Hepatocellular Jaundice due to Hydroxycut in Monozygotic Twins.

Liver injury associated with the use of a number of different of herbal and dietary supplements are increasingly recognized. It is though often unclear which of the sometimes multiple ingredients are responsible for the liver injury. Several case reports have been published on suspected liver injury due to Hydroxycut, which is a multi-ingredient supplement often used to induce weight loss. However, the hepatotoxic potential of Hydroxycut has though been disputed, and steatotic liver disease has also been implicated in patients who are found to have elevated liver enzymes while on Hydroxycut. We report clinically apparent liver injury with jaundice associated with the use of Hydroxycut in monozygotic twins with remarkably similar type of liver injury. Both had the genotype HLA-B 35:01 allele, a risk factor for green-tea extract induced liver injury, which is included in Hydroxycut.

Fatal infection in two Icelandic stallions caused by Halicephalobus gingivalis (Nematoda: Rhabditida).

Opportunistic infections with the free living nematode Halicephalobus gingivalis are infrequently reported in horses but the cases are widespread geographically. The nematodes are believed to penetrate wounds and subsequently reproduce within the host tissues. This paper reports two cases of a fatal disease in stallions of the Icelandic breed in Iceland. Case 1: a stallion, which sustained injuries to the mouth after an accident, developed severe neurological signs and had to be euthanatized. Histological examination revealed mild inflammation and malacia in the cerebellum associated with the presence of numerous H. gingivalis nematodes. Case 2: a stallion that started swerving to one side and lost balance was euthanatized due to lack of response to therapy and rapid deterioration. Histological examination revealed numerous H. gingivalis nematodes in the cerebellum, brain stem, cervical spinal cord and in the meninges, with minimal reactive changes. In case 1 the infection presumably was acquired by nematodes from soil penetrating through wounds in the mouth. The mode of the H. gingivalis infection in case 2 is uncertain. These are the first cases of H. gingivalis infection reported from Iceland and the second report from the Nordic countries.

[House dust mites at Icelandic farms]. / Maurar í húsryki á íslenskum bóndabaejum.

BACKGROUND: Sensitization to Dermatophagoides pteronyssinus (D. pteronyssinus) occurs in 9% of the Reykjavik population, despite the fact that no Der p 1 antigen has been found in the area. A recent study revealed that sensitized persons more often had a childhood history of work or holiday stay in rural areas than controls. As a follow up we studied the risk of exposure to mites in farmland dwellings. METHODS: In a survey of work-related lung disorders among farmers in the south and west of Iceland, 80 samples of house dust, representing 42 farms, were collected from bedroom mattresses and the floors in living rooms and examined for mites. Treatment of samples was identical with the method used earlier in the Reykjavik investigation (ECRHS II). RESULTS: In contrast to the Reykjavik results, dust from farm dwellings showed a large diversity of mites. Seventeen taxons were found, with Acarus siro and D. pteronyssinus in 13 and 8 farms respectively, but the samples did not show signs that any of the taxons actually had lived or reproduced where they were collected. CONCLUSION: The finding of D. pteronyssinus in farmland dwellings provides a possible explanation of why some Reykjavik citizens might have developed sensitization to this mite, even though cross sensitization to other species of mites could give a false positive reaction to D. pteronyssinus in at least some of those cases. Our observations did not support the idea that the mites were living in the dwellings and an explanation for their occurrence must be sought in the outdoor environment.

Respiratory disorders are not more common in farmers. Results from a study on Icelandic animal farmers.

