Aspetti clinici e molecolari nella lipodistrofia congenita generalizzata: descrizione di una mutazione in una paziente con Sindrome di Berardinelli-Seip.

Il termine “lipodistrofia” identifica un gruppo eterogeneo di sindromi contraddistinte da anomalie del tessuto adiposo, perdita generalizzata o parziale del grasso corporeo, alterazioni del metabolismo glucidico e lipidico, importante resistenza all'insulina endogena ed esogena e disordini immunologici. La lipodistrofia congenita generalizzata o Sindrome di Berardinelli-Seip, è una malattia rara a trasmissione autosomica recessiva caratterizzata dall’assenza quasi totale di tessuto adiposo fin dalla nascita. La prevalenza stimata è di 1 caso su 10 milioni di nati vivi e attualmente il numero di pazienti descritti in letteratura è di circa 200. I geni responsabili del 95% dei casi di lipodistrofia congenita generalizzata sono l’1-acil-sn-glicerol-3-fosfato aciltransferasi beta (AGPAT2) e il gene denominato Berardinelli-Seip congenital lipodystrophy 2 (BSCL2), entrambi coinvolti nel processo di differenziamento adipocitario. AGPAT2 è localizzato sul cromosoma 9q34 e codifica per l’enzima 1-acil-sn-glicerol-3 fosfato aciltransferasi, responsabile della conversione dell’acido lisofosfatidico in fosfatidato. BSCL2, localizzato sul cromosoma 11q13, codifica per la seipina, una proteina che se mutata risulta responsabile delle forme più gravi della malattia. In questa tesi viene presentato il caso di una paziente italiana di 54 anni giunta al Dipartimento di Endocrinologia nel Luglio 2009 per diabete mellito di tipo 2 scarsamente controllato con terapia insulinica. Nata da genitori consanguinei (cugini di primo grado), la donna presentava sin dall’infanzia fenotipo acromegaloide, lipoatrofia diffusa e pseudoipertrofia muscolare. Venivano inoltre riscontrate ipercolesterolemia, ipertrigliceridemia, ipoleptinemia (0,76 ng/ml) e ipoadiponectinemia (1,10 ng/ml). Tali caratteristiche orientavano verso la sindrome di Berardinelli-Seip (BSCL). Al fine di confermare questa impressione diagnostica venivano analizzate le sequenze dei due geni candidati. Il DNA della paziente veniva estratto dai leucociti di sangue periferico ed amplificato mediante PCR. Dallo screening genetico non risultavano mutazioni nella sequenza del gene BSCL2, mentre veniva riscontrata una variante in forma omozigote nell’esone 3 del gene AGPAT2, che determina la sostituzione dell’aminoacido prolina in posizione 112 con l’aminoacido leucina (P112L). I risultati ottenuti dallo screening genetico hanno permesso di confermare la diagnosi di sindrome di Berardinelli-Seip e di identificare per la prima volta la mutazione P112L in un soggetto di razza caucasica

Erratum to: pegylated liposomal doxorubicin in combination with dexamethasone and bortezomib (VMD) or lenalidomide (RMD) in multiple myeloma pretreated patients

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Fire Weather Index application in north-western Italy

International audiencePiedmont region is located in North-Western Italy and is surrounded by the alpine chain and by the Appennines. The region is covered by a wide extension of forests, mainly in its mountain areas (the forests cover 36% of the regional territory). Forested areas are interested by wildfire events. In the period 1997?2005 Piedmont was interested by an average 387 forest fires per year, covering an average 1926 ha of forest per year. Meteorological conditions like long periods without precipitation contribute to create favourable conditions to forest fire development, while the fire propagation is made easier by the foehn winds, frequently interesting the region in winter and spring particularly. The meteorological danger index FWI (Fire Weather Index) was developed by Van Wagner (1987) for the Canadian Forestry Service, providing a complete description of the behaviour of the different forest components in response to the changing weather conditions. We applied the FWI to the Piedmont region on warning areas previously defined for fire management purposes. The meteorological data-set is based on the data of the very-dense non-GTS network of weather stations managed by Arpa Piemonte. The thresholds for the definition of a danger scenarios system were defined comparing historical FWI data with fires occurred on a 5 years period. The implementation of a prognostic FWI prediction system is planned for the early 2008, involving the use of good forecasts of weather parameters at the station locations obtained by the Multimodel SuperEnsemble post-processing technique

