Huge Pseudoaneurysm of the Femoral Artery after Internal Fixation of Femoral Trochanteric Fracture.

Pseudoaneurysm is one of the most serious complications of femoral trochanteric fracture surgery. Since the rupture of pseudoaneurysm may lead to death, early detection is important. We report the case of an 80-year-old male who developed pain in the proximal thigh and severe swelling after internal fixation of a femoral trochanteric fracture with a hip nail. Angiography revealed a pseudoaneurysm of a branch of the deep femoral artery near the interlocking screw. The vascular lesion was immediately treated by transcatheter embolization, and the vascular leakage was completely resolved with catheter embolization. After embolization, the patient's clinical state improved rapidly, and the laboratory values improved to normal after several weeks. The current case study reminds us that pseudoaneurysm can occur after intramedullary nail placement to treat a femoral trochanteric fracture.

Evaluation of a relapse-prevention program for methamphetamine-dependent inmates using a self-teaching workbook and group therapy.

AIM: The aim of this study was to evaluate the effect of a relapse-prevention program for methamphetamine (MAP)-dependent inmates in a prison. METHODS: Participants were 251 male inmates with MAP-abuse problems. We compared scores on the Self-efficacy Scale for Drug Dependence (SSDD) and the Stages of Change Readiness and Treatment Eagerness Scale (SOCRATES) before and after intervention with a self-teaching workbook and group therapy. RESULTS: For all participants, only SSDD scores increased during the pre-intervention period. SOCRATES-8D scores increased after the start of the intervention using the self-teaching workbook, and both SSDD and SOCRATES-8D scores increased when group therapy was implemented. Changes in scores in participants with moderate and high MAP dependence were considerably different from the scores of those with low dependence during the pre-intervention and the self-teaching workbook periods. CONCLUSION: Intervention using a self-teaching workbook and group therapy in prisons might be effective for inmates with more than moderate severity of MAP abuse.

Immunochromatographic detection of the group B streptococcus antigen from enrichment cultures.

Group B Streptococcus (GBS; Streptococcus agalactiae) is a leading cause of serious neonatal infections. The Centers for Disease Control and Prevention recommends GBS screening for all pregnant women during the 35th to 37th weeks of gestation. Although GBS screening has been performed mainly by the culture-based method, it takes several days to obtain a reliable result. In this study, we developed a rapid immunochromatographic test (ICT) for the detection of GBS-specific surface immunogenic protein in 15 min using an overnight enrichment culture. The ICT was prepared using two anti-Sip monoclonal antibodies. This ICT was able to detect recombinant Sip levels of 0.5 ng/ml, or about 10(6) CFU/ml of GBS cells, in tests with 9 GBS strains of different serotypes. The cross-reactivity test using 26 species of microorganism showed no detectable false-positive result. Reactivity of the ICT with 229 GBS strains showed one false-negative result that was attributable to the production of truncated Sip. Among 260 enrichment cultures of vaginal swabs, 17 produced red to orange pigments in Granada medium, and they were all GBS and Sip positive. Among 219 pigment-negative cultures, 12 were GBS positive and 10 were Sip positive. Two Sip-negative cultures contained GBS cells below the limit of detection by the ICT. Among 207 GBS-negative cultures, only one was Sip positive, which was attributable to GBS cell debris. Thus, the sensitivity and specificity of the ICT appeared to be 93.1% and 99.6%, respectively. The newly developed ICT is readily applicable to clinical use in the detection of GBS.

[Evaluation of the Relapse Prevention Guidance for drug-dependent inmates: the intervention using self-teach workbook and group therapy in a "Private Finance Initiative" prison --the second report].

