Osteogénesis imperfecta, reporte de un caso / Osteogenesis imperfecta, a case report

INTRODUCCIÓN: La osteogénesis imperfecta (OI) es un trastorno hereditario del tejido conectivo fenotípicamente heterogéneo. Formas leves de OI suelen presentar fragilidad ósea mínima y estatura normal pudiendo manifestarse sólo por osteoporosis precoz o pérdida mineral ósea grave posmenopáusica. El cuadro moderado - severo presenta fracturas múltiples con trauma mínimo (o nulo) y deformidades óseas de grado variable. Forma más severa produce la muerte en el período perinatal. PRESENTACIÓN DEL CASO: Lactante varón 2 años 7 meses, nacido de término por parto normal, pequeño para edad gestacional severo, primogénito de madre adolescente y padre con antecedente OI. Se mantuvo hospitalizado para control de crecimiento ponderal, no encontrándose patología agregada. Tras alta, paciente fue citado a policlínico de genética por antecedente OI, sin asistir. Al año de edad, fue derivado por fractura fémur derecho posterior a trauma aparentemente mínimo, hospitalizándose para manejo con observación de OI y probable violencia intrafamiliar. Primera evaluación genética no impresionó OI, luego endocrinología solicitó estudio bioquímico y radiológico completo ambulatorio. Posteriormente, consultó por fractura fémur izquierdo con fractura tibial derecha previamente no diagnosticada. Tras reevaluación genética, destacaban retraso de talla y múltiples dismorfias corcordantes, diagnosticándose OI leve-moderada por clínica y antecedente familiar. Equipo endocrinología inició tratamiento con bifosfonatos. Evoluciona con fractura codo y nueva fractura fémur derecho tras caída. DISCUSIÓN: La OI es una patología frecuente con manifestaciones heterogéneas con diagnóstico sencillo ante fragilidad ósea, manifestaciones extraesqueléticas e historia familiar positiva. El diagnóstico y tratamiento oportuno permitirían minimizar complicaciones y maximizar capacidad funcional.

INTRODUCTION: The osteogenesis imperfecta (OI) is a phenotypically heterogeneous hereditary connective tissue disease. The mild forms of OI tends to show minimum fragility on bones and normal height which could only be manifested as an early osteoporosis or serious postmenopausal bone density loss. The severe clinic picture shows multiple fractures with minimum trauma and bone deformity. The most severe form causes perinatal death. CASE REPORT: A breastfed infant boy of two years and seven months, born by natural birth, very small for gestational age, first born of a teenage mother and a father with OI. He was, first hospitalized for weight and growth control. No pathological findings were recognized. After the discharge, he did not attend to the genetic control. At one year old, he was sent with a right femur fracture after a minimum trauma. He was hospitalized suspecting OI and possible domestic violence. A first genetic evaluation did not match with OI, then endocrinology requested a complete radiological study. The biochemical study was normal. Then, he presented left femur and right tibia fracture. The genetic reevaluation, found multiple dysmorphic characteristic and late size development, which confirmed a mild form of OI. A biphosphonates treatment was initiated. DISCUSSION: The OI is a frequent disease with heterogeneous manifestations. The diagnosis is simple, bases on bone fragility, extra skeletal manifestations and familiar history. An early diagnosis and treatment could minimize complications and maximize mobility and functional capacity.

Relevance of perceived childhood neglect, 5-HTT gene variants and hypothalamus-pituitary-adrenal axis dysregulation to substance abuse susceptibility.

The hypotheses of (1) gene x environment interaction in the susceptibility to experiment with drugs and (2) hypothalamus-pituitary-adrenal (HPA) axis involvement in mediating the effects of early adverse experiences and gene variants affecting serotonin function on substance abuse vulnerability were tested by investigating in 187 healthy adolescents the possible relevance of 5-HTT "S" polymorphism, childhood parental neglect reported retrospectively and HPA axis function to the susceptibility to experiment with illicit drugs. Higher frequency of the 5-HTT SS genotype seems to be associated with an increased susceptibility to use illegal psychotropic drugs among the adolescents. At the same time, reduced maternal care perception was found to represent a key intermediate factor of the association between SS polymorphism and drug use, suggesting that genetic factors and parental behavior concur to drug use susceptibility. Our results also confirm the relationship between basal plasma levels of cortisol and adrenocorticotropic hormone (ACTH) on the one hand, and retrospective measures of neglect during childhood: the higher the mother and father neglect CECA-Q scores, the higher the plasma levels of the two HPA hormones. Such positive relationship has been proved to be particularly effective and important when associated to the S-allele, both in homozygote and heterozygote individuals. However, when tested together with genotype and parental neglect, the effect of HPA hormones such as cortisol and ACTH was not found to improve significantly the explanatory power of the risk model.

