Agreement and accuracy of radiographic assessment using a decision aid for medial Oxford partial knee replacement: multicentre study.

BACKGROUND: Indication for mobile-bearing partial knee replacement (PKR) is made on the basis of a radiological decision aid. This study aimed to reveal the inter-rater reproducibility and accuracy of the decision aid when used by experienced surgeons. PATIENTS AND METHODS: Anonymised radiographic image sets (anteroposterior, lateral, varus/valgus stress in 20° knee flexion, and skyline views) from 20 consecutive patients who underwent knee replacement were assessed by 12 experienced surgeons. Agreements of each section and accuracy were compared by intra-operative inspection of the status of the anterior cruciate ligament (ACL) and medial and lateral cartilage according to the protocol of Radiographic Assessment for Medial Oxford PKR. Fleiss' kappa (κ) values were used as a statistical measure. RESULTS: Full-thickness medial cartilage had the best agreement between the surgeons (κ = 94.7%) and best accuracy (94.2%). Although functioning ACL (90.8%), intact cartilage (91.7%) and full-thickness lateral cartilage defects (86.1%) were accurately diagnosed, diagnoses of deficient ACL (up to 42.5%) and partial-thickness lateral cartilage defects (11.7%) were poor; they were sometimes misdiagnosed as being intact. Moreover, agreement of lateral and valgus stress radiographs regarding intact MCL function, as well as the overall decision, was considered to be inadequate (κ = 0.47, 0.58 and 0.51, respectively). CONCLUSIONS: Although the radiological aid is useful for selection of patients who are likely to be suitable for PKR, surgeons should still carefully assess the lateral weight-bearing area for partial-thickness loss and deficiency of the ACL because they were sometimes overlooked by surgeons using radiographs. MRI will be helpful to improve the accuracy of determination of Oxford PKR indication.

Uterine relapse of Philadelphia chromosome-negative acute lymphoblastic leukemia.

The relapse of acute lymphoblastic leukemia (ALL) usually involves the bone marrow, with the central nervous system being the most frequent extramedullary site. The relapse of ALL in the female genital organs, particularly the uterus, is markedly rare. We report such a patient who developed relapse in the bone marrow and uterus. The uterine lesion, which presented as abnormal uterine bleeding, consisted of a mass on MRI and proliferation of ALL cells on histology. MRI revealed a heterogeneous high-intensity mass (T2-WI/D-WI) with a diameter of 6.8 cm, a notable decrease in the apparent diffusion coefficient (ADC), and mild enhancement by contrast enhancement study. Histological findings of the uterine cervix demonstrated the infiltration of ALL. The patient achieved remission by allogeneic haplo-identical hematopoietic stem-cell transplantation, but died of complications of the transplantation. This case suggested that attention should be paid to the uterus as a site of extramedullary relapse. In addition, abnormal uterine bleeding, which is a common sign of hormonal imbalance and hormone replacement therapy after chemotherapy, may be an initial sign of extramedullary recurrence. To confirm uterine relapse as an intractable disease, the accumulation of more cases is required.

A comparison of the dose of anesthetic agents and the effective interval from the block procedure to skin incision for ultrasound-guided supraclavicular brachial plexus block in upper extremity surgery.

OBJECTIVE: The aim of this study was to review and evaluate the selection and dose of anesthetic agents and the interval from the block procedure to skin incision for supraclavicular brachial plexus block in upper extremity surgery. METHODS: We reviewed our cases that underwent upper extremity surgery using only ultrasound-guided supraclavicular brachial plexus block in our hospital between 2011 and 2016. Adverse events during surgery were evaluated. Receiver operating characteristic (ROC) curves were constructed to investigate the relationship between the time from the end of the block procedure to skin incision and the use of local anesthesia on the surgical site. RESULTS: There were 255 patients who were divided into three groups according to the anesthetic agents used: group 1, 1% lidocaine (L) 10 ml + 0.75% ropivacaine (R) 20 ml (n = 62); group 2, L 20 ml + R 10 ml (n = 93); and group 3, L 10 ml + R 15 ml (n = 100). The rate of use of local anesthesia on the surgical site was significantly higher in group 3 than in the other two groups. There were no significant differences in the other evaluated items among the three groups. ROC curve analysis indicated that ≥24 min from the end of the block procedure to skin incision might reduce the use of local anesthesia. CONCLUSION: The total volume of anesthetic agents had an important influence on the rate of the addition of local anesthesia for surgical pain; however, the combined dose of agents did not influence the evaluation items. For effective analgesia, ≥24 min should elapse from the end of the block procedure to skin incision.