RATIONALE: The current prevalence of respiratory disorders and symptoms in Icelandic farmers is unknown, but a high prevalence of respiratory symptoms has been reported in the past. Modern farming practices have been implemented in Iceland in the past decade and the processing of hay has changed markedly leading to less organic dust exposure. OBJECTIVE: The aim was to estimate the prevalence of respiratory disorders and symptoms in a nationwide study of Icelandic farmers. METHODS: We conducted a questionnaire-based study of all Icelandic farmers with a comparison group randomly selected from the national citizen registry of Iceland. The questionnaire included items regarding respiratory symptoms and disorders. RESULTS: Out of 2042 farmers invited to participate, 1107 responded (54%), as did 689 of 1500 controls (46%). Farmers were slightly older and more likely to be male (87% vs. 47%). Smoking rates were significantly lower among farmers than among controls. The prevalence of asthma was not significantly different between the two groups, with a lifetime prevalence of 9.4% (n=104) among farmers compared to 10.2% (n=70) among controls. Medication use for asthma was not significantly different. The prevalence of self-reported, physician-diagnosed chronic bronchitis and emphysema likewise did not significantly differ between the groups, but self-reported hay fever was significantly more prevalent among farmers. CONCLUSION: The prevalence of respiratory disorders and symptoms among Icelandic farmers is currently similar to non-farmers. This may suggest that modernization of the agricultural environment has had a positive effect on workers' health.

Glutathione peroxidase (GPX) activity in blood of ewes on farms in different scrapie categories in Iceland.

BACKGROUND: Preliminary studies indicated decreased glutathione peroxidase (GPX) activity in blood of ewes on scrapie-afflicted farms. Other studies have shown decreased GPX activity in brain of prion-infected mice and in prion-infected cells in vitro. The aim of this study was to examine the GPX activity in blood as well as the distribution of GPX-activity levels from ewes on farms in scrapie-afflicted areas in Iceland. METHODS: Blood samples were collected from 635 ewes (non-pregnant [n = 297] and pregnant [n = 338]) on 40 farms in scrapie-afflicted areas during the years 2001-2005, for analysis of GPX activity. The farms were divided into three categories: 1. Scrapie-free farms (n = 14); 2. Scrapie-prone farms (earlier scrapie-afflicted, restocked farms) (n = 12); 3. Scrapie-afflicted farms (n = 14). For comparison, 121 blood samples were also collected from non-pregnant ewes on one farm (farm A) in a scrapie-free area (scrapie never registered). Chi-square test was used to test for normal distribution of GPX-results, and Kruskal-Wallis test to compare GPX-results between categories. RESULTS: The GPX-results appeared to be biphasically distributed in ewes in all three scrapie categories and on farm A. The presumptive breaking point was about 300 units g Hb-1. About 30-50% of the GPX-results from ewes in all three scrapie categories were below 300 units g Hb-1 but only about 13% of the GPX-results from ewes on farm A. The mean GPX activity was highest on farm A, and was significantly lower on scrapie-prone farms than on scrapie-free or scrapie-afflicted farms (non-pregnant and pregnant ewes: P < 0.005, respectively; non-pregnant and pregnant ewes combined: P < 0.0005). CONCLUSIONS: 1) the distribution of GPX-results in blood of Icelandic ewes apparently has a biphasic character; 2) the GPX-results were higher in ewes on one farm in a scrapie-free area than in ewes on farms in the scrapie-afflicted areas; 3) GPX-activity levels were significantly lowest on earlier scrapie-afflicted, restocked farms, which might have a bearing on the recurrence of sporadic scrapie on these farms; 4) further study on the possible role of GPX activity in the occurrence of scrapie in Iceland is warranted.

High incidence of subclinical infection of lymphoid tissues in scrapie-affected sheep flocks.

Prion diseases are characterized by a long incubation period. In scrapie, sheep may incubate and spread the infection for several years before clinical signs evolve. We have previously studied the occurrence of subclinical infection in the brain. Now, we have studied the occurrence of subclinical infection in the brain and several lymphoid tissues in two scrapie-affected Icelandic sheep flocks by immunohistochemistry for PrP(Sc), a molecular marker for infectivity, and correlated this with results of PrP genotyping. At culling, one flock had one confirmed scrapie case, while the other flock had two. Analysis of 106 asymptomatic sheep by immunostaining for PrP(Sc) revealed that the incidence of subclinical infection was 58.3% in one flock and 42.5% in the other. PrP(Sc) was only detected in lymphoid tissues. The youngest positive sheep were 4 months old. PrP genotyping showed that over 90% of the sheep were of a genotype which is moderately sensitive to infection and may delay neuroinvasion. Our results show that asymptomatic sheep may spread the infection during the long incubation period of several years, which constitutes an important obstacle in the eradication of scrapie. Our findings indicate that contamination of the environment plays an important part in sustaining the infection.

