Developing a Model of Care for Healing Pressure Ulcers With Electrical Stimulation Therapy for Persons With Spinal Cord Injury.

Background: Electrical stimulation therapy (EST) has been shown to be an effective therapy for managing pressure ulcers in individuals with spinal cord injury (SCI). However, there is a lack of uptake of this therapy, and it is often not considered as a first-line treatment, particularly in the community. Objective: To develop a pressure ulcer model of care that is adapted to the local context by understanding the perceived barriers and facilitators to implementing EST, and to describe key initial phases of the implementation process. Method: Guided by the Knowledge-to-Action (KTA) and National Implementation Research Network (NIRN) frameworks, a community-based participatory research (CBPR) approach was used to complete key initial implementation processes including (a) defining the practice, (b) identifying the barriers and facilitators to EST implementation and organizing them into implementation drivers, and (c) developing a model of care that is adapted to the local environment. Results: A model of care for healing pressure ulcers with EST was developed for the local environment while taking into account key implementation barriers including lack of interdisciplinary collaboration and communication amongst providers between and across settings, inadequate training and education, and lack of resources, such as funding, time, and staff. Conclusions: Using established implementation science frameworks with structured planning and engaging local stakeholders are important exploratory steps to achieve a successful sustainable best practice implementation project.

Electrotherapy for neck disorders.

BACKGROUND: Neck disorders are common, disabling and costly. The effectiveness of electrotherapy as a physiotherapy option has remained unclear. OBJECTIVES: To assess whether electrotherapy, either alone or in combination with other treatments, relieves pain, or improves function/disability, patient satisfaction, and global perceived effect in adults with mechanical neck disorders (MND). SEARCH STRATEGY: Computer-assisted searches of bibliographic databases: CENTRAL, MEDLINE, EMBASE, MANTIS, CINAHL, and ICL, without language restrictions, from their beginning to March 2003. SELECTION CRITERIA: Randomised or controlled clinical trials with quasi-randomisation (alternate allocation, case record numbers, dates of birth, etc.), in any language, investigating the effects of electrotherapy as a treatment for MND. DATA COLLECTION AND ANALYSIS: At least two authors independently conducted citation identification, study selection, data abstraction, and methodological quality assessment. Using a random-effects model, relative risk, and standardized mean differences were calculated. The reasonableness of combining studies was assessed on clinical and statistical grounds. Due to heterogeneity, pooled effect measures were not calculated. MAIN RESULTS: Fourteen comparisons (525 people with MND), in 11 publications, were included in this review. The analysis was limited by underpowered low quality trials, paucity of literature, and heterogeneity of treatment subtypes. The results for the electrotherapy subtypes are: Limited evidence of benefit: low or high frequency pulsed electromagnetic field (PEMF) compared to placebo, provides immediate post treatment pain relief only for chronic MND, acute whiplash (WAD) Unclear or conflicting evidence: direct and modulated Galvanic current compared to other treatments for pain in acute, subacute, chronic occipital headache iontophoresis compared to other treatments for pain, RTW, and self-assessment of overall outcome in acute, subacute WAD TENS compared to placebo for pain in acute WAD, chronic MND PEMF compared to placebo for medium or long term effect on pain, patient assessment of improvement, ADL in acute WAD, chronic MND Limited evidence of no benefit: diadynamic current compared to placebo for reduction of trigger point tenderness in chronic MND with radicular findings, cervicogenic headache permanent magnets compared to a placebo for pain in chronic MND electric muscle stimulation compared to a sham control for pain in chronic MND. AUTHORS' CONCLUSIONS: We can not make any definitive statements on electrotherapy for MND. The current evidence on Galvanic current (direct or pulsed), iontophoresis, TENS, EMS, PEMF and permanent magnets is either lacking, limited, or conflicting. Possible new trials on these interventions should have larger patient samples and include more precise standardization and description of all treatment characteristics.

Effects of ultrasound delivered through a mist of saline to wounds in mice with diabetes mellitus.

