Inhibition mechanism of cordycepin and ergosterol from Cordyceps militaris Link. against xanthine oxidase and cyclooxygenase-2.

Cordyceps militaris Link. (C. militaris) is an entomopathogenic fungus that parasitizes the pupa or cocoon of lepidopteran insect larvae, with various bioactive compounds. Cordycepin and ergosterol are the two active components in C. militaris. This study aimed to evaluate the inhibitory activity of cordycepin and ergosterol against xanthine oxidase (XO) and cyclooxygenase-2 (COX-2), as well as investigate the inhibition mechanism. Cordycepin could better inhibit XO (IC50 = 0.014 mg/mL) and COX-2 (IC50 = 0.055 mg/mL) than ergosterol. Additionally, surface hydrophobicity and circular dichroism (CD) spectra results confirmed the conformational changes in enzymes induced by cordycepin and ergosterol. Finally, cordycepin and ergosterol significantly decreased uric acid (UA) and inflammatory factors to normal level in mice with gouty nephropathy (GN). This study could provide theoretical evidence for utilization of C. militaris in hyperuricemia-management functional foods.

[Connective tissue diseases and the liver injury].

Connective tissue disease (CTD) are closely related to liver abnormality. CTD can affect the liver causing various degrees of liver injury, coexist with other liver diseases, especially autoimmune liver disease (ALD). Medications for CTD can also lead to liver injury or reactivate the hepatitis B virus. CTD patients can also be positive for ALD-related autoantibodies without corresponding manifestation; and vis versa. The diagnosis and differential diagnosis should be made on integrating clinical presentation, laboratory, imaging, and histological studies, not solely relying on autoantibody positivity.

[Comparison of graft vessel versus native vessel strategies for late saphenous vein graft disease after coronary artery bypass grafting].

Objective: To compare clinical efficacy of interventional treatment with graft vessel and native coronary artery for patients with late saphenous vein grafts disease(SVGD) after coronary artery bypass grafting (CABG). Methods: A total of 1 608 patients underwent CABG in Tianjin Chest from March 2014 to December 2017 were screened. During the follow-up period, 165 hospitalized patients with recurrence of angina pectoris within one year after CABG, who had at least one narrow vein graft(≥50%) confirmed by the coronary angiography were enrolled. According to the results of angiography and surgeon's clinical experiences, the patients received interventional treatment to vein grafts(grafts group, n=53) or native coronary vessels(native group, n=112). The operation success rate, mortality and incidence of serious complications after interventional treatment in two groups at the time of hospitalization were compared.And the incidence of major adverse cardiovascular events(MACE) in two groups at one year after discharge were also compared. Kaplan-Meier survival curve was used to compare the cumulative event-free survival rates. The risk factors for the MACE in the patients with late SVGD and treated by interventional therapy were analyzed by Cox regression analysis. Results: A total of 165 patients were included for analysis, including 98 males(59.4%). The age was (64.2±7.1) years old. The follow-up time was 12 (8, 12) months. In the grafts group, operation success rate was 90.57%(48/53), and 3 cases(5.66%) suffered from serious complications after interventional treatment, 2 cases(3.77%) died. For native group the operation success rate was 88.39%(99/112), and 7(6.25%) cases suffered from serious complications after interventional treatment, and no deaths. The operation success rate and the incidences of serious complications after interventional treatment in two groups had no statistically significant difference(both P>0.05). The mortality in hospital of native group was lower than that in grafts group(P<0.05). Within 12 months after discharge, there was no statistically significant difference in incidence of MACE of two groups (11.32%(6/53) vs. 10.71%(12/112), P>0.05). Survival analysis showed that the cumulative event-free survival rates in two groups were 73.58% (39/53) and 66.13%(74/112), and there was no statistically significant difference (P>0.05). Cox regression analysis showed acute coronary syndrome (HR=41.203, 95%CI 4.859-349.361, P<0.01), and peripheral vascular diseases (HR=2.808, 95%CI 1.067-7.393, P<0.05) were the risk factors of the MACE for the patients treated by interventional therapy with late SVGD. Conclusion: For the patients with late SVGD after CABG, the success rate of intervention with vein grafts and own coronary vessels are both high with satisfactory safety.The in-hospital mortality of interventional therapy in own coronary vessels is lower than in graft vessel. Patients with acute coronary syndrome and peripheral vascular disease have a poor prognosis.

