Erythropoietin requires endothelial nitric oxide synthase to counteract TNF-[alpha]-induced microcirculatory dysfunction in murine striated muscle.

In the present study, we aimed to evaluate whether erythropoietin (EPO) treatment may exert nonhematopoietic endothelial protection against TNF-[alpha]-induced microvascular inflammation and to determine the involvement of the nitric oxide (NO)-producing enzyme isoforms endothelial NO synthase (eNOS) and inducible NO synthase (iNOS). Murine dorsal skinfold chambers of wild-type (WT) animals were topically stimulated with TNF-[alpha] after pretreatment with epoetin beta (1,000 IU/kg body weight i.p.) or physiological saline. Leukocyte behavior, microvascular perfusion, and apoptosis were assessed by in vivo fluorescence microscopy. To study the involvement of NO, we compared eNOS-deficient (eNOS-/-) and iNOS-deficient (iNOS-/-) mice with WT animals. TNF-[alpha]-associated leukocyte activation, perfusion failure, and apoptosis were substantially attenuated in EPO-pretreated WT mice, which was accompanied by marked reduction of perivascular infiltration with F4/80-stained macrophages. The anti-inflammatory protective effects of EPO were abolished in eNOS-/-, but not in iNOS-/- mice, both with unaffected intercellular adhesion molecule 1 expression. However, the antiapoptotic effect of EPO was maintained in both eNOS-/- and iNOS-/- mice, indicating that this mechanism might rather be independent of NO. We conclude that EPO treatment elicits protection against TNF-[alpha]-induced microcirculatory dysfunction, depending on NO derived from endothelial cells, but not on the inducible isoform.

A new technique for gluteal lifting using deepithelialized dermal flaps.

BACKGROUND: Gluteal ptosis may result from sagging of redundant skin and fat below the infragluteal fold. The correction of gluteal ptosis and the definition of gluteal prominence can be obtained by several gluteal lifting techniques. We present a new technique to correct gluteal ptosis using deepithelialized dermal flaps. METHODS: Eight female patients (39 + or - 4 years old) with gluteal ptosis were included in the study. Six patients had been previously operated on elsewhere (liposuction, body lift). Gluteal lifting is performed using a crescent-shaped deepithelialized flap. The cranial two-thirds of the flap is sutured to the gluteal fascia, thus creating the new gluteal curvature and the position of the new infragluteal fold. The lower third of the flap is then sutured back toward the two-thirds flap within the first suture line, resulting in a doubling of the deepithelialized area. RESULTS: The mean operating time was 100 + or - 20 min (range = 75-110 min). There were no complications in the study group. An analysis of postoperative results revealed a very good aesthetic aspect in all patients. All patients showed an improved definition of the infragluteal fold, with a symmetric shape of the gluteal region. All patients judged the outcome as very good. CONCLUSION: The use of a deepithelialized double dermal flap is a safe and new way to obtain excellent results in rejuvenation of the gluteal region. Our technique allows for the creation of a stable and long-lasting infragluteal fold with an aesthetic buttock curvature and a defined border to the thigh region.

A case-matched controlled study on high-voltage electrical injuries vs thermal burns.

The aim of this study was to provide an increased level of evidence on surgical management of high-tension electrical injuries compared with thermal burns using a case-controlled study design. Sixty-eight patients (64 males, 4 females, aged 33.7 +/- 13 years) with high-tension electrical burns were matched for age, gender, and burnt extent with a cohort of patients sustaining thermal burns. Data were analyzed for cause of accident (occupational vs nonoccupational), concomitant injuries, extent of burn and burn depth, surgical management, complications, and hospital stay. High-tension electrical burn patients required an average of 5.2 +/- 4 operations (range, 1-23 operations) compared with 3.3 +/- 1.9 (range, 1-10 operations) after thermal burns (P = .0019). Amputation rates (19.7% vs 1.5%), escharotomy/fasciotomy rates (47% vs 21%), and total hospitalization days (44 d vs 32 d) were significantly higher in high-tension electrical injuries (P < .05). Creatinine kinase levels were significantly elevated during the first 2 days in patients with subsequent amputations. Free flap failure was observed during the first 4 weeks after the trauma, whereas no flap failure occurred at later stages. Local, pedicled, and distant flaps were used in 15% of the patients. The mortality in both groups was 13.2% vs 11%, respectively (nonsignificant). High-voltage electrical injury remains a complex surgical challenge. When performing free flap coverage, caution must be taken for a vulnerable phase lasting up to 4 weeks after the trauma. This phase is likely the result of a progressive intima lesion, potentially hazardous to microvascular reconstruction. The use of pedicle flaps may resemble an alternative to free flaps during this period.

