Una década del Registro de Artroplastias de Cataluña (RACat): exhaustividad, variabilidad y supervivencia de las prótesis entre 2005 y 2014 / A decade of the Catalonian Arthroplasty Register (RACat): variability, exhaustivity, and survival of prostheses between 2005 and 2014

Antecedentes y objetivo. El Registro de Artroplastias de Cataluña (RACat) es un registro poblacional basado en el sistema sanitario público para analizar y evaluar artroplastias de cadera y rodilla en Cataluña. El objetivo de este estudio es presentar los resultados tras 10 años de funcionamiento (de enero de 2005 a diciembre de 2014). Metodología. A partir de la información del RACat y del conjunto mínimo básico de datos al alta hospitalaria, se analizó la calidad y exhaustividad de los datos y se realizaron análisis descriptivos de pacientes, prótesis y proceso asistencial. Además, se analizó la supervivencia calculando la incidencia acumulada de revisión (según causa de intervención en artroplastias de cadera y preservación o sacrificio del ligamento cruzado posterior en artroplastia de rodilla) y la asociación entre riesgo de revisión y técnica de fijación de las prótesis como modelos de riesgos competitivos ajustados por sexo, edad y comorbilidad. Resultados. El principal motivo de intervención en artroplastias primarias de cadera y rodilla fue la artrosis. La incidencia acumulada de revisión a los 10 años fue del 3,9% en artroplastias de cadera causadas por artrosis y del 2,3% en las causadas por fractura. Las artroplastias de rodilla que conservan el ligamento cruzado posterior son el 4,4% y las que no lo conservan, el 5,1%. Discusión. El RACat se consolida como herramienta para la evaluación de las artroplastias con gran potencial en el análisis de la efectividad a medio y largo plazo, el estudio de la variabilidad de la práctica clínica y la vigilancia poscomercialización (AU)

Background and aim. The Catalonian Arthroplasty Register (RACat) is a public health-based population register used to analyse and evaluate hip and knee replacements in Catalonia. The aim of this study is to present the outcomes after 10 years in operation (January 2005-December 2014). Methodology. Using the information from the RACat and the minimum basic data set at hospital discharge, an analysis was made of the quality and exhaustivity of the data, as well as a descriptive analysis of the patients, prostheses, and care process. Survival was also analysed by calculating the accumulated incidence of revisions (according to the cause of intervention in hip replacements and conservation or sacrifice of the posterior cruciate ligament in knee replacement). The relationship between revision risk and the fixation technique of the prosthesis is also analysed, using competitive risk models adjusted for gender, age, and comorbidities. Results. The main reason for the primary hip and knee replacement surgery was arthrosis. The accumulated incidence of revisions at 10 years was 3.9% in hip replacements caused by arthrosis, and 2.3% in those caused by fracture. Conservation of the posterior cruciate ligament was achieved in 4.4% of knee replacements, with sacrifice in 5.1%. Discussion. The RACat is consolidated as a tool for the evaluation of joint replacements, with great potential in the analysis of medium and long-term efficacy, the study of the variability in clinical practice, and post-marketing surveillance (AU)

A decade of the Catalonian Arthroplasty Register (RACat): Variability, exhaustivity, and survival of prostheses between 2005 and 2014. / Una década del Registro de Artroplastias de Cataluña (RACat): exhaustividad, variabilidad y supervivencia de las prótesis entre 2005 y 2014.

BACKGROUND AND AIM: The Catalonian Arthroplasty Register (RACat) is a public health-based population register used to analyse and evaluate hip and knee replacements in Catalonia. The aim of this study is to present the outcomes after 10 years in operation (January 2005-December 2014). METHODOLOGY: Using the information from the RACat and the minimum basic data set at hospital discharge, an analysis was made of the quality and exhaustivity of the data, as well as a descriptive analysis of the patients, prostheses, and care process. Survival was also analysed by calculating the accumulated incidence of revisions (according to the cause of intervention in hip replacements and conservation or sacrifice of the posterior cruciate ligament in knee replacement). The relationship between revision risk and the fixation technique of the prosthesis is also analysed, using competitive risk models adjusted for gender, age, and comorbidities. RESULTS: The main reason for the primary hip and knee replacement surgery was arthrosis. The accumulated incidence of revisions at 10 years was 3.9% in hip replacements caused by arthrosis, and 2.3% in those caused by fracture. Conservation of the posterior cruciate ligament was achieved in 4.4% of knee replacements, with sacrifice in 5.1%. DISCUSSION: The RACat is consolidated as a tool for the evaluation of joint replacements, with great potential in the analysis of medium and long-term efficacy, the study of the variability in clinical practice, and post-marketing surveillance.