2,3-Butandione 2-monoxime inhibits skeletal myosin II by accelerating ATP cleavage.

2,3-Butandione 2-monoxime (BDM) is a widely used myosin inhibitor with an unclear mode of action. In this report, we investigated the mechanism of BDM oxime group nucleophilic reactivity on the phosphoester bond of ATP. BDM increased the ATPase activity of skeletal myosin subfragment 1 (S1) under conditions in which ATP cleavage is the rate-limiting step (K+, EDTA-ATPase activity of native S1 and Mg2+-ATPase activity of trinitrophenylated S1 and partially unfolded S1). Furthermore, the effect of BDM on the S1-bound adenosine 5'-(ß,γ-imido) triphosphate (AMPPNP) 31P NMR spectrum suggests that BDM changes the microenvironment around the phosphorus atoms of myosin-bound nucleotide. A computational search for the BDM-binding site in the adenosine 5'-[γ-thio] triphosphate (myosin-ATPγS) complex predicted that BDM is located adjacent to the nucleotide on myosin. Therefore, we propose that the BDM oxime group catalytically assists in ATP cleavage, thereby enhancing the ATPase activity of myosin in a manner analogous to pralidoxime-mediated reactivation of organophosphate-inactivated acetylcholinesterase. This is the first study suggesting that oxime provides catalytic assistance for ATP cleavage by an ATP-hydrolyzing enzyme.

Optimal Imaging Parameters for Readout-segmented EPI of the Temporal Bone.

Readout-segmented echo planar imaging (rs-EPI) is a form of multi-shot EPI. rs-EPI is affected less by susceptibility artifacts than single-shot EPI (ss-EPI), which is widely used for diffusion-weighted imaging, so rs-EPI is expected to produce less image distortion. In this study, we compared rs-EPI and conventional ss-EPI of the temporal bone region, which contains abundant amounts of air and frequently exhibits changes in magnetic susceptibility. In addition, we used a phantom to determine the optimum rs-EPI acquisition conditions for clinical use and investigated the clinical utility of rs-EPI in 20 patients (8 men, 12 women, mean age, 54.3 ± 16.7-years-old) with cholesteatoma (mean apparent diffusion coefficient on ss-EPI, 0.88 × 10(-3) ± 0.18 mm(2)/s). The images of the temporal bone region produced using rs-EPI exhibited less distortion than those obtained with ss-EPI (P < 0.05).

[A case of mycotic pseudoaneurysm of the external carotid artery following a peritonsillar abscess].

Mycotic pseudoaneurysm is a rare complication of deep neck infection. We report herein on a case of mycotic pseudoaneurysm of the external carotid artery following myelodysplastic syndrome and a peritonsillar abscess. The patient was a male in his 60s, who complained of a sore throat and swelling of the left side of his neck. CT scan of the neck showed a left peritonsillar abscess and a pseudoaneurysm of the left external carotid artery. To correspond to airway obstruction in the event that the pseudoaneurysm might rupture to the pharyngeal space, the patient was transferred to our hospital. Surgical management was not selected, since MRI taken just after the admission to our hospital demonstrated remission of the pseudoaneurysm by organization of the structure and decrease of the blood flow. An antibacterial drug and an antifungal drug, SBTPC and VRCZ, were administered to the patient, the inflammatory signs reduced and the size of the pseudoaneurysm gradually diminished without sequela. These findings strongly suggest the importance of controlling the initial neck infection by administration of appropriate antibacterial and/or antifungal drugs to avoid the expansion of the mycotic pseudoaneurysm. Furthermore, MRI was useful to assess the state of the lesion and to determine the way of management.

Phase II study of SMILE chemotherapy for newly diagnosed stage IV, relapsed, or refractory extranodal natural killer (NK)/T-cell lymphoma, nasal type: the NK-Cell Tumor Study Group study.

