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Biomedical subjects

P E Butler

Publications and source records attributed to P E Butler.

At least 37 records · Page 2Linked to original sources
PubMed2000

Prolonged survival of musculoskeletal xenografts with combined cyclosporine and 15-deoxyspergualin.

This study was undertaken to evaluate the feasibility of performing vascularized musculoskeletal xenografts between mice and rats using immunosuppression. Vascularized musculoskeletal grafts were harvested from the hind limb of C57BL/6J (B6) mice, transplanted heterotopically into Lewis rats, and revascularized by microanastomoses of the graft artery and the recipient femoral artery and the graft vein to the recipient femoral vein. Recipient rats were divided into four groups. Group 1 received no immunosuppression (n = 10), group 2 was treated with cyclosporine (10 mg/kg/day; n = 10), group 3 was treated with 15-deoxyspergualin (5 mg/kg/day; n = 10), and group 4 received both cyclosporine and 15-deoxyspergualin (n = 10). Graft survival was directly examined on postoperative days 4, 7, and 14. In vitro assays were performed using mixed lymphocyte reactions and anti-donor cytotoxic antibody assays to assess the recipient's immune response. Grafts were examined by histology and immunohistochemistry. All grafts in group 1 were rejected by day 4. In groups 2 and 3, all grafts were rejected by day 7. In group 4, however, 8 of 10 recipients had viable grafts on day 14. Data from mixed lymphocyte reactions showed that cell-mediated immune responses were uniformly suppressed in groups 2, 3, and 4 compared with group 1. However, anti-donor antibody production was only partly suppressed in groups 2 and 3, suggesting that graft rejection was primarily caused by circulating cytotoxic anti-donor antibodies in groups 1, 2, and 3. Histologic observations in groups 1, 2, and 3 confirmed the important role of the humoral mechanism in xenograft rejection. Furthermore, immunohistochemical results demonstrated that the small vessels in the rejected grafts showed anti-rat immunoglobulin and complement depositions. Only a combination therapy of cyclosporine and 15-deoxyspergualin attenuated the rejection of xenografts.

Animals↗
PubMed2000

Neonatal induction of tolerance to skeletal tissue allografts without immunosuppression.

Vascularized allogeneic skeletal tissue transplantation without the need for host immunosuppression would increase reconstructive options for treating congenital and acquired defects. Because the immune system of a fetus or neonate is immature, it may be possible to induce tolerance to allogeneic skeletal tissues by alloantigen injection during this permissive period. Within 12 hours after birth, 17 neonatal Lewis rats were injected through the superficial temporal vein with 3.5 to 5 million Brown Norway bone marrow cells in 0.1 ml normal saline. Ten weeks after the injection, peripheral blood from the Lewis rats was analyzed for the presence of Brown Norway cells to determine hemopoietic chimerism. The Lewis rats then received a heterotopic, vascularized limb tissue transplant (consisting of the knee, the distal femur, the proximal tibia, and the surrounding muscle on a femoral vascular pedicle) from Brown Norway rat donors to determine their tolerance to the allogeneic tissue. A positive control group (n = 6) consisted of syngeneic transplants from Lewis rats into naive Lewis rats to demonstrate survival of transplants. A negative control group (n = 6) consisted of Brown Norway transplants into naive Lewis rats not receiving bone marrow or other immunosuppressive treatment. The animals were assessed for transplant viability 30 days after transplantation using histologic and bone fluorochrome analysis. All the syngeneic controls (Lewis to Lewis) remained viable throughout the experiment, whereas all the Brown Norway to Lewis controls had rejected. Ten of the 17 allografts transplanted into bone marrow recipients were viable at 30 days, with profuse bleeding from the ends of the bone graft and the surrounding graft muscle. The percent of chimerism correlated with survival, with 3.31 percent (SD = 1.9) of peripheral blood, Brown Norway chimerism present in the prolonged survival groups and 0.75 percent (SD = 0.5) of Brown Norway chimerism in the rejected graft group. This study demonstrated prolonged survival of allogeneic skeletal tissue without immunosuppression after early neonatal injection of allogeneic bone marrow in a rat model.

Animals↗
PubMed1999

A comparative study of nerve healing in adult, neonatal, and fetal rabbits.

