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Biomedical subjects

R Sherwood

Publications and source records attributed to R Sherwood.

At least 19 recordsLinked to original sources
PubMed2006

Effect of fat distribution on endothelial-dependent and endothelial-independent vasodilatation in healthy humans.

AIM: The present study aims to explore the relationship between inflammatory cytokines, plasma lipids, insulin, blood pressure (BP), total adiposity/markers of fat distribution and endothelial function in healthy people across a wide range of body fatness. METHODS: Seventy-three healthy people (44 women; age range: 24-64 years) with body mass index (BMI) range of 18.6-73.1 kg/m2 were recruited. All participants underwent assessment of conduit artery endothelial-dependent vasodilatation by using flow-mediated vasodilatation (FMD) of the brachial artery and endothelial-independent vasodilatation to sublingual GTN. They had blood taken for measurement of plasma markers of glucose homeostasis (fasting insulin and glucose), systemic inflammation (interleukin-6 (IL-6), C-reactive protein (CRP) and tumour necrosis factor-alpha receptor 2 (TNF-alpha R2)) and lipids (low-density lipoprotein (LDL), high-density lipoprotein (HDL) and triglycerides). Morphometric assessment (waist circumference, BMI and waist-to-hip ratio (WHR)) and systolic and diastolic arterial pressure were also measured. RESULTS: Markers of total body fat/fat distribution (waist circumference, BMI and WHR), inflammation (IL-6, CRP and TNF-alpha R2), metabolism (fasting insulin, HDL, LDL and triglycerides) and BP (systolic and diastolic) correlated with FMD. Among these measurements, WHR was the only independent predictor of FMD (r2 = 0.30; p = 0.0001). CONCLUSIONS: WHR is an important marker of endothelial dysfunction in healthy people across a wide range of body fatness.

Adult↗
PubMed2002

Serum S100 concentrations are not useful in predicting micrometastatic disease in cutaneous malignant melanoma.

BACKGROUND: S100 protein is an acidic calcium binding protein that is expressed by melanoma cells. Elevated serum values of S100 have been described in metastatic disease and it has been suggested that it may be used as an adjunct to staging and monitoring of treatment. Micrometastatic disease in the sentinel lymph node can be demonstrated by sentinel node biopsy (SNB) and the sentinel node status is known to be the most important predictor of relapse. OBJECTIVES: To determine whether serum S100 concentrations could predict the presence of micrometastatic disease. METHODS: Thirty-one patients with primary cutaneous melanoma > 1 mm were recruited from referrals to the Melanoma clinic. All patients had serum S100 concentrations evaluated prior to undergoing SNB. Serum S100 concentrations were established using an immunoluminometric method. Sentinel nodes were identified using a dual technique with both radiolabelled colloid (residual from preoperative lymphoscintigraphy) and blue dye according to the MD Anderson Cancer Center protocol. Results Nine of these 31 patients had evidence of micrometastatic disease on SNB. The mean serum S100 concentration of those with positive SNBs was 0.027 microg L-1 compared with 0.045 microg x L(-1) in patients with negative SNBs (normal < 0.14 microg x L(-1)). No patient in the study demonstrated raised concentrations of serum S100. CONCLUSIONS: We conclude that serum S100 concentrations do not predict the presence of micrometastatic melanoma in sentinel nodes in primary cutaneous melanoma.

Biomarkers, Tumor↗
PubMed2002

Glucose, insulin and potassium for heart protection during cardiac surgery.

BACKGROUND: Coronary artery bypass grafting with hypothermic cardiac arrest and cardiopulmonary bypass (CPB) is associated with myocardial injury. Our study investigated whether an infusion of glucose, insulin and potassium (GIK) during elective coronary artery bypass surgery decreases myocardial cell death. METHODS: We measured cardiac troponin I (cTnI), a myofibrillar structural protein, which is a sensitive and specific indicator of myocytic injury. With ethics committee approval, 42 patients were enrolled into a randomized, prospective, double-blinded study. In the GIK group, 500 ml of 50% dextrose solution containing 100 IU insulin and potassium 80 mmol was infused at the rate of 0.75 ml kg(-1) h(-1). Patients in the non-GIK group received 5% dextrose solution at the same rate. Arterial blood samples were taken before induction of anaesthesia, after removal of the aortic clamp and 6 and 12 h after CPB. RESULTS: In both groups there was an increase in cTnI concentration (P<0.05), which was greatest about 6 h after CPB. At no time did the cTnI concentration differ between the two groups. CONCLUSION: The results suggest that GIK does not decrease the irreversible myocardial damage associated with routine coronary artery bypass surgery.

