RESUMO
Hypertrophic scarring is a skin disorder that occurs after wounding and thermal injury. There is accumulating evidence that immunologic processes such as infiltration of activated T lymphocytes and altered cytokine production may play a role in the formation of hypertrophic scars. Interleukin-15, a cytokine identified as a T cell growth factor, also acts as a chemoattractant for T cells and has pro-inflammatory properties. We investigated the expression and the role of this cytokine in hypertrophic scarring. IL-15 expression was compared in skin biopsies of hypertrophic scars (HS) both in active (AHS) and in remission (RHS) phases, in normotrophic scars (NTS) and in normal skin using reverse transcriptase-polymerase chain reaction and immunohistochemistry. IL-15 expression in HS was significantly higher than in NTS or normal skin. Furthermore, AHS expressed higher levels of IL-15 than RHS. Immunohistologic analysis of AHS samples showed strong IL-15 immunoreactivity in keratinocytes and Langerhans cells in the epidermis and in macrophages, fibroblasts, and dermal dendritic cells in the dermis. High levels of IL-15 expression in AHS correlated with abundant infiltration of activated CD3+ cells. Ex vivo experiments indicate that IL-15 can sustain the proliferative response of T cells derived from AHS but not from RHS and NTS. In addition, IL-15 prevents both cytokine deprivation and activation-induced apoptosis of T cells derived from AHS. Taken together, these results suggest that IL-15 can be involved in the recruitment, proliferation, and apoptosis inhibition of T cells in AHS. The findings that the evolution from an AHS to a RHS is associated with a decrease in IL15 expression, and with a loss of IL-15 responsiveness in ex vivo-cultured T cells, indicate that this cytokine plays an important role in the biology of pathologic scar formation.
Assuntos
Cicatriz Hipertrófica/genética , Interleucina-15/genética , Interleucina-15/fisiologia , Adolescente , Adulto , Idoso , Apoptose/efeitos dos fármacos , Complexo CD3 , Ciclo Celular/efeitos dos fármacos , Divisão Celular/efeitos dos fármacos , Cicatriz Hipertrófica/metabolismo , Cicatriz Hipertrófica/patologia , Feminino , Expressão Gênica , Humanos , Imuno-Histoquímica , Interleucina-15/farmacologia , Interleucina-2/farmacologia , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas c-bcl-2/biossíntese , Proteínas Proto-Oncogênicas c-bcl-2/efeitos dos fármacos , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Linfócitos T/citologia , Linfócitos T/imunologiaRESUMO
Nineteen patients that had developed hypertrophic scars subsequent to thermal injury were typed for HLA class II allogenotypes with the restriction fragment length polymorphism technique. A significant association was found with DR beta 16 (pc = 1.45 x 10(-4); relative risk = 12.25). This finding adds evidence to other data suggesting that immunologic phenomena are involved in pathologic scarring. Moreover, the results presented here have allowed an identification of a genetically determined risk factor for hypertrophic scar formation located in the HLA region.
