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PubMed2004

Arthropods in dermatology.

Arthropods are important in medicine for a multitude of reasons. Their bites and stings may induce allergic reactions, ranging from annoying to life-threatening. Many arthropod products are also capable of inciting allergic responses in sensitized persons. In recent years, bites and stings have gained greater attention owing to increased concern about disease transmission. A common hypersensitivity response to arthropod bites, stings, and products is papular urticaria. This eruption occurs primarily in children, who eventually "outgrow" this disease, probably through desensitization after multiple arthropod exposures. Papular urticaria is most often caused by fleas or bedbugs, but virtually any arthropod is capable of inducing such a reaction. Two arthropod classes of medical importance are the Arachnida (spiders, scorpions, ticks, and mites) and the Insecta (lice, fleas, bedbugs, flies, bees, and ants). Animals in these two classes are probably responsible for more morbidity and mortality worldwide than are any other group of venomous creatures. In general, the diagnosis of arthropod bites and stings is dependent on maintenance of a high index of suspicion and familiarity with the arthropod fauna not only in one's region of practice, but also in the travel regions of one's patients. Learning objective At the completion of this learning activity, participants should be familiar with the clinical manifestations caused by a variety of arthropods as well as the treatment and possible sequelae of arthropod attacks.

Animals↗
PubMed2005

Atrazine effects on meiobenthic assemblages of a modular estuarine mesocosm.

Atrazine is a widely used herbicide in the US found at levels ranging from <10 ng/L to 62.5 microg/L in estuaries throughout the southeast. Effects of atrazine on estuarine meiobenthic assemblages chronically exposed to environmentally relevant concentrations are unknown. The purpose of our research was to assess effects of atrazine on meiobenthos at concentrations near the proposed USEPA SWQC (26 microg/L) using modular estuarine salt marsh mesocosms as a field surrogate. Indigenous copepod and nematode densities were assessed after 28 days of exposure in transplanted colonization chambers. Cluster analysis showed a group characterized by low copepod densities, mostly atrazine exposed chambers, and a group containing all but one control chamber. The later group included chambers with high densities of the copepods Paronychocamptus wilsoni and Enhydrosoma baruchi. Compared to controls, copepod densities was approximately 70% lower in atrazine chambers, with three of the most common copepod species (E. baruchi, Onychocamptus sp. and P. wilsoni) showing an average of 50-70% reduction in population densities (p<0.05). Although nematode density did not differ between atrazine and control chambers, the nematode-to-copepod ratio was significantly higher in atrazine (9.95+/-7.61; p=0.011) than in control chambers (0.61+/-0.35). Our findings suggest that chronic exposures over multiple generations to atrazine at concentrations near the proposed USEPA SWQC could have significant effects on the abundance and composition of estuarine meiobenthic copepod assemblages.

Analysis of Variance↗
PubMed2004

Is Gulf War Syndrome an autoimmune disorder of endogenous neuropeptides, exogenous sandfly maxadilan and molecular mimicry?

Gulf War Syndrome (GWS) remains a contentious diagnosis with conflicting laboratory investigation and lack of a biologically plausible aetiology. This paper discusses the potential role of maxadilan, a potent sandfly vasoactive peptide, in causing autoimmune responses in susceptible individuals through possible molecular mimicry with pituitary adenylate cyclase activating polypeptide (PACAP) and the PAC1R receptor. Gulf War Syndrome may share some causative pathology with Chronic Fatigue Syndrome (CFS), a disorder characterised by prolonged fatigue and debility mostly associated with post-infection sequelae although ongoing infection is unproven. Immunological aberration associated with an expanding group of vasoactive neuropeptides in the context of molecular mimicry and inappropriate immunological memory has been recently raised as possible cause of CFS. Vasoactive neuropeptides act as hormones, neurotransmitters, immune modulators and neurotrophes. They are readily catalysed to small peptide fragments. They and their binding sites are immunogenic and are known to be associated with a range of autoimmune conditions. Maxadilan, while not sharing substantial sequence homology with PACAP is a known agonist of the PACAP specific receptor (PAC1R) and therefore emulates these functions. Moreover a specific amino acid sequence peptide deletion within maxadilan converts it to a PACAP receptor antagonist raising the possibility of this substance provoking a CFS like response in humans exposed to it. This paper describes a biologically plausible mechanism for the development of a GWS-like chronic fatigue state based on loss of immunological tolerance to the vasoactive neuropeptide PACAP or its receptor following bites of the sandfly Phlebotomus papatasi and injection of the vasodilator peptide maxadilan. Exacerbation of this autoimmune response as a consequence of recent or simultaneous multiple vaccination exposures deserves further investigation. While the possible association between the relatively recently discovered vasoactive neuropeptides and chronic fatigue conditions has only recently been reported in the literature, this paper explores links for further research into GWS and CFS.

