Effects of lipo-prostaglandin E1 on wound bed microcirculation.

OBJECTIVE: Lipo-prostaglandin E1 (lipo-PGE1) is a well-known potent vasodilator that increases peripheral blood flow. However, the effects of this agent on wound bed microcirculation still remain unclear. The present study aims to improve the experimental model which our group developed to visualise wound bed microcirculation and to evaluate acute stimulation by lipo-PGE1. METHOD: The superficial stratum of the Wistar rat's ear skin was microsurgically excised preserving the subdermal vascular plexus. The preserved vessels, the wound bed microcirculation, were visualised under an intravital microscope-video-computer system. Animals were divided into three groups, a control group in which animals received vehicle control, a medium-dose group (6 µg/2 ml/kg lipo-PGE1) and a high-dose group (10 µg/2 ml/kg lipo-PGE1). The blood velocity and diameter of individual venules were measured from the recorded microcirculatory images, and the blood flow of the venule in the wound bed was evaluated. RESULTS: A significant increase in the wound bed blood flow was seen 10 minutes after lipo-PGE1 injection (p<0.05). This was approximately fourfold the baseline values. The increase was greatest in the medium-dose group. Extravasation and accumulation of lipo-PGE1 in the wound bed was observed. CONCLUSION: Lipo-PGE1 effectively increased wound bed microcirculation blood flow at the optimal dose. DECLARATION OF INTEREST: There is no conflict of interest.

Evidence-based recommendations for the use of negative pressure wound therapy in chronic wounds: steps towards an international consensus.

AIM: Negative Pressure Wound Therapy (NPWT) has become widely adopted over the last 15 years and over 1000 peer-reviewed publications are available describing its use. Despite this, there remains uncertainty regarding several aspects of usage. In order to respond to this gap a global expert panel was convened to develop evidence-based recommendations describing the use of NPWT. In this communication the results of the study of evidence in chronic wounds including pressure ulcers, diabetic foot ulcers (DFU), venous leg ulcers (VLU), and ischaemic lower limb wounds are reported. METHODS: Evidence-based recommendations were obtained by a systematic review of the literature, grading of evidence, drafting of the recommendations by a global expert panel followed by a formal consultative consensus development program in which 422 independent healthcare professionals were able to agree or disagree with the recommendations. The criteria for agreement were set at 80% agreement. Evidence and recommendations were graded according to the SIGN (Scottish Intercollegiate Guidelines Network) classification system. RESULTS: The primary treatment goal of NPWT in most chronic wounds is to achieve wound closure (either by secondary intention or preparing the wound for surgical closure). Secondary goals commonly include: to reduce wound dimensions, and to improve the quality of the wound bed. Thirteen evidence based recommendations were developed in total to address these treatment goals; 4 for pressure ulcers, 4 for DFU, 3 for ischaemic lower limb wounds and 2 for VLU. CONCLUSION: The present evidence base is strongest for the use of NPWT in non-ischaemic DFU and weakest in VLU. The development of evidence-based recommendations for NPWT with direct validation from a large group of practicing clinicians offers a broader basis for consensus than work by an expert panel alone.

Hydroxyurea-induced foot ulcer in a case of essential thrombocythaemia.

OBJECTIVE: To illustrate the association between hydroxyurea and the development of ulcers. METHOD: A case study is presented, in which histological changes, mean corpuscular volume (MCV) and transcutaneous oxygen tension (TcPO2) were all measured and analysed, both during hydroxyurea treatment and following it's discontinuation. RESULTS: Two months following the cessation of hydroxyurea therapy, the patient's ulcer had healed completely. Biopsy specimens taken before and after its discontinuation showed a considerable improvement in vascularity, with a capillary density 6.28 times higher after discontinuation of the drug. TcPO2 was just 8mmHg at the first measurement, and this increased to 65mmHg at the second. CONCLUSION: These findings suggest deficient neovascularisation and circulation during hydroxyurea treatment. Changes in MCV also appeared to have an effect on the progress of wound healing, which supports the hypothesis that macroerythrocytosis may be involved in the development of these rare ulcers, via impairment of the microcirculatory rheology.

