Prognostic relevance of histological grade and its components in node-negative breast cancer patients.

Available results highlight the lack of good level of evidence studies on the pure prognostic value of histological grade. In the present study, the prognostic relevance of histological grade and of its three components, tubule formation, nuclear pleomorphism and mitotic count, was analyzed in a series of 372 patients with node-negative breast cancer treated with locoregional therapy alone until early relapse. Histological grade was determined blindly by two observers and discordance between evaluations was resolved after joint review using a multihead microscope. No relation was observed between histological grade and any of its three components and disease-free survival. Conversely, a significant relation was observed between histological grade and distant metastasis-free survival (at 6 years, 94, 86 and 76% for grades 1, 2 and 3, respectively, P=0.013) as well as overall survival (98, 90 and 86%, P=0.001). A breakdown analysis as a function of the three components showed that neither tubule formation nor nuclear pleomorphism was associated with prognosis, and only mitotic count strongly influenced both distant metastasis-free survival (91, 82 and 74%, P=0.014) and overall survival (97, 87 and 85%, P=0.011). Histological grade suffers from a much higher subjectivity than any other microscopic evaluation of biomarkers as it is the sum of three different morphological features. Within the Italian Network for Quality Assessment of Tumor Biomarkers program we observed that histological grade is an independent prognostic variable, but also that this role is ascribable only to the number of mitotic figures. In conclusion, due to the ever smaller size of diagnosed breast cancers, resulting in less cancer tissue for biofunctional and molecular analysis, mitotic count evaluated under strict quality control conditions seems to be an accurate and feasible prognostic variable.     

Recommendations for participation in leisure-time physical activity and competitive sports of patients with arrhythmias and potentially arrhythmogenic conditions. Part II: ventricular arrhythmias, channelopathies and implantable defibrillators.

This consensus paper on behalf of the Study Group on Sports Cardiology of the European Society of Cardiology follows a previous one on guidelines for sports participation in competitive and recreational athletes with supraventricular arrhythmias and pacemakers. The question of imminent life-threatening arrhythmias is especially relevant when some form of ventricular rhythm disorder is documented, or when the patient is diagnosed to have inherited a pro-arrhythmogenic disorder. Frequent ventricular premature beats or nonsustained ventricular tachycardia may be a hallmark of underlying pathology and increased risk. Their finding should prompt a thorough cardiac evaluation, including both imaging modalities and electrophysiological techniques. This should allow distinguishing idiopathic rhythm disorders from underlying disease that carries a more ominous prognosis. Recommendations on sports participation in inherited arrhythmogenic conditions and asymptomatic gene carriers are also discussed: congenital and acquired long QT syndrome, short QT syndrome, Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia, arrhythmogenic right ventricular cardiomyopathy and other familial electrical disease of unknown origin. If an implantable cardioverter defibrillator is indicated, it is no substitute for the guidelines relating to the underlying pathology. Moreover, some particular recommendations for patients/athletes with an implantable cardioverter defibrillator are to be observed.     

Passive Pneumatic Stabilization Device for Assisting in Reduction of Femoral Shaft Fractures

Abstract During treatment of femoral shaft fractures, not only the actual fracture reduction but also the retention of the achieved reduction is essential. Substantial forces may apply to the bone fragments, due to multidirectional muscular contraction. Furthermore, forces from manipulation of one bone fragment may be transferred over the soft tissues onto the other fragments, thus hindering accurate fracture reduction. Once a sufficient reduction has been achieved, this position must be retained whilst definitive internal fixation is performed. Conventional methods comprise mounting patients on a traction table and applying manual distraction or employing special distraction devices, such as the AO distractor device. These approaches, however, only insufficiently stabilize both main fragments. For example, on the traction table the proximal femoral fragment can pivot around the hip joint thus complicating precise reduction. A novel pneumatic stabilization device to assist surgeons during operative procedures is described. This passive holding device “Passhold” connects to one main fragment through a minimally invasive bone interface and statically locks the fragment’s position. Thereafter, only the other main fragment is manipulated to achieve reduction. Mutual interference of the reciprocal fragment positions, due to soft-tissue force transfer during manipulation, is avoided. The authors examined the stability of the novel retention device on a test rig and proved its functionality under sterile settings using cadaver tests. It is concluded that this device largely facilitates the operative procedure in femoral shaft fractures, is sufficiently stable and ergonomically suitable for intraoperative deployment.     

Stimulus effects of ibogaine in rats trained with yohimbine, DOM, or LSD.

The stimulus effects of ibogaine were compared with those of yohimbine, an alpha 2-adrenoceptor antagonist, 2,5-dimethoxy-4-methylamphetamine (DOM), a 5-hydroxytryptamine2 (5-HT2) agonist, and lysergic acid diethylamide (LSD), a nonspecific 5-HT agonist. Rats were trained with either yohimbine (6 mg/kg), DOM (0.6 mg/kg), or LSD (0.1 mg/kg) vs. no treatment in a two-lever discrimination task. Tests of generalization were then conducted with ibogaine. In yohimbine-trained animals, 39.7% of responses following ibogaine (15 mg/kg) were on the drug-appropriate lever, but this response level was not significantly different from no treatment-appropriate responding. A response distribution that was significantly different from responding under both drug and no treatment training conditions was observed in DOM-trained rats after administration of 15 mg/kg ibogaine. Pizotyline (BC-105) blocked all DOM-appropriate responding produced by ibogaine. In LSD-trained animals, 20 mg/kg ibogaine mimicked LSD. Pizotyline blocked LSD-appropriate responding produced by ibogaine in five of six animals. The present data suggest the involvement of 5-HT2 receptor activity, and the possibility of a 5-HT1A contribution, in the stimulus properties of ibogaine.     

