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PubMed2002

Occupational rhinitis: a poorly diagnosed condition.

The civil claim of occupational rhinitis may be difficult to prove on the balance of probabilities and is the responsibility of the claimant. There are two types of occupational rhinitis, an allergic rhinitis or a rhinitis due to irritation. Occupational rhinitis can be likened to occupational asthma. Particular attention must be paid to the relationship to alleged exposure and symptoms. Irritation causes symptoms during exposure that cease afterwards unless clinically obvious damage has occurred. Tobacco smoke and nicotine may also cause symptoms. A full examination, both externally and internally of the nose, mouth and eyes should be undertaken. The presence of squamous metaplasia is important. The validity of a claimant's symptoms must be checked against the medical records. Details of all occupations, compounds and protection should be noted. Manufacturing data on the compounds should also be obtained. The Health and Safety Executive publish occupational exposure limits for many industrial chemicals. Allergen-specific IgE may be raised when an allergy is considered to cause the occupational rhinitis. Nasal challenge tests have been used in Scandinavia to diagnose allergic occupational rhinitis. The sense of smell should be tested. There are two approaches, detecting threshold or recognition, which is suprathreshold. When present, three degrees of social effect occur: impairment, disability and handicap. The degree depends on the occupation of the individual.

Chemical Industry↗

PubMed1978

Carcinoma of the tonsillar region. Aspects on treatment modalities with reference to a study on patients treated by irradiation.

Irradiation is the most common form of treatment of tonsillar region carcinomas in Scandinavia. During recent years, encouraging results have been reported when surgery has been performed. Therefore, an effort was made to compare different treatment principles on the basis of a study on patients treated by irradiation. This retrospective study comprised 37 patients over a 20-year period. The relative 5-year survival was 33%. Most of the patients died in the next two years after diagnosis. Seventy-three percent of the patients initially had signs of regional metastasis. Hardly 20% of these were still alive after 5 years, while patients without evidence of metastasis had a 5-year survival of 50%. Neither the size, nor the histopathological features of the primary tumor seemed to affect the incidence of regional metastasis. The duration of symptoms before diagnosis, however, seemed to influence prognosis. Surgical consideration alone, or in combination with irradiation, should be made in cases with large primary tumor with regional lymph node involvement. In other cases, however, there was no evidence suggesting surgery as a better form of therapy than irradiation alone.

Humans↗

PubMed2000

Endocrine disruptors and human health--is there a problem? An update.

It has been hypothesized that environmental exposure to synthetic estrogenic chemicals and related endocrine-active compounds may be responsible for a global decrease in sperm counts, decreased male reproductive capacity, and breast cancer in women. Results of recent studies show that there are large demographic variations in sperm counts within countries or regions, and analyses of North American data show that sperm counts have not decreased over the last 60 years. Analyses of records for hypospadias and cryptorchidism also show demographic differences in these disorders before 1985; however, since 1985 rates of hypospadias have not changed and cryptorchidism has actually declined. Temporal changes in sex ratios and fertility are minimal, whereas testicular cancer is increasing in most countries; however, in Scandinavia, the difference between high (Denmark) and low (Finland) incidence areas are not well understood and are unlikely to be correlated with differences in exposure to synthetic industrial chemicals. Results from studies on organochlorine contaminants (DDE/PCB) show that levels were not significantly different in breast cancer patients versus controls. Thus, many of the male and female reproductive tract problems linked to the endocrine-disruptor hypothesis have not increased and are not correlated with synthetic industrial contaminants. This does not exclude an endocrine-etiology for some adverse environmental effects or human problems associated with high exposures to some chemicals.

Adult↗

PubMed1978

Effect of H+ ion activity and Ca2+ on the toxicity of metals in the environment.

The role of acidity in determining and restricting plant distribution and performance is discussed. In soils especially, a key effect of H+ ion concentration is on the solubility of potentially toxic heavy metals such as aluminum, managenese, zinc, iron, copper, and nickel. Al has been reported from many studies since the 1920's as the key determining toxic factor in acid soils. Some acid-tolerant species have been shown to be especially tolerant of Al, and mechanisms of tolerance have been suggested. Mn is also a commonly toxic factor at soil pH less than 5.0. Calcium has been shown to alleviate Mn toxicity. Low pH soils are also generally low in Ca, K, Na, and P; all essential major elements for plant growth. In lakes and marine situations acidic waters are uncommon as the waters are buffered. Calcium is again ameliorative of metal toxicities. The pH, redox, and valency state are critical in determining nutrient availability and metal speciation. Recent increases in the H+ ion content of precipitation have caused increased acidities of freshwater lakes in Scandinavia and eastern North America, which have depleted biota, including fish populations.

