Maxillary single-jaw surgery combining Le Fort I and modified horseshoe osteotomies for the correction of maxillary excess.

A modified technique of horseshoe osteotomy combined with Le Fort I osteotomy for superior and posterior repositioning of the maxilla is presented. Eight patients with maxillary excess associated with retrogenia or microgenia were treated with this technique in combination with genioplasty. The maxillary segment was repositioned a maximum of 5.0mm posteriorly and 7.0mm superiorly at point A. The mandible autorotated anterosuperiorly to achieve sound occlusion. Point B moved 2.0-10.0mm anteriorly and 5.0-10.0mm superiorly. The pogonion moved 7.0-17.0mm anteriorly in combination with genioplasty. All patients obtained sound occlusion and a good profile after the operation. Almost no skeletal relapse was observed during 1 year of postoperative follow-up. Patients with long faces with maxillary excess and retrogenia often have small, unstable condyles. In these cases, because surgical intervention to the ramus can result in postoperative progressive condylar resorption, maxillary single-jaw surgery with a horseshoe osteotomy, thereby avoiding ramus intervention, is a less invasive option.

An osteonecrosis model induced by oral bisphosphonate in ovariectomised rats.

OBJECTIVE: To develop a model of osteonecrosis using oral bisphosphonate in ovariectomy-induced osteoporotic rats. MATERIALS AND METHODS: Thirty-six rats were subjected to ovariectomy or sham surgery. After 8 weeks, rats received oral alendronate (1.0 mg kg(-1) ) or saline once weekly for 4 weeks; then, serum C-telopeptide cross-linked collagen type I levels were measured to evaluate bone metabolism. Twelve rats from each group were injected with either lipopolysaccharide or saline into the bone marrow of the mandibles and femurs, and the areas of osteonecrosis were evaluated by histomorphometry. RESULTS: Serum C-telopeptide cross-linked collagen type I levels were significantly increased in the ovariectomy group (105.1 ± 2.1 ng ml(-1) ) compared with the sham group (78.9 ± 12.5 ng ml(-1) ); they were significantly reduced following oral alendronate administration in the ovariectomy group (91.0 ± 4.4 ng ml(-1) ). Following alendronate and lipopolysaccharide administration, extensive osteonecrosis was observed in the mandibles and femurs of ovariectomy (0.45 ± 0.08 mm(2) , 1.69 ± 0.72 mm(2) , respectively) and sham (1.12 ± 0.45 mm(2) , 1.84 ± 0.66 mm(2) , respectively) groups. Significantly wider osteonecrosis occurred in the mandibles of sham-operated rats than ovariectomy rats following alendronate or lipopolysaccharide treatment. CONCLUSIONS: We successfully developed a model of osteonecrosis in ovariectomised rats following oral bisphosphonate administration.

Intraoperative detection of viable bone with fluorescence imaging using Visually Enhanced Lesion Scope in patients with bisphosphonate-related osteonecrosis of the jaw: clinical and pathological evaluation.

UNLABELLED: There is no standard surgical protocol of bisphosphonate-related osteonecrosis of the jaws (BRONJ), because of the impossibility to visualize this feature intraoperatively. The aim of this study was to introduce how to provide preoperative labeling of the viable bone with minocycline bone fluorescence technique (MBFT) by using VELscope® and investigate histopathologically. INTRODUCTION: The American Association of Oral and Maxillofacial Surgeons (AAOMS) and the Japanese Society of Oral and Maxillofacial Surgeons (JSOMS) now recommend a more conservative treatment strategy. There is no standard surgical protocol of bisphosphonate-related osteonecrosis of the jaws (BRONJ) because of the impossibility to visualize this feature intraoperatively. The aim of this study was to introduce a mechanism providing preoperative labeling of a viable bone using minocycline bone fluorescence technique (MBFT) with VELscope® and to histopathologically investigate. METHODS: This report describes a surgical technique used in six patients with BRONJ who underwent jawbone resection under minocycline bone fluorescence imaging using VELscope®. Subsequently, we investigated and compared the clinical findings using VELscope® and histopathological findings. RESULTS: Histopathological examinations showed that the non-fluorescent moiety was consistent with the BRONJ lesions. CONCLUSIONS: The surgical treatments that were exactly performed using MBFT with VELscope® offered successful management of BRONJ. This bone fluorescence helped to define the margins of resection, thus improving surgical therapy for extended osteonecrosis.

