Long-term Data from the Swedish National Environmental Monitoring Program of Pesticides in Surface Waters.

Environmental monitoring is essential for assessing the impact of human activities on the environment. Monitoring data are used to ascertain that environmental standards are met, to inform policy making, to determine trends, and to provide parameterization data for prediction models. The design of monitoring programs depends on what is being monitored, for what purpose, and available resources. Here we describe the strategy and design of the Swedish environmental monitoring program for chemical pesticides in surface waters and provide data generated within this program since 2002 (). We include examples of how the data can be used for toxicity assessments, trend analyses, and comparison between sampling strategies. Our goal is to increase awareness of this dataset and provide detailed information about the data so that it may be incorporated into meta-analytical research, comparison studies, model validation, and other scientific efforts.

Intraoperative electrical stimulation of the stapedius reflex in children.

OBJECTIVE: To describe the use of intraoperative electrical stimulation on the stapedius reflex in children. SETTING: Hospital cochlear implantation center. PATIENTS AND METHODS: Eighteen children under the age of 10 years, who have undergone cochlear implantation, have been examined during surgery with the electrically elicited stapedius reflex in the monopolar stimulation mode. RESULTS: A stapedius reflex could visually be detected for all subjects. CONCLUSION: The responses serve to test the implant, provide guidance in avoiding overstimulation of the child when the device is switched on, and estimate the optimal C-levels.

Quality of life in children with congenital heart defects.

Quality of life was measured in children with congenital heart defects (CHDs) registered in a total population of infants born live in the period 1982-91 (n = 22,810), using essential life spheres: external living conditions, interpersonal and personal conditions. In 200 children with CHD alive at the time the investigation was performed, 164 (82%) of the families answered a questionnaire addressing different dimensions of these quality of life spheres. Three subgroups of CHDs were investigated: CHDs spontaneously cured (n = 80), CHDs treated by surgery (n = 56), and CHDs with associated syndromes/malformations (n = 29). 301 (75%) out of 400 controls, matched for age and habitat (county), answered the same questionnaire. The children's ages at investigation were 2 y 2 months-12 y 2 months (median 6 y 1 month). There were no statistically significant differences between the CHD groups and the controls for overall quality of life for any of the three life spheres (p > 0.05). In children with operated CHDs and CHDs associated with syndromes/malformations, quality of life was influenced at some aspects of the external as well as at the interpersonal and personal levels. A trend existed for a higher subjective experience of quality of life in the total CHD group as well as in all the subgroups. It is speculated that this may represent development of coping mechanisms and recalibration of values of life.

Chloroquine phosphate: a long-term follow-up of drug concentrations in skin suction blister fluid and plasma.

Chloroquine is known to bind strongly to melanin and is accumulated in the skin. In dermatology, the drug is mainly used to treat photosensitivity disorders, but it has also been reported to cause sun sensitivity, especially in patients with rheumatoid arthritis. In the present study the concentrations of chloroquine phosphate in plasma and skin suction blister fluid (interstitial fluid in the skin) from 16 patients were studied by HPLC at steady-state (after 2 months' ingestion of 250 mg of the drug daily) and 2, 4 and 6-7 months after cessation of therapy. At steady-state the concentrations were similar in the two compartments, whereas after discontinuation the drug remained much longer in the skin than in the plasma. In tests using cow's eye melanin in vitro, UV irradiation failed to interact with the binding of chloroquine to melanin. It is speculated that the prolonged storage of the drug in the skin could be of importance for its therapeutic as well as adverse effects.

Quality of life for children with disabilities.

Studies on children with special needs mainly concentrate on disease-oriented health problems and neglect the positive aspects of quality of life. In this study the quality of life of children with Cystic Fibrosis and Myelomeningocele, 951 children in all, in the five Nordic countries is compared to that of a random sample of 10,290 children. The aim of the study was to see how the issue of equity, a main objective of the WHO health for all policy, has been met in the Nordic countries. Quality of life is defined as one of the essential resources of a population in terms of external, inter-personal and personal conditions. The study shows that children with disabilities have, and perceive that they live in good material and socio-economic conditions. However, the personal psychological conditions are less favourable, which indicates that this is a priority area for future health policies.

Topical chloroquine applied before irradiation protects against ultraviolet B (UVB)- and UVA-induced erythema but not against immediate pigment darkening.