Autoimmune Diseases↗
PubMed2005

The effect of lifetime victimization on the mental health of children and adolescents.

This paper examines the cumulative prevalence of victimization and its impact on mental health in a nationally representative sample of 2030 children aged 2-17 in the USA. Telephone interviews conducted with both caregivers and youth revealed socio-demographic variations in lifetime exposure to most forms of victimization, with ethnic minorities, those lower in socio-economic status, and those living in single parent and stepfamilies experiencing greater victimization. Sexual assault, child maltreatment, witnessing family violence, and other major violence exposure each made independent contributions to levels of both depression and anger/aggression. Other non-victimization adversities also showed substantial independent effects, while in most cases, each victimization domain remained a significant predictor of mental health. Results suggest that cumulative exposure to multiple forms of victimization over a child's life-course represents a substantial source of mental health risk.

Adolescent↗
PubMed2004

Changes in ovarian, follicular, and oocyte morphology immediately after the onset of puberty are not accompanied by an increase in oocyte developmental competence in the pig.

This study was conducted to determine whether ovarian morphology and developmental competence of in vitro-matured (IVM) oocytes is immediately affected by the onset of puberty in the pig. Ovaries of peri-pubertal pigs were sorted into two groups according to the presence or absence of corpora lutea presence (CL and NCL, respectively. Ovary dimensions, follicle diameter and number, and oocyte diameter (with and without zona pellucidae) were determined. The developmental competence of in vitro-matured oocytes from these two groups was evaluated following parthenogenetic activation and culture in vitro. CL ovaries were significantly (P<0.01) larger than NCL ovaries (width: 22.3+/-0.9 mm versus 15.9+/-0.4 mm, length: 33.2+/-1 mm versus 24.1+/-0.4 mm). Although CL ovaries had fewer antral follicles in total compared with NCL ovaries (21.1+/-1.8 mm versus 46.8+/-2.2 mm), they had a similar number of follicles 3-8mm in diameter. The mean diameter of follicles that were aspirated was greater for CL ovaries than for NCL ovaries (4.5+/-0.1 mm versus 3.3+/-0.02 mm). Oocytes from CL ovaries were greater in diameter compared with those from NCL ovaries (zona retained: 159+/-1.3 microm versus 146.1+/-1.5 microm, zona free: 124.7+/-1.8 microm versus 113.1+/-1.6 microm). No differences were found between oocytes from CL and NCL ovaries for rates of meiotic maturation (91.6+/-3.2% versus 92.4+/-3.2%), cleavage (88.4+/-11% versus 90.7+/-2.6%) and blastocyst formation (21.0+/-3.7% versus 23.7+/-5.7%). Therefore, the onset of puberty coincides with immediate changes in ovarian morphology, increased ovary size, follicle and oocyte diameter, but not with improved oocyte developmental competence. This suggests that the higher developmental competence usually observed in adult oocytes is acquired gradually and requires exposure to multiple estrus cycles.

Animals↗
PubMed2004

Pesticide mixtures potentiate the toxicity in murine thymocytes.

