bluuebunny/crossref_metadata_2025 huggingface dataset:
APPLICATION OF COMPLEX WAVELETS FOR EMG ANALYSIS DURING GAIT OF ASYMPTOMATIC AND PATHOLOGICAL SUBJECTS
Authors: DE STEFANO A. , ALLEN R. , BURRIDGE J. H. , YULE V. T.
Published: December 2003

The wavelet transform seems particularly suited to analyse the electromyographic signal (EMG) during gait of asymptomatic and pathological subjects. Firstly, because physiologically the electrical activity generated by the muscles derives from a weighted sum of individual physiological components having limited support in time and in frequency. Secondly, because it is important to analyze muscle activity during specific phases of the cycle, and finally, because specific ranges of frequency are important pathological discriminators. In this paper we report the preliminary results of a project aimed at classifying asymptomatic and pathological subjects by analysing the complex wavelet transform of the EMG signal derived from two muscles (Tibialis Anterior and Lateral Gastrocnemius) during gait. An asymptomatic adult, an asymptomatic child and two pathological (cerebral palsy) children were examined using telemetric EMG devices and pressure footswitches. The results showed that the indices derived from the coefficient amplitudes (Gastrocnemius) and from frequency distribution (Tibialis) are capable of classifying the subjects into three groups. Despite the small number of cases analyzed, we believe that the relevance of the results deserves particular attention because of the novelty of the use of the wavelet transform for this application and of the potential application to monitor patients during interventions aimed at improving muscle behavior, particularly antispasticity treatment such as Botulinum Toxin injections.
MULTIRESOLUTION FORECASTING FOR US RETAILING USING WAVELET DECOMPOSITIONS
Authors: KUMAR ASHWANI , AGRAWAL D. P. , JOSHI S. D.
Published: December 2003

In this paper we propose a simple forecasting strategy which exploits the multiresolution property of the wavelet transform. US aggregate retail sales data have strong trend and seasonal patterns, providing a good testing ground for the proposed forecasting method. First a wavelet transform is used to decompose the time series into varying scales of resolution so that the underlying temporal structures of the original time series become more tractable; the decomposition is additive in details and approximation. Then a forecasting engine (neural network or fuzzy inference system) is trained on each of the relevant resolution scales, and individual wavelet scale forecasts are recombined to form the overall forecast. Substantial information in both the dynamic nonlinear trend and seasonal patterns of the time series is efficiently exploited: we choose short past windows for the inputs to the forecasting engines at lower scales and long past windows at higher scales. The forecasting engines learn the mapping hierarchically: using a scale-recursive strategy, we combine only those scales where significant events are detected. Univariate simulation results on US aggregate retailing indicate that the proposed method fares favourably in relation to forecasting results obtained by training a neural network on original time series. Multivariate simulation results obtained by including structural components inflation, recession, interest rates, unemployment, show improvement in sales-trend forecast.
p-FRAMES FOR SUBSPACES OF WIENER AMALGAMS ON A LOCALLY COMPACT ABELIAN GROUP
Authors: PANDEY S. S.
Published: December 2003

We prove a theorem to characterize the p-frames for a shift invariant closed subspace of Wiener amalgam spaces [Formula: see text], 1 ≤ p ≤ q ≤ ∞, [Formula: see text] being a locally compact abelian group. Also, we show that a collection of translates under approximate conditions generaltes a p-frames for the space [Formula: see text].
Thyrotropin-Releasing Hormone Stimulation Test in Patients with Pituitary Pathology
Authors: Hartoft-Nielsen Marie-Louise , Lange Martin , Rasmussen Åse Krogh , Scherer Susanne , Zimmermann-Belsing Tina , Feldt-Rasmussen Ulla
Published: December 2003

Objectives: To evaluate the value of the thyrotropin-releasing hormone (TRH) stimulation test in the diagnostic work-up of the thyroid function in patients with pituitary pathology. Methods: To compare the thyrotropin (TSH) response and the absolute and fold changes after TRH administration in 35 patients with pituitary pathology and 26 normal subjects. Results: Nine of the patients and 2 of the normal subjects had a pathological response. No difference in the thyrotropic response to TRH was found either for the actual values, or for the absolute or fold changes of TSH between the groups. Conclusion: The role of the TRH test in the evaluation of thyroid function in patients with pituitary pathology is modest. The best variables for evaluation of the presence of central hypothyroidism are still a free thyroxine estimate combined with an inappropriately low TSH.
Endocrine Disorders of Sodium Regulation
Authors: Kuhnle Ursula , Lewicka Sabina , Fuller Peter J.
Published: December 2003

Salt and water homoeostasis is tightly regulated by a variety of control mechanisms with the adrenal steroid hormone aldosterone playing a central role. Defects or disturbances in these systems lead to either salt loss, which is life threatening in the neonatal period, or sodium retention causing hypertension. Rapid and accurate diagnosis is required to avoid severe complications. During the last few years molecular genetic advances have been identified as the basic genetic defects for a number of clinical syndromes. This knowledge has considerably increased our understanding of the basic pathways involved in sodium and water homoeostasis and of the pathophysiology of these syndromes, particularly the hypertension. In this review we have summarized the biochemical, physiological and genetic basis for clinical syndromes presenting with salt loss and failure to thrive as well as the rare but important genetic syndromes causing sodium retention and hypertension. Early diagnosis and identification will help to prevent severe complications, but it has to be emphasized that the complicated cascade of aldosterone action is still relatively poorly understood. Further syndromes may exist which once identified will help to better understand the basic physiology of aldosterone action.
Cortisol Responses to the Insulin Hypoglycaemia Test in Children
Authors: Crofton P.M. , Don-Wauchope A.C. , Bath L.E. , Kelnar C.J.H.
Published: December 2003

