[A prospective study on acute poisonings presenting to the Emergency Department at Landspitali University Hospital in Iceland 2012].

INTRODUCTION: The purpose of the study was to assess the incidence and type of toxic exposures presenting to the Emergency Department (ED) at Landspitali University Hospital in Iceland over one year and compare the results to another study performed eleven years before. METHODS: The study was prospective and included all visits due to acute poisoning to the ED between January 1, and December 31, 2012. RESULTS: A total of 977 toxic exposures were documented. Females were 554 (57%) and males 423 (43%). The age range was from 2 months to 96 years old. More than half of the patients were under 30 years old. The majority of exposures occurred in private homes and ingestion was the most common route of exposure. Deliberate poisonings accounted for 66% of all the poisonings and 76% had drugs and/or alcohol as their main cause. Exposures to chemicals other than drugs were usually unintentional and 31% of them were occupational exposures. 80% of patients received treatment and were discharged from the ED, 20% were admitted to other departments, thereof 21% to ICU. Two patients died (0.2%). CONCLUSION: A slight but statistically unsignificant increase in incidence was observed. Females outnumbered males. Self-poisonings by ingestion of drugs and/or alcohol accounted for the majority of cases. The age range was wide, but the incidence was higher with young people. Mortality was low. Key words: toxicology, acute poisoning, epidemiology, self-poisoning. Correspondence: Gudborg Audur Gudjonsdottir, gudborgg@gmail.com.

[Injecting drug abuse: survival after intensive care admission and forensic toxicology reports at death]. / Notkun vímuefna í æð: Afdrif sjúklinga eftir innlögn á gjörgæslu og niðurstöður réttarefnafræðilegra rannsókna við andlát.

INTRODUCTION: Injecting drug abuse is a worldwide problem with serious consequences for the individual and for society. The purpose of this study was to gather information on the most serious complications of injecting drug use from two perspectives, intensive care admissions and forensic toxicology reports. MATERIAL AND METHODS: Firstly, intensive care admissions related to injecting drug abuse during a five year period were reviewed for demographics, complications and 5 year survival. Secondly, information from forensic toxicology reports regarding deaths amongst known injecting drug abusers were gathered for the same period. RESULTS: A total of 57 patients with a history of active injecting drug use were admitted to intensive care or approximately 1% of admissions, most often for overdose (52%) or life threatening infections (39%). Median age was 26, males were 66%. The most common substances used were prescription drugs. Hospital mortality was 16% and five year survival 65%. Average time from hospital discharge to death was 916±858 days. During the study period 38 deaths of individuals with a history of injecting drugs were identified by forensic toxicology reports or 4.1/10(5) population/year (age 15-59). Cause of death was most often overdose (53%), usually from prescription opiates but multiple drug use was common. DISCUSSION: The life expectancy of injecting drug abusers after intensive care admission is substantially decreased, with 35% death rate within five years. A widespread use of prescription drugs is of concern. Injecting drug abuse seems to be a similar health problem in magnitude in Iceland as in other Scandinavian countries.

Ceruloplasmin and iron in Alzheimer's disease and Parkinson's disease: a synopsis of recent studies.

Ceruloplasmin (Cp) concentration and oxidative activity in serum are lowered in Parkinson's disease (PD). In most PD patients, iron increases in the substantia nigra in the midbrain. In PD, the low Cp concentration and activity in serum and the high iron amounts in the substantia nigra appears to be correlated. An hereditary background is common in PD and variations in the Cp gene that have been found in PD are associated with high iron levels in the substantia nigra. Variations in Cp synthesis and in the incorporation of copper into the Cp molecule are essential features of PD. In Alzheimer's disease (AD), the Cp activity in serum is lowered but not the concentration, except in the advanced stages of the disease. Generally, iron is not increased in the AD brain. In the AD brain, iron accumulates in neuritic plaques and in neurofibrillary tangles. There is also increased risk of iron-mediated tissue damage, which may possibly be counteracted by Cp. At the same time, the AD brain is short in copper, which presumably results in the deficient activity of many copper enzymes in the brain, in addition to Cp. Lowered Cp activity in serum most likely stems from lessened incorporation of copper in the Cp molecule and similar incorporation defects might also apply to other copper enzymes in AD.

[Ceruloplasmin (Cp) and iron in connection with Parkinson's disease (PD) and Alzheimer's disease (AD)]. / Serúlóplasmin og járn. Tengsl vid Alzheimersjúkdóm og Parkinsonsjúkdóm.

