Characteristics of flexed knee gait and functional outcome of a patient who underwent knee reconstruction with a hingeless prosthesis for bone tumor resection: a case report with gait analysis and comparison with healthy subjects.

We report on a patient after knee reconstruction for osteosarcoma in the distal femur using a hingeless prosthesis K-MAX KNEE system K-5 who walked without ipsilateral knee extension in the latter half of the stance phase (flexed knee gait). We evaluated the patient using three-dimensional gait analysis and isokinetic knee strength measurement, and compared the patient with five healthy subjects. The Musculoskeletal Tumor Society (MSTS) score was also used for evaluation. The patient kept his operated knee flexed during mid stance. The maximal ankle plantarflexion internal moment was lower on the ipsilateral side than on the contralateral side, and lower than in the healthy subjects. The negative ankle power during the stance phase was generally stronger on the ipsilateral side than on the contralateral side, and also in the healthy subjects. Unusual contralateral hip flexion occurred after the initial contact, indicating increased joint load on the ipsilateral ankle and the contralateral hip. The ratios of the peak knee extension/flexion torque were 0.7 on the ipsilateral side, 1.9 on the contralateral side, and 1.7 in the healthy subjects. The MSTS score of the patient was 23/30 (76.6%). Flexed knee gait might account for the reduction of ipsilateral hip flexion and ankle plantarflexion moment during the late stance phase. These results suggest the importance of focusing more on the ipsilateral ankle joint and the contralateral hip joint to maintain the function of the entire limb joints of the patients with flexed knee gait.

Characteristics of flexed knee gait and functional outcome of a patient who underwent knee reconstruction with a hingeless prosthesis for bone tumor resection: a case report with gait analysis and comparison with healthy subjects.

We report on a patient after knee reconstruction for osteosarcoma in the distal femur using a hingeless prosthesis K-MAX KNEE system K-5 who walked without ipsilateral knee extension in the latter half of the stance phase (flexed knee gait). We evaluated the patient using three-dimensional gait analysis and isokinetic knee strength measurement, and compared the patient with five healthy subjects. The Musculoskeletal Tumor Society (MSTS) score was also used for evaluation. The patient kept his operated knee flexed during mid stance. The maximal ankle plantarflexion internal moment was lower on the ipsilateral side than on the contralateral side, and lower than in the healthy subjects. The negative ankle power during the stance phase was generally stronger on the ipsilateral side than on the contralateral side, and also in the healthy subjects. Unusual contralateral hip flexion occurred after the initial contact, indicating increased joint load on the ipsilateral ankle and the contralateral hip. The ratios of the peak knee extension/flexion torque were 0.7 on the ipsilateral side, 1.9 on the contralateral side, and 1.7 in the healthy subjects. The MSTS score of the patient was 23/30 (76.6%). Flexed knee gait might account for the reduction of ipsilateral hip flexion and ankle plantarflexion moment during the late stance phase. These results suggest the importance of focusing more on the ipsilateral ankle joint and the contralateral hip joint to maintain the function of the entire limb joints of the patients with flexed knee gait.

Impact of oesophagectomy on physical fitness and health-related quality of life in patients with oesophageal cancer.

Although several studies have reported the impact of oesophagectomy on health-related quality of life (HRQOL), none has objectively assessed its impact on physical fitness. This study aimed to evaluate the impact of oesophagectomy on physical fitness and HRQOL in patients with oesophageal cancer. In this prospective study, we investigated 30 consecutive patients with newly diagnosed resectable oesophageal cancer who were scheduled to receive either neoadjuvant chemotherapy followed by surgery or surgery alone. The primary end-points were change from baseline in two measures of physical fitness (knee-extensor muscle strength and 6-min walking distance) after oesophagectomy. The secondary end-point was change from baseline in HRQOL measured with the European Organization for the Research and Treatment of Cancer Quality of Life Core Questionnaire with 30 items (EORTC QLQ-C30). Physical fitness was significantly lower after oesophagectomy than before oesophagectomy (P < 0.001). With regard to HRQOL, there was a significant pre- to post-oesophagectomy change in most of the scales. In the multiple regression analysis, the change in 6-min walking distance was the only significant variable affecting the change in physical functional score on the EORTC QLQ-C30 (P = 0.032). In conclusion, oesophagectomy adversely affects physical fitness and HRQOL in patients with oesophageal cancer. Six-minute walking distance may be a good indicator of HRQOL shortly after oesophagectomy.