[Dynamic investigation of nutritional risk in patients with malignant tumor during hospitalization].

Objective: To prospectively investigate the changes in nutritional status of patients with malignant tumors during hospitalization by using nutritional risk screening (NRS2002), and to analyze the correlation between the nutritional status and clinical outcomes . Methods: This was a prospective and parallel research done by multi-center collaboration from 34 hospitals in China from June to September 2014.Hospitalized patients with malignant tumors inthese departments (Department of Gastroenterology, respiratory medicine, oncology, general surgery, thoracic surgery and geriatrics)were investigated. Only the patients with age≥ 18 years and hospitalization time between 7-30 days were included. During hospitalization, the physical indexes of human bodywere measured, and the NRS 2002 scores, and monitored the nutritional support at the time points of admission and 24 hours before discharge were recorded.And whether there was a nutritional risk in hospitalized patients and its association with clinical outcomes were investigated. Results: A total of 2 402 patients with malignancies were enrolled in this study. Seventy fourpatients who did not complete NRS2002 were eliminated, and 2 328 patients were included. The number of the main diseases was the top five, including 587 cases of colorectal cancer, 567 cases of lung cancer, 564 cases of gastric cancer, 146 cases of esophageal cancer, and 119 cases of liver tumor. At the time of discharge, compared with admission, the BMI, body weight, grip and calf circumferences of patients with malignant tumor were significantly decreased (P<0.05). The total protein, albumin, prealbumin and hemoglobin were significantly lower than those at admission (P<0.05). In 2 328 patients who were completed nutritional risk screening, the rate of malnutrition at admission was 11.1% (BMI =18.5, 258/2 328) and the rate of malnutrition at discharge was 10.9% (BMI =18.5, 254/2 328), there were no significant differences (χ(2)=0.019 7, P=0.888). There were 1 204 patients with nutritional risk at admission (51.7%, NRS2002 score≥3)and 1 352 patients with nutritional risk at discharge (58.1%, NRS2002 score≥3), with significant differences (χ(2)=49.9, P<0.001). The incidence of nutritional risk in patients with colorectal, stomach, and lung tumors at discharge was significantly higher than that at admission (P<0.05). The infective complications and other complications of patients with nutritional risk were significantly greater than those without nutritional risk at admission and at discharge.ICU hospitalization stay of patients with nutritional risk was increased significantly than those without nutritional risk at admission(P=0.042). Hospitalization expenses of patients with nutritional risk was increased significantly than those of patients without nutritional risk at discharge(P<0.01). Conclusion: The patients with malignant tumor have a higher incidence rate of malnutrition at both admission and discharge and malnutritionhas correlation with adverse clinical outcomes.The aboveindicators did not improve significantly at discharge.Doctors should pay more attention to the nutritional status (screening and evaluation)of patients before discharge and use appropriate and adequate nutrition support in order to prevent the weight loss and improve the life quality of patients.

The effect of saikosaponin D on doxorubicin pharmacokinetics and its MDR reversal in MCF-7/adr cell xenografts.