This experiment quantitatively compared the human equivalent of a nerve repair following surgical division in the fetal, adult, and early childhood period of development using a rabbit as an experimental animal model. Twelve time-dated pregnant New Zealand White rabbits at 24 days' gestation (term = 31 days) underwent hysterotomy; one hind limb was delivered through the uterine opening. The sciatic nerve was divided and repaired by primary neurorrhaphy using two 11-0 epineural sutures. Sciatic nerve repair was also performed in 10 neonatal and 10 adult New Zealand White rabbits. Following repair, each group was assessed using electromyography examination, measuring distal motor latency and amplitude at 1, 2, 3, and 4 months postrepair. There was no difference in any of the groups in distal motor latency. The amplitude rose incrementally in all groups, and the fetal group had significantly higher amplitudes (p < 0.02) at 1, 2, 3, and 4 months in comparison with the adult group. There was no statistically significant difference between fetal and neonatal nerve repairs at any of the time periods. At the completion of the study, the nerve repair sites were harvested for histologic estimation of mean myelinated fiber density and fiber diameter distribution distal and proximal to the repair site. A greater percentage of myelinated axons crossed the repair site in the fetal group (83 percent) in comparison with the adult group (63 percent) (p < 0.03). Our study also demonstrated significant increases in the number of larger myelinated fibers crossing the repair site in comparison with the neonatal and adult groups (p < 0.04). This study found that fetal nerve healing following surgical repair is superior to that found in adult animals and results in a higher number of larger myelinated fibers crossing the repair site in comparison with adult and neonatal repairs.

Aging↗
PubMed1999

Effect of early mobilization on healing of nerve repair: histologic observations in a canine model.

The effect of early mobilization on the healing of nerve repair was studied in a canine model. Median and ulnar nerves in the left wrist of 16 adult mongrel dogs were transected and immediately repaired. No motion of the repaired forelimb was allowed in the immobilized group (n = 10), while controlled passive motion between 30 and 90 degrees of wrist flexion was begun on the first postoperative day for 10 minutes twice daily in the mobilized group (n = 6). The pattern of revascularization and collagen formation at neurorrhaphy was examined by transillumination of India ink-injected specimen and by conventional histologic sections. Revascularization of nerve repair was found to occur by ingrowth of capillaries from proximal and distal nerve ends, which typically crossed the neurorrhaphy by 3 weeks in the immobilized group. Following early mobilization, there was a persistent "hypovascular zone" at the nerve repair site for up to 6 weeks. In addition, more scar tissue was generated by early motion according to gross observation and quantitative collagen analysis. Early mobilization, therefore, seems to impede nerve regeneration by delaying revascularization and enhancing scar formation.

Animals↗
PubMed1998

Tissue engineered neocartilage using plasma derived polymer substrates and chondrocytes.

This study demonstrates that fibrin monomers can be polymerized into moldable gels and used for the encapsulation of isolated chondrocytes. This biologically derived scaffold will maintain three-dimensional spatial support, allowing new tissue development in a subcutaneous space. Chondrocytes isolated from the glenohumeral and humeroradioulnar joints of a calf were combined with cyroprecipitate and polymerized with bovine thrombin to create a fibrin glue gel with a final cell density of 12.5 x 10(6) cells/ml. The polymer-chondrocyte constructs were implanted subcutaneously in 12 nude mice and incubated for 6 and 12 weeks in vivo. Histologic and biochemical analysis including deoxyribonucleic acid (DNA) and glycosaminoglycan quantitation confirmed the presence of actively proliferating chondrocytes with production of a well-formed cartilaginous matrix in the transplanted samples. Control specimens from 12 implantation sites consisting of chondrocytes alone or fibrin glue substrates did not demonstrate any gross or histologic evidence of neocartilage formation. Moldable autogenous fibrin glue polymer systems have a potential to serve as alternatives to current proprietary polymer systems used for tissue engineering cartilage as well as autogenous grafts and alloplastic materials used for facial skeletal and soft-tissue augmentation.

Animals↗
PubMed1998

Cell transplantation from limb allografts.

