Mutaciones y variaciones estructurales en el gen catecol-O-metiltransferasa de los pacientes que exhiben dolor quirúrgico persistente crónico

ObjectivesMutations in the exon 4 of the COMT gene are associated with chronic persistent surgical pain (CPSP). Especially COMT mutated allele G472A (Val158Met) associated with CPSP patients is reported in different ethnic population. The purpose of this study is to evaluate the prevalence of genetic mutations and structural variations in exon 4 of COMT that can be related to the appearance of CPSP in patients under sternotomy.Materials and methodsOne hundred patients with American Society of Anesthesiologists (ASA) physical status grades i, ii and iii, who underwent sternotomy procedures, were selected to assess the development and magnitude of the CPSP evaluated with pain questionaries’ at the end of three months after surgery. This was correlated with COMT allele presence. The exon 4 of COMT gene (that contains the G472A allele) was studied. The polymerase chain reaction (PCR) products were sequenced and mutated sequences were deposited in GenBank®. The structural analysis of COMT was performed using ProCheck® and distortions of three-dimensional tertiary structural orientation was evaluated with root-mean-square deviation (RMSD) score.ResultsGenetic analysis carried out through PCR showed 220 bp amplicons. The 25% of patients with CPSP showed a Numeric Rating Scale (NRS) > 4 pain score. The 20% of these patients have known Val158Met mutation, 5% of patients showed novel mutations c.382C>G, c.383G>C, p.(Arg128Ala). The mutations in COMT gene contributed major structural variations in COMT leading to the formation of inactive COMT that correlates with CPSP.ConclusionThe results of the present study showed that both novel and previously reported mutations in COMT gene has strong association with CPSP.     

The Potential Impact of Contemporary Transthoracic Echocardiography on the Management of Patients with Native Valve Endocarditis: A Comparison with Transesophageal Echocardiography

Background: Between 1987 and 1994, several studies demostrated transthoracic echocardiography (TTE) to be less sensitive than transesophageal echocardiography (TEE) in detecting native valve endocarditis. Recent technologic advances, especially the introduction of harmonic imaging and digital processing and storage, have improved TTE image quality. The aim of this study was to determine the diagnostic accuracy of contemporary TTE. Methods: Between 2003 and 2007, 75 patients underwent both TTE and TEE for clinically suspected infective endocarditis. The diagnostic accuracy of TTE was assessed using transesophageal echocardiography as the gold standard for diagnosis of endocarditis. Results: Of the 75 patients in this study, 33 were found to be positive by TEE. The sensitivity for detection of infective endocarditis by TTE was 81.8%. It provided good image quality in 81.5% of cases; in these patients sensitivity was even greater (89.3%). Conclusion: Contemporary TTE has improved the diagnostic accuracy of infective endocarditis by ameliorating image quality; it provides an accurate assessment of endocarditis and may reduce the need for TEE.     

Recurrent Diffuse Neurofibroma of Nose Associated with Neurofibromatosis Type 1: A Rare Case Report with Review of Literature

Diffuse neurofibroma is an unusual variant of neurofibroma with the head and neck being the common sites of involvement. It is benign in nature and spreads superficially and has many ectatic blood vessels. Histologically it is similar to conventional neurofibromas except for a few peculiar distinguishing features. We report a case of a 14-year-old boy who presented with a diffuse recurrent painless swelling over the dorsum of the nose with the clinical stigmata of neurofibromatosis. Microscopy revealed a diagnosis of diffuse neurofibroma with a few foci showing differentiation towards Meissner''s type of tactile corpuscles. It is important to recognize this entity as it has a tendency to recur, yet hardly ever become malignant and is almost always associated with neurofibromatosis type 1.     

Molecular mechanism and functional implications of thrombin-mediated tyrosine phosphorylation of PKCdelta in platelets

Thrombin has been known to cause tyrosine phosphorylation of protein kinase C delta (PKCdelta) in platelets, but the molecular mechanisms and function of this tyrosine phosphorylation is not known. In this study, we investigated the signaling pathways used by protease-activated receptors (PARs) to cause tyrosine phosphorylation of PKCdelta and the role of this event in platelet function. PKCdelta was tyrosine phosphorylated by either PAR1 or PAR4 in a concentration- and time-dependent manner in human platelets. In particular, the tyrosine 311 residue was phosphorylated downstream of PAR receptors. Also the tyrosine phosphorylation of PKCdelta did not occur in Galpha(q)-deficient mouse platelets and was inhibited in the presence of a phospholipase C (PLC) inhibitor U73122 and calcium chelator BAPTA (5,5'-dimethyl-bis(o-aminophenoxy)ethane-N, N, N ', N '-tetraacetic acid), suggesting a role for Galpha(q) pathways and calcium in this event. Both PAR1 and PAR4 caused a time-dependent activation of Src (pp60c-src) tyrosine kinase and Src tyrosine kinase inhibitors completely blocked the tyrosine phosphorylation of PKCdelta. Inhibition of tyrosine phosphorylation or the kinase activity of PKCdelta dramatically blocked PAR-mediated thromboxane A2 generation. We conclude that thrombin causes tyrosine phosphorylation of PKCdelta in a calcium- and Src-family kinase-dependent manner in platelets, with functional implications in thromboxane A2 generation.     

