Analysis of the intronic single nucleotide polymorphism rs#466452 of the nephrin gene in patients with diabetic nephropathy.

We present the analysis of an intronic polymorphism of the nephrin gene and its relationship to the development of diabetic nephropathy in a study of diabetes type 1 and type 2 patients. The frequency of the single nucleotide polymorphism rs#466452 in the nephrin gene was determined in 231 patients and control subjects. The C/T status of the polymorphism was assessed using restriction enzyme digestions and the nephrin transcript from a kidney biopsy was examined. Association between the polymorphism and clinical parameters was evaluated using multivariate correspondence analysis. A bioinformatics analysis of the single nucleotide polymorphism rs#466452 suggested the appearance of a splicing enhancer sequence in intron 24 of the nephrin gene and a modification of proteins that bind to this sequence. However, no change in the splicing of a nephrin transcript from a renal biopsy was found. No association was found between the polymorphism and diabetes or degree of renal damage in diabetes type 1 or 2 patients. The single nucleotide polymorphism rs#466452 of the nephrin gene seems to be neutral in relation to diabetes and the development of diabetic nephropathy, and does not affect the splicing of a nephrin transcript, in spite of a splicing enhancer site.

[Cystatin C and adiponectin in diabetics with and without coronary artery disease]. / Cistatina C y adiponectina en pacientes diabéticos tipo 2 coronarios y no coronarios.

BACKGROUND: Patients with type 2 diabetes have a high incidence of coronary artery disease, which is even higher among those with renal failure. A serum level of cystatin C are used to assess renal function and is a potential cardiovascular risk factor. Adiponectin is an anti-atherogenic factor. AIM: To measure cystatin C and adiponectin in type 2 diabetic patients with and without coronary artery disease. MATERIAL AND METHODS: Nine diabetic patients with coronary artery disease aged 76+/- 10 years, 20 diabetics without coronary artery disease aged 61 +/-5 years and 20 non diabetic subjects aged 57+/-10 years, were studied. RESULTS: Serum levels of cystatin C (mg/L) were 1.5 (range 0.89-219), 0.81 (range 0.71-1.08) and 0.68 mg/L (range 055-0.75) in diabetics with and without coronary artery disease and controls, respectively (p <0.0001). No differences in adiponectin between groups and no association between cystatin C and adiponectin, were observed. No association between both parameters and body mass index orglycosilated hemoglobin Ale was observed. Cystatin C had a positive correlation with serum creatinine (r =0.57 p <0.001). CONCLUSIONS: Diabetics with coronary artery disease have higher levels of cystatin C, that are closely correlated with serum creatinine levels.

Cuantificación del tamaño del infarto del miocardio con cintigrafía SPECT y ecocardiografía / Quantification of the myocardial infarction size by SPECT scintigraphy and echocardiography

Debido a la importancia que posee la cuantificación precisa del tamaño del infarto miocárdico (IM), se estudió la concordancia entre su tamaño determinado mediante cintigrafía miocárdica SPECT utilizando un programa de cuantificación automático independiente del operador y Ecocardiografía bidimensional, en 24 pacientes con antecedentes de IM antiguo (más de 1 mes). Los IM se dividieron en 3 categorías: grandes, medianos y pequeños. Se obtuvo concordancia estadísticamente significativa, aunque de grado moderado, entre ambas técnicas. Concluimos que el método cintigráfico asociado a este programa de cuantificación automático se compara bien a la Ecocardiografía, con la ventaja para el primero de ser operador independiente. Es posible que el grado de concordancia hubiese podido ser incluso mayor, si se hubiese usado en Ecocardiografía análisis con doppler tisular en forma sistemática.

Due to the importance of an accurate quantification of the myocardial infarction size, we studied the agreement between its magnitude as determined by gated SPECT with an automatic quantification program and echocardiography, in 24 patients with history of old MI (more than 1 month). The myocardial infarctions were divided into 3 categories: great, medium and small. Statistically significant agreement was obtained, although of moderate degree, between both techniques. We conclude that the nuclear method associated to this program of automatic quantification is compared well to echocardiography, with the advantage for the first one of being independent operator. It is possible that the agreement degree could have been even better, if systematic analysis with tissue Doppler had been performed during echocardiography.

