Inequities in access to information and inequities in health]

This piece presents evidence that inequities in information are an important determinant of health inequities and that eliminating these inequities in access to information, especially by using new information and communication technologies (ICTs), could represent a significant advance in terms of guaranteeing the right to health for all. The piece reviews the most important international scientific research findings on the determinants of the health of populations, emphasizing the role of socioeconomic inequities and of deteriorating social capital as factors that worsen health conditions. It is noteworthy that Latin America has both socioeconomic inequities and major sectors of the population living in poverty. Among the fundamental strategies for overcoming the inequalities and the poverty are greater participation by the poor in civic life and the strengthening of social capital. The contribution that the new ICTs could make to these strategies is analyzed, and the Virtual Health Library (VHL) is discussed. Coordinated by the Latin American and Caribbean Center on Health Sciences Information (BIREME), the VHL is a contribution by the Pan American Health Organization that takes advantage of the potential of ICTs to democratize information and knowledge and consequently promote equity in health. The "digital gap" is discussed as something that can produce inequity itself and also increase other inequities, including ones in health. Prospects are discussed for overcoming this gap, emphasizing the role that governments and international organizations should play in order to expand access to the global public good that information for social development is.     

Should the guidelines for monitoring serum cholesterol levels in the elderly be re-evaluated?

Elevated circulating cholesterol can have profound effects on the health of an individual. Such excess cholesterol can promote coronary artery disease, production and accumulation of β-amyloid in the brain, and possibly Alzheimer’s disease (AD). In a clinical trial evaluating the benefit of a cholesterol-lowering drug in the treatment of AD, mean cholesterol levels at baseline among individuals participating in the trial were found to be relatively high. Based on this observation we suggest that cholesterol levels should be actively monitored in the elderly, as many individuals with AD are over 65 years of age and therefore excluded by currently accepted guidelines.     

Peripheral blood immunological parameters for use as markers of pre-invasive to invasive colorectal cancer

In cancer, the extent to which the disease has spread is probably the most important factor in determining patient prognosis. Hence practical and non-invasive methods are needed to identify disease stage. In a previous paper we showed how diagnostic and prognostic indices for disease progression could be defined by evaluating parameters in peripheral blood. The aim of this study was to identify further serum parameters that could be used. Serum levels of interferon (IFN) gamma, interleukin (IL)4, IL8, IL7, IL1 beta, tumor necrosis factor (TNF) alpha, granulocyte macrophage-colony stimulating factor (GM-CSF), soluble (s) IL2 receptor (R) and sIL6R were studied but only levels of IL4, sIL2R, IL8 and IL7 were found to be significant and would therefore be of use in defining diagnostic and prognostic indices for disease progression. In further detail, our results indicate that when serum levels of sIL2R < 522 U/ml, IL4 < 159 pg/ml and IL8 > 339 pg/ml there is a 95% probability that the disease is in stage I or II where there is no infiltration of lymph nodes; when serum levels of sIL2R > or = 522 Ug/ml, 159 pg/ml < or = IL4 < or = 319 pg/ml, and IL7 < 54 pg/ml, there is a 95% probability that the disease is in stage III and the tumor has invaded the lymph nodes; when the serum levels of IL4 > or = 431 pg/ml and IL7 > or = 54 pg/ml, there is a 95% probability that the disease is in stage IV and there is metastasis.     

Generation of an apoptotic intracellular peptide by gamma-secretase cleavage of Alzheimer's amyloid beta protein precursor

The amyloid beta protein precursor (AbetaPP) is sequentially processed by beta- and gamma-secretases to generate the Abeta peptide. The biochemical path leading to Abeta formation has been extensively studied since extracellular aggregates of amyloidogenic forms of Abeta peptide (Abeta42) are considered the culprit of Alzheimer's disease. Aside from its pathological relevance, the biological role of AbetaPP proteolysis is unknown. Although never previously described, cleavage of AbetaPP by gamma-secretase should release, together with Abeta, a COOH-terminal AbetaPP Intracellular Domain, herein termed AID. We have now identified AID-like peptides in brain tissue of normal control and patients with sporadic Alzheimer's disease and demonstrate that AID acts as a positive regulator of apoptosis. Thus, overproduction of AID may add to the toxic effect of Abeta42 aggregates and further accelerate neurodegeneration.     

Comparison of advanced irradiation techniques with photons for benign intracranial tumours.

