Severe Tissue Damage Research Articles

The role of activated cytotoxic T cells in etiopathogenesis of periodontal disease: does it harm or does it heal?

The objective of this study was to determine the phenotypic profile of blood mononuclear cells, specifically CD8+/CD28+ cells, in patients with generalized aggressive periodontitis (GAgP) and chronic periodontitis (CP) in peripheral blood and in blood obtained from periodontal defect site which might contribute to tissue damage. 13 GAgP, 11 chronic periodontitis (CP) and 5 healthy controls (H) were included in the study. Plaque index (PI), bleeding on probing (BoP), periodontal probing depth (PPD) and clinical attachment level (CAL) were recorded. Blood from the base of periodontal defect site and peripheral blood from the antecubital vein were obtained. Relative counts of CD45+, CD3+, CD4+, CD8+/CD28+, CD8+/CD28−, CD19+, CD16+/CD56+/CD3, CD3+/CD16+/CD56+ receptors were determined with two color flow cytometry using monoclonal antibodies. BoP, PPD and CAL were significantly higher in both periodontitis groups than healthy controls (p <0.05). Activated cytotoxic T cells, CD8+/CD28+ cells, were significantly elevated in GAgP and CP groups compared to HC both in blood obtained from defect site and blood obtained from systemic circulation (p <0.05). GAgP and CP patients have an increased levels of activated cytotoxic T cells as a result of inflammation which may cause severe tissue damage that lead to severe and rapid loss of periodontal tissues.

ILIZAROV FRAME FOR FINAL TREATMENT OF SEVERE ANKLE FRACTURES

This article is about treatment of severe ankle injuries.Significant incidence of fractures of this localization and the problem of treatment of severe soft tissue damages make the work relevant. Despite advantages of internal fixation external osteosynthesis is often the only possible solution to a severe clinical situation.A significant number of patients justify rationale for the Ilizarov frame as the primary method of treatment. The most common technical problems and complications in the treatment of fractures the optimal starting date of treatment are analyzed. The criteria of satisfactory and unsatisfactory reduction, indications to a change of fixation for internal one are described. On clinical cases the authors show good results and alternative assembles of external devices.A feature of the work is its practical value and authors’ recommendations.

Development of histopathological indices in the digestive gland and gonad of mussels: Integration with contamination levels and effects of confounding factors

Bivalve histopathology has become an important tool in aquatic toxicology, having been implemented in many biomonitoring programmes worldwide. However, there are various gaps in the knowledge of many sentinel organisms and the interference of confounding factors. This work aimed (i) to develop a detailed semi-quantitative histopathological index of the digestive gland and gonad of the Mytilus galloprovincialis mussel collected from five sites contaminated with distinct patterns of organic and inorganic toxicants along the Basque coast (SE Bay of Biscay) and (ii) to investigate whether seasonal variability and parasitosis act as confounding factors. A total of twenty-three histopathological alterations were analysed in the digestive gland and gonad following a weighed condition index approach. The alterations were integrated into a single value for a better understanding of the mussels’ health status. The digestive gland was consistently more damaged than the gonad. Mussels from the most impacted sites endured the most significant deleterious effects showing inflammation-related alterations together with digestive tubule atrophy and necrosis. Neoplastic diseases were scarce, with only a few cases of fibromas (benign neoplasia). In contrast, in moderately or little impacted sites, contamination levels did not cause significant tissue damage. However, parasites contributed to overestimating the values of histopathological indices (i.e. more severe tissue damage) in mussels from little impacted sites, whilst the opposite occurred in mussels from highly polluted sites. Accordingly, inter-site differences were more pronounced in autumn when natural physiological responses of advanced maturation stages did not interfere in the histological response. In conclusion, although seasonal variability and parasitosis mask the response of histopathological indices, this biomonitoring approach may provide good sensitivity for assessing the health status of mussels if fluctuations of these confounding factors are considered.