Analysis of the intronic single nucleotide polymorphism rs#466452 of the nephrin gene in patients with diabetic nephropathy

We present the analysis of an intronic polymorphism of the nephrin gene and its relationship to the development of diabetic nephropathy in a study of diabetes type 1 and type 2 patients. The frequency of the single nucleotide polymorphism rs#466452 in the nephrin gene was determined in 231 patients and control subjects. The C/T status of the polymorphism was assessed using restriction enzyme digestions and the nephrin transcript from a kidney biopsy was examined. Association between the polymorphism and clinical parameters was evaluated using multivaríate correspondence analysis. A bioinformatics analysis of the single nucleotide polymorphism rs#466452 suggested the appearance of a splicing enhancer sequence in intron 24 of the nephrin gene and a modification of proteins that bind to this sequence. However, no change in the splicing of a nephrin transcript from a renal biopsy was found. No association was found between the polymorphism and diabetes or degree of renal damage in diabetes type 1 or 2 patients. The single nucleotide polymorphism rs#466452 of the nephrin gene seems to be neutral in relation to diabetes and the development of diabetic nephropathy, and does not affect the splicing of a nephrin transcript, in spite of a splicing enhancer site.

[Porphyria and pregnancy. Review of 17 women]. / Porfiria y embarazo.

BACKGROUND: Hormonal changes, prolonged fasting due to vomiting and some medications used during pregnancy, may cause an acute crisis of porphyria, sometimes unveiling a latent disease. Porphyria may also affect the evolution of pregnancy. AIM: To study the reciprocal influence in the evolution of both pregnancy and porphyria. MATERIAL AND METHODS: Retrospective review of medical records of women with porphyria followed by the authors. If additional information was required, an additional visit to the clinic was scheduled. The characteristics of pregnancy, delivery and the newborn were analyzed. RESULTS: Information about 60 pregnancies in 17 women aged 18 to 43 years was gathered. Among women with acute porphyria, one with coproporphyria had four pregnancies, nine with variegate porphyria had a total of 34 pregnancies and two with acute intermittent porphyria had six pregnancies. Five women with porphyria cutánea had a total of 16 pregnancies. Influence of porphyria in pregnancy: Compared to the general population, no differences were observed in birth weight of newborns, frequency of gestational hypertension, term or preterm deliveries of live newborns, spontaneous abortions nor in tubal pregnancies; there was a high frequency of hyperemesis gravidarum. Influence of pregnancy in porphyria: 5 of the 12 patients with acute porphyria, had an acute porphyria crisis, 3 during the puerperal period and 2 during pregnancy (42% of women, 11% of pregnancies). All these crisis were associated to the administration of medications. All patients survived. Two of these women had six ulterior pregnancies without complications. CONCLUSIONS: Women with porphyria that become pregnant have a higher frequency of hyperemesis gravidarum. Crises among women with acute porphyrias, were always associated with the use of potentially dangerous medications.

