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Biomedical subjects

T K Hunt

Publications and source records attributed to T K Hunt.

At least 55 records · Page 3Linked to original sources

The effect of insulinlike growth factor I on wound healing variables and macrophages in rats.

OBJECTIVE: To assess the effect of insulinlike growth factor I (IGF-I) depletion and restoration on the number of wound macrophages and wound healing variables. DESIGN: Fourteen-day, placebo-controlled trial. SETTING: Animal research laboratory. STUDY PARTICIPANTS: Sham-operated and hypophysectomized healthy male rats weighing 300 g. INTERVENTION: Random assignment to a 14-day IGF-I (10 micrograms per wound per day) or placebo infusion directly into standardized Hunt-Schilling dorsal wound chambers. MAIN OUTCOME MEASURES: Wound healing variables (dry tissue weight, total protein, DNA, and hydroxyproline content), and number and concentration of wound macrophages. RESULTS: The IGF-I depletion in hypophysectomized rats decreased wound protein, DNA, and hydroxyproline content of wounds by 50%, and IGF-I infusion returned these variables to near that of sham-operated rats. Wound macrophage concentrations decreased by 50% from control in the IGF-I depleted rats and increased to 75% of control with IGF-I infusion. CONCLUSION: Insulinlike growth factor I may have a fundamental role in wound healing and may exert part of its stimulatory effect through macrophages. Although an independent effect of hypophysectomy on macrophages and collagen deposition is not excluded, we believe it is unlikely given the return to normal values with IGF-I infusion.

Animals↗

Starch powder contamination of surgical wounds.

OBJECTIVES: To determine if (1) lubricating starch glove powder contaminates surgical wounds even after powdered gloves have been washed and/or wiped: (2) starch powder can be eliminated from surgical wounds when the surgical team wears only powderless gloves; and (3) starch powder introduced into surgical wounds may increase scar formation. DESIGN AND OUTCOME MEASURES: Human surgical wounds were irrigated at the end of operations in which various combinations of powdered and powderless gloves were used. Team members who wore powdered gloves washed them in a saline solution and wiped them on surgical towels. The starch particles in the irrigant were counted. In addition, two series of breast biopsies were performed, one in which the surgeon wore powdered gloves and the other, powderless gloves. Pathologic specimens from reexcisions (for carcinoma) were examined for starch granules and inflammation. RESULTS: Starch granules were found in proportion to the number of surgical team members who wore powdered gloves and to the proximity of the wearer(s) to the operative site. Exclusive use of powderless gloves eliminated the presence of starch powder. Starch-containing phagocytes in tissue were surrounded by an inflammatory reaction, and in one patient the inflammation and scarring were severe. CONCLUSIONS: Starch powder is introduced into wounds by the use of powdered gloves despite glove washing and wiping. It can be eliminated by the exclusive use of powderless gloves. The inflammatory reaction to starch is variable and can be severe.

Equipment Contamination↗

Comparison of Clark electrode and optode for measurement of tissue oxygen tension.

Measurement of PsqO2 has proven clinically valuable. The optode is more stable and reliable than the Clark electrode, does not consume oxygen, measures temperature, and is relatively simple to use. The good correlation between values obtained by the Clark electrode and the optode in this study demonstrate that the optode may replace the Clark electrode without loss of prior data.

Animals↗

Induction of neutrophil Mac-1 integrin expression and superoxide production by the medicinal plant extract gossypol.

Gossypol is present in antiinflammatory poultices made from the medicinal tree Thespesia populnea. Isolated human neutrophils exposed to 3-20 microM gossypol for 15-90 min were assayed in vitro for superoxide production and surface expression of Mac-1 (CD11b/CD18). Gossypol increased superoxide production in a time- and concentration-dependent fashion consistent with a moderate, delayed respiratory burst. Surface Mac-1 expression was increased within 15 min by 3-5 microM gossypol, resulting in a 14-fold increase over controls and a threefold greater increase over that produced by PMA. Staurosporine failed to block gossypol induction of superoxide and Mac-1, while EDTA inhibited induction of Mac-1 only, implicating a calcium-dependent mechanism. Gossypol increased intracellular calcium to peak levels, but in a delayed fashion as compared to FMLP. These findings demonstrate that gossypol is a highly potent stimulant of Mac-1 expression and suggest at least two protein kinase C-independent pathways of neutrophil activation. The resultant exhaustion of neutrophils may account for the antiinflammatory properties of plants containing gossypol.

