Long-term anti-TNF-alpha treatments reverse the endothelial dysfunction in rheumatoid arthritis: the biological coherence between synovial and endothelial inflammation.

Rheumatoid arthritis (RA) is associated with an excess cardiovascular morbidity and mortality, related to systemic inflammation with endothelial dysfunction (ED) and impaired flow-mediated vasodilation (FMD). We assessed the FMD response to anti-TNF-alpha treatments in 28 RA patients, aged 49.8+/-15.3 years: an unpaired FMD was found in 66.7 percent of our cases and was restored after 6 weeks of anti-TNF-á treatment (13.5+/-5.3 percent vs 4.6+/-4.1 percent, p less than 0.05). Twenty-five percent of the infliximab patients demonstrated a long term response, compared with 60 percent of etanercept and 100 percent of adalimumab patients, after 2 years (p less than 0.01). Infections (3 cases), myocardial ischemia (1 case) or loss of response (4 cases) were associated with a worsened FMD, restored by shifting to adalimumab. The present study confirms that ED is an RA systemic disease marker, responsive to anti-TNF-alpha treatment and sensitive to clinical events or to a loss of response, underlying the biological coherence between synovial and endothelial inflammation.

[Hyperammonemia during hypothyroidism: an unusual biohumoral finding normalized by hormonal replacement treatment]. / Iperammoniemia in corso di ipotiroidismo: un insolito reperto bioumorale normalizzato con il trattamento ormonale sostitutivo.

In this paper we describe 3 clinical cases of hypothyroidism causing myopathy and hyperammonemia. The patients, all females, aged 32 to 64 years, presented with hoarseness, fatigue, dyspepsia (case I), difficulty speaking secondary to the sensation of tongue swelling and hoarseness (case II), and progressive weight gain and difficulty speaking secondary to tongue swelling after delivery (case III). Laboratory tests showed a marked increase in creatine phosphokinase (up to 4090 U/L; normal values 24-176 U/L) of muscle origin, and an increase in transaminases and ammonia (124 to 150 micrograms/dL; normal values up to 75 micrograms/dL). Hypothyroidism was confirmed by TSH > 100 microIU/mL (normal values 0.3-5 microIU/mL). Treatment only with L-thyroxine determined the complete and persistent recovery of well-being and of biochemical abnormalities. The patients remained in good health after more than 2 years of follow-up. Our finding of hyperammonemia caused by the lack of thyroid hormones in 3 patients with hypothyroid myopathy appears to be of a certain interest as, to our knowledge, this phenomenon has not been previously described. In conclusion our hypothesis is that increased muscle production of ammonia secondary to the hypothyroid myopathy determined an increased ammonia load, resulting in hyperammonemia. Decreased liver ureagenesis induced by the lack of thyroid hormones also contributed to the hyperammonemia.

[The effects of a left bundle-branch block on ventricular repolarization dispersion]. / Effetti del blocco di branca sinistra sulla dispersione della ripolarizzazione ventricolare.

Patients with left bundle-branch block (LBBB) often present electrocardiographic abnormalities and, therefore, are excluded from studies concerning electrocardiographic evaluation of ventricular repolarization. The aim of the study was to assess whether LBBB could influence dispersion of ventricular repolarization. Surface electrocardiograms of 16 patients (9 males and 7 females, mean age 58 +/- 14 years) with episodes of intermittent LBBB were analyzed. Six patients were affected by coronary artery disease, 6 by hypertensive cardiomyopathy and 4 by dilated cardiomyopathy. Maximal QT and JT corrected intervals, QT and JT dispersion, and QT and JT dispersion corrected for heart rate, were obtained before and after LBBB. We observed a significant prolongation of maximal QT (412 +/- 29 vs 433 +/- 25 ms; p < 0.05), and of maximal corrected QT (457 +/- 37 vs 497 +/- 56 ms; p < 0.05) after LBBB. Maximal JT interval, also corrected for heart rate, did not show any significant modification after LBBB. Moreover, we did not observe any significant difference in electrocardiographic parameters of dispersion of repolarization. Our results seem to indicate that LBBB did not alter significantly dispersion of ventricular repolarization. QT dispersion is considered an important marker of risk for incidence of ventricular arrhythmias. If our results will be confirmed in larger groups of patients, analysis of QT dispersion could be extended even to patients with LBBB.

QT interval and QT dispersion in multiple system atrophy (Shy-Drager syndrome).