Porfiria y embarazo / Porphyria and pregnancy. Review of 17 women

Hormonal changes, prolonged fasting due to vomiting and some medications used during pregnancy, may cause an acute crisis of porphyria, sometimes unveiling a latent disease. Porphyria may also affect the evolution of pregnancy. Aim: To study the reciprocal influence in the evolution of both pregnancy and porphyria. Material and methods: Retrospective review of medical records of women with porphyria followed by the authors. If additional information was required, an additional visit to the clinic was scheduled. The characteristics of pregnancy, delivery and the newborn were analyzed. Results: Information about 60 pregnancies in 17 women aged 18 to 43 years was gathered. Among women with acute porphyria, one with coproporphyria had four pregnancies, nine with variegate porphyria had a total of 34 pregnancies and two with acute intermittent porphyria had six pregnancies. Five women with porphyria cutánea had a total of 16 pregnancies. Influence of porphyria in pregnancy: Compared to the general population, no differences were observed in birth weight of newborns, frequency of gestational hypertension, term or preterm deliveries of live newbornss, spontaneous abortions nor in tubal pregnancies; there was a high frequency of hyperemesis gravidarum. Influence of pregnancy in porphyria: 5 of the 12 patients with acute porphyria, had an acute porphyria crisis, 3 during the puerperal period and 2 during pregnancy (42 percent of women, 11 percent of pregnancies). All these crisis were associated to the administration of medications. All patients survived. Two of these women had six ulterior pregnancies without complications. Conclusions: Women with porphyria that become pregnant have a higher frequency of hyperemesis gravidarum. Crises among women with acute porphyrias, were always associated with the use of potentially dangerous medications.

Tratamiento con insulina aspártica bifásica en pacientes con diabetes en mal control metabólico: Experiencia clínica programada / Biphasic insulin aspart for the management of diabetic patients with unsatisfactory metabolic control

Background: Biophasic insulin aspart (InAsBi) is a mixture of 30 percent of rapid acting soluble aspart insulin and 70 percent aspart insulin retarded with protamine. The soluble portion reduces postprandial serum glucose rises and the retarded portion reduces basal glucose levels. Aim: To assess the efficacy of biphasic insulin aspart in diabetics with a bad metabolic control. Material and methods: Multicentríc study that included diabetic patients with a glycosilated hemoglobin over 7 percent that were transferred to treatment with InAsBi, given in one to three daily doses, according to glycemic control and followed for 12 weeks. At the end of follow up, glycosilated hemoglobin levels (HbA1c) were measured again. Results: One hundred ninety six patients were enrolled and 154, age 59± 12 (84 females), completed the follow up. HbA 1 c levels decreased in at íeast 1 percent in 96 and increased in eight cases. In the total group HbA1c decreased from 10.1± 1.7 to 8.4±1.4 percent (p <0.01). Those with higher initial values and with oral therapy, had the greatest reductions. At the end of the observation period, 29 patients received one daily dose of InAsBi, 114 two doses and 11 three doses. Two patients had allergy, one systemic and one in the injection site. Conclusions: In this group of diabetic patients with a bad metabolic control, the use of InAsBi was associated with a significant reduction of glycosilated hemoglobin levels.

[Biphasic insulin aspart for the management of diabetic patients with unsatisfactory metabolic control]. / Tratamiento con insulina aspártica bifásica en pacientes con diabetes en mal control metabólico: experiencia clínica programada.

BACKGROUND: Biophasic insulin aspart (InAsBi) is a mixture of 30% of rapid acting soluble aspart insulin and 70% aspart insulin retarded with protamine. The soluble portion reduces postprandial serum glucose rises and the retarded portion reduces basal glucose levels. AIM: To assess the efficacy of biphasic insulin aspart in diabetics with a bad metabolic control. MATERIAL AND METHODS: Multicentríc study that included diabetic patients with a glycosilated hemoglobin over 7% that were transferred to treatment with InAsBi, given in one to three daily doses, according to glycemic control and followed for 12 weeks. At the end of follow up, glycosilated hemoglobin levels (HbA1c) were measured again. RESULTS: One hundred ninety six patients were enrolled and 154, age 59+/- 12 (84 females), completed the follow up. HbA 1 c levels decreased in at least 1% in 96 and increased in eight cases. In the total group HbA1c decreased from 10.1+/- 1.7 to 8.4+/-1.4% (p <0.01). Those with higher initial values and with oral therapy, had the greatest reductions. At the end of the observation period, 29 patients received one daily dose of InAsBi, 114 two doses and 11 three doses. Two patients had allergy, one systemic and one in the injection site. CONCLUSIONS: In this group of diabetic patients with a bad metabolic control, the use of InAsBi was associated with a significant reduction of glycosilated hemoglobin levels.

