Prevalence of hypertrophic cardiomyopathy in a large sample of the Spanish working population. / Prevalencia de la miocardiopatía hipertrófica en una amplia muestra de la población laboral española.

BACKGROUND AND OBJECTIVES: To date, in Spain, there are no studies that have evaluated the prevalence of hypertrophic cardiomyopathy in the general population. The aim of this study was to assess the prevalence of hypertrophic cardiomyopathy in a large sample of the working population of Spain. MATERIALS AND METHODS: The study included 13,179 workers (73% men; mean age, 40 years) from 5 regions of Spain who, between May 2008 and November 2010, had a medical examination with an electrocardiogram. The workers with suggestive abnormalities in the electrocardiogram or a predisposing medical history (exertional syncope or sudden death of a family member younger than 50 years) were referred for an echocardiographic evaluation. We defined hypertrophic cardiomyopathy as a parietal thickness ≥13mm in any segment of the left ventricle. We estimated the prevalence of hypertrophic cardiomyopathy in the entire sample and in the workers without hypertension. RESULTS: A total of 1008 workers were selected for the echocardiogram, although only 496 (49.2% of those selected) of these attended the appointment. After the echocardiogram, we detected 16 cases of hypertrophic cardiomyopathy, estimating a prevalence of 0.24% for the entire sample. In the subgroup of workers with no hypertension, we observed 10 cases of hypertrophic cardiomyopathy, which corresponds to an estimated prevalence of 0.19%. CONCLUSIONS: In our sample of the working population in Spain, the estimated prevalence of hypertrophic cardiomyopathy was 0.24%. In the subgroup of patients with no hypertension, the estimated prevalence was 0.19%.

Horizontal equity in access to public GP services by socioeconomic group: potential bias due to a compartmentalised approach.

BACKGROUND: Horizontal equity in access to public general practitioner (GP) services by socioeconomic group has been addressed econometrically by testing the statement "equal probability of using public GP services for equal health care needs, regardless of socioeconomic status". Based on survey data, the conventional approach has been to estimate binomial econometric models in which when the respondent reports having visited a public GP, it counts as 1, otherwise it counts as 0. This is what we call a compartmentalised approach. Those respondents who did not visit a public GP but visited instead another doctor (specialist or private GP) would count as 0 (despite having used instead other modes of health care), thus conclusions of the compartmentalised approach might be biased. In such cases, a multinomial econometric model -that we called comprehensive approach- would be more appropriate to analyse horizontal equity in access to public GP services. The objective of this paper is to test for this potential bias by comparing a compartmentalised and a comprehensive approach, when analysing horizontal equity in access to public GP. METHODS: Using data from the 2016/17 Spanish National Health Survey, we estimate the probability of visiting a public GP as determined by socioeconomic status, health care need and demographic characteristics. We use binomial and multinomial logit and probit models in order to highlight the potential differences in the conclusions regarding socioeconomic inequities in access to public GP services. Socioeconomic status is proxied by education level, social class and employment situation. RESULTS: Our results show that conclusions are sensitive to the approach selected. Particularly, the horizontal inequity favouring individuals with lower education that resulted from the compartmentalised approach disappears under a comprehensive approach and only a social class effect remains. CONCLUSION: An analysis of horizontal equity in access to a particular health care service (like public GP services) undertaken following a compartmentalised approach should be compared with a comprehensive approach in order to test that there is no bias as a consequence of considering as zeros the utilisation of other types of health care.

Changes in liver fibrosis in HIV/HCV-coinfected patients following different outcomes with peginterferon plus ribavirin therapy.