Ceruloplasmin, a multi-copper oxidase with four active copper atoms, oxidizes Fe2+ to Fe3+ and concomittantly fully reduces oxygen to water. The oxygenation of iron is a requisite for transferrin transport of iron and keeping noxious Fe2+ low. In the central nervous system (CNS) Cp is mostly localized in end feet of astrocytes surrounding capillaries and attached by a glycosylphosphatidylinositol-anchor. In aceruloplasminaemia, a rare recessive hereditary disease, complete loss of Cp is accompanied by disorders of iron metabolism and lesions in CNS and outside. In PD Cp concentration and oxidative activity in serum are significantly lowered with iron deposits and lesions in substantia nigra and basal ganglia. Changes in Cp-genes might be causative in these disorders. By inducing neuromelanin synthesis Cp may protect neurons in substantia nigra. In AD Cp activity in serum, but not concentration, is significantly lowered. Changes in Cp-genes have not been verified in AD. Total amounts of iron are not increased in AD brains although iron deposits and cortical lesions are numerous. Total copper is significantly lowered in AD brains. This may result in defective synthesis of Cp and other copper enzymes. - In conclusion, the defective Cp activity, associated with iron disorders, is seemingly of importance in PD and also in AD with other copper enzyme defects possibly involved.

Ceruloplasmin and iron proteins in the serum of patients with Alzheimer's disease.

BACKGROUNDS/AIMS: The oxidative activity of ceruloplasmin (CP) in serum has been found to be lowered in patients with Alzheimer's disease (AD). We investigated whether changes in CP were reflected by altered iron parameters in AD patients. METHODS: Iron parameters, and CP concentration, activity and specific activity were determined in the serum of 41 AD patients and controls. RESULTS: CP activity and specific activity were significantly lower in the AD patients. CP concentration and activity were negatively correlated with the ferritin concentration in both groups. CP concentration was positively correlated with age in the control group but not in the patients group. CONCLUSION: The lowered CP activity in the serum of AD patients was not reflected by the iron parameters. As CP concentration only rises with age in the controls, this may indicate failing adaption to age-related alterations in iron metabolism in AD patients.

Drugs related to motor vehicle crashes in northern European countries: a study of fatally injured drivers.

The aim of this study was to find which drugs and drug combinations were most common in drivers who died, in particular, in single vehicle crashes where the responsibility for the crash would be referred to the driver killed. The study included all available blood samples from drivers, who died within 24h of the accident, in the years 2001 and 2002 in the five Nordic countries (total population about 24 million inhabitants). The samples were analysed for more than 200 different drugs in addition to alcohol, using a similar analytical programme and cut-off limits in all countries. In three countries (Finland, Norway and Sweden) blood samples were available for more than 70% of the drivers, allowing representative prevalence data to be collected. 60% of the drivers in single vehicle crashes had alcohol and/or drug in their blood samples, compared with 30% of drivers killed in collisions with other vehicles. In single vehicle accidents, 66% of the drivers under 30 years of age had alcohol and/or drugs in their blood (alcohol only - 40%; drugs only - 12%; alcohol and drugs - 14%). The drugs found were mostly illicit drugs and psychoactive medicinal drugs with warning labels (in 57% and 58% respectively of the drivers under 30 with drugs present). Similar findings were obtained for drivers 30-49 years of age (63% with alcohol and/or drugs). In drivers aged 50 years and above, killed in single vehicle crashes (48% with alcohol and/or drugs) illicit drugs were found in only one case, and psychoactive medicinal drugs were detected less frequently than in younger age groups. In 75% of single vehicle crashes, the driver was under 50 years. Thus, the majority of accidents where the drivers must be considered responsible, occurred with drivers who had recently used alcohol, or drugs, alone or in combination. The drugs involved were often illicit and/or psychoactive drugs with warning labels. Therefore a large proportion of single vehicle accidents appear to be preventable, if more effective measures against driving after intake of alcohol and drugs can be implemented.

Case-control studies on ceruloplasmin and superoxide dismutase (SOD1) in neurodegenerative diseases: a short review.

This short review describes a series of case-control studies on the concentration and oxidative activity of ceruloplasmin (CP) in serum and the activity of superoxide dismutase (SOD1) in erythrocytes in patients with Alzheimer's disease (AD), Parkinson's disease (PD) and Down's syndrome (DS). The same parameters were re-examined in the PD patients 5 years later. The specific oxidative activity (oxidative activity related to mass) of CP was calculated in PD and DS. In AD and PD the oxidative activity of CP and SOD1 activity was significantly lower in patients than controls. The specific oxidative activity of CP was also significantly lower in PD patients. The difference in all parameters determined was still present 5 years later in PD patients. There was no difference in the concentration or activity of CP in patients with DS and controls. Because of the gene-dose effect (the gene for SOD1 is located on chromosome 21); the SOD1 activity was 50% higher in the patients than the controls. The CP specific oxidative activity and SOD1 activity were found to be significantly lower in the older (>40 years) than the younger DS patients. Whether changes in CP and SOD1 in AD, PD and DS are primary changes or a result of prolonged disease burden needs to be examined.