[Mutations of hemochromatosis gene in volunteer blood donors and Chilean porphyria cutanea tarda patients]. / Mutaciones del gen de la hemocromatosis en donantes de sangre voluntarios y en pacientes con porfiria cutánea tarda en Chile.

In patients with porphyria cutanea tarda (PCT), hepatic iron accumulation associated to hereditary hemochromatosis (HH) could play a role in the etiology and in the clinical expression of the disease. The H63D and C282Y mutations of the HFE gene frequency were studied in a PCT group of patients and compared with the frequency observed in a group of volunteer blood donors. PCT patients were cataloged as hereditary or acquired PCT carriers, whether or not they presented uroporphyrinogen decarboxilase gene mutations. Fifty percent of PCT patients were carriers of the disease's genetic type. Such percentage is significantly higher than what other authors have previously informed. H63D and C282Y mutations were present in 23% and 2.4% of the volunteer blood donors, respectively. Similar frequencies were informed by others authors in Chilean white ethnic populations, and also in Spaniard and Argentinean populations, but significantly higher than that observed in Chile's Araucanean aboriginal population. Probably the frequency of H63D and C283Y mutations are related to the Spaniard ascendancy dominance of Chile's white ethnic population. The frequency of HFE gene mutations in PCT patients was not different than what was observed in volunteer blood donors. Similarly, there was no statistical difference in the frequency of these mutations among patients with acquired or genetic PCT disease. With the obtained results, it is not possible postulate an association between PCT and the hereditary hemochromatosis of HFE gene mutations carrier conditions.

[Identification of mutations in the protoporphyrin oxidase gene and its diagnostic implications in porphyria variegata in Chile]. / Porfiria variegata en chile: identificación de mutaciones en el gen protoporfirinógeno oxidasa y su implicancia diagnóstica.

Variegate porphyria (VP) results from a hereditary deficiency of protoporphyrinogen oxidase (PPOX) that is transmitted in an autosomal dominan fashion. The diagnosis is based on the clinical symptoms and is confirmed biochemically. Sometimes, however, these diagnostic tools reveal limitations in establishing the definitive diagnosis of the prevailing type of acute porphyria. In these patients, molecular genetic analyses can be useful. We performed molecular genetic studies in 13 Chilean families by PCR amplification of the PPOX gene, conformation sensitive gel electrophoresis, and automated DNA sequencing. In five symptomatic patients from different families, respectively, the biochemical data confirmed the diagnosis of VP. In seven other families, however, the biochemical studies were not conclusive. Furthermore, the original biochemical analysis in one clinically severely affected patient from a further family even suggested the diagnosis of erythropoietic protoporphyria (EPP). Beside the respective index patients, we studied 78 asymptomatic family members and 50 healthy, unrelated individuals for control purposes. In five families, the previous diagnosis of VP could be confirmed genetically. Further, half of the asymptomatic relatives revealed a mutation in the PPOX gene, consisting of three missense mutations and two deletion mutations. Mutation R168H that had been already described previously in German VP families was found in a Chilean family of German origin. Further, two novel missense mutations, designated L74P and G232S, could be detected. In four Chilean families, we found the deletion 1330deICT that had also been previously described in three Swedish VP families. The second deletion, 1239delTACAC, has not been described anywhere else but Chile and could be identified in seven families. One patient who was initially diagnosed with EPP turned out to be a compound heterozygote for mutations on both alleles of the PPOX gene. In conclusion, our molecular genetic analyses unequivocally confirmed the diagnosis of VP in seven families who originally had revealed inconclusive biochemical data. Further, early genetic analysis allows for the identification of asymptomatic mutation carriers, thereby offering the possibility of adequate counselling and the prevention of potentially life-threatening acute porphyric attacks.

