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Biomedical subjects

Michael P McDermott

Publications and source records attributed to Michael P McDermott.

At least 19 recordsLinked to original sources
PubMed2007

An evaluation of neurocognitive status and markers of immune activation as predictors of time to death in advanced HIV infection.

BACKGROUND: Several markers of immune activation have been identified as potential prognostic markers for human immunodeficiency virus (HIV)-associated morbidity and mortality, but the results from studies are conflicting. OBJECTIVE: To evaluate whether neurocognitive status and baseline levels of plasma and cerebrospinal fluid tumor necrosis factor alpha (TNF-alpha), macrophage chemoattractant protein 1 (MCP-1), matrix metalloproteinase 2 (MMP-2), or macrophage colony-stimulating factor (M-CSF) are associated with time to death in a cohort with advanced HIV infection. DESIGN: Cohort study. SETTING: Enrollees in the Northeast AIDS Dementia Study. PARTICIPANTS: Three hundred twenty-nine subjects who were positive for HIV-1 and had a CD4 cell count of less than 200/microL (or <300/microL but with cognitive impairment at baseline) were assessed for CD4 cell count, neurocognitive status, pertinent demographic and clinical variables, and plasma and cerebrospinal fluid HIV RNA, TNF-alpha, MCP-1, MMP-2, and M-CSF levels. MAIN OUTCOME MEASURES: Cox proportional hazards regression models were used to examine the associations between the variables of interest (using time-dependent covariates, where applicable) and time to death, adjusting for possible confounders. RESULTS: There were 50 deaths in the cohort after a median of 25.2 months of follow-up. The cumulative incidences of death were 7% at 1 year and 16% at 2 years. In Cox proportional hazards regression analyses adjusting for demographic, clinical, and immunological variables, HIV-associated dementia (hazard rate, 6.10; P = .001) was significantly associated with time to death; (log) plasma MCP-1 level (hazard rate, 3.38; P = .08) trended toward significance. CONCLUSION: In patients with advanced HIV infection, HIV-associated dementia is an independent predictor of time to death.

Adult↗
PubMed2006

A randomized trial comparing long-term and short-term use of umbilical venous catheters in premature infants with birth weights of less than 1251 grams.

BACKGROUND: Umbilical vein and percutaneous central venous catheters are often used in preterm infants, but they can lead to complications, including infection. OBJECTIVE: We hypothesized that long-term umbilical vein catheter use would result in fewer infections than short-term umbilical vein catheter use followed by percutaneous central venous catheter placement. DESIGN/METHODS: Infants < or = 1250 g with umbilical vein catheters placed at admission were randomly assigned to a long-term (umbilical vein catheter up to 28 days) or short-term (umbilical vein catheter for 7-10 days followed by percutaneous central venous catheter) group. Catheter infection was defined as symptoms and > or = 1 positive blood culture for definite pathogens or >1 positive culture for other organisms, with a catheter in place. Clinically significant echocardiogram findings were defined as thrombi threatening vascular occlusion, crossing/blocking heart valves, or otherwise felt to be significant by the cardiologist. The primary outcome was time from birth to catheter infection, analyzed by the log-rank test. RESULTS: There were 106 subjects in the short-term group and 104 in the long-term group with birth weights of 915 +/- 198 and 931 +/- 193 g and gestational ages of 27.8 +/- 2.0 and 27.7 +/- 2.2 weeks, respectively. The distribution of time to catheter infection did not differ between the groups. The overall incidence of catheter infection was 13% in the short-term group and 20% in the long-term group. Median age at catheter infection was 11.5 days in the short-term group and 14 days in the long-term group. There were 7.4 infections per 1000 catheter-days in the short-term group and 11.5 per 1000 in the long-term group. Seven infections in the short-term group were in umbilical vein catheters, and 18 infections in the long-term group were in umbilical vein catheter. Echocardiograms detected 4 infants in the short-term group and 7 infants in the long-term group with significant thrombosis. All significant thrombi were at the site of the umbilical vein catheter tip. No thrombus caused hemodynamic compromise, no child had clinical symptoms of thrombosis, and none required therapy. Of the 45 small-for-gestational-age infants in the study, 9 developed thrombi (short-term group, 4; long-term group, 5). The incidence of thrombi was higher in the small-for-gestational-age group (20%) versus other study subjects (9%). There were no differences in time to full feedings or to regain birth weight or in the incidence of necrotizing enterocolitis or death. CONCLUSIONS: Infection and complication rates were similar between infants managed with an umbilical vein catheter in place for up to 28 days compared with infants managed with an umbilical vein catheter replaced by a percutaneous central venous catheter after 7 to 10 days. Umbilical vein catheter durations beyond the current Centers for Disease Control and Prevention-recommended limit of 14 days may be reasonable.

