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Biomedical subjects

T K Hunt

Publications and source records attributed to T K Hunt.

At least 19 recordsLinked to original sources
PubMed1992

Insulin-like growth factor-I reverses the impairment of wound healing induced by corticosteroids in rats.

Corticosteroids are widely used therapeutic agents that have as a major side-effect the impairment of wound healing. Two hypotheses were tested: 1) that antiinflammatory corticosteroids decrease the local insulin-like growth factor-I (IGF-I) response to injury; and 2) that locally administered IGF-I would overcome methylprednisolone-mediated suppression of healing. The IGF-I concentration was measured in fluid from wire mesh cylinder wounds in rats given saline or methylprednisolone im. Rats receiving 8 and 16 mg had decreased wound IGF-I levels of 32% and 56%, respectively, compared to the saline-injected controls. IGF-I was infused (15 micrograms/day) by osmotic minipumps into wire mesh cylinder wound chambers of methylprednisolone (8 mg)-treated rats for 7 and 14 days. Methylprednisolone decreased wound DNA to 21%, hydroxyproline to 30%, and total protein to 5% of the values found in saline-infused controls. A 14-day treatment with IGF-I completely reversed the effect of methylprednisolone and increased DNA, hydroxyproline, and total protein to 216%, 109%, and 96% of saline control values, respectively. In conclusion, corticosteroids depressed wound IGF-I concentrations in rats, and an infusion of IGF-I into wound chambers reversed the corticosteroid-induced impairment of wound healing, as determined by the DNA, hydroxyproline, and total protein contents in wound chambers.

Adrenal Cortex Hormones↗
PubMed1992

Low-dose ultrasound effects on wound healing: a controlled study with Yucatan pigs.

This study reports on the effect of low-dose ultrasound in accelerating wound healing in matched pairs of surgically induced incisions and full-thickness and partial-thickness lesions in 11 Yucatan mini-pigs after 7 days of healing and 5 days of sonation. Tensile strength, collagen deposition (hydroxyproline), reduction in wound size (full-thickness lesion), and mast-cell degranulation were significantly greater in the sonated lesions than in the sham-treated controls (p = 0.01). Sonation enhanced strength by 24% and collagen deposition by 29%, when compared with controls. There were no significant differences in the quality of healing as measured by an ordinal scale. The results suggest that within the first week of healing, low-dose ultrasound facilitates wound healing. More research is needed to confirm the most effective dose, frequency, and treatment duration and intervention time for maximum healing.

Animals↗
PubMed1991

An adverse wound environment activates leukocytes prematurely.

This study was designed to evaluate the effect of different wound environments on wound activation. Our wound model provided two distinct environments, a well vascularized musculocutaneous flap and a poorly perfused random-pattern flap, in miniature swine. Leukocytes were isolated and analyzed by the following three variables: surface and total cellular Mac-1 (CD11b/CD18), superoxide anion expression, and lactoferrin release. Leukocytes from the unfavorable, poorly oxygenated wound environment activate on entry into the wound. Leukocytes from the musculocutaneous flap wound are better able to respond to a maximal challenge with the phorbol ester, phorbol myristate acetate. These findings may account for the enhanced bactericidal actions of the musculocutaneous flap compared with the random-pattern flap observed clinically.

Animals↗
PubMed1991

Cigarette smoking decreases tissue oxygen.

Subcutaneous wound-tissue oxygen (PsqO2) tension in eight volunteers fell rapidly and significantly in response to smoking, and remained low for 30 to 50 minutes. Sham "smoking" had no effect. These data suggest that a typical "pack-per-day" smoker experiences tissue hypoxia during a significant portion of each day. The degree of hypoxia found in these subjects has been associated with poor wound healing in animal and human studies. The onset and duration of tissue hypoxia paralleled the well-established plasma pharmacokinetics of nicotine. This suggests that peripheral vasoconstriction, induced by the adrenergic effects of nicotine, may contribute to the observed decrease in PsqO2.