Porfiria variegata en Chile: identificación de mutaciones en el gen protoporfirinógeno oxidasa y su implicancia diagnóstica / Identification of mutations in the protoporphyrin oxidase gene and its diagnostic implications in porphyria variegata in Chile

Variegate porphyria (VP) results from a hereditary deficiency of protoporphyrinogen oxidase (PPOX) that is transmitted in an autosomal dominan fashion. The diagnosis is based on the clinical symptoms and is confirmed biochemically. Sometimes, however, these diagnostic tools reveal limitations in establishing the definitive diagnosis of the prevailing type of acute porphyria. In these patients, molecular genetic analyses can be useful. We performed molecular genetic studies in 13 Chilean families by PCR amplification of the PPOX gene, conformation sensitive gel electrophoresis, and automated DNA sequencing. In five symptomatic patients from different families, respectively, the biochemical data confirmed the diagnosis of VP. In seven other families, however, the biochemical studies were not conclusive. Furthermore, the original biochemical analysis in one clinically severely affected patient from a further family even suggested the diagnosis of erythropoietic protoporphyria (EPP). Beside the respective index patients, we studied 78 asymptomatic family members and 50 healthy, unrelated individuals for control purposes. In five families, the previous diagnosis of VP could be confirmed genetically. Further, half of the asymptomatic relatives revealed a mutation in the PPOX gene, consisting of three missense mutations and two deletion mutations. Mutation R168H that had been already described previously in German VP families was found in a Chilean family of German origin. Further, two novel missense mutations, designated L74P and G232S, could be detected. In four Chilean families, we found the deletion 1330deICT that had also been previously described in three Swedish VP families. The second deletion, 1239delTACAC, has not been described anywhere else but Chile and could be identified in seven families. One patient who was initially diagnosed with EPP turned out to be a compound heterozygote for mutations on both alíeles of the PPOX gene. In conclusion, our molecular genetic analyses unequivocally confirmed the diagnosis of VP in seven families who originally had revealed inconclusive biochemical data. Further, early genetic analysis allows for the identification of asymptomatic mutation carriers, thereby offering the possibility of adequate counselling and the prevention of potentially life-threatening acute porphyric attacks.

La porfiria variegata (PV), enfermedad de origen genético con forma de herencia autosómica dominante, se debe a deficiencia en la actividad protoporfirinógeno oxidasa (PPOX). Su diagnóstico se basa en antecedentes clínicos y se confirma con análisis bioquímicos. Éstos, en algunos casos, pueden presentar limitaciones para establecer el diagnóstico definitivo de la variedad de porfiria aguda, situación en que el estudio genético molecular puede resultar útil. Se efectuó estudio genético en trece familias chilenas usando amplificación del gen PPOX por PCR, electroforesis conformacional y secuenciación automática de DNA. Cinco de estas familias incluían pacientes índices sintomáticos con diagnóstico bioquímico establecido de PV; otras siete familias incluían pacientes índices con estudio bioquímico no concluyente de la variedad de porfiria aguda y, finalmente, una familia con diagnóstico previo de protoporfiria eritropoyética (PPE). Además, se estudiaron 78 familiares asintomáticos y 50 personas sanas, no relacionadas, como controles. En cinco familias el estudio genético confirmó el diagnóstico bioquímico previo de PV. El 50% de los familiares asintomáticos resultaron ser portadores de una mutación en el gen PPOX. Se identificaron tres mutaciones por sustitución de bases: la R168H, descrita en familias de origen alemán y dos nuevas mutaciones, designadas L74P y G232S. También se identificaron dos mutaciones por deleción de bases designadas 1330delCT y la 1239delTACAC. La primera, que había sido descrita previamente en tres familias suecas, se encontró en cuatro familias chilenas. La segunda se encontró en siete familias y no ha sido descrita previamente. El estudio genético permitió mostrar que un paciente que originalmente fue diagnosticado con PPE correspondía a un heterocigoto compuesto para dos mutaciones en el gen PPOX. En conclusión, los estudios moleculares permitieron confirmar el diagnóstico de PV en cinco familias, efectuar diagnóstico de PV en familias en las cuales los datos bioquímicos no eran concluyentes, corregir el diagnóstico original en una familia e identificar portadores asintomáticos entre los familiares de los pacientes índices. Los estudios genéticos moleculares ayudan a realizar un adecuado consejo genético a pacientes y familiares y hace posible practicar prevención de las crisis agudas de porfiria, las que son potencialmente mortales.

