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B A Mast

Publications and source records attributed to B A Mast.

27 records · Page 2Linked to original sources

Models of wound healing.

The investigation of wound healing is dependent on the use of various models. This paper reviews several methods used to study wound healing, particularly in regard to connective tissue metabolism. The usefulness and potential pitfalls of cell culture are discussed. Several species of animals have been used as models for human healing, rodents being the most frequently employed. In an attempt to provide better wound tissue sampling from these animals, insertable devices have been developed that allow the ingrowth of healing tissue. Several of these devices are reviewed with reference to their advantages and disadvantages. Connective tissue deposition into wounds can be evaluated by wound strength measurement and hydroxyproline quantitation. Histologic methods are available to evaluate the cellular and matrix details within the wound. Additionally, methods developed in molecular biology are becoming applicable to healing studies and a safe means of investigating collagen metabolism in humans by the use of a stable oxygen isotope is being developed. The study of fetal wound healing provides an excellent example of the utility of many of these methods in achieving an understanding of the biology of this remarkable scarless process.

Animals↗

Comparison of five methods of assessment of intestinal viability.

A strain gauge device called the electronic contractility meter (ECM) was designed to measure quantitatively intestinal ischemic damage by delivering electrical stimuli to the intestine. Threshold stimulus level (TSL) was the minimum stimulus in milliamps necessary to produce a smooth muscle contractile response. TSL scale ranged from zero to 100 milliamps. Resection and anastomosis in ischemic intestinal segments was carried out in 30 dogs to compare TSL, intestinal color, peristalsis, Doppler ultrasound and resection margin histology with survival. There were five fatal anastomotic leaks, all resulting from intestinal necrosis. Doppler pulse in the marginal artery (MA) was absent at four of the five anastomoses that leaked versus eight of the 25 that healed (p less than or equal to 0.01). Mean TSL at the resection site was 38 +/- 7 milliamps in surviving dogs versus 51 +/- 4 milliamps in nonsurvivors (p less than or equal to 0.001). Mean TSL of normal intestine was 22 +/- 2 milliamps. Both TSL and Doppler ultrasound also correlated with resection margin histology (p less than or equal to 0.02 and p less than or equal to 0.005, respectively). Presence of peristalsis did not correlate with histologic grade or survival rate. Intestinal color correlated with resection margin histology (p less than or equal to 0.001) but not survival. The ECM and Doppler ultrasound were both superior to gross visual assessment in predicting intestinal survival. The ECM quantitatively measures tissue damage, a potential advantage over Doppler ultrasound, which provides only an estimate of local arterial blood flow.

Anastomosis, Surgical↗

Use of tubes and radiographs in the management of small bowel obstruction.

During the past 10 years 311 consecutive patients were admitted with 342 episodes of small bowel obstruction (SBO). There were 193 cases of partial small bowel obstruction (PSBO) and 149 cases of complete small bowel obstruction (CSBO) as determined by interpretation of the abdominal radiographs done on admission. The purpose of this review was to determine the reliability of the admission plain abdominal radiographs and subsequent upper gastrointestinal (UGI) contrast studies in predicting the need for operative intervention. The use of nasogastric tubes (NGT) versus nasointestinal (long) tubes (NIT) was correlated with the following outcome variables; length of hospital stay (LOS), timing of operative intervention, incidence of postoperative complications, and duration of postoperative ileus. Long tubes (NIT) were used in 64 episodes of PSBO and 81 episodes of CSBO, whereas nasogastric tubes (NGT) were used in 116 cases of PSBO and 68 cases of CSBO. Thirty-eight of 193 (19%) patients with PSBO required operation (20 of 116 with NGT and 18 of 64 with NIT), whereas 125 of 149 (84%) patients with CSBO required operation (60 of 68 with NGT and 65 of 81 with NIT). Need for operation was not correlated with whether or not long tubes passed beyond the pylorus; 50 passed versus 33 not passed in operative groups (p = 0.15). Twelve of 83 patients with NIT had operation within 24 hours versus 52 of 80 patients with NGT (p less than 0.001). In six of 64 patients who had surgery within 24 hours, complications developed versus in 39 of 99 patients operated on more than 24 hours after admission (p less than or equal to 0.001). In 29 of 83 patients treated with NIT, postoperative complications developed versus in 16 of 80 patients with NGT (p less than or equal to 0.04). The mean duration of postoperative ileus in patients with NIT was 7 days versus 4.1 days for NGT patients (p less than 0.001). The mean LOS was 12.2 days for NGT patients versus 21 days for patients with NIT (p less than 0.001). Barium UGI contrast studies were performed in 57 patients to establish the presence of obstruction. In 34 of 57 patients the UGI disclosed mechanical obstruction that required operative intervention. In the remaining 23 patients no obstruction was demonstrated, and all 23 patients recovered without operation. In conclusion, there is no inherent superiority of NIT versus NGT in the treatment of SBO.(ABSTRACT TRUNCATED AT 400 WORDS)

Humans↗

Myoelectric assessment of bowel viability.