BACKGROUND: There has been no relapse prevention program for drug dependent inmates in Japanese prisons. Recently, "Relapse Prevention Guidance" program is provided to the adult male inmates in Harima Rehabilitation Program Center (HRPC), one of the newly founded "Private Finance Initiative" prisons. AIMS: To evaluate the effectiveness of the program by comparing the outcomes between groups of inmates with different severity level of dependence. METHODS: The program was provided to 89 subjects in HRPC. Inmates were classified into 4 groups according to the severity measured by the Drug Abuse Screening Test (DAST). After a month of waiting period, self-teaching workbook was provided to each inmate for 4 weeks. The educational program consisting of 8 weekly psychoeducational group therapies was then provided to each group of 10 inmates. The evaluation was conducted both at the beginning and at the end of the workbook and the educational program intervention by administering 2 self-reporting questionnaires; the Self-efficacy Scale for drug dependence (SES), and the 8th version of the Stages of Change Readiness and Treatment Eagerness Scale for drug dependence (SOCRATES-8D). RESULTS: Only the "mild" group showed significant increase in SES during waiting period. After the workbook intervention, "moderate" group showed significant decrease in SES, and increase in the recognition and the ambivalence subscale of the SOCRATES-8D. The same increase in the subscales of SOCRATES-8D was noted in "Severe" group. Educational program produced increase in the recognition and the taking steps subscales of SOCRATES-8D in "mild" group, increase in SES score and the taking steps subscale in "moderate", increase in SES score and total score of SOCRATES-8D in "severe" group. No significant change was noted in "very severe" group in any of the interventions. CONCLUSION: The "Relapse Prevention Guidance" is sufficiently effective, improving self-efficacy and motivation for change in drug dependent adult male inmates.

[Evaluation of the relapse prevention guidance for drug-dependent inmates: the intervention using self-teach workbook and group therapy in a "private finance initiative" prison--the first report].

BACKGROUND: In Japan, methamphetamine (MAP) abuse has been a serious problem for 60 years, and many of MAP abusers have been incarcerated in prisons as a violator of the Stimulant Control Law in Japan. AIMS: The purpose of the present study is to evaluate effectiveness of the relapse prevention guidance for drug-dependent inmates using a self-teaching workbook for drug-abusing adolescents and group therapy, conducted in the Harima Rehabilitation Program Center, one of the new prisons which the Ministry of Justice founded cooperating private enterprises as a "Private Finance Initiative" project. METHODS: We provided for 89 male drug-dependent inmates, incarcerated in the Harima Rehabilitation Program Center, with the relapse prevention guidance consisting of a self-teaching workbook and group therapy, and implement pre-and post-evaluations by the Self-efficacy Scale for Drug Dependence (SES) and the Stages of Change Readiness and Treatment Eagerness Scale, 8th version for Drug Dependence (SOCRATES-8D). RESULTS: After a waiting term, the participants were provided with a self-teaching program, subsequently with a group program. At the point of completing the waiting term, no significant changes were observed in the SES and SOCRATES-8D scores. However, at the point of completing the self-teaching program, the SES scores significantly fell, while the total SOCRATES-8D score and the scores of the two subscales, the "Recognition" and "Ambivalence," significantly rose. Further, at the point of completing the group program, the total scores of the SES and SOCRATES-8D, and the score of the two SOCRATES-8D subscales, the "Recognition" and "Taking Steps," significantly rose. CONCLUSION: The relapse prevention guidance consisting of a self-teaching workbook and group therapy, conducted in the Harima Rehabilitation Program Center, were supposed to bring same internal changes as the "Stage of Changes" model, proposed by Prochaska and DiClemente, to drug-dependent inmates.

Confirmation by IR of the preferred conformations of CFTA esters in solution: a highly reliable criterion for the stereochemistry assignment of chiral alcohols.

Direct confirmation of the preferred conformation of diastereomeric esters derived from a chiral secondary alcohol and a chiral derivatizing agent in solution, which is crucial for reliable NMR-based assignment of absolute stereochemistry of the alcohol, has been attained for the first time by examination of IR spectra of the CFTA esters.

Usefulness of transesophageal echocardiographic observation during chemotherapy for cardiac metastasis of non-Hodgkin lymphoma complicated with left ventricular diastolic collapse.

A 53-year-old man, who had been treated for penile origin diffuse large B cell type non-Hodgkin lymphoma (NHL), suffered from right femoral pain and dyspnea. Positron emission tomography (PET) revealed abnormal accumulation in his right femur and cardiac segments. Transthoracic echocardiography revealed massive localized pericardial effusion with the collapse of both ventricles and the mass-like echo in the left atrium. We performed emergent pericardiocentesis and diagnosed this case as a recurrence of NHL with cardiac metastasis. With the use of transesophageal echocardiography (TEE), we confirmed the mass-like echo around the inter-atrial septum, which directly invaded to the aortic ring and the right atrial wall. In order to evaluate the effect of chemotherapy, we performed TEE and observed the precise changes of intra-cardiac tumor size. With the use of TEE monitoring, we could select the appropriate chemotherapeutic regimen, and the tumor became smaller and finally diminished. The femoral accumulation detected by PET also disappeared. We experienced a case of cardiac metastasis of NHL complicated with left ventricular diastolic collapse due to the massive localized pericardial effusion. TEE is a useful tool to evaluate precisely the efficacy of chemotherapy for intra-cardiac tumors.