Assuntos
Cicatriz/imunologia , Antígenos HLA-DR/fisiologia , Cicatrização/imunologia , Cicatriz/genética , Genótipo , Antígenos HLA-DQ/genética , Antígenos HLA-DR/genética , Subtipos Sorológicos de HLA-DR , Antígenos de Histocompatibilidade Classe II/genética , Teste de Histocompatibilidade , Humanos , Isoantígenos/fisiologia , Polimorfismo de Fragmento de Restrição , Fatores de RiscoRESUMO
This is the final report of a large, controlled, multicenter Italian study on immuno- and chemotherapy in adult patients with burns affecting 20 to 95% of total body surface area (mean 35%). The antibiotic treatment of burn patients consisted of topical silver sulfadiazine, short-term antimicrobial chemoprophylaxis with pefloxacin (800 mg i.v. qd) for the first 4 days and polychemotherapy with teicoplanin (800 mg i.v. qd) together with netilmicin (300 mg i.m. qd) in one or more cycles of 5-12 days. At random, half of the patients received thymostimulin, 70 mg i.m. qd for the first month and every other day thereafter. The analysis at completion of 634 valid cases showed that when the results are stratified by means of the Roi risk index, 396 of the 530 patients who contracted wound infection (84%) after chemoprophylaxis were in the first three categories and a mean of 95% survived. Of the remaining 134 patients (Roi index 4-5) only 50% survived. There was no difference in survival of the immunotherapy group in comparison with the parallel group without thymostimulin. The short-term antimicrobial prophylaxis prevented wound infection in only 104 of 634 patients (16%) and they were at low risk (84% Roi index 1). Of the bacterial pathogens involved in septic complications Staphylococcus aureus and Pseudomonas aeruginosa were prevalent (86%): eradication was achieved in 43% of patients and clinical cure or improvement were seen with combination chemotherapy in 64% of all patients, mainly with only one treatment cycle. This value increased to 79% for the 395 protocol-complying patients and went down to 20% in the 135 non-compliers. The total survival of complier and non-complier patients was 447 of the 530 valid patients (84%). The overall mortality of the 634 evaluable patients was 13.1%, ranging from less than 2% to 68%. Burn mortality was directly proportional to the percentage of burned body surface area, to increasing age and other variables of the Roi index, a 50% mortality being associated with a 72.5% total body surface area burned. Normoergic burn patients had a mortality rate of 9.1% versus 35.7% in anergic patients.
Assuntos
Antibacterianos/uso terapêutico , Anti-Infecciosos/uso terapêutico , Queimaduras/tratamento farmacológico , Gentamicinas/uso terapêutico , Netilmicina/uso terapêutico , Teicoplanina/uso terapêutico , Infecção dos Ferimentos/prevenção & controle , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/administração & dosagem , Anti-Infecciosos/administração & dosagem , Superfície Corporal , Queimaduras/mortalidade , Queimaduras/patologia , Criança , Quimioterapia Combinada , Feminino , Gentamicinas/administração & dosagem , Humanos , Imunoterapia , Injeções Intramusculares , Itália , Masculino , Pessoa de Meia-Idade , Netilmicina/administração & dosagem , Pefloxacina/administração & dosagem , Pefloxacina/uso terapêutico , Fatores de Risco , Sulfadiazina/administração & dosagem , Sulfadiazina/uso terapêutico , Teicoplanina/administração & dosagemRESUMO
In previous studies we have shown that HLA Class II antigens are expressed by keratinocytes and fibroblasts in hypertrophic scars. Because of the potential role of immunological events in the pathogenesis of hypertrophic scars, in the present study we have tested hypertrophic scars for the expression of intercellular adhesion molecule-1 (ICAM-1), a molecule which plays an important role in immunological phenomena. Immunoperoxidase staining with anti-ICAM-1 MoAb of 10 hypertrophic scar samples detected this molecule on epidermal keratinocytes and on about 30 per cent of fibroblasts at the site of lymphoid infiltration. The expression of ICAM-1 in hypertrophic scars was similar to that of HLA Class II antigens. Since the concomitant expression of ICAM-1 and HLA Class II by keratinocytes is known to enhance their antigen-presenting properties, the present results support the possibility that immunological events play a role in the disruption of the normal processes of wound healing and tissue remodelling which result in hypertrophic scars.
