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Biomedical subjects

D Jennings

Publications and source records attributed to D Jennings.

At least 19 recordsLinked to original sources
PubMed2005

Prevalence of parkinsonism and relationship to exposure in a large sample of Alabama welders.

OBJECTIVE: To estimate the prevalence of parkinsonism in welders in Alabama and to compare this prevalence with that in a general population sample. METHODS: The authors screened 1,423 welders from Alabama who were referred for medical-legal evaluation for Parkinson disease (PD). Standardized videotaped assessments using the Unified Parkinson's Disease Rating Scale motor subsection 3 (UPDRS3) were obtained. Patients provided information regarding exposure to welding fumes and job titles. Job titles were matched with Department of Labor Standard Occupational Codes (SOCs). Diagnoses were assigned based on quantitative criteria for the diagnosis of PD using two thresholds for diagnosis. With use of the number of active welders in this screening with parkinsonism as the numerator and the age-adjusted number of welders in each SOC as the denominator, the prevalence of parkinsonism in Alabama welders was estimated using conservative assumptions and compared with general population data from Copiah County, MS. RESULTS: With use of conservative and liberal case definitions of parkinsonism, the estimated prevalence of parkinsonism among active male welders age 40 to 69 statewide was 977 to 1,336 cases/100,000 population. The prevalence of parkinsonism was higher among welders vs age-standardized data for the general population (prevalence ratio = 10.19, 95% CI 4.43 to 23.43). CONCLUSION: The estimated prevalence of parkinsonism was higher within a sample of male Alabama welders vs the general population of male residents of Copiah County, MS.

Adult↗
PubMed2005

How to develop reliable sofware.

A well-defined method for the design and development of software leads to more reliable software and products that get to market quicker. This article describes how to achieve this and examines good practice, modelling and embedded systems.

Computer Simulation↗
PubMed2005

Unique roles of SPET brain imaging in clinical and research studies. Lessons from Parkinson's disease research.

The increasing availability of PET imaging in nuclear medicine expands the armamentarium of clinical and research tools for improving diagnosis and treatment of neuropsychiatric disorders. Nonetheless, the role of SPECT imaging remains critical to both research and clinical practice. The development of rational strategies for guiding the selection of imaging modalities flows from primarily the nature of the clinical or research question and the availability of appropriate radiopharmaceuticals. There has been extensive SPECT and PET work in Parkinson's disease (PD) which highlights the value of both these scintigraphic modalities. Three main areas of interest in PD include imaging for improving diagnostic accuracy, for monitoring the progression of disease, and for assessing the therapeutic efficacy of drugs with neuroprotective potential. The demands of the clinical or research question posed to imaging dictates the selection of radiotracer and imaging modality. Diagnosis of PD represents the easiest challenge with many imaging biomarkers showing high sensitivity for detecting abnormal reduction of dopaminergic function based on qualitative review of images. On the other hand, using imaging to evaluate treatments which purportedly slow the rate of disease progression, indicated by the reduction in the rate of loss in a quantitative imaging signal in patients studied over time, represents the most rigorous requirement of the imaging measure. In each of these applications presynaptic markers of dopaminergic function using SPECT and PET have been extremely valuable. Review of neuroimaging studies of PD provides a useful example of optimized approaches to clinical and research studies in neuropsychiatric disorders.

Animals↗
PubMed2005

The role of neuroimaging in the early diagnosis and evaluation of Parkinson's disease.

The development of imaging biomarkers which target specific sites in the brain represents a significant advance in neurodegenerative diseases and Parkinson's disease with the promise of new and improved approaches for the early and accurate diagnosis of disease as well as novel ways to monitor patients and assess treatment. The 3 major applications of imaging may play a role in Parkinson's disease include: 1) the use of neuroimaging as a biomarker of disease in order to improve the accuracy, timeliness, and reliability of diagnosis; 2) objective monitoring of the progression of disease to provide a molecular phenotype of Parkinson's disease which may illuminate some of the sources of clinical variability; 3) the evaluation of so-called ''disease-modifying'' treatments designed to retard the progression of disease by interfering with pathways thought implicated in the ongoing neuronal loss or replace dopamine-producing cells. Each of these areas has shown a numbers of critical clinical investigations which have better defined the utility of the imaging tools to these tasks. Nonetheless, current unresolved issues around the clinical role of neuroimaging in monitoring patients over time and validation of quantitative imaging measures of dopaminergic function are immediate issues for the field and the subject of current research efforts and the extension of the lessons learned in Parkinson's to other neurodegenerative diseases including Alzheimer's dementia.

Diagnostic Errors↗
PubMed2004

Current injection electrodes for electrical impedance tomography.

