Effect of high-potency cannabis on corpus callosum microstructure.

BACKGROUND: The use of cannabis with higher Δ9-tetrahydrocannabinol content has been associated with greater risk, and earlier onset, of psychosis. However, the effect of cannabis potency on brain morphology has never been explored. Here, we investigated whether cannabis potency and pattern of use are associated with changes in corpus callosum (CC) microstructural organization, in patients with first-episode psychosis (FEP) and individuals without psychosis, cannabis users and non-users. METHOD: The CC of 56 FEP (37 cannabis users) and 43 individuals without psychosis (22 cannabis users) was virtually dissected and segmented using diffusion tensor imaging tractography. The diffusion index of fractional anisotropy, mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity was calculated for each segment. RESULTS: Across the whole sample, users of high-potency cannabis had higher total CC MD and higher total CC AD than both low-potency users and those who never used (p = 0.005 and p = 0.004, respectively). Daily users also had higher total CC MD and higher total CC AD than both occasional users and those who never used (p = 0.001 and p < 0.001, respectively). However, there was no effect of group (patient/individuals without psychosis) or group x potency interaction for either potency or frequency of use. The within-group analysis showed in fact that the effects of potency and frequency were similar in FEP users and in users without psychosis. CONCLUSIONS: Frequent use of high-potency cannabis is associated with disturbed callosal microstructural organization in individuals with and without psychosis. Since high-potency preparations are now replacing traditional herbal drugs in many European countries, raising awareness about the risks of high-potency cannabis is crucial.

Trends in the prevalence of asthma and allergic rhinitis in Italy between 1991 and 2010.

The prevalence of asthma increased worldwide until the 1990s, but since then there has been no clear temporal pattern. The present study aimed to assess time trends in the prevalence of current asthma, asthma-like symptoms and allergic rhinitis in Italian adults from 1990 to 2010. The same screening questionnaire was administered by mail or phone to random samples of the general population (age 20-44 yrs) in Italy, in the frame of three multicentre studies: the European Community Respiratory Health Survey (ECRHS) (1991-1993; n = 6,031); the Italian Study on Asthma in Young Adults (ISAYA) (1998-2000; n = 18,873); and the Gene Environment Interactions in Respiratory Diseases (GEIRD) study (2007-2010; n = 10,494). Time trends in prevalence were estimated using Poisson regression models in the centres that repeated the survey at different points in time. From 1991 to 2010, the median prevalence of current asthma, wheezing and allergic rhinitis increased from 4.1% to 6.6%, from 10.1% to 13.9% and from 16.8% to 25.8%, respectively. The prevalence of current asthma was stable during the 1990s and increased (relative risk 1.38, 95% CI 1.19-1.59) from 1998-2000 to 2007-2010, mainly in subjects who did not report allergic rhinitis. The prevalence of allergic rhinitis has increased continuously since 1991. The asthma epidemic is not over in Italy. During the past 20 yrs, asthma prevalence has increased by 38%, in parallel with a similar increase in asthma-like symptoms and allergic rhinitis.

Defective group-II metaboropic glutamate receptors in the hippocampus of spontaneously depressed rats.

Spontaneously depressed flinders sensitive line (FSL) rats showed a reduced expression of mGlu2/3 metabotropic glutamate receptors in the hippocampus, as compared to "non-depressed" flinders resistant line (FRL) rats. No changes in mGlu2/3 receptor protein levels were found in other brain regions, including the amygdala, hypothalamus, and cerebral cortex. Biochemical analysis of receptor signalling supported the reduction of mGlu2/3 receptors in the hippocampus of FSL rats. Accordingly, the selective mGlu2/3 receptor agonist, LY379268 (1microM) reduced forskolin-stimulated cAMP formation by 56% and 32% in hippocampal slices from FRL and FSL rats, respectively. In addition, LY379268 enhanced 3,5-dihydroxyphenylglycine-stimulated inositol phospholipid hydrolysis from 65% to 215% in hippocampal slices from FRL rats, whereas it was inactive in slices from FRL rats. We also examined the behavioural response of FSL rats to systemic injection of LY379268 (0.5mg/kg, i.p., once a day for 1-21 days) by measuring the immobility time in the forced swim test, which is known to be increased in these rats. LY379268 was administered alone or combined with the classical antidepressant, chlorimipramine (10mg/kg, i.p.). LY379268 alone had no effect at any of the selected time-points, whereas chlorimipramine alone reduced the immobility time only after 21 days of treatment. In contrast, when combined with LY379268, chlorimipramine reduced the immobility time during the first 14 days of treatment. These data support the view that mGlu2/3 receptors might be involved in the pathophysiology of depressive disorders, and that pharmacological activation of these receptors may shorten the latency of antidepressant medication.

Similar discontinuation symptoms for withdrawal from medium-dose paroxetine and venlafaxine after nine years in the same patient.

A woman who had developed a discontinuation syndrome nine years ago with paroxetine tapered from 10 to 5 mg/day represented the same syndrome recently when she occasionally missed her 75 mg q 12 h venlafaxine doses. The symptoms, comprising agitation, numbness, pricking sensations, sweating, difficulty concentrating, weakness, derealisation and perceived xerophthalmia, immediately subside upon drug dose reinstitution. The patient had used cannabis irregularly before the onset of pauci-symptomatic panic attacks, but none of her panic symptoms were present in her withdrawal symptomatology. Some symptoms waxed and waned during the withdrawal period. The syndrome is compatible with both hyper- and hypoactivity of the central serotonergic system.