Animals↗

PubMed1983

Bioassay of extracts of ambient particulate matter.

Organic extracts from airborne particles collected at various sites in Scandinavia have been tested for mutagenicity in the Ames Salmonella/microsome assay. Extracts from particles in the respirable size fraction (diameter less than 3 microns) were mutagenic with and without metabolic activation. The mutagenic activity varied from day to day, mainly due to variations in meteorological parameters, especially wind speed and atmospheric stability. A seasonal variation could also be observed, with the highest average values in winter time. Samples collected in urban areas were considerably more mutagenic than samples from background areas. The results suggest that exhaust from motor vehicles are the most important source of mutagenic particles in urban areas. Comparison of roof top samples with street level samples indicated that atmospheric reactions cause transformation of nonpolar compounds in the primary emission to more oxygenated mutagenic compounds. It is, however, not known to which degree this causes an overall increase of the mutagenic activity. The mutagenic activity of emissions from stationary combustion sources have also been studied, and residential heating by burning solid fuels in small combustion units have been shown to be a major contributor to mutagens in the environment.

Air Pollutants↗

PubMed1999

International trends in rates of hypospadias and cryptorchidism.

Researchers from seven European nations and the United States have published reports of increasing rates of hypospadias during the 1960s, 1970s, and 1980s. Reports of increasing rates of cryptorchidism have come primarily from England. In recent years, these reports have become one focus of the debate over endocrine disruption. This study examines more recent data from a larger number of countries participating in the International Clearinghouse for Birth Defects Monitoring Systems (ICBDMS) to address the questions of whether such increases are worldwide and continuing and whether there are geographic patterns to any observed increases. The ICBDMS headquarters and individual systems provided the data. Systems were categorized into five groups based on gross domestic product in 1984. Hypospadias increases were most marked in two American systems and in Scandinavia and Japan. The increases leveled off in many systems after 1985. Increases were not seen in less affluent nations. Cryptorchidism rates were available for 10 systems. Clear increases in this anomaly were seen in two U.S. systems and in the South American system, but not elsewhere. Since 1985, rates declined in most systems. Numerous artifacts may contribute to or cause upward trends in hypospadias. Possible "real" causes include demographic changes and endocrine disruption, among others.

Cohort Effect↗

PubMed2001

An overview of reasons for the placement and replacement of restorations.

AIM: Surveys on reasons for the placement and replacement of restorations have been conducted in various countries. The purpose of this paper is to bring together and review the data of 10 such surveys with similar methodology. METHOD: The studies reviewed are all based on the protocol described by Mjör in 1981. RESULTS: The surveys reviewed provide data on the reasons for the placement and replacement of a total of 32,777 restorations. Notwithstanding differences between countries, different groups of practitioners and minor variations in methodology, the data included in the selected surveys indicate that everyday clinical practice in Scandinavia, UK and USA during the 1980s and 1990s has involved more replacement than initial restorations, with the ratio of initial to replacement restorations ranging from 1:1.1 to 1:2.4 for amalgam and 1:1.1 to 1:3.8 for composite materials. Primary caries has been consistently found to be the principal reason for the provision of initial restorations of amalgam and composite. The principal reason for the replacement of restorations of amalgam and composite has remained secondary caries as diagnosed clinically. Material failures (marginal degradation, discoloration, bulk fracture and loss of anatomic form) accounted for the replacement of more restorations of composite than amalgam. Recent surveys have reported secondary caries as the principal cause of failure of restorations of glass-ionomer cements and related materials. CONCLUSIONS: The clinical diagnoses of caries may continue to be found to account for the placement and replacement of most intracoronal restorations. Surveys of the type reviewed provide valuable insight into patterns of provision of dental care and highlight research priorities in relation to direct restorations.

