ECONOMIC ANALYSIS OF ENZYMATIC DEBRIDEMENT VERSUS STANDARD BURN CARE: A RETROSPECTIVE ANALYSIS.

When compared to standard surgical management, rapid enzymatic debridement of deep burns reduces the need for surgery while achieving similar long-term results. However, few studies have directly compared the costs of standard surgical and enzymatic burn care. We conducted a study comparing the care costs of 44 adult burn patients treated before (n=22) and after (n=22) introducing rapid bromelain-based enzymatic debridement (BED) of deep burns. Mean age was 59 years, 54% were male, and mean total body surface area (TBSA) was 23.5%. Burn etiology included flame and scalding burns (8). Groups treated with standard of care and enzymatic debridement were comparable in terms of age, sex and TBSA. Burn management with BED significantly reduced total debridement costs as well as grand total costs when compared with traditional surgical care. Such reduction was mostly related to lower costs associated with reduced surgical care and less facilities and resources consumption in the BED group.

Comparativement au traitement standard, l'excision enzymatique précoce (EEP) réduit la nécessité de chirurgie, à résultats égaux à long termes. Très peu d'études ont comparé les coûts de ces deux stratégies. Nous avons comparé 2 groupes de 22 patients profondément brûlés ayant pour l'un été pris en charge conventionnellement, l'autre ayant bénéficié d'une EEP. L'âge moyen était de 59 ans, 54% étaient des hommes, la surface brûlée moyenne de 23,5% (les 2 groupes étaient comparables). Seuls 8 patients avaient été ébouillantés, les autres étant brûlés par flamme. L'utilisation d'EEP réduisait significativement le coût de la prise en charge, en rapport avec la réduction de l'utilisation de locaux et de matériel consécutifs à la chirurgie.

Tumor and peritumoral adipose tissue crosstalk: De-differentiated adipocytes influence spread of colon carcinoma cells.

Colorectal cancer is the second leading cause of cancer and often has a fatal course. There are many studies in the literature that have described a close functional relationship between the tumor mass and surrounding tissue, or tumor stroma, which is affected by the continuous metabolic exchange that occurs at the interface between tumor and tissues in contact with it. There is much evidence that the presence of adipose tissue in stroma plays a fundamental role in modulating the tumor microenvironment and promote tumor development, growth, and angiogenesis due to its endocrine characteristics. In this analysis, we have studied the alterations of adipose tissue surrounding colorectal tumors with MRI and optical imaging in vivo techniques to monitor tumor progression and also performed histological and molecular analysis. We detected differences in the principal adipose markers expressed by adipocytes residing around the rectal colon and observed that peritumoral adipose tissue is exposed to a mesenchymal transition process that leads to the acquisition of a less differentiated phenotype of adipocyte that represents the main cellular type present in tumor stroma. The mesenchymal transition correlated with the acquisition of more aggressive tumor phenotype and could represent a valid target for tumor therapy.

[LaboRisCh: an algorithm for assessment of health risks due to chemicals in research laboratories and similar workplaces]. / LaboRisCh: un algoritmo per la valutazione dei rischi per la salute da agenti chimici nei laboratori di ricerca e negli ambienti di lavoro affini.

BACKGROUND: Chemical risk assessment in research laboratories is complicated by factors such as the large number of agents to be considered, each present in small quantities, and the very short and erratic periods of exposure, all of which make reliable environmental and biological monitoring particularly difficult and at times impossible. In such environments, a preliminary evaluation procedure based on algorithms would be useful to establish the hazard potential of a given situation and to guide the appropriate intervention. OBJECTIVES: The LaboRisCh model was expressly designed to assess the health risk due to chemicals in research laboratories and similar workplaces. METHODS: The model is based on the calculation of the value of a synthetic single risk index for each substance and compound found in a laboratory and, subsequently, of a further synthetic single risk index for the whole laboratory or, where required, a section thereof. This makes LaboRisCh a compromise between need for information, ease of use, and resources required for the assessment. The risk index includes several items, chiefly the physical and chemical properties, intrinsic hazard potential, amount, dilution, and time of exposure to each agent; waste management; possible interactions; presence and efficiency of collective and individual protection devices, and staff training in good laboratory practices. The value of the synthetic single index corresponds to one of three areas: no risk (green), possible risk (yellow), and certain risk (red). CONCLUSIONS: Preliminary data confirm the model. LaboRisCh appears to be a reliable method for chemical risk assessment in research laboratories and similar workplaces.