A device capable of quantitative measurement of intestinal ischemic damage has been designed. The device is called the electrical contractility meter and employs a clip-on strain gauge transducer that delivers a precisely controlled electrical stimulus to the bowel. Threshold stimulus level (TSL) is the stimulus current in milliamperes (mA) that is necessary to produce a clearly defined smooth-muscle contraction. In 30 dogs, TSL was used to establish viability boundaries in 40 cm ischemic bowel segments. Bowel viability was assessed with the use of TSL in comparison with gross features (color, peristalsis) and blood flow measured by means of Doppler ultrasound at 2 cm intervals in the ischemic small-bowel segments. The TSL scale ranges to 100 mA and varied from a low of 22 +/- 2 mA in normal bowel outside the ischemic segment to 97 +/- 4 mA in grossly gangrenous bowel. There was a consistent correlation between rising TSL and worsening bowel color, disappearance of visible peristalsis, and progressive disappearance of audible Doppler signals. Resection and anastomosis were performed in three groups of 10 dogs at TSL measurements of 30 mA, 40 mA, and 50 mA, respectively. Dogs were killed and anastomoses were inspected on the tenth postoperative day. There were no leaks at TSL = 30 mA, one leak at TSL = 40 mA, and four leaks at TSL = 50 mA. The number of leaks at TSL = 50 mA was significantly greater than at TSL = 30 mA (p less than 0.04, Fisher's exact test). These results show that the quantitative myoelectric parameters established by this device provide a reliable in vivo assessment of bowel viability. The electrical contractility meter is easy to use and may have clinical applicability.

Animals↗

Hyaluronic acid degradation products induce neovascularization and fibroplasia in fetal rabbit wounds.

Scarless fetal wound healing occurs with mild fibroplasia and neovascularization, while the wound is persistently enriched with hyaluronic acid. Conversely, adult wounds are characterized by prominent fibroplasia, neovascularization, and scar formation, and hyaluronic acid is a transient component of the early adult wound matrix. Our group has reported that enzymatic degradation of fetal rabbit wound hyaluronic acid results in marked increases in fibroplasia, collagen deposition, and neovascularization. This altered, adultlike healing response is hypothesized to have resulted from the generation of biologically active hyaluronic acid degradation products. Therefore, this study analyzes the fibrovascular inductive activity of hyaluronic acid degradation products. Fetal rabbit wounds were treated with hyaluronic acid degradation products generated by methods known to produce oligosaccharides with significant angiogenic activity. Implants from wounds treated with either of the control solutions (n = 4 for each control) had identical histologic features characterized by a mild mononuclear cell infiltrate but neither infiltrating fibroblasts nor collagen. In marked contrast, implants from wounds treated with hyaluronic acid degradation products contained infiltrating fibroblasts and collagen intermixed with numerous blood vessels. Quantitation of capillary ingrowth showed a sixfold increase in the neovascular response in wounds treated with hyaluronic acid degradation products compared with either controls (p < 0.05). This study shows that hyaluronic acid degradation products stimulate neovascularization and fibroplasia in fetal wounds. These observations suggest that a balance between hyaluronic acid accumulation and degradation has significant regulatory influence in fetal tissue repair.

Journal Article↗

Exposure to amniotic fluid inhibits closure of open wounds in the fetal rabbit.

In many species, open cutaneous fetal wounds do not heal in utero. Such open wounds have been shown to close only after their exclusion from amniotic fluid, thus leading to the hypothesis that amniotic fluid inhibits open wound healing. Therefore the effect of amniotic fluid exposure on the healing of open fetal skin wounds was studied. Fetuses of New Zealand White rabbits received a full-thickness circular 4 mm diameter skin punch biopsy wound. Wounds were left uncovered, covered with a latex patch, or covered with a latex patch with a central hole (doughnut). This third group provided for wound exposure to amniotic fluid while controlling for any wound splinting effect of the patch. Wounds were harvested after 5 days, the wound area was determined planimetrically, and wound edges were examined by means of light microscopy. Analysis of glycosaminoglycans in the wound extra-cellular matrix was performed on a separate group of wounds treated similarly. Uncovered wounds enlarged by an average of 60%, whereas wounds covered with the doughnut patch enlarged by an average of 24%. In contrast, the wounds in the patch-covered group decreased in size by an average of 84%. Histologically all groups contained proliferating fibroblasts and epithelial migration at the wound edge but also an absence of granulation tissue. The patch-covered wounds, which had decreased wound area, were significantly enriched in hyaluronic acid. These results suggest that the healing of the patch-covered wounds occurs without the formation of granulation tissue, presumably through a process of cellular migration and proliferation and that healing was inhibited by exposure to amniotic fluid. Hyaluronic acid has been shown to be permissive of cellular migration and to play a key role in tissue regeneration. Therefore, we speculate that direct exposure of open wounds to amniotic fluid during the late stages of fetal development in the rabbit prevents hyaluronic acid deposition, which in turn may alter wound closure.

