The epidemiology of childhood poisonings in Cyprus.

Information on childhood poisonings in Cyprus is limited. Our objective was to examine the epidemiology of poisonings among children in Cyprus. All children up to 15 years of age admitted for poisoning to the Archbishop Makarios Hospital in Nicosia, Cyprus between 2005 and 2008 were included in our study. All hospital poisoning records were reviewed. A total of 257 children were admitted for poisoning. The mean age of children was 3.1 years, of which 83.7% were below the age of 5 years old, while 53% were boys. The poisoning hospitalizations accounted for about 3% of all admissions to the pediatric department during the study period (4 years). The annual cumulative incidence of childhood poisoning hospitalizations was 116 per 100,000 children. Medications accounted for 46.1% of all poisonings, the most frequent cause being paracetamol (9.8%), cardiovascular medications (5.3%), antitussive medications (4.5%), and other painkillers (4.1%). Another 37.6% of hospitalizations involved household products such as household cleaning products (11.8%), petroleum products (11.0%), and rodenticides (5.7%). Among children who ingested petroleum distillates, 55.6% developed clinical symptomatology. The vast majority of cases were accidental (93.8%). Suicidal cases involved children 8-14 years old, mainly girls, and the most frequent poisoning ingested was paracetamol (46.7%). Poisoning hospitalizations represent an important cause of morbidity among children in Cyprus. Preventive strategies should include the education of caregivers on the handling of medications and household products as well as legislation requiring child-resistant packaging for all medications and household products including petroleum distillates.

Multiple organ failure following lamp oil aspiration.

CASE REPORT: A 26-month-old previously healthy boy of 15 kg was admitted to our hospital due to cyanosis following the aspiration of lamp oil. Aspiration resulted from the patient's father inducing emesis by digital stimulation of the boy's throat after the patient had ingested an unknown amount of lamp oil. Endotracheal intubation was done on the second hospital day in the Pediatric Intensive Care Unit (PICU) due to respiratory failure manifested by hypercapnia and hypoxemia. Mechanical ventilation, including high frequency oscillatory ventilation (HFOV) with iNO at 20 ppm, was started. However, he developed a spiked fever and developed an acute respiratory distress syndrome, a pneumothorax, and diffuse subcutaneous emphysema. His course was further complicated by anuric renal failure, rhabdomyolysis, severe hepatitis, pancytopenia, elevation of cardiac enzymes, and disseminated intravascular coagulation over the following days. He died on the ninth day of hospitalization because of multiorgan failure.

Bioavailability of polycyclic aromatic hydrocarbons from buried shoreline oil residues thirteen years after the Exxon Valdez oil spill: a multispecies assessment.

Seven taxa of intertidal plants and animals were sampled at 17 shoreline sites in Prince William Sound ([PWS]; AK, USA), that were heavily oiled in 1989 by the Exxon Valdez oil spill (EVOS) to determine if polycyclic aromatic hydrocarbons (PAH) from buried oil in intertidal sediments are sufficiently bioavailable to intertidal prey organisms that they might pose a health risk to populations of birds and wildlife that forage on the shore. Buried residues of EVOS oil are present in upper and middle intertidal sediments at 16 sites. Lower intertidal (0 m) sediments contain little oil. Much of the PAH in lower intertidal sediments are from combustion sources. Mean tissue total PAH (TPAH) concentrations in intertidal clams, mussels, and worms from oiled sites range from 24 to 36 ng/g (parts per billion) dry weight; sea lettuce, whelks, hermit crabs, and intertidal fish contain lower concentrations. Concentrations of TPAH are similar or slightly lower in biota from unoiled reference sites. The low EVOS PAH concentrations detected in intertidal biota at oiled shoreline sites indicate that the PAH from EVOS oil buried in intertidal sediments at these sites have a low bioavailability to intertidal plants and animals. Individual sea otters or shorebirds that consumed a diet of intertidal clams and mussels exclusively from the 17 oiled shores in 2002 were at low risk of significant health problems. The low concentrations of EVOS PAH found in some intertidal organisms at some oiled shoreline sites in PWS do not represent a health risk to populations of marine birds and mammals that forage in the intertidal zone.

