Reconstruction of bilateral extensive composite mandibular defects after osteoradionecrosis with two fibular osteoseptocutaneous free flaps.
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Small bone defects of the mandible and maxilla can be surgically treated with conventional bone grafts provided local conditions are optimal for bone healing. However, when the bone defect is large, is associated with soft tissue loss, or when conventional bone grafting fails, a free vascularized bone graft often becomes an important alternative to ensure adequate healing. As free vascularized bone grafting is today considered a more reliable procedure for bone reconstruction, with success rates over 96%, we prefer to treat even smaller segmental bone defects with this technique when local conditions are less than ideal. The technique also allows for simultaneous insertion of osteointegrated dental implants at the time of vascularized bone grafting, thereby facilitating earlier total oral rehabilitation.
Previous research demonstrated that exposing gonadectomized adult ferrets to odours in oestrous female bedding induced nuclear Fos-immunoreactivity (Fos-IR; a marker of neuronal activity) in the main as opposed to the accessory olfactory system in a sexually dimorphic fashion, which was further augmented in both sexes by treatment with testosterone propionate. Ferrets are born in an altricial state and presumably use maternal odour cues to locate the nipples until the eyes open after postnatal (P) day 23. We investigated whether maternal odours augment neuronal Fos preferentially in the main versus accessory olfactory system of neonatal male and female ferret kits. Circulating testosterone levels peak in male ferrets on postnatal day P15, and mothers provide maximal anogenital stimulation (AGS) to males at this same age. Therefore, we assessed the ability of maternal odours to augment Fos-IR in the accessory olfactory bulb (AOB), the main olfactory bulb (MOB) and other forebrain regions of male and female ferret kits on P15 and investigated whether artificial AGS (provided with a paintbrush) would further enhance any effects of maternal odours. After separation from their mothers for 4 h, groups of male and female kits that were placed for 1.5 h with their anaesthetized mother had significantly more Fos-IR cells in the MOB granule cell layer and in the anterior-cortical amygdala, but not in the AOB cell layer, compared to control kits that were left on the heating pad. Artificial AGS failed to amplify these effects of maternal odours. Maternal odours (with or without concurrent AGS) failed to augment neuronal Fos-IR in medial amygdaloid and hypothalamic regions that are activated in adult ferrets by social odours. In neonatal ferrets of both sexes, as in adults, socially relevant odours are detected by the main olfactory epithelium and initially processed by the MOB and the anterior-cortical amygdala. In neonates, unlike adults, medial amygdaloid and hypothalamic neurones either do not respond to these inputs or respond in a manner that fails to induce Fos expression.
BACKGROUND/PURPOSE: Postoperative cholangitis is one of the most common complications after bile duct reconstruction. The pathogenesis and early consequences of ascending cholangitis still are unidentified. METHODS: Male Sprague-Dawley rats were divided into 5 treatment groups: control (n = 4), blood sampling and liver biopsy only; group I, [BDL/Eschericha coli; n = 6], ligation of common bile duct (BDL) for a week, followed by Roux-en-Y choledochojejunostomy (RYCJ) and injection of E coli (ATCC 25922) into Roux limb after 24 hours; group II, [BDL/NS; n = 5], same procedures as in group I, with injection of normal saline (NS) into Roux limb; group III, [SBDL/E coli; n = 6], primary RYCJ was constructed 1 week after sham ligation of common bile duct (SBDL) followed by the same treatment as group I; Group IV, [SBDL/N.S; n = 6], same procedures as in group III, but injecting NS into Roux limb. All animals were killed after 24 hours of treatment. Blood was sampled for culture and serum cytokine levels. The liver was harvested for quantitative bacterial culture, as well as for MCP-1, interleukin (IL)-8 (CINC in the rat) and transforming growth factor beta1 mRNA expression by reverse transcriptase polymerase chain reaction (RT-PCR) and for immunohistochemistry. The choledochojejunostomy was resected for culture. Serum cytokine levels were detected by ELISA kits. RESULTS: A significant increase of E coli ATCC 25922, occurred in the livers of group I rats, compared with group IV (P =.037). MCP-1 expression increased in all groups, compared with control (P =.000). The IL-8 mRNA expression was significantly higher in group I than in control (P =.021). The expression of TGF-beta1 mRNA was similar among the groups (P =.361), consistent with the immunohistochemistry results. The serum MCP-1 and IL-8 levels were higher in the 4 groups than in the control (P =.000) and were significantly higher in group I than in group IV (P =.001). CONCLUSIONS: This study found that a significant colonization of E coli of the same strain was present in the cholestatic rat liver injected into the Roux limb, which was associated with a higher expression of liver MCP-1 and IL-8 mRNA, a significant increase of serum MCP-1 and IL-8, and a more evident inflammatory cell infiltration into the porta hepatis.