Changes in bacterial isolates from burn wounds and their antibiograms: a 20-year study (1986-2005).

BACKGROUND: Our aim is to elucidate shifts in the bacterial spectrum colonising burn wounds and corresponding antibiotic susceptibilities during a 20-year study period. METHODS: Microbiological results from burn patients collected between 1986 and 2005 were analysed retrospectively. RESULTS: Staphylococcus aureus was isolated most frequently (20.8%), followed by Escherichia coli (13.9%), Pseudomonas aeruginosa (11.8%), coagulase-negative staphylococci (CNS) (10.9%), Enterococcus sp. (9.7%), Enterobacter cloacae (5.6%), Klebsiella pneumoniae (5%), Acinetobacter sp. (3.2%), Proteus mirabilis (2%) and Stenotrophomonas maltophilia (1.4%). Susceptibility of S. aureus to broad-spectrum substances such as ciprofloxacin or penicillinase-stable penicillins has waned, others such as cotrimoxazole or netilmicin remained effective. Not a single resistance against vancomycin was recorded. Increases in methicillin-resistant S. aureus (MRSA) were pronounced (3% in 1986-1997 (the first of the three study periods) to 16% in 1998-2001 and 13% in 2002-2005). Results for methicillin-resistant CNS (MRCNS) show an even greater increase. P. aeruginosa has shown increasing susceptibility against netilmicin (1986-1989: 84%, 2002-2005: 95%). Susceptibility of P. aeruginosa to ceftazidime has decreased markedly. S. maltophilia has shown clinically relevant susceptibility mainly against ciprofloxacin. Acinetobacter sp. have shown little susceptibility to most antibiotics. Imipenem or meropenem have been very reliable reserve antibiotics throughout the study period for the fermenting Enterobacteriaceae (E. coli, K. pneumoniae, E. cloacae and P. mirabilis), with susceptibilities of or near 100%. CONCLUSION: In-depth knowledge of the bacteria causing infectious complications and of their antibiotic susceptibilities is a prerequisite for treating burn patients. Our study shows shifts in the microbial spectrum and their antibiogram, which mandate frequent reassessments.

Functional results of angular-stable plate fixation in displaced proximal humeral fractures.

INTRODUCTION: The availability of angular-stable plate/screw systems led to a euphoric use of these implants for the treatment of displaced proximal humerus fractures. The high implant costs seem to be justified by a potentially improved outcome. PATIENTS AND METHODS: Thirty one patients (20 female, 11 male, mean age: 62+/-16 years) with two-, three- and four-part proximal humerus fractures (Neer classification) were operated using the proximal humeral internal locking system (PHILOS). The mean follow-up time was 19+/-3 postoperative months (range: 340-720 days). Functional results (Constant score, UCLA-score) were analysed and compared to an equivalent historic control group of 60 patients operated for the same fracture types using two one-third tubular plates. Additionally, total implant costs for each technique were compared. RESULTS: Complications in the PHILOS group included one implant failure with refracture, one secondary dislocation, two cases of subacromial impingement, and two cases of partial avascular necrosis of the humeral head. The mean Constant score (age- and sex-matched) was 80+/-11% for the affected side and 104+/-13% for the healthy side. The UCLA scores were excellent in 10%, good in 67%, and fair in 23% of the patients. Complication rate and functional results did not differ significantly from the control group treated with one-third tubular plates. Implant costs were significantly higher for the PHILOS group (684+/-40 Euro vs. 158+/-20 Euro, p<0.05). CONCLUSION: Our study showed similar functional results using either plate. Although the PHILOS plate may provide important advantages in specific situations, such as osteoporotic bone, its use as a standard must be carefully judged under the economic aspect of the significant higher implant costs.

Leptin increases extracellular matrix mineralization of human osteoblasts from heterotopic ossification and normal bone.

Heterotopic ossification (HO) is the pathologic formation of bone in soft tissue. The exact pathomechanism is unknown but probably involves a disturbed osteoblast differentiation. Leptin, known as the obesity gene, may regulate normal osteoblast function in vitro. The aim of the present in vitro study was to further analyze the pathomechanisms of HO, including a possible role of leptin in ectopic bone formation. Human osteoblasts were cultivated either from normal bone or from resected HO. Both groups were incubated with increasing doses of leptin. Phenotype expression and mineralization of extracellular matrix were measured after 7, 14, and 21 days. In both groups, leptin increased both the formation of bone nodules and Ca-45 incorporation. This is the first study to analyze the effect of leptin on bone cells from ectopic ossification. Similar to the in vitro behavior of normal osteoblasts, cells from HO respond to leptin exposure with an increased mineralization of the extracellular matrix. This mechanism may be involved in the pathogenesis of ectopic bone formation in vivo.