Phase II study of gemcitabine plus oxaliplatin as first-line chemotherapy for advanced non-small-cell lung cancer.

This phase II study evaluated the response rate and tolerability of gemcitabine-oxaliplatin chemotherapy in non-small-cell lung cancer (NSCLC) patients. Chemonaive patients with stage IIIB or IV NSCLC received gemcitabine 1000 mg m(-2) on days 1 and 8, followed by oxaliplatin 130 mg m(-2) on day 1. Cycles were repeated every 21 days for up to six cycles. From February 2002 to May 2004, 60 patients were enrolled into the study in seven Italian institutions. We observed one complete response (1.7%) and 14 partial responses (23.3%), for an overall response rate of 25.0% (95% confidence interval, 14.7-37.9%). The median duration of response was 5.9 months (range 1.5-17.1 months). With a median follow-up of 6.7 months, median time to progressive disease and overall survival were 2.7 (range 1.9-3.4 months) and 7.3 months (range 7.2-8.6 months), respectively. The main grade 3-4 haematological toxicities were transient neutropenia in 11.7% and thrombocytopenia in 8.3% of the patients. Nausea/vomiting was the main grade 3-4 nonhaematological toxicity, occurring in 10.0% of the patients. Two (3.3%) patients developed grade 3 neurotoxicity. Our results show that gemcitabine-oxaliplatin chemotherapy is active and well tolerated in patients with advanced NSCLC, deserving further study, especially for patients not eligible to receive cisplatin.

Serotonin transporter promoter polymorphism genotype is associated with temperament, personality traits and illegal drugs use among adolescents.

Serotonin transporter promoter polymorphism (5-HTTLPR) genotype was previously found associated with substance use disorders, particularly in the subjects with comorbid antisocial behavior, and with temperament and personality traits at risk for substance abuse. Aim of the present study was to evaluate the possible association between 5-HTTLPR genotype and the availability to experiment illegal drugs among adolescents, in relationship with psychological characteristics. 216 caucasian high school students (aged 14-19 ys), 125 abstinent subjects, who have never experimented psychotropic drugs, and 91 experimenters of illegal drugs have been genotyped. Aggressiveness levels and temperamental traits were measured in both abstinent subjects and experimenters utilizing respectively Buss-Durkee-Hostility-Inventory (BDHI) and Cloninger Three-dimensional Personality Questionnaire (TPQ). Data about school performance have been also collected. The short-short (SS) genotype frequency was significantly higher among experimenters compared with abstinent subjects (p = 0.001). The odds ratio for the SS genotype vs the long-long (LL) genotype frequency was 4.67, 95% Cl (1.97-11.04), when experimenters were compared with abstinent students. The SS genotype frequency was significantly higher among aggressive/novelty seeker (NS) experimenters with poor school achievements, compared with drugs experimenters without aggressiveness and school failure (p = 0.02). When evaluated on the entire sample, BDHI mean total scores, NS scores at TPQ and school failure frequency were significantly higher in SS individuals, in comparison with LL subjects. Our data suggest that a decreased expression of the gene encoding the 5-HTT transporter, due to "S" promoter polymorphism, may be associated with an increased availability to experiment illegal drugs among adolescents, particularly in the subjects with more consistent aggressiveness, NS temperament and learning disabilities.

[Physics homogenization and the choice of screen-film combination in conventional thoracic radiography]. / L'omogeneizzazione fisica e la scelta della combinazione schermo-pellicola nel radiogramma toracico tradizionale.

