Enfermedad mitocondrial y ototoxicidad". Enfermedad mitocondrial sindrómica, mutación G7444A / Mitochondrial disease and ototoxicity

Como parte del programa de “screening” genético para la pérdida de la audición; se realizó el estudio de mutaciones en los genes rRNA 12S y tRNAser (UCN), a partir del DNA mitocondrial, que están asociadas con la pérdida de audición inducida por antibióticos aminoglucósidos (ATB-AG) y de presentación no sindrómica. Se estudiaron 40 pacientes con sorderaneurosensorial, la cual podría haber sido causada posterior al tratamiento con ATB-AG. El sujeto afectado y el control, luego del examen físico completo y extracción de DNA a partir de sangre periférica, se amplificó y estudió segmentos en el gen 12S rRNA y en el gen tRNAser (UCN) por PCR-RFLP. En presencia de una mutación, se analizó el genoma mitocondrial completo en el probando y su familia por línea materna. Estos resultadosse han correlacionado con los valores de la relación dela citocromo oxidasa / citrato sintasa, el cual indica unapobre actividad de la citocromo oxidasa. La clínica en el“pedigree” por línea materna y los estudios moleculares,bioquímicos y morfológicos, podría indicar que se tratade una presentación sindrómica de la mutación 7444G>Aen Córdoba - Argentina.

As part of the "screening" for genetic hearing loss,was performed to study mutations in 12S rRNA and tRNAser(UCN) genes from mitochondrial DNA, which are associatedwith hearing loss induced by antibiotics aminoglycosides(ATB-AG) and non-syndromic presentation. We studied40 patients with sensorineural hearing loss, which could have been caused subsequent to treatment with ATB - AG. The affected individual and control, after a completephysical examination and extraction of DNA fromperipheral blood, was amplified and studied segments inthe 12S rRNA and tRNAser (UCN) genes by PCR-RFLP. In the presence of a mutation, we analyzed the complete mitochondrial genome in the proband and his family from maternal line. These results werecorrelated with the values of the ratio of the cytochromeoxidase / citrate synthase, which indicates a poor activity of cytochrome oxidase. The clinic in the "pedigree" frommaternal line and molecular, biochemical and morphological might indicate that it is a syndromic presentation of the mutation 7444G> A in Córdoba - Argentina.

Anatomical patterns of patent foramen ovale (PFO): do they matter for percutaneous closure?

AIM: The aim of this study was to describe and classify the various anatomical pattern of patent foramen ovale (PFO) with transesophageal echocardiography (TEE) and to relate such classification to the selection of PFO closure devices. METHODS: This study enrolled 216 PFO patients (118 females) mostly with previous cryptogenic stroke or transitory ischemic attack (TIA) who underwent percutaneous closure of PFO with deep sedation under TEE control. Anatomical patterns were classified as follows: simple: PFO characterised by central/superior eccentric shunt or with a valve mechanism (45%); reduse: widely redundant septum primum (22%); ASA: atrial septal aneurysm (11%); EASA: entire atrial septal aneurysm (1.4%); CRIB: cribriform septum primum (9%); tunnel: tunnel between septum primum and secundum >10 mm (11%). Degree of right-to-left shunt, either at basal condition or at Valsalva manoeuvre, was classified as: 1=mild (45%); 2=moderate (42%); 3=severe (13%). Additional right-atrium anatomical features are also described. RESULTS: Procedure was successful in 100% of the cases. At follow-up recurrent TIA occurred in two patients. Residual shunts were present in 4.9% of the patients after Valsalva manoeuvre. Palpitations were reported in 4%. CONCLUSIONS: Closing the PFO choosing the device following strict anatomical criteria based on TEE assessment allowed excellent immediate and late results minimizing residual shunts.

Hiperhomocisteinemia como factor de riesgo trombótico en pacientes con lupus eritematoso sistémico y síndrome antifosfolípido / Hyperhomocysteine like thrombocytic risk factor in patient with systemic lupus erythematous with antiphospholipid syndrome

