Public health surveillance systems: let's not ask for the impossible

The publication of the Decree creating the National Epidemiological Surveillance Network, 7 years ago now, invites us to reflect on public health surveillance systems in our country and to highlight those aspects that help or obstruct these systems in meeting their basic objective of providing information that can be used to facilitate disease control. Many of the events that have taken place in the health arena in recent years, labeled as health crises by the communications media, have been considered by the population as unacceptable risks that the health system should have avoided; defects in surveillance systems are one of the errors always mentioned in this respect. Some of these defects arise because of limitations of the instruments used to measure and classify health problems, but others are due to an inappropriate understanding of surveillance, which make it difficult to assess the true impact of health problems. A discussion of the two types of defects will not solve surveillance problems, but it may help many people to stop asking our surveillance systems for what they cannot offer.     

Surgery for subfoveal choroidal neovascularization in toxoplasmic retinochoroiditis

PURPOSE: To report a case of subfoveal choroidal neovascularization in a patient with toxoplasmic retinochoroiditis who underwent surgical excision. DESIGN: Interventional case report. METHODS: A 36-year-old woman with toxoplasmic retinochoroiditis presented with sudden dimness of vision and metamorphopsia in the left eye. The patient was examined with ophthalmoscopy and fluorescein angiography. RESULTS: Fundus examination and fluorescein angiography of the left eye revealed a subfoveal choroidal neovascularization. Pars plana vitrectomy with submacular surgery was performed, with a postoperative improvement of visual acuity and resolution of the distortion. CONCLUSIONS: This case report describes a case of subfoveal choroidal neovascularization associated with toxoplasmic retinochoroiditis that responded remarkably well to vitrectomy surgery.     

Antiangiogenic therapy by local intracerebral microinfusion improves treatment efficiency and survival in an orthotopic human glioblastoma model.

Targeting active angiogenesis, which is a major hallmark of malignant gliomas, is a potential therapeutic approach. For effective inhibition of tumor-induced neovascularization, antiangiogenic compounds have to be delivered in sufficient quantities over a sustained period of time. The short biological half-life of many antiangiogenic inhibitors and the impaired intratumoral blood flow create logistical difficulties that make it necessary to optimize drug delivery for the treatment of malignant gliomas. In this study, we compared the effects of endostatin delivered by daily systemic administration or local intracerebral microinfusion on established intracranial U87 human glioblastoma xenografts in nude mice. Noninvasive magnetic resonance imaging methods were used to assess treatment effects and additional histopathological analysis of tumor volume, microvessel density, proliferation, and apoptosis rate were performed. Three weeks of local intracerebral microinfusion of endostatin (2 mg/kg/day) led to 74% (P < 0.05) reduction of tumor volumes with decreased microvessel densities (33.5%, P < 0.005) and a 3-fold increased tumor cell apoptosis (P < 0.002). Systemic administration of a 10-fold higher amount of endostatin (20 mg/kg/day) did not result in a reduction of tumor volume nor in an increase of tumor cell apoptosis despite a significant decrease of microvessel densities (26.9%, P < 0.005). Magnetic resonance imaging was used to successfully demonstrate treatment effects. The local microinfusion of human endostatin significantly increased survival when administered at 2 mg/kg/day and was prolonged further when the dose was increased to 12 mg/kg/day. Our results indicate that the local intracerebral microinfusion of antiangiogenic compounds is an effective way to overcome the logistical problems of inhibiting glioma-induced angiogenesis.     

Clonal plasma cells from monoclonal gammopathy of undetermined significance, multiple myeloma and plasma cell leukemia show different expression profiles of molecules involved in the interaction with the immunological bone marrow microenvironment.

The immunological bone marrow (BM) microenvironment plays a major role in controlling growth and survival of clonal plasma cells (PC); this might translate into different patterns of expression of molecules involved in immune responses on PC from different types of monoclonal gammopathies (MG). We have studied the expression of a group of nine such molecules on both BMPC and the plasma of 61 newly diagnosed MG patients (30 MG of undetermined significance (MGUS), 27 multiple myeloma (MM) and four plasma cell leukemia (PCL)) and five normal individuals. Clonal PC from all MG displayed significantly increased levels of CD56, CD86 and CD126, and decreased amounts of CD38 (P<0.001). Additionally, HLA-I and beta2-microglobulin were abnormally highly expressed in MGUS, while CD40 expression was decreased in MM and PCL (P<0.05). Interestingly, a progressive increase in the soluble levels of beta2-microglobulin was found from MGUS to MM and PCL patients (P=0.03). In contrast, all groups showed similar surface and soluble amounts of CD126, CD130 and CD95, except for increased soluble levels of CD95 observed in PCL. Overall, those phenotypic differences are consistent with increased antigen presentation and costimulatory capacities in MGUS, which progressively deteriorate in malignant MG (MM and PCL).     

H-cadherin expression inhibits in vitro invasiveness and tumor formation in vivo

H-cadherin is a newly characterized cadherin molecule whose expression is decreased in a variety of human carcinoma cells, suggesting that it may play a role in maintaining normal cellular phenotype. To investigate how re-expression of H-cadherin could influence the malignant phenotype of human breast carcinoma cells in vivo, we transfected both control and H-cadherin expression vectors into human breast cancer cells (MDAMB435), which do not express H-cadherin constitutively. We found that invasiveness of these cells could be prevented by transfection with H-cadherin. We also compared the ability of control- and H-cadherin-transfected cells to induce subcutaneous tumors after injection into mammary fat pads of nude mice. Our results show that H-cadherin transfection produced a marked inhibition of tumor growth and modified the morphology of tumor cells: tumors from mice injected with control cells were significantly larger and contained larger cells having a higher degree of pleomorphism than those of tumors generated from carcinoma cells expressing H-cadherin. Altogether, these results indicate that H-cadherin expression antagonizes tumor growth in nude mice, presumably by enhancing cell- cell association in a tissue environment. These findings strongly suggest that H-cadherin could provide a possible target for corrective gene therapy against breast cancer.      

Bulging fontanelle after supplementation with 25 000 IU of vitamin A in infancy using immunization contacts

To evaluate the safety of vitamin A supplementation in early infancy using DPT/OPV immunization contracts, a double-blind, randomized, placebo-controlled trial was conducted in Bangladesh. One hundred and sixty-seven infants received three doses of either 25 000 IU of vitamin A or a placebo at about 6.5, 11.8 and 17.0 weeks of age. Trained physicians examined each of the infants on days 1, 2, 3 and 8 after supplementation. Nine infants (10.5%) supplemented with vitamin A had episodes of bulging of the fontanelle compared with two infants (2.5%) in the placebo group (p < 0.05). Twelve of the 14 episodes occurred in infants supplemented with vitamin A. Of these 12 episodes, none occurred with the first dose, 3 occurred with the second and 9 with the third dose. The higher incidence of bulging of the fontanelle in the vitamin A group relative to the placebo group and its temporal association with the vitamin A doses are suggestive of a causal association. The finding that increased numbers of vitamin A doses were associated with a higher probability of bulging of the fontanelle suggests a cumulative effect. Bulging fontanelle, clinical trial, safety, toxicity, vitamin A
AH Baqui, Urban MCH-FP Extension Project, ICDDR.B, GPO Box 128, Dhaka 1000, Bangladesh