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Biomedical subjects

E Feldman

Publications and source records attributed to E Feldman.

At least 37 records · Page 2Linked to original sources
PubMed1999

Costs of antidepressant overdose: a preliminary study.

There is ongoing debate regarding the relative cost effectiveness of different classes of antidepressants. Although factors such as tolerability and discontinuation rates have been taken into account, there has been little consideration of the cost of overdose. In the current study we examined the cost of antidepressant overdose at four teaching hospitals over a four-week period and found that the cost of selective serotonin reuptake inhibitor overdose was less than half that of tricyclic anti-depressant overdose. The cost of overdose is often ignored and should be considered in future analyses of the cost effectiveness of different antidepressant prescribing policies in primary care.

Adult↗
PubMed1999

Neuropsychological test development and normative data on Hispanics.

The development of culturally relevant psychological assessment tools and intervention procedures has not been commensurate with the rate of Hispanic population growth in the United States. The development of valid and reliable test measures for the assessment of this population must be based on empirical investigations. In this article, we present normative data on multiple measures from the Benton Laboratory and the Wisconsin Card Sorting Test. Results revealed equivalent findings for our Hispanic subjects and the English-speaking samples utilized in the original normative studies within the United States. We additionally review current trends and specific problems encountered in neuropsychological research with Hispanics, and suggest guidelines and directions for future research.

Journal Article↗
PubMed1998

Deliberate self harm: systematic review of efficacy of psychosocial and pharmacological treatments in preventing repetition.

OBJECTIVE: To identify and synthesise the findings from all randomised controlled trials that have examined the effectiveness of treatments of patients who have deliberately harmed themselves. DESIGN: Systematic review of randomised controlled trials of psychosocial and physical treatments. Studies categorised according to type of treatment. When there was more than one investigation in a particular category a summary odds ratio was estimated with the Mantel-Haenszel method. SETTING: Randomised trials available in electronic databases in 1996, in the Cochrane Controlled Trials Register in 1997, and from hand searching of journals to 1997. SUBJECTS: Patients who had deliberately harmed themselves shortly before entry into the trials with information on repetition of behaviour. The included trials comprised 2452 randomised participants with outcome data. MAIN OUTCOME MEASURE: Repetition of self harm. RESULTS: 20 trials reported repetition of self harm as an outcome variable, classified into 10 categories. Summary odds ratio (all for comparison with standard aftercare) indicated reduced repetition for problem solving therapy (0.73; 95% confidence interval 0.45 to 1.18) and for provision of an emergency contact card in addition to standard care (0.45; 0.19 to 1.07). The summary odds ratios were 0.83 (0.61 to 1.14) for trials of intensive aftercare plus outreach and 1.19 (0.53 to 2.67) for antidepressant treatment compared with placebo. Significantly reduced rates of further self harm were observed for depot flupenthixol versus placebo in multiple repeaters (0.09; 0.02 to 0.50) and for dialectical behaviour therapy versus standard aftercare (0.24; 0.06 to 0.93). CONCLUSION: There remains considerable uncertainty about which forms of psychosocial and physical treatments of patients who harm themselves are most effective. Further larger trials of treatments are needed.

Aftercare↗
PubMed1998

Gene transfer of alpha interferon into hematopoietic stem cells.

Gene transfer or gene therapy has advantages in the treatment of a variety of disorders due to its selective expression within specific mammalian cells. IFN-alpha has been used in the management of leukemia, and gene transfer of the IFN-alpha gene into hematopoietic progenitor cells may have great potential for the treatment of chronic myelogenous leukemia (CML). Therefore, we examined the ability of adenovirus (Ad)-IFN-alpha gene construct to transfect normal bone marrow hematopoietic CD34+ stem cells and the production of IFN-alpha protein by these cells. Ad-cytomegalovirus (CMV) promoter-driven IFN-alpha at multiple doses was assessed to transfect highly purified CD34+ cells in liquid culture. Optimal transduction of CD34+ cells with the AdCMV-IFN-alpha construct was achieved using 120 plaque forming units (pfu). Flow cytometric determinations revealed that there was no significant difference in CD34+ cell viability for the 8 or 12-h transfection periods. Immunoassay of IFN-alpha produced by CD34+ cells shows that IFN-alpha levels increased several fold in transfected cells and this was not seen in CD34+ cells transfected with the heme oxygenase gene (HO-1). These in vitro data suggest that adenovirus-mediated gene transfer of IFN-alpha into hematopoietic stem cells can be achieved and that the IFN-alpha protein is produced by viable CD34 progenitor cells.