Catheterization, Central Venous↗
PubMed2006

Characteristics and acquisition of human herpesvirus (HHV) 7 infections in relation to infection with HHV-6.

Although both human herpesvirus (HHV) 6 and HHV-7 infections are ubiquitous during childhood, few acute HHV-7 infections are identified. It is unknown whether HHV-7 viremia indicates primary infection, as with HHV-6, or reactivation, and if these differ clinically. We studied, in otherwise healthy children < or =10 years old, HHV-7 and HHV-6 infections and their interaction by serologic assessment, viral isolation, and polymerase chain reaction. In children < or =24 months of age, HHV-7 infections occurred less often than HHV-6 infections (P< or =.002). Of 2806 samples from 2365 children < or =10 years old, 30 (1%) showed evidence of HHV-7 viremia; 23 (77%) of these were primary and 7 (23%) were reactivated HHV-7 infections. Four (13%) showed concurrent HHV-6 viremia, 2 associated with primary HHV-7 infections. The clinical manifestations of primary and reactivated HHV-7 infections were similar, except that seizures occurred more frequently in reactivated infections. These findings, previously unrecognized in otherwise healthy children, suggest that HHV-7 viremia could represent primary or reactivated infection and may be affected by the interaction between HHV-6 and HHV-7.

Antibodies, Viral↗
PubMed2006

Factors associated with the development of motor fluctuations and dyskinesias in Parkinson disease.

BACKGROUND: Motor fluctuations and dyskinesias can cause disability and reduce quality of life for patients with Parkinson disease (PD). OBJECTIVES: To evaluate factors associated with the development of motor fluctuations and dyskinesias and to assess the sequence in which they occur in individual patients. DESIGN: We performed a retrospective analysis of data from a randomized clinical trial comparing pramipexole dihydrochloride and levodopa as initial treatment for PD. Subjects were followed up for 48 to 58 months and evaluated at 3-month intervals for the presence of motor fluctuations and dyskinesias. SETTING: Academic and private practices. Patients Three hundred one patients with early Parkinson disease were enrolled in this study between October 2, 1996, and August 21, 1997, and were observed through August 24, 2001, when the last patient enrolled completed 4 years of follow-up. MAIN OUTCOME MEASURES: Order of appearance of motor fluctuations and dyskinesias, time to the first occurrence of motor fluctuations, and time to the first occurrence of dyskinesias. RESULTS: One hundred eighty-nine subjects (62.8%) developed motor complications. Of these, 71 (37.6%) developed fluctuations but not dyskinesias, 23 (12.2%) developed dyskinesias but not fluctuations, 48 (25.4%) developed fluctuations before dyskinesias, 33 (17.5%) developed dyskinesias before fluctuations, and 14 (7.4%) developed both at the same time. Factors significantly associated with earlier occurrence of dyskinesia were Hoehn and Yahr stage of 2 or higher, cumulative levodopa dose, cumulative levodopa equivalent dose (levodopa plus pramipexole), and occurrence of motor fluctuations. Pramipexole treatment was associated with later occurrence of dyskinesias. Factors associated with earlier occurrence of motor fluctuations were cumulative levodopa dose, cumulative levodopa equivalent dose, and occurrence of dyskinesias. Factors associated with later occurrence of motor fluctuations were age at onset of 65 years or older and pramipexole treatment. CONCLUSIONS: Higher cumulative levodopa doses and higher cumulative levodopa equivalent doses (levodopa plus pramipexole) were associated with the earlier occurrence of motor complications. Motor fluctuations and dyskinesias appear to be interrelated because the presence of one is associated with the earlier development of the other.

Age of Onset↗
PubMed2005

The p53 codon 72 proline allele is associated with p53 gene mutations in non-small cell lung cancer.

