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Biomedical subjects

D M Simpson

Publications and source records attributed to D M Simpson.

At least 19 recordsLinked to original sources
PubMed2006

HIV neuropathy natural history cohort study: assessment measures and risk factors.

BACKGROUND: Distal sensory polyneuropathy (DSP) is the most common neurologic complication of human immunodeficiency virus (HIV) infection. Risk factors for DSP have not been adequately defined in the era of highly active antiretroviral therapy. METHODS: The authors evaluated 101 subjects with advanced HIV infection over 48 weeks. Assessments included a brief peripheral neuropathy (PN) screen (BPNS), neurologic examination, nerve conduction studies, quantitative sensory testing (QST), and skin biopsies with quantitation of epidermal nerve fiber density. Data were summed into a Total Neuropathy Score (TNS). The presence, severity, and progression of DSP were related to clinical and laboratory results. RESULTS: The mean TNS (range 0 to 36) was 8.9, with 38% of subjects classified as PN-free, 10% classified as having asymptomatic DSP, and 52% classified as having symptomatic DSP. Progression in TNS from baseline to week 48 occurred only in the PN-free group at baseline (mean TNS change = 1.16 +/- 2.76, p = 0.03). Factors associated with progression in TNS were lower current TNS, distal epidermal denervation, and white race. As compared with the TNS diagnosis of PN at baseline, the BPNS had a sensitivity of 34.9% and a specificity of 89.5%. CONCLUSIONS: In this cohort of advanced human immunodeficiency virus (HIV)-infected subjects, distal sensory polyneuropathy was common and relatively stable over 48 weeks. Previously established risk factors, including CD4 cell count, plasma HIV RNA, and use of dideoxynucleoside antiretrovirals were not predictive of the progression of distal sensory polyneuropathy (DSP). Distal epidermal denervation was associated with worsening of DSP. As compared with the Total Neuropathy Score, the brief peripheral neuropathy screen had relatively low sensitivity and high specificity for the diagnosis of DSP.

Cohort Studies↗
PubMed2005

Objective selection of signals for assessment of cerebral blood flow autoregulation in neonates.

A number of different system identification techniques have been proposed to assess dynamic cerebral autoregulation in critically ill patients. From these methods, the response to a standard stepwise change in blood pressure can be estimated. Responses lacking physiological consistency are a common occurrence and could be the consequence of particular system identification procedures or, alternatively, caused by measurements with a poor signal-to-noise ratio. A multi-observer approach was adopted in this paper to classify cerebral blood flow velocity (CBFV) step responses to spontaneous changes in arterial blood pressure in a group of 43 neonates with a mean gestational age of 33.7 weeks (range 24-42 weeks) and a mean birthweight of 1,980 g (range 570-3,910 g). Three experienced observers independently analysed the estimated step responses in 191 recordings each lasting 100 s; for an autoregressive (ARX) model, 124 (65%) of the step responses were accepted by at least two of the three observers. Two other system identification methods, transfer function analysis and the moving average Wiener-Laguerre model, gave 90 (45%) and 98 (51%) acceptable responses, respectively. Only 54 epochs (28%) were accepted with all three methods. With 88 (46%) responses rejected by at least two methods, it can be concluded that signal quality was the main reason for nonphysiological step responses. To avoid the need for subjective visual selection, an automatic procedure for classifying step responses was implemented leading to sensitivities and specificities in the range 85-90%, with respect to the agreement with subjective evaluations. Objective selection of CBFV step responses is thus feasible and could also be adapted for other physiological measurement techniques relying on system identification methods.

Blood Flow Velocity↗
PubMed2005

High spontaneous fluctuation in arterial blood pressure improves the assessment of cerebral autoregulation.

