Transduction of non-dividing adult human pancreatic beta cells by an integrating lentiviral vector

This study assesses the long-term (mean 52+/-24 months) performance of the St. Jude Medical (SJM) valve in 200 young (mean age 31+/-13 years) rheumatic patients on low-level warfarin anticoagulation combined with dipyridamole. Follow-up was 95% complete and comprised 867 patient-years. There were 33 deaths (3.8%/patient-year). Death was valve related in 12 cases and due to left ventricular dysfunction in 10. Death due to left ventricular dysfunction occurred earlier after surgery than death due to other causes (10+/-7 vs 29+/-18 months, p <0.005); these patients had larger preoperative left ventricular dimensions than the rest of the group (end-systolic diameter 51+/-13 vs 37+/-16 mm, end-diastolic diameter 66+/-13 vs 50+/-19 mm, p = 0.006). Actuarial probability of survival was 81% at 86 months and probability of event-free survival was 71%. The median international normalized ratio was 1.88+/-0.54. Thromboembolism (13 events) occurred at a linearized rate of 1.5%/patient-year. There were 11 major bleeding episodes (1.3%/patient-year), 4 cases of prosthetic valve endocarditis (0.8%/patient-year), and 12 paraprosthetic leaks (1.4%/patient-year). No valve obstructions or reoperations occurred. Thus, the SJM valve performs well on low-level anticoagulation combined with dipyridamole. Left ventricular dysfunction was a common cause of death in the early postoperative period.     

Neural tube defects: a primary prevention role for nurses

Carvedilol has been shown to determine a significant improvement in left ventricular function, symptoms, clinical course and prognosis of patients with chronic heart failure. However, these results were obtained in medium-term studies of < 1 year duration. We report the results obtained with long-term (3-4 years) carvedilol administration to 40 patients with idiopathic dilated cardiomyopathy who were initially recruited in a 4-month double-blind placebo-controlled trial. In the initial 4-month double-blind trial, 20 patients were randomized to placebo and 20 to carvedilol treatment. All patients, except one who was not on ACE-inhibitors, were on digoxin, furosemide and ACE-inhibitors. Carvedilol or placebo doses were progressively titrated, at weekly intervals, up to the maximal doses of 25 mg bid. After the initial 4-month double-blind phase, all patients were followed long term. Mean follow-up duration was 52 +/- 12 months (range 48-61). Among the 20 patients initially randomized to carvedilol administration, 4 died (3 for cardiac and 1 for extracardiac causes) and 2 underwent heart transplant. Among the 20 patients initially randomized to placebo, 5 died for cardiac causes, 3 underwent heart transplant and 4 were started on carvedilol because of progressive heart failure during the initial 4 months of the study. The remaining 8 patients, who were kept on digoxin, furosemide and ACE-inhibitors, were used as control group. Each patient underwent an assessment of clinical conditions (NYHA functional classification and Minnesota Living with Heart Failure questionnaire), equilibrium radionuclide ventriculography, and maximal cardiopulmonary bicycle exercise testing. Exams were performed before treatment, after 4 and 12 months, and at the end of the follow-up period. No significant difference between the carvedilol and control group was present at baseline. Compared with baseline, patients in the control group presented a significant increase in left ventricular end-diastolic volume after long-term follow-up (from 126 +/- 62 to 138 +/- 43 and 158 +/- 52 ml/m2 after 12 and 48 months, respectively). No significant difference, compared to baseline values, was noted. Patients on carvedilol presented a persistent improvement in left ventricular function. This was shown by the progressive increment in left ventricular ejection fraction from 22 +/- 6 to 34 +/- 11, 37 +/- 11 and 37 +/- 13%, after 4, 12 and 48 months, respectively (p < 0.001) with a concomitant reduction in left ventricular end-diastolic volume from 147 +/- 54 to 101 +/- 44 ml/m2 at the end of the follow-up (p < 0.05). NYHA functional class remained significantly improved, in comparison with baseline (2.6 +/- 0.5 to 1.9 +/- 0.3, 1.9 +/- 0.8 and 2.0 +/- 1.0 after 4, 12 and 48 months, respectively; p < 0.01). Maximal functional capacity, assessed as peak VO2 was not significantly changed after 4 months (from 15.2 +/- 3.6 to 16.4 +/- 4.0 ml/kg/min) and showed a tendency towards a further improvement after 12 months and at the end of the follow-up (17.3 +/- 5.6 and 17.2 +/- 5.3 ml/kg/min, respectively). These results show that the favorable effects of carvedilol administration on left ventricular function and clinical symptoms are maintained also after long-term treatment.     

