A clinical experience with perforator flaps in the coverage of extensive defects of the upper extremity

Traditional skin free flaps, such as radial arm, lateral arm, and scapular flaps, are rarely sufficient to cover large skin defects of the upper extremity because of the limitation of primary closure at the donor site. Muscle or musculocutaneous flaps have been used more for these defects. However, they preclude a sacrifice of a large amount of muscle tissue with the subsequent donor-site morbidity. Perforator or combined flaps are better alternatives to cover large defects. The use of a muscle as part of a combined flap is limited to very specific indications, and the amount of muscle required is restricted to the minimum to decrease the donor-site morbidity. The authors present a series of 12 patients with extensive defects of the upper extremity who were treated between December of 1999 and March of 2002. The mean defect was 21 x 11 cm in size. Perforator flaps (five thoracodorsal artery perforator flaps and four deep inferior epigastric perforator flaps) were used in seven patients. Combined flaps, which were a combination of two different types of tissue based on a single pedicle, were needed in five patients (scapular skin flap with a thoracodorsal artery perforator flap in one patient and a thoracodorsal artery perforator flap with a split latissimus dorsi muscle in four patients). In one case, immediate surgical defatting of a deep inferior epigastric perforator flap on a wrist was performed to immediately achieve thin coverage. The average operative time was 5 hours 20 minutes (range, 3 to 7 hours). All but one flap, in which the cutaneous part of a combined flap necrosed because of a postoperative hematoma, survived completely. Adequate coverage and complete wound healing were obtained in all cases. Perforator flaps can be used successfully to cover a large defect in an extremity with minimal donor-site morbidity. Combined flaps provide a large amount of tissue, a wide range of mobility, and easy shaping, modeling, and defatting.     

Using wavelet analysis to examine bark microrelief

Key Message

An improved quantification of variations in bark microrelief is presented that uses wavelets on a circular domain from data acquired using the LaserBark? automated tree measurement system.

Abstract

An important metric of canopy structure, bark microrelief affects both the hydrology and biogeochemistry of forests. Increased bark microrelief leads to reduced stemflow volumes and higher concentrations of stemflow leachates and nutrient-ions. Consequently, an improved representation of bark microrelief would be useful to describe the influence of various tree species on water and solute contributions to the forest floor. Most existing methods to quantify bark microrelief are ‘global’ measures; that is, they provide a single number that represents the overall bark microrelief of the entire perimeter of the tree. To remedy this, wavelet analysis of LaserBark? automated tree measurement system data is proposed and described to quantify variations in bark microrelief around the perimeter of the tree. This measure describes the spatial differences in bark microrelief and allows representation of trees that exhibit directional variability in bark microrelief due to natural or anthropogenic effects. The results show that wavelet analysis is effective in quantifying both bark microrelief and large-scale tree asymmetry. The radial component highlights changes in the depth of bark microrelief while the tangential component relates to the distance between bark furrows in the bark cross section. Thus, wavelet analysis may be a useful tool for comparing bark structure that varies, for example, within- and between-tree species, at different stages of tree growth, and among trees grown under different environmental conditions.     

Weak Intra-Ring Allosteric Communications of the Archaeal Chaperonin Thermosome Revealed by Normal Mode Analysis

Chaperonins are molecular machines that use ATP-driven cycles to assist misfolded substrate proteins to reach the native state. During the functional cycle, these machines adopt distinct nucleotide-dependent conformational states, which reflect large-scale allosteric changes in individual subunits. Distinct allosteric kinetics has been described for the two chaperonin classes. Bacterial (group I) chaperonins, such as GroEL, undergo concerted subunit motions within each ring, whereas archaeal and eukaryotic chaperonins (group II) undergo sequential subunit motions. We study these distinct mechanisms through a comparative normal mode analysis of monomer and double-ring structures of the archaeal chaperonin thermosome and GroEL. We find that thermosome monomers of each type exhibit common low-frequency behavior of normal modes. The observed distinct higher-frequency modes are attributed to functional specialization of these subunit types. The thermosome double-ring structure has larger contribution from higher-frequency modes, as it is found in the GroEL case. We find that long-range intersubunit correlation of amino-acid pairs is weaker in the thermosome ring than in GroEL. Overall, our results indicate that distinct allosteric behavior of the two chaperonin classes originates from different wiring of individual subunits as well as of the intersubunit communications.     

