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Biomedical subjects

C S Miller

Publications and source records attributed to C S Miller.

At least 19 recordsLinked to original sources
PubMed1997

Toxicant-induced loss of tolerance--an emerging theory of disease?

This paper attempts to clarify the nature of chemical sensitivity by proposing a theory of disease that unites the disparate clinical observations associated with the condition. Sensitivity to chemicals appears to be the consequence of a two-step process: loss of tolerance in susceptible persons following exposure to various toxicants, and subsequent triggering of symptoms by extremely small quantities of previously tolerated chemicals, drugs, foods, and food and drug combinations including caffeine and alcohol. Although chemical sensitivity may be the consequence of this process, a term that may more clearly describe the observed process is toxicant-induced loss of tolerance. Features of this yet-to-be-proven mechanism or theory of disease that affect the design of human exposure studies include the stimulatory and withdrawallike nature (resembling addiction) of symptoms reported by patients and masking. Masking, which may blunt or eliminate responses to chemical challenges, appears to have several components: apposition, which is the overlapping of the effects of closely timed exposures, acclimatization or habituation, and addiction. A number of human challenge studies in this area have concluded that there is no physiological basis for chemical sensitivity. However, these studies have failed to address the role of masking. To ensure reliable and reproducible responses to challenges, future studies in which subjects are evaluated in an environmental medical unit, a hospital-based facility in which background chemical exposures are reduced to the lowest levels practicable, may be necessary. A set of postulates is offered to determine whether there is a causal relationship between low-level chemical exposures and symptoms using an environmental medical unit.

Adaptation, Physiological↗
PubMed1996

Potential animal model of multiple chemical sensitivity with cholinergic supersensitivity.

Multiple Chemical Sensitivity (MCS) is a clinical phenomenon in which individuals, after acute or intermittent exposure to one or more chemicals, commonly organophosphate pesticides (OPs), become overly sensitive to a wide variety of chemically-unrelated compounds, which can include ethanol, caffeine and other psychotropic drugs. The Flinders Sensitive Line (FSL) rats were selectively bred to be more sensitive to the OP diisopropylfluorophosphate (DFP) compared to their control counterparts, the Flinders Resistant Line (FRL) rats. The present paper will summarize evidence which indicates that the FSL rats exhibit certain similarities to individuals with MCS. In addition to their greater sensitivity to DFP, the FSL rats are more sensitive to nicotine and the muscarinic agonists arecoline and oxotremorine, suggesting that the number of cholinergic receptors may be increased, a conclusion now supported by biochemical evidence. The FSL rats have also been found to exhibit enhanced responses to a variety of other drugs, including the serotonin agonists m-chlorophenylpiperazine and 8-OH-DPAT, the dopamine antagonist raclopride, the benzodiazepine diazepam, and ethanol. MCS patients report enhanced responses to many of these drugs, indicating some parallels between FSL rats and MCS patients. The FSL rats also exhibit reduced activity and appetite and increased REM sleep relative to their FRL controls. Because these behavioral features and the enhanced cholinergic responses are also observed in human depressives, the FSL rats have been proposed as a genetic animal model of depression. It has also been reported that MCS patients have a greater incidence of depression, both before and after onset of their chemical sensitivities, so cholinergic supersensitivity may be a state predisposing individuals to depressive disorders and/or MCS. Further exploration of the commonalities and differences between MCS patients, human depressives, and FSL rats will help to elucidate the mechanisms underlying MCS and could lead to diagnostic approaches and treatments beneficial to MCS patients.

Animals↗
PubMed1996

Chemical sensitivity: symptom, syndrome or mechanism for disease?