Evolution of the alimentary toxic oil syndrome due to ingestion of denatured rapeseed oil.

Three hundred seventeen patients with toxic oil syndrome caused by ingestion of denatured rapeseed oil were followed up after one year. Total mortality for the 317 patients was 4.4%. After 12 months, 3.2% of the surviving patients have a severe motor neuropathy, 52.9% are asymptomatic, and the remaining 39.4% have mild residual myalgia. The cause of death in seven patients during the acute phase of toxic oil syndrome was respiratory failure due to interstitial pneumonitis with cerebral edema. The death of five patients in the second phase was due to motor neuropathy that involved respiratory muscles and was complicated by aspiration pneumonia.

Relationship between the amount of rice oil ingested by patients with yusho and their subjective symptoms.

The goal of this study was to clarify the subjective symptoms closely related to yusho by examining the relationship between the amount of PCB-contaminated rice oil ingested by patients and the subjective symptoms recorded on their questionnaires. The amount of PCB-contaminated rice oil consumed by the patients was obtained by interviewing the housewife in each yusho family. Individual consumption of the oil was estimated by taking into account age, sex and the number of meals at home. In 1970, 46 patients were available for analysis, and in 1971, 33 patients were available. Among 12 subjective symptoms studied, numbness of the limbs, coughing, expectoration, and the sensation of "elevated" teeth were considered to show a dose-response relationship, which suggests that these subjective symptoms are closely related to yusho. Consistent high rates of complaints of general fatigue and eye discharge were considered possibly to be connected with yusho, although no dose-response relationships have been determined. Other subjective symptoms, such as fever, headache, dizziness, abdominal pain, swelling in the joints, changes in menstruation, and loss of hair failed to show consistent dose-response relationships. It should be noted, however, that for these symptoms which failed to show dose-response relationships, it is impossible to deny a causal relationship.

Polychlorinated biphenyls, dibenzofurans and quaterphenyls in toxic rice-bran oil and in the blood and tissues of patients with PCB poisoning (Yu-Cheng) in Taiwan.

A mass outbreak of poisoning occurred in central Taiwan in 1979 due to the ingestion of rice-bran oil contaminated with polychlorinated biphenyls (PCBs), dibenzofurans (PCDFs) and quaterphenyls (PCQs). The incident was called PCB poisoning or Yu-Cheng in Taiwan. The major PCB and PCDF congeners in the toxic oil and in the blood and tissues of the poisoned patients were characterized by gas chromatography and gas chromatography-mass spectrometry using highly efficient glass capillary columns. The levels of toxic agents in the rice oil samples collected from the factory and school cafeterias and the families of the poisoned patients are in the range of 53 to 99 ppm, 0.18 to 0.40 ppm and 25 to 53 ppm for PCBs, PCDFs, and PCQs, respectively. The blood samples of 165 patients collected 9 to 18 months after the onset of poisoning contained 10 to 720 ppb of PCBs, with a mean value of 38 ppb. The blood samples of 10 patients collected 9 to 27 months after poisoning contained 0.02 to 0.20 ppb of PCDFs. Comparative rates of elimination of some PCB congeners from the blood of patients were studied. Various tissues from a patient who died 2 years after poisoning were analyzed for PCBs, PCDFs and PCQs. The intestinal fat contains the highest level of PCBs, while the liver contains the highest concentration of PCDFs. The PCB congeners retained in the tissues either do not have adjacent unsubstituted carbon atoms or have a pair at ortho-meta positions of the biphenyl ring. The major PCDF congeners retained in the tissues were 1,2,3,4,7,8-hexachloro-DF, 2,3,4,7,8-pentachloro-DF and 1,2,4,7,8-pentachloro-DF. The former two congeners, especially 2,3,4,7,8-pentachloro-DF, are very toxic PCDFs; they may play important roles in the etiology of Yu-Cheng.

Surveys of workers occupationally exposed to PCBs and of yusho patients.