Kidney Injury Molecule-1 Protects against Gα12 Activation and Tissue Damage in Renal Ischemia-Reperfusion Injury

Ischemic acute kidney injury is a serious untreatable condition. Activation of the G protein α12 (Gα12) subunit by reactive oxygen species is a major cause of tissue damage during renal ischemia-reperfusion injury. Kidney injury molecule-1 (KIM-1) is a transmembrane glycoprotein that is highly up-regulated during acute kidney injury, but the physiologic significance of this up-regulation is unclear. Here, we report for the first time that Kim-1 inhibits Gα12 activation and protects mice against renal ischemia-reperfusion injury. We reveal that Kim-1 physically interacts with and inhibits cellular Gα12 activation after inflammatory stimuli, including reactive oxygen species, by blocking GTP binding to Gα12. Compared with Kim-1(+/+) mice, Kim-1(-/-) mice exhibited greater Gα12 and downstream Src activation both in primary tubular epithelial cells after in vitro stimulation with H2O2 and in whole kidneys after unilateral renal artery clamping. Finally, we show that Kim-1-deficient mice had more severe kidney dysfunction and tissue damage after bilateral renal artery clamping, compared with wild-type mice. Our results suggest that KIM-1 is an endogenous protective mechanism against renal ischemia-reperfusion injury through inhibition of Gα12.

Characteristics and clinical outcome in patients after popliteal artery injury

The treatment of popliteal artery injury (PAI) caused by blunt or penetrating mechanism is demanding. Concomitant injuries and prolonged ischemia are the major causes of lower extremity morbidity and poor rates of limb salvage. This study assessed the amputation rate and, subsequently, the therapeutic management and clinical outcomes regarding the affect of concomitant injuries among patients with PAI in a setting of central European trauma care. Sixty-four patients (20 female and 44 male), with an average age of 44 years (range, 17-79 years) at the time of injury, were evaluated for clinical characteristics, concomitant injuries, complications, amputation rates, and functional outcome after traumatic PAI. The mechanism of injury was blunt trauma in 35 patients (54.7%) and penetrating trauma in 29 (45.3%). The Mangled Extremity Severity Score and the Injury Severity Score were assessed initially and the modified Functional Independence Measure (FIM) Score at 12 months after the primary surgery. Thirty patients (47%) returned to their normal activity level within 1 year after trauma, and 16 (25%) were limited in their daily activity or suffered from chronic pain symptoms. Within the blunt trauma group 26 of 35 patients (74%) sustained severe concomitant injuries, whereas two of 29 patients (7%) in the penetrating group showed severe concomitant injuries (P < .046). Eleven patients (17%) had to undergo revision surgery due to their associated injuries. The median modified FIM score was 10.3, whereas patients with blunt trauma had significantly lower FIM score (P < .0082). The median Mangled Extremity Severity Score was 6 points (range, 6-16 points). Primary or secondary amputation was required in 18 patients (28%) due to failure of revascularization. Patients who sustained blunt trauma had significantly higher amputation rates than those with penetrating injuries (P < .035). Clinical outcome and limb salvage of patients with PAI were influenced by the mechanism of trauma, concomitant injuries, prolonged ischemia time, and the type of surgical procedure. Patients after blunt trauma had a higher incidence of concomitant injuries, and (comminuted) fractures or knee dislocations and severe soft tissue damage had the highest effect on the amputation rate.

Super-low Dose Endotoxin Pre-conditioning Exacerbates Sepsis Mortality

Sepsis mortality varies dramatically in individuals of variable immune conditions, with poorly defined mechanisms. This phenomenon complements the hypothesis that innate immunity may adopt rudimentary memory, as demonstrated in vitro with endotoxin priming and tolerance in cultured monocytes. However, previous in vivo studies only examined the protective effect of endotoxin tolerance in the context of sepsis. In sharp contrast, we report herein that pre-conditioning with super-low or low dose endotoxin lipopolysaccharide (LPS) cause strikingly opposite survival outcomes. Mice pre-conditioned with super-low dose LPS experienced severe tissue damage, inflammation, increased bacterial load in circulation, and elevated mortality when they were subjected to cecal-ligation and puncture (CLP). This is in contrast to the well-reported protective phenomenon with CLP mice pre-conditioned with low dose LPS. Mechanistically, we demonstrated that super-low and low dose LPS differentially modulate the formation of neutrophil extracellular trap (NET) in neutrophils. Instead of increased ERK activation and NET formation in neutrophils pre-conditioned with low dose LPS, we observed significantly reduced ERK activation and compromised NET generation in neutrophils pre-conditioned with super-low dose LPS. Collectively, our findings reveal a mechanism potentially responsible for the dynamic programming of innate immunity in vivo as it relates to sepsis risks.

