Worsening of the Toxic Effects of (±)Cis-4,4'-DMAR Following Its Co-Administration with (±)Trans-4,4'-DMAR: Neuro-Behavioural, Physiological, Immunohistochemical and Metabolic Studies in Mice.

4,4'-Dimethylaminorex (4,4'-DMAR) is a new synthetic stimulant, and only a little information has been made available so far regarding its pharmaco-toxicological effects. The aim of this study was to investigate the effects of the systemic administration of both the single (±)cis (0.1-60 mg/kg) and (±)trans (30 and 60 mg/kg) stereoisomers and their co-administration (e.g., (±)cis at 1, 10 or 60 mg/kg + (±)trans at 30 mg/kg) in mice. Moreover, we investigated the effect of 4,4'-DMAR on the expression of markers of oxidative/nitrosative stress (8-OHdG, iNOS, NT and NOX2), apoptosis (Smac/DIABLO and NF-κB), and heat shock proteins (HSP27, HSP70, HSP90) in the cerebral cortex. Our study demonstrated that the (±)cis stereoisomer dose-dependently induced psychomotor agitation, sweating, salivation, hyperthermia, stimulated aggression, convulsions and death. Conversely, the (±)trans stereoisomer was ineffective whilst the stereoisomers' co-administration resulted in a worsening of the toxic (±)cis stereoisomer effects. This trend of responses was confirmed by immunohistochemical analysis on the cortex. Finally, we investigated the potentially toxic effects of stereoisomer co-administration by studying urinary excretion. The excretion study showed that the (±)trans stereoisomer reduced the metabolism of the (±)cis form and increased its amount in the urine, possibly reflecting its increased plasma levels and, therefore, the worsening of its toxicity.

Restless nocturnal eating: a common feature of Willis-Ekbom Syndrome (RLS).

STUDY OBJECTIVES: To determine the frequency of nocturnal eating (NE) and sleep related eating disorder (SRED) in restless legs syndrome (RLS) versus psychophysiological insomnia (INS), and the relationship of these conditions with dopaminergic and sedative-hypnotic medications. DESIGN: Prospective case series. SETTING: Sleep disorders center. PATIENTS: Newly diagnosed RLS or INS. INTERVENTION: RLS or INS pharmacotherapy with systematic follow up interview for NE/SRED. MEASUREMENTS AND RESULTS: Patients presenting with RLS (n = 88) or INS (n = 42) were queried for the presence of NE and SRED. RLS patients described nocturnal eating (61%) and SRED (36%) more frequently than INS patients (12% and 0%; both p < 0.0001). These findings were not due to arousal frequency, as INS patients were more likely to have prolonged nightly awakenings (93%) than RLS patients (64%; p = 0.003). Among patients on sedative-hypnotics, amnestic SRED and sleepwalking were more common in the setting of RLS (80%) than INS (8%; p < 0.0001). Further, NE and SRED in RLS were not secondary to dopaminergic therapy, as RLS patients demonstrated a substantial drop (68% to 34%; p = 0.0026) in the frequency of NE after dopamine agents were initiated, and there were no cases of dopaminergic agents inducing novel NE or SRED. CONCLUSION: NE is common in RLS and not due to frequent nocturnal awakenings or dopaminergic agents. Amnestic SRED occurs predominantly in the setting of RLS mistreatment with sedating agents. In light of previous reports, these findings suggest that nocturnal eating is a non-motor manifestation of RLS with several clinical implications discussed here.

Frequency and predictors of mass psychogenic illness.

BACKGROUND: Mass psychogenic illness refers to outbreaks of illness attributed to a toxic agent but for which no plausible organic cause is found. We determined the frequency and predictors of mass psychogenic illness within a sample of chemical incidents. METHODS: Information was collected on a random sample of 280 chemical incidents. We developed consensus operational criteria for mass psychogenic illness and estimated its frequency. We then assessed environmental, emergency, and health service indicators for their association with mass psychogenic illness. RESULTS: Nineteen "chemical incidents" were probable episodes of mass psychogenic illness. This represented 16% of incidents for which people reported symptoms and 7% of all incidents. Odor was a robust predictor of mass psychogenic illness. These illnesses were especially likely to occur in schools or healthcare facilities. CONCLUSIONS: A substantial minority of chemical incidents may be mass psychogenic illness.

