invasive procedures have been raised - including the use of pneumoperitoneum to facilitate laparoscopy. The aim of this study is to systematically review the data available to date regarding the potential risk posed to theatre staff by laparoscopy. METHOD: A systematic review and meta-analysis was carried out in accordance with PRISMA guidelines. Only publications in peer-reviewed journals were considered. PubMed, Ovid Embase, SCOPUS, and Cochrane Library were searched. The search period was between 1st January 1980 and 27th April 2020. Bias was assessed using the ROBINS-I tool. RESULTS: 4209 records were identified, resulting in 9 unique studies being selected. The included studies examined viral DNA aerosoliation generated by electrosurgery and CO2 laser ablation, with one study examining viral DNA aerosolisation following laparoscopy. Each of these demonstrated that viral DNA (Hepatitis B Virus and Human Papilloma Virus) was detectable in the surgical smoke plume. CONCLUSION: The data and analysis reported in this study reflect the most up-to-date evidence available for the surgeon to assess risk towards healthcare staff. It was constrained by heterogeneity of reporting for several outcomes and lack of comparable studies. There is currently insufficient data to recommend open or a minimally invasive surgical approach with regard to theatre team safety in the COVID-19 era.

Meta-analysis of patient-reported outcomes after laparoscopic versus open inguinal hernia repair.

BACKGROUND: Inguinal hernia repair is a common low-risk intervention. Patient-reported outcomes (PROs) are being used increasingly as primary outcomes in clinical trials. The aim of this study was to review and meta-analyse the PROs in RCTs comparing laparoscopic versus open inguinal hernia repair techniques in adult patients. METHODS: A systematic review and meta-analysis was carried out in accordance with PRISMA guidelines. Only RCTs in peer-reviewed journals were considered. PubMed, Ovid Embase, Scopus and the Cochrane Library were searched. In addition, four trial registries were searched. The search interval was between 1 January 1998 and 1 May 2018. Identified publications were reviewed independently by two authors. The review was registered in the PROSPERO database (CRD42018099552). Bias was assessed using the Cochrane Collaboration risk-of-bias tool. RESULTS: Some 7192 records were identified, from which 58 unique RCTs were selected. Laparoscopic hernia repair was associated with significantly less postoperative pain in three intervals: from 2 weeks to within 6 months after surgery (risk ratio (RR) 0·74, 95 per cent c.i. 0·62 to 0·88), 6 months to 1 year (RR 0·74, 0·59 to 0·93) and 1 year onwards (RR 0·62, 0·47 to 0·82). Paraesthesia (RR 0·27, 0·18 to 0·40) and patient-reported satisfaction (RR 0·91, 0·85 to 0·98) were also significantly better in the laparoscopic repair group. CONCLUSION: The data and analysis reported in this study reflect the most up-to-date evidence available for the surgeon to counsel patients. It was constrained by heterogeneity of reporting for several outcomes.

Birdlike growth and mixed-age flocks in avimimids (Theropoda, Oviraptorosauria).

Avimimids were unusual, birdlike oviraptorosaurs from the Late Cretaceous of Asia. Initially enigmatic, new information has ameliorated the understanding of their anatomy, phylogenetic position, and behaviour. A monodominant bonebed from the Nemegt Formation of Mongolia showed that some avimimids were gregarious, but the site is unusual in the apparent absence of juveniles. Here, a second monodominant avimimid bonebed is described from the Iren Dabasu Formation of northern China. Elements recovered include numerous vertebrae and portions of the forelimbs and hindlimbs, representing a minimum of six individuals. Histological sampling of two tibiotarsi from the bonebed reveals rapid growth early in ontogeny followed by unexpectedly early onset of fusion and limited subsequent growth. This indicates that avimimids grew rapidly to adult size, like most extant birds but contrasting other small theropod dinosaurs. The combination of adults and juveniles in the Iren Dabasu bonebed assemblage provides evidence of mixed-age flocking in avimimids and the onset of fusion in young individuals suggests that some of the individuals in the Nemegt Formation bonebed may have been juveniles. Regardless, these individuals were likely functionally analogous to adults, and this probably facilitated mixed-age flocking by reducing ontogenetic niche shift in avimimids.

A dinosaur community composition dataset for the Late Cretaceous Nemegt Basin of Mongolia.

