prhJ and hrpG, two new components of the plant signal-dependent regulatory cascade controlled by PrhA in Ralstonia solanacearum.

hrp gene expression in the phytopathogenic bacterium Ralstonia solanacearum GMI1000 is induced through the HrpB regulator in minimal medium and upon co-culture with plant cell suspensions. The putative outer membrane protein PrhA is specifically involved in hrp gene activation in the presence of plant cells and has been proposed to be a receptor of a plant-dependent signal transduction pathway. Here, we report on the identification of two regulatory genes, hrpG and prhJ, located at the right-hand end of the hrp gene cluster, that are required for full pathogenicity. HrpG belongs to the OmpR subclass of two-component response regulators and is homologous to HrpG, the activator of hrp genes in Xanthomonas campestris pv. vesicatoria. PrhJ is a novel hrp regulatory protein, sharing homology with the LuxR/UhpA family of transcriptional activators. As for HrpG of X. c. pv. vesicatoria, HrpG is required for hrp gene expression in minimal medium, but, in addition, we show that it also controls hrpB gene activation upon co-culture with Arabidopsis thaliana and tomato cell suspensions. In contrast, PrhJ is specifically involved in hrp gene expression in the presence of plant cells. hrpG and prhJ gene transcription is plant cell inducible through the PrhA-dependent pathway. From these results, we propose a regulatory cascade in which plant cell signal(s) sensed by PrhA are transduced to the prhJ gene, whose predicted product controls hrpG gene expression. HrpG then activates the hrpB regulatory gene, and, subsequently, the remaining hrp transcriptional units in all known inducing conditions.

Adjunctive stent implantation following directional coronary atherectomy in patients with coronary artery disease.

OBJECTIVES: This prospective case-control study evaluated the acute and long-term results of stent implantation preceded by debulking of the plaque by means of directional coronary atherectomy. BACKGROUND: In comparison with balloon angioplasty, intracoronary stenting produces a larger luminal diameter, maintains artery patency and reduces the incidence of restenosis. Optimal stent deployment is a pivotal factor for achieving the best results, but the bulk of the atherosclerotic plaque opposes stent expansion and may limit the success of the procedure. Debulking of the plaque may provide a better milieu for optimal stent deployment. METHODS: Directional coronary atherectomy followed by a single Palmaz-Schatz stent implantation was attempted in 100 patients. The successes, complications and angiographic results of the combined procedure were evaluated both acutely and during follow-up. Matched patients undergoing successful Palmaz-Schatz stent implantation alone during the same period served as controls. RESULTS: Atherectomy followed by stent implantation was performed in 94 patients with 98 lesions; periprocedural complications were observed in four cases. The stenosis diameter decreased from 76+/-9% at baseline to 30+/-13% after atherectomy (p < 0.0001), and 5+/-9% after stent implantation (p < 0.0001); it increased to 27+/-15% at 6-month angiography (p < 0.0001). During the 14+/-10 months of follow-up, none of the patients died or experienced myocardial infarction, but three patients underwent target lesion revascularization. The patients undergoing stent implantation alone achieved smaller acute gains, tended to have a higher late lumen loss, had a higher restenosis rate (30.5% vs. 6.8%, p < 0.0001) and showed a greater incidence of clinical events during follow-up (p < 0.0001). CONCLUSIONS: Debulking atherosclerotic lesions by means of directional coronary atherectomy before stent implantation is a safe procedure with a high success rate and a low incidence of restenosis at follow-up.

PrhA controls a novel regulatory pathway required for the specific induction of Ralstonia solanacearum hrp genes in the presence of plant cells.

