Trigeminal cold receptors and airflow perception are altered in chronic rhinosinusitis.

BACKGROUND: In chronic rhinosinusitis (CRS), nasal obstruction can often be explained by anatomical deformities, polyps, or congested nasal mucosa. However, in cases with little deformity or inflammation, perceived nasal obstruction may result from reduced airflow perception caused by an alteration of the intranasal trigeminal system. The aim of this study was to assess this association. METHODOLOGY: We performed a prospective case-control study of 15 CRS patients, 18 patients with a deviated nasal septum (DNS) and 16 healthy controls. We assessed olfactory function using the Sniffin' Sticks test and Visual Analog Scales (VAS). We used the Trigeminal Lateralization Task (TLT) with eucalyptol and cinnamaldehyde to examine intranasal trigeminal function. Further, we assessed nasal patency with Peak Nasal Inspiratory Flow and VAS. Finally, we measured protein levels of trigeminal receptors (TRPM8, TRPA1 and TRPV1) and inflammatory markers (IL-13, INF-y and eosinophils) in CRS and DNS patients' mucosal biopsies using Western Blots. RESULTS: CRS patients had significantly lower olfactory function than DNS and healthy controls. They also had significantly lower TLT scores for eucalyptol than both other groups. CRS patients had significantly lower nasal patency than controls; for DNS patients this was limited to subjective measures of nasal patency. In line with this, CRS patients exhibited significantly higher levels of sTRPM8-18 than DNS patients. CONCLUSIONS: Intranasal trigeminal function is decreased in CRS patients, possibly due to the overexpression of short isoforms of TRPM8 receptors.

Increased expression of the dopamine transporter leads to loss of dopamine neurons, oxidative stress and l-DOPA reversible motor deficits.

The dopamine transporter is a key protein responsible for regulating dopamine homeostasis. Its function is to transport dopamine from the extracellular space into the presynaptic neuron. Studies have suggested that accumulation of dopamine in the cytosol can trigger oxidative stress and neurotoxicity. Previously, ectopic expression of the dopamine transporter was shown to cause damage in non-dopaminergic neurons due to their inability to handle cytosolic dopamine. However, it is unknown whether increasing dopamine transporter activity will be detrimental to dopamine neurons that are inherently capable of storing and degrading dopamine. To address this issue, we characterized transgenic mice that over-express the dopamine transporter selectively in dopamine neurons. We report that dopamine transporter over-expressing (DAT-tg) mice display spontaneous loss of midbrain dopamine neurons that is accompanied by increases in oxidative stress markers, 5-S-cysteinyl-dopamine and 5-S-cysteinyl-DOPAC. In addition, metabolite-to-dopamine ratios are increased and VMAT2 protein expression is decreased in the striatum of these animals. Furthermore, DAT-tg mice also show fine motor deficits on challenging beam traversal that are reversed with l-DOPA treatment. Collectively, our findings demonstrate that even in neurons that routinely handle dopamine, increased uptake of this neurotransmitter through the dopamine transporter results in oxidative damage, neuronal loss and l-DOPA reversible motor deficits. In addition, DAT over-expressing animals are highly sensitive to MPTP-induced neurotoxicity. The effects of increased dopamine uptake in these transgenic mice could shed light on the unique vulnerability of dopamine neurons in Parkinson's disease.

Quantification of uncertainty of experimental measurement in leaching test on cement-based materials.

When mineral wastes are reused in construction materials, a current practice is to evaluate their environmental impact using standard leaching test. However, due to the uncertainty of the measurement, it is usually quite difficult to estimate the pollutant potential compared to other materials or threshold limits. The aim of this paper is to give a quantitative evaluation of the uncertainty of leachate concentrations of cement-based materials, as a function of the number of test performed. The relative standard deviations and relative confidence intervals are determined using experimental data in order to give a global evaluation of the uncertainty of leachate concentrations (determination of total relative standard deviation). Various combinations were realized in order to point out the origin of large dispersion of the results (determination of relative standard deviation linked to analytical measured and to leaching procedure), generalisation was suggested and the results were compared to literature. An actual example was given about the introduction of residue (meat and bone meal bottom ash--MBM-BA) in mortar, leaching tests were carried out on various samples with and without residue MBM-BA. In conclusion large dispersion were observed and mainly due to heterogeneity of materials. So heightened attention needed to analyse leaching result on cement-based materials and further more other tests (e.g. ecotoxicology) should be performed to evaluate the environmental effect of these materials.

