bluuebunny/crossref_metadata_2025 huggingface dataset:
Training in Mental Singing while Walking Improves Gait Disturbance in Parkinson’s Disease Patients
Authors: Satoh Masayuki , Kuzuhara Shigeki
Published: September 2008

Patients with Parkinson’s disease (PD) have various types of gait disturbance that are thought to result from impairments in motor timing. Gait disturbances are markedly improved with the use of appropriate visual and auditory cues. In this study, patients suffering from mild to moderate PD underwent a structured music therapy session in which they were trained to walk while mentally singing. The patients were trained in 7 progressive tasks, with a final goal of walking while mentally singing. Before and after the training session, they were videotaped. The video was analyzed for time and steps while walking straight paths and while turning. After a single session of training, the time and steps were significantly improved in both situations. Follow-up interviews with the patients indicated that they effectively utilized mental singing while walking in their daily lives. We propose that singing regulates basal ganglia function and allows patients with PD to keep time regularly. The task used in the present study was simple, required no special tools, and could be utilized anytime and anyplace. Thus, walking while mentally singing has potential for improving the gait of individuals with PD.
Perfusion CT Imaging Follows Clinical Severity in Left Hemispheric Strokes
Authors: Furtado A.D. , Smith W.S. , Koroshetz W. , Dillon W.P. , Furie K.L. , Lev M.H. , Vittinghoff E. , Schaeffer S. , Biagini T. , Hazarika O. , Wintermark M.
Published: September 2008

Objective: The purpose of this study was to assess how imaging findings on admission perfusion CT (PCT) and follow-up noncontrast CT (NCT), and their changes over time, correlate with clinical scores of stroke severity measured on admission, at discharge and at 6-month follow-up. Methods: Fifty-two patients with suspected hemispheric acute ischemic stroke underwent a PCT within the first 24 h of symptom onset and a follow-up NCT of the brain between 24 h and 3 months after the initial stroke CT study. NIH Stroke Scale (NIHSS) scores were recorded for each patient at admission, discharge and 6 months; modified Rankin scores were determined at discharge and 6 months. Baseline PCT and follow-up NCT were analyzed quantitatively (volume of ischemic/infarcted tissue) and semiquantitatively (anatomical grading score derived from the Alberta Stroke Program Early CT Score). The correlation between imaging volumes/scores and clinical scores was assessed. Analysis was performed for all patients considered together and separately for those with right and left hemispheric strokes. Results: Significant correlations were found between clinical scores and both quantitative and semiquantitative imaging. The volume of the acute PCT mean transit time lesion showed best correlation with admission NIHSS scores (R2 = 0.61, p < 0.001). This association was significantly better for left hemispheric strokes (R2 = 0.80, p < 0.001) than for right hemispheric strokes (R2 = 0.39, p = 0.131). Correlation between imaging and NIHSS scores was better than correlation between imaging and modified Rankin scores (p = 0.047). The correlation with discharge clinical scores was better than that with 6-month clinical scores (p = 0.012). Conclusions: Baseline PCT and follow-up NCT volumes predict stroke severity at baseline, discharge and, to a lesser extent, 6 months. The correlation is stronger for left-sided infarctions. This finding supports the use of PCT as a surrogate stroke outcome measure.
Independent Role of Hypertension in Bell’s Palsy: A Case-Control Study
Authors: Savadi-Oskouei Daryoush , Abedi Ali , Sadeghi-Bazargani Homayoun
Published: September 2008

Background/Aim: In this case-control study, our aim was to check for a possible independent role of hypertension in increasing the risk of developing Bell’s palsy. Methods: All patients diagnosed as having Bell’s palsy referred to a neurology clinic were enrolled as cases. Controls were selected among other patients referred to the same clinic. Data were analyzed using the Stata 8 statistical software package. To detect the independent effect of exposure variables, a multiple logistic regression test was used. Results: Bivariate analysis showed an increased risk of Bell’s palsy for patients with diabetes or hypertension. Logistic regression results stratified for patients younger than 40 years of age and others showed that diabetes was the independent predictor of Bell’s palsy in both age groups. Logistic regression results showed that hypertension could not independently predict the occurrence of Bell’s palsy among patients younger than 40 years but for older ones it could. Conclusion: Hypertension may increase the risk of Bell’s palsy among those aged above 40 years. Researchers should be very cautious when declaring an independent role of hypertension as a cause of Bell’s palsy.
Combined Transcranial Doppler and EEG Recording in Vasovagal Syncope
Authors: Vicenzini E. , Pro S. , Strano S. , Pulitano P. , Altieri M. , Di Piero V. , Lenzi G.L. , Accornero N. , Mecarelli O.
Published: September 2008