Oral submucous fibrosis is a collagen disorder affecting the submucosal layer and often severely limiting mouth opening. Previous surgical treatments have been disappointing. This article introduces a new surgical approach: reconstructing the bilateral buccal mucosa with two small radial forearm flaps. The surgical method includes the complete surgical release of fibrotic buccal mucosa and, if necessary, a bilateral coronoidectomy and temporalis muscle myotomy. From 1997 to 1999, 15 patients with moderate-to-severe trismus received reconstructive surgery, for a total of 30 small radial forearm flaps after surgical release. The flap size was between 1.5 x 5 and 2.5 x 7 cm. All donor sites were directly closed, and all flaps survived completely, except for one with partial necrosis. Six flaps required minor revisions because of size redundancy. Two patients developed buccal cancer in the area of reconstruction. At an average of 12 months' follow-up, the inter-incisal distance averaged 33 mm, an increase of 17 mm compared with the preoperative value. The donor-site morbidity was minimal, except in one heavy smoker who developed dry gangrene of his fingertips. The use of two small free forearm flaps for buccal mucosa reconstruction allows more radical release of fibrotic tissue. Coronoidectomy and temporal muscle myotomy further contribute to the effect of trismus release. The combined effects of this approach have consistently given good results. An aggressive approach toward surgical treatment of this precancerous lesion also facilitates the detection of cancer at an early stage.
Reconstruction of segmental mandibular defects resulting from trauma, infection, or tumor resection still remains difficult. Although cosmetic improvement was seen in patients who had immediate reconstruction of the mandibular continuity, normal mastication and deglutition could not be achieved by conventional removable dentures. Since 1988, the treatment protocol has been modified to use endosseous root-form implants to support dental prostheses instead of the conventional removable prostheses in these patients. There are 2 types of prostheses that can be constructed over dental implants: (1) a removable implant overdenture and (2) a fixed detachable prosthesis. Although the latter better meets in patients' psychological needs, it may present problems such as phonetic discrepancies, food impaction, difficult home care, and poor esthetics if the patient has a high lip line. In addition, it is not easy to fabricate accurately in the laboratory. To overcome these problems, a case is presented to illustrate the use of another fixed-type prosthesis, a double-coping technique, for fabricating dentures so that any discrepancy between the inner and outer copings can be filled by cement. The technique not only improves the shortcomings of fixed detachable prostheses but also satisfactorily meets patients' desire for normal mastication and deglutition. Follow-up after 4 years showed no significant changes around the implants by clinical and radiographic examinations.
The fibula osteoseptocutaneous free flap is ideal for reconstruction of composite mandible defects. Osseointegration is possible and advantageous. Primary osseointegration of dental implants is a safe and reliable procedure in selected groups of patients, promoting early total oral rehabilitation with restoration of both function and cosmesis. Further studies are necessary to assess the specific indications for osseointegration teeth in patients with malignant tumors and in those patients who have received radiation therapy.
