Dietmar Ulrich

Gracilis muscle interposition for the treatment of recto-urethral and rectovaginal fistulas: a retrospective analysis of 35 cases.

BACKGROUND Several surgical procedures for the repair of fistulas between the rectum and the urethra or vagina have been reported. Our study was designed to assess the efficacy of the gracilis muscle flap in repairing recto-urethral and rectovaginal fistulas. METHODS Gracilis muscle interposition flaps were performed in 35 patients (aged 38-78 years, mean: 58 years) using a perineal approach. Nine patients had rectovaginal fistulas due to Crohns disease (n=3), previous surgery and pelvic irradiation for rectal (n=2) or cervical cancer (n=4). Twenty-six fistulas were recto-urethral. The aetiologies were Crohns disease (n=4), brachytherapy after prostate cancer (n=14), iatrogenic injury to the rectum during radical retropubic prostatectomy (n=4), transurethral resection of the prostate (n=2) and recurrent peri-anal abscesses with fistulas (n=2). Twenty-five patients had undergone previous repair attempts; of these four underwent multiple procedures. Patient outcomes were assessed after surgical repair. The success rate was measured as the percentage of patients with a healed fistula after stomal closure. RESULTS The mean follow-up was 28+/-15 months from muscle transposition and 22+/-14 months from stomal closure. Fistula closure with no recurrence could be achieved in 33 patients (94%). Two of the seven patients (29%) with Crohns disease had a persistent fistula. There were neither intra-operative complications nor problems related to muscle desinsertion surgery. CONCLUSIONS Recto-urethral and rectovaginal fistula closure using the perineal approach with pedicled gracilis muscle interposition is associated with minimal morbidity and a high success rate. It is an excellent option for patients with complicated fistulas for whom other surgical treatments have failed. Underlying Crohns disease is associated with a higher complication rate.

TIMP-1, MMP-2, MMP-9, and PIIINP as serum markers for skin fibrosis in patients following severe burn trauma.

&NA; The wound‐healing process of patients with severe burns often leads to the formation of extensive fibrotic scars. In this study, serum concentrations of tissue inhibitors of metalloproteinase‐1 (TIMP‐1), matrix metalloproteinase‐2 (MMP‐2), matrix metalloproteinase‐9 (MMP‐9), and amino‐terminal propeptide of procollagen type III (PIIINP) were measured by enzyme‐linked immunosorbent assay as markers for excessive cicatrization in 22 patients with acute burn injuries. All patients were followed up for 6 months to determine a fibrotic reaction during the wound‐healing process after operative treatment using the Burn Scar Index. Blood samples were drawn immediately before the operation; at postoperative days 1, 3, 7, and 14; and 1, 3, and 6 months after the operation. Twenty patients who underwent elective plastic surgical operations served as the control group. There was a significant increase (p < 0.05) of TIMP‐1 in the burned patients by the third postoperative day. Later in the follow‐up period, the serum concentrations remained at a significantly elevated level (p < 0.05) compared with preoperative values. In comparison with the control group, the postoperative serum concentrations of TIMP‐1 of the burned patients were significantly higher (p < 0.05) at any time and correlated with the total body surface area burned at the third and seventh postoperative days (p < 0.05; &ggr;2 = 0.46 versus r2 = 0.53) and the Burn Scar Index after 6 months (p < 0.05; r2 = 0.65). Serum levels of MMP‐2 and MMP‐9 showed a significant elevation (p < 0.05) only between postoperative days 3 and 14 in patients with burn wounds. PIIINP increased significantly (p < 0.05) in the sera of the burned patients at postoperative day 3 and remained significantly elevated up to 6 months after injury. At any time after trauma, PIIINP serum levels were significantly higher (p < 0.05) in the burned patients than in the control group and correlated with the total body surface area burned at postoperative days 3 and 7 (p< 0.05; r2 = 0.41 versus r2 = 0.44) and the Burn Scar Index after 6 months (p < 0.05; r2 = 0.5). Obviously, the physiological balance between matrix metalloproteinases and their endogenous inhibitors is disturbed after burn trauma. The elevated systemic TIMP‐1 concentration might contribute to tissue fibrosis, leading to pathological scar formation. The increase of PIIINP after thermal trauma indicates a fibrogenic component of wound healing. (Plast. Reconstr. Surg. 111: 1423, 2003.)

Matrix metalloproteinases and tissue inhibitors of metalloproteinases in sera and tissue of patients with Dupuytren's disease.