Lipopolysaccharide aggravates bisphosphonate-induced osteonecrosis in rats.

The pathogenesis of bisphosphonate-related osteonecrosis of the jaw (BRONJ) is highly controversial. We have previously reported the development of osteonecrosis by periodontal pathogenic stimulation in the jaw and femur of rats treated with bisphosphonate. Since the major toxicity factor of Gram-negative bacteria is lipopolysaccharide (LPS), the present study aimed to evaluate the relationship between osteonecrosis and LPS in a rat model of BRON-like lesions. Seventeen male rats were injected subcutaneously with zoledronic acid weekly for 4 weeks and divided into three groups: LPS (LPS administered into the bone marrow of the mandible and femur) and LPS plus polymyxin B (PMB) and saline groups (given neutralized LPS with PMB or saline, respectively, using the same protocol). At 4 weeks after the procedure, harvested specimens were analyzed using histomorphology (n=5 from each group) and histochemistry (n=1 each from LPS and LPS plus PMB groups). There was a significantly wider area of osteonecrosis in the LPS group as compared to the saline and LPS plus PMB groups in both the mandible (P=0.030 and P=0.009, respectively) and femur (P=0.002 and P=0.020, respectively). Our results indicate that LPS stimulation is deeply involved in the development and promotion of BRON.

Bacterial promotion of bisphosphonate-induced osteonecrosis in Wistar rats.

Clinically, bisphosphonate-related osteonecrosis (BRON) only occurs in the jaw (BRONJ). We aimed to determine differences between the jaw and other bones, as well as the relationship between periodontal pathogens and BRON. Twelve male Wistar rats were divided into two groups: group Z (n=6) were subcutaneously injected with zoledronic acid weekly for 4 weeks; group C (n=6) were injected with saline. One week after the final injection, rats in both groups were divided into three subgroups: Aa subgroup was injected with freeze-dried Aggregatibacter actinomycetemcomitans into bone marrow of the mandibles and femurs, while CFA and saline subgroups were injected with complete Freund's adjuvant (CFA) or saline using the same protocol. Four weeks after those injections, the rats were euthanized. Areas of osteonecrosis were measured histologically. Statistically, rats in group Z showed significantly wider osteonecrosis areas in both mandibles and femurs with each type of local injection than rats in group C. In group Z, mandibles and femurs stimulated with A. actinomycetemcomitans or CFA had significantly wider osteonecrosis areas than those stimulated with saline. We have developed a rat model with BRONJ-like lesions. Our results showed BRON to develop not only in the jaw but also in other types of bone following an inflammatory stimulus.

Novel gene-transferring scaffolds having a cell adhesion molecule-DNA-apatite nanocomposite surface.

A low efficiency has long been the most critical problem of conventional gene-transferring systems using calcium phosphates, and this was successfully improved on by using a laminin-DNA-apatite composite (LD-Ap) layer. The gene-transferring efficiency of the LD-Ap surface was 1-2 orders of magnitude higher than that of a DNA-calcium phosphate composite surface. This is because laminin enhances cell adhesion and spreading, and this provides regions of high DNA concentration between a cell and the LD-Ap surface. The efficiency of gene transfer of the LD-Ap surface was equivalent to, or even higher than that mediated using a commercial lipid-based transfection reagent applied using the manufacturer's recommended optimum conditions. In addition, the gene-transferring efficiency of our system could be controlled by changing the laminin and DNA content in the LD-Ap layer. Moreover, our system is composed of highly safe reagents: apatite, DNA and laminin, all of which are present in the human body. Hence, the LD-Ap surface, which enhances cell attachment on its surface, and mediates a safe, highly efficient and controllable gene transfer, is highly applicable to tissue engineering and gene therapy applications.

Radioresponsive tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) gene therapy for malignant brain tumors.