The Ralstonia solanacearum hrp gene cluster is organized in five transcriptional units. Expression of transcriptional units 2, 3 and 4 is induced in minimal medium and depends on the hrp regulatory gene hrpB, which belongs to unit 1. This regulatory gene also controls the expression of genes, such as popA, located to the left of the hrp cluster. Here, we show that, upon co-culture with Arabidopsis thaliana and tomato cell suspensions, the expression of the hrp transcriptional units 1, 2, 3 and 4 is induced 10- to 20-fold more than in minimal medium. This induction is not triggered by diffusible signals but requires the presence of plant cells. Moreover, we show that this specific plant cell induction of hrp genes is controlled by a gene, called prhA (plant regulator of hrp genes), located next to popA. This gene codes for a putative protein of 770 amino acids, which shows similarities with TonB-dependent outer membrane siderophore receptors. Expression of prhA and hrp genes is not regulated by iron status, and we postulate that iron is not the signal sensed by PrhA. In prhA mutants, the induction of hrpB and other hrp genes is abolished in co-culture with Arabidopsis cells, partially reduced in co-culture with tomato cells and not modified in minimal medium. prhA mutants are hypo-aggressive on Arabidopsis (accessions Col-0 and Col-5) but remain fully pathogenic on tomato plants, suggesting that the co-culture assays mimic the in planta conditions. A model suggesting that PrhA is a receptor for plant specific signals at the top of a novel hrp regulatory pathway is discussed.

Dobutamine stress echocardiography early after myocardial infarction treated with thrombolysis. Identification of myocardial viability and ischemia and relation to spontaneous functional recovery.

The aim of the study was to assess the ability of dobutamine stress echocardiography to detect myocardial viability and ischemia in patients with acute myocardial infarction treated with thrombolysis and to correlate the acute response to dobutamine with late spontaneous functional recovery at follow-up. Forty-two consecutive patients with myocardial infarction treated with thrombolysis underwent low- (5 and 10 mcg/kg/min) and high-dose (20 to 40 mcg/kg/min) dobutamine stress echocardiography at a mean of 7 +/- 3 days of the acute phase. A follow-up 2D-echocardiogram was performed in all patients to evaluate the spontaneous recovery of function in the infarct area. On the basis of the response to the test, 3 groups of patients were identified: group 1 included 7 patients showing an improvement in left ventricular asynergy score index at low doses (from 1.5 +/- 0.3 to 1.3 +/- 0.2, p < 0.05) with no deterioration at high doses, indicative of myocardial viability without ischemia; group 2 (23 patients) showed a significant improvement in the asynergy index at low doses (from 1.58 +/- 0.3 to 1.32 +/- 0.32, p < 0.05) followed by a deterioration at high doses (1.68 +/- 0.4, p < 0.05 vs low-dose), suggestive of residual myocardial ischemia in the infarct zone; group 3 included 12 patients who showed no significant changes in the baseline asynergy score index (1.67 +/- 0.2) either at low or at high doses. The acute response to dobutamine stress echocardiography accurately predicted the spontaneous recovery of function in the infarct area at follow-up: both group 1 and group 2 patients showed a significant reduction in the asynergy score index (group 1: 1.16 +/- 0.3 vs 1.5 +/- 0.2, p < 0.001; group 2: 1.43 +/- 0.3 vs 1.58 +/- 0.3, p < 0.05), while group 3 had no recovery in the asynergy index (1.67 +/- 0.2 vs 1.67 +/- 0.2). Thus, in patients with acute myocardial infarction treated with thrombolysis dobutamine stress echocardiography can detect myocardial viability in 71% and ischemia in the infarct zone in 55% of patients; moreover, the response to the test during the acute phase is correlated with the degree of the late spontaneous recovery of function in the infarct area.

Thrombin activity and early outcome in unstable angina pectoris.

