Diagnostic accuracy of enzyme-linked immunosorbent assay (ELISA) and immunoblot (IB) for the detection of antibodies against Neospora caninum in milk from dairy cows.

The aim of the study was to estimate the sensitivity and specificity of enzyme-linked immunosorbent assay (ELISA) and immunoblot (IB) for detecting antibodies of Neospora caninum in dairy cows, in the absence of a gold standard. The study complies with STRADAS-paratuberculosis guidelines for reporting the accuracy of the test. We tried to apply Bayesian models that do not require conditional independence of the tests under evaluation, but as convergence problems appeared, we used Bayesian methodology, that does not assume conditional dependence of the tests. Informative prior probability distributions were constructed, based on scientific inputs regarding sensitivity and specificity of the IB test and the prevalence of disease in the studied populations. IB sensitivity and specificity were estimated to be 98.8% and 91.3%, respectively, while the respective estimates for ELISA were 60% and 96.7%. A sensitivity analysis, where modified prior probability distributions concerning IB diagnostic accuracy applied, showed a limited effect in posterior assessments. We concluded that ELISA can be used to screen the bulk milk and secondly, IB can be used whenever needed.

Small bowel obstruction caused by inflammatory cytomegalovirus tumor in a renal transplant recipient: report of a rare case and review of the literature.

Cytomegalovirus (CMV) infection in renal transplant recipients can present as asymptomatic viremia or CMV syndrome or, in more severe cases, as tissue-invasive disease. CMV enteritis, a common manifestation of CMV invasive disease, usually presents with fever, abdominal pain, anorexia, nausea, and diarrhea, and can be rarely complicated by colon perforation, hemorrhage, or megacolon. CMV infection occurs primarily in the first 6 months post transplantation, when immunosuppression is more intense. We describe the case of a female renal transplant recipient with small bowel obstruction caused by CMV disease 7 years post renal transplantation. The patient presented with diarrhea and abdominal pain. Because of elevated CMV viral load, she was initially treated with antiviral therapy with transient response. Endoscopy and imaging tests showed obstruction of the terminal ileum and, subsequently, the patient underwent exploratory laparotomy when a right hemicolectomy was performed. Biopsy results confirmed the diagnosis of CMV enteritis. Epidemiologic characteristics, clinical presentation, diagnostic workup, therapeutic options, and morbidity-mortality rates of CMV infection/disease, in renal transplant recipients, are reviewed.

Oxalate nephropathy in a diabetic patient after gastric by-pass.

We report a case of 48-year-old woman with history of diabetes and hypertension, who presented with acute to chronic kidney injury. Sixteen months before presentation, she had undergone Roux-en-Y gastric by-pass (RYGB) for morbid obesity. Kidney biopsy showed lesions consistent with oxalate nephropathy and deposition of calcium oxalate crystals. An extensive workshop excluded other causes of kidney injury. The patient subsequently required dialysis with no improvement of renal function on follow-up. The mechanism by which patients develop hyperoxaluria after RYGB remains obscure; it is suggested that RYGB provokes fat malabsorption, which results in increased load of free fatty acid in the intestine. Thus, calcium binds to free fatty acids provoking reduced synthesis of calcium oxalate. Consequently, increased quantity of oxalate remains free and is absorbed in the intestine causing hyperoxaluria. Similar to our case, oxalate nephropathy after RYGB is seen in patients with diabetes, hypertension and chronic kidney injury. Treatment includes low-fat, low-oxalate diet along with administration of calcium supplements. Unfortunately, prognosis is rather poor with the majority of patients eventually requiring permanent dialysis. Therefore, patients with history of chronic kidney disease undergoing RYGB should be closely monitored, particularly those with long standing history of diabetes and hypertension.

Prospective monitoring of BK virus replication in renal transplant recipients.