Alkaloids↗

Mild hypothermia during halothane-induced anesthesia decreases resistance to Staphylococcus aureus dermal infection in guinea pigs.

Because various immune functions are impaired at temperatures only 1 degrees to 3 degrees C less than normal, we tested the hypothesis that mild hypothermia during anesthesia impairs resistance to dermal infections. Guinea pigs were anesthetized for 6 hours with 1% inspired halothane. Their core temperatures were maintained at either 39 degrees C (normal for guinea pigs, n = 12) or 36 degrees C (n = 12). Two hours after induction of anesthesia, three doses each of Staphylococcus aureus (10(8), 10(7), and 10(6) organisms) were injected intradermally at nine sites on each animal's back. Core temperatures were not controlled after recovery from the anesthetic, and animals in each group were maintained in the same environment. Four days after anesthesia, each injection site was excised to obtain a count of viable bacteria. Subcutaneous oxygen partial pressure values, averaged over time, were 53 +/- 3 mm Hg (mean +/- SEM) in the hypothermic group and 62 +/- 4 mm Hg in the normothermic group (p = 0.06). Capillary perfusion, as assessed by laser Doppler flowmetry, was comparable in the two groups. One day after injection of 10(8) bacteria, the area of induration was 89 +/- 11 mm(2) in the hypothermic group but only 61 +/- 6 mm(2) in the normothermic group (p < 0.05). On postanesthetic day 4, the area of induration was 72 +/- 6 and 59 +/- 6 mm(2) in the hypothermic and normothermic groups, respectively (p > 0.05). After inoculation with 10(8) bacteria, the fraction recovered was 1.0 +/- 0.2 in the hypothermic groups and 0.6 +/- 0.2 in the normothermic group (p < 0.05). After inoculation with 10(7) and 10(6) bacteria, the fraction recovered was less than 0.2, and no difference was found between the hypothermic and normothermic animals. Thus mild hypothermia during halothane-induced anesthesia slightly impairs resistance to dermal infection.

Journal Article↗

Pulsed microamperage stimulation: a controlled study of healing of surgically induced wounds in Yucatan pigs.

BACKGROUND AND PURPOSE: Microamperage direct current and microamperage electromagnetic stimulation are used to accelerate healing in bone. Although many clinicians are using microamperage stimulation to relieve pain and facilitate wound healing, there is significant question regarding whether this low-intensity direct current significantly accelerates soft tissue wound repair. The purpose of this study was to determine whether low-voltage pulsed microamperage current (100 microA, 60 V, 0.1 Hz) enhances the healing of superficial, full-thickness, or incisional wounds created to simulate acute abrasions, ulcers, and lacerations. SUBJECTS: Ten adult Yucatan mini pigs served as the subjects for this study. METHODS: Variables associated with healing were measured in 60 matched pairs of surgically induced partial-thickness, full-thickness, and incisional wounds after either sham or anodal (positive-polarity) stimulation with pulsed microamperage current (100 microA) was administered for 1 hour per day for 5 days. Sterile, disposable electrodes (2 x 4 cm) were placed over each wound, which was kept wrapped and protected throughout the study. RESULTS: At 7 days postinjury, all wounds were healing well with no signs of infection. There were no differences in tensile strength, collagen density, maturity, or deposition (hydroxyproline), wound size, or visual appearance between the sham treatment and treatment lesions. No changes in local subcutaneous oxygen or temperature were found in the swine during or after microamperage stimulation. CONCLUSION AND DISCUSSION: This study did not provide any evidence to support the use of microamperage stimulation to accelerate wound healing. No negative effects, however, were found. Further research is needed to determine whether there is a critical interaction between the size of the electrode relative to the wound, the density of the current, the duration of the treatment, the polarity of the treatment electrode, and the acuity or chronicity of wounding and the effectiveness of microcurrent stimulation for wound healing.

Animals↗

MRI of a silicone breast implant surrounded by an enlarging hemorrhagic collection.

MRI yields cross-sectional image acquisition in multiple planes with very high contrast resolution. Additionally, in MRI of the breast, evaluation of the entire implant is possible. Not only is MRI very sensitive to loss of implant integrity and rupture, but also MRI can evaluate and characterize adjacent fluid collections or soft-tissue masses. Anatomic relationships of abnormalities and normal structures are well seen. In some situations, MRI may offer clinically relevant information not adequately addressed by other imaging modalities.