[Muscle-sparing latissimus dorsi flap. Vascular anatomy and indications in breast reconstruction]. / Le lambeau de grand dorsal avec conservation du muscle. Etude anatomique et indications en reconstruction mammaire.

BACKGROUND: The muscle-sparing latissimus dorsi flap pedicled on descending branch presents distinct advantages in breast reconstruction, specially when there is a transversely oriented skin paddle, including reduced donor site morbidity, sparing muscle function and greater freedom of orientation of the skin paddle. This study reports the anatomical basis, surgical technique, advantages and complications of this technique. Four clinical cases illustrate surgical indications in breast reconstructive surgery. METHODS: An anatomical cadaveric study underwent to University of Texas Southwestern Medical Center, Dallas. The goal was performed to determine the location of the bifurcation of the thoracodorsal artery and the course of its descending branch compare to the anterior side of latissimus dorsi muscle. Four clinical cases illustrated indications of muscle-sparing latissimus dorsi flap pedicled on descending branch in breast reconstruction. These cases showed advantages and complications of the technique, and impact on donor site. RESULTS: Fifteen descending branch muscle-sparing latissimus dorsi flaps were harvested. All flaps had a bifurcation of the thoracodorsal artery. The average was located at 5,1cm from posterior axillary side (from 2,1 to 7,5 cm) and average of 2,2 cm from the anterior side of latissimus dorsi muscle (from 1,3 to 3,1cm). To 5, 10 and 15 cm from posterior axillary side, the descending branch was located at respectively an average of 2,0 cm (from 1,4 to 2,5), 2,4 cm (from 1,3 to 3,3), and 2,9 cm (from 2,0 to 3,8) behind the anterior side of latissimus dorsi muscle. The average length of descending branch was measured at 15,2 cm (from 13,2 to 19,0). None clinical cases paddle suffering was observed. Donor site morbidity was less than classical or extended adipomuscular technique. Latissimus dorsi muscle function is spared. CONCLUSIONS: The muscle-sparing latissimus dorsi flap, pedicled on descending branch, is versatile and reproducible. It results in minimal functional deficit of the donor site, absence of seroma, large freedom of orientation of the skin paddle, low rate of flap complications, and a cosmetically acceptable scar. There are a lot of indications in breast reconstruction.

[Psychological and health sequelae of childhood sexual, physical and psychological abuse]. / Les conséquences à long terme de la violence sexuelle, physique et psychologique vécue pendant l'enfance.

BACKGROUND: The co-occurrence of child victimization experiences is not a rare phenomenon. However, few studies have explored the long-term consequences of such experiences. Empirical studies present important methodological limitations, namely the fact that few studies have documented more than two forms of victimization, that they rely on non representative samples and have not used multivariate analyses. The present study aims to evaluate the specific contribution of each form of child victimization (sexual, physical and psychological) on the outcomes in adulthood. Moreover, the study explores the role of co-occurrence on these symptoms. METHODS: A phone survey was conducted with a representative sample of 804 adults from the province of Quebec. Households were randomly selected among those having a telephone. Sociodemographic variables, child victimization experiences (sexual, physical and psychological) and partner violence were evaluated to explore their links with psychological distress, post-traumatic stress symptoms and physical health of participants. RESULTS: Higher psychological distress in men is associated with younger age, lower education level and having experienced sexual and physical violence in childhood. For women, psychological distress is linked to younger age, having experienced partner violence, childhood physical and psychological violence. Only experiencing partner violence and childhood sexual and psychological victimization are linked to greater post-traumatic stress symptoms in men and women. Finally, lower education level and childhood sexual and physical victimization increase physical health problems for men, while for women, only lower education level contributes to the prediction. CONCLUSION: The results of this study show that experiencing more than one form of childhood victimization increases the negative outcomes in adulthood, underlying the relevance of considering the phenomenon of co-occurring victimization in the elaboration and dissemination of intervention programs.

