William J. Meggs

Prevalence and Nature of Allergy and Chemical Sensitivity in a General Population

The objectives of this study were (a) to determine the self-reported prevalence of allergy and chemical sensitivity in a rural population of eastern North Carolina, (b) to determine the type and frequency of symptoms for each condition, and (c) to determine the demographic groups affected. A random general telephone survey was conducted during the period May 14, 1993, to September 10, 1993, and questions about allergy and chemical sensitivity were asked. Of the 1 446 households contacted, 1 027 (71%) individuals agreed to participate. Allergies were reported by 365 (35%) individuals. Thirty percent of allergic individuals reported that symptoms occurred once or more each week, whereas 61% reported that symptoms occurred, at most, once each month. Allergic symptoms that occurred daily were reported by 5.3% of the total population. Chemical sensitivity was reported by 336 (33%) individuals. Thirty-five per cent of chemically sensitive individuals reported symptoms at least once each week, whereas 53% reported that symptoms occurred once (or less) each month. Symptoms of chemical sensitivity that occurred daily were reported by 3.9% of the total population. Both allergy and chemical sensitivity were distributed widely across age, income, race, and educational groups. Simultaneous allergy and chemical sensitivity were reported by 16.9% of the population, allergy without chemical sensitivity by 16.0%, chemical sensitivity without allergy by 18.2%, and neither condition by 48.9%. If the prevalence of sensitivity to chemical irritants is, in fact, equivalent to that of allergy, as was found in this study, then support for the scientific investigation of chemical sensitivity is justified.The objectives of this study were (a) to determine the self-reported prevalence of allergy and chemical sensitivity in a rural population of eastern North Carolina, (b) to determine the type and frequency of symptoms for each condition, and (c) to determine the demographic groups affected. A random general telephone survey was conducted during the period May 14, 1993, to September 10, 1993, and questions about allergy and chemical sensitivity were asked. Of the 1 446 households contacted, 1 027 (71%) individuals agreed to participate. Allergies were reported by 365 (35%) individuals. Thirty percent of allergic individuals reported that symptoms occurred once or more each week, whereas 61% reported that symptoms occurred, at most, once each month. Allergic symptoms that occurred daily were reported by 5.3% of the total population. Chemical sensitivity was reported by 336 (33%) individuals. Thirty-five per cent of chemically sensitive individuals reported symptoms at least once each week, whereas 53% reported that symptoms occurred once (or less) each month. Symptoms of chemical sensitivity that occurred daily were reported by 3.9% of the total population. Both allergy and chemical sensitivity were distributed widely across age, income, race, and educational groups. Simultaneous allergy and chemical sensitivity were reported by 16.9% of the population, allergy without chemical sensitivity by 16.0%, chemical sensitivity without allergy by 18.2%, and neither condition by 48.9%. If the prevalence of sensitivity to chemical irritants is, in fact, equivalent to that of allergy, as was found in this study, then support for the scientific investigation of chemical sensitivity is justified.

Rads and Ruds the Toxic Induction of Asthma and Rhinitis

Inhalation exposures can produce asthma and rhinitis by several mechanisms. Sensitization with the production of IgE specific for a substance can lead to symptoms on reexposure via mast cell degranulation and the release of inflammatory mediators. Some substances, known as environmental adjuvants, enhance the immune response to concomitant exposures with the environmental adjuvant. Respiratory irritants can lead to asthma and rhinitis through interaction with chemical irritant receptors in the airway, leading to release of substance P from sensory nerves and neurogenic inflammation. The reactive airways dysfunction syndrome is a chronic asthma-like syndrome resulting from a single acute exposure to a respiratory irritant, while the reactive upper-airways dysfunction syndrome is chronic rhinitis stemming from an irritant exposure. The dysregulation of neurogenic inflammation by chemical exposures may be an important mechanism in the toxic induction of reactive airways dysfunction syndrome and reactive upper-airways dysfunction syndrome and may play a role in understanding the sick building syndrome and the multiple chemical sensitivity syndrome.

Rhinolaryngoscopic Examination of Patients with the Multiple Chemical Sensitivity Syndrome

Ten patients who met the Cullen case definition for the multiple chemical sensitivity syndrome were evaluated; a history was taken, and physical examination and fiberoptic rhinolaryngoscopy were performed. All patients had an initial chemical exposure, which was followed by multiple physical and mental complaints in response to subsequent exposure to a variety of odorous organic chemicals. Rhinitis was a prominent complaint in nine patients, but one patient denied any nasal symptoms. Rhinolaryngoscopic findings were abnormal in all patients; edema, excessive mucus, a cobblestone appearance of the posterior pharynx and base of the tongue, and mucosal injection were observed frequently. A particularly striking finding was focal areas of blanched mucosa that surrounded a prominent vessel. These results suggest that nasal pathology may be a prominent feature of this disorder.