Dinosaur community composition data for eleven fossil localities in the Late Cretaceous Nemegt Basin of Mongolia are compiled from field observations and records in the literature. Counts were generated from skeletons and represent numbers of individuals preserved in each locality. These data were used in the analyses of Funston et al. [1] "Oviraptorosaur anatomy, diversity, and ecology in the Nemegt Basin" in the Nemegt Ecosystems Special Issue of Palaeogeography, Palaeoclimatology, Palaeoecology, where the results are discussed.

Involvement of opioid signaling in food preference and motivation: Studies in laboratory animals.

Motivation is a complex neurobiological process that initiates, directs, and maintains goal-oriented behavior. Although distinct components of motivated behavior are difficult to investigate, appetitive and consummatory phases of motivation are experimentally separable. Different neurotransmitter systems, particularly the mesolimbic dopaminergic system, have been associated with food motivation. Over the last two decades, however, research focusing on the role of opioid signaling has been particularly growing in this area. Opioid receptors seem to be involved, via neuroanatomically distinct mechanisms, in both appetitive and consummatory aspects of food reward. In the present chapter, we review the pharmacology and functional neuroanatomy of opioid receptors and their endogenous ligands, in the context of food reinforcement. We examine literature aimed at the development of laboratory animal techniques to better understand different components of motivated behavior. We present recent data investigating the effect of opioid receptor antagonists on food preference and effort-related decision making in rats, which indicate that opioid signaling blockade selectively affects intake of relatively preferred foods, resulting in reduced willingness to exert effort to obtain them. Finally, we elaborate on the potential role of opioid system manipulations in disorders associated with excessive eating and obesity.

Continuous wave Doppler determination of right ventricular pressure: a simultaneous Doppler-catheterization study in 127 patients.

Simultaneous continuous wave Doppler echocardiography and right-sided cardiac pressure measurements were performed during cardiac catheterization in 127 patients. Tricuspid regurgitation was detected by the Doppler method in 117 patients and was of adequate quality to analyze in 111 patients. Maximal systolic pressure gradient between the right ventricle and right atrium was 11 to 136 mm Hg (mean 53 +/- 29) and simultaneously measured Doppler gradient was 9 to 127 mm Hg (mean 49 +/- 26); for these two measurements, r = 0.96 and SEE = 7 mm Hg. Right ventricular systolic pressure was estimated by three methods from the Doppler gradient. These were 1) Doppler gradient + mean jugular venous pressure; 2) using a regression equation derived from the first 63 patients (Group 1); and 3) Doppler gradient + 10. These methods were tested on the remaining 48 patients with Doppler-analyzable tricuspid regurgitation (Group 2). The correlation between Doppler-estimated and catheter-measured right ventricular systolic pressure was similar using all three methods; however, the regression equation produced a significantly better estimate (p less than 0.05). Use of continuous wave Doppler blood flow velocity of tricuspid regurgitation permitted determination of the systolic pressure gradient across the tricuspid valve and the right ventricular systolic pressure. This noninvasive technique yielded information comparable with that obtained at catheterization. Approximately 80% of patients with increased and 57% with normal right ventricular pressure had analyzable Doppler tricuspid regurgitant velocities that could be used to accurately predict right ventricular systolic pressure.

Comparison of three Doppler ultrasound methods in the prediction of pulmonary artery pressure.

Pulmonary artery pressure was noninvasively estimated by three Doppler echocardiographic methods in 50 consecutive patients undergoing cardiac catheterization. First, a systolic transtricuspid gradient was calculated from Doppler-detected tricuspid regurgitation; clinical jugular venous pressure or a fixed value of 14 mm Hg was added to yield systolic pulmonary artery pressure. Second, acceleration time from pulmonary flow analysis was used in a regression equation to derive mean pulmonary artery pressure. Third, right ventricular isovolumic relaxation time was calculated from Doppler-determined pulmonary valve closure and tricuspid valve opening; systolic pulmonary artery pressure was then derived from a nomogram. In 48 patients (96%) at least one of the methods could be employed. A tricuspid pressure gradient, obtained in 36 patients (72%), provided reliable prediction of systolic pulmonary artery pressure. The prediction was superior when 14 mm Hg rather than estimated jugular venous pressure was used to account for right atrial pressure. In 44 patients (88%), pulmonary flow was analyzed. Prediction of mean pulmonary artery pressure was unsatisfactory (r = 0.65) but improved (r = 0.85) when only patients with a heart rate between 60 and 100 beats/min were considered. The effect of correcting pulmonary flow indexes for heart rate was examined by correlating different flow indexes before and after correction for heart rate. There was a good correlation between corrected acceleration time and either systolic (r = -0.85) or mean (r = -0.83) pulmonary artery pressure. Because of a high incidence of arrhythmia, right ventricular relaxation time could be determined in only 11 patients (22%). Noninvasive prediction of pulmonary artery pressure is feasible in most patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluation of mitral leaflet motion by echocardiography and jet direction by Doppler color flow mapping to determine the mechanisms of mitral regurgitation.

