Usefulness of a simple self-administered joint condition assessment sheet to predict the need for orthopaedic intervention in the management of haemophilic arthropathy.

INTRODUCTION: Detecting signs of joint deterioration is important for early effective orthopaedic intervention in managing haemophilic arthropathy. AIM: We developed a simple, patient self-administered sheet to evaluate the joint condition, and assessed the predictive ability of this assessment sheet for the need for an orthopaedic intervention. METHODS: This was a single-centre, cross-sectional study. The association between the score of each of the four items of the assessment sheet (bleeding, swelling, pain and physical impairment) and the results of radiological findings and physical examinations based on Haemophilia Joint Health Score 2.1 was assessed. An optimal scoring system was explored by the area under the curve (AUC). The cut-off value for the need for surgery or physiotherapy was determined using the receiver operating characteristic curve procedure. RESULTS: Forty-two patients were included. The 'physical impairment' item showed the highest correlation coefficient with the results of radiographic and physical examinations (range: 0.57-0.76). The AUC of finally adjusted scoring indicates good ability to discriminate between patients with and without a need for orthopaedic intervention. The positive predictive value was the highest at a cut-off value of 4 points for knees (63.0%) and ankles (70.0%), at 5 points for elbows (66.7%) and the highest predictive accuracy at the cut-off value of 4 points for all the joints. The linear trend of the need for an orthopaedic intervention was observed with an increasing score. CONCLUSION: The joint condition assessment sheet can help clinicians assess the need for orthopaedic intervention for haemophilic arthropathy in Japanese patients with haemophilia.

Synthesis and biological assessment of 3,7-dihydroxytropolones.

3,7-Dihydroxytropolones (3,7-dHTs) are highly oxygenated troponoids that have been identified as lead compounds for several human diseases. To date, structure-function studies on these molecules have been limited due to a scarcity of synthetic methods for their preparation. New synthetic strategies towards structurally novel 3,7-dHTs would be valuable in further studying their therapeutic potential. Here we describe the successful adaptation of a [5 + 2] oxidopyrilium cycloaddition/ring-opening for 3,7-dHT synthesis, which we apply in the synthesis of a plausible biosynthetic intermediate to the natural products puberulic and puberulonic acid. We have also tested these new compounds in several biological assays related to human immunodeficiency virus (HIV), hepatitis B virus (HBV) and herpes simplex virus (HSV) in order to gain insight into structure-functional analysis related to antiviral troponoid development.

Possible molecular mechanism of promotion of repair of acute Achilles tendon rupture by low intensity-pulsed ultrasound treatment in a rat model.

OBJECTIVE: This study investigated the effect of Low Intensity-pulsed Ultrasound (LIPUS) on the repair process of ruptured Achilles tendon using a rat model and also examined the regulation of a biological molecule that may contribute to this in vivo and in vitro. METHODS: To investigate the effect of LIPUS and its biological mechanism of promoting Achilles tendon repair after acute injury, ninety-eight male Sprague-Dawley (SD) rats (mean body weight, 258 +/- 9.8 g) aged 12 weeks were used in this study. To create the model, the Achilles tendon attachment site and musculotendinous junction were ruptured under direct vision. The leg on one side was exposed to LIPUS (frequency at 1.5 MHz, the repetition cycle at 1.0 kHz, the burst width at 200 msec and the power output at 45 mW/cm2), for 20 minutes daily with a 0.7 mm diameter probe. RESULTS: Low Intensity-pulsed Ultrasound treatment accelerated the repair of the Achilles tendon compared to the untreated group, judged by electron microscopy. Both cyclo-oxygenase (COX)-2* and EP4* expressions were over-expressed in the LIPUS treated group in the inflammatory period, and TGFbeta1* expression was markedly induced in LIPUS treated groups followed by collagen I* and II* expression in the repair and reconstitution process. CONCLUSION: These findings suggest that LIPUS is potentially able to accelerate the repair of acute ruptured Achilles tendon in several ways: by exaggerating inflammation by inducing COX-2 and EP4 and reconstituting tissue by inducing TGFbeta1 followed by collagen I and III. (*: p < 0.05, **: 0.001).

Expression and function of laminin and integrins on adhesion/migration of primary culture cells derived from rat oral epithelium.