Recently intensified chemotherapy for high-grade osteosarcoma may affect fertility in long-term male survivors.

AIM: To investigate the marital status and fertility in long-term survivors of high-grade osteosarcoma. PATIENTS AND METHODS: We surveyed the marital rate (number of married persons/total number of persons) in 46 long-term survivors of osteosarcoma who were treated in our hospital between 1976 and 2002. In addition, we examined the fertility rate (number of persons having offspring/number of married persons) in 29 married patients. The participants were divided into 2 groups: one group (MC) in which moderate-dose chemotherapy was performed between 1976 and 1986; and another group (IC) in which intensive-dose chemotherapy was performed between 1987 and 2002. In each group, the fertility rate was investigated. As controls, we surveyed the marital and fertility rates in 52 siblings of the patients. RESULTS: In the patients, the marital rate was 63.0% (29/46). There was no significant difference in the marital rate between the patients and their siblings. In the patients, the overall fertility rate was 58.6% (17/29). The fertility rate of male patients in the IC group (16.7%, 1/6) was significantly lower than that of their male siblings (76.5%, 13/17) (p = 0.018). CONCLUSION: These results suggest that recently intensified chemotherapy for osteosarcoma affects fertility in long-term male survivors.

Mitral regurgitation resulting from the consecutive multiple perforations by infective endocarditis mimicking the isolated anterior mitral cleft.

A 60-year-old man, suffering from sustained cough and dyspnea on effort, was diagnosed as congestive heart failure. He did not yield the history of having fever or other inflammatory events. His physical examination disclosed a pan-systolic murmur at the apex. Transthoracic color Doppler echocardiography showed moderate to severe mitral regurgitation originated from the linear tear of the anterior mitral leaflet. The tear reached to the mid-portion of the leaflet just within the postero-medial commissure and the regurgitant flow convergence was not hemispheric, but box-like shaped, suggesting that the linear tear was the isolated mitral cleft. Transesophageal echocardiography showed the almost same findings and we found no other anomalies. Surgical treatment was selected to repair the mitral regurgitation. Under operation, we found three consecutive perforations located linearly in the anterior mitral leaflet. The mitral valve replaced with the prosthetic one. The pathological examination of the resected valve showed mucinous degeneration of the chordae tendineae and fibrinoid change without inflammatory cellular infiltration. These findings were compatible with the healed infective endocarditis. Here we experienced a curious case of mitral regurgitation, caused by consecutive three mitral perforations mimicking the isolated anterior mitral cleft.

Possible involvement of radical intermediates in the inhibition of cysteine proteases by allenyl esters and amides.

In order to investigate crystallographically the mechanism of inhibition of cysteine protease by alpha-methyl-gamma,gamma-diphenylallenecarboxylic acid ethyl ester 3, a cysteine protease inhibitor having in vivo stability, we synthesized N-(alpha-methyl-gamma,gamma-diphenylallenecarbonyl)-L-phenylalanine ethyl ester 4. Reaction of 4 with thiophenol, the SH group of which has similar pK(a) value to that of cysteine protease, produced oxygen-mediated radical adducts 6 and 7 in ambient air but did not proceed under oxygen-free conditions. Catalytic activities of two thiol enzymes including cathepsin B were also lowered in the absence of oxygen. These results suggest that cysteine protease can act through an oxygen-dependent radical mechanism.

Design of antiangiogenic hypoxic cell radiosensitizers: 2-nitroimidazoles containing a 2-aminomethylene-4-cyclopentene-1,3-dione moiety.