Surveys of workers occupationally exposed to polychlorinated biphenyls (PCBs) in the production of thread or of paint, and of yusho patients were carried out from 1973 to 1982. PCB concentrations in the plasma of the workers ranged from 2 to 521 ppb, and some showed higher PCB levels in the plasma than typical Japanese yusho patients. Gas chromatographic patterns of plasma PCBs of the workers with high PCB levels were shown to match the patterns of the PCBs to which they had been exposed in the workplace. Japanese yusho children showed remarkable decrease with time, but no such decrease was observed in the yusho adults and the workers. Polychlorinated quaterphenyls (PCQs) were detected in the blood of typical Japanese and Taiwanese yusho patients, but PCQ levels in the plasma of the workers were below the detection limit of 0.02 ppb. Clinical findings and subjective complaints of the workers were usually slight compared with typical yusho patients, though some of them had mild dermal manifestations and their PCB levels were suspected to be related to serum triglyceride values. On the basis of these results, we discussed the relationship between the health status of the subjects and their contamination with PCBs or related compounds.

Respiratory involvement and immune status in yusho patients.

Clinical and experimental studies on respiratory involvement and alterations in immune status were carried out. Respiratory distress occurring in these patients has improved gradually for 14 years but still remains. Copious expectoration at an early stage of the disease may be related to the fact that a number of discrete polychlorinated biphenyls (PCBs) are distributed throughout the lung parenchyma. For accumulation in the bronchial mucosa, structural requirements and specific dose dependence of PCBs have been clearly shown; however, pathological and physiological studies have indicated that respiratory involvement in yusho is mainly small airway disease that may be caused by involvement of cellular component (Clara cells) in bronchioles and/or associated infection. Respiratory distress is often exacerbated by viral or bacterial infection. Changes in the immune status in PCB and polychlorinated dibenzofuran (PCDF) poisoning are as follows: IgA and IgM in the serum are decreased at an early stage of the disease and then return to normal; suppression of cellular immunity was reported in Taiwanese patients and some may remain in the later stages of the disease, as shown in our patients. PCDFs now appear to be the main causal agents in yusho. Rats given PCDFs showed necrosis of the Clara cells in bronchioles and marked thymus atrophy, while few such changes were noted in rats given PCBs. Therefore, further examination is needed for the difference of the toxic effects between two compounds.

Association of blood pressure and PCB level in yusho patients.

Correlations of blood polychlorinated biphenyl (PCB) levels or PCB patterns and blood pressures were studied in 59 patients with yusho (PCB poisoning) above 40 years old. In spite of the passage of 13 years from the onset, 52.5% of these patients still have PCB levels higher than the range found in the general population. The frequency of hypertension in the patients was 16.9%, a value similar to that expected on the basis of the rate for a population of the same age and sex compositions. As an independent variable, the blood pressure of patients was not associated with blood PCB levels and PCB patterns. No PCB blood pressure association was confirmed in 20 patients with PCB levels persistently higher than 5 ppb for 9 years. On the other hand, age, obesity and habitual alcohol intake, known influencing factors for hypertension, tended to be positively associated with elevated blood pressure in these yusho patients.

PCB and PCDF congeners in the blood and tissues of yusho and yu-cheng patients.