Vasodilation of intramuscular arterioles under shear stress in dystrophin-deficient skeletal muscle is impaired through decreased nNOS expression.

Duchenne muscular dystrophy (DMD) is a lethal X-linked disorder of striated muscle caused by the absence of dystrophin. Recently, impairment of vascular dilation under shear stress has been found in DMD, but the underlying molecular mechanism is not fully understood. Moreover, dilation of intramuscular arterioles, which may be a key to the molecular pathogenesis, has not been addressed yet. We examined dilation of arterioles in the mouse cremaster muscle under shear stress due to ligation. The vasodilation was significantly impaired in dystrophin-deficient mdx mice as well as in neuronal nitric oxide synthase (nNOS)-deficient mice; however, neither endothelial NOS-deficient mice nor alpha1-syntrophin-deficient mice showed any difference in vasodilation from control mice. These results indicate that nNOS is the main supplier of nitric oxide in shear stress-induced vasodilation in skeletal muscle, but that the sarcolemmal localization of nNOS is not indispensable for the function. In contrast, the response to acetylcholine or sodium nitroprusside was not impaired in mdx or nNOS-deficient mice, suggesting that pharmacological treatment using a vasoactive agent may ameliorate skeletal and cardiac muscle symptoms of DMD.

Sprouting from arteriovenous shunt vessels with increased blood flow.

The purpose of this study was to evaluate the effect of increased blood flow on angiogenesis at the large vessels. The arteriovenous (AV) shunt was made on the thigh of male Wistar rats (n = 27) to increase blood flow, wrapped with artificial skin dermis, which consisted of a silicon outer layer, and isolated from surrounding tissues. Blood flow increased from 2.40 +/- 0.77 to 35.8 +/- 8.7 ml min(-1) (14.9 times), and the shear stress index (relative value of shear stress) increased from 10.7 +/- 3.6 to 73.4 +/- 18.1 (6.85 times) 60 min after the shunt formation. Newly formed vessels were observed around the AV shunt loop. Scanning electron micrographs at the AV shunt vessel lumen showed modified endothelial cells at day 7 and a remarkable number of pores at day 14. The volume of newly formed vessels was increased 12 times from day 5 to day 14. The mechanical factor of shear stress was considered the major stimulator of angiogenesis. This is the first report of electron-microscopic observation of sprouts from a large vessel lumen. The new AV shunt model is useful for basic research on angiogenesis at the large vessels in vivo and, furthermore, could generate vascularised tissues with various cultured cells.

Benefits of surgical reconstruction in pressure ulcers with a non-advancing edge and scar formation.

OBJECTIVE: To highlight the difficulty in treating pressure ulcers associated with scar formation and the benefits of surgical treatment in these cases by presenting a series of clinical cases. METHOD: Nine sacral ulcers surrounded by significant scar formation and 14 sacral ulcers without significant scars were treated using the same conservative management protocol. Healing status was quantitatively estimated using an assessment tool called DESIGN, which classifies pressure ulcer severity and allows healing to be monitored; a decreasing score indicates progressive improvement. RESULTS: Ulcers with scar formation showed little response to the treatment, while those without remarkable scars exhibited a significant decrease of the DESIGN scores. Surgical reconstruction was conducted in five ulcers surrounded by scar formation, and all showed complete healing within extremely short periods. CONCLUSION: Conservative treatment of pressure ulcers with a non-advancing edge surrounded by scar formation presents considerable difficulties. Surgical reconstruction offers many benefits for non-healing ulcers.

The positive experience of using a growth factor product on deep wounds with exposed bone.

Trafermin, a form of basic fibroblast growth factor, has been used in Japan since 2001. This study investigates whether it can facilitate closure in wounds with deep soft-tissue defects and exposed bone, where surgical closure is not possible.

Evaluating dressing materials for the prevention of shear force in the treatment of pressure ulcers.

