Angle closure: classification, concepts, and the role of ultrasound biomicroscopy in diagnosis and treatment

The angle closure glaucomas are a diverse group of disorders characterized by mechanical blockage of the trabecular meshwork by the peripheral iris leading to elevated intraocular pressure and glaucoma. Understanding the pathophysiologic mechanisms underlying these disorders is essential for both diagnosis and management. This review covers the anatomy, etiology, classification, and therapy of the various angle closure glaucomas and the role that ultrasound biomicroscopy has played in helping us understand these diseases.     

Olanzapine effects on auditory sensory gating in schizophrenia

OBJECTIVE: New-generation antipsychotics have been proposed to normalize the P50 sensory gating index in patients with schizophrenia. In the context of a double-blind comparison of olanzapine and haloperidol, the authors examined the effect of olanzapine on P50 suppression. METHOD: P50 measurements were obtained at baseline while patients were being treated with fluphenazine and after 12 weeks of double-blind treatment with either olanzapine (N=12) or haloperidol (N=12). RESULTS: There were no treatment group differences in P50 amplitude, latency, or sensory gating ratio. CONCLUSIONS: These results suggest that there is not a significant differential effect of olanzapine and haloperidol on the P50 sensory gating index in schizophrenia.     

The relationship of clozapine and haloperidol treatment response to prefrontal,hippocampal, and caudate brain volumes

OBJECTIVE: The study was designed to assess the predictive relationship between brain structure volume and positive and negative symptom response to clozapine and haloperidol. METHOD: Partially responsive outpatients with schizophrenia who participated in a 10-week, parallel-group, double-blind comparison of clozapine and haloperidol and who had an available magnetic resonance imaging scan were included in the current study. Prefrontal gray and white matter, hippocampal, and caudate volumes were manually measured. The Scale for the Assessment of Negative Symptoms (SANS) and the Brief Psychiatric Rating Scale (BPRS) were used to assess symptom changes. The Simpson-Angus Rating Scale was used to assess extrapyramidal symptoms. RESULTS: Twenty-two patients randomly assigned to clozapine and 23 patients assigned to haloperidol met study entry criteria. There were significant interactions between treatment and right prefrontal gray matter volume for BPRS total score and SANS total score. There were no significant treatment-by-brain structure interactions for BPRS positive symptom items. Right prefrontal gray matter volume was also related to differential treatment effects for the BPRS subscales of anxiety/depression and hostility and the Simpson-Angus Rating Scale akathisia item. CONCLUSIONS: These results suggest that there is a differential interaction among clozapine and haloperidol, brain structure, and treatment response. Partially responsive patients with larger brain volumes may be more likely to experience the benefits of clozapine treatment, but they may be more vulnerable to side effects and experience a subsequent worsening of their symptoms when treated with haloperidol.     

The hypothalamic paraventricular nucleus and carotid receptors modulate hyperglycemia induced by hemorrhage

The aim of this study was to assess the role of cholinergic transmission in the paraventricular nucleus of the hypothalamus (PVN) and carotid body receptors in mediating a rise in plasma glucose levels in response to hemorrhagic hypotension in rats. Methylatropine (1x10(-9) mol) or 0.15 M NaCl (0.2 microl) was injected into the PVN of Wistar rats weighing 250-300 g bearing a chronic jugular catheter for blood sampling and hemorrhage (1.2 ml/100 g/2 min). Polyethylene cannulae (PE-10) were inserted into the left femoral artery for cardiovascular monitoring. In the other experimental protocol, hemorrhage was performed on rats submitted to bilateral carotid receptor denervation (H-CD). The results show that the hyperglycemic response to hemorrhage was decreased by either methylatropine (H-MA) treatment or bilateral carotid receptor denervation (10.3+/-0.4 mM, control, n=15 vs. 7.7+/-0.2 mM, H-MA, n=12, and 7.6+/-0.3 mM, H-CD, n=5, p<0.01). Furthermore, methylatropine did not affect the recovery of blood pressure after hemorrhage-induced hypotension, suggesting that the metabolic and pressor adjustments have different efferent pathways. Our data demonstrate that cholinergic input from the PVN and carotid receptors (chemo- and/or baroreceptors) might participate in the same neural pathway activated by hemorrhage-induced hypotension that produces hyperglycemia.     