Current conveyors have been identified as a possible component within the current injection electrodes of an electrical impedance tomography system, where accurate current generation or precise measurement of the current injected is required. Several circuit configurations have been investigated through simulation to determine the most suitable to meet the specifications of the EIT system. A bipolar (floating source) circuit configuration employing the use of current conveyors has been designed, which achieves greater than 12 mA output current without saturation, over an accepted body impedance range. Simulations were performed over frequencies in excess of 1 MHz, and the output phase shift was less than 0.15 degrees up to 250 kHz, and 0.6 degrees up to 1 MHz.

Electric Impedance↗
PubMed2003

Health and safety implications of injury in professional rugby league football.

BACKGROUND: Professional sport is characterized by high injury rates but is also covered by health and safety legislation. AIM: To examine the incidence of injury in professional rugby league as defined by the Reporting of Diseases and Dangerous Occurrences Regulations 1995 (RIDDOR 95). METHODS: All injuries received during playing and training to both first-team and 'academy' (<19 years old) players during two playing seasons at one professional club were recorded. The length of time a player was unable to take part in full training and playing was used as a measure of severity. Injuries were classified into minor injuries (0-3 days), over 3 day injuries or major injuries, in which the final two categories corresponded with RIDDOR 95. RESULTS: Thirty-two per cent (95% confidence interval=26-39%) of all injuries received satisfied the RIDDOR 95 criteria. The overall injury rate was 8.5 per 1000 h (7.2-9.9) for the first team and 4.1 per 1000 h (3.2-5.4) for the academy team. During match play the first-team injury rate was 157.7 per 1000 h (133.5-185.1) and 67.7 (51-81.1) for the academy team. Training injury rates were lower, at 0.5 per 1000 h (0.2-1.0) and 0.3 per 1000 h (0.1-0.8), respectively. CONCLUSION: The injury rate for professional rugby league is much higher than reported in other high-risk occupations such as mining and quarrying. The large differences in injury rates between first and academy teams have implications for young players likely to progress to first-team status.

Adolescent↗
PubMed2002

Do dopamine agonists or levodopa modify Parkinson's disease progression?

During the past decade, in vivo imaging of the nigrostriatal dopaminergic system has been developed as a research tool to monitor progressive dopaminergic neuron loss in Parkinson's disease (PD) and to assess the effect of medication on imaging outcomes. Recently two similar studies compared the effect of initial treatment with a dopamine agonist (pramipexole (CALM-PD CIT) or ropinirole (REAL-PET)) or levodopa on the progression of PD as measured by [123I]beta-CIT or [18F]Dopa imaging. These two clinical imaging studies targeting dopamine function with different imaging ligands and technology both demonstrate slowing in the rate of loss of [123I]beta-CIT or [18F]Dopa uptake in early PD patients treated with dopamine agonists compared with levodopa. The relative reduction in the per cent loss from baseline of [123I]beta-CIT uptake in the pramipexole versus the levodopa group was 47% at 22 months, 44% at 34 months and 37% at 46 months after initiating treatment. The relative reduction of 18F-dopa uptake in the ropinirole group versus the levodopa group was 35% at 24 months. These results should be very cautiously interpreted with regard to the effect of dopamine agonists or levodopa on clinical disease progression. These data highlight the need to compare imaging outcomes of dopamine neuronal loss with multiple meaningful clinical endpoints of disease progression in placebo controlled, larger and long-term studies.

Animals↗
PubMed2002

Experimental evidence that changes in oocyte growth influence meiotic chromosome segregation.

BACKGROUND: It is well known that the fidelity of meiotic chromosome segregation is greatly reduced with increasing maternal age in humans. More recently, direct studies of human oocytes have demonstrated a striking age-related increase in oocytes exhibiting gross disturbances in chromosome alignment on the meiotic spindle. This abnormality, termed congression failure, has been postulated to be causally related to human non-disjunction and to result from subtle alterations in folliculogenesis that develop with advancing reproductive age. METHODS: Immunofluorescence staining, conventional cytogenetic analysis and spectral karyotyping of oocytes from mouse models were used to investigate the hypothesis that changes in the regulation of folliculogenesis induce meiotic defects. RESULTS: Mutations that affect oocyte growth were found to increase the frequency of congression failure at first meiotic metaphase. Importantly, increased congression failure was correlated with meiotic non-disjunction, suggesting a cause-and-effect relationship. CONCLUSIONS: Our findings support the hypothesis that congression failure results from disturbances in the complex interplay of signals regulating folliculogenesis and that these changes subtly alter the late stages of oocyte growth, increasing the risk of a non-disjunction error. These findings have important implications for human aneuploidy, since they suggest that it may be possible to develop prophylactic treatments for reducing the risk of age-related aneuploidy.

