Large triglyceride-rich lipoproteins from fasting patients with type 2 diabetes activate platelets.

AIMS: Type 2 diabetes (T2D) patients present with risk factors for atherothrombosis such as fasting hypertriglyceridaemia and platelet hyperactivity. Our study objective was to determine the effect of large triglyceride-rich lipoproteins (TGRL) from fasting T2D patients on platelet aggregation and, if any, to identify the signaling pathway involved. METHODS: Large TGRL were isolated from the plasma of 25 T2D patients by ultracentrifugation (density < 1.000 g/mL). Platelets were isolated from healthy blood donors (HBD) and suspended in buffer, then preincubated in the presence or absence of TGRL and stimulated with either collagen or thrombin. Platelet aggregation and the arachidonic acid (AA) signaling pathway were studied. RESULTS: Fasting T2D large TGRL were mostly of hepatic origin (apoB100/apoB48 ratio: 42 ± 7) and rich in triglycerides (TG/total apoB ratio: 4.2 ± 0.5), and able to potentiate agonist-stimulated platelet aggregation (collagen: +68%, P < 0.05; thrombin: +771%, P < 0.05). It should also be mentioned that TGRL from the plasma of HBD (n = 7) had no effect on platelet aggregation. In addition, T2D large TGRL increased thromboxane B2 (TxB2) concentration in platelets stimulated with either collagen (+34%, P < 0.05) or thrombin (+37%, P < 0.05) compared with platelets stimulated with either of these agonists without TGRL. Phosphorylation of p38 MAPK and cytosolic phospholipase A2 (cPLA2) was enhanced after incubation of platelets with T2D TGRL and thrombin (+87% and +32%, respectively, P < 0.05) compared with platelets incubated with thrombin only. CONCLUSION: Large TGRL from fasting T2D patients may play a role in the development of atherothrombosis by increasing platelet aggregation and activating the platelet AA signaling pathway.

[Mortality and associated factors of patients with complex chronic diseases in rural and social transformation areas in Andalusia]. / Mortalidad y factores asociados de los pacientes con enfermedades crónicas complejas del ámbito rural y zonas de transformación social en Andalucía.

OBJECTIVE: To determine one-year mortality and associated factors in patients with complex chronic diseases (CCP) in rural health centres and social transformation needs areas (STNA) in Primary Health Care (PHC) in Andalusia. MATERIAL AND METHODS: Design: 1-Year longitudinal observational prospective open study. SETTING: 40 health centre. SUBJECTS: consenting subjects over 18yr according multiple health condition criteria. SAMPLE SIZE: 814 subjects (confidence interval 95%, alpha risk 0.03%, p=.2; 20% of sample increase due to possible losses). End-point: 1-year Mortality. INDEPENDENT VARIABLES: socio-demographic, socio-familial, clinical, functional (Barthel Index -BI-, Lawton-Brody Index), cognitive (Pfeiffer Test), prescribed drugs, social healthcare resources consumption, and quality of life (EQ-5D). DATA SOURCE: Interview and computerised clinical history Results: A total of 832 CCP were included (48.8% women). One-year mortality was 17.8% (n=148). Logistic regression model for mortality included: aged 85 and over, having a caregiver, haemoglobin level less 10g/L, hospital admission in last year, BI under 60 points, and active neoplasia. The calibration obtained from model was good (p=.85 in the Hosmer-Lemeshow goodness-of-fit test), and the discrimination power also good (AUC=0.772 [0.68-0.77] in ROC curve). CONCLUSIONS: 1-year mortality of CCP in rural centres and STNA in PHC was 17.8%. Knowledge of the factors related to the mortality of CCP helps to approach the needs and social-health resources management.

Update on biosimilars in inflammatory bowel disease: Position and recommendations in Mexico. / Actualización sobre los medicamentos biocomparables en la enfermedad inflamatoria intestinal: posición y recomendación en México.