Results of rapid two-stage arterial switch operation in patients with transposition of the great arteries: one-year postoperation

The rapid two-stage arterial switch operation is an alternative therapy for patients with simple transposition of the great arteries who present beyond the neonatal period and have low left ventricular pressure. It provides normal ventricular function compared to the atrial switch operation. Between July 1994 and February 1997, there were 13 such infants who had rapid two-stage arterial switch operation performed at Siriraj Hospital. There was 1 late death (11 months after the operation). All 12 survivors (mean age 22.4 +/- 5.7 months) were clinically evaluated and had echocardiography performed at 14.8 +/- 4.9 months after the operation. All were asymptomatic. Echocardiogram revealed a residual small atrial septal defect (1 case), small ventricular septal defect (1 case), mild supravalvar neopulmonary stenosis (2 cases), bicuspid neoaortic valve without stenosis (2 cases), dilated neoaortic sinus of Valsalva (6 cases, 50%) and mild neoaortic insufficiency (11 cases, 91.7%). The left ventricular function was hyperdynamic after pulmonary artery banding and significantly decreased to normal level at the time of study (shortening fraction of 43.8 +/- 10.7 vs 29.2 +/- 3.8%, respectively, p = 0.0005). The wall thickness was significantly increased after pulmonary artery banding and decreased overtime (0.48 +/- 0.08 vs 0.32 +/- 0.05 cm, respectively, p < 0.0005). The left ventricular dimension was significantly increased both after pulmonary artery banding and at the time of study (2.06 +/- 0.42 vs 3.32 +/- 0.30 cm, respectively, p < 0.0005). The left ventricular mass was significantly increased after pulmonary artery banding and at the time of study (21.79 +/- 7.79 vs 33.08 +/- 7.40 g/m2, respectively, p = 0.0005). The mortality and morbidity of rapid two-stage arterial switch operation are low. However, long-term follow-up should be monitored.     

Assessment of ventricular diastolic function in AIDS patients from Congo: a Doppler echocardiographic study

The aim of this study was to evaluate the effect of transdermal clonidine on hemodynamic and metabolic parameters in patients who have elevated blood pressure and non-insulin-dependent diabetes mellitus (NIDDM). After a 2-week run in placebo period, 20 NIDDM patients who had diastolic blood pressure in the range of 90 to 105 mm Hg underwent a randomized, single blind, placebo controlled, cross-over study of 4 week treatment with clonidine (transdermal patch 2.5 mg/week) or placebo (inactive patch). Compared with placebo, clonidine significantly reduced systolic (153 +/- 6 v 163 +/- 8) and diastolic (88 +/- 2 v 98 +/- 3.5 mm Hg, P = .001) blood pressure, left ventricular mass (94 +/- 11 v 99 +/- 12 g/m2, P < .01) and fasting glucose levels. Total glucose disposal (glucose clamp) was 6.5 +/- 1.5 with placebo and 7.1 +/- 1.6 mg/kg/min with clonidine (P < .01). Oxidative glucose disposal (indirect calorimetry) was also greater after clonidine. Plasma glucose, insulin, and C-peptide responses following oral glucose (75 g) were significantly lower after clonidine, as well as urinary albumin excretion. Transdermal clonidine is effective in reducing blood pressure in hypertensive NIDDM patients and is well tolerated. It may be useful to reduce the cardiovascular impact of hypertension in diabetes mellitus.     