Several different meanings have been attached to the term "chemical sensitivity" by those who use it. Feeling ill from odors is a symptom reported by approximately one-third of the population. The syndrome of chemical sensitivity, frequently called "Multiple Chemical Sensitivity" or "MCS" has been the subject of three federally-sponsored workshops; at least five different case definitions for research on MCS have been proposed. In contrast, the hypothesis that chemical sensitivity may be a mechanism for disease posits that a broad spectrum of "recognized" chronic illnesses, ranging from asthma and migraine to depression and chronic fatigue, may be the consequence of environmental chemical exposures. According to this theory, a two-step process occurs: (1) an initial salient exposure event(s) (for example, a one-time, intermittent, or continuous exposure to pesticides, solvents, or air contaminants in a sick building) interacts with a susceptible individual, causing loss of tolerance for everyday, low level chemical inhalants (car exhaust, fragrances, cleaning agents), as well as for foods, drugs, alcohol, and caffeine; (2) thereafter, such common, formerly well-tolerated substances trigger symptoms, thus perpetuating illness. "Masking" (acclimatization, apposition, and addiction) may hide these exposure-symptom relationships, thus obfuscating the environmental etiology of the illness. Accumulating clinical observations lend credence to a view of chemical sensitivity as an emerging theory of disease causation and underscore the need for its testing in a rational, scientific manner. While chemical sensitivity may be the consequence of chemical exposure, the term "toxicant-induced loss of tolerance" more fully describes the two-step process under scrutiny.

Disease Susceptibility↗
PubMed1996

Viral infections in the immunocompetent patient.

Human herpesviruses and human papillomaviruses are ubiquitous and may cause an array of oral disease. Herpesviruses are unique because recurrent localized disease occurs after the primary infection. Human papillomaviruses are known for their ability to produce benign epithelial proliferations and increasingly are implicated in the development of oral cancer. This article reviews the pathogenesis of common oral lesions induced by these viruses.

Adult↗
PubMed1996

Human papillomavirus expression in oral mucosa, premalignant conditions, and squamous cell carcinoma: a retrospective review of the literature.

OBJECTIVES: The literature of human papillomavirus detection in normal oral mucosa and oral lesions associated with the dysplastic progression of epithelium was reviewed to help define the role of this virus in the development of oral squamous cell carcinoma. STUDY DESIGN: All available data from published studies were analyzed by chi-square test for association between the human papillomavirus and age, gender, race, DNA type, location, lesional dysplastic progression, method of detection, tissue preservation, and use of tobacco and alcohol. RESULTS: Human papillomavirus was identified with increasing frequency in normal oral mucosa (13.5%), benign leukoplakia (14.8%), intraepithelial neoplasia (18.5%), squamous carcinoma (26.2%), and verrucous carcinoma (27%). It was detected in oral squamous cell carcinoma significantly (p < 0.005) more often (37.1%; 122 of 329) in studies that used a high sensitivity assay (polymerase chain reaction) than studies that used moderate sensitivity assays (25.2%; 84 of 334) (e.g., Southern blot hybridization) and low sensitivity assays (16.9%; 61 of 362) (e.g., immunohistochemistry, in situ hybridization). Human papillomavirus DNA was detected significantly more often (p < 0.001) in frozen oral squamous cell carcinoma (51.6%; 115 of 223) than paraffin-embedded tissue (21.7%; 136 of 628). High-risk human papillomaviruses (2, 16, 18) were detected in 81.4% of OSCCs that contained the virus compared with low-risk human papillomavirus genotypes (6, 11) in 17.9% of oral squamous cell carcinoma that contained the human papillomavirus (p < 0.001). In studies that analyzed the use of chemical cofactors, the use of tobacco and alcohol (87.3%) was associated more often with oral squamous cell carcinoma than the presence of human papillomavirus (51.3%), however, the difference was not significant. CONCLUSION: High-risk human papillomavirus genotypes have a significant association with oral squamous cell carcinoma. However, the presence of this virus in a high proportion of oral normal mucosa makes the virus alone a poor prognosticator of progression to malignancy.

Adult↗
PubMed1995

Salivary cortisol response to dental treatment of varying stress.

