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Biomedical subjects

L G Phillips

Publications and source records attributed to L G Phillips.

At least 37 records · Page 2Linked to original sources

Effect of the combination of Aloe vera, nitroglycerin, and L-NAME on wound healing in the rat excisional model.

PURPOSE: Many systemic and topical therapeutic agents such as growth hormone, platelet-derived growth factor (PDGF), fibroblast growth factor (FGF), epidermal growth factor (EGF), and insulin-like growth factor (IGF) have been used as vulnerary agents. However, the role of nitric oxide (NO) as a wound-healing stimulant has been received with mixed reviews. NO is a potent vasodilator that is thought to be an endothelium-dependent relaxing factor, and a regulator of blood pressure and regional blood flow. It affects vascular smooth muscle proliferation and inhibits platelet aggregation and leukocyte adhesion. Therefore we compared the effects of several topical substances that have similar or reverse properties. METHODS: Using the excisional rat wound model, we evaluated the topical effects of Dermaide Aloe (D-Aloe, Dermaide Research Corp, Palos Heights, IL), nitroglycerin, Aquaphor (Beuersdorf, Inc., Norwalk, CT) alone, with D-Aloe with nitroglycerin, 2%, and L-NAME (NO inhibitor) with Aquaphor, and L-NAME with Aquaphor and D-Aloe for a 21-day period. All wounds were measured by planimetry at 1, 7, 10, 13, 16, 18, and 21 days. RESULTS: At day 1, all wounds had an average wound size of 2.27 cm2 (SD +/- 0.372) with no significant difference in wound size among the groups. Topically applied D-Aloe appeared to promote wound healing faster than the remaining other topicals (p < .05, Student-Newman-Keuls and Dunn's Method) over the study period. However, topicals combined with D-Aloe, the vehicle Aquaphor, and L-NAME improved the wound healing process when compared with nitroglycerin alone (p < .05). CONCLUSIONS: D-Aloe appears to have a wound-healing advancement factor that can reverse the effects of petrolatum- and nitroglycerin-based products as observed in the remaining groups when compared with nitroglycerin alone. It appears that D-Aloe's effect of preventing dermal ischemia by reversing the effects of thromboxane synthetase (TxA2) may act synergistically with NO or could be an oxygen radical scavenger.

Administration, Topical↗

The histological interpretation of high frequency cutaneous ultrasound imaging.

BACKGROUND: High frequency, high resolution B-scan ultrasound imaging (US) has been used to assess skin. The use of US is limited because of difficulty interpreting the various echoes. OBJECTIVES: To correlate the appearance of constant US echoes with histology in normal human skin. METHODS: Normal skin from eight volunteers was scanned with US at a frequency of 20-25 MHz, prior to excision for clinical reasons. The echogenic bands of the skin and histological measurements of various layers were related statistically. RESULTS: Three constant echogenic bands were identified, which correlated with skin surface, dermis, and subcutaneous fascia. CONCLUSION: The correct interpretation of echogenic bands in normal skin allows for the US to be more reliably used for assessment of skin disorders.

Adult↗

Influence of protein standardization by ultrafiltration on the viscosity, color, and sensory properties of skim and 1% milk.

Permeate and retentate (concentration factor ca. 2x) from UF of skim milk were combined, and cream was added to produce skim milk (0.1% fat) and 1% milk with a range of true protein contents (1.0 to 4.8%) within each fat level. A panel that had been trained for descriptive sensory analysis evaluated the appearance, aroma, flavor, and textural attributes of milks. Relative viscosity and Hunter color values for whiteness (L value), greenness to redness (a value), and blueness to yellowness (b value) increased when either protein or fat was increased. The rate of change of L, a, and b values as protein content changed was greater for skim milk than for 1% milk and was greater as protein contents decreased. Sensory scores for several descriptors of appearance, texture, and flavor had a stronger positive correlation with objective measurements of whiteness than with objective measurements of viscosity. Thus, the judgment of panelists about milk texture and flavor in milks that differed in protein content was influenced more by appearance than by viscosity. As the protein content of skim and 1% milk was increased from 2.9 to 4.8% true protein, the sensory properties of the milks were made more like those of higher fat milk, particularly those of skim milk, mainly because of whiter appearance. Panelists perceived changes in the sensory characteristics of both skim and 1% fat milk when the true protein content was increased by 0.9%, the smallest increase that was studied in the experiment.

Animals↗

Treatment of bilateral nasal polyposis and chronic refractory inhalant allergic rhinitis in a chimpanzee (Pan troglodytes).

