Erle E. Peacock

Pharmacologic control of surface scarring in human beings.

A hypothetical basis for control of surface scar in human beings is: lathyrism produces poorly cross-linked collagen in healing wounds; poorly cross-linked collagen is more susceptible to digestion by tissue collagenase than is normally cross-linked collagen; and colchicine stimulates tissue collagenase activity. Therefore, treatment of patients with abnormal deposits of surface scar by excising the scar, inducing lathyrism, and administering colchicine should tend to correct abnormal balance between collagen synthesis and collagenolysis and result in a small scar with improved physical properties. Ten patients with massive keloids, resistant to conventional therapy by excision, grafting, and/or intralesional injection of steroids, have been treated by excising the keloid, grafting the defect, inducing lathyrism with Beta aminopropionitrile fumurate or peniciliamine and administering colchicine. Patients were followed for 18 months to five years. No toxicity or untoward side effects from therapy were observed. No patients developed recurrent keloids while undergoing treatment. All patients showed some change in the amount of scar which persisted during the period of study. This data supports the hypothesis that lathyrism and colchicine therapy exert a measurable beneficial effect on surface scar in human beings.

Some studies on the etiology of inguinal hernia

Classic descriptions of the pathophysiology of inguinal hernia do not account for the initial appearance of an indirect hernia after the age of forty. Moreover, structural abnormalities alone do not adequately explain repeated recurrence of inguinal hernia after physical strength has been restored by surgical procedures. Thus, some indirect inguinal hernias may be the result of factors other than the presence of a congenital abnormality such as patent tunica vaginalis, and some repeatedly recurrent direct hernias may be the result of factors other than excess strain or intra-abdomiha| pressure. The notion that factors other than the presence of a congenital patent peritoneal sac are responsible for some indirect inguinal hernias is supported by the observation that some indirect hernias do not appear until relatively late in life. In addition, analysis of autopsy and surgical statistical data suggests that as many as 20 per cent of males have a patent sac that persists well into adult years without the appearance of a typical inguinal hernia [I-6], We have reasoned that an.apparent deficiency of collagenous tissue in the transversalis fascia of elderly men with direct hernias may offer a clue to the missing factor in the development of indirect hernia relatively late in life. If decreased collagen synthesis or increased collagen degradation is a fundamental process in the development of inguinal hernia late in life, the presence or absence of a patent peritoneal sac would be of little importance except in determining the side of

Administration of beta-aminopropionitrile to human beings with urethral strictures: A preliminary report

(1) No toxic signs or symptoms and no unusual laboratory determinations were observed in five patients with posterior urethral strictures treated by dilatation of the urethra and administration of 1 gm per day of beta-aminopropionitrile (BAPN) for twenty-one days. (2) Patients treated with 1 gm daily of BAPN for twenty-one days showed an increase in cold saline-extractable and acid-extractable collagen in proplast sponge-collected and dermal scar tissue comparable with that reported previously after doses of 3 to 5 gm of BAPN daily. (3) Significant reduction in the breaking strength of newly synthesized connective tissue was observed in patients treated with BAPN. (4) None of the patients in this study showed abnormalities in net collagen synthesis or in synthesis of noncollagenous protein. (5) The difference in the results of this study and two previous trials of BAPN in human beings which were discontinued because of toxic and or hypersensitivity signs and symptoms is hypothesized to be the result of development of highly purified BAPN fumarate.

Dynamics of the healing of skin wounds in the horse as compared with the rat.

Abstract The dynamics of skin wound healing were studied in three horses with either full thickness skin excision or with subcutaneously implanted polyvinyl alcohol sponges. Granulation tissue and reactive granuloma were harvested from three anatomical sites and were analyzed by morphological and biochemical methods at three time intervals. PVA sponges were also implanted in rats and studied by similar methods. No effect of wound or implant location on morphology or density of the sample tissue was found. In the horse, neutrophil infiltration was found in the tissue of wounds less than one day old. This tissue actively synthesized collagen and showed high activity of collagenase. The activity of prolyl hydroxylase (PH), however, was low. At later time sampling period (3, 7, 14 days), both granulation and granuloma tissue showed increasing PH activity, high activity of collagenase, and decreasing rate of collagen synthesis. Collagen content also increased with time. The reactive granuloma tissue found in rats showed less connective tissue reactivity than in the horse as seen by the dynamics of the morphological and biochemical changes of the tissue. We conclude that the healing in the horse is rather prompt and excessive and may tend toward abnormal repair reactions.

Colchicine and wound healing

Abstract Rats with incised and sutured wounds and having subcutaneously implanted polyvinyl alcohol sponges were treated with various doses of colchicine. Breaking strength of wound tissue and biochemical analysis of sponge-induced granuloma tissue were compared with similar measurements in pair-fed controls. Colchicine reduced breaking strength of wound scar tissue significantly while lysyl oxidase activity in sponge tissue was not affected. Synthesis of collagenous and noncollagenous protein was stimulated by colchicine but accelerated collagen synthesis did not result in increased deposition of collagen in sponge tissue. The increased urinary excretion of hydroxyproline in colchicine-treated rats was paralleled by loss of body weight. Colchicine-induced cytotoxicity was also identified in fibroblasts from sponge granuloma tissue examined by transmission electron microscopy. We conclude that some reduction of total collagen deposition and breaking strength of wound tissue in colchicine-treated animals may have been the result of general toxicity of the drug. A specific effect of colchicine on collagen metabolism cannot be ruled out.