BACKGROUND AND PURPOSE: The potential benefits and limitations of different radiation techniques (stereotactic arc therapy (SRS/T), intensity modulated radiotherapy (IMRT), helical tomotherapy (HT), Cyberknife and intensity-modulated multiple arc therapy (AMOA)) have been assessed using comparative treatment planning methods on twelve patients presenting with 'benign' brain tumours. MATERIALS AND METHODS: Plans for five acoustic neurinomas, five meningiomas and two pituitary adenomas were computed to generate dose distributions for all modalities using a common CT dataset to delineate planning target volume and organs at risk. RESULTS: HT, AMOA and IMRT resulted superior to SRS/T and Cyberknife for target coverage. For the first group V(95%) ranged from 98% to 100%, minimum dose ranged from 91% to 96% and standard deviation from 0.84% to 1.67%. For organs at risk all techniques respected planning objectives with a tendency of Cyberknife and SRS/T to better spare the brain stem and the healthy brain tissue (e.g., V(20Gy) of 2.0% and 2.3%, respectively, compared to 3.1-5.0% for the other techniques). AMOA is in general preferable to IMRT for all OARs. Conformity index (CI(95)) was better for HT and Cyberknife (both 1.8) and less for AMOA and IMRT (3.9 and 3.0, respectively). CONCLUSION: All techniques provided good OAR sparing and primarily differed in target coverage indices. For the class of tumours investigated in this report, HT, AMOA and IMRT had better target coverage with HT providing the best combination of indeces. Between AMOA and IMRT, target coverage was comparable and, considering organs at risk, AMOA was slightly preferable.     

Gene transfer of endothelial nitric oxide synthase to pulmonary allografts: impact on acute rejection

Experiments were designed to study whether overexpression of nitric oxide (NO) from endothelial nitric oxide synthase (eNOS) affects acute rejection. Allogenic, orthotopic single-lung transplantation was performed after transbronchial adenoviral-mediated gene transfer (3 × 10⁸ pfu) of either of eNOS or β-galactosidase to donor lungs of rats (n = 6 each). No immunosuppression was used. After 4 days, transplanted lungs were prepared for enzyme activity, cGMP and histology. Calcium-dependent NOS activity, reflecting eNOS, was greater in eNOS-transduced lungs (587 ± 97 vs 2.1 ± 1.4 pmol/mg protein per h, P <0.001). In contrast, calcium-independent NOS activity, reflecting iNOS, was comparable. Concentrations of cGMP were higher in eNOS-transduced lungs (13.2 ± 2.3 vs 4.9 ± 0.5 pmol/mg protein). Positive immunostaining for eNOS was present in pneumocytes only in eNOS-transduced lungs. No difference in histological grade of rejection was observed. eNOS gene transfer to pulmonary allografts results in a functionally active transgene product and increased NO production. Increasing NO from eNOS does not affect histogically identified acute rejection.     

Ambulatory surgery: preoperative assessment

Over the past 20 years public health expenditure has progressively increased for various reasons. With the aim of reducing public health expenditure and hospital stays, alternative models of public health care have been more widely adopted over the past two decades: Day Hospital, day surgery and ambulatory surgery. What is meant by ambulatory surgery is the clinical, organisational and administrative possibility of performing surgical operations and/or invasive and semi-invasive diagnostic procedures without hospitalisation of patients, in doctors' surgeries, outpatient departments or protected outpatient facilities. For both the patients and the centres providing the service to be able to exploit all the advantages stemming from this kind of health care provision, careful patient selection is mandatory, including assessment of the impact of any potential concomitant pathologies. Starting from their own personal experience and existing reports in the international literature, the authors analyse the impact that concomitant pathologies may have on patient selection for ambulatory surgery. The authors conclude that thorough preoperative evaluation of all the possible variables involved is the only way of ensuring the success of ambulatory surgery.     

Whole body protein metabolism in children with cancer

Whole body protein synthesis and catabolism were measured using the [ring-2H5]phenylalanine and [1-13C]leucine primed constant infusion technique in 32 paediatric patients with cancer at different stages of treatment. Rates of synthesis (S) and catabolism (C) derived from the [ring-2H5]phenylalanine and [1-13C]leucine models were 4.7 (SD 1.3) (S) and 6.0 (1.5) (C) g/d/kg, and 5.5 (0.8) (S) and 6.8 (1.2) (C) g/d/kg, respectively. These results show that these two tracer techniques give similar results in this study population. Comparison of these values with results previously reported for groups of control children using the [ring-2H5]phenylalanine model (S = 3.69 and 3.93; C = 4.09 and 4.28 g/d/kg) and the [1-13C]leucine model (S = 4.32; C = 4.85 g/d/kg) show that rates of synthesis and catabolism were higher in cancer patients than in controls. Thus whole body protein turnover is increased in children under treatment for cancer. Other indices of metabolism such as plasma amino acids and intermediary metabolites were also measured and showed that, although subjects were in isotopic steady state, there were significant metabolic changes during the course of the primed constant infusions used to measure protein turnover.     

Synthesis of N-substituted isocyanocarboxamides with antimicrobial activity.

The Ugi four-component condensation between isocyanides 1, cycloketones 2, and ammonium formate affords N-substituted formylaminocarboxamides 3 which are dehydrated with POCl3/NEt3 to give the title compounds 4. The structure of the compounds 3 and 4 was confirmed by spectral data and elemental analyses. In vitro tests of antibacterial activity showed that compounds 4 are ineffective against E. coli and fairly active against K. pneumoniae, B. subtilis and S. aureus. A very good antimicotic activity was shown against C. albicans.