Background: In neurally mediated syncope a ‘typical’ EEG pattern during hyperventilation (HV) may be observed. This study aimed to investigate transcranial Doppler (TCD) and EEG variations in response to hyper- and hypocapnia using simultaneous recording. Methods: Syncope patients with a typical EEG pattern during HV (SEEG+, n = 15) and those without abnormalities (SEEG–, n = 16) were compared with healthy controls (n = 20). Simultaneous TCD and EEG recordings were performed at rest (baseline), during 2 apnea tests and during HV. Cerebrovascular vasoreactivity, index for hypocapnia, total vasomotor reserve and time to flow velocity normalization after HV (t-norm) were recorded. Results: With TCD, a reduction in Vasomotor reserve was observed in SEEG+ compared with the other 2 groups (control: 67 ± 8%; SEEG–: 67 ± 10%; SEEG+: 57 ± 8%; p < 0.0001). t-norm was longer in all syncopal patients and in particular in SEEG+ (control: 20.2 ± 3 s; SEEG–: 40 ± 7 s; SEEG+: 123 ± 45s; p < 0.0001). Quantitative EEG showed an increase in slow bands in all subjects during HV, small and nonsignificant in controls and SEEG–, higher and significant in SEEG+, related with flow reduction. Conclusions: Changes in the sympathetic modulation of cerebral vasoconstriction may explain both the pathophysiology of vasovagal syncope and the typical paroxysmal EEG findings.
Enhancement of Ultrasonically Induced Cytotoxic Effect by Hematoporphyrin in vitro
Authors: Wang Pan , Wang Xiao Bing , Liu Quan Hong , Tang Wei , Li Tao
Published: September 2008

It was the aim of this study to investigate the ultrasonically induced cytotoxic effect of hematoporphyrin (Hp) on isolated sarcoma 180 (S180) cells and to explore the potential biological mechanism of this action. S180 tumor cells suspended in air-saturated phosphate-buffered saline (pH 7.2) were exposed to ultrasound at 1.6 MHz in a standing wave mode for up to 90 s with and without 100 µg/ml Hp. The intracellular Hp concentration was evaluated to determine the optimum timing of ultrasound exposure after its administration with a fluorescence spectrophotometer based on the standard curve. Cell viability was determined by the trypan blue exclusion test. The morphological changes of S180 cells induced by ultrasonic irradiation were evaluated by scanning electron microscope and transmission electron microscope observation. The participation of lipid peroxidation products in the cell damage process was investigated by the malon aldehyde content test. Our experiments suggested that an incubation time of 45 min after the addition of 100 µg/ml Hp was to be chosen as the best time for ultrasound exposure in vitro. The rate of ultrasonically induced cell damage was enhanced by the increase in ultrasound intensity and exposure time in the presence and absence of Hp. At an ultrasound intensity not less than 3 W/cm2 and an irradiation time not less than 60 s, a significant synergistic effect of ultrasound combined with Hp was observed, while no cell damage was observed with 100 µg/ml Hp alone. The malon aldehyde content test showed that the lipid peroxidation level significantly increased after sonodynamic therapy treatment. Scanning electron microscope and transmission electron microscope observation indicated that the changes in cell ultra-structure such as cell membrane destruction, mitochondria swelling and chromatin condensation are important factors that induced cell damage in S180 tumor cells. The results indicate that the biological mechanism might be involved in mediating the killing effect on S180 cells, and the ultra-structural changes may account for cell destruction induced by sonodynamic therapy treatment in our experiment mode.
Dose Escalation Study of Epirubicin and Docetaxel in Patients with Advanced or Recurrent Breast Cancer
Authors: Ichinose Ichiro , Hamada Yuzo , Mitsuyama Shoshu , Ishikawa Emi , Ikeda Tadashi , Kobayashi Sunao , Horikoshi Noboru , Tamura Kazuo
Published: September 2008

Background: Anthracyclines and taxanes are major cytotoxic drugs against breast cancer. To develop a combination of epirubicin (EPI) and docetaxel (DTX) in Japan, dose escalation and pharmacokinetic studies were performed in patients with advanced or recurrent breast cancer. Methods: Twenty patients received EPI (40, 50 or 60 mg/m2) as 5-min intravenous infusion, followed by DTX infusion (50 or 60 mg/m2) over 1 h in cohorts of 3–6 patients. The maximum tolerated dose (MTD) was defined during the first cycle when more than 2 of 3 or 3 of 6 patients suffered a dose-limiting toxicity (DLT). The DLT was based on febrile neutropenia (FN), prolonged neutropenia, thrombocytopenia and grade 3–4 nonhematological toxicity during the first cycle. Plasma sampling was performed to assess the pharmacokinetic study of these drugs. Results: The second level (EPI/DTX 50/50 mg/m2) was found to be a maximum tolerated dose because of a short duration of FN with no distress. Subsequently, the protocol was modified to permit a new DLT definition including FN lasting for more than 72 h. At the following levels of EPI/DTX 50/50, 50/60 or 60/60 mg/m2, the dose escalation study revealed a high incidence of grade 4 neutropenia (100%) and FN (67%), which did not reach DLT. However, the safety committee decided not to go further because of too high an incidence of FN lasting 3 days, although a little less than 72 h. The pharmacokinetic study with a combination of EPI and DTX showed comparable blood levels of DTX and EPI in relation to those seen when given alone. Conclusion: For further evaluation, the recommended dose and schedule of this combination is EPI 60 mg/m2 and DTX 60 mg/m2, given every 3 weeks to patients without prior chemotherapy and EPI 50 mg/m2 and DTX 50 mg/m2 given to patients with prior chemotherapy, respectively. The pharmacokinetic study indicates no interaction between EPI and DTX.
Changes in Body Mass of Expectant Male Cotton-Top Tamarins (Saguinus oedipus)
Authors: Sánchez Susana , Peláez Fernando , Fidalgo Ana , Morcillo Ana , Caperos José M.
Published: September 2008

