Analysis of serious non‐AIDS events among HIV‐infected adults at Latin American sites

Objective

Acquired immune deficiency appears to be associated with serious non‐AIDS (SNA)‐defining conditions such as cardiovascular disease, liver and renal insufficiency and non‐AIDS‐related malignancies. We analysed the incidence of, and factors associated with, several SNA events in the LATINA retrospective cohort.

Materials and methods

Cases of SNA events were recorded among cohort patients. Three controls were selected for each case from cohort members at risk. Conditional logistic models were fitted to estimate the effect of traditional risk factors as well as HIV‐associated factors on non‐AIDS‐defining conditions.

Results

Among 6007 patients in follow‐up, 130 had an SNA event (0.86 events/100 person‐years of follow‐up) and were defined as cases (40 with cardiovascular events, 54 with serious liver failure, 35 with non‐AIDS‐defining malignancies and two with renal insufficiency). Risk factors such as diabetes, hepatitis B and C virus coinfections and alcohol abuse showed an association with events, as expected. The last recorded CD4 T‐cell count prior to index date (P=0.0056, with an average difference of more than 100 cells/μL) and area under the CD4 cell curve in the year previous to index date (P=0.0081) were significantly lower in cases than in controls. CD4 cell count at index date was significantly associated with the outcome after adjusting for risk factors.

Conclusions

The incidence and type of SNA events found in this Latin American cohort are similar to those reported in other regions. We found a significant association between immune deficiency and the risk of SNA events, even in patients under antiretroviral treatment.     

Epilepsy in patients with brain tumours: epidemiology, mechanisms, and management

Epilepsy is common in patients with brain tumours and can substantially affect daily life, even if the tumour is under control. Several factors affect the mechanism of seizures in brain tumours, including tumour type, tumour location, and peritumoral and genetic changes. Prophylactic use of antiepileptic drugs is not recommended, and potential interactions between antiepileptic and chemotherapeutic agents persuades against the use of enzyme-inducing antiepileptic drugs. Multidrug-resistance proteins prevent the access of antiepileptic drugs into brain parenchyma, which partly explains why seizures are frequently refractory to treatment. Lamotrigine, valproic acid, and topiramate are first-line treatments of choice; if insufficient, add-on treatment with levetiracetam or gabapentin can be recommended. On the basis of clinical studies, we prefer to start treatment with valproic acid, adding levetiracetam if necessary. Risks of cognitive side-effects with antiepileptic drugs can add to previous damage by surgery or radiotherapy, and therefore appropriate choice and dose of antiepileptic drug is crucial.     

Lacrimal gland and perioptic nerve lesions due to Langerhans cell histiocytosis (2007: 9b)

We report a patient presenting with bilateral lacrimal gland involvement and perioptic nerve sheath lesions due to Langerhans cell histiocytosis (LCH) invasion. LCH is a rare multisystemic disease characterized by a clonal proliferation of Langerhans cells. All organs may be involved with a clinical spectrum ranging from a solitary bone lesion to a severe life-threatening multisystem disease. Osteolytic orbital bone lesions with extension into the adjacent orbital soft tissues have been described. To our knowledge, lacrimal gland involvement has probably been described only once before. Perioptic nerve lesions are also very rare, having been described only three times before. Precisely correct answers were received by closing date from: Kemal DEMIR, Istanbul, Turkey Jose Carlos GALLEGO, Ferrol, Spain Manabu MINAMI, Tsukuba, Japan Ram PRAKASH GALWA, Chandigarh, India Annemie SNOECKX, Zandhoven, Belgium Panagiotis TSIRKINIDIS, Athens, Greece Filip VANHOENACKER, Duffel, Belgium     

Nonrigid registration for subtraction CT angiography applied to the carotids and cranial arteries

RATIONALE AND OBJECTIVES: Computed tomography angiography (CTA) is an established tool for vascular imaging. However, high-intensity nonvascular structures in the contrast image can seriously hamper luminal visualization. This is an issue for three-dimensional visualization, where high-intensity structures might cover the underlying vasculature. But also in two dimensions, calcified plaques adjacent to the contrast-enhanced vessel lumen impede correct determination of the vessel boundary. High-intensity structures can be eliminated using subtraction CTA, where a native image is subtracted from the contrast image. However, patient and organ motion limits the widespread application of this technique. We propose to use nonrigid image registration to solve this problem. MATERIALS AND METHODS: For each patient, a native image and a contrast image are recorded, respectively, before and after contrast administration. The native image is registered to the contrast image using an automatic intensity-based nonrigid three-dimensional registration algorithm. Both images are merged in a fused image, allowing the user to switch between a view of the arteries, the bone or both. The procedure has been applied to 95 patients. RESULTS: In all cases, subtraction CTA using nonrigid registration allows for a significantly better artifacts removal than subtraction CTA without registration. Image quality of all images was judged adequate for clinical use. The average total processing time for each dataset is about 30 minutes. CONCLUSION: Nonrigid registration can allow for a great reduction in subtraction artifacts for subtraction CTA, resulting in a clear view of the vasculature.     