OBJECTIVE: To examine the effects of ultrasound administered through a fine mist of saline on surgically placed full-thickness excisional wounds in mice with experimental diabetes mellitus. METHOD: Fifty male CD-I mice received alloxan monohydrate (100 mg/kg), a drug known to induce diabetes mellitus. The animals received five ultrasound (n = 27) or sham (n = 23) treatments for 1.5 minutes, on alternate days, for 10 days, and were then sacrificed. Following sacrifice, each animal's wound was excised and the tissues prepared for qualitative and quantitative histological analysis. RESULTS: No difference in wound-surface area was found between the groups after the treatment period. However, blinded assessment of tissue sections revealed significantly increased deposition of collagen and blood vessels in the granulation tissue of animals treated with ultrasound compared with those that received sham therapy. CONCLUSION: Ultrasound delivered through a fine mist of saline significantly altered the composition of newly formed granulation tissue in animals with experimental diabetes mellitus. Further research needs to be completed to determine other effects of this novel ultrasound therapy and to examine its clinical effectiveness.

Effects of electrical stimulation on the histological properties of wounds in diabetic mice.

The purpose of this study was to identify mechanisms underlying electrically stimulated wound closure in diabetic mice. Adult male mice (n = 58) with full-thickness excisional wounds were treated five times using negative polarity over the wound site for 15 minutes each over a 16-day period with sham (0 Volts) or 5.0, 10.0, 12.5 Volts. In addition, animals (diabetic (n = 33) and nondiabetic (n = 22)) received treatments of electrical stimulation (12.5 V), or sham treatment (0 V) at wound sites which were then harvested and prepared for histological analysis at 2, 8, and 16 days postwounding. Using computerized image analysis of sections stained with a picro sirus red-fast green staining technique, we found that increasing doses of electrical stimulation reduced collagen/noncollagenous protein ratios measured in the superficial scar of nondiabetic animals, with no effect in diabetic animals. In the deep scar, lower doses of electrical stimulation (5.0 V) produced significantly (p < 0.01) increased collagen deposition in wounds of nondiabetic animals compared with sham controls. Higher doses of electrical stimulation (12.5 V) were required to produce changes in diabetic animals than were observed in nondiabetic animals. These results suggest that electrical stimulation altered collagen deposition in excisional wounds of diabetic and nondiabetic animals. Electrical stimulation had a differential effect on wound healing in diabetic compared with nondiabetic animals. These data speak to the need to study the effects of electrical stimulation on healing in disease-specific models.

Effect of maternal exercise on fetal and placental glycogen storage in the mature rat.

The purpose was to determine the effects of exercise on fetal and placental glycogen storage patterns at 20 days gestation (term 21 days) in mature (approximately 12 months of age) Sprague-Dawley rats. The exercise protocol consisted of treadmill running at 30 m min-1, on a 10 incline, for 60 min, 5 days per week, for 4 weeks prior to conception, which continued until day 19 of pregnancy. Exercise produced a significant reduction in fetal body weight, placental weight, and fetal organ weights (heart, kidney, brain, and liver) compared to sedentary control animals (p <.05). However, when fetal body size was taken into account, these differences disappeared, except for the fetal brain:body weight ratio, which was larger in the exercised animals compared to controls (p <.05). Fetal liver glycogen concentrations were significantly lower in exercised animals compared to nonrunning control animals (p <.05). These results demonstrate that exercise of mature rats may compromise fetal development and hepatic glycogen storage in the fetus.

Photographic assessment of the appearance of chronic pressure and leg ulcers.