Utilización de osteoinductores en niños y adolescentes / Use of bone inductors in children and adolescents

Objetivo: Revisar los resultados de Osigraft® (BMP-7) en el tratamiento de diferentes enfermedades en niños y adolescentes. Pacientes y metodología: Analizamos a 25 pacientes con enfermedades muy diversas que hemos agrupado en 4 categorías: 12 casos de afección del raquis, 4 infecciones, 4 malformaciones congénitas y 5 seudoartrosis. Resultados: No hemos documentado alteraciones por crecimiento anormal o deformidades angulares porque Osigraft® (BMP-7) se aplica lejos del cartílago de crecimiento. Tampoco hemos observado fiebre, reacciones cutáneas ni complicaciones infecciosas después del uso de Osigraft® (BMP-7). Conclusiones: Osigraft® (BMP-7) puede tener un valor coadyuvante para conseguir la regeneración ósea en pacientes seleccionados (AU)

Objective: To review the results of Osigraft® (BMP-7) in the treatment of distinct diseases in children and adolescents. Patients and methodology: We analyzed 25 patients with highly diverse entities grouped into 4 categories: 12 cases of spinal disease, four infections, four congenital malformations and five cases of pseudarthrosis. Results: We found no alterations due to abnormal growth or angular deformities because Osigraft® (BMP-7) was applied far from growth cartilage. No fevers, cutaneous reactions or infectious complications were observed after the use of Osigraft® (BMP-7). Conclusion: Osigraft® (BMP-7) can be useful as a coadjuvant therapy to help achieve bone regeneration in selected patients (AU)

COMT Val158Met polymorphism in relation to activation and de-activation in the prefrontal cortex: A study in patients with schizophrenia and healthy subjects.

The Val158Met polymorphism in the COMT gene has been found to be associated with differences in brain activation in both healthy subjects and patients with schizophrenia. The predominant finding has been increased prefrontal activation associated with the Val allele; however, genotype-related de-activations have not been studied. In this study 42 schizophrenia patients and 31 controls underwent fMRI while performing the n-back task. Brain differences related to presence/absence of disease and presence/absence of the Val/Val genotype were examined. Both disease and Val/Val genotype were associated with failure of de-activation in a cluster centred in the medial prefrontal cortex. There was no interaction between disease and genotype at this location, but clusters where there were significant interactions emerged in the right prefrontal cortex and left temporal/parietal cortex. These findings suggest that Val158Met polymorphism influences task-related de-activations in the default mode network in both healthy subjects and schizophrenia patients to an equivalent extent. However the Val158Met polymorphism also has disease-specific effects on DLPFC activation in schizophrenia.

Medial prefrontal cortex pathology in schizophrenia as revealed by convergent findings from multimodal imaging.

Neuroimaging studies have found evidence of altered brain structure and function in schizophrenia, but have had complex findings regarding the localization of abnormality. We applied multimodal imaging (voxel-based morphometry (VBM), functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) combined with tractography) to 32 chronic schizophrenic patients and matched healthy controls. At a conservative threshold of P=0.01 corrected, structural and functional imaging revealed overlapping regions of abnormality in the medial frontal cortex. DTI found that white matter abnormality predominated in the anterior corpus callosum, and analysis of the anatomical connectivity of representative seed regions again implicated fibres projecting to the medial frontal cortex. There was also evidence of convergent abnormality in the dorsolateral prefrontal cortex, although here the laterality was less consistent across techniques. The medial frontal region identified by these three imaging techniques corresponds to the anterior midline node of the default mode network, a brain system which is believed to support internally directed thought, a state of watchfulness, and/or the maintenance of one's sense of self, and which is of considerable current interest in neuropsychiatric disorders.

