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Biomedical subjects

I Hirsch

Publications and source records attributed to I Hirsch.

At least 19 recordsLinked to original sources
PubMed2006

[Morphology of drug induced liver damage].

Hepatotoxicity is a significant complication of therapeutic drug use. As ist can imitate nearly all hepatopathies, the diagnosis of drug-induced liver disease is difficult. Most often, it is a diagnosis of exclusion. The following morphological changes are known, dependent on the target cell type: acute and chronic hepatitis, granuloma formation, and fatty liver disease, cholestatic type acute and chronic liver damage with or without inflammation,or mixed forms of liver injury. Portal or perisinusoidal fibrosis can occur following each type of liver damage. Vascular changes or neoplasms are rare. Drug induced liver injuries are more likely induced by type B damage, which is not expected and cannot be reproduced in animal testing. Type A damage, which is known from toxicity assays, is less likely. A specific therapeutic regime is not available. Therefore, early recognition and cessation of the use of the drug is necessary.

Acute Disease↗
PubMed2006

Prediction of relapse by day 100 BCR-ABL quantification after allogeneic stem cell transplantation for chronic myeloid leukemia.

Chronic myeloid leukemia (CML) relapse after allogeneic stem cell transplantation (SCT) is a relatively frequent situation, which is correlated to disease status, time from diagnosis to transplant and T-cell depletion. We evaluated the potential for early minimal residual disease (MRD) BCR-ABL quantification to predict relapse of CML patients receiving allogeneic SCT. Minimal residual disease was analyzed by real-time quantitative reverse transcriptase-polymerase chain reaction (RQ-PCR) at day 100 (d100) in 38 patients with >1 year follow-up after conventional non-T-cell-depleted SCT. Normal ABL control values from 1724 follow-up blood samples were used to define an RQ-PCR amplifiability index and the limits of reliable use of BCR-ABL ratios. We then compared the 14 patients with a high-level d100 BCR-ABL/ABL ratio (> or = 10(-4)) to that of the 24 patients with a negative/low-level ratio (<10(-4)). Despite being comparable for all classical parameters, the incidence of relapse was significantly higher in the high MRD group (11/14 (79%)) compared to that of the low/negative MRD group (7/24 (29%)) (P = 0.009), with d100 MRD values representing an independent risk factor of relapse and disease-free survival, but not of overall survival, in multivariate analysis. These data should facilitate risk-adapted post-transplant immunosuppression and/or tyrosine kinase inhibitor therapy based on an early evaluation of MRD.

Adolescent↗
PubMed2005

[Adenocarcinoid of the appendix vermiformis].

Adenocarcinoids are rare tumors with histological features of both carcinoid tumor and adenocarcinoma. They show a more aggressive biological behaviour than conventional carcinoids. We report a case of a 64-years-old female patient with a diffuse infiltration of the appendicular wall by an adenocarcinoid. Due to the positive surgical margin and the tumor expansion a hemicolectomy was performed. There are no precise criteria to direct the operative choice between appendectomy and hemicolectomy. It is thought that appendectomy is sufficient in case of small tumors in the tip of the appendix. Patients with diffuse appendicular involvement require a more aggressive surgical therapy.

Adenocarcinoma↗
PubMed2004

Does haploidentical transplantation in children with primary immunodeficiencies have the potential to exploit donor NK cell alloreactivity?

Donor potential to exert NK cell alloreactivity has been shown to confer survival advantage in haploidentical hematopoietic cell transplantation for hematological malignancies. We investigated killer immunoglobulin receptor (KIR) ligand incompatibility in 40 children receiving haploidentical transplantation for primary immunodeficiencies. The conditioning regimen consisted of busulfan and cyclophosphamide. T-cell depletion of the graft used complement-dependent lysis or CD34+ selection. Two patients died in the first month. The remaining 38 patients were divided into those with (n=13) and those without (n=25) donor potential to exert NK cell alloreactivity. Engraftment was similar in the two groups (61.5 and 64%, respectively). The incidence of grade II-IV acute graft-versus-host disease (GVHD) tended to be lower in the group with donor potential to exert NK cell alloreactivity, but the difference was not significant. In conclusion, in this series of patients with primary immunodeficiencies, donor potential to exert NK cell alloreactivity was not associated with significant advantages in engraftment and prevention of acute GVHD.

Child, Preschool↗
PubMed2001

Production of HIV-1 by resting memory T lymphocytes.