The immunotoxic risks of multiple pesticide exposure were evaluated. C57BL/6 mouse thymocytes were exposed to lindane, malathion, and permethrin, either separately or in mixtures of two pesticides, in vitro. These pesticide exposures caused both apoptotic and necrotic cell death in thymocytes as evaluated by flow cytometric analysis in combination with 7-aminoactinomycin-D (7-AAD), Annexin-V/propidium iodide (PI) staining assays and lactate dehydrogenase release assays. When cells exposed to mixtures of two pesticides, a significantly greater than additive interaction was observed in both apoptotic and necrotic populations of cells. The gel electrophoresis of DNA of cells showed DNA ladder formation with limited genomic DNA and increased laddering in mixture exposures. Based on these findings, it is suggested that these pesticides are potent immunotoxicants, in vitro, and that the mechanism of cytotoxicity observed upon exposure to these pesticides may, at least in part, be due to induction of apoptosis. We also provided evidence that induction of drug metabolizing mixed function oxidase system with lindane may, in part, be responsible for the potentiation of cytotoxicity in the combined exposures. As more information is obtained on the potential immunotoxic effects of pesticides, further insights will be gained for the risk assessment of these environmental pollutants.

Animals↗
PubMed1990

Cigarettes, alcohol and marijuana are related to pyospermia in infertile men.

The relationship of current use of cigarettes, marijuana and alcohol to the parameters of seminal fluid analysis, sperm penetration assay and sperm autoimmunity was studied in 164 men from infertile couples. Current cigarette smokers, marijuana users and heavy alcohol users showed greater numbers of leukocytes in the seminal fluid than did nonusers (p less than 0.02, less than 0.007 and less than 0.01, respectively). In addition, cigarette smokers had lower sperm penetration assay scores than nonsmokers (median 2.5 versus 8.0, p = 0.05). Users of cigarettes, marijuana or alcohol showed no decrease in sperm count, motility or percentage of oval sperm, and no difference in prevalence of antisperm antibodies compared to nonusers. After controlling for past sexually transmitted diseases and multiple substance exposures in a multivariate model, use of cigarettes (p = 0.006), marijuana (p = 0.12) or alcohol (p = 0.098) continued to be associated with a trend toward increased number of seminal fluid leukocytes. Cigarette smoking continued to show a significant decrease in sperm penetration assay score (p = 0.03).

Adult↗
PubMed2001

Heroin-induced changes of catecholamine-containing particles in male rat cerebellar cortex.

The content and distribution of catecholamine-containing formations in the cerebellum of untreated and heroin-treated male rats, was visualized by glyoxylic acid-induced histofluorescence, in an attempt to define the adaptive mechanisms leading to heroin dependent tolerance as well as identify a biological role for these formations. Repeated heroin administration increased the number of specifically organized intracellular catecholamine containing particles, including grain (diameter less than 0.8 microm) and aggregate (diameter greater than 1 microm) forms, in all cerebellar cortical layers examined one hour after the last injection of the drug, relative to controls. The number of grains in all cerebellar cortical layers examined and aggregates in the granular layer, returned to normal or near normal baseline levels within twenty four hours after the last injection of the drug. The analogous baseline of the aggregates in the Purkinje cell layer primarily and the Molecular layer secondarily remained significantly elevated by 86% and 50% respectively, relative to controls. Catecholamine-heroin interactions most likely mediated this elevation that was related directly to the heroin-dependent state of tolerance. These findings indicate that heroin administration to heroin-tolerant rats leads to the formation of unusually large intracellular aggregates with catecholamines in the Purkinje cells of the cerebellum primarily and support a direct role for these formations in the modulation of biogenic amine bioavailability. We conclude that adaptation to drug exposure involves multiple homeostatic interactions, with sympathetic activation at the level of catecholamine reorganization and redistribution playing a major role in rat cerebellar cortex.

Animals↗
PubMed2003

The safety of aerosolized diethylenetriamine nitric oxide adduct after single-dose administration to anesthetized piglets and multiple-dose administration to conscious rats.

