Overweight is Associated With Increased Incidence of Minor Complications After Reduction Mammoplasty: A Retrospective Analysis of 453 Consecutive Cases.

BACKGROUND AND AIMS: Reduction mammoplasty alleviates macromastia symptoms and improves quality of life. We investigated a large series of consecutive reduction mammoplasties to assess various risk factors for both minor and major complications after the procedure. MATERIALS AND METHODS: A retrospective analysis of 453 consecutive reduction mammoplasties was performed between 2007 and 2010 at an academic tertiary referral center to evaluate risk factors and complications. RESULTS: The incidence of minor and major complications was 40.5% and 8.8%, respectively. Patients with minor complications had both a significantly higher mean body mass index (30.2 vs 28.0) and sternal notch to nipple distance (33.9 vs 32.4 cm) than patients who recovered without complications (p < 0.001 for both comparisons), as well as more visits to the outpatient clinic (p < 0.001). In the multivariate analysis, body mass index was found to be the only significant risk factor for minor complications (p < 0.001). Furthermore, patients with body mass index higher than 27 had a 2.6-fold greater risk of minor complications (p < 0.001). An increase of one unit in body mass index increased the probability of minor complications by 14.1% (p < 0.001). 22 (4.9%) patients developed a hematoma requiring evacuation in the operating room. The mean body mass index of patients who developed a hematoma was 26.4, a value lower than that of patients without this complication (mean 29.0; p = 0.003). This finding was significant also in the multivariate analysis (p = 0.002). CONCLUSION: A higher body mass index was strongly associated with an increased risk of minor complications after reduction mammoplasty. It is important to inform obese patients about the increased risk of complications and to encourage them to lose weight before surgery.

Expression and induction of collagenases (MMP-8 and -13) in plasma cells associated with bone-destructive lesions.

Matrix metalloproteinases (MMPs) collectively degrade extracellular matrix and basement membrane proteins in chronic inflammation and bone-destructive lesions. This study examined the ability of immunoglobulin-producing plasma cells, typically present in sites of chronic inflammation, to express collagenases (MMP-8 and -13) in vivo and in vitro. Phorbol-12-myristate-13-acetate, interleukin-6, and tumour necrosis factor-alpha and heparin with the tumour promoter or cytokines potently enhanced (up to nine-fold) MMP-8 and -13 expression by the RPMI 8226 myeloma cell line, as evidenced by western blotting and semi-quantitative reverse transcriptase-polymerase chain reaction. Immunohistochemical analysis and in situ hybridization revealed that plasma cells expressed MMP-8 and -13 focally in periapical granulomas, odontogenic cysts, and malignant plasmacytomas. MMP-8 and MMP-13 from plasma cells can participate in bone organic matrix destruction at sites of chronic inflammation and neoplastic growth. Since MMP-13 was more frequently expressed than MMP-8 in plasma cells of strongly recurring keratocysts and malignant plasmacytomas, it is concluded that plasma cell MMP-13 has a particularly important role in benign and malignant bone-destructive lesions.

Collagenase-3 (MMP-13) and its activators in rheumatoid arthritis: localization in the pannus-hard tissue junction and inhibition by alendronate.

The hypothesis of the present work was that the pannus tissue overlying the articular hard tissues has an aggressive phenotype and contains the newly discovered collagenase-3 and its endogenous inducers and activators. We therefore analyzed the eventual presence of collagenase-3 and its regulation at the pannus-cartilage junction. Collagenase-3 mRNA (in situ hybridization) and enzyme protein (ABC and immunofluorescence staining) were found in the pannocytes in the pannus-hard tissue junction. Inflammatory round cells associated with the critical interface contained TNF-alpha and IL-1beta. These cytokines induced collagenase-3 secretion in cultured rheumatoid synovial fibroblasts. Procollagenase-3 activators, stromelysin-1, 72 kDa type IV collagenase/gelatinase and membrane-type 1-MMP, were also found in the pannus-hard tissue junction. Active collagenase-3 was inhibited with alendronate (IC50 = 500-750 microM). Collagenase-3, due to its substrate profile and local synthesis in a milieu favoring its activation, might play a major role in the degradation of cartilage type II and bone type I collagens. Alendronate, at concentrations attainable in vivo, is able to inhibit collagenase-3. This might offer an option to control collagenase-3-mediated tissue destruction in rheumatoid arthritis.

