Allergic contact dermatitis caused by a new temporary blue-black tattoo dye - sensitization to genipin from jagua (Genipa americana L.) fruit extract.

BACKGROUND: Temporary tattoos made with an extract of the jagua fruit (Genipa americana L.) are becoming increasingly popular. It is claimed that it is 'dermatologically tested' and does not contain p-phenylenediamine. Extracts of jagua and gardenia fruits have been used by indigenous people in South America, as well as in traditional Chinese medicine, for centuries. Genipin is currently used for its cross-linking effect in the manufacture of polysaccharides, and is being investigated for its anti-inflammatory and other properties. OBJECTIVES: To report the presence of the allergenic substance genipin in a self-administered temporary tattoo dye made from the fruit juice of jagua (Genipa americana L.). PATIENTS AND METHODS: A 39-year-old female who repeatedly applied 'completely natural and 100% safe' Earth Jagua® tattoo, obtained via the internet, to her left hand developed allergic contact dermatitis within 6 weeks. Analysis of the dye showed the presence of geniposide and genipin. RESULTS: Patch tests with the dye and with its main components, including genipin, gave strong positive reactions to the latter. There was no sensitization to other ingredients or p-amino compounds. CONCLUSIONS: We report an extensively evaluated case of allergic contact dermatitis caused by a temporary Earth Jagua® tattoo. The allergen identified is genipin, a substance that is increasingly used for tattoos and as a therapeutic agent in medicine. This could result in an increase in the number of allergic reactions in the future.

Plunging when drilling: effect of using blunt drill bits.

OBJECTIVE: Plunging when drilling can be a detrimental factor in patient care. There is, although, a general lack of information regarding the surgeon's performance in this skill. The aim of this study was to determine the effect that using sharp or blunt instruments had on the drill bit's soft tissue penetration, using a simulator. MATERIALS AND METHODS: Surgeons taking part in an International Trauma Course were invited to participate. Two groups were defined: experienced and inexperienced surgeons. Twelve holes were drilled in the following order: 3 holes with a sharp drill bit in normal bone (SNB), 3 holes with a sharp drill bit in osteoporotic bone (SOB), 3 holes with a blunt drill bit in normal bone, and 3 holes with a blunt drill bit in osteoporotic bone. Mean values and Student t tests were used for statistical analysis. RESULTS: Thirty-seven surgeons participated, 20 experienced and 17 inexperienced surgeons. Mean plunging depths for SNB, SOB, blunt drill bit in normal bone, and blunt drill bit in osteoporotic bone were, respectively, 5.1, 5.4, 21.1, and 13.9 mm for experienced surgeons and 7.6, 7.7, 22, and 15.9 mm for inexperienced surgeons. Drilling with SNB and with SOB was statistically different, with inexperienced surgeons plunging 2.5 mm (P = 0.31) and 2.6 mm (P = 0.042) deeper, respectively. There was a difference (P < 0.001) between sharp and blunt drill bits in all drilling conditions for both the groups. CONCLUSIONS: Our study showed a significant difference in plunging depth when sharp or bunt drill bit was being used. Surgeons, regardless of their experience level, penetrate over 20 mm in normal bone and over 10 mm in osteoporotic bone.

Influence of material and microtopography on the development of local infection in vivo: experimental investigation in rabbits.

Polishing the surface of internal fracture fixation (IFF) implant materials can ease implant removal and reduce irritation to gliding tissues by reducing soft tissue adhesion and bony overgrowth. Thus, polishing the surface of these implants is expected to have significant clinical benefit in certain situations. The aim of the present study was to determine if polishing the surface of an IFF device influences susceptibility to infection. The local infection rate associated with 4-hole 2.0 mm Synthes locking compression plates (LCPs) composed of clinically available commercially pure titanium (cpTi) and titanium aluminium niobium (TAN) in their standard microrough form was compared with that of their test polished equivalents and also to clinically available electropolished stainless steel (EPSS). The LCPs were fixed in locking mode onto the tibia of mature, female New Zealand White rabbits and a clinical strain of Staphylococcus aureus was added to the implantation site. Twenty eight days after surgery the rabbits were euthanized and assessed for infection. The rank order based on descending ID50 was; polished TAN, standard TAN, standard cpTi, EPSS and finally polished cpTi, however, the ID50 values did not differ greatly between the groups with the same material. Using the LCP model in locking mode, polishing the surface of both cpTi and TAN was not found to influence the susceptibility to infection in our animal model.

