Acute Coronary Syndrome Subphenotypes Based on Repeated Biomarker Measurements in Relation to Long-Term Mortality Risk.

BACKGROUND: We aimed to identify patients with subphenotypes of postacute coronary syndrome (ACS) using repeated measurements of high-sensitivity cardiac troponin T, N-terminal pro-B-type natriuretic peptide, high-sensitivity C-reactive protein, and growth differentiation factor 15 in the year after the index admission, and to investigate their association with long-term mortality risk. METHODS AND RESULTS: BIOMArCS (BIOMarker Study to Identify the Acute Risk of a Coronary Syndrome) was an observational study of patients with ACS, who underwent high-frequency blood sampling for 1 year. Biomarkers were measured in a median of 16 repeated samples per individual. Cluster analysis was performed to identify biomarker-based subphenotypes in 723 patients without a repeat ACS in the first year. Patients with a repeat ACS (N=36) were considered a separate cluster. Differences in all-cause death were evaluated using accelerated failure time models (median follow-up, 9.1 years; 141 deaths). Three biomarker-based clusters were identified: cluster 1 showed low and stable biomarker concentrations, cluster 2 had elevated concentrations that subsequently decreased, and cluster 3 showed persistently elevated concentrations. The temporal biomarker patterns of patients in cluster 3 were similar to those with a repeat ACS during the first year. Clusters 1 and 2 had a similar and favorable long-term mortality risk. Cluster 3 had the highest mortality risk. The adjusted survival time ratio was 0.64 (95% CI, 0.44-0.93; P=0.018) compared with cluster 1, and 0.71 (95% CI, 0.39-1.32; P=0.281) compared with patients with a repeat ACS. CONCLUSIONS: Patients with subphenotypes of post-ACS with different all-cause mortality risks during long-term follow-up can be identified on the basis of repeatedly measured cardiovascular biomarkers. Patients with persistently elevated biomarkers have the worst outcomes, regardless of whether they experienced a repeat ACS in the first year.

Mode of delivery following obstetric anal sphincter injury: a 7-year retrospective review and follow-up cohort survey.

INTRODUCTION AND HYPOTHESIS: Limited evidence exists regarding long-term outcomes following birth after prior obstetric anal sphincter injury (OASI). This article set out to describe outcomes following birth after OASI by reviewing the grades of tear, endoanal ultrasound (EAUS) findings, subsequent delivery outcomes and long-term symptoms. METHODS: This study was conducted in two parts. The first involved a retrospective review of all OASI at a tertiary hospital in Australia over 7 years (2013-2019 inclusive) where the patient underwent a subsequent delivery. Following this, a retrospective cohort survey of this group was performed. RESULTS: There were 27,284 vaginal births and 828 OASIs (3.03%); 247 (29.8%) had at least one subsequent birth by January 2021. Vaginal delivery occurred in 68%; recurrence of OASI was 5.4%. There were 90 responses (36.4%) to the follow-up survey. EAUS had been performed in 87.5%; none demonstrated a defect. Vaginal birth was the preferred mode for 77.8%; this occurred in 64%. The majority had high levels of satisfaction, this related to communication rather than the mode of delivery itself. Ongoing faecal or flatal incontinence was reported by 12%. There was no statistically significant difference in St Mark's incontinence scores between modes of birth. CONCLUSIONS: In our unit most women who sustain OASI will have a subsequent vaginal delivery in future pregnancies. The majority remain asymptomatic at long-term follow-up with no statistically significant difference in incontinence scores regardless of mode of delivery. The rate of recurrent OASI was 5.4%.

Intestinal CD8+ T cell responses are abundantly induced early in human development but show impaired cytotoxic effector capacities.

Gastrointestinal viral infections are a major global cause of disease and mortality in infants. Cytotoxic CD8+ T cells are critical to achieve viral control. However, studies investigating the development of CD8+ T cell immunity in human tissues early in life are lacking. Here, we investigated the maturation of the CD8+ T cell compartment in human fetal, infant and adult intestinal tissues. CD8+ T cells exhibiting a memory phenotype were already detected in fetal intestines and increased after birth. Infant intestines preferentially harbored effector CCR7-CD45RA-CD127-KLRG1+/- CD8+ T cells compared to tissue-resident memory CD69+CD103+CD8+ T cells detected in adults. Functional cytotoxic capacity, including cytokine and granzyme B production of infant intestinal effector CD8+ T cells was, however, markedly reduced compared to adult intestinal CD8+ T cells. This was in line with the high expression of the inhibitory molecule PD-1 by infant intestinal effector CD8+ T cells. Taken together, we demonstrate that intestinal CD8+ T cell responses are induced early in human development, however exhibit a reduced functionality. The impaired CD8+ T cell functionality early in life contributes to tolerance during foreign antigen exposure after birth, however functions as an immune correlate for the increased susceptibility to gastrointestinal viral infections in infancy.