BACKGROUND: The blood coagulation system is frequently activated in the acute phase of unstable angina, but it is unknown whether the augmented function of the hemostatic mechanism may serve as a marker of increased risk for an early unfavorable outcome. METHODS AND RESULTS: Plasma concentrations and 24-hour urinary excretion of fibrinopeptide A were prospectively determined in 150 patients with unstable angina. All patients underwent 24-hour Holter monitoring, during which time urine was collected; at the end of this period, a blood sample was taken and coronary arteriography was performed. The patients were followed up for the occurrence of cardiac events (death and myocardial infarction) until they underwent coronary revascularization or until they were discharged from the hospital. Fibrinopeptide A plasma levels and 24-hour urinary excretion were found to be abnormally elevated in 50% and 45% of the study population, respectively. During hospitalization, 11 patients developed myocardial infarction and 2 patients died. Kaplan-Meier analysis demonstrated a significantly higher probability of developing cardiac events in patients with abnormal rather than normal plasma levels of fibrinopeptide A (P<.01), whereas no difference in outcome was observed between patients with normal and those with abnormal 24-hour urinary excretion. Cox regression analysis showed that the only variables independently related to an early unfavorable outcome were the presence of persistent ischemia during 24-hour Holter monitoring (P<.0001), the presence of intracoronary thrombosis at angiography (P=.016), and abnormal fibrinopeptide A plasma levels (P=.038). CONCLUSIONS: Patients with unstable angina pectoris and abnormal fibrinopeptide A plasma levels are at increased risk for an early unfavorable outcome.

Effect of the increasing use of coronary angioplasty on outcome at one year in patients with unstable angina.

OBJECTIVE: To determine whether the increasing use of percutaneous transluminal angioplasty in patients with unstable angina has reduced the need for bypass surgery and whether this change in the choice of treatment affected the outcome at one year in patients with unstable angina who were admitted to hospital in two different periods of time. DESIGN: Retrospective analysis of consecutive patients with unstable angina (angina at rest with ST-T changes during pain) who underwent coronary arteriography in two different periods of time. PATIENTS: 158 patients were admitted to hospital between January 1988 and June 1989 (group 1) and 140 patients admitted between January 1992 and June 1993 (group 2). RESULTS: Coronary angioplasty procedures nearly doubled from 29% in group 1 to 56% in group 2 whereas bypass surgery decreased from 36% in group 1 to 23% in group 2 (P < 0.01). Coronary angioplasty increased and bypass surgery decreased in patients with one vessel disease (P < 0.01), two vessel disease (P < 0.05), and three vessel disease (P < 0.01). Coronary angioplasty also increased and bypass surgery decreased in refractory angina and in patients with ejection fraction < 0.50 (both P < 0.05). At 1-year follow up, 14 patients in group 1 (9%) and 10 in group 2 (7%) either died or had myocardial infarction (P = NS). Revascularisation procedures were needed in 16 group 1 patients (10%) and 27 group 2 patients (19%, P < 0.05). CONCLUSIONS: Coronary angioplasty became more widely used in patients with unstable angina. This reduced the need for bypass surgery in patients with multivessel disease, refractory angina, and depressed left ventricular function. This change in treatment did not affect 1-year mortality or the myocardial infarction rate. More patients in the more recent group in which angioplasty was the preferred treatment required a further revascularisation procedure than in the earlier group in which bypass grafting was more often used as the initial treatment.

Results of dipyridamole plus atropine echo stress test for the diagnosis of coronary artery disease.

Sensitivity of dipyridamole stress echocardiography (DIP-E) has been reported to be less than ideal in particular subsets of patients such as those with less severe extent of coronary artery disease (CAD). To verify if sensitivity could be improved, ATRO (1 mg in 2 minutes) was added at the end of a negative high-dose (0.84 mg/kg over 10 minutes) DIP-E in 61 consecutive patients (58 men, aged 53 +/- 7 years) evaluated for chest pain (33%) or for detection of residual ischemia after acute myocardial infarction (AMI) or previous MI (67%). DIP-E was positive in 28/61 (46%) and negative in 33/61 (54%) patients. Additional echo positivity was obtained in 18/33 (54%) patients after ATRO. Coronary arteriography was normal in 6 patients (10%); 1-vessel CAD was diagnosed in 28 (46%), 2-vessel CAD in 16 (26%) and 3-vessel CAD in 11 (18%) cases. The sensitivity for CAD diagnosis was 49% (27/55) for DIP-E and 84% (46/55) for DIP-E+ATRO (p < 0.001). Specificity was 83% and 80%, respectively. Diagnostic accuracy increased from 52% to 83% (p < 0.001). The better diagnostic accuracy of DIP-E was mainly related to the significant increase in sensitivity of the combined test in patients with 1-vessel CAD (from 46% to 75%) (p < 0.005). At quantitative coronary evaluation, compared to patients with positive DIP-E+ATRO or negative DIP-E+ATRO test, patients with positive DIP-E had a higher mean % diameter stenosis: 80 +/- 13% vs 72 +/- 24% and 65 +/- 36%, respectively. Peak heart rate was significantly higher after the addition of ATRO vs basal and DIP alone in patients with a positive DIP-E+ATRO test. The addition of ATRO to DIP increases diagnostic accuracy of DIP-E particularly in patients with less severe extent of CAD; ATRO may be considered as a useful routine procedure for increasing diagnostic value of DIP-E test.