Patients with malignant gliomas have a very poor prognosis. To explore a novel and more effective approach for the treatment of malignant gliomas, a strategy that combined tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) gene therapy and radiation treatment (RT) was designed in this study. Plasmid pE4-GFP was constructed by including the radioinducible early growth response gene 1 (Egr-1) promoter, and it yielded the best response with fractionated RT. Plasmid pE4-TRAIL was constructed by including the Egr-1 promoter and evaluated using U251 and U87 glioma cells. In the assay of apoptosis and killing activities, pE4-TRAIL exhibited radioresponse. pE4-TRAIL combined with RT is capable of inducing cell death synergistically. The expression of TRAIL death receptors was evaluated; which may be influenced by RT. Glioma cells with wild-type p53 showed upregulated expression of death receptors, and more synergistic effects on killing activities are expected. pE4-TRAIL was transfected into the subcutaneous U251 glioma cells in nude mice by the in vivo electroporation method. In the mice treated with pE4-TRAIL and RT, apoptotic cells were detected in pathological sections, and a significant difference of tumor volumes was observed when compared with the other groups (P<0.001). Our results indicate that radioresponsive gene therapy may have great potential as a novel therapy because this therapeutic system can be spatially or temporally controlled by exogenous RT and provides specificity and safety.

Expression of enzymes and oncogene induced after radiotherapy and/or chemotherapy in patients with brain tumors.

The relationship between the degree of the expression of Cu/Zn SOD, GST-pi and bcl-2 in the initial and recurrent tumor tissue after radiotherapy and/or chemotherapy and the cellular heterogeneity obtained from DNA content by image cytometry was investigated. Subjects were 7 patients who had glial tumors which were surgically removed at onset and removed a second time at recurrence. Radiotherapy and chemotherapy were also administered after initial resection. Immunoreactivity for copper/zinc super oxide dismutase (Cu/Zn SOD), GST (glutathione-S-transferase)-pi, and bcl-2 were evaluated from routinely prepared tissue blocks. Tumors were classified into two groups by cytometric analysis of DNA ploidy in the G2M cell cycle phase. One tumor group consisted of single clonal cells in both the initial and recurrent tumors and the other group consisted of tumors with polyclonal cells in the initial and recurrent tumor. In this study, one patient (case 3) with single clonal cell glioblastoma at recurrence did not show high Cu/Zn SOD activity after radiotherapy and chemotherapy but showed a short survival time after recurrence. In three patients (cases 1, 2, 3) with single clonal-cell glioblastoma, the recurrent tumor cells showed high GST-pi immunoreactivity and survival time was short after recurrence. Tumor cells in two patients (cases 5, 7) with single clonal cell anaplastic glioma at recurrence, showed high GST-pi immunoreactivity and had a short survival time after recurrence. In three single clonal glioblastomas (cases 1, 2, 3), the recurrent tumor showed the increased bcl-2 immunoreactivity and showed a short survival time after recurrence. In two patients (case 5, 7) with single clonal cell anaplastic glioma at recurrence, tumor cells showed a high bcl-2 immunoreactivity and these patients showed a short survival time after recurrence. Although the number of subjects is very small, our study shows that the immunoreactivity of bcl-2 and GST-pi in malignant gliomas may be very important factors in radio- and chemosensitivity, and shows that GST-pi is induced by radiation and anti-cancer drugs.

Brain metastasis of epithelioid sarcoma--case report.

A 20-year-old-female first presented with an epithelioid sarcoma of the right thumb, and the right thumb was amputated. Five years later, a metastasis was found in the right lower lung and a partial lobectomy was performed. Three years later, computed tomography showed a metastatic brain tumor in the left frontal lobe, which was removed surgically. Adjuvant radiotherapy and chemotherapy were given after all operations. Histological examination showed all resected tumors were epithelioid sarcoma. She has maintained a good activity of daily living level as an outpatient for 2 years, although subcutaneous metastases and bronchial lymph node metastases have been observed. Such intensive treatment of slowly growing tumors often prolongs survival time, even in patients with multiple metastases.

Symptomatic arachnoid cyst of the left frontal convexity presenting with memory disturbance--case report.

