Magnetic resonance spectroscopy shows an inverse correlation between intramyocellular lipid content in human calf muscle and local glycogen synthesis rate

Intramyocellular lipid (IMCL) content of skeletal muscle, as measured with ¹H MRS, is inversely correlated with insulin sensitivity as determined by whole body glucose uptake. The latter, however, does not necessarily represent the actual glucose uptake in the corresponding skeletal muscle. In this study, we examined whether IMCL content in human calf muscle correlated with local glucose uptake assessed by measurement of glycogen synthesis rate within the same muscle compartment. We studied 20 subjects belonging to four subgroups of five persons each: young lean, elderly lean, young obese and elderly obese. IMCL content in the soleus and gastrocnemius muscle was determined using ¹H MR spectroscopic imaging and local glycogen synthesis rate in the calf muscle was measured by ¹³C MRS during a euglycaemic hyperinsulinaemic clamp with 20% w/v 30% ¹³C‐1‐labelled glucose infusion. Significantly higher IMCL contents were found in elderly (soleus: p < 0.0001 and gastrocnemius: p < 0.01) and obese subjects (p < 0.01 for both muscles). Local glycogen synthesis rate decreased significantly with obesity (p < 0.01). The principal finding of this study was that the mean IMCL content of the soleus and gastrocnemius muscles was indeed inversely correlated with the local glycogen synthesis rate in the calf muscle (r_s = ?0.50, p < 0.05), with a very similar dependency as the inverse correlation between mean IMCL content and total body glucose uptake (r_s = ?0.54, p < 0.05). We conclude that IMCL content of the soleus and gastrocnemius muscles reflects a measure for local insulin resistance within the same muscle compartment as determined by glycogen synthesis rate. Although the inverse correlation suggests that insulin sensitivity is affected by the local amount of fat present, it remains to be determined if this is a cause or a consequence. Copyright © 2009 John Wiley & Sons, Ltd.     

Magnetic resonance spectroscopy and chromatographic methods identify altered lipid composition in human renal neoplasms

We report on the characterization of the lipid obtained from cortical and medullary normal human kidney tissue, benign renal neoplasms (oncocytoma) and 2 different types of malignant renal neoplasms (chromophobic cell carcinoma and clear cell carcinoma). The total lipid fractions were analyzed by 13C magnetic resonance spectroscopy and thin-layer chromatography, whereas the composition of the total fatty acids and the content of total cholesterol were determined by gas chromatography. alpha-Tocopherol was detected and quantified by high-performance liquid chromatography. The spectroscopic and chromatographic analysis revealed significant differences in the renal tissues examined. It was confirmed that cholesteryl esters (mainly oleate) are typical of clear cell renal carcinomas. Their potential role as prognostic and diagnostic factors is discussed, with particular emphasis on its capability to indicate the tumor diffusion in healthy renal parenchyma. alpha-Tocopherol is prevalent in clear cell carcinoma and it is present in nearly the same low amounts in cortex, medulla and chromophobic cell renal carcinoma. Q10 coenzyme and dolichols were detected by thin-layer chromatography and they are present in significant amounts in the cortex and the benign oncocytoma. Great variations were found in the distribution of saturated and unsaturated fatty acids, especially in the docosapentaenoic, docosahexaenoic and arachidonic acids and the corresponding omega-6/omega-3 fatty acids ratio.     

HIV and antiretroviral therapy: lipid abnormalities and associated cardiovascular risk in HIV-infected patients

It has been demonstrated that patients on highly active antiretroviral therapy are at increased risk for developing metabolic abnormalities that include elevated levels of serum triglycerides and low-density lipoprotein cholesterol and reduced levels of high-density lipoprotein cholesterol. This dyslipidemia is similar to that seen in the metabolic syndrome, raising the concern that highly active antiretroviral therapy also potentially increases the risk for cardiovascular complications. This paper reviews the contribution of both HIV infection and the different components of highly active antiretroviral therapy to dyslipidemia and the role of these abnormalities toward increasing the risk of cardiovascular disease in HIV-infected patients; therapeutic strategies to manage these risks are also considered.     