Boesenmaxane Diterpenoids from Boesenbergia maxwellii.

Three new diterpenoids, boesenmaxanes A-C (1-3), with an unprecedented core skeleton consisting of an unusual C-C bond between C-12 and an exo-cyclic methylene C-13, were isolated from the rhizome extracts of Boesenbergia maxwellii. The structures were elucidated by analysis of spectroscopic and X-ray diffraction data. Electronic circular dichroism spectra were used to determine the absolute configuration. All the isolates were evaluated for their cytotoxic effects, anti-HIV activity, and antimicrobial activity. Boesenmaxanes A and C (1 and 3) showed significant inhibitory activity in the syncytium reduction assay, with EC50 values of 55.2 and 27.5 µM, respectively.

Evolution of renal function and predictive value of serial renal assessments among patients with acute coronary syndrome: BIOMArCS study.

BACKGROUND: Impaired renal function predicts mortality in acute coronary syndrome (ACS), but its evolution immediately following index ACS and preceding next ACS has not been described in detail. We aimed to describe this evolution using serial measurements of creatinine, glomerular filtration rate [eGFRCr] and cystatin C [CysC]. METHODS: From 844 ACS patients included in the BIOMArCS study, we analysed patient-specific longitudinal marker trajectories from the case-cohort of 187 patients to determine the risk of the endpoint (cardiovascular death or hospitalization for recurrent non-fatal ACS) during 1-year follow-up. Study included only patients with eGFRCr ≥ 30 ml/min/1.73 m2. Survival analyses were adjusted for GRACE risk score and based on data >30 days after the index ACS (mean of 8 sample per patient). RESULTS: Mean age was 63 years, 79% were men, 43% had STEMI, and 67% were in eGFR stages 2-3. During hospitalization for index ACS (median [IQR] duration: 5 (3-7) days), CysC levels indicated deterioration of renal function earlier than creatinine did (CysC peaked on day 3, versus day 6 for creatinine), and both stabilized after two weeks. Higher CysC levels, but not creatinine, predicted the endpoint independently of the GRACE score within the first year after index ACS (adjusted HR [95% CI] per 1SD increase: 1.68 [1.03-2.74]). CONCLUSION: Immediately following index ACS, plasma CysC levels deteriorate earlier than creatinine-based indices do, but neither marker stabilizes during hospitalization but on average two weeks after ACS. Serially measured CysC levels predict mortality or recurrence of ACS during 1-year follow-up independently of patients' GRACE risk score.

The temporal pattern of immune and inflammatory proteins prior to a recurrent coronary event in post-acute coronary syndrome patients.

PURPOSE: We assessed the temporal pattern of 29 immune and inflammatory proteins in post-acute coronary syndrome (ACS) patients, prior to the development of recurrent ACS. METHODS: High-frequency blood sampling was performed in 844 patients admitted for ACS during one-year follow-up. We conducted a case-control study on the 45 patients who experienced reACS (cases) and two matched event-free patients (controls) per case. Olink Proteomics' immunoassay was used to obtain serum levels of the 29 proteins, expressed in an arbitrary unit on the log2-scale (Normalized Protein eXpression, NPX). Linear mixed-effects models were applied to examine the temporal pattern of the proteins, and to illustrate differences between cases and controls. RESULTS: Mean age was 66 ± 12 years and 80% were men. Cases and controls had similar baseline clinical characteristics. During the first 30 days, and after multiple testing correction, cases had significantly higher serum levels of CXCL1 (difference of 1.00 NPX, p = 0.002), CD84 (difference of 0.64 NPX, p = 0.002) and TNFRSF10A (difference of 0.41 NPX, p < 0.001) than controls. After 30 days, serum levels of all 29 proteins were similar in cases and controls. In particular, no increase was observed prior to reACS. CONCLUSIONS: Among 29 immune and inflammatory proteins, CXCL1, CD84 and TNFRSF10A were associated with early reACS after initial ACS-admission.