OBJECTIVE: Multidrug resistance (MDR) is a major cause of chemotherapy failure in the treatment of cancer patients. This study aimed to determine whether saikosaponin D (SSd) can enhance the efficacy of the anticancer drug doxorubicin (Dox) both in vitro and in vivo and whether SSd can alter Dox pharmacokinetics in the serum of mice. MATERIALS AND METHODS: MCF-7/adr cells were used to investigate the effect of SSd on reversing MDR. Cell viability was assessed by MTT assay. Pharmacokinetic tests were used to evaluate the effects of SSd on serum Dox disposition. An MCF-7/adr cell xenograft model was established to investigate the effect of SSd on reversing MDR in vivo. Tumor growth and weights were measured. Immunohistochemistry staining was used to detect the expression of P-gp (P-glycoprotein), an ATP-dependent efflux pump that mediates MDR in xenograft tumor tissues. RESULTS: SSd could effectively reverse MDR in MCF-7/adr cells in vitro and had no cytotoxic effects on human amniotic epithelial cells (hAEC). There was no significant difference between the Dox pharmacokinetic parameters obtained in the mice that received Dox only and Dox combined with SSd, indicating that SSd did not alter the pharmacokinetic profiles of Dox. Furthermore, the combination of Dox and SSd had a stronger anticancer effect than Dox alone or SSd alone by inhibiting tumor growth and P-gp expression. CONCLUSIONS: Our results suggest that SSd could effectively reverse MDR in vitro and in vivo and could be a potential MDR reversal agent for P-gp-mediated MDR in breast cancer therapy.

Geometric Parameter Analysis of Ruptured and Unruptured Aneurysms in Patients with Symmetric Bilateral Intracranial Aneurysms: A Multicenter CT Angiography Study.

BACKGROUND AND PURPOSE: Previous studies of geometric and morphologic parameters of intracranial aneurysms have been conducted to determine rupture risk, which remains incompletely defined due to patient-specific risk factors, such as sex, hypertension, and age. To this end, we compared characteristics of ruptured and unruptured aneurysms in the same patients with symmetric bilateral intracranial aneurysms. MATERIALS AND METHODS: Between January 2008 and March 2014, 2361 patients with 2674 aneurysms were diagnosed by CT angiography or surgical findings at 4 medical centers. Geometric and morphologic parameters examined for symmetric bilateral intracranial aneurysms comprised aneurysm wall regularity, size, neck width, aspect ratio, size ratio, neck-to-parent artery ratio, and area ratio. Univariate and multivariate statistical analyses were performed to determine independent risk factors for rupture. RESULTS: Sixty-three patients (48 women, 15 men; mean age, 62.5 ± 9.8 years) with symmetric bilateral aneurysms were eligible for the study and were included. The most frequent aneurysm location was the posterior communicating artery. Univariate analysis disclosed that aneurysm size, aspect ratio, size ratio, area ratio, and irregular wall differed between patients with ruptured and unruptured aneurysms. Multivariate analysis indicated that aspect ratio of ≥1.6 (adjusted OR, 9.521; 95% CI, 2.182-41.535), area ratio of ≥1.5 (adjusted OR, 4.089; 95% CI, 1.247-13.406), and irregular shape (adjusted OR, 10.443; 95% CI 3.394-32.135) were significant predictive factors for aneurysm rupture after adjustment for aneurysm size. CONCLUSIONS: An aspect ratio of ≥1.6, area ratio of ≥1.5, and irregular wall are associated with aneurysm rupture independent of aneurysm size and patient characteristics. These characteristics alone can help in distinguishing ruptured bilateral intracranial aneurysms from unruptured ones.

Hrd1 facilitates tau degradation and promotes neuron survival.

