Femoral head injuries: Which treatment strategy can be recommended?

Despite different operative and non-operative treatment regimens, the outcome after femoral head fractures has changed little over the past decades. The initial trauma itself as well as secondary changes such as posttraumatic osteoarthritis, avascular necrosis or heterotopic ossification is often responsible for severe loss of function of the afflicted hip joint. Anatomic reduction of all fracture fragments seems to be a major influencing factor in determining the outcome quality. Eight years ago we inaugurated a new surgical approach for better access and visualisation for the treatment of femoral head fractures, using the "trochanteric flip" (digastric) osteotomy. Thus inspection of the entire hip joint and accurate fragment reduction under direct visual control are possible. After good initial experiences with this operative procedure we changed our standard treatment regimen to this approach in an attempt to achieve the most accurate anatomic reduction of the femoral head in every affected patient. Between 1998 and 2006 we operated on 12 patients with femoral head fractures associated with posterior hip dislocation, using the new surgical approach. Patients were followed for 2-96 months and outcome was documented with the Merle d'Aubigne and Postel score as well as the Thompson and Epstein score. The posttraumatic formation of heterotopic bone was documented with the Brooker score. Retrospective analysis of these 12 patients showed good or excellent results in 10 patients (83.3%). The two patients with poor outcome developed an avascular necrosis of the femoral head and underwent total hip arthroplasty. Periarticular heterotopic ossification was seen in five patients. In four patients this caused a significantly reduced range of motion and was therefore considered as a posttraumatic complication. The two patients with the most severe heterotopic bone formation (Brooker III and IV) had initially sustained multiple injuries including brain injury. Comparing our results with earlier published series including our own before changing the treatment protocol, the data suggest a favorable outcome in patients with trochanteric flip (digastric) osteotomy for the treatment of femoral head fractures.

Cardiovascular risk factors impair native collateral development and may impair efficacy of therapeutic interventions

Animal and early clinical studies of gene therapy for tissue ischaemia suggested that this approach might provide benefit to patients with coronary artery disease not amenable to traditional revascularization. This enthusiasm was then tempered by the subsequent disappointing results of randomized clinical trials and led researchers to develop strategies using progenitor cells as an alternative to improve collateral function. However, the recent publication of several randomized clinical trials reporting either negative or weakly positive results using this approach have led to questions regarding its effectiveness. There are several factors that need to be considered in explaining the discordance between the positive studies of such treatments in animals and the disappointing results seen in randomized patient trials. Aside from the practical issues of arteriogenic therapies, such as effective delivery, vascular remodelling is an extraordinarily complex process, and the administration of a single agent or cell in the hope that it would lead to lasting physiological effects may be far too simplistic an approach. In addition, however, evidence now suggests that many of the traditional cardiovascular risk factors-such as age and hypercholesterolemia-may impair the host response not only to ischaemia but, critically, also to treatment as well. This review discusses the evidence and mechanisms for these observations and highlights future directions that might be taken in an effort to provide more effective therapies.

Severe phenotype with cis-acting heterozygous PMP22 mutations

We report on a 20-year-old male with severe Charcot-Marie-Tooth (CMT) disease and a de novo deletion (c.281delG, p.G94AfsX17) on the paternal PMP22 allele harboring c.353C>T (p.T118M). RNA-based sequence analysis confirmed the absence of nonsense-mediated decay and the presence of the mutant transcripts in Epstein-Barr virus-transformed lymphoblastoid cells of our patient. His clinical findings included early onset of polyneuropathy, loss of muscle mass with distal pareses, hammer toes, and progressive scoliosis. There was no neuropsychological alteration. Our results suggest that the deletion c.281delG alone is responsible for the severe CMT phenotype. To the best of our knowledge, this is the second report on a proven paternal origin of a de novo single-base mutation in the PMP22 gene.

Orbitale Fettgewebsatrophie bei lokaler Bimatoprost-Therapie - Kann Bimatoprost einen Enophthalmus verursachen?

PURPOSE: The aim of this communication is to report enophthalmos as a possible new adverse effect of topical bimatoprost treatment. PATIENTS AND METHODS: A retrospective case series of five glaucoma patients under long-term topical bimatoprost treatment was evaluated. Documentation with photo and Hertel exophthalmometry was reviewed. RESULTS: In all five patients a deep lid sulcus, reduced infraocular fat pads and enophthalmos-suspicious Hertel values were found (mean 11.9 mm; SD 2.4). Other aetiologies for enophthalmos were excluded anamnestically and by clinical examination. CONCLUSION: Bimatoprost may lead to an alteration of the eyelid with deepening of the lid sulcus and may also be responsible for an iatrogenic orbital fat atrophy. A possible mechanism of action might be the induction of apoptosis of orbital fibroblasts with a remodelling of the extracellular matrix. Prospective studies are necessary to confirm this cross-sectional observation.