A murine model of skeletal tissue transplantation was developed to study the allograft rejection process in mice for limb allograft transplantation. Muscle, bone, and skin have been shown to be strong antigenic stimuli in vascularized allograft models, and cells from these sources were used for transplantation. Using enzymatic digestion, keratinocytes, myocytes, and osteocytes were harvested from B10.A mice tissues, dissociated into single cells, and then grown in culture for 14 to 21 days. Each cell type was marked with an intracellular fluorescent marker before transplantation of the cells into pockets in the rectus abdominis muscle of a syngenic host. All cell types remained viable and were detectable 2 weeks following transplantation when examined histologically and observed under a fluorescent microscope. Transplanted osteocytes were found to produce bone 8 weeks following transplantation. These results demonstrate that individual cells transplanted into muscle pockets survive and have the ability to produce extracellular matrix in this mouse model of skeletal tissue transplantation. Use of this model will allow transplantation of the cellular components comprising limb allografts to study the relative antigenicities and the rejection of the separate cells with the advanced immunologic techniques available for mice. A better understanding of immunologic responses to these individual tissue components may enable specific donor tissue or host immune modification to achieve skeletal tissue transplantation without immunosuppression. These findings are particularly valuable to the field of tissue engineering where allogeneic cells may be used in cell/polymer constructs for reconstructive procedures.

Animals↗
PubMed1997

Craniofacial skeletal fixation using biodegradable plates and cyanoacrylate glue.

This study examined the feasibility of fixation of craniofacial bone using Lactosorb biodegradable plates adhered to bone with butyl-2-cyanoacrylate adhesive (Histoacryl) in a pig. The stability and bone-healing characteristics of this rigid fixation method were studied and compared with standard rigid fixation using metal plates and screws on osteotomy sites in the frontal bones and infraorbital rims. Rectangular osteotomies (2.0 x 3.0 cm) were performed on the right and left sides of the frontal bone and wedge-shaped osteotomies (1.5 x 1.7 cm) were made on the left and right infraorbital rims in seven Yorkshire pigs. Metal plates were applied with screws to the osteotomies on one side, and the other side was fixed with a biodegradable plate and butyl-2-cyanoacrylate. The animals were sacrificed at 8 weeks, and both sides were compared biomechanically and histologically. Radiographic, biomechanical, and histologic analyses were performed to evaluate skeletal stability, contour, accurate positioning of bony fragments, bone healing, and maximum torque to failure of the repair sites. Clinical and radiographic observations demonstrated stability of the bone fragments without any evidence of displacement. According to Student's t test for paired data, no statistical difference was found in the maximum torque to failure of fragments fixed with biodegradable plates and glue compared with those fixed with metal plates and screws (p > 0.05), whether or not a gap existed at the osteosynthesis site. Although the sample size was small, no differences were noted between the two types of treatment groups. This study demonstrates that rigid internal fixation of osteotomized cranial bone fragments using biodegradable plates and butyl-2-cyanoacrylate is as effective as metal plate and screw fixation in this animal model.

Animals↗
PubMed1996

A 1-year prospective study of burns in an Irish paediatric burns unit.

Burns are the fourth leading cause of injury death in children in the USA, accounting for 1300 paediatric deaths annually. The majority of paediatric burns mortality and morbidity result from simple domestic accidents that are preventable. A prospective study of paediatric burns from 1 January 1992 to 1 January 1993 was undertaken at our burns unit to outline the profile of the Irish paediatric burns problem. A total of 336 burns were referred to our unit over the 12 months (80 per cent self-referrals, 15 per cent tertiary referrals from district hospitals and 5 per cent GP referrals). Sixteen per cent (57) of the patients required admission and 33 per cent (112) required prolonged dressings as outpatients. Mortality and morbidity rates were comparable to other centres at 1.8 per cent and 39 per cent respectively. The demographic analysis of the patient population was similar to that seen in other studies from developed countries but there were some notable differences. First, there was an alarmingly high incidence of serious sunburn injuries, especially among young infants. Most parents were unaware of the association between childhood sunburn and the development of skin cancer in later life. Second, 90 per cent of the accidents occurred in the home and almost all were preventable. A parent or guardian was present in 87 per cent of cases but parental knowledge of the appropriate first aid measures was poor. It is suggested that a public health education campaign on this issue would help in reducing the incidence and severity of paediatric burn injuries in Ireland.