Objetivos: Determinar la prevalencia de hiperhomocisteinemia (hiperhcy) en pacientes con lupus eritematoso sistémico (LES) con y sin síndrome antifosfolípido (SAF); comparar los niveles de homocisteína (Hcy) entre pacientes con LES (con y sin SAF asociado) y un grupo de controles sanos y determinar la correlación entre hiperhcy y la presencia de anticuerpos antifosfolípidos. Pacientes y métodos: Se estudiaron 44 ptes con LES, portadores o no de SAF. Se los dividió en 2 grupos: 17 con LES y SAF y 27 con LES sin SAF y se compararon con 24 controles sanos. A todos se les realizó interrogatorio, examen físico y pruebas de laboratorio: anticuerpo s anticardiolipinas (aCL), anticoagulante lúpico y Hcy. Se consideró hiperhcy a valores superiores a 9. A los ptes con hiperhcy se los trató con ácido fólico + B6 + B 12 durante un mes. Análisis estadístico: variables cualitativas: Chi cuadrado o Exacta de Fischer y cuantitativas: test T de Student o MannWhitney test. Resultados y conclusiones: Hubo 35 manifestaciones trombóticas en los 44 pacientes. Se encontró Hiperhcy en 27 ptes con LES (61.4%), de los cuales 12 tenían SAF. La diferencia entre los valores de Hcy de los pacientes con o sin SAF no fue significativa (p=0,42). Comparando las concentraciones de Hcy entre pacientes y controles, la diferencia fue muy significativa (p=O,002).También tuvo significación estadística la diferencia entre las concentraciones de Hcy de los pacientes con LES sin SAF vs. controles (p=0,015) y LES con SAF vs. controles (p=0,003). A 33 ptes se les dosó aCL: 20 (60,6%) fueron (+). De estos, 15 (75%) tenían hiperhcy. De los 27 pacientes con LES que tenían hiperhcy, sólo 18 cumplieron con el mes de tratamiento con a.fólico+ B6+ B 12. 16 de 18 (88,8%) normalizaron o disminuyeron la Hcy.

Objectives: to detect the prevalence of hyperhcy in SLE patients with and without antiphospholipid syndrome; to compare the Hcy levels between those patients and healthy controls and to determine the correlation between hyperhcy and antiphospholipid antibodies. Patients and methods: we studied 44 SLE patients: 17 had antiphospholipid syndrome and 27 didn't have it, and we compared them to 24 healthy controls. All of them where checked clinically and with laboratory tests like anticardiolypin antibodies, lupus anticoagulant and Hcy. Hcy > 9 was considered abnormal. Patient who had hyperhcy were treated with folic acid+vitB6+vitBI2 a month along. Statistical analysis: qualitative variables: chi square or Fischer's; quantitative variables: Student's T test or Mann Whitney’s test. Results and conc1utions: there were 35 trombotic manifestations in 44 patients. Hyperhcy was present in 27 SLE patients (61,4%), 12 of them had antiphospholipid syndrome. Hcy concentrations patients vs. controls was statistically different (p=0,002). There was also statistically different the hcy concentration from SLE patients with SAF vs controls (p=O,003) and without SAF vs. controls (p= 0,015). From 33 SLE patients, 20 (33%) were aCL( +). 15(75%) of them had hiperhcy.

Hiperhomocisteinemia como factor de riesgo trombótico en pacientes con lupus eritematoso sistémico y síndrome antifosfolípido / Hyperhomocysteine like thrombocytic risk factor in patient with systemic lupus erythematous with antiphospholipid syndrome

Objetivos: Determinar la prevalencia de hiperhomocisteinemia (hiperhcy) en pacientes con lupus eritematoso sistémico (LES) con y sin síndrome antifosfolípido (SAF); comparar los niveles de homocisteína (Hcy) entre pacientes con LES (con y sin SAF asociado) y un grupo de controles sanos y determinar la correlación entre hiperhcy y la presencia de anticuerpos antifosfolípidos. Pacientes y métodos: Se estudiaron 44 ptes con LES, portadores o no de SAF. Se los dividió en 2 grupos: 17 con LES y SAF y 27 con LES sin SAF y se compararon con 24 controles sanos. A todos se les realizó interrogatorio, examen físico y pruebas de laboratorio: anticuerpo s anticardiolipinas (aCL), anticoagulante lúpico y Hcy. Se consideró hiperhcy a valores superiores a 9. A los ptes con hiperhcy se los trató con ácido fólico + B6 + B 12 durante un mes. Análisis estadístico: variables cualitativas: Chi cuadrado o Exacta de Fischer y cuantitativas: test T de Student o MannWhitney test. Resultados y conclusiones: Hubo 35 manifestaciones trombóticas en los 44 pacientes. Se encontró Hiperhcy en 27 ptes con LES (61.4%), de los cuales 12 tenían SAF. La diferencia entre los valores de Hcy de los pacientes con o sin SAF no fue significativa (p=0,42). Comparando las concentraciones de Hcy entre pacientes y controles, la diferencia fue muy significativa (p=O,002).También tuvo significación estadística la diferencia entre las concentraciones de Hcy de los pacientes con LES sin SAF vs. controles (p=0,015) y LES con SAF vs. controles (p=0,003). A 33 ptes se les dosó aCL: 20 (60,6%) fueron (+). De estos, 15 (75%) tenían hiperhcy. De los 27 pacientes con LES que tenían hiperhcy, sólo 18 cumplieron con el mes de tratamiento con a.fólico+ B6+ B 12. 16 de 18 (88,8%) normalizaron o disminuyeron la Hcy.(AU)