Aim: To determine the timing of the peak cortisol response to the insulin hypoglycaemia (IH) test in children and to establish paediatric reference data. Methods: We retrospectively reviewed all IH tests in a tertiary paediatric endocrine referral centre over a 6-year period. Inclusion criteria were age <16 years and adequate hypoglycaemia (glucose ≤2.0 mmol/l). Patients with an impaired hypothalamic-pituitary-adrenal axis or receiving glucocorticoid medication were excluded. Fifty-four subjects (35 males) met the criteria. Blood samples were collected at –30, 0, 20, 30, 60, 90, 120, and 150 min in relation to insulin bolus injection (0.15 U/kg) at 0 min. Glucose, cortisol, and growth hormone (GH) were measured in all samples. Results: Peak cortisol and GH responses occurred by 90 min in all subjects. Peak cortisol was inversely correlated with age (rs –0.65, p < 0.0001). The median (5th centile) peak cortisol value was 689 nmol/l (547 nmol/l) in children younger than 10 years as compared with 555 nmol/l (468 nmol/l) in those older than 10 years (p < 0.0001). Peak cortisol was not related to peak GH (rs –0.20, p = 0.15). Conclusions: Blood sampling in the IH test may be curtailed 90 min after injection. The peak cortisol response to IH is age related.
Effects of Chronic Hypogonadism on Corticosterone Secretion and Cyclic AMP Production in Male Rat Adrenocortical Cells
Authors: Lo Ming-Jae , Kau Mei-Mei , Wang Paulus S.
Published: December 2003

Aim: To determine the secretion of corticosterone (CCS) both in vivo and in vitro during different intervals after orchidectomy in male rats. Methods: Three- and 12-month-old rats had been orchidectomized 0, 3, 6, or 9 months before decapitation. Results: Orchidectomy increased the concentrations of plasma CCS, the basal release of CCS, and the adenosine 3′, 5′-cyclic monophosphate (cAMP) production in rat zona fasciculata reticularis (ZFR) cells. The forskolin/3-isobutyl-l-methylxanthine-stimulated releases of CCS and cAMP production by ZFR cells were higher in rats with chronic hypogonadism. The CCS release from ZFR cells of orchidectomized rat was not altered by 8-bromo-cAMP treatment. Orchidectomy enhanced the stimulatory effect of deoxycorticosterone on CCS release in ZFR cells. Conclusion: These results suggest that orchidectomy-related increases of CCS secretion in rats are associated with an increase of adenylate cyclase activity, cAMP generation, and 11-β-hydroxylase activity in ZFR cells.
Increased fasting total homocysteine plasma levels as a risk factor for thromboembolism in children
Authors: Heinecke Achim , Kurnik Karin , Heller Christine , Nowak-Göttl Ulrike , Kosch Andrea , Koch Hans ,   for the Childhood Thrombophilia Study Group
Published: December 2003

Elevated total homocysteine (tHcy) concentrations are an inde- pendent risk factor for thromboembolic events in adults. In children with moderate hyperhomocysteinemia data are sparse. Therefore, between 1995 and 2002 we consecutively recruited 163 white pediatric patients with a first symptomatic thromboembolic event and 255 healthy controls (mean age: 6.4 years in patients vs. 6.6 years in controls, range: 3 months to 18 years) and measured fasting tHcy levels. Median tHcy levels in patients were significantly higher (6.6 µmol/l, range 2.9-20.4 µmol/l) than in controls (5.7 µmol/l, 2.0-14.0 µmol/l, p<0.0001). 48 of the 163 patients with thromboembolism (29.5%) versus 26 of the 255 controls (10.2%) had tHcy levels above the age- specific normal 90th percentile (OR 2.9, 95%CI: 1.7-4.8). The odds ratio for children in the highest quintile compared to chil- dren with levels in the lowest quintile was 4.3 (1.6-8.1; highest quintile: median tHcy level 9.6 µmol, range 8.0-20.4), showing a significantly increased risk for thromboembolic disease with even mild hyperhomocysteinemia. We conclude that hyperho- mocysteinemia above the age-specific cut-off values is a risk fac- tor for thromboembolic events in children. Therefore, screen- ing for elevated fasting tHcy levels of patients with thromboem- bolism is recommended to stratify the risk of thromboembo- lism.
Aberrant expression of the MEL1S gene identified in association with hypomethylation in adult T-cell leukemia cells
Authors: Yoshida Mika , Nosaka Kisato , Yasunaga Jun-ichirou , Nishikata Ichiro , Morishita Kazuhiro , Matsuoka Masao
Published: December 2003

DNA methylation plays critical roles in the development and differentiation of mammalian cells, and its dysregulation has been implicated in oncogenesis. This study was designed to determine whether DNA hypomethylation-associated aberrant gene expression is involved in adult T-cell leukemia (ATL) leukemogenesis. We isolated hypomethylated DNA regions of ATL cells compared with peripheral blood mononuclear cells from a carrier by a methylated CpG-island amplification/representational difference analysis method. The DNA regions identified contained MEL1, CACNA1H, and Nogo receptor genes. Sequencing using sodium bisulfite-treated genomic DNAs revealed the decreased methylated CpG sites, confirming that this method detected hypomethylated DNA regions. Moreover, these hypomethylated genes were aberrantly transcribed. Among them, MEL1S, an alternatively spliced form of MEL1 lacking the PR (positive regulatory domain I binding factor 1 and retinoblastoma-interacting zinc finger protein) domain, was frequently transcribed in ATL cells, and the transcriptional initiation sites were identified upstream from exons 4 and 6. Transfection of MEL1S into CTLL-2 cells conferred resistance against transforming growth factor β (TGF-β), suggesting that aberrant expression of MEL1S was associated with dysregulation of TGF-β-mediated signaling. Although Tax renders cells resistant to TGF-β, Tax could not be produced in most fresh ATL cells, in which MEL1S might be responsible for TGF-β resistance. Our results suggest that aberrant gene expression associated with DNA hypomethylation is implicated in leukemogenesis of ATL. (Blood. 2004;103:2753-2760)
The effects of different weaning modes on the endocrine stress response
Authors: Koksal Guniz Meyanci , Sayilgan Cem , Sen Oznur , Oz Huseyin
Published: December 2003