Dinámica renal: comparación entre el renogramadiurético y la resonancia magnética / Renal dynamics: Comparison between diuretic renogram and magnetic resonance imaging

Introducción. El objetivo del trabajo es comparar los datos obtenidos en el estudio funcional renal realizado mediante la resonancia magnética con gadolinio y carga diurética (RM-Gd-D) respecto a los parámetros obtenidos en el renograma diurético (RD) clásico (función renal diferencial –FRD– y curva renográfica – CR–).Material y Método. Fueron estudiados 10 pacientes de ambos sexos,6 hombres y 4 mujeres, entre 1 mes y 6 años de edad. A todos los pacientes se les practicó una RM-Gd-D y un RD. En ambos casos se empleó lafurosemida como sobrecarga. Las patologías observadas fueron síndrome de la unión pieloureteral, vaso polar, válvula de uréter, uréter ectópico, sistema doble, displasia renal, ectasia renal, riñón pélvico y riñón en herradura. Fue comparado el porcentaje de captación de gadolinioversus la FRD, y la curva de la RM versus la CR. Para describir el patrón de las curvas de RM-Gd-D fue adaptado un patrón similar al descrito por O’Reilly para la CR. En 5 casos fue necesario el tratamiento quirúrgico y en 3 se adoptó una conducta expectante. En los pacientes intervenidos, la sospecha diagnóstica fue confirmada en la cirugía y en el estudio patológico. El Chi-2 fue utilizado para el análisis estadístico. Resultados. Se encontró un 80% de concordancia (..) (AU)

Objective. This study aimed to establish a comparison between the data obtained in the renal functional study through magnetic resonance using gadolinium with diuretic (furosemide) charge (MR-Gd/F), on the one hand, and the parameters obtained with the classical diuretic renogram (DR) (differential renal function –DRF– and renographiccurve –RC–), on the other hand. Material and Method. 10 patients were studied, 6 male and 4female, aged between 1 month and 6 year-old. All the patients were submitted to a MR-Gd/F and a DR. In both cases, furosemide was used as overload. The pathologies observed included syndrome of the pyeloureteral junction, polar vessel, ureter valve, ectopic ureter, duplexkidney, renal dysplasia, renal ectasy, pelvic kidney and horseshoe kidney. The percentage of gadolinium uptake was compared versus the DRF, and the MR curve was compared versus the RC. Surgical treatment was required in 5 cases and an expectancy behaviour was taken in 3 cases. Among the operated patients, the diagnosis accurry was confirmed by the surgery and the pathological study. Results. A 80% consistency was found between the gadolinium uptake and the DRF. There was a 90% correlation between the MRGd/F curve and the RC. In two cases, the MR-Gd/F required to modify the surgical criterion –previously based on the DR- and an expectancy behaviour was taken. In 90% of the operated cases, the diagnostic assumption obtained through the MR-Gd/F coincided with the surgical and pathological findings, whereas there was a coincidence in just 60%of the cases studied through the DR (p>0,0008).Conclusions. The MR offers a real time study: anatomical, vascular and functional. Good correlation between DR and MR with respectto: (% DRF,%Gd MR and diuretic curve). The MR demonstrates greater precision in diagnosis. The MR allows recognition of non obstructive polar vessels that can then be conservatively managed (AU)

Creatine transporter deficiency in two adult patients with static encephalopathy.