Inhibition by adenylyl cyclase-cAMP system of ET-1-induced HSP27 in osteoblasts.

We have previously reported that endothelin-1 (ET-1) stimulates heat shock protein (HSP) 27 induction in osteoblast-like MC3T3-E1 cells and that p38 mitogen-activated protein (MAP) kinase acts at a point downstream from protein kinase C (PKC) in HSP27 induction. In the present study, we investigated the effect of the adenylyl cyclase-cAMP system on ET-1-stimulated induction of HSP27 in MC3T3-E1 cells. Dibutyryl-cAMP (DBcAMP) dose dependently inhibited the HSP27 accumulation stimulated by ET-1. Forskolin and cholera toxin significantly suppressed the ET-1-stimulated accumulation of HSP27. However, dideoxyforskolin, a forskolin derivative that does not activate cAMP, failed to suppress the ET-1-induced HSP27 accumulation. Forskolin reduced the p38 MAP kinase phosphorylation induced by ET-1 or 12-O-tetradecanoylphorbol-13-acetate (TPA). PGE(1), an extracellular agonist that activates cAMP production, reduced the ET-1-induced HSP27 accumulation. In addition, the phosphorylation of p38 MAP kinase induced by ET-1 or TPA was suppressed by PGE(1). Forskolin, DBcAMP, and PGE(1) suppressed the ET-1-stimulated increase in the mRNA level for HSP27. These results indicate that the adenylyl cyclase-cAMP system has an inhibitory role in ET-1-stimulated HSP27 induction in osteoblasts and that the effect is exerted at the point between PKC and p38 MAP kinase in osteoblasts.

Modified labial tissue sliding flaps for repairing large lower lip defects.

PURPOSE: Common flap techniques for reconstructing large defects in the lower lip are often destructive and complex and result in unsatisfactory function and appearance. This article describes a modified technique that uses sliding labial tissue flaps to avoid these problems. PATIENTS AND METHODS: Eight patients with lower lip carcinomas had defects ranging from one third to four fifths of the length of the lower lip after tumor resection. The defects were closed with sliding labial tissue flaps, taking advantage of the elasticity of soft tissue to reduce the loss of normal tissue. Patients were followed for 2 to 12 years. RESULTS: The functional and cosmetic results were good, and there were no intra- or postoperative complications. Some patients experienced tightness of the lower lip that disappeared within 6 months. Carcinoma did not recur in any patient after a median follow-up period of more than 5 years. CONCLUSIONS: This modified labial tissue sliding flap technique is simple, safe, functionally and aesthetically satisfactory, sacrifices little healthy tissue, heals rapidly, and requires no further revision. The technique is effective for repairing defects covering one third to four fifths of the lower lip.

Analysis of genetic alterations in salivary gland tumors by comparative genomic hybridization.

In order to define and map chromosomal copy number alterations in salivary gland tumors (SGTs), a comparative genomic hybridization (CGH) technique was applied to two pleomorphic adenomas (PAs), one adenoid cystic carcinoma (ACC), and one basal cell adenocarcinoma (BCAC). The PAs exhibited regional copy number losses at 5q12.4-q14.1, 9q12-q21.13, and 16q11.2, as well as a gain at 20p12.1; among these, the losses at the 9q12-q21.11 and 16q11.2 regions were common to both PAs. The ACC showed overrepresentations of the entire regions of chromosomes 16 and 20, a regional gain at 22q12.3-q13.1, and no losses. In the BCAC, regional gains at 9p21.1-pter, 18q21.1-q22.3, and 22q11.23-q13.31 as well as losses at 2q24.2 and 4q25-q27 were seen; the gain at 22q12.3-q13.1 was common in both the ACC and the BCAC. These CGH data indicate that different genetic alterations are present in the different types of SGTs, and that the alterations involve several chromosomes. The discovery of common alterations in the same and/or different types of tumors might be important in the understanding of the development and progression of the SGTs.