Aged↗
PubMed2002

Proportional assist ventilation as an aid to exercise training in severe chronic obstructive pulmonary disease.

BACKGROUND: The effects of providing ventilatory assistance to patients with severe chronic obstructive pulmonary disease (COPD) during a high intensity outpatient cycle exercise programme were examined. METHODS: Nineteen patients (17 men) with severe COPD (mean (SD) forced expiratory volume in 1 second (FEV(1)) 27 (7)% predicted) underwent a 6 week supervised outpatient cycle exercise programme. Ten patients were randomised to exercise with ventilatory assistance using proportional assist ventilation (PAV) and nine (two women) to exercise unaided. Before and after training patients performed a maximal symptom limited incremental cycle test to determine peak work rate (Wpeak) followed by a constant work rate (CWR) test at 70% of Wpeak achieved in the baseline incremental test. Minute ventilation (VE), heart rate, and arterialised venous plasma lactate concentration [La(+)] were measured before and after each test. RESULTS: Mean training intensity (Wt/Wpeak) at 6 weeks was 15.2% (95% CI 3.2 to 27.1) higher in the group that used ventilatory assistance (p=0.016). Peak work rate after training was 18.4% (95% CI 6.4 to 30.5) higher (p=0.005) in the assisted group (p=0.09). [La(+)] at an identical workload after training was reduced by 30% (95% CI 16 to 44) in the assisted group (p=0.002 compared with baseline) and by 11% (95% CI -7 to 31) (p=0.08 compared with baseline) in the unassisted group (mean difference 18.4% (95% CI 3.3 to 40), p=0.09). A significant inverse relationship was found between reduction in plasma lactate concentration (DeltaL) at an equivalent workload after training during the CWR test and Wt/Wpeak achieved during the last week of training (r=-0.7, p=0.0006). CONCLUSIONS: PAV enables a higher intensity of training in patients with severe COPD, leading to greater improvements in maximum exercise capacity with evidence of true physiological adaptation.

Aged↗
PubMed2001

In vivo protein synthetic rates of atrial, ventricular, and pulmonary tissue proteins in aortic constriction, goldblatt, and bromoethylamine models of hypertension.

Changes in tissue protein synthesis in hypertension have usually been measured in vitro in heart from acutely hypertensive rats without consideration of changes in atrial or pulmonary tissue or changes occurring in long-standing hypertension. The objective of the study was to investigate the in vivo changes in cardiopulmonary protein synthesis in three different rat models of chronic hypertension. Hypertension in aortic constriction, the Goldblatt model, and the bromoethylamine model were induced in rats for 30 days. At the end of the experimental period, in vivo rates of protein synthesis were measured with a flooding dose of [3H]phenylalanine (a method which effectively considers precursor pools). Concomitant measurements included quantification of contractile protein and RNA and DNA contents. Indices of protein breakdown were also assessed by selective measurement of protease activities. At the end of 30 days, aortic constriction induced marked increases in protein contents of the left ventricle, septum, left atria, and lungs. Accompanying changes included concomitant increases in RNA and DNA contents. Left ventricular myofibrillary, sarcoplasmic, and stromal protein contents increased in the aortic constriction model. Less marked changes occurred in the Goldblatt model, though the left atria were not significantly affected. In contrast, the bromoethylamine model had no effect on the protein or RNA contents of any region. In all cardiac regions of all three models, fractional rates of protein synthesis were not significantly affected. However, protein synthesis increased in the lungs of both the Goldblatt and bromoethylamine models at 30 days. Protease activities were decreased in the left ventricles of all three models at 30 days, with lysosomal protease activities declining in the aortic constriction model and cytoplasmic protease activities declining in the other two models. The failure of chronic hypertension to increase ventricular synthesis rates may represent inherent limitations in the time frame for measuring protein synthesis in vivo. However, at earlier time points (i.e., 10 days), the aortic constriction model was characterized by marked increases in left ventricular and atrial protein contents, RNA contents, and fractional rates of protein synthesis. This was consistent with the supposition that, in acute phases of hypertrophy, rates of protein synthesis increase, whereas in established hypertrophy, synthesis rates remain unchanged or decrease. The applicability of the aortic constriction model was investigated by examining the effects of the angiotensin converting enzyme inhibitor lisinopril (5 mg/kg/day). After 30 days treatment, lisinopril impeded the increase in left ventricular mixed and myofibrillar proteins. This effect was accompanied by an apparent increase in protein synthesis. In conclusion, although all three chronic models are able to induce hypertension, varying degrees of hypertrophy develop, which are more pronounced in the aortic constriction model. Accompanying changes include hypertrophy in the atria, reduced rates of ventricular proteolytic activity, and altered rates of protein metabolism in the lungs.