Creatine transporter deficiency is a recently identified X-linked inborn error of metabolism. The natural course of the disease is not well delineated since clinical data from adult patients have scarcely been reported. A progressive course of the disease has been noted in a few described cases. We report the first two Spanish adult patients with creatine transporter deficiency and compare their clinical phenotype and the evolution of the disease with those of other published cases. The two brothers were identified in a study of a cohort of 610 mentally handicapped male patients. The disease was detected by biochemical studies and confirmed by DNA studies. The most significant clinical features were mental retardation, epilepsy and autistic behaviour, and these symptoms did not worsen, in contrast to other reports. They did not present gastrointestinal problems or movement disorders. Creatine transporter deficiency could be an underdiagnosed metabolic disorder and should be considered in adult patients with mental retardation. Clinical presentation of this disorder showed marked differences among adult patients and the course of the disease was static in our cases. Detection of additional adult patients might allow better understanding of the phenotypic outcome at a later age.

[Renal dynamics: comparison between diuretic renogram and magnetic resonance imaging]. / Dimámica renal: comparación entre el renograma diurético y la resonancia magnética.

OBJECTIVE: This study aimed to establish a comparison between the data obtained in the renal functional study through magnetic resonance using gadolinium with diuretic (furosemide) charge (MR-Gd/F), on the one hand, and the parameters obtained with the classical diuretic renogram (DR) (differential renal function -DRF- and renographic curve -RC-), on the other hand. MATERIAL AND METHOD: 10 patients were studied, 6 male and 4 female, aged between 1 month and 6 year-old. All the patients were submitted to a MR-Gd/F and a DR. In both cases, furosemide was used as overload. The pathologies observed included syndrome of the pyeloureteral junction, polar vessel, ureter valve, ectopic ureter, duplex kidney, renal dysplasia, renal ectasy, pelvic kidney and horseshoe kidney. The percentage of gadolinium uptake was compared versus the DRF, and the MR curve was compared versus the RC. Surgical treatment was required in 5 cases and an expectancy behaviour was taken in 3 cases. Among the operated patients, the diagnosis accurry was confirmed by the surgery and the pathological study. RESULTS: A 80% consistency was found between the gadolinium uptake and the DRF. There was a 90% correlation between the MR-Gd/F curve and the RC. In two cases, the MR-Gd/F required to modify the surgical criterion -previously based on the DR- and an expectancy behaviour was taken. In 90% of the operated cases, the diagnostic assumption obtained through the MR-Gd/F coincided with the surgical and pathological findings, whereas there was a coincidence in just 60% of the cases studied through the DR (p > 0.0008). CONCLUSIONS: The MR offers a real time study: anatomical, vascular and functional. Good correlation between DR and MR with respect to: (% DRF,%Gd MR and diuretic curve). The MR demonstrates greater precision in diagnosis.The MR allows recognition of non obstructive polar vessels that can then be conservatively managed.

Stage 1B cervical cancer in a pregnant woman at 25 weeks of gestation.

Cervical cancer associated with pregnancy is rare (0.05%), although it is the most frequently diagnosed malignancy in pregnant women. We present the case of a 28-year-old woman at 25 weeks of gestation diagnosed with Stage 1B cervical cancer. Treatment was delayed until fetal maturity, and an elective cesarean section was performed at 33 weeks' gestation, followed by a total hysterectomy preserving the ovaries, and a pelvic lymphadenectomy. A review of the literature on the treatment of cervical cancer during pregnancy relevant to the case described is also presented.

Failure to deactivate in the prefrontal cortex in schizophrenia: dysfunction of the default mode network?

BACKGROUND: Functional imaging studies using working memory tasks have documented both prefrontal cortex (PFC) hypo- and hyperactivation in schizophrenia. However, these studies have often failed to consider the potential role of task-related deactivation. METHOD: Thirty-two patients with chronic schizophrenia and 32 age- and sex-matched normal controls underwent functional magnetic resonance imaging (fMRI) scanning while performing baseline, 1-back and 2-back versions of the n-back task. Linear models were used to obtain maps of activations and deactivations in the groups. RESULTS: The controls showed activation in the expected frontal regions. There were also clusters of deactivation, particularly in the anterior cingulate/ventromedial PFC and the posterior cingulate cortex/precuneus. Compared to the controls, the schizophrenic patients showed reduced activation in the right dorsolateral prefrontal cortex (DLPFC) and other frontal areas. There was also an area in the anterior cingulate/ventromedial PFC where the patients showed apparently greater activation than the controls. This represented a failure of deactivation in the schizophrenic patients. Failure to activate was a function of the patients' impaired performance on the n-back task, whereas the failure to deactivate was less performance dependent. CONCLUSIONS: Patients with schizophrenia show both failure to activate and failure to deactivate during performance of a working memory task. The area of failure of deactivation is in the anterior prefrontal/anterior cingulate cortex and corresponds to one of the two midline components of the 'default mode network' implicated in functions related to maintaining one's sense of self.

