Localised giant haematoma and subsequent widespread purpura as a sign of acquired haemophilia A.

Patients with acquired haemophilia A usually show widespread subcutaneous bleeding. We describe an 86-year-old man with acquired haemophilia A associated with prostate carcinoma, showing initial localised giant haematoma and subsequent widespread subcutaneous bleeding. A localised giant haematoma may present as a first and important sign of acquired haemophilia A.

Interleukin-8 in the pathogenesis of primary central nervous system lymphoma in association with HIV infection.

The pathogenesis of acquired immunodeficiency syndrome-associated primary central nervous system lymphoma (AIDS-associated PCNSL) remains unclear. However, cell adhesion molecules have been reported to be strongly associated with PCNSL. In this study, we established Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines (LCLs) from HIV-positive patients (LCL(HIV)) and normal individuals (LCL(N)). The expression of CD18 antigen by LCL(HIV) was stronger than that by LCL(N). We performed a cell adhesion assay using ISO-HAS, which is the human hemangiosarcoma cell line and expresses intercellular adhesion molecule 1 (CD54). The binding rates of LCL(HIV) and ISO-HAS without stimulation were higher than those of LCL(N). Further, we demonstrated that azidothymidine or simvastatin inhibited the binding rates of LCL(HIV) and ISO-HAS more significantly than those of LCL(N). Further, the levels of interleukin (IL)-8, a CD18 inducer, were higher in LCL(HIV) than in LCL(N). We conclude that interaction between IL-8 and CD18 may be critical to AIDS-related PCNSL.

Cellular HIV-1 DNA levels in patients receiving antiretroviral therapy strongly correlate with therapy initiation timing but not with therapy duration.

BACKGROUND: Viral reservoir size refers to cellular human immunodeficiency virus-1 (HIV-1) DNA levels in CD4(+) T lymphocytes of peripheral blood obtained from patients with plasma HIV-1-RNA levels (viral load, VL) maintained below the detection limit by antiretroviral therapy (ART). We measured HIV-1 DNA levels in CD4(+) lymphocytes in such patients to investigate their clinical significance. METHODS: CD4(+) T lymphocytes were isolated from the peripheral blood of 61 patients with a VL maintained at less than 50 copies/ml for at least 4 months by ART and total DNA was purified. HIV-1 DNA was quantified by nested PCR to calculate the copy number per 1 million CD4(+) lymphocytes (relative amount) and the copy number in 1 ml of blood (absolute amount). For statistical analysis, the Spearman rank or Wilcoxon signed-rank test was used, with a significance level of 5%. RESULTS: CD4 cell counts at the time of sampling negatively correlated with the relative amount of HIV-1 DNA (median = 33 copies/million CD4(+) lymphocytes; interquartile range [IQR] = 7-123 copies/million CD4(+) lymphocytes), but were not correlated with the absolute amounts (median = 17 copies/ml; IQR = 5-67 copies/ml). Both absolute and relative amounts of HIV-1 DNA were significantly lower in six patients in whom ART was initiated before positive seroconversion than in 55 patients in whom ART was initiated in the chronic phase, as shown by Western blotting. CD4 cell counts before ART introduction were also negatively correlated with both the relative and absolute amounts of HIV-1 DNA. Only the relative amounts of HIV-1 DNA negatively correlated with the duration of VL maintenance below the detection limit, while the absolute amounts were not significantly correlated with this period. CONCLUSIONS: The amounts of cellular HIV-1 DNA in patients with VLs maintained below the detection limit by the introduction of ART correlated with the timing of ART initiation but not with the duration of ART. In addition, CD4(+) T lymphocytes, which were newly generated by ART, diluted latently infected cells, indicating that measurements of the relative amounts of cellular HIV-1 DNA might be underestimated.

Relationship between expression of mutant type glutathione S-transferase theta-1 gene and reactivity of rapamycin in myelodysplastic syndrome.

