Agustín Gómez de la Cámara

The Spanish toxic oil syndrome 20 years after its onset: a multidisciplinary review of scientific knowledge.

In 1981, in Spain, the ingestion of an oil fraudulently sold as olive oil caused an outbreak of a previously unrecorded condition, later known as toxic oil syndrome (TOS), clinically characterized by intense incapacitating myalgias, marked peripheral eosinophilia, and pulmonary infiltrates. Of the 20,000 persons affected, approximately 300 died shortly after the onset of the disease and a larger number developed chronic disease. For more than 15 years, a scientific committee supported by the World Health Organizations Regional Office for Europe and by the Institute of Health Carlos III in Madrid has guided investigation intended to identify the causal agent(s), to assess toxicity and mode of action, to establish the pathogenesis of the disease, and to detect late consequences. This report summarizes advances in research on this front. No late mortality excess has been detected. Among survivors, the prevalence of some chronic conditions (e.g., sclerodermia, neurologic changes) is high. Attempts to reproduce the condition in laboratory animals have been unsuccessful, and no condition similar to TOS has been reported in the scientific literature. Laboratory findings suggest an autoimmune mechanism for TOS, such as high levels of seric soluble interleukin-2 receptor. Epidemiologic studies integrated with chemical analyses of case-related oils have shown that the disease is strongly associated with the consumption of oils containing fatty acid esters of 3-(N-phenylamino)-1,2-propanediol (PAP). These chemicals have also been found in oils synthesized under conditions simulating those hypothesized to have occurred when the toxic oil was produced in 1981. Whether PAP esters are simply markers of toxicity of oils or have the capability to induce the disease remains to be elucidated.

Derivation and validation of a set of 10-year cardiovascular risk predictive functions in Spain: The FRESCO Study

OBJECTIVE To derive and validate a set of functions to predict coronary heart disease (CHD) and stroke, and validate the Framingham-REGICOR function. METHOD Pooled analysis of 11 population-based Spanish cohorts (1992-2005) with 50,408 eligible participants. Baseline smoking, diabetes, systolic blood pressure (SBP), lipid profile, and body mass index were recorded. A ten-year follow-up included re-examinations/telephone contact and cross-linkage with mortality registries. For each sex, two models were fitted for CHD, stroke, and both end-points combined: model A was adjusted for age, smoking, and body mass index and model B for age, smoking, diabetes, SBP, total and HDL cholesterol, and for hypertension treatment by SBP, and age by smoking and by SBP interactions. RESULTS The 9.3-year median follow-up accumulated 2973 cardiovascular events. The C-statistic improved from model A to model B for CHD (0.66 to 0.71 for men; 0.70 to 0.74 for women) and the combined CHD-stroke end-points (0.68 to 0.71; 0.72 to 0.75, respectively), but not for stroke alone. Framingham-REGICOR had similar C-statistics but overestimated CHD risk. CONCLUSIONS The new functions accurately estimate 10-year stroke and CHD risk in the adult population of a typical southern European country. The Framingham-REGICOR function provided similar CHD prediction but overestimated risk.

Can partial nephrectomy preserve renal function and modify survival in comparison with radical nephrectomy

Abstract Objective. To investigate whether radical nephrectomy (RN) and nephron-sparing surgery (NSS) for T1 renal cell carcinoma influence renal function, oncological outcome or survival rate. Material and methods. A retrospective study was performed, including 290 nephrectomies for tumours of a diameter of less than 7 cm; 174 radical nephrectomies were compared to 116 nephron-sparing surgeries. Preoperative and pathological data were compared between the two groups. The glomerular filtration rate was estimated using the abbreviated Modification of Diet and Renal Disease (MDRD4) study equation. The evolution of renal function was analysed from 6 months to 4 years after surgery, and the oncological outcomes were evaluated by means of cancer and non-cancer survival curves. Results. The results showed a major impairment in renal function in the RN group compared to those who underwent NSS (25 vs 7 ml/min/1.73 m2, 6 months after surgery), a difference that was maintained over time. Moreover, patients undergoing RN had a greater chance of developing renal failure. Overall, the survival curves showed a higher mortality rate for the RN group (p = 0.034), although the cancer-specific mortality rate did not show any statistically significant differences (p = 0.079). Conclusions. For stage T1 renal cortical tumours, NSS should, whenever possible, be regarded as the primary therapeutic option, given that it obtains similar oncological outcomes to RN and preserves renal function, which seems to translate into a lower overall mortality rate.

Health Status Measurement in Toxic Oil Syndrome

Toxic Oil Syndrome (TOS) is a previously unreported condition which affected more than 20,000 people in Spain in 1981 and whose natural history is unknown. In 1993-94, a stratified random sample of 1400 survivors was drawn to measure their health status through clinical examination and their self-perception of well-being through the Nottingham Health Profile Questionnaire (NHPQ). Two-thirds of the sample population responded; indirect estimates suggest that selection bias was limited. Clear and intermediate signs of neuropathy were found in one-fifth and one-half of the patients, respectively. One-fourth and one-sixth showed some degree of scleroderma and contractures. All conditions were more frequent in women than in men and in age >50 than in younger ages. Although no concurrent control group was included in the study, prevalences of these conditions are well above expectations and are largely attributable to TOS. NHPQ scores increased with age in both sexes up to age 50, after which they reached a plateau (with values around 48 in men and 62 in women). Scores were associated to the occurrence of peripheral neurological changes, contractures, and scleroderma-like conditions. A multivariate analysis indicated age, sex, and severity of neurological conditions as major determinants of the NHPQ scores. This overall pattern of findings is peculiar to TOS and differs from the typical post-disaster nonspecific syndrome.