Early and late complications among 15 victims exposed to indoor fire and smoke inhalation.

AIM: To evaluate early and late complications among victims exposed to indoor fire and smoke inhalation. METHOD: An observational, descriptive and prospective longitudinal study of 15 victims of smoke inhalation admitted to the intensive care unit. RESULTS: Although without significant burns, 13 of the victims were unconscious, with airway injury, abnormal temperature and hypokalaemia, and underwent mechanical ventilation. Initial carbon monoxide concentration averaged 20.4+/-8.3%, dropping to 3.9+/-3.3% 4h later. On the 1st day, two victims recovered and were transferred, and another two died. Creatine kinase levels (2594+/-2455 U/l) correlated with duration of intensive care. Of the remaining 11 patients, 10 had early pneumonia. Steroid treatment was initiated for four patients receiving prolonged mechanical ventilation, because of persistent fever and dry cough without evidence of infection. CONCLUSIONS: Mortality and systemic involvement were related to burn of the upper airway and contact with combustion products. Initial creatine kinase levels emerged as a prognostic marker of injury severity. Bronchoscopy was useful in grading airway injury and obtaining bronchoalveolar culture. Corticosteroids were effective, after the acute phase, in treating non-infectious pulmonary complications.

A simple view of the brain through a frequency-specific functional connectivity measure.

Here we develop a measure of functional connectivity describing the degree of covariability between a brain region and the rest of the brain. This measure is based on previous formulas for the mutual information (MI) between clusters of regions in the frequency domain. Under the current scenario, the MI can be given as a simple monotonous function of the multiple coherence and it leads to an easy visual representation of connectivity patterns. Computationally efficient formulas, adequate for short time series, are presented and applied to functional magnetic resonance imaging (fMRI) data measured in subjects (N=34) performing a working memory task or being at rest. While resting state coherence in high (0.17-0.25 Hz) and middle (0.08-0.17 Hz) frequency intervals is bilaterally salient in several limbic and temporal areas including the insula, the amygdala, and the primary auditory cortex, low frequencies (<0.08 Hz) have greatest connectivity in frontal structures. Results from the comparison between resting and N-back conditions show enhanced low frequency coherence in many of the areas previously reported in standard fMRI activation studies of working memory, but task related reductions in high frequency connectivity are also found in regions of the default mode network. Finally, potentially confounding effects of head movement and regional volume on MI are identified and addressed.

[Comparison between MRI and the techniques traditionally used in the study of uropathies in children]. / Análisis prospectivo y comparativo entre la resonancia magnética y las exploraciones tradicionales utilizadas en el estudio de las uropatías con afectación funcional del niño.

BACKGROUND: To correlate the anatomical and functional information obtained using MRI in comparison to the techniques traditionally used in the study of uropathies, and to compare their physical and socioeconomic impacts. METHODS: For a period of eleven months we carried out a prospective study of 22 patients of both sexes ranging in age from 1 to 180 months. All suffered from one or another uropathy. Fifty-five percent of the patients were from external consultation while 45% had been diagnosed prenatally. The imaging techniques compared with MRI were as follows: echography, renogram, renal DMSA scan, urography and cystography. For the MRI gadolinium was used, as well as general anesthesia in some cases. RESULTS: There was a significant correlation (r = 0.942 p < 0.01) between MRI and the traditional explorations for the diagnosis of hydronephrosis, horseshoe kidney, kidney duplication, kidney hypoplasia and hypertrophy, multicystic kidney, ureterocele, pyeloureteral stenosis, vesicoureteral stenosis, atrophy of the renal artery, and missing kidney. It was not useful for reflux. Comparing to renal function differential on renogram there was an 86% agreement between the results. The average number of visits was 5.7 and missed workdays 4.1. The cost as a result of MRI was less than that for other explorations (Chi2 = 27,909 p < 0.001). CONCLUSIONS: MRI provides the same information, both morphological and concerning functional quality, as well as vascular, as that obtained through traditional explorations. Irradiation with MRI is nil. At times it requires anesthesia. Its practice reduces costs, visits, missed workdays, and travel time. In the future it could probably be possible to carry out cystography and hydric/diuretic overload testing at the same time, the efficacy will be increased.

