Assessing individual risk for AMD with genetic counseling, family history, and genetic testing.

PurposeThe goal was to develop a simple model for predicting the individual risk profile for age-related macular degeneration (AMD) on the basis of genetic information, disease family history, and smoking habits.Patients and methodsThe study enrolled 151 AMD patients following specific clinical and environmental inclusion criteria: age >55 years, positive family history for AMD, presence of at least one first-degree relative affected by AMD, and smoking habits. All of the samples were genotyped for rs1061170 (CFH) and rs10490924 (ARMS2) with a TaqMan assay, using a 7500 Fast Real Time PCR device. Statistical analysis was subsequently employed to calculate the real individual risk (OR) based on the genetic data (ORgn), family history (ORf), and smoking habits (ORsm).Results and conclusionThe combination of ORgn, ORf, and ORsm allowed the calculation of the Ort that represented the realistic individual risk for developing AMD. In this report, we present a computational model for the estimation of the individual risk for AMD. Moreover, we show that the average distribution of risk alleles in the general population and the knowledge of parents' genotype can be decisive to assess the real disease risk. In this contest, genetic counseling is crucial to provide the patients with an understanding of their individual risk and the availability for preventive actions.

Direct PCR: a new pharmacogenetic approach for the inexpensive testing of HLA-B*57:01.

One of the most successful applications of pharmacogenetics research is the genetic screening for HLA-B*57:01, strongly associated with an increased risk to develop hypersensitivity reaction in HIV-positive patients following abacavir administration. Taking into consideration the limits of current genotyping methodologies, we have developed and validated (150 buccal swabs) an inexpensive pharmacogenetic approach for HLA-B*57:01 typing. In our assay DNA extraction and amplification are combined in one single step (direct PCR protocol), which is performed directly on the biological sample without the need of extraction and sequencing passages. The amplicons obtained by direct PCR can be easily separated on the agarose gel under ultraviolet. As per our results, the direct PCR represents a good alternative to the traditional methods of HLA-B*57:01 pharmacogenetic test, especially for those laboratories or countries where currently available approaches are often not available or not affordable. Furthermore it is an innovative approach, promoting a personalized, safer and cost-effective therapy.

Association of KIF3A, but not OVOL1 and ACTL9, with atopic eczema in Italian patients.

BACKGROUND: Atopic eczema (AE) (OMIM %603165) is the most common chronic inflammatory skin disease characterized by xerosis, pruritus, and erythematous lesions with increased transepidermal water loss. It's a complex disease due to the interaction between environmental and genetics factors. To date, different loci have been related to the disease. OBJECTIVES: To verify the association, between AE and rs479844, rs2164983, and rs2897442, target for OVOLI (11q13), ACTL9 (19p13.2), and in KIF3A (5q31) genes in the Italian population. Recently, these SNPs have been validated as associated to the disease. METHODS: A case-control study testing a cohort of 359 AE cases and 778 controls. RESULTS: We confirmed the association between rs2897442 in KIF3A gene and the disease at both allele and genotype level (P-value: 4.8 × 10(-4) and P-value: 6.3 × 10(-4), respectively). The C allele of the SNP showed an Odds Ratio (OR) of 1.46 (95% CI 1.18-1.82), moreover the CC genotype achieved an OR of 2.77 (95% CI 1.66-4.61). We failed to reveal association between AE and the other two SNPs tested. CONCLUSIONS: Our study indicated KIF3A as a novel gene implicated in the development of AE in the Italian population.

Vascularized fibula flap reconstruction of the mandible in bisphosphonate-related osteonecrosis.

AIMS: To point out the feasibility of microsurgical reconstruction of the mandible in patients with bisphosphonate-related osteonecrosis (BRONJ). METHODS: Seven patients with extensive mandibular osteonecrosis underwent subtotal mandibulectomy and immediate reconstruction with a free fibula flap. They were six women and one man aged 49-72 years. The mean size of the bone and oral mucosa defects were 18.5 and 22.5 cm(2) respectively. RESULTS: The mean time of surgical intervention was 12 h. All flaps survived and the postoperative course was uneventful. Oral feeding was resumed 14 days after surgery in all cases. The donor legs healed without complications. The pathology report confirmed the diagnosis of BRONJ in all patients. Normal bone was detected at the resection margins in six out of seven patients. Patients were followed-up at intervals of 3 months. After a median follow-up time of 23 months, no clinical and radiographic evidence of recurrent BRONJ were detected in six patients. One patient with osteomyelitis at the resection margins had signs of recurrent BRONJ 6 months after surgery. The overall curative rate of the population was 86%. CONCLUSIONS: Despite the limited number of patients studied so far, our data show that mandible reconstruction with the fibula flap is feasible and does not influence the natural course of the primary disease in BRONJ-resected patients.