Animals↗
PubMed2001

The Interdisciplinary Generalist Curriculum (IGC) project: an overview of its experience and outcomes.

The Interdisciplinary Generalist Curriculum (IGC) Project was a competitive, seven-year demonstration project funded by the Health Resources and Services Administration (HRSA). It was established to determine whether specific interdisciplinary innovations in preclinical medical school curricula could affect students' selection of careers in family medicine, general internal medicine, or general pediatrics. Through collaboration among the three generalist disciplines, the IGC innovation exposed all preclinical students in ten demonstration schools to a new or significantly enhanced preclinical curriculum that included a direct supervised clinical experience with a generalist physician preceptor. The project was managed by an interdisciplinary executive committee that was codirected by one representative each from family medicine, general internal medicine, and general pediatrics. A national advisory committee with representation from the academic and professional organizations of family medicine, internal medicine, pediatrics, and osteopathy provided input to the executive committee in guiding the project. The project was externally evaluated. Major outcomes of the IGC Project include sustained curricular changes in ten institutions, prompted by relatively few dollars and demonstration of models for collaboration at institutional and national levels. This supplement describes the IGC Project's experience and outcomes so that others may draw pertinent information to apply to their own efforts in medical education.

Curriculum↗
PubMed2001

Curricular change: recommendations from a national perspective.

Recommendations on future directions, funding, and organizational and curricular issues have emerged from the complexity of the Interdisciplinary Generalist Curriculum (IGC) Project. For example, future demonstration projects aimed at innovations in medical education that are funded through the contracting mechanism are recommended, and funding intended to serve as institutional leverage for demonstrating desired curricular innovations in medical education is encouraged. Funding provided to entities that can maximize influence within the institutions is recommended. Also, the period of time over which funds are provided needs to take into consideration the breadth of the impact of the funded program on the larger curriculum and the length of time needed to measure desired outcomes. Organizational findings are that multi-site projects with administrative oversight bodies should be governed by representatives of concerned disciplines who have stakes in the demonstration of the innovations in medical education, and roles of the executive and advisory committees involved in the effort need to be made explicit at the onset and revisited over time. Similarly, the role of the funder needs to be explicit. Curricular recommendations are that medical schools are encouraged to develop longitudinal generalist preceptorship experiences early in medical education for all students, regardless of their eventual career choices. Schools should anticipate that curricular innovations in the preclinical years may require modifications of the educational process in the clinical years.

Curriculum↗
PubMed2001

Faecal calprotectin and faecal occult blood tests in the diagnosis of colorectal carcinoma and adenoma.

BACKGROUND AND AIMS: Testing for faecal occult blood has become an accepted technique of non-invasive screening for colorectal neoplasia but lack of sensitivity remains a problem. The aim of this study was to compare the sensitivity and specificity of faecal calprotectin and faecal occult blood in patients with colorectal cancer and colonic polyps. METHODS: Faecal calprotectin and occult blood were assessed in 62 patients with colorectal carcinoma and 233 patients referred for colonoscopy. The range of normality for faecal calprotectin (0.5-10.5 mg/l) was determined from 96 healthy subjects. RESULTS: Median faecal calprotectin concentration in the 62 patients with colorectal carcinoma (101 mg/l, 95% confidence interval (CI) 57-133) differed significantly from normal (2.3 mg/l, 95% CI 1.6-5.0) with 90% of patients having elevated levels (normal <10 mg/l) whereas only 36/62 (58%) had positive faecal occult bloods. There was no significant difference in faecal calprotectin levels when considering location or Dukes' staging of tumour. Percentage positivity of faecal occult bloods was significantly higher for Dukes' stage C and D cancers compared with Dukes' A and B. In the colonoscopy group, 29 patients with adenomatous polyps were detected in whom the median faecal calprotectin was 12 mg/l (95% CI 2.9-32). Sensitivity for detection of adenomatous polyps was 55% using the calprotectin method and 10% using faecal occult blood testing. The overall sensitivity and specificity of calprotectin for colorectal cancer and adenomatous polyps as a combined group was 79% and 72%, respectively, compared with a sensitivity and specificity of faecal occult blood of 43% and 92%. CONCLUSIONS: Faecal calprotectin is a simple and sensitive non-invasive marker of colorectal cancer and adenomatous polyps. It is more sensitive than faecal occult blood tests for detection of colorectal neoplasia at the cost of a somewhat lower specificity.