Assuntos
Queimaduras/imunologia , Cicatriz Hipertrófica/imunologia , Antígenos de Histocompatibilidade Classe II/análise , Molécula 1 de Adesão Intercelular/análise , Adulto , Queimaduras/complicações , Queimaduras/patologia , Cicatriz Hipertrófica/etiologia , Feminino , Fibroblastos/imunologia , Humanos , Técnicas Imunoenzimáticas , Queratinócitos/imunologia , Masculino , Pessoa de Meia-Idade , Pele/imunologiaRESUMO
In this study, skin-infiltrating cells were characterized in both the active and remission phases of post-burn hypertrophic scar biopsies. Immunohistochemistry examination of active phase samples showed an abundant presence of Langerhans cells, T cells, macrophages, a low presence of natural killer cells and the lack of B lymphocytes. In active hypertrophic scars T lymphocytes infiltrate deep into the superficial dermis and are also observed in the epidermis: CD3+ cells were present at about 222 +/- 107 per 0.25 mm2. In particular the analysis of lymphocyte subpopulations showed that CD4+ T cells predominate in the dermis as well as in the epidermis of active hypertrophic scars whereas CD8+ cells were less well represented (CD4/CD8 ratio is 2.06). This distribution was also shown in remission phase samples and in normotrophic scar specimens, although the lymphocyte number was significantly lower. Approximately 70 per cent of T lymphocytes present in the tissue involved in active phase hypertrophic scar samples were activated (positive with anti-HLA-DR and IL-2 receptor antibodies) which is significantly higher than remission phase hypertrophic and normotrophic scars, in which positivity was 40 and 38 per cent, respectively. Upon activation, the lesional lymphocytes release several cytokines, locally and transiently, that interact with specific receptors in response to different stimulation. Central to the immune hypothesis of hypertrophic scars is that some of the T-cell lymphokines act on keratinocytes, fibroblasts and other cell types to induce changes characteristic of these scars. The presence and close proximity of activated T lymphocytes and antigen-presenting cells of various phenotypes in both the epidermis and dermis of hypertrophic tissues provides strong circumstantial evidence of a local immune response. However, the manner in which T cells achieve and maintain their activated state in hypertrophic tissues is not yet known, and both antigen-dependent and independent mechanisms may contribute.
Assuntos
Queimaduras/imunologia , Cicatriz Hipertrófica/imunologia , Antígenos HLA-DR/análise , Receptores de Interleucina-2/análise , Subpopulações de Linfócitos T/patologia , Cicatrização/imunologia , Adolescente , Adulto , Idoso , Anticorpos Monoclonais/análise , Biomarcadores/análise , Biópsia por Agulha , Contagem de Linfócito CD4 , Relação CD4-CD8 , Cicatriz Hipertrófica/patologia , Técnicas de Cultura , Feminino , Humanos , Macrófagos/patologia , Masculino , Pessoa de Meia-Idade , Radioimunoensaio , Valores de Referência , Sensibilidade e EspecificidadeRESUMO
The present study shows that the decrease of TNF alpha in postburn hypertrophic scars is due to a decrease in the steady-state level of TNF alpha mRNA and thus to an altered biosynthesis of the cytokine. Thirteen scars, including seven hypertrophic and six normotrophic scars, were tested for TNF alpha mRNA production by a semiquantitative reverse polymerase chain reaction (PCR) method. TNF beta and beta actin were tested as a control. Six out of six normotrophic scar samples amplified with primers for TNF alpha showed a positive PCR signal up to the 1:32 dilution. On the contrary all the hypertrophic tested samples (7/7) had a positive PCR signal only at the 1:1 or 1:2 dilution. All samples, both normotrophic and hypertrophic, were homogeneous as to TNF beta production.
Assuntos
Queimaduras/complicações , Cicatriz Hipertrófica/metabolismo , Fator de Necrose Tumoral alfa/biossíntese , Actinas/biossíntese , Cicatriz Hipertrófica/etiologia , Humanos , Linfotoxina-alfa/biossíntese , Reação em Cadeia da PolimeraseRESUMO
The results of protein deficiency in major burn cases are examined. They include diminished organ resistance, deleyed wound haeling, proneness to infection, and increased sensitivity to liver-toxic substances, leading to the protracted course of the patient's conditions. Since his caloric intake also needs to be increased, the importance of protein replacement is apparent. A standardised 15-day treatment with daily administrations of 1000 cc of a 7.5% natural amino acid solution was experimented during the period following shock, to prevent loss of amino acids through the vessel walls, since permeability is high in this periodo. Marked improvement in blood proteins was noted, with normalisation in some instances. No chagens in blood chemistry attributable to the treatment were noted.