There is scarce information about the impact of antiviral treatment on subsequent progression of liver fibrosis in HIV-infected patients with chronic hepatitis C who experience different outcomes following peginterferon-ribavirin therapy. We conducted a retrospective study of a cohort of HIV/HCV-coinfected patients with longitudinal assessment of liver fibrosis using elastometry. Patients were split out into four groups according to the prior peginterferon-ribavirin response: sustained virological response (SVR), relapse (R), partial response (PR) and null response (NR). A group of untreated, coinfected patients was taken as control. Significant liver fibrosis progression (sLFP) was defined as a shift from baseline Metavir estimates ≤ F2 to F3-F4, or by >30% increase in liver stiffness in patients with baseline F3-F4. Conversely, significant liver fibrosis regression (sLFR) was defined as a shift from baseline Metavir estimates F3-F4 to ≤ F2, or by >30% reduction in liver stiffness in patients that kept on F3-F4. A total of 498 HIV/HCV-coinfected patients were examined. They were classified as follows: 138 (27.7%) SVR, 40 (8%) R, 61 (12.2%) PR, 71 (14.3%) NR and 188 (37.8%) naive. After a mean follow-up of 53.3 months, sLFP occurred less frequently in patients with SVR (7.2%) compared with R (25%; P = 0.002), PR (23%; P = 0.002), NR (29.6%; P < 0.001) and naïve (19.7%; P = 0.002). Conversely, sLFR was 26.1% in SVR compared with 10% in R (P = 0.03), 14.8% in PR (P = 0.06), 16.9% in NR (P = 0.07) and 10.6% in naïve (P < 0.001). Sustained clearance of serum HCV-RNA following a course of antiviral treatment is the major determinant of liver fibrosis regression in HIV/HCV-coinfected patients.

Design and baseline characteristics of SALT-HF trial: hypertonic saline therapy in ambulatory heart failure.

AIMS: Hypertonic saline solution (HSS) plus intravenous (IV) loop diuretic appears to enhance the diuretic response in patients hospitalized for heart failure (HF). The efficacy and safety of this therapy in the ambulatory setting have not been evaluated. We aimed to describe the design and baseline characteristics of the SALT-HF trial participants. METHODS AND RESULTS: 'Efficacy of Saline Hypertonic Therapy in Ambulatory Patients with HF' (SALT-HF) trial was a multicenter, double-blinded, and randomized study involving ambulatory patients who experienced worsening heart failure (WHF) without criteria for hospitalization. Enrolled patients had to present at least two signs of volume overload, use ≥ 80 mg of oral furosemide daily, and have elevated natriuretic peptides. Patients were randomized 1:1 to treatment with a 1-h infusion of IV furosemide plus HSS (2.6-3.4% NaCl depending on plasmatic sodium levels) versus a 1-h infusion of IV furosemide at the same dose (125-250 mg, depending on basal loop diuretic dose). Clinical, laboratory, and imaging parameters were collected at baseline and after 7 days, and a telephone visit was planned after 30 days. The primary endpoint was 3-h diuresis after treatment started. Secondary endpoints included (a) 7-day changes in congestion data, (b) 7-day changes in kidney function and electrolytes, (c) 30-day clinical events (need of IV diuretic, HF hospitalization, cardiovascular mortality, all-cause mortality or HF-hospitalization). RESULTS: A total of 167 participants [median age, 81 years; interquartile range (IQR), 73-87, 30.5% females] were randomized across 13 sites between December 2020 and March 2023. Half of the participants (n = 82) had an ejection fraction >50%. Most patients showed a high burden of comorbidities, with a median Charlson index of 3 (IQR: 2-4). Common co-morbidities included diabetes mellitus (41%, n = 69), atrial fibrillation (80%, n = 134), and chronic kidney disease (64%, n = 107). Patients exhibited a poor functional NYHA class (69% presenting NYHA III) and several signs of congestion. The mean composite congestion score was 4.3 (standard deviation: 1.7). Ninety per cent of the patients (n = 151) presented oedema and jugular engorgement, and 71% (n = 118) showed lung B lines assessed by ultrasound. Median inferior vena cava diameter was 23 mm, (IQR: 21-25), and plasmatic levels of N-terminal-pro-B-type natriuretic peptide (NTproBNP) and antigen carbohydrate 125 (CA125) were increased (median NT-proBNP 4969 pg/mL, IQR: 2508-9328; median CA125 46 U/L, IQR: 20-114). CONCLUSIONS: SALT-HF trial randomized 167 ambulatory patients with WHF and will determine whether an infusion of hypertonic saline therapy plus furosemide increases diuresis and improves decongestion compared to equivalent furosemide administration alone.