Introduction

The aim of the present study was to investigate the effects of the stress response on plasma insulin, cortisol, glucose, and urinary vanilmandelic acid during weaning and after extubation, using pressure support (PS), continuous positive airway pressure (CPAP) and T-piece modes.

Methods

Sixty patients were randomly divided into three groups (n = 20). The PS group received FiO2 ≤ 0.4, PS ≤ 10 cmH2O, and positive end expiratory pressure ≤ 5 cmH2O for 2 hours. The CPAP group was given FiO2 ≤ 0.4 and CPAP 5 ≤ cmH2O for 2 hours. The T-piece group (group T) received 4 l/min oxygen via a T-piece for 2 hours. After 1 hour and 2 hours in their respective weaning modes, blood and urine samples were taken for insulin, cortisol, glucose and vanilmandelic acid measurements. Forty-eight hours after extubation, blood and urine samples were again taken.

Results

Plasma insulin was greater in group T than in the PS and CPAP groups (P < 0.01 and P < 0.01). The plasma cortisol concentration was greater in group T than in group PS during weaning (P < 0.05) and after extubation (P < 0.05). Blood glucose concentrations were greater in group T than in the other groups (both P < 0.01) both during weaning and post extubation. Urine vanilmandelic acid was greater in group T than in the other groups during weaning and after extubation (both P < 0.001).

Conclusion

Weaning via the T-piece caused a greater stress response than the PS and CPAP modes.
Antipyretic Efficacy and Safety of Ibuprofen and Acetaminophen in Children
Authors: Goldman Ran D , Ko Karen , Linett Lauren J , Scolnik Dennis
Published: December 2003

OBJECTIVE:

To evaluate the antipyretic effects and safety of ibuprofen compared with acetaminophen in febrile children.

DATA SOURCES:

Searches of MEDLINE (1966–November 2003) and EMBASE (1988–November 2003) were conducted using the terms ibuprofen and acetaminophen. Bibliographies of selected articles were reviewed.

DATA SYNTHESIS:

Ibuprofen was significantly more effective than acetaminophen in reducing fever after a single dose. Ibuprofen was found to be more effective after 6 hours, but not after a longer period of time. Studies with multiple doses have also failed to show that one drug is better than the other.

CONCLUSIONS:

The efficacy and effectiveness of acetaminophen and ibuprofen in their recommended dosages are similar, with slightly more beneficial effects shown with ibuprofen.
Psoriasiform Eruption Induced by Infliximab
Authors: Verea María M , Pozo Jesús Del , Yebra-Pimentel M Teresa , Porta Angeles , Fonseca Eduardo
Published: December 2003

OBJECTIVE:

To report a case of psoriasiform eruption induced by infliximab.

CASE SUMMARY:

A 46-year-old woman with enterocutaneous fistula secondary to Crohn's disease developed pruriginous, erythematous, desquamative plaques on her elbows, knees, hands, and buttocks after receiving the second and third doses of intravenous infliximab. Histologic examination showed a lichenoid pattern. No new cutaneous lesions appeared after cessation of infliximab therapy.

DISCUSSION:

Several cutaneous reactions secondary to infliximab, a monoclonal antibody against tumor necrosis factor-alfa, have been described. Psoriasiform dermatitis has not been reported as a cutaneous reaction to infliximab, but there have been several previous reports of psoriasiform dermatitis secondary to other drugs. An objective causality assessment revealed that the adverse event was probable.

CONCLUSIONS:

This is the first report of a clinico-pathologic dissociated pattern of cutaneous reaction showing a histopathologic picture of lichenoid dermatitis resulting from infliximab treatment.
Cost Comparisons of Olanzapine and Risperidone in Treating Schizophrenia
Authors: Liu Gordon G , Sun Shawn X , Christensen Dale B , Luo Xuemei
Published: December 2003

OBJECTIVE:

To review the literature on the healthcare costs associated with olanzapine and risperidone in treating schizophrenia.

DATA SOURCES AND STUDY SELECTION:

Published English-language pharmacoeconomic studies on olanzapine and risperidone obtained through a MEDLINE search (1990–May 2003) were selected. Additional studies were identified from a manual search of the references of retrieved articles.

DATA EXTRACTION:

Based on the identified studies, data were extracted on various treatment costs associated with the use of antipsychotic drugs, concomitant drugs from other classes, inpatient care, outpatient care, and emergency care. Emphasis was placed on studies directly comparing olanzapine and risperidone.

DATA SYNTHESIS:

Both olanzapine and risperidone were generally associated with a trend of decrease in total medical costs compared with typical antipsychotics. When directly comparing the drugs, some studies found significant cost savings in favor of olanzapine and some suggested risperidone to save total costs. Still others showed no significant difference in total costs between the 2 drug regimens.