Cocaine snorting may induce ocular surface damage through corneal sensitivity impairment.

Cocaine abuse may cause severe ischemic and necrotic tissue damage in several organs, including the eye. However, the cornea is an avascular tissue relying on sensitive nerves for its trophic support, and the pathogenesis of cocaine-induced corneal lesions is unclear. In this study, we aimed to investigate if corneal sensitivity, ocular surface, and tear function are damaged by habitual cocaine snorting. Ocular examination, corneal sensitivity, and tear function testing were carried out in 48 cocaine addicts, and in 22 heroin addicts and 30 drug-free age/sex-matched individuals who served as controls. We also performed corneal confocal microscopy, conjunctival impression cytology, and tear sample collection to evaluate corneal and conjunctival morphology, and the presence of cocaine in tears. Statistical analysis was performed to compare groups and to correlate clinical findings with anamnestic data on cocaine use. We observed decreased corneal sensitivity in 26 cocaine addicts, and neurotrophic keratitis in six of them, with corneal damage, absence of symptoms, reduced tear production, and prolonged interblink-time. No significant changes in ocular surface parameters including corneal sensitivity were observed in heroin addicts. The major risk factors for developing cocaine-induced neurotrophic keratitis appeared to be duration and frequency of drug abuse. A complete ophthalmic evaluation including corneal sensitivity testing should be planned for an optimal management of cocaine addicts, even in the absence of ocular symptoms, to reduce the risk of corneal lesions and consequent vision impairment. Sensory nerve damage should also be evaluated in cocaine-induced lesions of other organs.

Low serum levels of alpha1 anti-trypsin (α1-AT) and risk of airflow obstruction in non-primary α1-AT-deficient patients with compensated chronic liver disease.

BackgroundAlpha1 anti-trypsin (α1-AT), a serine protease inhibitor synthesized in the liver, is a major circulating antiprotease that provides defense against proteolytic damage in several tissues. Its deficiency is associated with airflow obstruction. The present study aimed to explore the role of α1-AT as a biomarker of airflow performance in chronic liver disease (CLD).Material/MethodsSerum α1-AT levels and lung function (spirometry) were evaluated in non-primary α1-AT-deficient, alcoholic CLD patients without evident respiratory limitations.ResultsThirty-four patients with airflow obstruction (n=11), airflow restriction (n=12), and normal airflow (n=11, age-matched controls) were eligible. α1-AT was decreased in the airflow obstruction group. ROC-cutoff α1-AT=24 mg/dL effectively discriminated airflow obstruction (AUC=0.687) and was associated with a 10-fold higher risk (p=0.0007).ConclusionsLower α1-AT increased the risk of airflow obstruction in CLD patients without primary α1-AT deficiency.

High Expression Levels of Trigger Receptor Expressed on Myeloid Cells-1 on Neutrophils Associated with Increased Severity of Acute Pancreatitis in Mice.

Triggering receptor expressed on myeloid cells (TREM)-1 expression on neutrophils is associated with inflammation and infection. However, the dynamic changes of the TREM-1 expression on neutrophils have not been clarified in inflammatory acute pancreatitis (AP). The aim of this study was to longitudinally investigate the TREM-1 expression on peripheral blood and peritoneal neutrophils and its relationship with the levels of plasma cytokines and disease severity in a mouse model of AP following injection with varying doses of L-arginine to induce mild AP (MAP) or severe AP (SAP). The results indicated that induction of MAP or SAP was associated with moderate and severe pancreatic tissue damage and varying levels of serum and peritoneal fluid amylase as well as survival rates in mice. In comparison with that in the healthy controls, significantly increased percentages of peripheral blood and peritoneal fluid CD14-TREM-1(+) neutrophils and higher levels of TREM-1 mRNA transcripts in peripheral blood nuclear cells were detected in the MAP and SAP mice, particularly in the SAP mice. Higher levels of plasma tumor necrosis factor (TNF)-α and granulocyte-macrophage colony stimulating factor (GM-CSF), but lower levels of plasma interleukin (IL)-10, were detected in the MAP and SAP mice at varying time points post induction. The percentages of peripheral blood CD14-TREM-1(+) neutrophils were correlated positively with the levels of TNF-α, GM-CSF, and amylase as well as the pathogenic scores, but negatively with the levels of IL-10 in the AP mice. Therefore, TREM-1(+) neutrophils may participate in the pathogenesis of AP and serve as a biomarker for evaluating the severity of AP.