[Perianal Paget's disease: five cases report]. / Malattia di Paget perianale: presentazione di 5 casi.

AIM: Extramammary Paget's disease is a rare neoplastic condition, often associated with a synchronous or metachronous underlying skin or visceral malignancies. The aim of this study was to evaluate retrospectively the results we got in 5 cases of perianal Paget's disease and to revise what literature have reported about this issue. PATIENTS AND METHODS: Five patients with perianal EMPD were consecutively treated in our Division between March 1996 and December 2006. In 3 cases the disease was limited to the epidermidis, in one case with multiple recurrences there was dermal infiltration, and one patient had a low rectal adenocarcinoma with pagetoid phenomenon. The surgical treatment we performed in all patients was a wide perianal excision, followed by reconstruction with cutaneous grafts; the resection of rectal adenocarcinoma was carried out using the transanal approach. In two cases we performed a temporary stoma with the sigmoid colon to help the wound healing. RESULTS: We didn't record any complication neither postoperative nor at long time. Two patients developed a local recurrence, but none of our patients showed distant metastases. Four patients are alive and free from disease and one, who developed a multiple local recurrences, died for heart failure. DISCUSSION: The studies available in literature clearly distinguish between a primary EMPD (intraepidermal/intradermal) and secondary disease which is associated with anorectal adenocarcinomas and is thought to be a pagetoid phenomenon, while few informations can derive from those cases in which the disease is associated with an underlying cutaneous adnexal carcinoma. Disease tend to relapse even after a radical surgery and can have metastatic spread, also in intraepidermal form. CONCLUSIONS: Perianal EMPD is a complex disease, difficult to recognize and the association with synchronous or metachronous malignancies imposes long term clinical and instrumental follow up.

[Biomarkers for prevention and early diagnosis of malignant pleural mesothelioma]. / Utilizzo di biomarkers nella prevenzione e diagnosi precoce del Mesotelioma Maligno della pleura.

Improved detection methods for diagnosis of asymptomatic malignant pleural mesothelioma (MPM) are essential for an early and reliable detection and treatment of this disease. Thus, focus has been on finding tumour markers in the blood. 94 asbestos-exposed subjects, 22 patients with MM, and 54 healthy subjects were recruited for evaluation of the significance of 8-hydroxy-2'-deoxy-guanosine (80HdG) in white blood cells and plasma concentrations of soluble mesothelin-related peptides (SMRPs), angiogenic factors (PDGFbeta, HGF, bFGF, VEGFbeta), and matrix proteases (MMP2, MMP9, TIMP1, TIMP2) for potential early detection of MM. The area under ROC curves (AUC) indicates that 80HdG levels can discriminate asbestos-exposed subjects from controls but not from MPM patients. Significant AUC values were found for SMRP discriminating asbestos-exposed subjects from MPM patients but not from controls. VEGFbeta can significantly differentiate asbestos-exposed subjects from control and cancer groups. No diagnostic value was observed for MMP2, MMP9, TIMP1, TIMP2. The sensitivity and specificity results of markers were calculated at defined cut-offs. The combination of 80HdG, VEGFbeta and SMRPs best distinguished the individual groups, suggesting a potential indicator of early and advanced MPM cancers. The combination of blood biomarkers and radiographic findings could be used to stratify the risk of mesothelioma in asbestos-exposed populations.

Deep burn of the hands: Early surgical treatment avoids the need for late revisions?

An eight years experience in the management of deep hand burns is presented. We reviewed 116 cases of patients surgically treated with escarectomy and skin autograft. Seventy eight of them underwent early surgery within the first 4-6 days from injury, while 38 were conservatively treated in the fist stage and only lately surgery was performed (usually after the 14th day). In all patients, we applied the same post operative topic treatment and rehabilitation protocol. Several months after first admission, only 6(7.7%) of early treated patients needed secondary correction for unaesthetic and functionally debilitating scars versus 14(36.8%) of the late treated group. Our review confirm the importance of performing early surgery of deep burns of the hands, whenever possible, in order to achieve best results and shows it's utility in reducing re-admissions for secondary revisions.

