Search PubMed⌕ Search

Biomedical subjects

D Goldman

Publications and source records attributed to D Goldman.

At least 73 records · Page 4Linked to original sources
PubMed2000

Genotype influences in vivo dopamine transporter availability in human striatum.

In vivo availability of striatal dopamine transporter (DAT) protein has been reported to be reduced among alcoholics, and allelic variation of the DAT gene (SLC6A3) has been associated with severity of alcohol withdrawal. We examined the VNTR polymorphism of the 3' untranslated region of SLC6A3 and DAT protein availability in 14 abstinent alcoholics and 11 control subjects. Single photon emission computed tomography (SPECT) and plasma levels of the radioligand [I-123]beta-CIT were used to quantify DAT protein availability. Individuals with the 9-repeat/10-repeat genotype had a mean 22% reduction of DAT protein availability in putamen compared with 10-repeat homozygous individuals (t = 2.14, df = 23, p < .05). Consistent with earlier studies, alcoholism, per se, was not significantly associated with either DAT availability or DAT genotype. These findings suggest that the VNTR polymorphism of the DAT gene effects translation of the DAT protein. This effect may explain a variety of clinical associations that have been reported with this polymorphism.

3' Untranslated Regions↗
PubMed2000

Improving the quality of care through routine teleradiology consultation.

RATIONALE AND OBJECTIVES: The hypotheses of this study were as follows: (a) University subspecialty radiologists can provide consultations effectively to general radiologists as part of routine clinical operations; (b) these consultations will improve the quality of the final radiologic report; and (c) the consultations will improve the care process and may save money, as well. MATERIALS AND METHODS: For 2,012 consecutive computed tomographic or magnetic resonance (MR) imaging studies, the initial interpretations provided by radiology generalists were subsequently reviewed by specialists, with a final consensus report available. "Truth" was established by final consensus reports. To control for potential bias, 150 adult MR imaging and 250 pediatric radiologic studies were interpreted initially by specialists and then by generalists. Again, truth was established by final consensus reports. RESULTS: There was disagreement between generalist and specialist radiologist interpretations in 427 (21.2%) of the cases reviewed. These disagreements were stratified further by independent specialists, who graded them as important, very important, or unimportant. Differences were considered important or very important in 99% of the cases reviewed. CONCLUSION: Consultations by subspecialty radiologists improved the quality of the radiology reports studied and, at least in some cases, improved the process of care by eliminating unnecessary procedures or suggesting more specific follow-up examinations. The consultation services can be provided cost-effectively from the payer's perspective and may save additional costs when unnecessary procedures can be eliminated.

Humans↗
PubMed2000

Impulsiveness, serotonin genes and repetition of deliberate self-harm (DSH).

BACKGROUND: Few studies have investigated independent associations of psychological, biological and social variables with repeated deliberate self-harm (DSH). Serotonin function has been linked to impulsive and suicidal behaviour and genetic polymorphisms have been identified within the serotonin system that could account for this link. This study tested hypotheses linking impulsiveness, genetic polymorphisms of tryptophan hydroxylase (TPH) and the 5-HT2c receptor and repeated DSH. METHODS: Individuals presenting after DSH were interviewed, completed personality questionnaires and gave venous blood samples. Genotypes were determined for TPH intron7 and 5-HT2c (cys-ser) polymorphisms. Follow-up to identify repetition of DSH was for 1 year. RESULTS: Males with the 5-HT2c serine variant were more impulsive than those with the cysteine variant (039 standardized units, P = 0.041, 95% CI 0.017 to 0.076). There was no association between impulsiveness and the TPH intron7 polymorphism overall but a weak association with the L allele in men (0.41 standardized units, P = 0.05, 95 % CI 0.001 to 0.82). Impulsiveness, although high in the group as a whole, did not distinguish those who repeated DSH. CONCLUSIONS: The personality trait of impulsiveness may in part be related to genotypes of the 5-HT2c receptor and TPH gene in men. Impulsiveness does not differ between those who do and do not repeat DSH.

Adult↗
PubMed2000

A TNFR2 3' flanking region polymorphism in systemic lupus erythematosus.