BACKGROUND AND OBJECTIVE: It remains controversial whether or not the junctional epithelium cells that are directly attached to teeth migrate on the enamel surface, as those cells are able to adhere firmly to the enamel. The aim of this study was to investigate the expression patterns of laminin gamma(2), integrin beta(4) and integrin alpha(3), and to examine their potential function in cell migration. MATERIAL AND METHODS: Oral epithelium cells obtained from Sprague-Dawley rats were established in primary culture. We employed a wound-healing assay to characterize the direction of cell extension at the start of cell migration, and observed different localizations of laminin and integrins using immunofluorescence. For functional analyses of integrins, we employed a phosphatidylinositol-3-kinase (PI3K) activator to promote integrin beta(4) function and used P1B5 to inhibit integrin alpha(3) function, and we analyzed the percentage of re-epithelialization as the migration function. RESULTS: Marked accumulation of laminin gamma(2) was detected in the peripheral cytoplasm of cells adjacent to the wound area, as shown by the results of the migration assay. Integrin beta(4) was detected in the distal cell processes of actively migrating cells, while integrin alpha(3) was found in cell membranes of cells adjacent to the wound area. In the functional analyses, the percentage of re-epithelialization was significantly lower in the PI3K-activator group and in the P1B5-treated group (2.5% and 7.2%, respectively) than in the control group (39.0%) (p < 0.01). CONCLUSION: The results suggest that laminin gamma(2) is secreted as a foothold for cell migration, that integrin beta(4) participates in cell adhesion and that integrin alpha(3) is involved in cell migration in the primary culture cells.

Proliferation, migration and apoptosis of periodontal ligament cells after tooth replantation.

OBJECTIVE: The aim of this study was to investigate the proliferation, migration and death of periodontal ligament (PDL) cells after tooth replantation. MATERIALS AND METHODS: Maxillary first molars were extracted from 4-week-old male (n = 28) Sprague-Dawley rats and immediately replanted, after which, proliferation, migration and death of PDL cells were investigated. RESULTS: At 3 days after tooth replantation, many proliferative cell nuclear antigen (PCNA)-positive PDL cells were observed on the alveolar bone side, but fewer on the root side. However, while a gradual decrease was observed in number of PCNA-positive PDL cells on the alveolar bone side until 7 days, an increase was seen on the root side. At 3 weeks, cells labeled with PKH26 (fluorescent dye into plasma membrane) were located in the middle of the PDL space. However, these PKH26-labeled cells did not spread to the surface of the cementum or the alveolar bone. TUNEL-positive cells were observed on both the bone and root sides at 3 days. Number of apoptotic cells increased until 7 days on the bone sides, but decreased on root sides. CONCLUSION: These results suggest that both cell proliferation and apoptosis occur in different patterns and at different times to maintain regular spacing of the PDL after tooth replantation.

Effect of the dental adhesive, 4-META/MMA-TBB resin, on adhesion and keratinization of regenerating oral epithelium.

BACKGROUND AND OBJECTIVE: The 4-META/MMA-TBB [4-(2-methacryloxyethyl)trimellitic anhydride/methyl methacrylate-tributylborane] resin is widely used as a dental adhesive. It has also been applied in the dressing of gingival wound surfaces following periodontal surgery. However, its effect on the regeneration and/or cell attachment of the oral epithelium remains to be clarified. To evaluate the effect of the resin applied as a wound dressing, we investigated expression of laminin 5, integrin beta(4) and cytokeratin 14 in regenerating oral epithelium treated with this resin following gingivectomy from the viewpoint of cell attachment and differentiation. MATERIAL AND METHODS: The resin was applied to the entire wound surface in rats after gingival surgery, and regenerating epithelium was examined immediately and at 1, 3, 5, 7 and 14 days later. The resin was removed 2 weeks after application in some animals and tissue further examined at 1, 3, 5 and 7 days later. RESULTS: Regenerating epithelium under the resin was not keratinized, but became keratinized immediately after removal of the resin. Laminin 5 and integrin beta(4) were immunolocalized in the basal lamina, the internal basal lamina, in marginal cells of the regenerating epithelium and at the resin-regenerating epithelium interface. Cytokeratin 14 localized in the regenerating epithelium underneath the resin, as well as in healthy and regenerated junctional epithelial cells. CONCLUSION: These results suggest that this resin covers the wound surface and that the regenerating epithelium biologically adheres to the resin during the initial process of its regeneration.

Immunolocalization of laminin and integrin in regenerating junctional epithelium of mice after gingivectomy.