Over a 15-yr time span, a 30-yr-old female chimpanzee (Pan troglodytes) exhibited recurrent upper respiratory disease that was suspected to be allergen induced. Until 1993, symptomatic therapy with several different antibiotics and antihistamines yielded variable results. In early 1993, the chimpanzee was consistently observed to be open-mouth breathing despite medication. Nasal polyposis was diagnosed using rigid endoscopy in September 1993, and the polyps were removed by loop excision. A fluorescent allergosorbent test was performed to differentiate hypersensitivity to specific regional allergens causing chronic inhalant allergic rhinitis. Oral immunotherapy was then instituted using standard human treatment for Sacramento Valley pollens. This combination of polyp removal and immunotherapy resulted in a marked reduction of clinical signs, and continuous oral immunotherapy has controlled these signs. Hyposensitization therapy will continue for at least 2-3 yr. The chimpanzee continues to breath normally following occasional antihistamine treatment.

Animals↗

Herbs and HIV: the health food industry's answer.

Patients with tragic diseases such as AIDS (acquired immunodeficiency syndrome) may be at risk for using herbal remedies and other alternative medical therapies. To ascertain what products may be available for use among AIDS patients in our community, we surveyed 20 local health food stores. Store employees were asked the question, "What do you recommend for people with AIDS?" Many herbal products, as well as other alternative medicinal preparations, were being recommended by store employees. Physicians caring for patients with AIDS should be aware of the potential for herbal use among their patients and the possible side effects of these products.

Acquired Immunodeficiency Syndrome↗

In vivo ovine flap model to evaluate surgical infection and tissue necrosis.

Although the inciting causes and the end results of soft tissue infection are well described, we have not achieved a quantitative methodistic description of the sequence of events in between. The following study presents an isolated in vivo model which will allow specific manipulations and quantifications of the events of integumentary infection. Pedicle flaps were raised on the buttock of the adult range ewe and it was multiply inoculated with Staphylococcus aureus, and followed for 96 hr. This pedicle contains not only a well-defined artery, vein, and nerve, but also a well-developed efferent lymphatic vessel. In addition, the distal portion of the flap is primarily supplied by a musculocutaneous arterial perforator, making the distal flap a watershed area. Anatomic, radiologic, and vital stain injection studies confirmed these results. The sheep model was found to be superior to the pig model both in terms of its anatomy (the addition of an efferent lymphatic vessel) as well as the disposition of the sheep which was more compliant than that of the pig. We believe that this flap will allow multiple manipulations and provide an in vivo isolated system to study the pathobiology of soft tissue infection.

Animals↗

Safety and effect of topical recombinant human interleukin-1beta in the management of pressure sores.

Interleukin-1beta is produced by numerous cell types including monocytes and fibroblasts. It has been shown to stimulate multiple cell types including fibroblasts, keratinocytes, endothelial cells, neutrophils, macrophages, and lymphocytes. Previously, interleukin-1beta was shown to accelerate healing in partial-thickness and full-thickness wounds in animals and was also shown to be safe when applied topically in Phase I human trials. Therefore a prospectively randomized, blind, placebo-controlled trial was performed with patients with chronic pressure ulcers. Doses of interleukin-1beta of .01 microg, .10 microg, and 1.0 microg per square centimeter did not show acceleration of healing of the pressure ulcers. Therefore use of recombinant human interleukin-1beta in this study was safe but, at the dose levels tested, did not result in improvement in the healing ratio.

Journal Article↗

Application of basic fibroblast growth factor may reverse diabetic wound healing impairment.

This study examines the effect of application of basic fibroblast growth factor (bFGF) on the wound healing impairment seen in streptozotocin-induced diabetic (SD) rats compared with control nondiabetic (NL) animals. Under general anesthesia, a 6-cm dorsal incision was made through the skin and panniculus carnosus. Both the NL and SD wounds were injected with 0.1 ml of one of the following three solutions: saline, vehicle, and 10 micrograms of bFGF. The wounds were closed with interrupted sutures of 4-0 nylon. The animals were returned to their cages and sacrificed at 7, 10, 14, or 21 days later. Breaking strength of the wound was analyzed by using an Instron Tensiometer 4201 to assay for relative collagen maturation. Data among groups were compared using an analysis of variance. At 7 and 10 days, all NL wounds were stronger than all SD wounds. By 14 days there was no statistically significant difference in breaking strength between the bFGF-SD wounds and all subgroups of NL wounds. The bFGF-SD subgroup was statistically significantly stronger than the saline-SD (p < 0.02) and vehicle-SD (p < 0.01) wounds. At 21 days the bFGF-SD wounds were statistically significantly stronger than the vehicle-SD wounds to a confidence level of p < 0.001. These findings indicate that application of bFGF may reverse the impairment seen in diabetic wound healing.