Three cases of delusional parasitosis caused by dopamine agonists.

We report three cases of delusional parasitosis (DP) in patients with well-established Parkinson's disease, all of whom were taking dopamine agonists. In all three cases, the DP resolved rapidly when the drug was withdrawn.

Symptom screening in detection of occupational solvent-related encephalopathy.

OBJECTIVES: Sensitive and easily applicable methods are needed for early detection of central nervous system adverse effects related to occupational solvent exposure. The present study evaluates how symptom screening works in practice. METHODS: A cross-sectional questionnaire survey was conducted on 2,000 construction workers, including painters and carpenters, in Finland. Scores were calculated for symptoms relevant for chronic solvent encephalopathy (CSE). Responses on exposure and health were compared between subjects with high score (N = 28) and all other respondents. The respondents with the highest scores, regardless of their occupation and exposure, were invited for clinical examination to investigate the aetiologies of the symptoms. If the examination resulted in a suspicion of CSE, a multidisciplinary differential diagnostic follow-up procedure was performed. RESULTS: The respondents with highest symptom scores were more exposed to solvents than those with lower scores (P < 0.001) and reported more often physician-diagnosed diseases, especially psychiatric disorders (P < 0.001). They also consumed more alcohol (P = 0.005) and were more often unemployed or unable to work (P < 0.001). In the clinical examination, sleep disturbances, somatic disorders, depression, unemployment, and alcohol use were commonly found in addition to considerable solvent exposure history and clinical neurological findings. Further examinations and a diagnostic follow-up verified three cases of encephalopathy. One case was a CSE, an occupational disease. The other two encephalopathy cases had multifactorial aetiology including solvents. CONCLUSIONS: Screening in active workforce for symptoms of cognitive dysfunction identifies highly solvent-exposed workers and also reveals occupational and non-occupational cases of encephalopathy. Evaluation of differential diagnostic conditions is essential in the detection of CSE. A stepwise model is proposed.

Approach to patients with suspected hypersensitivity to local anesthetics.

Adverse reactions to local anesthetics are relatively common, but true IgE-mediated hypersensitivity is extremely rare. Fortunately, the vast majority of adverse reactions occur via nonimmunologic means, but considerable confusion still exists among providers. We conducted a review of the literature to determine if earlier estimates of IgE-mediated allergy are consistent with current reports and whether current management strategies are consistent with these findings. We identified several confounding variables involved in the evaluation, including the roles of preservatives/additives, epinephrine, latex, and inadequate testing procedures. These problems may cause significant diagnostic challenges for clinicians. It is in fact much more likely that there is an alternate diagnosis, and in many cases clinicians can begin the evaluation in the office. When local anesthetic allergy is still suspected, the patient should be referred to an allergist for testing to determine if the suspected culprit drug can be safely used, or, if necessary, identify a suitable alternative.

Urinary pentachlorophenol in painters and bricklayers in a four-years time interval after the PCP prohibition ordinance in Germany.

Pentachlorophenol (PCP) was widely used as a wood preservative in Germany until 1989, when it was prohibited by law. Within a cross-sectional study we investigated the internal PCP exposure of painters and bricklayers between one year and four years after the ban. PCP was analysed in post-shift urine samples of 189 painters and 148 bricklayers by gas chromatography and electron capture detection (GC-ECD). The median PCP concentration in the urine of painters was 2.4 microg/g creatinine (range: 0.2-52 microg/g creatinine). For the bricklayers a range of 0.1-25 microg/g creatinine (median: 1.8 microg/g creatinine) was determined. The difference between both groups was statistically significant, pointing to a small additional uptake of PCP by the painters probably from an exposure to contaminated wood surfaces or residual PCP containing preservatives. The biomonitoring results for both groups coincided with background values of the general population at that time.

