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Biomedical subjects

J Benjamin

Publications and source records attributed to J Benjamin.

At least 19 recordsLinked to original sources
PubMed2000

Autonomic dysregulation in panic disorder and in post-traumatic stress disorder: application of power spectrum analysis of heart rate variability at rest and in response to recollection of trauma or panic attacks.

Power spectral analysis (PSA) of heart rate variability (HRV) offers reliable assessment of cardiovascular autonomic responses, providing a 'window' onto the interaction of peripheral sympathetic and parasympathetic tone. Alterations in HRV are associated with various physiological and pathophysiological processes, and may contribute to morbidity and mortality. Previous studies of posttraumatic stress disorder (PTSD) found lower resting HRV in patients compared to controls, suggesting increased sympathetic and decreased parasympathetic tone. This article describes the analysis of HRV at rest and after psychological stress in panic disorder (PD) patients, in an enlarged sample of PTSD patients, and in healthy control subjects. Standardized heart rate (HR) analysis was carried out in 14 PTSD patients, 11 PD patients and 25 matched controls. ECG recordings were made while subjects were resting ('rest 1'), while recalling the trauma implicated in PTSD, or the circumstances of a severe panic attack, as appropriate ('recall'), and again while resting ('rest 2'). Controls were asked to recall a stressful life event during recall. While both patient groups had elevated HR and low frequency (LF) components of HRV at baseline (suggesting increased sympathetic activity), PTSD patients, unlike PD patients and controls, failed to respond to the recall stress with increases in HR and LF. HRV analysis demonstrates significant differences in autonomic regulation of PTSD and PD patients compared to each other and to control subjects. HRV analysis may augment biochemical studies of peripheral measures in these disorders.

Adult↗
PubMed2000

Apoptotic signaling through the beta -adrenergic receptor. A new Gs effector pathway.

Stimulation of beta-adrenergic receptor normally results in signaling by the heterotrimeric G protein G(s), leading to the activation of adenylyl cyclase, production of cAMP, and activation of cAMP-dependent protein kinase (PKA). Here we report that cell death of thymocytes can be induced after stimulation of beta-adrenergic receptor, or by addition of exogenous cAMP. Apoptotic cell death in both cases was observed with the appearance of terminal deoxynucleotidyl transferase-mediated UTP end labeling reactivity and the activation of caspase-3 in S49 T cells. Using thymocytes deficient in either Galpha(s) or PKA, we find that engagement of beta-adrenergic receptors initiated a Galpha(s)-dependent, PKA-independent pathway leading to apoptosis. This alternative pathway involves Src family tyrosine kinase Lck. Furthermore, we show that Lck protein kinase activity can be directly stimulated by purified Galpha(s). Our data reveal a new signaling pathway for Galpha(s), distinct from the classical PKA pathway, that accounts for the apoptotic action of beta-adrenergic receptors.

Animals↗
PubMed2000

Association between the serotonin transporter promoter polymorphism and personality traits in a primarily female population sample.

The serotonin transporter (5-HTT) regulates serotonergic neurotransmission and is thought to influence emotion. A 5-HTT-linked polymorphic region (5-HTTLPR) has two common variants, short (s) and long (l). We previously found population and within-family associations between the lower-expressing s allele and neuroticism, a trait related to anxiety, hostility, and depression, on a standard measure (the NEO Personality Inventory, Revised [NEO-PI-R]) in a primarily male population (n=505), and that the s allele was dominant. We investigated this association in a new sample (n=397, 84% female, primarily sib-pairs). The results robustly replicated the 5-HTTLPR neuroticism association, and the dominance of the s allele. Combined data from the two studies (n=902) showed a highly significant association between the s allele and higher NEO Neuroticism both across individuals and within families. Association between genotype and a related measure, Anxiety on the 16PF inventory, was replicated in the new population and within families in the combined sample. Association to another trait, estimated TPQ Harm Avoidance, was not replicated in the new sample but found only within the combined sibship group. Another association found in our original study, between the s allele and lower scores on NEO-PI-R Agreeableness, was also replicated and was more robust in the current and the combined samples. Associations between the functional 5-HTTLPR polymorphism were similar in women and men. These results help to define specific personality features reproducibly associated with 5-HTTLPR genotype. Such associations were strongest for traits defined by the NEO, enhancing the attractiveness of the five-factor personality model in genetic research on complex behavioral dimensions. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:202-216, 2000. Published 2000 Wiley-Liss, Inc.

Adolescent↗
PubMed2000

Necrolytic acral erythema associated with hepatitis C: effective treatment with interferon alfa and zinc.

