Hereditary renal amyloidosis caused by a new variant lysozyme W64R in a French family

BACKGROUND: The number of proteins with mutations resulting in amyloidosis has continued to increase. Five proteins--transthyretin, fibrinogen alpha-A chain, apolipoprotein AI, lysozyme, apolipoprotein AII, cystatin C and gelsolin--can be associated with hereditary amyloidosis involving the kidney. METHODS: A French family with a history of autosomal dominant hereditary amyloidosis with early sicca syndrome and nephropathy leading to renal failure after the fifth to the seventh decade was studied. Several tissue specimens obtained from the proband and his relatives were examined. Immunohistochemistry was performed on paraffin embedded sections using the indirect immunoperoxidase technique. We searched for mutations in the five exons and flanking introns of the lysozyme gene. RESULTS: Amyloid deposits from the bowel, labial salivary gland and kidney were intensively stained by anti-lysozyme antibody. Sequence analysis of lysozyme exon 2 from the affected individuals revealed a nucleotide substitution predicting a substitution of the amino acid at position 64 in the mature protein from tryptophane, an aromatic residue to the cationic residue arginine (W64R). CONCLUSION: We report a novel mutation (W64R) of the lysozyme that is associated with hereditary amyloidosis and prominent nephropathy. Since the treatment of hereditary amyloidosis greatly varies with the nature of the amyloid protein, thorough characterization of the latter is crucial for the management of the disease.     

Cardiac troponin I is an independent predictor of in-hospital death after adult cardiac surgery

BACKGROUND: Although myocardial injury during cardiac surgery is associated with impaired clinical outcome, little is known about the prognostic value of cardiac troponin I (cTnI), a cardiac-specific biologic marker. The purpose of this prospective study was to evaluate the prognostic value of cTnI concentrations measured 20 h after the end of surgery in adult patients undergoing coronary artery bypass grafting or conventional valve surgery. METHODS: Baseline and perioperative characteristics of 502 consecutive patients undergoing conventional heart surgery during a 1-yr period were collected. In-hospital death (n = 28) and major clinical outcomes, e.g., low cardiac output, ventricular arrhythmia, and renal failure, were recorded. RESULTS: Multivariate analysis, using a stepwise logistic regression, showed that cTnI concentration was an independent predictor of in-hospital mortality (for cTnI concentration > 13 ng/ml, odds ratio = 6.7 [95% confidence interval, 2.3-19.3]), as were diabetes, altered preoperative cardiac function, emergent surgery, cardiopulmonary bypass duration, postoperative Pao2 level and total chest drainage volume. Further, elevated cTnI concentrations were associated with a cardiac cause of death and with major clinical outcomes. CONCLUSIONS: Our results demonstrated that cTnI concentration measured 20 h after the end of surgery is an independent predictor of in-hospital death after cardiac surgery. In addition, elevated concentrations of cTnI are associated with a cardiac cause of death and with major postoperative complications.     

Evaluation of the viability and validity of an instrument to measure community activation

OBJECTIVE: This study examines psychometric properties of a community activation assessment scale used for the evaluation of the Quebec project within the Federal Provincial Heart Health Initiative. The scale is composed of three sub scales, one for each of the intervention target risk factors. METHODS: Data were collected by telephone interviews conducted with 199 key informants from the 24 communities of the project. Reliability was studied using Cronbach's alpha coefficients and intraclass correlations. Validity was explored with factor analysis techniques. RESULTS: Subscales' internal consistency were very good, ranging from 0.71 to 0.83, but intraclass correlations between informants from the same communities were low. Factor analyses indicated a unidimensional structure for each scale. INTERPRETATION: These results show that the scale seems to provide reasonable assessments of the opinion of key informants regarding activation in their community. However, ranking communities based on the aggregated scores from local key informants may lead to classification problems.     

