GPR91 deficiency exacerbates allergic contact dermatitis while reducing arthritic disease in mice.

BACKGROUND: Succinate, in addition to its role as an intermediary of the citric acid cycle, acts as an alarmin, initiating and propagating danger signals resulting from tissue injury or inflammatory stimuli. The contribution of this immune sensing pathway to the development of allergic and inflammatory responses is unknown. METHODS: Ear thickness of wild-type (wt) and Sucnr1-deficient (Sucnr1-/- ) mice, sensitized and challenged with oxazolone, was used as a criterion to assess the relevance of SUCNR1/GPR91 expression mediating allergic contact dermatitis (ACD). Results obtained in this system were contrasted with data generated using passive cutaneous anaphylaxis, ovalbumin-induced asthma and arthritis models. RESULTS: We found augmented ACD reactions in Sucnr1-/- mice. This observation correlated with increased mast cell activation in vitro and in vivo. However, exacerbated mast cell activation in Sucnr1-/- mice did not contribute to the enhancement of asthma or arthritis and seemed to be due to alterations during mast cell development as augmented mast cell responses could be recapitulated in wt mast cells differentiated in the absence of succinate. CONCLUSIONS: A deficiency in succinate sensing during mast cell development confers these cells with a hyperactive phenotype. Such a phenomenon does not translate into exacerbation of asthma or mast cell-dependent arthritis. On the contrary, the fact that Sucnr1-/- mice developed reduced arthritic disease, using two different in vivo models, indicates that GPR91 antagonists may have therapeutic potential for the treatment of allergic and autoimmune diseases.

Use of protein cross-linking and radiolytic footprinting to elucidate PsbP and PsbQ interactions within higher plant Photosystem II.

Protein cross-linking and radiolytic footprinting coupled with high-resolution mass spectrometry were used to examine the structure of PsbP and PsbQ when they are bound to Photosystem II. In its bound state, the N-terminal 15-amino-acid residue domain of PsbP, which is unresolved in current crystal structures, interacts with domains in the C terminus of the protein. These interactions may serve to stabilize the structure of the N terminus and may facilitate PsbP binding and function. These interactions place strong structural constraints on the organization of PsbP when associated with the Photosystem II complex. Additionally, amino acid residues in the structurally unresolved loop 3A domain of PsbP ((90)K-(107)V), (93)Y and (96)K, are in close proximity (≤ 11.4 Å) to the N-terminal (1)E residue of PsbQ. These findings are the first, to our knowledge, to identify a putative region of interaction between these two components. Cross-linked domains within PsbQ were also identified, indicating that two PsbQ molecules can interact in higher plants in a manner similar to that observed by Liu et al. [(2014) Proc Natl Acad Sci 111(12):4638-4643] in cyanobacterial Photosystem II. This interaction is consistent with either intra-Photosystem II dimer or inter-Photosystem II dimer models in higher plants. Finally, OH(•) produced by synchrotron radiolysis of water was used to oxidatively modify surface residues on PsbP and PsbQ. Domains on the surface of both protein subunits were resistant to modification, indicating that they were shielded from water and appear to define buried regions that are in contact with other Photosystem II components.

Use of Protein Cross-Linking and Radiolytic Labeling To Elucidate the Structure of PsbO within Higher-Plant Photosystem II.

We have used protein cross-linking with the zero-length cross-linker 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide, and radiolytic footprinting coupled with high-resolution tandem mass spectrometry, to examine the structure of higher-plant PsbO when it is bound to Photosystem II. Twenty intramolecular cross-linked residue pairs were identified. On the basis of this cross-linking data, spinach PsbO was modeled using the Thermosynechococcus vulcanus PsbO structure as a template, with the cross-linking distance constraints incorporated using the MODELLER program. Our model of higher-plant PsbO identifies several differences between the spinach and cyanobacterial proteins. The N-terminal region is particularly interesting, as this region has been suggested to be important for oxygen evolution and for the specific binding of PsbO to Photosystem II. Additionally, using radiolytic mapping, we have identified regions on spinach PsbO that are shielded from the bulk solvent. These domains may represent regions on PsbO that interact with other components, as yet unidentified, of the photosystem.

Radiolytic mapping of solvent-contact surfaces in Photosystem II of higher plants: experimental identification of putative water channels within the photosystem.