Extracellular matrix modulates epidermal growth factor receptor activation in rat glomerular epithelial cells.

To understand how glomerular epithelial cell (GEC) proliferation may be regulated in health and disease, we studied the effects of type I collagen extracellular matrices (ECM) on EGF receptor (EGF-R) activation in cultured rat GEC. EGF stimulated proliferation of GEC adherent to ECM, but not of GEC on a plastic substratum. Significant and prolonged EGF-R tyrosine autophosphorylation (which reflects receptor kinase activation) was induced by EGF in GEC adherent to collagen, but EGF did not stimulate EGF-R autophosphorylation in GEC on plastic (at 37 degrees C). However, EGF-R autophosphorylation increased significantly in plastic-adherent GEC that were stimulated with EGF at 4 degrees C or in the presence of vanadate, an inhibitor of phosphotyrosine phosphatases. Furthermore, dephosphorylation of EGF-R was enhanced in GEC on plastic as compared with collagen. At 4 degrees C, [125I]EGF binding was not different between substrata, and there was negligible accumulation of intracellular [125I]EGF (which reflects EGF-R internalization). At 37 degrees C, EGF-R internalization was reduced significantly in collagen-adherent GEC as compared with GEC on plastic. Thus, contact with ECM facilitates proliferation and EGF-R activation in GEC. The enhanced activity of EGF-R tyrosine kinase may be due to ECM-induced reduction in EGF-R internalization and dephosphorylation by phosphotyrosine phosphatase(s). Signals from ECM to growth factor receptors may regulate cell turnover in the glomerulus under normal conditions and during immune glomerular injury.

Systemic aspects of allergic disease: the role of the bone marrow.

In recent years, there has been an increasing appreciation of the important contribution of bone-marrow-related, hemopoietic mechanisms to allergic diseases. Eosinophil/basophil-progenitor levels fluctuate in the peripheral blood during allergen exposure and the cells home to peripheral tissue, where they differentiate. It is becoming apparent that several cytokines, particularly IL-5, have multiple effects on progenitors and allergic inflammation. Within the past few years, studies of the therapeutic implications of this bone marrow contribution to atopy have been initiated; the effects of corticosteroids, leukotriene-receptor blockers, antagonism of IL-5 and modulation of differentiation by retinoic acid on progenitors will be reviewed.

Prenatal and early-life predictors of atopy and allergic disease in Canadian children: results of the Family Atherosclerosis Monitoring In earLY life (FAMILY) Study.

Prenatal and early-life environmental exposures play a key role in the development of atopy and allergic disease. The Family Atherosclerosis Monitoring In earLY life Study is a general, population-based Canadian birth cohort that prospectively evaluated prenatal and early-life traits and their association with atopy and/or allergic disease. The study population included 901 babies, 857 mothers and 530 fathers. Prenatal and postnatal risk factors were evaluated through questionnaires collected during the antenatal period and at 1 year. The end points of atopy and allergic diseases in infants were evaluated through questionnaires and skin prick testing. Key outcomes included atopy (24.5%), food allergy (17.5%), cow's milk allergy (4.8%), wheezing (18.6%) and eczema (16%). The association between infant antibiotic exposure [odds ratio (OR): 2.04, 95% confidence interval (CI): 1.45-2.88] and increased atopy was noted in the multivariate analysis, whereas prenatal maternal exposure to dogs (OR: 0.60, 95% CI: 0.42-0.84) and acetaminophen (OR: 0.68, 95% CI: 0.51-0.92) was associated with decreased atopy. This population-based birth cohort in Canada demonstrated high rates of atopy, food allergy, wheezing and eczema. Several previously reported and some novel prenatal and postnatal exposures were associated with atopy and allergic diseases at 1 year of age.