Cohort profile of BIOMArCS: the BIOMarker study to identify the Acute risk of a Coronary Syndrome-a prospective multicentre biomarker study conducted in the Netherlands.

PURPOSE: Progression of stable coronary artery disease (CAD) towards acute coronary syndrome (ACS) is a dynamic and heterogeneous process with many intertwined constituents, in which a plaque destabilising sequence could lead to ACS within short time frames. Current CAD risk assessment models, however, are not designed to identify increased vulnerability for the occurrence of coronary events within a precise, short time frame at the individual patient level. The BIOMarker study to identify the Acute risk of a Coronary Syndrome (BIOMArCS) was designed to evaluate whether repeated measurements of multiple biomarkers can predict such 'vulnerable periods'. PARTICIPANTS: BIOMArCS is a multicentre, prospective, observational study of 844 patients presenting with ACS, either with or without ST-elevation and at least one additional cardiovascular risk factor. METHODS AND ANALYSIS: We hypothesised that patterns of circulating biomarkers that reflect the various pathophysiological components of CAD, such as distorted lipid metabolism, vascular inflammation, endothelial dysfunction, increased thrombogenicity and ischaemia, diverge in the days to weeks before a coronary event. Divergent biomarker patterns, identified by serial biomarker measurements during 1-year follow-up might then indicate 'vulnerable periods' during which patients with CAD are at high short-term risk of developing an ACS. Venepuncture was performed every fortnight during the first half-year and monthly thereafter. As prespecified, patient enrolment was terminated after the primary end point of cardiovascular death or hospital admission for non-fatal ACS had occurred in 50 patients. A case-cohort design will explore differences in temporal patterns of circulating biomarkers prior to the repeat ACS. FUTURE PLANS AND DISSEMINATION: Follow-up and event adjudication have been completed. Prespecified biomarker analyses are currently being performed and dissemination through peer-reviewed publications and conference presentations is expected from the third quarter of 2016. Should identification of a 'vulnerable period' prove to be feasible, then future research could focus on event reduction through pharmacological or mechanical intervention during such periods of high risk for ACS. TRIAL REGISTRATION NUMBER: NTR1698 and NTR1106.

Timing of intervention in high-risk non-ST-elevation acute coronary syndromes in PCI versus non-PCI centres : Sub-group analysis of the ELISA-3 trial.

AIMS: To compare the effect of timing of intervention in patients with non-ST-elevation acute coronary syndrome (NSTE-ACS) in percutaneous coronary intervention (PCI) versus non-PCI centres. METHODS AND RESULTS: A post-hoc sub-analysis was performed of the ELISA III trial, a randomised multicentre trial investigating outcome of early (< 12 h) versus late (> 48 h) angiography and revascularisation in 542 patients with high-risk NSTE-ACS. 90 patients were randomised in non-PCI centres and tended to benefit more from an early invasive strategy than patients included in the PCI centre (relative risk 0.23 vs. 0.85 [p for interaction = 0.089] for incidence of the combined primary endpoint of death, reinfarction and recurrent ischaemia after 30 days of follow-up). This was largely driven by reduction in recurrent ischaemia. In non-PCI centres, patients randomised to the late group had a 4 and 7 day longer period until PCI or coronary artery bypass grafting, respectively. This difference was less pronounced in the PCI centre. CONCLUSIONS: This post-hoc analysis from the ELISA-3 trial suggests that NSTE-ACS patients initially hospitalised in non-PCI centres show the largest benefit from early angiography and revascularisation, associated with a shorter waiting time to revascularisation. Improved patient logistics and transfer between non-PCI and PCI centres might therefore result in better clinical outcome.

Electrosurgical bipolar vessel sealing versus conventional clamping and suturing for vaginal hysterectomy: a randomised controlled trial.

