Temporal effects of low-dose ACE inhibition on endothelial function in Type 1 diabetic patients.

AIM: Increased asymmetrical dimethylarginine (ADMA) is known to disturb endothelial function. ACE inhibitors decrease plasma ADMA levels in diseases associated with endothelial dysfunction. The effects of ACE inhibition on endothelial function and plasma ADMA levels in Type 1 diabetic patients was evaluated in the study. METHODS: Thirty Type 1 diabetic patients [29+/-6 yr; females (F)/males (M): 18/12] and 29 controls (30+/-6 yr; F/M: 16/13) were recruited. Flow-mediated dilatation (FMD), plasma ADMAand thiobarbituric acid reactive substances (TBARs) were determined at baseline, on day 15 and 90 of 0.5 mg qd trandolapril therapy. RESULTS: Compared to controls, baseline FMD levels were lower (4.7+/-2.0% vs 11.2+/-3.9%) (p<0.001), plasma ADMA (271.1+/-48.1 nmol/l vs 237.5+/-25.1 nmol/l) (p<0.05) and TBARs levels [4517.1+/-2366.9 nmol/malondialdehyde (MDA) vs 1775.9+/-598.7 nmol/MDA] (p<0.001) were higher in diabetic patients. On day 90 of trandolapril treatment, FMD (8.6+/-4.1%) (p<0.01) increased, ADMA levels (229.6+/-42.9 nmol/l) (p<0.001) decreased and TBARs levels (1531.8+/-1036.0 nmol/MDA) (p<0.001) decreased significantly. FMD was negatively correlated with plasma ADMA (r=-0.228, p<0.01), and TBARs levels (r=-0.244, p=0.02), whereas ADMA and TBARs levels were correlated positively (r=0.399, p<0.0001). CONCLUSIONS: In conclusion, endothelial dysfunction is associated with elevated plasma ADMA levels in Type 1 diabetic patients. Low-dose ACE inhibition improves endothelial dysfunction and reduces ADMA levels. The antioxidant action of ACE inhibitors may play role in this process.

Night-time blood pressure load is associated with higher left ventricular mass index in renal transplant recipients.

The absence of nocturnal fall in blood pressure (BP) is named as nondipper status, which has been shown to be an additional risk factor for the development of left ventricular hypertrophy and cardiovascular events in several high-risk groups. The aim of this study was to determine the influences of the nondipper status and nocturnal blood pressure loads on left ventricular mass index (LVMI) in renal transplant recipients. A total of 35 nondiabetic renal transplant recipients were included into the study. A 24-h ambulatory blood pressure monitoring (ABPM) was performed for all recipients. The nondipper status was defined as either an increase in night-time mean arterial pressure (MAP) or a decrease of no more than 10% of daytime MAP. LVMI was measured by using two-dimensional guided M-mode echocardiography. The night-time systolic blood pressure (SBP) load was defined as the percentage of the time, during which SBP exceeded 125 mmHg during night time. The nondipping was common among renal transplant recipients, of whom 60% were nondipper in our study. LVMI was significantly higher in the nondipper group vs the dipper group (133 +/- 35 g/m(2) vs 109 +/- 26 g/m(2), P = 0.04). A fall in MAP at night time was 14.5 +/- 4.3% in the dipper group, while it was 1.4 +/- 6.1% in the nondipper group (P < 0.001). On stepwise multiple regression analysis, night-time SBP load and haemoglobin were independent predictors of LVMI (R(2) = 0.53). In conclusion, nondipping is common after renal transplantation. Night-time SBP load and low haemoglobin are closely related to the increase in LVMI in renal transplant recipients. ABPM may be a more useful tool in optimizing treatment strategies to reduce cardio-vascular events in renal transplant recipients.

The sensitivity and specificity of the case definition criteria in diagnosis of headache: a school-based epidemiological study of 5562 children in Mersin.