Risk of Cause-Specific Death in Individuals With Diabetes: A Competing Risks Analysis.

OBJECTIVE Diabetes is a common cause of shortened life expectancy. We aimed to assess the association between diabetes and cause-specific death. RESEARCH DESIGN AND METHODS We used the pooled analysis of individual data from 12 Spanish population cohorts with 10-year follow-up. Participants had no previous history of cardiovascular diseases and were 35–79 years old. Diabetes status was self-reported or defined as glycemia >125 mg/dL at baseline. Vital status and causes of death were ascertained by medical records review and linkage with the official death registry. The hazard ratios and cumulative mortality function were assessed with two approaches, with and without competing risks: proportional subdistribution hazard (PSH) and cause-specific hazard (CSH), respectively. Multivariate analyses were fitted for cardiovascular, cancer, and noncardiovascular noncancer deaths. RESULTS We included 55,292 individuals (15.6% with diabetes and overall mortality of 9.1%). The adjusted hazard ratios showed that diabetes increased mortality risk: 1) cardiovascular death, CSH = 2.03 (95% CI 1.63–2.52) and PSH = 1.99 (1.60–2.49) in men; and CSH = 2.28 (1.75–2.97) and PSH = 2.23 (1.70–2.91) in women; 2) cancer death, CSH = 1.37 (1.13–1.67) and PSH = 1.35 (1.10–1.65) in men; and CSH = 1.68 (1.29–2.20) and PSH = 1.66 (1.25–2.19) in women; and 3) noncardiovascular noncancer death, CSH = 1.53 (1.23–1.91) and PSH = 1.50 (1.20–1.89) in men; and CSH = 1.89 (1.43–2.48) and PSH = 1.84 (1.39–2.45) in women. In all instances, the cumulative mortality function was significantly higher in individuals with diabetes. CONCLUSIONS Diabetes is associated with premature death from cardiovascular disease, cancer, and noncardiovascular noncancer causes. The use of CSH and PSH provides a comprehensive view of mortality dynamics in a population with diabetes.

Infección crónica por Chlamydia pneumoniae en pacientes con enfermedad coronaria. Relación con el incremento de los valores de fibrinógeno

BACKGROUND: A number of studies have suggested that infection with Chlamydia pneumoniae can play a role in development of atherosclerosis. The goal of this study was to know the prevalence of chronic C. pneumoniae infection, evaluated with IgG antibodies seropositivity, in Spanish patients with coronary disease and its association with inflammatory markers and cardiovascular risk factors. PATIENTS AND METHOD: In 176 patients with coronary disease IgG and IgM antibodies to C. pneumoniae were determined by enzyme immunoassay. In addition, fibrinogen and C-reactive protein values were measured as inflammatory markers. Controls were 55 healthy subjects whose age was not different from patients. Seropositivity for C. pneumoniae was considered when indices of IgG and/or IgM antibodies were higher than mean plus two standard deviations of control values. Three patients with seropositivity for IgM were excluded. RESULTS: In 126 patients and 2 controls a seropositivity against C. pneumoniae was proved (72.8% vs 4.2%; p < 0.001). Cardiovascular risk factors were not different in seropositive and seronegative groups of patients. Prevalence of hyperfibrinogenemia was higher in the former group (38.8% vs 19.1%; p = 0.01). The number of the patients with increased values of C-reactive protein was similar in both groups, although these values could be modified by treatment with statins. In multivariate analysis an association between seropositivity for C. pneumoniae and hyperfibrinogenemia was found (odds ratio [OR] = 2.42; 95% confidence interval, 1.07-5.48; p = 0.03) after adjusting for age, gender, smoking, hypertension, hypercholesterolemia and diabetes. CONCLUSIONS: Chronic infection with C. pneumoniae in patients with coronary disease is very prevalent, and it is associated with increased fibrinogen values.

Homocisteína y progresión de la aterosclerosis de la arteria carótida en pacientes con enfermedad coronaria