Cerebral autoregulation maintains a relatively constant blood flow despite changes of blood pressure in the brain. Linear models have been extensively applied to identify this mechanism, using spontaneous arterial blood pressure (ABP) fluctuation as input and cerebral blood flow velocity (CBFV) change as output. Although valuable measurements have been achieved by these models, accuracy and consistency are of great concern due to the large variability of results. We therefore investigated whether more reliable measurements can be achieved by selecting only those recordings (or parts of recordings) with relatively high spontaneous variability of ABP. Twenty-four recordings, 7 from hypercapnia and 17 from normocapnia, of ABP and CBFV from 9 healthy adults were analyzed. Two conventional autoregulatory parameters were used to assess cerebral autoregulation. In the absence of a 'gold' standard for the study of dynamic cerebral autoregulation, lower variability of the parameters and higher correlation with pCO(2) were considered as criteria for identifying improved measures of autoregulation. Both significantly lower variability of the parameters, and higher correlation between the parameters and pCO(2) were achieved from the data with higher variability of blood pressure. We therefore conclude that ABP with high variability may effectively stimulate regulatory response in blood flow resulting in improved assessment of cerebral autoregulation.

Arteries↗
PubMed2005

Demystifying biomedical signals: a student centred approach to learning signal processing.

The processing and analysis of physiological signals has become firmly established in clinical medicine and biomedical research. Many of the users of this technology however do not come from an engineering or science background, and traditional approaches in teaching signal processing are thus not appropriate for them. We have therefore developed a series of modular courses that are aimed specifically at an audience with a background in medicine, health-care or the life-sciences. In these courses, we focus on the concepts, principles and rationale of applying signal processing methods, rather than the mathematical foundations of the techniques. Thus, we aim to remove some of the perceived 'mystery' often surrounding this subject. The very practical approach, with hands-on experience using the MATLAB software, has been well received, with strong evidence that students have learnt to apply their knowledge. This paper describes the learning and teaching approach taken, and some of the experience acquired.

Algorithms↗
PubMed2003

Lamotrigine for HIV-associated painful sensory neuropathies: a placebo-controlled trial.

OBJECTIVE: To evaluate the efficacy and tolerability of lamotrigine (LTG) for the treatment of pain in HIV-associated sensory neuropathies. METHODS: In a randomized, double-blind study, patients with HIV-associated distal sensory polyneuropathy (DSP) received LTG or placebo during a 7-week dose escalation phase followed by a 4-week maintenance phase. Randomization was stratified according to whether or not patients were currently using neurotoxic antiretroviral therapy (ART). RESULTS: The number of patients randomized was 92 (62 LTG, 30 placebo) in the stratum receiving neurotoxic ART and 135 (88 LTG, 47 placebo) in the stratum not receiving neurotoxic ART. Mean change from baseline in Gracely Pain Scale score for average pain was not different between LTG and placebo at the end of the maintenance phase in either stratum, but the slope of the change in Gracely Pain Scale score for average pain reflected greater improvement with LTG than with placebo in the stratum receiving neurotoxic ART (p = 0.004), as did the mean change from baseline scores on the Visual Analogue Scale for Pain Intensity and the McGill Pain Assessment Scale and patient and clinician ratings of global impression of change in pain (p </= 0.02). The incidence of adverse events, including rash, was similar between LTG and placebo. CONCLUSIONS: Lamotrigine was well-tolerated and effective for HIV-associated neuropathic pain in patients receiving neurotoxic antiretroviral therapy. Additional research is warranted to understand the differing response among patients receiving neurotoxic antiretroviral therapy compared with those not receiving neurotoxic antiretroviral therapy.

Adult↗
PubMed2002

Reduced intraepidermal nerve fiber density in HIV-associated sensory neuropathy.

