[The "dental amalgam syndrome" - an environmental somatization Syndrome? A comparison between chronic carbon monoxide intoxication and illness related to dental amalgam]. / Amalgamsjukan - ett yttre miljösyndrom? En jämförelse mellan den kroniska koloxidförgiftningen (gengasförgiftningen) och amalgamsjukan.

In 1940, during World War II, restrictions in import of petroleum products to Sweden necessitated the use of producer gas in motor traffic. In the following years, the incidence of acute carbon monoxide intoxications raised steeply. However, many patients with minor but longstanding exposition to producer gas exhibited a neurastenic syndrome (fatigue, headaches and vertigo) thought to be specific. In Stockholm, an epidemic of this syndrome can afterwards be traced to the personal conviction of an internist who also had an important influence on various authorities, leading to a forceful campaign to the public about the dangers of using producer gas. After some years, the frequency and even the existence of a chronic carbon monoxide intoxication was called in question and at the end of the war that diagnosis lost its actuality. In Sweden, oral galvanism attributed to dental amalgam was discussed in mass media in the 1970s, not least by evidence given by some well-known personalities. In the 1980s, the frequency of illness attributed to dental amalgam increased to an important epidemic. The question of the dangers of mercury released from amalgam fillings is still an important issue of debate among dentists and physicians, although the majority remains sceptical. Also medical authorities have found little evidence of the importance of dental amalgam toxicity. A patients organisation, Tandvårdsskadeförbundet, seems to have played a significant part in the acceptance of the syndrome among laymen. Thus, various psychosocial factors seem to have played a role in both syndromes which could thus be conceived as environmental somatization syndromes.

Selective blockade of metabotropic glutamate receptor subtype 5 is neuroprotective.

We have used potent and selective non-competitive antagonists of metabotropic glutamate receptor subtype 5 (mGlu5) -- 2-methyl-6-phenylethynylpyridine (MPEP), [6-methyl-2-(phenylazo)-3-pyridinol] (SIB-1757) and [(E)-2-methyl-6-(2-phenylethenyl)pyridine] (SIB-1893) - to examine whether endogenous activation of this particular metabotropic glutamate receptor subtype contributes to neuronal degeneration. In cortical cultures challenged with N-methyl-D-aspartate (NMDA), all three mGlu5 receptor antagonists were neuroprotective. The effect of MPEP was highly specific because the close analogue, 3-methyl-6-phenylethynylpyridine (iso-MPEP), which did not antagonize heterologously expressed mGlu5 receptors, was devoid of activity on NMDA toxicity. Neuroprotection by mGlu5 receptor antagonists was also observed in cortical cultures challenged with a toxic concentration of beta-amyloid peptide. We have also examined the effect of mGlu5 receptor antagonists in in vivo models of excitotoxic degeneration. MPEP and SIB-1893 were neuroprotective against neuronal damage induced by intrastriatal injection of NMDA or quinolinic acid. These results indicate that mGlu5 receptors represent a suitable target for novel neuroprotective agents of potential application in neurodegenerative disorders.

Selective activation of mGlu4 metabotropic glutamate receptors is protective against excitotoxic neuronal death.

Activation of group III metabotropic glutamate receptors (mGluR4, mGluR6, mGluR7, and mGluR8) has been established to be neuroprotective in vitro and in vivo. To disclose the identity of the receptor subtype(s) that exert(s) the protective effect, we have used group III agonists in combination with mGluR4 subtype-deficient mice (-/-). In cortical cultures prepared from wild-type (+/+) mice and exposed to a toxic pulse of NMDA, the selective group III agonist (+)-4-phosphonophenylglycine [(+)-PPG] reversed excitotoxicity with an EC(50) value of 4.9 microm, whereas its enantiomer (-)-PPG was inactive. This correlated closely with the potency of (+)-PPG in activating recombinant mGluR4a. In cortical neurons from -/- mice, (+)-PPG showed no protection against the NMDA insult up to 300 microm, whereas group I/II mGluR ligands still retained their protective activity. Classical group III agonists (l-2-amino-4-phosphonobutyrate and l-serine-O-phosphate) were also substantially neuroprotective against NMDA toxicity in +/+ and heterozygous (+/-) cultures but were inactive in -/- cultures. Interestingly, -/- cultures were more vulnerable to low concentrations of NMDA and showed higher extracellular glutamate levels compared with +/+ cultures. We have also examined neurodegeneration induced by intrastriatal infusion of NMDA in wild-type or mGluR4-deficient mice. Low doses of (R,S)-PPG (10 nmol/0.5 microl) substantially reduced NMDA toxicity in +/+ mice but were ineffective in -/- mice. Higher doses of (R,S)-PPG were neuroprotective in both strains of animals. Finally, microdialysis studies showed that intrastriatal infusion of NMDA increased extracellular glutamate levels to a greater extent in -/- than in +/+ mice, supporting the hypothesis that the mGluR4 subtype is necessary for the maintenance of the homeostasis of extracellular glutamate levels.