The objectives of the present study were to estimate the prevalence of recurrent headaches in schoolchildren (ranging from 2nd to 5th degrees) in Mersin city of Turkey and to determine the sensitivity, specificity, positive predictive value and positive likelihood ratio of the diagnostic headache characteristics in children with migraine and Tension Type Headache (TTH) using neurologist's diagnosis as the gold standard. The stratified sample of study was composed of 5562 children. The prevalence of recurrent headache was 49.2% (2739 of 5562) and the prevalence of current headache was 31.3% (859 of 2739). TTH was more common than migraine (24.7% vs. 10.4%). The most sensitive headache characteristic for migraine was 'severity of pain' and the most sensitive definitive symptom is 'duration of headache' in children with TTH. IHS-based symptom definition criteria are highly beneficial in diagnosis of childhood headache, if used together with detailed clinical assessment.

The sensitivity and specificity of the case definition criteria in diagnosis of headache: a school-based epidemiological study of 5562 children in Mersin.

The objectives of the present study were: (i) to estimate the prevalence of recurrent headaches in schoolchildren (ranging from 2nd to 5th degrees) in Mersin city of Turkey; (ii) to determine the sensitivity, specificity, positive predictive value and positive likelihood ratio of the diagnostic headache characteristics in children with migraine and tension-type headache (TTH) using neurologist's diagnosis as the gold standard. The stratified sample of study was composed of 5562 children. The prevalence of recurrent headache was 49.2% (2739 of 5562) and the prevalence of current headache was 31.3% (859 of 2739). TTH was more common than migraine (24.7% vs. 10.4%). The most sensitive headache characteristic for migraine was 'severity of pain' and the most sensitive definitive symptom was 'duration of headache' in children with TTH. International Headache Society-based symptom definition criteria are highly beneficial in diagnosis of childhood headache, if used together with detailed clinical assessment.

Coronary stent implantation in Behçet's disease.

Behçet's disease (BD) is a systemic vasculitis that rarely involves the coronary arteries. Coronary arteritis may lead to myocardial infarction and death, and the management of coronary lesions due to BD has been described only in a small number of patients. The outcome of a young patient with BD is reported who was admitted with acute coronary syndrome and underwent balloon angioplasty and coronary stent implantation. Coronary stent implantation is an alternative treatment for coronary artery lesions of BD but careful monitoring is mandatory due to the progressive vasculities.

Association between salt sensitivity and target organ damage in essential hypertension.

Cardiovascular events occur more frequently in sodium-sensitive patients with essential hypertension; recently, sodium sensitivity was shown to be a cardiovascular risk factor independently of other classic factors such as blood pressure and cigarette smoking This study examined the relationship between salt sensitivity status and target organ damage in hypertensive patients. Ninety-six patients (35 men, 61 women) with moderate essential hypertension were studied for salt sensitivity status and the presence of target organ damage, including hypertensive retinopathy, serum creatinine, creatinine clearance, and urinary albumin excretion (UAE). Four different patterns of left ventricular anatomic adaptation were identified by categorizing patients according to the values of left ventricular mass index and relative wall thickness by the means of echocardiography. Forty-five (47%) patients were shown to be salt-sensitive, in contrast to 51 (53%) salt-resistant subjects. Serum creatinine and UAE were significantly higher in the group of salt-sensitive hypertensives (P < .05 and P < .001, respectively). Left ventricular mass index (LVMI), relative wall thickness (RWT), and left atrial index (LAI) were all significantly higher in the group of salt-sensitive hypertensive patients. Concentric hypertrophy was significantly more prevalent in the salt-sensitive group (37.8% v 11.8%; P < .01). The prevalence of hypertensive retinopathy in the salt-sensitive group was 84.4%, in contrast to 59.6% in the salt-resistant group (P < .01). Multivariate regression analysis revealed salt sensitivity as a significant predictor of LVMI, RWT, and UAE, independently of age, body mass index, and mean blood pressure. In conclusion, salt-sensitive hypertensive patients are more prone to develop severe hypertensive target organ damage that may enhance their risk of renal and cardiovascular morbidity.

Correlation of myocardial fractional flow reserve with thallium-201 SPECT imaging in intermediate-severity coronary artery lesions.