The physiologic stress of various dental procedures (dental examination, dental prophylaxis, restoration, root canal therapy, and tooth extraction) was measured in 50 nonsmoking healthy men between the ages of 18 and 55 years (mean 34.6 years, range 21 to 53 years) with a salivary cortisol assay. Expectorated saliva was collected at four time points: 10 minutes before the start of the procedure, 15 minutes after the patient was seated, at the end of the procedure, and 1 hour after the completion of the procedure. Of the 196 samples included for analysis, mean cortisol values ranged from 0.1 to 3.8 micrograms/dl with a recovery of 100% +/- 8.4%. The mean cortisol value for the extraction group (1.09 +/- 0.42 microgram/dl) was significantly different (p < 0.05) from the mean values of the examination (0.46 +/- 0.10 microgram/dl), prophylaxis (0.64 +/- 0.64 microgram/dl), root canal (0.49 +/- 0.07 microgram/dl), and restorative (0.60 +/- 0.04 microgram/dl) groups as determined by the Duncan's multiple range test. Cortisol levels decreased from the initial reading to the end of the procedure by about 15% for patients undergoing an examination, root canal, and restorative procedure. Cortisol levels at the end of the procedure were elevated in the prophylaxis (55%) and extraction (148%) groups compared with the baseline cortisol recording. A minority of patients in the prophylaxis group had elevated cortisol levels throughout dental treatment, whereas cortisol levels were elevated during treatment in 80% of patients undergoing extraction. These data suggest that the adrenal stress response associated with tooth extraction(s) is greater than that associated with other routine dental procedures.

Adolescent↗
PubMed1994

Detection of HPV DNA in oral carcinoma using polymerase chain reaction together with in situ hybridization.

This study determined the prevalence of human papillomavirus 16/18 DNA in deparaffinized oral carcinoma specimens on slides with the use of the different sensitivities of in situ hybridization and a technique that combines polymerase chain reaction and in situ hybridization. Human papillomavirus DNA was not detected in the 30 biopsy specimens analyzed by in situ hybridization alone using biotinylated DNA probes specific for human papillomavirus 16/18. Twenty of 30 specimens (66.7%) were found to have human papillomavirus DNA (p < 0.001) with the use of the polymerase chain reaction-in situ hybridization technique. Human papillomavirus 16 was detected in 18 of 26 specimens (69.2%), and 7 of 25 carcinomas (28%) were found to contain human papillomavirus 18. Dual infections were present in 5 of 21 (23.8%) specimens. Human papillomavirus DNA was more prevalent in men (75%) than women (57.1%). However, there was no difference in the mean age of patients with oral carcinoma (men, 67.8 years; women, 67.5 years) who had human papillomavirus and those who did not (67.2 years). Carcinomas associated with dual infections occurred at a lower mean age (59.4 years) than those associated with a single human papillomavirus type (p < 0.005). We conclude that the polymerase chain reaction-in situ hybridization technique enhances our ability to demonstrate human papillomavirus types highly associated with oral squamous cell carcinoma.

Adult↗
PubMed1994

Psychological characteristics and subjective intolerance for xenobiotic agents of normal young adults with trait shyness and defensiveness. A parkinsonian-like personality type?

The present study examines the psychological characteristics and self-reported responses to xenobiotic agents such as tobacco smoke and pesticide of normal young adults with personality traits similar to those claimed for Parkinsonian patients. Previous research, though controversial, has suggested that persons with idiopathic Parkinson's disease (PD) have premorbid personality traits that may include shyness and repressive defensiveness. Other epidemiological evidence indicates that PD patients may have premorbidly increased prevalence of anxiety, affective, and/or somatoform disorders; decreased rates of smoking and alcohol consumption; and elevated exposure to herbicides or pesticides. A total of 783 college students enrolled in an introductory psychology course completed the Cheek-Buss Scale (shyness), the Marlowe-Crowne Social Desirability Scale (defensiveness), Symptom Checklist 90 (revised), the Mastery Scale, a health history checklist, and rating scales for frequency of illness from alcohol and 10 common environmental chemicals. Subjects were divided into four groups on the basis of above- versus below-median scores on the Cheek-Buss and Marlowe-Crowne scales (persons high in shyness and defensiveness, those high only in shyness, those high only in defensiveness, and those low in both shyness and defensiveness). The group high in shyness but low in defensiveness had the highest, whereas the group low in shyness but high in defensiveness had the lowest, total scores on the SCL-90-R; the two shyest groups were lowest in sense of mastery.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Herpes simplex virus and human papillomavirus infections of the oral cavity.

