Effect of insulin-like growth factor type I on critical size calvarial bone defects in irradiated rats.

Irradiated wounds are characterized by a slow healing process. Insulin-like growth factor-1 (IGF-1), a somatomedin C, has been shown in previous studies to stimulate collagen synthesis and bony repair. The purpose of this investigation is to evaluate the potential beneficial effects of recombinant IGF-1 in the healing of critical size calvarial defects in previously irradiated adult male Sprague-Dawley rats.

Hepatic ablation using bipolar radiofrequency electrocautery.

RATIONALE AND OBJECTIVES: Percutaneous methods have been used to treat primary and secondary hepatic neoplasms. In the current study, we evaluated the potential of bipolar radiofrequency (RF) electrocautery to increase in vitro liver tissue destruction when compared with monopolar RF electrocautery. METHODS: Two needles (electrodes) were placed into fresh bovine liver tissue for use with bipolar electrocautery. Needle tip exposure was kept constant at 3 cm while other parameters, including treatment time, power (wattage), interneedle distance, and needle tip temperature, were changed. Pathologic and histologic correlation was performed, and tissue necrosis was weighed in grams for individual parameters. RESULTS: There was a minimal threshold of approximately 45 degrees C where tissue coagulation occurred. Tissue coagulation increased the longer treatment went on. Increasing temperature, wattage, or both increased tissue coagulation such that necrosis was too rapid and char formation occurred, which prevented further coagulation. For all wattages and temperatures, there was increasing tissue necrosis with increasing needle separation, until a point at which further needle separation produced less tissue necrosis. Optimizing parameters allowed tissue coagulation of greater than 30 g. CONCLUSION: Bipolar RF electrocautery shows promise for increasing the tissue coagulation in fresh bovine liver compared with the previously described monopolar technique.

Cranial bone grafting: biodegradable versus titanium fixation in a rabbit model.

Rigid internal fixation with miniplates and screws has enabled reconstructive surgeons to position bony segments precisely. Unfortunately, our present systems have been associated with a potential adverse effect on ultimate craniofacial growth and development. Also, they may be palpable, necessitating secondary procedures for removal of the hardware. We have been involved in an ongoing study evaluating the efficacy of a commercially developed biodegradable system. In this study, we compared biodegradable lag screw fixation with traditional titanium screw fixation in full-thickness, membranous bone grafts harvested from the zygomatic arches to the snout in a rabbit model. The results were compared with standard hematoxylin and eosin stains and laser densometry. Although this study adds further credence to the resorption of bone grafts, those secured with the polyglycolic acid screws demonstrated significantly less resorption than those maintained in position by traditional methods.

Prognostic significance of DNA ploidy in Ta/Tl bladder cancer: A southwest oncology group study.

While 80% of transitional cell carcinomas (TCC) present as Ta Tl lesions, they account for only 15% of deaths caused by TCC. We have evaluated the ability of DNA ploidy analysis to predict outcome in 228 patients with Ta Tl TCC. All patients were judged to be at increased risk for tumor recurrence due to having two occurrences of Stage TI tumor within 56 weeks, or three or more tumors presenting simultaneously within 16 weeks of registration. Concurrent carcinoma in situ was acceptable. All patients were treated with either bacillus Calmette Guerin (BCG) immunotherapy or mitomycin-C (MMC) intravesical chemotherapy. Patients with nondiploid tumors had higher hazard rates for both tumor progression and death (p = 0.007 and p = 0.016, respectively); however, the prognostic information of DNA ploidy was not additive to tumor grade.

Polyglyconate fixation successfully stabilizes zygomatic osteotomies in a nonhuman primate.

Investigators have reported problems with metal plates and screws, including restriction of craniofacial growth necessitating secondary removal; bone resorption secondary to stress shielding; increased incidence of infection, extrusion, and palpability, especially in regions with minimal soft-tissue coverage; and interference with radiological studies and postoperative radiation therapy. Biodegradable rigid fixation can easily eliminate a majority of these problems because the material provides adequate fixation for a finite interval corresponding to bony repair. For this reason, there has been increasing interest in developing satisfactory biodegradable plate and screw systems. We tested a commercially developed polyglyconate plate and screw system to stabilize zygomatic osteotomies in a nonhuman primate model before embarking on clinical trials. In this experimental model, the stabilized segments revealed satisfactory alignment; in the control animals, the bony fragments became significantly displaced. This polyglyconate plate and screw system appears to have a promising role in the surgical correction of craniomaxillofacial deformities in humans, and clinical testing should commence.

Histogenesis of adenosquamous bronchogenic carcinoma.

In our hamster lung cancer model studies, among 463 non-small-cell lung cancers (NSCLC), there were 47 adenosquamous neoplasms. In 24 of 27 lesions with diameters of less than 3.0 mm, the adenocarcinoma and the squamous cell carcinoma components arose as separate, spatially discrete lesions, but these were separate in only 7 of 20 lesions with diameters of 30 mm or greater. Co-infiltration of the components became more frequent as tumor size increased. The usual adenosquamous variety of NSCLC is likely a collision tumor, with each component possessing separate biological characteristics. Thus, future prognostically directed studies of this variety of NSCLC must recognize that these neoplasms have two components, each of which needs to assessed.

