A Japanese Multicenter Study on PET and Other Biomarkers for Subjects with Potential Preclinical and Prodromal Alzheimer's Disease.

BACKGROUND: PET (positron emission tomography) and CSF (cerebrospinal fluid) provide the "ATN" (Amyloid, Tau, Neurodegeneration) classification and play an essential role in early and differential diagnosis of Alzheimer's disease (AD). OBJECTIVE: Biomarkers were evaluated in a Japanese multicenter study on cognitively unimpaired subjects (CU) and early (E) and late (L) mild cognitive impairment (MCI) patients. MEASUREMENTS: A total of 38 (26 CU, 7 EMCI, 5 LMCI) subjects with the age of 65-84 were enrolled. Amyloid-PET and FDG-PET as well as structural MRI were acquired on all of them, with an additional tau-PET with 18F-flortaucipir on 15 and CSF measurement of Aß1-42, P-tau, and T-tau on 18 subjects. Positivity of amyloid and tau was determined based on the positive result of either PET or CSF. RESULTS: The amyloid positivity was 13/38, with discordance between PET and CSF in 6/18. Cortical tau deposition quantified with PET was significantly correlated with CSF P-tau, in spite of discordance in the binary positivity between visual PET interpretation and CSF P-tau in 5/8 (PET-/CSF+). Tau was positive in 7/9 amyloid positive and 8/16 amyloid negative subjects who underwent tau measurement, respectively. Overall, a large number of subjects presented quantitative measures and/or visual read that are close to the borderline of binary positivity, which caused, at least partly, the discordance between PET and CSF in amyloid and/or tau. Nine subjects presented either tau or FDG-PET positive while amyloid was negative, suggesting the possibility of non-AD disorders. CONCLUSION: Positivity rate of amyloid and tau, together with their relationship, was consistent with previous reports. Multicenter study on subjects with very mild or no cognitive impairment may need refining the positivity criteria and cutoff level as well as strict quality control of the measurements.

Trapping of excess energy in a nano-layered microenvironment to promote chemical reactions.

Nano-layered hybrid compounds composed of a polyfluoroalkyl azobenzene surfactant (abbreviated as C3F-Azo-C6H) and layered inorganic nanosheets undergo three-dimensional morphological changes such as reversible shrinkage and expansion of interlayer spaces, and nanosheet sliding by photo-irradiation. Previously, we have investigated the photoreactivity of C3F-Azo-C6H/clay nano-layered hybrids in various microenvironments and found a remarkable enhancement in the photoreactivity for the cis-trans photo-isomerization reaction (Φcis-trans = 1.9). In this paper, nanosecond and microsecond dynamics of trans-C3F-Azo-C6H and its assembly in various microenvironments have been studied by laser flash photolysis to get deeper insight into the extraordinary reactivity of the molecular assembly in the nano-layered microenvironment. In solution, the molecular trans-C3F-Azo-C6H exhibited only a depletion of the trans-form of azobenzene upon the laser pulse excitation. On the other hand, in the case of the C3F-Azo-C6H/clay hybrid film, the depletion of the trans-form was drastically recovered in three steps on nano- and microsecond timescales. This indicates that the once reacted C3F-Azo-C6H molecule (cis-C3F-Azo-C6H) was reverted back to the trans-form after the laser pulse. It is considered that the excess energy provided by the photo-excitation, which is immediately dissipated to the surrounding media through the intermolecular vibrational modes in solution, is trapped in the nano-layered microenvironment to thermally revert the cis-form back to the trans-form. Conversely, in the case of cis-trans isomerization of the C3F-Azo-C6H/clay hybrid film upon photo-irradiation, the reactivity would be much enhanced by the additional contribution of the thermal excess energy efficiently trapped in the nano-layered microenvironment. As compared with the hydrocarbon analogue (C3H-Azo-C6H), the subsequent recovery was very much enhanced in the C3F-Azo-C6H/clay film. The polyfluoroalkyl part of the surfactant layer plays a key role in the retarded dissipation of the excess energy by photo-excitation, which might be coupled with the three-dimensional morphological motion with efficient isomerization reactions.