Animals↗

Platelet-derived growth factor BB for the treatment of chronic pressure ulcers.

A randomised, phase I/II, double-blind, placebo-controlled study was designed to assess the effect of topically applied recombinant human BB homodimeric platelet-derived growth factor (rPDGF-BB) on healing of chronic pressure ulcers. Twenty patients were randomly allocated daily treatment for 28 days with 1, 10, or 100 micrograms/ml rPDGF-BB (0.01, 0.1, or 1.0 micrograms per cm2 ulcer area) or placebo. Patients treated with 100 micrograms/ml rPDGF-BB showed a greater healing response than the placebo group, but the lower doses had little effect. After 28 days, ulcers treated with 100 micrograms/ml rPDGF-BB were smaller than those treated with placebo (mean [SE] volume 6.4 [4.0] vs 21.8 [5.6]% of day 0 volume). There were no toxic effects. These preliminary findings suggest that rPDGF-BB is a potent wound-healing agent in soft tissue.

Administration, Topical↗

A prospective randomized evaluator-blinded trial of two potential wound healing agents for the treatment of venous stasis ulcers.

Chronic wounds such as venous stasis ulcers have become a socioeconomic problem. Even with successful initial management, the recurrence rate approaches 70%. With the advent of new wound healing agents, nonoperative attempts to heal these wounds appear indicated. This study reports a prospective randomized evaluator-blinded trial comparing two potential wound healing agents to an inert vehicle placebo. Eighty-six evaluable patients completed the trial. Silver sulfadiazine 1% in a cream proved to statistically reduce the ulcer size compared with a biologically active tripeptide copper complex 0.4% cream formulation or the placebo. There was no difference between the latter two treatments. Silver sulfadiazine has been shown to allow keratinocyte replication and to have antiinflammatory properties. In this trial its antibacterial action was not used since all ulcers had comparable bacterial levels (less than or equal to 10(5)/gm of tissue) before treatment. These results suggest that the silver sulfadiazine cream used in this study may facilitate healing in wounds healing largely by the process of epithelialization.

Adult↗

Recombinant human platelet-derived growth factor-BB for the treatment of chronic pressure ulcers.

A randomized phase I/II double-blind, placebo-controlled study was designed to evaluate 1, 10, and 100 micrograms/ml (0.01, 0.1, and 1.0 micrograms/cm2) recombinant human BB homodimeric platelet-derived growth factor (rPDGF-BB) applied topically to chronic pressure ulcers for 28 days. Twenty patients were enrolled and completed the trial. No toxicities were associated with rPDGF-BB treatment. Patients treated with 100 micrograms/ml of rPDGF-BB had a pronounced healing response compared with placebo-treated patients. By day 29, ulcers treated with 100 micrograms/ml of rPDGF-BB were smaller in remaining size compared with those of placebo-treated patients when the following specific parameters were measured: percentage of initial depth (14.1 +/- 7.4 vs. 34.9 +/- 6.7) and percentage of initial volume (6.4 +/- 4.0 vs. 21.8 +/- 5.6). Histological analyses of biopsies revealed active wound healing processes in all groups with no disruption in the normal healing sequence in rPDGF-BB-treated wounds. The results of this small, descriptive study suggest rPDGF-BB is a potent vulnerary agent for accelerating soft-tissue repair, warranting further study.

Administration, Topical↗

The safety and effect of topically applied recombinant basic fibroblast growth factor on the healing of chronic pressure sores.

The first randomized, blinded, placebo-controlled human trials of recombinant basic fibroblast growth factor (bFGF) for pressure sore treatment were performed. Three different concentrations of bFGF in five dosing schedules were tested for safety using hematology, serum chemistries, urinalysis, absorption, antibody formation, and signs of toxicity. Efficacy was evaluated by wound volumes, histology, and photography. No toxicity, significant serum absorption, or antibody formation occurred. In six of eight subgroups, there was a trend toward efficacy with bFGF treatment. When all subgroups were combined, comparison of the slopes of the regression curves of volume decrease over initial pressure sore volume demonstrated a greater healing effect for the bFGF-treated patients (p < 0.05). Histologically, bFGF-treated wound sections demonstrated increased fibroblasts and capillaries. More patients treated with bFGF achieved > 70% wound closure (p < 0.05). Blinded observers were able to distinguish differences in visual wound improvement between bFGF and placebo groups. These data suggest that bFGF may be effective in the treatment of chronic wounds.

