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Biomedical subjects

R W Haley

Publications and source records attributed to R W Haley.

At least 19 recordsLinked to original sources
PubMed2001

Use of structural equation modeling to test the construct validity of a case definition of Gulf War syndrome: invariance over developmental and validation samples, service branches and publicity.

To attempt to replicate the syndrome-like structure identified by exploratory factor analysis of symptom reports from 249 Gulf War veterans of a Naval reserve battalion (the developmental sample), we administered Haley's original symptom questionnaire to 335 Gulf War veterans who served primarily in active-duty US Army units living in North Texas (the validation sample). On the basis of recently validated goodness-of-fit criteria (SRMR or=0.95), a structural equation model (Model 1) with four symptom scales loading on each of three first-order latent syndrome factors fit both the developmental and validation samples well and was invariant across both samples. Additional models validated a higher-order latent factor (a single Gulf War syndrome) explaining the variances and covariances of the first-order factors, four additional symptom scales loading on the higher-order factor, and four possible secondary factor loadings that also fit the data well. All structural models were invariant across cohorts of the validation sample surveyed before and after intense publicity following publication of the case definition. These findings suggest that the apparent syndrome structure of a single Gulf War syndrome with three variants may be found widely and justify a confirmatory sample survey of Gulf War-era veterans.

Adult↗
PubMed2001

Gene therapy to prevent organophosphate intoxication.

The specific hydrolytic activity of PON1 paraoxonase/arylesterase enzymes in liver and blood provides a natural barrier against the entry of organophosphate toxins into the central and peripheral nervous systems. Inherited differences in PON1 enzyme concentrations may determine levels of susceptibility to organophosphate injury in humans. To test whether boosting serum levels of PON1 enzymes by gene therapy might provide increased protection, we compared the degree of inactivation of whole brain acetylcholinesterase of mice exposed to chlorpyrifos 4 days after intravenous injection of recombinant adenoviruses containing PON1-LQ or PON1-LR genes or no PON1 gene. Both recombinant viruses containing PON1 genes boosted serum arylesterase concentrations by approximately 60% and significantly prevented the inactivation of brain acetylcholinesterase. Some mice were completely protected. These findings indicate that boosting serum levels of PON1 enzymes by a gene delivery vector raises the threshold for organophosphate toxicity by hydrolytic destruction before the chemical can enter the brain.

Acetylcholinesterase↗
PubMed2001

Commercial tattooing as a potentially important source of hepatitis C infection. Clinical epidemiology of 626 consecutive patients unaware of their hepatitis C serologic status.

Tattooing in commercial tattoo parlors is known to transmit blood-borne viral infections, including hepatitis C virus (HCV), in other countries, but its contribution to the high population prevalence of HCV infection in the United States has been incompletely evaluated. Risk factors for blood-borne infection were assessed by physician's interview of 626 consecutive patients undergoing medical evaluation for spinal problems in 1991 and 1992 while unaware of their HCV status. Later all were screened for HCV infection with enzyme-linked immunosorbent assay (EIA-1 and EIA-2), and positives were confirmed with second-generation recombinant immunoblot assay (RIBA). Forty-three patients were seropositive for HCV (sample prevalence 6.9%, population-standardized prevalence 2.8%). Logistic regression analysis identified 4 independent risk factors for HCV infection: injection-drug use (adjusted prevalence odds ratio [OR] = 23.0; 95% confidence intervals [CI] = 7.5-70.6), ancillary hospital jobs held by men (OR = 9.6; 95% CI = 3.8-24.3), tattoos from commercial tattoo parlors (OR = 6.5; 95% CI = 2.9-14.8), and drinking > or = 3 6-packs of beer per month (OR = 4.0; 95% CI = 1.8-8.7). If causal, these 4 risk factors account for 91% of HCV infections, with tattooing explaining 41%, heavy beer drinking 23%, injection-drug use 17%, and ancillary health care jobs for men 8%. Transfusions, promiscuous sexual activity, bone grafts, acupuncture, perinatal or intimate transmission in families, and other modes were not independently associated with serologic evidence of HCV infection. Unlikely to be explained by confounding or incomplete disclosure of other risk factors, tattooing in commercial tattoo parlors may have been responsible for more HCV infections than injection-drug use.