Successful xenotransplantation of human lung cancer correlates with the metastatic phenotype.

BACKGROUND: Occult micrometastases could explain deaths from stage I non-small cell lung cancer (NSCLC) after complete resections. If patients who have occult metastases could be identified, systemic therapy might be beneficial. METHODS: Non-small cell lung cancers from 81 patients in stages I, II, and III were transplanted to nude beige mice. Mean follow-up was 22.5 months (2 to 61 months). RESULTS: Twenty-one xenotransplants successfully took, and seven metastasized in the nude mice. Neither the predominant cell type nor the incidence of lymph node metastases correlated with the results of xenotransplantation. Of the 21 patients whose NSCLCs took in xenotransplantation, 13 (61.9%) have had development of metastases, and 9 (42.9%) have died of the cancer. Among the 57 patients whose NSCLCs did not take, 14 (24.6%) have had development of metastases, and 9 (15.8%) have died of their cancer. The higher incidence of metastases in association with xenotransplant take is significant (p = 0.0032). CONCLUSIONS: Patients whose NSCLCs take in xenotransplantation are at high risk for metastases. The xenotransplantation model is a step toward facilitating precise cellular biologic definition of the metastatic propensity of human NSCLC:

Biodegradable polyglyconate plates and screws: a histological evaluation in a rabbit model.

Within the zygomatic arch, bilateral osteotomies were performed on 20 adult male New Zealand white rabbits. These were stabilized in an anatomical position with polyglyconate acid plates and screws. At 3, 4, 6, 9, and 12 months, rabbits were killed and their zygomatic complexes removed en bloc. Specimens were serially sectioned for standard histological examination. Although no gross reactions were noted throughout the course of this investigation, histological reactions were brisk. At 3 months, particulate material was surrounded by a foreign body giant cell-type reaction. The quantity of foreign material appeared to decrease by 4 months, at which time the foreign body reaction was partially replaced by fibrous tissue. By 6 months, there was a thick periosteal scar at the osteotomy site with a few islands of persistent foreign material. These were primarily seen in small, irregular vesicular spaces surrounded by a large number of histiocytes with their characteristic foamy-cytoplasm. Although this foreign body reaction had subsided by 12 months, small foci of chronic inflammation still persisted.

Effect of insulin-like growth factor type 1 on critical-size defects in diabetic rats.

A number of investigators have reported on the clinically significant relationship between diabetes mellitus and impaired wound healing. Diabetic patients have an increased frequency of infection, delayed scar formation, and poor bony union. Investigations completed in our laboratory have demonstrated that insulin-like growth factor type 1 (IGF-1), a somatomedin C, has shown promise for accelerating bony repair. The purpose of this study was to examine the effects of recombinant IGF-1 on standardized, critical-size calvarial defects in 25 adult, male streptozocin-induced diabetic rats. From our study, it appears that IGF-1 exerts a potentiating effect on the repair of bony defects in diabetes-induced rats.

Repair of experimental calvarial defects with Bio-Oss particles and collagen sponges in a rabbit model.

Various materials have been used for reconstruction of both acquired and congenital calvarial defects. Unfortunately, each has its limitations. Autologous bone grafts have irregular rates of resorption that may require secondary corrective surgery, and individual harvest sites have limited stores that can necessitate additional donor locations. Alloplastic materials have unlimited quantities and volume stability but they may not become incorporated and are associated with a higher incidence of infection. The optimal bone substitute should stimulate new bone formation and permanently supplant the temporary space filler, thereby reconstituting the surgical defect. We evaluated 2 newly available bone substitutes, resorbable natural bone mineral (Bio-Oss particles) and a combination of collagen and natural bone mineral collagen combination (Bio-Oss sponges), to repair calvarial defects in an adult, male, New Zealand white rabbit model. We found that the particulate Bio-Oss material resorbed and then underwent the normal physiological stages of bone remodeling. The collagen and Bio-Oss combination was replaced by new bone ingrowth. These materials may have potential for use in the reconstruction of skull defects.

Retrograde ejaculation due to heterotopic erectile tissue.

We report a case of retrograde ejaculation due to an unusual prostatic urethral mass. The resected tissue was histologically indistinguishable from corpus spongiosum, and due to its location it was diagnosed as heterotopic erectile tissue. The embryological origin of this lesion is discussed.

Effect of insulin-like growth factor-1 on zygomatic arch bone regeneration: a preliminary histological and histometric study.

A number of physicians have attempted to pharmacologically manipulate the healing of bony fractures with a variety of agents such as growth hormone, thyroxine, chondroitin sulfate, and parathyroid hormone. Thus far, results from these experiments have been inconclusive. Previous research dealing with insulin-like growth factors has centered on cultures of osteoblast-like cells and has demonstrated a stimulatory effect on bone collagen synthesis, which may in fact play a critical role in the process of bone formation itself. The purpose of this investigation was to examine the effects of a genetically engineered growth factor, insulin growth factor type I, on midfacial fracture healing. In 24 adult male Sprague-Dawley rats, a standardized defect was created within the midportion of each zygomatic arch. One-half were treated with insulin growth factor type I administered with an osmotic infusion pump and the other half served as control subjects. At 2, 4, 8, and 12 weeks, animals from each group were killed and specimens of the defect obtained. Data were collected from radiographs and histological studies to compare the extent of bony repair. From this study, it appears that insulin growth factor type I could exert a potentiating effect on the repair of midfacial bone defects.

