Cytomegalovirus infection and development of allergic diseases in early childhood: interaction with EBV infection?

BACKGROUND: Chronic replication of cytomegalovirus and EBV in early life may affect the immune system and play a role in the development of allergy in children. OBJECTIVE: To assess the relation between cytomegalovirus infection and allergic disorders in children, including a possible interaction with EBV infection. METHODS: From a prospective birth cohort study in Stockholm, on factors of importance for development of allergy, 2581 four-year-old children were enrolled. The classification of allergic diseases was based on questionnaire answers and determination of IgE antibodies to common airborne and food allergens. IgG to cytomegalovirus was determined by a commercial ELISA and to EBV by indirect immunofluorescence. RESULTS: A total of 1191 (46%) children were cytomegalovirus-seropositive. There were no significant associations between seropositivity to cytomegalovirus and allergic manifestations, such as bronchial asthma, suspected allergic rhinitis, or atopic dermatitis. Seropositivity to cytomegalovirus alone, ie, without seropositivity to EBV, was related to IgE antibodies to airborne and food allergens (adjusted odds ratio, 1.8; 95% CI, 1.2-2.9). An antagonism between cytomegalovirus and EBV in relation to sensitization to airborne and food allergens was suggested ( P = .05). CONCLUSION: The study does not support the hypothesis that previous cytomegalovirus infection plays an important role in the pathogenesis of bronchial asthma, suspected allergic rhinitis, or atopic dermatitis in children. However, in the absence of EBV infection, cytomegalovirus infection may be related to sensitization to airborne and food allergens.     

Effects of intestinal microflora and the environment on the development of asthma and allergy

The aim of previous research into the causes of allergic diseases, including asthma was mostly to identify potential risk factors in the environment. No major risk factors have been identified, however. Over the past 10 years, focus has, therefore, more been directed towards protective factors that could enhance the development of tolerance to allergens which were previously encountered early in life, but are now lost in modern affluent societies. In particular, the role of childhood infections has been discussed, but so far these studies have not been conclusive. Recent epidemiological studies and experimental research suggest that the microbial environment and exposure to microbial products in infancy modifies immune responses and enhances the development of tolerance to ubiquitous allergens. The intestinal microflora may play a particular role in this respect, as it is the major external driving force in the maturation of the immune system after birth, and animal experiments have shown it to be a prerequisite for normal development of oral tolerance. Recent studies have shown differences in the composition of the microflora between healthy and allergic infants in countries with a high and low prevalence of allergies and between healthy and allergic infants within such countries. These differences are apparent within the first week of life and thus precede clinical symptoms. The use of live microorganisms that might be beneficial to health has a long tradition and the safety is well documented. Very recently, several prospective intervention studies, modifying the gut flora from birth have yielded encouraging results and may suggest a new mode of primary prevention of allergy in the future.     

Dietary intake in the diabetes prevention program cohort: baseline and 1-year post randomization

PURPOSE: To describe usual dietary intake assessment at baseline and 1-year post-randomization in the ethnically diverse Diabetes Prevention Program cohort. METHODS: Participants were randomized to Lifestyle Modification, Metformin, or Placebo. Usual diet was assessed by a modified, previously validated food frequency interview. RESULTS: Complete data were available for 2934 subjects (90.7% of those randomized). Baseline median estimated energy intake was 7676 kJ/d (1828 kcal/d) and 8585 kJ/d (2044 kcal/d) for women and men, respectively. The median percent of energy from fat ranged from 30.6% for Asian American men to 37.5% for American Indian men and women. After 1 year among the Lifestyle group, the median change in total energy and percent energy from fat was -1897 kJ/d (-452 kcal/d) and -6.6%, respectively. For the Metformin and Placebo groups, change in median total energy was -1235 kJ/d (-294 kcal/d) and-1051 kJ/d (-250 kcal/d), respectively, and change in median percent energy from fat was -0.8% and-0.8%, respectively (p < 0.001 for differences between groups, adjusted for gender and ethnicity). CONCLUSIONS: One-year post-randomization, significant differences in dietary intake were observed in the Lifestyle compared with the Metformin or Placebo group, and these were consistent with the general intent of the DPP lifestyle modification intervention.     