Accidents, Home↗
PubMed1996

Bacterial growth in saline implants: in vitro and in vivo studies.

The survival of bacteria was evaluated in custom-made saline breast implants with integral injection ports in vitro and in 10 New Zealand White rabbits for Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, and Serratia marcescens. Pseudomonas and Serratia survived in vitro in saline-filled implants and multiplied 24-fold and 22-fold, respectively, from the initial inocula of 300 colony-forming units per cubic centimeter in 21 days. Serratia alone survived in saline implants placed on the dorsum of rabbits, proliferated 80-fold in 7 days, and tapered to 10-fold at the end of 3 weeks. Chemical analysis revealed the presence of glucose in fluid from the implants in the animal study (mean, 1.2 mg per deciliter; standard error of mean [SEM], 0.6) after 21 days and from human subjects (mean, 3.8 mg per deciliter; SEM, 1.0) after 8 months to 10 years. Serratia incubated in human breast implant fluid samples proliferated 7-fold to 30-fold greater than in the saline control in a nonaerated environment. We conclude that some bacteria are able to proliferate in saline in breast implants. Furthermore, their survival may be facilitated by a substance (i.e., glucose) that diffuses across the implant outer shell.

Animals↗
PubMed1996

Surgical model to assess the effects and optimal timing of craniofacial fixation.

An in utero swine model of craniofacial deformity was developed as a potential alternative to neonatal models currently used for evaluating the optimal timing and long-term effects of rigid fixation techniques on a growing cranium. At 75% gestation, seven fetal piglets were randomly selected to undergo periosteal stripping of frontal and parietal bone segments with and without extensive coronal suture fusion procedures with cyanoacrylate adhesive. Fetal swine were killed postpartum at 4 and 11 weeks after fusion to assess craniofacial deformity. Piglets undergoing coronal fusion had slight deviation of the nose-snout toward the side of fusion and taller cranial vaults. The vertical cranial index of the experimental fusion group was 0.34 in comparison to a vertical index of 0.27 for the controls, suggesting abnormal vertical height expansion. There was no difference in the horizontal cranial index of either control or experimental fusion groups. Neither sows nor piglets were lost to anesthetic complications, uterine sepsis, or preterm labor during the initial laparotomy or subsequent cesarean delivery.

Animals↗
PubMed1996

Injectable cartilage using polyethylene oxide polymer substrates.

This study demonstrates that polyethylene oxide gels, which are biocompatible and biodegradable synthetic polymers, can be utilized for the encapsulation of isolated chondrocytes and maintenance of three-dimensional spatial support for new tissue development. Chondrocytes isolated from the glenohumeral and humeroradioulnar joints of a calf were added to a 20% polyethylene oxide solution in Ham's F-12 medium to generate a final cellular density of 10 x 10(6)/mL. The polymer-chondrocyte constructs were injected through a 22-gauge needle in 500-microliters aliquots subcutaneously in 12 nude mice and incubated for 6 and 12 weeks in vivo. Histologic and biochemical analyses including deoxyribonucleic acid and glycosaminoglycan quantitative analyses confirmed the presence of actively proliferating chondrocytes with production of a well-formed cartilaginous matrix in the transplanted samples. Control specimens from eight implantation sites consisting of chondrocytes alone or polyethylene oxide substrates did not demonstrate any gross or histologic evidence of neocartilage formation. These findings demonstrate the potential use of an injectable and moldable polymer substrate that can support cell proliferation and matrix synthesis after subcutaneous transplantation for neocartilage generation. The use of functional biologic tissue substitutes may serve as an alternative solution to current methods of augmentation or reconstruction of structural craniofacial contour deformities.

Animals↗
PubMed1995

Cervical spine injuries in patients with facial fractures: a 1-year prospective study.

A total of 582 consecutive patients with facial fractures were investigated prospectively for evidence of a concomitant cervical spine injury. Of them, 1.04% (6) were found to have a cervical spine injury, all having occurred in road traffic accidents. Only two of the injuries were diagnosable on standard, three-view, plain cervical spine radiographs. Four were diagnosable from computerized tomography scan, while the remaining two required stress views under radiographic screening for definitive diagnosis.