Cbfa-1 (Runx-2) and osteocalcin expression by human osteoblasts in heparin osteoporosis in vitro.

Heparin may cause adverse effects on bone formation following long-term application. The exact pathomechanism is unclear, but in vitro data suggest an impaired osteoblast function. The transcription axis of Cbfa-1 (Runx-2) and osteocalcin is crucial in maintaining an equilibrium of bone formation and resorption in vivo. We used a human osteoblast cell culture model to further investigate the effect of heparin (low-molecular-weight heparin, dalteparin) on the expression of these two regulators of osteoblast differentiation. At high doses, dalteparin caused a significant inhibition of both osteocalcin and Cbfa-1 expression in vitro. Our data support the hypothesis of a direct inhibition of osteoblast function underlying heparin osteoporosis.

Bacterial decontamination of surgical wounds treated with Lavasept.

In a prospective randomized controlled double-blind study in 50 acutely injured patients, bacterially contaminated type 2-4 soft tissue wounds were treated with moist dressings of 0.2% Lavasept (fractionated polyhexamethylenbiguanide and macrogolum 4000) solution (n=28) in comparison with Ringer solution (n=22). Standardized swabs were taken on days 0, 2, 8 and 15 and investigated for microorganisms. For a quantitative evaluation, the number of colony forming units (CFU) was determined by a serial dilution technique. The tissue compatibility and anti-inflammatory effect were rated on a scale of 0 (=bad) to 3 (=very good). The most frequently found microorganism was Staphylococcus aureus, which was isolated from 13 wounds. Use of Lavasept led to a faster and significant reduction in microorganisms on the wound surfaces. The number of CFU per wound remained constant or decreased, in contrast to the wounds treated with Ringer solution. This was true for both Gram-positive and Gram-negative bacteria. There was no evidence of impaired wound healing in either group. The anti-inflammatory effect and the tissue compatibility of Lavasept were rated significantly better than that of Ringer solution. It is concluded that Lavasept combines antiseptic action with good tissue compatibility.

A comparative analysis of phenotype expression in human osteoblasts from heterotopic ossification and normal bone.

BACKGROUND AND AIMS: Heterotopic ossification (HO) is a pathological bone formation process in which ectopic bone is formed in soft tissue. The formation of bone depends on the expression of the osteoblast phenotype. Earlier studies have shown conflicting results on the expression of phenotype markers of cells originating from HO and normal bone. The hypothesis of the present study is that cells from HO show an altered expression of osteoblast-specific phenotype markers compared to normal osteoblasts. The aims of the study were to further characterize the expression of osteoblast phenotypemarkers and to provide a comparison with other study results. PATIENTS AND METHODS: Using an in vitro technique, reverse transcription polymerase chain reaction (RT-PCR), real-time PCR and immunohistochemistry, we compared the phenotype gene expression (type I collagen, alkaline phosphatase, Cbfa-1, osteocalcin) of osteoblasts from resected HO and normal bone (iliac crest). RESULTS: Cells from HO expressed the osteoblast phenotype (type I collagen, alkaline phosphatase) but were characterized by a depleted osteocalcin expression. The expression of Cbfa-1 (osteocalcin transcription gene) showed a large variety in our study. Preoperative radiotherapy had no effect on phenotype expression in cells from HO. CONCLUSION: Our results provide a characterization of cells originating from HO and support the thesis of an impaired osteoblast differentiation underlying the formation of HO. The transcription axis from Cbfa-1 to osteocalcin could be involved in the pathogenesis of HO.

Influence of brain injury on early posttraumatic bone metabolism.

BACKGROUND: Various clinical studies and observations demonstrate enhanced osteogenesis in patients sustaining traumatic brain injury. It is presumed that the induction of this process starts early after trauma. The purpose of our study was to investigate humoral markers of bone metabolism during the early posttraumatic period, with special regard to traumatic brain injury. METHODS: Serum concentrations of biochemical markers of bone metabolism (calcium, inorganic phosphorus, carboxyl-terminal propeptide of type 1 procollagen, pyridinoline cross-linked telopeptide domain of type 1 collagen, Ostase, osteocalcin, intact parathyroid hormone, and calcitonin) were measured in three different groups of 80 patients during the first posttraumatic week. Patients were categorized into three groups: group I, fractures only; group II, isolated traumatic brain injury; and group III, traumatic brain injury in combination with fractures. RESULTS: Osteocalcin levels were significantly lower in the presence of traumatic brain injury (p < .05). Elevated pyridinoline cross-linked telopeptide domain of type 1 collagen levels expressed enhanced bone resorption in all groups, but levels were significantly higher in the absence of traumatic brain injury (p < .05). Intact parathyroid hormone levels were significantly higher on days 0 and 1 in the combined presence of traumatic brain injury plus fractures. CONCLUSION: These results demonstrate an imbalance of bone formation and resorption parameters in patients with traumatic brain injury during the early posttraumatic period, suggesting a central regulation in bone formation. The lower levels of osteocalcin detected in this study may play an important role in patients with brain injury and the later development of posttraumatic heterotopic ossification.