Optical Coherence Tomography May Be Used to Predict Visual Acuity in Patients with Macular Edema

Purpose. To determine whether the volume of retinal tissue passing between the inner and outer retina in macular edema could be used as an indicator of visual acuity. Methods. Diabetic and uveitic patients with cystoid macular edema (81 subjects, 129 eyes) were recruited. Best corrected logMAR visual acuity and spectral optical coherence tomography (OCT/SLO; OTI, Toronto, ONT, Canada) were performed in all patients. Coronal OCT scans obtained from a cross section of the retina between the plexiform layers were analyzed with a grid of five concentric radii (500, 1000, 1500, 2000, and 2500 μm centered on the fovea). The images were analyzed to determine the amount of retinal tissue present within each ring. A linear regression model was developed to determine the relationship between tissue integrity and logMAR visual acuity. Results. A linear relationship between tissue integrity and VA was demonstrated. The volume of retinal tissue between the plexiform layers in rings 1 and 2 (up to 1000 μm from the foveal center) predicted 80% of visual acuity. By contrast, central macular thickness within the central 1000 μm predicted only 14% of visual acuity. Conclusions. This study showed that the cross-sectional area of retinal tissue between the plexiform layers in cystoid macular edema, as imaged by OCT, is the best indicator of visual function at baseline. Further prospective treatment trials are needed to investigate this parameter as a predictor of visual outcome after intervention

Bortezomib with Thalidomide plus Dexamethasone Compared with Thalidomide plus Doxorubicin and Dexamethasone as Induction Therapy in Previously Untreated Multiple Myeloma Patients

We conducted a retrospective study to compare thalidomide, bortezomib and dexamethasone (VTD) with thalidomide plus doxorubicin and dexamethasone (TAD). Until now, first-line treatment with these combinations has not been reported in any comparative study. The principal objective of this study was to determine whether VTD would improve the complete response (CR) and CR plus very good partial response rates compared with TAD. Second, using additional methods, such as flow cytometric assays and polymerase chain reaction technology, we evaluated the molecular residual disease in the subgroup of patients that obtained CR. Our study shows that VTD is a superior induction regimen compared with TAD, with a higher response rate after induction, translating into greater CR plus very good partial response

Prospective qualitative and quantitative non-invasive evaluation of intestinal acute GVHD by contrast-enhanced ultrasound sonography.

Intestinal acute GVHD (I-aGVHD) is a life-threatening complication after allografting. Non-invasive bed-side procedures to evaluate extension and treatment response are still lacking. We hypothesized that, during I-aGVHD, contrast-enhanced ultrasound sonography (CEUS) could detect microcirculation changes (MVC) of the bowel wall (BW) and help to monitor treatment response. We prospectively employed CEUS in 83 consecutive patients. Of these, 14 patients with biopsy-proven intestinal GVHD (I-GVHD) were defined as the study group, whereas 16 patients with biopsy-proven stomach GVHD (U-GVHD) without intestinal symptoms, 6 normal volunteers and 4 patients with neutropenic enterocolitis were defined as the control group. All patients were evaluated with both standard ultrasonography (US) and CEUS at the onset of intestinal symptoms, during clinical follow-up and at flare of symptoms. Standard US revealed BW thickening of multiple intestinal segments, useful to determine the extension of GVHD. CEUS showed MVC, which correlated with GVHD activity, treatment response, and predicted flare of intestinal symptoms. US and CEUS findings were superimposable at diagnosis and in remission. CEUS was, however, more sensitive and specific to identify subclinical activity in patients with clinical relevant improvement. These findings were not observed in the control groups. CEUS is a non-invasive, easily reproducible bed-side tool useful to monitor I-aGVHD