Early reconstruction of the abdominal wall in giant omphalocele.

Omphalocele is the most common congenital defect of the abdominal wall. Mortality rate is between 20 and 70% and early closure of the abdominal wall, within 10 days of life, is vital to the successful outcome of the surgical treatment. The authors describe the use of two bipedicled flaps of abdominal skin to correct the defect of the midline as soon as the reduction of all viscera has been accomplished.     

Expression of c-fos, fos B, and egr-1 in the medial preoptic area and bed nucleus of the stria terminalis during maternal behavior in rats

The spatial and temporal pattern of expression of the protein products of immediate early genes (IEGs) c-fos, fos B, and egr-1 were mapped in medial preoptic area (MPOA) and ventral bed nucleus of stria terminalis (VBST) during maternal behavior in rats. Immunocytochemical analysis indicated significant increases in the number of cells expressing c-Fos after 2 h of pup exposure, while Fos B levels showed a delayed response, reaching maximal levels after 6 h.     

Transglutaminase in cell proliferation and transformation

Transglutaminase (TGase) activity was reduced in intact mitogen-stimulated human peripheral blood lymphocytes (PBL) when compared to intact resting PBL. Moreover, a treatment of the same quiescent immunocompetent cells with purified liver TGase and Ca²⁺ completely suppressed the mitogen-induced blast transformation. A decrease in TGase activity in neoplastically transformed seminal vesicle epithelial cells with respect to their normal parent counterpart was also observed. Our data support the notion of a possible implication of TGase in cell proliferation and transformation.     

Attachment and spreading of fibroblasts on an RGD peptide-modified injectable hyaluronan hydrogel

Hyaluronan (HA) hydrogels resist attachment and spreading of fibroblasts and most other mammalian cell types. A thiol-modified HA (3,3'-dithiobis(propanoic dihydrazide) [HA-DTPH]) was modified with peptides containing the Arg-Gly-Asp (RGD) sequence and then crosslinked with polyethylene glycol (PEG) diacrylate (PEGDA) to create a biomaterial that supported cell attachment, spreading, and proliferation. The hydrogels were evaluated in vitro and in vivo in three assay systems. First, the behavior of human and murine fibroblasts on the surface of the hydrogels was evaluated. The concentration and structure of the RGD peptides and the length of the PEG spacer influenced cell attachment and spreading. Second, murine fibroblasts were seeded into HA-DTPH solutions and encapsulated via in situ crosslinking with or without bound RGD peptides. Cells remained viable and proliferated within the hydrogel for 15 days in vitro. Although the RGD peptides significantly enhanced cell proliferation on the hydrogel surface, the cell proliferation inside the hydrogel in vitro was increased only modestly. Third, HA-DTPH/PEGDA/peptide hydrogels were evaluated as injectable tissue engineering materials in vivo. A suspension of murine fibroblasts in HA-DTPH was crosslinked using PEGDA plus PEGDA peptide, and the viscous, gelling mixture was injected subcutaneously into the flanks of nude mice; gels formed in vivo following injection. After 4 weeks, growth of new fibrous tissue had been accelerated by the sense RGD peptides. Thus, attachment, spreading, and proliferation of cells is dramatically enhanced on RGD-modified surfaces but only modestly accelerated in vivo tissue formation.     

Comparative genomic hybridization of 49 primary retinoblastoma tumors identifies chromosomal regions associated with histopathology,progression, and patient outcome

Forty-nine primary retinoblastoma (Rb) tumors were analyzed by the use of comparative genomic hybridization (CGH), and clinical/histological correlations were performed. Adverse histological factors were present in 13 patients. Chromosomal imbalance was a frequent phenomenon, seen in 96% of the tumors. Gain of 6p represented the most frequent event (69% of the tumors), whereas +1q was observed in 57%, confirming that these abnormalities are key secondary events in retinoblastoma tumor progression. Loss of 13q and 16 was significantly associated with tumors displaying adverse histo-prognostic factors, whereas -16q was significantly associated with tumors without adverse features. In three patients who developed an extra-ocular relapse, the tumors showed -13q and 2/3 had -5q, suggesting that these abnormalities may be associated with metastasis. Children >or= 36 months of age at enucleation tended to have more CGH abnormalities per tumor than children < 12 months (median numbers 11 vs. 3). In addition, +1q, +13q, -16, and -16q were more frequent in children with an older age at enucleation. Identical CGH changes were found in both tumors from one patient with bilateral tumors, suggesting a common origin. It is possible that tumors displaying loss of 13q and 5q indicate those patients who may suffer an adverse outcome and who would require alternative or more intensive therapy. CGH analysis on larger cohorts and in prospective clinical trials will be invaluable in determining whether a genetic classification of retinoblastoma represents a reliable measure of prognosis.     

Outbreak of Saccharomyces cerevisiae subtype boulardii fungemia in patients neighboring those treated with a probiotic preparation of the organism

We report an outbreak of Saccharomyces cerevisiae subtype boulardii fungemia among three intensive care unit roommates of patients receiving lyophilized preparations of this fungus. The fungemia was probably due to central venous catheter contamination and resolved after fluconazole treatment. The need for stringent application of proper hygiene when using a probiotic preparation of this organism is emphasized.