OBJECTIVE: To explore the relationship between intraepidermal nerve fiber (IENF) density in HIV-associated sensory neuropathy (HIV-SN) to measurements of neuropathy severity and progression of HIV disease. BACKGROUND: SN affects 30% of individuals with AIDS, and treatment is often ineffective. Recombinant human nerve growth factor (rhNGF) has been proposed as a trophic factor for unmyelinated nerve fibers injured in HIV-SN, and a clinical trial has recently concluded. Skin biopsy with IENF density determination has emerged as a diagnostic test for patients with small-fiber sensory neuropathy. METHODS: Sixty-two of the 270 patients with HIV-SN who participated in the trial of rhNGF were included in a substudy examining epidermal nerve fibers. IENF density was compared with neuropathic pain intensity (measured with the Gracely Pain Scale), patient and physician global pain assessments, quantitative sensory testing, CD4 counts, and plasma HIV RNA levels both at baseline and at conclusion of the placebo-controlled phase. RESULTS: IENF density was inversely correlated with neuropathic pain as measured by patient (p = 0.004) and physician (p = 0.05) global pain assessments, but not using the Gracely Pain Scale. Decreased IENF density at the distal leg was associated with lower CD4 counts and higher plasma HIV RNA levels. IENF density measurements were stable over time. CONCLUSIONS: IENF loss at the distal leg is associated with increased neuropathic pain, lower CD4 counts, and higher plasma viral load in HIV-SN. The robustness of the longitudinal measurement of IENF density supports its use in future longitudinal studies and clinical trials.

Acquired Immunodeficiency Syndrome↗
PubMed2002

Coherence between one random and one periodic signal for measuring the strength of responses in the electro-encephalogram during sensory stimulation.

Coherence between a pulse train representing periodic stimuli and the EEG has been used in the objective detection of steady-state evoked potentials. This work aimed to quantify the strength of the stimulus responses based on the statistics of coherence estimate between one random and one periodic signal, focusing on the confidence limits and power of significance tests in detecting responses. To detect the responses in 95% of cases, a signal-to-noise ratio of about -7.9 dB was required when using 48 windows (M) in the coherence estimation. The ratio, however, increased to -1.2 dB when M was 12. The results were tested in Monte Carlo simulations and applied to EEGs obtained from 14 subjects during visual stimulation. The method showed differences in the strength of responses at the stimulus frequency and its harmonics, as well as variations between individuals and over cortical regions. In contrast to those from the parietal and temporal regions, results for the occipital region gave confidence limits (with M = 12) that were above zero for all subjects, indicating statistically significant responses. The proposed technique extends the usefulness of coherence as a measure of stimulus responses and allows statistical analysis that could also be applied usefully in a range of other biological signals.

Adolescent↗
PubMed2002

Safety and clinical effects of topical histatin gels in humans with experimental gingivitis.

BACKGROUND: Our research group has recently reported that exogenously applied histatins can inhibit plaque accumulation and gingival inflammation in a preclinical canine model (Paquette et al. 1997). OBJECTIVES: The aims of the present double-blinded, randomized, controlled clinical trial were to evaluate the safety and toxicity of three histatin (P-113) concentrations in gel formulations, and to assess potential clinical benefit on the development of gingivitis (partial mouth design). MATERIAL AND METHODS: One hundred and six healthy subjects were recruited and brought to optimal gingival health (GI < 0.5) prior to treatment initiation. At baseline, eligible subjects were randomized for one of the following treatments: (1) placebo; (2) 0.0625% P-113; (3) 0.125% P-113; and (4) 0.375% P-113. Patients self-applied gels twice daily for 29 days to the maxillary right quadrant with the use of customized stents. In addition, patients deferred all oral hygiene procedures within this quadrant for the duration of the treatment period. Safety was assessed in terms of physical and oral examinations, clinical laboratory testing and recording of adverse events. Clinical indices were measured weekly and included gingival index (GI), plaque index (PI) and %BOP. RESULTS: All study formulations were well tolerated by patients, and no differences in adverse event occurrences were noted among treatment groups, including taste alteration or staining. For the intent-to-treat population, significantly smaller %BOP changes were noted in subjects treated with 0.0625, 0.125 and 0.375% P-113 gels (17.4, 18.18 and 17.9%, respectively) versus placebo (28.0%) (p < 0.05) at day 29. When groups were compared in terms of per cent responders (change in %BOP < 15 or < 20%), P-113 treatment groups exhibited a higher frequency of response, especially for the 0.0625 and 0.125% P-113 formulations (p < 0.05). Although no statistically significant intergroup differences were noted for changes in GI or PI among all subjects (intent-to-treat population), significantly smaller changes in PI at day 22 were observed among compliant individuals (defined as subjects using > 60% of the target gel mass) administering P-113 gels as compared with compliant placebo subjects (p < 0.05). CONCLUSIONS: These data indicate safety and tolerance of P-113 gels for topical oral use in human subjects. These data also suggest that P-113 gels administered twice daily may reduce experimental gingivitis as measured with bleeding on probing in humans.