Adenoma↗
PubMed2000

A quantitative evaluation of the permeability of the blood brain barrier of portacaval shunted rats.

The integrity of the blood-brain barrier (BBB) was measured in male Sprague Dawley rats subjected to 16 weeks of portacaval shunting (PCS), the optimal time required for the cerebral changes to develop, by using an in situ brain perfusion technique. The penetration of a vascular space marker 14C mannitol, and labelled amino acids 3H-phenylalanine or 3H-glutamate were measured in brain and cerebrospinal fluid (CSF) using an in situ brain perfusion technique, over 2 or 20 minutes. The patency of the surgical shunt was confirmed by measurement of significantly increased plasma ammonia (131.5 +/- 14.8 micromol x l(-1)) and AST (159.5 +/- 19.9 IU x l(-1)) concentrations compared to controls 39.9 +/- 3.7*, and 82.5 +/- 6.6* respectively. Brain and CSF 14C-mannitol space (ml x 100g(-1)), was not increased by PCS where brain space was 1.31 +/- 0.27 mL x 100g(-1) compared to control 1.19 +/- 0.49 mL x 100g(-1), and CSF was 0.14 +/- 0.06 mL x 100g(-1) compared to control 0.15 +/- 0.05 (PCS n=10, control n=8). The uptake for 3H-glutamate, which is required for cerebral ammonia detoxification, was also unchanged in both brain and CSF. However, brain uptake of 3H-phenylalanine was significantly reduced from 871 +/- 80 microL x min(-1) x g(-1) to 356 +/- 154* microl x min(-1) x g(-1) (n=4), although there was no change in CSF uptake. These data suggest that there is no generalized breakdown of the blood-brain or blood-CSF barriers during PCS as assessed by mannitol penetration. The reduction in phenylalanine uptake into the brain may help stabilize high cerebral aromatic amino acid levels. *P<0.05, Two-tailed, Student's unpaired t-test.

Acetates↗
PubMed2000

The prevalence and severity of intestinal disaccharidase deficiency in human immunodeficiency virus-infected subjects.

BACKGROUND: Gastrointestinal symptoms are distressing features of human immunodeficiency virus (HIV) infection, and management is often empirical, including withdrawal of dietary lactose. We assessed the prevalence and severity of intestinal disaccharidase deficiency in vitro and in vivo. METHODS: Fifty-four HIV-seropositive patients (19 HIV well +/- mild diarrhoea, 7 acquired immunodeficiency syndrome (AIDS) well, and 28 AIDS with diarrhoea) were studied with a combined non-invasive absorption-permeability-disaccharidase test that enables quantitative assessment of the rate of intestinal hydrolysis of lactose, sucrose, and palatinose. Thirty patients had jejunal biopsy specimens suitable for histomorphometric assessment, and 36 had in vitro disaccharidase activity measurement. RESULTS: Patients with HIV (with mild diarrhoea) and AIDS (with and without severe diarrhoea) had frequent but mild histomorphometric changes in jejunal specimens. This was associated with frequent (21%-100%) and often severe in vitro jejunal disaccharidase deficiency. In vivo hydrolysis of lactose, sucrose, and palatinose was impaired in 25%-75% of patients, apart from HIV well patients, who were normal. The prevalence of the in vivo lactase and sucrase deficiency was significantly (P < 0.006) lower than in vitro and severe in about 30%. CONCLUSIONS: Intestinal disaccharidase deficiency is common both in vitro and in vivo in HIV-seropositive patients but sufficiently severe to consider lactose withdrawal only in about a quarter of the patients with AIDS and diarrhoea.