BACKGROUND: BK virus-associated nephropathy (BKVAN) can be diagnosed only with renal graft biopsy. Definitive diagnosis of BKVAN requires demonstration of BK virus (BKV) replication in renal allograft tissues. Non-invasive analysis of urine and blood is considered essential in screening renal transplant recipients. PATIENTS AND METHODS: This study evaluated prospectively the replication of BKV in plasma and urine with qualitative and quantitative real-time polymerase chain reaction in 32 de novo (group A) and 34 chronic (group B) renal transplant recipients and the long-term impact on graft function. RESULTS: In group A, 456 samples (228 plasma, 228 urine) were examined and BKV was detected in 31 (31/228, 14%) samples of plasma and 57 (57/228, 25%) samples of urine in 20 (20/32, 62.5%) and 23 (23/32, 72%) recipients, respectively. Incidence of viremia and viruria increased during the first 6 months presenting a peak the third postoperative month (viremia: 28% and viruria: 31%). Immune suppressive treatment with tacrolimus showed significant relation with viremia. Renal graft function in de novo renal transplant recipients remained stable throughout the follow-up period without influence of BKV replication. In group B, incidence of viremia and viruria were 3% (1/34) and 9% (3/34) correspondingly, indicating that after the first post-transplant year the risk of BKV re-activation is diminished. CONCLUSION: The highest incidence of BK viremia and viruria is observed the third post-transplantation month, confirming previously published studies in Europe and the United States, and long-term follow up shows that BKV replication decreases significantly after the third post-transplant month and even transient viremia or viruria does not have an impact on renal function.

Monitoring of patients with type 2 diabetes and nephropathy in a specialized diabetic nephropathy clinic seems to be beneficial.

BACKGROUND: The purpose of this study was to evaluate the outcome of DM2 patients with nephropathy when they are under surveillance of a joined clinic run by endocrinologists & nephrologists. PATIENTS AND METHODS: A cohort of 106 patients with DM2, 42-83 years of age, and eGFR < 60 ml/min/m2 were included. Age, sex, duration of diabetes, duration of attending our clinic, smoking habits, BMI, data regarding ischemic heart disease and induction of hemodialysis, urine albumin excretion (UAE) levels, eGFR (MDRD equation) and values of various biochemical parameters were recorded too. Follow-up period ranged from one to 25 years. Paired samples t-test and non-parametrical Kruskal-Wallis test were used for the analyses of the data. RESULTS: Fifty percent of patients had no further progression, 25.9% improvement, while 24.1% had worsening of the UAE levels. During the follow-up in the joined clinic, there was a smaller than the expected from the medical literature decrease in median eGFR, i.e. 2,3 ml/min/m2 and a statistically significant improvement in glycosylated hemoglobin levels from 8.0% to 7.4% (p = 0.016). Time in years of follow-up in the joined clinic of our hospital appeared to be the most significant factor in the improvement or stabilization against deterioration of the UAE levels (p = 0.018). CONCLUSIONS: Close follow-up of DM2 patients with eGFR < 60 ml/min/m2 has resulted in a minor annual eGFR decrease. Monitoring of these patients in a specialized diabetic nephropathy clinic is beneficial for this group of patients for delaying the occurrence of end-stage renal disease.

Heparin-induced thrombocytopenia type II: a serious hazard in preemptive renal transplantation: a case report.

Heparin-induced thrombocytopenia (HIT) type II (HIT II), is an immune-mediated complication of heparin therapy, associated with arterial and venous thrombosis. Herein we have reported a case of a 23-year-old woman who developed HIT following a living related donor, preemptive, renal transplantation. The patient was preoperatively exposed to both unfractionated and low-molecular-weight heparin as she underwent five hemodialysis sessions. HIT caused right common and external iliac vein and renal graft artery thrombosis, resulting in graft loss. Heparin-free hemodialysis was continued, and the patient was successfully treated with anticoagulation by the direct thrombin inhibitor lepirudin for both the thromboses and for hemodialysis. Finally, she was accepted for the continuous ambulatory peritoneal dialysis program. This report highlighted the importance of clinical awareness as far as previous heparin exposure is concerned for establishing an early diagnosis and delivering treatment of this life-threatening prothrombotic complication of heparin administration.

Treatment of severe hypercalcemia due to refractory hyperparathyroidism in renal transplant patients with the calcimimetic agent cinacalcet.

Calcimimetic agents increase the sensitivity of calcium sensing receptors of parathyroid glands and suppress both serum calcium levels and parathyroid hormone. There are still limited data on the treatment of renal transplant patients with severe hypercalcemia and hyperparathyroidism with calcimimetics (cinacalcet). We describe two such renal transplant patients with chronic kidney disease Stage 3 who presented with persistent hypercalcemia (serum calcium 11.5-12 mg/dl) and refractory hyperparathyroidism (iPTH 194-547 pg/ml). Control of hypercalcemia with cinacalcet (serum calcium <10 mg/dl) resulted also in an improvement of hyperparathyroidism, but with a slower rate than that of the lowering of serum calcium. Addition of a vitamin D analog together with the calcimimetic agent resulted in faster control of the resistant hyperparathyroidism in both patients (iPTH <145 pg/ml) with clinical improvement and without any side effect. It seems that this new agent will improve our clinical approach of renal bone disease permitting a more integrated and successful treatment of hyperparathyroidism and its consequences on patients with chronic kidney disease.

