Severe HIV-1 encephalitis and development of cerebral non-Hodgkin lymphoma in a patient with persistent strong HIV-1 replication in the brain despite potent HAART -- case report and review of the literature.

A 39 year old patient with HIV-1 infection, who was asymptomatic without antiretroviral therapy (HAART) for ten years, developed severe encephalopathy. Despite therapy with a four drug antiretroviral combination regimen including two protease-inhibitors (PI), plasma viral load could not be suppressed sufficiently with persistence of low level viremia of 3.08-3.40 log copies/ml, even after addition of two other antiretroviral drugs. On therapy the patient showed improvement of clinical symptoms, however with severe persisting cognitive deficits. Repeated parallel measurements of viral load showed a far higher viremia in the cerebrospinal fluid than in the plasma. Resistance testing provided no evidence of relevant PI-mutations and analysis of protease inhibitor levels demonstrated good plasma levels. 17 months after start of HAART, the patient developed a cerebral Non-Hodgkin lymphoma, leading to his death despite radiation therapy. There has been a dramatic reduction in the prevalence of HIV-1 associated CNS events in the post-HAART era. Nevertheless, subgroups of patients are infected with neurotropic viral variants which could cause progressive neurological pathology as they can not be reached sufficiently by the available drugs. These patients require the development of new drugs that achieve a better penetration into the brain.

CGH-detected DNA sequence copy number amplifications can be confirmed by interphase-FISH: new possiblities for prognostic approaches in oral squamous cell carcinomas.

In order to control the data obtained by comparative genomic hybridization (CGH) on DNA sequence copy number amplifications, 20 oral squamous cell carcinomas (SCC) were subjected to interphase fluorescence in situ hybridization (I-FISH) examination using specific DNA probes for the oncogenes int2 and erbB-2, and the corresponding centromeric probes of chromosomes 11 and 17. In all cases characterized by distinct peaks of the CGH profile on the critical chromosomal segment 11q13, these data could be clearly substantiated by the I-FISH analyses using the int2 probe and estimating the signal index, the int2/centromer 11 relation, and the fraction of nuclei with high int2 signal numbers. In addition, I-FISH detected smaller cell fractions with high signal numbers (and/or signal clusters) in some tumors which were not definitely conspicuous in CGH. In contrast to int2, erbB-2 amplification apparently does not play a major role in oral SCCs, as the blurred peaks of CGH profiles on chromosome 17ql 1.2-q12 corresponded well with the findings of I-FISH using the erbB-2 probe. Gain of a whole chromosome 17 is apparently a rather common feature of these tumors. In conclusion, the combination of interphase FISH with oncogene-specific probes and CGH is regarded as a valuable means of practical molecular cytogenetic analysis of oral SCCs which could eventually achieve high practical importance in the pathologic analysis of these tumors and in prognosis of their development.