Intraneuronal accumulation of abnormal phosphorylated tau (p-tau) is a molecular pathology in many neurodegenerative tauopathies, including Alzheimer's disease (AD) and frontotemporal dementia with parkinsonism-linked to chromosome 17 (FTDP-17). However, the underlying mechanism remains unclear. Here, we showed an inverse relationship between endoplasmic reticulum membrane ubiquitin ligase (E3) Hrd1 expression and p-tau accumulation in the hippocampal neurons of AD, and proposed that Hrd1 may be a negative regulator of p-tau. This notion was further supported by in vitro study demonstrating that Hrd1 interacted with tau and promoted the degradation of total tau and p-tau as well. The degradation of tau depended on its Hrd1 E3 activity. Knockdown of endogenous Hrd1 with siRNA stabilized tau levels. In addition, inhibition of proteasome maintained tau level and increased Hrd1-mediated tau ubiquitination, suggesting the proteasome was involved in tau/p-tau degradation. Over-expression of Hrd1 significantly alleviated tau cytotoxicity and promoted cell survival. These results indicated that Hrd1 functions as an E3 targeting tau or abnormal p-tau for proteasome degradation. The study provides an important insight into the molecular mechanisms of human tauopathies.

Evaluation of the cytotoxicity of a two photon absorbing fluorescence compound on human HepG2 cells and its application to tracking human hepatic cancer cells in mice.

Small organic dyes have been applied widely in fluorescence imaging techniques for biomedical research. We investigated the cytotoxicity of a novel fluorescent dye, trans-4-(N-2-hydroxyethyl-N-ethyl amino)-4'-(dimethyl amino) stilbene (DMAHAS), on human hepatocellular carcinoma (HepG2) cells using methyl thiazolyl tetrazolium(MTT), a neutral red assay, a Coomassie brilliant blue assay, and flow cytometric analysis. Our results showed that DMAHAS had live cell permeability, stable cytosolic localization and no significant cytotoxicity to HepG2 cells. We explored its application further for tumor cell tracking in a human liver tumor xenograft mouse model. Tumor xenografts were examined by fluorescence imaging and conventional histological methods. In addition, a method based on DMAHAS release was developed for tumor-specific cytotoxicity analysis. Our study indicated that DMAHAS is a reliable probe for tumor tracking and fluorescence imaging.

Restricted and shared patterns of TCR beta-chain gene expression in silicone breast implant capsules and remote sites of tissue inflammation.

Silicone breast implants (SBI) induce formation of a periprosthetic, often inflammatory, fibrovascular neo-tissue called a capsule. Histopathology of explanted capsules varies from densely fibrotic, acellular specimens to those showing intense inflammation with activated macrophages, multinucleated giant cells, and lymphocytic infiltrates. It has been proposed that capsule-infiltrating lymphocytes comprise a secondary, bystander component of an otherwise benign foreign body response in women with SBIs. In symptomatic women with SBIs, however, the relationship of capsular inflammation to inflammation in other remote tissues remains unclear. In the present study, we utilized a combination of TCR beta-chain CDR3 spectratyping and DNA sequence analysis to assess the clonal heterogeneity of T cells infiltrating SBI capsules and remote, inflammatory tissues. TCR CDR3 fragment analysis of 22 distinct beta variable (BV) gene families revealed heterogeneous patterns of T cell infiltration in patients' capsules. In some cases, however, TCR BV transcripts exhibiting restricted clonality with shared CDR3 lengths were detected in left and right SBI capsules and other inflammatory tissues. DNA sequence analysis of shared, size-restricted CDR3 fragments confirmed that certain TCR BV transcripts isolated from left and right SBI capsules and multiple, extracapsular tissues had identical amino acid sequences within the CDR3 antigen binding domain. These data suggest that shared, antigen-driven T cell responses may contribute to chronic inflammation in SBI capsules as well as systemic sites of tissue injury.

Analysis of risk factors associated with rupture of silicone gel breast implants.

