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Biomedical subjects

Michael Stevens

Publications and source records attributed to Michael Stevens.

14 recordsLinked to original sources

Longitudinal dynamics of gene expression and metabolomics in an aging population cohort.

Multiomic profiling provides a comprehensive physiological overview at the molecular level, but understanding of its spatiotemporal dynamics remains limited in human populations. We profiled longitudinal whole-blood gene expression and metabolite levels in 335 females over 8 years. Levels of 5061 genes and 181 metabolites changed over time, with individual trajectories often diverging from population-level trends. Longitudinally variable genes showed cell type specificity and enrichment for aging-relevant pathways, including cardiometabolic and neurodegenerative disorders. Longitudinal trajectories were further shaped by genetics, circadian rhythm, seasonality, and environmental pollutant exposures. Integrative analyses revealed extensive static and time-variable cross-omic connectivity. Longitudinal profiling offers insight into the temporal evolution of age-related conditions at the molecular level, and understanding individual variation within these longitudinal patterns will be essential for future precision medicine approaches.

Female↗

Late effects in 164 patients with rhabdomyosarcoma of the bladder/prostate region: a report from the international workshop.

PURPOSE: We determined the late sequelae in children and adolescents with rhabdomyosarcoma of the bladder/prostate treated in the United States, Canada and selected Western European countries, primarily France, Germany, Italy and the United Kingdom, from 1979 to 1998. MATERIALS AND METHODS: We used a data collection form to record data from patient records available at the group statistical centers. RESULTS: A total of 164 patient charts had sufficient data available to be included in the study. Median patient age at diagnosis was 2.4 years. Median length of followup was approximately 8 years (range 3 to 24). Of the patients with available data 78 did not undergo cystectomy, 49 underwent partial cystectomy and 34 underwent complete cystectomy. Urinary continence was assessed at age 6 years or older in 62 patients who did not undergo cystectomy. Of these patients 43 (69%) were continent, 16 had nocturnal incontinence and 9 had diurnal incontinence. Of 44 patients who underwent partial cystectomy and had pertinent followup data 32 (73%) were continent, and 12 had nocturnal and/or diurnal incontinence. Only 11 patients underwent urodynamic investigation. Other nephrourological complications consisted of 3 or more urinary tract infections in 29 of 53 patients, abnormal renal function in 19 of 48 (tubulopathy 14, increased creatinine/blood urea nitrogen 5), chronic hematuria in 13 of 51 and hydronephrosis in 8 of 54 with available data. Vesicoureteral reflux, urinary stones and bowel problems were infrequent. CONCLUSIONS: Of the patients 48% had a relatively intact bladder after biopsy only. However, 31% of patients 6 years or older had some urinary incontinence, as did 27% of patients who had undergone partial cystectomy. In addition, 55% of all patients had 3 or more urinary tract infections, 40% had decreased renal function and 25% had chronic hematuria. Other complications were present in 15% or less of the patients with available data.

Adolescent↗

Sensorimotor performance in school-age children with autism, developmental language disorder, or low IQ.

The purpose of the study was to determine the prevalence of 'soft' motor deficits in school-aged children with either developmental language disorder (DLD), autism (with high IQ [HiAD] or low IQ [LoAD]), or low IQ without autism (LoIQ), and to evaluate the utility of a refined neurological examination to discriminate between these groups. A total of 242 children (74% male), aged 7 or 9 years, were evaluated as part of a longitudinal, multi-institutional study, with a standardized neurological examination that included Denckla's Physical and Neurological Examination for Soft Signs. Most of the scores separated children into two groups defined by nonverbal IQ, with the DLD and HiAD groups performing better than the LoAD and LoIQ groups. Exceptions included motor impersistence and stereotypies, which were more likely in the autistic groups. The neurologists' summary clinical impressions indicated better sensory/motor skills, oromotor skills, and praxis in the HiAD than in the DLD children. Inability/unwillingness to perform tasks was much more frequent in LoAD than LoIQ children.

Autistic Disorder↗

Tscope: A C library for programming cognitive experiments on the MS windows platform.

Tscope is a C/C+ + programming library designed for programming experiments that run on Windows 2000/XP. It is intended for a public of experimental psychologists with moderate programming skills, who are accustomed to writing their own experimental programs for DOS but have not made the step to Windows-based programming yet. It provides molecular functions for graphics, sound, timing, randomization, and response registration. Together with ANSI-C standard library functions and the powerful C syntax, this set of functions gives the experimenter the opportunity to program virtually any experiment one can come up with. Tscope is completely based on free software, is distributed under the GNU General Public License, and is available at expsy.ugent.be/tscope. An integrated development environment for compiling and running Tscope programs is also freely available.

Cognition↗

Pharmacokinetic evaluation and short-term activity of stavudine, nevirapine, and nelfinavir therapy in HIV-1-infected adults.