Effect of estrogen replacement on temporomandibular joint remodeling in ovariectomized rats.

PURPOSE: The investigation was performed to elucidate the effect of estrogen on the temporomandibular joint (TMJ) and to evaluate the therapeutic effect of 17beta-estradiol replacement in growing rats. MATERIALS AND METHODS: Thirty 4-week-old female albino Wistar rats were divided into 3 groups. Ten rats were ovariectomized followed by intramuscular administration of 17beta-estradiol for hormone replacement (OVX + E2), 10 were sham operated (CTL), and 10 were ovariectomized without hormone replacement (OVX). Five rats from each group were killed at 1 and 2 weeks postoperatively, and the serum estrogen was determined to verify the adequacy of replacement. The temporomandibular joints of the age-matched sham-operated control and ovariectomized groups were histomorphometrically evaluated at the same periods. RESULTS: In OVX animals, the thickness of the articular soft tissue was increased by a concomitant increase of the transitional and cartilage zones in the anterior and posterior portions at 1 and 2 weeks postoperatively. However, the bone volume was decreased in the anterior and posterior portions at 2 weeks after the surgery and the condyle was flattened. Replacement with 17beta-estradiol restored most of the histomorphometric parameters. The thickness of articular soft tissue was increased in the anterior portion by an increase in the cartilage zone in the OVX + E2 group at 2 weeks postoperatively. Increase of bone volume was found at 2 weeks after hormone replacement with a corresponding increased osteoid surface and decreased quiescent surface in the central portion at 1 week postoperatively. A flattened condyle was still noted at 2 weeks postoperatively in the OVX + E2 animals despite the hormone replacement. CONCLUSIONS: Estrogen in a physiologic concentration may play an important role in TMJ remodeling. Progesterone may be indispensable for remodeling, particularly contributing to morphogenesis.

[Clinical effects of adjuvant therapy using Z-100 (Ancer 20 injection) for oral cancer--prevention of stomatitis and hematopoietic impairment].

A combination of radiotherapy and chemotherapy is a usual treatment method for malignant head and neck tumors, however chemoradiotherapy is associated with hematopoietic impairment and serious stomatitis in patients. The clinical effects and evaluation of hematopoietic activity (e.g., leukocyte count) and the degree of stomatitis under adjuvant therapy using Z-100 (Ancer 20 injection) for oral cancer were investigated for preoperative cancer therapy. In order to evaluate the clinical effects of Ancer 20 injection with regard to hematopoietic activity and the degree of stomatitis, a clinical study was performed for 18 patients with oral cancer in our department. The 18 patients, who had oral squamous cell carcinomas (5 of the tongue, 4 of the mandibular gingiva, 3 of the maxillary gingiva, 1 of the floor of the mouth, 3 of the buccal mucosa, and 2 others), were treated with this combination of adjuvant therapy with Ancer 20 injection, from March, 1991 to March, 1997. They were injected with Ancer 20 (twice a week, 40 micrograms) during the cancer treatment period. We investigated hematopoietic activity, (e.g., leukocyte and platelet counts) and the degree of stomatitis periodically, before and after the combined radiotherapy and chemotherapy treatment period. It was found that in the patients who were treated with Ancer 20 injection, the decrease in leukocyte and platelet counts was prevented and the condition of stomatitis was improved. These results suggest that Ancer 20 injection may generally improve various dysfunctions due to hematopoietic impairment by radiotherapy combined with chemotherapy, and improve immunological factors. We conclude that Ancer 20 injection is a useful adjuvant treatment for oral cancer.