Despite many recent studies on breast implant rupture, there is no general consensus on causation or incidence. Existing studies have not reported a multivariate analysis of risk factors associated with breast implant rupture. Most studies lack adequate sample size to study the effect of implant type, manufacturer, and other patient-related factors that might affect rupture. This study addresses all of these shortcomings. Patients undergoing implant removal by a single surgeon between 1990 and 1996 were examined for rupture and for 16 potential risk factors. The association between rupture and various factors was analyzed by univariate and multivariate analyses. A total of 842 patients underwent removal of 1619 implants. Increasing age of implant [p < 0.0001; adjusted odds ratio (OR), 1.20; 95% confidence interval (CI), 1.15 to 1.23], retroglandular location (p = 0.0002; OR, 1.93; CI, 1.37 to 2.71), Baker contracture grades III and IV (p = 0.005; OR, 1.52; CI, 1.14 to 2.03), and presence of local symptoms (p = 0.05; OR, 1.37; CI, 1.00 to 1.89) were associated with rupture. When different implant types were compared with smooth gel implants, after adjustment, double-lumen (p < 0.0001; OR, 0.33; CI, 0.22 to 0.50) and polyurethane-covered implants (p < 0.0002; OR, 0.33; CI, 0.20 to 0.57) had significantly lower rupture rates. When various manufacturers were compared with Dow Corning after adjusting for other factors, rupture rates were significantly lower for McGhan (p < 0.0001; OR, 0.41; CI, 0.26 to 0.65), whereas higher for Surgitek (p < 0.019; OR, 1.52; CI, 1.05 to 2.18). Significant risk factors for breast implant rupture were identified: older implants, retroglandular implant location, implant contracture, local symptoms, certain implant type, and certain manufacturer. Although the results of this study are based on a nonrandomized explant population from a single surgeon's practice, knowledge of these risk factors will permit better interpretation of future data on rupture. The knowledge will enable the medical community to better advise their breast implant population regarding durability and appropriate time for removal or replacement.

Recipient vessels in free-flap breast reconstruction: a study of the internal mammary and thoracodorsal vessels.

The internal mammary vessels as recipient site for free flaps in breast reconstruction were investigated in this paper because of their ideal location for breast reconstruction. Comparisons were made with the thoracodorsal vessels in terms of external vessel diameter, vessel size discrepancy, flap loss and reexploration rates, and ease of flap placement. Eighty-one patients underwent 110 breast free-flap reconstructions (92 TRAM flaps and 18 superior gluteal flaps) between 1988 and 1994. Vessel size measurements were available on 75 flaps. The internal mammary artery diameter (2.36 +/- 0.50 mm, n = 51) was significantly larger than the thoracodorsal artery diameter (1.79 +/- 0.34 mm, n = 23; p < 0.001). There was no significant difference between the diameters of the internal mammary vein 2.6 +/- 0.58 mm, n = 52) and thoracodorsal vein (2.51 +/- 0.50 mm, n = 23; p = 0.93). The right internal mammary artery (2.52 +/- 0.51 mm) was significantly larger than the left internal mammary artery (2.30 +/- 0.55 mm; p = 0.046). The right internal mammary vein (2.89 +/- 0.56 mm) also was significantly larger than the left internal mammary vein (2.31 +/- 0.48 mm; p = 0.002). In terms of vessel size discrepancy, the internal mammary recipient artery tended to be greater in size than the TRAM flap donor artery (p = 0.003), while the thoracodorsal recipient artery tended to be smaller than the TRAM flap donor artery (p = 0.002). Flap failures and flap reexplorations occurred in the group using the thoracodorsal vessels but not in the internal mammary group. Correct flap placement using the internal mammary recipient site was achieved more easily for both unilateral and bilateral reconstructions because of the avoidance of lateral fullness and medial deficiency problems. The internal mammary recipient site is an important and at times superior alternative to the axillary recipient site because of its larger artery, especially when the axilla is scarred. For smaller free flaps such as a hemi-TRAM flap, as in bilateral TRAM flap reconstructions, the internal mammary site is invaluable because this recipient site allows exact placement of a smaller flap in the breast area.

Phenotype of lymphocytes associated with the inflammatory reaction to silicone gel breast implants.