Synergism between fluoxetine and the mGlu2/3 receptor agonist, LY379268, in an in vitro model for antidepressant drug-induced neurogenesis.

We examined the interaction between the selective serotonin reuptake inhibitor, fluoxetine, and group-II metabotropic glutamate (mGlu) receptors using progenitor cells isolated from cultured cerebellar granule cells, considered as an in vitro model of antidepressant-drug induced neurogenesis. These cells expressed mGlu3 receptors negatively coupled to adenylyl cyclase. A 72-h treatment with either fluoxetine or low concentrations of mGlu2/3 receptor agonists (LY379268 or 2R,4R-APDC) enhanced cell proliferation. The action of fluoxetine was mediated by the activation of 5-HT(1A) receptors. We found a strong synergism between fluoxetine and LY379268 in enhancing cell proliferation and inhibiting cAMP formation. The increased cell proliferation induced by fluoxetine+LY379268 was abrogated by the cAMP analogue, 8-Br-cAMP, as well as by drugs that inhibit the mitogen-activated protein kinase and phosphatidyilinositol-3-kinase pathways. Interestingly, fluoxetine and LY379268 also acted synergistically in promoting neuronal differentiation when progenitor cells were incubated in the presence of serum. These data support the hypothesis that a combination between classical antidepressants and mGlu2/3 receptor agonists may be helpful in the experimental treatment of depression.

Epidemiology of adult medulloblastoma.

Medulloblastoma is one of the most common primary tumors of the central nervous system seen in children; in contrast, it is somewhat uncommon in adult age. Due to the infrequent occurrence, data on incidence rates are sparse. The present study was aimed at ascertaining the epidemiological characteristics of medulloblastoma in adult age in Piedmont during the period 1976-1995. Piedmont is a region in northwest Italy, which had a total population of 4.30 millions/year for the period mentioned. From the files of clinical records of patients hospitalized in neurologic and neurosurgical departments, 45 cases (32 males, 13 females) of histologically verified medulloblastoma were recorded. The incidence rate (annual per million) in the whole period studied was 0.5 (95% confidence interval, 0.36-0.67). The incidence rate was high in the age group 15 to 19 years (2.33/million/year) and decreased up to age 40, consistent with the embryonal origin of the tumor. No time-trend of incidence rate was found. Male excess was evident in all age groups and in each time period. Median survival time was 17.6 years; the 5-year survival rate was 69.9%. Survival rate in the present group of adult medulloblastoma is slightly better than that reported in clinical series. A comparison was made with incidence data concerning pediatric medulloblastoma reported in the Registry of Childhood Cancer of Piedmont: from 1980 to 1989, adult medulloblastomas represented 34% of medulloblastomas. The figure is higher than that generally assumed, and indicates that the occurrence of this embryonal tumor in adult age is relevant. Our epidemiological data are consistent with an embryonal origin of medulloblastoma.

[Cognitive investigation on the quality of life of patients with oro-facial neoplasms in advanced stage]. / Indagine conoscitiva sulla qualità di vita dei pazienti con neoplasie oro-facciali in stadio avanzato.

As part of a Ministry of health founded research project into the quality of life among advanced cancer patients and in collaboration with the National Tumour Institutes of Milan, Naples and Genoa, an investigation was conducted on a national and international scale into the quality of the assistance given to cancer patients. Specific subjects of investigation included: the existence of pain treatment centres, home help and the type of psychological support offered such patients. In addition a questionnaire was presented to Italian oncologists, hospital staff and general practitioners covering areas like deontological problems of information, emotional, responses and quality of treatment. The answers revealed differences in the profiles of these three categories that make a significant contribution to the current discussion of the problem of the quality experienced by advanced cancer patients.

Treatment of colloid cysts of the third ventricle by aspiration in stereotactic conditions.

Two cases of colloid cysts of the third ventricle are reported. The etiology, clinical symptoms and radiological diagnosis of such lesions are briefly discussed. CT-guided stereotactic aspiration of the cyst's content was performed, with good results in both cases. CT-scan controls performed one year later showed that refilling of the cysts did not occur. The advantages of the technique are described. Review of the literature showed another 17 cases successfully treated by means of stereotactic aspiration. The reliability of this approach is supported by the good outcome and the long follow-up of cases previously reported by other Authors. In our opinion, stereotactic aspiration should thus be the first step in the management of colloid cysts.

[Changes in the bone marrow in cancer patients. 61 bone marrow biopsies]. / Les modifications de la moelle osseuse chez les cancéreux. A propos de 61 biopsies médullaires

The authors studied 61 bone marrow biopsies carried out in cancerous patients, presumably suffering from a bone metastasis and before any treatment. They feel that quantitative and qualitative changes in the bone marrow may be considered to be an indirect diagnostic indication of metastatic spread.

[Technic for the preparation of bone marrow biopsies. Evaluation of bone marrow cell count]. / Tehcnique de préparation des biopsies médullaires. Evaluation de la richesse médullaire

After having briefly reviewed the different subjective and objective procedures for interpreting Bone Marrow Biopsies from the standpoint of evaluating Bone Marrow Cellularity, the authors propose a method for overall morphological examination, controlled by a rapid evaluation by means of an integrator ocular. This simple, reliable and easily reproducible "semi-subjective" technique seems useful in routine pathological diagnosis, particularly to compare successive Bone Marrow Biopsies from the same patient when treated by antimitotics, or to study the changes of the hematopoietic tissue in the area of medullary metastasis.