Behcet disease: long-term follow-up of three children and review of the literature

Behcet disease is rare in children. There are only two reports of Behcet disease in childhood, describing seven patients. Three pediatric patients are described, in whom the age of onset ranged from 6 to 11 years. Aphthous stomatitis and arthritis were present in all of the patients; genital ulcers, iridocylitis, erythema nodosum, and CNS involvement were present in two patients. Other manifestations included Stevens-Johnson-like eruption, fever of unknown origin, and testicular involvement. All of the patients responded to glucocorticoids; two were also treated with colchicine and one was treated with chlorambucil. In two patients, follow-up of more than 10 years was done, with complete cure in one patient and benign course of illness in the other. Because of the rarity of the disease in childhood and the difficulty in making the diagnosis, there is not enough awareness by pediatricians concerning this disease.     

An innovative training experience in public health at the Cheikh Anta Diop University of Dakar

The Institute for Health and Development (ISED) at the University of Dakar, was created in 1987. Its mission is to fulfill the public health training needs of Senegalese health care professionals. ISED is responsible for a training program entitled "Certificat d'études Spéciales" (CES), the equivalent of a Masters of Public Health degree. The "CES" is a two-year program comprised of six modules, which last four months each. The ISED training approach stresses trainee responsibility above all. It is based on the trainee's professional tasks and is oriented toward the problems identified by the trainees themselves. In this sense it is highly adaptive and flexible. Each module is implemented in the same way; initially there is a 15 day residential phase for intensive theoretical courses, followed by an application period of 75 days in the trainee's work place, and then a final residential phase of 15 days for writing and presenting a technical report on the work in the field. This model allows trainees to bring together the theoretical and the practical. The trainers directly supervise each of these three phases. The two residential phases are conducted in the ISED training center, located in Mbour, 80 Km south of Dakar. 103 trainees are enrolled in the program in seven different classes. Of these trainees, 93 are health care specialists (85 physicians 7 pharmacists, 1 dentist). Ninety percent of previous graduates have been civil servants who work for the Ministry of Health in Senegal and the remaining 10% were from Burkina Faso and Togo. The training program is considered by all stockholders, beneficiaries, and relevant financial institutions, to be appropriate, beneficial and successful.     

Role of Orbscan II in screening keratoconus suspects before refractive corneal surgery

OBJECTIVE: To evaluate the relationship between videokeratographic keratoconus screening programs and Orbscan II topography. DESIGN: Prospective, observational case series and instrument validation study. PARTICIPANTS: Sixty consecutive eyes with suspicious videokeratography (TMS-1, Tomey Technology, Waltham, MA) were evaluated before undergoing laser in situ keratomileusis (LASIK) surgery. A control group of 50 consecutive eyes without suspicious features by videokeratography was also evaluated. METHODS: Keratoconus screening programs, using the Rabinowitz and Klyce/Maeda methods and Orbscan II (Bausch & Lomb, Claremont, CA) topographies were performed on these patients. MAIN OUTCOME MEASURES: Specific parameters evaluated on the Orbscan II topographies were anterior elevation, posterior elevation, and thinnest pachymetry. RESULTS: Compared with a control group of patients without suspicious videokeratography, there was a statistically significant difference in the mean posterior elevation and mean anterior elevation in the groups with positive keratoconus testing with the Rabinowitz or Klyce/Maeda methods. For patients who met both the Rabinowitz and Klyce/Maeda criteria for keratoconus, the mean posterior elevation was 44 +/- 2.5 micro m compared with a posterior elevation of 21 +/- 0.6 micro m for the control group. There was no statistically significant difference in the mean thinnest pachymetry between the control group and all keratoconus suspect groups. CONCLUSIONS: Patients with positive keratoconus screening tests have higher anterior and posterior elevation on Orbscan II topography. When used in combination with videokeratography, the Orbscan II topography system may be helpful in identifying patients who are potentially at high risk for developing ectasia after LASIK.     

