The paediatric thymus: recognising normal and ectopic thymic tissue.

The appearance of the paediatric thymus changes as the normal process of thymic involution occurs. Thymic tissue may be orthotopic within the anterior mediastinum or ectopically located along the course of its embryological development. The variable appearance of orthotopic and ectopic thymic tissue in children on imaging studies may lead to misinterpretation of the normal thymus as pathology. Recognition of normal thymic tissue can mitigate unnecessary further diagnostic testing and patient anxiety. In this review, we discuss the embryological development and anatomical variants of normal thymus, and demonstrate the multimodality imaging features of the normal thymus in children, including positron-emission tomography, and diffusion-weighted imaging and in- and opposed-phase imaging on magnetic resonance imaging. We demonstrate the normal thymus mimicking pathological processes and discuss features that distinguish normal thymus, including thymic rebound hyperplasia, from pathology.

Iatrogenic endometriosis harbors somatic cancer-driver mutations.

STUDY QUESTION: Does incisional endometriosis (IE) harbor somatic cancer-driver mutations? SUMMARY ANSWER: We found that approximately one-quarter of IE cases harbor somatic-cancer mutations, which commonly affect components of the MAPK/RAS or PI3K-Akt-mTor signaling pathways. WHAT IS KNOWN ALREADY: Despite the classification of endometriosis as a benign gynecological disease, it shares key features with cancers such as resistance to apoptosis and stimulation of angiogenesis and is well-established as the precursor of clear cell and endometrioid ovarian carcinomas. Our group has recently shown that deep infiltrating endometriosis (DE), a form of endometriosis that rarely undergoes malignant transformation, harbors recurrent somatic mutations. STUDY DESIGN, SIZE, DURATION: In a retrospective study comparing iatrogenically induced and endogenously occurring forms of endometriosis unlikely to progress to cancer, we examined endometriosis specimens from 40 women with IE and 36 women with DE. Specimens were collected between 2004 and 2017 from five hospital sites in either Canada, Germany or the Netherlands. IE and DE cohorts were age-matched and all women presented with histologically typical endometriosis without known history of malignancy. PARTICIPANTS/MATERIALS, SETTING, METHODS: Archival tissue specimens containing endometriotic lesions were macrodissected and/or laser-capture microdissected to enrich endometriotic stroma and epithelium and a hypersensitive cancer hotspot sequencing panel was used to assess for presence of somatic mutations. Mutations were subsequently validated using droplet digital PCR. PTEN and ARID1A immunohistochemistry (IHC) were performed as surrogates for somatic events resulting in functional loss of respective proteins. MAIN RESULTS AND THE ROLE OF CHANCE: Overall, we detected somatic cancer-driver events in 11 of 40 (27.5%) IE cases and 13 of 36 (36.1%) DE cases, including hotspot mutations in KRAS, ERBB2, PIK3CA and CTNNB1. Heterogeneous PTEN loss occurred at similar rates in IE and DE (7/40 vs 5/36, respectively), whereas ARID1A loss only occurred in a single case of DE. While rates of detectable somatic cancer-driver events between IE and DE are not statistically significant (P > 0.05), KRAS activating mutations were more prevalent in DE. LIMITATIONS, REASONS FOR CAUTION: Detection of somatic cancer-driver events were limited to hotspots analyzed in our panel-based sequencing assay and loss of protein expression by IHC from archival tissue. Whole genome or exome sequencing, or epigenetic analysis may uncover additional somatic alterations. Moreover, because of the descriptive nature of this study, the functional roles of identified mutations within the context of endometriosis remain unclear and causality cannot be established. WIDER IMPLICATIONS OF THE FINDINGS: The alterations we report may be important in driving the growth and survival of endometriosis in ectopic regions of the body. Given the frequency of mutation in surgically displaced endometrium (IE), examination of similar somatic events in eutopic endometrium, as well as clinically annotated cases of other forms of endometriosis, in particular endometriomas that are most commonly linked to malignancy, is warranted. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by a Canadian Cancer Society Impact Grant [701603, PI Huntsman], Canadian Institutes of Health Research Transitional Open Operating Grant [MOP-142273, PI Yong], the Canadian Institutes of Health Research Foundation Grant [FDN-154290, PI Huntsman], the Canadian Institutes of Health Research Project Grant [PJT-156084, PIs Yong and Anglesio], and the Janet D. Cottrelle Foundation through the BC Cancer Foundation [PI Huntsman]. D.G. Huntsman is a co-founder and shareholder of Contextual Genomics Inc., a for profit company that provides clinical reporting to assist in cancer patient treatment. R. Aguirre-Hernandez, J. Khattra and L.M. Prentice have a patent MOLECULAR QUALITY ASSURANCE METHODS FOR USE IN SEQUENCING pending and are current (or former) employees of Contextual Genomics Inc. The remaining authors have no competing interests to declare. TRIAL REGISTRATION NUMBER: Not applicable.