Abdominal compartment syndrome after liver transplantation.

The abdominal compartment syndrome is a well-known complication after abdominal trauma and is increasingly recognized as a potential risk factor for renal failure and mortality after adult orthotopic liver transplantation (OLT). We present a case report of a young patient who presented with acute liver failure complicated by an acute pancreatitis. The patient developed an acute abdominal compartment syndrome after OLT. Transurethral measurement of intraabdominal pressure indicated an abdominal compartment syndrome associated with impaired abdominal vascular perfusion, including liver perfusion. Renal insufficiency was immediately reversed after decompressive bedside laparotomy. The abdominal compartment syndrome is a potential source of posttransplant renal insufficiency and liver necrosis in OLT. It remains, however, a rarely described complication after liver transplantation, despite the presence of significant factors that contribute to elevated intraabdominal pressure.

Contrast-enhanced three-dimensional magnetic resonance angiography for visualization of ectopic varices.

We report the case of a 62-year-old male with portal hypertension and recurrent bleeding refractory to surgical intervention from varices in a sigmoid stoma. Although stomal varices were detected neither by physical examination, stomal endoscopy, nor duplex sonography, contrast-enhanced three-dimensional magnetic resonance angiography of the portal vein and its collateral branches demonstrated their presence. Surgical revisions of the stoma failed to prevent bleeding, but implantation of a transjugular intrahepatic shunt successfully prevented recurrent hemorrhage. This case indicates that contrast-enhanced, three-dimensional magnetic resonance angiography is useful to detect this rare complication of portal hypertension and helps to tailor adequate treatment in patients with recurrent bleeding from stomal varices.

Stapled vs excision hemorrhoidectomy: long-term results of a prospective randomized trial.

HYPOTHESIS: Stapled hemorrhoidectomy offers several advantages over excision hemorrhoidectomy, including reduced postoperative pain, a reduced hospital stay, and an earlier recovery time. Furthermore, stapled hemorrhoidectomy is associated with lower hemorrhoidal recurrence on long-term follow-up. DESIGN: A randomized prospective trial. Patients were blinded to the operation technique used. Follow-up occurred at 1 and 3 weeks and 12 months postoperatively. SETTING: A university hospital providing primary, secondary, and tertiary care. PATIENTS: Forty patients with second- and third-degree hemorrhoid disease were randomized to undergo either stapled or excision hemorrhoidectomy. Two patients were excluded. All patients were subject to a follow-up examination. INTERVENTIONS: Stapled hemorrhoidectomy (Longo technique) vs excision hemorrhoidectomy (Ferguson technique). MAIN OUTCOME MEASURES: Operating time, postoperative pain (measured by the visual analog scale), hospital stay, histologic features, morbidity, defecation habit, continence, recovery time (return to work), and hemorrhoid recurrence at 1 year. RESULTS: Stapled vs excision hemorrhoidectomy was associated with a significantly reduced operating time (30 vs 43.25 minutes; P<.001), reduced postoperative pain scores (visual analog score) on the first 4 postoperative days (day 1: 2.7 vs 6.3; day 2: 1.7 vs 6.3; day 3: 0.8 vs 5.4; and day 4: 0.5 vs 4.8, where 0 indicates no pain, and 10, maximum pain; P < or = .001), and an earlier return to work (6.7 vs 20.7 days;P =.001). There were no differences for stapled vs excision hemorrhoidectomy in length of hospital stay (2.4 vs 2.1 days), complications (3 [15%] of 20 patients vs 5 [25%] of 20 patients), and recurrence rate (1 [5%] of 20 patients vs 1 [5%] of 20 patients). CONCLUSIONS: Stapled hemorrhoidectomy is associated with reduced postoperative pain, earlier recovery time and return to work, and a similar recurrence rate compared with the excision technique. Provided further clinical trials confirm these findings, stapled hemorrhoidectomy may become a future gold standard.