Composite Resins↗

PubMed1999

Latanoprost in the treatment of glaucoma and ocular hypertension.

Latanoprost (Xalatan) is a prostaglandin F(2alpha) analog prodrug which is activated when hydrolyzed in the cornea and plasma. Latanoprost reduces the intraocular pressure (IOP) by increasing uveoscleral outflow. Other locally applied medications reduce IOP either by increasing the outflow of fluid through the trabecular drainage system or by reducing the production of fluid in the eye. Latanoprost, which is used topically in the eye at the low dose of 0.005% once daily, has been shown in phase III studies carried out in Scandinavia, the U.K. and the U.S. to be capable of lowering the IOP in patients with open-angle glaucoma and ocular hypertension by 35%. This low IOP is maintained over at least a 2-year period. Latanaprost is as effective, or possible slightly more effective than timolol in its pressure reducing effects. Additional pressure reduction can be achieved by adding latanoprost to existing glaucoma medications. Because latanoprost is rapidly metabolized outside the eye, systemic side effects do not occur. Increased iris pigmentation occurs in at least 10% of hazel (but not blue or dark-eyed patients). So far no ocular problem has occurred because of the increased production of pigment which is not released from the iris. Isolated cases of cystoid macular edema have occurred, so that anyone complaining of reduction of vision while using the drug should be fully investigated.

Journal Article↗

PubMed1996

Oral empiric treatment of community-acquired pneumonia. A multicenter, double-blind, randomized study comparing sparfloxacin with roxithromycin. The Scandinavian Sparfloxacin Study Group.

STUDY OBJECTIVE: Comparison of efficacy and safety of sparfloxacin (Spfx) vs roxithromycin (ROXI) for treatment of community-acquired pneumonia (CAP). DESIGN: Multicenter, double-blind, randomized study. SETTING: Twenty-three university and community hospitals in Scandinavia. PATIENTS: Three hundred four adults (> or = 18 years of age) with CAP treated as outpatients (25%) or inpatients (75%). INTERVENTIONS: Randomization 1:1 to Spfx, 400 mg on day 1, then 200 mg once daily, or ROXI, 150 mg twice daily, 10 to 14 days. Safety and efficacy analyses in intention-to-treat (ITT) and evaluable populations. RESULTS: Three hundred three of 304 patients were included in the ITT and safety analyses and 260 (86%) were evaluable at the end of follow-up. Streptococcus pneumoniae was the cause of pneumonia in 62 (20%) patients (11 with bacteremia), Chlamydia pneumoniae in 40 (13%), and Mycoplasma pneumoniae in 38 (13%) patients. The success rates for Spfx and ROXI at the end of follow-up were 82% and 72%, respectively, in the ITT population, and 94% and 79%, respectively, in the evaluable population. The odds ratio Spfx/ROXI for success was 4.5 (95% confidence interval, 1.9, 10.8) for the evaluable population. Both drugs were, overall, equally safe. GI symptoms were the most common adverse experiences in both groups. Prolongation of QTc, without clinical symptoms, was seen in 3% of Spfx patients and in 1% of ROXI patients, and photosensitivity, mostly mild to moderate, was seen in 5% of the Spfx group. CONCLUSIONS: Oral treatment with Spfx was superior to ROXI for the treatment of moderately severe CAP. Spfx was effective for all isolated pathogens, including S pneumoniae, and may be an alternative for empiric treatment of CAP, especially in areas with a high incidence of beta-lactam-resistant pneumococci.

Administration, Oral↗

PubMed1998

[Effect of mobile phone on life-saving and life-sustaining systems].