The role of pro-inflammatory cytokines in systemic lupus erythematosus (SLE) remains somewhat controversial. Several studies have shown increased production of TNF alpha and IL-6 in patients with SLE. Increased production of IL-6, TNF alpha, and IL-1 soluble receptors have also been reported. This finding is provocative because the soluble receptors have the capacity to act as antagonists. Several other inflammatory disorders are also associated with increased production of soluble TNF alpha receptors suggesting that this may be a general compensatory mechanism designed to down-regulate inflammation. The recent identification of an SLE disease susceptibility locus near the TNFR2 locus (TNFR p75) suggested the hypothesis that genetically driven differences in soluble TNFR2 production could play a role in the genetic susceptibility to SLE. We therefore characterized the frequency of a genetic polymorphism in the 3' untranslated region of the TNFR2 gene in Caucasoid SLE patients and geographically matched controls. No difference in the gene frequency of the two base-pair polymorphism in SLE patients compared to controls was found, nor was there any association with any particular clinical phenotype.

3' Untranslated Regions↗
PubMed2000

Identification of a naturally occurring Pro385-Ser385 substitution in the GABA(A) receptor alpha6 subunit gene in alcoholics and healthy volunteers.

In the rat, variation in alcohol and benzodiazepine sensitivity has been correlated with an inherited variant of the GABA(A)alpha6 receptor. Our goal was to identify polymorphisms in the human GABA(A)alpha6 receptor gene and determine whether a variant of the receptor is associated with alcoholism. The GABA(A)alpha6 receptor gene coding region was screened in 80 unrelated patients with alcoholism using single strand conformational polymorphism analysis. For rapid genotyping, a Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) assay was developed. A relatively abundant amino acid substitution and three synonymous DNA substitutions were detected. The synonymous variants, 35A>G, 665A>G, and 1031G>C had rare-allele frequencies of 0.25, 0.02, and 0.47, respectively. The Pro385Ser substitution is located in the second intracellular domain of the receptor adjacent to a putative phosphorylation site. Pro385Ser has rarer allele frequencies of 3.3% and 4.8% in 196 Finnish alcoholic patients and 189 controls, respectively (P = NS). A naturally occurring non-conservative Pro385Ser was detected in the GABA(A)alpha6 receptor. The variant is not associated with alcoholism.

Alcoholism↗
PubMed2000

Regulation of myogenin protein expression in denervated muscles from young and old rats.

Myogenin is a muscle-specific transcription factor participating in denervation-induced increases in nicotinic ACh receptor (nAChR) gene expression. Although myogenin RNA expression in denervated muscle is well documented, surprisingly little is known about myogenin protein expression. Therefore, we assayed myogenin protein and RNA in innervated and denervated muscles from young (4 mo) and old (24-32 mo) rats and compared this expression to that of the nAChR alpha-subunit RNA. These assays revealed increased myogenin protein expression within 1 day of denervation, preceding detectable increases in nAChR RNA. By 3 days of denervation, myogenin and nAChR alpha-subunit RNA were increased 500- and 130-fold, respectively, whereas myogenin protein increased 14-fold. Interestingly, old rats (32 mo) had 6-fold higher myogenin protein and approximately 80-fold higher mRNA levels than young rats. However, after denervation, expression levels were similar for young and old animals. The increased myogenin expression during aging, which tends to localize to small fibers, likely reflects spontaneous denervation and/or regeneration. Our results show that increased myogenin protein in denervated muscles correlates with the upregulation of its mRNA.

Aging↗
PubMed2000

The new drugs (chlorpromazine & reserpine): administrative aspects. 1956.

The article on the new drugs reprinted below appeared in the February 1956 issue of Mental Hospitals. It is based on a discussion held during the Seventh Mental Hospital Institute in October 1955 in Washington, D.C. Chlorpromazine and reserpine had been available in the United States less than two years when the institute participants met to discuss how their hospitals were coping with the demands of the new treatments. In a commentary and analysis beginning on page 333, Robert Cancro, M.D., considers the broader impact of the introduction of neuroleptics and examines the concerns of the 1956 institute participants in the context of today.

Antipsychotic Agents↗
PubMed2000

Freud comes to Palestine. A study of psychoanalysis in a cultural context.

The authors describe the founding of Hashomer Hatzair as a radical Zionist scouting movement in Eastern Europe between 1913 and 1919, a little known episode in the rich history of Freud's impact upon this century. As refugees in Vienna, the young adherents of the movement experienced enormous personal and collective turmoil. Desperate to construct new, viable identities, these intellectually vibrant young men and women were drawn to Freud as part of their project of self-creation. Beginning in the 1920s, as members of Hashomer Hatzair settled in agriculturally based collectives known as kibbutzim, the educational leadership of the movement argued that psychoanalytically informed education was the key to raising children free of bourgeois neuroses. They established strong ties with European analysts, translated and published psychoanalytic texts, insisted that educators be analysed or, at least, psychoanalytically informed, and built a complex educational system founded on their particular understanding of Freudian insights. For them, psychoanalysis was also seen as a general prophylactic guaranteeing the mental hygiene of the community as a whole. The authors examine the complex relationship between Hashomer Hatzair and psychoanalysis. In particular, they ask why these young adults were so drawn to Freud and what their particular reading of the psychoanalytic texts was, and demonstrate how these young pioneers created a 'usable Freud' as part of their project of designing and building a utopian society.