Connective Tissue↗
PubMed1991

Ontogeny of fetal sheep polymorphonuclear leukocyte phagocytosis.

Premature infants and neonates are vulnerable to bacterial sepsis. This susceptibility may be due to the relative immaturity of their immune systems. To determine if neonates and, in particular, premature infants have decreased polymorphonuclear leukocyte (PMN) phagocytosis, we tested PMN phagocytosis of Staphylococcus aureus as a function of gestational age in the fetal lamb model. Because phagocytosis is made more efficient by the presence of opsonins in plasma, fetal and postnatal PMN phagocytosis were also measured after exposure to fetal and adult plasma. PMNs were isolated from fetal lambs at 104, 114, 124, and 141 days' gestation (term gestation for the fetal lamb is 145 days), as well as from 10-day-old neonatal sheep and adult sheep. Labeled S aureus were opsonized by incubation in either fetal or adult plasma, or left unopsonized for baseline values. Phagocytosis was measured as a percent of adult PMN phagocytosis after adult plasma opsonization. It was found that fetal PMN function is limited by two factors during the early third trimester: a primary defect in the ability of the PMN to phagocytose S aureus despite adequate opsonization, and the diminished ability of autologous fetal plasma to opsonize bacteria. The defect in PMN phagocytosis disappears late in the third trimester, but the inability of the fetal plasma to opsonize effectively continues until after birth.

Age Factors↗
PubMed1991

Tissue oxygenation, anemia, and perfusion in relation to wound healing in surgical patients.

Oxygen tension and collagen deposition were measured in standardized, subcutaneous wounds in 33 postoperative surgical patients. Pertinent clinical and wound parameters were analyzed by Pearson's correlation test and sequential linear regression analysis. Collagen deposition was directly and significantly proportional to wound oxygen tension and measures of perfusion. There were no significant correlations with hematocrit, estimated blood loss, length of operation, smoking, age, weight, sex, or urine output. This study in humans confirms animal experiments showing that collagen deposition and tensile strength in wounds are limited by perfusion and tissue oxygen tension. It appears unnecessary to maintain hemoglobin at normal levels to support repair, provided that peripheral perfusion can be maintained at a high level in compensation for anemia. These circumstances reflect the fact that although oxygen is essential to many aspects of healing, and must be delivered at adequate partial pressures, reparative tissue consumes relatively little of it.

Anemia↗
PubMed1991

The wound healing curve as a practical teaching device.

Fundamental concepts of clinical wound healing are commonly misunderstood. A hypothetical curve that describes the relationship between wound perfusion and risk of infection is constructed as a teaching device. Although many factors influence this curve, the most important are the presence of bacteria, dead space, necrotic tissue and motion. Subjecting the curve to clinical illustrations enhances its value as a tool for medical education.

Audiovisual Aids↗
PubMed1991

Tissue oxygen tension and other indicators of blood loss or organ perfusion during graded hemorrhage.

Currently employed clinical indicators of perfusion provide inadequate warning of developing hazards caused by marginal perfusion in certain vital organs or "peripheral" tissues that are pivotal to postsurgical wound healing. In this study, mean arterial blood pressure, cardiac output, and transcutaneous and subcutaneous oxygen tensions (PtcO2 and PsqO2) were investigated during serial hemorrhage, as indicators of the degree of both hypovolemia and perfusion to specific tissues. Blood was removed in stages (10%, 20%, 30%, 40%, 55%, 60%, and 65% of original volume) from anesthetized dogs. Injections of variously radiolabeled microspheres allowed assessment of blood flow at each stage of hemorrhage in bone, brain, colon, heart, kidney, liver, muscle, pancreas, skin, small intestine, spleen, stomach, and subcutaneous tissue. PsqO2 was correlated more highly with blood volume lost than was PtcO2. Furthermore PsqO2 was more sensitive to blood loss than was either cardiac output or PtcO2 and, also during the early loss (0% to 40%), was more sensitive than mean arterial pressure. Some organs (e.g., pancreas) appeared to lose considerable blood flow with only small loss of blood volume, but their blood flow then stabilized at a low level despite further hemorrhage. Other organs, notably the kidney, appeared to be relatively unaffected by substantial loss of blood volume (20% to 40%), after which, however, their blood flow quite abruptly became sensitive to further hypovolemia. This explains why blood flow-related performance of the kidney (e.g., urine volume) may not adequately predict a developing hazard or peripheral perfusion. Some indicators were found to be better indexes of blood flow in some organs than in others (e.g., cardiac output and PsqO2 correlated more closely with skin, spleen, and intestinal flows [and one another] than with vital organ flows).