BACKGROUND: Necrolytic acral erythema is a recently described necrolytic erythema that is unique in its exclusive acral location and strong association with hepatitis C. OBSERVATION: We report the first case of necrolytic acral erythema in the United States. The patient is a 43-year-old black woman who presented with a 4-year history of tender, flaccid blisters localized to the dorsal aspect of her feet. Serum zinc and glucagon levels were normal. Serum antibodies were positive for hepatitis C, and a liver biopsy specimen showed chronic hepatitis. She was successfully treated with interferon alfa-2b and zinc. We review all previously reported cases. CONCLUSIONS: Necrolytic acral erythema is a distinct entity. In a review of the literature, most patients were between 35 and 55 years of age, although 1 patient was 12 years old. Five of 8 patients were female. Four of 7 patients described previously were treated with variable success using oral zinc sulfate and amino acids, whereas 2 were successfully treated with interferon alfa. All patients were infected with hepatitis C. Necrolytic acral erythema appears to be a skin disorder linked to infection with hepatitis C virus that responds to treatment with interferon alfa and oral zinc.

Acrodermatitis↗
PubMed2000

Double-blind placebo-controlled pilot study of paroxetine for specific phobia.

Drugs are not recognized as a standard treatment for specific phobia, despite its apparent similarities to other kinds of phobia. Reluctance on the part of patients and clinicians to see the disorder as more than normal anxiety may explain the apparent resistance to pharmacotherapy. Eleven patients fulfilling DSM-IV criteria for specific phobia were randomized to 4 weeks of double-blind treatment with placebo or paroxetine up to 20 mg/day. They were assessed weekly with the Fear Questionnaire and the Hamilton Rating Scale for Anxiety. Paroxetine showed significant superiority in reducing all measures (ANCOVA for reductions in phobia scores F=7.9, P=0.02). One out of six patients responded to placebo, compared to three out of five patients on paroxetine. This new therapeutic option (i.e. drug treatment) for specific phobia deserves further examination in a larger trial.

Antidepressive Agents, Second-Generation↗
PubMed2000

White blood cell counts and differential in synovial fluid of aseptically failed total knee arthroplasty.

A cell count and differential was obtained on synovial fluid samples from 79 total knee arthroplasties undergoing revision for aseptic failure over a 5-year period. The mean white blood cell count (WBC) was 782/mL (range, 11-7,200/mL). The mean percentage of monocyte cells was 87%, and the mean polymorphonuclear leukocyte (PML) cell count was 13%. Eight patients (10.4%) had leukocyte cell counts >2,000. Five knees in 4 patients with rheumatoid arthritis had PML counts >50%. There was a single postoperative infection. In patients with osteoarthritis as a primary diagnosis, a synovial WBC of <2,000 and a differential with <50% PMLs had a 98% negative predictive value for the absence of infection. Key words: synovial fluid, cell count and differential, failed total knee arthroplasty, revision total knee arthroplasty.

Adult↗
PubMed2000

Association between tridimensional personality questionnaire (TPQ) traits and three functional polymorphisms: dopamine receptor D4 (DRD4), serotonin transporter promoter region (5-HTTLPR) and catechol O-methyltransferase (COMT).

Dopamine D4 receptor (DRD4), serotonin transporter promoter regulatory region (5-HTTLPR) and catechol O-methyltransferase (COMT) polymorphisms were examined for association with TPQ personality factors in 455 subjects. Significant interactions were observed by multivariate analysis, (COMT x 5-HTTLPR: Hotelling's Trace = 2.3, P = 0.02) and by subsequent univariate 3-way ANOVA when Novelty Seeking (NS) was the dependent variable: 5-HTTLPR x D4DR (F = 6.18, P = 0.03) and COMT x 5-HTTLPR (F = 4.42, P = 0.03). In the absence of the short 5-HTTLPR allele and in the presence of the high enzyme activity COMT val/val genotype, NS scores are higher in the presence of the DRD4 seven-repeat allele. The effect of these three polymorphisms on NS was also examined using a within-families design. Siblings who shared identical genotype groups for all three polymorphisms (COMT, DRD4 and 5-HTTLPR) had significantly correlated NS scores (intraclass coefficient = 0.39, F = 2.26, P = 0.008, n = 49) whereas sibs with dissimilar genotypes in at least one polymorphism showed no significant correlation for NS scores (intraclass coefficient = 0.177, F = 1.43, P = 0.09, n = 110). Similar interactions were also observed between these three polymorphisms and Novelty Seeking when the 150 independently recruited and non-related subjects were analyzed. The current results are consistent with two earlier reports in which we demonstrated an interaction between the 5-HTTLPR and DRD4 polymorphisms in 2-week-old neonates, in the same children assessed again at 2 months of age and in adults. Molecular Psychiatry (2000) 5, 96-100.

Adolescent↗
PubMed2000

Association and linkage of anxiety-related traits with a functional polymorphism of the serotonin transporter gene regulatory region in Israeli sibling pairs.