Low complement C4B gene copy number predicts short-term mortality after acute myocardial infarction.

BACKGROUND AND OBJECTIVES: Some recent data indicate that risk of death after acute coronary syndrome is under genetic control. Previously, we found that the C4B*Q0 genotype (low copy number of the C4B gene that encodes the fourth component of complement) is strongly associated with morbidity and mortality of cardiovascular diseases (CVD). The +252 G allele of the lymphotoxin-alpha (LTA) gene encoded close to the C4B gene was also reported to be related to CVD-related mortality in an Oriental population. METHODS: The relationship between the copy number of the genes encoding the fourth component of complement (C4A and C4B) and LTA 252 single-nucleotide polymorphism (SNP) on the one hand and mortality after acute myocardial infarction (AMI) was studied in 142 Icelandic patients. The number of the C4A and C4B genes was determined in genomic DNA samples by a newly developed real-time PCR-based method; lymphotoxin-alpha (LTA) +252 A>G polymorphism was determined by PCR-restriction fragment length polymorphism analysis. RESULTS: The C4B*Q0 genotype was found to be strongly associated with 1-year mortality, with a hazard ratio of 3.50 (1.38-8.87) (P = 0.008) (adjusted Cox regression analysis). This association was, however, restricted to ever-smoking patients. By contrast, neither C4A gene copy numbers nor LTA 252 SNP did confer increased risk of mortality after AMI. CONCLUSIONS: This observation indicates that low C4B copy number is a strong risk factor for short-term mortality after AMI in smoking Icelandic patients, whereas LTA 252 G allele is not a risk factor in Caucasian population.

Infectious agent of sheep scrapie may persist in the environment for at least 16 years.

In 1978, a rigorous programme was implemented to stop the spread of, and subsequently eradicate, sheep scrapie in Iceland. Affected flocks were culled, premises were disinfected and, after 2-3 years, restocked with lambs from scrapie-free areas. Between 1978 and 2004, scrapie recurred on 33 farms. Nine of these recurrences occurred 14-21 years after culling, apparently as the result of environmental contamination, but outside entry could not always be absolutely excluded. Of special interest was one farm with a small, completely self-contained flock where scrapie recurred 18 years after culling, 2 years after some lambs had been housed in an old sheep-house that had never been disinfected. Epidemiological investigation established with near certitude that the disease had not been introduced from the outside and it is concluded that the agent may have persisted in the old sheep-house for at least 16 years.

School proximity to concentrated animal feeding operations and prevalence of asthma in students.

STUDY OBJECTIVES: Asthma prevalence and severity are rising in industrialized nations. Studies supporting the hygiene hypothesis suggest that being raised on a farm protects against atopy and, often, asthma. In rural United States, however, an increased rate of asthma has been found among schoolchildren. We hypothesized that the rural US environment may not be protective against airway inflammation, perhaps due to environmental effluents from a relatively high number of concentrated animal feeding operations (CAFOs). We compared the prevalence of asthma in two Iowa elementary schools, one adjacent to a CAFO, and the other distant from any large-scale farming operations. DESIGN: Cross-sectional questionnaire-based study. SETTING: Two rural Iowa elementary schools: the study school is located one-half mile from a CAFO, and the control school is distant from any large-scale agricultural operation. PARTICIPANTS: Children, kindergarten through grade 5, who attended either the study school or the control school. RESULTS: Children in the study school had a significantly increased prevalence of physician-diagnosed asthma (adjusted odds ratio, 5.71; p = 0.004). Although this group was more likely to live on a farm and have parents who smoke, these potentially confounding variables did not account for increased prevalence in a multivariate model. No difference in measures of asthma severity was found between the two populations. Because different sets of physicians are responsible for the medical care of the groups of children, it is possible that physician bias is responsible for the different prevalence of asthma diagnoses. This was not explored in the study. CONCLUSIONS: This study supports a role for exposure to rural environmental toxicants in the etiology of asthma, and suggests a need for further study of this relationship.

Acute toxic pneumonitis complicating chronic obstructive pulmonary disease (COPD) in a farmer.