Anaphase↗
PubMed2001

A randomized, controlled trial of remacemide for motor fluctuations in Parkinson's disease.

BACKGROUND: Preclinical studies suggest that glutamate antagonists help ameliorate motor fluctuations in patients with PD treated with levodopa. METHODS: In a multicenter, randomized, double-blind, placebo-controlled, parallel-group, dose-ranging study, the authors assessed the safety, tolerability, and efficacy of the glutamate receptor blocker remacemide hydrochloride in 279 patients with motor fluctuations treated with levodopa. The primary objective was to assess the short-term tolerability and safety of four dosage levels of remacemide during 7 weeks of treatment. Patients were also monitored with home diaries and the Unified PD Rating Scale (UPDRS) to collect preliminary data on treatment efficacy. RESULTS: Remacemide was well tolerated up to a dosage of 300 mg/d on a twice daily schedule and 600 mg/d on a four times daily schedule. The most common dosage-related adverse events were dizziness and nausea, as observed in previous studies of remacemide. The percent "on" time and motor UPDRS scores showed trends toward improvement in the patients treated with 150 and 300 mg/d remacemide compared with placebo-treated patients, although these improvements were not significant. CONCLUSION: Remacemide is a safe and tolerable adjunct to dopaminergic therapy for patients with PD and motor fluctuations. Although this study had limited power to detect therapeutic effects, the observed improvement is consistent with studies of non-human primates with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonian signs and symptoms. Additional studies are warranted to confirm these results over an extended period of observation, and to explore the potential neuroprotective effects of remacemide in slowing the progression of PD.

Acetamides↗
PubMed2001

[(123)I]beta-CIT SPECT imaging demonstrates reduced density of striatal dopamine transporters in Parkinson's disease and multiple system atrophy.

In vivo imaging of the dopamine transporter (DAT) with single photon emission computed tomography (SPECT) is a quantitative biomarker for Parkinson's disease (PD) onset and severity. This study has examined and compared the loss of striatal DAT in PD and multiple system atrophy (MSA) using [(123)I]beta-CIT SPECT imaging. One hundred and eighty-three patients (157 PD and 26 MSA) were studied. Clinical rating scales (Hoehn and Yahr stage and Unified Parkinson's Disease Rating Scale [UPDRS] scores) demonstrated that the MSA patients were more severely impaired than the PD patients. The striatal [(123)I]beta-CIT SPECT uptake was markedly reduced in both the PD and MSA groups. In addition, MSA patients showed more symmetric DAT loss compared with the PD patients, consistent with the more symmetric clinical motor dysfunction observed in MSA. While the loss of DAT was significantly reduced in all regions in both MSA and PD, comparison of the relative loss of the DAT did not significantly improve diagnostic accuracy in distinguishing between PD and MSA.

Adult↗
PubMed2001

Front-end architecture for a multi-frequency electrical impedance tomography system.

This paper provides a critical review of a number of the primary aspects of EIT system hardware presented in the literature. A thorough analysis of injection and measurement errors is presented to provide clarifying extensions to that provided by previous authors. From this basis, it proposes a novel design for a distributed parallel multi-frequency EIT system. The system described is modular, employs active electrodes to maximise CMRR (common mode rejection ratio) and was designed to employ digitally generated current injection and digital demodulation of the acquired signals.

Electric Impedance↗
PubMed2001

An operational model to investigate contact sports injuries.

PURPOSE: A cyclical operational model is proposed to examine the interrelationship of a number of factors that are involved in sports injury epidemiology. In sports injury research, investigations often attempt to identify a unique risk factor that distinguishes an injured player. However, a wide variety of factors can contribute to a sports injury occurring, and an understanding of the cause of injury is important to advance knowledge. METHODS: The proposed model identifies a healthy/fit player initially, although the player may exhibit a number of intrinsic risk factors for sports injury. Before exposure to extrinsic risk factors, there is the opportunity for implementation of prevention strategies by coaching personnel and the sports medicine team. These strategies might include, among others, appropriate warm-up, adequate hydration, wearing protective equipment, and prophylactic taping. Additionally, preventative screening could take place to assess the various intrinsic and extrinsic risk factors that could lead to sports injury. DISCUSSION: Two examples of how the operational model relates to contact sports injury cases are presented. Participating in sport inevitably exposes the player to external risk factors that predispose toward injury. The treatment of the injured player aims to restore the player to preinjury playing status and to prevent the injury from becoming chronic. CONCLUSIONS: It is suggested that the application of this proposed cyclical model may lead to greater success in understanding the multifaceted nature of sports injuries and furthermore help minimize injury risk and support the rehabilitation of injured contact sports participants.