Biologic frontiers in the control of healing

I never knew Thomas Grover Orr. The responsibility which the honor of giving the Orr Lecture before this distinguished society carries, however, has weighed heavily upon me. In looking over some of Dr Orrs contributions, it has been intere sting to find that much of his life in surgery is recorded in the Archives of the Southwestern Surgical Congress. There can be little doubt that our organization was important to Dr Orr and that the standard of his contributions played a prominent role in the success we have enjoyed on the national surgical scene. As I searched through Friesens superb 1968 Orr Lecture [1] reviewing Dr Orrs contributions to surgery, I was struck by the relevance of Dr Orrs laboratory research to the needs the patients under his care must have presented. Clearly, Dr Orr did not go to the laboratory or send a student to the laboratory to fill a block of time, produce a paper, or fulfill a grant contract. I strongly suspect that Thomas Orr, if the whole truth were known, disliked the laboratory except for what it could do for a sick person under his care. He must have been, therefore, a real human biologist who recognized that the scientific method could not be applied to solve some problems in human beings, and so animal models were developed and adapted to provide data which would be useful to his patients. Invariably, however, there is the return to the patient and often there was a reward because self-descipline in the laboratory provided an answer which was otherwise unobtainable. This is a remarkable achievement which I have found extremely difficult to emulate.

Preperitoneal abdominal wound repair: incidence of dehiscence.

Preperitoneal abdominal wound repair in 100 consecutive patients who required midline laparotomy resulted in one case of wound dehiscence. The risk of dehiscence did not increase with the use of vertical midline abdominal incisions repaired without inclusion of the peritoneum. Avoidance of suture penetration of the peritoneum may result in a reduction in postoperative adhesions and intestinal obstruction without increasing the risk of wound dehiscence.

Activity and Extractability of Lysyl Oxidase and Collagen Proteins in Developing Granuloma Tissue

Summary The total activity of lysyl oxi-dase and its extractability into phosphate and 4 M and 8 M urea solutions were studied in granuloma tissue formed around sub-cutaneously implanted polyvinylalcohol sponges in rats and harvested on days 10, 18, 26, and 34. Furthermore, total collagen content and fractions of collagen extractable into 0.45 M NaCl (NSC) and 0.5 M acetic acid (ASC) were studied. Lysyl oxidase activity was assayed by measuring the release of tritium from a substrate biosynthetically labeled with H3-6-Lysine. Biochemical data were compared to the histology of the tissue. With the maturation of the granuloma tissue, the total activity of lysyl oxidase significantly decreases, and its extractability into phosphate significantly increases. Extractability into 4M urea was the highest in 10-day-old granuloma and the lowest in 34-day-old tissue. Only 80% of the total activity was extracted into 4 M urea medium. Total collagen content and ASC fraction increased continuously, and NSC decreased from 2.5% to 1.2% in 34-day-old tissue. We conclude that the highest activity of lysyl oxidase in young granuloma is related to a high proportion of fibroblasts and that the enzyme at this time is tightly bound to the pellet, possibly to the collagen substrate.

Internal reconstruction of the pelvic floor for recurrent groin hernia.

Repeated recurrence of groin hernia is more than an anatomical derangement that any trained surgeon can correct. Attempts to improve results include application of local patches of Marlex. There are two reasons (one theoretical and one practical) why a local synthetic patch may not be as useful as total reconstruction of endopelvic fascia with a biologically active, as well as structurally strong, living material. Such a restoration can be accomplished with the entire fascia lata from one thigh utilized as a free graft extending from one pelvic wall to the other and from the symphysis to the pubic rami. The practical advantage of a single sheet of fascia extending across the pelvic floor (like an airplane wing) is that frequent medial recurrences are eliminated because there is no medial edge under which peritoneum can protrude. The theoretical advantage of a biologically active graft is based upon animal data revealing the inductive capacity of fascia in stimulating net collagen synthesis and deposition. Thirteen patients with multiple recurrences following conventional repair of groin hernia have been reconstructed with large fascia lata grafts restoring the entire endopelvic floor. Over a 5-year period no recurrences have been detected. A technique for removing the entire fascia lata from one thigh through a single transverse incision will be shown. There have not been any donor site complications and there is no disability caused by removing the fascia.

Subcutaneous Extraperitoneal Repair of Ventral Hernias: A Biological Basis for Fascial Transplantation

Two fundamental biological differences between normal fascia and scar tissue are rate of collagen turnover and physical weave of collagen subunits. Both factors account for unsatisfactory results following ventral hernia repair unless scar tissue is excised and normal fiscia used. Removal of scar and identification of normal fascia often require extensive dissection, entrance into the peritoneal cavity, and sometimes requires lysis of intestinal adhesions with occasional injury to bowel. Simple imbrication of the hernia sac, as in treatment of a direct inguinal hernia, without excision usually results in recurrence of the hernia because of remodeling and attenuation of scar tissue. A new procedure, based upon the technique of direct inguinal hernia repair without opening peritoneum, has been performed on 12 patients with large ventral hernias. The procedures, performed entirely in a subcutaneous plane, involves imbrication of scar, transfer of a massive fascial onlay graft, and use of an internal stent. Patients have been followed for one to 5 years; there have been no recurrences. Inductive influence of the fascial transplant has been measured in two patients; a tenfold increase in net collagen synthesis and deposition occurs for at least one year following transplantation of fascia to an imbricated scar recipient area.