Attitude to Death↗
PubMed2000

Association of coping responses with fibromyalgia tender points in patients with systemic lupus erythematosus.

OBJECTIVE: To determine the association between fibromyalgia (FM) tender points (TP) and psychological constructs in patients with systemic lupus erythematosus (SLE). METHODS: One hundred seventy-three patients with SLE were examined for FM TP, and asked to complete 2 questionnaires at the same visit, the Health-Related Hardiness Scale (HRHS), and the Mishel Uncertainty in Illness Scale (MUIS). RESULTS: The examination of FM TP showed that 38.2% had no TP, 44.5% had 1-10 TP, and 17.3% had > or = 11 TP. The mean +/- SD score of the HRHS was 155.6 +/- 19.7 (range 105.0-198.0; higher scores indicate greater hardiness), and the MUIS was 85.3 +/- 18.7 (range 41.0-132.0; higher scores indicate uncertainty). There were significant associations between FM TP and HRHS (no TP 161.2 +/- 20.2, 1-10 TP 152.5 +/- 19.7, > or = 11 TP 151.0 +/- 15.8; p = 0.0108) and between FM TP and MUIS (no TP 78.2 +/- 20.2, 1-10 TP 86.9 +/- 17.6, > or = 11 TP 95.8 +/- 14.7; p = 0.0001). CONCLUSION: This study shows a strong association between FM TP and uncertainty or lack of "hardiness." We conclude that SLE patients with FM TP are less likely to be good "copers." Prospective studies to determine if "poor coping" predicts FM in SLE are recommended. If the association between coping and FM is causal, it will justify interventions to improve coping and similar constructs, such as self-efficacy.

Adaptation, Psychological↗
PubMed2000

Access of vulnerable groups to antiretroviral therapy among persons in care for HIV disease in the United States. HCSUS Consortium. HIV Cost and Services Utilization Study.

OBJECTIVE: To employ the behavioral model of health services use in examining the extent to which predisposing, enabling, and need factors explain the treatment of the HIV-positive population in the United States with highly active antiretroviral therapy (HAART). DATA SOURCE: A national probability sample of 2,776 adults under treatment for human immunodeficiency virus (HIV) infection. STUDY DESIGN: The article uses data from the baseline and six-month follow-up surveys. The key independent variables describe vulnerable population groups including women, drug users, ethnic minorities, and the less educated. The dependent variable is whether or not a respondent received HAART by December 1996. DATA COLLECTION: All interviews were conducted using computer-assisted personal interview instruments designed for this study. Ninety-two percent of the baseline interviews were conducted in person and the remainder over the telephone. PRINCIPAL FINDINGS: A multistage logit regression shows that the predisposing factors that have previously described vulnerable groups in the general population with limited access to medical care also define HIV-positive groups who are less likely to gain early access to HAART including women, injection drug users, African Americans, and the least educated (odds ratios, controlling for need, ranged from 0.35 to 0.59). CONCLUSIONS: Those HIV-positive persons with the greatest need (defined by a low CD4 count) are most likely to have early access to HAART, which suggests equitable access. However, some predisposing and enabling variables continue to be important as well, suggesting inequitable access, especially for African Americans and lower-income groups. Policymakers and clinicians need to be sensitized to the continued problems of African Americans and other vulnerable populations in gaining access to such potentially beneficial therapies. Higher income, anonymous test sites, and same-day appointments are important enabling resources.

Adult↗
PubMed2000

An abundant proneurotensin polymorphism, 479A>G, and a test of its association with alcohol dependence in a Finnish population.