Breast↗

Mild hypothermia during isoflurane anesthesia decreases resistance to E. coli dermal infection in guinea pigs.

Small changes in core temperature profoundly alter cutaneous blood flow, a major factor influencing resistance to wound infection. Furthermore, when measured in vitro, various immune functions are temperature dependent in the physiological range. Accordingly, we tested the hypothesis that mild hypothermia impairs and mild hyperthermia improves resistance to dermal infections. Thirty-two guinea pigs were anesthetized for 6 h using 1.5% (1.25 MAC) inspired isoflurane. Their core temperatures were maintained at either 39 degrees C (normal for guinea pigs, n = 11), 36 degrees C (n = 12), or 41 degrees C (n = 9). One h after induction of anesthesia, 2 x 10(8) E. coli were injected intradermally with a 26-g needle at eight sites on each animal's back. Core temperatures were not controlled after recovery from anesthesia, and animals in each group were maintained in the same environment. Twenty-four h after injection, the area of induration surrounding each injection site was measured. This is a standard test of resistance to wound infection. Values were compared using one-way ANOVA and Scheffé's S tests. Results are presented as means +/- standard deviations; differences were considered significant when P < 0.05. Areas of inflammation on the hypothermic animals were significantly larger (48 +/- 10 mm2) than those on normothermic (36 +/- 10 mm2) or hyperthermic (37 +/- 6 mm2) animals. These data suggest that mild hypothermia during anesthesia significantly impairs resistance to dermal infection. In contrast, mild hyperthermia does not appear to be protective.

Anesthesia, Inhalation↗

Can wound healing be a paradigm for tissue repair?

This paper is written in the hope, if not the conviction, that it will be helpful to investigators of muscle physiology and development. Its thesis is that cell growth, connective tissue matrix deposition, and angiogenesis are stimulated in wounds in response to NAD+ depletion caused by a burst in lactate generation. We surmise that muscle development may also involve this metabolic control.

Adenosine Diphosphate Ribose↗

Transforming growth factor beta (TGF-beta) and dexamethasone have direct opposing effects on collagen metabolism in low passage human dermal fibroblasts in vitro.

Collagen metabolism is a balance between synthesis and lysis. Both are under tight regulatory control. TGF-beta reverse the impairment of healing seen after glucocorticoid treatment in vivo. Both TGF-beta and glucocorticoids are known to regulate collagen metabolism directly. We have examined the effect of dexamethasone and of TGF-beta individually and in combination on the regulation of procollagen type 1, interstitial collagenase and tissue inhibitor of metallo-proteinase-1 (TIMP-1) synthesis at both the protein and mRNA levels in low passage human dermal fibroblasts. Dexamethasone treatment decrease synthesis of procollagen and caused a dose dependent down-regulation of TIMP-1 synthesis. Interstitial collagenase synthesis by fibroblasts was detectable but low. Thus, glucocorticoid treatment of fibroblasts tilts the balance of collagen metabolism away from accumulation. TGF-beta had opposing effects, stimulating both procollagen and TIMP-1 synthesis at the protein and mRNA levels. TGF-beta was able to cause a dose-dependent reversal of the glucocorticoid induced decrease in procollagen and TIMP-1 synthesis. Stimulation of healing in glucocorticoid treated animals by TGF-beta may be by the direct action of this agent upon fibroblast collagen metabolism.

Blotting, Northern↗

Sequential changes in the cell mediators of peritoneal and wound fluids after surgery.

The concentrations of cell mediators in the peritoneal and wound fluids of patients who underwent abdominal surgery or mastectomy were determined sequentially and compared with the concomitant changes in blood components. The level of interleukin-6 (IL-6) in the peritoneal and wound fluids was significantly higher than the plasma level after gastrectomy (P < 0.001), cholecystectomy (P < 0.05), and mastectomy (P < 0.05), although the level of plasma IL-6 was also higher postoperatively than before surgery (P < 0.001, P < 0.05). Significantly higher levels of tumor necrosis factor-alpha were detected in the peritoneal and wound fluids (P < 0.01, P < 0.05, respectively) after surgery despite its absence in plasma. A platelet-specific protein and a protein specific for fibroblasts were also measured. Thus, mediators derived from various cells were shown to be present in human peritoneal and wound fluids, indicating that the local production of these mediators plays an important role in the process of tissue repair.

Adult↗

Editorials.

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Journal Article↗

Insulin-like growth factor binding protein-3 is present in the alpha-granules of platelets.