Fat extravasation due to unreamed and experimentally reamed intramedullary nailing of the sheep femur.

AIM: To compare systemic fat extravasation in unreamed and experimentally reamed nailing. METHODS: An osteotomy was created in the proximal third of the femoral shaft in 16 sheep, and intramedullary pressure increase and fat extravasation were monitored for the two nailing techniques. RESULTS: The highest intramedullary pressures, median 2700 mm Hg, and highest percentages of fat extravasation, peaking at almost 90% of fat, were found for the unreamed nailing technique. The values for the reamed group were significantly lower. CONCLUSIONS: The extravasation of intramedullary fat can be attributed to the great increase in intramedullary pressure that occurs during unreamed nailing. Correctly performed intramedullary reaming with the new reaming system produces lower pressures and much less systemic fat extravasation, reducing the risk for fat embolism.

Resecting the great saphenous stump with endothelial inversion decreases neither neovascularization nor thigh varicosity recurrence.

BACKGROUND: Neovascularization at the saphenofemoral junction is one of the principal causes of recurrent varicose veins after great saphenous vein surgery. Because angiogenic stimulation from the exposed endothelium of the great saphenous vein stump is considered an important trigger for this process, we hypothesized that complete resection of the stump with endothelial inversion might lessen grade 2 groin neovascularization and thereby decrease recurrence of thigh varicosities. METHODS: Two groups of consecutive patients with primary varicose veins of the great saphenous vein were studied. Group A was a historical control group of 70 limbs (48 patients) in which conventional flush ligation was performed at the level of the saphenofemoral junction. Group B was a prospectively studied clinical trial cohort of 65 limbs (45 patients), wherein the great saphenous vein stump was completely resected using a side-biting clamp to isolate the saphenofemoral junction, and the resulting common femoral vein venotomy was closed with a running inverting suture. Early postoperative follow-up was performed at 6 weeks. Clinical examinations and duplex ultrasound scans were performed after 2 years of follow-up. Grade 2 groin neovascularization was defined by the presence of >3 mm tortuous new refluxing veins, typically communicating with recurrent varicosities in the thigh. RESULTS: After 2 years, recurrent varicose veins were present in the thighs of 13 of 65 limbs (20%) in group A and in 22 of 61 limbs (36%) of group B (P = .049). Grade 2 neovascularization was present at the saphenofemoral junction in six of 65 limbs (9%) of group A and in 12 of 61 limbs (20%) of group B (P = .127). CONCLUSION: Complete resection of the great saphenous vein stump and inversion suturing of the common femoral vein venotomy, instead of simple flush ligation at the level of the saphenofemoral junction, do not appear to decrease grade 2 neovascularization and related thigh varicosity recurrence after great saphenous vein stripping for primary varicose veins.

Local application of basic fibroblast growth factor increases the risk of local infection after trauma: an in-vitro and in-vivo study in rats.