The biotechnology-derived medicines known as biosimilars are defined as non-originator treatments that have demonstrated quality, efficacy, and safety comparable to the reference biologic drug. Clinical trials have shown that the infliximab biosimilar, CT-P13, and the candidates for the adalimumab biosimilars, ABP 501 and ZRC 3197, are not significantly different, with respect to efficacy and safety, from the originator drugs in patients with other autoimmune diseases. However, controversy has arisen over the use of biosimilars in inflammatory bowel disease, due to the incipient evidence not only in patients with no previous biotechnology treatment, but also in patients in remission, that could be switched to a biosimilar for non-medical reasons. The present review is the first critical analysis by different specialists in the area of gastroenterology on the use of biosimilars in inflammatory bowel disease, the evidence on interchangeability, the extrapolation of indications, efficacy, safety, immunogenicity, and the clinical impact of the Mexican health regulations. The aim of our review was to make the positioning and recommendations of these new therapeutic options known, given that they have a potential cost-benefit for both patients and healthcare institutions.

Breast self-exam and patient interval associate with advanced breast cancer and treatment delay in Mexican women.

PURPOSE: The objective of this study was to compare treatment intervals in breast cancer patients according to the detection method (breast self-exam vs screening). PATIENTS AND METHODS: We conducted a retrospective analysis including 291 breast cancer patients at a Mexican tertiary referral hospital. RESULTS: Breast cancer detection method was mostly breast self-exam (60%). The median patient interval was 60.5 days, and was associated with marital status and socioeconomic level. Differences between the two groups were statistically significant for global interval, p = 0.002; however, health system interval was not statistically different. CONCLUSION: In our country, breast cancer screening is opportunistic, with several weaknesses within its management and quality systems. Our study showed that even in specialized health care centers, breast cancer is detected by self-exam in up to 2/3 of patients, which can explain the advanced stages at diagnosis in our country. In developing countries, the immediate health care access for breast cancer patients should be prioritized as an initial step to reduce the global treatment initiation interval in order to reduce mortality.

Functional fluxolipidomics of polyunsaturated fatty acids and oxygenated metabolites in the blood vessel compartment.

Synthesis of bioactive oxygenated metabolites of polyunsaturated fatty acids and their degradation or transformation products are made through multiple enzyme processes. The kinetics of the enzymes responsible for the different steps are known to be quite diverse, although not precisely determined. The location of the metabolites biosynthesis is diverse as well. Also, the biological effects of the primary and secondary products, and their biological life span are often completely different. Consequently, phenotypes of cells in response to these bioactive lipid mediators must then depend on their concentrations at a given time. This demands a fluxolipidomics approach that can be defined as a mediator lipidomics, with all measurements done as a function of time and biological compartments. This review points out what is known, even qualitatively, in the blood vascular compartment for arachidonic acid metabolites and number of other metabolites from polyunsaturated fatty acids of nutritional value. The functional consequences are especially taken into consideration.

Moderate oral supplementation with docosahexaenoic acid improves platelet function and oxidative stress in type 2 diabetic patients.

Platelets from patients with type 2 diabetes are characterised by hyperactivation and high level of oxidative stress. Docosahexaenoic acid (DHA) may have beneficial effects on platelet reactivity and redox status. We investigated whether moderate DHA supplementation, given as a triglyceride form, may correct platelet dysfunction and redox imbalance in patients with type 2 diabetes. We conducted a randomised, double-blind, placebo-controlled, two-period crossover trial (n=11 post-menopausal women with type 2 diabetes) to test the effects of 400 mg/day of DHA intake for two weeks on platelet aggregation, markers of arachidonic acid metabolism, lipid peroxidation status, and lipid composition. Each two week-period was separated from the other by a six-week washout. Daily moderate dose DHA supplementation resulted in reduced platelet aggregation induced by collagen (-46.5 %, p< 0.001), and decreased platelet thromboxane B2 (-35 %, p< 0.001), urinary 11-dehydro-thromboxane B2 (-13.2 %, p< 0.001) and F2-isoprostane levels (-19.6 %, p< 0.001) associated with a significant increase of plasma and platelet vitamin E concentrations (+20 % and +11.8 %, respectively, p< 0.001). The proportions of DHA increased both in plasma lipids and in platelet phospholipids. After placebo treatment, there was no effect on any parameters tested. Our findings support a significant beneficial effect of low intake of DHA on platelet function and a favourable role in reducing oxidative stress associated with diabetes.

[Treatment of the postoperative bowel obstructions in children: laparoscopic vs. open adhesiolysis]. / Tratamiento de las oclusiones postoperatorias en niños: ¿adhesiolisis abierta o laparoscópica?