Plitidepsin as a successful rescue treatment for prolonged viral SARS-CoV-2 replication in a patient with previous anti-CD20 monoclonal antibody-mediated B cell depletion and chronic lymphocytic leukemia.

BACKGROUND: There is an urgent need for highly efficacious antiviral therapies in immunosuppressed hosts who develop coronavirus disease (COVID-19), with special concern for those affected by hematological malignancies. CASE PRESENTATION: Here, we report the case of a 75-year-old male with chronic lymphocytic leukemia who was deficient in CD19+CD20+ B-lymphocyte populations due to previous treatment with anti-CD20 monoclonal antibodies. The patient presented with severe COVID-19 pneumonia due to prolonged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and was treated with two courses of the antiviral plitidepsin on a compassionate use basis. The patient subsequently achieved an undetectable viral load, and his pneumonia resolved. CONCLUSIONS: Treatment with plitidepsin was well-tolerated without any further hematological or cardiovascular toxicities. This case further supports plitidepsin as a potential antiviral drug in SARS-CoV-2 patients affected by immune deficiencies and hematological malignancies.

Reduced levels of anti-MDA LDL antibodies in patients with carbohydrate metabolism disorders.

BACKGROUND: Diabetic patients undergoing percutaneous coronary intervention (PCI) have a worse prognosis than non-diabetic patients. The anti-oxidized LDL antibodies (anti-LDLox ab) have recently been suggested to be protective against the development of diabetes. The aim of this study was to compare the levels of IgG and IgM anti-oxidized LDL antibodies with reference to the new diagnostic criteria for carbohydrate metabolism disorders after an oral glucose tolerance test (OGTT) in hospitalized patients scheduled to undergo percutaneous coronary intervention. METHODS: We undertook a cross-sectional study of 110 patients undergoing PCI. The patients were classified as being normal (oral glucose test tolerance normal, OGTT-N), or having impaired glucose tolerance (IGT) or type 2 diabetes mellitus (T2DM) according to their glucose levels at baseline and after an OGTT. RESULTS: An inverse slope was found in the levels of IgG anti-oxidized LDL antibodies between the OGTT-N patients (optical density (OD) = 0.109) and the patients with IGT (OD = 0.099) or T2DM (OD = 0.084) (p = 0.019). An inverse correlation was also detected between the levels of IgG anti-oxidized LDL antibodies and baseline glycemia (r = -0.23, p = 0.018). CONCLUSIONS: Patients with coronary disease and carbohydrate metabolism disorders have much lower levels of IgG anti-oxidized LDL antibodies than normoglycemic patients.

Prevalence of hypertrophic cardiomyopathy in a large sample of the Spanish working population.

BACKGROUND AND OBJECTIVES: To date, in Spain, there are no studies that have evaluated the prevalence of hypertrophic cardiomyopathy in the general population. The aim of this study was to assess the prevalence of hypertrophic cardiomyopathy in a large sample of the working population of Spain. MATERIALS AND METHODS: The study included 13,179 workers (73% men; mean age: 40 years) from 5 regions of Spain who, between May 2008 and November 2010, had a medical examination with an electrocardiogram. The workers with suggestive abnormalities in the electrocardiogram or a predisposing medical history (exertional syncope or sudden death of a family member younger than 50 years) were referred for an echocardiographic evaluation. We defined hypertrophic cardiomyopathy as a parietal thickness ≥13mm in any segment of the left ventricle. We estimated the prevalence of hypertrophic cardiomyopathy in the entire sample and in the workers without hypertension. RESULTS: A total of 1008 workers were selected for the echocardiogram, although only 496 (49.2% of those selected) of these attended the appointment. After the echocardiogram, we detected 16 cases of hypertrophic cardiomyopathy, estimating a prevalence of 0.24% for the entire sample. In the subgroup of workers with no hypertension, we observed 10 cases of hypertrophic cardiomyopathy, which corresponds to an estimated prevalence of 0.19%. CONCLUSIONS: In our sample of the working population in Spain, the estimated prevalence of hypertrophic cardiomyopathy was 0.24%. In the subgroup of patients with no hypertension, the estimated prevalence was 0.19%.