BACKGROUND: Toxic pneumonitis or Organic Dust Toxic Syndrome (ODTS) is a common, usually self-limiting condition among agricultural workers, occurring after high level exposure to agricultural dust. CASE REPORT: We describe the case of a 68-year-old smoker and farmer who became ill with dyspnea, flu-like symptoms, and hypoxia after cleaning out a grain bin. RESULTS: Chest radiograph was normal. He was treated with steroids, antibiotics, and oxygen supplementation and recovered over 3 months, but continues with lingering exercise intolerance after 2 years. DISCUSSION: Although toxic pneumonitis usually follows a relatively benign course with spontaneous recovery and no permanent sequale it can lead to the exacerbation of underlying lung conditions, resulting in incomplete or delayed recovery. Prevention is aimed at limiting exposure by avoidance, by increasing ventilation in closed spaces and by appropriate use of personal protective equipment.

Experimental human exposure to inhaled grain dust and ammonia: towards a model of concentrated animal feeding operations.

BACKGROUND: Ammonia and endotoxin-rich dust are present in high concentrations in swine confinement facilities; exposure to this environment is linked to workers' respiratory problems. We hypothesized that experimental exposure to ammonia and dust would impair pulmonary function, and that these exposures would be synergistic. METHODS: We exposed six normal subjects and eight subjects with mild asthma to ammonia (16-25 ppm) and/or endotoxin-rich grain dust (4 mg/m3). Pulmonary function and exhaled NOx were measured before and after exposure. RESULTS: There was no significant change in pulmonary function in the normal subjects following any of the exposure conditions. Among asthmatics, a significant transient decrease in FEV1 was induced by grain dust, but was not altered by ammonia; increased bronchial hyperreactivity was also noted in this group. CONCLUSION: In a vulnerable population, exposure to grain dust results in transient airflow obstruction. Short-term exposure to ammonia does not increase this response.

Characterization of a hooded human exposure apparatus for inhalation of gases and aerosols.

A human exposure apparatus was designed to administer a gas and/or aerosol directly to the subject's face. This apparatus utilized a hood associated with a powered air-purifying respirator. The design criteria included the need to maximize subject comfort, maintain consistent atmospheres of a gas or dust within the hood, and the accurate use of direct-reading instruments to monitor exposure levels. An 83-L drum was used to pre-mix the gas or aerosol with the main dilution air prior to entering the hood worn by the subject. A clear plastic oxygen tent, ventilated with room exhaust air, was used to contain contaminants exiting the hood. Bypass valves were added to allow for a startup period during which contaminant concentration levels were allowed to stabilize prior to exposing the human subject. Results from characterization studies demonstrated that the system adequately contained contaminants within the oxygen tent, provided adequate mixing of contaminant and dilution air, produced stable contaminant concentrations over time, and was responsive to sudden changes in contaminant generation rate.

PrP gene polymorphism and natural scrapie in Icelandic sheep.

The association between scrapie and polymorphism of the prion protein (PrP) gene was studied in the Icelandic sheep breed. Polymorphism of the three codons, 136, 154 and 171, that are important for scrapie susceptibility was determined. A BspHI restriction analysis was used to study the alleles of codons 136 and 154, while density gradient gel electrophoresis (DGGE) was used to analyse codon 171 and detect new polymorphisms. The PrP allelic variant, VRQ (amino acids at codons 136, 154 and 171), was found to be highly statistically associated with scrapie, whereas the allelic variant, AHQ, was never found in scrapie-affected animals, a finding that is statistically significant. Iceland has a few scrapie-free regions, which are a part of a quarantine network. Homozygotes for the VRQ variant were found there at a low frequency, indicating that genetic susceptibility is not enough for scrapie to develop and further evidence for the infectious nature of the disease. A comparison of PrP genotypes between sheep outside and within the scrapie-free zones revealed an increase in the AHQ allelic variant in the latter. No polymorphism was found at codon 171 in a total of 932 sheep studied, all individuals having the glutamine allele. Two novel, rare PrP alleles were found using DGGE at codons 138 and 151, i.e. S138N and R151C. Their relevance to scrapie is still unclear, but the former was found in scrapie-affected sheep as well as healthy sheep, whereas the latter was only found in healthy sheep.