[Fibromyalgia--a new name of an old "malady". Fatigue and pain syndrome with a historical background]. / Fibromyalgi--nytt namn på gammal "sjuka". Trötthets- och smärtsyndrom med historisk bakgrund.

Fibromyalgia is a good illustration of the fact that a smart new name of an old malady can spread like wildfire if well matched in time socioculturally. "Muscular rheumatism" has earlier been looked upon as a (rheumatic) inflammation of muscle cells or of muscular connective tissue. During the last decades the interest of leading clinicians and researchers have been directed against the pain perceiving system, suggesting defect pain modulating mechanisms peripherally and centrally. Fibromyalgia seems to supply several medical and social needs in our time and might be called a "fin-de-siècle" disease.

(R,S)-4-phosphonophenylglycine, a potent and selective group III metabotropic glutamate receptor agonist, is anticonvulsive and neuroprotective in vivo.

Group III metabotropic glutamate receptors (mGluRs) are thought to modulate neurotoxicity of excitatory amino acids, via mechanisms of presynaptic inhibition, such as regulation of neurotransmitter release. Here, we describe (R,S)-4-phosphonophenylglycine (PPG) as a novel, potent, and selective agonist for group III mGluRs. In recombinant cell lines expressing the human receptors hmGluR4a, hmGluR6, hmGluR7b, or hmGluR8a, EC50 values for (R,S)-PPG of 5.2 +/- 0.7 microM, 4.7 +/- 0.9 microM, 185 +/- 42 microM, and 0.2 +/- 0.1 microM, respectively, were measured. The compound showed EC50 and IC50 values of >/=200 microM at group I and II hmGluRs and was inactive at cloned human N-methyl-D-aspartate, alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionate, and kainate receptors (>300 microM). On the other hand, it showed micromolar affinity for a Ca2+/Cl--dependent L-glutamate binding site in rat brain, similar to other phosphono-substituted amino acids like L-2-amino-4-phosphonobutyrate. In cultured cortical neurons, (R, S)-PPG provided protection against a toxic pulse of N-methyl-D-aspartate (EC50 = 12 microM), which was reversed by the group III mGluR antagonist (R,S)-alpha-methylserine-O-phosphate but not by the group II antagonist (2S)-alpha-ethylglutamate. Moreover, (R,S)-PPG protected against N-methyl-D-aspartate- and quinolinic acid-induced striatal lesions in rats and was anticonvulsive in the maximal electroshock model in mice. In contrast to the group III mGluR agonists L-2-amino-4-phosphonobutyrate and L-serine-O-phosphate, (R,S)-PPG showed no proconvulsive effects (2200 nmol i.c.v.). These data provide novel in vivo evidence for group III mGluRs as attractive targets for neuroprotective and anticonvulsive therapy. Also, (R,S)-PPG represents an attractive tool to analyze the roles of group III mGluRs in nervous system physiology and pathology.

[Psychosomatic disease or infection? Peptic ulcer in the light of the history of ideas and of the philosophy of science]. / Psykosomatisk sjukdom eller infektion? Magsarssjukdomen i idehistorisk och vetenskapsfilosofisk belysning.

Chronic benignant ulcers of the stomach were considered as a disease entity not until in the 1830s, when Jean Cruveilhier and others compared disease history with pathological findings at autopsy. Ulcers of the duodenal bulb were thought unusual until in the beginning of the twentieth century, when abdominal surgery was rapidly developing and X-ray introduced as a diagnostic tool intra vitam. Duodenal ulcers and distal ventricular ulcers have a similar symptomatology and are often associated with hyperacidity. They are therefore jointly spoken as a peptic ulcer disease. Trauma and dietetic faults, hyperacidity and local circulatory disturbances were considered important etiological and pathogenetical factors in the nineteenth century. In the 1910s, instability of the vegetative (autonomic) nervous system was coined as an additional factor. However, the most important concept of the nature of peptic ulcer emerged in the 1940s, when it was appointed a psychosomatic disease. Psychoanalysis and stress research were the main sources of this concept which was predominant until recently. In the middle of the 1980s, gastric infection with a bacillus, later named Helicobacter pylori, was demonstrated to be strongly associated with peptic ulcer and is now considered as its main cause. This finding has also had an important impact on the treatment of peptic ulcer, which is now mainly pharmacological. Thus, a biogenetic view of peptic ulcer disease has superseded a psychogenetic one. The author thus proposes that the history of peptic ulcer can be divided into four periods or stages, comparable to the paradigmal shifts of Kuhn, according to the prevailing concepts of the disease. It is however concluded that peptic ulcer is no unicausal or monolithic unity but rather a syndrome with a complex etiology and pathogenesis. It is important to maintain a holistic view of the diseased individual.

Clinical trainees' recollections of their training in a diagnostic preschool program: a pilot study.

26 clinician trainees' recollections of experiences in a diagnostic preschool program were analyzed in terms of strength and weaknesses of the program.