Toxicity of methotrexate compared with azathioprine in the treatment of rheumatoid arthritis. A case-control study of 131 patients.

One hundred thirty-one patients with rheumatoid arthritis treated with either azathioprine sodium (n = 37, 102.7 +/- 32.9 mg/d) or methotrexate sodium (n = 94, 8.4 +/- 3.0 mg/wk) were followed up for 38 +/- 23.3 months to determine the nature, frequency, and potential predictors of "major" toxic reactions. Thirty-one methotrexate-treated patients (33%) and 11 patients (30%) receiving azathioprine experienced a major toxic reaction during the study period. With the case-control method, no predictors of major toxic reactions secondary to azathioprine therapy were found. Sex, drug dosage, response to prior slow-acting antirheumatic drug therapy, concurrent use of salicylates, and age did not predict major toxic reactions secondary to methotrexate treatment, but the methotrexate-treated patients who experienced a major toxic reaction had a significantly greater mean level of blood urea nitrogen at the time of their reaction compared with the control group. Life-table analysis suggested toxic reactions posed a greater risk of treatment termination in methotrexate-treated patients compared with the lack or loss of efficacy. This trend was not apparent in the azathioprine group. The majority of patients in each treatment group (79 for methotrexate and 29 for azathioprine) experienced one or more "minor" toxic reactions during the follow-up period.

Drugs with estrogen-like potency and brain activity: potential therapeutic application for the CNS.

Numerous reports, ranging from molecular investigations to clinical studies, demonstrate the potency of estrogens to modulate brain function and their implications in schizophrenia and depression. Alterations of dopaminergic, cholinergic, GABAergic, glutamatergic and serotonergic neurotransmission through estrogen-mediated mechanisms have been consistently established. Moreover, studies using in vivo and in vitro models as well as epidemiological data suggest that estrogens provide neuroprotection of central nervous system (CNS) cells implicated in the etiology of neurodegenerative disorders such as Alzheimer s (AD) and Parkinson s (PD) diseases. Numerous genomic or non-genomic mechanisms of actions of estrogens in the brain have been documented implicating classical nuclear estrogen receptors as well as possible estrogen membrane receptors, antioxidant activity of steroids, their effect on fluidity as well as on antiapoptotic proteins and growth factors. Selective estrogen receptor modulators (SERMs) have estrogenic and/or antiestrogenic activity depending on the target tissue. Hence, SERMs have the same beneficial effect as estrogen in skeleton and cardiovascular systems but act as antagonists in breast and uterus. The finding of beneficial side effects of SERMs in the CNS might improve their risk-benefit ratio in traditional indications. In this review, we will survey schizophrenia and depression as examples of mental diseases and AD and PD as neurodegenerative diseases. We will review brain effects of estrogens, steroids possibly acting as pro-drugs of estrogens such as testosterone and dehydroepiandrosterone (DHEA) and present novel findings with SERMs. Drugs with estrogen activity in the brain may have therapeutic potential either by modulating brain neurotransmitter transmission or through neuroprotective activity.

Modulation by estrogen-receptor directed drugs of 5-hydroxytryptamine-2A receptors in rat brain.

Hormonal specificity of modulation of brain 5-HT(2A) receptors was investigated by comparing activity of compounds with varying effects on estrogen response in breast, bone, and uterus. A two-week estradiol treatment stimulated the decreased uterine weight of ovariectomized rats to intact rat values whereas an increase of 29% with tamoxifen and 16% with raloxifene was observed compared to vehicle-treated ovariectomized rats. In 18 assayed brain regions, ovariectomy decreased 5-HT(2A) receptor binding and mRNA levels in anterior cingulate and frontal cortices, striatum, and nucleus accumbens; estradiol restored this decrease to intact rat values. Dehydroepiandrosterone (DHEA) increased ovariectomized rats 5-HT(2A) receptor expression only in striatum and cortical amygdala. Tamoxifen increased 5-HT(2A) receptor density only in striatum. Raloxifene, an uterine estrogen receptor (ER) antagonist, increased, like estradiol, 5-HT(2A) receptor density and expression in cingulate and frontal cortices, striatum, and nucleus accumbens. Brain regional specificity of estradiol, DHEA, tamoxifen, and raloxifene on 5-HT(2A) receptors was observed which can be dissociated from peripheral activity.

