Femoral and acetabular re-alignment in slipped capital femoral epiphysis.

NEW PATHOPHYSIOLOGICAL INSIGHTS: Based on improved knowledge of the vascular supply of the proximal femur, a safe surgical dislocation of the hip joint was established allowing direct insights to the pathomorphological malfunctioning of the joint. One insight was that slipped capital femoral epiphysis (SCFE) impingement leads to substantial damage of the chondrolabral rim area, even in the presence of minor slips. A further surgical development was the extended retinacular flap allowing for correction of the deformity with calculable risk for iatrogenic necrosis. CONSECUTIVE SURGICAL CONCEPT: In 20 years of experience, a treatment concept for SCFE could be established which replaces classic pinning in situ and indirect correction of the deformity with subcapital re-alignment when the physis is still open, with true femoral neck osteotomy for hips with closed physis. Pinning in situ still has a place in minor slips but should be combined with open or arthroscopic recreation of an anterior metaphyseal waisting. UNEXPECTED COMPLICATION: Loss of joint stability is a rare complication of anatomic re-alignment. It can be disease-related when the impingement has induced severe destruction of acetabular cartilage. It can be related to the surgical procedure, especially when the neck was excessively shortened and refixation of the trochanter was not advanced. Finally, in cases with severe and long-lasting deformity, the acetabulum may undergo adaptive flattening, being the cause of joint destabilisation with the correction of the deformity. Advancement of the greater trochanter and/or peri-acetabular osteotomy may be discussed to restabilise the joint.

Defective nef alleles in a cohort of hemophiliacs with progressing and nonprogressing HIV-1 infection.

Deletion of the nef gene results in viral attenuation and confers protection against challenge with wild-type simian immunodeficiency virus in macaques. Regarding HIV-1 infection, a few long-term nonprogressors (LTNP) with nef deletions have been described. In this study, the nef genes of a group of seven LTNP and eight progressors, all belonging to the same cohort of infected hemophiliacs, were analyzed by cloning and sequencing from both virion RNA and peripheral blood mononuclear cell-associated proviral DNA. Defective nef sequences coexisted with full-length nef open reading frames in five of seven LTNP and two of eight progressors. The proportion of disrupted nef sequences within each individual was significantly higher in LTNP (ranging from 10 to 63%) than in progressors (ranging from 9 to 21%) (P = 0.013). Moreover, in-frame small deletions predicting to encode Nef were found in all RNA- and DNA-derived clones from one LTNP and four progressors. A chimeric virus in which the nef gene of NL4.3 was substituted with the nef allele containing the deletion of two alanines at position 49-50 found in two progressors showed a defective replicative capacity compared to NL4.3 virus. In summary, hemophiliacs with either progressing or nonprogressing HIV-1 infection are characterized by the presence of defective nef variants.

Human CD34(+) cells express CXCR4 and its ligand stromal cell-derived factor-1. Implications for infection by T-cell tropic human immunodeficiency virus.

Human CD34(+) hematopoietic progenitor cells obtained from bone marrow (BM), umbilical cord blood (UCB), and mobilized peripheral blood (MPB) were purified and investigated for the expression of the chemokine receptor CXCR4 and its ligand, stromal cell-derived factor-1 (SDF-1). CXCR4 was found present on the cell surface of all CD34(+) cells, although it was expressed at lower density on MPB with respect to BM CD34(+) cells. Freshly isolated and in vitro-cultured CD34(+) cells also coexpressed SDF-1 mRNA, as determined by reverse transcriptase-polymerase chain reaction (RT-PCR). Of interest, CD34(+)/CD38(+) committed progenitor cells, unlike primitive CD34(+)/CD38(-) cells, expressed SDF-1 mRNA. Supernatants from in vitro-cultured CD34(+) cells contained substantial (3 to 8 ng/mL) amounts of SDF-1 by enzyme-linked immunosorbent assay and induced migration of CD34(+) cells. Because CD34(+) cells express low levels of CD4, the primary receptor of the human immunodeficiency virus (HIV), and CXCR4 is a coreceptor for T-cell tropic (X4) HIV strains, we investigated the susceptibility of CD34(+) cells to infection by this subset of viruses. Lack of productive infection was almost invariably observed as determined by a conventional RT activity in culture supernatants and by real-time PCR for HIV DNA in CD34(+) cells exposed to both laboratory adapted (LAI) and primary (BON) X4 T-cell tropic HIV-1 strain. Soluble gp120 Env (sgp120) from X4 HIV-1 efficiently blocked binding of the anti-CD4 Leu3a monoclonal antibody (MoAb) to either human CD4(+) T cells or CD34(+) cells. In contrast, sgp120 interfered with an anti-CXCR4 MoAb binding to human T lymphocytes, but not to CD34(+) cells. However, CXCR4 on CD34(+) cells was downregulated by SDF-1. These results suggest that CXCR4 and its ligand SDF-1 expressed in CD34(+) progenitors may play an important role in regulating the local and systemic trafficking of these cells. Moreover, these findings suggest multiple and potentially synergistic mechanisms at the basis of the resistance of CD34(+) cells to X4 HIV infection, including their ability to produce SDF-1, and the lack of CXCR4 internalization following gp120 binding to CD4.

Validated chiral high-performance liquid chromatographic method for the determination of trans-(-)-paroxetine and its enantiomer in bulk and pharmaceutical formulations.