FOXO3 is essential for CD44 expression in pancreatic cancer cells.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most fatal types of cancer and the 5-year survival rate is only 5%. Several studies have suggested that cancer stem cells (CSCs) are thought to be involved in recurrence and metastasis and so it is essential to establish an approach targeting CSCs. Here we have demonstrated that cyclic guanosine monophosphate (cGMP) suppressed CD44 expression and the properties of CSCs in PDAC. Microarray analysis suggested that cGMP inhibited Forkhead box O3 (FOXO3), which is known as a tumor suppressor. Surprisingly, our data demonstrated that FOXO3 is essential for CD44 expression and the properties of CSCs. Our data also indicated that patients with high FOXO3 activation signatures had poor prognoses. This evidence suggested that cGMP induction and FOXO3 inhibition could be ideal candidates for pancreatic CSC.

Polybacterial aetiology and outcomes in patients with community-acquired pneumonia.

SETTING: Community-acquired pneumonia (CAP) is a common cause of morbidity and mortality worldwide. While interactions among bacterial pathogens in the respiratory tract have been studied, the impact of polybacterial aetiology on mortality has not been fully elucidated. OBJECTIVE: To investigate the impact of polybacterial aetiology on mortality, prevalence, microbial patterns and clinical characteristics among CAP patients. DESIGN: Retrospective data analysis. RESULTS: Bacterial aetiology was established in 711 (46.0%) of 1544 enrolled hospitalised CAP patients. Of these, polybacterial aetiology was identified in 89 (12.5%): Streptococcus pneumoniae was the most frequently identified pathogen (n = 55, 61.8%). The most prevalent microbial combination was S. pneumoniae and Haemophilus influenzae (n = 19, 21.3%). Alcoholism and lack of previous antibiotic therapy were independent predictors of polybacterial aetiology. The proportion of patients with severe pneumonia was significantly higher in the polybacterial aetiology group than in the monobacterial group. Multivariate analysis showed that polybacterial aetiology was a predictor of 30-day mortality (OR 2.14, 95%CI 1.07-4.24, P = 0.030), independently of severe pneumonia status, pneumonia severity index, chronic obstructive pulmonary disease and inappropriate empirical therapy. CONCLUSION: Polybacterial CAP tends to advance in severity, and indicates adverse outcomes.

Impact of bacterial coinfection on clinical outcomes in pneumococcal pneumonia.

The aim of this study was to investigate the influence of bacterial coinfection on patients with pneumococcal pneumonia. We retrospectively analyzed the incidence, clinical features, microbial distributions, and outcomes of patients with bacterial coinfection in a cohort of 433 hospitalized patients with pneumococcal pneumonia. Eighty-five patients (19.6 %) were diagnosed with bacterial coinfection; the most frequent pathogens were Haemophilus influenzae (25 patients, 33.3 %), methicillin-susceptible Staphylococcus aureus (MSSA) (15 patients, 20.0 %), and Moraxella catarrhalis (13 patients, 17.3 %). The CURB-65 score and pneumonia severity index (PSI) were significantly higher in patients with bacterial coinfection (both P < 0.001). In addition, the proportion of patients with bacterial coinfection who met the Infectious Disease Society of America (IDSA)/American Thoracic Society (ATS) severe pneumonia criteria was significantly higher (P < 0.001). Multivariate logistic regression analysis identified three risk factors for bacterial coinfection in patients with pneumococcal pneumonia: alcoholism (odds ratio [OR], 5.12; 95 % confidence interval (95 % CI), 1.60-16.4; P = 0.006), hospitalization for 2 days or more within 90 days preceding admission (OR, 2.02; 95 % CI, 1.03-3.98; P = 0.041), and residence in a nursing home or extended care facility (OR, 3.22; 95 % CI, 1.48-6.97; P = 0.003). Multivariate analysis for 30-day mortality showed that bacterial coinfection was a significant adverse prognostic factor (OR, 2.50; 95 % CI, 1.13-5.53; P = 0.023), independent of IDSA/ATS severe pneumonia, PSI, or healthcare-associated pneumonia. In conclusion, bacterial coinfection may have an adverse impact on severity and outcomes of pneumococcal pneumonia.

Effect of highly lipolyzed goat cheese on HL-60 human leukemia cells: antiproliferative activity and induction of apoptotic DNA damage.