Chemopreventive effect of dietary flavonoid morin on chemically induced rat tongue carcinogenesis.

The modifying effects of dietary exposure of the flavonoid morin on 4-nitroquinoline 1-oxide (4-NQO)-induced tongue tumorigenesis, the activities of phase II detoxifying enzymes glutathione S-transferase (GST) and quinone reductase (QR) in liver and tongue, and cell proliferation activity in tongue were investigated in male F344 rats. At 7 weeks of age, all animals except those treated with morin alone and control group were given 4-NQO (20 ppm) in drinking water for 8 weeks to induce oral neoplasms. Starting 7 days before 4-NQO exposure, experimental groups were fed experimental diets containing morin (100 and 500 ppm) for 10 weeks ("initiation feeding"). Starting 1 week after the cessation of exposure to 4-NQO, other experimental groups given 4-NQO and a basal diet were given experimental diets for 22 weeks ("post-initiation feeding"). At week 32 week, "initiation feeding" of morin caused a significant reduction in the incidence of tongue carcinoma (by 44-100%). "Post-initiation feeding" with morin also significantly decreased the frequency of tongue carcinoma (by 44%). Morin feeding elevated liver GST and QR activities and GST activity in the anterior portion of tongue. Feeding with morin significantly lowered QR activity of the posterior part of the tongue. Dietary exposure to morin significantly decreased the proliferating cell nuclear antigen-positive index in the posterior portion. Also, morin feeding lowered tongue polyamine levels, especially in the "post-initiation feeding" group. Our results indicate that morin acts as a chemopreventive agent against tongue carcinogenesis induced by 4-NQO through modification of detoxifying enzyme activities and/or cell proliferation activities.

Incidence of Prevotella intermedia and Prevotella nigrescens carriage among family members with subclinical periodontal disease.

We established a typing system for Prevotella intermedia and Prevotella nigrescens using the combination of PCR ribotyping and arbitrarily primed PCR (AP-PCR) fingerprinting and applied this system to the study of intrafamilial incidence of these species in the oral cavity. PCR ribotyping followed by subtyping by AP-PCR fingerprinting was applied to each type strain of P. intermedia and P. nigrescens and 54 isolates (32 isolates of P. intermedia and 24 isolates of P. nigrescens) from extraoral infections, resulting in an excellent discriminatory power (discrimination index, 0.99) for both species. A total of 18 subjects from six families, with the subjects from each family comprising the mother, the father, and a child who had subclinical early-stage to moderate adult periodontitis or simple gingivitis and who carried P. intermedia or P. nigrescens, or both, were enrolled in the study of intrafamilial carriage. When 20 colonies per specimen of subgingival plaque, if available, were picked from primary culture, 115 P. intermedia and 178 P. nigrescens isolates were recovered from the 18 subjects. Among the subjects studied, family members shared the same subtype strain(s) but non-family members did not. Multiple subtypes were found in 8 (57%) of the 14 P. nigrescens-positive subjects but in only 3 (27%) of the 11 P. intermedia-positive subjects; the difference was, however, not statistically significant (P = 0.14). These results suggest that the combination of PCR ribotyping and AP-PCR fingerprinting is well suited for the epidemiological study of P. intermedia and P. nigrescens and that each family seems to carry a distinct subtype(s) of these species.

Calcitonin receptor binding properties in bone and kidney of the chicken during the oviposition cycle.