Adult↗
PubMed2001

Long-term treatment with recombinant nerve growth factor for HIV-associated sensory neuropathy.

HIV-associated distal sensory polyneuropathy (DSP) is a common complication of AIDS. No effective treatment is available. The authors investigated the long-term effect (48 weeks) of the neurotrophin nerve growth factor (NGF) in an open-label study of 200 subjects with HIV-associated DSP. Similar to their previously reported double-blind study, the authors showed that NGF was safe and well tolerated and significantly improved pain symptoms. However, there was no improvement of neuropathy severity as assessed by neurologic examination, quantitative sensory testing, and epidermal nerve fiber density.

Acquired Immunodeficiency Syndrome↗
PubMed2001

Randomized controlled trial of IVIg in untreated chronic inflammatory demyelinating polyradiculoneuropathy.

OBJECTIVE: To determine the efficacy of IV immunoglobulin (IVIg) given patients with untreated chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). METHODS: A randomized, double-blind, multicenter, investigator-initiated study compared IVIg (Aventis Behring LLC, King of Prussia, PA) with placebo (5% albumin). On days 1, 2, and 21, IVIg (1 g/kg) or placebo was given. The primary outcome measure was the change in muscle strength from baseline to day 42, using the average muscle score (AMS). Secondary outcome measures included change from baseline AMS at days 10 and 21, the Hughes' functional disability scale, forced vital capacity (FVC), and nerve conduction studies (NCS) of four motor nerves (median, ulnar, peroneal, and tibial). RESULTS: The patients (n = 33) were randomized. Of these, 30 (14 women, 16 men, aged 54 +/- 20 years, range 13 to 82) received IVIg and 23 were given placebo (12 women, 11 men, aged 50 +/- 18 years, range 23 to 73). Baseline AMS values of the groups were similar (IVIg 7.06 +/- 1.31 versus placebo 7.28 +/- 1.18, p = 0.53). There were two dropouts in placebo group and one in the IVIg group. Mean AMS improved at day 42 comparing IVIg with placebo (0.63 versus -0.1, p = 0.006). Improved strength was seen by day 10. The placebo group lost strength over this same interval. In the IVIg, 11 subjects improved by the functional disability scale; none worsened. This differed (p = 0.019) from those in the placebo-treated group (two improved, two got worse, remainder unchanged). Forced vital capacity did not improve with IVIg treatment. IVIg improved ulnar motor distal latency (p = 0.005), tibial distal compound muscle amplitude (p = 0.003), and peroneal nerve conduction velocity (p = 0.03). CONCLUSIONS: IVIg improves strength in patients with untreated CIDP by day 10 with continued benefit through day 42; more than one third improve by at least a functional grade on a disability scale. This study provides data supporting IVIg as the initial treatment for CIDP.

Adolescent↗
PubMed2001

Estimation and significance testing of cross-correlation between cerebral blood flow velocity and background electro-encephalograph activity in signals with missing samples.