Poor prediction of resting energy expenditure in obese women by established equations

The objective of the study was to evaluate the accuracy of established prediction equations that calculate resting energy expenditure (REE) in obese women. This was a cross-sectional study. In 273 mildly to severely obese women (age, 41.7 ± 13.2 years; body mass index, 42.8 ± 7.0 kg/m²), REE was measured by indirect calorimetry (mREE), along with fat mass (FM) and fat-free mass (FFM) by bioelectrical impedance analysis. Eleven established equations were used to predict REE (pREE), with 9 equations basing on the anthropometric parameters body weight and height and 2 equations including body composition parameters (FM, FFM). All equations provided pREE values that significantly correlated with mREE (r > 0.66, P < .001), although 8 equations systematically underestimated mREE (P < .05). Of note, even the best equation was not able to accurately predict mREE with a deviation of less than ±10% in more than 70% of the tested women. Furthermore, equations using body composition data were not superior in predicting REE as compared with equations exclusively including anthropometric variables. Multiple linear regression analyses revealed 2 new equations—one including body weight and age and another including FM, FFM, and age—that explained 56.9% and 57.2%, respectively, of variance in mREE. However, when these 2 new equations were applied to an independent sample of 33 obese women, they also provided an accurate prediction (±10%) of mREE in only 56.7% and 60.6%, respectively, of the women. Data show that an accurate prediction of REE is not feasible using established equations in obese women. Equations that include body composition parameters as assessed by bioelectrical impedance analysis do not increase the accuracy of prediction. Based on our results, we conclude that calculating REE by standard prediction equations does not represent a reliable alternative to indirect calorimetry for the assessment of REE in obese women.     

Role of glial cells in the functional expression of LL-37/rat cathelin-related antimicrobial peptide in meningitis

Antimicrobial peptides are intrinsic to the innate immune system in many organ systems, but little is known about their expression in the central nervous system. We examined cerebrospinal fluid (CSF) and serum from patients with active bacterial meningitis to assess antimicrobial peptides and possible bactericidal properties of the CSF. We found antimicrobial peptides (human cathelicidin LL-37) in the CSF of patients with bacterial meningitis but not in control CSF. We next characterized the expression, secretion, and bactericidal properties of rat cathelin-related antimicrobial peptide, the homologue of the human LL-37, in rat astrocytes and microglia after incubation with different bacterial components. Using real-time polymerase chain reaction and Western blotting, we determined that supernatants from both astrocytes and microglia incubated with bacterial component supernatants had antimicrobial activity. The expression of rat cathelin-related antimicrobial peptide in rat glial cells involved different signal transduction pathways and was induced by the inflammatory cytokines interleukin 1beta and tumor necrosis factor. In an experimental model of meningitis, infant rats were intracisternally infected with Streptococcus pneumoniae, and rat cathelin-related antimicrobial peptide was localized in glia, choroid plexus, and ependymal cells by immunohistochemistry. Together, these results suggest that cathelicidins produced by glia and other cells play an important part in the innate immune response against pathogens in central nervous system bacterial infections.     

Human neuromelanin induces neuroinflammation and neurodegeneration in the rat substantia nigra: implications for Parkinson's disease

Parkinson's disease (PD) is a common neurodegenerative disorder characterized by a selective loss of dopaminergic neurons in the substantia nigra (SN). It has been suggested that microglial inflammation augments the progression of PD. Neuromelanin (NM), a complex polymer pigment found in catecholaminergic neurons, has sparked interest because of the suggestion that NM is involved in cell death in Parkinson's disease, possibly via microglia activation. To further investigate the possible role of NM in the pathogenesis of PD, we conducted in vivo experiments to find out whether microglial cells become activated after injection of human neuromelanin (NM) into (1) the cerebral cortex or (2) the substantia nigra to monitor in this PD-relevant model both microglial activation and possible neurodegeneration. In this study, adult male Wistar rats received an intracerebral injection of either NM, bacterial lipopolysaccharide (LPS, positive control), phosphate-buffered saline (PBS, negative control) or colloidal gold suspension (negative particular control). After different survival times (1, 8 or 12 weeks), brain slices from the cerebral cortex or substantia nigra (SN, 1 week) were stained with Iba-1 and/or GFAP antibody to monitor microglial and astrocytic reaction, and with tyrosine hydroxylase (TH) to monitor dopaminergic cell survival (SN group only). The injection of LPS induced a strong inflammatory response in the cortex as well in the substantia nigra. Similar results could be obtained after NM injection, while the injection of PBS or gold suspension showed only moderate or no glial activation. However, the inflammatory response declined during the time course. In the SN group, there was, apart from strong microglia activation, a significant dopaminergic cell loss after 1 week of survival time. Our findings clearly indicate that extracellular NM could be one of the key molecules leading to microglial activation and neuronal cell death in the substantia nigra. This may be highly relevant to the elucidation of therapeutic strategies in PD.