BAL and serum IgG levels in healthy asymptomatic HIV-infected patients

OBJECTIVES: To determine if the increased susceptibility to bacterial infection in asymptomatic HIV-infected patients is associated with decreased total IgG or IgG2 levels in lung epithelial lining fluid. BACKGROUND: A decrease in lung IgG levels or subtypes has been proposed as contributing to the increased risk of bacterial lung infections in HIV-infected patients. Previous studies measuring lung lavage IgG concentrations have been inconsistent. METHODS: Twenty-three HIV patients and 25 control subjects underwent BAL. Both patient groups were of similar age, and had similar pulmonary function studies and body mass index. Smokers were equally represented in both groups, and the majority of subjects in both groups were male. Total IgG and IgG2 levels in lavage fluid were assayed in both cohorts and compared using a two-tailed Student's t test. RESULTS: The lung lining fluid IgG level in HIV-infected patients was 0.19 +/- 0.13 microg/microg of protein (mean +/- SD) vs 0.11 +/- 0.09 microg/microg of protein in control subjects (p < 0.05). The IgG(2) level in HIV patients was 0.034 +/- 0.038 microg/microg of protein and 0.014 +/- 0.01 microg/microg of protein in control subjects (p = 0.054). Lavage IgG levels reflected serum IgG values (correlation coefficient, 0.56; p < 0.001) but did not correlate with lung immunoglobulin-producing cells. CONCLUSIONS: The increased susceptibility to bacterial pneumonia in asymptomatic HIV-infected individuals is neither explained by depressed total IgG levels nor a deficiency in IgG(2) levels in the lungs. The strong correlation between serum and lavage IgG levels suggests that lavage IgG derives from serum.     

Dyslipidemia in HIV-infected individuals

Metabolic complications continue to play a major role in the management of HIV infection. Dyslipidemia associated with HIV infection and with the use of combined antiretroviral therapy includes elevations in triglycerides, reduced high-density cholesterol, and variable increases in low-density and total cholesterol. The association between dyslipidemia and specific antiretroviral agents has been underscored. Multiple pathogenic mechanisms by which HIV and antiretroviral agents lead to dyslipidemia have been hypothesized, but they are still controversial. The potential clinical and pathological consequences of HIV-associated hyperlipidemia are not completely known, but several studies reported an increased risk of coronary artery disease in HIV-positive individuals receiving combined antiretroviral therapy. HIV-infected persons who have hyperlipidemia should be managed similarly to those without HIV infection in accordance with the National Cholesterol Education Program. Life style changes are the primary target. Statins and fibrates and/or modification in antiretroviral therapy are possible approaches to this problem.     

Immunotherapeutic restoration in HIV-infected individuals

While the development of combined active antiretroviral therapy (cART) has dramatically improved life expectancies and quality of life in HIV-infected individuals, long-term clinical problems, such as metabolic complications, remain important constraints of life-long cART. Complete immune restoration using only cART is normally unattainable even in cases of sufficient plasma viral suppression. The need for immunologic adjuncts that complement cART remains, because while cART alone may result in the complete recovery of peripheral net CD4+ T lymphocytes, it may not affect the reservoir of HIV-infected cells. Here, we review current immunotherapies for HIV infection, with a particular emphasis on recent advances in cytokine therapies, therapeutic immunization, monoclonal antibodies, immune-modulating drugs, nanotechnology-based approaches and radioimmunotherapy.     

Altered glutamate metabolism is associated with reduced muscle glutathione levels in patients with emphysema

Chronic obstructive pulmonary disease (COPD) is often characterized by an impaired skeletal muscle energy metabolism, which is at least partly related to chronic hypoxia and a reduced diffusing capacity. We have found that muscle glutamate (Glu), which is negatively influenced by these conditions, was reduced in patients with severe COPD. The aim of this study was to investigate whether the reduced intracellular Glu level in patients with emphysema is associated with an increased muscle glycolytic metabolism. Since Glu is an important substrate in the synthesis of glutamine (Gln) and glutathione (GSH), the influence of Glu status on muscle GSH and Gln was also examined. In 13 patients with emphysema and 25 control patients, arterial blood and biopsies from the vastus lateralis muscle were obtained. Expressed as a percentage of the control values, the patients with emphysema had reduced values for muscle Glu (64 +/- 12%; p < 0.001), GSH (76 +/- 23%; p < 0.01), and Gln (93 +/- 5%; p < 0.01), and higher values for lactate (p < 0.01) and pyruvate (p < 0.05). No differences were found in plasma values. Muscle Glu was highly associated with GSH (R(2) = 0.61; p < 0.001), but not with Gln. This study illustrates that reduced Glu levels in skeletal muscle of patients with emphysema are possibly related to an enhanced glycolytic activity and associated with decreased GSH levels.     