CONCLUSIONS:

While both olanzapine and risperidone appear to be more cost saving than typical antipsychotics, the literature offers no conclusive evidence to determine the comparative advantage of one versus another in terms of total cost outcomes. Major factors that contribute to the inconclusive findings may include across-study variations in populations, design, outcome measures, dosage, severity of illness, inclusion criteria, and statistical methodologies.
Acute Delirium Associated with Combined Diphenhydramine and Linezolid Use
Authors: Serio Ryan N
Published: December 2003

OBJECTIVE:

To report a case of delirium with hallucinations presumably caused by the combination of diphenhydramine and linezolid.

CASE SUMMARY:

A 56-year-old white man was receiving diphenhydramine 300 mg/d for 2 days to treat pruritus caused by a bullous rash possibly induced by vancomycin. He subsequently developed visual and auditory hallucinations, with erratic, aggressive behavior persisting for 3 days. Central anticholinergic syndrome was first suspected, but the long duration and exaggerated response by a patient not prone to anticholinergic toxicity suggest that a second agent may have enhanced the reaction.

DISCUSSION:

The pharmacodynamic properties of linezolid make this drug a likely contributor to the marked, prolonged effects experienced by this patient. The Naranjo probability scale suggests a possible relationship between the reaction and the combination of diphenhydramine and linezolid.

CONCLUSIONS:

Drug-induced delirium can occur with several drugs, including diphenhydramine. Linezolid has dopaminergic properties that may enhance the central nervous system effects of anticholinergics. Precautionary monitoring of mental status should be advised when concomitantly administering linezolid with drugs in this class.
Vardenafil Treatment for Erectile Dysfunction
Authors: Crowe Susan M , Streetman Daniel S
Published: December 2003

OBJECTIVE:

To review the pharmacology, pharmacokinetics, clinical trial data, and adverse effects of vardenafil in the treatment of erectile dysfunction (ED).

DATA SOURCES:

Literature searches were performed using the MEDLINE database (referenced citations through December 2002), and the references of all identified articles were scanned for additional publications of interest. Unpublished information provided by the manufacturer and proceedings of professional meetings were also evaluated.

STUDY SELECTION AND DATA EXTRACTION:

All available studies were utilized to obtain information regarding pharmacology. Only human studies were used to gather pharmacokinetic, drug interaction, efficacy, and safety data.

DATA SYNTHESIS:

Vardenafil is a potent and selective inhibitor of the phosphodiesterase 5 (PDE5) enzyme that has been shown to improve erectile function in several populations of men with ED. Vardenafil has a rapid onset of action, is hepatically metabolized, and has a half-life of 4–6 hours. Clinical trials in otherwise healthy men with ED, men with ED and diabetes, and men with ED and a history of prostatectomy have demonstrated vardenafil's efficacy. Adverse effects appear to be relatively mild in intensity and dose dependent, with 22–61% of subjects reporting adverse effects.

CONCLUSIONS:

Vardenafil is a safe and effective oral agent for the treatment of ED. Its greater potency and PDE5 selectivity compared with sildenafil appear to confer a lower risk of vision-related adverse effects, but other clinical consequences of these differences are currently unclear.
Acute Interstitial Nephritis Due to Pantoprazole
Authors: Ra Amy , Tobe Sheldon W
Published: December 2003

OBJECTIVE:

To describe what is believed, as of November 4, 2003, to be the first case published in the literature of acute interstitial nephritis (AIN) due to pantoprazole.

CASE SUMMARY:

A 77-year-old white woman presented to the hospital with elevated serum creatinine, oliguria for the past 24 hours, arthralgia, fatigue, fever, and bilateral flank pain. The patient had initiated treatment with oral pantoprazole 40 mg/d for gastroesophageal reflux 2 months prior to admission. After 5 weeks of therapy, she stopped taking pantoprazole due to general malaise. Upon admission, all home medications, including pantoprazole, were reinitiated based on the patient's medication list. Serum creatinine increased to 6.1 mg/dL on day 4 of admission from a baseline of 1.0 mg/dL. Pantoprazole therapy was promptly discontinued, and prednisone 40 mg/d was initiated. Urinalysis revealed eosinophils, and a subsequent renal biopsy confirmed a diagnosis of AIN. The serum creatinine level gradually declined over 2 weeks, and the patient was discharged home with a serum creatinine level of 1.6 mg/dL. The Naranjo probability scale suggests a highly probable relationship between AIN and pantoprazole therapy in this patient.

DISCUSSION:

Drug hypersensitivity reactions are the most common cause of AIN. There have been several reported cases of omeprazole-induced AIN. Although there are very few prospective data on the efficacy of treatment of drug-induced AIN, corticosteroids may have a role in recovery of renal function. Prednisone doses of 1 mg/kg/d have been suggested.

CONCLUSIONS:

Physicians should be aware that drug-induced AIN can be associated with proton-pump inhibitors. Early detection of this rare adverse reaction may prevent acute renal insufficiency.
Use of β-Blockers in Patients with COPD
Authors: Andrus Miranda R , Holloway Katherine P , Clark Deidre B
Published: December 2003

OBJECTIVE:

To evaluate the safety and cardiovascular benefits of β-blocker therapy in patients with chronic obstructive pulmonary disease (COPD).

DATA SOURCES:

Clinical literature was accessed through MEDLINE (1966–February 2003). Key search terms included chronic obstructive pulmonary disease and adrenergic β-antagonists.

DATA SYNTHESIS:

β-Blockers are often avoided in patients with COPD because of fear of bronchoconstriction, despite the known cardiovascular mortality benefits. A review of studies evaluating the use of β-blockers in COPD was undertaken.