Assuntos
Aminoácidos/uso terapêutico , Queimaduras/tratamento farmacológico , Aminoácidos/administração & dosagem , Queimaduras/complicações , Queimaduras/metabolismo , Humanos , Deficiência de Proteína/etiologia , Choque Traumático/tratamento farmacológico , Soluções , Equilíbrio Hidroeletrolítico/efeitos dos fármacosRESUMO
Laurell's two-dimensional technique was employed in a study of the immunoelectrophoretic behaviour of caeruloplasmin in 10 major burn cases. A double peak was noted throughout the entire course. The second peak disappeared on recovery whereas it persisted and was well marked in the case of those who died. It is suggested that this pattern reflects the severe liver damage sustained by burn patients.
Assuntos
Queimaduras/sangue , Ceruloplasmina , Adulto , Queimaduras/complicações , Ceruloplasmina/análise , Pré-Escolar , Feminino , Humanos , Imunoeletroforese , Hepatopatias/diagnóstico , Hepatopatias/etiologia , MasculinoRESUMO
New surgical procedures requiring viable skin have increased rapidly over the last few years. The cell viability assessment in allograft skin is a major step forward in burn treatment, since it is well-known that taking is correlated with grafted tissue viability. Various methods, both qualitative and quantitative, are currently used. Although qualitative assays (histomorphology, immunocytochemistry) are routinely performed in our laboratory, there arose a need to set up a standardised quantitative assay in an attempt to obtain a cut-off value so that the skin sample could be determined valid or not for grafting. Therefore, two different tetrazolium salt compounds MTT and WST-1, were compared in order to determine their efficacy in the evaluation of tissue viability. Several experimental conditions were analysed: 1- cellular cultures of keratinocytes and fibroblasts, 2- fresh skin tissue samples, 3- the same specimen tested daily for at least 2 weeks, 4- after cryopreservation and thawing. Viable cells were analysed by the cleavage of tetrazolium salts to formazan by cellular enzymes. The formazan dye produced by metabolically active cells was then quantified by measuring the absorbance of the dye solution at the appropriate wavelength. It was seen that WST-1 is easier to handle, more stable, has a wider linear range, accelerated colour development and is more sensitive than MTT on fresh specimens and cell suspension. However, after 72 hours of storage at 4 degrees C, most of the WST-1 tested specimens no longer gave any absorbance signal, whilst MTT specimens were seen to give a signal for more than two weeks. Moreover, after thawing WST-1 tested samples were almost negative, whilst MTT samples continued to give strong signals. In conclusion, WST-1 assay offers rapid and precise results as to the cell viability of fresh allografts and cell cultures, whilst the MTT method is much more useful in establishing viability after long conservation and cryopreservation. In our clinical experience, allografts transplanted at 72 hr post-harvesting or after cryopreservation showed a mean of take more than of 80%, demonstrating that the MTT system is more reliable for the determination of allograft viability. Studies are ongoing with larger clinical cohorts to establish the precise cut-off value for skin graft validation.
RESUMO
Technological progress in reconstructive surgery, in particular the use of pedunculated or free flaps, has given new impetus to head and neck dissection. This stems from the fact that such techniques provide greater oncological radicality, reduce the number of severe post-operative complications and give better quality of life. The present study examines 154 patients suffering from upper aero-digestive tract neoplasms (131 males and 23 females; age range 23-82 years) who had undergone radical surgery. Reconstruction was performed with flaps in 154 cases: 119 pedunculated flaps (102 large myocutaneous pectoral and 17 temporal muscle flaps) and 35 free flaps (18 radial osteofasciocutaneous, 13 radial fasciocutaneous and 4 omentum flaps). Analysis of the individual districts showed that the flap of choice was the temporal muscle flap when surgery involved the soft parts of the orbital-maxilly-zigomatic area and the rhinopharynx. This is because it is highly moldable and reliable. In surgery of the oral cavity and oropharynx the grand pectoral flap is most frequently used as it provides enough tissue for the reconstruction, adequately protects the vascular-nerve axis in the neck and it is quick and easy. However, the functional results are not the best and there is some alteration in the initial phases of deglutition. To reduce these problems, the authors encourage the use of free flaps which provide good results from both the functional and esthetic points of view. They are, however, more difficult to perform and this leads the authors to conclude that they should only be selected for certain patients (long life expectancy, female, young, etc.). In the center where the authors work the flap of choice is the radial fasciocutaneous or osteofasciocutaneous flap. In surgery of the hypopharynx and larynx reconstruction is normally performed with a grand pectoral myocutaneous flap, sculpted as needed for the individual case. In this region, reconstruction proves functionally satisfactory even when there is a minimum of residual mucosa. Finally, for reconstructive surgery of the apex, the omentum free flap was used as it is malleable and can be used to reconstruct broad areas of dissection. The esthetic and functional results, the low incidence of complications and the greater quality of life suggest that this type of flap be extended to the surgery of locally advanced tumors in combination with an accurate, valid reconstructive solution.