Adolescent↗
PubMed2001

Serum paraoxonase (PON1) isozymes: the quantitative analysis of isozymes affecting individual sensitivity to environmental chemicals.

In a recent study on Gulf War veterans who developed delayed neurotoxicity symptoms, we found their levels of serum paraoxonase (PON1) isozyme type Q to be significantly lower than in the control, unaffected veteran group. These results were obtained in 25 ill veterans and 20 well control subjects, of which 10 were deployed and 10 were nondeployed battalion members who remained in the United States during the Gulf War. The blood samples were also assayed for serum butyrylcholinesterase in our laboratory, and more recently in Dr. C. Broomfield's laboratory for somanase and sarinase activities. The cholinesterase activities showed no significant correlation with the PON1 isozyme levels or the severity of the clinical symptoms, but the somanase and sarinase levels ran parallel to the PON1 type Q isozyme concentrations. Although there is no direct evidence that these Gulf War veterans were directly exposed to or encountered either of these nerve gases, they may have been exposed to some environmental or chemical toxin with a similar preference for hydrolysis by the PON1 type Q isozyme. The number of subjects is relatively small, but the results should encourage other investigators to examine both the individual phenotypes and the levels of PON1 isozymes in other groups exhibiting neurological symptoms.

Aryldialkylphosphatase↗
PubMed2001

Occipital brain perfusion deficits in children with major depressive disorder.

UNLABELLED: Occipital lobe perfusion defects have been identified on regional cerebral blood flow (rCBF) SPECT scans of adolescent children and young adults with major depressive disorder (MDD). We reinvestigated a series of rCBF SPECT scans obtained several years ago on drug-naive children with a clinical diagnosis of MDD and on healthy children. METHODS: To test whether visually apparent abnormalities in rCBF constitute statistically significant differences between patients, given the relatively small sample sizes, we applied the technique of statistical parametric mapping (SPM). RESULTS: Two groups of patients were identified: 8 with significant posterior flow deficits in the occipital cortex (Brodmann's areas 18 and 19), usually symmetric, and best visualized on paramedian sagittal sections, and 13 without obvious occipital perfusion deficits but with anterior rCBF deficits in a pattern often described in the literature, attaining statistical significance in the right frontal region. Other localizations in the left frontal and bilateral prefrontal regions did not attain significance, but each localization contained statistically significant maxima (z scores). The scan findings of all 18 healthy children were normal. CONCLUSION: With the aid of SPM, 2 groups of children with significantly different rCBF behavior were identified. The reason for this difference is not known but should be investigated to determine its possible significance to patients with MDD.

Adolescent↗
PubMed2000

Use of a secure Internet Web site for collaborative medical research.

Researchers who collaborate on clinical research studies from diffuse locations need a convenient, inexpensive, secure way to record and manage data. The Internet, with its World Wide Web, provides a vast network that enables researchers with diverse types of computers and operating systems anywhere in the world to log data through a common interface. Development of a Web site for scientific data collection can be organized into 10 steps, including planning the scientific database, choosing a database management software system, setting up database tables for each collaborator's variables, developing the Web site's screen layout, choosing a middleware software system to tie the database software to the Web site interface, embedding data editing and calculation routines, setting up the database on the central server computer, obtaining a unique Internet address and name for the Web site, applying security measures to the site, and training staff who enter data. Ensuring the security of an Internet database requires limiting the number of people who have access to the server, setting up the server on a stand-alone computer, requiring user-name and password authentication for server and Web site access, installing a firewall computer to prevent break-ins and block bogus information from reaching the server, verifying the identity of the server and client computers with certification from a certificate authority, encrypting information sent between server and client computers to avoid eavesdropping, establishing audit trails to record all accesses into the Web site, and educating Web site users about security techniques. When these measures are carefully undertaken, in our experience, information for scientific studies can be collected and maintained on Internet databases more efficiently and securely than through conventional systems of paper records protected by filing cabinets and locked doors. JAMA. 2000;284:1843-1849.