Recurrent congestive heart failure in a child due to probable myocarditis.

Recurrent congestive heart failure (CHF) attributable to myocarditis is a seldom-discussed entity in the scientific literature. This report describes the case of an 8-year-old girl who had three clinically identical episodes of CHF, beginning at the age of 5 years, with each episode preceded by a viral prodrome. The clinical features and the echocardiography and electrocardiogram findings were most supportive of myocarditis. Symptoms and investigations completely normalized between episodes. The third episode, associated with influenza A (strain H1N1) infection, led to cardiac arrest and death on day 2 after admission. Autopsy showed mild cardiomegaly with microscopic foci of myocardial fibrosis and extensive contraction band necrosis. This report is the first to describe recurrent CHF due to probable myocarditis in a pediatric patient.

Pore-expanded SBA-15 sulfonic acid silicas for biodiesel synthesis.

Here we present the first application of pore-expanded SBA-15 in heterogeneous catalysis. Pore expansion over the range 6-14 nm confers a striking activity enhancement towards fatty acid methyl ester (FAME) synthesis from triglycerides (TAG), and free fatty acid (FFA), attributed to improved mass transport and acid site accessibility.

Clinicopathological significance of survivin expression in patients with hepatocellular carcinoma.

AIMS: Survivin, a newly discovered member of the inhibitor of apoptosis protein family, is suggested to be involved in liver carcinogenesis. The aim was to investigate the clinical significance of survivin expression in resected hepatocellular carcinoma (HCC) and paired adjacent non-tumour tissue. METHODS AND RESULTS: Immunohistochemistry, reverse transcriptase-polymerase chain reaction and Western blots were used to examine survivin mRNA and protein levels in 94 specimens of HCC tissues at different TNM stages and the data were correlated with the clinicopathological profiles. Patients were categorized into those with high tumour survivin protein levels (T-N >or= -1) and those with low levels (T-N < -1). Follow-up data were collected prospectively. mRNA levels of survivin and its splice variants in tumour tissue were significantly higher than in paired non-tumour tissue. However, survivin protein levels in paired non-tumour tissue were significantly higher than in tumour tissue from all three TNM stages. Additionally, high tumour survivin protein levels (T-N >or= -1) correlated with a better prognosis and low levels (T-N < -1) with a worse survival rate. CONCLUSIONS: High cytoplasmic survivin protein levels in HCC tissues seem to be an indicator of better prognosis in HCC patients after resection.

Treatment persistence: a comparison among patients with schizophrenia who were initiated on atypical antipsychotic agents.

BACKGROUND: Although clinical trials have demonstrated the efficacy of atypical antipsychotic agents in reducing symptoms of schizophrenia, the likelihood of sustaining control of schizophrenic symptoms may depend on treatment persistence. OBJECTIVE: In this study, we compared treatment persistence between patients who were initiated on risperidone or olanzapine, the two most widely prescribed atypical antipsychotic agents. METHOD: We identified patients with schizophrenia by ICD-9-CM codes (> or =1 inpatient or > or =2 outpatient ICD-9-CM codes > or =7 days apart) between 1 July 1998 and 30 June 1999. We further selected those who were prescribed the target drug during 1 April 1999 through 31 March 2000 provided that they were not on any antipsychotic agents during the prior 6 months. Using event history analysis, we compared the treatment persistence in terms of hazard ratio between olanzapine and risperidone initiators, adjusting for patient's sociodemographic and clinical characteristics. RESULTS: Following the initiation of the target drug, more patients switched from risperidone to olanzapine than vice versa. However, among patients with schizophrenia who had comorbid diabetes, there were more patients who made a switch from olanzapine to risperidone; whereas among those who used anxiolytics, there were more patients who switched from risperidone to olanzapine. Finally, olanzapine initiators had decreased hazards of discontinuation by 14% (unadjusted; P < 0.001) and 12% (adjusted; P = 0.002), respectively, than risperidone initiators. CONCLUSIONS: Compared with risperidone, olanzapine seems to be better tolerated by patients as indicated by better treatment persistence. As such, initiation of olanzapine may increase the likelihood of sustaining control of symptoms of schizophrenia. Future research needs to provide a more comprehensive assessment of treatment persistence by considering other antipsychotic agents in the study and developing models to assess treatment persistence and switching as two interdependent competing risks.