Arctic patterned-ground ecosystems: A synthesis of field studies and models along a North American Arctic Transect

Arctic landscapes have visually striking patterns of small polygons, circles, and hummocks. The linkages between the geophysical and biological components of these systems and their responses to climate changes are not well understood. The "Biocomplexity of Patterned Ground Ecosystems" project examined patterned-ground features (PGFs) in all five Arctic bioclimate subzones along an 1800-km trans-Arctic temperature gradient in northern Alaska and northwestern Canada. This paper provides an overview of the transect to illustrate the trends in climate, PGFs, vegetation, n-factors, soils, active-layer depth, and frost heave along the climate gradient. We emphasize the thermal effects of the vegetation and snow on the heat and water fluxes within patterned-ground systems. Four new modeling approaches build on the theme that vegetation controls microscale soil temperature differences between the centers and margins of the PGFs, and these in turn drive the movement of water, affect the formation of aggradation ice, promote differential soil heave, and regulate a host of system propel-ties that affect the ability of plants to colonize the centers of these features. We conclude with an examination of the possible effects of a climate wan-ning on patterned-ground ecosystems.

Coronary artery injury due to catheter ablation in adults: presentations and outcomes

BACKGROUND: Currently, only anecdotal information exists on the presentation and outcome of coronary arterial injury after ablation procedures. METHODS AND RESULTS: Four patients who sustained coronary artery injury of a cohort of patients undergoing 4655 consecutive ablation procedures (0.09%) are described. The patients' mean age was 45+/-11 years, and 1.8+/-0.5 prior ablation attempts had been unsuccessful. Coronary injury occurred from epicardial ventricular tachycardia ablation in 2 patients (irrigated radiofrequency ablation in one and cryoablation in the other) and ablation within the middle cardiac vein with irrigated radiofrequency in 2 patients. All involved branches of the right coronary artery. Acute occlusion presenting with ST-segment elevation immediately after ablation was recognized during the procedure in 2 cases. Occlusion failed to respond to nitroglycerin or balloon dilation, and stenting was required in both cases. Acute myocardial infarction occurred 2 weeks after epicardial ablation as a result of occlusion of a right ventricular branch of the right coronary artery giving rise to the posterior descending coronary artery in 1 patient. A moderate asymptomatic stenosis was seen on angiography after epicardial cryoablation in 1 patient. All patients recovered and remained asymptomatic from the coronary injury and arrhythmias during 37+/-53 months of follow-up. CONCLUSIONS: Coronary arterial injury after ablation procedures is rare. It may present acutely or several weeks after an ablation procedure. Acute occlusion appears to require coronary stenting. Unanticipated anatomic variations can predispose to coronary injury.

Gene therapy for immunodeficiency due to adenosine deaminase deficiency

BACKGROUND: We investigated the long-term outcome of gene therapy for severe combined immunodeficiency (SCID) due to the lack of adenosine deaminase (ADA), a fatal disorder of purine metabolism and immunodeficiency. METHODS: We infused autologous CD34+ bone marrow cells transduced with a retroviral vector containing the ADA gene into 10 children with SCID due to ADA deficiency who lacked an HLA-identical sibling donor, after nonmyeloablative conditioning with busulfan. Enzyme-replacement therapy was not given after infusion of the cells. RESULTS: All patients are alive after a median follow-up of 4.0 years (range, 1.8 to 8.0). Transduced hematopoietic stem cells have stably engrafted and differentiated into myeloid cells containing ADA (mean range at 1 year in bone marrow lineages, 3.5 to 8.9%) and lymphoid cells (mean range in peripheral blood, 52.4 to 88.0%). Eight patients do not require enzyme-replacement therapy, their blood cells continue to express ADA, and they have no signs of defective detoxification of purine metabolites. Nine patients had immune reconstitution with increases in T-cell counts (median count at 3 years, 1.07x10(9) per liter) and normalization of T-cell function. In the five patients in whom intravenous immune globulin replacement was discontinued, antigen-specific antibody responses were elicited after exposure to vaccines or viral antigens. Effective protection against infections and improvement in physical development made a normal lifestyle possible. Serious adverse events included prolonged neutropenia (in two patients), hypertension (in one), central-venous-catheter-related infections (in two), Epstein-Barr virus reactivation (in one), and autoimmune hepatitis (in one). CONCLUSIONS: Gene therapy, combined with reduced-intensity conditioning, is a safe and effective treatment for SCID in patients with ADA deficiency. (ClinicalTrials.gov numbers, NCT00598481 and NCT00599781.)