Análisis prospectivo y comparativo entre la resonancia magnética y las exploraciones tradicionales utilizadas en el estudio de las uropatías con afectación funcional del niño / Comparison between MRI and the techniques traditionally used in the study of uropathies in children

Objetivo. Correlacionar la información anatómica y funcional obtenida mediante la resonancia magnética (RM) frente a las técnicas que se utilizan tradicionalmente en la estudio de las uropatías, y comparar sus repercusiones físicas y socio-económicas. Material y método. Durante un período de 11 meses fueron estudiados prospectivamente 22 pacientes de ambos sexos y edades comprendidas entre 1 y 180 meses, afectos de diversos tipos de uropatía. 55% de los pacientes procedían de la consulta externa y el 45% tuvieron diagnóstico prenatal. Las técnicas de imagen comparadas con la RM fueron: ecografía, renograma, gammagrafía, urografía y cistografía. Para la RM se utilizó gadolinio y en algunos casos anestesia general. Resultados. Existió una correlación significativa (r= 0,942 p < 0,01) entre la RM y las exploraciones tradiciones para los diagnósticos de hidronefrosis, riñón en herradura, duplicidad renal, hipoplasia e hipertrofia renal, riñón multiquístico, ureterocele, estenosis pieloureteral, estenosis vesicoureteral, atrofia de la arteria renal y ausencia renal. No fue útil para reflujo. Comparando con la función renal diferencial del renograma existió un 86% de concordancia en los resultados. El promedio de número de visitas fue de 5,7 y de ausencias laborales 4,1. El costo motivado por la RM respecto del resto de exploraciones, fue menor (Chi2= 27,909 p < 0,001). Conclusiones. La RM aporta la misma información morfológica y de función cualitativa, que la obtenida con las exploraciones tradicionales, además de la vascular. La irradiación de la RM es nula. En ocasiones precisa anestesia. Su práctica disminuye gastos, visitas, faltas laborales y desplazamientos. En un futuro, si en el curso de la misma se logra realizar la cistografía y la sobrecarga hídrica/diurética se incrementará su eficacia (AU)

Objetivo. Correlacionar la información anatómica y funcional obtenida mediante la resonancia magnética (RM) frente a las técnicas que se utilizan tradicionalmente en la estudio de las uropatías, y comparar sus repercusiones físicas y socio-económicas. Material y método. Durante un período de 11 meses fueron estudiados prospectivamente 22 pacientes de ambos sexos y edades comprendidas entre 1 y 180 meses, afectos de diversos tipos de uropatía. 55% de los pacientes procedían de la consulta externa y el 45% tuvieron diagnóstico prenatal. Las técnicas de imagen comparadas con la RM fueron: ecografía, renograma, gammagrafía, urografía y cistografía. Para la RM se utilizó gadolinio y en algunos casos anestesia general. Resultados. Existió una correlación significativa (r= 0,942 p < 0,01) entre la RM y las exploraciones tradiciones para los diagnósticos de hidronefrosis, riñón en herradura, duplicidad renal, hipoplasia e hipertrofia renal, riñón multiquístico, ureterocele, estenosis pieloureteral, estenosis vesicoureteral, atrofia de la arteria renal y ausencia renal. No fue útil para reflujo. Comparando con la función renal diferencial del renograma existió un 86% de concordancia en los resultados. El promedio de número de visitas fue de 5,7 y de ausencias laborales 4,1. El costo motivado por la RM respecto del resto de exploraciones, fue menor (Chi2= 27,909 p < 0,001). Conclusiones. La RM aporta la misma información morfológica y de función cualitativa, que la obtenida con las exploraciones tradicionales, además de la vascular. La irradiación de la RM es nula. En ocasiones precisa anestesia. Su práctica disminuye gastos, visitas, faltas laborales y desplazamientos. En un futuro, si en el curso de la misma se logra realizar la cistografía y la sobrecarga hídrica/diurética se incrementará su eficacia (AU)