Current functioning of cardio-oncology units in Spain.

PURPOSE: The aim of the current survey was to describe the functioning of cardio-oncology (C-O) units in Spain. METHODS: All members of the Spanish Society of Cardiology pertaining to scientific communities related to C-O received questionnaires on the existence of specific programs at their institutions. A second, more extensive questionnaire was sent to the centers which reported C-O organization. RESULTS: We identified 56 centers with C-O programs of which 32 (62.5%) replied to the extended questionnaire. 28% of all centers reported having a multidisciplinary unit involving specialists in several areas. More than 80% of the centers developed surveillance protocols locally adapted which included advanced echocardiographic techniques (68%) or troponin (82%). CONCLUSIONS: The number of institutions with C-O programs is still limited but higher than reported in a survey in 2017. Development of multidisciplinary units of C-O should be promoted to improve the cardiovascular health of cancer patients.

Endothelial progenitor cells in cell-based therapy for cardiovascular disease.

Coronary Artery Diseases (CAD) is the first mortality cause in industrialized countries. The possibility of regenerating myocardium injured tissue using the cell therapy is a promising option to regenerate cardiac tissue. Currently, a variety of adult stem/ progenitor cells are undergoing clinical evaluation, but it is very important to study and characterize the bone marrow-derived progenitor/ stem cells, the main source of cells used for human cardiac repair, before their clinical use. Bone marrow-derived endothelial progenitor cells (EPC) home sites of ischemia and differentiate into endothelial cells, increase the neovascularization of ischemic tissue. Moreover recently, it has been observed that EPC can be able to differentiate or transdifferentiate to like-adult cells resident in cardiac tissues. The characterization of phenotype EPC is complex, because express hematopoietic stem cells (CD133 and/or CD34) and endothelial markers such as vascular endothelial growth factor receptor 2 (KDR). Several studies described subpopulation of EPC expressing CD34+D133+KDR+ phenotype in literature, but some other authors suggest other phenotype. The EPC capacity of mobilization or recruitment/ homing to ischemic tissue areas by cytokines are reviewed. Finally are described clinical studies in CAD using bone marrow-derived progenitor cells permitting human cardiac tissue repair.

Medical assistance in dying for cancer patients one year after legalization: a collaborative approach at a comprehensive cancer centre.

Medical assistance in dying (maid) is a new medical service in Canada. Access to maid for patients with advanced cancer can be daunting during periods of declining health near the end of life. In this report, we describe a collaborative approach between the centralized coordination service and a regional cancer centre as an effective strategy for enabling interdisciplinary care delivery and enhancing patient-centred care at the end of the patient's cancer journey.

Applicability of the COPD-LUCSS-DLCO score for patients with chronic obstructive pulmonary disease: Analysis in standard clinical practice conditions. / Aplicabilidad del score COPD-LUCSS-DLCO en pacientes con enfermedad pulmonar obstructiva crónica: análisis en condiciones de práctica clínica habitual.