Herpes simplex virus and human papillomavirus are epitheliotrophic viruses common to the oral cavity. They produce acute and chronic disorders of oral mucosa of interest to the dermatologist. Most of these lesions are benign in nature. However, both viruses are harbored latently, and their malignant potential remains to be defined.

Adult↗
PubMed1994

Parents' responses to vaccine information pamphlets.

OBJECTIVE: To assess parents' knowledge and opinions about immunizations and immunization practices before and after introduction of vaccine information pamphlets. RESEARCH DESIGN: Telephone questionnaire administered to parents whose children received immunizations in the preceding week. SETTING: Six private pediatric practices in Nashville area and resident continuity clinic at Vanderbilt University Medical Center. PARTICIPANTS: Parents whose children were scheduled to receive immunizations were asked to participate. Interviews were completed with 177 parents whose children received immunizations before and 156 parents after pamphlets were introduced. These two groups of parents had similar demographic characteristics. RESULTS: Parents who received vaccine information pamphlets learned more about vaccines (2.38 facts/parent after vs 1.18/parent before vaccine information pamphlets, z = -6.28, P < .0001) and were more eager to obtain immunizations for their children (76% vs 38%, chi 2 = 47.24, P < .001). Receipt of pamphlets did not make parents significantly more likely to report side effects from vaccines (63% after vs 55% before, NS) but tended to make them less likely to turn to non health care providers for information (58% after vs 69% before, chi 2 = 3.73, P = .06). Parents who received pamphlets, however, said more often that they received too much information (20% vs 4%, chi 2 = 14.9, P < .001). CONCLUSIONS: Vaccine information pamphlets enhanced parents' knowledge and acceptance of immunizations. There is room for further improvement.

Child↗
PubMed1994

Pericoronal radiolucencies with and without radiopacities.

Pericoronal radiolucencies are common entities of the jaws that account for about 15% to 20% of all biopsy specimens. They are usually slow-growing, benign entities that involve odontogenic epithelium and the crown of a nonerupting tooth. Many lesions develop early in life and are detected during routine radiographic examination. Others are found in later years when a patient presents with a slow-growing swelling. The dentist is often the first provider to encounter these conditions. Thus, he or she must be familiar with their appearance and understand the proper management required.

Dental Sac↗
PubMed1993

UV-enhanced replication of herpes simplex virus in DNA-repair competent and deficient fibroblasts.

Replication of herpes simplex virus type 1 was enhanced in fibroblast cultures when cells were ultraviolet irradiated 12 to 48 hours before infection. Maximum enhancement (340% increase) occurred at exposures of 9.6 J/m2 in DNA-repair competent fibroblasts. Repair deficient xeroderma pigmentosum cells responded to lower ultraviolet exposures (1.6 to 5.6 J/m2) with lower levels of enhancement (37% to 140%). Ultraviolet irradiation of host cells before infection increased viral DNA synthesis, but did not alter the ability of the cell to adsorb virus. Prostaglandins were not shown to contribute to the process. These results suggest that ultraviolet-enhanced replication of herpes simplex virus may be associated with DNA-repair activities, and that ultraviolet-enhanced herpes simplex virus replication should be further examined for its contribution to herpes simplex virus recurrence in vivo.

DNA Repair↗
PubMed1993

In situ hybridization analysis of human papillomavirus in orofacial lesions using a consensus biotinylated probe.