Adenoviridae↗
PubMed1997

Expanded CAG/CTG repeats in bipolar disorder: no correlation with phenotypic measures of illness severity.

The hypothesis that expanded trinucleotide repeats (TNRs) contribute to the pathogenesis of bipolar disorder has received strong support from recent studies showing that, on average, bipolar patients carry larger repeat sequences of the TNR motif CAG/CTG than do controls. It has been postulated that intergenerational expansion of a TNR may be responsible for the tendency for age of onset to become earlier in younger generations (anticipation) observed in some bipolar pedigrees, and that length polymorphism may account for variability in clinical phenotype. We have used the method of repeat expansion detection to examine these predictions in a sample of 133 Caucasian DSM-III-R bipolar I probands from the British Isles. We found no evidence to support the notion that CAG/CTG TNR genes are major determinants of phenotypic severity or age at onset in the population examined, and conclude that for most cases of bipolar disorder TNR genes may operate as susceptibility genes rather than as single genes of major effect.

Adult↗
PubMed1997

Adenovirus mediated alpha interferon (IFN-alpha) gene transfer into CD34+ cells and CML mononuclear cells.

Gene transfer or gene therapy has advantages in the treatment of a variety of disorders due to its selective expression within specific mammalian cells. Interferon-alpha (IFN-alpha) has been used in the management of leukemia but its diverse adverse activities with multiple potential side effects, possibly unrelated to therapeutic targets, may negatively influence the ability of IFN-alpha to treat this disorder. Therefore, we examined the ability of adenovirus (Ad)-IFN-alpha gene construct to transfect normal (CD34+ cells) and chronic myelogenous leukemia (CML) bone marrow mononuclear cells (BMMNC) and the transient overexpression of IFN-alpha in these cells. Ad-cytomegalovirus promoter driven IFN-alpha (AdCMV-IFN-alpha) at multiple doses was assessed to transfect highly purified CD34+ cells in liquid culture, and optimal transduction of CD34+ cells was achieved using 120 plaque forming units. Flow cytometric determinations revealed that there was no significant difference in cell viability for the 4 h or 24 h transfection periods. Immunoassay of IFN-alpha produced by CD34+ cells shows that IFN-alpha levels increased several fold in transfected cells. Transient expression of the IFN-alpha gene did not suppress proliferation of CD34+ progenitors as indicated by BFU-E or colony forming units-granulocyte-macrophage (CFU-GM) growth. Reverse transcriptase/polymerase chain reaction analysis of RNA from CD34+ harvested CFU-GM progenitor cells demonstrated transient IFN-alpha mRNA expression. Similarly, CML BMMNC were transfected with AdCMV-IFN-alpha under similar conditions as described for CD34+ cells. BMMNC cells exposed to adenovirus for 24 h and 48 h were found to express IFN-alpha at a substantial level. This in vitro data suggest that Ad-mediated gene transfer of IFN-alpha into hematopoietic stem cells can be achieved and that the IFN-alpha gene can be translated into its specific mRNA in CD34 progenitor cells.

Adenoviridae↗
PubMed1997

Association studies of bipolar disorder at the human serotonin transporter gene (hSERT; 5HTT).