The p53 gene plays a critical role in cell cycle control, the initiation of apoptosis, and in DNA repair. An Arg/Pro polymorphism at codon 72 of the p53 gene alters the ability of the p53 protein to induce apoptosis, influences the behavior of mutant p53, decreases DNA repair capacity, and may be linked with an increased risk of lung cancer. To further define the role of the p53 codon 72 polymorphism on DNA repair, lung cancer risk, and mutant p53 function, we examined the effect of this polymorphism on mutation of the p53 gene and patient survival in non-small cell lung cancer (NSCLC). Tumor and nonneoplastic (lung or lymphocyte) samples were collected from 182 patients with NSCLC. p53 mutations were detected by direct sequencing and/or the Gene Chip p53 assay in 93 of 182 (51%) tumors. p53 codon 72 polymorphisms were identified by PCR/RFLP analysis. p53 mutations were significantly (P = 0.01) associated with the number of codon 72 Pro alleles: Pro/Pro homozygotes, 17 of 26 (65%); Arg/Pro heterozygotes, 45 of 79 (57%); and Arg/Arg homozygotes, 31 of 77 (40%). The number of codon 72 Pro alleles was independently associated with p53 mutations (odds ratio, 1.97; 95% confidence interval, 1.14-3.40; P = 0.01) in a multiple logistic regression model. The codon 72 polymorphism did not influence patient survival in either the entire patient group or among patients with p53 mutant tumors. In summary, the p53 Pro allele is associated with an increased frequency of p53 mutations in NSCLC.

Aged↗
PubMed2005

Psychosocial risk factors for postherpetic neuralgia: a prospective study of patients with herpes zoster.

UNLABELLED: The results of previous studies using retrospective methods or small samples have suggested that there may be psychosocial risk factors for postherpetic neuralgia (PHN). We conducted a prospective study in which 110 patients with herpes zoster were assessed within the first month after rash onset with measures of acute pain and five broad domains of psychosocial functioning-physical, role, social, and emotional functioning, and stress and social support. Twenty of the 102 patients with follow-up data were diagnosed with PHN, defined as pain that had persisted for 4 months after rash onset. Measures of role functioning, personality disorder symptoms, and disease conviction during herpes zoster each made independent contributions to predicting either presence or intensity of PHN in logistic and linear regression analyses that controlled for relevant demographic and clinical variables, including age and acute pain intensity. These findings indicate that psychosocial variables are risk factors for the development of PHN. PERSPECTIVE: The results of this prospective study of patients with herpes zoster suggest that future research on the mechanisms and prevention of PHN should consider psychosocial as well as neurobiologic processes.

Activities of Daily Living↗
PubMed2005

Establishment of an alternative intracellular cytokine staining assay for HIV/AIDS clinical studies.

To evaluate immune responses in large-scale clinical studies, it is crucial to use assays that are not only sensitive and specific, but also standardized and easily transferable. To this end, an intracellular cytokine staining (ICS) assay for quantifying HIV-specific CD8+ T cells has been established and its performance characteristics determined. PBMCs were stimulated using recombinant vaccinia expressing HIV-Env, -Gag, -Pol and -Nef proteins, or a protein from Escherichia coli (Eco); CD8+ T cell responses were assessed by intracellular IFN-gamma staining and flow cytometric (FC) analysis. In 15 HIV seronegative and 11 HIV seropositive individuals, a minimal background IFN-gamma staining was found after Eco stimulation with a median [inter-quartile range (IQR)] of 0.005% (0.000%, 0.030%) irrespective of HIV infection status. Recent smallpox vaccination was associated with a small but significant increase in background staining [0.02% (0.02%, 0.04%) versus 0.0% (0.0%, 0.01%) (p=0.039)] in HIV seronegative individuals. This assay detected moderate (>0.10%) HIV-specific responses in 64% (7/11) of HIV seropositive individuals. The results suggest that this ICS assay format is sensitive and specific, and is amenable to standardization for screening for HIV-specific CD8+ T cells in clinical trials.

CD8-Positive T-Lymphocytes↗
PubMed2004

Attenuated central nervous system infection in advanced HIV/AIDS with combination antiretroviral therapy.

