Showing papers by "Medical University of South Carolina published in 1988"

Alprazolam in Panic Disorder and Agoraphobia: Results From a Multicenter Trial: I. Efficacy in Short-term Treatment

Abstract: • Following promising preliminary evidence, the benzodiazepine-derivative alprazolam was studied in a large, placebocontrolled, eight-week, flexible-dose trial in patients with agoraphobia with panic attacks and panic disorder. Of 526 patients, 481 completed three weeks of treatment; however, significantly more placebo (102/234) than alprazolam (21/247) recipients subsequently dropped out of the trial, primarily citing ineffectiveness (of placebo) as the reason. Alprazolam was found to be effective and well tolerated. There were significant alprazolam-placebo differences in improvement for (1) spontaneous and situational panic attacks, (2) phobic fears, (3) avoidance behavior, (4) anxiety, and (5) secondary disability, all significant by the end of week 1. At the primary comparison point (week 4), 82% of the patients receiving alprazolam were rated moderately improved or better vs 43% of the placebo group. At that point, 50% of the alprazolam recipients vs 28% of placebo recipients were free of panic attacks.

Low circulating vitamin D in obesity.

Abstract: Previous studies demonstrated decreases in serum 25-hydroxyvitamin D in obese subjects. Studies were carried out to determine whether serum vitamin D is low in obesity. The results indicate that serum vitamin D is significantly lower in obese than in nonobese individuals and may contribute to lower serum 25-hydroxyvitamin D in obesity.

Granulocyte colony-stimulating factor enhances interleukin 3-dependent proliferation of multipotential hemopoietic progenitors.

Abstract: In cultures of spleen cells from normal mice, recombinant human granulocyte colony-stimulating factor (G-CSF) supported the formation of multipotential blast cell colonies. Serial replating of the blast cell colonies in the presence of G-CSF, however, failed to demonstrate any direct effect of G-CSF on murine multipotential progenitors. We therefore examined the effects of G-CSF in combination with murine interleukin 3 on proliferation of murine blast cell colony-forming cells. The time course of total colony formation and multilineage colony formation by spleen cells harvested from mice 4 days after injection of 5-fluorouracil at 150 mg/kg was significantly shortened in cultures containing both factors in contrast with cultures supported by either factor alone. Serial observations of individual multipotential blast cell colonies (mapping) revealed that blast cell colonies emerged at random time intervals in the presence of interleukin 3 or G-CSF. The appearance of blast cell colonies, however, was significantly hastened in cultures containing both factors relative to cultures grown with either factor. In cultures of day-2 post-5-fluorouracil bone marrow cells, G-CSF in concentrations as low as 1 unit/ml revealed synergism with interleukin 3 in supporting the proliferation of multipotential progenitors. This synergistic activity may explain the previous in vivo studies suggesting the effects of G-CSF on apparent multipotential stem cells.

The effects of race and body habitus on bone mineral density of the radius, hip, and spine in premenopausal women.

Abstract: The incidence of osteoporosis and fractures of the hip are diminished in blacks and in obese subjects. To determine whether bone mass is increased in them, bone mineral density (BMD) of the lumbar spine, trochanter, and femoral neck was measured by dual photon absorptiometry in 89 nonobese white and 51 nonobese black women, all of whom were within 30% of their ideal body weight and between the ages of 20 and 50 yr, and in 21 obese white women and 21 obese black women, all of whom weighed 30% on more than their ideal body weight and were in the same age range. The BMD of the mid radius was also measured by single photon absorptiometry. The mean BMD of the mid radius was higher in black than in white nonobese women [0.73 +/- 0.01 (+/- SE) vs. 0.70 +/- 0.01 g/cm2; P less than 0.01] and was not altered by obesity in either group. The mean BMD was higher in the black than in the white nonobese women at the lumbar spine (1.23 +/- 0.02 vs. 1.16 +/- 0.01 g/cm2; P less than 0.01), trochanter (0.78 +/- 0.02 vs. 0.72 +/- 0.01 g/cm2; P less than 0.01) and femoral neck (0.96 +/- 0.02 vs 0.90 +/- 0.02 g/cm2; P less than 0.02). The mean body weight was higher in the obese than in the nonobese white women (92 +/- 2 vs. 61 +/- 1 kg; P less than 0.001) and black women (94 +/- 3 vs. 63 +/- 1 kg; P less than 0.001). The mean BMD was higher in the obese than in the nonobese white women at the lumbar spine (1.24 +/- 0.03 g/cm2; P less than 0.05), trochanter (0.89 +/- 0.04; P less than 0.001), and femoral neck (0.99 +/- 0.03; P less than 0.01) and was higher in the obese than in the nonobese black women at the lumbar spine (1.33 +/- 0.03 g/cm2; P less tham 0.01), trochanter (0.88 +/- 0.04 g/cm2; P less than 0.05), and femoral neck (1.04 +/- 0.03 g/cm2; P less than 0.05). Multivariate regression analysis revealed positive correlations between body weight and BMD at each of the 3 weight-bearing sites, but not at the mid radius, in both the black women and white women.(ABSTRACT TRUNCATED AT 400 WORDS)