The homogenization of conventional chest radiographs is obtained with mechanical filtration of the X-ray beam and it allows opacity compensation of the different anatomical structures under examination; consequently, more pieces of diagnostic information on the mediastinum can be obtained. The authors used a mechanical device for equalization (Tau-Gil, Gilardoni SpA) with five different X-ray film/rare-earth screen combinations (3M Trimax) to investigate the following problems: a) choice of the best film-screen combination; b) results of the dosimetric comparison of filtered and non-filtered examinations; c) qualitative evaluation of equalization in terms of diagnostic information. One thousand analogic chest studies, 500 with and 500 without hard-filtering equalization, were performed with high-tension technique and statistically evaluated with a dedicated program. The authors concluded that: 1) the best qualitative results are obtained with GTU film/T6 screen combination, which seems to make the most satisfying compromise between sensitivity and spatial resolution and allows low X-ray exposure to be combined with good diagnostic results; 2) dosimetric tests clearly show that in hard-filtered studies the average incident dose to the patient is 12% lower than that given with no filter. Particularly, skin and lung doses decrease, while mediastinum dose doubles to allow the simultaneous visualization of mediastinum and parenchyma; 3) a substantial difference exists between the frequencies of excellent, good and bad results in the comparative series (with and without equalization) for the evaluation of central chest areas, especially for mediastinum, retrocardiac region and carena. The overall rate of poor results was reduced by equalization, ranging 11.6% to 2.8% (mean: 6.3%) in equalized studies, and topping 64.2% (average: 35.5%) in non-equalized studies. Therefore, in the authors' experience, equalization with this type of mechanical device improves the depiction of the mediastinal region, with no significant imaging loss in lung parenchyma demonstration. Moreover, hard-filtering decreases average incident dose to the chest and skin-lung dose, increasing mediastinum dose to allow its correct demonstration.

[Splenic embolization and hepatic chemoembolization: combined transcatheter treatment of hepatocellular carcinoma in cirrhosis with hypersplenism]. / Embolizzazione splenica e chemioembolizzazione epatica: trattamento combinato transcatetere del carcinoma epatocellulare su cirrosi con ipersplenismo.

Liver cirrhosis with hypersplenism is often associated with HCC. In many such cases, chemoembolization (TACE) may be very difficult because of the high incidence of hemorrhagic complications due to treatment and/or following portal hypertension, as well as for poor hematologic tolerance to antiblastic drugs in cirrhotic patients. Six patients with nodular HCC and cirrhosis (Child B) with hypersplenism were treated by combined TACE and partial splenic embolization (PSE) to reduce splenic size and to improve hematologic and hepatic function rates. Actual and long-lasting (up to 6 months since TACE/PSE) positive results were observed in splenic size and in hepatic function synthesis, as well as on hematologic and hemocoagulation factors. The clinical-laboratory improvement following TACE/PSE allowed TACE to be completed in all cases, following the usual protocol based on 3 procedures. Therefore, in the patients with advanced/decompensated cirrhosis and hypersplenism associated with HCC, the combined one-step TACE/PSE treatment can be said to improve patients' tolerance to antiblastic drugs and to reduce the risk of hemorrhagic complications due to invasive radiologic procedures and/or to portal hypertension.

[Bone metastasis of hepatocellular carcinoma: observations in patients treated with transcatheter arterial chemoembolization]. / Metastasi ossee da carcinoma epatocellulare: osservazioni nei pazienti trattati con chemioembolizzazione arteriosa transcatetere.

Bone metastases from hepatocellular carcinoma (HCC) are fairly rare, their average occurrence rate being 7.3%. Seven cases of secondary bone lesions (2%) were observed in a series of 347 consecutive cases treated with transcatheter arterial chemoembolization (TACE). The conventional X-ray and the CT patterns of secondary bone involvement were studied, together with histologic features, tumor and cirrhosis stage, and follow-up results. Bone metastases were detected in the early stages of cirrhosis and HCC, which suggested that patients might experience long survival if adequately treated. On the other hand, due to the lower rate of bone metastases in our series than in untreated cases, TACE cannot be said to be of even partial value in the treatment of distant HCC metastases. At any rate, bone metastasis alone is not necessarily a sign of poor prognosis, if it is adequately treated with radio-chemotherapy.

[Assisted reporting: preliminary evaluation of the effectiveness of the management of a Thoracic Radiology Unit]. / La refertazione assistita: valutazione preliminare dell'efficacia nella gestione di una Unità di Radiologia Toracica.

Conventional chest radiographs correspond to 50% of the normal workload of a diagnostic radiology department and account for the lengthening of reporting times, thus affecting the profit of a general hospital deeply. The authors describe a software specifically applied to the reporting of chest X-rays which allows "macro" reports for typical or negative findings and which makes reports by sequential questions for more complex conditions. Its value was investigated based on nearly two years' uninterrupted working experience. During four month 7175 examinations were performed: 6480 (90.3%) in the diagnostic room, plus 685 (9.5%) bedside and emergency exams. Computer-assisted reports amounted to 95% of the total figure in the first group and to 46% in the second one. The results follow: 1) waiting times were substantially reduced; 2) administrative workload was markedly decreased; 3) less expert medical staff greatly benefitted from an efficient didactic and learning activity. Thus, good results were obtained, especially relative to the possibility to obtained actual real-time reports of chest radiographs with no loss in diagnostic accuracy.