The effects of UV exclusion on the soluble phenolics of young Scots pine seedlings in the subarctic.

The characteristics of UV-absorbing compounds, particularly soluble phenolics, were studied in needles of 63-day-old seed-grown Scots pine (Pinus sylvestris L.) seedlings of two provenances in a UV exclusion field experiment at Pallas-Ounastunturi National Park in Finnish Lapland (68 degrees N, 270 m a.s.l.). The experiment used the following plastic filters in exclosure treatments to manipulate the spectral balance of natural irradiance: (1) 'control' (a polyethene plastic filter); (2) 'UV-B exclusion' (a clear polyester filter); and (3) 'UV-B/UV-A exclusion' (a clear acryl plate). Polyethene transmitted 89% of the ambient levels of total UV (280-400 nm), polyester transmitted 75% of the total UV, but only 0.6% of the UV-B (280-315 nm) component, while acryl plate transmitted 0.2% of UV (280-360 nm). The research also included (4) 'Ambient' plants that were not subjected to any treatment exclosures. After the 58 day UV exclusion, significant (p<0.0001) differences due to treatments were determined for a kaempferol derivative, kaempferol 3-glucoside, and a quercetin derivative, the quantities of which ranged from 0.23 to 0.45, 0.42 to 1.34 and 0.39 to 0.75 micromol g FW(-1), respectively, depending on treatment and provenance. Overall, Scots pine seedlings grown at ambient UV radiation (PAS300, Caldwell's generalized Plant Action Spectrum (PAS) normalized at 300 nm, 72 mW m(-2)) or under a control had significantly (p<0.05) higher quantities of soluble phenolics than seedlings grown under UV-B or UV-B/UV-A exclusion treatments. There were no significant differences in the quantity of soluble phenolics between the two exclosure treatments or between the two Scots pine provenances. The sums of diacylated flavonol glucosides ranging from 3.75 to 4.55 micromol g FW(-1) depending on treatment and provenance, were already present at very low UV-levels under the UV-B/UV-A exclusion treatment. The present study indicated that soluble phenolics, particularly the diacylated flavonol glucosides, may provide an effective preformed protection for young Scots pine seedlings against UV-B and UV-A radiation.

Expression of matrix metalloproteinases (MMP-1 and -2) and their inhibitors (TIMP-1, -2 and -3) in oral lichen planus, dysplasia, squamous cell carcinoma and lymph node metastasis.

Although matrix metalloproteinases (MMPs) are among the potential key mediators of cancer invasion, their involvement in premalignant lesions and conditions is not clarified. Therefore, we studied, using in situ hybridization, immunohistochemistry and zymography the expression and distribution of MMP-1 and -2, and their tissue inhibitors (TIMPs -1, -2 and -3) in oral squamous cell carcinomas (SCC) and lymph node metastases as well as in oral lichen planus, epithelial dysplasias and normal buccal mucosa. In oral SCC and lymph node metastasis, MMP-1 mRNA was detected in fibroblastic cells of tumoral stroma. In two out of ten carcinomas studied, the peripheral cells of neoplastic islands were also positive. MMP-2 mRNA expression was noted in fibroblasts surrounding the carcinoma cells, and no signal in carcinoma cells was detected. A clear TIMP-3 mRNA expression was seen in stromal cells surrounding the neoplastic islands in all SCCs and lymph node metastases studied. TIMP-1 mRNA was detected in some stromal cells surrounding the neoplastic islands, whereas the mRNA expression for TIMP-2 was negligible. On the other hand, expression of MMPs and TIMPs was consistently low in oral epithelial dysplasias, lichen planus and normal mucosa. In certain epithelial dysplasias and lichen planus, MMP-1 and -2 mRNA expressions were detected in few fibroblasts under the basement membrane zone, but normal mucosa was completely negative. In SCC and lymph node metastasis, a detectable immunostaining for MMP-1 in stromal cells and in some carcinoma cells was observed. MMP-2 immunoreactivity was detected in the peripheral cell layer in neoplastic islands and in some fibroblast-like cells of tumoral stroma. Immunostaining for TIMP-3 was detected in stromal cells surrounding the neoplastic islands. A weak positive staining for TIMP-1 was located in tumoral stroma, whereas the immunostaining for TIMP-2 was negative. Using zymography, elevated levels of MMP-2 and MMP-9 were observed in carcinoma samples in comparison with lichen planus or normal oral mucosa. Our results indicate that the studied MMPs and TIMPs are clearly up-regulated during invasion in oral SCC. However, there was also a clear, although weak, up-regulation of the expression of the MMPs but not TIMPs in some of the lichen planus and dysplastic lesions.