Analysis in serum-free culture of the targets of recombinant human hemopoietic growth factors: interleukin 3 and granulocyte/macrophage-colony-stimulating factor are specific for early developmental stages

Abstract: We have used a serum-free culture system for enriched human hemopoietic progenitors to analyze the developmental stages and lineage specificities of the human hemopoietic colony-stimulating factors. None of the individual factors alone efficiently supported hemopoietic colony formation. Neither interleukin 3 nor granulocyte/macrophage-colony-stimulating factor alone or in combination effectively supported proliferation of progenitor cells. However, when combined with granulocyte-colony-stimulating factor or erythropoietin, these factors yielded neutrophil colonies or erythroid bursts, respectively. Serial observations of interleukin 3-supported cultures revealed sequential emergence and subsequent degeneration of clusters of cells. These observations suggest that the primary targets of interleukin 3 and granulocyte/macrophage-colony-stimulating factor are multipotent progenitors at the early stages of development rather than cells in the terminal process of maturation.

Swine as models in experimental surgery.

Abstract: The use of swine in surgical research has undergone a dramatic increase in recent years, due to decreasing availability of dogs as surgical models and a renewed interest in the porcine model based on anatomic and physiologic characteristics. This article reviews the issues involved in selection of swine as experimental surgical subjects including procurement considerations, anesthetic selection, housing methods, and anatomic and physiologic characteristics.

Pleural fluid pH in malignant effusions. Diagnostic, prognostic, and therapeutic implications.

Abstract: STUDY OBJECTIVE To determine whether the measurement of pleural fluid pH in malignant effusions has diagnostic use, predicts survival, and has therapeutic implications. DESIGN A prospective comparison of cytologic examinations and pleural biopsy results, survival, and response to chemical pleurodesis with tetracycline in patients with normal-pH (7.30 or greater) and low-pH (less than 7.30) malignant pleural effusions. SETTING Academic medical center, university referral hospital, city hospital, and Veterans Administration hospital. PATIENTS Sixty patients with malignant pleural effusions, proven at either initial thoracentesis by cytologic examination or within 4 months of initial thoracentesis by repeat thoracentesis, thoracotomy, or autopsy, were followed until death. INTERVENTION Twenty-one patients, 12 with normal pleural fluid pH and 9 with low pleural fluid pH, were treated with tube thoracostomy and intrapleural tetracycline for symptomatic, recurrent pleural effusions. MAIN RESULTS The 20 patients with low-pH malignant effusions had a significantly greater positivity on initial pleural fluid cytologic evaluation, a shorter mean survival, and a poorer response to tetracycline pleurodesis compared with 40 patients with normal-pH malignant effusions. CONCLUSIONS Determination of pleural fluid pH in malignant effusions provides a rational approach to further diagnostic testing, prognostic information, and a rationale for palliative treatment.

Peroxisomal lignoceroyl-CoA ligase deficiency in childhood adrenoleukodystrophy and adrenomyeloneuropathy

Abstract: We previously reported that in childhood adrenoleukodystrophy (C-ALD) and adrenomyeloneuropathy (AMN), the peroxisomal beta-oxidation system for very long chain (greater than C22) fatty acids is defective. To further define the defect in these two forms of X chromosome-linked ALD, we examined the oxidation of [1-14C]lignoceric acid (n-tetracosanoic acid, C24:0) and [1-14C]lignoceroyl-CoA (substrates for the first and second steps of beta-oxidation, respectively). The oxidation rates of lignoceric acid in C-ALD and AMN were 43% and 36% of control values, respectively, whereas the oxidation rate of lignoceroyl-CoA was 109% (C-ALD) and 106% (AMN) of control values, respectively. On the other hand, the oxidation rates of palmitic acid (n-hexadecanoic acid) and palmitoyl-CoA in C-ALD and AMN were similar to the control values. These results suggest that lignoceroyl-CoA ligase activity may be impaired in C-ALD and AMN. To identify the specific enzymatic deficiency and its subcellular localization in C-ALD and AMN, we established a modified procedure for the subcellular fractionation of cultured skin fibroblasts. Determination of acyl-CoA ligase activities provided direct evidence that lignoceroyl-CoA ligase is deficient in peroxisomes while it is normal in mitochondrial and microsomes. Moreover, the normal oxidation of lignoceroyl-CoA as compared with the deficient oxidation of lignoceric acid in isolated peroxisomes also supports the conclusion that peroxisomal lignoceroyl-CoA ligase is impaired in both C-ALD and AMN. Palmitoyl-Coa ligase activity was found to be normal in peroxisomes as well as in mitochondria and microsomes. This normal peroxisomal palmitoyl-CoA ligase activity as compared with the deficient activity of lignoceroyl-CoA ligase in C-ALD and AMN suggests the presence of two separate acyl-CoA ligases for palmitic and lignoceric acids in peroxisomes. These data clearly demonstrate that the pathognomonic accumulation of very long chain fatty acids in C-ALD and AMN is due to a deficiency of peroxisomal very long chain (lignoceric acid) acyl-CoA ligase.