N-acetylglutamate synthase deficiency and the treatment of hyperammonemic encephalopathy

Carbamylphosphate synthase is the first enzymatic reaction of the urea cycle. Its activator, N-acetylglutamate, is synthesized from acetyl-CoA and glutamate in a reaction catalyzed by N-acetylglutamate synthase (NAGS). We have identified the putative human NAGS gene and report the first mutation in this gene in a family with carbamylglutamate responsive hyperammonemia and normal activity of the urea cycle enzymes. Mutation analysis has a higher diagnostic specificity than the enzymatic assay in NAGS deficiency. A therapeutic trial with carbamylglutamate is recommended whenever hyperammonemia without an organic aciduria, increased orotate excretion, or diagnostic amino acidemia/uria is detected.     

Immune-related mechanisms participating in resistance and susceptibility to glutamate toxicity

Glutamate is an essential neurotransmitter in the CNS. However, at abnormally high concentrations it becomes cytotoxic. Recent studies in our laboratory showed that glutamate evokes T cell-mediated protective mechanisms. The aim of the present study was to examine the nature of the glutamate receptors and signalling pathways that participate in immune protection against glutamate toxicity. We show, using the mouse visual system, that glutamate-induced toxicity is strain dependent, not only with respect to the amount of neuronal loss it causes, but also in the pathways it activates. In strains that are genetically endowed with the ability to manifest a T cell-dependent neuroprotective response to glutamate insult, neuronal losses due to glutamate toxicity were relatively small, and treatment with NMDA-receptor antagonist worsened the outcome of exposure to glutamate. In contrast, in mice devoid of T cell-dependent endogenous protection, NMDA receptor antagonist reduced the glutamate-induced neuronal loss. In all strains, blockage of the AMPA/KA receptor was beneficial. Pharmacological (with alpha2-adrenoceptor agonist) or molecular intervention (using either mice overexpressing Bcl-2, or DAP-kinase knockout mice) protected retinal ganglion cells from glutamate toxicity but not from the toxicity of NMDA. The results suggest that glutamate-induced neuronal toxicity involves multiple glutamate receptors, the types and relative contributions of which, vary among strains. We suggest that a multifactorial protection, based on an immune mechanism independent of the specific pathway through which glutamate exerts its toxicity, is likely to be a safer, more comprehensive, and hence more effective strategy for neuroprotection. It might suggest that, because of individual differences, the pharmacological use of NMDA-antagonist for neuroprotective purposes might have an adverse effect, even if the affinity is low.     

Sexual dimorphism in the spontaneous recovery from spinal cord injury: a gender gap in beneficial autoimmunity?

Immune cells have been shown to contribute to spontaneous recovery from central nervous system (CNS) injury. Here we show that adult female rats and mice recover significantly better than their male littermates from incomplete spinal cord injury (ISCI). This sexual dimorphism is wiped out and recovery is worse in adult mice deprived of mature T cells. After spinal cord contusion in adult rats, functional recovery (measured by locomotor scores in an open field) was significantly worse in females treated with dihydrotestosterone prior to the injury than in placebo-treated controls, and significantly better in castrated males than in their noncastrated male littermates. Post-traumatic administration of the testosterone receptor antagonist flutamide promoted the functional recovery in adult male rats. These results, in line with the known inhibitory effect of testosterone on cell-mediated immunity, suggest that androgen-mediated immunosuppression plays a role in ISCI-related immune dysfunction and can therefore partly explain the worse outcome of ISCI in males than in female. We suggest that females, which are more prone to develop autoimmune response than males, benefit from this response in cases of CNS insults.     

Implicit learning of emotional information under anesthesia

Surgical stress activates the amygdala and secretion of norepinephrine, both involved in memory and unconscious processing of emotionally negative information. This study examined surgically induced facilitation of implicit learning of emotionally negative information. Thirty patients undergoing laparoscopic cholecystectomy under general anesthesia were tested. Between 2 and 4 h after surgery, patients provided word-associates to cues previously presented (old) or not previously presented during anesthesia (new). Half the cues were emotionally negative and half neutral. Patients took less time to provide correct associates to old emotionally negative cues than to new emotionally negative cues (p < 0.05). Spectral edge frequency (SEF) of cerebral activity during surgery converged with this finding. Implicit learning during general anesthesia may be stronger for emotionally negative information and is detected by SE.     