The hrp gene locus of Pseudomonas solanacearum, which controls the production of a type III secretion system, encodes eight proteins related to components of the bacterial flagellar biogenesis complex.

Five transcription units of the Pseudomonas solanacearum hrp gene cluster are required for the secretion of the HR-inducing PopA1 protein. The nucleotide sequences of two of these, units 1 and 3, have been reported. Here, we present the nucleotide sequence of the three other transcription units, units 2, 4 and 7, which are together predicted to code for 15 hrp genes. This brings the total number of Hrp proteins encoded by these five transcription units to 20, including HrpB, the positive regulatory protein, and HpaP, which is apparently not required for plant interactions. Among the 18 other proteins, eight belong to protein families regrouping proteins involved in type III secretion pathways in animal and plant bacterial pathogens and in flagellum biogenesis, while two are related solely to proteins involved in secretion systems. For the various proteins found to be related to P. solanacearum Hrp proteins, those in plant-pathogenic bacteria include proteins encoded by hrp genes. For Hrp-related proteins of animal pathogens, those encoded by the spa and mxi genes of Shigella flexneri and of Salmonella typhimurium and by the ysc genes of Yersinia are involved in type III secretion pathways. Proteins involved in flagellum biogenesis, which are related to Hrp proteins of P. solancearum, include proteins encoded by fli and flh genes of S. typhimurium, Bacillus subtilis and Escherichia coli and by mop genes of Erwinia carotovora. P. solanacearum Hrp proteins were also found to be related to proteins of Rhizobium fredii involved in nodulation specificity.

[The evolution of the therapeutic choice in patients with the outcomes of non-Q myocardial infarct: 2 periods compared]. / Evoluzione della scelta terapeutica nei pazienti con esiti di infarto miocardico non-Q: due periodi a confronto.

BACKGROUND: Over the last years there has been a tremendous increase in coronary angioplasty procedures (PTCA), due to the availability of better materials and to the refinement of operators skill. It is not known however if this "PTCA boom" has modified our approach to the patients with particular clinical situations, such as those with non-Q wave myocardial infarction. The purpose of this study was to verify, in patients undergoing coronary angiography for clinical reasons after a non-Q wave myocardial infarction, the clinical decision concerning the therapeutical choice in two different periods (101 patients in 1988 vs. 102 patients in 1992). METHODS AND RESULTS: Patients in the two groups had similar clinical manifestations whereas patients observed in 1992 had more frequently 2-vessel disease than single vessel disease as compared to patients studied in 1988 (p < 0.05). The distribution of patients with normal coronary arteries or with 3-vessel disease was similar in the two periods. In 1988 medical therapy was the most recommended treatment at discharge (47%), followed by aorto-coronary bypass (29%) and coronary angioplasty (24%). On the contrary, in 1992 PTCA was performed in 48% of patients, medical therapy was recommended in 28% while the incidence of coronary surgery was reduced to 24% (p < 0.01). From a clinical point of view a significant increase in PTCA procedures was seen in patients presenting with unstable angina after the non-Q wave myocardial infarction (54% of these patients undergoing PTCA in 1992 vs. 30% in 1988, p = 0.03) and in patients with effort angina and a positive exercise test at low workload (53% of these patients undergoing PTCA in 1992 vs. 22% in 1988, p < 0.05). Moreover, in 1992 PTCA procedures increased in patients with single vessel disease (64% in 1992 vs. 49% in 1988) and in patients with 2-vessel disease (64% in 1992 vs. 9% in 1988). Therefore, in these patients the need of aorto-coronary by pass was reduced from 39% in 1988 to 19% in 1992 (p < 0.05). The success rate of PTCA procedures was 98% in 1992 and 83% in 1988. No major complications were observed in the two study periods and no patients underwent urgent coronary surgery. CONCLUSIONS: These data show an increase in PTCA procedures over the last years in patients undergoing coronary angiography for clinical reasons after a non-Q wave myocardial infarction. The greater experience of operators allowed for improved results, thus reducing the need of coronary surgery in these patients.

