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Encephale. 2002 Jul-Aug;28(4):291-7.
[Influence of attention on an auditory-verbal learning test in schizophrenic patients]

[Article in French]

Huguelet P, Nicastro R, Zanello A.

Departement de Psychiatrie, Hopitaux Universitaires de Geneve, 8, rue du 31 decembre, 1207 Geneve, Suisse.

Schizophrenic patients are known to feature alterations in their cognitive performances, principally in executive functions, attention and memory. In this last domain, studies have shown a relatively severe and global deficit, which can be assessed in chronic and first episode patients. It seems that the memory dysfunction is independent of age and intellectual level, but does correlate with negative psychopathology and global functioning. In the study of memory dysfunction, attentional capacities, information processing and symptomatology have to be considered as determining factors. It has been shown that patients with schizophrenia perform poorly in selective attention tasks and that this deficit may interfere with learning. In the same way, the slowing of information processing contributes to a superficial and incomplete learning. The impact of symptomatology has also to be considered, as negative and depressive symptoms are linked to mnesic performances. The majority of studies bearing on working memory and schizophrenia show an alteration of performances, but studies on long term memory are more equivocal. Procedural memory seems to be preserved, while declarative memory is impaired. These results support the hypothesis that in schizophrenia, memory processes that are consciously controlled are impaired, contrary to implicit learning which may be intact. Nevertheless, studies bearing on semantic memory and episodic memory show controversial results. Still, many authors argue that schizophrenic patients have difficulties in recalling learned material, specially when a delay or a interfering task are introduced in the test. Besides, the schizophrenic subjects do not use the semantic properties of the words, as well as the control subjects, when they have to learn a words list for example. The main goal of the present study was to examine the auditory-verbal learning capacities of 31 schizophrenic patients (20 men and 11 women, 19-56 years old), compared to 27 healthy subjects (11 men and 16 women, 23-56 years old). All subjects received an evaluation including the Rey Auditory-Verbal Learning Test, used to study the progressive acquisition of 15 disyllabic words which are successively orally presented five times to the subject. About forty-five minutes after the last of the five immediate recalls, the delayed recall is assessed and a percentage of retention is also calculated. Visual reasoning and attention capacities were studied with the Progressive Matrix and the d2 encumbrance test respectively. Global psychiatric symptomatology of the patients group was assessed with the Brief Psychiatric Rating Scale. Considering the literature existing on the verbal learning capacities of schizophrenic patients, it was expected that the patients would perform poorly and learn slower than controls. The initial learning of the material, which is a critical stage for schizophrenic patients, was studied with particular attention as well as the effect of the introduction of a delay upon the recall of the words list. A secondary objective of the study was to investigate the role of visual reasoning and attention upon auditory-verbal learning process. According to published studies, it is expected that schizophrenic patients manifest some impairment in the domains of visual reasoning and attention. The question is to know whether it alters performances in the auditory-verbal learning test or not. Finally, the links between clinical characteristics of the patients, like age and illness duration, and their learning performances were explored. Statistical analysis included first a descriptive analysis of data to examine differences between the two groups. Second, ANCOVAs were used in order to control the respective impact of educational level, attention capacities and verbal reasoning capacities upon learning performances. Third, Spearman's correlations were used to detect links between clinical characteristics of the patients and learning performances. The comparisons between patients and controls confirmed that schizophrenic patients scored less in the attentional and visual reasoning tasks. They also featured a lower educational level compared to the healthy subjects. In the auditory-verbal learning test, the patients showed altered performances in the five recalls, as well as in the delayed recall and for the retention percentage. In order to control the impact of educational level, attentional and visual reasoning capacities, these parameters were introduced in the statistical analyses. Educational level did not influence memory alterations in the schizophrenic group. However, attention and, to a lesser extend, visual reasoning had an impact on the comparison of memory scores: when controlling attention, almost no significant group effect remained. Finally, the exploratory analyses of links between clinical characteristics and memory only revealed the presence of a significant negative correlation between illness duration and learning performances. Thus, the analyze of data showed that schizophrenic subjects featured poor performances in the domains of attention, verbal reasoning and auditory-verbal memory. Further analyses taking into account group differences on attention suggest that the impairment featured by schizophrenic patients in the domain of verbal memory strongly relies on an attentional deficit. These results are discussed according to the existing literature and methodological limitations. Clinical implications are also discussed.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12232538&dopt=Abstract

Encephale. 2002 Jul-Aug;28(4):329-42.
[Use of atypical antipsychotics in Charles Perrens psychiatric hospital (Bordeaux) analysis of prescribing practices for Amisulpride, Clozapine, Olanzapine and Risperidone]

[Article in French]

Bret P, Bonnet F, Bret MC, Jaffre A.