Estrogen-like activity of tamoxifen and raloxifene on NMDA receptor binding and expression of its subunits in rat brain.

Hormonal specificity of modulation of N-methyl- D-aspartate (NMDA) receptors was investigated by comparing the effects of estradiol with tamoxifen or raloxifene, which display different responses in breast, bone, and uterus. Two weeks ovariectomy in rats decreased uterine weight, which was prevented by a two-week estradiol treatment; tamoxifen and raloxifene had weaker uterine stimulation than estradiol. Ovariectomy in rats decreased L-[3H]glutamate specific binding to NMDA receptors in CA1 and dentate gyrus but not CA2/3 regions of hippocampus and was without effect in cortex, striatum, nucleus accumbens, and olfactory tubercle. [3H]Ro 25-6981 (an NMDA antagonist selective for NR1/NR2B assembly) specific binding and mRNA levels of NMDA receptor subunits 1 and 2B decreased in CA1 after ovariectomy. Estradiol, tamoxifen, and raloxifene decreased L-[3H]glutamate specific binding to NMDA receptors and [3H]Ro 25-6981 specific binding in cortical area of ovariectomized rats and prevented the decrease of [3H]glutamate specific binding to NMDA receptors in CA1 and dentate gyrus, as well as [3H]Ro 25-6981 specific binding in CA1. Estradiol prevented the decrease of NMDA receptor subunits 1 and 2B mRNA levels in CA1 only; tamoxifen and raloxifene prevented the decrease of NMDA receptor subunit 1 mRNA levels in CA1. No effect of ovariectomy or treatments on L-[3H]CGP 39653 (an NMDA antagonist selective for NR1/NR2A assembly) specific binding and NMDA receptor subunit 2A mRNA levels was observed in all brain regions assayed. Our results showed brain regional and subunits specific agonist estrogenic activity of tamoxifen and raloxifene on NMDA receptors.

Gonadal hormones modulate 5-hydroxytryptamine2A receptors: emphasis on the rat frontal cortex.

The effect of short-term (Sprague-Dawley rats, two weeks) and long-term ovariectomy (Sprague-Dawley and Fischer rats, three months) on serotonin 5-hydroxytryptamine2A receptors in different regions of the brain and its possible correction with an 17 beta-estradiol treatment (10 micrograms, b.i.d., two weeks) were studied in comparison to intact rats. Saturation binding assays were performed using [3H]ketanserin to estimate 5-hydroxytryptamine2A receptor density and affinity in tissue homogenates of frontal cortex of Fischer rats and quantitative autoradiography was performed to evaluate receptor specific binding in frontoparietal cortex, nucleus accumbens, striatum and dorsal raphe nucleus of Fischer rats, and in frontal cortex of the two strains of rats. Messenger RNA levels of 5-hydroxytryptamine2A receptors were measured by in situ hybridization in frontal cortex of the two strains of rats. An overall decrease of 5-hydroxytryptamine2A receptor densities was found in all the brain regions of ovariectomized Fischer rats assayed, and this could be restored towards control levels by estradiol treatment. No change in the 5-hydroxytryptamine2A receptor affinity was measured in the frontal cortex. A similar pattern of changes was observed for the messenger RNA levels encoding the 5-hydroxytryptamine2A receptors and receptor density, suggesting the implication of a genomic mechanism. Experiments in Sprague-Dawley rats confirmed and extended the results obtained with Fischer rats. By analogy, in humans, this 5-hydroxytryptamine2A receptor modulation may underlie the mood and movement disorders associated with menopause.