Hypercalcemia due to resistant hyperparathyroidism in renal transplant patients treated with the calcimimetic agent cinacalcet.

INTRODUCTION AND AIMS: Calcimimetic agents increase the sensitivity of calcium-sensing receptors of parathyroid glands and suppress both serum calcium levels and parathyroid hormone (PTH). The use of these drugs in patients with a functioning graft suffering from resistant hyperparathyroidism and hypercalcemia is still under investigation. We report seven patients who were treated with the calcimimetic agent cinacalcet. METHODS: The four male and three female patients of 38 to 72 years of age received a renal transplant from 4 to 35 months before cinacalcet treatment. Serum creatinine was 1.2 to 1.8 mg/dL (estimated glomerular filtration rate between 40 and 75 mL/min). Immunosuppressive treatment consisted of interleukin-2 antibody induction therapy, calcineurin inhibitors (cyclosporine or tacrolimus), prednisolone, and mycophenolate mofetil. Mild to severe hyperparathyroidism resistant to vitamin D analog treatment (intact parathyroid hormone molecule [iPTH] 174 to 519 pg/mL) was accompanied by severe hypercalcemia (Ca >11 mg%). To date the patients have completed 3 to 18 months of therapy. Cinacalcet 30 mg/d was initially administered. RESULTS: This treatment resulted in a rapid decrease in total serum calcium (8.6 to 9.2 mg/dL) while PTH showed a milder, progressive decrease. Having controlled calcium levels, 1alpha OH vitamin D (0.25 microg/d per os) was added to the treatment, which resulted in a further decline of iPTH without producing an increase in serum calcium concentrations (median initial iPTH value 401 pg/mL, median value after treatment 176 pg/mL). Therapy was well tolerated without hypocalcemic events. CONCLUSION: Cinacalcet offered a better holistic treatment approach to such patients.

Relations of inflammatory markers to lipid levels and autonomic tone in patients with moderate and severe chronic kidney disease and in patients under maintenance hemodialysis.

BACKGROUND AND AIMS: Chronic kidney disease is associated with enhanced inflammatory response and autonomic dysfunction. Evidence exists of a potential interaction of inflammation and nervous system. We sought to investigate determinants of heart rate variability (HRV) and relations between the inflammatory markers C-reactive protein (CRP) and interleukin-6 (IL-6) and autonomic tone in patients with moderate and severe chronic kidney disease and in maintenance hemodialysis patients, and relations of CRP and IL-6 with clinical characteristics and lipid levels. METHODS: This was a cross-sectional study of 51 hemodialysis and 53 moderate and severe chronic kidney disease patients. Autonomic tone was assessed using 24-hour HRV analysis in time and frequency domain. All patients underwent measurements of high sensitivity CRP, IL-6 and lipid levels. RESULTS: CRP and IL-6 were elevated in the non-dialysis group at levels similar to hemodialysis patients. Hemodialysis patients had lower total cholesterol, LDL cholesterol and apolipoprotein B levels (p < 0.05), and in this group of patients lipids were related to CRP and IL-6 (p < 0.05). The inflammatory marker IL-6 was associated to HRV in the moderate and severe chronic kidney disease group (R = -0.4, p < 0.01 for standard deviation of RR intervals and very low frequency power, R = -0.5, p < 0.01 for standard deviation of all five-minute RR intervals, R = 0.35, p < 0.05, for total power and low frequency power). Adequacy of dialysis, but not the inflammatory markers, was associated to HRV in the hemodialysis group (R = 0.6, p < 0.01 for high frequency power). CONCLUSION: Enhanced inflammatory response occurs already in stages 3 and 4 chronic kidney disease. IL-6 is related to HRV in these patients, but not in the hemodialysis group, suggesting that IL-6 may interact with autonomic tone in that stage of disease.

Comparative haemodynamic responses to the first dose of short- and long-acting ACE inhibitors in patients with congestive heart failure.

