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Annals of the New York Academy of... Mar 2001In science, anomalies expose the limitations of existing paradigms and drive the search for new ones. In the late 1800s, physicians observed that certain illnesses... (Comparative Study)
Comparative Study Review
In science, anomalies expose the limitations of existing paradigms and drive the search for new ones. In the late 1800s, physicians observed that certain illnesses spread from sick, feverish individuals to those contacting them, paving the way for the germ theory of disease. The germ theory served as a crude, but elegant formulation that explained dozens of seemingly unrelated illnesses affecting literally every organ system. Today, we are witnessing another medical anomaly-a unique pattern of illness involving chemically exposed groups in more than a dozen countries, who subsequently report multisystem symptoms and new-onset chemical, food, and drug intolerances. These intolerances may be the hallmark for a new disease process or paradigm, just as fever is a hallmark for infection. The fact that diverse demographic groups, sharing little in common except some initial chemical exposure event, develop these intolerances is a compelling anomaly pointing to a possible new theory of disease, one that has been referred to as "Toxicant-Induced Loss of Tolerance" ("TILT"). TILT has the potential to explain certain cases of asthma, migraine headaches, and depression, as well as chronic fatigue, fibromyalgia, and "Gulf War syndrome". It appears to evolve in two stages: (1) initiation, characterized by a profound breakdown in prior, natural tolerance resulting from either acute or chronic exposure to chemicals (pesticides, solvents, indoor air contaminants, etc.), followed by (2) triggering of symptoms by small quantities of previously tolerated chemicals (traffic exhaust, fragrances, gasoline), foods, drugs, and food/drug combinations (alcohol, caffeine). While the underlying dynamic remains an enigma, observations indicating that affected individuals respond to structurally unrelated drugs and experience cravings and withdrawal-like symptoms, paralleling drug addiction, suggest that multiple neurotransmitter pathways may be involved.
Topics: Attitude; Comorbidity; Dose-Response Relationship, Drug; Dyspnea; Environmental Exposure; Environmental Pollutants; Fatigue; Female; Food; Humans; Male; Models, Biological; Multiple Chemical Sensitivity; Persian Gulf Syndrome; Severity of Illness Index; Substance Withdrawal Syndrome; Substance-Related Disorders; Surveys and Questionnaires
PubMed: 12000012
DOI: 10.1111/j.1749-6632.2001.tb05810.x -
Frontiers in Bioscience : a Journal and... Jan 2004Clinical organ transplantation only became a viable treatment option after the advent of effective pharmacologic immunosuppression. Azathioprine and steroids were among... (Review)
Review
Clinical organ transplantation only became a viable treatment option after the advent of effective pharmacologic immunosuppression. Azathioprine and steroids were among the first drugs available for pharmacologic immunosuppression allowed for the first long-term successes in kidney and liver transplantation, though survivors experienced significant adverse effects of the immunosuppression. Azathioprine is an antimetabolite which inhibits the de novo and salvage pathways of purine synthesis. This results in lymphocyte suppression but also toxicity to bone marrow, gastrointestinal tract, and liver. Mycophenolate mofetil (MMF), another antimetabolite drug, inhibits only the de novo purine synthesis pathway. Corticosteroids cause immunosuppression mainly by sequestration of CD4+ T-lymphocytes in the reticuloendothelial system and by inhibiting the transcription of cytokines. Corticosteroids have adverse effects on virtually every system in the body, producing many dose-limiting problems such as osteoporosis, obesity and glucose intolerance. The introduction of cyclosporine in 1983 allowed for further improvements in graft survival, and the incidence of acute rejection decreased. Cyclosporine and the more recently-introduced tacrolimus compose the class of immunosuppressive agents called calcineurin inhibitors. By binding calcineurin and preventing its translocation into the nucleus these drugs prevent transcription and subsequent secretion of IL-2. These drugs produce varying degrees of nephrotoxicity, neurotoxicity and glucose intolerance. Rapamycin also inhibits IL-2 expression, though by interaction with the mammalian Target of Rapamycin (mTOR) protein. The use of antibody to produce immunosuppression began with polyclonal sera developed in animals such as horses or goats. The mechanism by which polyclonal sera causes immunosuppression is not well understood, though cell-mediated cytotoxicity of lymphocytes in the circulation may be one major effect. In contrast, the monoclonal antibody OKT3 is specific for the T-cell receptor (TCR)/CD3 complex, thus preventing activation of T-lymphocutes. Most recently, human and chimeric murine monoclonal antibodies daclizumab and basiliximab have provided effective induction therapy with virtually no adverse effects. While the improved efficacy and decreased adverse effects immunosuppressive agents account for much of the progress in the field of transplantation, current immunosuppression medications not perfect. Ideally, medications would inducing graft tolerance while avoiding generalized immunosuppression and non-immunologic adverse effects. Future research will likely focus on molecular- and gene-level mechanisms to achieve this goal.