We designed chiral 2-nitroimidazole derivatives containing a 2-aminomethylene-4-cyclopentene-1,3-dione moiety as antiangiogenic hypoxic cell radiosensitizers. Based on results of molecular orbital calculations, the 2-aminomethylene-4-cyclopentene-1,3-dione moiety is expected to show high electrophilicity comparable to that of the 2-methylene-4-cyclopentene-1,3-dione moiety included in TX-1123 and tyrphostin AG17. We evaluated the antiangiogenic and radiosensitizing effects of the new compounds, along with other biological properties including their activities as hypoxic cytotoxicities and protein tyrosine kinase (PTK) inhibitory activities. Among the compounds tested, 5 (TX-2036) proved to be the strongest antiangiogenic hypoxic cell radiosensitizer. All the other chiral 2-nitroimidazole derivatives having 2-aminomethylene-4-cyclopentene-1,3-dione moiety tested were also antiangiogenic hypoxic cell radiosensitizers. The PTK inhibitory activity of 5 (TX-2036) showed this to be a promising and potent EGFR kinase inhibitor, having an IC(50) value of lower than 2microM. This compound also was an Flt-1 kinase inhibitor having an IC(50) value of lower than 20microM. Our results show that these chiral 2-nitroimidazole derivatives that contain the 2-aminomethylene-4-cyclopentene-1,3-dione moiety as a potent antiangiogenic pharmacophoric descriptor are promising lead candidates for the development of antiangiogenic hypoxic cell radiosensitizers.

The origin of an unusually large 19F chemical shift difference between the diastereomeric alpha-cyano-alpha-fluoro-p-tolylacetic acid (CFTA) esters of 3',4',5,7-tetra-O-methylepicatechin.

During a study on the relationship between the (19)F chemical shift difference for the diastereomeric alpha-cyano-alpha-fluoro-p-tolylacetic acid (CFTA) esters of chiral secondary alcohols and the absolute configurations of the alcohols, an unusually large 19F chemical shift difference has been observed for the CFTA esters of 3',4',5,7-tetra-O-methylepicatechin. This large chemical shift difference has been reproduced by ab initio calculations of molecular geometry and GIAO calculations of 19F chemical shifts on the stable conformations of the diastereomeric alpha-cyano-alpha-fluorophenylacetic acid (CFPA) esters of cis-flavan-3-ol as model systems. The origin of the large chemical shift difference has been further investigated using NBO analysis. This revealed that the interaction between pi(C=C) of the aryl group in the chiral auxiliary and sigma*(C--F) is a very important determinant of the 19F chemical shifts and this interaction depends on the torsion angle between the plane of aryl group and the C--F bond.

Synthetic Studies of 3-(3-Fluorooxindol-3-yl)-l-alanine.

Oxidative fluorination of several protected tryptophans 8b-g with Selectfluor proceeded smoothly in aqueous media to give a diastereomeric mixture of the corresponding 3-fluorooxindoles 9b-g. Attempted deprotection of the 3-fluorooxindoles 9b-g under various conditions did not afford 3-(3-fluorooxindol-3-yl)-l-alanine (6). Reaction of the suitably protected tryptophan derivative 16 with Selectfluor produced the fluorinated product 17. Simultaneous cleavage of all protective groups of 17 under acidic conditions successfully gave the target compound 6 in excellent yield.

Evaluation of quality of life (QOL) in long-term survivors of high-grade osteosarcoma: a Japanese single center experience.

BACKGROUND: This study aimed to evaluate the quality of life (QOL) in long-term survivors of high-grade osteosarcoma. PATIENTS AND METHODS: The QOL of 33 long-term survivors of osteosarcoma was evaluated using the Short Form 36 (SF-36) Health Survey Questionnaire. The patients were divided into a limb-sparing group (14 patients) and an amputation group (19 patients), and the QOL was compared between them. In addition, limb function was assessed using the system for functional evaluation of the limb of the American Musculoskeletal Tumor Society (MSTS score), and the relationship between the MSTS score and SF-36 scores was studied. RESULTS: The QOL of all patients was lower than the national standard concerning physical functioning but was higher than the national standards in the other parameters. The QOL of the limb-sparing group was significantly better than that of the amputation group with regard to social functioning. No significant correlation was noted between the MSTS score and the mental component summary. CONCLUSION: The QOL of the long-term survivors of osteosarcoma was satisfactory except for physical functioning. Limb-sparing surgery improved the QOL of long-term survivors of osteosarcoma with regard to social functioning, but no correlation was noted between limb function and mental QOL.

Ab initio molecular orbitals study of the conformational preference in alpha-cyano-alpha-fluorophenylacetic acid ester.