Recent research on Gulf War illness and other health problems in veterans of the 1991 Gulf War: Effects of toxicant exposures during deployment

Veterans of Operation Desert Storm/Desert Shield – the 1991 Gulf War (GW) – are a unique population who returned from theater with multiple health complaints and disorders. Studies in the U.S. and elsewhere have consistently concluded that approximately 25–32% of this population suffers from a disorder characterized by symptoms that vary somewhat among individuals and include fatigue, headaches, cognitive dysfunction, musculoskeletal pain, and respiratory, gastrointestinal and dermatologic complaints. Gulf War illness (GWI) is the term used to describe this disorder. In addition, brain cancer occurs at increased rates in subgroups of GW veterans, as do neuropsychological and brain imaging abnormalities. Chemical exposures have become the focus of etiologic GWI research because nervous system symptoms are prominent and many neurotoxicants were present in theater, including organophosphates (OPs), carbamates, and other pesticides; sarin/cyclosarin nerve agents, and pyridostigmine bromide (PB) medications used as prophylaxis against chemical warfare attacks. Psychiatric etiologies have been ruled out. This paper reviews the recent literature on the health of 1991 GW veterans, focusing particularly on the central nervous system and on effects of toxicant exposures. In addition, it emphasizes research published since 2008, following on an exhaustive review that was published in that year that summarizes the prior literature (RACGWI, 2008). We conclude that exposure to pesticides and/or to PB are causally associated with GWI and the neurological dysfunction in GW veterans. Exposure to sarin and cyclosarin and to oil well fire emissions are also associated with neurologically based health effects, though their contribution to development of the disorder known as GWI is less clear. Gene-environment interactions are likely to have contributed to development of GWI in deployed veterans. The health consequences of chemical exposures in the GW and other conflicts have been called “toxic wounds” by veterans. This type of injury requires further study and concentrated treatment research efforts that may also benefit other occupational groups with similar exposure-related illnesses.

Nasal pathology and ultrastructure in patients with chronic airway inflammation (RADS and RUDS) following an irritant exposure.

BACKGROUND Reactive airways dysfunction syndrome is a chronic asthma-like condition developing after an acute irritant exposure, and chronic inflammation has been seen on endobronchial biopsy. Reactive upper-airways dysfunction syndrome is chronic rhinitis developing in temporal association with a toxic inhalation exposure, but the pathophysiology is unknown. OBJECTIVES To study biopsies of the nasal mucosa in patients with reactive upper-airways dysfunction syndrome and in some cases reactive airways dysfunction syndrome developing in temporal association with a chlorine dioxide exposure, to see if a histologic basis for the persistent rhinitis and sensitivity to chemical irritants could be determined. METHODS Specimens were stained with hematoxylin-eosin and immunoperoxidase stains for substance P, vasointestinal peptide, and S-100 (nerve fibers), and fixed in glutaraldehyde for electron microscopy. Biopsies of three nonexposed subjects were performed for comparison. A pathologist blinded to clinical data interpreted the specimens. RESULTS Inflammation ratings of exposed individuals were higher than for the nonexposed individuals. The number of nerve fibers stained was greater for patients vs controls. Substance P and vasointestinal peptide staining was nonspecific. Electron microscopy showed desquamation of the epithelium and permeability of epithelial cell junctions. CONCLUSION This study suggests a mechanism by which ongoing low level exposures perpetuate airway inflammation after an inducing toxic inhalation. A possible overlap between reactive airways dysfunction syndrome, reactive upper-airway dysfunction syndrome and the multiple chemical sensitivity syndrome is suggested.

Clearance of metformin by hemofiltration in overdose.

Background: Metformin is prescribed with an increasing frequency for patients with Type II diabetes mellitus; the increasing availability increases the risk of intentional overdoses. Metformin may cause severe lactic acidosis in overdose, especially when accompanied by co-ingestants or other medical conditions that alter lactate handling or metformin elimination. Though the clearance of therapeutic metformin by hemodialysis is known, the clearance in the setting of a large overdose has not been reported. Case Report: A 58-year-old man with a history of Type II diabetes, hypertension, bipolar disease, and decreased renal function presented after ingestion of approximately 40 500-mg metformin tablets and 20 240-mg diltiazem sustained-release tablets. Clinical manifestations of poisoning included somnolence, hypotension, bradycardia, severe lactic acidosis, and ultimately death. Gastric decontamination was attempted with gastric lavage, multiple dose activated charcoal, and whole bowel irrigation. Hemodynamic support was provided with pressors, glucagon, insulin, and intra-aortic balloon pump. Due to hypotension, continuous renal replacement therapy, rather than hemodialysis, was initiated. Continuous veno-venous hemodialysis was performed with a blood flow of 180 mL/min and dialysate flow of 2.5 L/h. A Multiflow 60 kidney (Cobe) on a Prisma (Cobe) continuous renal replacement therapy machine was used. The initial metformin level was 110 μg/mL (therapeutic range 1–2 μg/mL). By continuous veno-venous hemodialysis, an absolute clearance of 50.4 mL/min was obtained. Conclusion: Metformin was cleared by the continuous veno-venous hemodialysis modality of continuous renal replacement therapy in this metformin overdose. Although a fatal outcome occurred in this patient, its utility in other patients with metformin overdose should be investigated.