A functional polymorphism in the regulatory region of the serotonin transporter gene (5-HTTLPR) has been reported to be both associated and linked to anxiety-related personality measures, although other studies have not replicated these findings. The current study examines both association and linkage of the gene to two major anxiety-related personality measures, the harm avoidance scale on the Tridimensional Personality Questionnaire and the neuroticism scale of the NEO-PI-R, in a sample of 148 Israeli subjects comprising 74 same-sex sibling pairs. We replicated the reported association between the short allele and higher scores on the TPQ harm avoidance scale (P = 0.03), including the subscale of shyness (P = 0.02), and also found association in the same direction between the short allele and the NEO-PI-R neuroticism subscales of anxiety (P = 0.03) and depression (P = 0.04). Sib-pair linkage analysis, using the regression method, further supported a role of the 5-HTTLPR in anxiety-related personality traits.

Adolescent↗
PubMed2000

An interaction between the catechol O-methyltransferase and serotonin transporter promoter region polymorphisms contributes to tridimensional personality questionnaire persistence scores in normal subjects.

Persistence (RD2) is a subscale of the reward dependence trait, one of the three major personality factors assessed by the Tridimensional Personality Questionnaire (TPQ). Subjects with high RD2 scores are characterized as industrious, hard-working, ambitious, perfectionistic. TPQ scores were examined in 577 normal subjects inventoried for two common genetic polymorphisms, the catechol O-methyltransferase (COMT) valine to methionine (val to met) amino acid substitution that determines high and low enzyme activity, and the serotonin transporter promoter region 44 bp deletion (5-HTTLPR) linked in some studies to harm avoidance or neuroticism. When TPQ RD2 scores are grouped by COMT and 5-HTTLPR polymorphisms and analyzed by two-way ANOVA, significant main effects for COMT (F = 2. 98, p = 0.05) and 5-HTTLPR (F = 4.27, p = 0.04) and a significant interaction COMT x 5-HTTLPR (F = 6.18, p = 0.002) are observed. In the presence of COMT homozygosity (val/val or met/met genotypes), the presence of the short 5-HTTLPR allele raises RD2 scores. The effect of these two polymorphisms on RD2 was also examined using a within-families design. Siblings in our data set who shared identical genotypes had significantly correlated RD2 scores (intraclass coefficient = 0.34, F = 2.03, p = 0.002, n = 67), whereas sibs with dissimilar genotypes in at least one polymorphism showed no significant correlation for RD2 scores (intraclass coefficient = 0.105, F = 1.23, p = 0.16, n = 92).

Adolescent↗
PubMed1999

Expression of the GDNF receptors ret and GFRalpha1 in the developing avian enteric nervous system.

The formation of the enteric nervous system (ENS) from neural crest-derived cell precursors requires the growth factor glial cell line-derived neurotrophic factor (GDNF) and the receptors Ret and GDNF family receptor alpha 1 (GFRalpha1). We investigated the location(s), the timing, and the extent to which these GDNF receptors appear in the population of crest-derived precursors that form the avian ENS using immunohistochemistry and in situ hybridization. Sections and whole mounts of embryonic chick gastrointestinal tract were costained with antibodies to the receptors and to HNK-1, a marker for crest-derived cells. Neural crest-derived precursors migrate through the primitive esophagus to colonize the gizzard where an extensive cellular network forms. Ret-immunoreactivity (ir) was found in a network of cells in the gizzard at embryonic day (E)3.5. As development proceeded, Ret-immunoreactive cells appeared at progressively more caudal positions and were present in the colon at E7.5. Costaining with Ret and HNK-1 was performed to determine the number of Ret-immunoreactive cells in the crest-derived population. Ret appeared in some HNK-1 cells in the esophagus and gizzard at embryonic day (E)3.5. During development, the number of crest cells with Ret increased in the ganglia of the gizzard and small intestine. GFRalpha1-ir was also found in HNK-1 cells in the esophagus at E3.5 but did not appear in the gizzard until E4.5. Surprisingly, the colonizing vanguard of crest-derived cells lacked both Ret- and GFRalpha-ir. Between E4.5 and E6.5, the fraction of HNK-1-positive cells expressing GFRalpha1 increased considerably in the foregut. Ret and GFRalpha1 were coexpressed in many cells at E6.5, and the number of such cells increased as development progressed. In the adult, GFRalpha1 and Ret were found in the neuropil of enteric ganglia. We conclude that the population of cells expressing the receptors increases during development and persists in the adult, findings that support a neurotrophic role for GDNF in the formation and maintenance of the avian ENS.

Age Factors↗
PubMed1999

A genetic association for cigarette smoking behavior.

