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Biomedical subjects

C Van Dyke

Publications and source records attributed to C Van Dyke.

At least 19 recordsLinked to original sources
PubMed1997

Acute lung injury induced by a commercial leather conditioner.

Following a formulation change, a leather conditioner was involved in a 1992 nationwide outbreak of respiratory illness. We investigated the composition and toxicity of the conditioner produced before (previous product) and after (new product) the disease outbreak. The new product induced tachypnea, pulmonary edema, pulmonary hemorrhage, and sporadic deaths in exposed guinea pigs and rats. Ultrastructurally, these changes were associate with direct pulmonary cytotoxicity characterized by necrosis of alveolar type I cells and alveolar septal interstitial edema. Chemical analyses suggested major alterations in the fluorohydrocarbon constituents in the new formulation of the leather conditioner. While these alterations could not be specifically identified, they appeared to include changes from fluoralkanes to fluoroalkenes, fluorophenyl, and/or fluoroalcohol compounds. Changes in solvent composition were consistent with traces of 2-butoxyethanol and isomers of dipropylene glycol methyl ether, and additional C10-C12 alkanes. In this study, we demonstrated the toxicity of the new product in laboratory animals. Some of the altered constituents of the new product have been identified and are potential candidates for additional investigations to identify specific etiologic agents.

Acetates↗
PubMed1997

Role of medical conditions in the exacerbation of self-injurious behavior: an exploratory study.

Self-injurious behavior (SIB) is common among people with severe mental retardation who may also have multiple complex medical problems coupled with communication difficulties. This combination of factors sometimes makes it difficult to obtain accurate and detailed medical histories. In this exploratory descriptive study of 25 patients with SIB, 28% had previously undiagnosed medical conditions that could be expected to cause pain or discomfort. Six of the 7 patients experienced decreased SIB with treatment of their medical conditions. In patients with SIB, impaired communication skills, and complex medical histories, medical conditions that may be associated with pain or discomfort must be a consideration in determining the etiology of the SIB.

Adolescent↗
PubMed1996

Low-dose oral methotrexate in chronic progressive multiple sclerosis: analyses of serial MRIs.

We monitored 56 patients with chronic progressive multiple sclerosis (MS) who participated in a clinical trial of weekly, low-dose oral methotrexate with annual gadolinium-enhanced MRIs of the brain (Gd + MRI). Not of these patients had clinical exacerbations during the 8 months preceding study entry. We also monitored 35 of the patients with serial Gd + MRIs every 6 weeks for 6 months. We observed a treatment effect, measured by absolute change in T2-weighted total lesion area (T2W-TLA), in the cohort that completed 6-week scans. We found change in T2W-TLA in this cohort to be significantly related to sustained change in performance on the nine-hold peg test but not to sustained change on the Expanded Disability Status Scale. Gadolinium enhancement of lesions on 6-week and annual scans was uncommon. Prestudy exacerbation frequency appears to be an important consideration in designing future clinical trials in patients with secondary and primary progressive MS.

Administration, Oral↗
PubMed1995

Low-dose (7.5 mg) oral methotrexate reduces the rate of progression in chronic progressive multiple sclerosis.

A randomized, double-blinded, placebo-controlled, clinical trial of low-dose, weekly, oral methotrexate was performed in 60 patients with clinically definite chronic progressive multiple sclerosis (MS) attending a referral-based outpatient MS clinic. Study patients were 21 to 60 years old with a disease duration of longer than 1 year. Patients' Expanded Disability Status Scale scores were 3.0 to 6.5 (ambulatory with moderate disability). Patients were first stratified by Expanded Disability Status Scale scores, 3.0 to 5.5 and 6.0 to 6.5, and then were randomized to receive methotrexate or placebo treatment. Treatment consisted of weekly, oral, low-dose (7.5 mg) methotrexate or identical placebo for 2 years, followed by observation for as long as 1 year. A composite outcome measurement instrument was used and consisted of (1) Expanded Disability Status Scale, (2) ambulation index, (3) Box and Block Test, and (4) 9-Hole Peg Test. Failure of therapy was indicated by a designated change that was sustained for more than 2 months in one or more components of this composite measure. Significantly less progression of impairment as measured by validated tests of upper-extremity function was observed in the methotrexate treatment group in the absence of clinically significant toxicity. We conclude that low-dose, weekly, oral methotrexate offers a new, relatively nontoxic treatment option for patients with chronic progressive MS.