Since the beginning of the nineties there have been warnings not to use mobile phones in the vicinity of medical devices. Functional failures of dialysis machines, respirators and defibrillators prompted the banning of their use in many hospitals in Scandinavia, and then in other countries. Since we believe that a general ban in hospitals is problematic, we decided to investigate the influence of mobile telephone on life-saving and/or life-support systems, with the aim of establishing rules for its use in hospitals. We investigated available phones of varying power of the C-, D- and E-net, as also of a cordless phone meeting the DECT standard. The aim was to identify the devices susceptible to interference and determine the minimum distances at which interference occurred. A total of 224 devices classified into 23 types of devices were examined. Nine different sets of transmission conditions were applied, giving a total of 2016 tests. Our results permit the conclusion that the ban on mobile phones in hospitals is based not on actual events, but on theoretical considerations in the absence of any practical information on the actual susceptibility of devices and their reaction to the electromagnetic fields involved. The fact that hazardous situations are very rare is due firstly to the need for the simultaneous occurrence of four coincidences, and the fail-save feature of medical devices. We would therefore recommend that all life-saving and life-support systems that can also be used outside the hospital should be made mobile phone-proof. When apnoea monitors and respirators are protected from such interference, hazardous situations could be avoided by establishing the rule: "No portables, and mobile phones only at a distance of at least 1 metre from medical devices". With regard to emergency telephones, the minimum distance to medical devices should be at least 1.5 metres.

Electromagnetic Fields↗

PubMed2003

Drunkenness among young people: a cross-national comparison.

OBJECTIVE: International studies show a rise in drunkenness among young people in recent years. In this study the number of drunkenness occasions among 15-year old students in 22 countries is reported. The cross-national association between drunkenness, on the one hand, and the frequency of alcohol intake and the preference for distilled spirits, on the other, is described. Variation between countries is examined on the basis of national characteristics, including national prevention policies. METHOD: Data on alcohol use were taken from the 1998 World Health Organization (WHO) collaborative, cross-national survey on Health Behaviour of School-Aged Children. The multinational representative sample consisted of 10,951 male and 11,451 female (drinking) students. County characteristics were derived from the WHO Global Alcohol Database. Hierarchical Generalized Linear Model was used to analyze the effects of country characteristics on individual drunkenness. RESULTS: The lifetime prevalence of drunkenness was 57.1% for males and 50.4% for females. The number of drunkenness occasions showed a significant variation in the 22 countries. The correlation between drunkenness and preference for distilled spirits was positive in 21 countries and strong (Spearman's p > 0.40) in some eastern countries. Geographic location turned out to be an important country-level association with drunkenness and its predictors. Southern European countries showed moderate associations, whereas strong associations were found in Scandinavia, the Baltic countries and Russia. CONCLUSIONS: Cultural differences in alcohol use exist, and frequency of alcohol intake and use of spirits influence drunkenness. Despite the potential influence of preventive policy measures on drunkenness, no preventive effect of the measures included in this study was found.

Adolescent↗

PubMed2000

Developmental dysplasia of the hip practice guideline: technical report. Committee on Quality Improvement, and Subcommittee on Developmental Dysplasia of the Hip.

OBJECTIVE: To create a recommendation for pediatricians and other primary care providers about their role as screeners for detecting developmental dysplasia of the hip (DDH) in children. PATIENTS: Theoretical cohorts of newborns. METHOD: Model-based approach using decision analysis as the foundation. Components of the approach include the following: PERSPECTIVE: Primary care provider. OUTCOMES: DDH, avascular necrosis of the hip (AVN). OPTIONS: Newborn screening by pediatric examination; orthopaedic examination; ultrasonographic examination; orthopaedic or ultrasonographic examination by risk factors. Intercurrent health supervision-based screening. PREFERENCES: 0 for bad outcomes, 1 for best outcomes. MODEL: Influence diagram assessed by the Subcommittee and by the methodology team, with critical feedback from the Subcommittee. EVIDENCE SOURCES: Medline and EMBASE search of the research literature through June 1996. Hand search of sentinel journals from June 1996 through March 1997. Ancestor search of accepted articles. EVIDENCE QUALITY: Assessed on a custom subjective scale, based primarily on the fit of the evidence to the decision model. RESULTS: After discussion, explicit modeling, and critique, an influence diagram of 31 nodes was created. The computer-based and the hand literature searches found 534 articles, 101 of which were reviewed by 2 or more readers. Ancestor searches of these yielded a further 17 articles for evidence abstraction. Articles came from around the globe, although primarily Europe, British Isles, Scandinavia, and their descendants. There were 5 controlled trials, each with a sample size less than 40. The remainder were case series. Evidence was available for 17 of the desired 30 probabilities. Evidence quality ranged primarily between one third and two thirds of the maximum attainable score (median: 10-21; interquartile range: 8-14). Based on the raw evidence and Bayesian hierarchical meta-analyses, our estimate for the incidence of DDH revealed by physical examination performed by pediatricians is 8.6 per 1000; for orthopaedic screening, 11.5; for ultrasonography, 25. The odds ratio for DDH, given breech delivery, is 5.5; for female sex, 4.1; for positive family history, 1.7, although this last factor is not statistically significant. Postneonatal cases of DDH were divided into mid-term (younger than 6 months of age) and late-term (older than 6 months of age). Our estimates for the mid-term rate for screening by pediatricians is 0.34/1000 children screened; for orthopaedists, 0.1; and for ultrasonography, 0.28. Our estimates for late-term DDH rates are 0.21/1000 newborns screened by pediatricians; 0.08, by orthopaedists; and 0.2 for ultrasonography. The rates of AVN for children referred before 6 months of age is estimated at 2.5/1000 infants referred. For those referred after 6 months of age, our estimate is 109/1000 referred infants. The decision model (reduced, based on available evidence) suggests that orthopaedic screening is optimal, but because orthopaedists in the published studies and in practice would differ, the supply of orthopaedists is relatively limited, and the difference between orthopaedists and pediatricians is statistically insignificant, we conclude that pediatric screening is to be recommended. The place of ultrasonography in the screening process remains to be defined because there are too few data about postneonatal diagnosis by ultrasonographic screening to permit definitive recommendations. These data could be used by others to refine the conclusions based on costs, parental preferences, or physician style. Areas for research are well defined by our model-based approach.

