Cytotoxic Mediators in Paradoxical HIV-Tuberculosis Immune Reconstitution Inflammatory Syndrome

Tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) frequently complicates combined antiretroviral therapy and antituberculosis therapy in HIV-1–coinfected tuberculosis patients. The immunopathological mechanisms underlying TB-IRIS are incompletely defined, and improved understanding is required to derive new treatments and to reduce associated morbidity and mortality. We performed longitudinal and cross-sectional analyses of human PBMCs from paradoxical TB-IRIS patients and non-IRIS controls (HIV-TB–coinfected patients commencing antiretroviral therapy who did not develop TB-IRIS). Freshly isolated PBMC stimulated with heat-killed Mycobacterium tuberculosis H37Rv (hkH37Rv) were used for IFN-γ ELISPOT and RNA extraction. Stored RNA was used for microarray and RT-PCR, whereas corresponding stored culture supernatants were used for ELISA. Stored PBMC were used for perforin and granzyme B ELISPOT and flow cytometry. There were significantly increased IFN-γ responses to hkH37Rv in TB-IRIS, compared with non-IRIS PBMC (p = 0.035). Microarray analysis of hkH37Rv-stimulated PBMC indicated that perforin 1 was the most significantly upregulated gene, with granzyme B among the top five (log(2) fold difference 3.587 and 2.828, respectively), in TB-IRIS. Downstream experiments using RT-PCR, ELISA, and ELISPOT confirmed the increased expression and secretion of perforin and granzyme B. Moreover, granzyme B secretion reduced in PBMC from TB-IRIS patients during corticosteroid treatment. Invariant NKT cell (CD3(+)Vα24(+)) proportions were higher in TB-IRIS patients (p = 0.004) and were a source of perforin. Our data implicate the granule exocytosis pathway in TB-IRIS pathophysiology. Further understanding of the immunopathogenesis of this condition will facilitate development of specific diagnostic and improved therapeutic options

Can depression be a menopause-associated risk?

There is little doubt that women experience a heightened psychiatric morbidity compared to men. A growing body of evidence suggests that, for some women, the menopausal transition and early postmenopausal years may represent a period of vulnerability associated with an increased risk of experiencing symptoms of depression, or for the development of an episode of major depressive disorder. Recent research has begun to shed some light on potential mechanisms that influence this vulnerability. At the same time, a number of studies and clinical trials conducted over the past decade have provided important data regarding efficacy and safety of preventative measures and treatment strategies for midlife women; some of these studies have caused a shift in the current thinking of how menopausal symptoms should be appropriately managed

How safe is twistdrill craniostomy?

The incidence of haemorrhagic complications of intracranial pressure monitoring (ICPM) has previously been reported. However, in these studies, the techniques employed to access the inside of the cranium varied. While 3-mm essentially blind 'twistdrill' craniostomies have been used, their role has been limited for fear of haemorrhagic sequelae. This has also restricted their use in clinical applications other than ICPM. We conducted a prospective observational study looking at haemorrhagic complications of the twistdrill in order to determine its safety and whether it has a role in other clinical settings. Over the period January 1994-February 2001, 941 patients had 1032 twistdrill procedures. There were 550 (58.4%) male patients and 391 (41.6%) female. The age range was 3 months to 93 years (median age 35 years). Only four procedures (0.38%) caused clinically significant bleeds attributable to the twistdrill --all of which were managed conservatively without requiring surgical evacuation. We conclude that twistdrill craniostomies are safe and that their use could be extended to other neurosurgical procedures and potentially to ICPM in non-neurosurgical centres

Treatment of intracerebral hematomas caused by aneurysm rupture: coil placement followed by clot evacuation.

OBJECT: The aim of this study was to evaluate the efficacy of a treatment combination of coil embolization and clot evacuation in patients presenting with an intracerebral hematoma (ICH) caused by the rupture of an aneurysm. METHODS: Twenty-seven patients were prospectively recruited in this study between 1996 and 2000. Endovascular treatment of the putative ruptured aneurysm was performed as soon as practical after diagnosis and before surgical evacuation of the ICH. The Glasgow Outcome Scale (GOS) was used during follow up. Despite admission World Federation of Neurosurgical Societies grades of IV or V in 25 patients (92%), 13 (48%) recovered well with GOS scores of 1 or 2, whereas six patients (21%) died. CONCLUSIONS: The combined result of a favorable outcome in 48% of the patients and a mortality rate of 21% indicates that this treatment may be a valuable alternative for this patient group and warrants further study