Administration, Oral↗
PubMed1994

Axonal injury and membrane alterations in Alzheimer's disease suggested by in vivo proton magnetic resonance spectroscopic imaging.

We used spin-echo magnetic resonance imaging and proton magnetic resonance spectroscopic imaging in 8 patients with probable Alzheimer's disease and in 10 age-matched elderly control subjects to assess the effects of Alzheimer's disease on the brain. On magnetic resonance images the patients showed significant ventricular enlargements relative to the control subjects. We measured the distribution and relative signal intensities of N-acetylaspartate (a putative neuronal marker), of choline residues representing lipid metabolites, and of creatine-containing metabolites in a large section of the centrum semiovale containing white and mesial gray matter. Throughout the white matter of the patients with Alzheimer's disease compared to elderly control subjects, N-acetylaspartate was decreased relative to choline (N-acetylaspartate-choline ratio) and creatine-containing metabolites (N-acetylaspartate-creatine ratio) with no changes in the choline-creatine ratio. The N-acetylaspartate-choline ratio was lower and choline-creatine higher in the mesial gray matter of AD patients relative to elderly controls. The posterior section of the centrum semiovale in the patients showed increased choline-creatine and choline-N-acetylaspartate ratios with the N-acetylaspartate-creatine ratio unchanged between the patients and control subjects. These spectroscopic findings give suggestive evidence of diffuse axonal injury and membrane alterations in gray and white matter of the centrum semiovale in patients with Alzheimer's disease.

Aged↗
PubMed1993

Computer-assisted molecular modeling: indispensable tools for molecular pharmacology.

Ball-and-stick mechanical models, typically associated with chemists, have been helpful in understanding structural problems and the relationship between structure and biologic activity. With progress in computer speed, graphics performance, and software innovation, molecules of biological interest can be subjected to rigorous calculations. Computational chemistry and biology are rooted in the belief that theoretical physics can be used to calculate accurate molecular structures. Although in its infancy, computer-assisted molecular modeling is gaining attention and acceptability as an increasing number of researchers turn their attention toward rational molecular design. The trend to use theoretical methods can be traced to the greater availability of computer graphics work-stations, decreasing computer costs, faster central processing units, more robust algorithms, and "user-friendly" software codes. Every major pharmaceutical company has invested in these resources to reduce the time it takes to design and develop pharmaceutical agents. Because of the vast financial and manpower investments needed to introduce a single drug, medicinal chemists and pharmacologists are interested in understanding and predicting drug action at the molecular level. Although drug action is still poorly understood, molecular modeling should reduce some of the labor in the development of pharmaceutical agents.

Computer Graphics↗
PubMed1992

Low-dose (7.5 mg) oral methotrexate for chronic progressive multiple sclerosis. Design of a randomized, placebo-controlled trial with sample size benefits from a composite outcome variable including preliminary data on toxicity.

OBJECTIVE: To present a detailed description of (1) the study design of this ongoing trial, (2) advantages of using a composite outcome variable instead of multiple individual outcome measures, (3) treatment group characteristics at baseline, and (4) observed short-term methotrexate (MTX) toxicity. DESIGN: Randomized, double-masked, placebo-controlled intervention study. SETTING: Referral-based outpatient multidisciplinary multiple sclerosis (MS) clinic. PATIENTS: Participation offered to all clinically definite chronic progressive multiple sclerosis (CPMS) patients attending clinic ages 21 to 60, disease duration > 1 year, Expanded Disability Status Scale (EDSS) score 3.0 to 6.5 (ambulatory with moderate disability). Patients first stratified by EDSS 3.0 to 5.5 and 6.0 to 6.5, then randomized to MTX or placebo treatment. INTERVENTION: Weekly oral low-dose (7.5 mg) MTX or identical-appearing placebo for 2 years followed by a 1-year observation period. MAIN OUTCOME MEASURES: Sample size calculations undertaken prior to enrolling patients based upon a composite outcome variable consisting of designated change in any of the following functional measures: (1) EDSS, (2) Ambulation Index (AI), (3) Box and Block Test (BBT), and (4) 9-Hole Peg Test (9HPT). RESULTS: (1) Treatment group characteristics were comparable at baseline, (2) no patient has been withdrawn for adverse effects or lost to follow-up, (3) no significant short-term MTX toxicity has been observed. CONCLUSIONS: (1) The use of a composite outcome measure in the design of MS clinical trials is a promising alternative to multiple individual outcome measures that are relatively insensitive to detecting clinical change, (2) low-dose oral weekly MTX does not appear to be associated with significant short-term toxicity in CPMS. Conclusions regarding therapeutic efficacy of MTX in MS must await completion of this clinical trial.