Fundamento y objetivo: El grosor intima-media (GIM) de la arteria carotida es un marcador de aterosclerosis generalizada. La evaluacion secuencial del GIM ha permitido conocer los factores implicados en su progresion. Sin embargo, hay pocos estudios que valoren el efecto de la homocisteina en esta progresion. El objetivo de este trabajo ha sido conocer si los valores de homocisteina influyen en la evolucion del GIM carotideo en pacientes con enfermedad coronaria. Pacientes y metodo: Se evaluo el GIM de la arteria carotida comun basalmente y a los 4 anos de seguimiento mediante una ecografia bidimensional en 187 pacientes con enfermedad coronaria (166 varones y 21 mujeres con una edad media [desviacion estandar] de 60 [7] anos); 185 pacientes se trataron con estatinas desde el comienzo del estudio. Resultados: Se comprobo progresion del GIM carotideo en 59 pacientes (31,6%; intervalo de confianza [IC] del 95%, 25,0-38,7%). Los factores de riesgo cardiovascular, los parametros bioquimicos basales y el polimorfismo de la metilentetrahidrofolato reductasa-C677T eran similares en los pacientes con progresion y sin ella, a excepcion de los valores de homocisteina que eran superiores en los primeros (13,3 [5,3] con un IC del 95% de 12,0-14,6 µmol/l frente a 11,1 [3,5] con un IC del 95% de 10,5-11,7 µmol/l; p = 0,001). Los cambios bioquimicos evidenciados al final del estudio no fueron diferentes en los dos grupos. El analisis multivariante demostro que la progresion del GIM se asociaba con los valores basales de homocisteina (odds ratio [OR] = 1,19; IC del 95%, 1,07-1,31; p = 0,0008) con el sexo femenino (OR = 3,50; IC del 95%, 1,17-10,50; p = 0,02), con la hipertension (OR = 2,52; IC del 95%, 1,14-5,59; p = 0,02) y con los valores basales de colesterol unido a las lipoproteinas de alta densidad (OR = 0,94; IC del 95%, 0,90-0,98; p = 0,009). Conclusiones: Las concentraciones de homocisteina se asocian a la progresion de la aterosclerosis carotidea en pacientes con enfermedad coronaria tratados con estatinas.

Epidemiology of the Toxic Oil Syndrome

During the early 1980’s importation of rapeseed oil into Spain for human consumption was illegal, except for the Canary Islands, although denatured rapeseed oil could be legally imported for industrial use. Denaturation of imported food oils with castor oil, methylene blue, or aniline was required by Spanish law and indicated that the oil was intended for industrial use due to undesirable properties of the denaturants.

Efecto de la hiperhomocisteinemia y de la mutación metilentetrahidrofolato reductasa 677C -> T en el riesgo de tromboembolia venosa en adultos jóvenes

Fundamento y objetivo: Conocer si la hiperhomocisteinemia y la mutacion de la metilentetrahidrofolato reductasa (MTHFR) 677C -> T se asocian a la tromboembolia venosa en adultos jovenes espanoles. Pacientes y metodo: Se estudiaron 100 pacientes adultos menores de 50 anos y 177 controles con edad y sexo similar a la de los pacientes. Resultados: Se comprobo la hiperhomocisteinemia en el 21% de los pacientes y en el 3,3% de los controles (p T en el 25 y en el 14,7% de ambos grupos, respectivamente (p = 0,03). La odds ratio (OR) de tromboembolia en los pacientes con hiperhomocisteinemia fue de 7,5 (intervalo de confianza [IC] del 95%, 2,9-19,2; p T fue de 1,9; (IC del 95%, 1,1-3,5; p = 0,03). En un subgrupo de 76 pacientes sin otros factores trombogenicos, la enfermedad tromboembolica persistia asociada a la hiperhomocisteinemia, pero no a la mutacion MTHFR 677C -> T. Conclusiones: La hiperhomocisteinemia, aunque no la mutacion MTHFR 677C -> T, es un factor de riesgo de tromboembolia venosa en adultos jovenes sin otros factores trombogenicos.

Hipertensión pulmonar con el ejercicio en el síndrome del aceite tóxico

Fundamento y objetivo Los pacientes con sindrome del aceite toxico son una poblacion de riesgo de padecer hipertension arterial pulmonar. La elevacion anomala de la presion sistolica pulmonary (PSP) durante el ejercicio podria considerarse un marcador temprano de hipertension pulmonar en poblaciones de riesgo. El objetivo del presente estudio ha sido analizar mediante ecocardiografia la respuesta de la PSP al ejercicio en pacientes con sindrome del aceite toxico. Pacientes y metodo Se estudio a 50 pacientes con sindrome del aceite toxico y a 20 voluntarios sanos con ecocardiograma en reposo y en el maximo ejercicio (cicloergometro semisupino) y se midio la PSP. En los pacientes se determino la capacidad de difusion de monoxido de carbono. Resultados No se observaron diferencias en el valor medio de la PSP en el ejercicio entre los pacientes y los voluntarios sanos. En un 8% de los primeros se observo un valor igual o superior a 80 mmHg, lo que se asocio a hipertension pulmonar leve en reposo, disminucion de la funcion ventricular derecha y trastornos de la difusion pulmonar. Un valor de corte de la PSP en reposo igual o superior a 27 mmHg tuvo una sensibilidad del 100% y una especificidad del 71% para predecir una PSP pico de 80 mmHg o superior. Conclusiones Una minoria de pacientes con sindrome del aceite toxico muestra hipertension pulmonar grave con el ejercicio. Este tipo de respuesta anormal se asocia a otros marcadores de vasculopatia pulmonar. Futuros estudios han de esclarecer la relacion entre estas anomalies y el riesgo de desarrollar ulteriormente hipertension arterial pulmonar.