Weight gain associated with chronic exposure to chlorpyrifos in rats.

ObjectiveThis work exposed rats to low levels of the organophosphate insecticide chlorpyrifos and monitored for toxic effects, including weight gain.MethodsRats received either a subcutaneous injection of chlorpyrifos, 5 mg/kg/day, or an equal volume of vehicle daily for 4 months. Subjects were observed for 30 minutes after injection for signs of acute toxicity. Body weights were recorded at baseline, 2 months, 3 months, and 4 months. At the end of the experiment, the weights of hearts, medial lobe of the livers, peri-nephric fat pads, and gastrocnemius muscles were recorded. Effects of chlorpyrifos on adipocyte differentiation in culture were studied. Results were compared using RMANOVA.ResultsNo signs of acute cholinergic toxicity were observed after injections in any subject. Rats in the 5 mg/kg group were significantly heavier than those in the control group by 2 months (335.7 ± 16.7 g vs. 318.6 ± 15.8 g; p = 0.034). This difference increased at 3 months (350.1 ± 16.4 g vs. 322.3 ± 21.3 g p = 0.006) and 4 months (374.4 ± 22.2 g vs. 340.2 ± 25.2 g p = 0.006). At 4 months, the weights of the perinephric fat pads were significantly increased in the chlorpyrifos group relative to controls (2.867 + 0.516 vs. 1.130 + 0.171, p = 0.0039). The two groups showed no weight differences between hearts, livers, and gastrocnemius muscles. Chlorpyrifos did not affect adipocyte differentiation in tissue culture.ConclusionsChronic exposure to chlorpyrifos at 5 mg/kg/day caused an increase in rat body weight when compared to controls. This increase was in adipose tissue. Chlorpyrifos did not induce differentiation of adipocytes in culture.

Thallium poisoning from maliciously contaminated food

Four young adults presented two days after one of them had received marzipan balls packaged in a box from an expensive candy manufacturer. Two ate one candy ball, while two others shared a third. The next day, variable gastrointestinal symptoms developed. On the third day, two patients developed painful paresthesiae of the hands and feet, an early but nonspecific clinical marker of thallium poisoning. A tentative diagnosis of thallium poisoning was made based on symptoms, and treatment was initiated. The remaining candies were radiographed. Metallic densities in the candies supported the diagnosis, and atomic absorption spectroscopy was used to quantitate thallium content. Each candy contained a potentially fatal dose. Five to seven days later, hypertension and tachycardia developed in the two patients who had ingested an entire candy. All patients developed alopecia but recovered without overt neurologic or other sequelae. While the diagnosis of thallium poisoning is often delayed until alopecia develops, an early diagnosis favors an effective treatment strategy.

The Treatment of Lead Poisoning from Gunshot Wounds with Succimer (DMSA)

Lead poisoning is an unusual complication of gunshot wounds that occurs when retained lead bullet fragments are in contact with body fluids capable of solubilizing lead. The epidemic of violence by gunfire may result in increasing numbers of lead poisoning cases from this exposure. The use of oral chelation for toxicity resulting from this mode of exposure has not been previously discussed. Cases of lead poisoning arising from bullet lead in the synovial cavity of the hip, synovial cavity of the chest, and pleural space are reported. A combination of surgical debridement and chelation therapy with oral succimer produced a satisfactory outcome in all three cases. Oral succimer may be a safe and effective chelation agent for treating lead toxicity in adults with high lead levels secondary to gun shot wounds.

Mechanisms of allergy and chemical sensitivity

Allergy and chemical sensitivity are closely related disorders in which environmental exposures produce inflammatory reactions. For allergy, environmental proteins bind to IgE antibody on mast cells leading to the release of inflammatory mediators. In chemical sensitivity, low molecular weight chemicals bind to chemoreceptors on sensory nerve C-fibers leading to the release of inflammatory mediators. Clinical manifestations are similar in the two conditions. The overlap between the two conditions has a basis in mechanism, so the similarity of clinical manifestations and high percentage of individuals with both conditions may have a biological basis. Chronic exposures can lead to adaptation phenomena. Depression has been associated with both allergy and chemical sensitivity. Both the allergic and chemical irritant responses may be subjected to conditioning so that the response is triggered by other stimuli. Evidence for conditioning is strongest for allergy. Both allergy and chemical sensitivity can be acquired in association with irritant exposures.