BACKGROUND: The persistence of HIV-1 within resting memory CD4 T cells constitutes a major obstacle in the control of HIV-1 infection. OBJECTIVE: To examine the expression of HIV-1 in resting memory CD4 T cells, using an in-vitro model. DESIGN AND METHODS: Phytohaemagglutinin-activated peripheral blood mononuclear cells were challenged with T cell-tropic and macrophage-tropic HIV-1 clones, and with a replication-incompetent and non-cytotoxic HIV-1-derived vector (HDV) pseudotyped by the vesicular stomatitis virus glycoprotein G. To obtain resting memory CD4 T cells containing HIV-1 provirus, residual CD25(+), CD69(+) and HLA-DR(+) cells were immunodepleted after a 3 week cultivation period. RESULTS: In spite of the resting phenotype, the majority of provirus-harbouring T cells expressed HIV-1 genomes and produced infectious virus into cell-free supernatant. The expression of HDV dropped by only 30% during the return of activated HDV-challenged cells into the quiescent phase. Although resting memory T cells generated in vitro expressed HIV-1 and HDV genome when infected during the course of the preceding T cell activation, they were resistant to HIV-1 and HDV challenge de novo. The infected culture of resting memory T cells showed a higher resistance to the cytotoxic effects of HIV-1 in comparison with the same cultures after reactivation by phytohaemagglutinin. CONCLUSION: The majority of resting memory T cells infected during the course of a preceding cell activation produces virus persistently, without establishing a true HIV-1 latency. The described system could be used as a model for testing new drugs able to control residual HIV-1 replication in resting memory T cells.

CD4-Positive T-Lymphocytes↗
PubMed2001

Extensively deleted simian immunodeficiency virus (SIV) DNA in macaques inoculated with supercoiled plasmid DNA encoding full-length SIVmac239.

Using long-distance DNA PCR, we prospectively followed rhesus monkeys that had been inoculated intramuscularly with supercoiled plasmid DNA encoding intact simian immunodeficiency virus (SIV). From 4 to 10 weeks postinoculation onward, we detected extensively deleted proviral genomes along with full-length viral genomes in peripheral blood mononuclear cells (PBMC) in adult macaques. During their chronic asymptomatic phase of infection, the frequency of deleted proviral genomes was similar in PBMC and lymph nodes. The latter, however, harbored significantly more full-length proviral DNA than PBMC, consistent with the lack of effective antiviral cytotoxic T-cell activity in lymph nodes described by others during human immunodeficiency virus infection. After the macaques progressed to AIDS, full-length proviral DNA became equally abundant in lymph nodes and in PBMC. We have demonstrated that although a single molecular species of proviral DNA was inoculated, genomic diversity was detected within a short time, thus confirming the genetic instability of the SIV genome in vivo.

Animals↗
PubMed1999

Multicomponent penile prosthesis implantation under regional anesthesia.

Fourteen consecutive patients underwent placement of a multicomponent penile prosthesis under regional anesthesia using a pudendal nerve block. Results demonstrated the need for minimal administration of intraoperative narcotics, no major fluctuations in the blood pressure or pulse rate during intraoperative monitoring, and only 1 of 14 patients was converted to general anesthesia. Postoperatively, our results show that there was no urinary retention or cardiac side effects, adequate postoperative analgesia was obtained, and 13 of the 14 patients were discharged within 24 hours. This method was safe, effective, easily performed, and does not carry the associated morbidity of general or spinal anesthesia.

Anesthetics, Local↗
PubMed1998

Primary intestinal epithelial cells can be infected with laboratory-adapted strain HIV type 1 NDK but not with clinical primary isolates.

Infectivities of HIV-1 primary isolates and laboratory-adapted strains were compared in primary fetal enterocytes and the colonic epithelial cell line HT29. Infection by two laboratory strains, HIV-1 NDK and HIV-1 NDK(A4), which were adapted on CEM and HT29 cells, respectively, produced significant amounts of virus in both target cell systems. Intestinal cells were resistant to infection with HIV-1 primary isolates regardless of their genetic subtype or SI/NSI phenotype. Biological properties of analyzed viruses rather than differences in cultivation system seem to be responsible for differences between these in vitro and ex vivo results.

Cells, Cultured↗
PubMed1998

The concept of enactment and theoretical convergence.

Classical analysts have recently become interested in the constructive use of countertransference. Some have extended the traditional conception of transference enactment to include the analyst's countertransference enactments. That is, the analyst may unwittingly actualize the patient's transference and, together with the patient, live out intrapsychic configurations. Awareness and interpretation are likely to occur only after there has been a transference-countertransference enactment. Some classical analytic writers have concluded that such experience may be both inevitable and a productive means of achieving analytic goals. This point of view corresponds closely to positions long expressed by interpersonal psychoanalytic contributors, thus signaling a trend toward a partial convergence of these two historically divergent theories of therapeutic action.

Countertransference↗
PubMed1997

Accumulation of defective viral genomes in peripheral blood mononuclear cells of human immunodeficiency virus type 1-infected individuals.