Polychlorinated biphenyl (PCB) poisonings occurred in western Japan, where it is called yusho, in 1968, and in central Taiwan, where it is called yu-cheng, in 1979. The average concentrations of PCBs in the adipose tissue, liver and blood of yusho patients and in the blood of yu-cheng patients were 1.9 ppm, 0.08 ppm, 6.7 ppb and 99 ppb, respectively. Seven PCB congeners, such as 2,4,5,3',4'-pentachloro-, 2,3,4,3',4'-pentachloro-, 2,4,5,2',4',5'-hexachloro-, 2,3,4,2',4',5'-hexachloro-, 2,3,4,5,3',4'-hexachloro-, 2,3,4,5,2',4',5'-heptachloro- and 2,3,4,5,2',3',4'-heptachloro biphenyls were identified in the blood and tissues of patients with yusho and yu-cheng and controls. The concentration of 2,3,4,5,3',4'-hexachlorobiphenyl was comparatively higher in the patients than in controls. The concentrations of polychlorinated dibenzofurans (PCDFs) in the adipose tissue and liver of yusho patients were 6 to 13 ppb and 3 to 25 ppb, respectively, while no PCDFs were detected in the controls. Major PCDF congeners identified in the tissues and blood of yusho and yu-cheng patients were the 2,3,6,8-tetrachloro-, 2,3,7,8-tetrachloro-, 1,2,4,7,8-pentachloro-, 2,3,4,7,8-pentachloro- and 1,2,3,4,7,8-hexachlorodibenzofurans (DFs), of which the 2,3,4,7,8-pentachloro compound was predominant. The concentrations of methylthio-PCB in the liver, lung and adipose tissue of yusho patients were 0.1 to 0.5, 0.2 to 1.4 and 0.5 to 1.0 ppb, respectively, and those of methysulfone PCBs were 0.3 to 0.7, 1.0 to 2.5 and 0.7 to 1.0 ppb, respectively. Some of the major peaks of the PCB methylthio and methylsulfone derivatives were identical in gas chromatographic retention times with those of 4-methylthio- and 4-methylsulfone-2,5,2',5'-tetrachlorobiphenyl PCDFs, especially 2,3,4,7,8-pentachloro DF, appear to be mainly responsible in the poisonings.

PCBs, PCQs and PCDFs in tissues of yusho and yu-cheng patients.

All five samples of oil involved in the recent yu-cheng outbreak were heavily contaminated with PCBs, PCQs and PCDFs at levels, on the average, of 62, 20 and 0.14 ppm, respectively. The samples not only had roughly one-tenth of the contamination by PCBs, PCQs and PCDFs but also three to four times lower ratios of PCQs and PCDFs to PCBs than samples of oil involved in yusho in Japan. PCBs, PCQs and PCDFs present were all composed of similar congeners to the ones found in the yusho specimens, though some variation of the component ratios of PCBs and PCDFs were observed. On the other hand, five patients with yusho who died 1 to 10 years following poisoning had markedly higher tissue levels of PCDFs and PCQs than did a worker occupationally exposed to PCBs. Taking great differences in the process of the healing and the tissue levels of PCBs, PCQs and PCDFs between the two poisoning cases into consideration, PCDFs and PCQs--especially the former--and not PCBs are deduced to be strongly associated with the development of yusho.

PCBs, PCQs and PCDFs in blood of yusho and yu-cheng patients.

Individual blood samples obtained from yusho and yu-cheng patients who had been poisoned by ingesting contaminated cooking oils, from workers occupationally exposed to polychlorinated biphenyls (PCBs) and from unexposed individuals were analyzed for PCBs, polychlorinated quaterphenyls (PCQs) and polychlorinated dibenzofurans (PCDFs) by gas chromatography and mass spectrometry. PCBs were found in the blood of all samples. PCQs were detected in the blood of 54 of 56 living yusho patients 11 years after the outbreak, and in all yu-cheng patients 6 months following poisoning. These facts indicate that the presence of PCQs in the blood was a good mark of past ingestion of the toxic oil. In the yu-cheng cases, PCDFs as well as PCBs and PCQs were detected in all blood samples. These identified isomers have been reported to be remarkably highly toxic compounds, i.e., both the 2,3,7,8-tetrachlorinated and 2,3,4,7,8-pentachlorinated compounds are toxicologically hundreds to thousands of times more toxic than PCB. In view of the high toxicity of PCDFs found in the yu-cheng patients' blood, we must deduce that they are the primary causal agents of yusho as well as of the yu-cheng incident.

Past and current dermatological status of yusho patients.

Skin symptoms of yusho and their subsequent change were described. In the early stage, skin eruptions were the most prominent features of yusho. Acneform eruptions and pigmentation were most conspicuous. With the passage of time, these symptoms have improved considerably and most patients have very slight eruptions now, except for the severely intoxicated group. In the analysis of polychlorinated biphenyl (PCB) in the blood, the severely intoxicated group with intense skin symptoms showed pattern A--a typical yusho-specific pattern. The blood PCB patterns of each patient were stable, with no alteration after many years; on the other hand, the blood PCB concentrations have diminished year by year.