BACKGROUND AND OBJECTIVE: The expression patterns of adhesive proteins and extracellular matrix proteins in regenerating gingival epithelium after gingivectomy are unknown. The aim of this study was to examine the expression of laminin 1, laminin gamma(2) (a specific component of laminin 5), integrin beta(4) and integrin alpha(3) in the regenerating gingival epithelium in order to understand the mechanism of wound healing during reconstitution of the sulcular environment. MATERIAL AND METHODS: The palatal gingivae of the maxillary molars of Institute of Cancer Research mice were excised, and the regenerating tissues were examined 1, 3, 5, 7 and 14 days later. Fresh, non-fixed and non-decalcified frozen sections were prepared and stained using immunofluorescence. RESULTS: At 1 day post-surgery, intense expression of laminin gamma(2), integrin beta(4) and integrin alpha(3) was distinct in the frontal margin of the regenerating oral epithelium. Laminin gamma(2) was diffusely detected on the root surface and in connective tissues beneath the regenerating oral epithelium at 3 and 5 days. At 7 days, laminin gamma(2) was intermittently recognizable in the internal basal lamina (IBL) close to tooth-facing cells, while laminin gamma(2), integrin beta(4) and integrin alpha(3) were observed in the IBL and in the external basal lamina (EBL) of the regenerating junctional epithelium at 14 days. CONCLUSION: These results suggest that secretion of laminin 5 in the connective tissue may induce epithelial cell migration, and that binding of laminin 5 to integrin alpha(6)beta(4) and integrin alpha(3)beta(1) in the IBL may provoke cell adhesion and migration of cells facing the tooth on the enamel surface of the regenerating junctional epithelium.

[Positron emission tomography (PET)-computed tomography (CT) suggesting small intestinal metastasis from lung cancer; report of a case].

A 75-year-old man admitted to our hospital due to an abnormal X-ray shadow detected during an annual health check-up. Chest computed tomography (CT) revealed 3.0 cm solid nodules with chest wall invasion in the left lung. We could not get a definitive diagnosis by transbronchial lung biopsy or CT-guided needle biopsy. Positron emission tomography (PET)-CT revealed positive findings in the tumor, aortopulmonary window lymph node and splenic flexure. Under a diagnosis of suspected lung cancer, thoracotomy was performed. As intraoperative diagnosis revealed a moderately differentiated squamous cell carcinoma, the patient underwent a left upper lobectomy, mediastinal lymph node dissection, and combined chest wall resection. Pathological stage was T3N2M0, stage IIIA. Ten days after surgery, the patient suffered from ileus and emergent surgery was performed. Subsequent pathological examination revealed lung cancer metastasis in the small intestine.

Emerging treatments in neurogastroenterology: Acotiamade, a novel treatment option for functional dyspepsia.

BACKGROUND: Acotiamide hydrochloride (Z-338) is a new therapeutic agent for functional dyspepsia (FD). In 2013, the use of acotiamide was approved by the Japanese health insurance system. PURPOSE: The aim of this review is to summarize the present staus of basic and clinical approach to acotiamide for the treatment of functional dyspepsia. The agent inhibits acetylcholinesterase in vitro and enhances muscle motility ex vivo. In phase-II studies, 100 mg three times daily (t.i.d.) was determined to be the optimal dose for the treatment of FD. In phase-III studies, overall treatment efficacy (OTE) was significantly better in the acotiamide group (52.2%) than in the placebo group (34.8%). However, the mechanism of its efficacy needs to be further elucidated. Acotiamide effectively improved FD symptoms, particularly postprandial distress syndrome symptoms, without causing major adverse effects.

A prospective study on symptom generation according to spicy food intake and TRPV1 genotypes in functional dyspepsia patients.