Photosystem II uses water as an enzymatic substrate. It has been hypothesized that this water is vectored to the active site for water oxidation via water channels that lead from the surface of the protein complex to the Mn4O5Ca metal cluster. The radiolysis of water by synchrotron radiation produces amino acid residue-modifying OH(•) and is a powerful technique to identify regions of proteins that are in contact with water. In this study, we have used this technique to oxidatively modify buried amino acid residues in higher plant Photosystem II membranes. Fourier transform ion cyclotron resonance mass spectrometry was then used to identify these oxidized amino acid residues that were located in several core Photosystem II subunits (D1, D2, CP43, and CP47). While, as expected, the majority of the identified oxidized residues (≈75%) are located on the solvent-exposed surface of the complex, a number of buried residues on these proteins were also modified. These residues form groups which appear to lead from the surface of the complex to the Mn4O5Ca cluster. These residues may be in contact with putative water channels in the photosystem. These results are discussed within the context of a number of largely computational studies that have identified putative water channels in Photosystem II.

Private GPs contribute to TB control in Myanmar: evaluation of a PPM initiative in Mandalay Division.

SETTING: Mandalay Division, Myanmar. AIM: To assess the effect of an initiative to involve private general practitioners (GPs) in the National Tuberculosis Programme (NTP) and to identify lessons learnt for public-private mix scale-up. METHODS: Source of referral/diagnosis and place of treatment were included in the routine recording and reporting systems to enable disaggregated analysis of the contribution of GPs to case notification and treatment outcomes. Case notification trends were compared between the intervention and control areas over a 4-year period. RESULTS: Private GPs contributed 44% of new smear-positive cases registered during the study period (July 2002-December 2004). The notification of new sputum smear-positive TB in the study area increased by 85% between the year prior to the GP involvement and 2 years after (from 46 to 85/100,000). Case notification increased by 57% in the control townships and by 42% in all of Mandalay Division. The treatment success rate for new smear-positive cases treated by GPs was 90%. CONCLUSIONS: The involvement of private GPs substantially increased TB case notification, while a high treatment success rate was maintained. Success factors include a well-developed local medical association branch, strong managerial support, training and supervision by the public sector and provision of drugs and consumables free of charge by the NTP.

Sixty-minute alteplase protocol: a new accelerated recombinant tissue-type plasminogen activator regimen for thrombolysis in acute myocardial infarction.

OBJECTIVES: Our aim was to design and evaluate a new and easily administered recombinant tissue-type plasminogen activator (rt-PA) regimen for thrombolysis in acute myocardial infarction (AMI) based on established pharmacokinetic data that improve the reperfusion success rate. BACKGROUND: Rapid restoration of Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow is a primary predictor of mortality after thrombolysis in AMI. However, TIMI grade 3 patency rates 90 min into thrombolysis of only 50% to 60% indicate an obvious need for improved thrombolytic regimens. METHODS: Pharmacokinetic simulations were performed to design a new rt-PA regimen. We aimed for a plateau tissue-type plasminogen activator (t-PA) plasma level similar to that of the first plateau of the Neuhaus regimen. These aims were achieved with a 20-mg rt-PA intravenous (i.v.) bolus followed by an 80-mg i.v. infusion over 60 min (regimen A). This regimen was tested in a consecutive comparative trial in 80 patients versus 2.25 10(6) IU of streptokinase/60 min (B), and 70 mg (C) or 100 mg (D) of rt-PA over 90 min. Subsequently, a confirmation trial of regimen A in 254 consecutive patients was performed with angiographic assessment by independent investigators of patency at 90 min. RESULTS: The comparative phase of the trial yielded, respectively, TIMI grade 3 and total patency (TIMI grades 2 and 3) of 80% and 85% (regimen A), 35% and 50% (B), 50% and 55% (C) and 60% and 70% (D). In the confirmation phase of the trial, regimen A yielded 81.1% TIMI grade 3 and 87.0% total patency. At follow-up angiography 7 (4.1%) of 169 vessels had reoccluded. In-hospital mortality rate was 1.2%. Nadir levels of fibrinogen, plasminogen and alpha2-antiplasmin were 3.6 +/- 0.8 mg/ml, 60 +/- 21% and 42 +/- 16%, respectively (mean +/- SD). Fifty-seven patients (22.4%) suffered from bleeding; 3.5% needed blood transfusions. CONCLUSIONS: The 60-min alteplase thrombolysis in AMI protocol achieved a TIMI grade 3 patency rate of 81.1% at 90 min with no indication of an increased bleeding hazard; it was associated with a 1.2% overall mortality rate. These results are substantially better than those reported from all currently utilized regimens. Head to head comparison with established thrombolytic regimens in a large-scale randomized trial is warranted.