PURPOSE: The purpose of this study was to compare the measurements of fractional flow reserve of the myocardium (FFRmyo) with results of quantitative coronary angiography (QCA) and stress single-photon emission computed tomography thallium-201 (SPECT 201Tl) imaging in patients with intermediate-severity coronary artery disease (ISCAD). METHODS: We prospectively evaluated 40 lesions of QCA-determined ISCAD in 30 patients (age, 53.3 +/- 10.2 years; 67% male) using a 0. 014 inch pressure wire during elective coronary angiography and compared the results with those of SPECT 201Tl performed within a week of angiography. RESULTS: There was a moderate negative correlation between percent diameter stenosis (%DS) and FFRmyo (53.1 +/- 13.4% and 0.75 +/- 0.09, respectively; r = -0.40; p = 0.01). Twenty-two out of 40 vascular territories (55%) were found to have perfusion defects (Group 1) and 18 territories (45%) were found to be normal (Group 2). While QCA-determined stenosis severity was not different between Group 1 and Group 2 (56 +/- 12% vs. 50 +/- 16%, respectively; p = 0.3), FFRmyo was found to be significantly different between the two groups (0.68 +/- 0.05 vs. 0.83 +/- 0.05, respectively; p = 0.001). When %DS and FFRmyo results were dichotomized as abnormal by 50% and < 0.75, respectively, and SPECT 201Tl was taken as the gold standard, sensitivity, specificity, positive predictive value and negative predictive value of %DS and FFRmyo were 0.55 vs. 0.91, 0.56 vs. 1.0, 0.60 vs. 1.0 and 0.50 vs. 0. 90, respectively. CONCLUSION: While FFRmyo seems to accurately predict the presence of ischemia on SPECT 201Tl in patients with ISCAD, QCA does not reliably assess the physiologic impact of the same lesions.

Measurement of myocardial fractional flow reserve during coronary angioplasty in infarct-related and non-infarct related coronary artery lesions.

Myocardial fractional flow reserve (FFRmyo) has been demonstrated to be a useful method for determining the physiologic importance of a given coronary lesion. However, the reliability of the FFRmyo measurement is unknown in infarct-related arteries (IRA). The aim of this study was to measure and correlate the FFRmyo results of 14 consecutive patients who had recent acute myocardial infarction (AMI) (Group 1) with 14 consecutive patients who didnOt have AMI (Group 2) before and after percutaneous transluminal coronary angioplasty (PTCA). Quantitative coronary angiography (QCA) and FFRmyo measurements were determined both before and after optimal PTCA for all patients. FFRmyo was measured by use of a 0.014 inch guidewire as the ratio of the pressure distal to the target lesion to the aortic pressure taken during the maximal hyperemia induced by intracoronary adenosine. There were no differences between the two groups related to gender, target artery reference diameter, minimal luminal diameter and percent diameter stenosis of the vessel both before and after PTCA. While FFRmyo results after PTCA were not different between the groups, they were statistically different before PTCA (Group 1: 77.6+/-5.4%, Group 2: 63.3+/-8.4%; p<0.001). Although QCA-determined percent diameter stenosis revealed a significant degree of stenosis (66.5+/-10.5%) for Group 1, FFRmyo values were higher than 75% (77.6+/-5.4%), indicating insignificant stenosis. Thus, it was concluded that FFRmyo measurements before PTCA were significantly different between IRA and non-IRA and that the method may not be valid for the determination of stenosis significance in IRA.

Effects of a single dose of oral estrogen on left ventricular diastolic function in hypertensive postmenopausal women with diastolic dysfunction.

OBJECTIVE: To evaluate the acute effects of a single dose of oral estrogen on left ventricular diastolic function in hypertensive postmenopausal women with diastolic dysfunction. DESIGN: Prospective, double-blind, placebo-controlled, clinical study. SETTING: Cardiology and postmenopausal outpatient clinics of a university hospital. PATIENT(S): Thirty postmenopausal women with hypertension (diastolic blood pressure of >90 mm Hg) and left ventricular diastolic dysfunction (mitral E/A ratio [the ratio of peak velocity of early mitral diastolic filling to late diastolic filling] of <1 and isovolumic relaxation time of >100 ms) were included in the study. Thirty normotensive postmenopausal women with normal left ventricular diastolic function served as the control group. INTERVENTION(S): Conjugated equine estrogen (0.625 mg) was given orally. Left ventricular diastolic function was assessed by Doppler echocardiography at baseline and 3 hours after the administration of estrogen. MAIN OUTCOME MEASURE(S): Left ventricular diastolic filling as assessed by Doppler echocardiography. RESULT(S): Estrogen had no effect on heart rate or blood pressure in either study group. The baseline E/A ratios were 0.72 +/- 0.26 and 1.22 +/- 0.30, and the isovolumic relaxation times were 122 +/- 18 ms and 89 +/-14 ms in the hypertensive and normotensive groups, respectively. Estrogen had no significant effect on any of the Doppler parameters in the normotensive group. In the hypertensive group, there was a trend toward normalization of the E/A ratio (from 0.73 +/- 0.11 to 0.84 +/- 20) and a significant improvement in the isovolumic relaxation time (from 124 +/- 20 ms to 105 +/- 13 ms) in response to the administration of estrogen compared with placebo. CONCLUSION(S): A single dose of oral estrogen caused a significant improvement in left ventricular diastolic filling in hypertensive postmenopausal women with diastolic dysfunction.