BACKGROUND: Angiotensin Converting Enzyme inhibitors (ACEi's) confer significant mortality and morbidity benefits in all functional grades of chronic heart failure (CHF). However, physicians' concerns regarding the possible occurrence of first-dose hypotension appear to be a contributing factor to their under-utilisation in both hospital and primary care settings. We investigated whether long-acting and short-acting ACEi's differ in their haemodynamic responses to the first-dose in patients with CHF. METHOD: This was a multicentre, randomised, open, two-parallel-group study of captopril 6.25 mg and perindopril 2 mg. 240 patients with CHF, age 68.9 +/- 8.9 years, of whom 66% were male, NYHA II-IV, with average blood pressure baseline values of 132.2 +/- 16.2/78.5 +/- 10.5 mmHg for systolic and diastolic blood pressure, and left ventricular ejection fraction (LVEF) of 31.3 +/- 7.4% received either captopril (n = 124) or perindopril (n = 116). Blood pressure was continuously monitored during the 8 h following drug intake. Minimum levels and maximum decreases in systolic, diastolic and mean arterial pressures were measured, along with the incidence of hypotensive episodes defined as mean blood pressure (MBP) fall > 20 mmHg, whether symptomatic or not. Subgroups of patients distributed according to age, baseline blood pressure (BP) and LVEF were subsequently analysed. RESULTS: Overall, a statistically significant treatment effect in favour of perindopril was observed. First-dose hypotension was observed more frequently following captopril than perindopril administration, with lower MAP minimal levels (78.0 +/- 8.9 vs. 84.5 +/- 10.1 mmHg, p < 0.0001), greater maximum falls (17.6 +/- 8.3 vs. 12.8 +/- 7.3 mmHg, p < 0.0001) and more frequent hypotensive episodes (42% vs. 15%, p < 0.0001). The incidence of at least one symptomatic episode was also significantly higher with captopril (10 patients vs. one patient, p = 0.029). Subgroup analyses according to age (< or = 70 years or > 70 years) or LVEF (< or = 30% or > 30%) reflected the main result. CONCLUSION: Initiation of treatment with ACE inhibitors is associated with different haemodynamic and clinical tolerances in CHF patients, regardless of their risk for hypotension, with possible clinical implications.

Intracoronary cyclic-GMP and cyclic-AMP during percutaneous transluminal coronary angioplasty.

We investigated intracoronary cyclic-guanosine monophosphate (c-GMP) levels during percutaneous transluminal coronary angioplasty (PTCA) since experimental studies have shown the endothelial origin of c-GMP production. Intracoronary c-GMP and cyclic adenosine monophosphate (c-AMP) were measured during coronary angioplasty in 24 patients with chronic coronary artery disease. Four coronary blood samples were taken through a catheter from the coronary artery the first sample before coronary angiography and the other three from distal to coronary obstruction, as follows: before the balloon inflation, at the maximum inflation and 5 min after restoration of coronary flow. c-GMP increased from 7.9 +/- 1.0 pmol/ml and 7.5 +/- 0.9 pmol/ml before angiography and balloon inflation to 11.1 +/- 1.3 pmol/ml at the maximum inflation (P < 0.01), with a trend to decrease 5 min after the end of the intervention (9.5 +/- 1.0 pmol/ml, P: NS). Intracoronary c-AMP levels remained almost unchanged. Five venous samples were taken to measure c-AMP before coronary angiography, before PTCA, and 5 min, 2 h and 24 h after PTCA. c-AMP values 2 and 24 h after PTCA (17.8 +/- 1.7 pmol/ml and 17.5 +/- 1.7 pmol/ml, respectively) were lower than the highest value (22.1 +/- 2.1 pmol/ml) found 5 min after PTCA, (P < 0.001). c-GMP increases distal to coronary obstructive lesion during PTCA at the time of balloon inflation, while c-AMP remains unchanged. c-AMP rises in venous circulation only. PTCA stimulates the mechanism of c-GMP release, while systemic c-AMP increase seems to be related to the stress occurring during catheterisation and PTCA.

Correlation of bone mineral density with the histological findings of renal osteodystrophy in patients on hemodialysis.