Long-term follow-up in managing anaplastic astrocytoma by multimodality approach with surgery followed by postoperative radiotherapy and PCV-chemotherapy: phase II trial

Overall survival and progression-free survival after 5 and 10 years of 31 patients with malignant glioma treated by a combination of surgery, postoperative radiotherapy, and chemotherapy with a PCV regimen (procarbazine, CCNU [lomustine] and vincristine) is described. Parameters were evaluated by age at diagnosis, gender, ethnic origin, pre- and postsurgery Karnofsky Performance Status (KPS) score, limit and amount of surgical resection, histopathologic type, number of chemotherapy courses, time between surgery and radiotherapy, response to combined therapy, and dosage and type of radiotherapy. Progression-free survival was 29% at 24 months and 22% at 60 and 120 months. Overall survival was 47%, 36%, and 36% after 24, 60, and 120 months, respectively. Favorable prognostic factors for survival in univariate analysis were pre- and postoperative KPS (> or =70; p = 0.015; p = 0.0025, respectively), age of patients (<40; p = 0.01), number of chemotherapy cycles (> or =6; p = 0.02), and radiation dose (> or =60 Gy; p = 0.0015). The only significant prognostic factors for overall survival in a stepwise multivariate analysis were irradiation dose (p = 0.0001), number of chemotherapy cycles (p = 0.001), and preoperative KPS (p = 0.05); for progression-free survival it was number of chemotherapy cycles (p = 0.004). Survival was not affected by excision size, radiation method, histopathologic type of tumor, gender, ethnic origin, or time lapsed between surgery and irradiation.     

Caspase-9 and Apaf-1 are expressed and functionally active in human neuroblastoma tumor cell lines with 1p36 LOH and amplified MYCN

Important roles have been suggested for caspase-8, caspase-9 and Apaf-1 in controlling tumor development and their sensitivity to chemotherapeutic agents. Methylation and deletion of Apaf-1 and CASP8 results in the loss of their expression in melanoma and neuroblastoma, respectively, while CASP9 localization to 1p36.1 suggests it is a good candidate tumor suppressor. The status of CASP9 and Apaf-1 expression in numerous neuroblastoma cell lines with/without amplified MYCN and chromosome 1p36 loss-of-heterozygosity (LOH) was therefore examined to test the hypothesis that one or both of these genes are tumor suppressors in neuroblastoma. Although CASP9 is included in the region encompassing 1p36 LOH in all neuroblastoma cell lines examined, the remaining CASP9 allele(s) express a functional caspase-9 enzyme. Apaf-1 is also expressed in all neuroblastoma tumor cell lines examined. Thus, the CASP9 or Apaf-1 genes do not appear to function as tumor suppressors in MYCN amplified neuroblastomas. However, approximately 20% of the neuroblastoma cell lines with methylated CASP8 alleles are also highly resistant to staurosporine (STS)- and radiation-induced cell death, presumably because cytochrome c is not released from mitochondria. This suggests that a second, smaller sub-group of MYCN amplified neuroblastoma tumors exists with defect(s) in apoptotic signaling components upstream of caspase-9 and Apaf-1. Since no consistent differences in Bcl-2, Bcl-x(L) or Bax expression were seen in the STS- and radiation-resistant neuroblastomas, it suggests that a unique mitochondrial signaling factor(s) is responsible for the defect in cytochrome c release in this sub-group of tumors.     

Myelin specific Th1 cells are necessary for post-traumatic protective autoimmunity

This study examined the expression of constitutive endothelial nitric oxide synthase (eNOS) and inducible NOS (iNOS) in the sciatic nerve of Lewis rats with experimental autoimmune neuritis (EAN). Western blot analysis showed that both eNOS and iNOS expressions in the sciatic nerves of rats increased significantly during the peak stage of EAN, but declined thereafter. Only minimal amounts of these enzymes were identified in normal rat sciatic nerves. Immunohistochemical studies showed that eNOS was increased in vascular endothelial cells and Schwann cells, but not in inflammatory cells, during the peak stage of EAN. However, iNOS was found mainly in inflammatory macrophages in sciatic nerve EAN lesions.These findings suggest that, depending on the stage of peripheral nervous system autoimmune disease, the increased expressions of both eNOS and iNOS might be involved in either the production of detrimental effects during the induction stage of EAN or in the recovery from EAN paralysis.