Progression of coronary artery disease is dependent on anatomic location and diameter. The INTACT investigators.

OBJECTIVES: This study represents the first prospective, quantitative analysis of the association of progression of coronary atherosclerosis with anatomic site and diameter. BACKGROUND: The progressive course of coronary artery disease has been documented in many angiographic follow-up trials. METHODS: The data of 348 patients with coronary artery disease from the International Nifedipine Trial on Antiatherosclerotic Therapy (INTACT) were reviewed. Standardized coronary angiograms were taken 3 years apart and were analyzed quantitatively. The coronary tree was subdivided into 25 segments. The progression of 1,063 preexisting coronary stenoses and the appearance of 247 newly formed stenoses was assessed in relation to the mean diameter of segments (< 2 mm, 2 to 3 mm, > 3 mm) and to their position in the coronary tree (proximal, mid, distal) and in the three major coronary arteries. RESULTS: Decreases in the minimal diameter of preexisting stenoses were largest in segments that were > 3 mm in diameter (mean +/- SD 0.23 +/- 0.5 mm vs. 0.10 +/- 0.4 mm and 0.02 +/- 0.3 mm, p < 0.001), in a proximal position (0.14 +/- 0.5 mm vs. 0.09 +/- 0.4 mm and 0.06 +/- 0.3 mm, p = 0.081) and in the right coronary artery (0.14 +/- 0.4 mm vs. 0.07 +/- 0.4 mm and 0.07 +/- 0.3 mm, p < 0.01). Changes in percent diameter stenosis of preexisting stenoses were lowest in segments that were < 2 mm in diameter and in a distal position (p = NS). The number of new stenoses/segment was lowest in segments that were < 2 mm in diameter (44 of 1,756 vs. 139 of 1,967 and 64 of 1,125, p < 0.001) and in a distal position (77 of 2,370 vs. 84 of 1,193 and 86 of 1,285, p < 0.001) and was highest in segments of the right coronary artery (100 of 1,546 vs. 66 of 1,496 and 72 of 1,492, p = 0.044). CONCLUSIONS: Progression of coronary artery disease occurs most frequently in coronary segments that are > 2 mm in diameter, in a proximal or midartery position and in the right coronary artery.

Role of thrombolysis and thrombin in patients with acute coronary occlusion during percutaneous transluminal coronary angioplasty.

In a series of 447 patients with single vessel angioplasty, 27 (6.0%) had acute thrombotic occlusion early after the procedure. They were treated with combined intracoronary (20 mg)/intravenous (50 mg) thrombolysis with recombinant tissue-type plasminogen activator (rt-PA) and repeat mild balloon inflations. Reopening of the vessel was achieved in 22 patients (81.5%). Follow-up coronary angiography 24 to 36 h later revealed reocclusion in 12 patients (54.5%). Thrombin levels measured as thrombin-antithrombin-III complex in patients with successful thrombolysis and persistent patency decreased from 8.5 +/- 11.4 micrograms/liter at baseline to 3.5 +/- 1.4 micrograms/liter 120 min after the start of thrombolysis; these levels increased from 9.4 +/- 15.0 micrograms/liter at baseline to 15.7 +/- 13.5 micrograms/liter 120 min after the start of thrombolysis in the patients with unsuccessful thrombolysis or early reocclusion (p less than 0.05). When a borderline value for thrombin-antithrombin-III complex level of 6 micrograms/liter was selected to separate the two groups of patients, patients with an unfavorable clinical course were identified 120 min after the start of thrombolysis by levels greater than 6 micrograms/liter (sensitivity 100%, specificity 92.8%). Thus, after abrupt thrombotic vessel closure during coronary angioplasty, the short-term results of thrombolysis seem to be governed by the release of thrombin. In two thirds of patients, however, the thrombin release cannot be suppressed by concomitant aspirin and heparin therapy. Even after successful reopening of the vessel these patients should therefore undergo immediate aortocoronary bypass grafting.