OBJECTIVE: Shear force is believed to affect pressure ulceration. Therefore, dressing materials that reduce shear force may prevent ulceration and facilitate healing. METHOD: We measured the following three properties: the coefficient of friction between the outer layer of the dressings and the patient's clothes; the degree of adhesiveness between the inner layer of the dressing and the patient's skin; the transmissibility of shear force of the dressing. RESULTS: The coefficients of static friction were 1.01 for hydropolymer, 0.72 for hydrofoam and 0.48 for hydrocolloid. Adhesiveness was tested by rolling different sized ball bearings down a slope and over the adhesive lining under both wet and dry conditions. Under dry conditions, the heaviest ball bearing that stopped rolling for five seconds was 111.9g for both hydrofoam and hydrocolloid. Under wet condition, it was 11.9g for hydrofoam and under 1g for hydrocolloid. Tests showed the very low transmissibility (I N buffer) of shear force for hydrofoam, with significant differences between the dressings. Clinical observation has identified good results for hydrofoam when used under highly exuding conditions and for hydrocolloid when used with relatively slight or decreased exudate. CONCLUSION: Existing dressing materials are being developed and evaluated for wound healing. However, if innovations in the raw materials from which dressings are manufactured could lead to a reduction in shear force and the prevention of pressure ulcers, then dressing materials could be discussed from a viewpoint that is quite different from wound healing.

Microvascular and interstitial PO(2) measurements in rat skeletal muscle by phosphorescence quenching.

To clarify the transport of O(2) across the microvessels in skeletal muscle, we designed an intravital laser microscope that utilizes a phosphorescence quenching technique to determine both the microvascular and tissue PO(2). After we injected the phosphorescent probe into systemic blood, phosphorescence excited by a N(2)-dye pulse laser was detected with a photomultiplier over a 10 microm in diameter area. In vitro and in vivo calibrations confirmed that the present method is accurate for PO(2) measurements in the range of 7-90 Torr (r = 0.958) and has a rapid response time. This method was then used to measure the PO(2) of microvessels with different diameters (40-130 microm) and of interstitial spaces in rat cremaster muscle. These measurements showed a significant drop in PO(2) in the arterioles after branching (from 74.6 to 46.6 Torr) and the presence of a large PO(2) gradient at the blood-tissue interface of arterioles (15-20 Torr). These findings suggest that capillaries are not the sole source of oxygen supply to surrounding tissue.

Clinical use of amrinone (a selective phosphodiesterase III inhibitor) in reconstructive surgery.

Amrinone is a selective phosphodiesterase III inhibitor that increases cyclic adenosine monophosphate by preventing its breakdown. It is effective in the treatment of congestive heart failure because of its ability to increase myocardial contractility and vascular smooth muscle relaxation. This study was designed to clarify the potential efficacy of amrinone in plastic surgery by clinically assessing its ability to enhance flap blood flow after reconstructive surgery and relieve intraoperative vasospasm. Its effects were compared with those of prostaglandin E1 and lidocaine, which are widely approved agents for improving the hemodynamics of flaps. In the first clinical study, the effects on flap blood flow after flap transfers were investigated. Twenty-six patients underwent reconstructive surgery with vascularized free or pedicled flaps. Blood flow was measured before and 60 minutes after intravenous infusion of lactated Ringer solution (control), amrinone (10 microg/kg/min), or prostaglandin E1 (10 ng/kg/min) using a laser Doppler flowmeter. In the second study, the effects on relief of vasospasm during operation were evaluated. The blood flow of 28 island flaps was measured by laser Doppler flowmetry immediately after flap elevation and 10 minutes after topical application of saline (control), amrinone (5 mg/ml), or lidocaine (10%) to the pedicle in an attempt to resolve the vasospasm. In both clinical studies, the effects of amrinone were statistically no less than those of prostaglandin E1 and lidocaine. The results show that amrinone positively influences the microcirculatory blood flow of transferred flaps and relieves intraoperative vasospasm in clinical cases. The present study suggests that amrinone could be useful for postoperative and intraoperative care in reconstructive surgery.

Prefabricated free jejunal transfer: a new reconstructive technique for high pharyngeal defects.