Effects of the novel antimigraine agent, frovatriptan, on coronary and cardiac function in dogs

The effects of frovatriptan (VML 251/SB-209509) on coronary artery function were investigated in isolated coronary arteries from beagle dogs. Low concentrations of frovatriptan produced contraction with -logEC50 7.55 +/- 0.08 (n = 11). The maximal observed contraction attained was 56 +/- 7% of the control 5-hydroxytryptamine (5-HT; 10 microM) response. At high concentrations of frovatriptan (>6 microM), reversal of sumatriptan (10 microM)-induced contractions was noted. In arteries precontracted with the thromboxane mimetic, U46619, frovatriptan produced a bell-shaped concentration-response relation with a maximal response at 600 nM. Concentrations of frovatriptan >2 microM produced marked reversal of tone, with full relaxation of precontracted tissues at 200 microM. In anesthetized, open-chest mongrel dogs, intravenous (n = 5) or intracoronary (n = 5) artery administration of frovatriptan (0.0001-1 mg/kg) had no consistent effect on left ventricular end-diastolic pressure, left end-systolic pressure, cardiac contractility, aortic blood flow, systemic peripheral resistance, coronary blood flow, coronary vascular resistance, mean arterial blood pressure, or heart rate when compared with vehicle (n = 3). Intravenous sumatriptan produced minor effects on blood pressure and heart rate. Intracoronary artery administration of sumatriptan (0.0003 mg/kg) produced an increase in systemic peripheral resistance to 120.5 +/- 8.2% compared with vehicle (97.8 +/- 5.4%; p < 0.05). This dose of sumatriptan also produced a significant increase in coronary blood flow and decrease in coronary vascular resistance. Intravenous administration of sumatriptan produced a dose-related reduction in left ventricular diastolic pressure with a reduction to 58.3 +/- 8.3% and 41.7 +/- 25% of control values observed at 0.3 and 1 mg/kg, respectively; however, administration of sumatriptan by an intracoronary route had no effect. In a model of myocardial infarction, comparable doses of sumatriptan (1.0 mg/kg) or frovatriptan (0.1 mg/kg), in terms of their effect on carotid vascular resistance, had no significant effect on infarct size. Frovatriptan had no effect on coronary blood flow after reperfusion; however, sumatriptan produced a significant reduction in coronary blood flow for < or =3 h. These studies show that frovatriptan has the capability of relaxing coronary arteries in vitro, has no overall effect on cardiac function at rest with no effect on coronary hemodynamics after myocardial infarction, and has a profile superior to that of sumatriptan.     

Misoprostol has no favorable effect on bronchial hyperresponsiveness in mild asthmatics

Misoprostol, a synthetic prostaglandin E1 analogue, has been reported to have antibronchoconstricive and antiinflammatory effects in animal studies. We investigated the effect of misoprostol on FEV1 and bronchial hyperresponsiveness (BHR) to histamine in mildly asthmatics. 14 mildly asthmatic patients were given 400 mg/day oral misoprostol. Four patients had to left the study either due to the side effects. The remaining 10 patients (all women and mean age was 33.2 +/- 3.3) underwent the histamine challenge test before and after the treatment with misoprostol. Mean values of FEV1 obtained before and after the treatment were as follows respectively: 2.79 +/- 0.17 L; 2.78 +/- 0.18 L. Mean log PC20 values were as follows respectively: 0.60 +/- 0.23 mg/ml; 0.60 +/- 0.14 mg/ml. There was no difference either in FEV1 and log PC20 values before and after the treatment with misoprostol (p > 0.05). As a result administered misoprostol has no favorable effect on expiratory flow rates and BHR in asthmatic patients.     

TRP trapped in fly signaling web

BACKGROUND: Recent reports indicate that myocarditis can be associated with acute myocardial ischemia and even myocardial infarction in patients with normal arteriograms. We therefore tested the hypothesis that patients with biopsy-proven myocarditis have endothelial dysfunction despite angiographically smooth epicardial coronary arteries. METHODS AND RESULTS: Graded concentrations of the endothelium-dependent vasodilator acetylcholine (10(-6) to 10(-4) mol/L) and for comparison, the non-endothelium-dependent vasodilator nitroglycerin (0.3 mg intracoronary), were infused into the left coronary arteries of 18 patients (mean age 47+/-9 years, 8 women and 10 men) with biopsy-proven myocarditis but without angiographically demonstrable coronary artery disease. Vascular responses were analyzed by quantitative coronary angiography. Three patients had an intact vasodilator response to acetylcholine concentrations of up to 10(-4) mol/L in all segments of the left coronary artery, with a mean dilatation of +9.9%+/-2%. In contrast, paradoxical constriction by acetylcholine occurred in 9 patients, who showed a mean change in coronary artery diameter of - 11%+/-3%. Six patients had no significant change in any segments in response to acetylcholine (-2.5%+/-4%). There was a significant inverse correlation between the number of T-lymphocytes in the myocardium and the response of the epicardial coronary arteries to acetylcholine (Pearson correlation coefficient -0.49, P=.03). CONCLUSIONS: It can be assumed that the process of myocarditis is associated with impairment of endothelium-dependent vasodilation in response to acetylcholine in most patients. Vasoconstriction in the presence of acetylcholine in myocarditis is likely to reflect an abnormality of endothelial function. Endothelial dysfunction of coronary arteries may explain the occurrence of myocardial ischemia in patients with myocarditis.     