Decision Support Techniques↗

PubMed1996

[Implications in terms of costs and manpower of using the Scandinavian dental care model in Brazil].

The implications in terms of dental manpower and costs of applying the Scandinavian system of dental care in Brazil are specified and analysed. Two societies were chosen for study: those of Sweden, in Scandinavia and Santa Catarina, State in southern Brazil. The theoretical analysis of the implications was undertaken on the basis of an estimate of dental and auxiliary manpower required to deal with the high levels of oral disease and needs (caries, teeth needing extraction, periodontal diseases and the need for full dentures) in Santa Catarina. This estimate was undertaken by means of the World Health Organization-Fédération Dentaire Internationale (WHO-FDI) Model "Health Through Oral Health" (1989). The implications in costs, taking the total Swedish expenditure per dentist as a basis, were calculated and applied to the manpower calls for by the WHO-FDI model. The high costs resulting showed that the application of the Swedish model of dental care to Santa Catarina would be unrealistic. The implications in terms of manpower were calculated by applying the manpower ratios considered desirable in Sweden to Santa Catarina. In order to achieve the Swedish dentist: population ration, Santa Catarina would need 85% more dentists that it had in 1990. Regarding auxiliary personnel, the Brazilian State of Santa Catarina would need to train a large number of new personnel in order to attain the Swedish auxiliary: dentist ratio. In the light of the findings of this study, the adoption of the Swedish model of providing dental care by Santa Catarina in terms of costs and manpower is not feasible. Therefore, alternative approaches for the improvement of oral health in Santa Catarina and in the rest to Brazil should be sought. These approaches should take consider political, cultural and socio-economic aspects of Brazilian society into consideration.

Adult↗

PubMed2006

A resource-depletion model of forest insect outbreaks.

Detailed analyses of thresholded ecological interactions can improve our understanding of the transition from aperiodic to periodic dynamics. We develop a threshold model of the population dynamics of outbreaking bark beetle populations that alternate between non-epidemic and epidemic behavior. The model involves accumulation of resources during low-density periods and depletion during outbreaks. The transition between the two regimes is caused by disturbance events in the form of major tree felling by wind. The model is analyzed with particular reference to the population dynamics of the spruce bark beetle (Ips typographus) in Scandinavia for which a comprehensive literature allows full parameterization. The fairly constant outbreak lengths and the highly variable waiting time between outbreaks that are seen in the historical records of this species agree well with the predictions of the model. The thresholded resource-depletion dynamics result in substantial variation in the degree of periodicity between stochastic realizations. The completely aperiodic tree colonizations are partly predictable when the timing of the irregular windfall events are known. However, the predictability of inter-outbreak periods is low due to the large variation of cases falling most frequently in the middle between the extremes of purely nonperiodic (erratic) and periodic (cyclic) fluctuations.