It has been noted that expectant cotton-top tamarin males in captivity experience a body mass increase during the last months of their mates’ pregnancies, and this has been explained as being a male physiological response. We studied the body mass of 4 inexperienced and 4 experienced expectant males, and we expected to observe a larger body mass increase among the experienced ones since they undergo multiple hormonal changes in comparison to inexperienced expectant males. However, while inexperienced expectant males gained body mass during months 4–6 of the pregnancy period by a mean ±SD of 5.4 ± 3.1% (i.e. 29 ± 17 g), the experienced ones did not (mean ± SD of months 4–6, 0.5 ± 1.7%, i.e. 5 ± 12 g). The results suggest that other factors, such as behavioural communication between pairs and feeding and resting behaviour, should be studied in order to clarify the basis of this body mass increase.
Mortality at Low and High Estimated Glomerular Filtration Rate Values: A ‘U’ Shaped Curve
Authors: Cox Heidi J. , Bhandari Sunil , Rigby Alan S. , Kilpatrick Eric S.
Published: September 2008

Background: While a low estimated glomerular filtration rate (eGFR) confers an increased risk of dying, the mortality associated with high eGFR values has not been ascertained. Methods: Four variable MDRD-derived eGFR was calculated in a total of 33,386 patients (18,620 F, 14,766 M) aged ≧50 years (median 68 years, IQR 60–76 years) collected by family doctors in 2000. They were then classified according to their eGFR into 30 ml/min/1.73 m2 bands (<30, 30–59, 60–89, 90–119, 120–150). The subsequent mortality status of each patient was determined at 31st December 2006 and cause of death recorded where available. Results: Applying Cox proportional hazards models (adjusted for age and gender), the hazard ratio (HR) of dying compared to a reference of patients with eGFRs of 60–89 ml/min/1.73m2 was, as expected, higher in the low eGFR bands (HR 1.37 (95% CI 1.29–1.45) for 30–59; HR 2.60 (2.31–2.93) for <30 ml/min/1.73 m2, both p < 0.0001). However, it was also greater amongst patients with higher eGFRs (HR 1.29 (1.19–1.41) for 90–119; HR 2.63 (2.16–3.21) for 120–150 ml/min/1.73 m2, p < 0.0001). Circulatory disease was the main cause of death in patients with low eGFRs and respiratory disease/cancer, in patients with high eGFRs. Conclusions: As a marker of mortality, both low and high eGFRs are equally predictive of increased mortality in community patients, exhibiting a ‘U’ shaped curve. Thus, current CKD guidelines which recommend inaction or even the non-reporting of eGFR values greater than 60–90 ml/min/1.73 m2 may not identify patients who are at an equally high risk of dying as those where intervention is recommended.
Mizoribine Treatment of Young Patients with Severe Lupus Nephritis: A Clinicopathologic Study by the Tohoku Pediatric Study Group
Authors: Tanaka Hiroshi , Oki Eishin , Tsuruga Kazushi , Sato Norihiro , Matsukura Hiroyoshi , Matsunaga Akira , Kondo Yoshiaki , Suzuki Junzo
Published: September 2008

Background: A novel purine synthesis inhibitor, mizoribine (MZR), with a similar activity to that of mycophenolate mofetil, was developed in Japan. We suspected that long-term oral MZR intermittent pulse therapy (MZR-P) might be more effective than the conventional daily MZR regimen due to the higher peak serum MZR levels that are achieved. Here, we examined the clinicopathologic efficacy of MZR-P treatment in 10 young patients with diffuse proliferative lupus nephritis (DPLN), including 3 patients who received MZR-P as their primary cytotoxic therapy. Methods: After their most recent renal flare-ups, all the patients were treated using MZR-P combined with oral prednisolone (PDN). MZR was administered as a single daily dose of 6–10 mg/kg per day (maximum dose of 500 mg) on 2 days of the week (Monday and Thursday) for at least 12 months or longer. The concomitantly administered PDN dose was gradually reduced. Results: The baseline characteristics of the patients were as follows: mean age 15 years; urinary protein/creatinine (Up/cr) ratio 1.57 ± 1.05 mg/mg; serum C3 level 50.3 ± 19.7 mg/dl; serum complement hemolytic activity (CH50) 18.1 ± 9.9 U/ml; serum anti-dsDNA antibody titer 177.5 ± 152.7 IU/ml; serum creatinine 0.6 ± 0.1 mg/dl, and European Consensus Lupus Activity Measurement (ECLAM) index 4.9 ± 2.6. Despite the gradual tapering of the PDN dose, marked improvements compared with the baseline values were observed at the last observation, mean interval of 29 months after the start of treatment: Up/cr ratio 0.19 ± 0.14; ECLAM index 1.3 ± 0.7 (p < 0.01); serum C3 level 76.5 ± 22.1 mg/dl; serum CH50 value 31.9 ± 8.7 U/ml, and anti-dsDNA antibody titer 34.2 ± 20.5 IU/ml (p < 0.05). The serum creatinine level remained within the normal range in all study participants. Post-treatment renal biopsies were performed in 5 of the patients; histology showed a marked attenuation of lesion progression. No serious adverse effects were observed. Conclusion: We believe that long-term MZR-P may prove to be a treatment of choice for young patients with DPLN. However, confirmation is needed as this preliminary study is limited by the small number of subjects, lack of controls, and its retrospective nature.
Calcium Requirements after Parathyroidectomy in Patients with Refractory Secondary Hyperparathyroidism
Authors: Viaene Liesbeth , Evenepoel Pieter , Bammens Bert , Claes Kathleen , Kuypers Dirk , Vanrenterghem Yves
Published: September 2008