CONCLUSIONS:

The literature supports the safety and mortality benefits of using β-blockers in COPD. Patients with mild to moderate COPD should receive cardioselective β-blocker therapy when a strong indication exists.
Atomoxetine Treatment of Attention-Deficit/Hyperactivity Disorder
Authors: Eiland Lea S , Guest Abby L
Published: December 2003

OBJECTIVE:

To review the literature of the first nonstimulant approved for treatment of attention-deficit/hyperactivity disorder (ADHD). data sources: Primary literature and review articles were obtained through PubMed/MEDLINE (1966–February 2003).

STUDY SELECTION AND DATA EXTRACTION:

Literature evaluating atomoxetine in ADHD was selected. Animal data were excluded.

DATA SYNTHESIS:

Stimulants are currently first-line therapy for ADHD. However, their use raises several concerns including the potential for abuse and adverse effects. Atomoxetine introduces a new therapeutic drug class, selective norepinephrine-reuptake inhibitors, for ADHD management. This additional treatment option offers potential advantages over current therapies.

CONCLUSIONS:

Clinical trials demonstrate that atomoxetine is a safe and effective alternative for ADHD treatment in children and adults; however, its disadvantages may hinder it from becoming a first-line agent.
Listeria Meningitis Associated with Infliximab
Authors: Bowie Venita L , Snella Kathleen A , Gopalachar Anuradha S , Bharadwaj Parag
Published: December 2003

OBJECTIVE:

To report a case of Listeria monocytogenes meningitis in a 73-year-old man receiving infliximab for rheumatoid arthritis.

CASE SUMMARY:

A 73-year-old white man taking infliximab for rheumatoid arthritis developed listeria meningitis following his second dose. He was receiving other immunosuppressants; however, these remained constant immediately prior to the infection. Diagnosis was confirmed with L. monocytogenes isolated in the cerebrospinal fluid. The patient received 21 days of antibiotic therapy and recovered without any complications.

DISCUSSION:

L. monocytogenes is a gram-positive, non—spore-forming rod that has been associated with the ingestion of undercooked foods. This organism can cause sepsis or meningitis; however, immunocompromised patients, elderly patients, pregnant women, and neonates appear to be at greater risk for this type of infection. Tumor-necrosis factor-α (TNF-α) plays an important role in resistance to this type of infection, and listeria infections have been reported in 26 patients receiving TNF-α inhibitors. In our patient, the listeria infection occurred following his second course of infliximab, which provides a temporal relationship between the listeria infection and infliximab. However, his underlying rheumatoid arthritis and chronic steroid therapy would also increase his risk for a listeria infection.

CONCLUSIONS:

The listeria infection in our patient was a possible adverse event of infliximab according to the Naranjo probability scale. Because the majority of listeria infections occur in patients who are immunosuppressed, it would be reasonable to provide education for healthcare professionals on preventing these infections in all patients receiving immunosuppressants, including anti—TNF-α therapy. Those at risk due to their underlying health conditions should also be monitored closely.
Recent Changes in Quality in Japanese Clinical Trials
Authors: Saito Kazuyuki , Kodama Yasuo , Ono Shunsuke , Fujimura Akio
Published: December 2003

BACKGROUND:

Japanese clinical trials have some unique characteristics in both design and conduct. We have studied recent changes in quality in Japanese clinical trials.

OBJECTIVE:

To describe quantitatively recent drastic changes in Japanese clinical trial environments by comparing the results of Good Clinical Practice (GCP) audits conducted from April 1997 to March 2000 (fiscal year [FY] 1997–1999) with those from April 2000 to March 2001 (FY2000).

METHODS:

The numbers and proportions of various types of deficiencies described in GCP audit reports were compared between the 2 periods. The audit findings in the former period were based on official audits that covered 331 hospitals and 775 trials. The audits in the latter period targeted 123 hospitals and 279 trials. In both periods, inspections were undertaken by the Organization for Pharmaceutical Safety and Research (OPSR).

RESULTS:

The total number of deficiencies detected in GCP audits in the former 3-year period (FY1997–1999) was 1529; the number in the next single year (FY2000) was 1151. The total number of deficiencies detected and reported was more than double on an annual basis between the periods. By category of deficiencies, the proportion of protocol deviations increased from 14.7% (n = 225) to 41.4% (n = 477), while the proportion of errors in Case Report Forms decreased from 43.6% (n = 666) to 34.1% (n = 392).

CONCLUSIONS:

This study shows that the protocol deviations increased in FY2000. The increase in deficiencies may be associated with the regulatory change of applicable standards, increasing attention of the OPSR to such deficiencies, difficulties in improving investigators' behaviors during a short period of time, and insufficient numbers of support staff including clinical research coordinators in research institutions.
Vancomycin Ointment for MRSA Infection at a Cranioplasty Site
Authors: Ikeda Hiroaki , Kurisu Kaoru , Kihira Kenji
Published: December 2003

OBJECTIVE:

To report a case illustrating therapeutic success with long-term topical application of aseptic vancomycin ointment to treat methicillin-resistant Staphylococcus aureus (MRSA) infection at a cranioplasty site.

CASE SUMMARY:

A 63-year-old Japanese woman underwent evacuation of a subdural hematoma complicated by subarachnoid hemorrhage. Subsequent craniotomy for clipping and external decompression of an aneurysm of the neck was followed by cranioplasty using an autologous bone graft. The graft became infected with MRSA, which responded to intravenously infused vancomycin. The graft was then replaced with a ceramic implant. The implant site became reinfected with MRSA. Vancomycin infusion failed on this occasion, despite a favorable in vitro sensitivity test. After obtaining patient consent, investigative treatment was begun using long-term aseptic application of vancomycin 2.5% ointment, resulting in control of the infection and negative cultures.

DISCUSSION:

The care of an infection at the site of cranioplasty with a ceramic artificial bone implant is difficult. Our patient's infection resolved with the use of vancomycin ointment. In this case, blood concentrations of vancomycin remained below detectable levels, and no adverse effects resulted from application of vancomycin ointment.