[Adding atropine improves the diagnostic accuracy of dipyridamole-echo test]. / L'aggiunta di atropina migliora l'accuratezza diagnostica del test eco-dipiridamolo.

BACKGROUND: The clinical experience with dipyridamole stress echocardiography for the diagnosis of coronary artery disease (CAD) revealed that patients with less severe extent of CAD and limited impairment of coronary reserve are frequently not recognized by the test. Increasing myocardial oxygen consumption adding atropine to dipyridamole may improve the diagnostic accuracy of dipyridamole for the detection of CAD. METHODS: Fifty-two patients (48 men, aged 53 +/- 7 years) underwent a high-dose dipyridamole-echo stress test (0.84 mg/kg over 10 minutes) and coronary arteriography within 15 days from the test. Eighteen out of 52 patients were referred for chest pain; 11 suffered from a previous myocardial infarction (MI) and 23 were studied in the early phase after a first acute MI. Starting after 4 minutes from the end of dipyridamole infusion, atropine was added, in 2 doses of 0.5 mg each, at 1-minute interval in those patients with no echocardiographic evidence of myocardial ischemia after dipyridamole alone. Left ventricular wall motion was analyzed on a 11-segment left ventricular model in a qualitative manner. RESULTS: Dipyridamole-echo stress test was positive in 23/52 (44%) and negative in 29/52 (56%) patients. In these patients atropine was added resulting in an additional echo positivity in 14/29 patients. Coronary arteriography was normal in 6 patients (12%); 1-vessel CAD was diagnosed in 23 (44%), 2-vessel CAD in 13 (25%) and 3-vessel CAD in 10 (19%) cases. The sensitivity for CAD diagnosis was 48% (22/46) for dipyridamole alone and 76% (35/46) for dipyridamole-atropine echo (p < .005), while the specificity was 83% (5/6) and 80% (4/5) respectively. Diagnostic accuracy increased from 52% (27/52) to 75% (39/52) (p < .001). The better diagnostic accuracy of dipyridamole-atropine echo stress test was mainly related to the increased sensitivity of the combined test in patients with 1-vessel CAD (from 39% to 70%) (p < .005). Peak heart rate was significantly higher after the addition of atropine (100 +/- 17 beats/min) compared to basal (64 +/- 10) and dipyridamole (85 +/- 12) in those patients with a positive dipyridamole-atropine echo stress test. No limiting side effects were elicited with the addition of atropine to dipyridamole. CONCLUSIONS: The combination of atropine and dipyridamole induces a chronotropic stress adjunctive to flow maldistribution phenomena that permits to increase diagnostic accuracy of dipyridamole-echo stress test particularly in patients with less severe extent of CAD; it is usually well tolerated and safe and may be considered as a useful procedure for optimizing diagnostic value of dipyridamole-echo stress test.

Effects of coronary angioplasty on left ventricular function.

It is well known that myocardial revascularization after successful coronary bypass surgery results in improved left ventricular function. Coronary angioplasty also results in successful revascularization, favorably affecting both stunned and hibernating myocardium. We studied 22 patients with chronic stable angina who underwent successful angioplasty for an isolated narrowing of the proximal or midportion of the left anterior descending artery. These patients also performed isometric exercises before and after angioplasty, which can be used to characterize left ventricular function. Revascularization after angioplasty induced an immediate improvement in left ventricular function in those patients with dysfunction secondary to hibernating myocardium. Further studies are needed to assess the possibility of the myocardial stunning phenomenon occurring after angioplasty in those patients without left ventricular improvement.