Polymorphisms of Immunity Genes and Susceptibility to Otitis Media in Children

Background

Acute otitis media (OM) is a common disease which often develops through complex interactions between the host, the pathogen and environmental factors. We studied single nucleotide polymorphisms (SNPs) of genes involved in innate and adaptive immunity, and other host and environmental factors for their role in OM.

Methods

Using Sequenom Massarray platform, 21 SNPs were studied in 653 children from prospective (n = 202) and retrospective (n = 451) cohorts. Data were analyzed for the relationship between SNPs and upper respiratory infection (URI) frequency, risk of acute OM during URI episodes, and proneness to recurrent OM.

Results

Increased risk for OM proneness was associated with CX3CR1 (Thr280Met) SNP and with a jointly interactive group of IL-10 (−1082) SNP, IL-1β (−511) wild type genotype and white race. Family history of OM proneness independently increased the risk for frequent URIs, OM occurrence during URI, and OM proneness. Additionally, IL-1β (−31) SNP was associated with increased risk for frequent URIs, but IL-10 (−592), IL-1β (−511), IL-5 (−746) and IL-8 (−251) SNPs were associated with decreased risk of URI.

Conclusion

IL-1β (−31), CX3CR1 (Thr280Met), IL-10 (−1082) and IL-1β (−511) SNPs were associated with increased risk for frequent URIs or OM proneness.     

Regulated expression of osteopontin in the peri-implantation rabbit uterus

Blastocyst attachment to the lining of the mammalian uterus during early implantation involves the initial apposition of the trophoblast to the uterine epithelial surface. Osteopontin (OPN) is a glycoprotein component of the extracellular matrix that is secreted by the glandular epithelium of mammalian uteri at the time of implantation. This protein is recognized by several members of the integrin family and promotes cell-cell attachment and adhesion. In the present study, rabbit uteri were examined using Northern and in situ hybridization to evaluate the temporal and spatial distribution of OPN mRNA during early pregnancy. Northern blot analysis demonstrated a dramatic increase in OPN expression on Days 4-7 of pregnancy, corresponding to the rise in circulating progesterone and the time of initial embryo attachment in this species. In situ hybridization analysis revealed OPN mRNA expression on Day 6.75 of pregnancy, which was most prominent on endometrial epithelium. Using immunofluorescence, OPN protein was present on the glandular epithelium on Day 6.75 of pregnancy, but was absent on blastocysts. Further, no expression of OPN mRNA or protein was found in the nonpregnant endometrium. Induction of endometrial OPN expression was observed in unmated rabbits treated with progesterone alone and was prevented by cotreatment with the antiprogestin ZK137.316. Estradiol-17beta had no effect on OPN expression by itself, and estrogen priming was not necessary to demonstrate the stimulatory effect of progesterone. In The rabbit uterus, as in other mammalian species studied, OPN is expressed in a stage-specific manner by the endometrial glands during the peri-implantation period and is regulated by progesterone.     

N-(4-{[4-(1H-Benzoimidazol-2-yl)-arylamino]-methyl}-phenyl)-benzamide derivatives as small molecule heparanase inhibitors

A novel class of N-(4-{[4-(1H-benzoimidazol-2-yl)-arylamino]-methyl}-phenyl)-benzamides are described as inhibitors of the endo-beta-glucuronidase heparanase. Among them are N-(4-{[4-(1H-benzoimidazol-2-yl)-phenylamino]-methyl}-phenyl)-3-bromo-4-methoxy-benzamide (15h), and N-(4-{[5-(1H-benzoimidazol-2-yl)-pyridin-2-ylamino]-methyl}- phenyl)-3-bromo-4-methoxy-benzamide (23) which displayed good heparanase inhibitory activity (IC(50) 0.23-0.29 microM), with the latter showing oral exposure in mice.     