Objectives: to detect the prevalence of hyperhcy in SLE patients with and without antiphospholipid syndrome; to compare the Hcy levels between those patients and healthy controls and to determine the correlation between hyperhcy and antiphospholipid antibodies. Patients and methods: we studied 44 SLE patients: 17 had antiphospholipid syndrome and 27 didnt have it, and we compared them to 24 healthy controls. All of them where checked clinically and with laboratory tests like anticardiolypin antibodies, lupus anticoagulant and Hcy. Hcy > 9 was considered abnormal. Patient who had hyperhcy were treated with folic acid+vitB6+vitBI2 a month along. Statistical analysis: qualitative variables: chi square or Fischers; quantitative variables: Students T test or Mann Whitneyãs test. Results and conc1utions: there were 35 trombotic manifestations in 44 patients. Hyperhcy was present in 27 SLE patients (61,4%), 12 of them had antiphospholipid syndrome. Hcy concentrations patients vs. controls was statistically different (p=0,002). There was also statistically different the hcy concentration from SLE patients with SAF vs controls (p=O,003) and without SAF vs. controls (p= 0,015). From 33 SLE patients, 20 (33%) were aCL( +). 15(75%) of them had hiperhcy.(AU)

Contrast enhanced imaging of left internal mammary artery after vasodilation improves the evaluation of the bypass graft.

AIM: The aim of the study is to evaluate patency and flow reserve by echocardiography in arterial grafts using the left internal mammary artery (LIMA) to the left anterior descending coronary artery (DA). The main limitations in performing this study routinely are the weakness of the Doppler signal and the exact chest localization of the graft. The purposes of the study were: to verify the feasibility of the echo color Doppler method on LIMA; to verify which between the parasternal or supralavicular view is the better approach to obtain a clear signal; to verify the increase of systolic and diastolic flow velocity of LIMA in basal conditions and after infusion of dipyridamole, and if the visualization of the Doppler signal improves after contrast infusion. METHODS: Twenty patients (all males, mean age 63+/-7.8 years) with previous coronary artery bypass in the last 10 years, and without any significant stenosis in the left mammary artery graft as proved by a recent coronary angiogram (within 6 months), were selected for our study. LIMA was evaluated by two echocardiographic approaches. Patients were studied at rest and after pharmacological infusion of dipyridamole using the protocol of 0.56 mg/kg in 4 minutes. Contrast enhancement was infused in order to improve the Doppler signal using Levovist contrast agent at rest and after vasodilatation. Diastolic and systolic peak flow velocities, their ratio and the diastolic and total velocity time integrals were evaluated. RESULTS: The results showed that using the supraclavicular approach we obtained the visualization of the graft at rest in all patients (100%) and using the parasternal approach in 19 out of 20 (95%) even without contrast injection. At rest, the diastolic and systolic peak flow velocities were 0.417+/-0.133 m/s and 0.368+/-0.1291 m/s; their ratio (diastolic/systolic) was 0.882+/-0.7362. The overall and diastolic velocity time integrals were 0.1571+/-0.0645 m and 0.2232+/- 0.0701 m. After dipyridamole infusion we observed in all patients an increase in diastolic and systolic peak flow velocities as expected by 0.582+/-0.342 m/s (p<0.005) and 0.73+/-0.427 m/s (p<0.005). Contrast injection at rest and after peak dipyridamole infusion showed a better and clearer Doppler signal of the graft allowing an easier evaluation of the velocity curves in all patients. In fact using the association dipyridamole-Levovist the velocity ratio and the total and diastolic velocity time integral values were 1.268+/-0.368 (p<0.05), 0.3492+/-0.131 m (p<0.05) and 0.2309+/-0.153 m (p<0.05). CONCLUSION: In conclusion, this new echo-color-Doppler approach seems to be valid for the evaluation of the patency rate and flow reserve of the internal mammary artery graft, and helps to better select patients who really need angiography.

Transoesophageal echocardiography in patients without arterial and major cardiac sources of embolism: difference between stroke subtypes.

