Minimum effective doses of haloperidol for the treatment of first psychotic episode: a comparative study with risperidone and olanzapine

Minimum doses of haloperidol might show similar efficacy and side-effects compared to atypical antipsychotics. The objectives of this study were to compare the efficacy of minimum doses of haloperidol with standard doses of risperidone and olanzapine on a 6-month open trial in first psychotic episode patients and to examine the effect of compliance on their outcome. Forty-two patients were recruited and started on flexible doses of these drugs. Olanzapine was given with no cost to the patients. Efficacy and side-effects were monitored every 3 months using standardized assessments. Thirty patients completed the study. All treatment groups showed improvement in positive, negative and depressive symptoms. There were no differences in side-effects among them. The haloperidol group required higher doses of anticholinergics. The rate of treatment discontinuation was higher in the risperidone group due to the direct cost. Minimum doses of haloperidol might prove to be a good choice of treatment for patients with a first episode of psychosis.     

Estimating the incidence of typhoid fever and other febrile illnesses in developing countries

To measure the incidence of typhoid fever and other febrile illnesses in Bilbeis District, Egypt, we conducted a household survey to determine patterns of health seeking among persons with fever. Then we established surveillance for 4 months among a representative sample of health providers who saw febrile patients. Health providers collected epidemiologic information and blood (for culture and serologic testing) from eligible patients. After adjusting for the provider sampling scheme, test sensitivity, and seasonality, we estimated that the incidence of typhoid fever was 13/100,000 persons per year, and the incidence of brucellosis was 18/100,000 persons per year in the district. This surveillance tool could have wide applications for surveillance for febrile illness in developing countries.     

PRELI, the human homologue of the avian px19, is expressed by germinal center B lymphocytes

We report the identification of a human cDNA encoding a 25 kDa protein of relevant evolutionary and lymphoid interest (PRELI). PRELI was cloned by screening a B lymphocyte-specific cDNA library with a probe generated by mRNA differential display. PRELI amino acid sequence is 85% similar to the avian px19 protein, expressed within the blood islands and in the liver during avian embryo development. PRELI and px19 contain tandem repeats (A/TAEKAK) of the late embryogenesis abundant (LEA) motif, characteristic of a group of survival molecules and originally thought to be present only in plant proteins. Interestingly, PRELI expression is high in the fetal liver, a major site for B cell lymphopoiesis, while the mRNA levels in other fetal tissues such as the brain, lung, and kidney are comparatively low. At the adult stage, PRELI expression is drastically reduced in the liver but exhibits high mRNA levels in the spleen, brain, lung and kidney tissues, suggesting that PRELI expression may be important for the development of vital and immunocompetent organs. Moreover, PRELI is also highly expressed in the adult lymph nodes and peripheral blood leukocytes, further stressing that at the adult stage, PRELI expression may be important during secondary immune responses. Consistent with this hypothesis, the expression of PRELI is predominant within germinal centers (GC), a stage in which B lymphocytes are under a stressful selection pressure. Taken together these data: (i) strongly support the notion that the conserved LEA motif represents a phylogenetic link between plants and animals, (ii) reveal a novel molecule whose expression may play a role in the maturation of distinct human tissues, and (iii) suggest that PRELI expression may be important for GC B lymphocytes.     

Proposal of a new PAF pharmacophoric map by the AM1 method

PAF is a powerful phospholipid-derived autacoid involved in many pathophysiological processes. Many PAF antagonists have been synthesized and assayed for therapeutic purposes. We have synthesized derivatives ( ), structurally related to WEB 2086 ( ), which were rationally designed based on a planar PAF receptor model previously described by Bures et al. (1994; J. Chem. Inf. Comput. Sci. 24, 218–223). However, pharmacological studies revealed that derivatives ( ) were inactive as PAF antagonists. AM1 quantum calculations of classical PAF antagonists ( ), as well as of our derivatives ( ), demonstrated that electronic features alone are unable to explain the lack of the activity of ( ). These results induced us to propose a new tridimensional PAF receptor pharmacophoric map by analyzing all stable conformations obtained for derivatives ( ). The interpoint distances (D1–D5) revealed that the lowest-energy conformers of ( ) had similar geometries to derivatives ( ). So, these aspects could not explain the inactivity of the compounds ( ). The proposed model suggests that the best fit of antagonist compounds may involve the participation of a sulfur atom electron lone pair adequately oriented in relation to the plane of a N-aromatic ring present in the compounds investigated.