To establish cheese as a dairy product with health benefits, we embarked on examining the multifunctional role of cheeses, especially in the field of cancer prevention. The current study was designed to investigate whether different types of commercial goat cheeses may possess antiproliferative activity, using an HL-60 human promyelocytic leukemia cell line as a cancer cell model. Among 11 cheese extracts tested at 500µg/mL, 6 (Crottin de Chavignol, Pouligny Saint-Pierre, Chabichou du Poitou, Valencay, Kavli, and Sainte-Maure de Touraine) resulted in a significant decrease of cell viability, which is consistent with a decrease in viable cell number. Compared with the half-maximal inhibitory concentration (IC(50)) value of individual cheeses in cellular proliferation assays, the Pouligny Saint-Pierre extract showed strong inhibition. Incubation of cells in the presence of Pouligny Saint-Pierre extract resulted in induction of cellular morphological changes and apoptotic DNA fragmentation as well as expression of the active form of caspase-3 protein. Based on the quantification of the ratio of free fatty acids to triglycerides in different cheese samples, a significant correlation was detected between lipolytic ripeness and IC(50) values for antiproliferative capacity tested in HL-60 cells. Collectively, these results support a potential role of highly lipolyzed goat cheeses in the prevention of leukemic cell proliferation.

Predictive factors for radiation pneumonitis in oesophageal cancer patients treated with chemoradiotherapy without prophylactic nodal irradiation.

OBJECTIVE: The objective of this study was to identify clinical and dosimetric factors for the development of radiation pneumonitis (RP) among patients with oesophageal cancer treated with three-dimensional radiotherapy without prophylactic nodal irradiation. METHODS: 125 patients with oesophageal cancer had undergone dose-volume histogram (DVH) metrics and received chemoradiotherapy (CRT). Several clinical and dosimetric factors with regard to the lung were evaluated as predictive factors for the development of symptomatic RP. RESULTS: 26 patients (20.8%) developed symptomatic RP classified as greater than or equal to Grade 2. By univariate analysis, body weight loss, tumour length, Stage IV, response to treatment and all DVH parameters proved to be significant factors for the development of RP (p < 0.05). By multivariate analysis, Stage IV and all dosimetric factors were independent predictive factors for the development of symptomatic RP (p < 0.05). Recursive partitioning analysis indicated that V10 values of 24.8% or more and Stage IV were associated with higher development of RP (odds ratio 6.53). CONCLUSIONS: Our study demonstrated that severe RP was also developed in patients treated with the minimal radiation field. Stage IV and the dosimetric factors were identified as independent predictive factors for symptomatic RP in oesophageal cancer patients treated with CRT without prophylactic nodal irradiation.

SU-E-T-555: Weighted Four-Dimensional IMRT Planning for Dynamic MLC Tracking Using a Practical and Simple Framework.

PURPOSE: We present a simple, practical framework for truly 4D lung IMRT planning based on a weighted individual-phase optimization paradigm. This strategy is specifically developed for use in real-time tumor tracking delivery systems so as to utilize respiratory motion as an additional degree of freedom rather than a constraint. METHODS: A 4D-CT scan from a lung SBRT patient was loaded into the Eclipse treatment planning system. The target and normal structures were manually contoured on each of the ten phases. For each phase, the total dose prescription was scaled by the number of phases and a seven-field plan was developed. An open-source deformable image and dose registration engine (DIRART) was used to deform the dose map at each phase to a reference phase. DVH data from the individually optimized phase plans were input into an in-house linear programming-based optimizer implemented in MATLAB, in order to determine dose-weighting factors for each phase. The objective function aimed to maintain PTV coverage while keeping normal structure dose as low as possible. This weighted-4D plan (W-4D) was compared to an ITV-based plan and a 4D plan with equal dose-weights to individual phases (E-4D). RESULTS: The W-4D dose fractions were determined to be 0.33, 0.01, 0.65 and 0.02 at phase 0%, 30%, 40%, and 90%, respectively (and zero elsewhere). PTV coverage (V95) was close to identical for all three strategies. The W-4D plan exhibited mean lung dose 18.8% and 8.5% lower and mean liver dose 23.3% and 5.7% lower than corresponding values from ITV-based and E-4D plans, respectively. CONCLUSIONS: By significantly improving normal structure sparing while maintaining PTV coverage, weighted 4D planning represents a more attractive solution than ITV-based planning for (currently investigational) real-time tumor tracking-based delivery systems.