Effects of simvastatin only or in combination with continuous combined hormone replacement therapy on serum lipid levels in hypercholesterolaemic post-menopausal women.

AIMS: To evaluate the effects of simvastatin only or combined with continuous hormone replacement therapy on the serum lipid profile in hypercholesterolaemic post-menopausal women. METHODS AND RESULTS: One hundred hypercholesterolaemic post-menopausal women were given either simvastatin 10 mg daily together with oestrogen 0.625 mg and medroxyprogesterone 2.5 mg daily (HRT+simvastatin group) (n:50) or simvastatin 10 mg daily (simvastatin only group) (n:50) in a prospective manner. Serum total, low density lipoprotein, and high density lipoprotein cholesterol and triglyceride levels were measured at baseline, at 3 and 6 months. The initial mean (+/-SD) cholesterol values were as follows for the HRT+simvastatin group and the simvastatin only group, respectively: total cholesterol 240. 0+/-28.0 and 248.9+/-28.2 mg x dl(-1); low density lipoprotein cholesterol 174.7+/-25.6 and 175.1+/-25.9 mg x dl(-1); high density lipoprotein cholesterol 37.2+/-5.0 and 39.9+/-7.3 mg x dl(-1). Compared with the baseline, total and low density lipoprotein cholesterol levels decreased; and high density lipoprotein cholesterol levels increased significantly at 3 and 6 months in both groups. However, the mean percent reduction in total cholesterol and low density lipoprotein cholesterol was significantly greater in the HRT+ simvastatin group compared with the simvastatin only group both at 3 months (12.3+/-7.0% vs 8.9+/-6.2%;P<0.01; and 19.0+/-10.6% vs 13.2+/-10.4%;P< 0.005, respectively) and at 6 months (14.6+/-7.7% vs 11.3+/-7.4%;P<0.05 and 23.3+/-9.7% vs 15.8+/-12.3%;P<0.005, respectively). The mean percent increase in serum high density lipoprotein cholesterol concentrations was also significantly greater in the HRT+simvastatin group compared with the simvastatin only group at both times (14.6+/-11.8% vs 9.8+/-11.8%;P<0.005, at 3 months, and 21.3+/-15.2% vs 11.1+/-12.5;P<0.005, at 6 months, respectively). Furthermore, significantly more patients in the HRT+simvastatin group than in the simvastatin only group attained their target treatment goals dictated by the National Cholesterol Education Program Adult Treatment Panel II Guidelines. Although the mean percent decrease in triglyceride levels was significantly greater in the HRT+simvastatin group at 3 months, the significance disappeared at 6 months. CONCLUSION: The combination of simvastatin and continuous combined hormone replacement therapy seems to be more effective than simvastatin only in the treatment of hypercholesterolaemia in post-menopausal women.

Limited stage I and II follicular non-Hodgkin's lymphoma: the Nebraska Lymphoma Study Group experience.