Seventeen healthy volunteers were phototested with ultraviolet B (UVB) and UVA before and after topical treatment with chloroquine phosphate. The skin areas treated before but not after irradiation showed higher minimal erythema dose values for UVB and UVA than control skin. The effect was clearly spectral with greater protection afforded against UVB than UVA. The immediate pigment darkening after irradiation with UVA, however, was not affected by pretreatment with the drug. The mechanism of action for this protective effect did not seem to be related to merely absorption and screening, inhibition of the inflammatory reaction or a UV-induced effect on the stereo-isomerization of the drug.

Endometrial carcinoma; ovarian dysfunction--a risk factor in young women.

From a referral area comprising one-fifth of the Swedish female population we investigated possible risk factors for endometrial cancer (EC) in different age groups. Seventy-seven women aged 31-45 with EC were collected retrospectively, and 99 women aged 46-65 were consecutively collected. Both groups were compared to referents randomly selected from a population based study from the city of Göteborg. The referents consisted of 1746 women aged 39-65 years. All cases were studied by hospital record and 82% of the women aged 31-45 years and 85% of those aged 46-65 years were studied by an extensive questionnaire. Among the referents 1409 (81%) were investigated by the above-mentioned questionnaire. Hirsutism, increased body mass index (BMI) and hypertension were significantly more common in both EC groups compared to referents. Nulliparity and infertility were significantly more common in the young EC group. Referents used combined oral contraceptives significantly more often than women developing EC. There was, however, no difference between the groups with respect to the duration of medication with combined oral contraceptives. There was a significant negative correlation between cigarette smoking and the development of EC. These findings indicate that untreated ovarian dysfunction like that present in polycystic ovarian disease (PCO) with unopposed estrogen action on the endometrium is associated with EC in younger women, and that smoking may protect against EC by an 'anti-estrogenic' effect.

Pharmacokinetics and effects of 9-amino-1,2,3,4-tetrahydroacridine in the immediate postoperative period in neurosurgical patients.

STUDY OBJECTIVE: To determine the effects of intravenous (IV) 9-amino-1,2,3,4-tetrahydroacridine (THA) on postoperative somnolence in comparison to its pharmacokinetics. DESIGN: Open-label study of the pharmacokinetics and effects of THA. SETTING: Postoperative intensive care ward at the Department of Neurosurgery, Uppsala University Hospital, Sweden. PATIENTS: Ten neurosurgical patients immediately after their operations were given 30 mg of THA for reversal of postoperative somnolence. INTERVENTIONS: Plasma concentrations of THA and, in seven cases, the metabolite 1-hydroxy-THA were assayed using high-performance liquid chromatography. The pharmacokinetic data were compared to the degree of sedation and pain relief. After an IV dose of 30 mg THA, plasma concentrations were fit to an open two- or three-compartment model. MEASUREMENTS AND MAIN RESULTS: The antagonistic effect of THA on sedation occurred immediately following IV administration and lasted 60 to 90 minutes. At a mean plasma THA concentration of 44 +/- 18 ng/ml, patients were resedated. There was no obvious relation between analgesia and plasma THA concentrations. Side effects such as nausea, salivation, and lower heart rate (HR) were observed in several patients. Plasma clearance (C1) was high and showed a twofold inter-individual variation, with a mean of 2.64 +/- 1.17 L/h. Volume of distribution (Vd gamma) varied between 300 and 850 liters, with a mean of 477 +/- 185 liters. The plasma half-lives of rapid and slow distribution, and elimination were 2.1 +/- 0.7 minutes, 26 +/- 18 minutes, and 133 +/- 48 minutes, respectively. Maximum plasma concentrations of 1-hydroxy-THA were 27 to 90 ng/ml in five patients; the concentration was below 1 ng/ml in two other patients. CONCLUSIONS: The duration of the effects of THA as an antagonist of postoperative sedation was only about double that seen previously after the IV administration of physostigmine in a similar group of patients, although the elimination half-life of THA was six times longer than that of physostigmine. A larger dose of THA possibly could have been given to prolong the period of antagonism of sedation, but the profile of adverse effects seen even at the doses used precluded that option.

Youth, disability and quality of life.