INTRODUCTION: Local application of growth factors to stimulate wound and fracture healing is attracting increasing interest. We studied the effect of local application of a potent angiogenic growth factor, basic fibroblast growth factor (bFGF), on resistance to local infection after soft tissue trauma. METHODS: For in-vitro and in-vivo experiments, we used recombinant human bFGF. The in-vitro investigations were performed by isolation of human leukocyte fractions, cytokine analysis, phagocytosis assay, flow cytometry, and LDH assay. For the in-vivo investigation, a paired comparison of infection rates was carried out on Sprague-Dawley rats after standardized, closed soft tissue trauma and local, percutaneous bacterial inoculation of different concentrations of Staphylococcus aureus (2 x 10(4) to 2 x 10(7) colony-forming units (cfu)). The lower leg was treated with 1, 10 or 100 ng bFGF (16 animals for each concentration) and without bFGF (16 animals). RESULTS: Cytotoxic reactions due to the concentrations of bFGF used could be excluded in the in-vitro tests since incubations of isolated peripheral blood mononuclear cells (PBMCs) with increasing concentrations of bFGF for 24 h did not lead to an increase in the release of lactate dehydrogenase in the culture supernatants compared to corresponding control incubations without any bFGF added. A significant increase in cytokine release was observed after the co-incubation of PBMCs with 100 or 200 ng of the same bFGF that was used for the animal experiments. Furthermore, the capacity of phagocytes in whole blood to phagocytose bacteria was suppressed in the presence of 100 ng exogenously added bFGF. We found continuously reduced granulocytic phagocytosis in FGF-supplemented blood compared to non-supplemented blood. In the in-vivo investigation, the infection rate for the group without bFGF was 0.25. In the groups with 1, 10 and 100 ng bFGF, the infection rates were 0.5, 0.7 and 0.8, respectively. A dose-dependent increase in infection rate was observed after local application of bFGF, compared to the untreated control group. The difference in infection rates for the groups in which 10 and 100 ng bFGF was used, relative to the group without bFGF, was statistically significant. INTERPRETATION: If these initial results are confirmed for other potent angiogenic growth factors, then the local use of growth factors for stimulation of wound and bone healing--a main focus of current research in traumatology--will have to be reconsidered and preceded with a strict evaluation of the risks and benefits.

Mechanical and radiological assessment of the influence of rhTGFbeta-3 on bone regeneration in a segmental defect in the ovine tibia: pilot study.

Limitations in the use of autologous bone graft, which is the gold standard therapy in bone defect healing, drive the search for alternative treatments. In this study the influence of rhTGFbeta-3 on mechanical and radiological parameters of a healing bone defect in the sheep tibia was assessed. In the sheep, an 18-mm long osteoperiosteal defect in the tibia was treated by rhTGFbeta-3 seeded on a poly(L/DL-lactide) carrier (n = 4). In a second group (n = 4), the defect was treated by the carrier only, in a third group (n = 4) by autologous cancellous bone graft, and in a fourth group (n = 2) the defect remained blank. The healing process of the defect was assessed by weekly in vivo stiffness measurements and radiology as well as by quantitative computed tomographic assessment of bone mineral density (BMD) every 4 weeks. The duration of the experiment was 12 weeks under loading conditions. In the bone graft group, a marginally significant higher increase in stiffness was observed than in the PLA/rhTGFbeta-3 group (p = 0.06) and a significantly higher increase than in the PLA-only group (p = 0.03). The radiographic as well as the computed tomographic evaluation yielded significant differences between the groups (p = 0.03), indicating the bone graft treatment (bone/per area, 83%; BMD, 0.57 g/cm(3)) performing better than the PLA/rhTGFbeta-3 (38%; 0.23 g/cm(3)) and the PLA-only treatment (2.5%; 0.09 g/cm(3)), respectively. Regarding the mechanical and radiological parameters assessed in this study, we conclude that rhTGFbeta-3 has a promoting effect on bone regeneration. However, under the conditions of this study, this effect does not reach the potential of autologous cancellous bone graft transplantation.

Effect on infection resistance of a local antiseptic and antibiotic coating on osteosynthesis implants: an in vitro and in vivo study.