Animals↗

PubMed2000

Occurrence of Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, and Prevotella intermedia in progressive adult periodontitis.

BACKGROUND: Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, and Prevotella intermedia are the major periodontal bacteria species in most forms of progressive periodontitis in Scandinavia and the United States. The occurrence of periodontal pathogens appears to be different in subjects of different ethnic origin, and geographical factors may influence the distribution of these species. METHODS: The occurrence of A. actinomycetemcomitans, P. gingivalis, and P. intermedia was determined using a DNA probe in progressive adult periodontitis in Chileans. Sixty patients (mean age 43.6 +/- 8 years) who had not previously received any type of periodontal therapy were selected. Bleeding on probing, probing depth, and clinical attachment level measurements were made with an automated probe. Patients were monitored at 2-month intervals until at least 2 sites exhibited > or =2 mm attachment loss. Two subgingival plaque samples from active sites were taken in 56 subjects and matched with 2 plaque samples from inactive sites in the same individuals. RESULTS: P. gingivalis was found in 75% of active sites and in 59.7% of inactive sites in 96% of the patients (P = 0.022). P. gingivalis at high levels of detection was significantly more frequent in active sites (48.2%) than in inactive sites (31.2%) (P = 0.014). A. actinomycetemcomitans was detected in 6.25% of active sites and in 12.5% of inactive sites in 11.6% of patients. P. intermedia was found in 33% of patients and at a significantly higher proportion in active sites (49.1%) than in inactive sites (30.3%) (P = 0.006). There was a significantly higher proportion of inactive sites (34.8%) than active sites (19.6%) without any of the 3 pathogens (P = 0.016). Bleeding on probing was significantly more associated with active sites with high levels of P. gingivalis and with active sites with P. intermedia than with inactive sites. CONCLUSIONS: A high prevalence of P. gingivalis and P. intermedia was found in adult periodontitis, and the occurrence of these bacteria appears to be higher in Chileans than in other populations. No apparent association exists between A. actinomycetemcomitans and progressive adult periodontitis in Chileans.

Actinobacillus Infections↗

PubMed1998

How aspartame prevents the toxicity of ochratoxin A.

The ubiquitous mycotoxin ochratoxin A (OTA) is found as a frequent contaminant of a large variety of food and feed and beverage such as beer, coffee and win. It is produced as a secondary metabolite of moulds from Aspergillus and Penicillium genera. Ochratoxin A has been shown experimentally to inhibit protein synthesis by competition with phenylalanine its structural analogue and also to enhance oxygen reactive radicals production. The combination of these basic mechanisms with the unusual long plasma half-life time (35 days in non-human primates and in humans), the metabolisation of OTA into still active derivatives and glutathione conjugate both potentially reactive with cellular macromolecules including DNA could explain the multiple toxic effects, cytotoxicity, teratogenicity, genotoxicity, mutagenicity and carcinogenicity. A relation was first recognised between exposure to OTA in the Balkan geographical area and Balkan Endemic Nephropathy (BEN) with a high incidence (nearly 50 times higher than normal) of urinary tract tumours. Exposure rates of OTA are measurable in blood of humans and animals and are established in several countries including Scandinavia, Germany, France, Italy, Canada, Japan and Northern Africa mainly Tunisia and Egypt. The impact of OTA exposure in non- endemic areas in the world is not known, the rates of exposure being not correlated with the disease records, especially in developed countries, due to lake of well- designed epidemiological studies, genetic polymorphism and maybe to dietary contents of radical scavengers and antioxidants. However the incidence and mortality rates of renal cancer are increasing in European countries and Northern Africa which could be a global resultant of human exposure to natural compounds in food such as mycotoxins and especially ochratoxin A. In addition to special care to prevent the growth of moulds and detoxification measures there was a need for the prevention of the OTA-induced toxic effects once the toxin is ingested. For this purpose several compound have been studied including some therapeutic agents such as piroxicam which cannot be proposed for a large scale use in humans for preventive purpose. Among other compounds, Aspartame, already used as sweetener has shown a real effectiveness in vivo confirmed largely in vitro. When rats exposed to OTA (289 micrograms/kg) by oral route every two days are given 25 mg/kg similarly for several weeks, all the toxic effects including genotoxicity are very efficiently prevented as shown for example by the disappearance of DNA- adducts in tissues excised from treated animals. Aspartame is also effective in washing out the toxin when given afterwards to animals intoxicated by the same oTA doses for several weeks. In vitro, provided that it is added in cell culture medium before OTA it prevent significantly the inhibition of protein synthesis and lipid peroxidation induced by the toxin. Obviously the molecular mechanism mediating the preventive effect of Aspartame is the delivery of phenylalanine by cleavage of the peptide but also the direct effect of the peptide on the bending capacity and transport of the toxin in vivo and in vitro. As a matter of fact when Aspartame is given to animals or added in culture medium the amount of peptide found unchanged (10-15%) may account for a preventive effect as entire peptide.