The purpose of this paper was to examine the validity and reliability of using photographs of wounds to accurately assess wound status. The results of assessing wound appearance using wound photographs was compared to results obtained from a bedside assessment using the Pressure Sore Status Tool (PSST). The photographic wound assessment tool (PWAT) used in this comparison represents a modified version of the PSST and includes the six domains that can be determined from wound photographs. The PWAT was used on photographs of both chronic pressure ulcers (n = 56) and leg ulcers due to vascular insufficiency (n = 81). The photographic tool has excellent intrarater (ICC = 0.96) and interrater (ICC = 0.73) reliability and good concurrent validity (r = 0.70) compared with a full bedside assessment PSST. The PWAT has also shown to be sensitive to change in wound appearance of healing ulcers, but not nonhealing ulcers. These results would suggest that in the event that a full bedside assessment is not possible, wound photographs may be used to accurately assess wound appearance of both chronic pressure ulcers located on the trunk and vascular ulcers of the lower extremity. Establishing a valid and reliable assessment of wound healing using photographic images is of great relevance to the advancing fields of computer image analysis and telemedicine.

Validation of an experimental model of fetal limb growth and development: practical applications for the study of fetal defects associated with therapeutic agents in pregnant women.

Numerous musculoskeletal disorders which occur during pregnancy require an effective, nonpharmacological treatment that is known to have no adverse effects on fetal development. The present report describes morphological and histological changes occurring in fetal mouse limbs maintained in a serum-free organ culture system. Limbs maintained in this organ culture system show a progressive rise in limb dimensions including surface area, perimeter, and limb length. Histological analysis of serial cross sections of the limbs revealed a statistically significant increase in histological scores of limb development, thickness of epidermal layer, and amount of collagen deposited in the bone and dermis of limbs by Day 4 of culture. Therefore, this in vitro model combined with contemporary computer image analysis represents an excellent experimental model which can be used readily to examine the effects of therapeutic modalities on the growth and development of many different organ systems.

Effect of laser irradiation on the growth and development of fetal mouse limbs in an in vitro model.

BACKGROUND AND OBJECTIVE: The purpose of the present study was to examine the effects of laser irradiation on the growth and development of fetal limb tissue. STUDY DESIGN/MATERIALS AND METHODS: Day 14 fetal mouse limbs (n=168) were irradiated with gallium arsenide laser (904 nm, spot size=0.002 cm2, pulse duration=200 nanoseconds, peak power=30 mW) for 1 minute each day while being maintained in an organ culture system for 3 or 5 days at the following energy densities [O (control), 0.23, 1.37, 2.75, 3.66, and 4.58 J/cm2]. RESULTS: Computer image analysis of photographic images showed that there was a significant inhibition (P < 0.05) of new tissue growth after administration of lower energy densities of laser (0.23 and 1.37 J/cm2). These low-energy densities of laser irradiation also produced increased dermal cell number and collagen fiber thickness as assessed with qualitative histologic analysis of limb development by a blinded observer. Quantitative analysis of collagen distribution by color densitometric analysis of tissue sections stained with sirus red and fast green confirmed that there was a significantly greater (P < 0.05) amount of collagen present in the dermis of limbs treated with low-energy densities of laser (0.23 and 1.37 J/cm2). CONCLUSIONS: Laser irradiation directly affected the growth and development of day 14 fetal mouse limbs in an organ culture system.

Choosing an adjunctive therapy for the treatment of chronic wounds.

Adjunctive therapies such as ultrasound, laser, ultraviolet light, superficial heating, pulsed electromagnetic fields, and electrical stimulation have all been indicated in the treatment of chronic wounds. The purpose of this article is to outline the issues a healthcare professional must consider when choosing the best adjunctive therapy for a chronic wound. It summarizes the effects of therapeutic modalities on the wound healing process, analyzes the clinical research evidence, discusses practical considerations, and reviews indications, contraindications, precautions, and safety considerations. Finally, an algorithm is presented to help guide the clinician in selecting a modality. In summary, research evidence exists in the literature that suggests these adjunctive therapies can directly stimulate new tissue growth, augment wound tissue strength, improve local circulation and oxygenation, reduce edema, and/or inhibit bacterial growth. Electrical stimulation and ultrasound are the only therapeutic modalities that currently have sufficient clinical research evidence to support their use in the treatment of chronic wounds. Practical issues such as cost, time and training required, and patient and therapist safety concerns, will ultimately influence the selection of these modalities.