Gonadectomized male and female ferrets (Mustela putorius furo) given either testosterone propionate (TP) or oil vehicle preferred to investigate the side of a test cage previously soiled by a breeding male or female as opposed to a clean side. Male and female ferrets receiving TP showed more urogenital wiping than oil-treated animals in either side of the test cage. In a 2nd experiment, ferrets treated sequentially with TP, oil, and estradiol benzoate (EB) were given simultaneous access to sides of a test cage previously soiled by either a breeding female or male. Either EB or TP treatment of females and TP treatment of males facilitated the investigation of odors of opposite-sex ferrets. Females given TP and males given either TP or EB showed increased urogenital wiping in both sides of the test cage. Sex steroids modulate scent investigation and marking in adult ferrets in a sexually differentiated fashion.
The effect of diets prepared from whorl tissue of resistant and susceptible corn genotypes, Zea mays L., on the larval growth, development, and physiology of fall armyworm, Spodoptera frugiperda (J. E. Smith), was analyzed. Larvae reared on an optimized artificial diet had a higher growth rate and developed faster than those reared on lyophilized whorl tissue from resistant and susceptible genotypes. Larvae reared on the resistant material were smaller and had a longer developmental period. Larvae reared on yellow-green and green whorl sections from resistant plants were significantly smaller than those reared on the same sections of susceptible plants. There was no significant difference in weight when larvae were reared on the yellow whorl regions from either resistant or susceptible lines. Physiological indices were determined for larvae fed resistant and susceptible lyophilized and fresh whorl material. Larvae fed resistant lyophilized material had significantly lower growth rate (GW) and efficiency of conversion of ingested food to body substance (ECI) than those reared on artificial diet or susceptible material. However, there were no significant differences in consumption index (CI), approximate digestibility (AD) and efficiency of conversion of digested food to body substance (ECD) between larvae reared on lyophilized tissue from resistant and susceptible genotypes. Larvae reared on fresh yellow-green whorl sections from resistant plants had significantly lower GW, ECI, and ECD than those reared on susceptible material. In contrast, no significant differences in any of the estimated food consumption and utilization indices were observed between larvae reared on fresh yellow whorl sections from resistant or susceptible plants. These results suggest that some components of whorls from resistant plants, especially the yellow-green region, inhibit food utilization in fall armyworm larvae.
The leukocyte NADPH oxidase of neutrophils is a membrane-bound enzyme that catalyzes the production of O2- from oxygen using NADPH as the electron donor. Dormant in resting neutrophils, the enzyme acquires catalytic activity when the cells are exposed to appropriate stimuli. During activation, the cytosolic oxidase components p47phox and p67phox migrate to the plasma membrane, where they associate with cytochrome b558, a membrane-integrated flavohemoprotein, to assemble the active oxidase. In whole cells and under certain circumstances in the cell-free system, the phosphorylation of p47phox mediates the activation process. It has been proposed that conformational changes in the protein structure of cytosolic factor p47phox may be an important part of the activation mechanism. The total protein steady-state intrinsic fluorescence (an emission maximum of 338 nm) exhibited by the tryptophan residues of p47phox was substantially decreased, reflecting on the conformational change that occurs when p47phox was phosphorylated with protein kinase C. We show here that the phosphorylation of p47phox by protein kinase A or mitogen-activated protein kinase, however, had little effect on the intrinsic fluorescence of p47phox. In addition, the present experiments indicate that in the mutant p47phoxS379A, only the single S-->A mutation appears to be a major importance for the function of p47phox, which is able to undergo the change in conformation that takes place when p47phox is phosphorylated by protein kinase C.