BACKGROUND: Capsaicin is an ingredient of red peppers that binds to transient receptor potential vanilloid subtype 1 (TRPV1), and Koreans eat more capsaicin-rich food than do Japanese. This study aimed to compare symptom generation according to TRPV1 genotypes and the intake of spicy foods. METHODS: Consecutive functional dyspepsia (FD) patients who were evaluated at Konkuk University Medical Centre (Korea) and Keio University Hospital (Japan) were included. Questionnaires on spicy food intake, patient assessment of gastrointestinal symptoms (PAGI-SYM), patient assessment of quality of life, and hospital anxiety and depression scale were provided. Blood was sampled for the detection of TRPV1 polymorphisms, and upper gastrointestinal endoscopy was performed with biopsies. KEY RESULTS: Of 121 included subjects, 35 and 28 carried the TRPV1 CC and GG genotypes, respectively, with the prevalence rates not differing between Japan and Korea. The prevalence of FD subtypes did not differ with the spicy food intake, TRPV1 genotypes, or Helicobacter pylori infection. Neither TRPV1 polymorphisms nor H. pylori infections were related to scores on the PAGI-SYM questionnaires, but spicy food intake was positively correlated with the scores for stomach fullness (p = 0.001) and retching (p = 0.001). Using the linear regression analysis, stomach fullness was associated with spicy food intake (p = 0.007), whereas retching was related to younger age (p < 0.001) and female gender (p = 0.014). CONCLUSIONS & INFERENCES: Upper gastrointestinal symptoms are more common in subjects with a higher consumption of spicy foods, younger age and female gender, regardless of TRPV1 genotypes and the H. pylori infection status. Capsaicin-rich foods may induce stomach fullness.

An early phase II study of CPT-11: a new derivative of camptothecin, for the treatment of leukemia and lymphoma.

An early phase II study of a new camptothecin analog and an inhibitor of topoisomerase I, CPT-11, was conducted in 62 patients with refractory leukemia and lymphoma by four different treatment schedules in a multiinstitutional cooperative study. CPT-11 therapy resulted in four complete remissions (CRs) and three partial remissions (PRs) in 29 assessable non-Hodgkin's lymphoma (NHL) patients, one PR in three Hodgkin's disease (HD), one CR and one PR in 11 acute lymphoblastic leukemia (ALL), and one PR in 15 acute myelogenous leukemia (AML) patients. Single infusion of 200 mg/m2 every 3 to 4 weeks produced no response in both leukemia and lymphoma patients. Sixty-minute infusions of 40 mg/m2/d for 5 days every 3 to 4 weeks or for 3 days weekly produced four CRs (17%) and four PRs (17%) in 24 patients with malignant lymphoma. Sixty-minute infusions of 20 mg/m2 twice a day for 7 days every 3 to 4 weeks resulted in one CR and two PRs in 12 patients with acute leukemia. No response was seen in an acute leukemia patient by another treatment schedule. CPT-11 was effective in two (15%) of 13 primarily refractory leukemia and lymphoma cases, in two of four relapsed cases, and in seven (17%) of 41 relapsed and refractory cases. Major side effects were leukopenia (91%) and gastrointestinal (GI) (76%). CPT-11 was shown to be effective against refractory leukemia and lymphoma, and thus deserves further clinical study; the novel antitumor activity mode of this drug predicts no cross-resistance to presently available antitumor drugs.

Human urinary macrophage colony-stimulating factor reduces the incidence and duration of febrile neutropenia and shortens the period required to finish three courses of intensive consolidation therapy in acute myeloid leukemia: a double-blind controlled study.

PURPOSE: To determine whether macrophage colony-stimulating factor (M-CSF) reduces the incidence and duration of febrile neutropenia during three courses of intensive consolidation therapy and whether it shortens time to complete consolidation therapy. PATIENTS AND METHODS: In 198 adult patients with acute myeloid leukemia (AML) in complete remission (CR), M-CSF (8 x 10(6) U/d) or placebo was administered from 1 day after the end of each consolidation chemotherapy for 14 days. RESULTS: The duration and incidence of febrile neutropenia was significantly reduced by 34% (P = .00285) and 17% (P = .02065), respectively, in 88 assessable patients in the M-CSF group compared with those in 94 assessable patients in the placebo group. Patients in the M-CSF group had 565 days and 133 episodes of febrile neutropenia during 7,901 days at risk, while patients in the placebo group had 977 days and 185 episodes during 9,077 days at risk. The median period required to finish the three courses of consolidation therapy was 93 days in the M-CSF group, which was significantly shorter than 110 days in placebo group (P = .0050). In the M-CSF group, the recovery of neutrophils and platelets was significantly faster (P = .0348 and P = 0.0364, respectively), the administration of systemic antimicrobial agents tended to be less (P = .0839), and the frequency of platelet transfusion (P = .0259) and the total volume of transfused platelets (P = .0292) were significantly less. However, there was no significant difference in the disease-free survival. CONCLUSION: M-CSF significantly reduced the incidence and duration of febrile neutropenia during the intensive consolidation therapy, and shortened the time to complete consolidation chemotherapy in AML.