Pressure ulcer assessment instruments: a critical appraisal.

Numerous evaluation tools have been developed to document various aspects of wound status or appearance of pressure ulcers. These include the Pressure Sore Status Tool (PSST), Pressure Ulcer Scale for Healing (PUSH Tool), Sussman Wound Healing Tool (SWHT), Sessing scale, and the Wound Healing Scale (WHS). A critical appraisal of the literature was undertaken to examine the purpose and methods for the development of each instrument, the extent to which the instruments have been validated to date, the practicality of their use, and the work that remains to be done to establish their suitability for clinical and/or research purposes. All of these instruments have been developed to describe and evaluate change in pressure ulcer status over time with the exception of the WHS, which was developed as an alternative to reverse staging. More of the validation parameters have been addressed for the PSST and the Sessing scale than for the PUSH Tool, the SWHT, and the WHS. All of the instruments can be completed within approximately 5 minutes except the PSST, which requires 10 to 15 minutes to complete. For all instruments, experience with wounds and training in the use of the instrument are required to improve reliability. For each of the measurement instruments, suggestions are made that would complete necessary validation procedures and thus prepare the instruments for clinical and/or research purposes.

Glycogen storage in fetuses of trained pregnant rats.

The purpose was to determine if running 30 m/min on a 10 degrees incline, 60 min/day for 5 days/ week altered fetal glycogen storage in prepregnancy trained rats. Animals that exercised for 3 weeks prior to pregnancy either continued the same exercise program until Day 19 of gestation (pregnant running group [PR]), or ceased exercising at conception (pregnant controls [PC]). A separate set of animals did not exercise either before or during pregnancy (pregnant nonrunning control group [PNRC]). On Day 20 of gestation, fetal organs and placenta were weighted and analyzed for glycogen concentration. Glycogen concentrations were not different in either fetal liver, heart, or placenta of PR rats compared to PNRC animals. However, fetal liver glycogen concentration was significantly lower in the fetal heart and liver of PC animals compared to glycogen measured in both PNRC and PR animals (p < .05). These results suggest that exercise of this intensity does not compromise fetal glycogen storage in trained pregnant rats. However, chronic prepregnancy exercise and then abrupt cessation of exercise at conception may compromise fetal growth and development.

A simple method to assess the relative amount of collagen deposition in wounded fetal mouse limbs.

A modification of the Sirius red and fast green dye staining technique which binds selectively to collagen and noncollagenous proteins, respectively, has been used to quantify the amount of collagen deposition occurring in wounded fetal mouse limbs. Wounded day 14 and 18 fetal mouse limbs were grown in serum-free organ culture for 1 to 7 days, fixed in formalin, embedded in paraffin, and sectioned. The sections were stained with Sirius red and fast green dyes, and those sections obtained from either wounded or unwounded tissue were identified microscopically. The sections were then scraped off microscopic slides. Dye bound to the tissue sections was then eluted with a mixture of sodium hydroxide and methanol, and the optical densities were determined spectrophotometrically. There was a 98.5% correlation between the absorbance of Sirius red dye (collagen) and fast green dye (noncollagenous proteins) of eluted stain and hydroxyproline and leucine content, respectively, as determined by high-performance liquid chromatography. In addition, there was a greater collagen/protein ratio in wounded compared with unwounded sections of day 18 limbs at 7 days after wounding (p = 0.005). However, no difference in the collagen/protein ratio was detected between wounded and unwounded regions of day 14 limbs at either day 1 or 7 after wounding. These results are consistent with previous histologic observations indicating greater collagen deposition in wounded regions of day 18 compared with day 14 limbs at 7 days after wounding. With the use of this technique, it is now possible to quantify the effects of putative fibrogenic agents on collagen deposition in wounded embryonic tissue.