Diagnosis of asbestos-related pleuropolmonary diseases.

A revision of criteria for diagnosis of asbestos-related pathological conditions was performed studying specially asbestosis, pleural plaques and malignant mesothelioma, also taking into account the problems connected with histopathology. As regards the histological diagnosis of asbestosis, it requires the presence of diffuse interstitialfibrosis in a well inflated tissue remote from the site of a tumour or other large lesion, plus the presence of two or more asbestos bodies in a 1 cm2 section. As regards the imaging diagnosis, the HRTC 4-point scale proposed by Paris et al. (2004) has been adopted:--0 images not suggestive of interstitial pneumonia;--1 modest unilateral or bilateral interstitial abnormalities, involving restricted areas if bilateral;--2 interstitial abnormalities of limited extent, but consistent with a diagnosis of asbestosis, i.e. honeycombing, even without other parenchymal changes and even though unilateral, or else any two abnormal findings among thickened interlobular septa, intralobular lines or subpleural curved lines;--3 numerous bilateral changes on several slices involving more than 2/3 of the posterior third of each hemi thorax. Only points 2 and 3 were considered consistent with the diagnosis of lung fibrosis. Such HRCT findings are not specific for asbestosis, changes in the pleural wall such as diffuse plaques and thickenings contribute to the diagnosis of asbestosis. As regards the pleural plaques and asbestos bodies we remark that they are merely exposition markers. We also discussed the problems the pathologist may encounter in diagnosing mesothelioma; in this field the prospects are encouraging as microarray analysis are beginning to identify new molecular markers for mesothelioma.

Increased membrane heterogeneity in stimulated human granulocytes.

TMA-DPH fluorescence decay in human PMN before and after stimulation with FMLP was studied using frequency domain fluorometry. Membrane heterogeneity was assessed by the width of the continuous distributions of lifetime values of Lorentzian shape used to describe the fluorescence decay. In non-stimulated granulocytes TMA-DPH fluorescence decay is characterized by two distributions of lifetime values centered at 6.5 and 1.0 ns and full width at half maximum of 0.3 and 1.2 ns, respectively. Within 15 min after stimulation, the center values of the two distribution components were 5.1 and 0.8 ns and the distribution width was 0.8 and 0.6 ns, respectively. These results indicate changes of membrane domain organization which can be ascribed to compositional changes and redistribution of membrane components.

Decrease in peripheral blood polymorphonuclear leukocyte chemotactic index in endometriosis: role of prostaglandin E2 release.

OBJECTIVE: To investigate the effect of disease on peripheral blood polymorphonuclear leukocyte chemotactic index and natural killer cell cytotoxicity and to provide additional information concerning the cell-mediated immune function in endometriosis. METHODS: Chemotactic index of peripheral blood polymorphonuclear leukocytes, natural killer cell activity, and plasma estradiol (E2) and plasma prostaglandin (PG) E2 levels were evaluated in 46 women who underwent laparoscopy or laparotomy for pelvic pain, infertility, and/or benign adnexal masses. RESULTS: The 20 women (43%) with endometriosis showed a decrease in peripheral blood polymorphonuclear leukocyte chemotactic index, related to advanced disease stage (P < .001). A significant inverse correlation was observed between plasma PGE2 levels and chemotactic index in stage III and IV endometriosis (r = -.73, P = .004). Similarly, natural cytotoxicity was decreased significantly with respect to the stage of endometriosis (P = .004) and related inversely to plasma PGE2 levels (r = -.74, P = .003). A direct relationship was observed between PGE2 and plasma E2 levels (r = .59, P = .006). CONCLUSION: Advanced endometriosis is associated with decreased peripheral blood polymorphonuclear leukocyte chemotactic index and natural killer cytotoxicity, which may be related to plasma PGE2 and E2 levels.

Wollastonite fibers in vitro generate reactive oxygen species able to lyse erythrocytes and activate the complement alternate pathway.

