Cardiac involvement in Lysosomal Storage Diseases.

Lysosomal storage diseases (LSDs) include a heterogeneous group of rare, inborn, metabolic diseases characterized by deficiency of lysosomal enzymes or of other proteins involved in lysosomal function, leading to multi organ system substrates accumulation, with consequent multi systemic clinical presentation. Cardiac disease is particularly important in some group of LSDs as glycogen storage diseases (Pompe), mucopolysaccharidoses and in glycosphingolipidoses (Anderson-Fabry disease and less frequently Gaucher disease). Various cardiac manifestations may be observed including hypertrophic and dilated cardiomyopathy, coronary artery disease and valvular disease. The availability of enzyme replacement therapy (ERT) has changed the natural history of some LSDs such as Pompe disease, thanks to the significant effects on cardiological involvement. In other LSDs such as MPSs or Fabry disease, ERT has been shown to stabilize or slow the progression of heart damage. This imposes the need for a timely diagnosis that allows a rapid onset of ERT.

Alport's syndrome.

Alport's syndrome (AS, OMIM 301050) is a hereditary disorder characterized by progressive renal failure, hearing impairment and ocular changes. It is clinically and genetically heterogeneous and in its natural history, renal disease progresses from microscopic haematuria to proteinuria, and finally to progressive renal insufficiency. AS is caused by an inherited defect in a type IV collagen, a structural material, expressed in many tissues that is essential for the normal function of different parts of the body. In most of cases, about the 85%, Alport's syndrome is X-linked and is originated by mutations in the COL4A5 gene. In the remaining cases, it may be inherited in either an autosomal recessive, or rarely in an autosomal dominant manner. Mostly, the condition is caused by mutations in the COL4A3 or COL4A4 genes. Coexisting mutations in COL4A3, COL4A4, COL4A5 or COL4A6 were found to cause an Alport's syndrome phenotype with digenic inheritance. Diagnosis of the condition is based on family history, clinical signs, and specific procedures such as a kidney biopsy. The diagnosis can be confirmed by genetic testing. Treatment may include use of a hearing aid, hemodialysis, and peritoneal dialysis to treat those with end-stage renal failure, and, as the last step, kidney transplantation. Firstly described by Arthur C. Alport's, in 1927, over the years it has become a pathology of high scientific interest. At the moment, thanks to advances in diagnostic techniques, it is possible to make an early diagnosis avoiding irreversible damages and life -threatening complications.

Renal involvement in paediatric Fabry disease.

Anderson-Fabry Disease (AFD) is a rare, X-linked inborn error of glycosphingolipid catabolism caused by a deficient or absent activity of the lysosomal enzyme, α-galactosidase A, resulting in the progressive multisystem lysosomal accumulation of glycosphingolipids, mainly globotriaosylceramide (Gb3). Among the wide spectrum of clinical signs and symptoms and the life-threatening complications of Fabry disease, renal failure causes significant morbidity and mortality. Various evidence shows that the accumulation of Gb3 in different renal cells is present since the first years of life, many years and usually decades before manifest symptoms and signs of renal involvement. Early renal damage can be demonstrated by clinical signs as microalbuminuria and proteinuria, developing as early as in the second decade of life. A decline in GFR is uncommon at paediatric ages but may be seen as early as adolescence. Renal biopsy is rarely used in paediatric patients with Fabry disease although evidence shows that it may be considered a valid tool for the diagnosis of early and potentially reversible nephropathy, as well as for the evaluation of the effectiveness of enzyme replacement therapy (ERT). Although there is consensus in considering the early initiation of ERT as the only tool able to prevent the progression of nephropathy, the issue on the correct timing for the onset of ERT in pediatric age remains open in the management of this chronic and progressive disease.

Synthetic cyanoacrylic glue in the prevention of post-operative lymphocele after pelvic lymphadenectomy in patients with uterine malignancies: A prospective, single-blind, preliminary study.