OBJECTIVE: To compare the results of laparoscopic versus open adhesiolysis in children affected by postoperative bowel obstruction. METHODS: Retrospective study reviewing charts of all patients who were operated on due to postoperative adhesions in our Department. Demographic data, clinical characteristics and postoperative data were collected. RESULTS: During the last 8 years, 37 patients were operated on for postoperative intestinal obstructions. 40.5% were operated by laparoscopy and 59.5% by laparotomy. Mean ages were 6.31 and 4.32 years in laparoscopic and open groups, respectively. There were no differences in days of evolution of the occlusion, neither in their medical history. Patients in laparoscopic group had better outcomes in the need of central lines (15% vs 61.90% p= 0.012), use of parenteral nutrition (38.46% vs 83.33% p= 0.005), beginning of the enteral nutrition (4.04 vs 8.17 days p= 0.004) and hospital stay (7.77 vs 13.05 days p= 0.027). CONCLUSIONS: Open and laparoscopic adhesiolysis are effective to treat adhesive cases. Laparoscopic adhesiolysis has some advantages over open surgery: less need of central lines and parenteral nutrition, earlier start of enteral nutrition, less rate of complications and shorter hospital stay.

OBJETIVO: Comparar los resultados de la adhesiolisis laparoscópica frente a la técnica abierta en niños con oclusiones postoperatorias. METODO: Estudio retrospectivo de los pacientes intervenidos por oclusiones postoperatorias en nuestro centro. Se recogieron variables demográficas, las características clínicas del paciente y del cuadro oclusivo y los resultados postoperatorios. RESULTADOS: En los últimos 8 años, se han realizado 37 intervenciones por oclusiones intestinales postoperatorias: un 40,5% mediante laparoscopia y un 59,5% mediante laparotomía. La media de edad fue 6,31 y 4,32 años para la técnica laparoscópica y abierta, respectivamente. No encontramos diferencias en el tiempo de evolución del cuadro oclusivo, ni en los antecedentes quirúrgicos. Sin embargo, el grupo de adhesiolisis laparoscópica presentó mejores resultados que el de cirugía abierta en: necesidad de vía central (15% frente a 61,90% p= 0,012), uso parenteral (38,46% frente a 83,33% p= 0,005), reinicio de la nutrición enteral (4,04 días frente a 8,17 p= 0,004) y estancia postoperatoria (7,77 frente a 13,05 días p= 0,027). CONCLUSIONES: Ambos abordajes son eficaces para la resolución de la oclusión. La adhesiolisis laparoscópica aporta ventajas frente a la cirugía abierta: menor necesidad de vía central y de nutrición parenteral, reinicio precoz de la nutrición enteral y menor estancia hospitalaria.

Sensitivity of Colletotrichum truncatum to Four Fungicides and Characterization of Thiabendazole-Resistant Isolates.

Anthracnose, caused by Colletotrichum truncatum (syn. C. capsici), has become a common disease of tropical crops, severely affecting the quantity and quality of fruit and seed and, therefore, reducing their market value. For years, chemical control has been extensively used for managing this disease. However, the appearance of isolates that are resistant to the most commonly employed fungicides is increasingly widespread. Twenty C. truncatum isolates from pepper, papaya, and physic nut were tested in vitro against four fungicides to determine their sensitivity. All evaluated isolates were resistant to azoxystrobin and thiabendazole and susceptible to cyprodinil + fludioxonil and mancozeb. To determine the molecular mechanism conferring thiabendazole resistance, the TUB-2 gene was characterized, revealing a glutamic acid to alanine substitution at position 198 in 6 of the 20 isolates that were tested. This work confirms the emergence of benzimidazole-based fungicide resistance in C. truncatum populations and highlights the need for monitoring fungicide sensitivity as an essential activity for the development of effective control schemes.

Compliance with quality prescribing indicators linked to financial incentives: what about not incentivized indicators?: an observational study.