The effectiveness of the Viratype Omniprobe in situ human papillomavirus tissue hybridization kit (Digene Diagnostics) was evaluated for the detection of HPV DNA in common orofacial lesions. Seventy mucocutaneous lesions were hybridized with a biotinylated Omniprobe that was specific for HPV types 6, 11, 16, 18, 31, 33, 35, 42, 43, 44, 45, 51, 52, and 56. Eighteen (25.7%) of the specimens analyzed had intranuclear positive signals for HPV. Probing with HPV 6/11, 16/18, and 31/33/35 to delimit the HPV genotype yielded HPV DNA 6/11 in 16 (88.9%) of the Omniprobe-positive specimens. Only squamous papilloma and condyloma acuminatum were found to harbor HPV DNA. Sites most frequently infected were the labial and buccal mucosa (21.7%) and the floor of the mouth (17.4%). These results suggest that hybridization with the Omniprobe provides appropriate sensitivity and specificity for detecting HPV in some benign proliferations of the oral cavity. However, the detection of HPV in oral squamous cell carcinoma, lichen planus, and keratoacanthoma remains problematic until more sensitive and specific molecular techniques are used.

Carcinoma, Squamous Cell↗
PubMed1992

An olfactory-limbic model of multiple chemical sensitivity syndrome: possible relationships to kindling and affective spectrum disorders.

This paper reviews the clinical and experimental literature on patients with multiple adverse responses to chemicals (Multiple Chemical Sensitivity Syndrome-MCS) and develops a model for MCS based on olfactory-limbic system dysfunction that overlaps in part with Post's kindling model for affective disorders. MCS encompasses a broad range of chronic polysymptomatic conditions and complaints whose triggers are reported to include low levels of common indoor and outdoor environmental chemicals, such as pesticides and solvents. Other investigators have found evidence of increased prevalence of depression, anxiety, and somatization disorders in MCS patients and have concluded that their psychiatric conditions account for the clinical picture. However, none of these studies has presented any data on the effects of chemicals on symptoms or on objective measures of nervous system function. Synthesis of the MCS literature with large bodies of research in neurotoxicology, occupational medicine, and biological psychiatry, suggests that the phenomenology of MCS patients overlaps that of affective spectrum disorders and that both involve dysfunction of the limbic pathways. Animal studies demonstrate that intermittent repeated low level environmental chemical exposures, including pesticides, cause limbic kindling. Kindling (full or partial) is one central nervous system mechanism that could amplify reactivity to low levels of inhaled and ingested chemicals and initiate persistent affective, cognitive, and somatic symptomatology in both occupational and nonoccupational settings. As in animal studies, inescapable and novel stressors could cross-sensitize with chemical exposures in some individuals to generate adverse responses on a neurochemical basis. The olfactory-limbic model raises testable neurobiological hypotheses that could increase understanding of the multifactorial etiology of MCS and of certain overlapping affective spectrum disorders.

Air Pollutants↗
PubMed1992

Pharmacists' compensation and work patterns, 1990-91.

Several major trends were observed in these findings from the 1990-91 National Pharmacists' Compensation Survey (for details see the final report). Only 72.6% of licensed pharmacists were working full-time in pharmacy; another 14.4% were working part-time in pharmacy, and nearly 13.0% were either not working in pharmacy or not working at all. Although 90.0% of active men pharmacists were working full-time, only 70.7% of active women pharmacists were working full-time. Men were more likely to be working in independent and chain pharmacies as a manager or owner. Women were more likely to be working in hospital or chain pharmacies as a staff pharmacist. Pharmacists' base salary in 1990 was substantially higher for men than for women with averages of $46,661 versus $42,668. Total pharmacy compensation showed a similar pattern but an even greater spread between men and women with averages of $51,032 versus $44,751. However, after adjusting for years in practice and number of hours worked per week, the base HWE for employee pharmacists shows that men and women pharmacists do get "equal pay for equal work" in the first 20 years of practice. The difference that develops between men and women with more years in practice is probably due to the higher proportion of men in management positions and to differences in practice setting preferences.(ABSTRACT TRUNCATED AT 250 WORDS)

Career Mobility↗