Wollastonite fibers were tested in vitro for their ability to produce reactive oxygen species (ROS) with two different systems: a cell-free reactive mixture containing deoxyribose and a polymorphonuclear leukocyte suspension. After adding the fibers, we measured the thiobarbituric acid-reactive substances produced by deoxyribose degradation and luminol-enhanced chemiluminescence, respectively. Compared with asbestos, wollastonite fibers produced higher ROS levels both in the PMN suspensions and in the cell-free reactive mixtures. A large amount of these ROS were not hydroxyl radicals. Indeed we obtained remarkable differences in ROS generation between unground and ground wollastonite fibers and negative results with fibers modified with ferric chloride and dithionite. In addition, ROS generation was partially inhibited (by 46-54%) in the reactions performed in the presence of 1,3-dimethyl-2-thiourea (DMTU), a strong hydroxyl radical scavenger. Wollastonite fibers were also analyzed for their ability to lyse erythrocytes and activate complement. Hemolytic potency was about twice that of chrysotile and half that of crocidolite. The levels of complement activation (via the alternate pathway) were about four-fifths of those measured in zymosan-activated plasma (a typical stimulus used to activate the alternate pathway), equal to those obtained with crocidolite, and two-thirds of those found with chrysotile. The addition of DMTU markedly reduced both these activities. Since asbestos fiber toxicity is mainly due to hydroxyl radical generation, our results indicate that wollastonite fibers are probably less toxic than asbestos fibers.

Chemotactic activity of human polymorphonuclear leukocytes and industrial xenobiotics: a brief review.

This review deals with some of our contributions to the use of chemotaxis, as a tool in evaluating effects of industrial xenobiotics on PMN, either in vitro or ex vivo. In vitro experiments have shown that lead, arsenic, styrene and 2,5-hexanedione, a major neurotoxicant metabolite of n-hexane, reduce chemotaxis. The most important results of ex vivo experiments have confirmed those obtained in vitro with styrene and 2,5-hexanedione: a significant reduction of chemotaxis was indeed observed in PMN harvested from workers exposed to low levels of n-hexane or styrene who did not show any sign of biochemical or clinical alteration. After 3 weeks under non-exposed conditions, the chemotactic indexes were markedly increased in most of the workers which were exposed to styrene and in all the workers exposed to n-hexane, all of whom have shown a reduced chemotaxis at the first blood sampling. Moreover chemotaxis was found to be significantly reduced at relative low levels of lead: results of the in vitro and ex vivo experiments show a comparable ranking of midpoint inhibition concentrations. We are only at the dawn of the understanding of the relation between occupational xenobiotics and PMN chemotaxis. This research area is still promising for the future, since PMN chemotaxis seems to be adequate and it must therefore enter in well-defined study protocols for investigating the potential immunotoxicity of occupational chemicals to which humans are exposed at low levels.

In vitro effect of acrylonitrile on specific activities of human polymorphonuclear leucocytes.

N-Formyl-methionyl-leucyl-phenylalanine (F-MLP)-induced chemotaxis and luminolamplified chemiluminescence were studied in isolated human polymorphonuclear leucocytes (PMN) and exposed to acrylonitrile (ACN) in vitro. Chemotaxis was reduced at ACN concentrations of 3 mm and above, while respiratory burst was affected at ACN concentrations of 18mm and above. The ACN concentrations were highly correlated both with decreased chemotactic activity (r = 0.75; P < 0.05) and with decreased respiratory burst (r = 0.93; P < 0.01).

Biological effects of contaminated silicon carbide particles from a workstation in a plant producing abrasives.

A sample of silicon carbide dust taken in the field from a plant producing abrasives was studied in vitro. The SiC particles (part unmilled and part milled) were able to disturb the structure of erythrocyte membranes and to lead to blood red-cell lysis; they also either interfered with complement and activated the alternate pathway, or interacted with biological media and polymorphonuclear leucocyte membranes, thus eliciting reactive oxygen species production. These in vitro properties were detected both in original large particles and unmilled particles, over 40% of which were of respirable size. The ability of these SiC particles to produce complement activation in vitro lends support to the previous hypothesis, that the radiographic opacities found in two workers employed in the same area of the plant from which the dust tested was taken are due to a reaction by pulmonary interstitial structures to SiC particle inhalation. It is speculated that SiC particles could act like asbestos, the ability of which to activate complement through the alternate pathway is considered to be one of the mechanisms by which the initial asbestotic lesions and subsequent fibrotic inflammatory infiltrates are generated in the lung.