OBJECTIVE: The aims of this study were to investigate whether general practitioners (GPs) who complied with quality prescribing indicators included in the pay-for-performance programmes also complied with quality prescribing indicators which are not linked to incentives and to compare the prescribing behaviour between those GPs who showed compliance with quality prescribing indicators linked to financial incentives and those who did not. DESIGN AND METHODOLOGY: This was a descriptive cross-sectional study which was conducted in 2007 in the Aljarafe Primary Care Area (Andalusia, Spain) and involved 37 Health Care Centres and 176 GPs. The main outcome was the results of a comparison of six quality prescribing indicators linked to incentives and 14 quality prescribing indicators not linked to incentives. The chi-square test was used to compare qualitative variables. Quantitative variables were tested using Student's t test upon confirmation of normality. RESULTS: Those GPs showing compliance with the indicators included in the pay-for performance programme showed low levels of compliance with quality prescribing indicators that were unincentivised. With respect to compliance with the indicators not linked to financial incentives, we found no statistical difference between GPs who showed compliance with incentivised indicators (n = 57) and those showing non-compliance (n = 112) in terms of drug selection, with the exception of the selection of second- and third-line antibiotics and antihistamines, nor in terms of the appropriate use of drugs linked to patient's clinical conditions. CONCLUSIONS: The compliance of GPs showing compliance with quality prescribing indicators included in pay-for-performance programmes was not better than that of those who showed no compliance with other relevant quality prescribing indicators not linked to financial incentives.

Tibolone induces serotonin, estrogen, and progesterone receptor expression but not contractile response to serotonin in the rat uterus.

Most studies on the effect of tibolone on the uterus have focused on the endometrium dismissing the importance of the myometrium. The aim of the present study was to investigate some estrogen-like actions of tibolone in the uterus assessed by: 1) the expression of estrogen, progesterone, and serotonin receptors, and 2) the myometrial contraction induced by serotonin. Estradiol (250 µg), progesterone (50 mg), or testosterone (25 mg) pellets were implanted to ovariectomized rats. Tibolone (0.5 mg/day) was orally administered. An implanted pellet containing vehicle or an equivalent volume of water p.o., were used as controls. Sixty days after beginning the treatments, rats were killed and uterus removed. One horn was processed to evaluate estrogen-alpha, progesterone A and B, and serotonin-2A receptors expression, and the other one was used for studying contraction to serotonin and 60 mM potassium solution. The present data showed that tibolone-induced expression of estrogen, progesterone, and serotonin receptors, but did not induce uterine contractile response to either serotonin or potassium solution. These findings suggest that, in the uterus, tibolone may exert molecular estrogenic actions such as the induction of receptor expression, but not a physiological response as the estrogen-dependent contraction to serotonin.

Dose-effect and metabolism of docosahexaenoic acid: pathophysiological relevance in blood platelets.

Docosahexaenoic acid (DHA) is known as a major nutrient from marine origin. Considering its beneficial effect in vascular risk prevention, the effect of DHA on blood components, especially platelets, will be reviewed here. Investigating the dose-effect of DHA in humans shows that daily intake lower than one gram/day brings several benefits, such as inhibition of platelet aggregation, resistance of monocytes against apoptosis, and reinforced antioxidant status in platelets and low-density lipoproteins. However, higher daily intake may be less efficient on those parameters, especially by losing the antioxidant effect. On the other hand, a focus on the inhibition of platelet aggregation by lipoxygenase end-products of DHA is made. The easy conversion of DHA by lipoxygenases and the formation of a double lipoxygenation product named protectin DX, reveal an original way for DHA to contribute in platelet inhibition through both the cyclooxygenase inhibition and the antagonism of thromboxane A2 action.

Accuracy of noninvasive estimation of pulmonary wedge pressure by echocardiographic indices in heart transplant recipients.