A new method that uses a prefabricated free jejunal transfer has been applied to three cancer patients with pharyngoesophageal defects with a high pharyngeal deficit extending up to the nasopharynx. In this method, the jejunum harvested in the usual manner is divided into two segments with a single vascular pedicle. Its distal segment is used to reconstruct the cervical esophagus, and its proximal segment is turned over to create a mucosal patch to cover the high pharyngeal defects. The two segments are then co-apted in a side-by-side anastomosis. The esophagus can be reconstructed in a naturally straight shape without a curved portion or blind loop formation, thus leading to good swallowing function. In our series, all grafts survived well and there was no complication directly related to jejunal transfer. All patients could tolerate a soft diet without difficulty. This method is easy to perform and applicable to any shape or size of very high pharyngeal defects that cannot be reconstructed properly by other methods. Although patients with an advanced hypopharyngeal cancer usually have a poor prognosis, this technique allows a better quality of life for a probable short life span.

A case of cystic dermal duct tumor corresponding to poroid hidradenoma.

A case of dermal duct tumor on the back of a 61-year-old male, representing a cystic lesion, is reported. Such cystic dermal duct tumors seem to be considered poroid hidradenomas according to the recently suggested classification of poromas. Poroid hidradenoma is rarely mentioned in the literature, and no description of its clinical features has yet been published. Carcinoembryonic antigen (CEA) immunostaining was positive in the tumor cells adjacent to the cystic space. We suppose that these CEA-positive cells were associated with cyst formation in our case.

Ultrasonographic demonstration of a skin metastasis of adenocarcinoma.

A case of skin metastasis of adenocarcinoma on the back of a 69-year-old female was reported. The ultrasound appearance of the tumor indicated a malignant lesion prior to the detection of a primary lung carcinoma.

Dual-beam laser illuminator of fluorescence microscope for in vivo microcirculation studies.

A new fluorescence intravital microscope of long working distance (39 mm) has been developed for the observation of microcirculation in a wide visual field by designing a simple epi-illumination technique with dual laser beams. Cross-illumination, in which a pair of laser beams is symmetrically placed on either side of the objective such that they intersect at the focal plane of the objective, was employed to produce uniform distribution of the incident light in the object plane. In vitro experiments using a fluorescein isothiocyanate dextran (FITC-dextran; molecular weight = 70,000) solution of known concentration confirmed uniform tracer excitation in a wide visual field (approximately 30 mm2), and a linear correlation between fluorescence intensity and tracer concentration (r = 0.999), ranging between 5 mumol l-1 and 25 mumol l-1. In vivo observations in the microcirculation of a hamster cheek pouch indicated that the present technique had the advantage of high contrast compared with the image obtained by bright-field transillumination. This microscope illuminator may prove useful for the evaluation of vascular permeability under physiological and inflammatory conditions, with sufficient quantitative reliability to determine tracer concentrations in all parts of the microvascular network. Furthermore, a long working distance in this technique could have considerable advantages for the application to nail-fold capillaroscopy in humans.

Biological effects of static magnetic fields on the microcirculatory blood flow in vivo: a preliminary report.

There have been few studies of the effect of static magnetic fields on microcirculatory haemodynamics in vivo. The rat skinfold transparent chamber technique was used, which provides an excellent means of observing and quantifying direct in vivo microvascular haemodynamic responses to static magnetic fields up to 8 T. An intravital videomicroscope was used to measure the changes in blood flow before and after exposure to a magnetic field for 20 min in a horizontal type superconducting magnet with a bore 100 mm in diameter and 700 mm long. After exposure, microcirculatory blood flow showed an initial increase for about 5 min followed by a gradual decrease and a return to the control value. It is hypothesised that these changes represent rebound hyperaemia following reduced blood flow during exposure.

An experimental comparison of hydrocolloid and alginate dressings, and the effect of calcium ions on the behaviour of alginate gel.