The human serotonin transporter gene (hSERT) is a strong candidate for involvement in the pathogenesis of mood disorder and, using a UK Caucasian case-control sample, Collier et al found a significant association between bipolar disorder and the 12 allele of the VNTR polymorphism in intron 2 of this gene. In a European collaborative sample, Collier et al found a significant association between affective disorder and a functional deletion polymorphism in the promoter of hSERT. We have undertaken association studies using these polymorphisms in a British Caucasian sample comprising 171 DSM-IV bipolar probands, 80 DSM-IV major depression probands and 121 unrelated controls matched to bipolar probands for age, sex and ethnicity. We found no association between the promoter deletion and affective disorder but our findings with the VNTR polymorphism are similar to those of Collier and colleagues: we found a significant excess of the 12 repeat allele in bipolar probands (P = 0.031, one-tall) with a suggestion of a gene dosage effect (using genotypes bearing no 12 repeat allele as baseline, the increased risks conferred by genotypes bearing 12 repeat alleles were: heterozygote, OR = 1.24; homozygote, OR = 1.76). Our findings add to the evidence that variation at or near hSERT influences susceptibility to bipolar disorder in the British Caucasian population.

Adult↗
PubMed1997

Heme induces the expression of adhesion molecules ICAM-1, VCAM-1, and E selectin in vascular endothelial cells.

Heme is an important immunostimulating agent and oxidative factor contributing to endothelial cell activation. To investigate the mechanism of heme-induced endothelial cell activation, we analyzed the effect of heme and the inflammatory cytokine, tumor necrosis factor-alpha (TNF-alpha), on the expression of the heme-degrading stress protein, heme oxygenase (HO), and adhesion molecules in human umbilical vein endothelial cells (HUVEC). Indirect immunofluorescence double labeling studies demonstrated a simultaneous increase of ICAM-1 and HO-1 after exposure of cells to heme for 24 hr. Co-expression of HO-1 and ICAM-1 was also demonstrated in TNF-alpha-exposed cells. Dot blot immunoassay and quantitative analysis by ELISA demonstrated that heme treatment for 24 hr caused a 2-fold increase in ICAM-1 expression (P < 0.002) compared with quiescent cells, while in cells stimulated by TNF-alpha for 24 hr ICAM-1 gene expression increased by 5-fold. Moreover, heme exposure also resulted in a marked increase in VCAM-1 and E selectin expression (three and four times over control levels, respectively). On the other hand, TNF-alpha treatment showed similar expression levels for VCAM-1 and E selectin, compared with stimulation by heme (100 microM). The level of HO activity in endothelial cells exposed to heme or TNF-alpha was increased from 24.7 +/- 5.7 pmol bilirubin/mg protein/min in control to 70.0 +/- 9.5 and 36.7 +/- 3.1 pmol bilirubin/mg protein/min in heme- and TNF-alpha-stimulated cells, respectively. These results suggest that upregulation of ICAM-1, VCAM-1, and E selectin expression is associated with oxidative stress induced by hemoglobin/heme and that HO-1 may play a modulating role via its ability to degrade heme to a substance with antioxidant properties.

Cell Adhesion Molecules↗
PubMed1996

The differentiation and maturation mediator for human myeloid leukemia cells shares homology with neuroleukin or phosphoglucose isomerase.

The identity of the maturation inducer capable of mediating the differentiation of human myeloid leukemic HL-60 calls to terminal monocytic cells was investigated. One of such inducers from T cells was purified as a 54.3-kD peptide. The amino acid sequence of a tryptic peptide and the enzyme cleavage sites revealed 100% homology to neuroleukin or phosphoglucose isomerase (PGI). Neuroleukin mediates differentiation of neurons and is homologous to PGI, which catalyzes the interconversion of glucose-6-phosphate and fructose-6-phosphate. The 54.3-kD inducer was shown to have PGI enzymatic activity. Separately purified PGI by substrate-elution exhibited identical specificity as the maturation inducer for HL-60 cell differentiation. They mediated a reduction of proliferating S and G2M cells, and the mature monocytic calls acquired complement receptors, phagocytic capacity, and adherence morphology. The magnitude of differentiation was dosage dependent on the inducer, with a bell-shaped curve. At the excess dose range cells did not undergo differentiation and remained in a proliferating cycle. Abnormally elevated PGI enzyme activities were detected in the plasma of acute myelogenous leukemia patients. Whether they represent an excess of the differentiation regulator in patients and are important in leukemogenesis remain to be investigated.