Dopaminergic genes are likely candidates for heritable influences on cigarette smoking. In an accompanying article, Lerman et al. (1999) report associations between allele 9 of a dopamine transporter gene polymorphism (SLC6A3-9) and lack of smoking, late initiation of smoking, and length of quitting attempts. The present investigation extended their study by examining both smoking behavior and personality traits in a diverse population of nonsmokers, current smokers, and former smokers (N = 1,107). A significant association between SLC6A3-9 and smoking status was confirmed and was due to an effect on cessation rather than initiation. The SLC6A3-9 polymorphism was also associated with low scores for novelty seeking, which was the most significant personality correlate of smoking cessation. It is hypothesized that individuals carrying the SLC6A3-9 polymorphism have altered dopamine transmission, which reduces their need for novelty and reward by external stimuli, including cigarettes.

Adult↗
PubMed1999

Increasing recruitment contacts between generalist residents at the Medical College of Georgia and rural and underserved communities.

To increase the number of residents choosing to practice in rural and underserved areas, the Medical College of Georgia in 1994 created the Office of Recruitment and Retention (ORR) for generalist physicians as part of its participation in The Robert Wood Johnson Foundation's Generalist Physician Initiative. Its major purpose is to increase the contact between generalist residents and practice opportunities, especially those in rural and underserved areas. The office has helped residents better understand the resources available in rural settings and has helped these communities better understand the needs of graduates in generalist residency programs. It became a point of contact for residents and communities. It also organized on-campus "practice opportunity fairs" that permitted community representatives to meet formally with generalist residents to provide information on practice opportunities and community resources. The office organized practice management sessions and provided legal consultation to residents desiring to enter private practice in rural settings. This program has already been instrumental in furthering contact between generalist residents and the rural communities they selected as clinical practice sites during training. Although it is too early to know the impact of these activities, communities increasingly use the office to recruit generalist physicians, and residents use it to identify appropriate practice sites.

Career Choice↗
PubMed1999

Enhancement of CO2-induced anxiety in healthy volunteers with the serotonin antagonist metergoline.

OBJECTIVE: The mechanism of action of CO2-induced anxiety is unknown and has been little studied. The authors studied healthy volunteers for the possible influence of serotonin (5-HT) on CO2-induced anxiety. METHOD: Fourteen healthy volunteers received two vital capacity inhalations each of 35% CO2 and of air, preceded once by placebo and once by the 5-HT antagonist metergoline in a double-blind, randomized crossover design. RESULTS: Mean National Institute of Mental Health self-rating anxiety subscale scores increased nonsignificantly after CO2 inhalation; this effect was significantly enhanced by the administration of metergoline. CONCLUSIONS: The authors hypothesize that 5-HT may inhibit CO2-induced anxiety, a function that is lessened by metergoline.

Administration, Inhalation↗
PubMed1999

The Functional Assessment Measure (FIM + FAM) as part of the hospital discharge summary after brain injury rehabilitation.

OBJECTIVE: To assess the value of providing Functional Assessment Measure (FIM + FAM) data as part of the hospital discharge information after brain injury rehabilitation. DESIGN: Postal survey of general practitioners (GPs) and consultants. SUBJECTS: Consecutive discharges (n = 117) from an early brain injury rehabilitation unit over one year. RESULTS: Response rates were 81% from GPs and 54% from consultants. Eighty-four (89%) of GPs and 57 (82%) of consultants rated the information as useful; 87 (92%) and 51 (84%) respectively described the accompanying notes as easy to understand. CONCLUSIONS: The incorporation of FIM + FAM data in discharge summaries is worthwhile but the utility of this practice is still to be established.

Activities of Daily Living↗
PubMed1998

Delayed obsessive-compulsive disorder symptom exacerbation after a single dose of a serotonin antagonist in fluoxetine-treated but not untreated patients.

Enhanced serotonergic transmission may underlie therapeutic effects of serotonin reuptake inhibitors in obsessive-compulsive disorder. However, such treatment may decrease serotonin receptor responsivity. We investigated whether the serotonin antagonist metergoline would exacerbate or further improve systems in fluoxetine-responsive patients. Pilot results suggested open metergoline produced delayed symptom worsening in fluoxetine-treated patients. Fourteen patients continuing fluoxetine received metergoline and placebo (double-blind, randomized). Symptom ratings continued for 1 week afterwards. Ten unmedicated patients underwent the same procedures. Symptoms improved 4 h after both metergoline and placebo. The day after metergoline but not placebo, fluoxetine-treated patients had significantly increased anxiety, obsessions and compulsions, abating over several days. Depression was unchanged. Metergoline had no similar delayed effects in unmedicated patients. Metergoline levels were higher in fluoxetine-treated patients. These results, consistent with less conclusive earlier findings, suggest that prolonged changes in brain serotonin function underlie symptom re-emergence following administration of metergoline to fluoxetine-treated patients with obsessive-compulsive disorder.

Adult↗