Computer Security↗
PubMed2000

Stressful manipulations that elevate corticosterone reduce blood-brain barrier permeability to pyridostigmine in the Rat.

Pyridostigmine bromide (PB), a reversible inhibitor of acetylcholinesterase (AChE), is used for the treatment of myasthenia gravis. PB has also been provided to military personnel for preexposure protection against potential soman release. The entry of PB into the brain is typically minimal, but recently published data in mice suggest that a brief forced swim stress increases the permeability of the blood-brain barrier to PB. From these results, PB administered under stressful conditions was proposed to induce long-lasting central cholinergic deficits, potentially explaining the neurological and neuropsychological symptoms presented by some Gulf War veterans. In undertaking to replicate these results in the Long-Evans rat, no evidence of a stress-potentiated central effect of PB, administered at doses up 5.0 mg/kg ip, was found. Three stress protocols were used: restraint, forced swim, or a combined restraint/forced swim. Wistar rats were also tested in some of the protocols to ensure that the results were generalizable across rat strains, and plasma corticosterone levels were measured to test the effectiveness of the stressors employed. In contrast to the previously reported findings in the mouse, stress significantly reduced the entry of PB into rat brain, as measured by reduced inhibition of AChE activity: a 12.5% reduction in whole brain AChE activity after treatment with 5.0 mg/kg PB under control conditions declined to 9% after stress exposure. It is apparent, therefore, that the interaction between stress and PB requires further study, and previous data should be reassessed before they are used as a basis for interpreting symptoms presented by veterans.

Acetylcholinesterase↗
PubMed2000

Effect of basal ganglia injury on central dopamine activity in Gulf War syndrome: correlation of proton magnetic resonance spectroscopy and plasma homovanillic acid levels.

BACKGROUND: Many complaints of Gulf War veterans are compatible with a neurologic illness involving the basal ganglia. METHODS: In 12 veterans with Haley Gulf War syndrome 2 and in 15 healthy control veterans of similar age, sex, and educational level, we assessed functioning neuronal mass in both basal ganglia by measuring the ratio of N-acetyl-aspartate to creatine with proton magnetic resonance spectroscopy. Central dopamine activity was assessed by measuring the ratio of plasma homovanillic acid (HVA) and 3-methoxy-4-hydroxyphenlyglycol (MHPG). RESULTS: The logarithm of the age-standardized HVA/MHPG ratio was inversely associated with functioning neuronal mass in the left basal ganglia (R(2) = 0.56; F(1,27) = 33.82; P<.001) but not with that in the right (R(2) = 0. 04; F(1,26) = 1.09; P =.30). Controlling for age, renal clearances of creatinine and weak organic anions, handedness, and smoking did not substantially alter the associations. CONCLUSIONS: The reduction in functioning neuronal mass in the left basal ganglia of these veterans with Gulf War syndrome seems to have altered central dopamine production in a lateralized pattern. This finding supports the theory that Gulf War syndrome is a neurologic illness, in part related to injury to dopaminergic neurons in the basal ganglia.

Basal Ganglia Diseases↗
PubMed2000

Vestibular dysfunction in Gulf War syndrome.