Intermediate-term outcome of mitral reconstruction in cardiomyopathy

OBJECTIVE: Severe mitral regurgitation is a frequent complication of end-stage cardiomyopathy that contributes to heart failure and predicts a poor survival. We studied the intermediate-term outcome of mitral reconstruction in 48 patients who had cardiomyopathy with severe mitral regurgitation and were operated on between June 1993 and June 1997. METHODS: Ages ranged from 33 to 79 years (63 +/- 6 years) with left ventricular ejection fractions of 8% to 25% (16% +/- 3%). All patients were receiving maximal drug therapy and were in New York Heart Association class III-IV with severe, refractory 4+ mitral regurgitation. Operatively, all 48 had undersized flexible annuloplasty rings inserted, 7 had coronary bypass grafts for incidental disease, 11 had prior bypass grafts, and 11 also had tricuspid valve repair. RESULTS: One operative death occurred as a result of right ventricular failure. Postoperative transesophageal echocardiography revealed mild mitral regurgitation in 7 patients and no mitral regurgitation in 41. There were 10 late deaths, 2 to 47 months after mitral reconstruction. The 1- and 2-year actuarial survivals have been 82% and 71%. At a mean follow-up of 22 months, the number of hospitalizations for heart failure has decreased, and 1 patient has had heart transplantation. Significantly, New York Heart Association class improved from 3.9 +/- 0.3 before the operation to 2.0 +/- 0.6 after the operation. Twenty-four months after the operation, left ventricular volume and sphericity have decreased, whereas ejection fraction and cardiac output have increased. CONCLUSION: Whether this favorable modification of left ventricular function and geometry will persist remains unknown. However, mitral repair for cardiomyopathy with mitral regurgitation allows new strategies for these patients.     

Vitamin E in the treatment of tardive dyskinesia: a preliminary study over 7 months at different doses

Vitamin E has been suggested to be a promising new treatment for tardive dyskinesia. However, little is known about the optimum dose. Twenty patients with tardive dyskinesia whose medication had been unchanged for at least 1 month were selected and randomly divided into a treatment group with 11 patients and a control group with nine patients. The treatment group was started on 600 mg of vitamin E per day, and this dose was increased over the 7 months of the trial to 1600 mg per day. The medication for the control group was unchanged. Severity of tardive dyskinesia was rated on the Abnormal Involuntary Movement Scale. Patients in the treatment group initially showed a significant response to the lower dose of 600 mg per day. However, this improvement was not maintained and differences between the two groups reached significant levels only after the dose of vitamin E was increased to 1600 mg per day. At this dose, there was a significant and sustained reduction in the severity of tardive dyskinesia. The results suggest that vitamin E is of value in the treatment of tardive dyskinesia and that the optimum dose for treating tardive dyskinesia is 1600 mg per day. In addition, there may be a dose related therapeutic effect of Vitamin E in tardive dyskinesia.     