Results of allogeneic bone marrow transplants for leukemia using donors other than HLA-identical siblings.

PURPOSE: To compare outcomes of bone marrow transplants for leukemia from HLA-identical siblings, haploidentical HLA-mismatched relatives, and HLA-matched and mismatched unrelated donors. PATIENTS: A total of 2,055 recipients of allogeneic bone marrow transplants for chronic myelogenous leukemia (CML), acute myelogenous leukemia (AML), and acute lymphoblastic leukemia (ALL) were entered onto the study. Transplants were performed between 1985 and 1991 and reported to the International Bone Marrow Transplant Registry (IBMTR). Donors were HLA-identical siblings (n = 1,224); haploidentical relatives mismatched for one (n = 238) or two (n = 102) HLA-A, -B, or -DR antigens; or unrelated persons who were HLA-matched (n = 383) or mismatched for one HLA-A, -B, or -DR antigen (n = 108). HLA typing was performed using serologic techniques. RESULTS: Transplant-related mortality was significantly higher after alternative donor transplants than after HLA-identical sibling transplants. Among patients with early leukemia (CML in chronic phase or acute leukemia in first remission), 3-year transplant-related mortality (+/-SE) was 21% +/- 2% after HLA-identical sibling transplants and greater than 50% after all types of alternative donor transplants studied. Among patients with early leukemia, relative risks of treatment failure (inverse of leukemia-free survival), using HLA-identical sibling transplants as the reference group, were 2.43 (P < .0001) with 1-HLA-antigen-mismatched related donors, 3.79 (P < .0001) with 2-HLA-antigen-mismatched related donors, 2.11 (P < .0001) with HLA-matched unrelated donors, and 3.33 (P < .0001) with 1-HLA-antigen-mismatched unrelated donors. For patients with more advanced leukemia, differences in treatment failure were less striking: 1-HLA-antigen-mismatched relatives, 1.22 (P = not significant [NS]); 2-HLA-antigen-mismatched relatives, 1.81 (P < .0001); HLA-matched unrelated donors, 1.39 (P = .002); and 1-HLA-antigen-mismatched unrelated donors, 1.63 (P = .002). CONCLUSION: Although transplants from alternative donors are effective in some patients with leukemia, treatment failure is higher than after HLA-identical sibling transplants. Outcome depends on leukemia state, donor-recipient relationship, and degree of HLA matching. In early leukemia, alternative donor transplants have a more than twofold increased risk of treatment failure compared with HLA-identical sibling transplants. This difference is less in advanced leukemia.

Synergistic effects of basic fibroblast growth factor and hematopoietic growth factors on colony formation of K562 human leukemic cells.

The effect of basic fibroblast growth factor (bFGF) alone and in combination with other hematopoietic growth factors on the colony formation of K562 human leukemic cells was studied using soft agar colony assay. bFGF was found to have a weak colony-stimulating activity on K562 cells derived from the blastic crisis cells of human chronic myelogenous leukemia and to potentiate the K562 cell colony-stimulating activity of granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3) and stem cell factor (SCF) at a low concentration of below 1 ng/ml. These findings suggested that bFGF stimulates the growth of human leukemic cells directly in vivo alone and in synergy with other hematopoietic growth factors.

No correlation between locations of bcr breakpoints and clinical states in Ph1-positive CML patients.

The majority of patients with chronic myelogenous leukemia (CML) have a characteristic reciprocal translocation between chromosome 9 and 22, resulting in the Philadelphia (Ph1) chromosome. During this translocation, the c-abl oncogene on chromosome 9 is transferred to the Ph1 chromosome and linked to a breakpoint cluster region (bcr), which is part of a large bcr gene. This phenomenon results in the formation of a bcr-c-abl fusion gene, which is transcribed into an 8.5 kb chimeric mRNA encoding a 210 kd bcr-c-abl fusion protein. The fusion protein has tyrosine kinase activity implicated in the pathogenesis of CML. The breakpoint near the c-abl locus on chromosome 9 can occur within a large area. In contrast, the breakpoints on chromosome 22 cluster within the bcr region of 5.8 kb. A chronic phase lasts for an average of 2 to 3 years; and, subsequently, most patients enter blast crisis. In the present study, we examined 15 Ph1-positive CML patients (eight in chronic phase, one in accelerated phase, and six in blast crises) as to whether the identifiable difference in the locations of the bcr breakpoints exist between CML patients in chronic phase and those in blast crisis. In seven of eight CML patients in chronic phase, in one in accelerated phase, and in four out of six CML patients in blast crisis, the bcr breakpoints clustered in the 3' portion of the bcr. Thus, we could not find out the correlation between the locations of the bcr breakpoints and the clinical stage of the CML patients. This might imply that blastic transformation in Ph1-positive CML was caused by other mechanisms than the transition of the bcr breakpoints.