OBJECTIVE: Evaluate pharmacokinetic interaction, short-term safety, and antiretroviral activity of stavudine (d4T), nevirapine (NVP), and nelfinavir (NFV) as combination HIV-1 therapy. DESIGN: Prospective, open-label study investigating the pharmacokinetic interactions between d4T, NVP, and NFV and documenting short-term tolerability and virologic and immunologic activity. METHODS: Twenty-five HIV-1-infected adults, naive to nonnucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs), < or = 6 months of d4T treatment, CD4 > or = 100 cells/mm, and viral load > = 5,000 copies/mL enrolled. All received NFV 750 mg 3 times daily and d4T 30-40 mg twice daily for 1 week, then added NVP at 200 mg once daily for 2 weeks and 200 mg twice daily thereafter. Steady-state pharmacokinetic parameters of NFV, AG1402 (metabolite of NFV), and d4T were compared before and after the addition of NVP. RESULTS: No statistically significant changes in NFV or d4T pharmacokinetics were observed following the addition of NVP. Levels of AG1402 were suppressed 60-70%. Drug-related adverse events were seen at expected rates. At day 36, median viral load suppression was 2.0 log10 and absolute CD4 count increased by 111 cells/mm. CONCLUSIONS: NVP administration did not significantly affect the steady-state pharmacokinetic parameters of NFV or d4T. The combination of d4T, NVP, and NFV induced rapid suppression of HIV-1 viral load and rises in CD4 cell count.

Adolescent↗

Activity, safety, and immunological effects of hydroxyurea added to didanosine in antiretroviral-naive and experienced HIV type 1-infected subjects: a randomized, placebo-controlled trial, ACTG 307.

We performed a 24-week, placebo-controlled, comparative trial of hydroxyurea (HU) monotherapy, didanosine(ddI) monotherapy, and the combination of ddI plus HU administered as 1000 mg qd or 1500 mg qd in antiretroviral-naive and experienced subjects with CD4+ lymphocyte counts of 200-700 cells/mm3. Enrollment included 134 subjects. HU enhanced the antiviral activity of ddI by 1.0 log10 copies/ml after 8 weeks of therapy, with sustained responses over 24 weeks. HU alone over 4 weeks had no effect. Lamivudine resistance had little impact on antiretroviral activity when examined across treatment arms. Increases in absolute CD4+ T cell counts, but not CD4+ T cell percentages, were less in subjects who received HU compared to ddI monotherapy, and lymphoproliferative responses to antigenic and mitogenic stimuli were not altered. Subjects who received HU 1500 mg were more likely to experience dose-limiting hematological toxicities compared to those who received 1000 mg, without any additional antiviral benefit. HU may continue to have a role as a component of HIV therapy.

Anti-HIV Agents↗

Once-daily quadruple-drug therapy with adefovir dipivoxil, Lamivudine, Didanosine, and efavirenz in treatment-naive human immunodeficiency virus type 1-infected patients.

A 48-week open-label study of 11 antiretroviral-naive, human immunodeficiency virus type 1 (HIV-1)-infected adults evaluated once-daily treatment with adefovir dipivoxil, lamivudine, didanosine, and efavirenz. At baseline, the median plasma HIV-1 RNA level was 4.99 log(10) copies/mL, and the median CD4 cell count was 471 cells/mm(3). At 24 and 48 weeks after initiation of treatment, median HIV-1 RNA levels decreased from baseline by 4.77 and 4.99 log(10) copies/mL, respectively, and median CD4 cell counts increased by 135 and 177 cells/mm(3), respectively. The regimen was generally well tolerated. No patients withdrew from the study because of adverse events. However, 7 patients developed adefovir-related nephrotoxicity after >/=20 weeks of treatment; this resolved without sequelae after adefovir was discontinued. Overall adherence was 85%. Once-daily quadruple-drug therapy with adefovir, lamivudine, didanosine, and efavirenz provides pronounced and durable suppression of HIV-1 RNA and elevation of CD4 cell counts over the course of 48 weeks, with generally good tolerability and adherence.

Adenine↗

One-step synthesis and structure of an oligo(spiro-orthocarbonate).

The reaction of pentaerythritol and tetraethylorthocarbonate at 260 degrees C for 12 h yields a white crystalline material that was characterized by 13C CPMAS NMR, CHN analysis, FT-IR, electron and X-ray powder diffraction, and Rietveld analysis. The white crystalline material was found to have the formula C6H8O4 and a crystal structure with a monoclinic cell [a = 9.167 A, b = 5.681 A, c = 5.880 A, beta = 90.0 degrees , space group I2] of hexagonally arranged spiro-oligomeric chains.

Journal Article↗

Supportive use of megestrol acetate (Megace) with head/neck and lung cancer patients receiving radiation therapy.