Clinical findings and immunological abnormalities in Yu-Cheng patients.

An outbreak of poisoning caused by ingestion of rice bran oil which was accidentally contaminated with polychlorinated biphenyls (PCBs) broke out in Taiwan in February 1979. Diagnosis, management, and follow-up of the patients were performed at special clinics, and subjective symptoms and cutaneous changes such as peculiar acneform eruptions and pigmentation were recorded. The patients were divided into six age groups of both essex, and the body surface of the patients was divided into 12 sections according to the nature of skin. The prevalence of each type of cutaneous change was proved statistically by the chi-square test. The examination of the immune system function in the patients at 1 year revealed: decreased concentration of IgM and IgA but not of IgG; decreased percentage of total T-cells, active T-cells, and helper T-cells, normal percentage of B-cells and suppressor T-cells; suppression of delayed type response to recalling antigens; enhancement of lymphocyte spontaneous proliferation; and enhancement of lymphocyte proliferation with PHA, PWM, and PPD stimulation but not ConA. Follow-up studies 3 years later showed decreased blood PCB levels; some improvement of subjective symptoms and cutaneous changes; recovery of skin testing response to PPD; normal percentage of total T-cells and increased percentage of suppressor T-cells; and enhancement of lymphocyte proliferation spontaneously or under the stimulation of various mitogens.

Fetal PCB syndrome: clinical features, intrauterine growth retardation and possible alteration in calcium metabolism.

Pregnant mothers with yusho in Fukuoka, Nagasaki and Kochi Prefectures delivered babies with a peculiar clinical manifestation which will be called fetal PCB syndrome (FPS). The birth rate incidences were 3.6% (Fukuoka Prefecture), 4% (Nagasaki Prefecture), 2.9% (Kochi Prefecture) and 3.9% (total). The manifestations consisted of dark brown pigmentation of the skin and the mucous membrane, gingival hyperplasia, exophthalmic edematous eye, dentition at birth, abnormal calcification of the skull as demonstrated by X-ray, rocker bottom heel and high incidence of light for date (low birth weight) babies. We suggest that there may be a possible alteration in calcium metabolism in these babies, related to the fragile egg shells observed in PCB-contaminated birds and to the female hormone-enhancing effect of PCB. The high incidence of low birth weight among these newborns and two other similar studies indicated that PCBs suppress fetal growth.

Discovery and epidemiology of PCB poisoning in Taiwan: a four-year followup.

An outbreak of polychlorinated biphenyl (PCB) poisoning from the consumption of contaminated rice oil, covering four counties in central Taiwan, was investigated. There were 1843 cases by the end of 1980. The highest frequency of incidence occurred during the period from March to July 1979. The severity of clinical manifestations varied. Most patients showed symptoms of mild or moderate severity. The major age group affected was between 11 and 20 years old. Most of the victims were students and factory workers. The amount of PCB intake in each victim was estimated to be 0.7 to 1.84 g and the latent period from the time of intake to the onset of clinical manifestations was approximately 3 to 4 months. The patients' blood PCB concentrations ranged from 3 ppb to 1156 ppb; 44.27% of 613 patients had levels of 51 to 100 ppb and 27.6% PCB blood levels over 100 ppb. In the course of 3.5 years, 2061 persons were determined to be PCB poisoning victims. Now, except for a few severe cases, their skin symptoms are very much improved. Thirty-nine babies showing hyperpigmentation were born from PCB-poisoned mothers. The fatality rate was high: eight of them died. Another 24 deaths were reported among the PCB-poisoned group, almost half of them (12) from hepatoma, liver cirrhosis or liver diseases with hepatomegaly.

Biological effect of PCBs, PCQs and PCDFs present in the oil causing yusho and yu-cheng.