SU-E-J-165: Development of a Low-Cost and Clinically Available Patient Intrafraction Motion Monitoring System.

PURPOSE: We have developed a flexible system in order to monitor the intrafraction motion. The purpose of our study is to extend the monitoring system to clinically available system with low cost. METHODS: Our system is composed of a standard web camera with a low-cost and 8x magnitude telescope, a personal computer with our in-house software and a specific marker box. The telescopic lens was attached with the web camera to extend more effective distance of the measurement in order to avoid patient's interference. The dynamic calibration algorithm was developed to take into account patient's rotation during treatment in order to measure the intrafraction motion more accurately. Tracking three markers simultaneously based on a template matching technique using parallel CPU computing was performed to measure the intrafraction motion with dynamic calibration. To evaluate our new system, a respiratory motion QA phantom with 10 mm-amplitude was used in order to measure the amplitudes under the different angles of web camera setting (0 to 50 degree, 5 degree step) using our system and Varian Real-Time Position Management Respiratory Gating (Varian-RPM) System. The results of our system were compared with the results of Varian-RPM System. RESULTS: The result of the amplitudes measured by our system and Varian RPM-System are 10.2±0.3 mm and 10.3±0.1mm at the angle of 0 deg., respectively. The values of both systems were within the tolerance value of AAPM Task group 142. The results of the amplitude of our system and Varian-RPM system were 10.2±0.3mm and 10.4±0.1mm, respectively, while the angle was changed. Under the parallel CPU computing, the calculation time to measure the position of the marker was about 50msec including the latency. CONCLUSIONS: Our proposed system could have clinically acceptable accuracies. The system would be contributed broadly to improve the treatment accuracy because of low-cost installation of it.

Efficacy and safety of vildagliptin and voglibose in Japanese patients with type 2 diabetes: a 12-week, randomized, double-blind, active-controlled study.

AIM: To confirm the efficacy of vildagliptin in patients with type 2 diabetes (T2D) by testing the hypothesis that glycosylated haemoglobin (HbA1c) reduction with vildagliptin is superior to that with voglibose after 12 weeks of treatment. METHODS: In this 12-week, randomized, double-blind, active-controlled, parallel-group study, the efficacy and safety of vildagliptin (50 mg bid, n = 188) was compared with that of voglibose (0.2 mg tid, n = 192) in patients with T2D who were inadequately controlled with diet and exercise. RESULTS: The characteristics of two groups were well matched at baseline. The mean age, body mass index (BMI) and HbA1c were 59.1 years, 24.9 kg/m(2) and 7.6%, respectively. At baseline, fasting plasma glucose (FPG) and 2-h postprandial glucose (PPG) were 9.01 mmol/l (162.2 mg/dl) and 13.57 mmol/l (244.3 mg/dl), respectively. The adjusted mean change in HbA1c from baseline to endpoint was -0.95 +/- 0.04% in the vildagliptin-treated patients and -0.38 +/- 0.04% in those receiving voglibose (between-group change = 0.57 +/- 0.06%, 95% confidence interval (CI) (-0.68 to -0.46%), p < 0.001), showing that vildagliptin was superior to voglibose. Endpoint HbA1c < or = 6.5% was achieved in 51% vildagliptin-treated patients compared with 24% patients who were on voglibose (p < 0.001). Vildagliptin also exhibited significantly (p < 0.001) greater reduction compared with voglibose in both FPG [1.34 vs. 0.43 mmol/l (24.1 vs. 7.8 mg/dl)] and 2-h PPG [2.86 vs. 1.1 mmol/l (51.5 vs. 19.8 mg/dl)]. Overall adverse events (AEs) were lower in the vildagliptin-treated patients compared with that in the voglibose-treated patients (61.2 vs. 71.4%), with no incidence of hypoglycaemia and serious adverse events with vildagliptin. Gastrointestinal AEs were significantly lower with vildagliptin compared with that of the voglibose (18.6 vs. 32.8%; p = 0.002). CONCLUSIONS: Vildagliptin (50 mg bid) showed superior efficacy and better tolerability compared with voglibose in Japanese patients with T2D.