The molecular basis of glucocorticoid-induced skin atrophy: topical glucocorticoid apparently decreases both collagen synthesis and the corresponding collagen mRNA level in human skin in vivo.

The effects of topical betamethasone-17-valerate on collagen propeptide levels, collagen mRNA level, lysyl oxidase mRNA and matrix metalloproteinase (MMP)-1 and MMP-2 mRNA levels were studied in human skin. Three days' treatment of healthy skin with topical betamethasone caused a 70-80% decrease in type I and III collagen propeptides in suction blister fluid. A similar decrease was found in type I collagen mRNA when assayed by either slot-blot hybridization or a quantitative polymerase chain reaction method, indicating that the decrease in collagen synthesis after topical glucocorticoid treatment is apparently due to a decrease in corresponding mRNA. mRNA of lysyl oxidase, which is an important enzyme catalysing the cross-linking of collagen chains, and collagen-degrading enzyme MMP-1 and MMP-2 mRNAs were not decreased in the same skin samples. This suggests that in vivo, glucocorticoids modulate variably the genes involved in collagen synthesis and degradation. Our study provides a solid molecular basis for glucocorticoid-induced dermal atrophy, which results from the decrease in functional collagen mRNA in the skin.

New collagenolytic enzymes/cascade identified at the pannus-hard tissue junction in rheumatoid arthritis: destruction from above.

Our aim was to investigate the collagenolytic potential and localization of matrix metalloproteinase-2 (MMP-2) in relation to its regulatory proteins membrane type MT1-MMP and tissue inhibitor of metalloproteinases-2 (TIMP-2) in rheumatoid arthritis (RA). For this purpose, we have used purification of MMP-2, MMP-8, MMP-9 and interstitial type I, II and III collagens; SDS-PAGE/densitometric collagenase activity assay; zymography; Western blotting; reverse transcriptase polymerase chain reaction; in situ hybridization; and immunofluorescence, ABC, ABC-APAAP double immunostainings. MMP-2 degraded human type II collagen almost as effectively as MMP-8, whereas MMP-9 did not cleave type II collagen. In synovial tissue, MT1-MMP, TIMP-2 and MMP-2 were found in synovial lining in fibroblast- and macrophage-like cells, in stromal cells and in vascular endothelium. MT1-MMP, TIMP-2 and MMP-2 were strongly expressed in the pannocytes of the invasive pannus at the interface, but staining was weak and/or there were few positive cells both "above" and "below" the soft-to-hard tissue (cartilage and/or bone) interface. Rheumatoid synovial tissue extract contained proteolytically active 62/59 kDa MMP-2 and 43 kDa MT1-MMP, but no free TIMP-2. These results indicate that components of the ternary MT1-MMP/TIMP-2/MMP-2 complex are coexpressed in the normal synovial lining and in its pathological extension on the hyaline articular cartilage. MMP-2 may participate in the remodeling of the normal lining and also seems to be localized/focalized to pannocytes at a site critical for tissue destruction in arthritis.

Effect of topical tretinoin on non-sun-exposed human skin connective tissue: induction of tenascin but no major effect on collagen metabolism.