Magnetic resonance spectroscopy of normal and diseased muscles

Phosphorus magnetic resonance spectroscopy (P MRS) affords and innovative approach to the study of the oxidative enzyme content of normal and diseased muscles. Examples of the evaluation of the enzyme content of normal muscles by an exercise protocol are provided. The protocol affords a hyperbolic work/cost profile, the Vmax of which is calculated by the reciprocal plots giving the enzyme content and the "effective Michaelis constant" with an evaluation of the resting metabolism. This steady state protocol clearly illustrates enzyme adaptation, on the one hand, and tissue atrophy particularly in the case of tissue injury, Duchenne's dystrophy, and genetic deletion of specific enzymes, on the other hand. The method is rapid, safe, and affords a quantitative evaluation of the disease process and possibilities for following appropriate therapies. So far, approx 1000 examinations of normal and diseased human limbs have been carried out in our laboratory in over the past four years.     

Case-control study of risk factors for incident HIV infection in rural Uganda

OBJECTIVE: To identify risk factors associated with HIV incidence in a rural Ugandan population. DESIGN: Case-control study. METHODS: Men and women who seroconverted between 1990 and 1997 (cases) and seronegative subjects (controls) were drawn from a general population cohort of approximately 5000 adults in rural, southwestern Uganda. Information on risk factors was ascertained through a detailed interview and physical examination by clinicians who were blind to the study subjects' HIV status. All patients were interviewed within 2 years of their estimated date of seroconversion. RESULTS: Data were available on 130 men (37 cases, 93 controls) and 133 women (46 cases, 87 controls). There was a significantly higher risk of infection in men (odds ratio [OR], 6.51; 95% confidence interval [CI], 1.06-39.84) and women (OR, 4.75; 95% CI, 1.26-17.9) who were unmarried and in a steady relationship, and in men who were divorced, separated, or widowed (OR, 4.33; 95% CI, 1.32-14.25) compared with those who were married. There was a significantly higher risk of HIV infection in men (OR, 3.78; 95% CI, 1.20-11.93) and women (OR, 20.78; 95% CI, 2.94-141.2) who reported > or =5 lifetime sexual partners compared with those who reported at most 1 partner. For men, there was an increased risk of infection associated with receiving increasing numbers of injections in the 6 months prior to interview (p < .001 for trend). Women reporting sex against their will in the year prior to interview were at higher risk of infection (OR, 7.84; 95% CI, 1.29-47.86; p = .020). CONCLUSIONS: The strongest risk factor for HIV incidence in this rural Ugandan population is lifetime sexual partners. The increased risks found for women reporting coercive sex and men reporting injections require further investigation.     

Anemia prevalence and associated risk factors in a single-center ambulatory HIV clinical cohort

The prevalence of anemia in HIV-infected persons has not been well characterized in the HAART era. In a single-center, retrospective study, anemia prevalence and risk factors, including use of HAART, were assessed in an ambulatory clinical cohort of 758 HIV-infected patients for the calendar year 2000. The relationships between anemia (hemoglobin level less than 12.5 g/dL) and demographic variables, antiretroviral treatment regimens, and disease markers were analyzed. Mean baseline patient characteristics were hemoglobin level, 13.7 +/- 1.9 g/dL; CD4+ cell count, 405 +/- 293/microL; and HIV RNA level, 77,841 +/- 148,394 copies/mL. Overall anemia prevalence was 30.3%. Multivariate logistic regression analysis demonstrated that anemia was associated with a CD4+ cell count below 50/microL, female sex, black race, a viral load above 100,000 copies/mL, zidovudine use, and older age. Severe anemia was less prevalent in this study population than in historical comparators; however, mild to moderate anemia rates remain high.     