Isolation and characterization of a potentially virulent species Entamoeba nuttalli from captive Japanese macaques.

We have recently proposed revival of the name Entamoeba nuttalli Castellani, 1908 for a virulent amoeba (P19-061405 strain) isolated from a rhesus monkey (Macaca mulatta) and located phylogenetically between E. histolytica and E. dispar. In this study, E. nuttalli was isolated from feces of captive Japanese macaques (M. fuscata) in an open-air corral in Japan. The sequence of the 18S rRNA gene in the isolates differed from the P19-061405 strain in 2 nucleotide positions, but was identical to the EHMfas1 strain isolated previously from a cynomolgus monkey (M. fascicularis). One of the E. nuttalli isolates from Japanese macaques, named the NASA6 strain, was axenized and cloned. In isoenzyme analysis, the mobilities of hexokinase and phosphate glucose isomerase in the NASA6 strain were identical to those in the P19-061405 and EHMfas1 strains, but the mobility of phosphoglucomutase was different. These results were supported by gene analyses of these enzymes. Inoculation of NASA6 strain trophozoites into the liver of hamsters led to formation of an amoebic liver abscess. The liver lesions were characterized by extensive necrosis associated with inflammatory reactions. These results demonstrate that the NASA6 strain is potentially virulent and that E. nuttalli should be recognized as a common parasite in macaques.

A comparison of radiation treatment plans using IMRT with helical tomotherapy and 3D conformal radiotherapy for nasal natural killer/T-cell lymphoma.

The purpose of this study was to compare radiation treatment plans (RTPs) that used intensity-modulated radiation therapy (IMRT) with helical tomotherapy (HT) or three-dimensional conformal radiation therapy (3D-CRT) for nasal natural killer/T-cell lymphoma (NNKTL). We created RTPs that used IMRT with HT or 3D-CRT for eight NNKTL patients previously treated at our institution and conducted a pilot comparison between the two modalities using the parameters of the target coverage and homogeneity for the planning target volume (PTV) and the maximum and mean doses for organs at risk (OARs). The clinical target volume (CTV) included the gross tumour volume with an additional margin of 1.5 cm and the nasopharynx, palates and nasal cavity; the PTV with the CTV plus a 2 mm margin received a total dose of 50 Gy. IMRT achieved significantly better PTV coverage, with more than 99% of the PTV receiving 90% and 95% of the prescribed dose, whereas 3D-CRT could not provide adequate coverage of the PTV, with 89.1+/-2.6% and 84.5+/-2.7% of the PTV receiving 90% and 95% of the prescribed dose, respectively (both p <0.0001). The homogeneity index was 0.29+/-0.06 for IMRT and 0.046+/-0.022 for 3D-CRT, which was statistically significant (p <0.0001). IMRT tended to provide equivalent or slightly better OAR avoidance than 3D-CRT. In conclusion, 3D-CRT could not provide adequate coverage of the PTV because the PTV was close to many OARs. IMRT should be used for NNKTL because a lack of optimal RTPs could cause local failure.

False-positive positron emission tomography appearance with 18F-fluorodeoxyglucose after definitive radiotherapy for cancer of the mobile tongue.

(18)F-fluorodeoxyglucose-positron emission tomography (FDG-PET) is an effective tool for evaluating the results of radiotherapy. However, some false-positive appearances caused by physiological or pathological accumulation are reported. We report on three patients who showed a high accumulation of FDG in the lingual muscles but had no recurrent tumour after definitive radiotherapy for the mobile tongue. All patients had squamous cell carcinoma of the tongue and received interstitial radiotherapy with small sources. High uptake was seen in the lingual muscles without recurrence or inflammation, based on physical and MR examinations. This false-positive appearance is thought to relate to ill-balanced high activity of the lingual muscles after definitive radiotherapy.

Helical tomotherapy for brain metastases: dosimetric evaluation of treatment plans and early clinical results.