PURPOSE: To explore a more effective treatment for newly diagnosed stage IV, relapsed, or refractory extranodal natural killer/T-cell lymphoma, nasal type (ENKL), we conducted a phase II study of the steroid (dexamethasone), methotrexate, ifosfamide, L-asparaginase, and etoposide (SMILE) regimen. PATIENTS AND METHODS: Patients with newly diagnosed stage IV, relapsed, or refractory disease and a performance status of 0 to 2 were eligible. Two cycles of SMILE chemotherapy were administered as the protocol treatment. The primary end point was the overall response rate (ORR) after the protocol treatment. RESULTS: A total of 38 eligible patients were enrolled. The median age was 47 years (range, 16 to 67 years), and the male:female ratio was 21:17. The disease status was newly diagnosed stage IV in 20 patients, first relapse in 14 patients, and primary refractory in four patients. The eligibility was revised to include lymphocyte counts of 500/µL or more because the first two patients died from infections. No treatment-related deaths were observed after the revision. The ORR and complete response rate after two cycles of SMILE chemotherapy were 79% (90% CI, 65% to 89%) and 45%, respectively. In the 28 patients who completed the protocol treatment, 19 underwent hematopoietic stem-cell transplantation. The 1-year overall survival rate was 55% (95% CI, 38% to 69%). Grade 4 neutropenia was observed in 92% of the patients. The most common grade 3 or 4 nonhematologic complication was infection (61%). CONCLUSION: SMILE chemotherapy is an effective treatment for newly diagnosed stage IV, relapsed or refractory ENKL. Myelosuppression and infection during the treatment should be carefully managed.

Fractal dimension analysis and mathematical morphology of structural changes in actin filaments imaged by electron microscopy.

In this work, we examined structural changes of actin filaments interacting with myosin visualized by quick freeze deep-etch replica electron microscopy (EM) by using a new method of image processing/analysis based on mathematical morphology. In order to quantify the degree of structural changes, two characteristic patterns were extracted from the EM images. One is the winding pattern of the filament shape (WP) reflecting flexibility of the filament, and the other is the surface pattern of the filament (SP) reflecting intra-molecular domain-mobility of actin monomers constituting the filament. EM images were processed by morphological filtering followed by box-counting to calculate the fractal dimensions for WP (D(WP)) and SP (D(SP)). The result indicates that D(WP) was larger than D(SP) irrespective of the state of the filament (myosin-free or bound) and that both parameters for myosin-bound filaments were significantly larger than those for myosin-free filaments. Overall, this work provides the first quantitative insight into how conformational disorder of actin monomers is correlated with the myosin-induced increase in flexibility of actin filaments along their length as suggested by earlier studies with different techniques. Our method is yet to be improved in details, but promising as a powerful tool for studying the structural change of protein molecules and their assemblies, which can potentially be applied to a wide range of biological and biomedical images.

Hydration properties of adenosine phosphate series as studied by microwave dielectric spectroscopy.

Hydration properties of adenine nucleotides and orthophosphate (Pi) in aqueous solutions adjusted to pH=8 with NaOH were studied by high-resolution microwave dielectric relaxation (DR) spectroscopy at 20 °C. The dielectric spectra were analyzed using a mixture theory combined with a least-squares Debye decomposition method. Solutions of Pi and adenine nucleotides showed qualitatively similar dielectric properties described by two Debye components. One component was characterized by a relaxation frequency (f(c)=18.8-19.7 GHz) significantly higher than that of bulk water (17 GHz) and the other by a much lower f(c) (6.4-7.6 GHz), which are referred to here as hyper-mobile water and constrained water, respectively. By contrast, a hydration shell of only the latter type was found for adenosine (f(c)~6.7 GHz). The present results indicate that phosphoryl groups are mostly responsible for affecting the structure of the water surrounding the adenine nucleotides by forming one constrained water layer and an additional three or four layers of hyper-mobile water.

Hyper-mobility of water around actin filaments revealed using pulse-field gradient spin-echo 1H NMR and fluorescence spectroscopy.

