Resolution of skin fibrosis and joint contractures in aggressive diffuse systemic sclerosis using autologous stem cell transplantation

The use of haematopoietic stem cell transplantation (HSCT) has now expanded beyond the domain of haematological diseases. Increasingly, the benefits of intense immunosuppression in the management of severe autoimmune diseases are being recognized. In diffuse systemic sclerosis (SSc), there has been increasing evidence of the efficacy of HSCT in improving morbidity and mortality. We present the first Australian patient to undergo autologous HSCT for SSc and review the current literature in the use of HSCT in SSc. Remarkably, the patient had complete resolution of skin disease (modified Rodnan skin score 27/51–0/51), tenosynovitis, synovitis and myositis.     

Influence of statins on postoperative wound complications after inguinal or ventral herniorrhaphy

The lipid-lowering agents, statins, are the most commonly prescribed class of drugs in the western world. Because of their widespread use, many patients undergo surgical procedures while on statins. Statins, in addition to cholesterol-lowering effects, also have anticoagulant, immunosuppressive, and antiproliferative properties that may affect the risk of local wound complications. This study investigated the relationship between statins and postoperative wound complications in a large cohort of patients undergoing inguinal or ventral hernia repair. Data mining was performed in the Veterans Integrated Service Network (VISN)16 Data Warehouse. This database contains clinical and demographic information about all veterans cared for at the ten VA Medical Centers that comprise the South Central VA Healthcare Network in the mid-south region of the US. Aggregate data (age, body mass index, smoking history, gender, race, history of diabetes, statin use, and postoperative wound complications) were obtained for all patients who underwent inguinal or ventral hernia repair during the period October 1, 1996–November 30, 2004. During the period of the query, 10,782 patients (10,676 male, 106 female), 1,242 (11.5%) of whom received statins, underwent herniorrhaphy. Statin use did not affect the risk of wound infection or delayed wound healing. Statin use was, however, associated with an increased rate of local postoperative bleeding complications (P=0.01). When the type of hernia, age, smoking, diabetes, and body mass index were included in a multivariate analysis, statins remained borderline significant as an independent predictor of wound hematoma/postoperative bleeding (P=0.04), odds ratio 1.6 (95% CI 1.03–2.44). Patients who undergo inguinal herniorrhaphy while on statins have an increased risk of postoperative wound hematoma/hemorrhage. Focus on additional factors that may affect the propensity to postoperative bleeding and on meticulous intraoperative hemostasis are particularly important in such patients.     

Sequential comparison of low dose rate and hyperfractionated high dose rate endobronchial radiation for malignant airway occlusion.

A pilot trial (S2) was conducted at the University of Wisconsin to determine the feasibility, efficacy, and toxicity of hyperfractionated high dose rate endobronchial radiation. To avoid multiple bronchoscopies, an optimized hyperfractionated schema was derived from the linear-quadratic model. Utilizing a single bronchoscopy, 31 patients with malignant airway occlusion received 4 Gy x 4 fractions over 2 days at 2 cm from source center using a high dose rate remote afterloader. Response and morbidity were compared to a previous trial (S1) in which 66 patients were treated with conventional low dose rate endobronchial radiation. Response was assessed by change in performance status, symptom resolution, percent of lifetime rendered symptom-free or improved, and radiographic reaeration. These parameters were highly comparable between the two groups. The mean ECOG performance status improved from 2.2 to 1.8 for S1 and 2.1 to 1.6 for S2; symptom improvement or resolution was noted in 78% for S1 and 79% for S2; lifetime rendered symptom-free or improved was 54% for S1 and 57% for S2; and the overall radiographic response rate was 78% for S1 and 85% for S2. The overall incidence of fistulae was 7/101. We conclude that endobronchial radiation is an effective and safe modality for palliation, and hyperfractionated high dose rate endobronchial radiation achieves responses similar to low dose rate endobronchial radiation with a similar complication rate.     

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.