An interim report on the development of the Psychological Trauma and Resources Scales.

The William S. Hall Psychiatric Institute Psychological Trauma and Psychological Resources Scales is a preliminary measure for the assessment of psychological trauma and psychological health from a developmental perspective. This three-part article (1) discusses the various rationales leading to the development of the scales, (2) provides a factor-analysis of responses of 336 college students, and (3) addresses current (N = 37) and planned efforts to establish reliability and validity of a more refined version.

A novel splice variant of a metabotropic glutamate receptor, human mGluR7b.

Two splice variants of the human metabotropic glutamate receptor 7, named hmGluR7a and hmGluR7b, were isolated from a human brain cDNA library. The isoforms differ by an out-of-frame insertion of 92 nucleotides close to the C-terminus of the hmGluR7 coding region, hmGluR7a has a length of 915 amino acids and represents the human homolog of the recently cloned rat mGluR7. hmGluR7b is seven amino acids longer and exhibits a novel C-terminus of 23 amino acids in length. RT-PCR analysis demonstrated the existence of mGluR7b transcripts in wild-type mouse brain and its absence in mGluR7 knockout mice. Northern blot analysis indicate that mGluR7 expression is developmentally regulated. It is expressed at high levels in human fetal brain and at a lower level in many regions of adult human brain. Stimulation of hmGluR7b with L-2-amino-4-phosphonobutyrate (L-AP4), L-serine-O-phosphate (L-SOP) or L-glutamate in stably transfected Chinese hamster ovary (CHO) cells depressed forskolin-induced cAMP accumulation, whereas (1S,3R)-1-aminocyclopentane-1,3,-dicarboxylic acid ((1S,3R)-ACPD) and quisqualate (both at 1mM) had no significant effects. As described for rat mGluR7, the rank order of agonist potencies is: L-SOP, L-AP4 > L-glutamate > (1S,3R)-ACPD, quisqualate.

Case study: fluoxetine in the multimodal treatment of a preschool child with selective mutism.

Selective mutism is a rare disorder with poor treatment outcome. The current study describes the successful treatment of selective mutism in a preschool-age girl, using a comprehensive multifaceted therapeutic approach. The components of this intervention reflect a conceptualization of selective mutism that emphasizes anxiety as a core feature but also focuses on associated factors such as oppositional behaviors.

Molecular cloning, functional expression and pharmacological characterization of the human metabotropic glutamate receptor type 4.

A cDNA encoding the human metabotropic glutamate receptor type 4 (hmGluR4) was isolated from human brain cDNA libraries by cross-hybridization with rat mGluR4 probes. The deduced amino acid sequence of human mGluR4 consists of 912 residues and shows a sequence identity of 96% to the amino acid sequence of rat mGluR4. Northern blot analyses indicate that hmGluR4 is strongly expressed in the cerebellum of the adult human brain but also at low levels in hippocampus, hypothalamus and thalamus. Stimulation of hmGluR4 with L-2-amino-4-phosphonobutyrate (L-AP4), L-serine-O-phosphate (L-SOP), L-glutamate or (1S,3R)-1-aminocyclo-pentane-1,3-dicarboxylic acid ((1S,3R)-ACPD) in stably transfected Chinese hamster ovary (CHO) cells depressed forskolin-induced cAMP accumulation, whereas quisqualate (0.5 mM) was ineffective. The rank order of agonist potencies is: L-AP4 > L-SOP > L-glutamate > (1S,3R)-ACPD >> quisqualate. (R,S)-alpha-methyl-4-carboxyphenylglycine (1 mM), a reported antagonist at some mGluR subtypes, did not reduce the depression of forskolin-induced cAMP accumulation by L-AP4.

A guided bibliography of the selective mutism (elective mutism) literature.

This guided bibliography of 122 articles on selective mutism covers nearly all of the English language publications on the topic. Index Medicus and Psychological Abstracts were the major source documents for the citations.

[Clinico-genetic diagnosis of ataxia telangiectatica (Louis-Bar syndrome)]. / Klinisch-genetische Diagnose der Ataxia telangiectatica (Louis-Bar-Syndrom).

We describe the possible difficulties in getting the diagnosis "ataxia telangiectasia" using the example of a 16 years old girl. If cases of cerebellar ataxia in childhood present without classical symptoms, the diagnosis of ataxia telangiectasia should not be excluded before chromosome analysis. In our case, first signs of cerebellar ataxia were observed from the age of 11 years and we found only mild, atypical located and late onset telangiectasis. Other signs of the syndrome, such as elevated alpha-fetoproteine and deficiency of IgA or IgE could not be detected. Chromosome analysis, however, demonstrated a breakage syndrome with chromosome 14 to 7 translocation and established a firm diagnosis of ataxia telangiectasia. Patients with chromosome breakage syndromes including the Louis-Bar-syndrome have an increased risk for malignomas. Therefore chromosome analysis should be undertaken in cases of children with cerebellar ataxia, and frequent radiological examination avoided.