Obesity and surgical wound healing: a current review.

Objective. The correlation between obesity and deficient wound healing has long been established. This review examines the current literature on the mechanisms involved in obesity-related perioperative morbidity. Methods. A literature search was performed using Medline, PubMed, Cochrane Library, and Internet searches. Keywords used include obesity, wound healing, adipose healing, and bariatric and surgical complications. Results. Substantial evidence exists demonstrating that obesity is associated with a number of postoperative complications. Specifically in relation to wound healing, explanations include inherent anatomic features of adipose tissue, vascular insufficiencies, cellular and composition modifications, oxidative stress, alterations in immune mediators, and nutritional deficiencies. Most recently, advances made in the field of gene array have allowed researchers to determine a few plausible alterations and deficiencies in obese individuals that contribute to their increased risk of morbidity and mortality, especially wound complications. Conclusion. While the literature discusses how obesity may negatively affect health on various of medical fronts, there is yet to be a comprehensive study detailing all the mechanisms involved in obesity-related morbidities in their entirety. Improved knowledge and understanding of obesity-induced physiological, cellular, molecular, and chemical changes will facilitate better assessments of surgical risks and outcomes and create efficient treatment protocols for improved patient care of the obese patient population.

Identification of dAven, a Drosophila melanogaster ortholog of the cell cycle regulator Aven.

Aven is a regulator of the DNA-damage response and G2/M cell cycle progression. Overexpression of Aven is associated with poor prognosis in patients with childhood acute lymphoblastic leukemia and acute myeloid leukemia, and altered intracellular Aven distribution is associated with infiltrating ductal carcinoma and papillary carcinoma breast cancer subtypes. Although Aven orthologs have been identified in most vertebrate species, no Aven gene has been reported in invertebrates. Here, we describe a Drosophila melanogaster open reading frame (ORF) that shares sequence and functional similarities with vertebrate Aven genes. The protein encoded by this ORF, which we named dAven, contains several domains that are highly conserved among Aven proteins of fish, amphibian, bird and mammalian origins. In flies, knockdown of dAven by RNA interference (RNAi) resulted in lethality when its expression was reduced either ubiquitously or in fat cells using Gal4 drivers. Animals undergoing moderate dAven knockdown in the fat body had smaller fat cells displaying condensed chromosomes and increased levels of the mitotic marker phosphorylated histone H3 (PHH3), suggesting that dAven was required for normal cell cycle progression in this tissue. Remarkably, expression of dAven in Xenopus egg extracts resulted in G2/M arrest that was comparable to that caused by human Aven. Taken together, these results suggest that, like its vertebrate counterparts, dAven plays a role in cell cycle regulation. Drosophila could be an excellent model for studying the function of Aven and identifying cellular factors that influence its activity, revealing information that may be relevant to human disease.

Clinical challenge: cutaneous Kaposi's sarcoma of the lower extremity.

Kaposi's sarcoma (KS) typically presents as multiple bilateral cutaneous patches or plaques of the lower extremities. This malignancy, however, can evolve with atypical presentation masquerading as a chronic wound. Lesions can mimic venous stasis ulcers, arterial insufficiency, vascular ulcers or chronic-infected wounds. With acquired immune deficiency syndrome (AIDS)-associated KS, lesions are even more widespread, and can affect the respiratory tract, lymph nodes, gastrointestinal tract, spleen, liver and, rarely, bone. As the initial diagnosis of KS is generally determined clinically, a high index of suspicion is necessary for all patients with a known or suspected history of HIV/AIDS. Tissue biopsy with histological analysis is essential for all wound types in this patient subset, regardless of wound presentation. The purpose of this report is to review the pathogenesis as well as the typical and atypical presentations of KS with an example of a diagnostic dilemma.

Regulation of the ATM-activator protein Aven by CRM1-dependent nuclear export.