This paper reports that water molecules around F-actin, a polymerized form of actin, are more mobile than those around G-actin or in bulk water. A measurement using pulse-field gradient spin-echo (1)H NMR showed that the self-diffusion coefficient of water in aqueous F-actin solution increased with actin concentration by ∼5%, whereas that in G-actin solution was close to that of pure water. This indicates that an F-actin/water interaction is responsible for the high self-diffusion of water. The local viscosity around actin was also investigated by fluorescence measurements of Cy3, a fluorescent dye, conjugated to Cys 374 of actin. The steady-state fluorescence anisotropy of Cy3 attached to F-actin was 0.270, which was lower than that for G-actin, 0.334. Taking into account the fluorescence lifetimes of the Cy3 bound to actin, their rotational correlation times were estimated to be 3.8 and 9.1ns for F- and G-actin, respectively. This indicates that Cy3 bound to F-actin rotates more freely than that bound to G-actin, and therefore the local water viscosity is lower around F-actin than around G-actin.

[Value of diffusion-weighted MR imaging in the detection of middle ear cholesteatoma].

OBJECTIVE: This study, was conducted to determine the clinical value of diffusion-weighted MR imaging (DWI) in detecting the presence of cholesteatoma. SUBJECT AND METHODS: Fifty-six patients (21 female and 35 male patients; mean age, 43 years) who underwent middle ear surgery were referred to the radiology department for a preoperative DWI study. RESULTS: DWI depicted 41 out of 48 cholesteatomas involving the middle ear cavity (sensitivity, 85.4%). Seven patients with middle ear cholesteatoma who showed negative DWI findings (false-negative cases) had limited keratin accumulation due to simple atelectasis or meticulous evacuation of keratin debris before the MRI study. No falsepositive cases were found in this study (specificity, 100%). The positive predictive value and negative predictive value were 100% and 53.3%, respectively. The minimum size of middle ear cholesteatoma detected by the current MRI system was 5mm. CONCLUSION: Diffusion-weighted MR imaging was useful for the detection of middle ear cholesteatoma.

Adenoid glioblastoma arising in a patient with neurofibromatosis type-1.

An unusual case of glioblastoma with adenoid structures arising in a 30-year-old Japanese woman with neurofibromatosis type-1 (NF1) is reported. The patient was admitted to University of Miyazaki Hospital, complaining of headache, nausea and vomiting. From the neuroradiological findings the patient was diagnosed as having glioblastoma, and the tumor was surgically resected. Histologically, the tumor consisted mainly of dark basophilic cells showing prominent tubular or glandular structures surrounded by large eosinophilic cells, in addition to the typical glioblastoma features in the periphery of the tumor. Both cells showed strong stainability with glial fibrillary acidic protein (GFAP) and S-100 protein immunohistochemically, so that the tumor was classified as adenoid glioblastoma. Several cases of glioblastoma have been reported to reveal the adenoid or epithelioid differentiation. The patients with NF1 are prone to develop malignant tumors including glioblastoma, but no cases representing adenoid glioblastoma associated with NF1 have been reported. This report is considered to be the first case of adenoid glioblastoma arising in a patient with NF1. The recognition of the existence of epithelial features of glioblastoma would be important in differential diagnosis of epithelioid tumors of the brain including metastatic carcinomas.

Cerebral blood flow abnormalities induced by transient hypothyroidism after thyroidectomy--analysis by tc-99m-HMPAO and SPM96.

