Journal of internal medicine
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Vaccine-induced antibodies that interfere with viral entry are the protective correlate of most existing prophylactic vaccines. However, for highly variable viruses such as HIV-1, the ability to elicit broadly neutralizing antibody responses through vaccination has proven to be extremely difficult. The major targets for HIV-1 neutralizing antibodies are the viral envelope glycoprotein trimers on the surface of the virus that mediate receptor binding and entry. ⋯ The primary challenge in the development of an HIV-1 vaccine that elicits broadly neutralizing antibodies therefore lies in the design of suitable envelope glycoprotein immunogens that circumvent these barriers. Here, we describe neutralizing determinants on the viral envelope glycoproteins that are defined by their function in receptor binding or by rare neutralizing antibodies isolated from HIV-infected individuals. We also describe the nonvariable cellular receptors involved in the HIV-1 entry process, or other cellular proteins, and ongoing studies to determine if antibodies against these proteins have efficacy as therapeutic reagents or, in some cases, as vaccine targets to interfere with HIV-1 entry.
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Tuberculosis (TB) continues to kill more than 2 million people globally each year. Annual TB case notification rates have risen up to fourfold since the mid-1980s, with the highest rate of 1000/100,000 around Cape Town, South Africa. ⋯ The rising incidence of TB has been attributed to HIV co-infection especially in developing countries. The threat of drug resistance arising from ineffective TB treatment programmes is looming and could potentially lead to loss of any gains made in controlling the disease globally.
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The incidence of obesity-hypoventilation syndrome (OHS) has greatly increased over time, but data on long-term outcome are limited. We investigated survival and prognostic factors in these patients undergoing noninvasive positive pressure ventilation (NPPV). ⋯ Gas exchange and lung function in OHS were improved after initiation of NPPV. Hypoxemia, high pH and elevated inflammation markers predicted poor survival. Overall, NPPV was well tolerated and survival was excellent when compared with data from historical matched controls.
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The long-term health consequences of diets used for weight control are not established. We have evaluated the association of the frequently recommended low carbohydrate diets - usually characterized by concomitant increase in protein intake - with long-term mortality. ⋯ A diet characterized by low carbohydrate and high protein intake was associated with increased total and particularly cardiovascular mortality amongst women. Vigilance with respect to long-term adherence to such weight control regimes is advisable.
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To estimate changes in coronary risk factors and their implications for coronary heart disease (CHD) rates in men starting highly active antiretroviral therapy (HAART). ⋯ Coronary heart disease rates will increase in a majority of patients starting HAART: however the increases corresponding to typical changes in risk factors are relatively modest and could be offset by lifestyle changes.