Diethylenetriamine nitric oxide adduct (DETA/NO) is a slow-release NO donor. It has been shown to be a selective pulmonary vasodilator in acute pulmonary hypertension. However, its potential toxicity after inhalation is unknown. This study investigated the potential toxicity of aerosolized DETA/NO after single- and multiple-dose exposure in animals. In the first part of the study, a single dose of DETA/NO (60 micromol) or placebo was aerosolized into the lungs of anesthetized piglets. Arterial methemoglobin and serum nitrite (NO2-) concentrations were measured after exposure. In the second part of the study, rats were exposed to aerosolized DETA/NO (60 micromol) or placebo for 7 days, and animals were euthanized 1, 3, 7, and 14 days after the first exposure. Serum NO2- and plasma surfactant protein B (SP-B) concentrations were measured. In both studies, acute lung inflammation was evaluated histopathologically (polymorphonuclear leucocytes (PMN) infiltration) and by measuring lung wet to dry weight ratio (LWDR). The tracheas of rats, which had the highest exposure, were further examined for ultrastructural changes using electron microscopy. In both rats and pigs, serum NO2- concentrations were elevated in all the DETA/NO-treated animals, indicating significant exposure to DETA/NO. Arterial methemoglobin was not increased by DETA/NO treatment. In the rats, plasma SP-B was not elevated by DETA/NO treatment. In addition, DETA/NO had no effects on PMN infiltration or LWDR in either animal model nor on the ultrastructure of large airways in rats. This study shows no evidence of pulmonary or hematological toxicity following single or repeated doses of DETA/NO in animals.

Administration, Inhalation↗
PubMed1997

The safety of asthma and allergy medications during pregnancy.

BACKGROUND: Although no asthma or allergy medications can be considered proven safe for use during pregnancy, these medications are often used to prevent the potential direct and indirect consequences of uncontrolled asthma or allergy. OBJECTIVE: The safety of asthma medications, antihistamines, and decongestants was assessed in a prospectively monitored cohort of 824 pregnant women with and 678 pregnant women without asthma. METHODS: Medications used since conception were recorded on each subject's initial visit (< 28 weeks' gestation). Thereafter, diary cards for medications were completed by the patient through the time of delivery. Perinatal outcomes were compared in exposed versus unexposed individuals. A multivariate analysis accounted for the potential effects of age, parity, smoking, race, weight gain during pregnancy, maternal pulmonary function, acute asthmatic episodes, and multiple medication exposure. RESULTS: No significant relationships were identified between major congenital malformations and first trimester or any exposure to beta-agonists, theophylline, cromolyn, corticosteroids, antihistamines, or decongestants. In the multivariate analyses, oral corticosteroids were independently associated with preeclampsia (odds ratio = 2.0, p = 0.027), but no other independent associations were observed between asthma or allergy medications and adverse perinatal outcomes. CONCLUSION: Use of most common asthma and allergy medications during pregnancy was not associated with increased perinatal risks. Maternal use of oral corticosteroids was independently associated with the occurrence of preeclampsia in this study, although the mechanism of this association is not clear. However, because prior observations suggest that severe asthma may be associated with maternal and/or fetal mortality, risk-benefit considerations still favor the use of oral corticosteroids when indicated for the treatment of asthma during pregnancy.

Administration, Inhalation↗
PubMed2002

Risk factors for suicide in China: a national case-control psychological autopsy study.

BACKGROUND: Suicide is the fifth most important cause of death in China, but the reasons for the high rate and unique pattern of characteristics of those who kill themselves are unknown. METHODS: We pretested, and then administered a comprehensive interview to family members and close associates of 519 people who committed suicide and of 536 people who died from other injuries (controls) randomly selected from 23 geographically representative sites in China. FINDINGS: After adjustment for sex, age, location of residence, and research site, eight significant predictors of suicide remained in the final unconditional logistic regression model. In order of importance they were: high depression symptom score, previous suicide attempt, acute stress at time of death, low quality of life, high chronic stress, severe interpersonal conflict in the 2 days before death, a blood relative with previous suicidal behaviour, and a friend or associate with previous suicidal behaviour. Suicide risk increased substantially with exposure to multiple risk factors: none of the 265 deceased people who were exposed to one or fewer of the eight risk factors died by suicide, but 30% (90/299) with two or three risk factors, 85% (320/377) with four or five risk factors, and 96% (109/114) with six or more risk factors died by suicide. INTERPRETATION: Despite substantial differences between characteristics of people who commit suicide in China and the west, risk factors for suicide do not differ greatly. Suicide prevention programmes that concentrate on a single risk factor are unlikely to reduce suicide rates substantially; preventive efforts should focus on individuals exposed to multiple risk factors.

Adolescent↗
PubMed2004

Zinc for severe pneumonia in very young children: double-blind placebo-controlled trial.