Morphological studies on the ageing and osteoarthritis of the articular cartilage in C57 black mice.

PURPOSE: To study the cause and mechanism of joint degeneration in osteoarthritis, through histopathological and ultrastructural-histochemical experiments on the articular cartilage of the knees of the C57 black mouse. METHODS: 192 C57 black mice and a control group of 64 C57BL/6J mice were used in this study. The left and right knee articular capsules of the joints were removed and stained. Each articular cartilage sample was examined and osteoarthritic changes were assessed using a transmission electron microscope. The severity of osteoarthritis in the knee joint cartilage of C57 black mice was histologically assessed using a classification system described by Okabe, based on Maier's system. RESULTS: The incidence and the severity of osteoarthritis gradually increased with age; the incidence increased from 20% at 2 months to 80% at 16 months. Irreversible changes appeared at an advanced stage, and the process of degeneration was quite similar to that in human osteoarthritis. Through transmission electron microscopy, we observed poorly developed Golgi apparatus, markedly increased intracellular microfilaments, decreased proteoglycan granules, and broken collagen networks in all stages of osteoarthritis. By contrast, Golgi apparatus and other organelles were well developed in histologically normal mice of all ages. Proteoglycan granules, which mainly consisted of keratan sulphate, were observed; collagen networks were maintained. CONCLUSION: Disturbed protein transport and sugar synthesis in chondrocytes, caused by the deficient development of the Golgi apparatus, could result in degenerative changes in articular cartilage. The structure and function of the matrix were maintained mainly because of the continued presence of keratan sulphate.

Clinical results of modified Mitchell's osteotomy for hallux valgus augmented with oblique lesser metatarsal osteotomy.

PURPOSE: To evaluate postoperative results of modified Mitchell's osteotomy and its combination with oblique metatarsal osteotomy for the treatment of hallux valgus. METHODS: A total of 93 feet of 53 patients (2 men and 51 women) with hallux valgus underwent modified Mitchell's osteotomy and were followed up for at least 5 years. Patients' age ranged from 17 to 83 years, and the duration of follow-up ranged from 5 years one month to 18 years 4 months. Modified Mitchell's osteotomy was performed on 53 feet in 31 patients (group A), whereas modified Mitchell's osteotomy augmented with oblique lesser metatarsal osteotomy was performed to the remaining 40 feet in 22 patients (group B). Postoperative results were assessed using a clinical assessment system developed by the Tokyo Medical University based on 5 categories: pain in the first metatarsophalangeal, deformity of the metatarsophalangeal, plantar callosity and/or metatarsalgia of lesser metatarsals, the use of commercially available shoes, and local inflammatory symptoms. RESULTS: Mean total score improved from 3.8 to 7.9 on a 10-point scale. Scores for 2 categories--plantar callosity and/or metatarsalgia and the use commercially available shoes--were significantly higher in group B at postoperative 5 years. Before surgery, at postoperative 3 weeks, and at postoperative 5 years, respectively, the mean hallux valgus angles were 34.2, 12.0, and 17.1 degrees; mean M1-M2 angles were 16.7, 7.4, and 8.7 degrees; mean M1-M5 angles were 34.9, 25.8, and 26.6 degrees; and mean sesamoid bone shifts were 8.7 mm, 4.3 mm, and 5.9 mm. CONCLUSION: Modified Mitchell's osteotomy shortens the length of the first metatarsal bone and thus relieves tension in soft tissues such as the adductor hallucis. Nonetheless, the procedure can induce metatarsophalangeal joint malalignment and metatarsalgia, and plantar callosity may develop or persist after surgery. Combining oblique metatarsal osteotomy of the lesser metatarsal bones is useful in patients with uneven metatarsal bone lengths and metatarsophalangeal joint malalignment.