BACKGROUND: Before the introduction of combination antiretroviral therapy (CART), neurological disease correlated with cerebrospinal fluid (CSF) levels of human immunodeficiency virus (HIV) RNA. OBJECTIVE: To investigate the relationships among HIV RNA levels, immune activation markers, and neurological status in patients receiving CART. DESIGN: Multicenter cohort study. SETTING: Academic neurology departments. PATIENTS: A total of 371 patients unselected for neurological complaints and with CD4 cell counts less than 200/microL or with cognitive symptoms and CD4 cell counts less than 300/microL were enrolled into the Northeastern AIDS Dementia cohort in 1998-2002. Diagnoses of HIV-associated dementia (HIV-D) and minor cognitive-motor disorder (MCMD) were obtained with a computerized algorithm. Plasma and CSF levels of HIV RNA, monocyte chemotactic protein 1, macrophage colony-stimulating factor, and tumor necrosis factor alpha were quantified. RESULTS: The mean +/- SD age was 41.5 +/- 7.2 years, and the mean +/- SD educational level was 12.3 +/- 2.2 years. Seventy percent of the cohort was black, and 30% were women. The mean +/- SD CD4 cell count was 136.8 +/- 87.9/microL, and CART was used in 71%. Twenty-nine percent of the patients were unimpaired (n = 106), 36% had MCMD (n = 133), and 35% had HIV-D (n = 128). Mean log(10) CSF HIV RNA copies per milliliter was 2.6 +/- 0.8, with no differences among the neurological groups, even after adjustments for baseline CD4 cell counts and antiretroviral therapy. Cerebrospinal fluid HIV RNA was undetectable in 47% of unimpaired, 46% of MCMD, and 43% of HIV-D patients (P = .91). Plasma levels of monocyte chemotactic protein type 1 and tumor necrosis factor alpha correlated weakly with HIV RNA levels but did not distinguish those with neurological deficits. CONCLUSIONS: In contrast to observations in individuals not treated with CART, we found no relationship between CSF markers and neurological status in this CART-using cohort with advanced HIV/AIDS. This was not explicable by demographic differences or plasma virological control. CART may substantially attenuate the degree of central nervous system HIV infection and immune activation, and in CART users, CSF HIV RNA and immune activation markers may fail to discriminate milder degrees of HIV-D and MCMD.

Acquired Immunodeficiency Syndrome↗
PubMed2004

Epidermal nerve fiber density, axonal swellings and QST as predictors of HIV distal sensory neuropathy.

We investigated the associations of baseline epidermal nerve fiber (ENF) densities and morphology (percent ENF swellings) and quantitative sensory testing (QST) with clinically defined human immunodeficiency virus (HIV)-associated distal polyneuropathy (DSP) and whether these measures are predictive of development of symptomatic DSP over time. Fifty-seven HIV-infected subjects with and without DSP and 19 controls participated. Mean ENF densities were lower at the distal leg and proximal thigh in asymptomatic or symptomatic DSP than in controls. Mean ENF densities did not differ significantly among the HIV groups. Percent ENF swellings was higher in patients with symptomatic DSP than controls at the distal leg, and was also greater at the proximal thigh in patients with asymptomatic or symptomatic DSP than in controls. The percent ENF swellings at the distal leg correlated with the thresholds for both minimal (HP 0.5) and intermediate (HP 5.0) heat pain (HP) intensity. A higher percent ENF swellings in the distal leg [hazard ratio (HR) 1.16, 95% CI 1.02-1.31] and HP 0.5 thresholds (HR 1.03, 95% CI 1.01-1.05) were the only two measures associated with a shorter time to development of symptomatic DSP. Quantitation of ENF swellings and heat pain thresholds deserve further study as predictors of symptomatic neuropathy.

Adult↗
PubMed2004

Human herpesvirus 6 (HHV6) DNA persistence and reactivation in healthy children.