INTRODUCTION: The COPD-LUCSS-DLCO score had been validated as a predictive tool capable of identifying patients with chronic obstructive pulmonary disease (COPD) and a high mortality risk associated with lung cancer (LC); however, studies have not been conducted yet on its use in standard clinical practice. The aim of this study was to estimate the COPD-LUCSS-DLCO scores for patients with COPD treated in Pulmonology consultations and to determine the incidence of LC in each of the subgroups. MATERIAL AND METHODS: A retrospective observational study was conducted with a cohort of 159 patients with COPD in Pulmonology outpatient follow-up consultations. We calculated the COPD-LUCSS-DLCO score (0-8) for each patient, with low risk considered at 0-3 points and high risk at ≥3.5 points. We calculated the incidence rate of LC in each of the subgroups. RESULTS: Sixty-two percent of the patients had a high-risk score. We estimated an overall LC rate of 30 per 1000 patients with COPD-year (95% CI: 16-53), 44 per 1000 patients with COPD-year (95% CI: 18-76) among those categorised as high risk and 17 per 1000 patients with COPD-year among those categorised as low risk (95% CI: 4-50). CONCLUSIONS: The use of the COPD-LUCSS-DLCO score in standard clinical practice could help detect patients with a greater risk of developing LC, which could help to better manage cases in an LC screening programme.

Prevalence of M. tuberculosis infection and tuberculosis disease among HIV-infected people in Spain.

OBJECTIVE: To study the prevalence of Mycobacterium tuberculosis infection (MTBI) and past/current tuberculosis (TB) among human immunodeficiency virus (HIV) infected persons in Spain. DESIGN: Longitudinal study conducted between 2000 and 2003 at 10 HIV hospital-based clinics. Data were drawn from clinical records. Associations were measured using odds ratios (ORs) and their 95% confidence intervals (95%CI). RESULTS: Of the 1242 persons who met the eligibility criteria, most were male (75%), aged <40 years (75%) and unemployed (40%). HIV infection occurred through intravenous drug use (53%), heterosexual sex (29%) and sex between men (16%). In the initial evaluation, 315 subjects had evidence of MTBI: 84 (6.8%) had a history of TB, 23 (1.8%) current TB and 208 (16.8%) latent tuberculosis infection (LTBI). MTBI was associated with male sex, age 30-49 years, contact with a TB case, homelessness, poor education, and negatively with CD4 <100 cells/mm(3). Among subjects with MTBI, past/current TB was associated with retirement/disability (OR 6, 95%CI 1.6-22.5), CD4 <200 cells/mm(3) (OR 9.7, 95%CI 3.8-24.6), viral load >55,000 copies (OR 5.3, 95%CI 1.4-20.0), and negatively, with skilled work (OR 0.4, 95%CI 0.1-1.0) or administrative/managerial/professional work (OR 0.05, 95%CI 0.01-0.4). CONCLUSION: Social context has an impact on the effectiveness of HIV and TB control programmes even in industrialised countries with free access to health care.

Consensus Document of the Spanish Society of Cardiology and the Spanish Society of Internal Medicine on the diagnosis and treatment of iron deficiency in heart failure. / Documento de consenso de la Sociedad Española de Cardiología y la Sociedad Española de Medicina Interna sobre el diagnóstico y tratamiento del déficit de hierro en la insuficiencia cardíaca.

Iron deficiency in patients with heart failure is a medical problem of recent particular interest. This interest has resulted from the publication of several clinical trials that demonstrated that the administration of intravenous iron to such patients improved their functional capacity and even reduced the number of hospitalisations for heart failure decompensation. However, applying the evidence from these studies in clinical practice is still controversial, both in terms of the diagnostic criteria for iron deficiency (absolute and functional) and the optimal method for iron replenishment. This article is a consensus document that integrates the recommendations of the Spanish Society of Internal Medicine and the Spanish Society of Cardiology. The article reviews the scientific evidence and proposes a diagnostic and therapeutic performance protocol for iron deficiency in heart failure.

Prevalence of comorbidities and the prognostic value of the PROFUND index in a hospital cardiology unit. / Prevalencia de pluripatología y valor pronóstico del índice PROFUND en una unidad de hospitalización de Cardiología.