The purpose of this study was to evaluate the feasibility and treatment plans of intensity-modulated radiation therapy using helical tomotherapy (HT) for brain metastases. Twenty-three patients with 1 to 4 brain metastases were treated with HT. In combination with whole-brain radiotherapy (simultaneous plans), metastatic lesions, and the whole brain were treated with 50 Gy and 30 Gy, respectively, in 10 fractions, with a simultaneous integrated boost technique. In patients treated for brain metastases alone (focal plans), metastatic lesions were treated with 35 or 37.5 Gy in 5 fractions. The treatment plans were compared regarding the conformation number (CN) and homogeneity index (HI), and differences in these indexes between simultaneous and focal plans were examined by Student's t-test. Seven and 16 patients were treated with simultaneous plans and focal plans, respectively. The mean +/- SD of CN and HI values were 0.75 +/- 0.13 and 0.063 +/- 0.042, respectively, for simultaneous plans, and 0.73 +/- 0.12 and 0.052 +/- 0.023, respectively, for focal plans. The CN and HI between the two plans were not significantly different. Response rates in 13 patients with follow-up imaging were approximately 90% for both plans and the local control rate at 1 year was 69%. One patient with a huge tumor (34.0 cc) and WHO performance status 3 treated with focal plans experienced severe headache, requiring prolongation of the treatment time, and died at 8 days after completion of treatment. The exact cause of deterioration was uncertain as no radiological investigation was performed in this patient. No late complications were observed during follow-up periods up to 20 months. HT is a viable non-invasive technique for treatment of brain metastases and achieves high accuracy in terms of dose conformity and homogeneity.

Identifying patients with peripheral-type early non-small cell lung cancer (T1N0M0) for whom irradiation of the primary focus alone could lead to successful treatment.

We investigated the indication of radiotherapy in operable patients with peripheral-type early non-small cell lung cancer (T1N0M0 (TNM staging in 1997)). The subjects comprised 396 patients with non-small cell lung cancer in whom the clinical stage was evaluated as IA. We examined age, gender, Brinkmann's index, histopathological type, the grade of histopathological differentiation, tumour diameter and the level of carcinoembryonic antigen as factors involved in lymph node metastasis. Lymph node metastasis was detected in 79 patients (20%). Factors such as the grade of histopathological differentiation and tumour diameter were involved in lymph node metastasis. In well-differentiated lesions, the probability of metastasis was <10% even when the tumour diameter exceeded 2 cm. However, the probability rapidly increased with tumour size in moderately and poorly differentiated lesions. Among the patients with peripheral-type early non-small cell lung cancer (T1N0M0), the risk of lymph node metastasis was low in those with well-differentiated carcinoma and those with moderately differentiated lesions measuring

Treatment results of boron neutron capture therapy using intra-arterial administration of boron compounds for recurrent head and neck cancer.

The effect of boron neutron capture therapy (BNCT) is correlated with the density of boron in the tumour. BNCT using intra-arterial administration of boron compounds was performed for recurrent head and neck cancer. Of the five patients treated, one achieved a complete response and four achieved a partial response. There was one case of transient headache but no severe adverse effects were observed. The advantages of using an intra-arterial administration route for BNCT, which causes the selective killing of tumour cells, might offer a new option in the treatment of recurrent head and neck malignancies. These promising results require further verification and optimization of the BNCT schedule; however, dose escalation would appear to be justified because the toxicity appears to be very low.

Intra-arterial chemoradiotherapy for locally advanced oral cavity cancer: analysis of therapeutic results in 134 cases.

The objective of this study was to investigate the therapeutic results of arterial injection therapy via the superficial temporal artery for 134 cases of stages III and IV (M0) oral cavity cancer retrospectively, and to clarify the prognostic factors. We administered intra-arterial chemoradiotherapy by continuous infusion of carboplatin in 65 cases from January 1993 to July 2002. Systemic chemotherapy was performed on 26 cases at the same time. We administered intra-arterial chemoradiotherapy by cisplatin with sodium thiosulphate in 69 cases from October 2002 to December 2006. Systemic chemotherapy was performed on 48 cases at the same time. The 3-year local control rate was 68.6% (T2-3: 77.9%; T4: 51.3%), and the 3-year survival rate was 53.9% (stage III: 62.9%; stage IV: 45.3%). Regarding the results of multivariate analysis of survival rates, age (<65), selective intra-arterial infusion, and the use of cisplatin as an agent for intra-arterial infusion were significant factors. The therapeutic results of intra-arterial chemoradiotherapy via the superficial temporal artery were not inferior to the results of surgery. In particular, the results of arterial injection therapy by cisplatin with sodium thiosulphate were excellent, so we believe that it will be a new therapy for advanced oral cavity cancer.