Pharmacien, Service Pharmacie, CH Charles Perrens, 121 rue de la Bechade, 33076 Bordeaux cedex, France.

The commercial introduction of atypical antipsychotics (AAP) constitutes a considerable step forward in the sense that it has led to a world-wide reappraisal of the established treatment strategies for people with psychoses (including schizophrenia and affective psychoses). They have allowed refinements in the pharmacologic management of psychoses but they have a higher acquisition cost than conventional neuroleptics. The cost of the newer AAP had a substantial effect on medical resources: the AAP account for only 43.2% of neuroleptic prescriptions, but 76.1% of medical costs associated with neuroleptic drugs, and in terms of treatment costs, a reduction (50%) was found with risperidone compared with olanzapine for a same number of treated patients. The aim of this paper was to examine the use of these drugs, to compare them and to assess their impact within the context of psychiatric hospital practice, by means of analysis of prescribing practices for amisulpride, clozapine, olanzapine and risperidone for all treated patients. We conducted an observational, naturalistic study at Charles Perrens psychiatric Hospital in Bordeaux (France) that reproduced the clinical conditions in which these new drugs are used. Four photographies of all the medical prescriptions concerning atypical antipsychotic drugs were done between October 1999 (four months after the introduction in France of the olanzapine, the last of the new antipsychotics) and June 2001 (n=682 prescriptions). The total amount of these prescriptions corresponded to 527 patients. Treatment groups were compared - first overall and after by considering 2 groups: psychotic and non-psychotic patients - through descriptive analyses of sociodemographic characteristics of patients, diagnosis, percentages of patients receiving concomitant psychotropic medication and/or receiving treatment-emergent side effects and mean dosages of AAP therapy according to concomitant medication. In the same way, we compared the four AAP through their prescribing practices'evolution during the four survey. Results: AAP drugs account for 43.2% of prescriptions (and conventional neuroleptics 56.8% of them). We recorded a significant increase between the four surveys (p<0.02): 36.6% at the beginning to 47.8% at the end of the study. From the 682 collected prescriptions, 72 (10.6%) included clozapine, 130 (19.1%) amisulpride, 229 (33.6%) olanzapine and 251 (36.8%) risperidone. Sixty five percent of AAP prescriptions involved psychotic patients. A relative stability in characteristics of AAP prescriptions during the four surveys was found. So, no significant differences were observed between amisulpride, olanzapine, risperidone, in terms of age, sex, sociodemographic characteristics, unlike clozapine. However, there were statistical differences between all the AAP in the concurrent use of other neuroleptic agents (p<0.02), hypnotic drugs (p<0.006), mood stabilizer drugs (p<0.03), and anticholinergic drugs (p<0.007). Statistically, the mean dosage of amisulpride increased when a mood stabilizer drug was coprescribed (p<0.0007), but it decreased with an antidepressant drug (p<0.004) or an hypnotic drug (p<0.02); clozapine 's one decreased every time an antidepressant drug was coprescribed (p<0.02); with olanzapine, there was a significant increase every time an other neuroleptic agent (p<0.03) or an anticholinergic drug (p<0.006) was associated; then for risperidone, the mean dosage increased with the coprescription of an other neuroleptic agent (p<0.00002), an anticholinergic (p<0.00003) or an adrenolytic drug (p<0.04). The pattern of prescribing practices that emerges from our four surveys suggests that these new AAP are significantly more and more often associated with a stabilizer mood drug (p<0.009) (particularly the olanzapine) or/and an anxiolytic drug (p<0.05) (like the amisulpride in particular). Considering the four AAP globally, but more with the risperidone, the association with a neurovegetative corrector agent decreased (p<0.004) during the four surveys. Then, concerning the psychoticng the four surveys. Then, concerning the psychotic patients, the AAP were significantly more often associated with other neuroleptic agents (p<0.03), the amisulpride in particular, with anticholinergic drugs (p<0.00005), but significantly less with mood stabilizer drugs (p<0.00003) principally the amisulpride and the risperidone, with antidepressant drugs (p<0.02) particularly the risperidone. This kind of survey, however it is too much rare, is very important because it shows the clinical conditions in which these new drugs are really used. The results show that AAP appear to be the replacements of the older neuroleptics used in the treatment of psychoses, including particularly schizophrenia, but also in the treatment of mood disorders, and they reflect actual clinical practices. Other surveys must be achieved to see if our study confirms the general trend concerning the use of these drugs and so as to reassess these prescribing practices.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12232542&dopt=Abstract