Dupuytren’s contracture is a fibroproliferative disorder characterized by progressive deposition of mature collagen fibers. In other fibrotic diseases affecting organs such as the liver, lung, heart, and skin, matrix metalloproteinases (MMPs) and their natural inhibitors, the tissue inhibitors of metalloproteinases (TIMPs), play an important role. In this study, serum concentrations of MMP-1, MMP-2, MMP-9, TIMP-1, and TIMP-2 were determined in 22 patients (five women and 17 men; average age, 67 ± 11 years) with Dupuytren’s disease using an enzyme-linked immunosorbent assay. Tissue samples were obtained for standard histological and immunohistochemical analyses. Sera and samples of palmar fascia from 20 patients (13 women and seven men; average age, 60 ± 15 years) who had undergone hand surgery for carpal tunnel syndrome were used as the control group. Statistical analysis was performed using the Mann-Whitney test. Patients with Dupuytren’s contracture presented with a TIMP-1 concentration of 437 ± 160 ng/ml, a significantly higher TIMP-1 concentration than that seen in the control patients, who had a concentration of 321 ± 70 ng/ml (p < 0.05). Patients with a proliferative active disease (n = 14) had a significantly higher TIMP-1 concentration (525 ± 136 ng/ml) than patients (n = 8) with a contracture in the late involutional and residual phase (286 ± 41 ng/ml; p < 0.05). There were no significant differences in the TIMP-2, MMP-1, MMP-2, and MMP-9 serum concentrations between patients with palmar fibromatosis and the control group. Patients with Dupuytren’s disease had a significantly lower MMP-to-TIMP ratio (1.1 ± 0.3; p < 0.05) than the control group (1.5 ± 0.35). Patients with an active palmar fibromatosis presented a significantly (p < 0.05) reduced ratio (1 ± 0.2) compared with those in later phases (1.4 ± 0.3). TIMP-1 and TIMP-2 could be detected in tissue of patients with Dupuytren’s contracture, with an accumulation in proliferative areas. MMPs could be detected locally in Dupuytren’s tissue in a few patients, with less positive staining than for TIMPs. In the control group, there was just little or no staining for TIMPs and MMPs. The data indicate that the physiological balance between MMPs and their natural inhibitors is disturbed in patients with a proliferative active Dupuytren’s disease. The decrease in the systemic MMP-to-TIMP ratio can cause increased synthesis and deposition of collagen, leading to palmar fibromatosis.

Matrix metalloproteinases and tissue inhibitors of metalloproteinases in patients with different types of scars and keloids.

BACKGROUND Hypertrophic scars and keloids are fibroproliferative skin disorders characterised by progressive deposition of collagen. Our study is designed to investigate the expression and concentration of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in different types of scars and keloids. METHODS Total RNA from 19 proliferative hypertrophic scar samples of patients with extended burns (total body surface area (TBSA): 21+/-12%), 18 mature hypertrophic scar samples from patients after elective surgery, 14 keloid samples and 18 normotrophic scar samples was, respectively, extracted, and then mRNA was isolated. Besides, biopsies were obtained from non-scarred skin of the patients and extraction of total RNA performed. Relative mRNA expression of MMP 2, MMP 9, TIMP 1 and TIMP 2 was measured with reverse transcriptase polymerase chain reaction (RT-PCR). Serum concentrations of MMP-1, -2, -9, TIMP-1, and -2 were determined using an enzyme-linked immunosorbent assay (ELISA). RESULTS Patients with extended hypertrophic scars after burn trauma presented a significantly higher TIMP-1 concentration (p<0.05) in their sera than the other patients. The relative expression of MMP 2 was significantly higher in samples of proliferative hypertrophic scars after burn injury. The relative expression of TIMP 1 and TIMP 2 was significantly higher in scar tissue of patients with proliferative and mature hypertrophic scars and keloids than in their regular skin and in scar samples of patients with normotrophic scars. The expression of TIMP 1 was significantly higher in samples of patients with keloids than in patients with hypertrophic scars. CONCLUSIONS The concentration of TIMP-1 in sera of patients varies depending on the size of the involved fibrotic scar tissue. A decrease in MMP-to-TIMP expression in scar tissue may contribute to increased synthesis and deposition of collagen, leading to a severe fibrotic reaction with pathologic scar formation. The results implicate non-operative therapy options in these patients that not only down-regulate TIMPs but also increase the activity of MMPs.