BACKGROUND: Pneumonia is a leading cause of morbidity and mortality in young children. Early reversal of severity signs--chest indrawing, hypoxia, and tachypnoea--improves outcome. We postulated that zinc, an acute phase reactant, would shorten duration of severe pneumonia and time in hospital. METHODS: In a double-blind placebo-controlled clinical trial in Matlab Hospital, Bangladesh, 270 children aged 2-23 months were randomised to receive elemental zinc (20 mg per day) or placebo, plus the hospital's standard antimicrobial management, until discharge. The outcomes were time to cessation of severe pneumonia (no chest indrawing, respiratory rate 50 per min or less, oxygen saturation at least 95% on room air) and discharge from hospital. Discharge was allowed when respiratory rate was 40 per minute or less for 24 consecutive hours while patients were maintained only on oral antibiotics. FINDINGS: The group receiving zinc had reduced duration of severe pneumonia (relative hazard [RH]=0.70, 95% CI 0.51-0.98), including duration of chest indrawing (0.80, 0.61-1.05), respiratory rate more than 50 per min (0.74, 0.57-0.98), and hypoxia (0.79, 0.61-1.04), and overall hospital duration (0.75, 0.57-0.99). The mean reduction is equivalent to 1 hospital day for both severe pneumonia and time in hospital. All effects were greater when children with wheezing were omitted from the analysis. INTERPRETATION: Adjuvant treatment with 20 mg zinc per day accelerates recovery from severe pneumonia in children, and could help reduce antimicrobial resistance by decreasing multiple antibiotic exposures, and lessen complications and deaths where second line drugs are unavailable.

Anti-Bacterial Agents↗
PubMed1997

Gulf War syndrome: is it due to a systemic shift in cytokine balance towards a Th2 profile?

The symptoms of Gulf War syndrome are compatible with the hypothesis that the immune system of affected individuals is biased towards a Th2-cytokine pattern. Factors that could lead to a Th2 shift among Gulf War veterans include exposure to multiple Th2-inducing vaccinations under stressful circumstances and the way in which such vaccinations were administered, which would be expected to maximise Th2 immunogenicity. These factors may have led to a long-term systemic shift towards a Th2-cytokine balance and to mood changes related to the immunoendocrine state. Other vaccines that lead to similar long-term, non-specific shifts in cytokine balance are well-established. If our hypothesis is proven, treatment may be possible with regimens that induce a systemic Th1 bias.

Affect↗
PubMed2000

Antibiotics and Clostridium difficile diarrhea in the ambulatory care setting.

OBJECTIVE: The goal of this study was to determine the prevalence of Clostridium difficile diarrhea (CDD) and the risk for CDD associated with different oral antibiotics commonly used in the ambulatory care setting. METHODS: The prevalence of CDD was determined for enrollees in 4 UnitedHealth Group-affiliated health plans between January 1, 1992, and December 31, 1994. Cases were identified based on the presence of an inpatient or outpatient claim with a primary diagnosis of diarrhea, a pharmacy claim for a prescription drug used to treat CDD, or a physician or facility claim for the C. difficile toxin test, and were confirmed using full-text medical records. Within a retrospective cohort design, periods of risk for CDD were defined on the basis of duration of antibiotic therapy. To control for potential selection bias created by heterogeneous rates of C. difficile testing and to limit confounding due to multiple antibiotic exposures, we used a nested case-control design, restricting eligibility to subjects who underwent screening for C. difficile and who had been exposed to only 1 antibiotic risk period with a single antibiotic. RESULTS: The global prevalence of CDD in 358,389 ambulatory care enrollees was 12 per 100,000 person-years. In the nested case-control study, after controlling for other risk factors, 2 antibiotics demonstrated an increased association with CDD: cephalexin (odds ratio [OR] = 7.5, 95% CI = 1.8 to 34.7) and cefixime (OR = 6.4, 95% CI = 1.2 to 39.0). CONCLUSIONS: Although CDD is thought to occur primarily in hospitalized patients, it was found to be present in an ambulatory care population, but at a low frequency. In this population, it appeared to be associated with 2 cephalosporins but not with other types of antibiotics usually linked with nosocomial CDD. Because the frequency of C. difficile testing was shown to be more common with high-risk antibiotics, CDD may be underdiagnosed in the ambulatory care setting.

Adolescent↗
PubMed2001

Delayed effects of embryonic exposure of zebrafish (Danio rerio) to methylmercury (MeHg).