INTRODUCTION: The aim of this study was to understand the prevalence of comorbidities and the usefulness of the PROFUND index for the prognostic stratification of patients with comorbidities in a hospital cardiology unit. PATIENTS AND METHODS: We consecutively analysed all patients hospitalized in 2012 in the department of cardiology. We recorded the comorbidities, length of stay, hospital mortality, Charlson indices and PROFUND indices. In the patients with comorbidities, we also recorded the readmissions and mortality during a 1-year follow-up. RESULTS: The study included 1,033 patients (mean age, 67±13.1 years; 35% women), 381 (36.9%) of whom had comorbidities, with a mean Charlson index of 6.4±1.7 and a mean PROFUND index of 2.5±2.5. Compared with the other patients, the patients with comorbidities were older (72 vs. 64 years, p<.001), had a higher mortality rate (2.9% vs. 1.1%, p=.046) and longer hospital stays (8±5.5 vs. 6±5.7 days, p<.001) and were more often admitted for heart failure (42.3% vs. 15.8%, p<.001). The PROFUND index was independently associated with overall mortality (hazard ratio [HR], 1.13; 95% CI: 1.01-1.27; p=.034) and with the presence of major adverse events during the 12-month follow-up (HR, 1.09; 95% CI: 1.01-1.18; p=.026). CONCLUSIONS: A high percentage of patients hospitalized in the department of cardiology had comorbidities. These patients had a higher prevalence of cardiovascular risk factors, longer stays and greater hospital mortality. The PROFUND index independently predicted mortality and adverse events during the follow-up.

Validation of the use of exogenous gonadotropins (PG600) to increase the efficiency of gilt development programs without affecting lifetime productivity in the breeding herd.

The objective of this study was to validate the use of exogenous gonadotropin (PG600) treatment for stimulating estrus in noncyclic gilts and to compare lifetime productivity of gilts recorded as having natural (NAT) versus PG600-induced (PG600) first estrus in a commercial setting. Prepubertal Camborough gilts ( = 4,489) were delivered to a gilt development unit (GDU) with the goal of delivering known cyclic breeding-eligible females to the sow farm (SF). A boar exposure area (BEAR) was designed to facilitate stimulation and detection of puberty by providing fence line and direct contact (15 min daily) with mature boars over an intensive 28-d period, starting at approximately d 160 (d 0). At d 14, nonpubertal gilts were mixed in new pen groups. At d 23, noncyclic "opportunity" gilts with no record of vulval development and required to meet breeding targets, were eligible for treatment with PG600 to induce puberty. Overall, 77.6% ( = 3,475) of gilts exhibited standing estrus (NAT = 2,654; PG600 = 821) and were eligible for shipping to the SF at approximately 35 d, and 76.6% of gilts that were administered PG600 exhibited the standing reflex within 13 d of treatment. Ultimately, 72.0% of gilts entering the GDU were delivered to the SF as breeding-eligible females. Considering the gilts delivered, a greater proportion of NAT than PG600 gilts were successfully bred ( < 0.001) and had better farrowing rates to first service, and overall farrowing rates (including gilts that returned to estrus and were rebred) were greater for NAT compared to PG600 gilts ( < 0.001) . Farrowing rates at second and third parity were similar between NAT and PG600 gilts; however, at fourth parity, a greater proportion of NAT gilts farrowed. In comparison, considering only gilts served, there was no difference ( > 0.05) in the proportion of NAT and PG600 gilts farrowing a third litter, but a greater proportion of NAT than PG600 gilts farrowed their fourth litter ( < 0.001). There was no difference between NAT and PG600 gilts for litter size at parity 1 through 4 or total pigs born over 4 parities ( > 0.05). A negative correlation ( < 0.0001) was detected between age at puberty and lifetime growth rate at puberty, and growth rate classification affected age and weight at puberty. However, retention rates and total sow productivity to parity 4 were not affected by growth rate classification at puberty.