A 48-year-old female presented with vertiginous feeling and behavior disturbance. Computed tomography showed an arachnoid cyst on the left cerebral convexity. Single photon emission computed tomography revealed decreased cerebral blood flow (CBF) in the left frontal lobe. The Wechsler Memory Scale-Revised test demonstrated memory dysfunction. The arachnoid cyst was partially removed. Disturbances in CBF and behavior disappeared postoperatively. Local ischemia induced by compression due to arachnoid cyst may cause memory dysfunction and behavior disturbance. Neuropsychometric examination is useful for the evaluation of such symptoms.

Shunt tube problems due to placement of valves on the chest wall--three case reports.

Programmable valves are often used for ventriculoperitoneal (VP) shunts with the shunt valve positioned on the chest wall. Three cases of shunt problems occurred due to placement of the valve on the chest wall. A 43-year-old male was treated with a VP shunt, and suffered shunt malfunction due to dislocation of the ventricular tube. A 21-year-old male was treated with a VP shunt, and suffered shunt malfunction due to disconnection of the shunt tube. A 4-day-old female neonate was treated with a VP shunt, and suffered migration of the shunt valve. The shunt system has two anchor sites on the head and chest wall, with the neck between the two anchor sites. High tension is sometimes caused in the shunt tube between the two points due to movement of the neck or growth, and may induce such dislocation and disconnection of the shunt tube. We recommend a longer shunt tube in such cases.

Complications associated with intraarterial administration of papaverine for vasospasm following subarachnoid hemorrhage--two case reports.

Complications associated with intraarterial papaverine infusion occurred in two patients treated for vasospasm due to subarachnoid hemorrhage (SAH). A 42-year-old male with an anterior communicating artery aneurysm underwent craniotomy and aneurysm clipping. Five days after the SAH occurred, angiography demonstrated moderate vasospasm in spite of hypervolemic-hypertensive therapy. During papaverine infusion into the carotid artery, he suffered loss of consciousness due to a seizure for a few minutes. A 61-year-old female with a right internal carotid-posterior communicating artery aneurysm underwent clipping. Six days after the SAH occurred, angiography demonstrated severe vasospasm in spite of hypervolemic-hypertensive therapy. Angiography performed immediately after papaverine infusion into the carotid artery revealed exacerbation of the vasospasm. Finally she suffered cerebral infarction and died. Complications of intraarterial papaverine infusion are potentially dangerous. We recommend trial administration of papaverine with angiography and neurological examination before full dose infusion to avoid complications.

[Recent progress in intravascular neurosurgery for the treatment of cerebrovascular disease].

With the recent advances in the devices and techniques in intravascular neurosurgery such as microcatheters or a digital subtraction angiography, intravascular neurosurgery plays an important role for the treatment of cerebrovascular disease. We describe here, a recent progress in intravascular neurosurgery for the treatment of cerebrovascular disease. As a treatment of cerebrovascular disease, we discuss the treatment of cerebral aneurysm using Guglielmi detachable coils (GDC), and the treatment of ischemic cerebrovascular disease such as the thrombolytic therapy for the acute embolic occlusion of the cerebral artery, and a percutaneous transluminal angioplasty (PTA) or a stenting for the stenotic lesion of the cerebral arteries. Embolization of the cerebral aneurysm using GDC is less invasive method compare to the standard neurosurgical clipping of aneurysm. So, recently it becomes one of standard methods of the treatment of cerebral aneurysm. Thrombolytic therapy, PTA and stenting also become an important treatment for the ischemic cerebrovascular disease.

Recycled addition of CD4+ T cell-rich population for induction of human autologous cytotoxic T lymphocytes: A practically efficient method.

When CD4(+) T cell-rich population appears in theinitial trial in induction cultures of humanautologous cytotoxic T lymphocytes (CTL), the cultureresults frequently in no or weak killing activity andtherefore usually be discarded as an ;unsuccessful'CTL induction culture. However, addition of theinitial CD4(+) T cell-rich population enabledefficient induction of the autologous CTL in theensuing trials. The CTL thus generated exhibitedstronger killing activities against autologous braintumor cells and ovarian tumor cells than previouslyobserved. This simple recycling of the primed butinert CD4(+) T cell-rich population for CTLinduction will promote clinical practice of adoptiveimmunotherapy of human tumors with autologous CTL.