OBJECTIVE: To compare the effects of electrical bipolar vessel sealing and conventional suturing on postoperative pain, recovery, costs and micturition symptoms in women undergoing vaginal hysterectomy. DESIGN: Randomised controlled trial. SETTING: Eight teaching hospitals in the Netherlands. POPULATION: One hundred women scheduled to undergo vaginal hysterectomy for benign conditions excluding pelvic organ prolapse. METHODS: Women were randomised to vessel sealing or conventional surgery. The quality of life related to pelvic floor function was assessed using validated questionnaires before surgery and 6 months after surgery. Pain scores and recovery were assessed using a diary, including daily visual analogue scale scores, starting from the day before surgery until 6 weeks after surgery. MAIN OUTCOME MEASURES: Visual analogue scale pain scores, surgery time, blood loss, complications, quality of life related to pelvic floor function and costs. RESULTS: The evening after surgery, women in the vessel-sealing group reported significantly less pain (5.7 versus 4.5 on a scale of 0-10, P = 0.03), but after that pain scores were similar. Operation duration was shorter for vessel sealing (60 versus 71 minutes, P = 0.05). Blood loss and hospital stay did not differ. We observed no major difference in costs between the two interventions (2903 versus 3102 €, P = 0.26). Changes in micturition and defecation symptoms were not affected by the surgical technique used. CONCLUSION: Using vessel sealing during vaginal hysterectomy resulted in less pain on the first postoperative day, shorter operating time, similar morbidity and similar pelvic floor function. No major differences in costs were found between the two interventions.

Atypical diverticular disease: surgical results.

PURPOSE: Patients with diverticular disease may present with chronic symptoms but never develop diverticulitis. The purpose of this research was to review the outcome of surgical intervention in this subgroup of patients with atypical "smoldering" diverticular disease. METHODS: Records of 930 patients who underwent sigmoid resection for diverticular disease during a ten-year period at the Mayo Clinic in Rochester, Minnesota, were reviewed. Forty-seven patients (5 percent) fit our inclusion criteria for smoldering diverticular disease and underwent sigmoid colectomy with primary anastomosis. A minimum of 12 months of follow-up was completed in 68 percent of these patients. RESULTS: Evidence of acute or chronic inflammatory changes was present in 76 percent of resected specimens. Complete resolution of symptoms occurred in 76.5 percent, with 88 percent being pain free. CONCLUSIONS: We conclude that the diagnosis and presentation of atypical smoldering diverticular disease is an uncommon and poorly defined entity. However, sigmoid resection in this subgroup of patients is safe and is associated with resolution of symptoms in the majority of cases.

Efficacy and tolerability of a new estradiol delivering matrix patch (Estraderm MX) in postmenopausal women.

OBJECTIVE: To examine the efficacy and tolerability of a new matrix patch delivering estradiol (E2 Matrix) at doses of 0.05 and 0.10 mg per day (Estraderm MX 50, 100) in the treatment of moderate to severe postmenopausal symptoms. METHODS: A total of 254 postmenopausal women were randomized to receive treatment with E2 Matrix 0.10 mg (N = 86), E2 Matrix 0.05 mg (N = 82), or placebo (N = 86) in a double-blind, double-dummy fashion for a period of 12 weeks continuously. Patches were applied twice weekly to the buttocks with each patient wearing two patches at all times. The primary efficacy criterion was the difference from baseline of the mean number of moderate to severe hot flushes per 24 h during the last 2 weeks of treatment. Other efficacy variables included reduction in hot flushes at 4 and 8 weeks, reduction in daytime flushing and night sweats, and Kupperman Index at 4, 8, and 12 weeks. RESULTS: E2 Matrix 0.10 and 0.05 mg were both significantly superior to placebo in reducing hot flushes per 24 h after 4, 8, and 12 weeks of treatment (P < 0.001). Also, for all other efficacy parameters studied, both dosage strengths of E2 Matrix were statistically significantly superior to placebo at all time points (P < 0.001). Local tolerability was good in both groups. A slight increase in estrogen related adverse effects (breast tenderness, leukorrhoea) was seen with the 0.10 mg patch. Adhesion of patches and compliance were good. Overall systemic tolerability was good in both treated groups. However, a 4.8% overall incidence of endometrial hyperplasia was observed in patients with an intact uterus. CONCLUSIONS: This new matrix patch offers an effective and well tolerated dosage form for delivery of 0.05 and 0.1 mg estradiol per day. It may be particularly suitable for those women who experience local sensitivity to alcohol-containing systems. In light of the observed hyperplasia after treatment in five patients, estrogen therapy should as yet be supplemented monthly with a progestogen in women with an intact uterus.

An in vitro evaluation of the line pattern of the near and far walls of carotid arteries using B-mode ultrasound.