Aven is a regulator of apoptosis whose overexpression is associated with poor prognosis in several cancers, including childhood acute lymphoblastic leukemia and acute myeloid leukemia. We have recently shown that Aven serves as an activator and substrate of ATM, thereby modulating the DNA-damage response and G(2)/M cell cycle progression. Under physiological conditions, the cellular localization of Aven is mainly cytosolic, but a small fraction of the protein is present in the nucleus. Here, we show that treatment of cells with leptomycin B, an inhibitor of Exportin-1/CRM (chromosomal region maintenance) 1, resulted in nuclear accumulation of Aven. Furthermore, we identified a functional LR-NES between amino acid residues 282-292 of the human Aven protein, a sequence that is evolutionary conserved among a range of vertebrate species. Disruption of this LR-NES by site-directed mutagenesis resulted in enhanced nuclear localization of Aven, but did not alter the ability of the protein to induce G(2)/M cell cycle arrest in interphase Xenopus laevis extracts. However, elimination of the LR-NES sequence led to a reduction in the capacity of Aven to arrest Xenopus oocytes containing intact nuclei. Our results suggest that the regulation of nucleocytoplasmatic traffic of Aven could modulate its ability to influence cell cycle progression.

Primary breast lymphoma after mastectomy with reconstruction.

Primary breast lymphoma accounts for only 0.05%-1.1% of all breast malignancies, and less than 1% of all cases of non-Hodgkin lymphoma. Although primary breast lymphoma may present clinical similarities to breast carcinoma, the majority of cases lack the typical features of breast malignancy or lymphoma. We describe a case of primary breast lymphoma in a reconstructed breast, 8 years after a mastectomy for breast cancer. To the best of our knowledge, this is the first reported case in the worldwide literature of primary breast lymphoma in a reconstructed breast. We will discuss the diagnostic and treatment strategies involved in the management of primary breast lymphoma, and the effect of breast reconstruction on the detection of recurrent breast cancer.

The use of amnion-derived cellular cytokine solution (ACCS) in accelerating closure of interstices in explanted meshed human skin grafts.

UNLABELLED: Meshed, split-thickness skin grafts, especially when required to be widely spread, do not obtain immediate biologic closure. In patients with burns that cover a large percentage of the body surface area, this leaves the patient at risk for metabolic problems and life-threatening infection. OBJECTIVE: The purpose of this study was to determine whether amnion-derived cellular cytokine solution could improve epithelialization kinetics and accelerate closure of meshed skin graft interstices. METHODS: Human meshed, split-thickness skin grafts were explanted to athymic "nude" rats and treated with 3 different regimens of amnion-derived cellular cytokine solution (groups I, II, and III) or normal saline (group IV) as a control. Serial wound tracings of unepithelialized interstitial wound areas were compared over time. Two different preparations of amnion-derived cellular cytokine solution were also compared with one another, one containing animal components and the other free of animal components. RESULTS: Only 67.03% of interstices in control animals closed by day 9. This compared with 92.2% closure for group I, 83.72% for group II, and 90.64% for group III. Interstices in all 3 groups treated with amnion-derived cellular cytokine solution (with or without animal-derived components) closed faster statistically than in the control animals (P < .05). There were no statistical differences among the 3 amnion-derived cellular cytokine solution-treated groups. CONCLUSIONS: These data suggest that epithelialization kinetics and interstitial closure of meshed skin grafts can be accelerated with the use of amnion-derived cellular cytokine solution, a physiologic cocktail of cytokines, and provide support for a future clinical trial.

Nail-gun injuries to the hand.

BACKGROUND: The nail gun is a commonly utilized tool in carpentry and construction. When used properly with appropriate safety precautions, it can facilitate production and boost efficiency; however, this powerful tool also has the potential to cause serious injury. The most common site of nail-gun injuries in both industrial and nonoccupational settings is the hand. MATERIALS AND METHODS: We report on two patients with nail-gun injuries to the hand. A review of the literature and discussion of clinical evaluation and treatment of nail-gun injuries to the hand are presented. RESULTS: Two patients present with soft tissue injuries to the hand with the nail embedded and intact at the injury site. Operative removal of the nail and wound care resulted in successful treatment in both cases. Nail-gun injuries to the hand vary in severity on the basis of the extent of structural damage. Treatment is based on the severity of injury and the presence and location of barbs on the penetrating nail. CONCLUSION: Healthcare providers must understand and educate patients on the prevention mechanics of nail-gun injuries. Nail-gun injuries to the hand necessitate appropriate evaluation techniques, understanding of surgical management versus nonsurgical management, and awareness of potential pitfalls in treatment.

Computerized dynamic visual acuity with volitional head movement in patients with vestibular dysfunction.