Multicentric hepatic EBV-associated smooth muscle tumors in an AIDS patient: a case report, investigation of mTOR activation and review of the literature.

Epstein-Barr virus (EBV) - associated smooth muscle tumors (EBV-SMT) are a rare, recently recognized distinct group of mesenchymal tumors that develop exclusively in patients with immunosuppression. It is believed that tumorigenesis is, at least in part, through the activation of the Akt/mammalian target of rapamycin (mTOR) signal pathway. We describe the clinicopathologic and immunohistochemical features of a multifocal hepatic EBV-SMT in a 34-year-old acquired immunodeficiency syndrome (AIDS) patient and investigate the activation status of the mTOR signal pathway in this tumor. In addition, we provide a review of the literature on the clinicopathologic findings of hepatic EBV-SMT in adult AIDS patients, and discuss their biologies and possible therapeutic strategies.

Unique structures in a tumor herpesvirus revealed by cryo-electron tomography and microscopy.

Gammaherpesviruses, including the human pathogens Epstein-Barr virus and Kaposi's sarcoma-associated herpesvirus, are causative agents of lymphomas and other malignancies. The structural characterization of these viruses has been limited due to difficulties in obtaining adequate amount of virion particles. Here we report the first three-dimensional structural characterization of a whole gammaherpesvirus virion by an emerging integrated approach of cryo-electron tomography combined with single-particle cryo-electron microscopy, using murine gammaherpesvirus-68 (MHV-68) as a model system. We found that the MHV-68 virion consists of distinctive envelope and tegument compartments, and a highly conserved nucleocapsid. Two layers of tegument are identified: an inner tegument layer tethered to the underlying capsid and an outer, flexible tegument layer conforming to the overlying, pleomorphic envelope, consistent with the sequential viral tegumentation process inside host cells. Surprisingly, comparison of the MHV-68 virion and capsid reconstructions shows that the interactions between the capsid and inner tegument proteins are completely different from those observed in alpha and betaherpesviruses. These observations support the notion that the inner layer tegument across different subfamilies of herpesviruses has evolved significantly to confer specific characteristics related to viral-host interactions, in contrast to a highly conserved capsid for genome encapsidation and protection.

The Weekly Adjustment Indicators Checklist: An Application in the Child Welfare Field

Research on the effectiveness of various home-based interventions implemented in the 1980s and 1990s indicates that results have been equivocal. Because of the unique and complex behavioral challenges presented by each family and the need for individualized treatments and long-term interventions for these families, group research and evaluation designs are often insufficient in assessing effectiveness of home-based interventions. Alternative evaluation strategies are needed. The purpose of this exploratory study was two-fold: (a) to investigate the applicability and acceptability of the Weekly Adjustment Indicators Checklist (WAIC) in monitoring adult and child behaviors and (b) to monitor, on an on-going basis, the progress of a family referred to an urban family preservation and reunification program. The target family on whom data were collected consisted of a 13-year old girl and her foster parent who was her maternal aunt. The findings of this study indicate that the WAIC is applicable in monitoring the progress of children and adults in care and that it has the endorsement of its user, namely, the direct care provider. Other results of the study, limitations of the study, and future research needs are discussed.

Current Resources

Reviews of: Children Who Could Have Been: The Legacy of Child Welfare in Wealthy America. (1999) William M. Epstein Madison, Wisconsin: University of Wisconsin Press Reviewed by: Leroy H Pelton Skills for Families Skills for Life. (1999) Linda M. Shadoin, Joni Cook-Griffin, and JaneL. Peterson. Nebraska: Boys Town Press. Reviewed by Shelley Leavitt Attachment Disorganization. (1999) J. and George C. Solomon, Eds. New York: The Guilford Press. Reviewed by Alice Chornesky Infants. Toddlers. and Families: A Framework for Support and Intervention. (1999) Martha Farrell Erickson and Karen Kurz-Riemer.New York: The Guilford Press.Reviewed by Halaevalu F. Vakalahi Solution-Based Casework: An Introduction to Clinical and Case Management Skills in Casework Practice. (1999) D. N. Christensen, J. Todahl, and W. C. Barrett New York: Aldine De Gruyter.Reviewed by Charles H Huber Childhood Sexual Abuse: An Evidence-Based Perspective. (1999) David M. Fergusson and Paul E. Mullen Thousand Oaks, Sage Publications, Inc.Reviewed by Elaine S. LeVine Spiritual Resources in Family Therapy. (1999) F. Walsh. New York: Guilford Press.Reviewed by David Derezotes