The binding property of calcitonin (CT) in the membrane fraction of calvaria and kidney of egg-laying and nonlaying hens was analyzed using a [125I] CT binding assay system. Binding properties of CT receptors in both tissues satisfy the authentic criteria of a receptor-ligand interaction in terms of specificity, reversibility, and saturation. Scatchard plots revealed a single class of binding sites. Values of the equilibrium dissociation constant (Kd) and binding capacity (Bmax) in laying hens showed a decrease during the period between 3 h before and 2 h after oviposition. No change was observed in nonlaying hens. In vivo administration of 17beta-estradiol or progesterone caused the decrease in Kd and Bmax values. The results suggest that the binding affinity and capacity of the CT receptor in the calvaria and the kidney of the hen may be modulated by the ovarian steroid hormone.

Involvement of Rho family proteins in prostaglandin F2 alpha-induced phospholipase D activation in the osteoblast-like cell line MC3T3-E1.

To examine the role of Rho family proteins in prostaglandin F2 alpha (PGF2 alpha)-mediated phospholipase D (PLD) activation of osteoblast-like cell line MC3T3-E1 cells, we used Toxin-B from Clostridium difficile, which inhibits Rho family proteins by monoglucosylation. Pretreatment of [3H]myristic acid-labeled MC3T3-E1 cells with Toxin B induced rounding-up of the cells and inhibited the PGF2 alpha-induced PLD activation by 60%, but not the phospholipase C (PLC) activation. Cytochalasin D also induced rounding the cells, but showed a small inhibition in the PLD activation. Brefeldin A (BFA) had marginal inhibitory effect on the PGF2 alpha-induced PLD activation. In digitonin-permeabilized MC3T3-E1 cells, [3H]P But formation was stimulated by guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) or 4 beta-phorbol 12-myristate 13-acetate (PMA) in the presence of Ca2+ (1 microM) and ATP (1 mM), and phosphatidylinositol 4,5-bisphosphate (PIP2) was also required for its full PLD activation. Pretreatment of the digitonin-permeabilized MC3T3-E1 cells with Toxin B reduced the GTP gamma S- and PMA-stimulated PLD activities by 80% and 60%, respectively. On the other hand, C3 toxin which inhibits Rho by ADP-ribosylation, exerted a partial inhibitory effect on the GTP gamma S-stimulated PLD activity. These results suggest that Cdc42 as well as RhoA appear to be involved in the PLD activation mediated by PGF2 alpha and also that the PLD activation may be independent of actin cytoskeleton in MC3T3-E1 cells.

[Bacteriological study of oral open abscesses].

Although studies of bacteriology of closed oral abscesses have been extensively done, there are few studies on microorganisms involving open oral abscesses. We examined bacteriologically three open abscesses with precaution against bacterial contamination with oral normal flora and saliva, when sampling. The specimens were subjected to aerobic and anaerobic cultures within 2 hours after sampling. All three cases were infected with 5 to 14 species of aerobic and anaerobic bacteria; Streptococcus spp., Prevotella intermedia and other Prevotella spp. were predominant in all three cases. All six Prevotella spp. isolated were beta-lactamase producers, being resistant to beta-lactam antibiotics. These results emphasize the importance of prompt anaerobic culture for the bacteriological study of open oral abscess and the significance of nitrocefin test to detect beta-lactamase produced by oral isolates, especially Prevotella spp.

Chemoprevention of 4-nitroquinoline 1-oxide-induced rat oral carcinogenesis by the dietary flavonoids chalcone, 2-hydroxychalcone, and quercetin.

