Acute neurite retraction triggered by lysophosphatidic acid: timing of the inhibitory effects of genistein

Acute neurite retraction, elicited by diverse agents in several neuronal cell types, has been reported to be inhibited by genistein, a kinase antagonist that is relatively (though not absolutely) selective for tyrosine kinases. It was hypothesized that genistein acts upon ssome final common pathway that integrates multiple extrinsic and intrinsic signals to regulate whether neurites will execute a retraction response (J. Neurochem., 61 (1993) 340–343). To define this pathway in more detail, a quantitative study of NG108-15 cell rapid-onset neurites was carried out as they retract in response to lysophosphatidic acid (LPA, 10 μM). Following the application of LPA, most neurites exhibited early morphologic changes between 0.5 and 1.5 min, followed by progressive shortening and eventual retraction, with 50% of neurites completely retracted by 5 min and 80% gone by 10 min. Genistein did not inhibit the formation of subcortical F-actin, nor its functional competence in several assays. Genistein protected neurites when added at any time prior to the onset of the earliest morphologic changes, but failed to block progression when added to neurites that were already undergoing retraction. These findings imply that the final common pathway (i.e. the critical target(s) for genistein) must be activated late, after the increase in F-actin levels has peaked and just before retraction is initiated.     

Prospective clinical and histological study to evaluate the efficacy and safety of a targeted high-intensity narrow band UVB/UVA1 therapy for striae alba.

OBJECTIVE: The purpose of this study was to determine the efficacy and safety of a targeted narrow band UVB/UVA1 therapy for the treatment of striae alba. METHODS: Fourteen individuals with skin types II-VI were enrolled in this 22-week trial that consisted of up to 10 treatments with a combination of UVB/UVA1 (MultiClear, Curelight Ltd, Israel). Participants were treated with a maximum of 10 treatments unless 100% repigmentation of stretch was achieved prior to the tenth treatment. Biopsies were taken from willing participants at baseline, immediately after the final treatment and 12 weeks after the last treatment. RESULTS: Nine participants completed all treatment visits. After the final treatment, all the participants had >51% repigmentation of the treated striae. At the 4-week follow-up visit, 67% of participants had greater than 51% improvement, and 56% had greater than 51% improvement at the 8-week and 12-week follow-ups. Hyperpigmentation of striae was seen in >50% of the participants treated. The pretreatment biopsies were confirmatory of striae. There were no diagnostic light microscopic differences in the 4-week post-treatment biopsy set available in one patient. CONCLUSION: This high intensity UVB\UVA1 device is an effective and safe modality for the short-term repigmentation of hypopigmented stretch marks. Additional morphologic studies over time are needed to confirm these clinical findings.     

Septal-lateral annnular cinching perturbs basal left ventricular transmural strains.

OBJECTIVE: Septal-lateral annular cinching ('SLAC') corrects both acute and chronic ischemic mitral regurgitation in animal experiments, which has led to the development of therapeutic surgical and interventional strategies incorporating this concept (e.g., Edwards GeoForm ring, Myocor Coapsys, Ample Medical PS3). Changes in left ventricular (LV) transmural cardiac and fiber-sheet strains after SLAC, however, remain unknown. METHODS: Eight normal sheep hearts had two triads of transmural radiopaque bead columns inserted adjacent to (anterobasal) and remote from (midlateral equatorial) the mitral annulus. Under acute, open chest conditions, 4D bead coordinates were obtained using videofluoroscopy before and after SLAC. Transmural systolic strains were calculated from bead displacements relative to local circumferential, longitudinal, and radial cardiac axes. Transmural cardiac strains were transformed into fiber-sheet coordinates (X(f), X(s), X(n)) oriented along the fiber (f), sheet (s), and sheet-normal (n) axes using fiber (alpha) and sheet (beta) angle measurements. Results: SLAC markedly reduced (approximately 60%) septal-lateral annular diameter at both end-diastole (ED) (2.5+/-0.3 to 1.0+/-0.3 cm, p=0.001) and end-systole (ES) (2.4+/-0.4 to 1.0+/-0.3 cm, p=0.001). In the LV wall remote from the mitral annulus, transmural systolic strains did not change. In the anterobasal region adjacent to the mitral annulus, ED wall thickness increased (p=0.01) and systolic wall thickening was less in the epicardial (0.28+/-0.12 vs 0.20+/-0.06, p=0.05) and midwall (0.36+/-0.24 vs 0.19+/-0.11, p=0.04) LV layers. This impaired wall thickening was due to decreased systolic sheet thickening (0.20+/-0.8 to 0.12+/-0.07, p=0.01) and sheet shear (-0.15+/-0.07 to -0.11+/-0.04, p=0.02) in the epicardium and sheet extension (0.21+/-0.11 to 0.10+/-0.04, p=0.03) in the midwall. Transmural systolic and remodeling strains in the lateral midwall (remote from the annulus) were unaffected. CONCLUSIONS: Although SLAC is an alluring concept to correct ischemic mitral regurgitation, these data suggest that extreme SLAC adversely effects systolic wall thickening adjacent to the mitral annulus by inhibiting systolic sheet thickening, sheet shear, and sheet extension. Such alterations in LV strains could result in unanticipated deleterious remodeling and warrant further investigation.     