Topics: Adrenal Cortex Hormones; Animals; Antimetabolites; Calcineurin Inhibitors; Cyclosporine; Fingolimod Hydrochloride; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Immunotherapy; Muromonab-CD3; Propylene Glycols; Sphingosine
PubMed: 14766378
DOI: 10.2741/1249 -
JAMA Sep 1971
Topics: Administration, Oral; Adult; Alcoholism; Diabetes Mellitus; Ethanol; Fasting; Female; Glucose; Glucose Tolerance Test; Growth Hormone; Humans; Insulin; Male; Time Factors
PubMed: 5109749
DOI: 10.1001/jama.217.11.1513 -
The Journal of Allergy and Clinical... 2014A large percentage of patients with aspirin exacerbated respiratory disease (AERD) report the development of alcohol-induced respiratory reactions, but the true...
BACKGROUND
A large percentage of patients with aspirin exacerbated respiratory disease (AERD) report the development of alcohol-induced respiratory reactions, but the true prevalence of respiratory reactions caused by alcoholic beverages in these patients was not known.
OBJECTIVE
We sought to evaluate the incidence and characteristics of alcohol-induced respiratory reactions in patients with AERD.
METHODS
A questionnaire designed to assess alcohol-induced respiratory symptoms was administered to patients at Brigham and Women's Hospital and Scripps Clinic. At least 50 patients were recruited into each of 4 clinical groups: (1) patients with aspirin challenge-confirmed AERD, (2) patients with aspirin-tolerant asthma (ATA), (3) patients with aspirin tolerance and with chronic rhinosinusitis, and (4) healthy controls. Two-tailed Fisher exact tests with Bonferroni corrections were used to compare the prevalence of respiratory symptoms among AERD and other groups, with P ≤ .017 considered significant.
RESULTS
The prevalence of alcohol-induced upper (rhinorrhea and/or nasal congestion) respiratory reactions in patients with AERD was 75% compared with 33% with aspirin-tolerant asthma, 30% with chronic rhinosinusitis, and 14% with healthy controls (P < .001 for all comparisons). The prevalence of alcohol-induced lower (wheezing and/or dyspnea) respiratory reactions in AERD was 51% compared with 20% in aspirin-tolerant asthma and with 0% in both chronic rhinosinusitis and healthy controls (P < .001 for all comparisons). These reactions were generally not specific to one type of alcohol and often occurred after ingestion of only a few sips of alcohol.
CONCLUSION
Alcohol ingestion causes respiratory reactions in the majority of patients with AERD, and clinicians should be aware that these alcohol-induced reactions are significantly more common in AERD than in controls who are aspirin tolerant.
Topics: Adult; Aged; Asthma, Aspirin-Induced; Cerebrospinal Fluid Rhinorrhea; Dyspnea; Ethanol; Female; Humans; Leukotriene E4; Male; Middle Aged; Respiration Disorders; Respiratory Sounds
PubMed: 24607050
DOI: 10.1016/j.jaip.2013.12.003 -
Annals of Family Medicine 2012This study extends previous community-based studies on the prevalence and clinical characteristics of chemical intolerance in a sample of primary care clinic patients....
PURPOSE
This study extends previous community-based studies on the prevalence and clinical characteristics of chemical intolerance in a sample of primary care clinic patients. We evaluated comorbid medical and psychiatric disorders, functional status, and rates of health care use.
METHODS
A total of 400 patients were recruited from 2 family medicine clinic waiting rooms in San Antonio, Texas. Patients completed the validated Quick Environmental Exposure and Sensitivity Inventory (QEESI) to assess chemical intolerance; the Primary Care Evaluation of Mental Disorders (PRIME-MD) screen for possible psychiatric disorders; the Dartmouth-Northern New England Primary Care Cooperative Information Project (Dartmouth COOP) charts for functional status; and the Healthcare Utilization Questionnaire.
RESULTS
Overall, 20.3% of the sample met criteria for chemical intolerance. The chemically intolerant group reported significantly higher rates of comorbid allergies and more often met screening criteria for possible major depressive disorder, panic disorder, generalized anxiety disorder, and alcohol abuse disorder, as well as somatization disorder. The total number of possible mental disorders was correlated with chemical intolerance scores (P <.001). Controlling for demographics, patients with chemical intolerance were significantly more likely to have poorer functional status, with trends toward increased medical service use when compared with non-chemically intolerant patients. After controlling for comorbid psychiatric conditions, the groups differed significantly only regarding limitations of social activities.
CONCLUSIONS
Chemical intolerance occurs in 1 of 5 primary care patients yet is rarely diagnosed by busy practitioners. Psychiatric comorbidities contribute to functional limitations and increased health care use. Chemical intolerance offers an etiologic explanation. Symptoms may resolve or improve with the avoidance of salient chemical, dietary (including caffeine and alcohol), and drug triggers. Given greater medication intolerances in chemical intolerance, primary care clinicians could use the QEESI to identify patients for appropriate triage to comprehensive nonpharmacologic care.