When broader aspects of health are considered especially when assessing the life of the disabled it becomes necessary to reach beyond physical measurements to more dynamic aspects including the individual's other resources and demands. In such a context issues of quality of life are important. Quality of life is here defined as a term describing the total existence of an individual or a group and is operationalized in three life spheres: external conditions, interpersonal conditions and personal psychological conditions. National samples of youths aged 12-18 years with cystic fibrosis and myelomeningocele are compared to a reference group of normal youths in the five Nordic countries. The study was based on a mailed questionnaire. The results show that the disabled groups had equal external conditions as their peers while they rated lower on the interpersonal and personal levels. This indicates that the Nordic countries have succeeded in providing a good material support for families with handicapped youths. The fact that these families are also more satisfied with the different life spheres means that both objective and subjective needs are met. The social networks and personal psychological conditions, though, proved to be less sufficient and there is still a lot to be done to give handicapped youngsters a full life.

A model for prediction of endometrial cancer.

An epidemiological statistical model was designed to identify women at low and high risk of developing endometrial cancer (EC). The model was based on a number of easily identified clinical factors such as hirsutism, parity, diabetes mellitus, body mass index (BMI) and smoking. A retrospectively collected series of 77 women aged 31 to 45 years with EC and a prospectively collected series of 122 women aged 43 to 70 years with EC were compared with 1409 controls. The participation frequencies in the two case materials were 83 and 87%, respectively. The series were examined by means of a questionnaire. In a stepwise multiple logistic regression analysis of the entire series the following variables were found to be significant; hirsutism, parity, BMI, diabetes mellitus and smoking.

Inactivation of lactate dehydrogenase by UV radiation in the 300 nm wavelength region.

The effect of UV radiation on lactate dehydrogenase (LDH) was investigated. LDH from bovine heart was exposed to 3.6-18 kJ/m2 of ultraviolet (UV) radiation in the 300 nm wavelength region. The activity of LDH was observed to decrease as a function of the dosage of UV radiation. The inactivation of LDH was independent of exposure rate at constant dosage of UV radiation. The decrease of LDH activity caused by UV 300 nm radiation was coupled to a decrease of the maximal velocity (Vmax) while the Michaelis constant (Km) remained unchanged. The absorption spectrum of the LDH changed during exposure to UV radiation suggesting an alteration of tryptophan in the LDH molecule.

Oral mercaptopurine in childhood leukemia: influence of food intake on bioavailability.

Plasma concentrations of 6-mercaptopurine (6-MP) were determined by gas chromatography-mass spectrometry. Ten children (nine with acute lymphatic leukemia) were studied on 2 consecutive days after oral intake of 6-MP. On one day the drug was administered in the fasting state and on the other (in random order) together with breakfast. The peak plasma concentrations of 6-MP after the dose intake with breakfast in percent of that in the fasting state (meal in % of fasting for each individual) varied between 33 and 181% (mean 111), and the area under the plasma concentration-time curve varied between 47 and 186% (mean 103). Thus, there were considerable variations among patients, but, for the group as a whole, there were no statistically significant differences between the two experimental conditions. This study cannot therefore form the basis for a recommendation as to whether 6-MP should be administered on an empty stomach or together with food.

Human liver morphine UDP-glucuronyl transferase enantioselectivity and inhibition by opioid congeners and oxazepam.

1. Morphine uridine diphosphate glucuronyl transferase (UDP-GT) was studied in human liver microsomes. The (-)- and (+)-morphine enantiomers were used as substrates and inhibitors, such as oxazepam and various opioid congeners were employed to characterize the different glucuronidation pathways. The kinetics of the oxazepam inhibition were studied in the rat liver. 2. The overall glucuronidation of (+)-morphine was higher than that of (-)-morphine. The morphine congeners tested, potently inhibited the formation of (-)-morphine-3-glucuronide ((-)-M3G), except for normorphine and codeine. The formation of (+)-morphine-6-glucuronide [+)-M6G) was potently inhibited by only dextromethorphan and (+)-naloxone. All drugs except normorphine inhibited the formation of (+)-M3G by 18-50%. 3. The metabolism of (-)-morphine to (-)-M3G was more sensitive to oxazepam inhibition than the formation of (+)-M3G from (+)-morphine in the rat liver. 4. The glucuronidation of natural morphine is subject to in vitro interaction with oxazepam and several opiate drugs. Our study supports the theory of more than one type of UDP-GT being involved in morphine glucuronidation.

Oral praziquantel kinetics in normal and Schistosoma haematobium-infected subjects.