Assessment of left ventricular function by isometric handgrip exercise after thrombolysis in patients with refractory unstable angina.

The handgrip test has been proposed for the evaluation of the hemodynamic reserve in patients with coronary artery disease and to quantitate the impairment of left ventricular (LV) function. The present study was designed to evaluate the effect of thrombolytic therapy in patients with refractory unstable angina in order to test the hypothesis that a reduction in intracoronary thrombosis could ameliorate their hemodynamic response to the handgrip test. During left heart catheterization, 20 patients with refractory unstable angina of recent onset performed a handgrip test before (HG1) and 24-72 hours after (HG2) being randomized to receive recombinant tissue-type plasminogen activator or placebo, according to a double-blind parallel group design. HG1 induced an increase in heart rate (p < 0.001), in systolic pressure (p < 0.001), and a reduction in ejection fraction (p < 0.05). Changes in LV end-diastolic pressure during baseline handgrip were highly different in individual patients, resulting in a trend toward an increase. Similarly, a different individual response was observed in the behavior of the isovolumetric and relaxation indices. In comparison with HG1, no difference was detected during HG2 in the 2 treatment groups with respect to changes in LV volumes, ejection fraction, LV systolic and diastolic pressures, +dP/dt, (dP/dt)/P, -dP/dt, and tau index. In patients with refractory unstable angina of recent onset, the handgrip test performed before and after thrombolysis did not prove to be useful in assessing directional changes of LV performance, mainly because of the different individual response to the baseline handgrip test.

Influence of elastic recoil on restenosis after successful coronary angioplasty in unstable angina pectoris.

The elastic behavior of the dilated coronary vessel has been reported to affect the immediate results of coronary angioplasty. To determine whether elastic recoil may also influence the long-term restenosis process, 98 consecutive patients with unstable angina and 1-vessel disease were studied. An automated coronary quantitative program was used for the assessment of balloon and coronary luminal diameters. Elastic recoil was defined as the percent reduction between minimal balloon diameter at the highest inflation pressure and minimal lesion diameter immediately after coronary angioplasty. Follow-up coronary arteriography was performed 8 to 12 months after the procedure in all patients. The mean elastic recoil averaged 17.7 +/- 16% and was correlated to the degree of residual stenosis immediately after coronary angioplasty (r = 0.64; p < 0.001). Restenosis, defined as > 50% diameter stenosis at follow-up, developed in 53 patients (54%). There was no correlation between the degree of elastic recoil and the changes in minimal lesion diameter observed during follow-up, whereas a positive correlation between the amount of elastic recoil and the incidence of restenosis was documented (r = 0.84; p < 0.05). Thus, the elastic properties of the dilated vessel do not influence the active process of restenosis. However, because elastic recoil negatively influences the initial results of angioplasty, it is more likely that further reductions in lumen diameter during follow-up can reach a threshold of obstruction considered critical for a binary definition of restenosis.

Transcriptional organization and expression of the large hrp gene cluster of Pseudomonas solanacearum.

Cloning and localized mutagenesis of the larger cluster of hrp genes of Pseudomonas solanacearum strain GMI1000 allowed the definition of the borders of this cluster, which now extends about 2 kb to the left of the insert of the previously described plasmid pVir2 (Boucher et al. 1987, J. Bacteriol. 169:5626-5632). The size of the cluster has also been expanded 3 kb to the right to include a region previously described as dsp; our present data demonstrate that insertions occurring in these 3 kb lead to leaky mutations affecting both pathogenicity on tomato and ability to induce the hypersensitive response (HR) on tobacco. Therefore, the size of the entire hrp gene cluster is estimated to be about 22 kb. The use of transposon Tn5-B20, which promotes transcriptional gene fusions, allowed us to demonstrate that the hrp gene cluster is organized in a minimum of six transcriptional units, which are transcribed when the culture is grown in minimal medium but are repressed during growth in rich medium or in the presence of peptone or Casamino Acids. The level of expression in minimal medium is modulated by the carbon source provided; pyruvate is the best inducer. Under these conditions the level of expression observed in vitro appears to be representative of the actual expression observed in planta.