Neither L-arginine nor L-NAME affects neurological outcome after global ischemia in cats

BACKGROUND AND PURPOSE: We attempted to determine whether N-nitro-L-arginine methyl ester (L-NAME) would improve neurological outcome and whether L-arginine (L-ARG) would worsen neurological outcome after transient global ischemia. METHODS: Halothane-anesthetized cats (n = 6 for each group) were treated with intravenous saline, L-NAME (5 mg/kg or 10 mg/kg), or L-arginine (300 mg/kg) 30 minutes before 10 minutes of ischemia (temporary ligation of the left subclavian and brachiocephalic arteries with hemorrhagic hypotension to 50 mm Hg). At 30 minutes of reperfusion, cats in the L-ARG group were administered an additional 300 mg/kg dose of intravenous L-arginine. RESULTS: Time (mean +/- SE) to isoelectric electroencephalography was similar among groups (saline, 26 +/- 11 seconds; L-NAME-5, 15 +/- 4 seconds; L-NAME-10, 36 +/- 27 seconds; and L-ARG, 22 +/- 7 seconds). At 72 hours, reperfusion pathological injury was severe and neurological deficit score (mean, range) was similar among groups (saline, 38[11 to 70]; L-NAME-5, 52 [40 to 73]; L-NAME-10, 47 [23 to 70]; and L-ARG, 40 [0 to 79]). CONCLUSIONS: Nitric oxide is not important in the mechanism of brain injury after global ischemia in cats.     

Effects of histamine type 2-receptor antagonists cimetidine and famotidine on left ventricular systolic function in chronic congestive heart failure

Twelve patients with stable congestive heart failure and left ventricular dysfunction were enrolled in a double-blind, randomized crossover trial of famotidine, cimetidine and placebo to determine whether histamine type 2 (H2) antagonists adversely affect left ventricular systolic performance. Two-dimensional echocardiograms were obtained at baseline, after 4 days of oral treatment with standard doses of famotidine and cimetidine, and placebo, and at the conclusion of the trial. The baseline mean ejection fraction was 19 +/- 7%. The changes in ejection fraction were +2 +/- 11% (95% confidence interval [CI] -5 to 9%) with famotidine, +3 +/- 10% (95% CI -3 to 10%) with cimetidine, and -3 +/- 7% (95% CI -8 to 2%) with placebo. There were no significant differences in changes in ejection fraction among the 3 experimental treatments (p = 0.22; analysis of variance). The changes in end-systolic wall stress/volume ratios from baseline were +6 +/- 21% (95% CI -6 to 18%) for famotidine, +8 +/- 29% (95% CI -8 to 25%) for cimetidine, and +2% +/- 29% (95% CI -15 to 18%) for placebo (p = 0.69; analysis of variance). No patient had a worsening of symptoms during therapy. Despite previous reports that H2 antagonists may depress left ventricular systolic function, at standard doses these agents result in no decrease in left ventricular systolic function in patients with chronic congestive heart failure.     

Systemic chemotherapy alone for patients with non-acquired immunodeficiency syndrome-related central nervous system lymphoma: a pilot study of the BOMES protocol

BACKGROUND: Anecdotal reports have suggested that systemic chemotherapy with agents that better cross the blood-brain barrier may result in long term disease remission in some patients with central nervous system (CNS) lymphoma. This treatment strategy has the advantage of sparing patients the late neurologic complications from brain irradiation. METHODS: Eligible patients were required to 1) have tissue-proven and measurable non-acquired immunodeficiency syndrome (AIDS)- related primary or metastatic CNS lymphoma; 2) have normal hemogram, renal function, and hepatic function; 3) be age < or = 75 years; and 4) have provided informed consent. Patients with lymphoblastic lymphoma or patients who previously had been exposed to nitrosoureas, etoposide, or high dose methotrexate were not eligible. The systemic chemotherapy (BOMES regimen) included carmustine, 65 mg/m2/day, intravenously (i.v.) on Days 1-2; vincristine, 2 mg/day, i.v. on Days 1 and 8; methotrexate, 1.5 g/m2, i.v. on day 15 followed by leucovorin rescue; etoposide, 50 mg/m2/day, i.v. on Days 1-5; and methylprednisolone, 200 mg/day, i.v. on Days 1-7; repeated every 4 weeks (BOMES regimen). Four doses of intrathecal methotrexate were given to patients who had involvement in the cerebrospinal fluid. RESULTS: Between March 1991 and March 1997 a total of 19 patients were enrolled on the study. There were 13 men and 6 women, with a median age of 57 years. Fourteen patients had primary CNS lymphoma and 5 patients had concurrent extra-CNS lymphoma. Nine patients previously had been treated by radiotherapy (four patients), chemotherapy (three patients), or both (two patients). There were 11 complete remissions (CR) (57.9%) and 5 partial remissions (26.3%), with a total remission rate of 84.2%. One patient had had progressive brain lymphoma during systemic chemotherapy with the conventional cyclophosphamide, doxorubicin, vincristine, and prednisolone regimen, but achieved CR soon after the regimen was changed to BOMES. The median time to progression of the responders was 6 months. At last follow-up, 4 patients were alive without lymphoma at 10, 47, 64, and 66 months, respectively. There were two treatment-related deaths due to sepsis. Another two patients died of fulminant hepatitis that most likely was chemotherapy-related reactivation of chronic B viral hepatitis. CONCLUSIONS: The authors believe systemic chemotherapy alone may result in long term disease remission in some select patients with non-AIDS-related CNS lymphoma. Further investigation for better protocols is mandatory.     