Background/Aims: Calcium supplements are often required following successful parathyroidectomy (PTX) in order to prevent overt hypocalcemia. The current study aims to quantify these calcium needs and to identify predictors of a high calcium need present at the time of surgery. Methods: Charts of 42 patients with chronic kidney disease stage 5D, who underwent a successful subtotal PTX, were reviewed in detail. Biochemical indices of mineral metabolism available within a time frame of 4 weeks before and 6 weeks after the surgery were registered. Details concerning active vitamin D (1-α-calcidiol and calcitriol) and calcium supplementation were recorded as well. Results: Serum calcium, phosphorus and PTH levels declined whereas total alkaline phosphatase levels increased significantly in the early post-PTX period. Transient hypocalcemia was observed in 83% of the patients. The median daily postoperative elemental calcium requirements amounted to 3.2 g during week 1, and declined to 2.4 g during week 6. A high preoperative PTH level and a low serum calcium level were identified as independent predictors of a high postoperative calcium need. Conclusion: Substantial amounts of elemental calcium are required following successful subtotal PTX in order to avoid frank hypocalcemia, especially in patients with a high PTH level and a low calcium level before surgery.
A Systems Approach to Prefrontal-Limbic Dysregulation in Schizophrenia
Authors: Rădulescu Anca R. , Mujica-Parodi L.R.
Published: September 2008

Introduction: Using a prefrontal-limbic dysregulation model for schizophrenia, we tested whether a dynamic control systems approach in conjunction with neuroimaging might increase detection sensitivity in characterizing the illness. Our analyses were modeled upon diagnostic tests for other dysregulatory diseases, such as diabetes, in which trajectories for the excitatory and inhibitory components of the negative feedback loops that reestablish homeostasis are measured after system perturbation. We hypothesized that these components would show distinct coupling dynamics within the patient population, as compared to healthy controls, and that these coupling dynamics could be quantified statistically using cross-correlations between excitatory and inhibitory time series using fMRI. Methods: As our perturbation, we activated neural regions associated with the emotional arousal response, using affect-valent facial stimuli presented to 11 schizophrenic patients (all under psychotropic medication) and 65 healthy controls (including 11 individuals age- and sex-matched to the patients) during fMRI scanning. We first performed a random-effects analysis of the fMRI data to identify activated regions. Those regions were then analyzed for group differences, using both standard analyses with respect to the time series peaks, as well as a dynamic analysis that looked at cross-correlations between excitatory and inhibitory time series and group differences over the entire time series. Results: Patients and controls showed significant differences in signal dynamics between excitatory and inhibitory components of the negative feedback loop that controls emotional arousal, specifically between the right amygdala and Brodmann area 9 (BA9), when viewing angry facial expressions (p = 0.002). Further analyses were performed with respect to activation amplitudes for these areas in response to angry faces, both over the entire time series as well as for each time point along the time series. While the amygdala responses were not significantly different between groups, patients showed significantly lower BA9 activation during the beginning of the response (0.000 ≤ p ≤ 0.021) and significantly higher BA9 activation towards the end of the response (0.008 ≤ p ≤ 0.025), suggesting longer time-lags between patients’ excitatory responses and the inhibitory activation that modulates it. Conclusions: Our results capture a significant dysregulation between the excitatory (amygdala) and inhibitory (prefrontal) limbic regions in medicated schizophrenic patients versus healthy controls. They suggest that, analogously to diagnostic tests used in other physiological diseases, quantifying dysregulation using a control systems approach may provide an appropriate model to investigate further in developing presymptomatic neurobiological assessments of risk, or illness severity in symptomatic patients.
New Insight into the Species Barrier of Mammalian Prions Obtained from Structure-Based Conservation Analysis
Authors: Wang Yaofeng , Hu Bingjie , Liu Yuan , Zhang Huili , Song Youtao
Published: September 2008

Objectives: The structures of several mammalian prions have been determined by NMR; however, their transmission and evolutionary features are still unclear. The objective of this study is to explore species barrier information from their structures. Methods: In this study, we compared the functional domains (121–231) of 8 mammalian prions with structure-based conservation analysis using visual molecular dynamic software (version 1.8.5). Results: Residues 184, 203 and 205, which play important roles in modulating the transmission of prion diseases, were identified as a structure-conserved domain rather than sequence-conserved domain of mammalian prions. The phylogenetic tree was reconstructed based on structure conservation. The topology of the tree explains the species barrier during the transmission of mammalian prions which cannot be deduced by the sequence phylogenetic tree. Conclusions: These results suggest that structure-based analysis is more accurate and informative than sequence-based analysis in the study of prion transmission and evolution.
Long-Term Prospective Follow-Up Study of Myopic Photorefractive Keratectomy
Authors: Liu Zhaoqiang , Wang Lihua , Xu Xiaoyi , Cheng Zhenying , Zhou Fang , Li Jinghai
Published: September 2008

The aim of this study was to evaluate the long-term outcome of excimer laser myopic photorefractive keratectomy (PRK). We undertook an 11-year prospective follow-up study of visual and refractive outcomes in 46 patients (85 eyes). The main outcome measures were predictability, efficacy, stability and safety of PRK. At 11 years after the operation, 56.5% of eyes were within ±0.5 D of attempted correction and 81.2% were within ±1.0 D; 87% had vision of 20/40 or better, and 52% had 20/20 or better. The best spectacle-corrected visual acuity was unchanged or improved in 91% of eyes at 11 years. Eyes with moderate and severe myopia showed a significant change between 3 and 11 years. PRK surgery for myopia shows predictable and stable results in the long term, with a slight regression in refraction, mainly for patients with severe myopia.
Topical Cyclosporine A in the Prevention of Pterygium Recurrence
Authors: Yalcin Tok Ozlem , Burcu Nurozler Ayse , Ergun Gul , Akbas Kocaoglu Fatma , Duman Sunay
Published: September 2008