A new tool for the early diagnosis of carbon monoxide intoxication

Invasive measurement of carboxyhemoglobin (COHb) by blood gas analysis (BGA) is accepted as the standard diagnostic procedure in diagnosis of inhalation injury and carbon monoxide (CO) intoxications. The main disadvantage of BGA with COHb testing is the unavailability in pre-hospital rescue conditions. The non-invasive SpCO analysis using pulse CO oximetry (Rad57, Masimo Corp., USA) represents an easy-to-handle device to facilitate the diagnosis of CO intoxication. Between January 2006 and August 2008, 20 patients who were admitted with CO intoxication to our burn centre were included in this study. Blood gas analysis including COHb testing was performed on the first day, hourly. At the same time, SpCO was determined using the Rad57 pulse CO oximeter. Patients received inhalative oxygen according to the parameters of blood gas analysis or hyperbaric oxygenation if COHb > 10%. Five young healthy volunteers served as control group. The SpCO of the volunteers was cross-checked against their COHb levels, which were measured by blood gas analysis. Results of pulse CO oximetry revealed a mean error of approximately 3.15% from the results achieved by blood gas analysis. If COHb resulted in values higher than 10%, the bias remained approximately the same (3.43%/precision 2.362%). When different blood gas analyzers in our department were tested with the same patient sample, a mean error of 2.4% was found. This is only 1% lower compared to the mean error of pulse CO oximetry. Therefore, pulse CO oximetry represents a reliable measurement technique that is easy to handle and could facilitate the early diagnosis of CO intoxication in pre-hospital rescue conditions.

Effect of oxidised regenerated cellulose/collagen matrix on proteases in wound exudate of patients with chronic venous ulceration.

Oxidised regenerated cellulose/collagen matrix (ORC/collagen matrix) modifies wound microenvironments by binding and inactivating excess levels of proteases such as elastase, plasmin and gelatinases in wound exudates. To compare levels of the gelatinases matrix metalloproteinase 2 (MMP‐2), elastase and plasmin in wound exudates collected from chronic venous insufficiency patients with venous leg ulcers treated with either an ORC/collagen matrix or a standard control therapy. During a 12‐week treatment period, wound exudate samples were obtained from a control group of 10 patients treated with a hydrocolloid dressing and a treatment group of 17 patients treated with a combination of ORC/collagen matrix and hydrocolloid dressing. On admission and days 5, 14 and every subsequent 14th day, ulcers were photographed to determine healing rate and changes in ulcer appearance, and MMP‐2 concentration and the gelatinase, elastase and plasmin activities were analysed from wound exudates. The patients treated with ORC/collagen matrix showed a significant decrease in elastase, plasmin and gelastinase activity as compared with the control group, with no significant difference in the MMP‐2 concentrations between the two groups. The results show a significant and immediate reduction in protease activity in wound exudates from venous leg ulcers treated with ORC/collagen.

Effect of chronic wound exudates and MMP-2/-9 inhibitor on angiogenesis in vitro.

Background: New evidence suggests that matrix metalloproteinases (MMPs) may facilitate angiogenesis as well as function to generate angiogenesis inhibitors. In this study, the angiogenic effect of wound exudates from patients with venous insufficiency ulcers was examined in an in vitro angiogenesis model with and without synthetic MMP-2/-9 inhibitor. Methods: Wound exudates were obtained from 20 patients with venous insufficiency ulcers and 20 control patients with donor-site wounds after skin grafting for burns. In the angiogenesis model, suramin (20 &mgr;g/ml) was used in five wells without wound fluid as negative control, and vascular endothelial growth factor (1 &mgr;g/ml) was used in five other wells as positive control. Chronic wound fluids were analyzed without and with a synthetic MMP-2/-9 inhibitor with a concentration of 2 &mgr;M and 20 &mgr;M in the medium. The total length of tubules was calculated by map reader. Statistical analysis was performed using the Mann-Whitney test. The level of significance was considered to be p < 0.05. Results: Chronic ulcer exudates inhibited angiogenesis significantly (490 ± 130 &mgr;m) compared with acute wound fluids (1740 ± 320 &mgr;m; p < 0.05). In wells with chronic wound exudates and high concentrations of MMP-2/-9 inhibitor, angiogenesis was stimulated significantly (870 ± 220 &mgr;m, p < 0.05). Conclusions: In this model, reduced angiogenesis might be due to an antiangiogenic effect of MMP-2 and MMP-9. MMP-2/-9 inhibition results in a stimulation of angiogenesis and might be an approach for the treatment of patients with chronic wounds and reduced angiogenesis.