PURPOSE: The purpose of this study was to measure the effect of megestrol acetate (MA) on weight loss and quality of life (QOL) in patients with cancer of the lung or head and neck undergoing curative radiation therapy. METHODS AND MATERIALS: This was a Phase III, placebo-controlled, double-blind randomized study. Patients received either 800 mg/day of MA (20 milliliters po qAM) or placebo over a 12-week period. Patients received radiation of the head and neck or thorax using a dose of at least 50 Gy, either alone or with chemotherapy. Weight was assessed weekly, whereas QOL was assessed at baseline and at 4, 8, and 12 weeks. RESULTS: Patient characteristics on the MA arm (16 lung, 12 head/neck; mean age: 60 years) were similar to those on the placebo arm (17 lung, 11 head/neck; mean age: 65.8 years). Patients in the MA group had a mean weight loss over 12 weeks of 2.7 pounds, whereas the placebo group had a mean weight loss of 10.6 pounds. There was a significant time by treatment interaction (p = 0.001), with the difference in weight between treatment groups being most pronounced after 6 weeks. Although overall QOL was similar in both arms of the study, several QOL subscale items did differ significantly. Compared to the placebo-treated patients, head-and-neck cancer patients in the MA arm reported the ability to eat as much as they liked (p = 0.02 at 12 weeks), and lung cancer patients in the MA arm reported significantly better appetite at 4 weeks (p = 0.03) and 8 weeks (p = 0.001). CONCLUSION: MA used prophylactically is useful as an appetite stimulant; it can help patients maintain weight over the course of curative radiotherapy of the head and neck or lung and can improve specific aspects of QOL.

Adult↗

A review of adult ADHD: a neuropsychological and neuroimaging perspective.

Attention-deficit/hyperactivity disorder (ADHD) is a developmental disorder which effects an estimated 3% to 5% of children. Despite estimates that ADHD persists in 30% to 70% of adults having had the disorder in childhood, ADHD in adulthood remains controversial. This report summarizes current thinking in the diagnosis and etiology of adult ADHD. Most theories posit that ADHD is related to anomalies in frontal lobe function and dopaminergic transmission. However, there is debate as to whether ADHD is a unitary disorder with different manifestations, a syndrome, or multiple disorders. The Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, classifies ADHD into inattention, hyperactivity-impulsivity, and combined subtypes. Although problems with cognition are core ADHD symptoms, self-reporting has not been a reliable predictor of neuropsychological test performance. Nevertheless, we suggest that a performance-based diagnosis, including empirically derived, age-sensitive neuropsychological tests, provides the best hope of dissociating ADHD from psychiatric disorders with similar symptoms. We also describe the promise of new neuroimaging technologies, such as functional magnetic resonance imaging, in elucidating the pathophysiology of ADHD and similar psychiatric disorders.

Journal Article↗

Paramedic compliance with ACLS epinephrine guidelines in out-of-hospital cardiac arrest.

OBJECTIVE: The purpose of this observational study was to determine the baseline rate of adherence to current American Heart Association guidelines with regard to use of epinephrine in out-of-hospital cardiac arrests. METHODS: A structured explicit retrospective review of all adult victims of cardiac arrest logged in the EMSCQI.com database during its first 20 months in operation from February 2004 to October 2005. Noncompliance was defined as epinephrine administration on average less than every three minutes or greater than every five minutes regardless of dosage. Primary determination of noncompliance was calculated by dividing the time from first epinephrine dose to hospital arrival by the number of subsequent doses given during that time frame. RESULTS: Seventy-five of 11,000 advanced life support calls were identified as out-of-hospital cardiac arrests. The overall rate of noncompliance was 86% (95% confidence interval, 75-93%). The average time from the first epinephrine administration to hospital arrival was 22.6 minutes. The median number of epinephrine doses per patient was three. All patients in the noncompliant group received epinephrine less often than every five minutes. The data did not allow for examination of noncompliance predictors. CONCLUSIONS: Epinephrine administration in accordance with current advanced cardiac life support guidelines occurred in 14% of out-of-hospital cardiac arrest patients.

Adult↗

Traditional sampling with laboratory analysis and solid phase microextraction sampling with field gas chromatography/mass spectrometry by military industrial hygienists.

The opinions or assertions contained herein are the private ones of the authors and are not to be construed as official or reflecting the views of the United States Department of Defense or the Uniformed Services University of the Health Sciences. Rapid on-site detection and identification of environmental contaminants to which personnel may be exposed is often needed during military deployment situations. The availability of military industrial hygienists with capabilities for "complete" on-site exposure assessment of chemical species should allow detection and identification of a number of important stressors almost immediately following sample collection. Portable gas chromatography/mass spectrometry (GC/MS) provides a rapid and efficient separation of volatile and semivolatile organic analytes, accompanied by sensitive electron impact ionization-mass spectrometry (EI-MS) detection. The use of GC/MS in the field is limited, however, by equipment cost, complexity of the equipment, and the analytical process. Additionally, a skilled operator is needed to obtain useful separations and to interpret mass spectral data. To demonstrate benefits and limitations of "complete" exposure assessment capabilities, a previously unidentified complex mixture, produced by thermal dispersion of riot control agents, was examined. Established active sampling methods were used with laboratory analyses. Solid phase microextraction, a passive sampling method that simplifies preparation for GC/MS analysis, also was used with a field-portable GC/MS system. Both sampling/analysis methods were used to detect CS riot control agent-derived air contaminants dispersed from riot control type canisters through oxidizer-supported combustion of a chemical fuel.

Chemistry Techniques, Analytical↗