CONCLUSIONS:

Topical administration of vancomycin was more effective than systemic administration in the treatment of our patient's MRSA skull implant infection. No adverse effects from topical treatment were encountered over 3 years.
Cushing's Syndrome Due to Interaction Between Inhaled Corticosteroids and Itraconazole
Authors: Bolland Mark J , Bagg Warwick , Thomas Mark G , Lucas Jennifer A , Ticehurst Rob , Black Peter N
Published: December 2003

OBJECTIVE:

To report a case of an interaction between inhaled corticosteroids and itraconazole causing iatrogenic Cushing's syndrome and provide a review of the relevant literature.

CASE SUMMARY:

A 70-year-old white woman on long-term treatment with high-dose inhaled corticosteroids for asthma was diagnosed as having Scedosporium apiospermum infection of the skin and subcutaneous tissues. As a result, she was treated with itraconazole for 2 months. She subsequently developed Cushing's syndrome due to a probable cytochrome P450–mediated interaction between itraconazole and budesonide. She also had secondary adrenal insufficiency requiring prolonged treatment with replacement hydrocortisone.

DISCUSSION:

Budesonide is a potent glucocorticoid that is metabolized in the liver by the CYP3A4 isoenzyme to inactive metabolites. Itraconazole is a potent cytochrome P450 inhibitor. It can inhibit the metabolism of oral or inhaled corticosteroids, producing cortisol excess leading to Cushing's syndrome and adrenal insufficiency. An assessment of causality indicated a possible adverse interaction between itraconazole and budesonide.

CONCLUSIONS:

The combination of itraconazole and inhaled corticosteroids is increasingly being used to treat conditions such as allergic bronchopulmonary aspergillosis. Clinicians need to be aware of the potential for an interaction between such a combination.
Monitoring Pulmonary Function in Asthma and COPD: Point-of-Care Testing
Authors: Tovar John M , Gums John G
Published: December 2003

OBJECTIVE:

To provide pharmacists and other healthcare providers with a better understanding of new monitoring technologies for asthma and chronic obstructive pulmonary disease (COPD) available to clinics and pharmacies.

DATA SOURCES:

Forty scientific articles were identified through a MEDLINE search (1990–June 2003), additional references listed in articles, and abstracts from scientific meetings.

STUDY SELECTION AND DATA EXTRACTION:

English-language literature of controlled human clinical studies was reviewed to evaluate the accuracy, reliability, validity, and response of the new monitoring technologies.

DATA SYNTHESIS:

The In-Check DIAL is a pulmonary airflow meter that identifies the most appropriate inhaler for a patient and is useful in determining how efficiently patients use their inhalers. Electronic peak flow meters such as the AirWatch, VMX Wright Mini-Log, PiKo-1, and electronic asthma monitor store and download multiple pulmonary function test (PFT) readings to a personal computer, allowing easy identification of patients who are fabricating results. The AirWatch also has the ability to measure forced expiratory volume in 1 second. The Spirophone AG-SP, VM Plus, and Micro DiaryCard spirometer are portable spirometers that can be used at home without the need for supervision. Bronchial challenge tests have been recently standardized and may prove to be beneficial in modifying drug therapy in patients with asthma and COPD.

CONCLUSIONS:

Despite recent advances in medical technology, monitoring of asthma and COPD has not changed significantly. PFTs continue to be the gold standard for evaluating airway obstruction and/or restriction. Clinical trials that will evaluate outcomes such as decreased number of hospitalizations, emergency department visits, unscheduled visits to physicians, and days absent from school or work are needed to determine the utility of new monitoring technologies.
Decreased Phenobarbital Absorption with Charcoal Administration for Chronic Renal Failure
Authors: Tanaka Chie , Yagi Hidefumi , Sakamoto Michio , Koyama Yasuhiro , Ohmura Tadahiro , Ohtani Hisakazu , Sawada Yasufumi
Published: December 2003

OBJECTIVE:

To report a case of impaired absorption of orally administered phenobarbital associated with the concomitant administration of activated charcoal, and recovery of the absorption after administration of the 2 drugs was separated by a 1.5-hour interval.

CASE SUMMARY:

A 78-year-old woman, weighing 50 kg, who had undergone brain surgery was prescribed phenobarbital 120 mg/day for postoperative convulsions. Her serum phenobarbital concentration reached 24.8 μg/mL (therapeutically effective level 10–30). Thereafter, her renal function worsened, and activated charcoal 6 g/day was started. Four months after the start of activated charcoal, blood analysis revealed that the serum phenobarbital concentration was as low as 4.3 μg/mL. The phenobarbital dose was increased to 150 mg/day. Further evaluation revealed that activated charcoal and phenobarbital had been administered concomitantly. The dosage regimen was altered to separate the administration of the agents by at least 1.5 hours. Subsequently, the patient's serum phenobarbital concentration increased to 11.9 μg/mL within 3 weeks. Her serum phenobarbital concentration was measured monthly thereafter and remained stable in the range of 14.8–18.6 μg/mL.

DISCUSSION:

Our patient's low serum phenobarbital concentration was considered likely to have been due to impaired gastrointestinal absorption of phenobarbital as a result of adsorption of phenobarbital on the activated charcoal. An objective causality assessment showed that the interaction was probable.