Since previous short-term bioassays of methylmercury (MeHg) indicated no morphological effects in zebrafish (Danio rerio) after embryonic exposures below 20 microg/l MeHg, studies were done to determine whether embryonic exposure to MeHg at lower concentrations would induce behavioral effects. Newly fertilized embryos were exposed to 0, 5, 10 or 15 microg MeHg/l for selected exposure durations: single day, multiple day or continuous exposure from fertilization through hatching. Larvae were maintained in an essential salt solution after hatching. Spontaneous swimming performance and prey capture experiments were conducted. Continuous embryonic exposure to 15 microg/l caused delayed mortality syndrome (DMS). These larvae hatched normally and appeared normal, but beginning at Day 3 post-hatch (ph), general activity was severely reduced and by Day 5 ph, larvae were completely moribund; many had faint heartbeats, severely enlarged body cavities and upward flexures of the spinal cord. Most of these larvae were dead by Day 6 ph. Multi- and single-day embryonic exposures to 15 microg/l caused reduced swimming activity and prey capture ability, and by Day 4 ph, these larvae also began to show signs of DMS. Continuous embryonic exposure to 10 microg/l significantly reduced spontaneous swimming activity, which did not improve after 5 days in clean water. Similar results were seen in larvae exposed during the last 24 h of embryonic development. Prey capture ability was also impaired in larvae exposed continuously to 10 microg/l, even after 4 days in clean water. Single-day exposures to 10 microg/l did not affect prey capture ability. Larvae from the 5-microg/l exposures were not significantly different from controls for either parameter. This study reinforces the idea that functional impairment is a more subtle response to developmental toxicants than mortality or the production of morphological defects.

Animals↗
PubMed1996

Clinical and histopathologic features of hair loss in patients with HIV-1 infection.

BACKGROUND: Hair loss is common in patients with HIV-1 infection, and in black patients this loss may be associated with straightening. Possible causes are frequently present in patients with HIV-1. These causes include chronic HIV-1 infection itself and recurrent secondary infections, nutritional deficiencies, immunologic and endocrine dysregulation, and exposure to multiple drugs. However, histopathologic features have rarely been reported in these patients. OBJECTIVE: The objective was to evaluate the changes in the hairs of a group of these patients and to identify the light microscopic and ultrastructural changes in the hairs and the histologic changes in the scalp. METHODS: Hair plucks and pulls with scanning electron microscopy of the hairs were done on 10 patients with late-stage HIV-1 infection. In addition, scalp biopsy specimens were examined in both vertical and transverse sections. RESULTS: All patients had telogen effluvium. Numerous apoptotic or necrotic keratinocytes were seen in the upper external root sheath follicular epithelium in addition to a mild to moderate perifollicular mononuclear cell infiltrate often containing eosinophils. Variable dystrophy of the hair shafts was also a consistent feature. CONCLUSION: Although telogen effluvium is a common response to a wide spectrum of biologic stresses, the presence of apoptotic or necrotic keratinocytes within the upper end of the external root sheath epithelium and dystrophy of hairs may be markers of hair loss in patients with HIV-1 infection.

Acquired Immunodeficiency Syndrome↗
PubMedDate not supplied

Application of physiologically based pharmacokinetic modelling to combination toxicology.

Non-additive toxicity has been demonstrated in laboratory animals for a large number of temporally separated or concurrent multiple chemical exposures. These exposures are typically at concentrations higher than those found in the environment, leading to the question of the applicability of the results to the human situation. Physiologically based pharmacokinetic (PBPK) modelling has been applied successfully to single chemicals; its utility for extrapolation across species and dose has been demonstrated. Use of PBPK modelling in the study of chemical mixtures is increasing although still limited. The use of PBPK modelling by various investigators in the field of combination toxicology is reviewed. PBPK modelling has been used to examine: the role of increased metabolism in non-additive toxicity resulting from temporally separated exposures; the influence of the time interval separating two chemical exposures; and the role of inhibition of metabolism in concurrent exposure to two chemicals. In summary, development of a PBPK or PBPK/pharmacodynamic model for a combined exposure provides a basis for extrapolation across species, route and dose, and a useful tool for risk assessment.

Animals↗