Relation of antianginal efficacy of nifedipine to degree of coronary arterial narrowing and to presence of coronary collateral vessels.

Thirty-six patients with chronic stable angina pectoris or with stable and vasospastic components of angina pectoris were classified by coronary arteriographic findings into 4 groups. Patients in group A had a single stenotic coronary artery; patients in groups B, C and D had occluded arteries, but these arteries had been collateralized to varying degrees, and an epicardial coronary steal phenomenon was possible. All patients underwent multiple exercise tests before and after randomized, double-blind, crossover treatment with 20 mg of nifedipine, 20 mg of isosorbide dinitrate, a combination of both, and placebo. Maximal and mean ST-segment depression, occurrence of angina pectoris and heart rate were evaluated. After nifedipine treatment, mean ischemic ST-segment depression was reduced 21% in group A (p less than 0.05), but was not significantly altered in the other groups (group B, 2% decrease; group C, 10% increase; group D, 3% decrease). However, isosorbide dinitrate reduced ST-segment depression significantly in all groups (group A, 29%, p less than 0.001; group B, 18%, p less than 0.01; group C, 19%, p less than 0.05; group D, 33%, p less than 0.05). The combination with nifedipine did not further improve the effect of isosorbide dinitrate. Maximal ST-segment depression and angina pectoris paralleled the changes in mean ST depression during the different medications. Heart rate at rest was not significantly changed after nifedipine treatment in any group, but increased significantly after isosorbide dinitrate treatment in groups B and C (group B, 12%, p less than 0.01; group C, 9%, p less than 0.05); heart rate during exercise did not differ significantly in any group or after any form of medication from placebo.

Standardization of coronary vasomotor tone with intracoronary nitroglycerin.

Maximal, reproducible, and thus "standardized" dilation of epicardial coronary arteries can be easily achieved with intracoronary bolus administration of 0.1 mg nitroglycerin without considerable decrease in blood pressure. The addition of other nitrocompounds or calcium antagonists cannot increase coronary dilation after nitroglycerin, but may be hampered by adverse effects.

Protection from digoxin-induced coronary vasoconstriction in patients with coronary artery disease by calcium antagonists.

Intravenous digoxin induces constriction of normal and stenotic coronary arteries in patients with coronary artery disease, which may lead to ischemic complications. We found that pretreatment with oral nisoldipine and intracoronary nitroglycerin neutralizes this digoxin-induced effect.

Percutaneous transluminal angioplasty of aortocoronary venous bypass grafts and effect of the caliber of the grafted coronary artery on graft stenosis.

The influence of morphologic parameters on the recurrence of stenosis after percutaneous transluminal coronary angioplasty of 49 stenoses in aortocoronary venous bypass grafts of 41 patients was investigated. Vessel dimensions were measured quantitatively. Angioplasty was successful in 46 stenoses (94%) of 38 patients (93%). In 35 patients (92% of successfully treated patients) with 42 stenoses, control angiography was performed after a mean interval of 189 +/- 186 days. In 9 patients (26%), 9 stenoses (21%) had recurred. The diameter of the grafted coronary artery distal to the anastomosis was significantly smaller in grafted arteries with than without recurrent stenoses (1.92 +/- 0.52 vs 2.45 +/- 0.50 mm; p less than 0.01). Recurrence also correlated with the ratio between graft diameter and coronary artery diameter greater than 1.35 (p less than 0.02) and with the stenosis length greater than 10 mm before angioplasty (p less than 0.01). Graft age, graft diameter and stenosis location in the graft had no significant influence on recurrence. Thus, the diameter of the grafted coronary artery and the length of the critical stenosis are parameters for recurrence after angioplasty of graft stenoses and should be considered in the selection of patients for this intervention.

The neuropsychology of blunt head injury in the early postacute stage: effects of focal lesions and diffuse axonal injury.