CONCLUSIONS:

Administration of activated charcoal and phenobarbital should be separated by an interval of at least 1.5 hours.
Entwurf von Nanosystemen für Ambient Intelligence (Designing Nano-Scale Systems for the Ambient-Intelligence World)
Authors: De Man Hugo
Published: December 2003

While process technologists are obsessed to follow Moore´s curve down to nanoscale dimensions, design technologists are confronted with gigascale complexity required for the smart objects of the ambient-intelligence world of tomorrow. This world requires zero cost, zero energy yet software programmable novel system architectures to be sold in huge volumes and be designed in exponentially decreasing time. What are these novel silicon architectures? What challenges in research does this create? How to create the necessary tools and skills and how to organise research and education in a world driven by shareholders value? Let us try to make some educated guesses about these questions.
Codeübersetzung unter Zeitvorgaben für eingebettete Signalprozessoren (Performance Controlled Compilation for Embedded Signal Processors)
Authors: Jess Jochen A. G.
Published: December 2003

This work deals with the problem of code optimization under the condition of compulsory cycle budgets for audio and video applications implemented on embedded signal processors. It shows the concepts of the "distance matrix" and the "conflict graph" and illustrates their inclusion into an optimizing enumeration process. The paper concludes with indications of the performance of the strategy, which has been extensively documented in a series of dissertations from Eindhoven University (NL).
Vergleich von Hardware- und Software-Implementierungen in der digitalen Kommunikation am Beispiel der Kanalcodierung (Hardware-/Software Trade-Offs in Digital Communication Systems with Special Emphasis on Channel-Coding)
Authors: Wehn Norbert
Published: December 2003

Unsere heutige Informationsgesellschaft erfordert Datenzugriffe an jedem Ort und zu jeder Zeit. Bandbreite und Energie sind hierbei kritische Ressourcen. Deshalb benötigen drahtlose Kommunikationsstandards effiziente Fehlerkorrekturverfahren. In diesem Beitrag diskutieren wir den Entwurfsraum für fortgeschrittene Kanalcodierungsverfahren und präsentieren verschiedene Hardware- und Softwareimplementierungen.
Eine neue DSP Plattform für Multimedia-Anwendungen (A New Platform For Multimedia Applications)
Authors: Temerinac Miodrag , Noeske Carsten , Herz Ralf , Zimmermann Steffen , Wagner Volker
Published: December 2003

Die Konvergenz zwischen Rundfunksystemen und neuen digitalen Services durch gemeinsame Multimediaanwendungen stellt neue Anforderungen an die DSP-Plattformen: sie sollten für die Implementierung aufwändiger Algorithmen bei minimalem Stromverbrauch hochoptimiert sein, und gleichzeitig sollten sie möglichst offen und wiederverwendbar bleiben. Die existierende Submikrontechnologie macht eine Integration der komplexen Architekturen technisch und wirtschaftlich möglich und verschiebt die Entwicklungsherausforderungen eher zu Themen der Programmierbarkeit. Modularität, Interoperabilität und Wiederverwendbarkeit sind Hauptanforderungen für neue DSP-Plattformen geworden. Der vorliegende Artikel präsentiert eine neue DSP-Plattform für Multimedia-Produkte. Ausgehend von den neuesten Algorithmen für Audio- und Videokompression und von existierenden Plattformen werden sowohl eine optimierte Prozessorarchitektur mit speziellen Coprozessoreinheiten, so genannte Streaming Units, für kritische Engpässe in Kompressionsverfahren, als auch die benötigten Programmierwerkzeuge, vorgestellt.
Beobachten des Internet: Traum und Wirklichkeit (How to observe the Internet)
Authors: Gärtner Felix C.
Published: December 2003

Die Möglichkeit, verteilte Systeme wie das Internet zu beobachten, ist der erste Schritt, um solche Systeme zu beherrschen. Dieser Beitrag gibt eine kurze Einführung in die Schwierigkeiten, die beim Beobachten großer verteilter Systeme auftreten. Grund für diese Schwierigkeiten sind (neben dem inhärenten Nichtdeterminismus) das Fehlen einer exakten globalen Zeit sowie das partielle Fehlverhalten von Komponenten im System.
Tc(IV) chemistry in mixed chloride/sulphate acidic media. Formation of polyoxopolymetallic species
Authors: Vichot L. , Fattahi M. , Musikas C. , Grambow B.
Published: December 2003

The substitution of the Cl-ions of TcCl62-in various media (Cl-, SO42-, TFMS-) at various pH or the electroreduction of TcO4-in the same media led to a common Tc(IV) species characterized by an UV-visible absorption band at 500nm. This band was present in the spectra of Tc(IV) in all the media investigated, except in chloride at low pH. The analysis of the spectroscopic data showed that it can be attributed to a Tc(IV) oxopolymeric species.The data fits better with a trimeric species Tc3O44+which reminds the Mo3O4·9H2O4+clusters known for Mo(IV). The stability of 3×10-5M Tc3O44+solutions has been investigated as a function of pH with respect to the formation of Cl-complexes at low pH, and precipitation of TcO2at pH, higher than 3. The anions of the media interact with Tc3O44+clusters as shown by small changes in their UV-visible spectra. We observed that the affinity of Tc3O44+for these ions is in the order: SO42->Cl->TFMS-. Neutral species Tc3O4(SO4)2are observed in 0.1M sulphate solutions.
The substitution reactions of [Tc(tu)6]3+with CyDTA and citrate
Authors: Wang Y. , Liu X. , Liu Y. , Wang Xi.
Published: December 2003

The ligand substitution reactions of [Tc(tu)6]3+with cyclohexane-1,2-diaminetetraacetic acid (CyDTA) and citrate (cit) have been investigated by spectrophotometry. These studies indicate that stabilities of resulted Tc(III) complexes and rates of substitution reactions are different with substituting ligands. An attempt has been taken to understand the kinetics of the substitution reactions, which reveals that the rate law of the reaction of [Tc(tu)6]3+with CyDTA can be written as, while the rate law of the reaction of [Tc(tu)6]3+with cit can be written as.
Investigation of chemical equilibrium kinetics by the electromigration method
Authors: Bozhikov G. A. , Ivanov P. I. , Bontchev G. D. , Maslov O. D. , Milanov M. V. , Dmitriev S. N.
Published: December 2003