Adult↗
PubMed1992

Proton magnetic resonance spectroscopy of human brain: applications to normal white matter, chronic infarction, and MRI white matter signal hyperintensities.

A modified ISIS method, for image-selected localized proton magnetic resonance spectroscopy (1H MRS), was used to determine the ratios and T2 relaxation times of proton metabolites in normal subjects and in patients with chronic infarction and MRI white matter signal hyperintensities (WMSH). First, in patients with cerebral infarctions, increased concentrations of lactate were found in the majority of patients, and N-acetyl aspartate (NAA) was reduced to a significantly greater extent than choline (Cho) or creatine (Cre). For TE = 270 ms, the raw ratios of Cho/NAA, Cre/NAA, and Lac/NAA were significantly (P less than 0.05) increased from 0.23 +/- 0.02 (mean +/- SE), 0.20 +/- 0.01, and 0.05 +/- 0.01, respectively in the normal group to 0.39 +/- 0.08, 0.37 +/- 0.05, and 0.48 +/- 0.15 in the stroke group. Also, the T2 relaxation time of creatine was significantly (P = 0.007) increased from 136 ms in normal white matter to 171 ms in cerebral infarcts. Second, in patients with WMSH, no significant change of the proton metabolite concentrations could be detected with the exception of the choline which was significantly (P = 0.003) altered. The Cho/NAA ratio, after T2 and excitation profile correction, increased from 0.47 +/- 0.02 in the normal group to 0.64 +/- 0.05 in the WMSH group. Third, in normal white matter, the concentration of N-acetyl aspartate, choline, and lactate was estimated to 11.5, 2.0, and 0.6 mM, respectively, by assuming a total creatine concentration of 10 mM.

Aged↗
PubMed1992

Alterations in brain phosphorus metabolite concentrations associated with areas of high signal intensity in white matter at MR imaging.

Areas of high signal intensity in white matter are identified on brain magnetic resonance (MR) imaging studies in 25%-50% of elderly subjects. The authors used phosphorus-31 MR spectroscopy to characterize the metabolic status of hemispheric white matter brain volumes in 30 elderly subjects with white matter areas of high signal intensity at MR imaging. Compared with white matter volumes with no or minimal areas of high intensity, white matter volumes with extensive areas of high intensity evidenced a 26% decrease in the adenosine triphosphate (ATP)/inorganic phosphate (Pi) ratio (P = .03) and a 21% decrease in the ATP concentration (P = .05), with the Pi level unchanged. A pilot P-31 spectroscopic imaging study in a subject with a large, coalescing white matter area of high signal intensity demonstrated large reductions in metabolite concentrations in the high-signal-intensity area. These results suggest that extensive white matter areas of high signal intensity indicate a process that affects white matter cellular energy metabolism.

Adenosine Triphosphate↗
PubMed1991

Epidemiology of colonic symptoms and the irritable bowel syndrome.

Functional gastrointestinal disease is believed to be very common, but reports of its prevalence have not usually evaluated random community samples, and validated questionnaires have not been used to elicit symptoms. The prevalence of specific colonic symptoms and the irritable bowel syndrome among representative middle-aged whites was determined from a defined population, and the impact of these symptoms on presentation for medical care was measured. An age- and sex-stratified random sample of 1021 residents of Olmsted County, Minnesota, aged 30-64 years, was obtained. All subjects were mailed a valid self-report questionnaire that identified gastrointestinal symptoms and functional gastrointestinal disorders. The response rate was 82% (n = 835). The age- and sex-adjusted prevalence of abdominal pain (more than six times in the prior year) was 26.2 per 100 (95% confidence interval, 23.1-29.2). The prevalence of chronic constipation (hard stools and straining and/or less than 3 stools per week greater than 25% of the time) was 17.4 (95% confidence interval, 14.8-20.0), whereas the prevalence of chronic diarrhea (loose watery stools, and/or greater than 3 stools per day greater than 25% of the time) was 17.9 (95% confidence interval, 15.3-20.5). The prevalence of abdominal pain and disturbed defecation was similar in women and men, except that infrequent defecation and straining at stool were more common in women. Using the Manning symptom criteria to identify irritable bowel syndrome (greater than or equal to 2 of 6 symptoms in those with abdominal pain more than six times in the prior year), the prevalence of irritable bowel syndrome was 17.0 per 100 (95% confidence interval, 14.4-19.6). Overall, 71 persons (9%) reported visiting a physician for abdominal pain or disturbed defecation in the prior year; a subset of variables related to pain severity were the best predictors of health care seeking after adjustment for age and gender. However, these accounted for only 22% of the log likelihood. In conclusion, more than one third of an unselected middle-aged population reported chronic abdominal pain or disturbed defecation, and more than one in six had symptoms compatible with the irritable bowel syndrome. Only a minority had presented for medical evaluation; moreover, the characteristics of the abdominal complaints did not explain the seeking of health care in most cases.