[Psychological side effects during interferon-alpha therapy -- a case study]. / Psychische Nebenwirkungen unter Therapie mit Interferon-alpha -- Eine Fallstudie.

OBJECTIVE: Psychological side effects of the therapy with interferon-alpha (IFN-alpha) have frequently been reported. The symptomatology varies, although there seems to be a predominance of depressive complaints. Mediating somatopsychological vs. psychosomatic pathways remain unknown so far. PATIENT: We describe the case of a 26-year old female inpatient suffering from hepatitis C infection. During medical treatment with interferon-alpha, a transfer to a psychosomatic unit became necessary due to increasing agitation, somatization and a lacking response to psychopharmacological medication. RESULTS: After the discontinuation of IFN-alpha-treatment, the patient's gradual emotional stabilization could be attained. In psychotherapy, inner conflicts as well as fears about possible side effects of the medication were worked through. After discharge, parallel to an ambulatory psychotherapy, the IFN-alpha medication was readministered and completed successfully. CONCLUSIONS: As long as aetiology and mechanisms of psychic side effects of IFN-alpha-treatment remain unclear, ward-based integrative psychosomatic psychotherapy can be supportive and enlightening with regard to psychosocial factors of influence on the IFN-alpha-induced side effects.

Central neurological abnormalities and multiple chemical sensitivity caused by chronic toluene exposure.

Multiple chemical sensitivity (MCS) is a syndrome in which multiple symptoms occur with low-level chemical exposure; whether it is an organic disease initiated by environmental exposure or a psychological disorder is still controversial. We report a 38-year-old male worker with chronic toluene exposure who developed symptoms such as palpitation, insomnia, dizziness with headache, memory impairment, euphoria while working, and depression during the weekend. Upon cessation of exposure, follow-up neurobehavioural tests, including the cognitive ability screening instrument and the mini-mental state examination, gradually improved and eventually became normal. Although no further toluene exposure was noted, non-specific symptoms reappeared whenever the subject smelled automotive exhaust fumes or paint, or visited a petrol station, followed by anxiety with sleep disturbance. During hospitalization for a toluene provocation test, there was no difference between pre-challenge and post-challenge PaCO(2), PaO(2), SaO(2) or pulmonary function tests, except some elevation of pulse rate. The clinical manifestations suggested that MCS was more relevant to psychophysiological than pathophysiological factors.

Multidisciplinary examination of patients with illness attributed to dental fillings.

OBJECTIVE AND METHODS: In 1993, a special Amalgam Clinic was established at Huddinge University Hospital. Residents in the Stockholm County area with morbidity attributed to dental fillings ('amalgam disease'), were referred to this clinic. Patients were examined by a dentist (n 428), a physician (n 379), and a psychologist (n 360). Sixty-nine per cent were women and 31% men; the mean patient age was 46 years. RESULTS: Oral symptoms included tender or aching teeth (60%), metallic taste (54%), sore mouth (43%) and dry mouth (43%). Signs of moderate or severe temporomandibular joint dysfunction were found in 81 cases, glossitis in 30 and oral lichen in 26 cases. Common general symptoms included diffuse pain (78%), general weakness (75%), extreme fatigue (68%) and dizziness (68%). Seven per cent of the patients suffered from previously undiagnosed medical conditions (thyroid dysfunction, anaemia, cardiopathy, renal disease, cancer). In 26 subjects, skin patch testing revealed allergy to mercury, gold or palladium. The median concentration of mercury was 10 nmol L-1 in whole blood, 3 nmol L-1 in plasma and 10 nmol L-1 in urine, i.e. normal levels. Earlier mental trauma was common, and in the psychological questionnaire SCL-90, clear tendencies to somatization were found. Only a few cases of severe psychiatric illness were observed. No positive correlation was found between the amount of amalgam and somatic symptoms or psychological effect parameters. CONCLUSIONS: The results do not support the hypothesis that release of mercury from amalgam fillings is the cause of 'amalgam disease', but suggest that there may be various explanations for the patient's complaints.