The tissue response to silicone gel breast implants typically includes an inflammatory infiltrate that consists of macrophages, foreign body-type giant cells, and a variable number of lymphocytes and plasma cells. The phenotype of the lymphocytic component was investigated with three-color flow cytometry. Lymphocytes were obtained by collecting fluid from the space between the implant and the fibrous capsule or by washing cells from the fibrous capsule at the time of implant removal with total capsulectomy. Eighty-nine percent of the implant-associated lymphocytes were T cells. Twenty-five percent of the CD3+ T cells coexpressed HLA-DR compared with only 7.9% of matched peripheral blood lymphocytes. Sixty-eight percent of the implant-associated T cells coexpressed CD4 and CD29, while only 3% of the T cells coexpressed CD4 and CD45RO. The expression of HLA-DR and the predominance of CD29+ CD4+ T cells indicate that there is immune activation with the potential for stimulating antigen-specific antibody production. The role of silicone gel breast implants in immune activation and its clinical significance require further investigation.

Autogenous tissue breast reconstruction in the silicone-intolerant patient.

BACKGROUND: Concerns regarding the safety of silicone gel breast implants have motivated many patients with complications from their silicone breast implants to search for alternatives for breast reconstruction. Although autogenous tissue has been used for primary breast reconstruction after mastectomy, few studies have described its use in the patient in whom silicone-implant breast reconstruction has failed. METHODS: Between 1988 and 1993, 33 patients who had previous unsuccessful breast reconstruction with silicone breast implants underwent implant removal and autogenous tissue reconstruction. Preoperative evaluation included implant-related problems, such as capsular contracture, pain, and loss of implant shell integrity. Systemic symptoms that developed after implantation also were evaluated. Three types of myocutaneous flaps were used for breast reconstruction: the latissimus dorsi pedicle flap, the transverse rectus abdominis free flap, and the superior gluteus maximus free flap. Follow-up evaluation was done for both implant-related problems and issues related to patient satisfaction after autogenous tissue reconstruction. RESULTS: The overall flap survival rate for 33 women who underwent flap reconstruction was 94%. All flap losses occurred in the first nine flaps. Ninety-two percent of patients felt their autogenous tissue reconstructions were aesthetically superior to their previous implant reconstruction. All but one patient felt complete resolution in their chest wall discomfort and pain. Eighty-one percent of patients with systemic symptoms also felt improvement in their systemic symptoms. CONCLUSIONS: Autogenous tissue reconstruction from multiple areas of the body is an effective and aesthetically superior alternative for the patient who no longer desires the silicone implant option.

Dynamic properties of blood flow and leukocyte mobilization in infected flaps.

Two aspects of the inflammatory response to infection--blood flow alteration and leukocyte mobilization--are investigated in the canine model. The elevation of paired musculocutaneous (MC) and random pattern (RP) flaps allowed comparison of healing flaps with significant differences in blood flow (lower in random pattern flaps) and resistance to infection (greater in musculocutaneous flaps). Blood flow changes as determined by radioactive xenon washout were compared in normal skin and distal flap skin both after elevation and following bacterial inoculation. Simultaneous use of In-111 labeled leukocytes allowed determination of leukocyte mobilization and subsequent localization in response to flap infection. Blood flow significantly improved in the musculocutaneous flap in response to infection. Although total leukocyte mobilization in the random pattern flap was greater, the leukocytes in the musculocutaneous flap were localized around the site of bacterial inoculation within the dermis. Differences in the dynamic blood flow and leukocyte mobilization may, in part, explain the greater reliability of musculocutaneous flaps when transposed in the presence of infection.

Soft-tissue infection in lower-extremity trauma.

Soft-tissue infection after lower-extremity trauma has not been studied in detail in light of recent data on the biology of infection. This article examines specific problems in lower-extremity trauma that allow the wound to become susceptible to wound infection. It also illustrates the various principles of wound management in lower-extremity trauma that serve to prevent infection. Two case examples are used to illustrate principles of management. Other wound problems in lower-extremity trauma are also discussed, such as rabies, necrotizing soft-tissue infection, tetanus, and diabetic foot infections.