Transthoracic and transesophageal echocardiographic indices predictive of sinus rhythm maintenance after cardioversion of atrial fibrillation: an echocardiographic study during direct current shock.

BACKGROUND: Up to 57% of atrial fibrillation (AF) recurrences after cardioversion take place during the first 30 days following direct current shock (DCS) delivery. Previous echocardiographic studies on sinus rhythm (SR) maintenance after cardioversion have focused mainly on parameters recorded before DCS, while other studies have reported on the indices recorded soon after delivery of the shock. METHODS: Therefore, we investigated 18 patients with nonrheumatic AF, selected to undergo DCS, by both transthoracic (TTE) and transesophageal (TEE) echocardiography performed within 10 minutes before and after the electrical shock delivery. TTE was utilized for the evaluation of left atrium and left ventricle shape as well as for mitral Doppler flow sampling, while TEE was used to evaluate left atrial appendage (LAA) morphology and function, to score the LAA spontaneous echo contrast, and to evaluate the flow of left superior pulmonary vein; the transesophageal probe was left in situ during the electrical procedure. Thirty days after cardioversion, 10 (55%) patients maintained SR (Group 1) while 8 (45%) reverted to AF (Group 2). We compared the mean values of the parameters recorded in the two groups both before and after DCS. RESULTS: Although many parameters of pre- and postcardioversion analysis proved to be significantly different between the two groups, the most marked differences were exhibited by the following postcardioversion indices: Peak Doppler flow velocity of the end-diastolic mitral flow (30.10 +/- 5.24 vs. 20.50 +/- 6.32 cm/sec, P = 0.003); sum of peak velocities of the end-diastolic contraction (A) and relaxation (A(1)) of LAA (A + A(1) = 58.20 +/- 17.02 vs. 31.25 +/- 9.27 cm/sec, P = 0.001); duration of A + A(1) (162.70 +/- 27.01 vs. 133.75 +/- 5.31 msec, P = 0.002); and sum of durations of the early diastolic forward (E) and reverse (E(1)) flow of LAA (101.90 +/- 35.15 vs. 53.33 +/- 16.33 msec, P = 0.006). CONCLUSIONS: Using a single echocardiographic examination during DCS and after induction of anesthesia, without further discomfort to patients, we were able to identify useful parameters for the prediction of future electrical activity of the heart before as well as soon after DCS. Postcardioversion indices, derived by both TTE and TEE, were even more predictive of SR maintenance after 1 month than precardioversion parameters.

[Adrenal adenoma and myelolipoma in an elderly patient with Conn's syndrome]. / Adenoma surrenalico e mielolipoma in paziente anziano con sindrome di Conn.

Adrenal myelolipoma is an uncommon benign tumor usually discovered by chance in patients with hypertension, obesity, atherosclerosis, cancer or endocrine disorders. The association with adrenal endocrine dysfunctions appears to be the most frequent. Myelolipoma has been found in patients affected by Cushing's syndrome, hyperaldosteronism, Addison's disease, virilization. We report herein a case of association, based on clinical and radiological signs, between myelolipoma and adrenal adenoma in a patient with Conn's disease. The myelolipoma was localized in the opposite adrenal gland to that of adenoma, at difference with the other cases described.

Clinical usefulness of slow pathway ablation in patients with both paroxysmal atrioventricular nodal reentrant tachycardia and atrial fibrillation.

Some patients with atrioventricular (AV) node reentrant tachycardia (AVN RT) also presented with atrial fibrillation (AF). In this study we demonstrate that slow pathway ablation is able to suppress both AVN RT and AF in subjects without structural heart abnormalities, whereas in patients with structural heart abnormalities after ablation AF frequently recurs.