Effectiveness of the Androctonus Australis Hector Nanobody Nbf12-10 Antivenom to Neutralize Significantly the Toxic Effect and Tissue Damage Provoked by Fraction of Androctonus mauretanicus (Morocco) Scorpion Venom

Scorpion stings are life threatening in large parts of the world. Toxins from scorpion venom are responsible for severe metabolic and tissue disruption and immunotherapy is the only specific treatment able to neutralize the toxic effects of scorpion venom. The Androctonus mauretanicus (Am) is the most dangerous scorpion in Morocco, whereas in Tunisia Androctonus australis hector (Aah) is causing most casualties. In this work, we investigated the potential of NbF12-10, a new immunotherapeutic concept based on anti-toxin Nanobodies (Nbs) to neutralize Am scorpion venom. We first explored the immune cross-reactivity between Am and Aah scorpions venoms using anti-AahI and anti-AahII polyclonal, NbAahI’F12 (anti-AahI’), monospecific NbAahII10 (anti-AahII) and bispecific NbF12-10 (anti-AahI’/anti- AahII) monoclonal antibodies and subsequently we study the histological damages observed after envenomation with the F3 toxic fraction of Am scorpion venom by intra-cerebroventricular (i.c.v) injection and the capacity of NbF12-10 to reduce tissue damage induced by F3 fraction after i.c.v administration of F3:NbF12-10 mixture, in mice. Results showed significant para-specific activity of anti-Aah polyclonal and monoclonal antibodies towards Am venom fractions. Histological investigations revealed severe tissue damage in brain, lung and liver after i.c.v. administration of F3 fraction. The NbF12-10 pre-mixed with F3 fraction showed an efficient neutralizing capacity against lethal effect of this toxic fraction. Moreover, in vitro pre-incubation of F3 with NbF12-10 at 8-fold molar excess led to significantly reduced tissue damage. Further, NbF12-10 displays a noteworthy potential to neutralize Am toxins and to rescue 50% of envenomed mice from dying. This study provides first evidence that NbF12-10 nano-therapeutic has promising prospective to treat scorpion envenoming in the Maghreb area.

Severe Burns and Amputation of Both Arms in the First Psychotic Episode of a Schizophrenic Patient.

An alleged reduction of sensitivity to pain in people with schizophrenia has been reported, but the nature of this complex phenomenon has not been elucidated yet. Reports of insensitivity to burns from people with schizophrenia are extremely rare. We report the case of a 24-year-old man who set both of his arms on fire during the first break of paranoid schizophrenia. As a result of severe tissue damage, both of his limbs had to be amputated. Today, at the age of 59, the patient is physically and mentally rehabilitated and is adherent to treatment. Additionally, given the uncertainty about the true nature of the alleged hypoalgesia in schizophrenia, we postulate the need for a comprehensive phenomenological approach in the study of embodiment in people with this condition.

Gene expression profiling and verification for severe secondary pulmonary tuberculosis patients

To explore the gene expression profiles of severe secondary pulmonary tuberculosis patients. From May 2012 to October 2013, a total of 103 eligible patients with secondary pulmonary tuberculosis were recruited from Institution of Tuberculosis Research of PLA Hospital No. 309. They were divided into severe secondary pulmonary tuberculosis (severe group) (n = 57) and mild secondary pulmonary tuberculosis (mild group) (n = 46) by the severity of disease . At the same time age-matched healthy controls (n = 45) were selected from healthy subjects undergoing physical examination. Whole genome expression profiling was performed with Affymetrix Gene expression chips for 4 cases in severe group, 3 in mild group and 5 in healthy group. Cluster and bioinformatics analysies were performed on differentially expressed genes in severe versus mild group. The remainders of three groups were 53, 43 and 40 cases respectively used for verify the results of gene chip by real-time fluorescence quantitative PCR (RT-PCR). And 20 cases in severe group, 20 in mild group and 8 in control group were used to verify the expression level of jun oncogene (JUN) on behalf of differential expressed genes. Analysis of variance and non-parametric tests were used for statistic difference analysis among three groups. There were 406 differentially expressed genes for severe and mild groups. There were 264 down-regulated gene and 142 up-regulated ones. The down-regulated genes were predominant. Cluster analysis show the similarity of gene expression profile in the same group . The result confirmed that the gene chip experiments were both repeatable and reliable. According to gene ontology, the differentially expressed genes were mainly involved in such biological processes as immune response, signal transduction, regulation of transcription (DNA-dependent), inflammatory response, antigen processing and presentation and chemotaxis, etc. Pathway analysis showed differentially expressed genes were involved in 22 pathways of immune response and inflammation. The major pathways included B cell receptor signaling, antigen processing and presentation, Toll-like receptor signaling, MAPK signaling and transforming growth factor-beta (TGF-β) signaling.Real-time fluorescence quantitative PCR (RT-PCR) analysis showed that the statistics of optical density for JUN was P < 0.001 in severe versus mild group. It was down-regulated in severe group. And the expression of JUN was conformed with the result of gene expression chip. The patients of severe group have a larger number of differential expressed genes versus those of mild group. And severe lung tissue damage in severe group may be correlated with differences in gene expression.