Assuntos
Neoplasias de Cabeça e Pescoço/cirurgia , Retalhos Cirúrgicos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Estudos Retrospectivos , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Appearance of acute renal failure (ARF) in severely burnt patients (GU) is a serious complication. It has a negative prognostic value and almost always develops in the context of multiple organ dysfunction syndrome (MODS) induced by sepsis. Over the last 20 years, according to data available, the mortality rate has been reported to reach about 75%. We have analyzed the initial results obtained in GU patients who were admitted to the Intensive Care Unit of the Burns Center in Turin. METHODS: Out of 105 GU patients admitted between July 1999 and September 2000 (burned surface area (BSA) 23.8%, range 2-95%, mortality rate 13.7%), 7 patients (6.4%) had complications of ARF requiring extracorporeal dialytic therapy (38 HF sessions lasting 4-6 hours, 2 HF + 12 HDF + 1 UF sessions lasting 8-11 hours). RESULTS: Total BSA of 7 GU patients with ARF was 62.5+/-11.3% (mean +/-SEM). Mortality rate was 71.4% which was due to septic shock and MODS. ARF onset was at 28.4+/-8.4 days from admission. Dialytic treatment started at Crs 2.3+/-0.42 mg/dl, and patients were treated for 7.6+/-3.5 days with a weight loss of 1859+/-161 gr/die. Circuit anticoagulation was obtained by minimal amount of heparin (132.2+/-26.5 U/hour) and no hemorrhagic complications were observed. CONCLUSIONS: In GU patients with ARF the dialytic treatment with daily long-lasting convective- diffusive techniques permitted us to achieve a survival and dialytic adequacy similar to those reported with continuous renal replacement therapies; however, mortality rate is high and related to septic shock and MODS.
Assuntos
Injúria Renal Aguda/terapia , Queimaduras/complicações , Diálise Renal , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/mortalidade , Adulto , Idoso , Anticoagulantes/uso terapêutico , Unidades de Queimados/estatística & dados numéricos , Queimaduras/mortalidade , Queimaduras/cirurgia , Queimaduras/terapia , Terapia Combinada , Feminino , Hidratação , Hemofiltração/estatística & dados numéricos , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/etiologia , Insuficiência de Múltiplos Órgãos/mortalidade , Diálise Renal/métodos , Diálise Renal/estatística & dados numéricos , Estudos Retrospectivos , Choque Séptico/etiologia , Choque Séptico/mortalidade , Síndrome de Stevens-Johnson/complicações , Simpatomiméticos/uso terapêutico , Resultado do TratamentoAssuntos
Queimaduras/cirurgia , Queratinócitos/transplante , Transplante de Pele/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Queimaduras/patologia , Queimaduras/terapia , Células Cultivadas , Criança , Pré-Escolar , Humanos , Pessoa de Meia-Idade , Pele/citologia , Transplante Autólogo , Cicatrização/fisiologiaAssuntos
Adaptação Psicológica , Queimaduras/psicologia , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ajustamento SocialAssuntos
Queimaduras/cirurgia , Traumatismos Faciais/cirurgia , Lesões do Pescoço , Dermabrasão , Feminino , Humanos , MasculinoRESUMO
During a 10-year period, 467 patients with burns involving the hands have been treated, 290 of whom during the past 5 years. Two groups of patients were examined: the first were those who had received treatment between 1967 and 1971 using the exposure method and the reconstruction with skin grafts only after the spontaneous separation of the eschars, and the second, using the closed method and early or late excision of the necrotic tissue followed by covering with split-thickness grafts. In this second group are included also those patients whose burns can be classified as medium depth at the time of admission but in whom experience has shown that one is dealing with lesions with a tendency to become deeper during the post-burn period. For these cases a dermabrasion of the lesions was performed without covering with free grafts. In the cases subjected to surgery using the technique of tangential excision and dermabrasion in order to reach the more difficult areas such as the interdigital spaces, dermabrasion was only performed between the 2nd and the 28th day. The removal of the burned tissue was followed by covering with free grafts, except in those cases in which the depth was in doubt. The results obtained have demonstrated that in the first group the scars have led to serious invalidating consequences which have necessitated long and complex surgical reconstruction programmes. In the second group almost complete function has been restored with the aid of only minimal surgical correction, most often in the interdigital spaces. We would like to emphasize the usefulness of surgery in those cases on the borderline between medium and full thickness. The tendency of these lesions to become deeper has often led to scars which are very similar to those following the deep lesions.