The visual word form area: a prelexical representation of visual words in the fusiform gyrus

Event-related fMRI was used to test the hypothesis that the visual word form area in the left fusiform gyrus holds a modality-specific and prelexical representation of visual words. Subjects were engaged in a repetition-detection task on pairs of words or pronounceable pseudo-words that could be written or spoken. The visual word form area responded only to written stimuli, not to spoken stimuli, independently of their semantic content. We propose that the occasional activation of the fusiform gyrus when listening to spoken words is due to the topdown recruitment of visual orthographic or object representations.     

Involvement of FAK, PI3-K and PKC in cell adhesion induced by microtubule disruption

We have previously shown that microtubule disruption results in an increase in cell adhesion to ECM proteins. In this work we show that this enhanced cell attachment was completely abolished by specific inhibitors of tyrosine-kinases, PI3-K and PKCs. Microtubule depolymerisation was associated with an important increased in tyrosine phosphorylation of FAK and paxilline, as well as with subcellular localisation of PKCgamma, delta and epsilon. We also observed significant alterations in actin cytoskeleton leading to reduced cell spreading. Thus, microtubule depolymerisation appears to activate various intracellular kinases that lead to actin cytoskeletal changes and to an increase of integrin-dependent adhesion. Whether this enhanced attachment is due to intracellular events resulting in changes in integrin affinity or avidity remains to be determined.     

Effect of impaired recognition and expression of emotions on frontocingulate cortices: an fMRI study of men with alexithymia

OBJECTIVE: Although the brain areas involved in emotional response and in the recognition of others' emotions have been reported, the neural bases of individual differences in affective style remain to be elucidated. Alexithymia, i.e., impairment of the ability to identify and communicate one's emotional state, influences how emotions are regulated. Alexithymia has been hypothesized to involve anterior cingulate dysfunction. Therefore, the authors searched for differential cerebral regional activation in response to emotional stimuli in subjects with alexithymia. METHOD: Two groups of eight men each were selected from 437 healthy subjects on the basis of high or low scores on the 20-item Toronto Alexithymia Scale. Using functional magnetic resonance imaging (fMRI), the authors compared the two groups for their regional cerebral activation in response to the presentation of pictures with validated positive or negative arousal capabilities. RESULTS: Men with alexithymia demonstrated less cerebral activation in the left mediofrontal-paracingulate cortex in response to highly negative stimuli and more activation in the anterior cingulate, mediofrontal cortex, and middle frontal gyrus in response to highly positive stimuli than men without alexithymia. CONCLUSIONS: These findings provide direct evidence that alexithymia, a personality trait playing a role in affect regulation, is linked with differences in anterior cingulate and mediofrontal activity during emotional stimuli processing.     

Direct transoral approach to C2 for percutaneous vertebroplasty

Percutaneous vertebroplasty was performed via a transoral route in a 70-year-old woman with a C2 metastasis of thyroid origin involving anterior vertebral elements. Complete pain relief was obtained after an uncomplicated minimally invasive procedure. This preliminary experience demonstrates that a transoral approach under fluoroscopic control can provide safe access to the upper cervical spine at C2 level.     

PMMA cementoplasty in symptomatic metastatic lesions of the S1 vertebral body

We describe a lateral transiliac direct puncture approach to the S1 vertebral body for polymethylmethacrylate (PMMA) cementoplasty of painful metastatic lesions. This approach was performed using a 15-cm-long trocar needle with 3-mm outer diameter, introduced under general anesthesia and fluoroscopic control. A lateral projection was used to center the needle just in front of the spinal canal and subjacent to the superior plate of the S1 vertebral body. Needle progression was controlled using anteroposterior and lateral fluoroscopic projections alternately with a needle course parallel to an axial plane, avoiding conflict with the S1 foramen. After needle tip placement in the center of the S1 vertebral body, diluted PMMA with a setting time of 8 min was delivered. Ipsilateral lesions of the lateral sacral compartment were filled with the same needle by stepwise withdrawal and continuous PMMA injection.