Gender-related differences in urinary 6-sulfatoxymelatonin levels in obese pubertal individuals

The objective of this study was to measure the urinary excretion of the main melatonin metabolite 6-sulfatoxymelatonin in obese and normal weight (wt) boys and girls. The study included 94 subjects, aged 4-15.7 yr (50 obese and 44 normal wt; 48 boys) classified as: mid-childhood (4-7.99 yr), late-childhood (8-12 yr) and pubertal (10.1-15.7 yr, Tanner II-IV). Normal wt subjects were children with a body mass index (BMI) between the 25th and 75th percentiles, and the group of obese subjects included children whose BMI was above the 97th percentile. A 24-hr urine sample was collected during two intervals: (i) 18:00-08:00 hr, and (ii) 08:00-18:00 hr. Analysis of urinary 6-sulfatoxymelatonin levels was performed by radioimmunoassay. Excretion of 6-sulfatoxymelatonin was expressed as: (i) total amount excreted (microg); (ii) mug excreted per time interval, nocturnal or diurnal; and (iii) the difference between nocturnal and diurnal samples (microg, estimated amplitude). A factorial analysis of variance indicated that nocturnal 6-sulfatoxymelatonin excretion and amplitude were significantly higher in the obese individuals. A significant interaction 'BMI x age' was detected, i.e. the effect of BMI was significant in the pubertal group only. Total, nocturnal and diurnal 6-sulfatoxymelatonin excretion was significantly higher in girls. The increase in 6-sulfatoxymelatonin excretion found in obesity occurred only in boys and at the pubertal age. To what extent this increase in melatonin production contributes to a delayed puberty in some pubertal obese males remains to be established.     

Physical activity and immunity in HIV-infected individuals

The purpose of this study was to determine what relationship exists among physical activity levels and viral load and CD4+ cell count in HIV-infected individuals. Increased viral load is associated with disease progression and symptom severity. A convenience sample of 66 male and female subjects between the ages of 18 and 64 years of age (mean 39 +/- 8) was recruited from a hospital-based HIV/AIDS clinic. Components of PA were assessed for three continuous days using a mini-motion logger wrist actigraph. These components included mean PA level, and PA index and acceleration index. Pearson's correlational analysis was used to test the strength of association between PA components and viral load or CD4+ cell count. A significant inverse relationship was found between mean PA level and viral load (p=0.047). An inverse relationship was also observed between PA index and viral load (p=0.0061). Neither mean PA nor PA index scores correlated with CD4+ cell counts. Acceleration index, a measure of PA intensity, showed no correlation to viral load or CD4+ cell counts. These findings suggest that increasing levels of physical activity might have beneficial effects on viral load in HIV-infected individuals.     

Counteracting muscle wasting in HIV-infected individuals

HIV-infected persons often experience a loss of lean tissue mass, which includes decreases in skeletal muscle mass. This HIV-associated wasting is significant because it has been associated with accelerated disease progression and increased morbidity. Signalling related to several circulating molecules, including tumour necrosis factor (TNF)-alpha, growth hormone, insulin-like growth factor (IGF)-1 and testosterone, has been associated with the aetiology of muscle wasting. Additionally, nutritional status related to malnutrition and specific dietary deficiencies may be involved. In an attempt to counter muscle wasting in HIV-infected persons, treatments have been suggested that target these mechanisms. Nutritional supplementation, cytokine reduction, hormone therapy and resistance exercise training are potential treatments for this condition. Resistance exercise training, which is more easily accessible to this population than other treatments, holds promise in counteracting the process of HIV wasting, as it has been successfully used to increase lean tissue mass in healthy and clinical populations. This review will explore the HIV/AIDS muscle-wasting syndrome, its aetiology, and the treatments used to counteract wasting.     