Pramipexole safely replaces ergot dopamine agonists with either rapid or slow switching.

This prospective, open-label, multicentre study examined the efficacy and safety of rapidly (overnight) or slowly (after 2 weeks of concomitant usage) switching patients with Parkinson's disease (PD) from conventional ergot dopamine agonists (DAs) to the non-ergot DA, pramipexole. Fifty-nine early-to-advanced PD patients with motor symptoms that were inadequately controlled by ergot DAs were enrolled. Patients were switched from ergot derivatives to pramipexole and evaluated every 2 weeks for 12 weeks by Hoehn and Yahr staging, Unified Parkinson's Disease Rating Scale (UPDRS) and a modified Epworth Sleepiness Scale (mESS). The UPDRS III subscores and total UPDRS scores significantly improved, independent of switching method. Adverse events, all of which were mild, occurred in 29.2% of patients. No sudden onset of excessive daytime sleepiness or significant worsening in mESS was seen. Switching patients with PD from ergot DA to pramipexole, using either a slow or rapid switching method, appeared to be well tolerated and effective, although further dose adjustment may be necessary in some patients after the switch.

Primary structure, expression and localization of two intermediate subunit lectins of Entamoeba dispar that contain multiple CXXC motifs.

We have recently identified 2 surface proteins in Entamoeba histolytica as intermediate subunits of galactose- and N-acetyl-D-galactosamine-inhibitable lectin (EhIgl1 and EhIgl2); these proteins both contain multiple CXXC motifs. Here, we report the molecular characterization of the corresponding proteins in Entamoeba dispar, which is neither pathogenic nor invasive. Two Igl genes encoding 1110 and 1106 amino acids (EdIgl1 and EdIgl2) were cloned from 2 strains of E. dispar. The amino acid sequence identities were 79% between EdIgl1 and EdIgl2, 75-76% between EdIgl1 and EhIgl1, and 73-74% between EdIgl2 and EhIgl2. However, all the CXXC motifs were conserved in the EdIgl proteins, suggesting that the fold conferred by this motif is important for function. Comparison of the expression level of the Igl genes by real-time RT-PCR showed 3-5 times higher expression of EdIgl1 compared to EdIgl2. Most EdIgl1 and EdIgl2 proteins were co-localized on the surface and in the cytoplasm of trophozoites, based on confocal microscopy. However, a different localization of EdIgl1 and EdIgl2 in intracellular vacuoles and a different level of phenotypic expression of the two Igls were also observed. These results demonstrate that Igls are important proteins even in non-pathogenic amoeba and that Igl1 and Igl2 may possess different functions.

Bite force, occlusal contact area and masticatory efficiency before and after orthognathic surgical correction of mandibular prognathism.

The purpose of this study was to evaluate bite force, occlusal contact area and masticatory efficiency before and after sagittal split ramus osteotomy in 27 patients with mandibular prognathism, in comparison with 27 control subjects with normal occlusion. Bite force and occlusal contact area were simultaneously measured with a computerized occlusal analysis system, the Dental Prescale system. Masticatory efficiency was estimated by a low-adhesive colour-developing chewing-gum system. The data were collected at initial medical consultation, immediately before surgery, and at 6 weeks, 3 months, 6 months, 1 year and more than 2 years after surgery. Both bite force and occlusal contact area of the patients before surgery were significantly less than those of the controls. Although all three parameters had improved after orthognathic surgery, the bite force and occlusal contact area did not reach the values of the controls within 2 years postoperatively; masticatory efficiency at 2 years after surgery drew near to control levels. Bite force correlated with occlusal contact area in the patients postoperatively, whereas masticatory efficiency did not correlate with either of the other two parameters. These results suggest that further adjustment of occlusion and mechanical advantage should be considered before the end of treatment.