AIMS: To examine the distribution of bone mineral density (BMD) in different histological groups of renal osteodystrophy. PATIENTS: We prospectively studied 62 patients, 41 men and 21 women, aged 57+/-11.5 years, who had been on hemodialysis for 60+/-55 months. The women had been amenorrheic for 13+/-4 years and 7 patients (11%) had a positive fracture history. METHODS: A bone biopsy was taken after tetracycline labelling and BMD of the lumbar spine and proximal femur was measured by dual-energy X-ray absorptiometry (DEXA); serum intact parathyroid hormone (iPTH), bone Gla protein (BGP), phosphorus, calcium and alkaline phosphatase (ALP) were also determined. RESULTS: Histologically, 40 patients showed secondary hyperparathyroidism (sHPT), 6 mixed bone disease, 14 adynamic bone disease (A) and 2 osteomalacia. BMD of the lumbar spine was decreased in 43 patients (69%) and in 9 (14.5%) it was lower than -2 Z score units. BMD of the femoral neck was low in 55 patients (89%) and in 22 (35.5%) it was lower than -2 Z scores. BMD was lower in patients with sHPT than in those with adynamic bone disease (p<0.05) in which it was close to normal. BMD in both these sites correlated inversely with the biochemical markers (serum iPTH, BGP and ALP) and the histomorphometric indices of bone turnover. CONCLUSIONS: Osteopenia is frequent in patients on hemodialysis, especially those with biochemical and histological findings of sHPT.

Regression of massive tumoral calcinosis of the ischium in a dialysis patient after treatment with reduced calcium dialysate and i.v. administration.

BACKGROUND: Tumoral calcinosis, an inherited metabolic disorder, has been described with increasing frequency over the last 20 years [Drueke 1966]. It is characterized by massive calcium phosphate deposits in periarticular tissues, usually around large joints, especially the hips, knees and elbows (editorial in Lancet 1987). PATIENT AND METHOD: We describe a 58-year-old male patient with tumoral calcinosis of the ischium and severe hyperparathyroid bone disease, successfully treated with reduced calcium dialysate and vitamin D. CONCLUSION: We believe that in cases of tumoral calcification with histologically proven hyperparathyroid bone disease, lowering the calcium dialysate concentration together with careful administration of vitamin analogs and monitoring of serum calcium, phosphate and parathyroid hormone levels, may be the ideal therapeutic approach. Control of hyperphosphatemia would be best achieved with measures other than administration of aluminium phosphate binders if one wishes to avoid the induction of adynamic bone.

Severe acute renal failure in a 19-year-old woman following laparoscopic cholecystectomy.

A case of severe acute renal failure in a young female patient necessitating renal replacement therapy after laparoscopic cholecystectomy is described. The histology of the renal lesion assigned to the effects of laparoscopic surgery is relevant for the pathogenesis of renal complications after such procedures. This explains part of the pathogenesis of the ischemic lesions in kidney structure that increased intra-abdominal pressure can provoke. Emphasis is given on the prevention of such side effects.

Prospective randomized trial of external versus internal transcatheter cardioversion in patients with chronic atrial fibrillation.

To evaluate the safety and long-term efficacy of internal transcatheter cardioversion, forty patients with chronic, lone atrial fibrillation were studied. The patients were randomised to internal transcatheter cardioversion or to conventional external cardioversion. In cases where the procedure was unsuccessful, cross-over to the alternate method was performed. Oral anticoagulation therapy was started three weeks prior to the procedure and was maintained for another three weeks following successful cardioversion. Sinus rhythm was restored in 16/18 patients (88%) in the internal cardioversion group, versus 9/22 patients (40%) in the external cardioversion group (p < 0.01). In addition, 8/13 (61%) patients who were crossed-over to internal cardioversion were successfully cardioverted to sinus rhythm. In contrast, both patients who were crossed-over to external cardioversion remained in atrial fibrillation. During a mean follow-up period of 23 months, 13 (39.3%) patients maintained sinus rhythm. Using the intention to treat principle, the recurrence rate was not statistically different between the two methods. It is concluded that internal cardioversion is more effective in acutely restoring sinus rhythm compared to external cardioversion. However, both methods have similar long-term recurrence rates.

Neuropathy and quality of life in diabetic continuous ambulatory peritoneal dialysis patients.