The lysis of the alpha-granules of platelets has been shown to release insulin-like growth factors (IGFs). One of the major regulators of the activity of IGFs is the IGF binding proteins (IGFBPs), but IGFBPs were thought to be absent from platelet alpha-granules. Human platelets were isolated, and the contents of the alpha-granules were released by thrombin digestion. IGFBP-3 was identified in the lysate by RIA and a ligand-binding Western blot; no other IGFBPs were observed. Platelet IGFBP-3 was present as the characteristic glycosylated doublet at 45 and 43 kilodaltons on ligand-binding Western blot, but was not associated with the acid-labile subunit in the alpha-granule. Thus, the IGFs in platelet alpha-granules coexist with IGFBP-3, which can play a major role in regulating and targeting the actions of IGFs when released by lysis.

Blood Platelets↗

Incisional wound healing: a controlled study of low and high dose ultrasound.

Ultrasound is commonly used by physical therapists, but there is no consensus regarding the most effective therapeutic dose for accelerating healing of open or closed wounds. A controlled, single-blind, posttest experimental study was carried out to compare differences in wound breaking strength and collagen deposition [hydroxyproline (HoPro)]. Forty-eight incisions were surgically induced in three mini Yucatan pigs. Each incision was randomly assigned to a control or an ultrasound treatment group with the sonated incisions further randomly assigned to 5 or 10 days of ultrasound treatment with either high dose ultrasound (HUS) (1.5 W/cm2, continuous mode, 1 MHz, 5 minutes) or low dose ultrasound (LUS) (0.5 W/cm2, pulsed mode, 20% duty cycle, 1 MHz, 5 minutes). Using the nonparametric two-sample Wilcoxon test, the breaking strength was found to be significantly higher in the sonated incisions compared with the control incisions (p < or = 0.02), but there were no significant differences in HoPro. For all groups, the level of HoPro measured the second week was significantly higher (an average of 60%) than measured the first week (p < or = 0.001). A significant interaction was found between the number of days of treatment and the dose of ultrasound. Hydroxyproline was significantly higher in the LUS group compared with the HUS group after 5 days of ultrasound. Both the wound breaking strength and the HoPro levels were significantly higher in the LUS group compared with the HUS group after 10 days of treatment (p < or = 0.02 and 0.01, respectively). The findings from this study suggest that physical therapists can use either LUS or HUS for approximately 1 week to enhance wound breaking strength in an acute incisional wound. However, if the goal is to continue to facilitate collagen deposition and wound strength, then a low dose of ultrasound should be used when treatment is continued for 2 weeks or more.

Animals↗

In vivo effects of systemic insulin-like growth factor-I alone and complexed with insulin-like growth factor binding protein-3 on corticosteroid suppressed wounds.

Glucocorticoids are known to decrease wound healing by inhibiting the inflammatory response and collagen synthesis. In patients on steroids requiring emergency surgery, a safe agent that can be administered systemically is needed to reverse the deleterious effects of corticosteroids. TGF-beta and PDGF work topically but are not candidates for systemic administration. IGF-I and IGF-I:BP-3 are logical choices for systemic administration to improve wound healing. Both have been found in our laboratory to repair the corticosteroid-induced defect in wound healing when applied topically; the IGF-I:BP-3 complex gave significantly better results than IGF-I alone. Therefore, we asked whether these agents administered systemically could reverse the impaired wound healing caused by corticosteroids and whether the IGF-I:BP-3 complex was superior. Sprague-Dawley rats 350 g had 4 Hunt-Schilling wire mesh wound cylinders implanted s.c. on the back. Depo-Medrol (8 mg) was given s.c. at the time of surgery. Experimental rats were given daily s.c. injections of IGF-I or IGF-I:BP-3 (supplied by Celtrix Pharm, Santa Clara, CA) in PBS and 0.1% rat serum albumin, pH 6.0. The groups were: vehicle; IGF-I 125 micrograms/d; IGF-I:BP-3 complex containing 125 micrograms IGF-I/d. On post-op. day 17, the tissue in the wound cylinders was harvested and dried at 37 degrees C. Dry weight, DNA, total protein, and hydroxyproline (collagen) contents were obtained by our published procedures. Wound cylinder dry weight, DNA, total protein and hydroxyproline were increased by IGF-I 250%, 340%, 200% and 205%, respectively, over controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex Hormones↗

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↗