Combined ultrasound and photoacoustic imaging to noninvasively assess burn injury and selectively monitor a regenerative tissue-engineered construct.

Current biomedical imaging tools have limitations in accurate assessment of the severity of open and deep burn wounds involving excess bleeding and severe tissue damage. Furthermore, sophisticated imaging techniques are needed for advanced therapeutic approaches such as noninvasive monitoring of stem cells seeded and applied in a biomedical 3D scaffold to enhance wound repair. This work introduces a novel application of combined ultrasound (US) and photoacoustic (PA) imaging to assess both burn injury and skin tissue regeneration. Tissue structural damage and bleeding throughout the epidermis and dermis till the subcutaneous skin layer were imaged noninvasively by US/PA imaging. Gold nanoparticle-labeled adipose-derived stem cells (ASCs) within a PEGylated fibrin 3D gel were implanted in a rat model of cutaneous burn injury. ASCs were successfully tracked till 2 weeks and were distinguished from host tissue components (e.g., epidermis, fat, and blood vessels) through spectroscopic PA imaging. The structure and function of blood vessels (vessel density and perfusion) in the wound bed undergoing skin tissue regeneration were monitored both qualitatively and semi-quantitatively by the developed imaging approach. Imaging-based analysis demonstrated ASC localization in the top layer of skin and a higher density of regenerating blood vessels in the treated groups. This was corroborated with histological analysis showing localization of fluorescently labeled ASCs and smooth muscle alpha actin-positive blood vessels. Overall, the US/PA imaging-based strategy coupled with gold nanoparticles has a great potential for stem cell therapies and tissue engineering due to its noninvasiveness, safety, selectivity, and ability to provide long-term monitoring.

Histomorphometric evaluation of ischemia-reperfusion injury and the effect of preservation solutions histidine-tryptophan-ketoglutarate and University of Wisconsin in limb transplantation.

The effect of cold ischemia (CI) in vascularized composite allotransplantation is unknown. We herein assess tissue-specific damage, acceptable CI time, and the effect of preservation solutions in a syngenic rat hindlimb transplant model. Lewis rat limbs were flushed and stored for 2, 10, or 30 hr CI in saline, histidine-tryptophan-ketoglutarate or University of Wisconsin preservation solution before transplantation. Morphologic alterations, inflammation, and damage of the individual tissues were analyzed on day 10 using histomorphology, confocal, light, and transmission-electron microscopy. Two-hour CI led to mild inflammation of tissues on day 10, whereas 10-hr and 30-hr CI resulted in massive inflammation and tissue damage. Although muscle was mainly affected after prolonged CI (≥10 hr), nerve was affected in all CI groups. A perineural cell infiltrate, hypercellular appearance, pronounced vacuolization, and mucoid degeneration, appearing as Wallerian degeneration, were observed. Staining with propidium iodide and Syto 16 revealed a decrease in viable muscle cell nuclei in the anterior tibial muscle on day 10 in all groups, which was most pronounced in 10-hr and 30-hr CI animals. Transmission-electron microscopy indicated that a large number of mitochondria were degenerated in the 10-hr and 30-hr CI groups. Histidine-tryptophan-ketoglutarate preservation solution slightly decreased inflammation and tissue damage compared to University of Wisconsin-treated and saline-treated animals, especially in skin and muscle when CI times did not exceed 10 hr. Severe inflammation and tissue damage are observed after prolonged CI in muscle and nerve. Ischemia times in vascularized composite allotransplantation should be kept as short as possible and certainly below 10 hr.