BACKGROUND: High-dose therapy with peripheral blood stem cell (PBSC) transplantation has been used increasingly for chemosensitive malignancies. The conventional procedures for collection and freezing of PBSCs are time-consuming and expensive. The optimal conditions for priming, collection and freezing of PBSCs have yet to be simplified. METHODS: Simplified procedures for mobilization, collection and freezing were developed to provide PBSC transplantation. Twenty-two cancer patients were given intensive chemotherapy with a variety of regimens using granulocyte-colony stimulating factor (G-CSF, filgrastim) 300 micrograms/d subcutaneously to mobilize PBSCs. A rapidly rebounding white blood cell (WBC) count from nadir was used to predict the time of peak PBSC release and plan leukapheresis. Leukapheresis was performed, when the WBC count was greater than 1.0 x 10(9)/l. RESULTS: Leukapheresis was performed in all 22 patients on day 10 to 14 after completing intensive chemotherapy. G-CSF to mobilize PBSCs was administered for a median of 10 days (range, 7-12 days). Twenty-one of 22 patients achieved the target yield of greater than 2 x 10(6) CD34+ cells/kg of body weight (BW). This was achieved in a median of two harvests (range, 2-4), with a median processed blood volume of 10.2 l/apheresis. A median of 6.4 x 10(8) mononuclear cells/kg BW and 5.2 x 10(6) CD34+ cells/kg BW for each patient were obtained. After high-dose cancer chemotherapy and PBSC transplantation, rapid and sustained hematopoietic engraftment occurred in all but one patient who had an inadequate number of CD34+ cells. In patients with an adequate target yield of CD34+ cells, the median times to achieve an absolute neutrophil count of greater than 0.5 x 10(9)/l and a platelet count of greater than 20 x 10(9)/l were nine days (range, 7-12 days) and 12 days (range, 8-14 days), respectively. CONCLUSIONS: Adequate PBSCs can be achieved within a median of two aphereses in most eligible cancer patients. Apheresis should be performed on day 10 to 14 after completing intensive chemotherapy, followed by G-CSF 300 micrograms/d. This simple and effective approach makes PBSC transplantation more practicable for a wider range of malignant diseases.
Excessive thickness and mobility of the skin flap and lack of a vestibular sulcus in composite vascularized bone grafts for mandibular reconstruction limit the usefulness of endosteal implants to support a prosthetic device. Palatal mucosal grafts and a simple acrylic stent are an excellent means to overcome these problems. The technique is presented in this paper.
Mandibular tumors such as ameloblastoma or fibrous dysplasia frequently follow a relentless course despite the fact that they are pathologically benign. Patients suffered from multiple recurrences and repeated surgery, and might still lose their masticatory function. To solve the above problems, a new combined approach--segmental mandibulectomy, free fibular flap reconstruction and primary osseointegration--was applied to three cases of aggressive mandibular tumors. The pathology spectrum included an enormous ameloblastoma, a fibrous dysplasia and a multiple recurrent ameloblastoma. Fixed partial prosthesis were loaded 6 months after the procedure. There were no detectable recurrence after 30 months' follow-up. The patients regained their facial contour, dental occlusion and masticatory function in a relatively short period of time. Segmental mandibulectomy lessens the likelihood of recurrence, free fibular flap transfer restores the dental articulation function and facial contour, and immediate osseointegration has further enhanced the masticatory function. This combined approach thus improves the patients' satisfaction and ensure their social interactions. It is justified for some selected aggressive mandibular tumors.
A carnivore, the ferret possesses a vomeronasal organ--accessory olfactory bulb (VNO-AOB) projection to the hypothalamus; however, little is known about its function. Pheromones in soiled bedding from estrous female ferrets or an artificial peppermint odor significantly augmented nuclear Fos protein immunoreactivity (Fos-IR), a marker of neural activation, in several main olfactory bulb (MOB) sites but not in the AOB of gonadectomized male and females. Testosterone propionate (TP) significantly augmented the MOB's neuronal Fos responses to estrous females' pheromones, but not to peppermint. Estrous odors, but not peppermint, also augmented neuronal Fos-IR in the medial preoptic area (mPOA) of female, but not male, subjects. Pheromones in soiled bedding from breeding male ferrets significantly augmented neuronal Fos-IR in the MOB and in the medial amygdala of gonadectomized, TP-treated male and female subjects. Again, male pheromones failed to influence neuronal Fos-IR in the AOB of either sex, and only females showed significant increases in neuronal Fos-IR in the lateral aspect of the ventromedial nucleus and mPOA. These results point to an essential role among higher mammals of the main olfactory epithelium-MOB projection to the hypothalamus in detecting and processing pheromones. Gonadectomized ferrets showed significant increases in sniffing behavior when placed on either female or male bedding. This occurred regardless of whether they had received TP or oil vehicle, suggesting that testosterone's facilitation of neuronal Fos responses to estrous females' odors in the MOB of both sexes cannot be attributed to increased scent gathering. Androgen receptor-IR was present in the MOB granule cell layer of male and female ferrets, raising the possibility that testosterone acts directly on these cells to augment their responsiveness to pheromones.