A stereospecific high-performance liquid chromatography method for the determination of trans-(-)-paroxetine and its enantiomer in bulk raw material and pharmaceutical formulations was developed and validated. The enantiomeric separation was achieved, without any derivatization, on a carbamate derivative-based column (Chiralpak AD). The effect of the organic modifiers, 2-propanol and ethanol, in the mobile phases was optimised to obtain enantiomeric separation. Limits of detection and quantitation of 2 and 6 ng, respectively, were obtained for both of the enantiomers. The linearity was established in the range of 5-41 microg for trans-(-)-paroxetine and in the range of 10-160 ng for trans-(+)-paroxetine. The accuracy of the method was 102.3% (mean value) for trans-(-)-paroxetine and 99.9% (mean value) for trans-(+)-paroxetine. For the precision (repeatability), a relative standard deviation value of 1.5% (mean value) for trans-(-)-paroxetine and of 2.1% (mean value) for trans-(+)-paroxetine was found. The method is capable of determining a minimum limit of 0.2% of trans-(+)-isomer in commercial samples.

Hemophilia and nonprogressing human immunodeficiency virus type 1 infection.

Seven of 112 hemophiliacs infected with human immunodeficiency virus type-1 (HIV-1) before 1986 through contaminated plasma products are currently healthy, with CD4 T-cell counts above 500 cells/microL, and have never received antiretroviral therapy (long-term nonprogressors [LTNPs]). Seven age and sex-matched hemophiliacs infected in the same period but who have progressive HIV disease (progressors) and one additional slow-progressing individual were also studied. One hundred-fold, 20-fold, and 10-fold lower levels of full-length HIV RNA in plasma, peripheral blood mononuclear cells (PBMCs), and proviral DNA in PBMCs, respectively, were found in LTNPs compared with progressors. Plasma and cell-associated HIV RNA and proviral DNA were lower in LTNPs who tested negative for viral isolation from PBMCs or who were positive only after removal of CD8+ cells. No substantial differences were observed in the in vitro production of chemokines including RANTES, MIP-1 alpha, MIP-1 beta, MCP-1, and interleukin-8 (IL-8) in supernatants of activated PBMCs or CD8-depleted PBMCs of LTNPs, even when HIV isolation was simultaneously accomplished exclusively after removal of CD8+ cells. Low levels of HIV load and replication in peripheral blood are the strongest correlates of nonprogression in this small number of infected hemophiliacs.

HTLV-I and HTLV-II Tax: differences in induction of micronuclei in cells and transcriptional activation of viral LTRs.

Human T-cell leukemia virus (HTLV) types I and II are highly related viruses that differ in disease manifestations. HTLV-I has been linked unmistakably to adult T-cell leukemia-lymphoma. On the other hand, there is little evidence that prior infection with HTLV-II increases risk for lymphoproliferative disorders. Both viruses encode homologous transcriptional-activating proteins (respectively designated as Tax1 and Tax2) which have been suggested to be important mediators of viral pathogenesis. Previously, we reported that Tax1 is a potent inducer of micronuclei formation in cells. Here, we present evidence that Tax2 lacks micronuclei inductive ability. We contrast this phenotypic difference between Tax1 and Tax2 at the cellular level with their similarities at the molecular level in transcriptional activation.

Tax protein of human T-lymphotropic virus type I triggers DNA damage.

Previous findings indicated that in vitro HTLV-I-infected cells are highly susceptible to spontaneous and chemically induced DNA-damage. To further study the role of different virus gene products in inducing chromosome abnormalities, MOLT-3 cells were transiently transfected with a tax expressing plasmid (pTax), and assayed for genetic damage by the micronucleus test. We found that pTax-transfected cells not only had a statistically higher baseline micronucleus value than non-transfected control cells, but also were more susceptible to Mitomycin C (MMC)-induced DNA damage. Furthermore, the use of human serum containing anti-kinetochore antibodies disclosed that tax enhances the clastogenic effect of MMC. No increase in total micronucleus frequency was observed when MMC treatment preceded pTax transfection, thus suggesting that the micronucleus increase might not be due to the additive effect of tax and MMC. These findings indicate that the viral tax protein could play an important role in inducing the chromosome damage frequently observed in HTLV-I-infected cells.

A case of rupture of the deep tendon of the third palmar interosseous muscle.

The authors present a case of traumatic subcutaneous rupture of the deep tendon of the third palmar interosseous muscle. This injury is characterized primarily by the abduction of the little finger. Surgical fixation of the proximal loose end of the tendon to the base of the proximal phalanx yields excellent clinical and functional results.

Studies on the mechanisms of HTLV-I leukemogenesis.

The factors that regulate low viral expression and long latency after HTLV-I infection are poorly understood. To study the possible mechanisms involved in the regulation of gene expression and cell transformation, we studied whether (1) methylation could play a role in viral transcription, and (2) tax product could favor chromosomal instability. The results indicate that methylation of HTLV-I LTRs blocks their transcriptional activity and that tax protein triggers DNA damage.

[Allergenic impurities in medicinal preparations containing aminopenicillin. I. Ampicillin sodium]. / Impurezze allergogene in specialità medicinali contenenti amino-penicilline. I. Ampicillina sodica.

High-performance liquid chromatography (HPLC) with gradient elution has been used for the determination of degradation products in pharmaceutical preparations containing sodium ampicillin. In all preparations resulting by lyophilization process, the degradation products amount, almost exclusively constituted of allergenic polymeric substances deriving from condensation reactions, is more than 10%. On the contrary, the sodium ampicillin prepared by precipitation in non aqueous solvents, only contains the 2% of polymeric impurities.