Food safety knowledge and practices in ready-to-eat food establishments

Safe food handling in ready-to-eat food establishments is a basic element in the reduction of foodborne illness. The aim of this research was to investigate (using a questionnaire), knowledge and attitudes about food safety held by management and staff in ready-to-eat food establishments. Fieldwork was conducted in 2002 in Wellington City, New Zealand. Managers rated 'staff with good food safety knowledge' the most important aspect of ensuring safe food. Half of these managers were prepared to pay higher wages to staff holding a current food safety certificate. Although respondents considered that closure of the establishment was the most serious business consequence of a breakdown in safe food handling, less than half (49%) were prepared to pay an additional insurance premium to cover this risk. All food handling workers should be encouraged to obtain and maintain a current food safety certificate. Environmental health officers who inspect ready-to-eat food establishments play an important role in guiding and assisting owners and staff in improving food handling standards.     

Meta-analysis of feeding trials investigating cadmium accumulation in the livers and kidneys of sheep

Human cadmium intake derives mainly from food sources, and cadmium can be present in high concentrations in some offal. A meta-analysis using random effects modeling was carried out to integrate the results of 21 controlled randomized trials in which sheep were fed diets with elevated cadmium levels and cadmium concentrations in their livers and kidneys were recorded after slaughter. Resulting predictions of cadmium accumulation in sheep are applicable to a broad set of exposure situations allowing the critical examination of cadmium in the human food chain. The product of the cadmium concentration in the feed and the duration of exposure to that feed were significant predictors of the cadmium concentration in livers and kidneys. The predominantly organic rather than inorganic form of cadmium in the feed further increased accumulation. Other variables (dry matter intake, the vehicle of the elevated cadmium in the diet, animal age, weight, and sex) were not significant. As a result, the prime measure to decrease the risk of cadmium from animal origin adversely affecting human health should be restricting the animals' cumulative cadmium intake. It is suggested that this might be achieved by preventing the livers and kidneys of older animals from entering the human food chain.     

Effects on cocaine and food self-administration of (+)-HA-966, a partial agonist at the glycine/NMDA modulatory site, in rats

Rationale (+)-HA-966, a partial agonist at the glycine/NMDA modulatory site, significantly reduced IV cocaine self-administration in a fixed-ratio (FR) schedule. Since this effect was observed studying only one dose of cocaine and considering the characteristic bell-shaped curve generated by cocaine in self-administration studies under FR schedules, the precise nature of the effect is not clear.Objective To identify the nature of the effect of (+)-HA-966 on cocaine self-administration under fixed ratio (FR) and progressive ratio (PR) schedules of reinforcement.Methods Rats were prepared with IV catheters and trained to self-administer cocaine. In the first experiment three doses of (+)-HA-966 (10, 30 and 100 µg/5 µl ICV) were evaluated for their effects on 0.25 mg/0.1 ml per infusion cocaine self-administration on FR1 with 20-s time-out (TO). Next, 30 µg/5 µl ICV (+)-HA-966 was evaluated as pretreatment on a complete dose-response for cocaine self-administration. In a third experiment the effect of the same dose was evaluated on cocaine or food self-administered on the PR schedule.Results (+)-HA-966 at doses of 10 or 30 µg reduced cocaine self-administration in an FR1 schedule during the first hour interval of the 2-h session. This partial agonist at the glycine/NMDA modulatory site also reduced the number of injections of cocaine earned during the first hour of the session but not the final ratio reached under a PR schedule. However, under this schedule (+)-HA-966 also reduced operant responding for food reinforcement.Conclusions (+)-HA-966 reduced responding maintained by cocaine or food. Whether (+)-HA-966 induces a general motivational rather than a performance deficit, leading to reduced responding for either cocaine and food, is unclear.     

Combined in vivo and in vitro approach for the characterization of penicillin-specific polyclonal lymphocyte reactivity: tolerance tests with safe penicillins instead of challenge with culprit drugs

BACKGROUND: Amino-penicillins are a major cause of delayed-type reactions to penicillins. OBJECTIVES: The aim of this study was to establish a diagnostic approach for the characterization of the individual penicillin-specific polyclonal lymphocyte reactivity in order to detect side chain-specific sensitization to amino-penicillins. Patients can then be advised to undergo a tolerance test with safe penicillins instead of provocation with culprit penicillins for confirmation of penicillin allergy. METHODS: We investigated penicillin-specific polyclonal lymphocyte reactivity in nine patients with delayed-type reactions to amino-penicillins by a combined in vivo (patch, prick and intracutaneous tests with delayed readings) and in vitro (lymphocyte transformation test, LTT) approach. RESULTS: A combination of LTT and skin tests improved the sensitivity for the characterization of penicillin-specific polyclonal lymphocyte reactivity and allowed the detection of three different patterns of lymphocyte reactivity. Four patients showed a side chain-specific sensitization to amino-penicillins in vivo and in vitro and were advised to undergo tolerance tests with safe penicillins. Two patients agreed and were exposed to parenteral benzyl-penicillin and oral phenoxymethyl-penicillin which they tolerated without complications. CONCLUSIONS: These data suggest that a combined in vivo and in vitro approach is helpful for the detection of side chain-specific sensitization to amino-penicillins. Patients with such sensitization are very likely to tolerate safe penicillins, thereby expanding their therapeutic options when antibiotic treatment is required.     