The effect of delays in feeding colostrum and the relationship between immunoglobulin concentration in the serum of neonatal calves and their rates of growth

Eighty-five unsuckled newborn calves, were fed 1.5 L of colostrum of known IgG concentration at either 2, 4, 6 or 8 hours after birth with no additional colostrum feeding. Another group of 11 calves were left with their dam for 16 hours after birth, before separation. Blood samples were taken from all calves 24 hours after colostrum feeding or separation from the dam and serum Ig concentrations were measured by electrophoresis. There were no significant differences in mean serum Ig concentrations between calves fed at the different times after birth. Three of the 11 calves left to suckle were hypogammaglobulinaemic. Other calves in this group had higher serum Ig concentrations than the means of all other groups. All groups had mean serum Ig concentrations higher than the suggested minimum concentration required for adequate calf health. There were a number of calves that did not reach the suggested minimum serum concentration after feeding, but calf mortality was low and all calves were healthy apart from a slight scour for a few weeks after birth. There was no significant relationship between serum Ig concentration 24 to 48 hours after birth and either calf mortality or average growth rate over an 8- to 10-month period.     

Pulmonary function in patients with trophoblastic disease treated with low-dose methotrexate

The Sheffield Trophoblastic Disease Centre treats about 25 patients with persistent trophoblastic disease each year. A total of 75% of patients are classified as low risk according to the Charing Cross Hospital prognostic scoring system and receive methotrexate (MTX) 50 mg, i.m., on days 1, 3, 5, 7 with folinic acid 7.5 mg orally 24 h after each methotrexate injection. There is a 7-day rest between treatment cycles. Remission is achieved in 85% of cases. Approximately 20% of patients experienced pleuritic chest pain and dyspnoea. We have evaluated prospectively lung function in 16 low-risk patients receiving methotrexate. All patients had pulmonary function tests [spirometry-forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), peak expiratory flow rate (PEFR), and transfer factor - TLCO, kCO] performed before and after completed treatment. A mean of 7.5 cycles of MTX were administered (range 4-11). There was a significant reduction in the mean TLCO (mean pre/post 8.15/7.38 mmol min-1 kPa-1, P = 0.01), but there were no other statistically significant changes. Three patients experienced respiratory symptoms and were found to have a 39%, 28%, and 11% reduction in TLCO from baseline, improving on follow up to pretreatment levels. Low-dose MTX is an effective therapy but may cause troublesome pulmonary toxicity.     

Effect of the angiotensin converting enzyme inhibitor, captopril, on proteinuria in chronic glomerular disease

The antiproteinuric effect of the angiotensin-I-converting enzyme inhibitor, captopril, was studied in 14 patients (10 men and 4 women, age range of 24 to 60 years) with chronic glomerulonephritis in whom IgA nephritis had been confirmed by renal biopsy. Eight of the 14 patients had received antihypertensive drugs such as calcium channel blockers, diuretics or beta-blockers. Captopril was added to these regimens at 25 mg twice daily in 3 patients, and 37.5 mg in 11 patients. Proteinuria decreased from 2.55 +/- 0.48 g/day to 1.58 +/- 0.35 g/day within three months after the start of administration. In 4 patients (28.6%), the extent of reduction was over 50%, and in 8 patients (57.1%), over 25%. Blood pressure, creatinine clearance and serum creatinine were not changed significantly. There was a positive linear correlation between the extent of reduction of proteinuria and the increase in plasma renin activity (r = 0.93, p < 0.001). We conclude that captopril reduces proteinuria in some patients with IgA nephritis whose plasma renin activity responds to the drug.     