The purpose of this study was to acquire information about the effect of an antibacterial and biodegradable poly-L-lactide (PLLA) coated titanium plate osteosynthesis on local infection resistance. For our in vitro and in vivo experiments, we used six-hole AO DC minifragment titanium plates. The implants were coated with biodegradable, semiamorphous PLLA (coating about 30 microm thick). This acted as a carrier substance to which either antibiotics or antiseptics were added. The antibiotic we applied was a combination of Rifampicin and fusidic acid; the antiseptic was a combination of Octenidin and Irgasan. This produced the following groups: Group I: six-hole AO DC minifragment titanium plate without PLLA; Group II: six-hole AO DC minifragment titanium plate with PLLA without antibiotics/antiseptics; Group III: six-hole AO DC minifragment titanium plate with PLLA + 3% Rifampicin and 7% fusidic acid; Group IV: six-hole AO DC minifragment titanium plate with PLLA + 2% Octenidin and 8% Irgasan. In vitro, we investigated the degradation and the release of the PLLA coating over a period of 6 weeks, the bactericidal efficacy of antibiotics/antiseptics after their release from the coating and the bacterial adhesion of Staphylococcus aureus to the implants. In vivo, we compared the infection rates in white New Zealand rabbits after titanium plate osteosynthesis of the tibia with or without antibacterial coating after local percutaneous bacterial inoculations at different concentrations (2 x 10(5)-2 x 10(8)): The plate, the contaminated soft tissues and the underlying bone were removed under sterile conditions after 28 days and quantitatively evaluated for bacterial growth. A stepwise experimental design with an "up-and-down" dosage technique was used to adjust the bacterial challenge in the area of the ID50 (50% infection dose). Statistical evaluation of the differences between the infection rates of both groups was performed using the two-sided Fisher exact test (p < 0.05). Over a period of 6 weeks, a continuous degradation of the PLLA coating of 13%, on average, was seen in vitro in 0.9% NaCl solution. The elution tests on titanium implants with antibiotic or antiseptic coatings produced average release values of 60% of the incorporated antibiotic or 62% of the incorporated antiseptic within the first 60 min. This was followed by a much slower, but nevertheless continuous, release of the incorporated antibiotic and antiseptic over days and weeks. At the end of the test period of 42 days, 20% of the incorporated antibiotic and 15% of the incorporated antiseptic had not yet been released from the coating. The antibacterial effect of the antibiotic/antiseptic is not lost by integrating it into the PLLA coating. The overall infection rate in the in vivo investigation was 50%. For Groups I and II the infection rate was both 83% (10 of 12 animals). In Groups III and IV with antibacterial coating, the infection rate was both 17% (2 of 12 animals). The ID50 in the antibacterial coated Groups III and IV was recorded as 1 x 10(8) CFU, whereas the ID50 values in the Groups I and II without antibacterial coating were a hundred times lower at 1 x 10(6) CFU, respectively. The difference between the groups with and without antibacterial coating was statistically significant (p = 0.033). Using an antibacterial biodegradable PLLA coating on titanium plates, a significant reduction of infection rate in an in vitro and in vivo investigation could be demonstrated. For the first time, to our knowledge, we were able to show, under standardized and reproducible conditions, that an antiseptic coating leads to the same reduction in infection rate as an antibiotic coating. Taking the problem of antibiotic-induced bacterial resistance into consideration, we thus regard the antiseptic coating, which shows the same level of effectiveness, as advantageous.

Surgical aspects of infection involving osteosynthesis implants: implant design and resistance to local infection.

Infection is still a major complication associated with surgery in orthopedics and traumatology. The implant design, the implant material, and the implantation technique may play essential roles in preventing infection. The goal of this paper is to discuss a series of experiments evaluating different aspects of both surgical procedures and implants. For this purpose, standardized local application of the human pathogen Staphylococcus aureus was performed in an animal model. Although these experimental results may be clinically relevant, direct extrapolation to clinical infection rates should be avoided.

The analgesic effects of intrathecal xylazine and detomidine in sheep and their antagonism with systemic atipamezole.