OBJECTIVES: Lymphoceles are among the most common post-operative complications of pelvic lymphadenectomy, with a reported incidence of 1% to 29% in gynecology oncology. Several studies evaluated the effectiveness of biological glues on reducing lymphoceles, but no data on gynecological patients are available. We evaluated the effectiveness of cyanoacrylic glues (n-butyl cyanoacrylate) (Glubran 2 - GEM s.r.l., Italy) in preventing lymphocele on 30 patients who underwent pelvic lymphadenectomy for endometrial or cervical cancer. METHODS: Single-blind prospective randomized study. Patients were divided into 2 groups: pelvic lymphadenectomy plus n-butyl cyanoacrylate (treatment group: 44 patients) and pelvic lymphadenectomy without n-butyl cyanoacrylate (control group: 44 patients). Primary endpoint was incidence of pelvic lymphocele in the two groups 30 days after surgery, and evaluated with pelvic ultrasound and RMI examination. Secondary endpoints evaluated drainage volume of lymphorrhea 36, 48, 72 and 96 h after surgery. RESULTS: 15% in the treatment group and 36.6% in the control group had lymphocele 1month after the procedure (p<0.03; RR 0.4 [95% CI 0.152-0.999]). Concerning the secondary outcome in group A the amount of lymphorrhea presented a constant significant decrease during evaluation; on the contrary, in group B, after an initial decrease at 48 h, the amount of lymphorrhea remained unchanged; at all considered times the amount of lymphorrhea resulted significantly greater in controls. CONCLUSION: Intraoperative application of n-butyl cyanoacrylate seems to reduce lymph production after pelvic lymphadenectomy, providing a useful additional treatment option for reducing drainage volume and preventing lymphocele development after pelvic lymphadenectomy.

Quantitative structure-property relationships of potentially bioactive fluoro phospho-silicate glasses.

In this work, the glass transition temperature and chemical durability of bioactive phospho-silicate glasses were experimentally determined and correlated to the structural descriptor Fnet derived from classical molecular dynamics simulations. The replacement of CaF2 for Na2O in the parent glass 45S5 enhances both chemical durability and density, while the replacement of CaF2 for CaO lowers chemical durability. The proposed descriptor, Fnet, provides satisfactorily correlations with glass transition temperature and chemical durability over a wide range of compositions.

Huge primary retroperitoneal mucinous cystadenoma of borderline malignancy mimicking an ovarian mass: case report and review.

BACKGROUND: Primary retroperitoneal mucinous cystadenoma is a rare tumor only 48 cases have been reported in international literature. Patients affected by primary retroperitoneal mucinous cystadenoma/cystadenocarcinoma ranged in age from 17 to 86 years (median, 42.3 years) and the size of the cystis ranged from 5 to 35 cm (median, 16.1 cm). There is no unanimous opinion on the genesis of these tumors and, due to their extreme rarity, its histogenesis, biological behavior and the optimal management strategy remain at a speculative level. CASE REPORT: We report the case of a huge borderline primary retroperitoneal mucinous cystadenoma (24 x 25 cm) in a 35-year-old woman and the strategies adopted for the diagnosis and surgical management. CONCLUSION: Primary mucinous cystic tumor of the retroperitoneum was correctly diagnosed only at the time of surgery. As well as in the majority of cases reported in the literature, preoperative investigations were not able to give information about the tumor site. In spite of the short follow-up (two years), the patient's favorable course supports the hypothesis that primary retroperitoneal mucinous cystadenoma may be treated in the same manner as a primary ovarian tumor of the same grade and comparable stage.