Patch test results with the metalworking fluid series of the German Contact Dermatitis Research Group (DKG)

Based on the information of the interdisciplinary task force on allergy diagnostics in the metal branch, in 2001, the German Contact Dermatitis Research Group (DKG) compiled two metalworking fluid (MWF) test series with currently and previously used components, respectively. After 2 years of patch testing, we present results obtained with these series, based on data of the Information Network of Departments of Dermatology (IVDK). 251 metalworkers who were patch tested because of suspected MWF dermatitis in 2002 and 2003 were included in this retrospective data analysis. Of these, 206 were tested with the current MWF series and 155 with the historical MWF series. Among the current MWF allergens, monoethanolamine ranked 1st with 11.6% positive reactions. Diethanolamine (3.0%), triethanolamine (1.1%), and diglycolamine (1.9%) elicited positive reactions far less frequently. Allergic reactions to p-aminoazobenzene were frequently observed (6.0%), but the relevance of these reactions is still obscure. Positive reactions to biocides ranged from 4.5% for Bioban CS 1135 to 0.5% for iodopropynyl butylcarbamate and 2-phenoxyethanol. Concomitant reactions to formaldehyde, which caused positive reactions in 3.3%, and formaldehyde releasers occurred to varying extents without conclusive pattern. No positive reactions were seen to dibutyl phthalate, di-2-ethylhexyl phthalate, tricresyl phosphate, isopropyl myristate or benzotriazole. With the historical MWF test series, positive reactions to methyldibromo glutaronitrile (MDBGN) were observed most frequently. However, sensitization via allergen sources other than MWF seems likely, as MDBGN, during the study period, has been one of the most frequent preservative allergens in cosmetics and body care products. Other historical MWF allergens comprised morpholinyl mercaptobenzothiazole (3.3%), benzisothiazolinone (BIT; 2.0%) and Bioban P 1487(1.3%). BIT is currently used in MWF again, so it was shifted to the current MWF test series. As decreasing reaction frequencies to former MWF allergens that are no longer used can be expected, the historical series should be re-evaluated after some years. The test series with current MWF allergens has to be kept up-to-date based on information from industry and to be kept concise by eliminating test substances which never cause positive reactions.     

Contact dermatitis to cosmetics, fragrances, and botanicals

Cosmetics, fragrances, and botanicals are important causes of allergic contact dermatitis. Identifying and avoiding the causative allergens can pose a challenge to both the patient and the dermatologist. The site of involvement can give the investigator clues to the cause of the eruption in many cases. Fragrances and preservatives are the two most clinically relevant allergens in cosmetics. Botanicals are being added to cosmetics because of consumer demand and are now being recognized as sources of allergy as well. Patch testing allows for the detection of allergens that are potentially relevant in the genesis of the patient's eczema. Common skin-care product allergens, including fragrances and botanicals as well as those found in sunscreen, nail, and hair-care products, are reviewed. Practical methods of allergen avoidance are also discussed.     

Food deprivation after treatment blocks the multiple-day hyperphagic response to SHU9119 administration

The multiple-day hyperphagic effect of the melanocortin 3/4 receptor antagonist, SHU9119, is apparently abolished when rats are food-deprived for 24 h after central (4th-ventricular) injection. Here, we affirmed this indication, and addressed the possibility that the orexigenic potency of SHU9119 is simply masked by the refeeding hyperphagia that follows food deprivation. This explanation is discounted by our finding that the drug response in ad libitum-fed rats and the deprivation response are expressed at different, and non-overlapping, times of day. We then asked whether food consumption during a hypothesized critical period in the hours after treatment is necessary for expression of the hyperphagic response to SHU9119, or alternatively, whether blood-borne signals that emerge only after an extended period of food restriction underlie the drug-state interaction. Evidence favoring the latter interpretation was derived from a series of four experiments over which the timing and duration of food access after drug administration was varied. The results indicate an interaction between melanocortin receptor activity and the metabolic state of the animal, and constrain our thinking about the peripheral signals and central mechanisms that underlie this interaction.