Acquired Immunodeficiency Syndrome↗
PubMed2000

A simple method for assessing intestinal inflammation in Crohn's disease.

BACKGROUND AND AIMS: Assessing the presence and degree of intestinal inflammation objectively, simply, and reliably is a significant problem in gastroenterology. We assessed faecal excretion of calprotectin, a stable neutrophil specific marker, as an index of intestinal inflammation and its potential use as a screening test to discriminate between patients with Crohn's disease and those with irritable bowel syndrome. METHODS: The validity of faecal calprotectin as a marker of intestinal inflammation was assessed in 22 patients with Crohn's disease (35 studies) by comparing faecal excretions and concentrations using four day faecal excretion of (111)indium white cells. A cross sectional study assessed the sensitivity of faecal calprotectin concentration for the detection of established Crohn's disease (n=116). A prospective study assessed the value of faecal calprotectin in discriminating between patients with Crohn's disease and irritable bowel syndrome in 220 patients referred to a gastroenterology clinic. RESULTS: Four day faecal excretion of (111)indium (median 8.7%; 95% confidence interval (CI) 7-17%; normal <1.0%) correlated significantly (p<0.0001) with daily (median ranged from 39 to 47 mg; normal <3 mg; r=0.76-0.82) and four day faecal calprotectin excretion (median 101 mg; 95% CI 45-168 mg; normal <11 mg; r=0.80) and single stool calprotectin concentrations (median 118 mg/l; 95% CI 36-175 mg/l; normal <10 mg/l; r=0.70) in patients with Crohn's disease. The cross sectional study showed a sensitivity of 96% for calprotectin in discriminating between normal subjects (2 mg/l; 95% CI 2-3 mg/l) and those with Crohn's disease (91 mg/l; 95% CI 59-105 mg/l). With a cut off point of 30 mg/l faecal calprotectin has 100% sensitivity and 97% specificity in discriminating between active Crohn's disease and irritable bowel syndrome. CONCLUSION: The calprotectin method may be a useful adjuvant for discriminating between patients with Crohn's disease and irritable bowel syndrome.

Adolescent↗
PubMed2000

Inspiratory pressure support prolongs exercise induced lactataemia in severe COPD.

BACKGROUND: A physiological benefit from pulmonary rehabilitation in chronic obstructive pulmonary disease (COPD) is more probable if exercise is performed above the lactate threshold. This study was undertaken to investigate whether it was possible to extend the lactataemia of exercise using non-invasive inspiratory pressure support (IPS). METHODS: Plasma lactate levels were measured in eight men with severe COPD who performed two treadmill walks at an identical constant work rate to a condition of severe dyspnoea; the second walk was supported by IPS. RESULTS: Mean plasma lactate levels before the free and IPS assisted walks were 1.65 mmol/l and 1. 53 mmol/l, respectively (p = NS). Lactate levels increased during both walks to 2.96 mmol/l and 2.42 mmol/l, respectively (p = 0.01 for each) but the duration of the IPS assisted walk was significantly greater than the free walk (13.6 minutes versus 5.5 minutes, p = 0.01). CONCLUSIONS: Patients with severe COPD can sustain exercise induced lactataemia for longer if assisted with IPS. This technique may prove to be a useful adjunct in pulmonary rehabilitation.

Acidosis, Respiratory↗
PubMed2000

Comparison of five cyclosporin immunoassays with HPLC.

High performance liquid chromatography (HPLC) is the reference method for cyclosporin (CyA) measurements but therapeutic monitoring of the drug is frequently made using the more practical immunoassays. Cross-reactivity with CyA metabolites may compromise the specificity of immunoassays, particularly in liver graft recipients where metabolites may accumulate. The aim of this study was to compare with HPLC the performance of two recently introduced CyA immunoassays (the AxSYM fluorescent polarisation immunoassay (FPIA) and non-extraction CEDIA assay). The comparison was extended to the well-established TDx monoclonal FPIA (TDx mono) and the enzyme multiplied (EMIT)-specific assays and to the polyclonal FPIA (TDx poly), in which metabolite cross-reactivity is extensive. Assays were performed on 106 blood samples (taken 6 days to 118 months post-liver transplant) and results were compared by non-parametric regression analysis and difference plots. AxSYM and CEDIA showed both constant and proportional bias against HPLC (unlike EMIT) but the mean difference from HPLC was least for AxSYM (2.7 microg/l vs. 11.7, 9.4 and 54 microg/l for CEDIA, EMIT and TDx mono, respectively. (TDx poly - HPLC) values were proportional to all immunoassay results, with slopes of 0.33, 0.38 and 0.45 for EMIT, AxSYM and CEDIA, respectively. Our data suggest close agreement between AxSYM, CEDIA and EMIT results.