Role of iron in asbestos-body-induced oxidant radical generation.

Asbestos bodies (AB) were harvested from human lung tissue digests and isolated from uncoated asbestos fibers. Samples containing 1000 AB were added to a reactive solution to investigate the ability of AB to oxidize deoxy-D-ribose and generate reactive oxygen species (ROS) in the presence of ascorbate and hydrogen peroxide as determined by formation of thiobarbituric acid (TBA)-reactive products. Three types of asbestos fibers were tested for comparison, since they are known to be able to produce ROS. The absorbance values measured with 1000 AB were significantly higher than those observed with 1000 fibers of the three types of asbestos. Since in our reaction system the only source of transition metals was the iron-rich AB, data suggest iron derived from the ferritin coating of AB was involved in oxidant generation. Addition of iron to AB enhanced TBA-reactive product formation, while chelation of Fe with deferoxamine reduced this reaction. Hydroxyl radical scavengers 1,3-dimethyl-2-thiourea (DMTU) and mannitol (MN) also effectively blocked TBA-reactive product generation. Data indicate the importance of Fe in AB-induced oxidant damage. With the addition of polymorphonuclear leukocytes (PMN) to AB, incubation in the reactive solution gave very high amounts of TBA-reactive products, but using a reactive solution devoid of ascorbate, very low amounts of TBA-reactive products were generated. In the latter condition, the superoxide of cell membranes probably reduced and removed iron from AB-coating ferritin, but less effectively than ascorbate. Further after the possible reoxidation of Fe2+, Fe3+ could be coordinated by lactoferrin. Since such availability of reductant is never approached in living systems, the iron in the AB coating is unlikely to function as a catalyst of Fenton-type reactions in vivo.

In vitro cleavage by asbestos fibers of the fifth component of human complement through free-radical generation and kallikrein activation.

Chrysotile and crocidolite fibers incubated in normal human plasma (NHP) generated from the C5 component of complement C5a-type fragments that stimulated polymorphonuclear leukocyte (PMN) chemotaxis. Absorption of NHP with antiserum against C5a totally abolished neutrophil chemotactic activity. Asbestos fibers also produced C5a small peptides in the presence of ethylene glycol bis(beta-aminoethyl ether) N,N,N'N'-tetraacetic acid (EGTA) but not ethylene diamine tetraacetic acid (EDTA). Activation of C5 was significantly inhibited when asbestos fibers were pretreated with iron chelators such as sodium dithionite (DTN), deferoxamine (DFX), or ascorbate (AA). Concentration-related inhibition of C5 activation was also observed when asbestos fibers were added concurrently to plasma in the presence of DFX, 1,3-dimethyl-2-thiourea (DMTU), a strong hydroxyl scavenger, or aprotinin (APR), a specific protease inhibitor. Further, chrysotile and crocidolite significantly increased plasma kallikrein activity. Data demonstrate that asbestos-induced C5 activation plays a role in inflammatory reactions characteristic of asbestosis through mechanisms involving iron ions, hydroxyl radicals, and oxidized C5-ike fragments. The ferrous ions present at the asbestos fiber surface trigger this activation and catalyze, via Fenton reaction, the production of hydroxyl radicals, which in turn convert native C5 to an oxidized C5-like form. This product is then cleaved by kallikrein, activated by the same asbestos fibers, yielding an oxidized C5a with the same functional properties as C5a.

Impairment of chemotaxis of polymorphonuclear leukocytes from lead acid battery workers.

Since lead impairs in vitro the functions of macrophagic cells, we have studied the chemotactic activity of polymorphonuclear leukocytes (PMNs) obtained from lead acid battery workers who were removed from exposure one month before, because they had an abnormal lead absorption. Controls were 18 age matched subjects without any history of occupational lead exposure. Both lead acid battery workers and controls had no alterations of the blood haematological and metabolic parameters. Chemotaxis was carried on in Boyden chambers using zymosan activated serum as chemotactic stimulus. The chemotactic indexes are 56.4 +/- 8.7 in acid battery workers and 75.6 +/- in controls. The difference, which is statistically significant, shows that lead workers have an impairment of PMNs chemotactic activity.