Accidents, Traffic↗
PubMed1993

Risberg retroperitoneal approach to the abdominal aorta.

In a study of the best approach to the infrarenal abdominal aorta, 47 patients were compared retrospectively: 15 underwent a standard transperitoneal incision, 15 a retroperitoneal left flank incision and 17 a new modified lateral pararectus incision, the Risberg approach. Operating time, length of postoperative intubation and hospital stay, mortality rate, morbidity rate and cost were assessed. There was a significant reduction (P < 0.05) in mean(s.d.) operating time (141(21) versus 198(41) min), intraoperative cross-clamping time (74(13) versus 104(46) min) and postoperative intubation time (6.5(8.0) versus 13.3(7.3) h) associated with the Risberg retroperitoneal incision compared with the left flank retroperitoneal route. There was also a significant decrease (P < 0.02) in mean(s.d.) postoperative intubation time (6.5(8.0) versus 17.5(12.0) h), time after operation to discharge (11.0(2.4) versus 17.3(7.6) days) and hospital cost (4885(670) pounds versus 7732(580)) pounds associated with the Risberg incision compared with the transperitoneal approach. The Risberg incision gives better access to the infrarenal abdominal aorta while maintaining the advantages of other retroperitoneal approaches. This technique is recommended as the incision of choice for the retroperitoneal approach to the aorta.

Aged↗
PubMed1993

Bupivacaine and Kaltostat reduces post-operative donor site pain.

A prospective double blind controlled trial was carried out to examine the differences in post-operative split skin graft donor site pain between sites dressed with three differently treated types of dressing; a dry calcium alginate dressing (Kaltostat Britcair), a saline moistened Kaltostat dressing and a bupivacaine hydrochloride (0.5%) moistened Kaltostat dressing. There was a significant reduction in post-operative pain in the Kaltostat and bupivacaine group (group 3) at 24 and 48 h when compared to the other two groups (p < 0.04). There was no difference in ease of removal of dressings or the quality of wound healing on day 10 between the three groups. This study demonstrates a significant reduction in post-operative pain in bupivacaine soaked Kaltostat without reducing the beneficial effects of Kaltostat on donor site healing and we recommend its use in clinical practice.

Adult↗
PubMed1991

Improved wound healing with a modified electrosurgical electrode.

Previous studies comparing standard electrosurgical (ES) electrode and steel scalpel (SS) wound healing have reported poor initial tensile strength, a delay in reaching maximum tensile strength and an increased inflammatory response in the ES wounds. The hypothesis that a smaller needle (modified) electrode would give better wound healing than a standard electrode was tested. Using histology as a parameter of wound healing, incisions created by a modified electrode, a standard electrode and a steel scalpel were compared. Sixty Sha Sha mice were divided into 10 groups. Standardised dorsal skin incisions were made using steel scalpel, standard and modified electrosurgical cutting electrodes. Mice were sacrificed on days 0, 1, 2, 3, 5, 7, 9, 14, 28 and 42. The incised skin was processed for standard and immunohistochemical staining. The standard ES wound had significantly higher numbers of polymorphonuclear leukocytes in comparison to the SS and modified ES wounds (p less than or equal to 0.01). However, macrophage numbers were found to be significantly lower in the ES wounds when compared to the SS wounds on days two and five (p less than or equal to 0.05). The fibroblast response was delayed by up to two days in the ES wounds when compared to the SS wounds. Epithelialisation was completed by day two in the SS and modified ES groups but was only complete by day three in the standard ES group (p less than or equal to 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Regulation of a membrane-bound proteinase in mammalian cells.

Cellular proteolytic enzymes are regulated by multiple mechanisms that affect gene expression, enzyme concentration, and enzyme activity. The expression of the membrane-bound metallo-endopeptidase, meprin, in different mammalian species, strains, tissues and cell types is highly variable. Meprin is exclusively localized to the plasma membrane, and this determines the types of substrates the enzyme will encounter and the microenvironment for activity. Recent studies have revealed an inactive form of a meprin-like proteinase that can be activated in vitro by proteases, and this raises the possibility of regulation of enzyme activity at the cell surface in response to environmental stimuli. In this chapter, the current knowledge about meprin, and the meprin-like inactive forms in mouse kidney is discussed.

Animals↗