Reduction of end-stage malignant glioma by injection with autologous cytotoxic T lymphocytes.

Autologous cytotoxic T lymphocytes (CTL) against primary-cultured malignant gliomas were generated from peripheral blood mononuclear cells in vitro in 4 patients. Activities of the CTL were highly specific to the corresponding autologous glioma and were inhibited, in one patient, with antibodies against CD3, CD8 and MHC-class I molecules. When the CTL were injected 3 times into the primary-tumor-resected cavity via an Ommaya tube, reduction of the recurrent tumors with magnetic resonance imaging (MRI)-measured volumes exceeding 45 cm3 was observed in 3 patients. In a patient with glioblastoma multiforme (GBM), the tumor volume (estimated, 130 cm3) was rapidly reduced to 1/3, although re-recurrence of the tumor followed 40 days later. A slight but distinct rapid reduction of the tumor volume was observed in another GBM patient and in an anaplastic astrocytoma patient; essentially no change was observed in a further GBM patient. These results suggest that adoptive immunotherapy with autologous CTL will be clinically effective against end-stage malignant gliomas.

[Management of putaminal hemorrhage in patients with chronic renal failure].

The treatments of putaminal hemorrhages (PH) were evaluated in 14 patients (15 hematomas) with chronic renal failure (CRF). We compared the data of our series with the data of co-operative study (1990) on PH. With regard to consciousness level (Neurological Grading, NG) and hematoma volume, significantly more serious cases were observed in PH with CRF than in PH of the co-operative study. In PH with CRF, mortality (40%) was significantly higher than that in PH of the co-operative study. However, the mortality rate was 0%, 0%, 20%, and 100% in NG1, 2, 3, and over 4b. The mortality rate was 0% in non-surgically treated cases with 0 to 30 ml of hematoma volume, and 0% in surgically treated cases with 10 to 50 ml of hematoma volume. These mortality rates were equal to those of the co-operative study with the same NG, and equal to those of the co-operative study with the same hematoma volume. With respect to functional prognosis, "good" (ADL1 and 2) resulted in 67% of non-surgically treated cases with NG1 to 2, and in 33% of surgically treated cases with NG3 to 4a. "Good" resulted in 33% of non-surgically treated cases with 0 to 30 ml of hematoma volume, and in 40% of surgically treated cases with 10 to 50 ml of hematoma volume. These morbidity rates were equal to those of the co-operative study with the same NG, and equal to those of the co-operative study with the same hematoma volume. Therefore, the high mortality in PH with CRF was suspected to be due to the fact that, in our study, there was a higher distribution of serious cases. These findings indicate that protection against enlargement of hematomas in the acute phase may bring about improvement of prognosis in PH with CRF.

Expansion of human autologous cytotoxic T lymphocytes on fixed target tumor cells.

Human tumor specific cytotoxic T lymphocytes (CTL) were expanded on formalin-fixed autologous target tumor cells derived from glioblastoma multiforme. Growth response of the CTL restimulated with the fixed target cells was larger than those with live target cells. The results suggest that formalin-fixed tumor cells will be stable sources of tumor antigen for efficient autologous CTL expansion and be useful for adoptive immunotherapy of tumors.

[Subependymal tumor with metaplastic bone formation: a case report].

A 26-year-old woman was admitted to our hospital because of headache. CT scan and MRI showed a right subependymal nodule and a left ventricular tumor, neither of which had any enhancement nor were they stained in angiography. Although no skin abnormality was detected, the patient was suspected of tuberous sclerosis. The diagnosis was made because of the subependymal nodule on CT scan and MRI. On June 29, 1995, total removal of a left ventricular tumor was performed by a transcortical approach. Histological sections of this tumor consisted of astrocytic and meningothelial components, containing metaplastic bone formation. Histological diagnosis was dysplastic subependymal tumor. Postoperative course was uneventful. Regrowth of the tumor has not been observed as of now. This case was suspected to involve factors of tuberous sclerosis from a subependymal nodule. However, the ventricular tumor was not diagnosed as a subependymal giant cell astrocytoma.