We previously reported mRNA expression of glutathione S-transferases theta (GSTT)-1, wild type (623 bp) and mutant (500 bp), in patients with myelodysplastic syndrome (MDS). The deletion of 123 bp creates a sequence that is homologous to the mammalian target of rapamycin (mTOR). To analyze the function of mutant GSTT-1 gene, stable transformants for the mutant and wild-type GSTT-1 gene, respectively, were established. In this study, the expression of the wild and mutant type of the GSTT-1 gene of those stable transformants in cell lines and in bone marrow cells from MDS patients by reverse-transcription polymerase chain reaction (RT-PCR) was observed in the presence or absence of rapamycin. Significant growth inhibition by rapamycin was observed among stable transformants for the mutant GSTT-1 gene, but not wild type GSTT-1 gene, and was indicative of typical apoptosis.

Liposomal amphotericin B for a case of intractable cryptococcal meningoencephalitis and immune reconstitution syndrome.

We examined the efficacy of liposomal amphotericin B (L-AMB) for intractable cryptococcal meningoencephalitis in a patient with acquired immunodeficiency syndrome (AIDS) and the presence of immune reconstitution syndrome (IRS) caused by the treatment. A 34-year-old patient presented with meningitis. Cryptococcal organisms were detected microscopically in the cerebrospinal fluid (CSF) with Indian ink staining, and were then cultured from the CSF. Initial treatment with amphotericin B and flucytosine (5-FC) or voriconazole and/or fluconazole failed to eradicate cryptococcal organisms from the CSF. Secondary treatment with L-AMB and 5-FC following seven months of antiretroviral therapy was successful. Simultaneously, treatment with L-AMB caused severe brain edema likely due to IRS. There were large differences in immune function improvement and liposomalization of the fungicide between the initial and secondary treatments. In conclusion, differences in immune status should be considered when administering L-AMB, in order to prevent IRS-related complications.

Problems in three Japanese drug users with Human Immunodeficiency Virus infection.

Numbers of individuals infected with Human Immunodeficiency Virus (HIV) are increasing in Japan. The majority of them are Men who have sex with men and a part of them take drugs as 'Sex drug' at their sexual intercourse. Especially, Amyl nitrite, Methamphetamine, 5-methoxy-N, N-diisopropyltryptamine (5-MeO-DIPT; Foxy), and 3, 4-methylenedioxy- methamphetamine (MDMA; Ecstasy) are used, and they sometimes cause the physical and mental disorders. However, the actual drug inducing troubles among Japanese HIV-infected drug users had not yet been discussed enough. In this report, we describe three cases with HIV infection; a case developed severe neuroleptic malignant syndrome (NMS) after taking 5-MeO-DIPT, a case with persistent convulsion due to multiple drug intake and a case with rhabdomyolysis due to the non-subjective methamphetamine intake. Through these cases, we raise and discuss several underlying problems associated with drug use among HIV-infected individuals.

Predicting tenofovir concentration on the basis of renal factors determined by routine tests.

Although it has not caused overt renal damage in clinical trials, tenofovir disoproxil fumarate (TDF) has been associated with renal dysfunction in isolated cases. The objective of this study was to assess the TDF concentration with use of the glomerular filtration rate (GFR) and blood urea nitrogen (BUN) level. Serum creatinine (used to calculate GFR), BUN, and plasma TDF trough values were measured in 51 patient volunteers at pretreatment and post-treatment time points. The post-treatment GFR (post_GFR) and the difference between the pretreatment and post-treatment BUN levels (dif_BUN) were strongly related to TDF concentration. A piecewise multiple regression technique was applied to the nonlinear TDF distribution, revealing a significant association of the post_GFR and dif_BUN values with TDF concentration (P=0.002 and P= 0.003, respectively). Post_GFR values below 125 mL/min/1.73 m(2) and/or dif_BUN values below -3 mg/dL are predicted to cause a marked increase in the TDF concentration. The relationship between TDF and BUN is a new finding. Knowledge of the pretreatment and post-treatment serum creatinine and BUN levels is important for the safe clinical administration of TDF.