The outcome of proliferative lupus nephritis with pulse cyclophosphamide therapy.

Proliferative lupus nephritis deserves aggressive therapy and cyclophosphamide plays a pivotal role. Thirty nine patients with proliferative lupus nephritis (Class III-7 patients and Class IV- 32 patients) with a median follow up of 38 months were considered for this observational study. All the patients received induction therapy with intravenous methylprednisolone. Cyclophosphamide was given intravenously initially in monthly pulses for six months and later quarterly pulses until remission was achieved or until the target dose (200 mg/kg) was reached. The treatment with intravenous methylprednisolone was repeated in the event of a nephritic flare. Later the corticosteroid was reduced to a minimum effective dose and cyclophosphamide was changed to either azathioprine or mycophenolate mofetil. At the time of the last follow up, 82.05% of the patients were in remission (complete remission 51.28% and partial remission 30.77%). The median interval to achieve remission in responders was 15 months. Early diagnosis (P=0.04), a higher creatinine clearance at presentation (P=0.02), and concurrent use of an ACEI or an ARB (P=007) significantly favored attaining remission. Five patients experienced a doubling of serum creatinine and one of them became dialysis dependent. Risk of doubling of serum creatinine correlated with a low Ccr (P=0.03) at presentation, occurrence of renal flares (P=0.034) and failure to achieve remission (P=0.0001). The parameters like serum creatinine, serum C3, serum C4, activity and chronicity indices on renal biopsy, hypertension were not statistically significant. Therapy with cyclophosphamide, if initiated early, helps in inducing remission and hence can retard the progression to CKD.

Defining a left-lateralized response specific to intelligible speech using fMRI.

Functional imaging studies of language have shown bilateral superior temporal activations in response to 'passive' perception of speech when the baseline condition did not control for the acoustic complexity of speech. Controlling for this complexity demonstrates speech-specific processing lateralized to the left temporal lobe, and our recent positron emission tomography study has emphasized a role for left anterolateral temporal cortex in speech comprehension. This contrasts with the more usual view that relates speech comprehension to left temporal-parietal cortex, the ill-defined area of Wernicke. This study attempted to reconcile these differences, using a more sensitive 3 T functional magnetic resonance imaging system, and a sparse sampling paradigm. We found left lateralized activations for intelligible speech with two distinct foci, one in the anterior superior temporal sulcus and the other on the posterior temporal lobe. Therefore, the results demonstrate that there are neural responses to intelligible speech along the length of the left lateral temporal neocortex, although the precise processing roles of the anterior and posterior regions cannot be determined from this study.

Exacerbation of pain by anxiety is associated with activity in a hippocampal network.

It is common clinical experience that anxiety about pain can exacerbate the pain sensation. Using event-related functional magnetic resonance imaging (FMRI), we compared activation responses to noxious thermal stimulation while perceived pain intensity was manipulated by changes in either physical intensity or induced anxiety. One visual signal, which reliably predicted noxious stimulation of moderate intensity, came to evoke low anxiety about the impending pain. Another visual signal was followed by the same, moderate-intensity stimulation on most of the trials, but occasionally by discriminably stronger noxious stimuli, and came to evoke higher anxiety. We found that the entorhinal cortex of the hippocampal formation responded differentially to identical noxious stimuli, dependent on whether the perceived pain intensity was enhanced by pain-relevant anxiety. During this emotional pain modulation, entorhinal responses predicted activity in closely connected, affective (perigenual cingulate), and intensity coding (mid-insula) areas. Our finding suggests that accurate preparatory information during medical and dental procedures alleviates pain by disengaging the hippocampus. It supports the proposal that during anxiety, the hippocampal formation amplifies aversive events to prime behavioral responses that are adaptive to the worst possible outcome.