Clinical study of hereditary disorders of connective tissues in a Chilean population: joint hypermobility syndrome and vascular Ehlers-Danlos syndrome.

OBJECTIVE: To demonstrate the high frequency and lack of diagnosis of joint hypermobility syndrome (JHS) and the seriousness of vascular Ehlers-Danlos syndrome (VEDS). METHODS: Two hundred forty-nine Chilean patients with hereditary disorders of the connective tissues (CTDs) and 64 control subjects were evaluated for the diagnoses of JHS and VEDS using the validated Brighton criteria, as compared with the traditional Beighton score. In addition, the presence of blue sclera was determined, with the degree of intensity graded as mild, moderate, or marked. RESULTS: The frequency of hereditary CTDs was 35%, with diagnoses of JHS in 92.4% of subjects, VEDS in 7.2%, and osteogenesis imperfecta in 0.4%. The Beighton score proved to be insufficient for the diagnosis of JHS (35% of subjects had a negative score), whereas the Brighton criteria yielded positive findings (a diagnosis of JHS) in 39% of control subjects. Blue sclera was frequent, being identified in 97% of JHS patients and 94% of VEDS patients. Moderate osteopenia/osteoporosis was observed in 50% of patients with VEDS and 26% of those with JHS. Dysautonomia, dyslipidemia, and scoliosis were more frequent in VEDS patients than in JHS patients. The typical JHS facial appearance and the "hand holding the head sign" were identified. Raynaud's phenomenon was extremely rare in JHS patients (2%). Ruptured uterus and cerebral aneurysm occurred in 12% and 6% of VEDS patients, respectively. Spontaneous pneumothorax was more frequent in VEDS patients (11%) than in JHS patients (0.9%). CONCLUSION: JHS is very frequent but usually undiagnosed. The Beighton score is an insufficient method for JHS diagnosis. We recommend that physicians learn to recognize the typical facial features of JHS and be able to identify blue sclera. We also propose that validated hypermobility criteria be routinely used. Further research is needed to determine why the prevalence of JHS is so high in Chile.

Congenital erythropoietic porphyria in an African hedgehog (Atelerix albiventris).

A 6-mo-old, male African hedgehog (Atelerix albiventris) presented with a history of pink urine and demonstrating pink-colored teeth and mild hepatomegaly on examination. Urinalysis revealed no physical, chemical, or cellular abnormalities other than a pink color and fluorescence under ultraviolet light (UV). Also under UV, intense fluorescence of teeth, feet, and spines was noted. Porphyria was suspected. Spectrophotometric evaluation of urine showed extremely elevated levels of copro- and uroporphyrins. Analysis of the urine by thin-layer chromatography showed an abnormal pattern of excreted porphyrin intermediates. Urine high-performance thin-layer chromatography showed that excreted porphyrins were 90-95% of the type-I isomeric form, suggestive of congenital erythropoietic porphyria.

[Tc 99M DMSA scintigraphy in children with a first episode of acute pyelonephritis: correlation with laboratory tests, echography and the presence of vesico-ureteral reflux]. / Cintigrama renal DMSA en niños con primera pielonefritis aguda: correlación con exámenes de laboratorio, ecografía y la presencia de reflujo vésico ureteral.