Adjunctive use of atypical antipsychotics and anticholinergic drugs among patients with schizophrenia.

BACKGROUND: Treatment of schizophrenia with antipsychotics is often associated with extrapyramidal symptoms (EPS), a disorder involving involuntary muscle movement. Because EPS are often associated with the use of antipsychotics, anticholinergic agents are often indicated. OBJECTIVE: In this observational, retrospective study, we examined whether the initiation of olanzapine or risperidone, the two most widely prescribed atypical antipsychotics, is related to the adjunctive use of anticholinergic agents. METHOD: We identified patients with schizophrenia from outpatient clinics in the Veterans Health Administration (VA) and defined initiation of olanzapine or risperidone as patients who were not on any antipsychotics for 6 months and subsequently initiated on the target drug between 1/4/1999 and 31/3/2000. The data were analysed using tests of means or chi-square tests. RESULTS: The study yielded two major findings. First, compared with risperidone initiators, there were significantly fewer olanzapine initiators who used at least one anticholinergic agent adjunctively. Secondly, among olanzapine or risperidone initiators, patients who used at least one anticholinergic agent adjunctively tended to stay on the target drug significantly longer than those who did not use any anticholinergic agent adjunctively with the target drug. CONCLUSION: As the use of anticholinergics is a proxy for the presence of EPS, these findings suggest that risperidone may be more associated with EPS than olanzapine. However, to assess the benefits and side effects associated with olanzapine or risperidone, future research needs to examine various patient outcomes resulting from the initiation of each drug.

Initiation of atypical antipsychotic agents and health outcomes in patients with schizophrenia.

BACKGROUND: Although pharmacological treatments are available for patients with schizophrenia, there is a lack of systematic and comprehensive evaluation of health outcomes following the initiation of atypical antipsychotic agents. OBJECTIVE: To assess the effects of the initiation of olanzapine or risperidone, the two most widely prescribed atypical antipsychotics, on patients' health outcomes, as measured by changes in patient clinical characteristics between 6 months prior to and post-initiation. METHOD: We identified patients with schizophrenia by >1 inpatient or > or = 2 outpatient ICD-9-CM codes (> or = 7 days apart) between 1 July 1998 and 30 June 1999, and those who were initiated on olanzepine or risperidone during the period 1 April 1999 to 31 March 2000 inclusive. We then subdivided these patients into three groups: (i) those who were not on olanzapine or risperidone, (ii) those who were not on any atypical agents, and (iii) those who were not on any antipsychotic agents, for 6 months prior to being issued with the new prescription. Using test of means or chi-square tests, we examined whether the initiation of olanzapine or risperidone is related to different changes in patient clinical indicators, such as number of drugs for psychiatric conditions, use of psychiatric services, and use of non-psychiatric services. RESULTS: Between pre- and post-initiation, olanzapine initiators had a greater decrease in the number of psychiatric hospitalizations and use of psychotropic agents, whereas risperidone initiators had a greater reduction in the number of non-psychiatric hospitalizations. The initiation of olanzapine and risperidone appear to be associated with different patient health outcomes. Compared with olanzapine initiators, risperidone initiators had a greater increase in the use of treatments related to mental health, but had greater decrease in the use of treatments related to physical health. CONCLUSION: Despite olanzapine and risperidone being often perceived as similar antipsychotic agents, our results suggest that the clinical outcomes associated with their use are different. Outcome data from routine clinical practice are required to provide a more comprehensive assessment of these drugs.

Pulsatile ocular blood flow of choroidal neovascularization in asymmetric age-related macular degeneration after transpupillary thermotherapy.