Analisis de pacientes con pancreatitis aguda (PA), decada (1984-1994) comparacion con serie anterior / Analysis of patients with acute pancreatitis (AP), (1984-1994) comparation with serie anterior

Se revisaron las historias clínicas de 190 pacientes internados entre 1984 y 1994 con diagnóstico de pancreatitis aguda. Tuvieron confirmación quirúrgica 141, necrópsica 1 (75 por ciento), y las restantes confirmadas por la evolución clínica y TAC. El sexo femenino 122 (64 por ciento), masculino 68 (36 por ciento), media de edad de 41 años (mínima 7, máxima 82). La etiología fue biliar en 129 (68 por ciento) con 4 fallecidos (3 por ciento), alcohólica en 26 (14 por ciento), con 5 fallecidos (19 por ciento), idiopática en 24 (13 por ciento) y miscelánea 11 (5 por ciento), las dos últimos sin mortalidad. La mortalidad global fue del 5 por ciento (9/190). Se efectuó tratamiento quirúrgico en 141 (74 por ciento) y endoscópico en 2 (1 por ciento), 47 pacientes (25 por ciento) no fueron operados. El grupo PA leve estuvo conformado por 154 pacientes (81 por ciento) con un score de Tanson promedio de 2.2 y sin mortalidad. Se indicó cirugía de urgencia en 7 (6 por ciento), temprana en 3 (3 por ciento), tardía en 1 (0,9 por ciento) u programada en 99 (90 por ciento). En el grupo de PA grave hubo 36 pacientes (19 por ciento) con un score promedio de Ranson de 4.2. Fallecieron 9 (25 por ciento). Se operaron 31 pacientes, de estos 17 (47 por ciento) de urgencia, 1 (3 por ciento) cirurgía temprana y 13 (36 por ciento) tardía. Se compararon las cifras de mortalidad de este grupo, con otra serie del mismo Hospital entre 1975-1984. Comparando los dos series se observó en el grupo 1984-1994: disminución significativa de la mortalidad global 4.7 por ciento vs 12.7 por ciento (p=0.0047); en la mortalidad de la etiologia biliar 3.1 por ciento vs 11.2 por ciento (p=0.0087); sin mortalidad en las etiologías idiopáticas y miscelánea, comparada 18.7 por ciento y 20 por ciento respectivamente de la serie anterior; mortalidad nula de la PA leve comparada con el 5 por ciento de la serie anterior y por último de la PA leve comparada con el 5 por ciento de la serie anterior y por último la mortalidad en la forma grave fue menor 25 por ciento vs 40.8 por ciento. Consideramos como causa de este avance mejor diagnóstico, evaluación temprana de la severidad, medidas de apoyo sistémico en las formas graves, la administración de antibióticos de mayor espectro y penetración en el páncreas y especialmente el cambio en el tiempo de indicación quirúrgica. Mientras que en el primer período se optó por la cirurgía temprana sobre el páncreas, en el segundo se indicó intervención diferida, salvo en casos especiales.

Analisis de pacientes con pancreatitis aguda (PA), decada (1984-1994) comparacion con serie anterior / Analysis of patients with acute pancreatitis (AP), (1984-1994) comparation with serie anterior