METHODS: Vestibular complaints of Gulf War veterans were characterized by a nested case-control study of 23 veterans with 3 different Gulf War syndromes and 20 matched control subjects. All subjects completed a standardized symptom questionnaire and underwent standard audiovestibular tests administered by audiologists blinded to group identities. RESULTS: The prevalence of reported dizzy spells was higher in veterans with Gulf War syndromes 1 (100%), 2 (85%), and 3 (100%) than in controls (25%, P < 0.0001). Dizzy spells were more frequent, lasted longer, and involved a wider variety of accompanying symptoms in veterans with syndrome 2 than in those with syndromes 1 and 3. Audiovestibular testing showed greater interocular asymmetry of nystagmic velocity on sinusoidal harmonic acceleration in syndromes 1 (P = 0.015) and 2 (P = 0.002), greater asymmetry of saccadic velocity in syndrome 2 (P = 0.4), diminished nystagmic velocity after caloric stimulation bilaterally in syndrome 3 (P = 0.02 to 0.04), more subjects with pathologic nystagmus (P = 0. 09), and greater interside asymmetry of wave I to III interpeak latency on auditory brain stem response in syndromes 1 (P = 0.005) and 2 (P = 0.07). Asymmetry of gain on sinusoidal harmonic acceleration and pathologic nystagmus were most strongly associated with symptoms of paroxysmal vertigo (P = 0.002 and 0.07, respectively); asymmetry of saccadic velocity, with the severity of vertigo (P = 0.004); and abnormal caloric response, with chronic dysequilibrium (P = 0.006). CONCLUSIONS: The findings are compatible with a subtle neurologic injury from organophosphate-induced delayed neurotoxicity.

Adult↗
PubMed2000

Alternative case definitions of ventilator-associated pneumonia identify different patients in a surgical intensive care unit.

Diagnostic criteria that define ventilator-associated pneumonia (VAP) remain controversial. The purpose of this study was to evaluate common definitions of VAP and determine their relationship to each other and clinical treatment. This study prospectively evaluated several diagnostic criteria that define VAP in a cohort of 255 consecutive SICU patients ventilated for < 48 h. Definitions evaluated include the CDC definitions, the Johanson definitions which do not rely on culture data, the Physician's Probable diagnosis which relies on positive quantitative cultures, and the antibiotic treatment group. Forty-four patients (17%) received antibiotic treatment for VAP. Depending on the definition evaluated, criteria were met for a diagnosis of VAP from as low as 4% of patients by the Johanson definition to as high as 48% of patients by the CDC definition. There was poor agreement among the definitions in their ability to select the same patient as having VAP. Besides duration of mechanical ventilation and tube feeding, which were risk factors that predicted meeting the criteria for all groups, risk factors predicting VAP varied among the definitions. This study demonstrates that in a surgical ICU, the candidate definitions of pneumonia evaluated show little agreement. The particular case definition chosen to diagnose VAP will determine the incidence rate of pneumonia, the time to onset of pneumonia, and the risk factors of the type of patient treated.

Adult↗
PubMed2000

Brain abnormalities in Gulf War syndrome: evaluation with 1H MR spectroscopy.

PURPOSE: To test for neuronal brain damage in the basal ganglia and brainstem in Gulf War veterans by using magnetic resonance (MR) spectroscopy. MATERIALS AND METHODS: Twenty-two Gulf War veterans with one of three factor analysis-derived syndromes (case patients); 18 well veterans matched for age, sex, and education level (control subjects); and six Gulf War veterans with syndrome 2 from a different population (replication sample) underwent long echo time (272 msec) proton (hydrogen 1) MR spectroscopy on a 4 x 2 x 2-cm voxel in the basal ganglia bilaterally and a 2 x 2 x 2-cm voxel in the pons. Syndromes 1-3 are described as "impaired cognition," "confusion-ataxia," and "central pain," respectively. RESULTS: The N-acetylaspartate-to-creatine (NAA/Cr) ratio, which reflects functional neuronal mass, was significantly lower in the basal ganglia and brainstem of Gulf War veterans with the three syndromes than in those structures of the control subjects (P =.007). The finding was corroborated in the replication sample (P =.002). Veterans with syndrome 2 (the most severe clinically) had evidence of decreased NAA/Cr in both the basal ganglia and the brainstem; those with syndrome 1, in the basal ganglia only; and those with syndrome 3, in the brainstem only. CONCLUSION: Veterans with different Gulf War syndromes have biochemical evidence of neuronal damage in different distributions in the basal ganglia and brainstem.

Adult↗