PURPOSE: A previous study has shown that the pulsatile ocular blood flow (POBF) in eyes with asymmetric age-related macular degeneration (AMD) differs. Whereas eyes with drusen have higher POBF than contralateral eyes with disciform scarring, the POBF of eyes with drusen is lower relative to contralateral eyes with choroidal neovascularization (CNV). This study was designed to assess whether the POBF of eyes with CNV changes after transpupillary thermotherapy (TTT), using the contralateral eyes with drusen or scarring without TTT as controls. METHODS: In total, 26 patients with CNV in one eye and drusen or scarring in the other were enrolled in this prospective case series. Eyes with CNV were treated with TTT. POBF was measured monthly in both eyes of each subject. RESULTS: Before TTT, the POBF of eyes with CNV was 1179+/-317 microl/min. After TTT, the POBF of CNV eyes had decreased at 1 month (1015+/-273 microl/min, P=0.002) and 2 months (945+/-398 microl/min, P=0.011) of follow-up, but had rebounded at 3 months (P=0.441) and 6 months (P=0.084). CONCLUSIONS: These findings suggest that TTT decreases the pulsatile choroidal blood flow in eyes with CNV in patients with asymmetric AMD and the effects persist for 2 months. POBF may be used as a modality to monitor the therapeutic effects of CNV in asymmetric exudative AMD.

Patient characteristics and prescription patterns of atypical antipsychotics among patients with schizophrenia.

BACKGROUND: Schizophrenia, one of the leading causes of disability, contributes substantially to the use of medical and mental health services. The treatment of schizophrenia is therefore particularly important to reduce deficits across a large number of neurocognitive domains. OBJECTIVE: To describe the prescription (e.g. initiation and switching) patterns of atypical antipsychotic agents and examine the extent to which patient sociodemographic and clinical characteristics are associated with the prescription patterns of atypical antipsychotics among patients with schizophrenia. METHODS: Using unique data sources from the Veterans Health Administration (VA), the study identified 89 107 patients with schizophrenia based on at least one inpatient or more than or equal to two outpatients' ICD-9-CM codes (> or =7 days apart). We defined a prior 6-month (1/1/99 to 6/30/99) and a post 6-month (7/1/99 to 12/31/99) period to describe patterns of initiation and switching of atypical antipsychotics. RESULTS: Only a small number of patients were on clozapine (1.8%) and quetiapine (1.4%). More patients were prescribed olanzapine (23%) than risperidone (20%) (P < 0.001). Compared with patients who were on risperidone, those who were on olanzapine were younger (P < 0.001), more likely Hispanic (P < 0.001), more likely married (P < 0.05), had more service-connected disability (P < 0.001), had fewer numbers of physical comorbidities (P < 0.001), and a lower body mass index (BMI) (P < 0.05). CONCLUSION: Olanzapine and risperidone appear to be prescribed to patients with different sociodemographic and clinical characteristics. Future research needs to explore the reasons for those differences.

Pulsatile ocular blood flow in asymmetric exudative age related macular degeneration.

BACKGROUND/AIMS: Decreased perfusion or increased vascular resistance of the choroidal vessels had been proposed as the vascular pathogenesis for age related macular degeneration (AMD). This study planned to answer the question whether pulsatile ocular blood flow (POBF) was different in patients with asymmetric exudative AMD between eyes with drusen, choroidal neovascularisation (CNV), or disciform scar. METHODS: 37 patients with asymmetric exudative AMD were enrolled in this observational case series study. POBF were measured in both eyes of each subject. Eyes with high myopia, anisometropia, recent laser treatment, and glaucoma were excluded. RESULTS: After adjusting for ocular perfusion pressure, intraocular pressure, and pulse rate, multivariate regression analysis with generalised estimating equation showed POBF was significantly higher in eyes with CNV (1217 (SD 476) microl/min) than the contralateral eyes with drusen (1028 (385) microl/min) (p = 0.024). Eyes with disciform scar had lower POBF than the contralateral eyes with drusen (999 (262) microl/min and 1278 (341) microl/min, respectively, p<0.001). There was no significant correlation between the POBF and the lesion size of the CNV. CONCLUSION: The POBF in eyes with drusen was lower than their fellow eyes with CNV, but higher than their fellow eyes with disciform scar. This finding suggests that haemodynamic differences between fellow eyes in individuals are relevant to the development of CNV and the formation of disciform scar. Further studies on the follow up patients might shed light on the pathogenesis of exudative AMD.

Optic neuritis in herpes zoster ophthalmicus.