The effects of insulin-like growth factor-1 on critical-size calvarial defects in Sprague-Dawley rats.

In a previous study prepared in 1992, we found that insulin-like growth factor-1 showed promise in hastening intramembranous bone repair in midfacial bone defects. For the present study, we created critical-size calvarial defects in 36 adult male Sprague-Dawley rats. The rats were then divided into two groups and killed at 1, 2, 3, 4, 5, 6, and 8 weeks. Twenty-one rats were administered insulin-like growth factor-1 subcutaneously with a 14-day osmotic infusion pump. An untreated group served as controls. Results were compared using routine histology to examine bone reconstitution of the surgical defects. Within the experimental group, we observed repair commenced at approximately 1 week and the critical-size calvarial bone defects were completely obliterated by 6 weeks; in the control group, even by 8 weeks, the surgical defects remained almost unchanged. In summary, this is further evidence that insulin-like growth factor-1 may have the potential to accelerate repair of intramembranous bone defects.

Polyglyconate plates and screws to stabilize zygomatic osteotomies in a rabbit model.

Rigid internal fixation with miniplates and screws continues to be widely used in the correction of both congenital and acquired craniomaxillofacial deformities. This technique allows precise three-dimensional stabilization of bony segments. A number of recent reports have detailed some disadvantages, including potential growth restriction in developing children, bone resorption, infection, extrusion, and palpability. These problems have often necessitated secondary surgery for hardware removal. A biodegradable plate and screw system would eliminate these potential and real problems. Over the last 2 decades, there has been an escalating interest in developing satisfactory biodegradable materials for bony fixation. We have previously reported the initial phases of a long-term evaluation of various biomaterials currently available. The purpose of this study is to examine a biodegradable plate and screw system fabricated from a faster resorbing material--polyglyconate. This system would be applicable to pediatric reconstructive problems. Earlier studies have shown its tissue compatibility and feasibility for multiple surgical uses. Osteotomies were created at the midpoint of each zygomatic arch of 42 adult male white New Zealand rabbits. The animals were then divided into two equal groups. The first group served as a control and the bony segments were permitted to heal without stabilization, whereas in the experimental group, the bony segments were stabilized with biodegradable plates and screws made from polyglyconate. Animals were then sacrificed at 2, 4, 6, 8, 12, and 16 weeks, at which time radiographs were obtained. Zygomatic complexes were then removed en bloc, and routine hematoxylin and eosin slides were made for light microscopy. Without fixation, fracture segments became significantly displaced.(ABSTRACT TRUNCATED AT 250 WORDS)

Midfacial fracture repair in the adult rat.

The consensus in the literature is that fracture healing within the midface occurs via fibrous union. Clinical experience with the surgical correction of established traumatic deformities has not borne this out. An earlier histological examination with human biopsy specimens demonstrated that eventually repair occurred by direct bony union. However, a recent study in a rabbit model challenged this conclusion and indicated that the process of new formation resembles secondary bone formation as in endochondral formed bone. The purpose of our inquiry is to elucidate further the process of midfacial bony repair in an adult male Sprague-Dawley rat model.

Reconstruction of calvarial defects with anorganic bovine bone mineral (Bio-Oss) in a rabbit model.

Reconstructive surgeons have employed various procedures using either autogenous or alloplastic materials to repair cranial defects secondary to trauma, extirpative surgery, or congenital anomalies. Currently, the choice appears to be dependent on the personal choice or background of the operating surgeon. For years, our preference has been to use calvarial bone grafts as our primary source of reconstructive material. Disadvantages include uneven resorption of the bone grafts and limited quantities. For these reasons, bony substitutes present new possibilities for reconstruction of craniomaxillofacial defects. We evaluated Bio-Oss, which is a natural bone mineral derived from a bovine source that is chemically and physically identical to human bone, as a possible replacement material to reconstruct skull defects in a rabbit model.

The effect of insulin growth factor-1 on calvarial sutures in a Sprague-Dawley rat.

Early investigations attempting to determine the exact pathogenesis of premature closure of the cranial sutures were limited by the untoward sequelae caused by surgical procedures in animal models to simulate the development of craniosynostosis. In an attempt to create a model for evaluating the effects of manipulating the craniofacial sutures without the limitations of associated scarring, we conceived an animal prototype dependent on the effects of insulin growth factor-1 on the anterior frontal suture in a Sprague-Dawley rat model. The experimental group received 2 mg of IGF-1 over a 14-day period via a subcutaneously placed osmotic infusion pump, whereas the age-matched control group received no treatment. We present our preliminary histological results describing the effect of IGF-1 on calvarial sutures.