Abdominal Pain↗
PubMed1990

Preservation of normal cognitive functioning in elderly subjects with extensive white-matter lesions of long duration.

Although deep white-matter brain lesions are seen on magnetic resonance imaging in about one third of elderly subjects, their clinical significance is not known. In 1984, we studied three retired teachers who had extensive deep white-matter brain lesions on magnetic resonance imaging, yet functioned cognitively at an above-average level. Blinded review of 1981 computed tomographic scans revealed patchy white-matter lucencies for two of the subjects. Repeated magnetic resonance imaging in 1987 showed that the deep white-matter brain lesions were at least as extensive as in the initial study. One subject had developed renal failure, while the other two continued to function at a high level with no evidence of cognitive decline or psychiatric or neurologic impairment. The presence of extensive deep white-matter brain lesions for up to 7 years in two subjects whose cognitive, behavioral, and neurologic functioning is unimpaired suggests that deep white-matter brain lesions do not necessarily indicate a clinically significant central nervous system disease process.

Age Factors↗
PubMed1987

The onset of Munchausen's syndrome.

Although Munchausen's syndrome is well known, its mode of onset and development are poorly understood. The authors describe an individual whose developmental history was notable for dyslexia and pathological lying from early childhood, and who later developed Munchausen's syndrome following an explosive separation from his terminally ill father. The patient's simulated genitourinary problems related directly to his father's renal malignancy. The development of his Munchausen syndrome is discussed with reference to his traumatic separation from his father as well and to his preexisting character pathology and probable central nervous system dysfunction.

Adult↗
PubMed1987

Meperidine-induced delirium.

Despite the widespread use of meperidine as an analgesic, its potential for producing delirium has been overlooked. Six cases demonstrating meperidine-induced behavioral toxicity are reported. Toxicity was more likely when meperidine was combined with cimetidine or drugs having anticholinergic activity. Discontinuation of meperidine and substitution of morphine for analgesia were usually successful in treating the delirium. Physostigmine reversed the delirium in one patient. The authors suggest that the delirium results from the excessive anticholinergic activity of meperidine or its only active metabolite, normeperidine.

Adult↗
PubMed1987

The Neurobehavioral Cognitive Status Examination: a brief but quantitative approach to cognitive assessment.

The Neurobehavioral Cognitive Status Examination (NCSE), a screening examination that assesses cognition in a brief but quantitative fashion, uses independent tests to evaluate functioning within five major cognitive ability areas: language, constructions, memory, calculations, and reasoning. The examination separately assesses level of consciousness, orientation, and attention. This instrument quickly identifies intact areas of functioning, yet provides more detailed assessment in areas of dysfunction. Standardization data are provided for 119 healthy adults (age range, 20 to 92 years) and for 30 patients receiving neurosurgical care for brain lesions (range, 25 to 88 years). Cognitive profiles for several common neuropsychiatric conditions illustrate the usefulness of this examination in clinical practice.

Adult↗
PubMed1987

The Neurobehavioral Cognitive Status Examination: comparison with the Cognitive Capacity Screening Examination and the Mini-Mental State Examination in a neurosurgical population.

Studies to determine the validity of the Mini-Mental State Examination (MMSE) and the Cognitive Capacity Screening Examination (CCSE) have indicated unacceptably high false-negative rates for these tests. To determine whether a new examination, the Neurobehavioral Cognitive Status Examination (NCSE), is more sensitive in the detection of cognitive dysfunction, we compared the three examinations in 30 patients with documented brain lesions. The CCSE had a false-negative rate of 53%; the MMSE, of 43%; and the NCSE, of 7%. The sensitivity of the NCSE is derived from two features of its design: the use of independent tests to assess skills within five major areas of cognitive functioning, and the use of graded tasks within each of these cognitive domains.

Adult↗