The clinical nurse leader: a response from practice.

In October 2003, over 200 nurse leaders from education and practice met at the invitation of the American Association of Colleges of Nursing. A newly released white paper, describing the role of the clinical nurse leader, was discussed at the conference. This article outlines a response to that white paper from one practice setting. The article shares information about another role, that of team coordinator, that is similar to clinical nurse leader and has been implemented at an integrated not-for-profit health care system in 5 hospitals. The comparison of the team coordinator role to the clinical nurse leader role might assist in visualizing such a role in practice. Although the roles are not identical, many of the driving forces for change were similar; these included the need to meet the changing demands for improved patient outcomes and nurse retention. The team coordinator role has 4 domains of practice that are crosswalked against the clinical nurse leader 15 core competencies. An evaluation of the team coordinator role showed changes that need to be made, such as placing more emphasis on clinical progression of patients. Lessons learned are shared, including keeping the scope of the role manageable, providing documentation standards for new roles, and the leadership required of the nursing executive to implement change.     

How does the mode of inheritance of a genetic condition influence families? A study of guilt,blame, stigma,and understanding of inheritance and reproductive risks in families with X-linked and autosomal recessive diseases

PURPOSE: While the mode of inheritance of a genetic condition has long been considered to have not only medical, but also psychosocial consequences for families, this supposition has never been tested. METHODS: We surveyed 112 members of 51 families (59% response) with chronic granulomatous disease to determine the influence of mode of inheritance on parents', siblings', and patients' (1) knowledge of inheritance and reproductive risk; (2) concern about risk to future family-members; (3) feelings of guilt and blame; and (4) feelings of stigmatization. Ninety-six members of 51 families (49% response) with Duchenne/Becker muscular dystrophy and spinal muscular atrophy types II/III were also studied. RESULTS: X-linked families had better understanding of inheritance (P < 0.001) and reproductive risks (P < 0.01). X-linked mothers worried more about risks to future generations; other autosomal-recessive family members were as worried. X-linked mothers were more likely to feel guilty (P < 0.01) and blame themselves (P < 0.001). X-linked fathers blamed their child's mother (P < 0.05) and X-linked mothers felt more blamed by the father (P < 0.01). X-linked family-members were more likely to consider being a carrier stigmatizing (P < 0.05). CONCLUSION: When providing genetic counseling, attention should be given to guilt and blame in X-linked families and understanding reproductive risks in autosomal recessive families.     

Ten-year trends in neonatal assisted ventilation of very low-birthweight infants.

OBJECTIVES: To examine ventilatory support for the VLBW infant over the past 10 years in a single academic NICU and determine factors that predicted length of ventilation, death, and CLD. STUDY DESIGN: A retrospective cohort review of neonatal blood gases, ventilatory support, and clinical outcomes. RESULTS: From 1992 through October 2002, 6254 infants were admitted, of whom 2388 required intubation for mechanical ventilation. Of these, 837 were <1500 g at birth (VLBW) infants and 453 were less than 1000 g (ELBW). Total duration of ventilation decreased in all weight groups. Noninvasive ventilatory support increased from 20 to 55% of total ventilation from 1997 to 2002. During this same period, CLD decreased from 20 to 11% in ventilated VLBW infants. Duration of total ventilation was best predicted by birth weight, with each 100 g increment decreasing the duration of ventilation by 71 hours. Lower birth weight, male sex, and a longer total duration of ventilatory support were significant factors in predicting the occurrence of CLD. Death alone was best predicted by lower birth weight and maximum oxygen index (OI). Transported infants had significantly increased maximal OIs, durations of ventilation, and incidence of death. A total of 48% of infants with a single OI >10 either died or survived with CLD. CONCLUSIONS: Birth weight is the best predictor of duration of ventilation, and CLD is best predicted by birth weight, duration of ventilation and male sex. The increasing use of noninvasive strategies has not been associated with an observable increase in respiratory morbidity. VLBW infants with a single OI>10 may benefit from inclusion in future interventional rescue studies.     

Tamponade caused by cardiac lipomatous hypertrophy.

Cardiac lipomatous hypertrophy is an unusual disorder that typically affects the interatrial septum. We report a case in which large subpericardial deposits of fat were initially mistaken for a pericardial effusion and the subsequent clinical picture resembled tamponade. The patient improved following a pericardiectomy.     

How brief is solution focussed brief therapy? a comparative study

Solution Focused Brief Therapy (SFBT) focuses on clients' strengths and expressed goals in an attempt to produce therapeutic change as quickly as possible. This study examined whether clients seen for SFBT were seen for fewer sessions than those seen for cognitive behaviour therapy (CBT) in a clinical psychology service taking adult referrals from primary care. The study was a retrospective one using pseudo-randomization. The results indicated that SFBT clients (n = 41) were seen for two sessions on average compared to five for CBT (n = 119). This difference was accounted for by a higher proportion of the SFBT group being seen for one session only, which is consistent with the approach. A simple therapist-rated outcome scale showed no significant difference between the two groups. Copyright © 2005 John Wiley & Sons, Ltd.