The role of transforming growth factor-beta in the conversion from "scarless" healing to healing with scar formation.

The objective of this study was to elucidate mediators responsible for conversion of "scarless" wound healing seen in wounded, day 14 fetal mouse limbs to healing with scar formation seen in wounded, day 18 fetal mouse limbs. Wounded, day 14 limbs were grown in a serum-free organ culture system in which either phosphate-buffered saline solution or human recombinant transforming growth factor beta-1 (1 microg/ml) was added daily. Wounded, day 18 limbs were also maintained in the same organ culture system with either phosphate-buffered saline solution or neutralizing antibody to transforming growth factor-beta (1 microg/ml) treatment. Limb cross sections were examined qualitatively with Masson's Trichrome stain and quantitatively by spectrophotometric analysis of Sirius Red and Fast Green dyes which bind to collagen and noncollagenous protein, respectively. Both qualitative and quantitative analyses showed the following: there was greater collagen deposition in day 18 versus day 14 limbs by 7 days after wounding, scar formation in day 18 limbs was attenuated by the addition of anti-transforming growth factor-beta, and there was the addition of transforming growth factor-beta-augmented collagenous scar formation in wounded regions of day 14 limbs. These results strongly suggest that transforming growth factor-beta present in the local wound environment is, at least in part, responsible for the conversion of "scarless" healing occurring in wounded, day 14 limbs to scar formation present in wounded, day 18 limbs.

The extracellular matrix of the fetal wound: hyaluronic acid controls lymphocyte adhesion.

Adhesive interactions between lymphocytes and components of the extracellular matrix (ECM) within a wound environment play a crucial role in determining the inflammatory response following tissue injury. In fetal wounds the extracellular matrix is composed predominantly of hyaluronic acid. Within this environment the inflammatory reaction as a result of injury is minimal. We propose that this lack of an inflammatory cell response in the fetal wound is due to the high levels of hyaluronic acid within the ECM and the inability of lymphocytes to adhere to this matrix component. Therefore, we examined the adhesive properties of fetal lymphocytes to fibronectin, vitronectin, collagen types I, III, IV, V, and hyaluronic acid--ECM components involved in fetal and adult wound environments. Fetal lymphocytes from both spleen and thymus demonstrated significant binding capabilities to fibronectin, vitronectin, and collagen types I and III. No intrinsic binding capabilities were detected to hyaluronic acid. Adhesion was not affected by the addition of IL-1, IFN-gamma, or phorbol dibutyrate. The inability of lymphocytes to adhere to hyaluronic acid helps to explain the lack of inflammation found in fetal wounds and serves to demonstrate the importance of ECM-lymphocyte interactions in determining the inflammatory response during fetal wound healing.

Diminished insulinotropic effects of gastrin-releasing peptide in pregnant sheep are reproduced by progesterone treatment of nonpregnant animals.

Gastrin-releasing peptide (GRP) is insulinotropic in several species, but possible alterations in this action during pregnancy have not been explored. Therefore, changes in plasma insulin and glucagon concentrations were examined in response to exogenous GRP in nonpregnant and pregnant sheep that were feed restricted, fed ad libitum, or infused with glucose. Administered GRP provoked insulin and glucagon release in pregnant and nonpregnant fed animals. This effect was reduced with feed restriction and potentiated in the presence of glucose. The responses were less in pregnant than in nonpregnant animals. Interpretation of this result, however, was confounded by lower plasma immunoreactive concentrations of GRP achieved in pregnant than in nonpregnant sheep in response to the same infusion rate (picomoles per kg BW) of exogenous GRP. Therefore, nonpregnant ovariectomized sheep were treated with estradiol (E2) or E2 plus progesterone (P4), given to reproduce circulating steroid levels in pregnancy, in order to examine insulinotropic responses to GRP in the absence or presence of concurrent glucose administration. Similar plasma GRP and glucose concentrations were achieved by exogenous infusions in the different groups of nonpregnant animals treated with steroids and in control animals not receiving steroids. E2 alone did not alter the insulin response to GRP compared to control, but E2 plus P4 treatment attenuated these responses to values similar to those in pregnant animals. We conclude that GRP is insulinotropic in sheep, and this action is modulated by the circulating glucose concentration. The response to GRP is less in pregnant than in nonpregnant animals, and this attenuation is mimicked in nonpregnant animals treated with E2 plus P4. We suggest that in species such as sheep, GRP is a potentiator of glucose-stimulated insulin release. This action is diminished in response to the altered endocrine environment of pregnancy and may contribute to the metabolic changes that occur at this time.