OBJECTIVE: To evaluate the analgesic and adverse side effects of intrathecal (IT) xylazine (XYL) and detomidine (DET) and the subsequent effects of two doses of intravenous (IV) atipamezole (ATI). STUDY DESIGN: Prospective, randomized, cross-over. ANIMALS: Five adult healthy female sheep with mean body mass of 55 +/- 2.3 kg. Material and methods Each sheep underwent four treatments: 1) 50 microg kg(-1) XYL IT and 5 microg kg(-1) ATI IV, 2) 50 microg kg(-1) XYL IT and 2.5 microg kg(-1) ATI IV, 3) 10 microg kg(-1) DET IT and 5 microg kg(-1) ATI IV, 4) 10 microg kg(-1) DET IT and 2.5 microg kg(-1) ATI IV. Pain threshold (TH) was tested by applying pulsed and stepwise incremental direct current to the skin overlying the pastern. The current at the point of foot lift was recorded as the TH. Heart rate (HR), mean arterial pressure, arterial oxygen (PO(2)) and carbon dioxide (PCO(2)) tensions were monitored. Outcomes were derived as differences between baseline assessment and measurements after treatment. Two-way anova was used to analyse drug effects, treatment differences between groups were examined with an F-test or Wilcoxon's rank sum test in case of non-parametric data distribution. p was set at 0.05. RESULTS: Both drugs increased the pain TH, caused small increases in PCO(2), and small decreases in HR, the latter was only significant for XYL recipients. Xylazine produced a significantly higher TH, more rapidly and for longer than DET. Atipamezole only significantly affected PaCO(2) in the XYL group 2. The pain TH was not affected in either group after IV ATI. CONCLUSIONS: At the doses used, IT XYL, and to a lesser extent DET, induced pastern analgesia. Atipamezole 5 microg kg(-1) IV antagonized some side effects without affecting analgesia. CLINICAL RELEVANCE: Intrathecal XYL may be useful as an analgesic in sheep. Its safety is increased because IV ATI antagonizes side effects, but not analgesia.

Influence of a standardized closed soft tissue trauma on resistance to local infection. An experimental study in rats.

PURPOSE: The etiology of local posttraumatic infection in the locomotor system depends on the amount, virulence and pathogenicity of the inoculated microorganisms and the local/systemic host damage due to the type and extent of the accident or iatrogenic trauma. The relative effect of these factors remains unclear. In particular, it is still unclear today whether--in presence of microorganisms--soft tissue damage and its pathophysiological consequences lead to infection after soft tissue trauma, or whether the bacterial contamination is the primarily cause for posttraumatic infection. The aim of the project was to gain information on the consequences of a soft tissue injury in terms of resistance to local infection. Since clinical populations are too heterogeneous, the problem was investigated in a standardized, reduced (no surgery or implants) experimental in vivo model. METHOD: In female Sprague-Dawley-rats with a standardized closed soft tissue trauma to the tibialis anterior muscle (group I: n=13) or without (group II: n=13), we compared the incidence of local infection after a pairwise local, percutaneously injected bacterial challenge with various concentrations of Staphylococcus aureus (2 x 10(4)-2 x 10(6) colony forming units, CFU). The standardized closed soft tissue trauma was created by application of a specially designed, computer controlled impact device. The contaminated soft tissue and the underlying bone were removed under sterile conditions after five days and quantitatively evaluated for bacterial growths. Infection was defined as positive bacterial growth at the soft tissue and/or bone. A stepwise experimental design with an "up-and-down" dosage technique was used to adjust the bacterial challenge in the area of the ID50 (50% infection dose). Statistical evaluation of the difference between the infection rates of both groups was performed by two-sided fisher exact test (p<0.05). RESULTS: The overall infection rate was 46%. For the group with soft tissue trauma the ID50 was 1.32 x 10(5) CFU and 1.05 x 10(6) CFU for the group without soft tissue trauma. The infection rate was 69% (9 of 13 animals) for the group with soft tissue trauma and 23% (3 of 13 animals) for the group without soft tissue trauma. This difference is statistically significant (p=0.047). CONCLUSIONS: The infection rate after a standardized closed soft tissue injury was significantly higher and the ID50 lower than without soft tissue trauma. Our results demonstrate that in presence of microorganisms it is not primarily the bacterial contamination but rather the soft tissue damage and its pathophysiological consequences resulting in decreased infection resistance that secondarily lead to infection.