OBJECTIVES: Patients with uncompensated vestibular dysfunction frequently report blurred vision during head movement, a symptom termed oscillopsia. One way to measure the functional deficit associated with an impaired vestibulo-ocular reflex is by comparing visual acuity from a baseline condition in which there is no head movement to visual acuity obtained during a dynamic condition with head movement. A previously described test incorporated a treadmill upon which patients walked during assessment of visual acuity. The objective of the current investigation was to evaluate an alternative method of assessing dynamic visual acuity that uses volitional head movement instead of walking on a treadmill. METHODS: Fifteen participants with normal vestibular function and 16 participants with impaired vestibular function were enrolled. All participants performed the visual acuity task under baseline conditions with no movement and also under dynamic conditions that included 1) walking on a treadmill and 2) volitionally moving their head in the vertical plane. RESULTS: No difference in performance was observed between the treadmill task and the volitional head movement task. Participants with impaired vestibular function performed more poorly under the dynamic conditions than did participants with normal vestibular function. CONCLUSIONS: The results suggest that the volitional head movement paradigm may be useful in identification of patients with functional deficits of the vestibulo-ocular reflex.

Propane and n-butane oxidation by Pseudomonas putida GPo1.

Propane and n-butane inhibit methyl tertiary butyl ether oxidation by n-alkane-grown Pseudomonas putida GPo1. Here we demonstrate that these gases are oxidized by this strain and support cell growth. Both gases induced alkane hydroxylase activity and appear to be oxidized by the same enzyme system used for the oxidation of n-octane.

Induction of methyl tertiary butyl ether (MTBE)-oxidizing activity in Mycobacterium vaccae JOB5 by MTBE.

Alkane-grown cells of Mycobacterium vaccae JOB5 cometabolically degrade the gasoline oxygenate methyl tertiary butyl ether (MTBE) through the activities of an alkane-inducible monooxygenase and other enzymes in the alkane oxidation pathway. In this study we examined the effects of MTBE on the MTBE-oxidizing activity of M. vaccae JOB5 grown on diverse nonalkane substrates. Carbon-limited cultures were grown on glycerol, lactate, several sugars, and tricarboxylic acid cycle intermediates, both in the presence and absence of MTBE. In all MTBE-containing cultures, MTBE consumption occurred and tertiary butyl alcohol (TBA) and tertiary butyl formate accumulated in the culture medium. Acetylene, a specific inactivator of alkane- and MTBE-oxidizing activities, fully inhibited MTBE consumption and product accumulation but had no other apparent effects on culture growth. The MTBE-dependent stimulation of MTBE-oxidizing activity in fructose- and glycerol-grown cells was saturable with respect to MTBE concentration (50% saturation level = 2.4 to 2.75 mM), and the onset of MTBE oxidation in glycerol-grown cells was inhibited by both rifampin and chloramphenicol. Other oxygenates (TBA and tertiary amyl methyl ether) also induced the enzyme activity required for their own degradation in glycerol-grown cells. Presence of MTBE also promoted MTBE oxidation in cells grown on organic acids, compounds that are often found in anaerobic, gasoline-contaminated environments. Experiments with acid-grown cells suggested induction of MTBE-oxidizing activity by MTBE is subject to catabolite repression. The results of this study are discussed in terms of their potential implications towards our understanding of the role of cometabolism in MTBE and TBA biodegradation in gasoline-contaminated environments.

Use of antibiotic resistance analysis for representativeness testing of multiwatershed libraries.

The use of antibiotic resistance analysis (ARA) for microbial source tracking requires the generation of a library of isolates collected from known sources in the watershed. The size and composition of the library are critical in determining if it represents the diversity of patterns found in the watershed. This study was performed to determine the size that an ARA library needs to be to be representative of the watersheds for which it will be used and to determine if libraries from different watersheds can be merged to create multiwatershed libraries. Fecal samples from known human, domesticated, and wild animal sources were collected from six Virginia watersheds. From these samples, enterococci were isolated and tested by ARA. Based on cross-validation discriminant analysis, only the largest of the libraries (2,931 isolates) were found to be able to classify nonlibrary isolates as well as library isolates (i.e., were representative). Small libraries tended to have higher average rates of correct classification, but were much less able to correctly classify nonlibrary isolates. A merged multiwatershed library (6,587 isolates) was created and was found to be large enough to be representative of the isolates from the contributing watersheds. When isolates that were collected from the contributing watersheds approximately 1 year later were analyzed with the multiwatershed library, they were classified as well as the isolates in the library, suggesting that the resistance patterns are temporally stable for at least 1 year. The ability to obtain a representative, temporally stable library demonstrates that ARA can be used to identify sources of fecal pollution in natural waters.