OBJECTIVES: This study was designed to assess the accuracy of two-dimensional and Doppler echocardiography in determining the mechanism of mitral regurgitation, as compared with direct inspection of the valve at operation. BACKGROUND: Valve repair for mitral regurgitation offers substantial advantages over valve replacement, but it is technically more demanding and requires understanding of the mechanism of dysfunction. METHODS: We studied 286 patients undergoing mitral valve repair. Intraoperative two-dimensional echocardiography was used to classify mitral leaflet motion as excessive, normal or restricted. Doppler color flow mapping was used to evaluate the direction and origin of the mitral regurgitant jet. Two-dimensional and Doppler echocardiography were compared with intraoperative surgical determination of the mechanism of dysfunction, which also classified leaflet motion as excessive, normal or restricted. RESULTS: Two-dimensional and Doppler echocardiography accurately diagnosed the mechanism of mitral regurgitation in 123 (93%) of 132 patients with posterior leaflet prolapse or flail, 30 (94%) of 32 patients with anterior leaflet prolapse or flail, 11 (44%) of 25 patients with bileaflet prolapse or flail, 6 (75%) of 8 patients with papillary muscle elongation or rupture, 31 (91%) of 34 patients with restricted leaflet motion or rheumatic thickening, 21 (72%) of 29 patients with ventricular-annular dilation and 8 (62%) of 13 patients with a leaflet perforation or cleft. Of 13 patients with two mechanisms of dysfunction by surgical inspection, two-dimensional and Doppler echocardiography correctly diagnosed one of the two mechanisms in 12 patients (92%), and both mechanisms in 5 patients (38%). Overall, echocardiographic determination of leaflet motion and Doppler determination of jet direction accurately diagnosed the mechanism of dysfunction in 242 (85%) of 286 patients. CONCLUSIONS: Echocardiography before mitral valvuloplasty provides a dynamic appraisal of the mechanism of dysfunction, enabling the surgeon to systematically understand the dysfunction and successfully apply the correct procedures to eliminate mitral regurgitation without valve replacement.

Instantaneous pressure gradient: a simultaneous Doppler and dual catheter correlative study.

To more precisely measure the beat to beat and instantaneous pressure gradients across outflow stenotic lesions, simultaneous Doppler and dual catheter pressure gradient measurements were performed in 95 patients (mean age 42 years, range 1.5 to 85). There were 38 right ventricular and 62 left ventricular outflow obstructive lesions. Forty-nine patients also had a nonsimultaneous Doppler study performed within 7 days before catheterization. The simultaneous pressure waveforms and Doppler spectral velocity profiles were digitized at 10 ms intervals deriving maximal, mean and instantaneous gradients (mm Hg). For simultaneous maximal Doppler and catheter gradient measurements, the correlation coefficient (r) was 0.95 (SEE = 10 mm Hg), for Doppler and catheter mean gradients it was 0.94 (SEE = 8 mm Hg) and for maximal Doppler and peak to peak catheter gradients it was 0.92 (SEE = 13 mm Hg). The correlation of maximal and mean Doppler gradients with the respective catheter gradients was similarly high when the right and left ventricular outflow lesions were analyzed separately. However, the maximal Doppler gradient was significantly higher than the peak to peak catheter gradient. This was more evident with left ventricular outflow stenotic lesions. The correlation of the outpatient maximal Doppler and catheter gradients (r = 0.80, SEE = 17 mm Hg) was significantly lower than the simultaneous correlation (r = 0.96, SEE = 10 mm Hg) in the 49 patients with two Doppler studies. Continuous wave Doppler echocardiography accurately measures the instantaneous pressure gradient across both left and right ventricular outflow obstructive lesions. The maximal Doppler gradient should not be equated with the peak to peak catheter gradient.(ABSTRACT TRUNCATED AT 250 WORDS)

Oral beta-adrenergic blockade with metoprolol in chronic severe dilated cardiomyopathy.