X-ray phase-contrast tomography of renal ischemia-reperfusion damage.

PurposeThe aim of the study was to investigate microstructural changes occurring in unilateral renal ischemia-reperfusion injury in a murine animal model using synchrotron radiation.Material and MethodsThe effects of renal ischemia-reperfusion were investigated in a murine animal model of unilateral ischemia. Kidney samples were harvested on day 18. Grating-Based Phase-Contrast Imaging (GB-PCI) of the paraffin-embedded kidney samples was performed at a Synchrotron Radiation Facility (beam energy of 19 keV). To obtain phase information, a two-grating Talbot interferometer was used applying the phase stepping technique. The imaging system provided an effective pixel size of 7.5 µm. The resulting attenuation and differential phase projections were tomographically reconstructed using filtered back-projection. Semi-automated segmentation and volumetry and correlation to histopathology were performed.ResultsGB-PCI provided good discrimination of the cortex, outer and inner medulla in non-ischemic control kidneys. Post-ischemic kidneys showed a reduced compartmental differentiation, particularly of the outer stripe of the outer medulla, which could not be differentiated from the inner stripe. Compared to the contralateral kidney, after ischemia a volume loss was detected, while the inner medulla mainly retained its volume (ratio 0.94). Post-ischemic kidneys exhibited severe tissue damage as evidenced by tubular atrophy and dilatation, moderate inflammatory infiltration, loss of brush borders and tubular protein cylinders.ConclusionIn conclusion GB-PCI with synchrotron radiation allows for non-destructive microstructural assessment of parenchymal kidney disease and vessel architecture. If translation to lab-based approaches generates sufficient density resolution, and with a time-optimized image analysis protocol, GB-PCI may ultimately serve as a non-invasive, non-enhanced alternative for imaging of pathological changes of the kidney.

The Role of CD4 and CD8 T Cells in Human Cutaneous Leishmaniasis.

Leishmaniasis, caused by infection with parasites of the Leishmania genus, affects millions of individuals worldwide. This disease displays distinct clinical manifestations ranging from self-healing skin lesions to severe tissue damage. The control of Leishmania infection is dependent on cellular immune mechanisms, and evidence has shown that CD4 and CD8 T lymphocytes play different roles in the outcome of leishmaniasis. Although the presence of CD4 T cells is important for controlling parasite growth, the results in the literature suggest that the inflammatory response elicited by these cells could contribute to the pathogenesis of lesions. However, recent studies on CD8 T lymphocytes show that these cells are mainly involved in tissue damage through cytotoxic mechanisms. In this review, we focus on the recent advances in the study of the human adaptive immunological response in the pathogenesis of tegumentary leishmaniasis.

Intramedullary nailing after external fixation of the femur and tibia: a review of advantages and limits.

External fixation is a safe option for stabilisation of extremity lesions in the polytraumatised patient as well as in fractures with severe soft tissue damage. Nevertheless, long-term-complications are to be expected when external fixation is chosen as a definitive treatment. The purpose of this review article is twofold: primarily, to define the rationale of a procedural change from an external fixator to an intramedullary nail; secondarily, to assess the possible advantages and pitfalls of a single- or two-staged procedure. External fixation of the femur is recommended in multiply injured patients who are critically ill to avoid an additional inflammatory response caused by the surgical trauma of primary nailing. The conversion towards nailing must be done as soon as the clinical condition of the patient has been stabilised. Stable polytraumatised patients do not benefit from initial stabilisation with an external fixator and should immediately be treated with a definitive osteosynthesis. In tibial fractures, external fixation followed by intramedullary nailing is recommendable in fractures with severe soft tissue injuries. Conversion should be done as soon as the soft tissues allow before pin-tract infections occur and performed in a one-staged procedure.