Studies on the psychosomatic functioning of ill-health according to eastern and western medicine 7. Psychoimmuno-endocrinological changes induced by Kampo medication and relaxation training.

Using the anxiety-affinitive constitution index (AACI) that we created, we measured the degree of the anxiety-affinitive constitution as an equivalent of ill-health for the study of psychoimmuno-endrocrinological changes induced by Kampo medication and relaxation training (RT). With 20 sixth-year Saga Medical School students (average age: 24.8 +/- 1.4) as the subjects, we obtained three results: (1) relaxation training produced lowered STAI trait and state anxiety scores and tended to transform the respiratory pattern from thoracic to abdominal; (2) Kampo medication generated lowered GHQ-30 total scores and lowered the depression factor scores for its symptom components; and (3) Kampo medication for overcoming blood stagnation induced lowered NK cell activity, whereas Kampo medication for providing a tonic effect on vital energy and enriching blood brought about elevated NK cell activity and blood cortisol concentration. These results strongly suggest that while Kampo medication alleviated psychological distress as demonstrated by lowered GHQ-30 scores, RT improved the respiratory pattern, as demonstrated by increased abdominal dominance. The utmost attention must be paid to the prolonged administration of drugs for overcoming blood stagnation because of their possible immunosuppressive action.

Serotonin production in lymphocytes and mercury intolerance.

Patients with suspected illness due to mercury in dental amalgam were classified as tolerant or intolerant depending on their psychosomatic responses following in vivo epicutaneous provocation with low doses (patch test doses) of metallic mercury and phenylmercuric acetate. Ten intolerant patients and nine tolerant patients plus seven healthy amalgam-free and metal non-allergic controls were recruited to the study. Peripheral blood lymphocytes were exposed in vitro to three concentration of mercuric chloride (0.92, 1.83 and 3.68 microM) with and without 10 microg phytohaemagglutinine (PHA)/ml and the release of serotonin into the supernatant was measured. Lymphocytes exposed only to HgCl(2) showed no significant dose-dependent increase of serotonin, but the response of the tolerant patients was significantly higher compared with the controls. No other differences were found. Co-culture with mercuric chloride and PHA showed a statistically significant dose-dependant release of serotonin, but no differences between the three clinical groups could be detected. Thus, our results could not validate the concept of mercury tolerance and intolerance.

Relation between mercury concentrations in saliva, blood, and urine in subjects with amalgam restorations.

The aim was to determine the relationship between mercury content of resting and stimulated saliva, and blood and urine. Eighty subjects participated; 40 of them attributed their self-reported complaints to dental amalgam (patients), the others were matched with respect to age, sex and amalgam restorations (controls). Serum, 24-h urine, resting and chewing stimulated saliva were analyzed for mercury using the ASS-technique. Quality, number, surfaces and total area of amalgam fillings were recorded clinically and using study models. Median (range) mercury levels in serum were 0.67 (0.1-1.52) microgram/l for patients and 0.60 (0.1-1.3) for controls. In urine levels were found to be 0.77 (0.11-5.16) and 0.94 (0.17-3.01) microgram/g creatinine respectively. No significant differences were found between the groups. Resting saliva contained 2.97 (0.10-45.46) micrograms/l in patients and 3.69 (0.34-55.41) in controls (not significant). Chewing mobilized an additional amount of 16.78 (-6.97 to 149.78) micrograms/l in patients and 49.49 (-1.36 to 504.63) in controls (P < or = 0.01). Only a weak correlation was found between mobilized mercury in saliva and serum (r = 0.27; P < or = 0.05) or urine (r = 0.47; P < or = 0.001). For resting saliva the respective values were r = 0.45 (P < or = 0.001) and r = 0.60 (P < or = 0.001). Saliva testing is not an appropriate measure for estimating the mercury burden derived from dental amalgam.