The kinetics of praziquantel was studied in normal and Schistosoma haematobium-infected Ghanaian subjects. There was a wide interindividual variation in half-life (t1/2), Cmax, Tmax, area under the curve (AUC) (0-8 h), and urinary recovery. No differences were noted between the two groups with regard to Tmax, AUC (0-8 h), and t1/2. Mean Cmax was higher in the patients than in the control subjects. The 8-hr urinary recovery of praziquantel was higher in the subjects with urinary schistosomiasis. The amount of praziquantel excreted unchanged in urine was 0.0052 +/- 0.0027% (SD) of the dose for the control subjects and 0.0054 +/- 0.0027% (SD) for the patients.

Fibrinopeptide A and fibrinogen fragment B beta 15-42 and their relation to the operative trauma and post-operative thromboembolism in neurosurgical patients.

In an earlier study on post-operative thromboembolism in neurosurgery the incidence of deep vein thromboses (DVT) diagnosed by the fibrinogen uptake test and phlebography was reduced to the same extent by two different prophylactic methods (low dose heparin or calf muscle stimulation + dextran). However, patients with lower limb paresis due to a brain lesion experienced relatively often a less successful prophylaxis compared to patients with spinal lesions. There are few reports on successful clinical methods for haematological screening of post-operative DVT. The aim of this study was to examine possible haematological indicators for post-operative thromboembolism and secondarily to elucidate whether there exist some special coagulatory or fibrinolytic characteristics in patients who had been operated upon for brain lesions. We have studied two specific coagulatory factors (FPA reflecting thrombin generation and B beta 15-42 reflecting plasmin activity) in connection with neurosurgical operations. Patients in the above-mentioned study on post-operative DVT operated upon for malignant cerebral tumours or intracranial vascular disease exhibited post-operatively higher values for FPA compared to other neurosurgical diagnoses. B beta 15-42 was higher in the malignant tumour group and almost significantly higher in the intracranial vascular group (p less than 0.065). These differences could not be ascribed to the occurrence of DVT. Another 15 patients divided into a minor and a major lesion group were investigated with determination of both parameters pre- and post-operatively. Concerning FPA an increase was noticed post-operatively compared to pre-operatively in the major lesion group.(ABSTRACT TRUNCATED AT 250 WORDS)

Unscheduled DNA synthesis in lens epithelium after in vivo exposure to UV radiation in the 300 nm wavelength region.

A quantitative autoradiographic method was developed to study the pattern of DNA synthesis in the rat lens epithelium after in vivo exposure to UV radiation in the 300 nm wavelength region. It was found that UV radiation (peak transmission = 298 nm, half-width = +/- 10 nm) induces unscheduled DNA synthesis and that the proportion of nuclei in S-phase concurrently is reduced indicating an inhibition of the scheduled DNA synthesis. The registered unscheduled DNA synthesis is believed to be excision repair of DNA damage induced by the UV radiation. Excision repair in lens epithelial cells could be one mechanism involved in the correlation between exposure to sunlight and cataracts.

Pharmacokinetics of physostigmine after intravenous, intramuscular and subcutaneous administration in surgical patients.

The pharmacokinetics of physostigmine after intravenous, intramuscular or subcutaneous administration as well as its arousal effect after anaesthesia have been studied in surgical patients in the early postoperative period. After intravenous administration physostigmine had a very rapid plasma elimination with a plasma clearance ranging from 47 to 163 l/h with a mean +/- s.d. of 92.5 +/- 37.7 l/h. The volume of distribution was 46.5 +/- 19.2 l, while distribution and plasma elimination half-lives were 2.3 and 22 min, respectively. A fraction of the dose was probably hydrolyzed in blood since its blood elimination half-life in vitro was approximately 190 min. After both intramuscular and subcutaneous administration the systemic availability was almost complete, the plasma terminal half-lives only being somewhat longer than after intravenous administration. Plasma clearance, volume of distribution and elimination half-life of physostigmine were not correlated to age or body weight of the patients. The rapid plasma clearance of physostigmine resulted in a short duration of antisedative effect. After administration of 1 mg physostigmine salicylate i.v., drug-induced sedation was rapidly reversed with a duration of 30-60 min. The duration of action was similar after intramuscular injection but onset was delayed by 20-30 min. It was concluded that a plasma concentration of 3-5 ng/ml of physostigmine should be exceeded if an adequate analeptic effect is to be achieved, meaning that 2 mg of physostigmine had to be administered subcutaneously in order to achieve a satisfactory reversal of sedation. The short duration of action may hamper the use of physostigmine as an agent for reversal of drug-induced sedation and anticholinergic effects after surgery.