A double-blind crossover trial was performed to assess the effect of metoprolol in 10 patients (mean age 55 years) with severe dilated cardiomyopathy. All patients clinically had idiopathic dilated cardiomyopathy; however, at coronary angiography, four had occult coronary disease. All were in New York Heart Association functional class III with a left ventricular ejection fraction less than 35% as assessed by rest radionuclide ventriculography. Studies were performed before treatment, after 4 weeks of metoprolol therapy and after 4 weeks of placebo administration. Erect bicycle sprint exercise was used to determine maximal work load. Hemodynamic variables and radionuclide left ventricular ejection fraction were recorded at rest and during graded supine bicycle exercise. Cardiac medications were unchanged throughout the trial. The mean (+/- standard error of the mean) dose of metoprolol was 130 +/- 13 mg/day. Metoprolol did not change symptoms, chest X-ray findings or exercise tolerance (baseline 700 +/- 73, placebo 690 +/- 85, metoprolol 710 +/- 81 kilopond-meters [kpm]/min). Metoprolol produced a significant decrease in heart rate at rest and during exercise (p less than 0.001). Mean blood pressure and left ventricular filling pressure did not differ significantly in the baseline, placebo and metoprolol studies. There was a slight, but significant (p less than 0.05) decrease in cardiac index with metoprolol compared with placebo and baseline studies. The small, but significant increase in left ventricular ejection fraction from baseline to the metoprolol and placebo studies (p less than 0.001) was considered a result of spontaneous improvement rather than of therapy. No significant differences were found between the patients with and without coronary disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Extracardiac conduit obstruction: initial experience in the use of Doppler echocardiography for noninvasive estimation of pressure gradient.

Extracardiac valved conduits are often employed in the repair of certain complex congenital heart defects; late obstruction is a well recognized problem that usually requires catheterization for definitive diagnosis. A reliable noninvasive method for detecting conduit stenosis would be clinically useful in identifying the small proportion of patients who develop this problem. Continuous wave Doppler echocardiography has been used successfully to estimate cardiac valvular obstructive lesions noninvasively. Twenty-three patients with prior extracardiac conduit placement for complex congenital heart disease underwent echocardiographic and continuous wave Doppler echocardiographic examinations to determine the presence and severity of conduit stenosis. In 20 of the 23 patients, an adequate conduit flow velocity profile was obtained, and in 10 an abnormally increased conduit flow velocity was present. All but one patient had significant obstruction proven at surgery and in one patient, surgery was planned. In three patients, an adequate conduit flow velocity profile could not be obtained but obstruction was still suspected based on high velocity tricuspid regurgitant Doppler signals. In these three patients, subsequent surgery also proved that conduit stenosis was present. Doppler-predicted gradients and right ventricular pressures showed an overall good correlation (r = 0.90) with measurements at subsequent cardiac catheterization. Continuous wave Doppler echocardiography appears to be a useful noninvasive tool for the detection and semiquantitation of extracardiac conduit stenosis.

Comparison of supine and erect bicycle exercise electrocardiography in coronary heart disease: accentuation of exercise-induced ischemic ST depression by supine posture.

Exercise-induced electrocardiographic ST depression was compared during supine and erect graded bicycle exercise in 43 patients with chest pain but no prior myocardial infarct; all had greater than or equal to 1 mm of ST depression during either erect or supine exercise; 16 had multivessel, 24 had 1-vessel and 3 had no coronary artery disease. Supine exercise used 4 minutes/stage and erect exercise used either 4 minutes or 3 minutes/stage with identical graded work loads for both postures. Chest pain occurred in 31 patients during erect and in 29 during supine exercise. ST depression was greater than or equal to 1 mm in 28 patients during erect exercise and in all 43 during supine exercise (p less than 0.001); mean maximal ST depression was 1.3 +/- 0.2 mm during erect and 2.6 +/- 0.2 mm during supine exercise (p less than 0.001). Maximal work load was higher during erect than supine exercise (745 +/- 32 versus 678 +/- 32 kpm/min; p less than 0.001). The accentuation of ST depression by supine posture was not attributable to the changes in heart rate, rate-pressure product or mean blood pressure during supine versus erect exercise. In the 10 patients who had 2 erect bicycle tests using work load durations of 3 and 4 minutes, the maximal ST depression was not significantly different (erect 3 minutes 1.3 +/- 0.5 mm and erect 4 minutes 1.4 +/- 0.4 mm).(ABSTRACT TRUNCATED AT 250 WORDS)

Assessment of hemodynamic significance of isolated stenoses of the left anterior descending coronary artery using thallium-201 myocardial scintigraphy.

