Michael J. Terry

Repair of palatal bone defects using osteogenically differentiated fat-derived stem cells.

Background: Although autogenous bone grafting remains the standard in the reconstruction of bone defects, disadvantages may include limited amount of bone and donor-site morbidity. Tissue engineering approaches can potentially obviate these problems. Fat contains a population of stem cells that can be isolated and differentiated into various cell lines, including osteocytes, adipocytes, and myocytes, depending on the culture conditions. In this study, the authors used osteogenically differentiated fat-derived stem cells to repair rat palatal bone defects. Methods: Fat-derived stem cells were isolated, differentiated into osteocytes in osteogenic medium, and seeded onto poly-L-lactic acid scaffolds. Rat palatal bone defects were surgically made and animals divided into four groups according to the type of implant for bone repair: group I, empty defect; group II, poly-L-lactic acid without cells; group III, poly-L-lactic acid with undifferentiated fat-derived stem cells; and group IV, poly-L-lactic acid with osteogenically differentiated fat-derived stem cells. Palates were harvested at 6 or 12 weeks after implantation (n = 8 per group at each time interval). Hematoxylin and eosin staining, immunohistochemical staining for osteocalcin, and histomorphometric measurements of new bone were performed. Results: Defects in groups I, II, and III had no bone and were primarily filled with fibrous tissue. In contrast, there was substantial bone regeneration in group IV, which was statistically significant by histomorphometry compared with groups I, II, and III. Newly formed bone in group IV stained positive for osteocalcin. Conclusions: The authors successfully reconstructed palatal bone defects using absorbable three-dimensional scaffolds seeded with osteogenically differentiated fat-derived stem cells. This study demonstrates the feasibility of reconstructing bony defects with fat-derived stem cells.

HOX gene clusters are hotspots of de novo methylation in CpG islands of human lung adenocarcinomas

CpG island methylation results in the silencing of the associated gene and is an important step in tumorigenesis. Following a comprehensive isolation of CpG islands that were methylated in human lung adenocarcinoma, we found that in cancer cells de novo CpG island methylation generally occurred in a sporadic manner. However, some methylated CpG islands appeared to cluster in discrete chromosomal regions. In this study, we have investigated the methylation status of CpG islands located at such chromosomal loci. We have found that many CpG islands at the HOXA and HOXD loci were methylated in human lung adenocarcinoma. The de novo methylation of these CpG islands was also observed in patients DNA from noncancerous portions of lung tissue. These results indicate the presence of specific chromosomal regions that are susceptible to de novo methylation.

A comprehensive catalog of CpG islands methylated in human lung adenocarcinomas for the identification of tumor suppressor genes

CpG island methylation is an important mechanism in gene silencing and is a key epigenetic event in cancer development. As yet, the number and identities of the genes that are inactivated in cancer cells has not been determined. In order to address this issue, we have performed a comprehensive isolation of CpG islands that are methylated in human lung adenocarcinomas. We have isolated approximately 200 CpG islands that are methylated in tumor DNA including those of known tumor-associated genes such as the HOXA5 gene. As the library contains the CpG islands of a number of known tumor suppressor genes it is highly likely that additional, previously unidentified tumor suppressor genes, will be present. On average, 1–2% of CpG islands were methylated specifically in tumors although this figure differed greatly between patients. This study provides an important resource in the search for genes inactivated in tumors and for the investigation of epigenetic dysregulation of gene expression by CpG island methylation.

Lentiviral gene therapy with platelet-derived growth factor B sustains accelerated healing of diabetic wounds over time.

The treatment of diabetic wounds is a formidable clinical challenge. In this study, lentiviral vectors carrying the human platelet-derived growth factor B (PDGF-B) gene were used to treated diabetic mouse wounds. Full-thickness 2.0-cm × 2.0-cm excisional wounds were created on the dorsa of genetically diabetic C57BL/KsJ-m+/+Leprdb mice. Lentiviral vectors containing the PDGF-B gene were injected into the wound margins and base. Mice were killed at 14-, 21-, and 35-day intervals. Measurement of the residual epithelial gap showed a trend towards increased healing in lentiviral PDGF-treated wounds compared with untreated and saline-treated wounds at all time points. At 21 days, there was significantly increased healing in lentiviral PDGF-treated wounds (0.98 ± 0.17 cm) compared with saline-treated wounds (1.22 ± 0.30 cm; P < 0.05). Immunohistochemistry for CD31 revealed significantly increased neovascularization in lentiviral PDGF-treated wounds compared with untreated and saline-treated wounds at 14 and 21 days (P < 0.01). Picrosirius red staining demonstrated thicker and more highly organized collagen fibers in treated wounds compared with untreated and saline-treated wounds. Quantitative analysis of collagen content showed a 3.5-fold and 2.3-fold increase in lentiviral PDGF-treated wounds versus untreated and saline-treated wounds, respectively (P < 0.01). Lentiviral gene therapy with PDGF-B can sustain diabetic wound healing over time and may possess promising potential in the clinical setting.

Use of face masks by non‐scrubbed operating room staff: a randomized controlled trial

Background:  Ambiguity remains about the effectiveness of wearing surgical face masks. The purpose of this study was to assess the impact on surgical site infections (SSIs) when non‐scrubbed operating room staff did not wear surgical face masks.