Ultrasound screening for familial ovarian cancer.

We have used transvaginal ultrasonography to screen 776 asymptomatic women for familial ovarian cancer. Every woman had at least one first- or second-degree relative develop the disease (677, 87%; and 98, 13%, respectively). The mean age of the study population was 51 years (range, 24 to 78 years); 52% were premenopausal, 36% were naturally postmenopausal, and 12% had undergone a hysterectomy. Overall, 43 women (5.5%) were referred for surgical investigation and 39 had a laparatomy. Nineteen/thirty-nine (48%) had bilateral ovarian masses, and 15% of abnormal ovaries had more than one type of histopathology. Twenty-three tumors and thirty-two tumor-like conditions were detected. There were 3 cases of primary ovarian cancer (prevalence, 3.9/1000), all FIGO stage Ia. None of the women has developed ovarian cancer within the first year of the scan (giving a provisional detection rate of 100%). The false positive rate was 40/773 (5.2%), the predictive value of a positive screen result was 7.7%, and the odds in favor of finding any mass at laparotomy were about 19 to 1 or for any tumor, 1 to 1. At surgery the odds against finding primary ovarian cancer were 12 to 1. The positive predictive value of the screening procedure and the prevalence of the disease were significantly higher than the corresponding values from a previous population-based screening program.     

Characteristics of persistent ovarian masses in asymptomatic women

Persistent ovarian masses have been found in a substantial proportion of 5479 self-selected asymptomatic women who were screened for early ovarian neoplasia. Each woman was scheduled to undergo three ultrasound screens (consisting of 1-12 scans) to detect regressing and non-regressing masses. A total of 14,594 screens (15,977 scans) was performed. The average interval between successive screens was 595 days (range 214-1134 days). Overall, 650 screens (4.4%; 10.1% of women) produced a positive result which became negative with successive scans (four times more frequently in pre- than naturally postmenopausal women), and 338 screens (2.3%; 5.9% of women) had a final positive result (at least one ovary that was grossly abnormal or contained a persistent mass). Biopsies were taken from 336 ovaries (89% of total, 271 women). Overall, 134 tumour-like conditions and 119 benign tumours were identified. The detection rate of tumour-like conditions was 1.5 times higher in premenopausal than naturally postmenopausal women, whereas the proportion of tumours to normal ovaries was similar in both groups. Overall, 51% of tumour-like conditions and 70% of all tumours were detected at screen 1. Four women had metastatic ovarian cancer (three at screen 1, one at screen 2; two were bilateral). Five women (0.1%) had a primary malignant tumour (two at screen 1, three at screen 2; four were stage 1a and one was stage 1b). All women are being monitored to obtain additional information about the significance of the findings.     

Leucocyte migration inhibition in cow's milk protein intolerance

The leucocyte migration inhibition (LMI) was determined in an assay after in vitro challenge with beta-lactoglobulin. The assay was considered positive when migration inhibition index was greater than 20% (mean +3 SD of healthy infants). Ninety-eight infants with protracted diarrhoea and failure to thrive, 16 healthy, 12 malnourished, and 16 infants suffering from acute gastroenteritis were studied. Of the 98 patients with protracted diarrhoea, 12 fulfilled Goldman's criteria for cow's milk protein intolerance, 63 had lactose malabsorption, and in 15 no associated causative factor was identified. The mean index of migration inhibition in the cow's milk allergic group (58.83 +/- 11.98) was higher than in healthy controls (8.25 +/- 3.91), the difference being statistically significant (p less than 0.05). The test was positive in all patients with cow's milk protein intolerance. The assay was also positive in four other patients suffering from protracted diarrhoea, two of whom had lactose malabsorption. All the infants with acute gastroenteritis and malnutrition had values within the normal range. The migration inhibition index in five patients with cow's milk intolerance had declined to 24.74 +/- 4.87 in assays performed 1-6 weeks after return of clinical tolerance to cow's milk (p less than 0.05) but the test was still within the positive range in three of the five infants. These results suggest that this cell mediated immune assay is a sensitive test for the diagnosis of cow's milk protein intolerance in infants. The specificity needs to be reassessed in the light of more objective criteria for the diagnosis of cow's milk protein intolerance.