To evaluate the influence of autonomic function on the QT interval and QT dispersion, 18 patients (10 males and 8 females; mean age 61 +/- 9 years) with multiple system atrophy (MSA, Shy-Drager syndrome) were studied. Cardiovascular tests were performed to assess the degree of autonomic dysfunction. The QT interval, corrected QT (QTc), QT dispersion (QTd), corrected and adjusted QTd were calculated from a standard 12-lead electrocardiogram. Fifteen healthy subjects matched for sex and age were studied as controls. Nine MSA patients showed severe autonomic dysfunction with orthostatic hypotension. In the remaining patients definite autonomic impairment was found. No statistically significant difference was found in QTd and only a trend towards higher values of maximal QTc was found in patients compared with controls. QTc prolongation, defined as greater than the mean +/- 2 SD of the controls, was detected only in three out of the 18 MSA patients (17%). No correlation was found between the severity of autonomic impairment and repolarization parameters. Our data suggest that chronic autonomic impairment in patients with MSA does not significantly affect ventricular repolarization and ventricular dispersion.

Signal-averaged electrocardiography in myotonic dystrophy.

We performed signal-averaged electrocardiography and 24-h ambulatory electrocardiographic monitoring in 53 patients with myotonic dystrophy to determine the incidence and clinical significance of ventricular late potentials. Patients were followed up for a mean period of 31 +/- 17 months (range 11-68 months). At entry, none of the patients had bundle branch block on 12-lead electrocardiogram and none had wall motion abnormalities on routine echocardiogram. Also, no patient had history of syncope or clinical evidence of ischemic heart disease or a documented sustained ventricular tachycardia. A group of 47 healthy subjects matched for age and sex also underwent signal-averaged electrocardiography for comparison with the patient group. Late potentials were diagnosed in the presence of at least two of the following measures: duration of the filtered QRS > 114 ms, root-mean-square voltage of the terminal 40 ms of the filtered QRS < 20 microV, and duration of the low-amplitude (< 40 microV) signals of terminal filtered QRS > 38 ms. Late potentials were more frequent in patients than in controls: 18 of the 53 patients (34%) showed late potentials compared with four of the 47 controls (8.5%) (P < 0.01). In 45 patients (85%) no ventricular ectopy (40 cases) or infrequent premature ventricular complexes (five cases) were detected on Holter monitoring. Complex ventricular arrhythmias were traced in the remaining eight patients. These were six of the 18 patients with, and two of the 45 patients without late potentials (33% vs. 6%, respectively; P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

[The role of diuretics in antihypertensive therapy]. / Il ruolo dei diuretici nella terapia antiipertensiva.

Hypertensive therapy based on diuretics is time-honored. Thiazides represent the most commonly used class of diuretics for uncomplicated hypertension because of economic motivations, their tolerance and efficacy both as monotherapy and in combined treatment with other agents. Clinical studies using diuretics and beta-blockers reported that thiazide treatment prevents the development of malignant hypertension, renal and heart failure, hypertensive retinopathy, and reduces in five years overall mortality of 33%, cardiovascular mortality of 41%, fatal and non-fatal cerebrovascular events of 51% and the risk of coronary events of 15%. The less than expected risk reduction of cardiovascular disease raised many concerns about the possibility of adverse biochemical changes of thiazides through their effects on lipids, electrolytes and glucose metabolism. However, the real clinical significance of these metabolic effects remains actually uncertain and needs further investigation. The treatment of the hypertensive patient cannot be adequately managed using a merely adjunctive step-care criterium. Hypertensive subjects have different haemodynamic, metabolic and endocrine disorders and a tailored treatment should consider the different activities of the various agents as monotherapy or in association in the single patient.

Use of the signal-averaged QRS duration for diagnosing left ventricular hypertrophy in hypertensive patients.