HIV and cardiovascular risk factors

There is growing concern that the metabolic complications associated with HIV and antiretroviral therapy may lead to accelerated coronary artery disease (CAD). Traditional cardiovascular risk factors, such as hypertension, hyperlipidemia, diabetes mellitus, and visceral fat accumulation, are increasingly seen in HIV patients receiving HAART. These factors are in addition to nonreversible risk factors, such as male sex, age greater than 40 years, and family history of premature CAD. Patients may also be smokers and may have a sedentary lifestyle, both of which predispose to significant CAD. In older patients and those with other risk factors, there may be an accentuation of these risk factors by HAART, although these factors also occur in young patients with no other risk factors. It is still unknown whether the factors predispose HIV patients to accelerated cardiovascular disease. Short-term studies, including 2 large cross-sectional studies, do not show an increased risk of cardiovascular complications or cardiac death, but longer follow-up is needed to answer such questions effectively. Even if patients are not at increased risk for cardiovascular disease, they are at least at the same risk as HIV-negative, age-matched persons with similar risk factors. It is, therefore, pertinent to identify and effectively manage those risk factors that can be modified.     

Magnetic resonance imaging and spectroscopy of the intervertebral disc

Intervertebral disc disease is an emerging health concern and has a considerable negative effect on the economy and on society. MRI has a critical role in assessing the disc, but it is still a challenge to objectively correlate disc health and pain with images. In this paper, a review of MR disc imaging techniques including grading, relaxation time measurements, diffusion, and contrast perfusion is presented. In addition, high-resolution magic-angle spinning methods to correlate in vitro disc degeneration (with pain, etc) are discussed. With the potential for gaining morphological and biochemical information, MRI shows promise for quantitative assessment of disc health.     

Risk factors associated with HIV infection among young gay and bisexual men in Canada

OBJECTIVE: To assess risk factors associated with HIV prevalence and incidence among gay and bisexual men in two prospective Canadian cohorts. METHODS: The Vanguard Project and the Omega Cohort are prospective cohort studies of gay and bisexual men ongoing in Vancouver and Montreal, respectively. For this analysis, baseline sociodemographic characteristics, sexual behavior, and substance use data from these two cohorts were combined. Assessment of risk factors for HIV seroprevalence and seroconversion were carried out using univariate and multivariate analysis. RESULTS: This analysis was based on 1373 gay and bisexual men aged 16 to 30 years. Men who were HIV-seropositive at baseline (n = 48) were more likely to report living in unstable housing, to have had less than a high school education, and to have been unemployed than those who were HIV-negative (n = 1325). HIV-positive men were also more likely to report having engaged in sexual risk behavior, including having had consensual sex at a younger age, having had at least 6 partners during the previous year, ever having been involved in the sex trade, and having engaged in unprotected receptive anal intercourse. With respect to substance use, HIV-positive men were more likely to report the use of crack, cocaine, heroin, and marijuana and to use injection drugs. Similarly, men who seroconverted during the course of the studies (n = 26) were more likely to report having less than a high school education and having lived in unstable housing at baseline. Compared with HIV-negative men, men who seroconverted were more likely to report ever having been involved in the sex trade and engaging in unprotected receptive anal intercourse. Reports of cocaine use and injection drug use were also significantly higher for men who seroconverted compared with HIV-negative men. CONCLUSIONS: Our data indicate that HIV-positive gay and bisexual men are more likely to be living in unstable conditions and to report more risky sexual and substance use behaviors than HIV-negative men.     