Athletic Injuries↗
PubMed2000

Design of an electrical impedance tomography phantom using active elements.

The architecture of a novel phantom for electrical impedance tomography (EIT) is proposed. The design employs active elements, which include multiplying digital to analogue converters (MDAC), so that the impedance distribution in the phantom may be varied dynamically using computer control. The phantom is designed to assist in the validation of an EIT system under test. A number of published layouts for passive phantoms are analysed, and the requirements for an active element are specified for the most applicable of these. The use of active elements throughout a phantom imposes significant costs because of the need for each active element to operate independently. This proposal limits the cost and complexity by employing active elements in a restricted region of the phantom. Currently available technology, principally due to the limited analogue bandwidth of the MDAC, precludes the construction of a fully capable phantom from active elements. However, a design is specified that would enable its future development to cover the frequency range from 10 kHz to 1 MHz.

Electric Impedance↗
PubMed2000

Synthesis of a digitally controlled impedance element.

A practical design for the synthesis of a digitally controlled electrical impedance element is presented. The impedance element comprises a real impedance element in series with a voltage source whose magnitude is determined by the applied voltage multiplied by a factor k. The value of k is shown strongly to affect the circuit's performance. Results are presented which demonstrate the correspondence between circuit models and practical measurements. When negative values for k were employed the circuit element offered a controlled impedance range of 1:1000 and was stable to at least 1.5 MHz, providing that low source impedance values were used. With a positive k, a restricted range of impedance values could be obtained and the value of source impedance was less critical, though the circuit's performance was acceptable only to about 100 kHz. Consideration is given to the specification of a multiplier that would permit the circuit's range of application to be extended to low megahertz frequencies.

Electric Impedance↗
PubMed1999

Localization of a gene for myoclonus-dystonia to chromosome 7q21-q31.

Essential myoclonus-dystonia is a neurological condition characterized by myoclonic and dystonic muscle contractions and the absence of other neurological signs or laboratory abnormalities; it is often responsive to alcohol. The disorder may be familial with apparent autosomal dominant inheritance. We report a large kindred with essential familial myoclonus-dystonia and map a locus for the disorder to a 28-cM region of chromosome 7q21-q31.

Adolescent↗
PubMed1999

Safety profile of Lansoprazole: the US clinical trial experience.

OBJECTIVE: Lansoprazole has undergone extensive clinical evaluation for the treatment of acid-peptic diseases. The aim of this study was to define the safety profile of lansoprazole and compare it to that of other therapeutic agents evaluated in the same controlled trials. METHODS: The clinical safety profile of lansoprazole and comparative agents (placebo, ranitidine and omeprazole) was reviewed for 3281 patients who participated in short term (up to 8 weeks) and long term (up to 56 months) clinical trials conducted in the US. Adverse events, laboratory value changes and gastric biopsy changes that occurred during treatment were compared statistically for differences between treatments. RESULTS: The incidence of adverse events and number of patients discontinuing treatment because of adverse events was similar for lansoprazole and comparative agents. Other than elevated serum gastrin levels, a known effect of proton pump inhibitors, no trends in laboratory changes were observed. Median values for gastrin levels remained within the normal range; about 2% of patients had gastrin levels >400 pg/ml at any time, while <1% had 2 or more gastrin values >500 pg/ml. Values returned to baseline levels after therapy was discontinued. No significant changes in gastric endocrine cell growth from baseline to final visit were observed, nor was there evidence of dysplasia or neoplasia. CONCLUSION: Lansoprazole is well tolerated for both short and long term treatment of acid-related disease. The tolerability of lansoprazole is comparable to that of ranitidine, omeprazole and placebo in the treatment of these diseases.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1998

Identical twin marrow transplantation for venous thrombosis in paroxysmal nocturnal hemoglobinuria; long-term complete remission as assessed by flow cytometry.

Paroxysmal nocturnal hemoglobinuria (PNH), an acquired clonal hematopoietic disorder characterized by protean clinical manifestations, is associated with significant morbidity and mortality. We report a 24-year-old patient with PNH complicated by deep vein thrombosis who underwent syngeneic bone marrow transplantation. No clinical symptomatology or stigmata of disease have recurred. Immunophenotyping of this patient over 12 years after her procedure revealed all peripheral circulating cells to express normal levels of CD59. Histocompatible marrow transplantation remains the definitive method of treatment for PNH with modern immunophenotyping capable of sensitive follow-up post-transplant.

Adult↗