Hueston Revisited: Use of Acellular Dermal Matrix Following Fasciectomy for the Treatment of Dupuytren's Disease

AbstractVarious surgical treatment modalities have been advocated for the treatment of Dupuytren’s disease. However, recurrence following surgical treatment of Dupuytren’s disease remains a common problem. Previous studies have demonstrated lower recurrence rates with use of a full-thickness skin graft. We therefore postulated that use of acellular dermal matrix may be associated with a similar outcome, based on the common inhibitory effect on underlying myofibroblasts. We performed a retrospective cohort study of 43 patients undergoing open fasciectomy for Dupuytren’s disease from years 2005 to 2012 at our academic institution. Standard fasciectomies of the affected palmar and digital fascia were performed via Brunner incisions on all patients. Patients in the experimental group had a sheet of acellular dermal matrix (Alloderm; LifeCell, Bridgewater, NJ) sutured into the surgical bed with interrupted absorbable sutures before closure, whereas patients in the control group were not closed with acellular dermal matrix. Patients were then evaluated at follow-up for disease recurrence, defined as presence of Dupuytren’s tissue in an area previously operated on with a contracture greater than that recorded following the surgical fasciectomy, or presence of contracture requiring surgery. Among our cohort of 43 patients, 23 (53.5%) were treated with acellular dermal matrix while 20 (46.5%) were not. The median age of our cohort was 66.5 years (range 54–91 years). The median follow-up was 1.8 years. During this follow-up period, recurrence of contracture was observed in 1 of 23 patients in the group receiving acellular dermal matrix, compared to 5 of 20 in the control group (P = 0.045). No differences in the incidence of minor wound complications were observed. Our novel technique of placement of acellular dermal matrix into the wound bed following fasciectomy for Dupuytren’s disease may be an important surgical strategy to reduce recurrence rates in patients with Dupuytren’s disease.

Obstacles to the Care of Patients With Multicomponent Volar Wrist Lacerations at a County Hospital.

BackgroundMulticomponent volar wrist lacerations of “spaghetti wrist” injuries are devastating injuries of the upper extremity. These patients require long-term commitment to rehabilitation. Patients presenting to our county hospital represent a unique and complex patient population in terms of psychosocial considerations. We aimed to identify obstacles to care and optimal recovery in this patient population. MethodsA patient database was queried for ICD-9 codes related to major upper extremity nerve injuries, which were treated by plastic surgery faculty at San Francisco General Hospital from 2008 to 2014. A retrospective chart review was performed to identify patients with spaghetti wrist injuries. Charts were reviewed for patient demographics including age, occupation, handedness, psychiatric illness, isolated versus polytrauma, and employment status. Injuries were categorized for mechanism of injury, structures involved, and timing and method of surgical treatment. Outcomes were assessed for motor recovery, sensory recovery, and tendon function. ResultsWe identified 18 patients with multicomponent volar wrist lacerations. Average patient age was 31 years. The most common mechanism of injury was accidental/work-related (n = 9, 50%), followed by self-inflicted (n = 4, 22%). Thirty-nine percent (n = 7) of patients had a psychiatric diagnosis, most commonly depression (n = 4, 22%). Eighty-nine percent (n = 16) of patients had an isolated injury to the upper extremity, and 39% (n = 7) had an injury to the dominant hand. Fifty percent (n = 9) of patients were lost to follow-up, with 28% (n = 5) having no known care plan. Motor, sensory, and tendon function outcomes for those with adequate follow-up were comparable to previously published studies. DiscussionMulticomponent volar wrist lacerations can be devastating, and although we are able to provide patients with appropriate timely surgical care, these patients require long-term care far beyond the operating room for optimal outcomes. Psychiatric illness, socioeconomic limitations, poor patient compliance, and irregular follow-up are obstacles to care. These issues highlight the need for better social support systems and mental health care to provide access to the services necessary to optimize recovery.

A Case of Unilateral Coronal Synostosis in a Child With Craniofacial Microsomia

Craniofacial microsomia is a congenital malformation complex associated with a wide array of craniofacial and extracraniofacial anomalies. Frontal plagiocephaly has been shown to occur in approximately 5% to 12% of patients with craniofacial microsomia. The etiology of craniofacial microsomia–associated frontal plagiocephaly is unclear; of the cases described in the literature, all but one had physical findings suggestive of deformational plagiocephaly. In the case with equivocal physical findings, radiographic studies showed no evidence of craniosynostosis. Unlike the above cases, we report a documented case of radiologically-confirmed unilateral coronal synostosis in a child with craniofacial microsomia.

Erratum: A comprehensive catalog of CpG islands methylated in human lung adenocarcinomas for the identification of tumor suppressor genes (Oncogene (2002) 21 (3804-3813))

Correction to: Oncogene (2002) 21, 2309–2319.doi:10.1038/sj.onc.1205297 Since the publication of the above paper, the authors have identified errors in the spelling of their names and E-mail address. The correct spellings are shown on the left in each instance below:David TULASNE not David TULASHE,Sylvie REVENEAU not Syline REVENEAU,veronique.