This in vitro study was executed to evaluate the double line pattern generated at both near and far walls of human carotid arteries using B-mode ultrasound. Therefore, extravascular (7.5 MHz) and intravascular (30 MHz) ultrasound imaging were performed at the same locations of the carotid artery. The thickness of the double line pattern of the extravascular image (7.5 MHz) was compared to the thickness of the intima-media complex seen on the corresponding intravascular image (30 MHz) and on the histologic section. At the far wall of the extravascular image, the measurements were executed at the leading edge of the echo. The data showed high correlation and agreement with the intravascular (r = 0.91, p < 0.001; mean(diff) = -0.01 and SDdiff = 0.12) and the histologic measurements (r = 0.87, p < 0.001; mean(diff) = -0.12 and SDdiff = 0.13). In addition, the results of the measurements of the intravascular image showed high correlations and agreement with the histologic data (r(near) = 0.86, p < 0.001; mean(diff) = -0.08 and SDdiff = 0.15, respectively, r(far) = 0.92, p < 0.001; mean(diff) = -0.12 and SDdiff = 0.12). For comparison with other studies, near wall measurements were also included. These had to be performed at the trailing edge of the echoes to be compatible with these studies. The results of the measurements of the extravascular image showed poor correlations and lack of agreement with those of the intravascular (r = 0.49, p = 0.03; mean(diff) = 0.09 and SDdiff = 0.25) and of the histologic (r = 0.37, p = 0.03; mean(diff) = 0.04 and SDdiff = 0.23) measurements. These results can easily be explained from the physical limitations of measuring at the trailing edges. We conclude that the double line pattern seen at the far wall of the extravascular image is representative of the intima-media complex.

Intravascular ultrasound predictors of outcome after peripheral balloon angioplasty.

OBJECTIVE: This study investigates the potential role of intravascular ultrasound (IVUS) in the outcome in patients undergoing percutaneous transluminal angioplasty (PTA) of the superficial femoral artery. MATERIALS: Angiographic and the qualitative and quantitative IVUS data obtained at the narrowest site derived from 39 patients before and after PTA were analysed. RESULTS: Angiographically the diameter of the remaining stenosis seen after PTA was classified as < 50% in 31 patients (success); in eight patients a failure was encountered. Evaluating at 6 months the functional and anatomic results of the PTA in 31 patients, the intervention was a success in 14 patients (Group I) and a failure in 17 patients (Group II). The remaining eight patients defined as angiographic failure following PTA comprised Group III. Neither qualitative nor quantitative IVUS data obtained before PTA could predict outcome. Conversely, after PTA, the extent of dissection was significantly more severe in Groups II and III than in Group I. Similarly, significant differences were found between Groups I and II for mean free lumen area (13.2 vs. 9.7 mm2, respectively) and mean free lumen diameter (4.1 vs. 3.5 mm, respectively). Quantitative data obtained in Group II were similar to those in Group III. CONCLUSION: This preliminary study demonstrates that following PTA the extent of dissection, free lumen area and diameter seen with IVUS are predictive factors of patency. Future studies with more patients are mandatory to further highlight the sensitivity of these observations.

Remodeling of De Novo atherosclerotic lesions in femoral arteries: impact on mechanism of balloon angioplasty.

OBJECTIVES: Using 30-MHz intravascular ultrasound in the human femoral artery, we related the mode of arterial remodeling to the immediate result and the mechanism of balloon angioplasty. BACKGROUND: The atherosclerotic femoral artery may undergo three modes of remodeling in response to plaque formation: compensatory enlargement, failure of compensatory enlargement and paradoxic shrinkage. METHODS: In 83 patients an ultrasound catheter pullback maneuver was performed before and after balloon angioplasty. For each lesion (n = 121), the cross section with the narrowest lumen was selected for further analysis. For each cross section, the lumen area stenosis was expressed as percent of the lumen area at an adjacent reference site. Similarly, the media-bounded area was expressed as percent of the media-bounded area at the reference site. Cross sections were classified into one of three groups based on percent relative media-bounded area: 1) > 105% (group A, compensatory enlargement, n = 24); 2) 95% to 105% (group B, failure of compensatory enlargement, n = 26); and 3) < 95% (group C, arterial wall shrinkage, n = 71). The power of the present study was 99.3% to demonstrate a difference in lumen gain of 2.5 mm2 among groups. RESULTS: The gain in lumen area induced by balloon angioplasty did not differ significantly among the three groups (group A, 7.0 +/- 4.0 mm2 [mean +/- SD]; group B, 8.6 +/- 4.8 mm2; group C, 8.9 +/- 4.9 mm2). Stretch of the media-bounded area was observed in all three groups, but it was significantly larger in group C (7.5 +/- 5.2 mm2) than in the other two groups (group A, 3.9 +/- 5.1 mm2; group B, 5.1 +/- 4.1 mm2). A significantly positive correlation between balloon/media-bounded area ratio and elastic recoil was observed for cross sections in groups A and B (r = 0.71 and r = 0.69, respectively). However, no correlation was observed between balloon/media-bounded area ratio and elastic recoil for cross sections in group C (r = 0.17). CONCLUSIONS: We conclude that lumen gain by balloon angioplasty is not related to the mode of atherosclerotic arterial remodeling. However, the mode of arterial remodeling affects the dilation mechanism.