A cluster of HIV infection among heterosexual people without apparent risk factors

Human immunodeficiency syndrome (HIV) epidemiology in Belgium shows that 66% of all acquired immunodeficiency syndrome patients were infected heterosexually. Since 1985, all HIV-seropositive patients in Brussels and Antwerp who have been heterosexually infected have been offered participation in a partner notification program; this article reports the case study of 1 HIV infected male and his 19 identified previous women sexual partners. This report describes the patient's background and the type and frequency of sexual intercourse he had with each partner. The characteristics of each of the sexual partners were also described. An important consideration of this case was that 11 of the tested partners (56%) were HIV seropositive. Several factors were discussed concerning the cause of this high rate of transmission (e.g. high disseminator patient, highly virulent HIV strain, and presence of genital herpes). This study emphasizes the fact that middle class women with low risk sexual practices were infected with AIDS from as little as 1 sexual encounter with this infected individual. To stop a false sense of security among people with few sexual partners, it was advised that a program of partner notification targeted to heterosexuals be implemented along with other public health policies.     

A case-control study of factors associated with HIV infection among black women

OBJECTIVE: To identify social, behavioral and epidemiologic factors associated with HIV infection among HIV-infected and HIV-uninfected black women residing in North Carolina. DESIGN: A case-control study conducted in August 2004 in North Carolina. METHODS: Cases were 18-40-year-old women with HIV infections diagnosed from 2003-2004. Controls were 18-40-yearold, HIV-negative heterosexually active women recruited from HIV testing sites. Five focus group discussions were also conducted with women not participating in the case-control study. RESULTS: Multivariate analyses of 31 cases and 101 controls showed that HIV-positive women were more likely to receive public assistance [adjusted odds ratio (aOR) 7.3; 95% confidence interval (CI) 2.1, 26.0], to report a history of genital herpes infection (aOR 10.6; 95% CI 2.4, 47.2), and were less likely to have discussed a variety of sexual and behavioral issues relevant to risk of HIV infection with their male partners (aOR 0.6; 95% CI 0.4, 0.8). Focus group participants indicated that financial and social demands created competing challenges for making HIV prevention a priority. CONCLUSIONS: Inadequate communication between black women and their sexual partners may create barriers to sexual and behavioral risk reduction. A multidimensional approach that addresses both biological factors such as herpes infection and socioeconomic factors may be needed to reduce HIV transmission in this population.     

Prevalence and associated factors of intestinal parasite infection by HIV infection status among asymptomatic adults in rural Gabon

IntroductionIntestinal parasites infections are endemic in Gabon. Nevertheless, they are rarely described in people living with HIV (PLHIV).ObjectiveThe frequency of intestinal parasite infection was estimated and compared between HIV-positive and HIV uninfected individuals in Gabon; factors associated with intestinal parasites were also analysed.Material and MethodsUsing a cross-sectional study design sociodemographic data, life style habits, antiretroviral therapy, cotrimoxazole use and CD4 cell count were recorded.. Stool samples from participants living in Koulamoutou and Oyem were analysed using microscopy. Chi-squared or fisher''s exact tests and logistic regression were performed.ResultsAmong participants (n=332), female gender was predominant (73.7%; n=135/183) and the median age was 45 [33–57] years old. Among 183 samples, 53.6% (n = 98/183) were infected by intestinal parasites. The proportion was higher (72.1%) in HIV negative participants compared to PLHIV (42.6%) (p <0.01). PLHIV were more frequently poly-infected. Infection was frequent in patients using external toilets and tap water (>70.0%).ConclusionPrevalence of intestinal parasites is higher in seronegative participants but polyparasitism is more frequent in PLHIV. Strategies are focused on HIV negative population, but this study shows the importance of sensitization for PLHIV to improve their quality of life.     

Characteristics of African-Americans with multiple risk factors associated with HIV/AIDS

Multiple risk factors in young African-Americans have tremendous implications for the spread of AIDS. Two hundred forty-two heterosexual college students were classified as having low, moderate, or high risk for HIV infection based upon their self-reported sexual practices. Results indicated that subjects differed in AIDS knowledge and attitudes toward condoms with respect to both Gender and Risk level, with men and High Risk individuals being less knowledgeable and having more negative attitudes than their female and Low Risk counterparts respectively. Interaction effects revealed that High Risk men were less knowledgeable than both Low Risk men and High Risk women. High Risk men as well as High and Low Risk women reported more anger surrounding condom usage than Low Risk men. Low perceptions of vulnerability for AIDS were reflected in the entire sample. The implications of this study for primary prevention and future research are discussed.     