Improvement in mitral regurgitation after aortic valve replacement

This study sought to determine whether there is a quantitative improvement in mitral regurgitation (MR) after aortic valve replacement (AVR) for aortic stenosis (AS) and, if so, the mechanisms for this change. MR frequently accompanies AS. The addition of mitral valve replacement to AVR significantly increases the risk of surgery. Although previous studies have suggested a qualitative improvement in MR severity after AVR, semiquantitative analysis of this improvement has not been documented nor have the underlying mechanisms been examined. We evaluated 28 patients who had undergone 2-dimensional echo and color flow Doppler imaging an average of 1.5 +/- 2.5 months before and 2.5 +/- 4.2 months after AVR. Maximum MR area, MR percentage (MR area/left atrial area), mitral annular area, left atrial area, aortic gradient, and parameters of left ventricular geometry were measured to evaluate MR severity and to assess functional mechanisms for improvement in MR. There was a significant decrease in MR area (5.5 +/- 2.8 cm2 vs 2.5 +/- 1.9 cm2, p < or =0.0001) and MR percentage (25 +/- 11% vs 12 +/- 10% after operation, p < or =0.0001) between preoperative and postoperative studies. There was a significant reduction in aortic gradient, mitral annular area, left atrial area, and left ventricular length postoperatively. In univariate analysis, MR improvement was related to the lower preoperative left ventricular fractional area change (p = 0.027) and to the changes in fractional area change (p = 0.001) and left ventricular systolic area (p = 0.001). Thus, improvement in MR after AVR is related to changes in left ventricular function postoperatively. These data suggest that reduction in MR is due not only to decreased intraventricular pressure, but also to changes in ventricular morphology.     

Heart rate variability index in congestive heart failure: relation to clinical variables and prognosis

AIM: To evaluate the clinical and prognostic value of the heart rate variability index in patients with congestive heart failure. METHODS: Sixty-four patients with chronic congestive heart failure and sinus rhythm underwent clinical assessment, 24-h ambulatory electrocardiography and echocardiography. Patients were followed for 6 to 30 months. Cardiac death or heart transplantation constituted the primary end-point of the study. RESULTS: The heart rate variability index was related to left ventricular ejection fraction (r=0.29, P=0.02) and New York Heart Association class (P=0.01). Patients with a restrictive left ventricular filling pattern had a lower heart rate variability index compared to patients with a non-restrictive pattern (26+/-11 vs 33+/-9 units, P=0.01). Patients who died (n=11) or underwent heart transplantation (n=4) had a lower heart rate variability index compared to survivors (21+/-10 vs 33+/-9 units, P<0.0001). In multivariate survival analysis, a reduced heart rate variability index was related to survival independent of parameters of left ventricular function. CONCLUSION: The heart rate variability index provides independent information on clinical status and prognosis in patients with chronic congestive heart failure.     

Exercise echocardiography in postmenopausal hormone users with mild systemic hypertension

Rest and exercise echocardiography (at dynamic and isometric exercise) were performed in 30 postmenopausal women (aged 54 +/- 4 years) with borderline to mild hypertension. They were then divided into 2 groups: 17 women who started oral hormone replacement therapy (0.625 mg/day conjugated estrogens or 2 mg/day estradiol) and a control group of 13 nonusers. After 6 to 9 months, a second echocardiography was performed in 26 women (4 withdrew). There were only a few changes in values obtained in the 12 controls at the end of follow-up compared with baseline. Primarily, these changes included a slight decrease in systolic blood pressure at rest and on exercise. Several significant morphologic and hemodynamic alterations appeared in 14 hormone users. Left ventricular cavity dimensions and mass became smaller: mean end-diastolic diameter decreased from 45.9 +/- 3 mm at baseline to 44.4 +/- 3 mm at study termination (p = 0.007). The corresponding values for end-systolic diameter were 25.8 +/- 4 mm and 23.9 +/- 4 mm (p = 0.006); for left atrium diameter, it was 34.5 +/- 4 mm and 32.5 +/- 4 mm (p = 0.001); for left ventricular wall width, it was 19.9 +/- 2 mm and 19.3 +/- 2 mm (p = 0.02); for left ventricular mass, it was 197 +/- 28 g and 179 +/- 32 g (p = 0.006). The resting aortic blood flow velocity and acceleration increased: 119 +/- 18 cm/s before therapy versus 129 +/- 23 cm/s while on hormone substitution (p = 0.04), and 13.6 +/- 3 m/s2 versus 16.5 +/- 4 m/s2 (p = 0.008), respectively. Mean rest to peak exercise systolic blood pressure difference became smaller after hormones: 39 +/- 19 mm Hg versus 28 +/- 13 mm Hg (p = 0.03) during dynamic exercise, and 43 +/- 22 mm Hg versus 25 +/- 13 mm Hg (p = 0.004) during isometric exercise. The above data probably indicate that with hormone replacement therapy, there is an improvement in cardiac function both at rest and during exercise.     