The distribution of four trace elements (Fe, Mn, Cu, Zn) in forage and the relation to scrapie in Iceland.

BACKGROUND: Previous studies indicated that the iron (Fe)/manganese (Mn) ratio in forage of sheep was significantly higher on scrapie-afflicted farms than on farms in other scrapie categories. This study was conducted to examine whether Fe and Mn in forage of sheep varied in general according to the scrapie status of different areas in the country. Copper (Cu) and zinc (Zn) were also included because of a possible relation to scrapie. METHODS: The country was subdivided into seven Areas (I-VII). Three Areas (I, IV, VII) were designated scrapie-free (never diagnosed or eradicated) and three as scrapie-endemic (II, III, VI); status of Area V was taken as unsettled. Of the harvest 2007 1552 samples were analysed from 344 farms all over the country, mostly grass silage from plastic bales (>90%) and from the first cut (70% or more). Results were expressed as mg kg(-1) dry matter. RESULTS: Fe varied enormously from less than 100 mg kg(-1) to 5000 mg kg(-1). Mn varied nearly thirtyfold (17-470 mg kg(-1)). Fe concentration was significantly lower in Area I than in Areas II, V and VI. Mn concentration was significantly higher in Areas I, IV and VII than in Areas II, III, V and VI. The Fe/Mn ratio was significantly less in Area I than in the other areas (except Area IV). Mean Cu concentration was 6.6-8.3 mg kg(-1) and the mean Zn concentration was 24-29 mg kg(-1). They differed significantly in some areas. CONCLUSIONS: 1) Fe tended to be in lower amounts in sheep forage in scrapie-free than in endemic areas; 2) Mn was in higher amounts in forage in scrapie-free than endemic areas; 3) the Fe/Mn ratio was lower in scrapie-free than in endemic areas; 4) the Fe/Mn ratio may possibly be used as an indicator of scrapie status; 5) Cu and Zn in sheep forage were not related to scrapie; 6) further study on the role of Fe and Mn in the occurrence of scrapie in Iceland is needed.

Ceruloplasmin and superoxide dismutase (SOD1) in heterozygotes for Wilson disease: A case control study.

At the time of this study, there were five known patients with Wilson disease (WD) in Iceland. The mutation, a 7-bp deletion in exon 7 on chromosome 13 for WD, is only known in Iceland. In twenty healthy Icelandic heterozygotes for WD and their age- and gender-matched controls, copper concentration in plasma, ceruloplasmin (CP) concentration, CP oxidative activity and CP-specific oxidative activity in serum and superoxide dismutase (SOD1) activity in erythrocytes were determined. The same determinations were done on the five WD patients. There was no significant difference in these parameters between the heterozygotes and the controls, although an inclination toward lower CP determinations and higher SOD1 activity in the heterozygotes was noted. As expected the WD patients were low on the copper and CP parameters, but their SOD1 activity was within the upper normal range. In conclusion, the CP parameters and SOD1 activity are within the normal range in Icelandic heterozygotes for WD, although with a trend toward mild dyshomeostasis. This may indicate subclinical copper retention in the heterozygotes, but a bigger study group is needed to confirm this.

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.

Acute poisonings in Iceland: a prospective nationwide study.

INTRODUCTION: Poisoning is a common cause of emergency visits and hospital admission in Western countries. The purpose of this study was to assess the incidence and type of toxic exposures presenting to emergency medical facilities in Iceland. MATERIALS AND METHODS: The study was prospective and included all patients with confirmed or suspected poisoning presenting to hospitals and rural medical centers providing emergency services in Iceland during the twelve-month period from April 2001 until March 2002. RESULTS: A total of 1,121 toxic exposures were documented representing an incidence of 3.91 cases per 1,000 inhabitants per year. The female to male ratio was 1.23. The majority of exposures (56.7%) occurred in the patient's home, 60% were deliberate, 72% had drugs and/or alcohol as their main cause, and 11% involved illicit drugs. Exposures to chemicals other than drugs were usually unintentional. CONCLUSION: Toxic exposures requiring emergency medical care are common in Iceland. Self-poisonings by ingestion of prescription drugs and/or alcohol accounted for the majority of cases.

Ceruloplasmin and superoxide dismutase (SOD1) in Parkinson's disease: a follow-up study.