We studied the records of 175 consecutive patients referred to our neurologic ward between January 1994 and February 2000 with a diagnosis of ischaemic cerebrovascular disease (ICVD) (stroke or transient ischaemic attack - TIA) who underwent transoesophageal echocardiography (TEE). We excluded patients with large vessel disease, high-risk embolic cardiopathies and other rare causes of stroke. According to clinical and neuroimaging findings, patients were divided into two groups. The lacunar (LAC) group (69/175 (39.4%)) and the nonlacunar (N-LAC) one (106/175 (60.6%)). The control population consisted of 78 consecutive patients, referred to the echocardiography laboratory for TEE without history of ICVD and known heart disorders. Patent foramen ovale (PFO) frequency was significantly higher in case patients than in control subjects (55/175 (31.4%) vs. 13/78 (16.6%); p = 0.02). Among case patients, PFO was more prevalent in the N-LAC group than in the LAC one (43/106 (40.6%) vs. 12/69 (17.4%); p = 0.0005). A large degree of shunt occurred in 53.5% of N-LAC patients and in 16.7% of LAC ones (p = 0.04). Atrial septal aneurysm (ASA) was detected in 12% of case patients and 1.3% of control subjects (p = 0.003) and was more frequent in the N-LAC group than in the LAC one (16 vs. 5.8%; p = 0.05). Mitral prolapse (MP) was present in 6/175 (3.4%) ICVD patients (vs. 1/78 among controls) in most cases associated with myxomatous valve redundancy. Aortic arch atheromas (AA) were detected in 12% of ICVD patients and in 10.2% of controls. The frequency was 9.4% in N-LAC and 15.9 in LAC. No complicated AA (plaque thickness >4 mm, ulcerated atheroma, superimposed thrombus) were detected. After multivariate analysis, PFO (OR = 3.8; 95% CI = 2.7-7.9) and ASA (OR = 8.01; 95% CI = 3.0-16.1) appeared to be independent predictors of ICVD. PFO (OR = 2.24; 95% CI = 1.24-4.92) was also independently associated with N-LAC stroke subtype and its importance was even higher in younger patients. Our study provides further evidence that TEE is a helpful diagnostic tool in stroke patients without arterial and major cardiac sources of embolism. However, its utility differs according to type and localization of the ischaemic lesion being more relevant in patient with N-LAC infarctions.

Mesangial nephropathy in Sjögren's syndrome.

We describe a 36-year-old woman with Primary Sjögren's Syndrome (PSS). Purpura, corneal perforation, metabolic acidosis, decreased glomerular filtration, hypokalemia, hyposthenuria, and polyuria were present. Chronic renal insufficiency and renal tubular acidosis type I were diagnosed. Kidney biopsy revealed mesangial glomerulonephritis, interstitial nephritis, and tubular atrophy. Replacement treatment with saliva, tears, and potassium citrate was started. She was given prednisone and cyclophosphamide. This would be the first description of PSS, mesangial glomerulonephritis, and chronic renal insufficiency.

Soluble HLA class I, HLA class II, and Fas ligand in blood components: a possible key to explain the immunomodulatory effects of allogeneic blood transfusions.

The immunomodulatory effect of allogeneic blood transfusions (ABT) has been known for many years. However, a complete understanding of the effects of ABT on the recipient's immune system has remained elusive. Soluble HLA class I (sHLA-I), HLA class II (sHLA-II), and Fas ligand (sFasL) molecules may play immunoregulatory roles. We determined by double-determinant immunoenzymatic assay (DDIA) sHLA-I, sHLA-II, and sFasL concentrations in different blood components. sHLA-I and sFasL levels in red blood cells (RBCs) stored for up to 30 days and in random-donor platelets are significantly (P <.001) higher than in other blood components and their amount is proportionate to the number of residual donor leukocytes and to the length of storage. Blood components with high sHLA-I and sFasL levels play immunoregulatory roles in vitro as in allogeneic mixed lymphocyte responses (MLR) and antigen-specific cytotoxic T-cell (CTL) activity, and induce apoptosis in Fas-positive cells. These data suggest that soluble molecules in blood components are functional. If these results are paralleled in vivo, they should be taken into account in transfusion practice. Blood components that can cause immunosuppression should be chosen to induce transplantation tolerance, whereas blood components that lack immunosuppressive effects should be preferred to reduce the risk of postoperative complications and cancer recurrence.

In vitro synthesis of prostaglandin E2 by synovial tissue after helium-neon laser radiation in rheumatoid arthritis.

This paper reports the effect of helium-neon laser radiation (power of 5 mW and 632.8 nm wave length) on the synthesis of PGE2 in vitro in synovial tissue of biopsy samples of knee joints in patients with chronic rheumatoid arthritis stages II or III. Twelve patients were studied. Each patient received 15 applications of He-Ne laser. Eleven points for He-Ne laser applications were selected in one of the affected knees. The energy density used was 8 J/cm2 per application point. The He-Ne laser therapy reduced the synthesis of PGE2. The analysis of the data revealed a statistically significant difference between the levels of the synthesis of PGE2 before treatment (17.69 +/- 2.65 ng mg-1 of dry tissue h-1) and after treatment (13.85 +/- 2.73 ng mg-1 of dry tissue h-1), with p < 0.01 comparing mean values. This was also accompanied by relief of pain (91.6%), and a favorable subjective report from the patient. We conclude that PGE2 is a quantifiable parameter that could explain what causes pain relief in patients with rheumatoid arthritis that are treated with He-Ne laser.