Journal Article↗

Ultrastructural analysis of fetal rabbit wounds.

Fetal wound healing proceeds rapidly with minimal inflammation and fibroplasia and little or no scar formation. These observations have led to the hypothesis that fetal wound healing more closely resembles regeneration rather than adult wound repair. To test this hypothesis, this study used ultrastructural analysis of fetal and adult fibroblasts and collagen to gain greater insight into differences in the healing processes. Full-thickness, primarily closed linear incisions were created dorsally on 24-day gestational age fetal rabbits (n = 9). The fetuses were killed 5 days later, and the wounds were excised and evaluated with transmission electron microscopy. Similarly, uninjured fetal skin of the same gestational age was obtained and analyzed. Adult rabbit dermal wounds were analyzed after 8 days of healing. Resting adult dermal fibroblasts had features of quiescent, inactive cells, whereas adult wound fibroblasts were highly active and filled with secretory vesicles. In contrast, both fetal normal dermal and wound fibroblasts appeared highly active and contained numerous secretory vesicles. In the adult wound, collagen fibril diameter was only 45% of the diameter of normal dermal collagen. However, fetal wound collagen fibrils were basically the same as normal dermal collagen, having a diameter that was 82% of the size of dermal collagen. These observations suggest that fetal wound fibroblasts do not require activation from an inactivated state and that fetal wound collagen deposition undergoes more rapid organization and maturation. These findings have significance in extending our understanding of the rapidity and functional superiority of fetal wound healing compared with adult wound healing.

Journal Article↗

Molecular and mechanistic validation of delayed healing rat wounds as a model for human chronic wounds.

The purpose of this study was to provide molecular and mechanistic evaluation of an ischemic wound model in rats to determine if it is a valid model for human chronic wounds. Compared to acute wounds, human chronic wounds contain markedly elevated levels of proinflammatory cytokines and matrix metalloproteinases, while matrix metalloproteinase inhibitors and growth factor activity are diminished. Accordingly, tissue from ischemic and normal rat wounds were analyzed for cytokine, proteases and growth factor levels. Dorsal full thickness punch wounds were created in rats using a reproducible template. The ischemic wound group (n = 10) had six uniformly placed wounds within a bipedicled dorsal flap. The control group (n = 10) had the same wounds created without elevation of a flap. On postwound days 3, 6 and 13 wounds were excised and analyzed. Protein levels for tumor necrosis factor-alpha were determined with a rat-specific enzyme-linked immunosorbent assay, while mRNA was determined by RNase protection assay. Matrix metalloproteinases and serine protease detection was done using gelatin and casein zymography, respectively. Significant delay in healing was achieved in the ischemic group: 50% healing for control wounds was at 7 days and 11 days for ischemic wounds (p < 0.001). No significant differences between wound groups were found for interleukin-1beta, and mRNA for tumor necrosis factor-alpha and interleukin-1beta. However, at day 13 ischemic wounds contained significantly more tumor necrosis factor-alpha than controls and normal skin (586 +/- 106 pg/biopsy vs. 79 +/- 7 pg/biopsy vs. 52 +/- 2 pg/biopsy; p < 0. 001). Zymography showed substantially greater quantities of matrix metalloproteinase-2, matrix metalloproteinase-9, and serine proteases in ischemic wounds. This model of delayed healing in rats shares many of the key biochemical, molecular and mechanistic characteristics found in human chronic wounds, namely elevated tumor necrosis factor-alpha and protease levels. As such, this model will likely prove to be useful in chronic wound research, particularly in developing novel therapeutics.

Animals↗

Diagnosis-related group impact of nutrition support in cardiac surgery patients.

We studied the diagnosis-related groups (DRG) impact of nutrition support on 80 consecutive cardiac surgery patients operated upon during a 6-month period. Six of 80 patients were nutritionally depleted preoperatively. Seven received postoperative supplemental nutrition, all of whom had major postoperative complications. Patients were arbitrarily placed into three outcome groups: group I consisted of seven patients who received postoperative nutrition support; group II included 38 patients who received no nutrition support and did not develop complications; Group III consisted of 35 patients who received no nutrition support but developed postoperative complications. All group I patients were length of stay (LOS) outliers. Group I patients were significantly older than groups II and III (p less than 0.0003) and had a significantly longer average length of stay (ALOS) (p less than 0.001), ALOS in SICU (p less than 0.0001) and greater incidence of both septic complications (p less than 0.02) and mortality (p less than 0.02). Nutrition support in cardiac surgery patients warrants special DRG consideration in light of the significantly increased hospitalization and resource utilization as compared with all other patients in cardiac surgery.

Adult↗