English

BACKGROUND: Fractures of distal femur are complex injuries that can be difficult to manage. Due to poor bone stock, less cortical bone in this region, wide medullary cavity and frequently associated severe soft tissue damage. METHODS: From June 2008 to April 2012, a prospective study of 46 patients, with distal femoral fractures, including supracondylar and inter condylar fractures, treated with intramedullary supracondylar nail, was done to evaluate its results and final functional outcome and its applicability in open as well as closed distal femoral fractures. Four cases were lost to follow up; six had followed up for less than six months. These ten cases were excluded from the study hence effectively the study included total thirty six cases. Average age of patients was 41.7 yrs. with Male: Female ratio of 2.6:1. Among 36 fractures 16.6% were of type A1, 44.4% were of type A2, 27.7% were of type A3 and 11.1% were of type C1. 27.7% fractures were open and associated injuries were present in 22.2% of cases. Second generation supracondylar nail was used for definitive fixation in all eighteen cases, through percutaneous patellar tendon splitting approach in 26 patients and medial parapatellar arthrotomy approach in ten patients. RESULTS: At an average follow up of 9 months, final functional outcome was evaluated as per Neer's criteria (1967). Average time of union was 17.5 weeks, with an average range of movement being 101.38. Functional results were excellent in 20 (55.5%) cases, satisfactory in 10 (27.7%) cases, unsatisfactory in 2 (5.5%) and poor in 4 (11.1%) cases. No significant correlation was observed in this study between the age of the patient, fracture type and the final functional outcome achieved. Similarly no significant difference was observed between the final functional outcomes achieved in open versus closed fracture. However patients treated with medial parapatellar arthrotomy approach were found to be associated with increased incidence of complications and relatively low range of movement at knee joint. CONCLUSION: According to this study it is concluded that supracondylar nailing is useful for fixation of closed as well as open distal femoral and less comminuted inter condylar fractures, preferably to be done by percutaneous patellar tendon splitting approach. The simplicity of the procedure also facilitated fracture fixation in those with multiple fractures.

Le fratture del calcagno: fissazione esterna

The treatment of calcaneal fractures remains controversial. Several techniques have been described since 1900 (traction techniques, less-invasive techniques, open techniques). In intra-articular fractures no treatment has been shown to be superior to others. To date, open reduction with internal fixation through a side access has represented the gold standard in the treatment of this type of injury, owing to the possibility of reducing articular fragments. Minimally invasive techniques are generally used only with exposed fractures. For some time now, minimally invasive techniques have become remarkably popular, especially when the need arises to treat patients with severe soft tissue damage and local or systemic diseases, in whom the classical open technique is contraindicated. We use the Ilizarov technique or a mini external fixator, with 6 chips, which produce a distraction to three points in the longitudinal, angular and cranio-caudal directions. The surgical technique provides closed or minimally invasive reduction, under scopic control. Then Kirschner, chips and external fixator are positioned, with distraction, if necessary. These techniques, such as external fixation, were born to associate the benefits of surgical reduction and stable fixation with those of a minimally invasive technique. In addition to a purely clinical discussion, the use of external fixation proved to be a mechanically sound system able to anticipate and grant the possibility of earlier load after surgery. We think that fixators mechanically express their function by crystallizing the position of fragments and by making the calcaneus a single body, thus maintaining the volume of the calcaneus. This leads to advantages that could be correlated with a positive clinical outcome, because the foot is not subtracted from the load during long periods. These techniques also allow for early mobilization of the neighbouring joint districts, and fixation devices are easy to remove.

The role of dead cell clearance in the etiology and pathogenesis of systemic lupus erythematosus: dendritic cells as potential targets

Overwhelming apoptosis combined with a deficiency in clearing apoptotic cells is thought to be an important etiopathogenic event in the autoimmune disease systemic lupus erythematosus (SLE). Lazy macrophages, complement or DNase I deficiency as well as insufficient natural IgM might be important factors leading to such a clearance deficiency. A defective clearance of apoptotic cells leads to the activation and maturation of plasmacytoid and myeloid dendritic cells (DCs) by material derived from secondary necrotic cells carrying modified autoantigens. This results in the presentation of autoantigens to autoreactive T and B cells in an immunogenic manner, thereby leading to autoantibody production, chronic inflammation and severe tissue damage. Since DC activation and IFN-α production by plasmacytoid dendritic cells play a critical role in the course of SLE pathogenesis, therapeutic intervention to end this vicious cycle might be a promising approach for treating the disease.