BACKGROUND: Tc99m DMSA (dimercaptosuccinic acid) scintigraphy has a high sensitivity for the detection of cortical kidney damage. AIM: To evaluate the Tc99m DMSA renal scintigraphy in children with a first episode of acute pyelonephritis and its association with laboratory parameters, kidney ultrasound and vesicoureteral reflux. PATIENTS AND METHODS: We studied 143 children (age range 8 days, 12 years, 66% female) hospitalized with the clinical diagnosis of acute pyelonephritis (first episode) with a positive urine culture and a renal scintigraphy performed within seven days of diagnosis. DMSA was considered the gold standard for the detection of cortical lesions. Its results were related to the presence of fever, C-reactive protein (CRP), erythrocyte sedimentation rate (VHS), white blood count (WBC), ultrasound examination and vesicoureteral reflux. RESULTS: Seventy nine percent of the population had an abnormal DMSA scan. There were no differences between sex, age and laboratory parameters in children with normal or abnormal DMSA scans, except for CRP (p <0.005). Ultrasound was coincident with the scan in 32% of patients. Eighteen percent had vesicoureteral reflux. CONCLUSIONS: There is a high proportion of abnormal DMSA scans in children with a first episode of acute pyelonephritis.

The molecular basis of porphyria cutanea tarda in Chile: identification and functional characterization of mutations in the uroporphyrinogen decarboxylase gene.

The porphyrias are heterogeneous disorders arising from predominantly inherited catalytic deficiencies of specific enzymes in heme biosynthesis. Porphyria cutanea tarda (PCT) results from a decreased activity of uroporphyrinogen decarboxylase, the fifth enzyme in heme biosynthesis. The disorder represents the only porphyria that is not exclusively inherited monogenetically. In PCT, at least two different types can be distinguished: acquired/sporadic (type I) PCT, in which the enzymatic deficiency is limited to the liver and inherited/familial (type II) PCT, which is inherited as an autosomal dominant trait with a decrease of enzymatic activity in all tissues. In an effort to characterize the molecular basis of PCT in Chile, we identified eight mutations in 18 previously unclassified PCT families by polymerase chain reaction, heteroduplex analysis, and automated sequencing. To study the role of these mutations in disease causality, in vitro expression of all novel missense mutations was studied. Our results indicate that the frequency of familial PCT in Chile is approximately 50%, thus, to our knowledge, representing the highest incidence of familial PCT reported to date. The data further emphasize the molecular heterogeneity in type II PCT and demonstrate the advantages of molecular genetic techniques as a diagnostic tool and in the detection of clinically asymptomatic mutation carriers.

Reproducibilidad de la ventriculografía radioisotópica gatillada (VRG) en el cálculo de la fracción de eyección del ventrículo izquierdo (FE): comparación entre pacientes con infarto extenso de miocardio y un grupo control / Reproducibility of radionuclide gated ventriculography in measure the left ventricle ejection fraction: comparisson between patients with large myocardial infarction and a control group

La ventriculografía radioisotópica gatillada permite estudiar la contractilidad global y segmentaria del ventrículo izquierdo, calculando de manera confiable y sencilla la FE. La reproducibilidad intra e inter observador de este cálculo depende de múltiples factores, como el grupo clínico estudiado, parámetros de adquisición del examen, gammacámara y software empleado, y operador. El objetivo de este trabajo fue evaluar la reproducibilidad en el cálculo de la FE en un grupo de pacientes con infarto miocárdico extenso y en un grupo control, utilizando dos gammacámaras diferentes. Pacientes y Método. Se realizó VRG a 13 pacientes con infarto miocárdico extenso antiguo y 12 controles jóvenes normales, utilizando secuencialmente gammacámaras Picker 37/15 y SMV XLi DST, con idénticos parámetros de adquisición en ambos estudios. Los pacientes fueron sometidos a una sola inyección de 925 MBq (25 mCi) de GR-Tc99m ev marcados in vitro. Se efectuaron 10 mediciones de FE por individuo, calculándose el coeficiente de variación de estos valores para cada grupo clínico en ambos equipos, comparándose entre sí. Se efectuó además estudio de correlación y análisis de Bland-Altman de los valores de FE obtenidos. Resultados. Los pacientes con infarto miocárdico tuvieron un coeficiente de variación más alto que los controles (3.5 por ciento vs 2.3 por ciento en Picker, 3.5 por ciento vs 2.1 por ciento en SMV DST XLi). La variabilidad en las mediciones de la FE fue casi idéntica en ambos equipos. La gammacámara Picker obtuvo valores de FE levemente mayores que el equipo SMV, especialmente en los pacientes infartados. Sin embargo, se encontró una alta correlación entre las mediciones de ambas máquinas (r:0.97). Conclusión. La reproducibilidad de ambas gammacámaras es casi idéntica, muy alta, y significativamente mayor en los individuos controles que en el grupo infartado