This investigation evaluated the neuropsychological symptoms in the early posttraumatic period following blunt head injury and their correlation to routine imaging data in a consecutive series of TBI patients (Magdeburg Neurotrauma Databank). Of 135 consecutive patients, 68 could be assessed neuropsychologically 8-21 days after trauma. In 61 patients, routine clinical CT data were sufficient for neuroradiological analysis focusing on the presence or absence of CT signs of diffuse axonal injury (DAI) or focal traumatic injury. In these patients, the initial GCS score was significantly correlated with the presence of DAI but not with focal pathology. The presence of DAI was correlated with behavioral and cognitive symptoms of frontal lobe dysfunction, especially in interference tasks (Go/NoGO and Stroop reaction times) and semantic fluency. The presence of local frontal or temporal traumatic lesions was associated with deficits in concept formation, fluency tasks and behavioral symptoms, but not with increased interference. Patients with frontal contusions were impaired in a task of visuomotor planning and performance (Block design). Our data indicate that both traumatic DAI and focal lesions result in frontal lobe symptoms. We conclude that, even in clinically "mild" TBI, brain imaging should be used to identify patients with substantial brain damage. These should be assessed neuropsychologically for possible posttraumatic cognitive or behavioral impairment. In consideration of its easy accessibility, the refined use of the CT is considered a promising and valid tool for patient stratification. The application of MRI and biochemical markers may further improve prognostic predictions.

Temporal profile of release of neurobiochemical markers of brain damage after traumatic brain injury is associated with intracranial pathology as demonstrated in cranial computerized tomography.

This study aimed at the investigation of release patterns of neuron specific enolase (NSE) and protein S-100B after traumatic brain injury (TBI) and their association with intracranial pathologic changes as demonstrated in computerized tomography (CT). We analyzed NSE and S-100B concentrations in serial venous blood samples taken one to three days after TBI in 66 patients by the use of immunoluminometric assays. These markers are considered to be specific neurobiochemical indicators of damage to glial (S-100B) or neuronal (NSE) brain tissue. Standardized neurological examination and plani- and volumetric evaluation of computerized tomography scans were performed in all patients. Patients with medium severe to severe TBI [Glasgow Coma Scale (GCS) score at the site of accident < or =12] exhibited significantly higher NSE and S-100B concentrations and a significantly longer release compared to patients with minor head injury (GCS: 13-15). Both, patients with and without visible intracerebral pathology in CT scans exhibited elevated concentrations of NSE and S-100B after TBI and a significant decrease in the follow-up blood samples. Release patterns of S-100B and NSE differed in patients with primary cortical contusions, diffuse axonal injury (DAI), and signs of cerebral edema (ICP) without focal mass lesions. All serum concentrations of NSE and S-100B were significantly correlated with the volume of contusions. The data of the present study indicate that the early release patterns of NSE and S-100 may mirror different pathophysiological consequences of traumatic brain injury.

Protein S-100B and neuron specific enolase as early neurobiochemical markers of the severity of traumatic brain injury.

The present study aimed at the predictive value of early release patterns of protein S-100B and neuron specific enolase (NSE) in patients with traumatic brain injury. We investigated 69 patients who were admitted to the Department of Neurosurgery following traumatic brain injury. Both NSE and S-100B serum concentrations during the first three days after admission were highly and significantly correlated with Glasgow Coma and Coma Remission Scale scores at the respective blood sampling times as well as 2 weeks later. Signs of intracranial pathology as evaluated by CCT or MRI scans showed no association with NSE or S-100B release patterns. Our data support the hypothesis that NSE and protein S-100B are useful and sensitive neurobiochemical markers for the early clinical outcome of traumatic brain injury.

The adverse effects of angiographic radiocontrast media.

Radiographic procedures which require the intravascular administration of water-soluble radiocontrast media are performed with increasing frequency. Each examination carries risks that are related either to the technique itself or to the opaque medium chosen. The pathogenesis of radiocontrast media-related adverse effects cannot be explained by a unique theory. The major factors implicated are direct chemotoxic effects and the physicochemical properties of contrast media, the latter being the basis for development of new contrast agents. With nonionic opaque media cardiovascular adverse effects, heat sensation and local pain are observed less frequently. However, it remains unclear whether the incidence of organ dysfunction or anaphylactic reactions with nonionic contrast media currently used can be reduced. This review compares ionic and nonionic contrast media, and current thoughts on the pathophysiology and treatment of adverse reactions are presented.

Molecular size distribution of somatostatin-like immunoreactivity in the cerebroventricular fluid of neurosurgical patients.