We analysed the diagnostic performance of the signal-averaged QRS duration for the detection of left ventricular hypertrophy in 100 consecutive outpatients (62 men and 38 women; mean age, 49.8 +/- 11.8 years) with essential hypertension and compared the results with some of the currently employed electrocardiographic criteria. Forty-eight healthy subjects (24 men and 24 women; mean age, 46.4 +/- 12.1) with normal physical, electrocardiographic and echocardiographic findings served as a control group to derive normal reference values for signal-averaged QRS duration. Twenty-six (26%) hypertensives (22 men and 4 women) had left ventricular hypertrophy echocardiographically defined as a left ventricular mass > or = 261 g in men and > or = 172 g in women or left ventricular mass index > or = 125 g/m2 in men and > or = 112 g/m2 in women. The signal-averaged QRS duration was different in patients with than in those without left ventricular hypertrophy (102.1 +/- 10.8 vs. 95.8 +/- 8.4 ms; P < 0.01). Also, in the group with left ventricular hypertrophy QRS duration was longer, although not significantly different, in men than in women (103.5 +/- 10.7 vs. 94.2 +/- 8.8 ms; P n.s.). The correlation between the signal-averaged QRS duration and left ventricular mass was weak but statistically significant in men (r = 0.34; P < 0.05) in women (r = 0.30; P < 0.05) and in men and women together (r = 0.42; P < 0.01). Partition values of filtered QRS duration > or = 114 ms in men and > or = 107 ms in women were used to diagnose left ventricular hypertrophy as these values were above the upper limits in our control men and women when 95% confidence intervals were calculated. These criteria were insensitive (12%) but highly specific (99%) for left ventricular hypertrophy. The use of a single threshold value of filtered QRS duration > or = 111 ms in both sexes combined improved sensitivity modestly (15%) while maintaining a good specificity (95%). Also, we tested the following standard electrocardiographic criteria: the Sokolow-Lyon index, the Romhilt-Estes point score > or = 4 points and > or = 5 points, the Cornell voltage criteria, the sum of QRS voltages in all 12 leads > 175 mm, and the QRS duration > 90 ms. Sensitivities ranged from 4% to 58% and specificities from 74% to 99%.(ABSTRACT TRUNCATED AT 400 WORDS)

Complete regression of iatrogenic Kaposi's sarcoma due to corticosteroid treatment in a patient with tubercular pericarditis. A case report.

We report a case of drug-induced Kaposi's sarcoma (KS) on the sole of the right foot in a 71-year-old man, treated for 6 months with corticosteroid therapy (prednisolone 25 mg/day) for pericardial effusion. After corticosteroid withdrawal, a tuberculin skin test became strongly positive and pericardial effusion was considered to be of tubercular origin. The patient remained constantly HIV negative during 14 months of follow-up. Seven months after continuous antitubercular treatment, the KS nodules regressed spontaneously and finally disappeared. Histological studies confirmed the diagnosis of KS and documented its complete regression. Laboratory investigation confirmed prior exposure to CMV, EBV and HSV and suggested drug-induced immunological suppression. Analysis of the HLA system revealed the positivity of locus DR5, associated with classical KS. This case report underscores the relationship between genetic background, environmental factors, drug-induced immunosuppression and the evolution of this peculiar neoplasm.

Ventricular conduction defects and atrial fibrillation after coronary artery bypass grafting. Multivariate analysis of preoperative, intraoperative and postoperative variables.

Preoperative, intraoperative and postoperative variables, which might play a role in the development of ventricular conduction defects (VCD) and atrial fibrillation (AF) following coronary artery bypass grafting (CABG), were evaluated in 236 consecutive patients. VCD and AF developed postoperatively in 15.5% of patients: 4.5% had VCD (subgroup A), 11.0% had AF (subgroup B). In 84.5% of patients VCD and AF did not occur (subgroup C). Univariate analysis showed statistically significant differences between subgroups A and C with respect to: left main significant stenoses and number of diseased vessels. Bypass pump time and aortic cross-clamp time were significantly longer in subgroup B. Multivariate analysis showed a significantly greater incidence of left main disease and of right coronary artery occlusion associated with significant stenosis of the proximal left anterior descending artery in subgroup A. In subgroup B, the duration of aortic cross-clamp time was significantly higher. Ischaemic injury, with increasing duration of cardioplegic arrest, seems to play a key role in the development of AF. Nonhomogeneous cardioplegic delivery to critical areas of myocardium, and particularly to the specialized conducting system, may cause VCD after CABG.

The role of indium-111 antimyosin (Fab) imaging as a noninvasive surveillance method of human heart transplant rejection.

The identification of rejection after heart transplantation in patients receiving cyclosporine immunosuppressive therapy requires the endomyocardial biopsy, an invasive method associated with a finite morbidity. To evaluate the role of indium-111 antimyosin (Fab) scintigraphy as a noninvasive surveillance method of heart transplant rejection, the Fab fragment of murine monoclonal antimyosin antibodies labeled with indium-111 was administered intravenously in 30 scintigraphic studies to 10 consecutive heart transplant recipients. Endomyocardial biopsy specimens were obtained 72 hours after each scintigraphic study. Nineteen scintigraphic studies had negative findings; no false negative finding was obtained. Eleven antimyosin scintigraphic studies had positive findings, and in these studies endomyocardial biopsy revealed mild rejection in two cases, moderate acute rejection with myocyte necrosis in two cases, myocyte necrosis as a consequence of ischemic injury in six cases, and possibly cytotoxic damage in one case. Antimyosin scintigraphy may represent a reliable screening method for the surveillance of heart transplant patients. In the presence of a negative finding from antimyosin scintigraphy, it may be possible to avoid endomyocardial biopsy. Conversely, in patients who have a positive finding from antimyosin scintigraphy, the endomyocardial biopsy is mandatory to establish the definitive diagnosis by histologic examination of the myocardium.