Felodipine (once daily) versus nifedipine (four times daily) for Prinzmetal's angina pectoris.

In 30 consecutive patients with Prinzmetal's angina pectoris, the antiischemic effect of felodipine, a new long-acting vasoselective calcium antagonist, administered at doses of 10 and 20 mg once daily was compared with that of the well-established therapeutic regimen with nifedipine administered at a dose of 20 mg 4 times daily. Twenty-four-hour Holter monitoring was performed during a 2-day placebo run-in and at the end of each of 3 consecutive 6-day periods during which the 3 active treatments were administered in randomized sequence. Three patients withdrew, whereas 27 completed the study. The therapeutic regimens tested proved to be similarly effective; primary end points (ischemic episodes recorded by Holter monitoring, and anginal attacks reported on diary cards) occurred in 5 patients (19%) during nifedipine treatment, and in 7 (26%) and 3 (11%) during felodipine treatment with 10 and 20 mg, respectively (p = not significant). The distribution of residual ischemic episodes demonstrated that treatment with felodipine once daily provides 24-hour antiischemic protection. Twenty-six patients were followed up with 20 mg of felodipine once daily for a mean of 6 +/- 5 months, and 21 of them (81%) remained free of symptoms and Holter-recorded ischemic attacks. It is concluded that for Prinzmetal's angina pectoris, 24-hour antiischemic protection may be achieved with administration of felodipine once daily. The availability of a simplified therapeutic approach may constitute a real advantage in terms of patient compliance and improving the quality of life.

Abnormal coronary vasoconstriction as a predictor of restenosis after successful coronary angioplasty in patients with unstable angina pectoris.

BACKGROUND: High rates of restenosis after coronary angioplasty have been reported in patients with vasospastic angina. This study was designed to determine whether the occurrence of abnormal coronary vasoconstriction, detected by means of hyperventilation testing before angioplasty, influences the risk of restenosis after successful dilation. METHODS: Hyperventilation testing was performed 0 to 4 days before coronary angioplasty in 106 consecutive patients with unstable angina and single-vessel coronary artery disease. Abnormal coronary vasoconstriction was considered present if hyperventilation-induced myocardial ischemia occurred during the recovery phase of the test. All patients had follow-up angiography 8 to 12 months after angioplasty. RESULTS: Abnormal coronary vasoconstriction was observed in 48 patients (group 1), whereas 58 patients (group 2) had either a negative response throughout the test or a positive response only during the overbreathing phase of the hyperventilation test. Angioplasty was successful in 40 patients in group 1 and 51 in group 2. Restenosis was documented in 29 patients (73 percent) in group 1 and 13 (25 percent) in group 2 (relative risk of restenosis, 2.84; 95 percent confidence interval, 1.69 to 4.28; P less than 0.001). In a multivariate analysis, the following three characteristics were independently related to the risk of restenosis (in descending order of importance): ST-segment elevation during spontaneous ischemic attacks (P less than 0.001), hyperventilation-induced abnormal coronary vasoconstriction (P less than 0.001), and the presence of a lesion more than 10 mm long in the left anterior descending coronary artery (P less than 0.05). CONCLUSIONS: In patients with unstable angina and single-vessel coronary artery disease who have been selected for coronary angioplasty, the presence of hyperventilation-induced abnormal coronary vasoconstriction identifies a subgroup at high risk for restenosis.

Fibrinopeptide A excretion in urine: a marker of the cumulative thrombin activity in stable versus unstable angina patients.