Twelve patients with segmental mandibular defects were reconstructed with fibula osteoseptocutaneous flaps and simultaneous placement of osseointegrated implants. Decision to perform this procedure was based on the facts that all patients had benign diseases, did not require postoperative radiotherapy, were in good general and oral conditions, and were psychologically motivated. A total of 34 fixtures was inserted in the first stage. Eight patients underwent second stage surgery, which consisted of connection of the implant abutments to the fixtures and the use of palatal mucosal grafts around the implants. Final dental prostheses were fixed 1 month later in seven patients, at this time. All flaps survived after surgery, and no implant failure was observed after a mean follow-up period of 25 months. Only one fixture was not used during the subsequent stage and was left as a sleeper. Fixed dental prostheses were used in five patients and removable overlay prostheses in the other two. Chewing function was recovered between 4 and 6 weeks after the start using the definitive dental prosthesis. In contrast to previous results, we conclude that excellent results can be achieved when this combined procedure is used in carefully selected patients. In addition, it is confirmed that the fibula osteoseptocutaneous flap is a versatile, reliable composite tissue that facilitates primary placement of osseointegrated dental implants during mandible reconstruction, thus allowing full oral rehabilitation in a shorter period of time.
The cytotoxic effect of sequence and dose of Tomudex (TX) and 5-fluorouracil (FUra) on an HCT-8 colon carcinoma cell line using a clonogenic assay was evaluated. Synergistic cell kill was obtained with 24 h of exposure to TX followed by 4 h of exposure to FUra. Marginal synergy was obtained with the same sequence but with a 5-day exposure to FUra. The reverse sequence, FUra (either 4 h or 5 days), followed by TX (24 h), resulted in less-than-additive cell kill. The synergistic effect was not due to augmented inhibition of thymidylate synthase, as determined by the measurement of thymidylate synthase activity by tritium release from [5-3H]2'-deoxyuridine. Surprisingly, an increase in intracellular levels of phosphoribosylpyrophosphate was observed after 24 h of exposure to TX, suggesting the possibility of an indirect effect of TX and/or its polyglutamates on purine biosynthesis. Moreover, we observed an increased formation of FUra nucleotides in the cells preexposed to TX, likely due to the increased intracellular levels of phosphoribosylpyrophosphate, that as a consequence led to an enhanced incorporation of FUra into RNA and increased cell killing.
Ganglion cysts and synovial cysts are lesions rarely associated with the temporomandibular joint. Ganglion cysts arise from myxoid degeneration of the connective tissue of the joint capsule, are filled with viscoid fluid or gelatinous material, and have a fibrous lining. Synovial cysts also contain gelatinous fluid and are lined with cuboidal to somewhat flattened cells consistent with a synovial origin. One case of a ganglion cyst and one case of a synovial cyst of the temporomandibular joint are presented, and their differential diagnosis and management are discussed.
Insertion of osseointegrated dental implants several months after mandibular reconstruction using vascularized composite bone grafts has proved to be a successful method to achieve mastication and complete oral rehabilitation. Theoretically with primary placement of implants into the new mandible a better access to the bone is achieved, interdental relationships are easier to determine, and oral rehabilitation can be attained in a shorter period of time. Previous results describing this approach, however, are inconclusive and controversial. This review describes our experience with primary insertion of dental implants into fibular flaps used for mandibular reconstruction during ablative surgery. Adequate selection of patients for this combined procedure depends mainly on the pathological nature of the mandible and perioperative radiotherapy. Preoperative determination of soft-tissue and bone requirements, number of osteotomies, rigid fixation method, and familiarity with the use of osseointegrated implants are important factors that must be considered for adequate surgical planning and to achieve good results.