The effects of topical tretinoin on collagen synthesis and degradation were studied in 29 volunteers. The subjects applied 0.1% tretinoin cream on their non-sun-exposed abdominal skin once a day for 1 week (n = 10) (experiment 1) or twice a day for 2 weeks (n = 8) (experiment 2) or once a day for 2 months (n = 11) (experiment 3). After the treatments, suction blisters were induced and amino-terminal propeptides of type I and III procollagens (PINP, PIIINP, respectively) (experiments 1 and 3) and carboxy-terminal propeptide of type I procollagen (PICP) (experiment 2) were assayed as an index of de novo collagen synthesis by radioimmunoassays. Matrix metalloproteases 2 (MMP-2) and 9 (MMP-9) were assayed by the zymography method in experiment 2. In experiment 3, histology, immunohistochemistry of type I and III procollagens, tenascin, mRNA levels of type I collagen alpha 1-chain [alpha 1 (I)], interstitial collagenase (MMP-1), MMP-2, MMP-9 by slot-blot analysis and the levels of alpha 1 (I) collagen mRNA by a quantitative polymerase chain reaction method were studied. The proportional area of elastic fibres visualized in Verhoeff-stained sections was analysed by computerized digital image analysis. The results indicated that treatment with topical tretinoin does not markedly induce de novo synthesis of collagen in vivo or affect matrix metalloproteases. In the immunohistochemical staining, tenascin was increased in the papillary dermis. As it has been suggested that tretinoin could counteract the atrophogenic effect of corticoids on the dermis, the effect of a combination of betamethasone-17-valerate (once a day) and tretinoin (once a day) on the propeptide levels was also studied. Betamethasone alone caused a 60% decrease in the concentrations of PINP and PIIINP, and a similar decrease was found after the combination treatment, indicating that topical tretinoin administered during short treatment periods does not counteract the inhibitory effect of a potent corticoid on collagen propeptides.

Matrix metalloproteinase-8 is expressed in rheumatoid synovial fibroblasts and endothelial cells. Regulation by tumor necrosis factor-alpha and doxycycline.

Neutrophil collagenase (matrix metalloproteinase-8 or MMP-8) is regarded as being synthesized exclusively by polymorphonuclear neutrophils (PMN). However, in vivo MMP-8 expression was observed in mononuclear fibroblast-like cells in the rheumatoid synovial membrane. In addition, we detected MMP-8 mRNA expression in cultured rheumatoid synovial fibroblasts and human endothelial cells. Up-regulation of MMP-8 was observed after treatment of the cells with either tumor necrosis factor-alpha (10 ng/ml) or phorbol 12-myristate 13-acetate (10 nM). Western analysis showed a similar regulation at the protein level. The size of secreted MMP-8 was 50 kDa, which is about 30 kDa smaller than MMP-8 from PMN. Conditioned media from rheumatoid synovial fibroblasts contained both type I and II collagen degrading activity. However, degradation of type II collagen, but not that of type I collagen, was completely inhibited by 50 microM doxycycline, suggesting specific MMP-8 activity. In addition, doxycycline down-regulated MMP-8 induction, at both the mRNA and protein levels. Thus MMP-8 exerts markedly wider expression in human cells than had been thought previously, implying that PMN are not the only source of cartilage degrading activity at arthritic sites. The inhibition of both MMP-8 activity and synthesis by doxycycline provides an incentive for further studies on the clinical effects of doxycycline in the treatment of rheumatoid arthritis.

Effects of emissions from copper-nickel smelters on the frost hardiness of Finns sylvestris needles in the subarctic region.