The modifying effects of dietary exposure of three flavonoids, chalcone, 2-hydroxychalcone, and quercetin, during the initiation and postinitiation phases of oral tumorigenesis initiated with 4-nitroquinoline-1-oxide (4-NQO) were investigated in male F344 rats. At 6 weeks of age, animals were divided into experimental and control groups. At 7 weeks of age, all animals except those treated with test chemicals alone and the untreated control group were given 4-NQO [20 parts/million (ppm)] in the drinking water for 8 weeks to induce oral neoplasms. For chemopreventive study by feeding of test compounds during the initiation phase, groups of animals were given diets containing 500 ppm chalcone, 500 ppm 2-hydroxychalcone, or 500 ppm quercetin for 10 weeks, starting 1 week before 4-NQO exposure. Seven days after stopping 4-NQO exposure, these groups were switched to the basal diet and kept on this diet until the end of the experiment. For chemopreventive study by treatment with test chemicals during the postinitiation phase, starting 1 week after the cessation of 4-NQO administration, the groups given 4-NQO and the basal diet were switched to the diets mixed with test chemicals and maintained on these diets for 22 weeks. The other groups consisted of rats fed diets containing 500 ppm test chemicals alone or of untreated rats. Thirty-two weeks after the start of the study, the incidence of tongue neoplasms and preneoplastic lesions, polyamine levels in the tongue epithelium, and cell proliferation activity estimated by bromodeoxyuridine labeling index were compared among the different dietary groups. Feeding of all test chemicals during either initiation or postinitiation phases caused a significant reduction in the frequency of tongue carcinoma (68-88% reduction; P < 0.05). Dietary administration of these test chemicals also significantly decreased the bromodeoxyuridine labeling index of the tongue squamous epithelium (P < 0.05). In addition, polyamine levels in the oral mucosa were lowered in rats treated with 4-NQO and test chemicals when compared to those given 4-NQO alone. These results indicate that the flavonoids chalcone, 2-hydroxychalcone, and quercetin present in our daily foods have an inhibitory effect on oral carcinogenesis initiated with 4-NQO, and such a modifying effect may be related partly to the suppression of cell proliferation.

[The clinical effect of cisplatin and 5-FU infusion in oral cancer].

The combination chemotherapy of cisplatin and 5-fluorouracil (5-FU) is more effective than monotherapy of either drug in the head and neck cancer. In 1982, Kish reported that CF-therapy, the combination of cisplatin and 5-FU, had a high curative rate (about 82%). CF-therapy was utilized in 9 patients with carcinoma of the oral region from March, 1987 to September, 1990 in our hospital. The patients' ages ranged from 23 to 74 years old with an average of 55. All tumor were squamous cell carcinoma. There were 2 cases in stage II, 4 cases in stage III and 3 cases in stage IV. Two patients treated with only CF-therapy and the other patients treated with radiotherapy and operation in addition to CF-therapy. Our regimen is cisplatin 80-100 mg i.v. or i.a. in day 1 and 5-FU 250 mg i.a. or 5-FU 750 mg i.v. in day 2-6. The therapeutic results showed a 78% response rate to the therapy with 4 cases of CR (complete response), 3 cases of PR (partial response), 1 case of MR (minor response) and 1 case of PD (progressive disease). Side effects of cisplatin plus 5-FU (eg. nausea and vomiting) were so severe that the treatment had to the stopped in many patients. The method we have reported here was evaluated, and it is concluded that this CF-therapy is very effective as a first treatment of oral cancer.

Intermaxillary fixation using screws. Report of a technique.

A technique of intermaxillary fixation using screws anchored in the maxilla and mandible has been described. AO (Synthes) screws with a diameter of 3.5 mm and 12 mm to 16 mm in length were inserted at the antero-lateral surface of the maxilla and the buccal surface of the mandible. This technique is particularly suitable for mandibular fractures in denture wearing patients.

Malignant mixed tumor (malignant ameloblastoma and fibrosarcoma) of the maxilla.

We present a rare case of carcinosarcoma (malignant ameloblastoma and fibrosarcoma) of the left maxilla that developed in a 63-year-old Japanese man. The tumor recurred repeatedly despite multiple surgical removals, radiotherapy, and chemotherapy and led to progressive cachexia; the patient died after 3.8 years of hospitalization. Histopathologic examination revealed that the recurrent tumor was carcinosarcoma, which had progressed from malignant ameloblastoma with fibroma. An autopsy confirmed the diagnosis of malignant mixed tumor with lung metastasis of malignant ameloblastoma and fibrosarcoma.