The measurement of the chemical reaction rates for complex formation as well as hydrolysis type reactions by the method of horizontal zone electrophoresis is outlined. The correlation between chemical equilibrium kinetics and electrodiffusion processes in a constant d.c. electric field is described. In model electromigration experiments the reaction rate constant of the formation a complex by Hf(IV) and diethylenetriaminepentaacetic acid (DTPA) is determined. The electrophoretic mobility, diffusion coefficient and stability constant of the [HfDTPA]- complex are calculated, taking into account experimental electrophoretic data obtained at 298.15±0.05K and constant ionic strength. No-carrier-added 175Hf radionuclide was used in electromigration experiments at concentrations of 10-10-10-11M.
Equilibrium constants in aqueous lanthanide and actinide chemistry from time-resolved fluorescence spectroscopy: The role of ground and excited state reactions
Authors: Billard I. , Lützenkirchen K.
Published: December 2003

Equilibrium constants for aqueous reactions between lanthanide or actinide ions and (in-) organic ligands contain important information for various radiochemical problems, such as nuclear reprocessing or the migration of radioelements in the geosphere. We study the conditions required to determine equilibrium constants by time-resolved fluorescence spectroscopy measurements. Based on a simulation study it is shown that the possibility to determine equilibrium constants depends upon the reaction rates in the photoexcited states of the lanthanide or actinide ions.
Destruction of 1,1-dichloroethylene/air mixture under gamma-ray irradiation
Authors: Sun Y.-X. , Hakoda T. , Chmielewski A. G. , Hashimoto S.
Published: December 2003

Radiation-induced decomposition of 1,1-dichloroethylene(1,1-DCE)) in air was investigated in the experiment. The model gas prepared by mixing 1,1-dichloroethylene vapor with air was sealed in batch reactors and subjected to gamma irradiation. Inorganic products (CO+CO2) and organic products were analyzed by means of a TOC analyzer and gas-chromatography, respectively. It was found that chloroacetyl chloride (CH2ClCOCl) was present as the main organic product while inorganic products (CO+CO2) occurred in quantities below 10 based on relative carbon balance. Energy consumption of 1,1-DCE by using gamma-ray irradiation was compared with that by using electron beam irradiation.
Additivity rule and its application to the sorption of radionuclides on soils
Authors: Zuyi Tao , Wenming D.
Published: December 2003

Previous authors reported that for some sorption systems the overall distribution coefficient (Kd) for a radionuclide or trace element on a mixture of minerals could be predicted from the additivity rule, the distribution coefficients on individual minerals and their mass fractions and that for some sorption systems, deviations from the additivity rule were found. In this paper, the additivity rule and its applicability to soils were analyzed from the theoretical considerations and the nature of soils. It was found that under the simplifying assumptions: 1) reversible and independent sorption reactions, 2) at equilibria of sorption reactions, 3) homogeneous surfaces, 4) insolubility of ion exchangers or sorbents, 5) no new phase formation, and 6) no interactions between individual minerals of the mixture, the additivity rule is formally valid. In practice, because of these crucial assumptions, the nature of soils and the difference in the experimental conditions for the sorption on mixtures and for the sorption on individual minerals, in general, the additivity rule is not applicable to the sorption systems of soils.
Globule formation of a clay mineral and a rapid method for the treatment of liquid radioactive waste
Authors: Ali Ab. , Rashid F. , Orfi S. D.
Published: December 2003

A technique has been proposed for the grain formation of a naturally available clay mineral (inorganic sorbent). The clay mineral was processed to form the globules to ease the decontamination of low and intermediate levels of liquid radioactive wastes. The purpose of this study is to develop a new form of inorganic sorbing material in the form of beads for the treatment of liquid radioactive waste originating from different types of nuclear installations. This material in the form of spherical beads can also be used for the immobilization of secondary waste that results as a byproduct from processing of nuclear wastes. As it is a major radiotoxic nuclide present in the nuclear wastes, the sorption of cesium from the low level liquid radioactive waste has been described. The potential utilization of this porous clay as an inexpensive material for the final disposal of radioactive wastes has been suggested.
Verkürzung der Messzeit beim AC-DC-Transfer mit Thermokonvertern (Fast AC-DC Transfer with Thermal Converters)
Authors: Mohns Enrico , Ihlenfeld Waldemar Guilherme Kürten
Published: December 2003

Die Messung von Wechselspannungsgrößen mit Thermokonvertern ist sehr zeitintensiv. Eine einfache und effiziente Methode, den AC-DC-Transfer zu verkürzen, ohne die Messgenauigkeit zu beeinträchtigen, wird beschrieben.
Laufzeitmessung durch Analyse des Summensignals (Transit Time Measurement by the Analysis of Sum Signals)
Authors: Niemann Mathias J.
Published: December 2003

Als gängiges Verfahren zur Bestimmung der Laufzeitverschiebung zweier ähnlicher Signale dient die Bestimmung der Kreuzkorrelationsfunktion. Das Maximum der Funktion tritt an der Stelle der Laufzeit auf. Eine Alternative besteht in der Addition der Signale. Im Spektrum der addierten Signale kann nach geeigneter Filterung eine Cosinus-Schwingung detektiert werden. Die Frequenz dieser Schwingung ist direkt proportional zu der gesuchten Laufzeit.