Aims: To investigate the efficacy and safety of postoperative topical cyclosporine A 0.05% (tCsA) (Restasis®, Allergan Pharmaceutical) eye drops in preventing the recurrence of pterygium. Methods: 31 patients with bilateral pterygium were examined between January 2006 and February 2007. During a 1-year follow-up, the right eyes of the patients assigned as the treatment group were treated by tCsA and the left eyes were considered as the control group. Results: The pterygium recurred in 4 (12.9%) of 31 right eyes in the treatment group and in 14 (45.2%) of 31 left eyes in the control group (p = 0.005). The mean follow-up ± SD was 9.39 ± 4.14 months (range, 1 to 12 months). The control group had a 7.37 times higher risk of recurrence in pterygium compared with the treatment group (OR = 0.1357, p = 0.0051). A statistically significant difference in recurrence-free probabilities was found for the treatment and control groups (log-rank test; p = 0.006). A multivariate Cox regression model showed that age (p = 0.0093) and tCsA (p = 0.0103) were independent statistically significant impacts on recurrence-free time for pterygium. Conclusion: This study suggests that primary excision of pterygium with postoperative instillation of 0.05% cyclosporine is both safe and efficient.
Pilot Study of Combination Chemotherapy Using Irinotecan plus S-1 for Metastatic Pancreatic Cancer
Authors: Shitara Kohei , Komatsu Yoshito , Yuki Satoshi , Munakata Masaki , Muto Osamu , Shimaya Sen , Sakata Yuh
Published: September 2008

Objective: The aim of this study was to evaluate the efficacy and safety of a combination regimen using irinotecan plus S-1 in patients with metastatic pancreatic cancer. Methods: Based on the results of our previous phase I/II study in patients with gastric and colorectal cancer, we initiated a regimen with irinotecan at 100 mg/m2 on days 1 and 15 and S-1 at 80 mg/m2 starting at day 1 for 14 consecutive days, followed by a 14-day rest period. This treatment was repeated every 28 days. Results: From November 2003 to December 2006, a total of 16 patients were enrolled. All patients presented with metastatic disease. Six patients had received prior gemcitabine. The median number of treatment cycles was 4 (range 1–16) and the response rate was 43.7% (95% confidence interval 19.5–68.1). The median time to progression was 4.9 months, and the median survival time was 11.3 months. Grade 3–4 neutropenia developed in 5 of 16 patients and grade 3 diarrhea in 1 patient. Conclusions: The combination of irinotecan and S-1 is feasible and promising for pancreatic cancer. Further evaluation of this combination chemotherapy is required.
Perceived Stigmatization of Children with Speech-Language Impairment and Their Parents
Authors: Macharey Georg , von Suchodoletz Waldemar
Published: September 2008

Objective: Developmental disorders in childhood are generally assumed to have stigmatizing effects. The goal of the present study was to assess whether parents of children with speech-language impairment perceive stigmatization of their child or themselves and which variables influence the degree of negative labeling. Subjects and Methods: The study was based on 362 questionnaires completed by parents of children with speech-language impairment. The questionnaires concerned perceived stigmatization by other children, other adults and family members as a result of the child’s developmental problems. Results: In our sample, about 50% of the parents reported negative labeling of their child and about 30% felt they were involved in the stigmatizing process. Parents whose children also had behavioral problems more often reported negative labeling than parents whose children did not. Conclusion: The findings suggest that parents of children with speech-language disorders often perceive stigmatization of their children or themselves. In counseling such families, professionals should therefore address stigmatization and its consequences as a separate and important issue.
Bone Turnover, Osteopenia and Vascular Calcifications in Hemodialysis Patients
Authors: Coen G. , Ballanti P. , Mantella D. , Manni M. , Lippi B. , Pierantozzi A. , Di Giulio S. , Pellegrino L. , Romagnoli A. , Simonetti G. , Splendiani G.
Published: September 2008

Background: Several classical risk factors are at the base of vascular calcifications in hemodialysis patients. Among these, according to a general opinion, also bone turnover plays a role, which, however, requires a better definition. In addition, it has been suggested that there is a relationship between primary osteoporosis and vascular calcifications. This bone biopsy-based study on a hemodialysis patient cohort is a contribution to the evaluation of these alleged relations. Methods: This study has been carried out on a cohort of 32 patients on maintenance hemodialysis, who were subjected to transiliac bone biopsy for histomorphometric, histodynamic and bone aluminum deposit evaluation. The patients were also examined with multislice computerized tomography for quantitation of heart and coronary calcifications. Results: The patients were affected by renal osteodystrophy with a wide range of bone formation rate values. A significant negative correlation was found between the rate of bone turnover and log-transformed cardiac calcification score (p < 0.003). There were also negative significant correlations between the cardiac and coronary calcification score log and trabecular number (p < 0.02 and p < 0.05, respectively), while the correlations were positive with trabecular separation (p < 0.03 and p < 0.05, respectively). However, multiregression analysis, forward method, selected only age, hemodialysis age and serum Ca as predictive variables of cardiac and coronary calcification score log, while the histomorphometric and histodynamic variables were excluded. Conclusions: In this study, in spite of the suggestive findings of the univariate statistical approach, a further multivariate analysis was indicative of a spurious association between calcification scores and both bone turnover and histomorphometric parameters of trabecular mass and connectivity. Bone turnover and trabecular mass do not appear to be prominently connected with the extent of cardiac and coronary calcifications in hemodialysis patients.
Tetracycline-Inducible Gene Expression in Conditionally Immortalized Mouse Podocytes
Authors: Kajiyama Hiroshi , Titus Steve , Austin Christopher P. , Chiotos Kathleen , Matsumoto Takayuki , Sakairi Toru , Kopp Jeffrey B.
Published: September 2008