BACKGROUND: Optic neuritis in herpes zoster ophthalmicus (HZO) has been reported rarely. We report two cases of HZO optic neuritis with detailed magnetic resonance imaging study and treatment responses. CASES: One patient presented with anterior optic nerve involvement, and the second presented with retrobulbar optic neuritis. Contrast enhanced T(1)-weighted images were obtained in these 2 patients. Intravenous acyclovir and oral prednisolone were given simultaneously. OBSERVATIONS: Magnetic resonance imaging revealed peripheral enhancement of the optic nerve sheath complex on T(1)-weighted scan. Both patients recovered their vision within 3 months following the start of treatment. CONCLUSIONS: Magnetic resonance imaging is helpful for the diagnosis of HZO optic neuritis. Systemic acyclovir and steroid are effective in the treatment of HZO optic neuritis.

Ovarian hormones in man: their effects on resting vascular tone, angiotensin converting enzyme activity and angiotensin II-induced vasoconstriction.

AIMS: Oestrogens in women have been shown to cause vasodilation which may reflect alterations in the activity of vascular angiotensin converting enzyme (ACE) and/or sensitivity to angiotensin II. The aim of this study was to assess the effect of ovarian hormones on vascular tone, vascular ACE activity and vasoconstriction to angiotensin II in males. METHODS: Eight volunteers were randomised in a crossover design to oestradiol, medroxy-progesterone, and placebo. Vasoconstriction to angiotensin I and angiotensin II was assessed by forearm plethysmography. RESULTS: Although baseline forearm flow was increased with oestradiol, suggesting generalized vasodilation, there were no changes in the vasoconstrictor responses to angiotensin I or angiotensin II. Medroxy-progesterone affected neither baseline flow nor vasoconstrictor responses. The results expressed as percentage reduction in flow (mean +/- s.d.) were: angiotensin I 48 pmol ml-1: placebo -48 +/- 14%; oestradiol -42 +/- 16%; medroxyprogesterone -43 +/- 8% and for angiotensin II 16 pmol ml-1: placebo -42 +/- 10%; oestradiol -39 +/- 11%; medroxyprogesterone -46 +/- 13%. CONCLUSIONS: Acute administration of oestradiol caused vasodilation in males, the effect was not due to alterations in vascular ACE activity or to altered sensitivity to angiotensin II.

The effect of nitric oxide inhibition on the renin response to frusemide, in man.

AIMS: We wished to see if renin release in man was inhibited by nitric oxide blockade, suggesting a role for nitric oxide in renin release. Evidence from animal studies has shown variable effects on renin release depending on the model and stimulus used. METHODS: Ten normal male volunteers, received either L-NMMA as a front loaded infusion (4 mg kg-1 bolus, with 4 mg kg-1 infusion), or placebo, followed by an intravenous bolus of 5 mg frusemide to stimulate renin. To investigate whether any alteration in renin release was due to the pressor effect of the L-NMMA, the experiment was repeated using an equipressor dose of phenylephrine (0.5 microg kg-1 min-1 ). RESULTS: L-NMMA caused the expected increase in mean arterial pressure (96+/-2.6 vs 89+/-3.3 mmHg P<0.05 [mean+/-s.e.mean]), and a reduction in heart rate (59+/-3.6 vs 67+/-2.5 beats min-1 P<0.05). L-NMMA completely blocked the renin rise following the bolus of frusemide (1.18+/-0.196 vs 1.96+/-0.333 ng ml-1 h-1 P<0.01). Phenylephrine 0.5 microg kg-1 min-1 produced very similar haemodynamic effects to L-NMMA, and also suppressed the renin response to frusemide (1.43+/-0.290 vs 2.67+/-0.342 ng ml-1 h-1 P<0. 01). CONCLUSIONS: In man, the renin inhibition seen with NO synthesis inhibition is similar to that seen with a standard pressor stimulus, hence inhibition of renin in man by L-NMMA, may be due to both direct effects on macula densa cells and indirect haemodynamic effects.

Indocyanine green angiography of central serous chorioretinopathy.