Dopaminergic activity in transgenic mice underexpressing glucocorticoid receptors: effect of antidepressants.

Transgenic mice bearing a transgene coding for a glucocorticoid receptor antisense mRNA, which partially blocks glucocorticoid receptor expression, were used to investigate the long-term effect of hypothalamic-pituitary-adrenal axis dysfunction on brain dopamine transmission. Compared to control mice, the transgenic animals showed increased amphetamine-induced locomotor activity and increased concentrations of striatal dopamine and its metabolites dihydroxyphenylacetic acid and homovanillic acid. Binding of [3H]SCH 23390 and [3H]spiperone to, respectively, D1 and D2 dopamine receptors was increased in transgenic mice. In contrast, autoradiography of striatal [3H]GBR 12935 binding to the dopamine transporter was decreased and the mRNA levels of this transporter, measured by in situ hybridization, remained unchanged in the substantia nigra pars compacta. The effect of chronic treatment for two weeks with amitriptyline or fluoxetine was compared in control and transgenic mice. No significant changes were observed in control mice following antidepressant treatment, whereas in transgenic mice both antidepressants reduced striatal [3H]SCH 23390 and [3H]raclopride specific binding to D1 and D2 receptors. Amitriptyline, but not fluoxetine, increased striatal [3H]GBR 12935 binding to the dopamine transporter, whereas its mRNA level in the substantia nigra pars compacta was decreased in fluoxetine, compared to vehicle- or amitriptyline-treated transgenic mice. From these results we suggest that hyperactive dopaminergic activity of the nigrostriatal pathway controls motor activity in the transgenic mice. Furthermore, antidepressant treatment corrected the increased striatal D1 and D2 receptors and decreased dopamine transporter levels in the transgenic mice.

Current drug therapy recommendations for the treatment of attention deficit hyperactivity disorder.

Attention deficit hyperactivity disorder (ADHD) is characterised by symptoms of inattentiveness and/or hyperactivity-impulsivity which are not appropriate to the child's age. This disorder usually manifests by age 3 and affects up to 5% of school-age children. Although the aetiology is unknown, ADHD appears to have a strong genetic component and to involve dysregulation of the CNS dopaminergic system. Psychostimulants are the mainstay of therapy. The majority of patients will respond to an adequate trial of one of the 3 available stimulants, methylphenidate, dexamphetamine or pemoline. Use of the tricyclic antidepressants as second-line agents is supported by substantial literature. Third-line agents include amfebutamone (bupropion) and clonidine. Other modalities have been studied, but sufficient research is not available to recommend their use over the abovementioned treatments. Assessment of response is best achieved by objective rating scales which allow for input from various environments.

Regional and selective effects of oestradiol and progesterone on NMDA and AMPA receptors in the rat brain.

We investigated the effect of 10 months ovariectomy and a correction therapy, 2 weeks before the rats were killed, of oestradiol, progesterone or their combination on NMDA and AMPA receptor binding in the hippocampus, dentate gyrus, striatum, nucleus accumbens and frontal cortex of the rat brain as well as on amino acid levels in frontal cortex. NMDA and AMPA binding densities were assayed by autoradiography using, respectively, L-[3H]glutamate and [3H]AMPA; amino acid concentrations were measured by high performance liquid chromatograhy (HPLC) coupled with UV detection. Ovariectomy was without effect on NMDA and AMPA binding density in all brain regions assayed except in the hippocampal CA1 region and dentate gyrus where it decreased NMDA binding density compared to intact rats values. Oestradiol restored and increased NMDA binding density in the CA1 subfield and the dentate gyrus of ovariectomized rats but, by contrast, it decreased binding density in the striatum and in the frontal cortex while having no effect in the CA2/3 subfield of the hippocampus and in the nucleus accumbens. Oestradiol was without effect on AMPA binding density in the hippocampus and the dentate gyrus but it reduced AMPA binding density in the striatum, the frontal cortex and the nucleus accumbens. Progesterone, and oestradiol combined with progesterone, decreased NMDA but not AMPA binding density in the frontal cortex of ovariectomized rats, and they were without effect on these receptors in the other brain regions assayed. Amino acid concentrations in the frontal cortex were unchanged after ovariectomy or steroid treatments. The effect of oestradiol in the hippocampus confirmed in the present study and our novel findings in the frontal cortex, striatum and nucleus accumbens may have functional significance for schizophrenia and neurodegenerative diseases.