Background: Conditionally immortalized podocytes are valuable research tools but are difficult to efficiently transfect and do not provide graded transgene expression. Methods: Conditionally immortalized mouse podocyte cell lines were established employing a tetracycline-inducible system. Glomerular cells, isolated from transgenic mice bear- ing two transgenes, NPHS2-reverse tetracycline-controlled transactivator, rtTA (A transgene) and H2-Kb-thermosensitive SV40 T, ts58A (I transgene), were cloned. One clone (AI podocytes) expressing WT1 and synaptopodin was transfected with pBI-EGFP (enhanced green fluorescent protein, G transgene) and separately with ptTS-Neo (transcriptional suppressor, T transgene) to produce stable transformants, AIG podocytes and AIT podocytes. Results: AIG podocytes expressed EGFP at 33 and 37°C after doxycycline treatment, and retained podocin and rtTA mRNA expression and temperature-sensitive growth regulation. AIT podocytes, transiently transfected with luciferase-BI-EGFP (LG transgene), showed reduced background expression of EGFP and luciferase in the absence of doxycycline. In AITLG podocytes, generated by stable transfection of AIT podocytes with the LG transgene, luciferase expression was tightly regulated by doxycycline in a time- and concentration-dependent manner both at 33 and 37°C, although background expression was not entirely eliminated. These podocytes retained temperature-sensitive growth regulation and expression of podocyte differentiation markers. Conclusion: Mouse podocytes expressed tetracycline-induced transgenes efficiently while retaining differentiation markers.
Functional and Partial Morphological Regression of Established Renal Injury in the Obese Zucker Rat by Blockade of the Renin-Angiotensin System
Authors: Šebeková Katarína , Lill Maria , Boor Peter , Heidland August , Amann Kerstin
Published: September 2008

Background/Aims: In experimental nephropathies, inhibitors of the renin-angiotensin-system (RAS) halted the progression, or even induced a regression in renal injury. We studied the potential of the angiotensin-converting enzyme (ACE) inhibitor perindopril and the angiotensin receptor blocker candesartan to reverse the established renal injury in the obese Zucker rat (OZR). Methods: Forty 4-week-old OZRs were uninephrectomized and fed a high-protein diet. After 16 weeks, they were randomized into 4 groups (n = 10 each) with comparable proteinuria: (1) control group sacrificed immediately for baseline data, and groups gavaged daily for 8 weeks with (2) placebo, (3) perindopril (1 mg/kg/day), or (4) candesartan (10 mg/kg/day). Results: Both drugs reduced systolic blood pressure (perindopril –16%, p < 0.001; candesartan –10%, p < 0.05), renal hypertrophy, and proteinuria (perindopril to 32%; candesartan to 37% of pretreatment values). Glomerulosclerosis was halted (perindopril p < 0.001; candesartan p < 0.05), and the numbers of glomerular endothelial and podocyte cells were restored. Mesangiolysis was reversed by perindopril. Metabolic and oxidative parameters were either stabilized (perindopril), or improved (candesartan). Conclusion: In the OZR late inhibition of RAS halts the progression of glomerulosclerosis, reverses mesangiolysis and prevents the decline in glomerular endothelial cell and podocyte numbers. Tubulointerstitial fibrosis and vascular injury remain unchanged. Proteinuria shows marked regression.
Reversible Acute Kidney Injury following Contrast Exposure and the Risk of Long-Term Mortality
Authors: Goldenberg Ilan , Chonchol Michel , Guetta Victor
Published: September 2008

Background: Contrast-induced acute kidney injury (AKI) is a significant cause of morbidity and mortality among hospitalized patients. However, data regarding the long-term prognostic implications of reversible AKI following contrast exposure are limited. Methods: We carried out a prospective 5-year follow-up study of 78 patients with chronic kidney disease who underwent coronary angiography, employing a uniform intravenous hydration protocol supplemented by either acetylcysteine (600 mg orally t.i.d.) or placebo. Results: Contrast-induced AKI (defined as ≥0.5 mg/dl increase in serum creatinine, SCr, or >25% increase above baseline 48 h following contrast exposure) developed in 10 of the 78 patients (13%). All SCr changes were reversible, and were no longer evident 7 days following contrast exposure. At 5 years of follow-up, mortality rates were significantly higher among patients who developed reversible AKI (90%) as compared with those who did not (32%; p < 0.001). Accordingly, multivariable analysis demonstrated that reversible AKI was independently associated with a significant 2.7-fold increase (p = 0.001) in the risk of long-term mortality. Conclusions: Our findings indicate that short-term reductions in renal function following contrast exposure have important long-term prognostic implications in patients with chronic kidney disease. Careful follow-up of SCr levels following contrast exposure is warranted for long-term risk assessment in this population.
Impact of Interventional Bronchoscopy on Quality of Life in Malignant Airway Obstruction
Authors: Amjadi Kayvan , Voduc Nha , Cruysberghs Yves , Lemmens Roel , Fergusson Dean A. , Doucette Steve , Noppen Marc
Published: September 2008