The origin of conformational preference in alpha-cyano-alpha-fluorophenylacetic acid (CFPA) methyl ester that is a model system of alpha-cyano-alpha-fluoro-p-tolylacetic acid (CFTA) esters was theoretically investigated by means of DFT and MP2 calculations. Two stable conformations having the C-F bond syn and anti to the C=O bond, respectively, were obtained for CFPA methyl ester. A small energy difference (0.9 kcal mol-1 at the MP2(fc)/6-31++G(d,p)) was found between the two conformations. From the molecular orbital analysis based on the Natural Bond Orbital analysis and supported by calculations using the Orbital Deletion Procedure technique, we found that sigma-(sigma*+pi*)(C=O) and sigma-sigma*(Ph) and pi(Ph)-sigma* hyperconjugations are the main factors responsible for the conformational preference. The role of the fluorine atom on the stereogenic center was also clarified.

Biological evaluation of 2-aryl-2-fluoropropionic acids as possible platforms for new medicinal agents.

We investigated the cyclooxygenase (COX) inhibitory and anticancer activities of 2-aryl-2-fluoropropionic acids 1a-e. These fluorinated compounds showed lower inhibitory activity toward COX-1 than the corresponding non-fluorinated compounds 2a-e with retained inhibitory activity against COX-2 resulting in modification of the balance of COX-1/COX-2 inhibitions, and they showed little anticancer activity. Interesting differences of the activities between (S)- and (R)-enantiomers were observed in some cases.

Histological vascular invasion by tumors is a risk factor for distant metastasis in malignant fibrous histiocytoma.

BACKGROUND: The appearance of distant metastasis is a fatal sign in patients with soft tissue sarcoma. Therefore, we studied the risk factors associated with distant metastasis that appear in malignant fibrous histiocytoma. MATERIALS AND METHODS: The study group comprised sixty patients treated for malignant fibrous histiocytoma at our hospital between 1991 and 2002. We retrospectively studied whether age, tumor size, tumor site, developmental form, surgical margin, local recurrence, histological subtype, vascular invasion and histological grade are risk factors associated with the appearance of distant metastasis. RESULTS: A univariate analysis showed that, for those patients older than 70 years of age, insufficient surgical margin, the presence of local recurrence and vascular invasion are significant risk factors associated with the appearance of distant metastasis. A multivariate analysis showed only the presence of vascular invasion to be a significant risk factor as well. CONCLUSION: Histological vascular invasion by tumors is a risk factor associated with distant metastasis that appears in malignant fibrous histiocytoma. Taking early measures for patients with vascular invasion is necessary to improve the prognosis.

Synthesis and optical resolution of 2-aryl-2-fluoropropionic acids, fluorinated analogues of non-steroidal anti-inflammatory drugs (NSAIDs).

We report the synthesis of optically active 2-aryl-2-fluoropropionic acids 2 as non-epimerizable mimics of 2-arylpropionic acids 1, a class of compounds which have been widely used as non-steroidal anti-inflammatory drugs (NSAIDs). This is a continuation of our research involving the design, synthesis, and evaluation of chiral fluorine-containing organic molecules as effective analogues of pharmacologically important compounds.

Mitochondrial localization of cellular prion protein (PrPC) invokes neuronal apoptosis in aged transgenic mice overexpressing PrPC.

Recent studies suggest that the disease isoform of prion protein (PrPSc) is non-neurotoxic in the absence of cellular isoform of prion protein (PrPC), indicating that PrPC may participate directly in the neurodegenerative damage by itself. Meanwhile, transgenic mice harboring a high-copy-number of wild-type mouse (Mo) PrPC develop a spontaneous neurological dysfunction in an age-dependent manner, even without inoculation of PrPSc and thus, investigations of these aged transgenic mice may lead to the understanding how PrPC participate in the neurotoxic property of PrP. Here we demonstrate mitochondria-mediated neuronal apoptosis in aged transgenic mice overexpressing wild-type MoPrPC (Tg(MoPrP)4053/FVB). The aged mice exhibited an aberrant mitochondrial localization of PrPC concomitant with decreased proteasomal activity, while younger littermates did not. Such aberrant mitochondrial localization was accompanied by decreased mitochondrial manganese superoxide dismutase (Mn-SOD) activity, cytochrome c release into the cytosol, caspase-3 activation, and DNA fragmentation, most predominantly in hippocampal neuronal cells. Following cell culture studies confirmed that decrease in the proteasomal activity is fundamental for the PrPC-related, mitochondria-mediated apoptosis. Hence, the neurotoxic property of PrPC could be explained by the mitochondria-mediated neuronal apoptosis, at least in part.