The purpose of this study was to evaluate the outcome and prognostic factors of patients with limited stage follicular non-Hodgkin's lymphoma treated prospectively by the Nebraska Lymphoma Study Group (NLSG). Forty previously untreated patients, median age 64 years, with limited stage follicular lymphoma were prospectively treated according to the protocols of the NLSG between January 1980 and December 1990. The follicular large cell type represents 75% of the cases, and 14 of the biopsies also had a diffuse component (composite lymphoma). The initial treatment was radiation therapy (RT) to the involved field in 15 patients, anthracycline-containing combination chemotherapy (CT) in 20, and combined RT and CT in 5. Thirty-seven patients (92.5%) achieved a complete remission (CR). The median follow-up is 120 months (range, 20 to 214). Of the 37 patients achieving a CR, 7 patients are alive in first CR, one died due to sepsis, another because of a myeloproliferative disorder at 77 months following chemotherapy, 6 died because of unrelated causes in first CR. Twenty-two patients relapsed between 1 to 128 months following a CR. The estimated 10-year event-free survival is 21% (95% CI: 7 to 35). Two patients received no or palliative therapy after relapse and both died of progressive disease. Nineteen patients received salvage therapy and 15 achieved a second remission. The median survival after first relapse is 55 months. The estimated 10-year overall survival is 44% (95% CI: 28 to 60). Various factors including sex, histologic subtype, stage, and degree of follicularity do not influence the overall survival or event-free survival. CT with or without RT resulted in a better trend for 10-year event-free survival in stage IA patients compared to RT alone but estimated 10-year overall survival is no different. The overall survival is worse in the > or = 60 age group but this difference is not evident if data is adjusted for cause specific death. In conclusion, limited stage follicular lymphoma has an excellent initial response to radiation therapy or chemotherapy; however the recurrence rate is high and cure is limited.

Tissue plasminogen activator (tPA) as therapy for hepatotoxicity following bone marrow transplantation.

The treatment of established veno-occlusive disease (VOD) of the liver with tissue plasminogen activator (tPA) has been disappointing. In attempts to improve upon these results we identified a subgroup of patients with consistently elevated bilirubin levels who did not meet conventional criteria for VOD (Susp VOD) but who had a significant risk of later developing clinical VOD. In January 1994 we began to treat patients who developed Susp VOD with tPA rather than waiting until they developed clinical VOD. We now report on the results of the first 37 patients who ultimately developed clinical VOD and received tPA therapy prior to Susp VOD, or at the time they had established VOD. Significant bleeding complications occurred in 13 (35%) patients but resolved with discontinuation of therapy in all but one. We found that patients treated early in the course of hepatotoxicity prior to the development of overt VOD had a significantly higher response rate and 100 day survival than patients treated at the time of established VOD. Given the poor results seen in treating late VOD, we suggest that early treatment with tPA may improve the outcome in patients who develop signs of hepatotoxicity following marrow transplantation.

Severe cerebellar swelling and thrombotic thrombocytopenic purpura associated with FK506.

Two patients with CsA-associated neurotoxicity developed severe cerebellar swelling and thrombotic thrombocytopenic purpura after switching to FK506 and high-dose corticosteroids. The prodrome of CsA-associated neurotoxicity, TTP and hypertension while receiving FK506, and high-dose corticosteroids could all be implicated in the development of this syndrome. Close monitoring of patients receiving FK506 and high-dose corticosteroids, for the development of TTP is warranted. Early radiological examination should also be considered in such patients to allow early surgical intervention.

Intravenous Propafenone for Conversion of Atrial Fibrillation or Flutter to Sinus Rhythm: A Randomized, Placebo-controlled, Crossover Study.

BACKGROUND: Propafenone has been claimed to be effective in converting atrial fibrillation and flutter to sinus rhythm; however, controlled clinical trials have reported variable results, and data about the safety of propafenone in the setting of heart failure are lacking. The aim of the present study was to evaluate the efficacy and safety of intravenous propafenone in converting atrial fibrillation and flutter to sinus rhythm. METHODS: Sixty patients with acute (<72 h) or chronic atrial fibrillation or flutter were included in a randomized, placebo-controlled, conditional cross-over study. Twenty eight patients, of whom 12 were in New York Heart Association class III and IV, had heart failure. Patients received intravenous propafenone (2 mg/kg in 10 minutes) and placebo subsequently at 1 hour intervals if sinus rhythm was not achieved. The patients' rhythms were continuously monitored for 1 hour and a 12-lead electrocardiogram, a 1-minute continuous rhythm strip and vital signs were recorded at baseline and at 15, 30, 45, and 60 minutes after the administration of each drug. RESULTS: Twenty of teh 59 patients (34%) treated with propafenone converted to sinus rhythm, while only 4 of the 50 patients (8%) treated with placebo converted (P <.001). Propafenone was more effective in patients with acute (<72 h) atrial fibrillation (64.5%). The conversion rate with propafenone was not significantly different from placebo in patients with atrial flutter and chronic atrial fibrillation (>72 h). Propafenone significantly decreased (P <.005 vs placebo) mean ventricular rate in nonresponders with a baseline heart rate of more than 100 beats/min. No clinically significant adverse effect occurred. CONCLUSIONS: We conclude that intravenous propafenone treatment is effective for converting acute atrial fibrillation; however, it seems unlikely to be beneficial in atrial flutter and chronic atrial fibrillation. Propafenone decreases ventricular rate in nonresponders, and a single dose of propafenone is relatively safe even in moderate-to-severe heart failure.