Human immunodeficiency virus type 1 (HIV-1) genomes present in peripheral blood mononuclear cells (PBMCs) of infected persons or in lymphocytes infected in vitro were studied by long-distance PCR (LD-PCR) using primers localized in the HIV-1 long terminal repeats. The full-length 9-kb DNA was the only LD-PCR product obtained in peripheral and cord blood lymphocytes from seronegative donors infected in vitro. However, a high proportion (27% to 66%) of distinct populations of extensively deleted HIV-1 genomes of variable size was detected in PBMCs of 15 of 16 HIV-1-infected persons. Physical mapping of defective genomes showed that the frequency of deletions is proportional to their proximity to the central part of HIV-1 genome, which is consistent with a deletion mechanism involving a single polymerase jump during reverse transcription. Sequencing of deletion junctions revealed the presence of short direct repeats of three or four nucleotides. The number of defective HIV-1 genomes decreased after in vitro activation of PBMCs. Persistence of full-length and deleted genomes in in vitro activated PBMCs correlated with isolation of an infectious virus. Our results represent the first quantitative assessment of intragenomic rearrangements in HIV-1 genomes in PBMCs of infected persons and demonstrate that, in contrast to in vitro infection, defective genomes accumulate in PBMCs of infected persons.

Adult↗
PubMed1997

Insulin analogues: new agents for improving glycemic control.

For years, it has been recognized that "reasonable" control of blood glucose levels reduces the acute complications of diabetes mellitus. Recent studies have conclusively shown that strict glycemic control reduces the appearance and progression of chronic complications. Thus, strict glycemic control is the most salient goal of insulin therapy. Insulin regimens that closely mimic physiologic insulin secretory patterns have been inadequate because of limitations imposed by the pharmacokinetic profiles of commercially available preparations. The newer insulin analogues, both rapid-acting and long-acting, have more appropriate pharmacokinetic profiles. Lispro (Humalog) is the first human insulin analogue to be approved in the United States. Its pharmacokinetic and pharmacodynamic profile makes it amenable for use before meals. The search for long-acting and hepatospecific analogues continues.

Blood Glucose↗
PubMed1996

Genetic control of infection of primary macrophages with T-cell-tropic strains of HIV-1.

Human immunodeficiency virus type 1 (HIV-1) NDK, a Zairian subtype D virus highly cytopathic for CD4-positive lymphocytes, and the prototype subtype B virus HIV-1 LAV are about 10(4) and 10(5) times more infectious, respectively, for T lymphocytes than for blood-derived macrophages (BDM). Recombinant viruses derived from HIV-1 LAV and HIV-1 NDK were used to determine the genetic control and the step of the virus/cell cycle responsible for infection of BDM with T-cell-tropic viruses. We found that recombinants bearing the envelope glycoprotein of HIV-1 NDK are able to enter more efficiently into BDM than recombinants with HIV-1 LAV envelope glycoprotein. We also found that a genetic region outside of the env gene is responsible for production of HIV-1 NDK infectious progeny from BDM. This region consists of the vif gene and the C- and N-terminal portions of pol and vpr genes, respectively. Our results suggest that productive infection of primary macrophages with T-cell-tropic strains of HIV-1 is determined by two different genetic mechanisms: one effective at the virus/cell entry, controlled by the env gene, and the second after entry, controlled by genes vif and vpr. In comparison with HIV-1 LAV, HIV-1 NDK has been able to more easily overcome both restriction mechanisms.

Cell Line↗
PubMed1995

Fusogenic determinants of highly cytopathic subtype D Zairian isolate HIV-1 NDK.

Phenotypic characterization of subtype B strains of human immunodeficiency virus type 1 (HIV-1) indicates that the major determinants of their cytopathogenicity and tropism are contained in the gene coding for the envelope glycoprotein gp120, namely in its variable regions V1, V2, and V3. Recombinant viruses derived from HIV-1 LAV, the subtype B prototype virus, and HIV-1 NDK, the Zairian subtype D virus highly cytopathic for CD4-positive lymphocytes, were used to elucidate genetic control of fusogenic functions in subtype D viruses. Our data demonstrate that multigenic determination of fusogenic properties is more complex in the subtype D than in clade B viruses. Variability in three regions of HIV-1 NDK genome correlated with formation of large syncytia. These regions consisted of the matrix protein, the C-terminal portion of vpr up to the C1 region of gp120, and the V1-V3 regions of gp120. Variability in the envelope glycoprotein but not in other regions of the HIV-1 genome was related to enhanced resistance of HIV-1 NDK to treatment of target cells with OKT4-A anti-CD4 MAb. Therefore, a different genetic control affects two aspects of HIV-1 fusogenicity: (i) variability in the envelope glycoprotein itself is sufficient to influence a virus-to-cell fusion at the virus/cell entry, and (ii) a more complex genetic function including genes of matrix protein and envelope glycoprotein is related to variability of cell-to-cell fusion during formation of syncytium.

Antibodies, Monoclonal↗