Background: Interventional bronchoscopic procedures can re-establish airway patency in the majority of individuals suffering from endobronchial obstruction. However, literature provides limited data on the impact of these procedures on the individual’s quality of life (QoL). Objectives: We evaluated the impact of interventional bronchoscopic procedures aimed at re-establishing airway patency on symptoms and QoL of individuals who do not receive concomitant chemotherapy or radiation therapy. Methods: Over a 6-month period, we prospectively enrolled patients with symptomatic central airway obstruction related to malignancy and performed laser ablation, cryotherapy, and/or airway stenting in order to re-establish airway patency. QoL was evaluated by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire at one day before, 7 days after, and 1 month after procedure. Dyspnea was also assessed by the Borg scale before the procedure and one day after. Results: Final analysis could be performed on 83% (20/24) of the participants. Improvement in airway diameter was achieved in all patients, and >80% patency was established in 80% (16/20) of the patients. Dyspnea scores had improved in 85% of participants (p = 0.01). Thirteen patients experienced an improvement in QoL, although QoL scores remained stable for the group as a whole. Conclusion: Endoscopic procedures can effectively reduce dyspnea associated with malignant central airway obstruction, but this may not always translate into improvements in overall QoL. Administration of QoL questionnaires is feasible, and may help identify domains contributing to patient’s decline, and thereby improve overall patient care.
Presence of β-Follicle-Stimulating Hormone and β-Luteinizing Hormone Transcripts in the Brain of Cichlasoma dimerus (Perciformes: Cichlidae)
Authors: Pandolfi Matías , Pozzi Andrea G. , Cánepa Maximiliano , Vissio Paula G. , Shimizu Akio , Maggese M. Cristina , Lobo Guillermo
Published: September 2008

Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) play key roles in vertebrate gametogenesis and steroidogenesis. They are mainly synthesized in the pituitary gland. While investigating the ontogeny of FSH and LH cells in the cichlid fish Cichlasoma dimerus by immunohistochemistry (IHC), we unexpectedly found immunoreactive neurons in the preoptic area, sending their projections through different brain areas and neurohypophysis. Our previous work using Western blot and IHC techniques applied to the adult brain confirmed these findings. To further demonstrate the extrapituitary expression of these hormones, we performed RT-PCR detecting sequences coding for β-FSH and β-LH subunits in the C. dimerus pituitary and brain (preoptic-hypothalamic area). The expression of these transcripts in both organs was consistent with their peptide expression showing a high sequence homology when compared with other phylogenetically related fish. An individual pituitary in vitro culture system was utilized to study the possible modulatory effect of brain-derived gonadotropins on pituitary hormone secretion. Pituitary explants were cultured with different concentrations of LH or FSH, and the culture media were analyzed by Western blot. Exogenous LH produced a dose-dependent increase in pituitary β-LH, β-FSH and somatolactin (SL) releases. No effect was observed on growth hormone (GH). The effect on prolactin (PRL) was not consistent among treatments. Exogenous FSH produced an inhibition in β-LH release, dose-dependent increases in β-FSH and SL releases, and no effect on PRL and GH releases. These findings support the concept of regulation of pituitary trophic hormones by brain-derived gonadotropins.
Tissue- and Cell-Specific Alternative Splicing of NFIC
Authors: Lamani Ejvis , Wu Yixin , Dong Juan , Litaker Mark Stephen , Acevedo Ana Carolina , MacDougall Mary
Published: September 2008

Alternative splicing is an important mechanism for increasing genetic complexity leading to multiple transcripts from single genes and gene regulation through alternative promoters. Splicing often leads to unique tissue-specific patterns of mRNAs with specific biological functions. Nuclear factor I-C (NFI-C), a member of the NFI gene family, is expressed in numerous tissues including brain, liver, spleen and heart. However, the unique dental phenotype of Nfic–/– mice lacking molar roots demonstrates a critical role for this transcription factor in root formation. In humans, the NFI-C gene is alternatively spliced producing 4 isoforms. However, different spliced variants have not been studied in association with tissue specificity. The main objective of this study is to identify the NFI-C isoforms expressed in dental cells/tissues, comparing them to the spliced variants in nondental cells/tissues and to analyze their relative expression levels in various cell types. Using bioinformatics, we analyzed the NFI-C gene structure, identifying 2 potential alternative promoters driving expression of selective mRNA transcripts. Our studies show the expression of 3 NFI-C transcripts with the overall splicing pattern conserved between dental and nondental cells tested. Furthermore, by quantitative real-time PCR analysis, we found that although the relative levels of these transcripts were similar in dental and nondental cells, significant differences were observed within the dental cells tested. These are the first studies to analyze the expression of NFI-C isoforms in dental versus nondental cells/tissues, finding subtle cell-/tissue-specific expression patterns that could explain the dental phenotype of Nfic–/– mice.
Inhibition of Phosphate-Induced Apoptosis in Resting Zone Chondrocytes by Thrombin Peptide 508
Authors: Zhong Ming , Carney Darrell H. , Ryaby James T. , Schwartz Zvi , Boyan Barbara D.
Published: September 2008