BACKGROUND: Neurotensin is a 13-amino acid neuropeptide that endogenously modulates dopamine release in the central nervous system. In substance dependence, the mesolimbic dopamine system has been postulated to be a central structure that mediates rewarding and reinforcing effects. Neurotensin receptors in the neurons of the ventral tegmental area facilitate dopamine release, making the neurotensin gene an excellent candidate gene for alcohol dependence and for other behaviors that involve reinforcement. METHODS: A total of 639 psychiatrically interviewed Finns were genotyped for proneurotensin 479A>G polymorphism. We used the polymorphism as a marker to study the association between proneurotensin gene and alcohol dependence by comparing 229 unrelated Finnish healthy controls to 134 unrelated alcohol-dependent (DSM-III-R criteria) subjects who were also criminal offenders. In addition, 276 relatives of the alcohol-dependent and control subjects were genotyped. RESULTS: The frequencies of the genotypes in the whole sample (n = 639) were 0.84 for 479A/A, 0.16 for 479A/G, and 0.003 for 479G/G. The frequency of the rarer 479G allele was 0.07 and 0.06 in controls and alcohol-dependent subjects, respectively, and this difference was not statistically significant (chi2 = 0.264, df = 1, p = 0.61, controls vs. alcohol-dependent subjects). CONCLUSIONS: The results of the comparison between psychiatrically interviewed controls and alcoholics from a relatively well defined population indicate that the proneurotensin 479A>G polymorphism is not strongly associated with alcohol dependence. The results do not rule out a role for this gene in the pathogenesis of alcoholism or in differential vulnerability.

Alcoholism↗
PubMed1999

HTR2C Cys23Ser polymorphism in relation to CSF monoamine metabolite concentrations and DSM-III-R psychiatric diagnoses.

BACKGROUND: Heritable variation in brain monoaminergic activity has been suggested to lead to interindividual differences in vulnerability to alcoholism, and many other behavioral disorders. We evaluated if a functional Cys23Ser polymorphism in the 5-HT2C receptor gene, the principal serotonin receptor in the brain, contributes to variation in serotonin, norepinephrine and dopamine activity, as indexed by their major metabolite concentrations in cerebrospinal fluid (CSF). Genotype-monoamine metabolite concentration associations were subsequently correlated to risk for alcoholism. METHODS: The study sample consisted of unrelated Finnish males, including 214 alcoholic, violent offenders and 222 population controls who were interviewed using the Structured Clinical Interview for DSM-III-R, blind rated for psychiatric diagnoses and typed for the HTR2C Cys23Ser polymorphism. CSF concentrations of 5-hydroxyindoleacetic acid (5-HIAA), the major metabolite of serotonin, 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG), the major metabolite of norepinephrine, and homovanillic acid (HVA), the major metabolite of dopamine were available from 195 individuals. RESULTS: The major finding in this study was that HTR2C CysSer23 significantly contributed to CSF MHPG concentrations (p = .012). Higher concentrations of CSF MHPG were observed both in alcoholic violent offenders and population controls with HTR2C Ser23 genotype. Despite the association of Cys23Ser to CSF MHPG, HTR2C genotype was not associated with alcoholism, nor with other psychiatric disorders present in this sample. CONCLUSIONS: We conclude that a functional HTR2C Cys23Ser polymorphism contributes to the interindividual genetic variation of CSF MHPG explaining 3% of the total variance. This finding suggests that 5-HT2C receptors are involved in the regulation of norepinephrine turnover in humans; however, HTR2C Cys23Ser does not appear to contribute to the risk of alcoholism, or its contribution to this complex and heterogenous disorder is too small to be detected by a sample of this size and structure.

Alcoholism↗
PubMed1999

The importance of local-regional radiotherapy with conventional or high-dose chemotherapy in the management of breast cancer patients with > or = 10 positive axillary nodes.

