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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

Disease-specific alterations in frontal cortex brain proteins in schizophrenia, bipolar disorder, and major depressive disorder. The Stanley Neuropathology Consortium.

Severe psychiatric disorders such as schizophrenia, bipolar disorder and major depressive disorder are brain diseases of unknown origin. No biological marker has been documented at the pathological, cellular, or molecular level, suggesting that a number of complex but subtle changes underlie these illnesses. We have used proteomic technology to survey postmortem tissue to identify changes linked to the various diseases. Proteomics uses two-dimensional gel electrophoresis and mass spectrometric sequencing of proteins to allow the comparison of subsets of expressed proteins among a large number of samples. This form of analysis was combined with a multivariate statistical model to study changes in protein levels in 89 frontal cortices obtained postmortem from individuals with schizophrenia, bipolar disorder, major depressive disorder, and non-psychiatric controls. We identified eight protein species that display disease-specific alterations in level in the frontal cortex. Six show decreases compared with the non-psychiatric controls for one or more diseases. Four of these are forms of glial fibrillary acidic protein (GFAP), one is dihydropyrimidinase-related protein 2, and the sixth is ubiquinone cytochrome c reductase core protein 1. Two spots, carbonic anhydrase 1 and fructose biphosphate aldolase C, show increase in one or more diseases compared to controls. Proteomic analysis may identify novel pathogenic mechanisms of human neuropsychiatric diseases.

Amino Acid Sequence↗

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↗

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↗

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↗

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↗

Porous polyethylene implant for orbital wall reconstruction.

Short-term and intermediate-term results from clinical use of high-density porous polyethylene implants for reconstructive orbital surgery have been encouraging. This article presents an intermediate-term result from one institution with a comprehensive comparative analysis of other available alloplastic materials. A patient survey of 32 cases of orbital reconstruction using porous polyethylene sheet implants was performed, with a mean follow-up period of 32 months (range 15 to 67). All cases were trauma-related injuries. The result was compared with that of published reports of other alloplastic materials with specific emphasis on complication rates. Complication rate following the use of porous polyethylene sheet implants was 6%. This finding was consistent with those of other reports on porous polyethylene sheet implants. A consistent, satisfactory surgical outcome and low complication rate were observed. In the authors' review, the porous polyethylene implants compared favorably in a comparative analysis of other alloplastic materials.

Adolescent↗

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↗