Administration, Topical↗

The effect of denervation on soft-tissue infection pathophysiology.

Pressure is the sine qua non in the etiology of pressure sores; however, ischemia, denervation, edema, and infection also have been implicated. The role of denervation in tissue infection was studied in an isolated in vivo ovine flap model. Twenty-six adult ewes, divided into three groups, had 29 island pedicle flaps raised on their buttocks. In group I, the cutaneous nerve remained intact, while group II had its nerve divided acutely. Group III had prolonged denervation, where the nerve was divided 7 days before flap elevation. All flaps received intradermal inoculations of 10(7) Staphylococcus aureus. Ninety-six hours later, quantitative bacteriology showed counts of 10(7), 10(7), and 10(9) colony-forming units (CFU) per gram of tissue in groups I, II, and III, respectively. Septic foci were larger in group III, and there was a significant increase in tissue edema between groups I and III. A 25-fold increase in bacterial counts seen in the prolonged denervation group may help explain why neurologically injured patients are more susceptible to infection and pressure ulcerations.

Abscess↗

Effect of bFGF on the inhibition of contraction caused by bacteria.

Bacterial contamination of open wounds significantly inhibits wound contraction required in the healing process. Basic fibroblast growth factor (bFGF) has been shown to overcome contraction inhibition in wound-healing models impaired by diabetes or steroids. This study was designed to determine the effect of bFGF on wound contraction inhibition in an area contaminated with bacterial overgrowth. The topically applied bFGF reversed inhibition to wound contraction that normally occurs with bacterial contamination. This reversal does not appear to be due to increased collagen synthesis since bFGF has been shown to decrease collagen synthesis and the treated wounds showed no increase in breaking strength. The use of bFGF significantly decreased the number of days required for wound healing (P less than 0.01) despite active bacterial invasion and may be of value in the treatment of human contaminated wounds.

Animals↗

Erythrocyte deformation in ischemic acute tubular necrosis and amelioration by splenectomy in the dog.

Bilateral renal artery occlusion (RAO) for 120 minutes in dogs results in acute tubular necrosis (ATN) and peritubular capillary (PTC) congestion with rapidly deteriorating renal function. We have shown that prior splenectomy minimizes RAO-induced renal functional and histopathologic changes. The purpose of this study was to examine whether this renal protection is due to prevention of red blood cell echinocyte formation and resultant renal PTC congestion. Echinocytes (burr cells) are poorly deformable, impart high viscosity to the blood, and may hinder reperfusion by increasing resistance to renal capillary blood flow. Splenectomized (SPLX) or sham-SPLX dogs were treated with bilateral RAO for 120 minutes. After RAO, renal function and renal blood flow were monitored, and peripheral blood red blood cells were examined at 1 hour and at 24-hour intervals for 96 hours. Renal biopsies were taken 1 hour after RAO and the kidneys removed 96 hours after RAO. The RBCs and renal tissues were studied using scanning electron microscopy. Renal function was assessed by endogenous creatinine clearance. Sham-SPLX animals showed a marked and sustained decrease in creatinine clearance, consistently elevated serum creatinine levels and fractional excretion of sodium, and diffuse ATN and PTC congestion with echinocytes. These animals had a peak in circulating echinocytes 1 hour after RAO (p less than 0.05), which showed an excellent negative correlation with creatinine clearance (r = -0.999; p less than 0.001). On the contrary, SPLX animals had essentially no change in serum creatinine or fractional excretion of sodium, minimal tubular changes, no PTC congestion, and no rise in circulating echinocytes during the 96-hour observation. In vitro treatment of the postischemic red blood cells from sham animals with adenosine-inosine or fresh postischemic plasma from the SPLX animals showed almost complete reversal to discocytes (normal red blood cells), whereas in vitro treatment of postischemic red blood cells from the SPLX animals with fresh postischemic plasma from the sham animals resulted in a marked echinocytic response. We conclude that 1) a marked echinocyte response in the immediate postischemic period is an important mechanism in initiating ischemic ATN, 2) an echinocyte inducing factor may reside in the plasma of spleen-intact animals, and 3) mitigation of ATN and PTC congestion by splenectomy is, at least in part, consequential to attenuated echinocytic response in the immediate postischemic period.

Animals↗