Animals↗

PubMed2001

Behavioural effects of the new anticonvulsants.

Of the 9 new anticonvulsants that have been marketed recently in the UK or US, a number appear to have either adverse or beneficial effects on behaviour. There is now a considerable database of information, in terms of the number of patients treated and/or the number of published reports, on vigabatrin, lamotrigine, gabapentin and topiramate. Oxcarbazepine has been available in some centres for several years and there is extensive experience with the drug in Scandinavia. It appears that the profile of adverse and beneficial effects is similar to that of carbamazepine. Behavioural effects have probably been greatest with vigabatrin, with psychosis, depression and other behavioural problems recorded, but the use of this drug has been limited because of the concern about visual field constriction. The cognitive and behavioural effects of topiramate have caused concern, but these may be much less of a problem if lower starting dosages and escalation rates are used. Psychosis and depression have been associated with topiramate, as they have with another carbonic anhydrase inhibiting drug, zonisamide. Although zonisamide has been used for many years in Japan and Korea, experience elsewhere with this drug is currently very limited. Gabapentin seems to be less associated with adverse behavioural effects than some of the other new anticonvulsant drugs. The reports of behavioural disturbance with gabapentin in children may be related to dose escalation. Behavioural disturbance as a direct result of lamotrigine seems to be uncommon, although indirect effects on behaviour, through the so-called 'release phenomenon' from improved seizure control and consequent ability to misbehave, can occur. Positive behavioural effects have been described with several of the new anticonvulsants, particularly gabapentin, lamotrigine and oxcarbazepine; all of these drugs may have mood-levelling effects that could be of value in treating affective disorders. The information on tiagabine and levetiracetam is too limited to allow any firm conclusions to be drawn with regard to positive or negative behavioural effects. When interpreting reports of behavioural changes with anticonvulsants, it is important to avoid attributing the effect to the drug when one or more of the other multiple causes of behavioural disturbance in people with epilepsy may be responsible or when an indirect effect such as 'forced normalisation' may be the cause. Many of the published studies are retrospective and unblinded rather than double-blind, placebo-controlled, prospective trials, implying that much of the data must be interpreted with caution at this stage.

Anticonvulsants↗

PubMedDate not supplied

Clinical pharmacokinetics of phenytoin.

Phenytoin is a relatively insoluble weak acid, usually administered as the sodium salt. Bioavailability is dependent upon particle size and problems of generic inequivalence have therefore arisen, particularly in Scandinavia. The drug has a moderately large volume of distribution and is approximately 90% bound to plasma proteins. Clinically important displacement can be caused by bilirubin and several drugs, particularly sodium valproate, which is often combined with phenytoin. Displacement will lower the total serum concentration but will little affect the free drug concentration. The metabolism of phenytoin to the major metabolite, 5-(p-hydroxyphenyl)-5-(phenylhydantoin, is saturable, giving rise to a non linear dose-serum concentration relationship. Therefore, the dose range compatible with a therapeutic serum concentration is narrow within subjects, and monitoring serum concentrations is of particular value in dosage tailoring. In renal failure, the binding of phenytoin to plasma proteins is reduced and therefore a lower range of serum drug concentrations is compatible with therapeutic control. In liver disease, binding may also be impaired but delayed metabolism may occur in addition. During pregnancy the serum concentration may fall progressively as pregnancy advances, probably due to an increased rate of metabolism. Phenytoin readily crosses the placenta, and is metabolised rapidly by the neonate exposed in utero.

Aged↗