Quality of life in children with congenital heart defects

PURPOSE: The antiepileptic effects of zonisamide (ZNS) have been well documented experimentally and clinically. The purpose of this study was to examine whether ZNS reduces cerebral damage after transient focal ischemia in rats. METHODS: Ischemia was induced by a transient occlusion of the left middle cerebral artery (MCA) with a 3-0 nylon monofilament for 90 min. Neurological evaluation was performed by measuring the event of neurological deficit of the contralateral forepaw and hindpaw at 10 min and 1 day after MCA occlusion (MCAo). Brain infarct size was determined by measuring triphenyltetrazonium chloride-negative stained area of the serial brain sections 1 day after MCAo. RESULTS: The pre- or postischemic treatment with ZNS [(10-100 mg/kg p.o.), 30 min before and 4 h after or 15 min and 4 h after the occlusion] markedly reduced cerebral damage in the ipsilateral hemisphere and the neurological deficit induced by transient ischemia. The reducing effect on the damage was observed in the cortical and subcortical regions. Preischemic treatment with carbamazepine (CBZ 60 mg/kg p.o. twice 30 min before and 4 h after MCAo) tended to reduce the cerebral damage and neurological deficit, but the lower dose (20 mg/kg p.o. twice) did not. Valproate (VPA 1,000 mg/kg p.o. twice) also had no effect. CONCLUSIONS: ZNS at the anticonvulsant dose, unlike CBZ and VPA, ameliorated the brain infarction and the event of neurological deficit after transient focal cerebral ischemia. These data suggest that ZNS has therapeutic potential in protecting against ischemic cerebral damage, such as stroke.     

Clinical and hemodynamic follow-up of left ventricular to aortic conduits in patients with aortic stenosis

To assess the long-term results of left ventricular outflow tract reconstruction utilizing an apical left ventricular to aortic valved (porcine) conduit the clinical and hemodynamic data were reviewed from 24 patients who had placement of an apico-aortic conduit. Eighteen of the patients are asymptomatic and taking no cardiac medications. Three patients were reoperated on, one patient 1.5 years after his original operation for subacute bacterial endocarditis and two patients 3 to 4 years after their original operation for severe conduit valve insufficiency. None of the patients is taking anticoagulants and no thromboembolic events have occurred. Postoperative catheterization has been performed 1 to 1.5 years (mean 1.2) after repair in 15 of 21 patients. The rest left ventricular outflow tract gradient has decreased from 102.5 +/- 20 mm Hg preoperatively to 14.8 +/- 9.9 mm Hg postoperatively (probability [p] less than 0.001). Some degree of conduit obstruction was demonstrated by catheter passage in 11 of the 15 patients. In these 11 patients, the obstruction occurred at three distant sites: at the egress of the left ventricle in 9, at the porcine valve in 5 and at the aortic to conduit junction in 1. Isometric exercise in five and supine bicycle exercise in six patients increased the left ventricular outflow tract gradient by 2.5 +/- 1.1 and 20.8 +/- 11.8 mm Hg, respectively, despite an increase in cardiac index of 1 +/- 0.3 and 3.7 +/- 0.4 liters/min per m2, respectively. The data suggest that a left ventricular to aortic conduit is an effective form of therapy for severe left ventricular outflow tract obstruction.