Phylogenetic analysis of the envelope protein (domain III) of dengue 4 viruses

OBJECTIVE: To evaluate the genetic variability of domain III of envelope (E) protein and to estimate phylogenetic relationships of dengue 4 (Den-4) viruses isolated in Mexico and from other endemic areas of the world. MATERIAL AND METHODS: A phylogenetic study of domain III of envelope (E) protein of Den-4 viruses was conducted in 1998 using virus strains from Mexico and other parts of the world, isolated in different years. Specific primers were used to amplify by RT-PCR the domain III and to obtain nucleotide sequence. Based on nucleotide and deduced aminoacid sequence, genetic variability was estimated and a phylogenetic tree was generated. To make an easy genetic analysis of domain III region, a Restriction Fragment Length Polymorphism (RFLP) assay was performed, using six restriction enzymes. RESULTS: Study results demonstrate that nucleotide and aminoacid sequence analysis of domain III are similar to those reported from the complete E protein gene. Based on the RFLP analysis of domain III using the restriction enzymes NIa III, Dde I and Cfo I, Den-4 viruses included in this study were clustered into genotypes 1 and 2 previously reported. CONCLUSIONS: Study results suggest that domain III may be used as a genetic marker for phylogenetic and molecular epidemiology studies of dengue viruses. The English version of this paper is available too at: http://www.insp.mx/salud/index.html.     

Epstein-Barr viral load, interleukin-6 and interleukin-10 levels in post-transplant lymphoproliferative disease: a nested case-control study in a renal transplant cohort

The possible correlation among Epstein-Barr virus (EBV) load, interleukin-6 (IL-6) and interleukin-10 (IL-10) levels has become an attractive issue and can provide a useful tool for diagnosis and monitoring of patients at risk for post-transplant lymphoproliferative disease (PTLD) development. At the time of diagnosis of PTLD, 11 patients were prospectively enrolled and 55 nested controls were selected from a 1800 renal transplant cohort. Real-time polymerase chain reaction (PCR) was used to quantify EBV load in peripheral blood mononuclear cells (PBMC). Serum IL-6 and IL-10 levels were determined using an enzyme-linked immunosorbent assay (ELISA). The median EBV load of PTLD cases was 17400 copies/10(6) PBMC, statistically different from controls (P=0.001). The median IL-6 level of PTLD cases was not different from controls (P=0.079). However, median IL-10 levels showed a significant difference in both groups (P < or = 0.001). The receiver-operating characteristic (ROC) curve analysis was applied to estimate the IL-10 cut-off value predictive of PTLD development. We found that 73.5 pg/ml has high sensitivity (1.00) and specificity (0.85). Also, Pearson's analysis showed a strong correlation between EBV load and serum IL-10 concentration (P < or = 0.001). This nested case-control study demonstrates that EBV load at diagnosis of PTLD correlates with IL-10 levels, and that monitoring of IL-10 can provide a less expensive and less time-consuming tool for PTLD diagnosis and close follow-up of patients at risk. Furthermore, we were able to define a cut-off value of IL-10 mostly predictive of PTLD development in this cohort. Our data suggest that serial measurements prior to PTLD development must be carried out to validate our hypothesis.     

A monitoring system for work-related accidents in Piracicaba, São Paulo, Brazil

The authors report on the development of a work accident monitoring system in Piracicaba, S?o Paulo State, Brazil, with the following characteristics: information feeding the system is obtained in real time directly from accident treatment centers; the system has universal monitoring, covering all work-related accidents in Piracicaba, regardless of the nature of the worker's employment conditions, place of work, or place of residence; health surveillance and promotion of health initiatives are triggered by identification of sentinel events; spatial distribution analysis of work-related accidents is a basic tool in designing accident awareness strategies and accident prevention policies. The system was implemented in November 2003 and by October 2004 had identified 5,320 work-related accidents, or a 3.8% annual proportional incidence of work-related accidents in the municipal area. We illustrate spatial analysis of registered work-related accidents and present a detailed investigation of one example of a serious accident.     

Induction of protective antibodies against dengue virus by tetravalent DNA immunization of mice with domain III of the envelope protein

Dengue fever is a growing public health concern around the world and despite vaccine development efforts, there are currently no effective dengue vaccines. In the present study we report the induction of protective antibodies against dengue virus by DNA immunization with domain III (DIII) region of the envelope protein (E) in a mouse model. The DIII region of all four dengue virus serotypes were cloned separately into pcDNA 3 plasmid. Protein expression was tested in COS-7 cells. Each plasmid, or a tetravalent combination, were used to immunize BALB/c mice by intramuscular route. Presence of specific antibodies was evaluated by ELISA, and neutralizing antibodies were tested using a cytopathogenic effect (CPE) inhibition assay in BHK-21 cells, as well as in newborn mice challenged intracranially with dengue 2 virus. Mice immunized with individual DIII constructs or the tetravalent formulation developed antibodies against each corresponding dengue serotype. Antibody titers by ELISA were similar for all serotypes and no significant differences were observed when boosters were administered, although antibody responses were dose-dependent. CPE inhibition assays using Den-2 virus showed neutralization titers of 1:10 in mice immunized with individual DIII plasmid or those immunized with the tetravalent formulations. 43% of newborn mice challenged with Den-2 in combination with sera from mice immunized with Den-2 DIII plasmid were protected, whereas sera from mice immunized with the tetravalent formulation conferred 87% protection. Our results suggest that DIII can be used as a tetravalent DNA formulation to induce neutralizing and protective antibodies against dengue virus.