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Biomedical subjects

C D Sims

Publications and source records attributed to C D Sims.

At least 19 recordsLinked to original sources

In vitro prefabrication of human cartilage shapes using fibrin glue and human chondrocytes.

We report the first generation of human cartilage from fibrin glue using a technique of molding chondrocytes in fibrin glue developed in our laboratory. Human costal chondrocytes were suspended in cryoprecipitate and polymerized into a human nasal shape with bovine thrombin. After culture in vitro for 4 weeks, this construct was implanted subcutaneously into a nude mouse. The final construct harvested after 4 weeks in vivo demonstrated some preservation of its original features. Histological analysis showed features of native cartilage, including matrix synthesis and viable chondrocytes by nuclear staining. Biochemical analysis demonstrated active matrix production. Biomechanical testing was performed. To our knowledge this is the first reported creation of human cartilage from fibrin glue, and the first creation of human cartilage in vitro. This technique may become a promising means of engineering precisely designed autogenous cartilage for human reconstruction.

Adolescent

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

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

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

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

Cryosurgical treatment of cervical intra-epithelial neoplasia.

This report describes 154 patients treated with cryosurgery for cervical intra-epithelial neoplasia (CIN) over a 3-year period. Standard colposcopic criteria were used to select patients for conservative primary treatment. Treatment failed in 12.5% of 112 patients treated for CIN I (mild dysplasia) and II (moderate dysplasia). Of 42 patients treated for CIN III (severe dysplasia/carcinoma in situ) 45.2% showed persistence of the lesion after primary cryosurgery A second course of treatment resulted in a 98% cure rate for patients with CIN I and II and an 85.7% rate for patients with CIN III. However, 14.3% of patients with CIN III required alternative management after further cryosurgery. Because of this experience the treatment of CIN III has been reviewed at this clinic.

Cryosurgery

Prostaglandin vaginal suppositories: a simple and safe approach to the induction of labor.

The results of 1000 consecutive unselected cases of induction of labor for medical or obstetric reasons using prostaglandin E2 suppositories are presented. The overall rate of failed induction resulting in a cesarean section in those patients with an unfavorable cervix has fallen from 42 to 2.5%. Only 27% of the entire series required augmentation of labor with intravenous oxytocin, the range being from 9.9% of multigravidas with a favorable cervix to 42.4% of primigravidas with an unfavorable cervix. Both low- and high-risk pregnancies are suitable for induction by this method and trials of vaginal breech delivery and of uterine scars have been safely and successfully carried out. This method has now become routine for the induction of labor at the authors' institution. It has proved to be simple, safe, and highly acceptable to patients and obstetricians alike in all cases in which a simple amniotomy would not suffice.

Delivery, Obstetric

Induction of labour using prostaglandin E2 pessaries.

The routine method of induction at Queen Charlotte's Maternity Hospital is now by the use of prostaglandin E2 pessaries. The first 502 consecutive patients thus induced are presented: the caesarean section rate for a failed induction with an unfavourable cervix has fallen to 2%. The prostaglandin E2 pessary is highly efficient and acceptable for all cases in which a simple amniotomy will not suffice.

Adolescent

Prostaglandin E, pessaries for induction of labour.

Vaginal pessaries containing 3 mg of prostaglandin E2 were used to induce labour in 200 patients with variable induction features. Prostaglandin-induced labour was augmented where necessary by synthetic oxytocin. There was on failed induction. Only 23% of patients with favourable induction features and 53% of patients with unfavourable features needed oxytocin. There were no adverse fetal or maternal effects. The prostaglandin E2 pessary was as effective in inducing labour as 350 microgram extra-amniotic prostaglandin E2 in tylose in a comparable group of 200 patients in which there were 4 failed inductions.

Animals

Prospective study of different methods and routes of administration of prostaglandin E2 to improve the unripe cervix.

Methods of vaginal and extra-amniotic prostaglandin administration to achieve ripening of the cervix as a preliminary to induction of labour are described. Three groups of twenty patients with unfavourable induction features were studied, each receiving prostaglandin E2 the evening prior to planned induction. One group received PGE2 500 micrograms suspended in a viscous medium extra-amniotically. One group received PGE2 3 mg suspended in a viscous medium into the vaginal vault. A third group received a 3 mg PGE2 vaginal pessary to the posterior fornix. Improvement in cervical status at time of induction occurred in all groups but no single group had a significant advantage when regarding mean improvement, the induction-delivery interval or the number of patients in whom labour began before formal induction. However, with regard to relative cost, ease of preparation and storage, as well as patient and medical staff convenience, Prostaglandin E2 in pessary form is a superior form of administration.

Cervix Uteri

Routine induction of labour with extra-amniotic prostaglandin E2 in a viscous gel.

Prostaglandin E2, 350 microgram dispersed in a viscous gel, tylose, was introduced into the extra-amniotic space as a single dose in 285 patients to induce labour. With a favourable cervix, 82 per cent of multiparae and 50 per cent of primiparae were successfully induced. With unfavourable induction features, the success rates were 48 per cent and 24 per cent respectively. In the remaining patients, all but four were successfully delivered when intravenous oxytocin was also used. The method was safe, simple and inexpensive and had many advantages for patients and nursing staff.

Amnion

A comparison of salbutamol and ethanol in the treatment of preterm labour.

Intravenous salbutamol and ethanol were compared as treatments for preterm labour, 42 patients being assigned randomly to salbutamol and 46 to ethanol. There was no statistically significant difference in outcome between patients in the two groups, the mean delay in delivery achieved being 15 days with salbutamol and 20 days with ethanol. Neither treatment was very effective since only 10 patients given salbutamol and 14 given ethanol had their delivery postponed to 37 weeks or later. Salbutamol was more rapidly acting than ethanol but produced more cardiovascular side effects.

Albuterol

Lung function tests in bronchial asthma during and after pregnancy.

Respiratory function tests (forced vital capacity and forced expiratory volume in one second) were performed serially in pregnancy, the puerperium, and at least six weeks post partum in 27 patients with a history of asthma and in 12 control subjects. Eleven asthmatic patients with spirometric evidence of respiratory obstruction in pregnancy on at least one occasion were considered to have active disease. This group had significantly impaired respiratory function tests when compared to controls. The remaining 16 asthmatic patients were considered to be in remission. No changes in respiratory function tests attributable to pregnancy could be demonstrated in the asthma or control groups. Patients with active asthma tended to have smaller babies than patients with asthma in remission or the control patients.

Apgar Score