BACKGROUND: Pulmonary capillary wedge pressure (PCWP) can be estimated from transmitral or color M-mode Doppler flow propagation velocities. However, it has been recommended to not use these indices in heart transplant recipients. Our aim was to compare the accuracy of color M-mode, Doppler, and Doppler tissue imaging (DTI)-derived indices to predict PCWP in heart transplant recipients. METHODS: We studied 50 consecutive heart transplant recipients scheduled for routine right-sided heart catheterization and endomyocardial biopsy. Their mean age was 49 ± 17 years and the mean time after heart transplantation was 29 ± 41 months. An echocardiogram was performed immediately after the invasive procedure. We analysed PCWP, transmitral flow velocity variables (peak velocity during early filling (E) and deceleration time [DT]), color M-mode Doppler flow propagation velocity (Vp), and mitral annulus peak early diastolic velocity (E') from DTI. Doppler estimated-PCWP (ePCWP) was calculated as follows: (5.27 × E/Vp) + 4.6. RESULTS: Mean ejection fraction was 66 ± 11%. The mean invasive measured PCWP was 11.14 ± 5.4 mm Hg and the mean noninvasive ePCWP was 11.13 ± 1.8 mm Hg (r = 0.66; P < .0001). A good correlation was present between invasive PCWP and mitral PW-Doppler and DTI parameters: peak E 91 ± 22 cm/s (r = 0.34; P = .02) and DT 143 ± 26 s (r = -0.436; P = .002), E/E' ratio medial mitral annulus 10 ± 4 cm/s (r = 0.353; P = .026) and E/E' ratio lateral mitral annulus 6 ± 2 cm/s (r = 0.462; P = .002). E/Vp was the most accurate index for predicting PCWP (r = 0.615; P < .0001). CONCLUSIONS: Compared with other indirect Doppler indices, E/Vp showed the best correlation to predict PCWP in heart transplant recipients. Despite previous recommendations, PCWP can be accurately estimated from color M-mode indices, giving useful information and avoiding the risks of invasive measurements.

[Conservative management of retained central venous catheters]. / Manejo conservador de los catéteres venosos centrales retenidos.

BACKGROUND: Withdrawal of central venous catheters (CVCs) is usually a simple surgical procedure. However, in some cases, the catheter is stuck in the vessel wall and its removal is not possible if more invasive interventions are not performed. MATERIAL AND METHODS: We performed a retrospective study from 2003 to 2011 of patients who were clearing a CVC and the factors that could have intervened in the removal impossibility. We compared the type of catheter, the insertion site, the time between its insertion and removal, the primary diagnosis and the treatment. In addition, a monitoring by clinical and imaging tests has been made in patients with retained CVCs. RESULTS: An amount of 174 interventions were carried out. In 5 cases the CVC could not been removed. These 5 cases were patients diagnosed with ALL B and were treated with identical chemotherapy treatment. In addition, at the time of its retirement, all the patients had the CVC for a period longer than 2 years -29 to 84 months-. In patients with retained fragments, no complication arose from this condition. The mean follow-up period was 36 months -maximum 48 months-. CONCLUSIONS: The potential complications arising from the presence of the retained CVCs fragments include infection, venous thrombosis and catheter migration. Based on our results, we propose that a conservative management might be considered as an option in these patients.

LDL from obese patients with the metabolic syndrome show increased lipid peroxidation and activate platelets.

AIMS/HYPOTHESIS: This study assessed oxidative stress in LDL from obese patients with the metabolic syndrome and compared it with that in LDL from type 2 diabetic patients or control volunteers. It also determined the effect on platelets of LDL from the three groups. METHODS: The profiles of lipids, fatty acids and fatty acid oxidation products were determined in LDL isolated from plasma of patients with the metabolic syndrome, patients with type 2 diabetes and volunteers (n = 10 per group). The effects of LDL from the participant groups on the platelet arachidonic acid signalling cascade and aggregation were investigated. RESULTS: Compared with LDL from control volunteers, LDL from obese metabolic syndrome and type 2 diabetic patients had lower cholesteryl ester, higher triacylglycerol and lower ethanolamine plasmalogen levels. Proportions of linoleic acid were decreased in phosphatidylcholine and cholesteryl esters in LDL from both patient groups. Among the markers of lipid peroxidation, oxidation products of linoleic acid (hydroxy-octadecadienoic acids) and malondialdehyde were increased by 59% and twofold, respectively in LDL from metabolic syndrome and type 2 diabetic patients. LDL from metabolic syndrome and type 2 diabetic patients were equally potent in activating the platelet arachidonic acid signalling cascade through increased phosphorylation of p38 mitogen-activated protein kinase and cytosolic phospholipase A(2), and through increased thromboxane B(2) formation. LDL from patients with the metabolic syndrome and type 2 diabetes potentiated platelet aggregation by threefold and 3.5-fold respectively, whereas control LDL had no activating effects on platelets. CONCLUSIONS/INTERPRETATION: The metabolic syndrome in obese patients, without or with diabetes, is associated with increased oxidative stress in LDL, which triggers platelet activation.

Functional lipidomics of oxidized products from polyunsaturated fatty acids.