Long saphenous vein grafts as an aid to microsurgical reconstruction of the trunk.

The authors describe a method of closing truncal defects using free-tissue transfer when neither local tissue or vascular access are available. The long saphenous vein is dissected free as far distally as necessary and turned up, leaving its upper drainage intact. The distal end is then anastomosed to the femoral artery to create a temporary arteriovenous loop. After placing an appropriate free flap in the defect, the A-V loop is divided and used to provide both arterial supply and venous drainage for the flap. Anatomy, technique, and representative cases in which this method has been used for closing traumatic tissue defects of the trunk are presented and discussed.

Vasoactive prostaglandins in the impending no-reflow state: evidence for a primary disturbance in microvascular tone.

The impending no-reflow (NRF) state was studied in the rat hindlimb to identify possible biochemical mediators producing the no-reflow phenomenon. After 5 hours of ischemia, the venous effluents draining the ischemic limb and the contralateral nonischemic limb were collected for three 30-minute time periods. Thromboxane B2 (TxB2), prostaglandin E2 (PGE2), and 6-ketoprostaglandin F1 alpha, the stable metabolite of prostacyclin (PGI2), were measured by radioimmunoassay. Venous outflow rate, distal skin perfusion assessed by dermofluorometry, and histology of muscle and skin were examined in control limbs, ischemic limbs, and limbs with impending no reflow. The no-reflow state was characterized by a significantly decreased venous outflow (less than 0.01 ml per minute), decreased skin perfusion (index of fluorescence of 15 percent in no-reflow limbs versus 70 percent in reflow limbs), and absence of thrombosis of the vasculature. The no-reflow state also was associated with 2.4 times more thromboxane B2 and 1.5 times more 6-ketoprostaglandin F1 alpha than that observed in ischemic limbs with reflow. The biosynthesis of vasodilating prostaglandin E2 in the no-reflow state, however, was only 40 percent of the prostaglandin E2 measured in limbs with reflow. We propose that the impending no-reflow state may reflect a state of global microcirculatory "agonal" vasoconstriction, most probably due to an overabundant release of the vasoconstrictor thromboxane relative to the vasodilating prostaglandin E2 and prostacyclin. The likelihood of specific biochemical mechanisms producing the no-reflow state suggests that pharmacologic agents may be able to reverse the impending no-reflow state to improve tissue survival.

Soft-tissue infection in lower extremity trauma.

Soft-tissue infection following lower extremity trauma has not been studied in detail in light of recent data on biology of infection. This article examines specific problems in lower extremity trauma that allow the wound to become susceptible to wound infection. It also illustrates the various principles of wound management in lower extremity trauma that serve to prevent infection. Two case examples are used to illustrate principles of management. Other wound problems in lower extremity trauma are also discussed, such as rabies, necrotizing soft-tissue infection, tetanus, and diabetic foot infections.

Coverage of the infected wound.

Fifty-four consecutive patients with chronic wounds were identified by the following criteria: (1) established infection for 6 months, (2) exposure of bone, mediastinum, or other vital structure, (3) mechanical and/or vascular limitations to delayed closure techniques, (4) no response to wound debridement in prolonged antibiotic therapy. These wounds were divided into four groups: osteomyelitis (21), pressure sore (17), soft tissue wound (10), and osteoradionecrosis (6). Wound treatment in all patients included debridement, muscle flap closure, and culture specific antibiotic therapy. These consecutively treated patients over a 4-year period presented with an average duration of chronic infection of 2.9 years. Ninety-three per cent of these patients after treatment have demonstrated stable coverage without recurrent infection with a minimum of 1 year and a maximum of 4.6 years follow-up. The results demonstrate safe, effective coverage (93% of patients) of chronic infected wounds associated with long bone and pelvic osteomyelitis as well as chronic perineal sinuses following proctocolectomy and osteoradionecrosis. Debridement with short-term (average 12 days) antibiotic therapy has been effective when muscle flap coverage is provided.