Clinical effects of recombinant human granulocyte colony-stimulating factor in leukemia patients: a phase I/II study.

A phase I/II study of recombinant human granulocyte colony-stimulating factor (rhG-CSF) in 24 leukemia patients was conducted at our institute. Recombinant human G-CSF (50-200 micrograms/m2/day) was administered i.v. In seven allogeneic bone marrow transplantation (BMT) recipients, treatment with rhG-CSF was started 5 days after BMT. Neutrophils began to increase within 3 days after the start of rhG-CSF administration in five of seven patients. The mean duration necessary for recovery of neutrophils to greater than 500/microliters was 11.3 days after BMT with rhG-CSF; 26.8 days is the figure for recovery without rhG-CSF from Japanese historical data. In seven out of eight patients who received rhG-CSF administration after the first remission-induction chemotherapy, the neutrophil counts increased from less than 300/microliters to greater than 4000/microliters within 10 days. Blasts did not increase in all patients including four acute nonlymphocytic leukemia (ANLL) patients. Severe infections such as septicemia and pneumonia, which were unable to be controlled by antibiotics only, were successfully treated with rhG-CSF and antibiotics. rhG-CSF either stimulated or inhibited myeloid leukemic cells in some refractory cases. Mild bone pain occurred in one patient while receiving rhG-CSF i.v. rhG-CSF seems to have the ability to shorten the period of neutropenia, prevent infections after allogeneic BMT and remission-induction chemotherapy for acute leukemia, and support therapy for infections.

Randomized trial of cefepime monotherapy or cefepime in combination with amikacin as empirical therapy for febrile neutropenia.

A multicenter open randomized trial was conducted to compare cefepime monotherapy with cefepime/amikacin combination (dual) therapy in treating febrile neutropenic patients with hematologic disorders. Among the 189 evaluable patients, 5.8% had microbiologically and 10.6% had clinically documented infections. Excellent response was seen in 32.6% and 45.7% of monotherapy and dual therapy recipients, respectively, at day 3 (P=.065). At day 3, patients with neutrophil counts of <500/ mu L receiving dual therapy had a better response than did those receiving monotherapy (45% vs. 27.6%; P=.024). The same was true for patients with leukemia. Adverse events were minimal, and early death was observed in 7 patients in the dual therapy group and 5 patients in the monotherapy group. Overall, cefepime monotherapy is as effective as dual therapy for the initial treatment of febrile neutropenic patients. Further study is warranted for patients with severe neutropenia and leukemia who may benefit from dual therapy.

A phase II comparative study of idarubicin plus cytarabine versus daunorubicin plus cytarabine in adult acute myeloid leukemia.

In previously untreated adult patients with acute non-lymphocytic leukemia (ANLL), idarubicin (IDA) and daunorubicin (DNR) were compared for efficacy and safety when used in combination with cytarabine (Ara-C). IDA 12 mg/m2/d and DNR 40 mg/m2/d were administered by intravenous (i.v.) bolus for 3 consecutive days (days 1 to 3), respectively, in combination with Ara-C 80 mg/m2 given by 2-hour i.v. infusion, every 12 hours for 7 consecutive days. The number of assessable patients was 32 for each group. The rate of complete remission (CR) was 59.4% (19/32) in the IDA group and 40.6% (13/32) in the DNR group. The clinical equivalence test with delta = 10% demonstrated that the remission rate in the IDA group was equal or superior (P = .010) to the DNR group. In addition, the Cochran-Mantel-Haenszel test for response means with scores of 3 (CR), 2 (partial response [PR], and 1 (no response [NR]) showed the IDA group to be significantly superior (P = .044) to the DNR group. The duration needed to attain less than 5% leukemic cells in the bone marrow tended to be shorter in the IDA group (P = .072), and in CR patients, the number of days needed to reach the nadir value for leukemic cells was significantly fewer in the IDA group (P = .037). The nadir value for WBC count was significantly lower in the IDA group (P = .022). As for adverse reactions, high incidences of diarrhea and stomatitis were observed in the IDA group, while the incidences of other adverse reactions were similar between the two groups. When the effects of the drug on the ECG were examined, significant changes in ECG parameters were observed after treatment in the DNR group but not in the IDA group. Based on these findings, it was surmised that the combination of IDA plus Ara-C is the treatment of first choice for adult ANLL patients.