Expression of cystathionine beta-synthase and histopathological observations in placentas of patients with Down syndrome.

UNLABELLED: Down syndrome is the most frequent aneuploidy in live births, with an overall frequency of 1/600-700 births. The overexpression of cystathionine ß-synthase is thought to participate in the presentation of some phenotypes observed in Down syndrome. OBJECTIVE: The aim of this study was to compare the expression levels of cystathionine ß-synthase and histopathological observations from placentas of infants with Down syndrome and healthy newborns. MATERIALS AND METHODS: Six placentas of fetuses/infants with Down syndrome and sixteen placentas of healthy fetuses were studied. Cystathionine ß-synthase mRNA and protein expression were performed by real-time PCR and immunohistochemistry, respectively. RESULTS: We observed an increase in cystathionine ß-synthase mRNA expression (p = 0.0465) and protein levels (p = 0.009) in placentas of fetus/infants with Down syndrome compared with controls. Significantly more circinate edges (p = 0.0007) and trophoblast inclusions (p = 0.0037) were observed in the group with Down syndrome compared with control group. CONCLUSION: The results demonstrate overexpression of cystathionine ß-synthase mRNA and protein in placentas of fetuses/infants with trisomy 21. Further histological abnormalities were found in placentas of patients with Down syndrome, suggesting an alteration in the development of placenta.

Incidence and risk factors for developing cytomegalovirus retinitis in HIV-infected patients receiving protease inhibitor therapy. Spanish CMV-AIDS Study Group.

OBJECTIVE: To assess the incidence and risk factors for cytomegalovirus (CMV) retinitis in HIV-infected patients who initiated protease inhibitor-containing antiretroviral therapy. DESIGN AND SETTING: Prospective, multicentre study. PATIENTS: A cohort of 172 HIV-infected patients with a CD4 cell count below 100x10(6) cells/l at the time of protease inhibitor introduction. MAIN OUTCOME MEASURES: Confirmed CMV retinitis and mortality, according to CD4 cell count, HIV load, and CMV viraemia. RESULTS: The cumulative incidence of CMV retinitis was 5% at 1 year and 6% at 2 years. Only a positive CMV polymerase chain reaction (PCR) test at therapy initiation was significantly associated with the development of disease (relative hazard, 4.41; 95% confidence interval, 2.12-8.93; P<0.00001). The 12-month Kaplan-Meier CMV retinitis event rate was 38% in patients who were CMV PCR-positive compared with 2% in those who were CMV PCR-negative (P<0.001). Mean CMV load was significantly higher in those individuals who went on to develop CMV retinitis (3700 versus 384 copies/ml, P = 0.002). Only 2% of patients remained CMV PCR-positive after 3 months of protease inhibitor therapy, and CMV viraemia was not associated with a worse therapy response or shorter survival. Transient CMV positivity without a higher risk of disease was observed in 7% of patients at the first month on therapy. CONCLUSIONS: Protease inhibitor-containing antiretroviral therapy significantly reduces the incidence of CMV viraemia and disease. Although a positive CMV PCR test identifies those patients on therapy at highest risk of CMV retinitis, it is not associated with an increased risk of death or a worse response to protease inhibitor therapy.

Salt-induced increase in arterial pressure during nitric oxide synthesis inhibition.