Mast cells impair the development of protective anti-tumor immunity

Mast cells have emerged as critical intermediaries in the regulation of peripheral tolerance. Their presence in many precancerous lesions and tumors is associated with a poor prognosis, suggesting mast cells may promote an immunosuppressive tumor microenvironment and impede the development of protective anti-tumor immunity. The studies presented herein investigate how mast cells influence tumor-specific T cell responses. Male MB49 tumor cells, expressing HY antigens, induce anti-tumor IFN-??⁺ T cell responses in female mice. However, normal female mice cannot control progressive MB49 tumor growth. In contrast, mast cell-deficient c-Kit^Wsh (W^sh) female mice controlled tumor growth and exhibited enhanced survival. The role of mast cells in curtailing the development of protective immunity was shown by increased mortality in mast cell-reconstituted W^sh mice with tumors. Confirmation of enhanced immunity in female W^sh mice was provided by (1) higher frequency of tumor-specific IFN-??⁺ CD8⁺ T cells in tumor-draining lymph nodes compared with WT females and (2) significantly increased ratios of intratumoral CD4⁺ and CD8⁺ T effector cells relative to tumor cells in W^sh mice compared to WT. These studies are the first to reveal that mast cells impair both regional adaptive immune responses and responses within the tumor microenvironment to diminish protective anti-tumor immunity.     

Preparative Electrophoresis of Isotopically Labeled L-Cell Interferons

The preparative method of polyacrylamide gel electrophoresis was adapted for purification and characterization of isotopically labeled L-cell interferons. Re-covery of interferon activity was quantitative, and purification and resolution were comparable to those obtained by analytical polyacrylamide gel electrophoresis. Ultimate specific activities attainable ranged from 2 x 10(6) to 3 x 10(6) international units per mg of protein.     

The response of a classical Hodgkin–Huxley neuron to an inhibitory input pulse

A population of uncoupled neurons can often be brought close to synchrony by a single strong inhibitory input pulse affecting all neurons equally. This mechanism is thought to underlie some brain rhythms, in particular gamma frequency (30–80 Hz) oscillations in the hippocampus and neocortex. Here we show that synchronization by an inhibitory input pulse often fails for populations of classical Hodgkin–Huxley neurons. Our reasoning suggests that in general, synchronization by inhibitory input pulses can fail when the transition of the target neurons from rest to spiking involves a Hopf bifurcation, especially when inhibition is shunting, not hyperpolarizing. Surprisingly, synchronization is more likely to fail when the inhibitory pulse is stronger or longer-lasting. These findings have potential implications for the question which neurons participate in brain rhythms, in particular in gamma oscillations.     

Survival of Listeria monocytogenes and Enterococcus faecium in sludge evaluated by real-time PCR and culture methods

AIMS: This study evaluates the behaviour in spiked sludge of a pathogenic bacteria, Listeria monocytogenes, by cultural and molecular techniques, and compares its survival with the one of a faecal indicator, Enterococcus faecium. METHODS AND RESULTS: Listeria monocytogenes strain Scott A and E. faecium(T) were followed for 17 days after inoculation in sludge. Kinetics of survival depended on the bacteria and on the technique used [most probable number method, direct plate count or real-time quantitative PCR (qPCR)]. The concentration of L. monocytogenes decreased rapidly regardless of the technique, but the decrease was much more dramatic with culture techniques than with qPCR. On the contrary, the concentrations of culturable E. faecium(T) were stable. CONCLUSIONS: The results suggest that the cells of L. monocytogenes strain Scott A might have entered a viable, but nonculturable (VBNC) status, whereas cells of the indicator bacteria, E. faecium(T), maintained themselves better and stayed culturable. SIGNIFICANCE AND IMPACT OF THE STUDY: The difference of survival kinetics in the sludge of a faecal indicator (E. faecium) and a pathogenic bacterium (L. monocytogenes) may be linked to the fact that they either enter or do not enter into a VBNC status.