In this follow-up study concentration, oxidative activity and specific oxidative activity of ceruloplasmin (CP) in serum and the activity of superoxide dismutase (SOD1) in erythrocytes were reexamined in 28 of originally 40 patients with Parkinson's disease (PD), and their age- and gender-matched controls. The mean CP and SOD1 parameters were significantly lower in the patients than in the controls. SOD1 activity and age of the patients were inversely correlated. The patients were divided into two subgroups based on their H&Y score i.e. groups II and III (12 patients) versus groups IV and V (16 patients). No significant difference was found in the CP or SOD1 parameters between the subgroups. Patients were also divided into two subgroups based on treatment with levodopa and decarboxylase blocker alone (12 patients) or given additionally a dopamine agonist (15 patients). No significant difference in the parameters was found between these subgroups in relation to intake of dopamine agonists. Results of this study are in agreement with results of the former study 5 years earlier. There is considerable overlap in individual values between patients and controls of the parameters studied. Thus CP and SOD1 have no obvious value for diagnosis or clinical evaluation of PD.

Validity of self-reports and drug use among young people seeking treatment for substance abuse or dependence.

The present study assessed drug use and the validity of self-reports of drug use among young people seeking treatment. On admission the participants (n = 316), 215 males and 101 females, were interviewed about their drug use. Urine samples were collected to screen for alcohol, amphetamine, benzodiazepines, cannabis, cocaine, methylenedioxymethamphetamine (MDMA) and opiate use. Self-reports of substance use were compared with urinalysis results. Seventy-three percent of the participants reported use of two or more substances. Single substance users were primarily alcohol users. Kappa agreement between self-report and urinalysis results was of acceptable concordance (> or = 0.65) except for alcohol (kappa = 0.19). Conditional kappa values were good (> or = 0.85) with exception of opiates (cond. kappa = 0.57). The self-reports were generally reliable among young people seeking treatment. No significant differences (p > or = 0.54) were found in the validity of self-reports between the genders.

[Neurodegenerative diseases, antioxidative enzymes and copper. A review of experimental research.].

INTRODUCTION: In almost all degenerative diseases of the brain aggregation of proteins inside neurons or extracellulary, is a common pathological phenomenon regardless of etiology. It is assumed that the biochemical pathways leading to aggregation are more harmful than the aggregations themselves and most likely imply production of free oxygen radicals. This oxidative stress is in the body met by free radical scavengers in the form of specific chemical substances and antioxidative enzymes. It has therefore been postulated that defective free radical defense is a common pathway in most neurodegenerative diseases in humans as well as in other mammals. MATERIAL AND METHODS: The concentration of copper and the activity of two antioxidative copper containing enzymes, ceruloplasmin and superoxide dismutase (SOD 1), was analyzed in the blood. A series of case control studies were performed in Alzheimer s disease (AD), Parkinson s disease (PD) and amyotrophic lateral sclerosis (ALS) as well as in Down s syndrome and autism. Furthermore, a study in sheep was conducted in different areas with different risks of infection of scrapie. In that study, in addition, the activity of the selenium-containing enzyme, glutathione peroxidase, was determined as well as the concentration of manganese in blood. RESULTS: The oxidative activity of ceruloplasmin and SOD1 was shown to be significantly lowered in Alzheimer s disease without any signs of copper deficiency. In Parkinson s disease, the oxidative activity of ceruloplasmin was also on the whole shown to be signifcantly lowered, and furthermore, it decreased significantly as well as the SOD1 activity with duration of the disease. In ALS, the means of all of the determinations were shown to be the same, but the equality of variances differed significantly in the patients compared to their controls. In Down s syndrome past the age of 40, when Alzheimer s type changes appear in the brain, the SOD1 activity and the ceruloplasmin specific oxidative activity (activity in relation to concentration) was significantly lowered compared with the younger patients. In autism, a non-degenerative affection of the central nervous system, there was no difference between patients and their controls. In the sheep, the results indicated a relationship between decreased glutathione peroxidase activity, and possibly also SOD1 activity, and increased susceptibility to scrapie infection. No connection was found between ceruloplasmin oxidative activity and susceptibility to scrapie infection. Susceptibility to scrapie infection was apparantly not conntected with low levels of copper or high levels of manganese in blood of the animals. DISCUSSION: The results indicate that the oxidative defenses in four neurodegenerative diseases with different clinical features are defective as the activity of two copper containing antioxidative enzymes, ceruloplasmin and SOD1, was found defective in all of them. In a developmental syndrome (autism), where neither active degenerative changes nor aggregations are found, no such changes in enzyme activity were detected. The results thus support the idea that deranged oxidative defense is a common denominator in the pathogenesis of these diseases. As far as sheep is concerned, the results also indicate, that there is a defect in oxidative defense connected with increased susceptibility to scrapie infection in the form of lowered glutathione peroxidase activity.