Because of their high degree of unsaturation, polyunsaturated fatty acids (PUFA) in mammals, with mainly 18, 20 and 22 carbons, can easily be autooxidized, and converted into many oxidized derivatives and degradation products. This short review reports on some of those relevant to the evaluation of oxidative stress in situ. In addition, the enzyme-dependent oxygenation by both dioxygenases and monooxygenases is briefly reviewed by functional and/or metabolic categories, pointing out the structure variety and the analytical approaches.

A species-specific polymerase chain reaction assay for rapid and sensitive detection of Colletotrichum capsici.

Colletotrichum capsici is an important fungal species that causes anthracnose in many genera of plants causing severe economic losses worldwide. A primer set was designed based on the sequences of the ribosomal internal transcribed spacer (ITS1 and ITS2) regions for use in a conventional PCR assay. The primer set (CcapF/CcapR) amplified a single product of 394 bp with DNA extracted from 20 Mexican isolates of C. capsici. The specificity of primers was confirmed by the absence of amplified product with DNA of four other Colletotrichum species and eleven different fungal genera. This primer set is capable of amplifying only C. capsici from different contaminated tissues or fungal structures, thereby facilitating rapid diagnoses as there is no need to isolate and cultivate the fungus in order to identify it. The sensitivity of detection with this PCR method was 10 pg of genomic DNA from the pathogen. This is the first report of a C. capsici-specific primer set. It allows rapid pathogen detection and provides growers with a powerful tool for a rational selection of fungicides to control anthracnose in different crops and in the post-harvest stage.

Effect of different pharmacologic agents to reverse severe pulmonary hypertension among end-stage heart failure patients.

OBJECTIVE: The goal of this study was to analyze the hemodynamic responses during vasoreactivity tests among candidates for heart transplantation who displayed severe pulmonary hypertension seeking to identify risk markers of nonresponse to the test. MATERIALS AND METHODS: In this observational retrospective study we evaluated demographic, clinical, echocardiographic, and hemodynamic variables. The target hemodynamic goal in the vasoreactivity test was to achieve a transpulmonary gradient (TPG) <12 mm Hg and/or pulmonary vascular resistances (PVR) <2.5 Wood Units (WU). RESULTS: We analyzed medical records from 79 patients. Inotropes (dopamine or dobutamine) were used to treat 33 patients, nonselective vasodilators (nitroglycerin or sodium nitroprusside) were used in 22 patients, and prostacyclin (PC) was used in 24 patients. The study observed a significant decrease in pulmonary pressures, PVR, and TPG, with increased cardiac output (CO) compared with baseline hemodynamics in all groups. No significant differences were observed between agents except for an increase in CO, which was greater in the PC group. Also, 49.4% of patients were considered responders to the vasoreactivity test without significant differences between groups. Risk markers for absence of a response to the vasoreactivity test were a CO <2.5 L/min (odds ratio [OR] = 2.1; confidence interval [CI] 95%, 1.1-3.9; P = .035) and a PVR >6 WU (OR = 3.7; CI 95%, 1.8-7.6; P < .001) in the baseline hemodynamic study. CONCLUSIONS: Inotropes, nonselective vasodilators, and prostacyclin produced effective vasodilator responses in the pulmonary vascular bed during the vasoreactivity test. The presence of a baseline high PVR or a low CO were predictors of nonresponse to the test.

Efficacy of sildenafil as a rescue therapy for patients with severe pulmonary arterial hypertension and given long-term treatment with prostanoids: 2-year experience.

BACKGROUND: Both prostanoids and sildenafil are effective treatments for severe pulmonary arterial hypertension (PAH). The combined use of these drugs to maximize the clinical benefit is an emerging treatment option. This study describes a 2-year experience with adjunct sildenafil as a rescue therapy for patients with severe PAH treated long term with prostanoids and who showed clinical deterioration or onset of heart failure. METHODS: Twenty patients (11 men, 9 women; mean age 42 +/- 11 years) with severe PAH, who showed clinical or functional worsening despite ongoing treatment with prostanoids (8 subcutaneous, 7 intravenous, 5 inhaled), were started on adjunct oral sildenafil. New York Heart Association (NYHA) functional class, 6-minute walking test, signs of right ventricular failure and echocardiography were assessed before and after 1 and 2 years of combined therapy. RESULTS: There was a significant improvement of NYHA functional class and signs of right heart failure after 1- and 2-year follow-up. Patients showed a mean increase in 6-minute walking distance of 79 m and 105 m after 1 and 2 years of adjunct sildenafil, respectively. Two patients died during follow-up. The echocardiographic parameters showed a significant reduction of right ventricular end-diastolic diameter and left ventricular diastolic eccentricity index. No serious side effects related to sildenafil were observed. CONCLUSIONS: Adjunct sildenafil to long-term prostacyclin therapy in patients with severe PAH provided sustained clinical stabilization and an improved clinical situation, exercise capacity and echocardiographic parameters of right ventricular function. The beneficial effects were strong and lasted >24 months.