The molecular size distribution of somatostatin-like immunoreactivity (SLI) in the cerebroventricular fluid of patients with Parkinson's disease, dystonic syndromes, multiple sclerosis, basal and midline tumors, epilepsy and pain syndromes was investigated by separation with a Sephadex G-50f column and subsequent radioimmunoassay of the eluate. Marked heterogeneity of SLI was observed in most of the pools investigated. The most conspicuous feature of the elution profiles was the preponderance of the peak coeluting with synthetic somatostatin-14, whereas the peaks comigrating with synthetic somatostatin-28 and attributable to precursor-like SLI represented only minor or trace amounts of total immunoreactivity. These findings are consistent with the greater biological activity of somatostatin-14 in the human central nervous system, whereas somatostatin-28 appears to represent the more active form in the pituitary and in the intestinal mucosa. Solely in the case of brain tumor patients, some differences could be seen, resulting in an approximately equal distribution of somatostatin-14 and somatostatin-28 in two pools of ventricular fluid and by the detection of a degradation product of somatostatin-14 in another one. These observations could be explained by a lowered barrier function as a consequence of increased intracranial pressure in case of brain tumors, which is well in accordance with a markedly elevated total protein content being a sign of a lowered barrier function.

Ventricular fluid neuropeptides in Parkinson's disease. I. Levels and distribution of somatostatin-like immunoreactivity.

We have measured somatostatin-like immunoreactivity SLI in cerebroventricular fluid of patients with Parkinson's disease (PD) and other extrapyramidal disorders with hyperkinesia. Patients with PD showed a significantly lower concentration of SLI when compared with levels in control patients with chronic stable multiple sclerosis or temporal lobe epilepsy. Less markedly decreased levels of SLI were also noted in patients with torsion dystonia. Of two patients with Huntington's disease one showed a high and one a medium concentration of SLI. According to the site of the stereotactic cannula, verified by ventriculopathy, SLI concentrations in CSF specimen obtained from the foramen Monro tended to be higher than in specimen from a supraforaminal level. Of 5 other patients with lateral and third ventricle being accessible during the passage of the stereotactic cannula, 4 showed higher SLI concentrations in the third ventricle compared to the lateral ventricle. High performance liquid chromatographic analysis combined with radioimmunoassay showed molecular heterogeneity of SLI in CSF. The ratio of SST-14 to SST-28 was higher in the third ventricle than in the lateral ventricle.

Ventricular fluid neuropeptides in Parkinson's disease. II. Levels of substance P-like immunoreactivity.

Substance P-like immunoreactivity (SPLI) was determined in cerebrovascular fluid of patients with extrapyramidal motor diseases. Patients with Parkinson's disease (PD) showed a SPLI concentration decreased by 30% compared with patients without extrapyramidal disease. No differences were apparent for patients with dystonia. Fluid obtained from the foramen Monro showed higher SPLI concentrations than fluid from a lateral ventricle, indicating that hypothalamic sources are important for ventricular substance P. Lateral ventricular SPLI was particularly low in parkinsonian patients which raises the possibility of a decreased SPergic activity in basal ganglia occurring in PD.

Comparative in-vitro validation of eight first- and second-generation quantitative coronary angiography systems.

BACKGROUND: It is known that first-generation quantitative coronary angiography (QCA) systems overestimate small vessel sizes owing to the point-spread function of the respective X-ray imaging chain. With second-generation systems new algorithms were introduced to correct for this source of error. OBJECTIVE: To evaluate the efficiency of the modified contour detection algorithms. METHODS: Six second-generation QCA systems (CMS, QANSAD, AWOS, CAAS II, Cardio 500, and Angioimage) were validated and compared with first-generation systems (CAAS and ARTREK). By using an arterial phantom consisting of stenotic and nonstenotic glass tubes (of diameters 0.5-5.0 mm) the accuracy and precision of each analysis system, as well as their additional accuracy and precision values for phantom diameters < or = 1.0 mm were determined. RESULTS: All systems had high accuracy and precision values, but first-generation systems overestimated small vessel diameters. With second-generation systems a significantly improved accuracy in the submillimeter range (an accuracy within +/-0.028 mm) was obtained. This improvement was accompanied by a moderate reduction in precision in the submillimeter range. CONCLUSION: The new algorithms of the second-generation QCA systems allow accurate and reliable measurements of small coronary dimensions and, therefore, precise analysis of coronary stenoses of moderate-to-high grade seems feasible with the improved accuracy of the new systems.