The history of lupus erythematosus. From Hippocrates to Osler.

Hippocrates (460-375 BC) was the first to describe cutaneous ulcers under the heading of herpes esthiomenos. From what we can tell, Herbernus of Tours was the first to apply the term lupus to a skin disease in 916 AD. Following this, a number of terms including lupus, noli me tangere, and herpes esthiomenos were used to describe cutaneous ulcers. Willan (1757-1812) expanded the classification of skin diseases using the term herpes for vesicular diseases and lupus for destructive and ulcerative diseases of the face. The first clear description of lupus erythematosus was by Biett and was reported by his student Cazenave under the term erythema centrifugum in 1833. In 1846 Hebra, under the name of Seborrhea Congestiva described disc-shaped patches and introduced the butterfly simile for the malar rash. In 1851 Cazenave renamed erythema centrifugum, calling it lupus erythematosus and gave a classic description of discoid lupus erythematosus. In 1872 Kaposi subdivided lupus into the discoid and systemic forms and introduced the concept of systemic disease with a potentially fatal outcome. Hutchinson alluded to the photosensitive nature of the rash and may have provided the earliest description of what is now called annular subacute cutaneous lupus. In 1894 Payne used quinine in the treatment of patients with LE and postulated the presence of a vascular disturbance. In 1902, Sequira and Balean published a large series of patients with discoid and systemic LE and provided clinical and pathologic details of a young woman who died of glomerulonephritis. In 1904, Jadassohn published an exhaustive review of discoid and systemic LE, including clinical features and pathologic findings. Between 1895 and 1904 Sir William Osler published 29 cases of what was termed the erythema group of diseases. Perhaps his major contribution was to show that skin diseases could be accompanied by a variety of systemic manifestations. In retrospect most of his patients suffered from diseases other than SLE and it was only in his 1904 paper that two cases with SLE were described. He did not acknowledge this diagnosis in his cases and we share the viewpoint that his contribution to the study of SLE has been overemphasized.

Estrogenic activity of tamoxifen and raloxifene on rat brain AMPA receptors.

We have previously shown in rats that estradiol has brain regionally specific effects on AMPA receptors. The present study investigated hormonal specificity of AMPA receptors by comparing the effect of estradiol with tamoxifen or raloxifene, which have varying effects on estrogen response in breast, bone and uterus. Ovariectomy in rats decreased uterus weight which was restored by estradiol treatment, whereas tamoxifen and raloxifene had only a weak effect. Ovariectomy left unchanged AMPA receptor specific binding in rat brain whereas estradiol, tamoxifen and raloxifene decreased it in cortical and striatal regions of ovariectomized rats. Hence, tamoxifen and raloxifene showed agonist estrogenic activity on AMPA receptors in specific brain regions, which can be dissociated from their antagonist estrogenic activity in the periphery.

Women and substance abuse.

Chemically dependent women face special problems. This article reviews the epidemiology, screening, clinical consequences, and treatment of substance-abusing women. Alcohol, opiate, and cocaine abuse are often linked in women, and the individual and overlapping effects of these drugs are described. Gender difference also are highlighted.

Methazolamide-induced delirium.

A 74-year-old man became delirious 2 days after beginning oral therapy with methazolamide. The delirium was manifested by intermittent psychosis, incontinence of bowel and bladder, lethargy, and disorientation. These symptoms continued for 25 days despite many changes in his drug regimen, and complete laboratory, urologic, and neurologic work-ups. The symptoms resolved completely within 1 week of discontinuing methazolamide. This is the first case reported of delirium associated with methazolamide not accompanied by a metabolic imbalance.