Ontogeny of the distribution and colocalization of calbindin D28K within neural and endocrine cells of the gastrointestinal tract of fetal and neonatal sheep.

Using immunocytochemical techniques we have demonstrated that Calbindin D28K (CaBP) is present in the gastrointestinal tract of ovine fetuses early in development (by day 45). At day 45, CaBP was limited to neuronal elements in the developing intestine. By day 100, CaBP immunoreactivity was abundant in both epithelial endocrine cells and nerves of the submucous and myenteric ganglia. The location of CaBP containing cells and fibers was similar in duodenal sections taken from day 100 and term (145 days), as well as those taken from 24-48 h postnatal lambs. CaBP is colocalized in endocrine cells containing gastrin, glucagon, somatostatin and neurotensin, but not glucose dependent insulinotrophic peptide (GIP). Furthermore, it is extensively colocalized in nerve fibers and cells containing neurotensin but not somatostatin or vasoactive intestinal peptide. The colocalization of CaBP within various endocrine and nerve cells does not change in fetal sheep over the last one-third of gestation and there is no difference between fetal and neonatal sheep.

Ontogeny of the insulin response to glucose in fetal and adult sheep.

The purpose of the present experiments was to examine in sheep whether the fetal insulin response to glucose was present by day 110 (d110) of pregnancy and whether the magnitude of the fetal insulin response changed between d110 and d145 (term). We also compared the responses observed in fetuses to those of adult nonpregnant sheep. Basal concentrations of glucose measured in plasma collected from the fetal femoral artery rose progressively between d110 and d145 of gestation, but did not attain the plasma glucose concentrations measured in adult sheep. Peak glucose concentrations in fetuses were achieved 10 min following the bolus injection of glucose (0.8 g/kg estimated fetal body weight) into the fetal femoral vein, and peak values increased with gestational age. Significantly higher peak glucose concentrations were achieved in adult sheep. The concentration of insulin rose rapidly in fetuses at d110, and a similar time course of insulin release in plasma was seen at all gestational ages. The peak plasma insulin concentrations were achieved at 20 min and were significantly greater in older (d140-145) than younger (d125-130) fetuses (p less than 0.05). Peak insulin values in fetuses were much less than in adult sheep. In adult sheep glucose and insulin concentrations remained elevated at 120 min following the injection of glucose, whereas in the fetus the concentration of insulin had returned to preinjection values by 60 min. The insulin/glucose ratio did not change in fetal lambs over the last one third of gestation and was not different from the adult sheep.(ABSTRACT TRUNCATED AT 250 WORDS)

Involvement of neuronal cell bodies of the mesencephalic locomotor region in the initiation of locomotor activity of freely behaving rats.

The locomotor activity of freely-moving rats was increased substantially by injections of L-sodium glutamate or of picrotoxin, a GABA antagonist, into the region of the tegmental pedunculopontine nucleus. The onset of hyper-motility was more rapid with L-glutamate than with picrotoxin and the duration shorter. Locomotor activity from injecting amphetamine unilaterally into the nucleus accumbens was reduced by injections of GABA into the ipsilateral pedunculopontine nucleus. These observations provide additional evidence implicating neurons of the MLR and possibly GABA synaptic inputs to these neurons in locomotor activity and suggest that they may mediate indirect inputs from the nucleus accumbens.