Family Preservation Journal, 1998, Volume 3, Issue 1. (Entire issue)

Entire issue (large pdf file) Articles include: The Role of Consistency and Diversity in Building Knowledge in Family Preservation. Debora J. Cavazos Dylla and Marianne Berry The Weekly Adjustment Indicators Checklist: An Application in the Child Welfare Field. Michael H. Epstein, Madhavi Jayanthi, Janet McKelvey, Deborah Holderness, Erin Frankenberry, Cassandra Lampkin, Molly McGrath, and Kari White Intensive Family Preservation Services: a Short History but a Long Past. Kellie B. Reed and Raymond S. Kirk Collaborative Conversations for Change: A Solution-Focused Approach to Family Centered Practice. Donald F. Fausel

Stability of specific immunoglobulin secretion by EBV-transformed lymphoblastoid cells and human-murine heterohybridomas

The purpose of this project was to determine if stability of specific antibody secretion improved after fusion of Epstein-Barr virus (EBV)-transformed lymphoblastoid cells with P3X63Ag8.653 murine myeloma cells. Production of human monoclonal antibodies by Epstein-Barr virus transformation and somatic cell fusion has been used by many laboratories, however the steps involved have not been fully optimized. B lymphocytes isolated from the peripheral blood of normal donors were enriched for Thomsen-Friedenreich (T) antigen-reactive cells by panning on asialoglycophorin. The EBV-transformed lymphoblastoid cell lines generated from asialoglycophorin-adherent B lymphocytes were treated in three different manners: (1) cloned and maintained in culture as monoclonal lymphoblastoid cell lines, (2) cloned and fused with murine myeloma cells or (3) fused shortly after transfomation without prior cloning. Cloned lymphoblastoid cell lines maintained in culture without fusion either died or lost specific antibody secretion within five months. Uncloned lymphoblastoid cells remained viable for up to three months but lost specific antibody secretion within two months probably due to overgrowth by nonspecific clones. In an attempt to increase longevity and to stabilize specific antibody secretion by these cells, the cloned lymphoblastoid cells were fused with murine myeloma cells. In nine of ten fusions no hybrids were recovered. As an alternate approach, uncloned lymphoblastoid cells secreting T antigen-specific antibody were hybridized with murine myeloma cells, hybrids secreting T antigen-specific antibody were recovered in six of seven fusions. Furthermore, T antigen-specific antibodies of high titer were secreted by the heterohybridoma clones for more than five months of continuous culture. These heterohybridoma cells secreted more immunoglobulin, produced greater titers of antibody and maintained specific antibody secretion longer than either monoclonal or polyclonal EBV-transformed lymphoblastoid cells. These studies have conclusively demonstrated that fusion of polyclonal lymphoblastoid cells secreting T antigen-specific antibody with murine myeloma cells results in prolongation of human monoclonal antibody production compared with unfused monoclonal or polyclonal lymphoblastoid cell lines. This procedure should be generally applicable for the production of stable human monoclonal antibody-secreting cells lines from peripheral blood lymphocytes. ^

A comparative assessment of endothelium from pseudophakic and phakic donor corneas stored in organ culture

AIMS To evaluate the endothelial quality of corneas obtained from pseudophakic donors and to compare the data with matched phakic controls. METHODS Corneas from eyes with posterior chamber intraocular lenses (PCIOLs) and corneas from phakic eyes (controls) were stored for 1-2 weeks in organ culture and then examined after staining with Alizarin red S. The corneas were divided into two groups according to the duration of storage. Endothelial cell density, the percentage of hexagonal cells, and the coefficient of variation (CV) were determined. RESULTS There was no statistically significant difference between the 14 PCIOL corneas and the 13 controls stored in organ culture for 7 days for any of the three parameters studied. The mean cell density was 2155 (SD 529) cells/mm(2) in the PCIOL corneas and 2118 (453) cells/mm(2) in the controls (p=0.85). The mean percentage of hexagonal cells was 52% (8%) and 58% (7%), respectively (p=0.06). The mean CV was 0.32 (0.18) in the pseudophakic corneas and 0.39 (0.18) in the controls (p=0.33). Moreover, there was no significant difference between the PCIOL corneas and the controls stored for up to 2 weeks. CONCLUSIONS The corneal endothelium from eyes with PCIOLs appears to be similar to that of phakic eyes after 1-2 weeks in organ culture. This finding suggests that corneas from pseudophakic eyes should not routinely be disqualified for transplantation. The use of at least some pseudophakic corneas may substantially increase the potential donor pool.