Plasma S-adenosylhomocysteine is a more sensitive indicator of cardiovascular disease than plasma homocysteine.

BACKGROUND: Although plasma total homocysteine has been identified as an independent risk factor for vascular disease in a multitude of studies, there is a considerable overlap in values between patients at risk and control subjects. The difference in values can be used to distinguish statistically between the 2 groups, provided each group is large enough; however, discriminating between individual patients at risk and control subjects is difficult. OBJECTIVE: We investigated whether the precursor of homocysteine, S-adenosylhomocysteine, is a more sensitive indicator of risk. DESIGN: We measured plasma total homocysteine, S-adenosylhomocysteine, S-adenosylmethionine, creatinine, folate, and vitamin B-12 in 30 patients with proven cardiovascular disease and 29 age- and sex-matched control subjects. RESULTS: The homocysteine values (+/-SD) were 12.8 +/- 4.9 (95% CI: 11.0, 14.7) micromol/L for patients and 11.0 +/- 3.2 (9.8, 12.2) micromol/L for control subjects. The S-adenosylhomocysteine values were 40.0 +/- 20.6 (32.3, 47.7) nmol/L for patients and 27.0 +/- 6.7 (24.5, 30.0) nmol/L for control subjects (P = 0.0021). The S-adenosylmethionine values were 121.8 +/- 42.9 (105.8, 137.8) nmol/L for patients and 103.9 +/- 21.8 (95.6, 112.2) nmol/L for control subjects (P = 0.0493). The creatinine values were 110 +/- 27 (97, 120) micromol/L for patients and 97 +/- 9 (80, 100) micromol/L for control subjects (P = 0.0025). Values for folate and vitamin B-12 did not differ significantly between groups. CONCLUSIONS: Plasma S-adenosylhomocysteine appears to be a much more sensitive indicator of the difference between patients with cardiovascular disease and control subjects than is homocysteine. Both plasma total homocysteine and S-adenosylhomocysteine are significantly correlated with plasma creatinine in patients.

Glycine N-methyltransferase deficiency: a novel inborn error causing persistent isolated hypermethioninaemia.

This paper reports clinical and metabolic studies of two Italian siblings with a novel form of persistent isolated hypermethioninaemia, i.e. abnormally elevated plasma methionine that lasted beyond the first months of life and is not due to cystathionine beta-synthase deficiency, tyrosinaemia I or liver disease. Abnormal elevations of their plasma S-adenosylmethionine (AdoMet) concentrations proved they do not have deficient activity of methionine adenosyltransferase I/III. A variety of studies provided evidence that the elevations of methionine and AdoMet are not caused by defects in the methionine transamination pathway, deficient activity of methionine adenosyltransferase II, a mutation in methylenetetrahydrofolate reductase rendering this activity resistant to inhibition by AdoMet, or deficient activity of guanidinoacetate methyltransferase. Plasma sarcosine (N-methylglycine) is elevated, together with elevated plasma AdoMet in normal subjects following oral methionine loads and in association with increased plasma levels of both methionine and AdoMet in cystathionine beta-synthase-deficient individuals. However, plasma sarcosine is not elevated in these siblings. The latter result provides evidence they are deficient in activity of glycine N-methyltransferase (GNMT). The only clinical abnormalities in these siblings are mild hepatomegaly and chronic elevation of serum transaminases not attributable to conventional causes of liver disease. A possible causative connection between GNMT deficiency and these hepatitis-like manifestations is discussed. Further studies are required to evaluate whether dietary methionine restriction will be useful in this situation.