Plasma levels and 24-hour urine excretion of fibrinopeptide A were measured in a consecutive series of 179 patients with angina pectoris. Sixty-four patients had stable angina and 115 patients had unstable angina. Urine was collected over 24 hours the day before coronary arteriography, and blood samples were taken at the end of urine collection. When the values of fibrinopeptide A in plasma and in the 24-hour urine specimens were compared, no significant correlation was found in patients with either stable (rs = 0.16, difference not significant) and unstable (rs = 0.07, difference not significant) angina. The concentrations of fibrinopeptide A in the plasma did not differ significantly when patients with stable angina (range 0.1 to 82.6, median 7.4 ng/mL) were compared with patients with unstable angina (range 0.2 to 61.7, median 14 ng/mL, p = 0.055), whereas fibrinopeptide A 24-hour urinary excretion was significantly higher in patients with unstable angina (range 0.3 to 38.1, median 11.8 micrograms/24 hr) than in patients with stable angina (range 0.4 to 38.1, median 3.8 micrograms/24 hr, p less than 0.001). Twenty-four-hour urine excretion of fibrinopeptide A in patients with unstable angina and angiographically documented intracoronary thrombi were higher than the corresponding values in patients with unstable angina without such angiographic characteristic (p less than 0.001). The largest increase in plasma and urine concentration of fibrinopeptide A was observed in patients whose first episode of angina at rest occurred within the previous 48 hours. We conclude that the cumulative thrombin activity, assessed by 24-hour urinary excretion of fibrinopeptide A, is a more useful index, compared with single fibrinopeptide A measurement in plasma, for discriminating between patients with stable and with unstable angina pectoris.

Diagnostic, morphologic, and histopathologic correlates in bronchogenic carcinoma. A review of 1,045 bronchoscopic examinations.

Information on the correlation between bronchoscopically visible aspects, histopathologic classification, and diagnostic yield is very scarce. To contribute to the knowledge of the subject, we reviewed the bronchoscopic charts of 1,045 patients with lung cancer who were seen in the years from 1983 to 1989 at the Bronchology Service of the A. Carle Hospital. Tumors were more often located centrally and superiorly. No preference as to side was found. Squamous carcinomas were, by far, the most frequent cell type. Forceps biopsies, brushings, and washings were positive in 79 percent, 38 percent, and 32 percent of the obtained specimens, respectively. Bronchoscopically, squamous and small-cell carcinomas were more often visualized as central tumor-like lesions, which were better diagnosed by forceps biopsies. Adenocarcinomas, on the contrary, were more frequently peripheral and showed infiltrative, compressive, or aspecific findings. In these latter tumors, cytologic studies were more fruitful. Large-cell anaplastic carcinomas had an intermediate behavior. Cell type, endoscopic appearance, and diagnostic success are interrelated features. Visible characteristics at bronchoscopy can therefore anticipate the more likely histotype and guide the diagnostic approach.

Ability of calcium-entry blockade by felodipine to disclose different pathogenetic mechanisms behind hyperventilation-induced myocardial ischemia in men.

To verify that myocardial ischemia occurring during either the overbreathing or recovery phase of the hyperventilation test is based on different pathogenetic mechanisms, 2 consecutive series of patients, selected on the basis of their response to a run-in hyperventilation test, were studied. Group I comprised 15 patients who developed ST-segment depression early during overbreathing, whereas group II consisted of 12 patients showing ST-segment depression late during the recovery phase. A single oral dose of felodipine 10 mg or of placebo was administered on 2 consecutive days according to a randomized, double-blind, crossover design, and the hyperventilation test was repeated, on both days of the study, 3 to 5 hours after drug intake. In group I, ST-segment depression occurred after placebo in all patients during overbreathing, with an increase in rate pressure product (from 112 +/- 31 at baseline to 168 +/- 55 mm Hg x beats/min/100 at the onset of ST-segment depression; p less than 0.01). After felodipine, 13 patients continued to show ST-segment depression during overbreathing, together with an increase in rate pressure product (from 107 +/- 24 at baseline to 158 +/- 46 mm Hg x beats/min/100 at the onset of electrocardiographic changes; p less than 0.01). In group II, all 12 patients showed ST-segment depression during recovery after placebo, with a rate pressure product comparable to baseline conditions (112 +/- 35 at baseline vs 102 +/- 27 mm Hg x beats/min/100 at the onset of ST-segment depression; difference not significant). After felodipine, no patient developed ST-segment depression or chest pain.(ABSTRACT TRUNCATED AT 250 WORDS)