SPECT gatillado Tl-201 stress-redistribución-reinyección en pacientes con infarto miocárdico antiguo: relación entre existencia de isquemia residual y volúmenes ventriculares, tamaño del infarto y captación pulmonar de Tl-201 / Gated SPECT Tl-201 stress-redistribution-reinjecion in patients with old myocardial infarction: relation between residual ischemia and ventricular volumes, infarction size and lung capture of Tl-201

El SPECT de perfusión miocárdica gatillado proporciona una serie de datos cuantitativos de utilidad en el diagnóstico, estratificación y pronóstico de pacientes coronarios. El objetivo de este trabajo es correlacionar entre sí algunos de estos parámetros cuantitativos y evaluar su relación con la existencia de isquemia residual en pacientes con infarto miocárdico antiguo. Pacientes y Método. Se revisaron 49 SPECT Tl-201 gatillados stress-redistribución-reinyección realizados a pacientes con infarto de miocardio antiguo en los cuales se deseaba evaluar isquemia residual, obteniendo en las imágenes de stress y de reinyección los siguientes parámetros: fracción de eyección del ventrículo izquierdo (FE), volumen de eyección (VE) y de fin de diástole (VFD). Además se calculó la captación pulmonar de Tl-201 en stress (P/M) y la superficie miocárdica residual no infartada (SMR) en el bullïs eye de reinyección (miocardio con perfusión > -2.5 DS de la base de datos). Estos parámetros fueron correlacionados entre sí, calculándose además con algunos de ellos el siguiente índice de "preservación miocárdica" (IPM): IPM = VE (ml) x SMR (por ciento) x 10 VFD (ml) x P/M (por ciento). Los valores representados en la ecuación fueron calculados usando las imágenes de reinyección, excepto la captación pulmonar. Los estudios fueron clasificados en con y sin isquemia residual peri-infarto de acuerdo a los informes originales, comparando los parámetros cuantitativos obtenidos entre ambos grupos de pacientes. Resultados. Se encontró correlación significativa entre los datos cuantitativos evaluados. Sólo la SMR mostró una discreta asociación con la existencia de isquemia post infarto, con mayor frecuencia de reversibilidad en pacientes con SMR = 50 por ciento (p:0.025). Por otro lado, los pacientes con isquemia tuvieron valores de IPM significativamente mayores (p<0.05) que aquellos sin isquemia (mediana:5.98, rango:0.63-8.16 vs mediana:2.24, rango:0.83-6.63, respectivamente).
El mejor punto de corte del IPM para separar pacientes con y sin isquemia fue 3.2, permitiendo distinguir dos grupos con distinta probabilidad de presentar isquemia (p:0.008), con valor predictivo positivo de 87.5 por ciento (sensibilidad: 63.6 por ciento , especificidad: 81.3 por ciento). Conclusión. 1)Existe correlación entre volúmenes ventriculares, FE, SMR y P/M 2) Sólo el IPM mostró una clara relación con la existencia de reversibilidad en los defectos de perfusión

[Acute Liver Failure in patient with liver amyloidosis associated to multiple myeloma]. / Insuficiencia hepática aguda en amiloidosis hepática asociada a mieloma múltiple. Caso clínico.

We report a 67 years old woman admitted to the hospital for the study of a cholestatic jaundice and massive hepatomegaly. On admission, the patient did not have liver failure. During hospital stay, the patient experienced a progressive deterioration of liver function and a monoclonal gammopathy was detected. An IgG Kappa myeloma-was diagnosed. A fine needle liver biopsy disclosed the presence of amyloid. The patient developed acute liver failure and died three weeks after admission.