Animals↗
PubMed1990

Superoxide production by wound neutrophils. Evidence for increased activity of the NADPH oxidase.

Oxygen radical secretion by neutrophils is potentiated or "primed" by extravascular migration into wounds. To define this change in responsiveness more precisely we measured superoxide production by blood and wound neutrophils from rabbits using formylmethionyl-leucyl-phenylalanine and phorbol myristate acetate as agonists. In all experiments, the time- and dose-dependency of superoxide secretion were the same for blood and wound neutrophils. However, wound neutrophils produced significantly more superoxide. Furthermore, the cytochrome b component of the NADPH oxidase was found in greater quantities within wound neutrophils. We conclude that priming does little to alter the requirements for activating the NADPH oxidase but does significantly increase the velocity of superoxide generation. The data suggest that alterations in the assembly and function of the NADPH oxidase may contribute to enhanced superoxide secretion by wound neutrophils.

Animals↗
PubMed1990

Peptides from live yeast cell derivative stimulate wound healing.

Live yeast cell derivative is an alcoholic extract from yeast (Saccharomyces cerevisiae) that has previously been shown by three groups of workers to stimulate wound healing. Live yeast cell derivative is a complex mixture, and it was not known which of its many components was responsible for the biological activity. This study describes the separation and analysis of the major components, one of which is a peptide fraction that stimulates wound healing. The fraction consists of a mixture of peptides from 6000 to 17,000 d. It causes angiogenesis in a chick embryo yolk sac membrane assay and in a rabbit cornea assay, and it dramatically stimulates wound healing in the "Schilling/Hunt" wire mesh cylinder model at concentrations 25-fold lower than those required for the intact live yeast cell derivative.

Animals↗
PubMed1990

Oxygen and wound healing.

Surgeons have been aware of the detrimental effect of ischemia and hypoxia on healing tissues. In order to assist repair in such circumstances, a variety of modalities including revascularization, flaps, and hyperbaric O2 have been developed. Although these are apparently successful from a clinical standpoint, only recently has experimental evidence demonstrated conclusively that oxygen is a controlling factor in wound repair. Furthermore, it is now clear that traditional expectations of repair can often be exceeded by increasing the partial pressure at which oxygen is supplied to wounds.

Humans↗
PubMed1990

A study of the relationship between blood flow and bacterial inoculation in musculocutaneous and fasciocutaneous flaps.

Regional nutrient blood flow to musculocutaneous and fasciocutaneous flaps was studied in dogs using 15-microns radiolabeled microspheres, and correlations to bacterial inoculation into closed wound spaces were sought. During the 6-day study period, no differences were found between blood flow to noinoculated versus inoculated flaps. Comparisons of blood flow to the deep surfaces of the flaps showed that blood flow to muscle in musculocutaneous flaps increased rapidly during the first 24 hours and then plateaued, while that to subcutaneous tissue plus fascia in fasciocutaneous flaps demonstrated a gradual and steady increase. The most rapid decline in bacterial counts at the undersurface of both flaps occurred within 24 hours, dropping significantly lower within musculocutaneous flaps. In addition to such surface properties of muscle as tissue ingrowth, rapid early augmentation of muscle blood flow may be largely responsible for superior bacterial suppression observed beneath musculocutaneous flaps.

Animals↗