Effects of uncomplicated coronary artery bypass graft surgery on global and regional left ventricular function at rest. Study by equilibrium radionuclide angiocardiography.

To evaluate the effects of uncomplicated revascularization surgery on resting global and regional left ventricular function we studied 34 patients, enrolled consecutively, by radionuclide angiocardiography. After surgery, we found no significant change in global left ventricular ejection fraction; this was true even in the subgroup of 14 patients who developed paradoxical septal motion. This finding indicates that the development of paradoxical septal motion after uncomplicated cardiac surgery does not compromise global left ventricular function. Both in the subgroup of patients with paradoxical septal motion and in the subgroup without paradoxical septal motion regional ejection fraction calculations showed the same postoperative pattern consisting of increase of the proximal and distal posterolateral regional ejection fraction, increase in the inferoapical regional ejection fraction and unchanged proximal and distal septal regional ejection fraction. In our patients paradoxical septal motion is not due to pericardial effusion, conduction disturbance, septal ischemia or infarction. Our data suggest that the anteromedial translation of the entire heart during systole, due to surgical removal of constraints, may account for both the false improvement of posterolateral and inferoapical regional wall motion and the development of paradoxical septal motion.

Effects of left bundle branch block on left ventricular function in apparently normal subjects. Study by equilibrium radionuclide angiocardiography at rest.

To determine the independent effects of left bundle branch block (LBBB) on global and regional left ventricular (LV) function we performed equilibrium radionuclide angiocardiography at rest in 3 patients with chronic LBBB (group I, mean age 53.6 years and in 6 patients with intermittent LBBB (group II, mean age 41.5 years). All patients were judged to have an apparently normal heart. In 2 of 3 patients of group I a LV ejection fraction lower than 50% was observed, and in all 3 patients septal motion abnormalities were present. In all patients of group II the global LV ejection fraction was normal during normal conduction and decreased during LBBB; the inferoapical regional ejection fraction decreased in 5 of 6 cases and the posterolateral regional ejection fraction in 3 of 6 cases. Moreover, septal hypokinesis was observed both during normal and abnormal conduction in all group II patients. These findings seem to confirm that LBBB, chronic or intermittent, is able to deteriorate LV performance at rest, even in patients with an otherwise normal heart.

[Dipyridamole test and myocardial scintigraphy with Tl-201 in the diagnosis of myocardial ischemic pathology]. / Il test al dipiridamolo e la scintigrafia miocardica con 201-Tl nella diagnosi della patologia ischemica miocardica.

We studied 19 consecutive subjects affected by effort angina using following tests: ecg stress test, stress 201-Tl scan, coronary arteriography; 201-Tl scan, coronary arteriography, hemodynamic, echo 2 D, ecgraphic monitoring during Dipyridamole test (D). Basing on coronary arteriography results we divided patients; in the group A (10 patients with significant stenoses greater than or equal to 50%) stress ecg and scintigraphy were positive in 9 patients; Dipyridamole test induced angor and ecgraphic changes in 5 patients and in 4 left ventricle wall motion disorders, 201-Tl scan was positive in all 9 patients tested. In the group B (9 subjects with no significant stenosis) ecgraphic changes were observed in 2 subjects and 201-Tl scan was positive in 6 subjects; D induced in 2 cases angor, in 1 case ecgraphic changes, in 1 case left ventricle wall motion disorders and the same 201-Tl defects in 6 previously individualized patients. In both groups we observed at coronary arteriography during D identical findings in comparison with the immediately before performed. In our experience D infusion is confirmed as provocative test of ischemia. The same ischemic pattern observed at stress and Dipyridamole scintigraphy in patients with no significant coronary stenosis suggests as pathogenetic mechanism the regional lack of dilatory reserve.

Injury to the left coronary artery during repair of tetralogy of Fallot: successful aorta-coronary polytetrafluoroethylene graft.

Inadvertent transection of an anomalous left coronary artery, which originated from the right coronary artery, occurred during repair of tetralogy of Fallot in a 2-year-old child. An aorta-coronary bypass graft was constructed with a size 4 polytetrafluoroethylene conduit. Early recatheterization showed patency of the polytetrafluoroethylene graft, but a myocardial scintiscan done 3 months after operation demonstrated reduced perfusion of the areas supplied by the left coronary system. Preoperative aortography or selective coronary angiography is mandatory to avoid this potentially lethal complication. Future surgical options are discussed.