The Effects of Amlodipine on Left Ventricular Mass and Diastolic Function in Concentric and Eccentric Left Ventricular Hypertrophy.

BACKGROUND: The effects of the antihypertensive therapy with amlodipine (5-10 mg/day) on left ventricular mass and diastolic function were examined in 30 mild to moderate essential hypertensive patients who have left ventricular hypertrophy (LVH) and diastolic dysfunction. METHODS AND RESULTS: Each patient's left ventricular mass was measured, and left ventricular diastolic function was assessed by echocardiographic Doppler examination at entry, and at 3 and 6 months after the initiation of the treatment. Amlodipine reduced both blood pressure (from 164 +/- 14/104 +/- 6 mmHg to 134 +/- 9/83 +/- 4 mmHg) and left ventricular mass index (from 160 +/- 30 g/m(2) to 137 +/- 26 g/m(2)) significantly at 3 months and both parameters maintained at these levels for 6 months. When the patients were classified according to the type of the LVH, a significant regression in left ventricular mass index was seen only in the patients who had concentric LVH was a relative wall thickness >/=0.44 (n = 16), but not in the eccentric LVH group (n = 14), although both groups were not significantly different from each other regarding the basal hemodynamic parameters, baseline left ventricular mass index and the decrease in blood pressure in response to amlodipine treatment. The mitral inflow E/A ratio did not show any significant change in either group. CONCLUSIONS: Amlodipine produced significant regression in LVH only in the patients with concentric LVH, but not those with eccentric LVH, while it did not change the diastolic dysfunction. Therefore, the type of LVH seems to be an important feature in determining the effects of antihypertensive treatment on left ventricular mass index.

Treatment of acute promyelocytic leukemia in patients presenting at Vancouver General Hospital from 1983 to 1992.

Between 6/83 and 8/92, 23 of 361 patients (6.4%) presenting at Vancouver General Hospital with acute myelogenous leukemia had acute promyelocytic leukemia (APL). Treatment plan was: 1) induction with high-dose cytosine arabinoside and an intercalator; and 2) consolidation with allogeneic bone marrow transplantation (BMT) for those aged < or = 50 years with a sibling donor or repeat of induction for the the others. Complete remission (CR) was achieved in 20 patients (87%). Eleven patients in CR were eligible for allogeneic BMT; 4 were considered unsuitable, 2 refused, and 5 underwent this treatment--1 died of acute graft-versus-host disease, 1 relapsed and 3 are leukemia-free and well 1.6, 3.3 and 3.9 years after diagnosis. Fifteen patients did not undergo allogeneic BMT in CR; 4 received no further treatment and all died, 2 relapsed before consolidation therapy and both died, 1 underwent autologous BMT and died of complications, and 8 received consolidation treatment as planned--1 died of sepsis, 2 relapsed and 5 are leukemia-free and well 1.0, 3.8, 4.5, 4.9 and 8.5 years after diagnosis. The actuarial overall survival for all 23 patients was 38% (95% confidence interval [CI] 18-57%). The actuarial 2-year leukemia-free survival was 60% (95% CI 20-85%) for the 8 patients who underwent consolidation chemotherapy as planned and 53% (95% CI 68-86%) for the 5 patients who underwent allogeneic BMT in CR. These results suggest that patients with APL who are able to undergo consolidation chemotherapy have a relatively good prognosis and allogeneic BMT may reasonably be held in reserve for salvage therapy.