Factors associated with renal dysfunction within an urban HIV-infected cohort in the era of highly active antiretroviral therapy

Background

Kidney disease remains a prevalent problem in HIV care. The contribution of highly active antiretroviral therapy (HAART), HIV disease factors and traditional factors needs further evaluation.

Methods

A cross‐sectional study of all patients seen at an HIV outpatient clinic during 2005 was performed. All data were collected from medical record review. Multivariate regression modelling was used to identify independent predictors of lower glomerular filtration rate (eGFR) and chronic renal failure (CRF) from factors significant in univariate analysis. eGFR was calculated using the simplified modification of diet in renal disease equation. Results were compared with those for persons from the National Health and Nutrition Examination Survey (NHANES) matched for age, race and gender.

Results

Of 845 HIV‐infected persons, 64% were men and 34% were Caucasian, and the mean age was 39.8 years. Thirty per cent of the patients had proteinuria and 43% had eGFR<90 mL/min/1.73 m². Persons on HAART (63%) had a lower mean eGFR than those not on HAART (92.0 vs. 101.6). In multivariate analyses, significant predictors of eGFR decline were diagnoses of hypertension, hyperlipidaemia, proteinuria, use of tenofovir or stavudine, and lower viral load. Compared with those in NHANES, HIV‐infected persons had a lower mean eGFR (94.9 vs. 104.2) and a higher prevalence of CRF (8%vs. 2%).

Conclusion

In this cohort, the prevalence of CRF is low, but remains higher than that of the general population. Clinicians should routinely screen for early asymptomatic kidney disease to address risk factors that can be treated.     

淋病流行特征与淋球菌药物敏感性的流行病学研究

目的 为控制淋病的增长，探讨淋病流行病特征与淋球菌对常用药物敏感性的流行病学关系。方法 完整收集淋病的流行病学资料，测定每年淋球菌对各种药物的敏感度及耐药率，药物包括青霉素，四环素，环丙沙星，壮观霉素和头孢三嗪。结果 性病流行在10年内稳定上升，但淋病则由1993年开始呈稳定的负增长，壮观霉素及头孢三嗪在4年间未发现耐药菌株；环丙沙星的耐药率显上升，由1998年的56.4%上升至2001年的71.4%，产青霉素的耐药菌株（PPNG）和四环素耐药菌株（TRNG）在4年内分别上升10%和16.3%，结论 随淋病的有效控制，淋球菌对常用药物的敏感性降低，PPNG和TRNG菌株的明显上升表明淋球菌的耐药趋势正逐渐增强，喹诺酮类药物的高耐药率表明该类药物已不再适宜被推荐用于治疗淋病的首选药物，头孢三嗪和壮观霉素尚没有耐药菌株，但必须强调规范使用，保证在性病防治工作中有足够可供选择有效药物。     

Volumetric vs. surface-based alignment for localization of auditory cortex activation

The high degree of intersubject structural variability in the human brain is an obstacle in combining data across subjects in functional neuroimaging experiments. A common method for aligning individual data is normalization into standard 3D stereotaxic space. Since the inherent geometry of the cortex is that of a 2D sheet, higher precision can potentially be achieved if the intersubject alignment is based on landmarks in this 2D space. To examine the potential advantage of surface-based alignment for localization of auditory cortex activation, and to obtain high-resolution maps of areas activated by speech sounds, fMRI data were analyzed from the left hemisphere of subjects tested with phoneme and tone discrimination tasks. We compared Talairach stereotaxic normalization with two surface-based methods: Landmark Based Warping, in which landmarks in the auditory cortex were chosen manually, and Automated Spherical Warping, in which hemispheres were aligned automatically based on spherical representations of individual and average brains. Examination of group maps generated with these alignment methods revealed superiority of the surface-based alignment in providing precise localization of functional foci and in avoiding mis-registration due to intersubject anatomical variability. Human left hemisphere cortical areas engaged in complex auditory perception appear to lie on the superior temporal gyrus, the dorsal bank of the superior temporal sulcus, and the lateral third of Heschl's gyrus.     

Target cell-induced apoptosis of interleukin-2-activated human natural killer cells: roles of cell surface molecules and intracellular events

We previously reported that natural killer (NK)-sensitive target cells, K562, kill interleukin-2-stimulated (lymphokine-activated killer [LAK]) but not unstimulated NK cells. We have now investigated the molecular basis of this phenomenon. Soluble monoclonal antibody (MoAb) to CD18 inhibited 75% of K562-induced DNA fragmentation and membrane disruption, whereas blocking MoAb to Fas partially inhibited only the DNA fragmentation. MoAbs to CD2, CD11a, CD11b, B7, or CD16 had limited or no effect on K562-induced death of LAK cells. Receptor ligation with either immobilized MoAb to CD18 or Fas induced membrane disruption and DNA degradation in LAK cells independently of K562, and MoAb to CD18, CD11a, or CD11b enhanced DNA fragmentation induced by anti-Fas. Fas-L- transfected Raji cells also killed LAK cells, but only if Fas-L expression was amplified. K562 cells rapidly triggered protein phosphorylation in LAK cells, and the tyrosine kinase inhibitor, Herbimycin A, inhibited DNA fragmentation and membrane disruption. Protease inhibitors strongly suppressed K562-mediated DNA fragmentation of LAK cells, but not membrane disruption. In conclusion, (1) K562- induced death of LAK cells involves primarily CD18, although other molecules, such as Fas, may also be involved; (2) K562-mediated apoptosis of LAK cells requires tyrosine phosphorylation and protease activity; (3) engagement of Fas by immobilized MoAb or Fas-L on target cells can also kill LAK cells; and (4) Fas-immobilized MoAb synergizes with coimmobilized MoAb to CD11a, CD11b, or CD18 for LAK cell killing. Activation-induced death of NK cells may represent a mechanism for NK cell regulation.     

Human temporal lobe activation by speech and nonspeech sounds

Functional organization of the lateral temporal cortex in humans is not well understood. We recorded blood oxygenation signals from the temporal lobes of normal volunteers using functional magnetic resonance imaging during stimulation with unstructured noise, frequency-modulated (FM) tones, reversed speech, pseudowords and words. For all conditions, subjects performed a material-nonspecific detection response when a train of stimuli began or ceased. Dorsal areas surrounding Heschl's gyrus bilaterally, particularly the planum temporale and dorsolateral superior temporal gyrus, were more strongly activated by FM tones than by noise, suggesting a role in processing simple temporally encoded auditory information. Distinct from these dorsolateral areas, regions centered in the superior temporal sulcus bilaterally were more activated by speech stimuli than by FM tones. Identical results were obtained in this region using words, pseudowords and reversed speech, suggesting that the speech-tones activation difference is due to acoustic rather than linguistic factors. In contrast, previous comparisons between word and nonword speech sounds showed left-lateralized activation differences in more ventral temporal and temporoparietal regions that are likely involved in processing lexical-semantic or syntactic information associated with words. The results indicate functional subdivision of the human lateral temporal cortex and provide a preliminary framework for understanding the cortical processing of speech sounds.