This study tests the hypothesis that the results of stress thallium-201 myocardial perfusion scans (TI-201) are related to the mean transstenotic pressure gradient of coronary stenoses independent of the percent luminal diameter narrowing seen at angiography. The 22 study patients (20 men, 2 women, mean age 47 years, range 30 to 62) had no previous myocardial infarction. Each underwent a symptom-limited, erect bicycle TI-201 test off antianginal therapy, shortly before percutaneous transluminal coronary angioplasty for isolated left anterior descending coronary artery stenosis. The percent narrowing, mean gradient at percutaneous transluminal coronary angioplasty and presence of a visually apparent TI-201 defect were independently evaluated and results compared. All 4 patients with 90% or greater diameter narrowing had positive TI-201 responses, and the mean gradient was 72 +/- 11 mm Hg. Among the 18 patients with less than 90% diameter narrowing, the mean gradient was higher (p less than 0.001) in the 11 with a positive TI-201 (63 +/- 15 mm Hg) than in the 7 with a negative TI-201 (33 +/- 20 mm Hg), but their percent narrowing did not differ significantly (72 +/- 14% vs 66 +/- 19%). Multiple regression analysis showed that the presence of a TI-201 defect was a strong (p = 0.003) and percent narrowing (p = 0.048) a weak independent predictor for gradient. When the mean gradient was normalized for the prestenotic pressure, both percent narrowing (p = 0.003) and TI-201 defects (p = 0.006) were significant independent predictors.(ABSTRACT TRUNCATED AT 250 WORDS)

Incremental value of clinical assessment, supine exercise electrocardiography, and biplane exercise radionuclide ventriculography in the prediction of coronary artery disease in men with chest pain.

The incremental value of clinical assessment, exercise electrocardiography (ECG) and biplane radionuclide ventriculography (RVG) in the prediction of coronary artery disease (CAD) was assessed in 105 men without myocardial infarction who were undergoing coronary angiography for investigation of chest pain. Independent clinical assessment of chest pain was made prospectively by 2 physicians. Graded supine bicycle exercise testing was symptom-limited. Right anterior oblique ECG-gated first-pass RVG and left anterior oblique ECG-gated equilibrium RVG were performed at rest and exercise. Regional wall motion abnormalities were defined by agreement of 2 of 3 blinded observers. A combined strongly positive exercise ECG response was defined as greater than or equal to 2 mm ST depression or 1.0 to 1.9 mm ST depression with exercise-induced chest pain. A multivariate logistic regression model for the preexercise prediction of CAD was derived from the clinical data and selected 2 variables: chest pain class and cholesterol level. A second model assessed the incremental value of the exercise test in prediction of CAD and found 2 exercise variables that improved prediction: RVG wall motion abnormalities, and a combined strongly positive ECG response. Applying the derived predictive models, 37 of the 58 patients (64%) with preexercise probabilities of 10 to 90% crossed either below the 10% probability threshold or above the 90% threshold and 28 (48%) also moved across the 5 and 95% thresholds. Supine exercise testing with ECG and biplane RVG together, but neither test alone, effectively adds to clinical prediction of CAD. It is most useful in men with atypical chest pain and when the ECG and RVG results are concordant.

Left ventricular outflow tract obstruction related to a valve prosthesis: case caused by a low-profile mitral prosthesis.

Mechanical and bioprosthetic mitral prostheses may have many potential complications. In patients with isolated mitral stenosis and a small left ventricular cavity, low-profile prostheses are recommended to avoid myocardial impingement that can result from a high-profile valve and lead to possible left ventricular inflow or outflow obstruction or ventricular arrhythmias. This case report illustrates that left ventricular outflow obstruction may also result from a low-profile mitral valve prosthesis. This obstruction was not diagnosed before cardiac catheterization. Assessment of patients with suspected prosthetic valve dysfunction is difficult and may necessitate cardiac catheterization or even direct surgical inspection for conclusive information.

Use of Doppler techniques (continuous-wave, pulsed-wave, and color flow imaging) in the noninvasive hemodynamic assessment of congenital heart disease.