Aged↗
PubMed1996

Confirmation of association between expanded CAG/CTG repeats and both schizophrenia and bipolar disorder.

Recent studies have suggested that expanded CAG/CTG repeats contribute to the genetic aetiology of schizophrenia and bipolar disorder. However, the nature of this contribution is uncertain and difficult to predict from other known trinucleotide repeat diseases that display much simpler patterns of inheritance. We have sought to replicate and extend earlier findings using Repeat Expansion Detection in an enlarged sample of 152 patients with schizophrenia, 143 patients with bipolar disorder, and 160 controls. We have also examined DNA from the parents of 62 probands with schizophrenia or bipolar disorder. Our results confirm our earlier, preliminary findings of an association between expanded trinucleotide repeats and both schizophrenia and bipolar disorder. However, our data do not support the hypothesis that trinucleotide repeat expansion can alone explain the complex patterns of inheritance of the functional psychoses neither can this mechanism fully explain apparent anticipation.

Adult↗
PubMed1996

Association study of bipolar disorder at the phospholipase A2 gene (PLA2A) in the Darier's disease (DAR) region of chromosome 12q23-q24.1.

We have previously described a pedigree in which affective disorder and Darier's disease cosegregate and, in an independent sample of 45 bipolar pedigrees, reported evidence in support of linkage between a putative susceptibility locus for bipolar disorder and markers in the Darier's disease region of chromosome 12q23-q24.1. The maximum evidence for linkage was given by a polymorphism at the gene encoding secretory phospholipase A2 (PLA2A), a candidate gene for affective disorder. Dawson et al. (Psychiatric Genetics, 5, 177-180) recently reported allelic association with the same polymorphism at PLA2A in a sample of 54 bipolar probands and 56 controls. We have been unable to replicate the association in 127 Caucasian British DSMIII-R bipolar probands and 223 Caucasian British controls. However, on the basis of several lines of evidence discussed in the paper, we believe that this genomic region in general, and the PLA2A gene in particular, are worthy of further study as candidates in the search for susceptibility genes for the functional psychoses.

Alleles↗
PubMed1996

Cytarabine with high-dose mitoxantrone induces rapid complete remissions in adult acute lymphoblastic leukemia without the use of vincristine or prednisone.

PURPOSE: To evaluate the efficacy and safety of a new induction regimen for adult acute lymphoblastic leukemia (ALL) that does not contain vincristine or corticosteroids. PATIENTS AND METHODS: Thirty-seven adult patients with newly diagnosed ALL and lymphoblastic lymphoma were treated with a dose-intense induction regimen. This regimen was designed to increase the fraction of patients achieving an early complete remission (CR) in an attempt to increase long-term disease-free survival. The induction regimen was cytarabine (Ara-C) 3 g/m2/d for 5 days and mitoxantrone 80 mg/m2 as a single dose on day 3. Granulocyte colony-stimulating factor (G-CSF) 200 micrograms/ m2/d beginning on day 7 was used to promote early myeloid recovery. RESULTS: There were 31 CRs (84%). Median time to CR was 34 days, median hospital stay was 28 days, and the median number of days with a neutrophil count less than 500/microL was 18. There were three patients with resistant disease who experienced treatment failure and three early deaths from sepsis. Four patients with Philadelphia chromosome-positive (Ph+) ALL achieved hematologic and cytogenetic CRs. CONCLUSION: This dose-intense induction regimen produced a high incidence of CRs with acceptable toxicity without the use of vincristine or corticosteroids. Comparisons with our prior vincristine/prednisone-based induction regimen (the L-20 protocol) suggest that patients treated on the current study were more likely to achieve a CR and that they achieved this remission earlier than patients treated with a traditional four-drug (vincristine, prednisone, doxorubicin, and cyclophosphamide) induction regimen.

Adolescent↗