Se revisaron las historias clínicas de 190 pacientes internados entre 1984 y 1994 con diagnóstico de pancreatitis aguda. Tuvieron confirmación quirúrgica 141, necrópsica 1 (75 por ciento), y las restantes confirmadas por la evolución clínica y TAC. El sexo femenino 122 (64 por ciento), masculino 68 (36 por ciento), media de edad de 41 años (mínima 7, máxima 82). La etiología fue biliar en 129 (68 por ciento) con 4 fallecidos (3 por ciento), alcohólica en 26 (14 por ciento), con 5 fallecidos (19 por ciento), idiopática en 24 (13 por ciento) y miscelánea 11 (5 por ciento), las dos últimos sin mortalidad. La mortalidad global fue del 5 por ciento (9/190). Se efectuó tratamiento quirúrgico en 141 (74 por ciento) y endoscópico en 2 (1 por ciento), 47 pacientes (25 por ciento) no fueron operados. El grupo PA leve estuvo conformado por 154 pacientes (81 por ciento) con un score de Tanson promedio de 2.2 y sin mortalidad. Se indicó cirugía de urgencia en 7 (6 por ciento), temprana en 3 (3 por ciento), tardía en 1 (0,9 por ciento) u programada en 99 (90 por ciento). En el grupo de PA grave hubo 36 pacientes (19 por ciento) con un score promedio de Ranson de 4.2. Fallecieron 9 (25 por ciento). Se operaron 31 pacientes, de estos 17 (47 por ciento) de urgencia, 1 (3 por ciento) cirurgía temprana y 13 (36 por ciento) tardía. Se compararon las cifras de mortalidad de este grupo, con otra serie del mismo Hospital entre 1975-1984. Comparando los dos series se observó en el grupo 1984-1994: disminución significativa de la mortalidad global 4.7 por ciento vs 12.7 por ciento (p=0.0047); en la mortalidad de la etiologia biliar 3.1 por ciento vs 11.2 por ciento (p=0.0087); sin mortalidad en las etiologías idiopáticas y miscelánea, comparada 18.7 por ciento y 20 por ciento respectivamente de la serie anterior; mortalidad nula de la PA leve comparada con el 5 por ciento de la serie anterior y por último de la PA leve comparada con el 5 por ciento de la serie anterior y por último la mortalidad en la forma grave fue menor 25 por ciento vs 40.8 por ciento. Consideramos como causa de este avance mejor diagnóstico, evaluación temprana de la severidad, medidas de apoyo sistémico en las formas graves, la administración de antibióticos de mayor espectro y penetración en el páncreas y especialmente el cambio en el tiempo de indicación quirúrgica. Mientras que en el primer período se optó por la cirurgía temprana sobre el páncreas, en el segundo se indicó intervención diferida, salvo en casos especiales. (AU)

[Analysis of patients with acute pancreatitis (AP), (1984-1994) decade. Comparison with a past series]. / Análisis de pacientes con pancreatitis aguda (PA), Década (1984-1994). Comparación con serie anterior.

Between 1984-1994 records of 190 patients with acute pancreatitis (AP) were reviewed. Diagnosis was confirmed by surgery in 141, by necropsy 1 (75%), and for the remaining patients, by CT and clinical evaluation. Female 122 were female (64%), male 68 (36%), mean age 41 years (range 7-82 years). The etiologic factors were gallstones in 129 (68%) with 4 deaths (3%), alcoholic in 26 (14%) with 5 (19%) deaths, idiopathic in 24 (13%) and miscellaneous 11 (5%), the last 2 without mortality. The overall mortality was 5% (9/190). Surgical treatment was indicated in 141 (74%) and endoscopic treatment in 2 (1%), 47 patients (25%) received only medical treatment. One-hundred and fifty-four patients (81%) were mild forms with a Ranson mean score 2.2 without mortality. In this group, emergency surgery was indicated in 7 (6%), early in 3 (3%), late in 1 (0.9%) and elective in 99 (90%). In the severe group were 36 patients (19%) with a mean Ranson score of 4.2. Nine patients died (25%), 31 were surgically treated, by emergency surgery in 17 (47%), 1 (3%) early surgery and 13 (36%) late surgery. The mortality rate of this group was compared with previous series of the same hospital (1975-1984 series). The 1984-1994 group showed a significant overall mortality decrease 4.7% vs 12.7% (p = 0.0047); 3.1% vs 11.2% (p = 0.0087) for the gallstones group; without mortality in the idiopathic and miscellaneous form compared with 18.7% and 20% respectively of the previous series; no mortality was observed in the mild AP compared with 5% of the previous series. The mortality in the severe form was 25% vs 40.8% (1975-1984 group). We consider that the decreased mortality could be attributed to the improvement in the diagnosis, early recognition of the severe forms, systemic supportive care in the severe forms, the use of antibiotics with wide spectrum and deeper penetration in the pancreas and specially in the change of the surgical timing. Although, in the first period the option was the early pancreatic surgery, in the second this was indicated only in particular cases.