OBJECTIVE: To determine in healthy children after primary infection the persistence of human herpesvirus 6 (HHV6) DNA, the presence and frequency of HHV6 re-activation or re-infection, and the relationship of both to illness and the presence of human herpesvirus 7 (HHV7) infection. STUDY DESIGN: Children 1 to 12 years of age with previous HHV6 infection were prospectively evaluated by HHV6 and HHV7 DNA polymerase chain reaction (PCR) and reverse transcription (RT)-PCR for HHV6. HHV6 plasma antibody titers were measured. Illnesses were recorded by diary, and physician records were reviewed. RESULTS: HHV6 DNA was detected in >or=1 peripheral blood mononuclear cell (PBMC) samples in 89% of children. HHV6 reactivation and re-infection were detected by RT-PCR in 1.1% of samples. Detection of HHV6 DNA was intermittent in 76% of children and was not associated with cumulative rates of illness. Illness at a study visit was significantly associated with the absence of HHV6 and HHV7 DNA in PBMC samples and was not associated with HHV6 antibody titer or the presence of HHV6 DNA in saliva. CONCLUSIONS: HHV6 DNA persists in most children intermittently following primary infection and is unrelated to illness. Reactivation of HHV6 occurs in healthy children without apparent illness.

Child↗
PubMed2004

Congenital infections with human herpesvirus 6 (HHV6) and human herpesvirus 7 (HHV7).

OBJECTIVE: To examine whether: (1) congenital human herpesvirus 6 (HHV6) and human herpesvirus 7 (HHV7) infections occur; whether (2) their manifestations differ from postnatal infections; and whether (3) HHV6 and HHV7 infections differ despite their close relatedness. STUDY DESIGN: HHV6 and HHV7 infections acquired congenitally and postnatally in normal children were compared using viral isolation, serology, reverse-transcription polymerase chain reaction (RT-PCR) and nested DNA-PCR for HHV6 variant A (HHV6A), HHV6 variant B (HHV6B), and HHV7. RESULTS: HHV6 DNA was detected in 57 (1%) of 5638 cord bloods. HHV7 DNA, however, was not detected in 2129 cord bloods. Congenital HHV6 infections differed from postnatal infections, which were acute febrile illnesses. Congenital infections were asymptomatic, 10% demonstrated reactivation at birth, and HHV6 DNA persistence in follow-up blood samples was significantly more frequent. One-third of congenital infections were HHV6A, whereas all postnatal infections were HHV6B. CONCLUSIONS: Congenital HHV6 infections occurred in 1% of births, similar to the rate for cytomegalovirus infection. Congenital infections were clinically and virologically distinct from postnatal infections. Congenital HHV7 infections, however, were not detected, suggesting considerable differences in transmission and pathogenesis in these closely related beta-herpesviruses.

Antibodies, Viral↗
PubMed2004

The ups and downs of Parkinson disease: a prospective study of mood and anxiety fluctuations.

BACKGROUND: Parkinson disease (PD) patients with motor fluctuations experience mood fluctuations, but studies have been limited in number and methodology. OBJECTIVES: To better understand the phenomenology of mood, anxiety, and motor fluctuations in PD. METHOD: Eighty-seven PD patients and 19 spouse controls completed questionnaires, rating scales, and diaries using visual analogue scales (VAS) to rate mood, anxiety, and motor states. Average daily variance in VAS scores was determined, and PD patients whose average daily variance was larger than that for all of the control subjects were considered to have fluctuations. RESULTS: Twenty-nine percent of patients had fluctuations in anxiety, 24% motor, and 21% mood; 65% had no fluctuations. Seventy-five percent of patients with motor fluctuations had mood and/or anxiety fluctuations, but 5 subjects reported emotional fluctuations without motor fluctuations. The combination of mood and anxiety fluctuations was frequent, but anxiety and mood did not always appear to fluctuate together. Visual inspection of diaries revealed that not all patients exhibited a temporal relationship between emotional and motor fluctuations. Compared with nonfluctuators, those with mood or anxiety fluctuations were more likely to have higher scores on psychiatric rating scales, report histories of depression or anxiety, and use psychotropic medications. CONCLUSIONS: PD patients are heterogeneous with regard to the presence, range, and pattern of fluctuations. In general, patients with mood fluctuations also have anxiety fluctuations.

Affective Symptoms↗
PubMed2003

p53 mutations and survival in stage I non-small-cell lung cancer: results of a prospective study.