Male Sprague-Dawley rats were daily given orally for 22 days a regimen consisting of polychlorinated biphenyls (PCBs), 1 mg/day; polychlorinated quaterphenyls (PCQs), 1 mg/day; polychlorinated dibenzofurans (PCDFs), 10 micrograms/day; or a mixture of PCBs, PCQs and PCDFs (Mix-1, 1 mg + 1 mg + 10 micrograms/day). Female Cynomolgus monkeys were daily administered PCBs (5 mg), PCQs (5 mg) or a mixture (Mix-2) containing 5 mg PCBs + 20 micrograms PCDFs for 20 weeks. The PCBs, and PCDFs had the components of PCBs, PCQs and PCDFs similar to those contained in Japanese yusho oils, respectively. The PCB-treated rats and monkeys showed hepatic hypertrophy, immunosuppression and increased drug-metabolizing enzyme activities in hepatic microsomes, but were devoid of the dermal symptoms characteristic of yusho. PCQs caused an increase in drug-metabolizing enzyme activities in hepatic microsomes and immunosuppression in monkeys, but these effects were much smaller than those found with PCBs treatment. On the other hand, treatment with PCDF or Mix-1 or Mix-2 caused hypertrophy of the liver, immunosuppression, increase in drug-metabolizing enzyme activities of hepatic microsome to much greater extent than observed with PCBs, being more than 100 times as effective as PCBs. In addition PCDFs and the mixtures containing PCDFs caused weight loss and thymic atrophy. PCDFs and Mix-2-treated monkeys showed the dermal symptoms that are characteristic of yusho patients but were not observed in monkeys treated with PCBs and PCQs alone. These results suggest that PCDFs are the primary causative agent of yusho.

Toxic oil syndrome: a syndrome with features overlapping those of various forms of scleroderma.

Thirty-two toxic oil syndrome (TOS) patients were selected because they presented with scleroderma-like changes and were observed during the first 36 months of evolution of the disease. Initially, these patients presented with a noncardiogenic pulmonary edema, eosinophilia, arthralgia/arthritis, peripheral edema, and myositis. Histologic investigations showed a widespread chronic interstitial infiltrate with lymphocytic vasculitis. They subsequently developed peripheral neuropathy, joint contractures, scleroderma-like changes, Raynaud phenomenon, pulmonary hypertension, sicca syndrome, and liver disease. Biopsy studies during this stage showed fibrosis and obliterating arteriopathy. Late features of TOS are musculoskeletal pain, cramps, livedo reticularis, carpal tunnel syndrome, and digital tuft changes. TOS is a new chemically induced scleroderma-like syndrome with features overlapping those of eosinophilic fasciitis, systemic sclerosis, and forms of localized scleroderma.

Treatment of hydrocarbon pneumonitis. High frequency jet ventilation as an alternative to extracorporeal membrane oxygenation.

A child presented with hydrocarbon ingestion leading to pneumonitis and adult respiratory distress syndrome (ARDS). Treatment with conventional ventilation in this child led to very high pressures and pulmonary air leaks. Treatment with high frequency jet ventilation (HFJV) resulted in less barotrauma, resolution of air leak, and clinical improvement. Thus, HFJV is an acceptable alternative to both conventional ventilation and extracorporeal membrane oxygenation in the treatment of hydrocarbon pneumonitis leading to ARDS.

Neurotransmitter changes in cerebrospinal fluid in the Spanish toxic oil syndrome: human clinical findings and experimental results in mice.

Patients with Spanish Toxic Oil Syndrome (TOS) complaining of neuromuscular symptoms had increased levels of homovanillic acid and 5-hydroxyindoleacetic acid (5-HIAA) in cerebrospinal fluid. Severity of pain and muscle cramps correlated with the magnitude of increment in levels of monoamine metabolites. Mice treated with oleyl anilide, a putative toxic compound found in some stocks of the toxic rapeseed oil, did not present clinical or anatomical findings compatible with TOS. However, biochemical studies in these mice revealed a depletion of serotonin and an elevation of 5-HIAA levels. Our findings suggest that the unidentified toxic agent of the TOS and oleyl anilide induce pharmacological changes in monoamine neurons of the brain.