Chromatography, High Pressure Liquid↗
PubMed1999

Screening for hypercholesterolaemia in 10,000 neonates in a multi-ethnic population.

UNLABELLED: An immunoassay was developed for the detection of hypercholesterolaemia in dried blood spots collected from 6-day-old neonates. Blood spot samples (9,673) were subjected to immunoturbidimetric assay to determine the levels of apolipoprotein B (apoB), an index of plasma low density lipoprotein, and of apolipoprotein A-1 (apoA-1), an index of plasma high density lipoprotein. Infants with raised apoB or a reduced apoA-1/apoB ratio were recalled, retested and, if appropriate, referred to the Vascular Risk Clinic at King's College Hospital for medical management. A total of 189 were recalled for further testing; of whom 82 (45%) attended the recall clinic. A group of 16 families (24 individuals) had abnormal lipid profiles; of these, 7 families (14 individuals) had lipid profiles consistent with inherited hypercholesterolaemia. CONCLUSION: Neonatal screening for hypercholesterolaemia using blood spot apolipoprotein measurements is feasible but ethnic variations in disease prevalence must be considered in the design of a screening programme.

Adult↗
PubMed1999

Small intestinal transit, absorption, and permeability in patients with AIDS with and without diarrhoea.

BACKGROUND: Diarrhoea in AIDS is associated with anorexia and weight loss. The importance of gastrointestinal transit in such symptoms has not been addressed. AIMS: To assess jejunal to caecal transit times in subjects with AIDS related diarrhoea and weight loss and correlate these with measures of absorptive capacity and intestinal permeability. METHODS: Jejunal to caecal transit times were assessed in 20 seronegative controls and 60 HIV seropositive subjects from serum analysis of 3-O-methyl-D-glucose and sulphapyridine after ingestion of the monosaccharide and sulphasalazine in aqueous solution. The method also allows an estimation of gastric emptying times for liquids. Intestinal absorptive capacity and permeability were assessed by a combined test using 3-O-methyl-D-glucose, D-xylose, L-rhamnose, and lactulose. RESULTS: Gastric emptying was significantly delayed in all groups of patients with AIDS. Mean jejunal to caecal transit times were not significantly different between controls (246 (62) minutes) and patients without diarrhoea (AIDS, well: 278 (103) minutes; AIDS, wasting: 236 (68) minutes), cytomegalovirus colitis (289 (83) minutes), pathogen negative diarrhoea (192 (100) minutes), or microsporidiosis (190 (113) minutes), although 30% of patients had values below the control range. Patients with cryptosporidiosis differed significantly from controls (135 (35) minutes, p<0.0001), seven of 10 having rapid transit times. Absorptive capacity was reduced and intestinal permeability significantly increased in AIDS, but did not correlate significantly with transit times. CONCLUSION: Small bowel transit is accelerated in many patients with AIDS, particularily in protozoal diarrhoea, but is not the sole explanation for malabsorption of monosaccharides.

AIDS-Related Opportunistic Infections↗
PubMed1999

Trait hostility and prolactin response to tryptophan enhancement/depletion.

This study investigated the relationship between trait hostility and aspects of serotonergic function by assessing the prolactin (PRL) response to acute tryptophan depletion and enhancement in 28 healthy male volunteers. Serum PRL was assessed immediately before, and 4.5 h after, administration of an amino acid drink enhanced with, or depleted of, the 5-HT precursor tryptophan. Trait hostility and DeltaPRL (value at 4.5 h minus baseline) correlated negatively following enhancement and positively following depletion, indicating that the higher the hostility the smaller the change in PRL in either direction. This is consistent with previous research reporting an association between aggression and blunted neuroendocrine responses to serotonergic agents. The results indicate the possibility that, in people high on hostility, part of the serotonergic pathway that leads to modulation of PRL release is characterised by a stage with either low capacity relative to input availability or a strong negative feedback component.

Adolescent↗