Determination of serum fibrosis indexes in patients with capsular contracture after augmentation with smooth silicone gel implants

Background: Several studies have confirmed a correlation between the concentration of serum hyaluronan and progressive fibrotic disorders such as liver cirrhosis. The aim of this study was to explore the relationship between serum hyaluronan levels and capsular contracture after aesthetic breast augmentation. Methods: The study included 25 female patients (average age, 40 ± 12 years) with capsular contracture after cosmetic breast augmentation with smooth silicone gel implants (Mentor, Santa Barbara, Calif.). The implants were placed in a submuscular position through an inframammary fold incision. The implant removals were prompted by development of capsular fibrosis (Baker grades I through IV). Samples of capsular tissue were obtained from all patients for standard histologic and immunohistochemical analysis. Blood samples were drawn from all patients immediately before operation. Sera from 20 healthy female patients (average age, 34 ± 9 years) were used as control. Results: Capsular tissue revealed significantly higher thickness in patients with grade III/IV contracture than in women with grade II contracture, according to Bakers classification. There was a moderate (n = 15) or severe (n = 10) chronic inflammatory reaction in the capsules around the implants. Fibroblasts, fibroblast-like cells, and macrophages represented the major cell populations found within the fibrous capsules, along with scattered polymorphonuclear leukocytes, lymphocytes, plasma cells, and mast cells. In addition, activated CD4+ cells were detected. An inner layer with synovia-like metaplasia and multinucleated giant cells was found. There was a significantly higher level (p < 0.05) of hyaluronan serum concentration in patients with capsular contracture (26 ± 14 &mgr;g/liter) compared with control subjects (12 ± 6 &mgr;g/liter). There was a positive correlation between the grade of capsular contracture (Baker grades I through IV) and the hyaluronan serum concentration (Baker grade II, 15 ± 3 &mgr;g/liter; Baker grade III, 34 ± 13 &mgr;g/liter; Baker grade IV, 42 ± 11 &mgr;g/liter) (r2 = 0.73; p < 0.05). Conclusions: Serum hyaluronan levels were significantly elevated in patients with capsular contracture after breast augmentation, and there was a positive correlation with stage of capsular contracture. Further study is necessary to determine whether hyaluronan might be useful as a predictor for the development and progress of capsular fibrosis.

Effect of oxidized regenerated cellulose/collagen matrix on proteases in wound exudate of patients with diabetic foot ulcers

PURPOSE: The aim of this study was to investigate the influence of oxidized regenerated cellulose/collagen matrix on the concentration and activity of gelatinases, elastase, and plasmin in wound exudate. SUBJECTS AND SETTING: The study included 32 patients with diabetic foot ulcers. Ten patients with a mean age of 66 ± 9 years (mean ± SD) were treated with hydrocolloid dressings; 22 patients with a mean age of 57 ± 12 years were treated with oxidized regenerated/collagen matrix and hydrocolloid dressings. METHODS: Wound exudate was collected on days 0, 5, 14, and every 14 days thereafter for 12 weeks. Total protein was determined according to Bradfords technique. The levels of elastase and plasmin were measured spectrofluorometrically. Besides, gelatinase activity and matrix metalloproteinase-2 concentration were analyzed. The surface area of all ulcers was measured by planimetry. RESULTS: Patients treated with oxidized regenerated cellulose/collagen matrix showed a significant decrease in elastase, plasmin, and gelatinase activities in wound exudates. The matrix metalloproteinase-2 concentration was significantly reduced on days 14, 28, 42, and 56 in comparison to day 0. Furthermore, wound size was significantly reduced at days 14 and 28 in oxidized regenerated cellulose/collagen matrix-treated patients (P < .05). CONCLUSION: Our results showed a significant and immediate reduction in the levels of all tested proteases in the wound exudate of diabetic foot ulcer patients treated with oxidized regenerated cellulose/collagen matrix. These patients also experienced a significantly greater reduction in wound size.

Burn injuries caused by air bag deployment

Automobile air bags have gained acceptance as an effective measure to reduce the morbidity and mortality associated with motor vehicle accidents. As more cars have become equipped with them, new problems have been encountered that are directly attributable to the deployment of the bag itself. An increasing variety of associated injuries has been reported, including minor burns. We present two automobile drivers who were involved in front-impact crashes with air bag inflation. They sustained superficial and partial-thickness burns related to the deployment. The evaluation of these cases shows mechanisms involved in burn injuries caused by the air bag system. Most of the burns are chemical and usually attributed to sodium hydroxide in the aerosol created during deployment. Also direct thermal burns from high-temperature gases or indirect injuries due to the melting of clothing, as well as friction burns from physical contact are possible. However, the inherent risks of air bag-related burns are still outweighed by the benefits of preventing potentially life-threatening injuries.