Assuntos
Queimaduras/terapia , Traumatismos da Mão/terapia , Queimaduras/complicações , Queimaduras/cirurgia , Desbridamento , Seguimentos , Traumatismos da Mão/complicações , Traumatismos da Mão/cirurgia , Humanos , Transplante de Pele , Fatores de Tempo , Transplante Autólogo , Infecção dos Ferimentos/prevenção & controleRESUMO
Among acute "traumatisms", occupational and domestic accidents chiefly share burn. To compare these two causes of severe burns, we examined clinical records of patients hospitalized from January 1986 to February 1989 in the "Grand Burns Center" at the C.T.O. hospital in Turin. Data exclusively refer to patients over 12 years old. 61 out of 313 cases (19%) were due to occupational burns, 221 (71%) to domestic ones (left cases including burns occurred in different surroundings). Males predominance was very high (95%) in the occupational settings, lower though still relevant (60%) in the domestic ones. The topographic distribution of the burns did not show any relevant difference. Similarly, the two groups did not differ as the affected percent of the body surface area (BSA) is concerned: in both cases burns extended cases. Decreased patients were fairly more numerous among the domestic burns (33%) as compared to the occupational ones (18%). The overwhelming majority (90.5%) of domestic burns were caused by fire; such a predominance, though present, was lower (68.8%) among occupational accidents. More in detail, domestic burns were caused as follows: alcohol spraying to stir a fire (26%), gas burst (25%), flammable substances exposed to heat sources (18%), hot water or different liquid (8%), fall over heating devices (6%), fires from cigarettes in bed (5%), kitchen stoves (with or without clothing fire) (5%), brushwood burning (4%), other (3%). It is worth noting that in as many as 40% of the cases of domestic burns patients were affected by a pre-existing neuro-psychic disorder, namely: personality disorders (15%), psychiatric disorders (%), epilepsy (9%), mental debility (7%).
Assuntos
Acidentes Domésticos , Acidentes de Trabalho , Queimaduras/etiologia , Adolescente , Adulto , Idoso , Queimaduras/classificação , Queimaduras/epidemiologia , Feminino , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-IdadeRESUMO
The results obtained with early surgical treatment of burns have been re-examined from various aspects. Early escharectomy, which tranforms the necrobiotic tissue into a surgical lesion, reduces the chemical factors of inflammation, lowers the lactic acid level and depresses the activity and disordered proliferation of the fibroblasts and the consequent laying down of immature collagen which is responsible for the pathological evolution of the burn scar. The removal of toxic material with proteasic activity, the reduction in the risk of sepsis, the saving of work for the immunopoietic mechanism, a reduction in the weight loss through improved nitrogen balance and an increase in the anabolic phase of muscular metabolism by early movement as well as a shortening of the period of hospitalization--all are factors in favour of the early surgical technique. Better healing is obtained by the elimination of the necrotic tissue, a reduction in the haematologic tissue inflammation mediators, an increase in the antibacterial defence following the reconstruction of the skin surface with covering materials and the rapid articular reduction; not to mention the inhibition of the formation of granulation tissue.