Distally based dorsalis pedis island flap for a distal lateral electric burn of the big toe.

Reconstruction of the small defects in the distal portion of the foot has always represented a difficult problem. A case of a young man with a deep electric burn of the distal lateral side of the big toe successfully treated with a distally based dorsalis pedis island flap based on the first dorsal metatarsal artery (FDMA) is presented. The donor site area of the dorsum of the foot was grafted, and deambulation was reassumed 3 weeks later. Advantages; limits and anatomical consideration regarding the viability of the flap are also discussed.

Mortality rate and prognostic indices in 2615 burned patients.

Two thousand six hundred and fifteen burned patients are analysed according to mortality rate and the results are compared with other prognostic indices. Our statistical data are similar to those reported by Feller et al. (1976), but differ from those expected by Roi et al. (1983) and Bull (1971). It is suggested that other burns centres should produce their statistical figures in the same way, thereby producing a wider statistical experience and a more accurate prognostic index. The improvement in the survival rate in our centre in the past 5 years is also discussed.

Human polymorphonuclear leukocyte chemotaxis as a tool in detecting biological early effects in workers occupationally exposed to low levels of n-hexane.

Human polymorphonuclear leukocytes (PMN) were chosen to measure two cellular end points--chemotaxis and respiratory burst--and to verify whether they could function as biomarkers of early effect in detecting occupational exposure to n-hexane of apparently healthy shoe workers, without any electroneuromyographic (ENMG) abnormality. Chemotaxis, but not respiratory burst, was found to be impaired. A negative linear correlation between chemotaxis of PMN of those workers that had been exposed to n-hexane versus 2,5-hexanedione (2,5-HD) urinary concentrations were found. This negative trend is consistent with our previous in vitro experimental findings: it was observed that the progressive addition of 2,5-HD to PMN suspensions inhibited chemotaxis in a dose-dependent mode, while chemiluminescence was not modified. Now we have confirmed in vivo that chemotaxis is more sensitive than the respiratory burst response to 2,5-HD. Such results justify the interest in the behaviour of PMN harvested from workers exposed to n-hexane. Since significant inhibition of chemotactic activity was observed in some workers whose urinary 2,5-HD levels were lower than 5 mg l-1, which is the biological exposure index suggested by ACGIH, this study suggests that PMN chemotaxis may be proposed as a useful biomarker in detecting occupational exposure to low level of n-hexane.

Fluid replacement in burned patients.

Burn injury involves a large amount of water, electrolytes and proteins loss trough the burn wound. For this reason, to avoid shock, a wide infusion of fluid is necessary in the first hours after trauma. Many reanimation formulas were proposed in the past years, with different composition: saline, colloids, plasma. The authors have studied 40 burned patients admitted in Verona Burn Center within 4 hours after burn, with burns over 30% of the body surface area. Twenty of them were treated with Baxter reanimation formula (ringer lactated saline, RLS) while the others with Monafo hypertonic lactated saline (HLS), modified by Milan Burn Center. The two randomized groups were assessed and compared. In RLS group total fluid volume infused was higher while sodium requirements was lower than in HLS patients, with statistically significative difference (p < 0.01). On the contrary, in HLS group, potassium administered was perhaps twice if compared with the other. Haematocrit, urine output and urine osmolarity were adequate in both the groups, and did not showed statistical differences, such as serum proteins concentration, that was low in all patients, while a significative difference was noted in urine osmolarity (p < 0.01). A metabolic alkalosis was present in HLS patients, while, on the other hand, serum nitrogen was significantly higher (p < 0.05), in the first 48 hours after burn, in RLS group. Patients were assessed for pre-existing diseases too, and data showed that complications were lower in HLS than in RLS group. HLS resuscitation formula guarantees a good electrolytes balance with lower fluid load, reducing tissue oedema and complication rate. Mortality rate was higher in HLS, may be for an higher Roy index in this group.