Topics: Analysis of Variance; Chi-Square Distribution; Comorbidity; Female; Humans; Male; Mental Disorders; Middle Aged; Multiple Chemical Sensitivity; Odds Ratio; Physicians, Primary Care; Prevalence; Primary Health Care; Psychometrics; Self Report; Statistics as Topic; Surveys and Questionnaires; Texas; Treatment Outcome
PubMed: 22778124
DOI: 10.1370/afm.1346 -
Brain, Behavior, and Immunity Nov 2021Prenatal alcohol exposure (PAE) can result in neurobehavioral anomalies, that may be exacerbated by co-occurring metabolic and immune system deficits. To test the...
Prenatal alcohol exposure (PAE) can result in neurobehavioral anomalies, that may be exacerbated by co-occurring metabolic and immune system deficits. To test the hypothesis that the peripheral inflammation in adult PAE offspring is linked to poor glucose metabolism and neurocognitive deficits, pregnant Sprague-Dawley rats were exposed to ethanol vapor or ambient air during the latter half of gestation. We assessed, in adult offspring of both sexes, performance on a battery of neurocognitive behaviors, glucose tolerance, circulating and splenic immune cells by flow-cytometry, and circulating and tissue (liver, mesenteric adipose, and spleen) cytokines by multiplexed assays. PAE reduced both the ratio of spleen to body weight and splenic regulatory T-cell (Treg) numbers. PAE males, but not females exhibited an increase in circulating monocytes. Overall, PAE males exhibited a suppression of cytokine levels, while PAE females exhibited elevated cytokines in mesenteric adipose tissue (IL-6 and IL1α) and liver (IFN-γ, IL-1β, IL-13, IL-18, IL-12p70, and MCP-1), along with increased glucose intolerance. Behavioral analysis also showed sex-dependent PAE effects. PAE-males exhibited increased anxiety-like behavior while PAE-females showed decreased social interaction. PAE offspring of both sexes exhibited impaired recognition of novel objects. Multilinear regression modeling to predict the association between peripheral immune status, glucose intolerance and behavioral outcomes, showed that in PAE offspring, higher levels of adipose leptin and liver TNF- α predicted higher circulating glucose levels. Lower liver IL-1 α and higher plasma fractalkine predicted more time spent in the center of an open-field with sex being an additional predictor. Higher circulating and splenic Tregs predicted better social interaction in the PAE-offspring. Collectively, our data show that peripheral immune status is a persistent, sex-dependent predictor of glucose intolerance and neurobehavioral function in adult PAE offspring.
Topics: Animals; Anxiety; Ethanol; Female; Male; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Rats, Sprague-Dawley; Sex Characteristics
PubMed: 34390803
DOI: 10.1016/j.bbi.2021.08.207 -
Expert Review of Clinical Immunology 2023
Topics: Humans; Anaphylaxis; Food Hypersensitivity; Allergens; Epinephrine
PubMed: 37753864
DOI: 10.1080/1744666X.2023.2265069 -
Allergology International : Official... Dec 2006We report a case of an urticarial reaction after drinking alcohol beverages. The patient was a 47-year-old man suffering urticarial and anaphylactoid reaction to alcohol... (Review)
Review
BACKGROUND
We report a case of an urticarial reaction after drinking alcohol beverages. The patient was a 47-year-old man suffering urticarial and anaphylactoid reaction to alcohol for two years. These reactions were observed at every alcohol beverages intake.
CASE SUMMARY
We performed a prick test with diluted ethanol, alcohol beverages and their metabolites (acetaldehyde, acetic acid). Only acetic acid showed a positive result. Oral challenge test with diluted-ethanol caused pruritus and swelling of his lips. An oral challenge test with 8% diluted Shochu (Japanese distilled alcohol from rice or wheat) caused wheals on his upper back.
DISCUSSION
Only acetic acid, a metabolite of alcohol, induced a positive prick test in the patient with alcohol-induced urticaria. This result was not observed in normal volunteers. An oral challenge test with diluted-alcohol or Shochu showed a positive wheal reaction in a dose dependent-manner which suggests that urticaria seen in this patient might be induced by alcohol-intolerance. However possible allergic reaction to acetaldehyde could not be excluded.
Topics: Acetaldehyde; Acetic Acid; Alcoholic Beverages; Anaphylaxis; Angioedema; Beer; Dose-Response Relationship, Immunologic; Ethanol; Haptens; Humans; Immunoglobulin E; Male; Middle Aged; Models, Immunological; Mouthwashes; Patch Tests; Skin Tests; Urticaria; Wine
PubMed: 17130684
DOI: 10.2332/allergolint.55.411 -
The New England Journal of Medicine Mar 1973
Topics: Adult; Cannabis; Drug Tolerance; Ethanol; Female; Hodgkin Disease; Humans; Male
PubMed: 4684194
DOI: 10.1056/nejm197303082881023 -
Contact Dermatitis Sep 2001
Topics: Benzyl Alcohol; Dermatitis, Allergic Contact; Female; Humans; Middle Aged; Patch Tests; Urticaria
PubMed: 11553157
DOI: 10.1034/j.1600-0536.2001.045003182.x