It has been proposed that freezing injuries play an important role in the forest decline phenomenon. In this study, the effect of emissions from the copper-nickel smelters in Monchegorsk and Nikel-Zapolyarnyi in the Kola Peninsula, south-west Russia, on seasonal changes in the frost hardiness of Pinus sylvestris L. needles were studied. The frost hardiness of current-year needles during autumn, winter, spring and early summer in 1991-1993 was estimated by the electrolyte leakage method and by visual estimation of the proportion of damaged needles at nine sites in Finnish Lapland, at five sites in the vicinity of Monchegorsk and at two sites in Norway, in the vicinity of Nikel. The foliar S, Cu, and Ni concentrations also analysed. There were no significant differences at any time of the year between the frost hardiness of pine needles at the sites in Norway and Finnish Lapland. However, in the winter, the degree of visual damage at -45 °C, the temperature close to the lowest recorded temperature in this area, was slightly higher at the sites near to Nikel than at the sites in Finnish Lapland. In the Kola Peninsula the frost hardiness was consistently lower at the sites located 10 km to the south and 36 km to the south-west of Monchegorsk than at the other sites (48-110 km to the south-west). The differences were greatest in early June, 1991, when frost hardiness was -2 °C and -8°C at the sites closest to Monchegorsk. At the same time, the frost hardiness at the other sites was e.-20 °C. There were slight differences between years, but the trends were the same. A clearly increasing gradient in the S, Cu and Ni concentrations was observed on moving towards the emission point source at Monchegorsk. Highly elevated concentrations were found within 40 km of the smelter. The results suggest that air pollutants from the copper-nickel smelter have predisposed the pines to freezing injuries, rhus contributing to forest decline in the Kola Peninsula.

Seasonal differences in freezing stress resistance of needles of Pinus nigra and Pinus resinosa: evaluation of the electrolyte leakage method.

Seasonal changes in freezing stress resistance of needles of red pine (Pinus resinosa Ait.) and Austrian pine (Pinus nigra Arnold) trees were measured by an electrolyte leakage method and by visual observation. During most of the year, freezing stress resistance determined by the two methods gave similar results. The electrolyte leakage method provided a good estimate of seasonal changes in freezing stress resistance except for red pine needles in their most winter-hardy state. To obtain a reliable estimate of freezing stress resistance in winter-hardy red pine needles it was necessary to combine the electrolyte leakage method with visual observations. When red pine needles survived exposure to -80 degrees C or lower, electrolyte leakage was never more than 30% even when the needles were exposed to a slow freeze-thaw stress of -196 degrees C. However, rapid freezing of red pine needles to -196 degrees C resulted in electrolyte leakage of over 80%. Red pine needles attained a much higher freezing stress resistance during the winter than Austrian pine. Red pine needles also acclimated and deacclimated faster than Austrian pine needles. An index of injury was developed based on the electrolyte leakage method ((R(2) + R(1))/2, where R(1) is the minimum % electrolyte leakage from noninjured tissue and R(2) is the maximum % electrolyte leakage at the highest injury) that reliably predicted freezing stress resistance of pine needles for most of the year. Important aspects for developing a successful index of injury for pine needles are: use of cut needles, vacuum infiltration and shaking during incubation in water.We conclude that: (1) during cold acclimation the cell wall properties of the pine needles changed and these changes, which appeared to differ in the two species, might explain the very low leakage of electrolytes from winter-hardy needles of red pine; (2) pine needles survive winter by developing the ability to tolerate extracellular ice formation, because after rapid freezing the needles were severely injured; and (3) red pine is adapted to a shorter growing season and colder winters than Austrian pine.

Characterization of a monoclonal antibody to human alpha-fetoprotein and its use in affinity chromatography.

A hybrid cell line secreting monoclonal antibodies to human alpha- fetoprotein (AFP) was produced by fusion of a mouse myeloma cell line with spleen cells from a BALB/c mouse immunized with human AFP. The affinity constant of the antibody was about 1.7 X 10(9) l/mol. When clones were grown in vitro, the highest concentration of specific antibody in the culture medium was 25 microgram/ml. A clone was transplanted intraperitoneally into pristine-primed BALB/c recipients. Ascites developed within 3-4 weeks of transplantation, and the maximal antibody concentration in the ascitic fluid was 2.5 mg/ml. The immunoglobulin fraction of ascitic fluid was coupled to cyanogen bromide-activated Sepharose and used for affinity chromatography of AFP. AFP containing less than 1% contaminating proteins was obtained by passing amniotic fluid through the column and eluting the adsorbed AFP with 4 mol/l urea. The monoclonal antibody was used for radioimmunoassay (RIA). The sensitivity obtained was 50 microgram/l, which is adequate for certain clinical applications.