BACKGROUND: The p53 gene is frequently mutated in non-small-cell lung cancer (NSCLC); however, the effect of p53 gene mutations on patient prognosis remains unclear. Therefore, we initiated a prospective study to determine the association of p53 gene mutations with survival in patients with stage I NSCLC. METHODS: Tumor samples were collected prospectively from 188 patients with operable NSCLC (stages I, II, and IIIA). p53 mutations were detected by direct dideoxynucleotide sequencing and p53 GeneChip analysis. Association of clinical and pathologic variables (e.g., alcohol consumption, sex, age, pathologic stage) with mutation of the p53 gene was determined by logistic regression. Associations between p53 mutation status, clinical and pathologic variables, and survival were assessed using a Cox proportional hazards regression model. All statistical tests were two-sided. RESULTS: p53 mutations were detected in 55% (104/188) of tumors. These mutations were associated with non-bronchoalveolar tumors, a history of alcohol consumption, and younger patient age. The risk of death was statistically significantly higher in patients with p53 mutations in their tumors (hazard ratio [HR] = 1.6, 95% confidence interval [CI] = 1.0 to 2.4; P =.049) than in patients with wild-type p53 in their tumors. Tumor stage, the presence of a p53 mutation, and increasing patient age were statistically significant predictors of patient death in the entire patient group; however, the statistically significant prognostic effect of p53 mutation was limited to patients with stage I NSCLC (stage I HR = 2.8, 95% CI = 1.4 to 5.6; stage II HR = 1.8, 95% CI = 0.74 to 4.4; and stage III HR = 0.70, 95% CI = 0.32 to 1.5). Among patients with stage I NSCLC, actuarial 4-year survival was statistically significantly higher in those with wild-type p53 than in those with mutant p53 (78% versus 52%, respectively; difference in 4-year survival = 26%, 95% CI = 6% to 46%; P =.009, log-rank test). CONCLUSION: Tumor p53 mutations are a statistically significant predictor of poor outcome in patients with stage I NSCLC.

Adult↗
PubMed2003

Development and testing of the Parkinson's disease quality of life scale.

We report on the development and results of preliminary psychometric testing of a disease specific health-related quality of life (HRQoL) scale intended for use in individuals diagnosed with idiopathic Parkinson's disease (PD). Results from an initial qualitative study provided content for item development and scale construction of the Parkinson's disease quality of life scale (PDQUALIF). The 33-item instrument includes seven domains: social/role function, self-image/sexuality, sleep, outlook, physical function, independence, and urinary function, plus one item of Global HRQoL. Initial psychometric testing of the instrument was conducted in 233 outpatient clinic attendees with physician-confirmed idiopathic PD. Factor structure, reliability and validity of the scale have been established in this cross-sectional study. Continuing development of the PDQUALIF will be directed at enhancing the psychometric properties, establishing responsiveness and determining appropriateness in culturally diverse samples.

Aged↗
PubMed2003

Core outcome domains for chronic pain clinical trials: IMMPACT recommendations.

OBJECTIVE: To provide recommendations for the core outcome domains that should be considered by investigators conducting clinical trials of the efficacy and effectiveness of treatments for chronic pain. Development of a core set of outcome domains would facilitate comparison and pooling of data, encourage more complete reporting of outcomes, simplify the preparation and review of research proposals and manuscripts, and allow clinicians to make informed decisions regarding the risks and benefits of treatment. METHODS: Under the auspices of the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT), 27 specialists from academia, governmental agencies, and the pharmaceutical industry participated in a consensus meeting and identified core outcome domains that should be considered in clinical trials of treatments for chronic pain. CONCLUSIONS: There was a consensus that chronic pain clinical trials should assess outcomes representing six core domains: (1) pain, (2) physical functioning, (3) emotional functioning, (4) participant ratings of improvement and satisfaction with treatment, (5) symptoms and adverse events, (6) participant disposition (e.g. adherence to the treatment regimen and reasons for premature withdrawal from the trial). Although consideration should be given to the assessment of each of these domains, there may be exceptions to the general recommendation to include all of these domains in chronic pain trials. When this occurs, the rationale for not including domains should be provided. It is not the intention of these recommendations that assessment of the core domains should be considered a requirement for approval of product applications by regulatory agencies or that a treatment must demonstrate statistically significant effects for all of the relevant core domains to establish evidence of its efficacy.

Chronic Disease↗