In vivo measurement of regional large artery compliance by intravascular ultrasound under pentobarbital anesthesia.

BACKGROUND: The presence of smooth muscle fibers on the wall of large arteries would suggest that arterial compliance might change in response to vasoactive substances. The purpose of this study is to determine the basal level of vasomotor tone in these arteries in a commonly used animal preparation and to learn whether the compliance of large conductance arteries can be altered in vivo by vasoactive agents. METHODS: Proximal iliac arterial compliance was measured in 7 pentobarbital-anesthetized pigs, before and during local infusions of adenosine and norepinephrine. Luminal area was measured every forty milliseconds by means of a 30 MHz intravascular ultrasound catheter and an automatic edge detection program. Simultaneous high-fidelity pressure measurements were obtained by means of a catheter-tipped pressure microtransducer positioned at the origin of the iliac artery. Linear regression analysis of the area/pressure relationship in two consecutive cardiac cycles (systolic phase only) was performed before and during adenosine and norepinephrine infusions. The slope of the area/pressure regression line was defined as an index of arterial compliance. Measurements after three minutes of infusions of adenosine (5-5000 micrograms/minute) and norepinephrine (0.001-10 micrograms/minute) were compared with the control measurements. RESULTS: Even at the highest infusion rate, adenosine did not significantly increase arterial compliance as compared with baseline (25 +/- 7 vs 19 +/- 4 mm2/mmHg x 10(-3), respectively, P = ns). In contrast, norepinephrine decreased arterial compliance as compared with the second baseline control (13 +/- 3 vs 20 +/- 3 mm2/mmHg x 10(-3), respectively, P < 0.01). CONCLUSIONS: In this animal model with pentobarbital anesthesia, arterial compliance may be modified more by the acute infusion of norepinephrine than by adenosine in large conductance arteries such as the proximal iliac. Thus, in this preparation, smooth muscle tone tends to be minimal and arterial compliance near maximal (ie, mostly a passive phenomenon). However, in response to norepinephrine, arterial compliance can decrease significantly as smooth muscle tone increases. Intravascular ultrasound allows continuous and accurate monitoring of these changes of arterial dimensions, suggesting that this technique may be useful in the evaluation of pharmacologically induced changes in the compliance of large arteries by vasoactive agents.

Femorodistal venous bypass evaluated with intravascular ultrasound.

OBJECTIVE: To evaluate the feasibility of intravascular ultrasound imaging during femorodistal venous bypass procedures to assess qualitative and quantitative parameters of the greater saphenous vein and to detect potential causes for (re)stenosis and/or occlusion. METHODS: Intravascular ultrasound data obtained from 15 patients were reviewed and compared with angiographic data. RESULTS: Intravascular ultrasound enabled differentiation between normal and thickened vein wall. Venous side-branches could be located. Intact valves could be differentiated from valves disrupted by valve cutting. Patent anastomoses could be distinguished from anastomoses with some degree of obstruction. Intravascular ultrasound imaging of the inflow and outflow tracts revealed obstructive lesions, not evidenced angiographically. Quantitative analysis revealed that the median normal vein wall thickness (tunica intima and tunica media) was 0.25 mm (range 0.17-0.40 mm). The distinct vein wall thickening encountered in three patients measured 0.82, 0.95 and 1.06 mm, respectively, and was associated with narrowing in two patients. In five of 15 patients intravascular ultrasound findings altered surgical management. CONCLUSION: Intravascular ultrasound is able to assess qualitative and quantitative parameters of the venous bypass and has the potential to influence surgical management based on morphologic and quantitative data.