Growth plate chondrocytes are susceptible to apoptosis. Terminally differentiated chondrocytes are deleted via apoptosis, which primes the growth plate to vascular invasion and subsequent bone formation. Whether less differentiated resting zone chondrocytes are subject to the same mechanism that governs the apoptotic pathway of more differentiated growth zone chondrocytes is not known. In our current study, we demonstrated that inorganic phosphate, a key inducer of growth plate chondrocyte apoptosis, also causes apoptosis in resting zone chondrocytes, via a pathway similar to the one in growth zone chondrocytes. Our results demonstrated that the conditions that cause growth plate chondrocyte apoptosis lie in the external environment, instead of the differences in differentiation state.
Isolation of Calcospherulites from the Mineralization Front of Bone
Authors: Midura Ronald J. , Vasanji Amit , Su Xiaowei , Midura Sharon B. , Gorski Jeff P.
Published: September 2008

Calcium-containing spherical bodies (calcospherulites) exist along the mineralization front of bone and are thought to play a role in bone formation. Existing methods to isolate calcospherulites involve harsh treatments that remove much of their organic matter. This study sought to isolate them using a less destructive approach to better preserve their organic components. Juvenile rats were injected with a low dose of calcein to label the newly formed mineral at the mineralization front of bone in vivo. Periosteum was completely dissected from the tibial diaphysis and unmineralized osteoid matrix was removed by collagenase in order to expose calcospherulites. Calcein-labeled calcospherulites of approximately 0.5 μm average diameter were observed all along the mineralization front and they exhibited a Ca/P ratio of 1.3 in situ. Calcospherulites were released from the mineralization front by a short dispase digestion and isolated via fluorescence flow sorting. X-ray diffraction revealed they contained apatite crystals (c-axis length of 17.5 ± 0.2 nm) and their Ca/P ratio was preserved during isolation. Calcospherulites treated with ice-cold ethanol exhibited a Ca/P ratio of 1.6, suggesting the presence of some extractable phospholipids. Proteins extracted from isolated calcospherulites were resolved by SDS-PAGE into more than 20 distinct bands. Western blot analyses showed the presence of matrix proteins in these preparations. These results indicate that calcospherulites can be isolated from the mineralization front of bone in a form that can be used to study their proteome and lipid composition.
Osteonecrosis of the Jaw: An Update and Review of Recommendations
Authors: Novince Chad M. , Ward Brent B. , McCauley Laurie K.
Published: September 2008

Bisphosphonates have had a very positive impact as therapeutic agents for cancer and osteoporosis, but have also been associated with osteonecrosis of the jaw (ONJ) which has emerged as an idiosyncratic oral complication. Bisphosphonate-associated ONJ has generated wide attention despite its considerably rare occurrence. Many speculations exist as to why bisphosphonates may increase the incidence of ONJ. The American Society for Bone and Mineral Research established a task force on bisphosphonate-associated ONJ and recently released a summary report of their findings. A case definition delineated a confirmed case of ONJ as ‘an area of exposed bone in the maxillofacial region that did not heal within 8 weeks after identification by a health care provider, in a patient who was receiving or had been exposed to a bisphosphonate and had not had radiation therapy to the craniofacial region’. Treatment recommendations have been developed by the American Dental Association, the American Association of Oral and Maxillofacial Surgeons and the American Society for Bone and Mineral Research. Considering the scientific evidence, little is known about the true incidence and pathophysiology, and many questions persist. New epidemiologic studies are surfacing and attempts to ameliorate the condition may shed light on the likely complex etiology. The bones of the oral cavity provide a unique environment relative to blood flow, oral microbiota, bone structure and function. Although little is known of the mechanisms and course of ONJ, even less is known about the spectrum of issues of altered healing that could fall short of defined ONJ.
A New N-Acetyl-ß-D-hexosaminidase Disease with Late Onset of Progressive Neurological Symptoms
Authors: Chester M.A. , Hultberg B. , Liedholm H. , Öckerman P.A.
Published: September 2008

Clinical data are presented on a 30-year-old male with normal early development (4-5 years) but subsequent progressive impairment of psychomotor functions. He has marked kyphoscoliosis and talipes calcaneovalgus. The organs appear normal and the patient can walk unaided and feed himself although he does not recognize his parents. He has normal fundi oculi. Biochemical data show an absence of mucopolysacchariduria and very low but detectable levels of N-acetyl-Β-D-hexosaminidase in serum and leucocytes. The clinical symptoms are much milder than would normally be expected from such a profound enzyme deficiency (Sandhoff disease).
A Modified Ultimate Failure Criterion and Material Degradation Scheme in Bridging Model Prediction for Biaxial Strength of Laminates
Authors: Zhou Ye-Xing , Huang Zheng-Ming
Published: September 2008

The first worldwide failure exercise (WWFE-I) indicated that the bridging micromechanics model exhibited a unique feature in calculating internal thermal stresses in the constituent fiber and resin materials of a laminated composite. Once applied to laminate strength prediction, however, the model only gave moderate correlation with the experiments. In this article, a material degradation scheme and a modified ultimate failure criterion for laminates are incorporated into the bridging model to improve its predictive capacity. Pure resin inter-layers are also introduced to simulate the effect of interfaces in between the lamina plies. With these modifications, much more accurate predictions have been obtained for the majority of the exercise problems, especially for the ultimate strengths and deformations of the multi-directional laminates. The correlation of the present theory predictions with the experiments is even better than that of any other theory predictions made in the exercise.