Magnetic resonance imaging and spectroscopy of transgenic models of cancer

The complexity of cancer, where a single genetic alteration can have multiple functional effects, makes it a fascinating but humbling disease to study, and the necessity of investigating it in its entirety is more imperative than ever before. Advances in transgene technology have made it possible to create cancer cells, or mice with specific genetic alterations, and the application of an array of both functional and molecular non-invasive MR methods to these transgenic cancer cells and mice to characterize their phenotypic traits is revolutionizing our understanding of cancer. With the establishment of multi-modality molecular imaging centers within barrier or pathogen-free facilities, multi-parametric and multi-modality imaging of transgenic mouse models of human cancer are becoming increasingly prevalent. In this review, we outline some of the methods currently available for generating transgenic mice and cancer cell lines. We also present examples of the application of MR methods to transgenic models that are providing novel insights into the molecular and functional characteristics of cancer and are leading to an era of "non-invasive phenotyping" of the effects of specific molecular alterations in cancer.     

Pulmonary cryptococcosis in patients without HIV infection: factors associated with disseminated disease

Cryptococcus neoformans is an uncommonly recognized cause of pneumonia in HIV-negative patients. Because of its propensity to disseminate to the meninges and other sites, a lumbar puncture is recommended for patients with pulmonary cryptococcosis, regardless of other risk factors. This study explored clinical and laboratory features to help predict which patients had pulmonary disease alone versus those who had pulmonary plus extrapulmonary disease. A retrospective chart review at 15 medical centers was performed from 1990 to 2000 of all HIV-negative patients who had pulmonary cryptococcosis. Demographic, clinical, radiographic, and laboratory features were evaluated to determine factors that differentiated those patients who had extrapulmonary disease. Among 166 patients who had pulmonary cryptococcosis, 122 had pulmonary infection only and 44 had pulmonary plus extrapulmonary (disseminated) disease. A negative serum cryptococcal antigen titer was more common in patients with pulmonary disease alone (p < 0.01). Multivariate analysis demonstrated that patients who had disseminated disease were more likely than those who only had pulmonary disease to have cirrhosis (p = 0.049), headache (p < 0.001), weight loss (p = 0.003), fever (p = 0.035), altered mental status (p < 0.001), and to be receiving high-dose corticosteroids (p = 0.008). In this large cohort of HIV-negative patients with pulmonary cryptococcosis, there were easily distinguished clinical and laboratory features among patients with pulmonary disease alone versus those with pulmonary plus extrapulmonary disease. These findings may be helpful in the evaluation of HIV-negative patients with pulmonary cryptococcosis with regard to the need for lumbar puncture or to search for disseminated disease.     

Cardiovascular risk factors and HIV disease

An increased rate of coronary heart diseases is becoming an important cause of morbidity and mortality among HIV-infected patients. This emerging problem is due to the antiretroviral therapy success that allows HIV-positive patients to live longer. Increased coronary heart disease rates in the HIV population, as in the noninfected population, may be related to traditional risk factors, including advancing age, higher smoking rates, dyslipidemia, insulin resistance, and impaired glucose tolerance. Some nontraditional factors have to be considered too: these are due to the direct effects of the virus on the vasculature, as well as to direct effects of specific antiretroviral drugs, including inflammation, endothelial dysfunction, metabolic disorders, prothrombotic state, and changes in body composition with loss of subcutaneous fat and/or accumulation of visceral fat. The aim of this paper is to review traditional and emerging cardiovascular risk factors and consider their possible interactions in HIV-infected patients.