Doppler echocardiography is a relatively new technique that has become an integral part of the cardiovascular ultrasound examination. The hemodynamic information provided by the Doppler technique is complementary to the tomographic anatomy depicted by the two-dimensional examination and, in some patients, may obviate the need for cardiac catheterization. In this article, we focus on the role of Doppler echocardiography in the noninvasive diagnosis of congenital cardiac abnormalities.

Continuous-wave Doppler determination of the pressure gradient across pulmonary artery bands: hemodynamic correlation in 20 patients.

The feasibility and accuracy of continuous-wave Doppler echocardiography in measuring pressure gradients across the pulmonary artery band were assessed. Simultaneous continuous-wave Doppler and catheter pressure measurements were prospectively performed in 20 patients with complex congenital heart disease and prior pulmonary artery banding. In two other patients, adequate Doppler signals could not be obtained. Doppler velocity was converted to pressure gradient by using the modified Bernoulli equation. Simultaneous continuous-wave Doppler spectral envelopes and catheter pressure wave forms were digitized at 10-ms intervals to obtain maximal instantaneous, mean, and peak-to-peak pressure gradients. The maximal Doppler gradient ranged from 23 to 154 mm Hg, and the simultaneous maximal catheter pressure gradient ranged from 34 to 168 mm Hg. The correlation (r) between these two measurements had a coefficient of 0.98 and a standard error of the estimate (SEE) of 7 mm Hg. The peak-to-peak systolic gradient ranged from 17 to 156 mm Hg and correlated with the maximal Doppler gradient (r = 0.95; SEE = 11 mm Hg). The mean Doppler and mean catheter pressure gradients also were correlated (r = 0.93; SEE = 9 mm Hg). As Doppler echocardiography measures instantaneous velocity and therefore instantaneous pressure gradient, the more precise correlation was between Doppler gradient and maximal instantaneous catheter gradient rather than peak-to-peak systolic gradient. Continuous-wave Doppler echocardiography is an accurate noninvasive technique for measurement of pressure gradients across pulmonary artery bands. In combination with clinical evaluation and two-dimensional echocardiography, it should substantially aid clinical decision making.

Diurnal variations in the feeding response to 8-OH-DPAT injected into the dorsal or median raphe.

To determine the impact on food intake of the 5-HT1A agonist, 8-OH-DPAT, administered at various times throughout the nocturnal cycle, rats were implanted with cannulae in either the dorsal or median raphe nuclei and injected with saline or 8-OH-DPAT (0.4, 0.8 or 1.6 nmol) immediately following dark onset, or during the mid or late dark periods. 8-OH-DPAT potentiated feeding when administered in the mid or late dark phase, whereas treatment during the early dark actually suppressed food intake. These findings indicate that the feeding responses to dorsal and median raphe 8-OH-DPAT vary greatly depending on the time of administration in the diurnal cycle and are consistent with recent reports of a biphasic action of this compound on ingestive behaviour.

Central injection of 5-hydroxytryptamine reduces food intake in obese and lean mice.

The effects of intracerebroventricular (ICV) administration of 5-hydroxytryptamine creatinine sulphate complex (5-HT), 35-140 nmol, on food intake in genetically obese (ob/ob) and lean mice were investigated. 5-HT (70-140 nmol) decreased feeding in a dose-related manner on 1 h and 2 h postinjection measures. Intake in lean mice was reduced by over 70% of the control condition. Obese mice, however, demonstrated a reduced sensitivity to the anorectic effect of 5-HT, and reduced 1 h intake by only 40% of saline control. Although these results are consisted with a role for serotonin in the control of food intake in mice, the altered sensitivity of the ob/ob to serotonergic stimulation may result, in part, from an impaired satiety control mechanism in this mutant.

Effect of the CCKA antagonist devazepide on eating stimulated by raphe injection of 8-OH-DPAT.

Several recent studies have suggested that feeding suppression is mediated jointly by enhanced neurotransmission of cholecystokinin (CCK) and serotonergic (5-HT) systems. In the present study the CCKA receptor antagonist devazepide (50-200 micrograms kg-1, s.c.) was found reliably to potentiate the feeding response elicited by dorsal or median raphe injection of the 5-HT1A agonist 8-OH-DPAT (0.2-0.8 nmol). This effect was evident following co-administration of both feeding threshold and subthreshold doses of either compound, suggesting that the simultaneous suppression of CCK and 5-HT function may interact as joint effectors of overeating.