Antimalarial drug induced decrease in creatinine clearance.

OBJECTIVE: To confirm the antimalarial drug induced increase of creatinine to determine the factors contributing to this effect. METHODS: Patients with rheumatoid arthritis (RA) (n = 118) who have used or still use antimalarials (chloroquine or hydroxychloroquine). Serum creatinines prior to antimalarials and serum creatinines during antimalarials were recorded and the creatinine clearance was estimated. RESULTS: The mean creatinine clearance decreased from 99 ml/min to 92 ml/min (p < 0.001) after the start of antimalarial drugs. Fifty-five percent of the patients with chloroquine compared to 15% of the patients with hydroxychloroquine (chi 2 = 17.8; p < 0.001) had more than 10% decrease of the creatinine clearance. Age (beta = 0.004; p = 0.0002) and the kind of antimalarial (beta = 0.095; p = 0.0002) were strong independent predictors of the decrease of the creatinine clearance in the multiple regression analysis. For patients using chloroquine the mean age adjusted decrease of creatinine clearance was 11.2%. CONCLUSION: Antimalarials cause a significant reduction of the creatinine clearance. The use of chloroquine and older age were associated with decreased creatinine clearance. Whether antimalarials affect glomerular filtration or tubular excretion of creatinine remains to be investigated.

Assessment of regional vascular distensibility in diseased iliofemoral arteries by intravascular ultrasound.

The influence of atherosclerosis on distensibility of iliac and superficial femoral arteries was assessed retrospectively in 28 patients using intravascular ultrasound. Distensibility was related to lesion morphology, lesion geometry, percentage area stenosis, effect of balloon angioplasty, hypertension and patient's age. In 10 patients, free lumen area remained unchanged during the cardiac cycle. From the remaining 18 patients, a total of 135 cross-sections underwent qualitative and quantitative analysis. Cross-sections without a lesion were compared with those showing; soft/hard and eccentric/concentric lesions. At normal sites, iliac arteries showed greater distensibility than femoral arteries (6.5 +/- 2.4% vs. 3.5 +/- 0.9%; p < or = 0.05). Hard lesions in iliac arteries were less distensible than lesions; in femoral arteries this difference was less pronounced. Lesion geometry did not influence arterial distensibility. Intravascular ultrasound revealed no difference in distensibility when normal cross-sections were compared with those having a < 50% or a 50% to 90% area stenosis. In contrast, a significant decrease in femoral artery distensibility was found in the presence of > 90% stenosis (0.4%). Comparison of cross-sections before and after balloon angioplasty revealed a marked increase in distensibility of iliac arteries following intervention; in the femoral artery, there was practically no change in distensibility. Hypertension and increasing age proved to have no significant influence on arterial distensibility. This study demonstrates that intravascular ultrasound is potentially a powerful tool to assess arterial distensibility and the influence of atherosclerosis on vascular dynamics.

Temporal averaging for quantification of lumen dimensions in intravascular ultrasound images.

Quantitative analysis of arterial dimensions from high frequency intravascular ultrasound images (30 MHz) may be hampered by strong blood scattering. Replacement of blood by saline is one method to provide a clear view of the arterial lumen; another method is that of temporal averaging of successive ultrasound images. The accuracy of this latter method was tested by comparing the lumen area measurements on the temporal-averaged image, with the data of the same cross-section obtained from the single-frame and saline-filled images. The mean lumen area measured on the temporal-averaged images was similar to that measured on the single-frame images (mean difference: -0.02 +2- 1.16 mm2; p = ns). The mean lumen area of the saline-filled images was 8% larger than the values obtained from the temporal-averaged and single-frame images (mean difference: -1.14 +/- 0.85 mm2, p < 0.05), probably due to the difference in sound velocity between saline and blood. Intraobserver variation in the averaging method were 2.4 times smaller than the measurements of the single-frame images and close to the data obtained by saline injection (variation coefficient: single-frame: 8.8%; temporal-averaged: 3.6%; saline-filled: 2.9%). It is concluded that analysis from temporal-averaged images is more efficient, enabling accurate and reproducible measurement of the luminal dimensions from images containing blood scattering echoes. This technique is suitable to replace the laborious saline injection method and facilitates off-line quantitative analysis.