PURPOSE: To assess the effect of local-regional radiotherapy (RT) on the outcome of breast cancer patients with > or = 10 positive axillary lymph nodes who have received modern conventional or high-dose systemic therapy. METHODS AND MATERIALS: A total of 55 women with local-regionally confined breast cancer involving 10 or more axillary nodes were treated between October 1983 and January 1996. Local-regional therapy consisted of modified radical mastectomy in 39 and breast-conserving surgery in 16. Postoperative radiotherapy was given to 44 of the 55 patients. Radiotherapy consisted of tangential fields to the chest wall or intact breast to a median dose of 50.40 Gy. A total of 86% (38 of 44) received regional nodal irradiation as follows: 35 patients received RT to the supraclavicular (SC) region and axillary midplane to a median dose of 50.40 Gy and 46.20 Gy, respectively; 3 patients received RT to the SC region without inclusion of the axilla to a median dose of 50. 40 Gy. All patients received adjuvant standard-dose systemic chemotherapy, 9 of whom received additional intensification chemotherapy followed by autologous bone-marrow transplant (ABMT) or peripheral blood stem-cell transplant (PBSC). Twenty-five patients received adjuvant tamoxifen. RESULTS: With a median follow-up of 30 months, the crude overall survival (OS) and disease-free survival (DFS) for the entire group were 67% and 53%, respectively. On univariate analysis of various clinical, pathological, and therapy-related features, radiotherapy emerged as the most important factor influencing the relapse rate. The addition of RT was significantly associated with an improved DFS (p = 0.003), specifically by prolonging the time to disease progression. The median time to failure was 61 months and 12.5 months with and without RT, respectively. Patients receiving RT also appeared to survive longer; however, the groups were not statistically different (p = 0.10). Analysis of the patterns of failure showed local-regional recurrence (LRR) as the first site of failure in 12 (22%) of 55 and distant failure in 20 (36%) of 55. Univariate results revealed both radiotherapy and tamoxifen to be significantly associated with decreased LRR rates (p = 0.0001 and p = 0.03, respectively); only RT remained independently significant on multivariate analysis. CONCLUSION: Local-regional radiotherapy is an essential component of the management of breast cancer patients with extensive nodal involvement, despite the use of contemporary adjuvant chemotherapy including high-dose regimens with autologous rescue. In addition to the expected improvement in LRR, radiotherapy is also associated with significantly prolonged DFS and a trend for improvement in OS.

Analysis of Variance↗
PubMed1999

Cladistic association analysis of Y chromosome effects on alcohol dependence and related personality traits.

Association between Y chromosome haplotype variation and alcohol dependence and related personality traits was investigated in a large sample of psychiatrically diagnosed Finnish males. Haplotypes were constructed for 359 individuals using alleles at eight loci (seven microsatellite loci and a nucleotide substitution in the DYZ3 alphoid satellite locus). A cladogram linking the 102 observed haplotype configurations was constructed by using parsimony with a single-step mutation model. Then, a series of contingency tables nested according to the cladogram hierarchy were used to test for association between Y haplotype and alcohol dependence. Finally, using only alcohol-dependent subjects, we tested for association between Y haplotype and personality variables postulated to define subtypes of alcoholism-antisocial personality disorder, novelty seeking, harm avoidance, and reward dependence. Significant association with alcohol dependence was observed at three Y haplotype clades, with significance levels of P = 0.002, P = 0.020, and P = 0.010. Within alcohol-dependent subjects, no relationship was revealed between Y haplotype and antisocial personality disorder, novelty seeking, harm avoidance, or reward dependence. These results demonstrate, by using a fully objective association design, that differences among Y chromosomes contribute to variation in vulnerability to alcohol dependence. However, they do not demonstrate an association between Y haplotype and the personality variables thought to underlie the subtypes of alcoholism.

Alcoholism↗
PubMed1999

No coding variant of the tryptophan hydroxylase gene detected in seasonal affective disorder, obsessive-compulsive disorder, anorexia nervosa, and alcoholism.

BACKGROUND: The goal of this study was to evaluate the role of genetic variation in the coding sequence of tryptophan hydroxylase (TPH) in the pathogenesis of several psychiatric diseases in which altered serotonin function has been implicated: bipolar affective disorder (BP), obsessive-compulsive disorder (OCD), anorexia nervosa (AN), seasonal affective disorder (SAD), panic disorder (PD), and alcoholism (Alc). METHODS: Ninety-three percent of the TPH coding sequence was screened by polymerase chain reaction single-strand conformation polymorphism (SSCP) for DNA sequence variations in 128 AN, 88 OCD, 72 SAD, 45 PD, and 36 BP patients and 142 normal volunteers. Also included in the screening were 61 Alc randomly selected from a Finnish alcoholic population in which an association of a TPH intron 7 polymorphism with suicidality was previously observed. Polymorphisms detected by SSCP were characterized by DNA sequencing and by allele-specific restriction enzyme digestion. Genotyping was then performed in 34 Finnish alcoholic suicide attempters. RESULTS: A rare silent mutation was identified in exon 10 and is designated T1095C. The C1095 allele was found in 1 OCD and in 2 AN subjects; all 3 individuals were heterozygous (C1095/T1095) for the variant allele. No association was observed between this TPH T1095C variant with either OCD, AN, Alc, or suicidality. CONCLUSION: These results suggest that the coding sequence of the TPH gene does not contain abundant variants, and may not play a major role in vulnerability to several psychopathologies in which reduced serotonin turnover has been implicated.

Alcoholism↗