UNLABELLED: The current study is an investigation of alterations in regional cerebral blood flow (rCBF) distribution in patients with transient hypothyroidism after thyroidectomy. In addition, the effects of thyroxine treatment on rCBF changes were studied. METHODS: Noninvasive rCBF measurements using 99mTc-HMPAO SPECT were performed on 24 post-thyroidectomy patients who were in a hypothyroidic state. The measurements were conducted before 131I therapy and after thyroid hormone (thyroxine) replacement. We used adjusted rCBF images (normalization of global CBF for each subject to 50 ml/100 g/min with proportional scaling) to compare these data with age-matched normal control groups (n =15) using SPM96. We also compared the absolute rCBF value of hypothyroidic patients with those of normal control groups. In addition, the association between rCBF alteration and the severity of depression was also analyzed. Finally, the effect of thyroid hormone replacement on rCBF was investigated individually using the Jack-knife test, in which patient data were compared with those from healthy volunteers. According to the result of this test, all cases were categorized into three subgroups, namely, improved, unchanged group and normal. To prove the reversibility of rCBF alteration after thyroid hormone replacement, a group comparison test between the normal controls and the improved group was done before and after thyroid hormone replacement. Similarly a group comparison test between the unchanged group and normal controls was also performed. RESULTS: In the hypothyroidic condition, there was a significant decrease in the posterior part of the bilateral parietal lobes and in part of the bilateral occipital lobes, including the cuneus. These decreased rCBF areas extended to the bilateral prefrontal cortices as deterioration became more profound. On individual analysis, 16 of 24 patients (66.7%) demonstrated rCBF reduction, while 8 patient did not show significant rCBF change (33.3%, the normal group). After thyroxine replacement, improvement of rCBF was noted in nine of 16 patients (56.3%, the improved group). In seven of 16 patients (43.7% the unchanged group), the significant low rCBF area remained unchanged. Compared with the normal controls, the improved group showed significantly decreased rCBF of the bilateral parietal lobe and the occipital lobe in the hypothyroic condition. After thyroid hormone replacement, these abnormal rCBF areas disappeared. In contrast, in the unchanged group, the significant hypoperfusion area became localized but remained. CONCLUSION: 99mTc-HMPAO SPECT and SPM96 analysis demonstrated a significant rCBF decrease in the parietal lobe and part of the occipital lobe in patients with induced transient hypothyroidism after thyroidectomy. This phenomenon might contribute to understanding of the depressive state. Recovery of rCBF after thyroid hormone replacement was confirmed in some patients. However, rCBF improvement did not always occur in every patient during the follow up period. The reversibility of rCBF in transient hypothyroidism may be dependent on individual characteristics during a short-term period.

Single-molecule imaging of the dynamic interactions between macromolecules.

In recent years, the development of single-molecule detection techniques has allowed the dynamic properties of biomolecules, which are normally obscured in conventional ensemble measurements, to be measured. One of these single-molecule detection techniques allows the measurement of dissociation and association events of individual molecules to be measured. This technique is based on the unique premise that the mobility between molecules that are bound and the mobility between those that are free in solution are different. The binding of ATP at the beginning and its dissociation at the end of the hydrolysis reaction were detected at the single-molecule level in real time. In this study, we extended this technique to image the dynamic interactions between large biomolecules (protein/protein and protein/polysaccharide). The binding and dissociation of fluorescently labeled macromolecules to partner molecules fixed on a glass surface were visualized by total internal reflection fluorescence microscopy. The dynamic interactions between the proteins in two energy conversion systems, that is, signaling proteins and enzyme molecules moving on dextran, have been measured. In these systems, the dynamic interactions were sensitive to the factors determining the chemical reactions. Thus, the dynamic interactions monitored in the single-molecule measurements provided useful information to further the understanding of the underlying mechanisms of energy conversion systems.

Myosin-induced volume increase of the hyper-mobile water surrounding actin filaments.

Microwave dielectric spectroscopy can measure the rotational mobility of water molecules that hydrate proteins and the hydration-shell volume. Using this technique, we have recently shown that apart from typical hydrating water molecules with lowered mobility there are other water molecules around the actin filaments (F-actin) which have a much higher mobility than that of bulk water [Biophys. J. 85 (2003) 3154]. We report here that the volume of this water component (hyper-mobile water) markedly increases without significant change of the volume of the ordinary hydration shell when the myosin motor-domain (S1, myosin subfragment-1) binds to F-actin. No hyper-mobile component was found in the hydration shell of S1 itself. The present results strongly suggest that the solvent space around S1 bound to F-actin is diffusionally asymmetric, which supports our model of force generation by actomyosin proposed previously [op. cit.].

Modulation of actomyosin motor function by 1-hexanol.

This study examines the effects of 1-hexanol as a perturbing agent on actomyosin ATPase and its related functions in the concentration range between 0 and 20 mM. In this range the denaturation of myosin subfragment 1 (S1), as measured by the inactivation rate of its K-EDTA-ATPase, and depolymerization of F-actin were insignificant. Major findings showed that hexanol had the following effects which were fully reversible, (a) a marked activation of S1 MgATPase (approximately 10-fold at 20 mM) without greatly affecting the enhancement of tryptophan fluorescence by formation of S1.ADP.Pi intermediate and the rate of ADP release from S1.ADP; (b) an inhibition of the maximum actin-activated ATPase activity; (c) an increase in the affinity of S1 for actin in the presence of ATP and a decrease in the presence of ADP or the absence of nucleotide; (d) a reduction in the sliding velocity of actin filaments in in vitro motility assays with myosin, and (e) a decrease in isometric tension of single skinned muscle fibers. Thus, the effects of hexanol on actomyosin interaction are distinct for the weak and strong binding states, consistent with a change in the hydrophobic interaction in the interface between myosin and actin accompanying the transition from the weak to the strong binding state. Hexanol also accelerates the Pi release from S1.ADP.Pi, which is the transition step from the weak to the strong binding state. The fact that hexanol accelerates Pi release suggests that this alcohol perturbs the S1.ADP.Pi conformation. We speculate that this intermediate-specific structural perturbation is related to the inhibition of the maximum actin-activated ATPase, in vitro motility, and isometric tension.