BACKGROUND: Fluorescein angiography has not been particularly useful in studying the choroidal vasculature because of limited fluorescence transmission through the retinal pigment epithelium (RPE). Indocyanine green (ICG), a dye that absorbs and fluoresces in the near-infrared range and does not leak extensively through the choriocapillaries, because of its highly protein-bound nature, allows improved imaging of the choroid compared with fluorescein angiography. This study was performed to evaluate changes in the choroidal circulation in the eyes of patients with central serous chorioretinopathy (CSCR) using ICG angiography. METHODS: We prospectively performed ICG angiography and fluorescein angiography in 41 eyes with classic or chronic CSCR (diffuse retinal pigment epitheliopathy) to investigate the choroidal abnormalities. RESULTS: The ICG angiographic studies revealed choroidal staining in all eyes of the two forms of CSCR. Classic CSCR (35 eyes), when compared with the chronic form (6 eyes), were associated with more RPE leakage (89% vs 33%; p = 0.008), more prominent ischemic lobules (69% vs 0; p = 0.003), and less late phase hypofluorescent spots (46% vs 100%; p = 0.02). CONCLUSIONS: Choroidal hyperpermeability may be a causative factor of acute or chronic CSCR and may help in the diagnosis of atypical cases of CSCR. The differences in the results between these two types of CSCR using ICG angiography, allowed for a better understanding of the choroidal hemodynamic change than fluorescein angiography.

How often are angiotensin II and aldosterone concentrations raised during chronic ACE inhibitor treatment in cardiac failure?

OBJECTIVE: Angiotensin II (AII) and aldosterone are not always fully suppressed during chronic angiotensin converting enzyme (ACE) inhibitor treatment. In congestive heart failure (CHF) such failure of hormonal suppression is associated with increased mortality. This study examined how common AII and aldosterone increases are observed during routine clinical practice. PATIENTS AND METHODS: 91 patients with symptomatic (mean New York Heart Association class 2.7) CHF (mean (SD) left ventricular ejection fraction 29.9 (8)%, range 9-46%) were studied 4-6 hours after ACE inhibitor dosing. A representative range of ACE inhibitors (enalapril, lisinopril, captopril, perindopril, and fosinopril) was examined. RESULTS: Supine measurements showed a wide range of AII (10.5 (25.5) pg/ml), aldosterone (130.8 (136) pg/ml), and serum ACE (12.1 (13.3) EU/l; excludes captopril data) concentrations on diuretics. AII concentrations > 10 pg/ml were seen in 15% of patients, and aldosterone concentrations > 144 pg/ml were seen in 38% of patients. AII concentrations were significantly correlated (p < 0.001) with ACE but not with aldosterone concentrations. Aldosterone concentrations were not significantly correlated with ACE concentrations. CONCLUSIONS: AII "reactivation" occurred in 15% and failure of aldosterone suppression in 38% of routine CHF patients taking ACE inhibitor treatment. AII "reactivation" was associated with both low and high levels of ACE activity, which suggests that multiple different mechanisms are at play. In patients with high plasma ACE concentrations, non-compliance should be considered along with inadequate dose titration. In patients with low plasma ACE and high AII concentrations, non-ACE mediated production of AII may be operative. Raised aldosterone concentrations appear to be more common than AII "reactivation". It is important to establish the cause of detectable or increased AII concentrations in a heart failure patient treated with an ACE inhibitor. The measurement of serum ACE may help to identify the likely cause as poor compliance or inadequate dose.

Lisinopril improves arterial function in hyperlipidaemia.

Endothelial function is defective in hypercholesterolaemia, and animal models have suggested that angiotensin-converting enzyme inhibitors may prevent arterial damage. We studied the effect of 6 months treatment with lisinopril on endothelial function in a group of patients with hypercholesterolaemia. Forty patients were studied. Forearm blood flow responses to acetylcholine and sodium nitroprusside were assessed by venous occlusion plethysmography. Subjects were then randomized in a double-blind fashion to receive either lisinopril, 20 mg/day (n=20), or placebo (n=20) for 6 months. Plethysmography was then repeated. Baseline variables between groups were comparable. In the lisinopril group blood pressure fell significantly [systolic: 145+/-4 to 128+/-4 mmHg (P<0.001); diastolic: 84+/-2 to 74+/-2 mmHg (P<0.001)]. An improvement was found in the vasodilatory response (expressed as a ratio of the infused/control arm) to acetylcholine, e.g. 3.33+/-0.3 (pre) versus 4.45+/-0.48 (post) at 30 microg/ml (P<0.03), and also to nitroprusside, e.g. 3.0+/-0.2 (pre) versus 3.86+/-0.3 (post) at 3.2 microg/ml (P<0.01). In the placebo group vasodilatation did not change significantly in response to acetylcholine, and nitroprusside responses were unchanged. The data presented suggest that 6 months of lisinopril therapy have a beneficial effect on arterial function in subjects with hyperlipidaemia. Further work should now investigate whether angiotensin-converting enzyme inhibitors are beneficial in reducing mortality and morbidity in hypercholesterolaemia.