Mol Psychiatry. 2002;7(8):837-44.
NMDA receptor antagonists ketamine and PCP have direct effects on the dopamine D(2) and serotonin 5-HT(2)receptors-implications for models of schizophrenia.

Kapur S, Seeman P.

Center for Addiction and Mental Health, Clarke Site, Department of Psychiatry, University of Toronto, 250 College Street, Toronto, Ontario, Canada M5R 1T8. skapuamhpet.on.ca

Ketamine and PCP are commonly used as selective NMDA receptor antagonists to model the putative hypoglutamate state of schizophrenia and to test new antipsychotics. Recent findings question the NMDA receptor selectivity of these agents. To examine this further, we measured the affinity of ketamine and PCP for the high-affinity states of the dopamine D(2) and serotonin 5-HT(2) receptor and found that ketamine shows very similar affinity at the NMDA receptor and D(2) sites with a slightly lower affinity for 5-HT(2) (0.5 microM, 0.5 microM and 15 microM respectively), while PCP shows similar affinity for the NMDA and 5-HT(2) sites, with a slightly lower affinity for the D(2) site (2 microM, 5 microM and 37 microM respectively). Further, ketamine and PCP in clinically relevant doses caused a significant increase in the incorporation of [(35)S]GTP-gamma-S binding in CHO-cells expressing D(2) receptors, which was prevented by raclopride, suggesting a partial agonist effect at the D(2) receptor. Thus, ketamine and PCP may not produce a selective hypoglutamate state, but more likely produce a non-selective multi-system neurochemical perturbation via direct and indirect effects. These findings confound the inferences one can draw from the ketamine/PCP models of schizophrenia.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12232776&dopt=Abstract

Mol Psychiatry. 2002;7(8):851-9.
A genome screen of 13 bipolar affective disorder pedigrees provides evidence for susceptibility loci on chromosome 3 as well as chromosomes 9, 13 and 19.

Badenhop RF, Moses MJ, Scimone A, Mitchell PB, Ewen-White KR, Rosso A, Donald JA, Adams LJ, Schofield PR.

Garvan Institute of Medical Research, 384 Victoria Street, Sydney 2010, Australia.

Bipolar affective disorder is a severe mood disorder that afflicts approximately 1% of the population worldwide. Twin and adoption studies have indicated that genetic factors contribute to the disorder and while many chromosomal regions have been implicated, no susceptibility genes have been identified. We undertook a combined analysis of 10 cM genome screen data from a single large bipolar affective disorder pedigree, for which we have previously reported linkage to chromosome 13q14 (Badenhop et al, 2001) and 12 pedigrees independently screened using the same 400 microsatellite markers. This 13 pedigree cohort consisted of 231 individuals, including 69 affected members. Two-point LOD score analysis was carried out under heterogeneity for three diagnostic and four genetic models. Non-parametric multipoint analysis was carried out on regions of interest. Two-point heterogeneity LOD scores (HLODs) greater than 1.5 were obtained for 11 markers across the genome, with HLODs greater than 2.0 obtained for four of these markers. The strongest evidence for linkage was at 3q25-26 with a genome-wide maximum score of 2.49 at D3S1279. Six markers across a 50 cM region at 3q25-26 gave HLODs greater than 1.5, with three of these markers producing scores greater than 2.0. Multipoint analysis indicated a 20 cM peak between markers D3S1569 and D3S1614 with a maximum NPL of 2.8 (P = 0.004). Three other chromosomal regions yielded evidence for linkage: 9q31-q33, 13q14 and 19q12-q13. The regions on chromosomes 3q and 13q have previously been implicated in other bipolar and schizophrenia studies. In addition, several individual pedigrees gave LOD scores greater than 1.5 for previously reported bipolar susceptibility loci on chromosomes 18p11, 18q12, 22q11 and 8p22-23.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12232778&dopt=Abstract

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