The objective of this study was to determine in conscious dogs the role of endothelium-derived nitric oxide in mediating the arterial pressure and renal response to a prolonged increment of sodium intake. After a control period of 3 days, an inhibitor of nitric oxide synthesis, NG-nitro-L-arginine-methyl ester, was infused intravenously during 5 consecutive days (0.1 micrograms/kg per minute). Sodium intake (80 mmol/d) did not change throughout the experiment in one group (n = 4). In another group (n = 6), 1 day after infusion of this inhibitor was started, sodium intake increased from 80 to 300 mmol/d during 4 consecutive days. Inhibition of nitric oxide synthesis in dogs with normal sodium intake induced a significant decrease in natriuresis and diuresis (P < .05) without changes in arterial pressure. However, in dogs treated with the nitric oxide synthesis inhibitor, mean arterial pressure increased from 95.2 +/- 3.3 to 106.2 +/- 4.0 mm Hg (P < .01) the first day that sodium intake was elevated and remained increased the following 3 days. In a different group of dogs (n = 5), the increment of sodium intake during 4 days did not induce changes in arterial pressure when nitric oxide synthesis was not inhibited. Cumulative sodium balance was higher (P < .01) in dogs treated simultaneously with the nitric oxide synthesis inhibitor and high sodium intake (158 +/- 21 mmol sodium) than in those treated only with the nitric oxide synthesis inhibitor (82 +/- 19 mmol sodium) or with high sodium intake (36 +/- 13 mmol sodium).(ABSTRACT TRUNCATED AT 250 WORDS)

Renal effects of prolonged synthesis inhibition of endothelium-derived nitric oxide.

The aim of the present study was to investigate in conscious dogs the long-term effects of nitric oxide synthesis inhibition on glomerular filtration rate, sodium and water excretion, and plasma levels of renin and aldosterone. After a control period of 3 days, an inhibitor of endothelium-derived nitric oxide synthesis, NG-nitro-L-arginine-methyl ester, was infused for 3 consecutive days at a dose (50 ng/kg/min) that did not induce significant changes in arterial pressure (n = 6). The inhibition of nitric oxide synthesis led to a large and sustained decrease (p less than 0.05) in glomerular filtration rate of approximately 35%. This change was accompanied by a decrease (p less than 0.05) in urinary sodium excretion from 78.9 +/- 4.6 meq/day to 49.8 +/- 6.8, 60.1 +/- 4.2, and 53.5 +/- 9.0 meq/day by days 1, 2, and 3 of nitric oxide synthesis inhibition, respectively. Changes in fractional sodium excretion failed to achieve statistical significance. Nitric oxide synthesis inhibition also induced a significant and sustained decrease in urine flow rate. The decrease in glomerular filtration rate, natriuresis, and diuresis was accompanied by a 45% increase in plasma renin activity (p less than 0.05) and no change in plasma aldosterone concentration. By day 3 of the recovery period, glomerular filtration rate, natriuresis, diuresis, and plasma renin activity returned to values similar to those found during the control period. The administration of L-arginine during 3 consecutive days (5 micrograms/kg.min i.v.) did not modify any of the parameters measured but effectively prevented all the renal changes induced by the 3 days of nitric oxide synthesis inhibition.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of nitric oxide in mediating renal response to volume expansion.

The objective of the present study was to determine the role of endothelium-derived nitric oxide in mediating the renal response to extracellular volume expansion with isotonic saline (5% body weight). In anesthetized dogs (n = 7) and before volume expansion, nitric oxide synthesis was inhibited in the right kidney by continuous intrarenal infusion of NG-nitro-L-arginine-methyl ester (1 microgram/kg/min). Arterial pressure and renal hemodynamics of both kidneys did not change significantly either during nitric oxide synthesis inhibition or during 5% volume expansion. However, in response to extracellular volume expansion, increases in natriuresis, diuresis, and fractional excretion of lithium (an index of proximal sodium reabsorption) were inhibited in the right kidney by 27%, 28%, and 41%, respectively, when compared with the contralateral kidney. Increases of renal interstitial hydrostatic pressure during 5% volume expansion were not statistically different between both kidneys. In another group of dogs (n = 4), the administration of L-arginine (0.5 mg/kg/min) into the right renal artery prevented the renal effects induced by the nitric oxide synthesis inhibitor during volume expansion. The findings in this study suggest that nitric oxide production plays an important role in regulating the renal response to extracellular volume expansion. The proximal tubule seems to be involved in the reduced renal excretory response to volume expansion during nitric oxide synthesis inhibition.