The impact of a very high purity factor VIII concentrate on the immune system of human immunodeficiency virus-infected hemophiliacs: a randomized, prospective, two-year comparison with an intermediate purity concentrate [see comments]

Pathophysiologic considerations as well as non-comparative clinical results suggest that very high purity concentrates may slow immunologic deterioration in human immunodeficiency virus (HIV)-infected hemophiliacs. In an attempt to evaluate this hypothesis, we prospectively compared CD4 cell counts, skin testing responses, and changes of the clinical status in 20 asymptomatic HIV-positive hemophiliacs, randomly assigned to continue the treatment with an intermediate purity concentrate or to receive a very high purity product, purified by immunoaffinity chromatography with monoclonal antibodies. In the group switched to the very high purity concentrate there was no significant change of the CD4 cell counts over the 96-week follow-up period, whereas in the group continued on the intermediate purity concentrate, a highly significant decline was detected (P less than .013). Furthermore, in the very high purity group, four of six anergic patients at entry acquired reactivity to skin testing. The results of this study clearly support the use of very high purity concentrates for the replacement therapy of HIV-infected hemophiliacs.     

Simultaneous measurement of gallbladder emptying with cholescintigraphy and US during infusion of physiologic doses of cholecystokinin: a comparison

Both ultrasonography (US) and cholescintigraphy are used to study gallbladder dynamics. The present study was undertaken to determine whether the two methods provide the same or different information relating to gallbladder emptying. Emptying was simultaneously studied with both methods during infusion of graded physiologic doses of cholecystokinin (CCK) in six healthy subjects. Infusion of stepwise increasing doses of CCK, ranging from 0.03 to 0.5 Ivy dog units per kilogram of body weight per hour (IDU/kg.h), induced significant dose-related increases in plasma CCK, decreases in gallbladder volume assessed with US, and gallbladder emptying assessed with cholescintigraphy. The threshold dose for inducing significant gallbladder emptying was 0.13 IDU/kg.h, as determined with both techniques, indicating similar detection limits. There was a highly significant correlation between decreases in gallbladder volume and decreases in radioactive counts over the gallbladder region, with a tendency toward greater gallbladder responses at sonography during the early phase of gallbladder contraction and toward greater responses at cholescintigraphy during the later phase of gallbladder contraction. It is concluded that these methods can be used interchangeably for the quantitation of gallbladder emptying.     

Direct demonstration of transsynaptic degeneration in the human visual system: a comparison of retrograde and anterograde changes

Transneuronal degeneration of retinal ganglion cells was directly demonstrated in a patient who had unilateral removal of the striate cortex forty years prior to necropsy. For comparison, another case is presented showing anterograde transneuronal atrophy forty years after enucleation of one eye.     

Update: current management issues in malignant melanoma

The incidence of melanoma has increased continuously during the last decade. Surgery is the mainstay of therapy but, for patients with thick lesions or regional metastatic lymph nodes, there is a high risk of relapse. For this group of patients, there is no standard therapy or general agreement amongst oncologists. In this article, we review the current management of melanoma with regard to past completed adjuvant trials and open trials. Moreover, we discuss the role of chemotherapy in metastatic melanoma, in particular with attention to the use of fotemustine.     

Tinnitus: neurobiological substrates

Tinnitus is an auditory phantom sensation of ringing in the ears that is experienced when no external sound is present. It is a prevalent disorder that is frequently caused by insults to the peripheral auditory and somatosensory systems, especially in the elderly. This creates an imbalance between inhibitory and excitatory transmitter actions in the midbrain, auditory cortex and brainstem (where neural activity from somatosensory and auditory stimuli interact). This imbalance causes hyperexcitability often leading to the perception of phantom sounds. Although changes in transmitter-receptor systems have become better documented, there are currently no proven drug treatments for humans. Methods for preventing tinnitus have been demonstrated in animal studies.     

Cross-correlation and joint spectro-temporal receptive field properties in auditory cortex

Recordings were made from the right primary auditory cortex in 17 adult cats using two eight-electrode arrays. We recorded the neural activity under spontaneous firing conditions and during random, multi-frequency stimulation, at 65 dB SPL, from the same units. Multiple single-unit (MSU) recordings (281) were stationary through 900 s of silence and during 900 s of stimulation. The cross-correlograms of 545 MSU pairs with peak lag times within 10 ms from zero lag time were analyzed. Stimulation reduced the correlation in background activity, and as a result, the signal-to-noise ratio of correlated activity in response to the stimulus was enhanced. Reconstructed spectro-temporal receptive fields (STRFs) for coincident spikes showed larger STRF overlaps, suggesting that coincident neural activity serves to sharpen the resolution in the spectro-temporal domain. The cross-correlation for spikes contributing to the STRF depended much stronger on the STRF overlap than the cross-correlation during either silence or for spikes that did not contribute to the STRF (OUT-STRF). Compared with that for firings during silence, the cross-correlation for the OUT-STRF spikes was much reduced despite the unchanged firing rate. This suggests that stimulation breaks up the large neural assembly that exists during long periods of silence into a stimulus related one and maybe several others. As a result, the OUT-STRF spikes of the unit pairs, now likely distributed across several assemblies, are less correlated than during long periods of silence. Thus the ongoing network activity is significantly different from that during stimulation and changes afterng arousal during stimulation.