Chronic cyclosporine-induced nephrotoxiciy in heart transplant patients: long-term benefits of treatment with mycophenolate mofetil and low-dose cyclosporine.

BACKGROUND: Cyclosporine-induced nephropathy is a major limitation in heart transplant patients. Cyclosporine dose reduction may lead to substantial early improvement in renal function. Our aim was to study the long-term benefits of therapy with low doses of cyclosporine plus mycophenolate mofetil in heart transplant patients with drug-induced nephrotoxicity. METHODS: Twenty-five adult heart transplant patients with cyclosporine-related nephrotoxicity (mean posttransplant = 41.7 +/- 25.7 months) were included in the retrospective analysis (22 men, mean age = 58.8 +/- 7.9 years.). Patients were switched from azathioprine to mycophenolate mofetil (1 to 3 g/d), followed by a stepwise reduction in cyclosporine dosage (trough cyclosporine level maintained around 100 ng/mL). Renal function was determined by serial measurements of serum creatinine and glomerular filtration rate at 3-month intervals. RESULTS: With a mean follow-up of 30 +/- 13 months, the baseline creatinine of 2.37 +/- 0.5 mg/dL decreased to 1.59 +/- 0.40 mg/dL (P < .0001). The baseline glomerular filtration rate of 36.77 +/- 10.10 mL/min improved to 54.98 +/- 13.80 mL/min (P < .0001). The cyclosporine level was the unique independent variable associated with renal functional improvement (partial R(2) = 0.4). Within the first 3 months, renal function displayed a rapid improvement after conversion to mycophenolate mofetil (P < .001), reaching a plateau, without further significant improvement over the course of time. CONCLUSIONS: Cyclosporine-induced nephrotoxicity is not a progressive, irreversible disease. Reduction in cyclosporine exposure by addition of mycophenolate mofetil is useful to achieve long-term renal functional improvement, thereby avoiding chronic renal failure. A unique, significant factor associated with this improvement was the reduction in cyclosporine level.

Systolic left atrial failure in elderly women with severe aortic stenosis: mitral and pulmonary vein Doppler analysis by transesophageal echocardiography.

We studied prospectively 35 elder women aged 65-82 years, with isolated severe symptomatic aortic stenosis, referred for aortic valve surgery. We assessed diastolic function by TEE before and after cardiac surgery, although follow-up data were collected in 26 patients. The examination was performed prior to surgery and 6 months after. The control group consisted of 32 patients referred for TEE. In the preoperative study, the velocities and integrals of the waves in the pulmonary vein flow were similar to the people of their same age, except the A-wave of atrial contraction and the integral of the systolic wave, which were significantly smaller (Control A-wave 26.1 +/- 5.1 vs preoperative A-wave 22.6 +/- 5.6, P = 0.009 and control double product A vel xA dur 2,748 +/- 835 vs preoperative 2,273 +/- 968, P = 0.03; systolic integral 14.6 +/- 3.8 vs 11.3 +/- 4, P = 0.0009). Six months after surgery, the PV flow was similar to the control group except for the wave of atrial contraction, which was significantly smaller but tended to normalization (postoperative A-wave 23.3 +/- 5, P = 0.04 vs control, and postoperative double product A vel x A dur 2460 +/- 893, P = 0.21 vs control). Mitral flow parameters did not change in the preoperative and postoperative period. Left ventricular mass index changed from 166 +/- 54 g/m(2) to 105 +/- 39 g/m(2) (P< 0.0001). The results of this study show that in elderly women with symptomatic severe AS, diastolic function does not change, left ventricular mass reduces, with improvement in symptoms, and the left atrium function, considered by pulmonary vein flow, is preoperative depressed and tends to mild recovery in the postoperative period, suggesting systolic LA failure.