HIV感染伴发溶组织内阿米巴感染概况

溶组织内阿米巴是侵袭性阿米巴病的病原体,据估计每年全世界约有5000万人感染。同时据已报道的为数不多的流行病学调查数据显示,溶组织内阿米巴感染在HIV感染者这一特殊人群中正呈上升趋势。尽管溶组织内阿米巴并未归入机会致病寄生虫,但其和HIV感染的相关性越来越受到关注。本文就溶组织内阿米巴在HIV感染者中流行情况、感染的危险因素、临床表现、诊断及治疗方面进行综述。     

Non-cirrhotic portal hypertension in HIV-infected individuals

Non-cirrhotic portal hypertension (NCPH) has been associated with didanosine (ddI) exposure. We aimed to determine the number of individuals with NCPH within our cohort and define their characteristics. We identified individuals within our cohort with NCPH and performed a retrospective case note review. Cumulative antiretroviral therapy (ART) use was calculated and a statistical analysis performed to compare exposure to the rest of the clinic cohort for the same time period. Where available, data was collated on FibroScan?, echocardiography and coagulation profile. Seventeen patients were identified. Upper gastrointestinal bleeding was the most common presenting feature. Liver biopsy showed mild portal or periportal fibrosis in 13 (81%) and four with features of nodular regenerative hyperplasia. There was significantly greater exposure to ddl in this group (59.5 months) compared to the rest of the HIV cohort (21.1 months) P = <0.001. Eleven subjects has a liver elastography performed, six (55%) had a result greater than 9.6 kPa (consistent with greater than F2 disease by Metavir scoring). Echocardiography was performed in seven patients: four met criteria for pulmonary hypertension. This is consistent with other cohorts demonstrating an association between the didanosine exposure and NCPH. Our data also suggest an increased risk of pulmonary hypertension.     

Sex differences in severe pulmonary emphysema

RATIONALE: Limited data on sex differences in advanced COPD are available. OBJECTIVES: To compare male and female emphysema patients with severe disease. METHODS: One thousand fifty-three patients (38.8% female) evaluated for lung volume reduction surgery as part of the National Emphysema Treatment Trial were analyzed. MEASUREMENTS AND MAIN RESULTS: Detailed clinical, physiological, and radiological assessment, including quantitation of emphysema severity and distribution from helical chest computed tomography, was completed. In a subgroup (n = 101), airway size and thickness was determined by histological analyses of resected tissue. Women were younger and exhibited a lower body mass index (BMI), shorter smoking history, less severe airflow obstruction, lower Dl(co) and arterial Po(2), higher arterial Pco(2), shorter six-minute walk distance, and lower maximal wattage during oxygen-supplemented cycle ergometry. For a given FEV(1)% predicted, age, number of pack-years, and proportion of emphysema, women experienced greater dyspnea, higher modified BODE, more depression, lower SF-36 mental component score, and lower quality of well-being. Overall emphysema was less severe in women, with the difference from men most evident in the outer peel of the lung. Females had thicker small airway walls relative to luminal perimeters. CONCLUSIONS: In patients with severe COPD, women, relative to men, exhibit anatomically smaller airway lumens with disproportionately thicker airway walls, and emphysema that is less extensive and characterized by smaller hole size and less peripheral involvement.     

Human papillomavirus infection and disease in HIV-infected individuals

The possibility of increases in both oral and anogenital pathologic conditions due to human papillomavirus (HPV) in patients infected with the human immunodeficiency virus (HIV) is of concern and is the focus of numerous current research studies. HIV-infected women are at higher risk for cervical HPV detection, for infection with high-oncogenic-risk types of HPV, for persistent HPV infection, for cervical cytologic abnormalities, and for cervical intraepithelial neoplasms. HIV-infected men are at increased risk for anal HPV infection, for anal infection with high oncogenic-risk types of HPV, for persistent anal HPV infection, and for anal intraepithelial defects. Recent studies have shown an increased risk of oral warts in HIV-infected individuals despite treatment with highly active antiretroviral therapy (HAART). Oral HPV infection rates have not declined since the initiation of HAART, and evidence suggests that the rates may have actually increased in white HIV-infected males.