Cross-correlation between cerebral blood flow (CBF) and background EEG activity can indicate the integrity of CBF control under changing metabolic demand. The difficulty of obtaining long, continuous recordings of good quality for both EEG and CBF signals in a clinical setting is overcome, in the present work, by an algorithm that allows the cross-correlation function (CCF) to be estimated when the signals are interrupted by segments of missing data. Methods are also presented to test the statistical significance of the CCF obtained in this way and to estimate the power of this test, both based on Monte Carlo simulations. The techniques are applied to the time-series given by the mean CBF velocity (recorded by transcranial Doppler) and the mean power of the EEG signal, obtained in 1 s intervals from nine sleeping neonates. The peak of the CCF is found to be low (< or = 0.35), but reached statistical significance (p < 0.05) in five of the nine subjects. The CCF further indicates a delay of 4-6s between changes in EEG and CBF velocity. The proposed signal-analysis methods prove effective and convenient and can be of wide use in dealing with the common problem of missing samples in biological signals.

Blood Flow Velocity↗
PubMed2001

AIDS and AIDS-treatment neuropathies.

AIDS and AIDS-treatment neuropathies are common in individuals infected with HIV. As patients live longer due to improved antiretroviral therapies, the impact of painful neuropathy on patients' lives may increase. Several antiretroviral medications are known to cause toxic neuropathy in AIDS patients; but this may be outweighed by the beneficial effects of viral suppression. Current theories on the pathogenesis of AIDS neuropathies include mitochondrial toxicity secondary to gamma-DNA polymerase inhibition and subsequent abnormal mitochondrial DNA synthesis. Treatment of AIDS neuropathies is directed toward relief of symptoms, however, new evidence suggests that aggressive antiretroviral therapy may also be effective.

Acquired Immunodeficiency Syndrome↗
PubMed2001

Neurological manifestations of HIV-1 infection in the HAART era.

Neurologic complications in patients with AIDS are diverse and include opportunistic infections and lymphoma, as well as HIV-related peripheral neuropathy, myelopathy, and dementia. Improved prophylaxis and antiretroviral therapies have modified the approach to neurologic disease in the setting of AIDS.

AIDS Dementia Complex↗
PubMed2001

Lumbar back muscle activity of helicopter pilots and whole-body vibration.

Several studies have attributed the prevalence of low back pain (LBP) in helicopter pilots mainly to poor posture in-flight and whole-body vibration, with the latter hypothesis particularly related to a cyclic response of the erector spine (ES) muscle to vibration. This work aims to determine if helicopter vibration and the pilot's normal posture during flight have significant effects on the electromyogram (EMG) of the ES muscle. The bilateral surface EMG of the ES muscle at the L3 level was collected in 10 young pilots before and during a short flight in UH-50 helicopters. The vibration was monitored by a triaxial accelerometer fixed to the pilots' seat. Prior to the flight, the EMG was recorded for relaxed seated and standing postures with 0 degrees (P0) and 35 degrees (P35) of trunk flexion. The effect of the posture during the flight was tested by comparing left and right EMG (normalized with respect to P35). The in-flight muscle stress was evaluated by histograms of EMG activity, and compared to P0 values. Only one pilot in ten showed significant (p<0.05) correlation between the vibration and the EMG over cycles of vibration, and no consistent causal effect was found. The pilots' posture did not show significant asymmetric muscular activity, and low EMG levels were observed during most of the duration of the flight. The results do not provide evidence that LBP in helicopter pilots is caused by ES muscle stress in the conditions studied.

Adult↗
PubMed2001

National, state and urban-area vaccination-coverage levels among children aged 19-35 months, United States, 1999.

BACKGROUND: Assessment of vaccination coverage is an important component of the U.S. vaccination program and is primarily measured by the National Immunization Survey (NIS). METHODS: The 1999 NIS is a nationally representative sample of children aged 19 to 35 months, verified by provider records, that is conducted to obtain estimates of vaccination coverage rates. Coverage estimates are calculated for the nation, states, and selected urban areas for recommended vaccines and selected vaccine series. RESULTS: Coverage estimates are presented by a variety of demographic and healthcare-related factors: overall, by poverty status, race/ethnicity, selected milestone ages, participation in WIC, level of urbanicity, provider participation in VFC, and by provider facility type. In 1999, national coverage estimates were high for most vaccines and among most demographic groups. State and urban-area level estimates varied.

Aid to Families with Dependent Children↗