Diabetes mellitus is the commonest cause of end-stage renal failure and is associated with considerable morbidity. Neuropathy is one of the most serious complications of diabetes, linked to the incidence of nephropathy and retinopathy. The prevalence of neuropathy increases with age and duration of diabetes. Peripheral sensorimotor neuropathy is the main manifestation of neurological damage in diabetes, while autonomic neuropathy, a devastating complication, is also present in a large number of patients with long-term diabetes. Clinical features of autonomic neuropathy are mainly cardiovascular disorders and abnormal visceral function. One of the most important sequelae of neuropathy is the development of the insensitive foot at risk of ulceration, deformation, Charcot neuroarthropathy, and amputation. Prevention, education, and identification of the at-risk patient are the key elements in managing these severe complications. Dialysis, and mainly peritoneal dialysis, still remains the main renal replacement therapy for end-stage renal disease (ESRD) diabetic patients. It is obvious from many studies that diabetes and its complications are major risk factors associated with poorer survival rates, increased morbidity, and decreased quality of life. Few, if any, data are available specifically evaluating quality of life in continuous ambulatory peritoneal dialysis (CAPD) diabetic patients. Fewer data are available estimating the impact of neuropathy on the quality of life of such patients. Specific studies must be carried out to further investigate quality-of-life issues and neuropathy in this vulnerable group of patients.

Transplantation of pediatric kidneys to adult recipients: an analysis of 13 cases.

INTRODUCTION: The shortage of cadaveric donors for kidney transplantation has prompted many centers to expand the criteria used for donor selection to increase the organ supply. The use of cadaveric pediatric kidneys has been suggested as a means to overcome the shortage. However, some studies indicate that kidneys from pediatric donors show inferior results to those from adult donors. In this retrospective study we examined the outcome of kidney transplantation using cadaveric pediatric donors. MATERIALS AND METHODS: From October 1990 to May 2002, 13 adult patients received pediatric renal transplants including two that were transplanted en bloc. The patients were divided into two groups based upon donor age: group I donors were 18 months to 6 years old; the seven recipients were of mean age 47.3 years. Group II donors were 7 to 15 years old; the six recipients were of mean age 43.6 years old. Cyclosporine-based immunosuppressive regimens were used in both groups. RESULTS: The patient survival rate was 85.7% in group I and 100% in group II. The graft survival rates at the first and third posttransplant year in group I were 71.4% (5/7) and 57.1% (4/7) and in group II, 66.7% and 50%, respectively. The frequency of urinary complications in group I was 28.5% (2/7) and in group II 33.3% (2/6). There was one case of venous thrombosis in group II. CONCLUSION: Pediatric renal grafts may be used with reasonable safety. However, surgical complications remain a significant problem especially with younger pediatric grafts.

Segmental spinal correction of idiopathic scoliosis. Luque rods and Hartshill rectangle in 30 patients followed for 2-6 years.

30 patients with idiopathic scoliosis were treated by posterior spinal arthrodesis using the Luque (8 patients) and Hartshill (22 patients) rodding systems with sublaminar segmental wiring. Patients were followed for 2 to 6 years. In most cases, postoperative correction exceeded safety correction limits (lateral bending film plus 10 degrees). Final correction was 55%, while derotation was not significant (average 3 degrees). No neurological deficit was noted. Postoperative bracing was not applied and there was 1 patient with broken rods (Luque trolley system without fusion) and 1 patient with broken wires in 4 segments. Allogenic blood transfusion was avoided in 19 patients by preoperative donation of autologous blood, in combination with salvage of intraoperative shed blood. We found segmental spinal wiring with either rods or rectangles to be a safe method for correction of scoliosis in experienced hands. It offered satisfactory stability and fusion rate with no need for external support.

Comparison of endothelin-1 levels at rest and during exercise between patients with cardiac syndrome-X and healthy people.

Several previous studies have shown that endothelin-1 (ET 1) plasma levels are raised in cases of endothelial abnormality and microvascular dysfunction. Syndrome-X constitutes an important clinical entity characterized by angina-like pain and normal coronary arteries which is believed to reflect microvascular dysfunction. The aim of the present study was to investigate the role of ET 1 in the pathophysiology of the above syndrome. For that purpose the plasma ET 1 concentrations, measured by radioimmunoassay, between 28 X-syndrome patients (group A) and 10 age-matched normal control subjects (group B) at rest and at the peak of the exercise testing were compared. We specify that all individuals of group A were referred to our Department for effort angina and were found to have normal coronary arteriograms, negative ergonovine and hyperventilation test and positive exercise test. Our results showed that while at rest ET 1 plasma concentrations did not differ significantly between the two groups, at the peak of the exercise test its levels were found to be significantly higher in syndrome-X patients as compared with those of normal subjects (p< 0.001). In addition, in healthy control subjects ET 1 levels decreased during exercise as compared with the baseline values and that difference was found to be statistically significant (p approximately 0.01). The above finding suggests opposite kinetics during exercise of ET 1 between the two groups studied, which could explain effort angina onset in patients with syndrome-X.