Gel-forming dressings, which absorb the wound exudate to form a non-adherent gel, accelerate wound healing in a moist environment. The most commonly used of these dressings are calcium alginate and hydrocolloid membranes. This study was designed to evaluate the physical properties of these dressings, including fluid retaining ability, gel formation, and the dissolution process to clarify the mechanisms that promote healing. A simple immersion method was used for measurement. This technique was useful for the quantitative assessment of gel-forming dressings and may help to evaluate potential application of these dressings. A comparative analysis showed that alginate dressings remained gelled longer than hydrocolloid dressings. This result was consistent with previously reported clinical features of these dressings. The absence of calcium in wound fluid induced rapid resolution of alginate gel while the presence of a certain concentration of calcium prevented degradation of the gel for as long as one month.

[Recent advance in head and neck reconstruction].

The clinical application of microvascular free-flap transfers in reconstructive surgery has expanded tremendously since their introduction. Difficult reconstruction in the head and neck region can now be accomplished in a one-stage procedure using these techniques. Free flaps such as rectus abdominis, forearm, and scapular flap have been used frequently in this region because of their many advantages. They have a long vascular pedicle of a large-caliber vessel with anatomic stability and have ample blood supply. It is easy to harvest, and donor site morbidity in negligible. However, further improvement and refinement of surgical procedures are required to obtain better functional results and increase patients' quality of life. In this article, we describe the most recent concepts and techniques in head and neck reconstruction.

Evidence-based recommendations for the use of Negative Pressure Wound Therapy in traumatic wounds and reconstructive surgery: steps towards an international consensus.

Negative pressure wound therapy (NPWT) has become widely adopted over the last 15 years and over 1000 peer reviewed publications are available describing its use. Despite this, there remains uncertainty regarding several aspects of usage. In order to respond to this gap a global expert panel was convened to develop evidence-based recommendations describing the use of NPWT. In this paper the results of the study of evidence in traumatic wounds (including soft tissue defects, open fractures and burns) and reconstructive procedures (including flaps and grafts) are reported. Evidence-based recommendations were obtained by a systematic review of the literature, grading of evidence, drafting of the recommendations by a global expert panel, followed by a formal consultative consensus development program in which 422 independent healthcare professionals were able to agree or disagree with the recommendations. The criteria for agreement were set at 80% approval. Evidence and recommendations were graded according to the SIGN (Scottish Intercollegiate Guidelines Network) classification system. Twelve recommendations were developed in total; 4 for soft tissue trauma and open fracture injuries, 1 for burn injuries, 3 for flaps and 4 for skin grafts. The present evidence base is strongest for the use of NPWT on skin grafts and weakest as a primary treatment for burns. In the consultative process, 11/12 of the proposed recommendations reached the 80% agreement threshold. The development of evidence-based recommendations for NPWT with direct validation from a large group of practicing clinicians offers a broader basis for consensus than work by an expert panel alone.

Evidence-based recommendations for negative pressure wound therapy: treatment variables (pressure levels, wound filler and contact layer)--steps towards an international consensus.

Negative pressure wound therapy (NPWT) is becoming a commonplace treatment in many clinical settings. New devices and dressings are being introduced. Despite widespread adoption, there remains uncertainty regarding several aspects of NPWT use. To respond to these gaps, a global expert panel was convened to develop evidence-based recommendations describing the use of NPWT. In a previous communication, we have reviewed the evidence base for the use of NPWT within trauma and reconstructive surgery. In this communication, we present results of the assessment of evidence relating to the different NPWT treatment variables: different wound fillers (principally foam and gauze); when to use a wound contact layer; different pressure settings; and the impact of NPWT on bacterial bioburden. Evidence-based recommendations were obtained by a systematic review of the literature, grading of evidence and drafting of the recommendations by a global expert panel. Evidence and recommendations were graded according to the Scottish Intercollegiate Guidelines Network (SIGN) classification system. In general, there is relatively weak evidence on which to base recommendations for any one NPWT treatment variable over another. Overall, 14 recommendations were developed: five for the choice of wound filler and wound contact layer, four for choice of pressure setting and five for use of NPWT in infected wounds. With respect to bioburden, evidence suggests that reduction of bacteria in wounds is not a major mode of action of NPWT.