Hyper-mobile water is induced around actin filaments.

When introduced into water, some molecules and ions (solutes) enforce the hydrogen-bonded network of neighboring water molecules that are thus restrained from thermal motions and are less mobile than those in the bulk phase (structure-making or positive hydration effect), and other solutes cause the opposite effect (structure-breaking or negative hydration effect). Using a method of microwave dielectric spectroscopy recently developed to measure the rotational mobility (dielectric relaxation frequency) of water hydrating proteins and the volume of hydration shells, the hydration of actin filament (F-actin) has been studied. The results indicate that F-actin exhibits both the structure-making and structure-breaking effects. Thus, apart from the water molecules with lowered rotational mobility that make up a typical hydration shell, there are other water molecules around the F-actin which have a much higher mobility than that of bulk water. No such dual hydration has been observed for myoglobin studied as the representative example of globular proteins which all showed qualitatively similar dielectric spectra. The volume fraction of the mobilized (hyper-mobile) water is roughly equal to that of the restrained water, which is two-thirds of the molecular volume of G-actin in size. The dielectric spectra of aqueous solutions of urea and potassium-halide salts have also been studied. The results suggest that urea and I(-) induce the hyper-mobile states of water, which is consistent with their well-known structure-breaking effect. The molecular surface of actin is rich in negative charges, which along with its filamentous structure provides a structural basis for the induction of a hyper-mobile state of water. A possible implication of the findings of the present study is discussed in relation to the chemomechanical energy transduction through interaction with myosin in the presence of ATP.

Osteoma of the frontal sinus complicated by intracranial mucocele.

We present a rare case of intracranial mucocele associated with frontal sinus osteoma in a patient suffering from generalized convulsion. The intracranial mucocele occurs as a complication of obstruction of sinus drainage caused by osteoma, but it is often diagnosed preoperatively as an intracranial or intracerebral cyst because of the rarity of these combined lesions in neurosurgical practice. However, once the mucocele extends intracranially, several other complications, including infections and/or a convulsion, can occur, indicating the necessity for surgical treatment. Moreover, the differentiation of the mucocele from the intracranial endodermal cyst predominantly depends upon its continuity with the intracranial osteoma portion or the sinus. Thus, knowledge of this rare lesion is important for accurate diagnosis and clinical management.

Hepatocyte nuclear factor-4 alpha/gamma and hepatocyte nuclear factor-1 alpha as causal factors of interindividual difference in the expression of human dihydrodiol dehydrogenase 4 mRNA in human livers.

Human dihydrodiol dehydrogenase (DD) catalyses the oxidation of trans-dihydrodiols of polycyclic aromatic hydrocarbons and the reduction of several ketone-containing drugs. About 40-fold interindividual difference in DD activities has been noted. Recently, we found that transcriptional factors, hepatocyte nuclear factor (HNF)-1 alpha, HNF-4 alpha and HNF-4 gamma were essential for the expression of DD4 mRNA, which is a major form of DDs. Thus, to clarify a possible mechanism(s) underlying the interindividual difference in DD activities, we investigated the sequences of genes and the expression levels of mRNA for DD4 and HNFs in human livers. We found no clear relationship between the genotypes of DD4 and HNF genes and the expression levels of DD4 mRNA in the subjects. The expression level of DD4 mRNA significantly correlated with that of HNF-1 alpha, HNF-4 alpha or HNF-4 gamma. These results suggest that the expression level of DD4 mRNA is cooperatively regulated by the amounts of HNF-1 alpha, HNF-4 alpha and HNF-4 gamma.