The therapeutic role of a structured life review process in homebound elderly subjects.

Abstract: This study examined the therapeutic role of a structured life review process in a randomly selected group of 60 homebound elderly subjects. Subjects were placed in three groups and tested on four dependent variables at the beginning and end of an 8-week period. These variables were life satisfaction, psychological well-being, depression, and activities of daily living (ADL). One group, the experimental group, received the treatment of life review process; another, the control group, received a friendly visit; and the third, the no-treatment group, received pretests and posttests only. Two dependent variables, life satisfaction, as operationalized by the Life Satisfaction Index A (LSIA), and psychological well-being, as operationalized by the Affect-Balance Scale (ABS), were significant in the experimental group when tested statistically through analysis of covariance (ANCOVA). These results suggest that a structured process of life review can serve as a therapeutic intervention for homebound elderly persons.

Low density lipoprotein metabolism by human macrophages activated with low density lipoprotein immune complexes. A possible mechanism of foam cell formation.

Abstract: Human macrophages play a key role in atherogenesis and are believed to be the progenitors of the cholesteryl ester (CE)-laden foam cells present in early atherosclerotic lesions. Several mechanisms by which macrophages accumulate CE have been recently described. One involves a perturbation in LDL metabolism subsequent to macrophage activation. Thus, we decided to study the effect of macrophage activation by immune complexes on N-LDL metabolism. Initially, LDL-containing immune complexes (LDL-IC) were chosen, since increased plasma levels of these IC have been reported in patients with coronary heart disease. Human macrophages stimulated for 22 h with LDL-IC (250 micrograms/ml) and incubated afterwards for 20 h with 10 micrograms/ml 125I-N-LDL showed a six- and fourfold increase in the accumulation and degradation, respectively, of 125I-N-LDL over the values observed in nonstimulated cells. Scatchard analysis of 125I-N-LDL-specific binding suggests an increase (20-fold) in the number of LDL receptors in macrophages stimulated with LDL-IC. We studied other immune complexes varying in size and antigen composition. Some of the IC were able to stimulate, although to a lesser degree, the uptake of N-LDL by macrophages. Lipoprotein IC are more efficient and have the greatest capacity to increase N-LDL uptake and CE accumulation. We conclude that human macrophage activation by LDL-IC leads to an increase in LDL receptor activity and promotes in vitro foam cell formation.

Rapid assessment of islet viability with acridine orange and propidium iodide.

Abstract: A simple, rapid method for estimating the viability of isolated islets of Langerhans with fluorescent dyes is described. Low concentrations of acridine orange and propidium iodide (AO/PI) were used to visualize living and dead islet cells simultaneously. AO/PI-stained islets can be divided into three distinct groups. Group A islets fluoresce green, contain insulin, and have normal ultrastructure; group C islets fluoresce primarily red, contain little or no insulin, and have cells with disrupted cellular membranes. Group B islets fluoresce red, green, and yellow. The yellow color is due to the addition of two primary colors from the superimposed red and green fluorescing cells. In this assay, the interpretation that red islet cells are dead and green islet cells are alive was confirmed by sequentially staining single islet cells with AO/PI and trypan blue. The observation that red islets are dead was confirmed by heat-killing, enzymatically damaging, treating with ethanol, or depriving islets of nutrients and observing the red fluorescence. This assay should be useful in studies where the assessment of islet viability is essential.

Epithelial restitution in the gastrointestinal tract.

Abstract: Injury to the gastrointestinal mucosa can be divided into two types: (a) deep injury involving extensive hemorrhage and large areas of tissue necrosis, and (b) superficial injury confined to the upper regions of the mucosa and not involving hemorrhagic lesions. Mucosal repair differs according to the severity of the damage. Repair of deep injury takes weeks because large regions of the mucosa must be replaced with new tissue, a process involving mitosis. Superficial injury is initially repaired rapidly over hours by epithelial restitution that does not involve mitosis but proceeds in the following sequence of events: First, the damaged surface epithelial cells are shed and form a layer that protects the restituting mucosa. Then the viable epithelial cells that remain attached to the mucosa at the margin of the wound become flattened and rapidly migrate over the denuded basal lamina. The superficial epithelium is re-established when migrating cells touch, form new tight junctions, and repolarize their organelles. This rapid protective mechanism, called restitution, has recently been documented in the stomach, duodenum, colon, and rectum. The cellular mechanisms, speed of migration, recovery of transmucosal electrical potential difference, and specific peculiarities of rapid epithelial restitution in the various regions of the gastrointestinal tract are reviewed here.

Current Psychological Functioning of Child Sexual Assault Survivors A Community Study

Abstract: We interviewed a community sample of 391 women to obtain a thorough history of lifetime victimization experiences, including experiences such as childhood and adult sexual assault, aggravated assault, robbery, and burglary. In order to assess current psychological functioning, participants were administered the Derogatis Symptom Checklist-90 Revised, the Modified Fear Survey, and the Impact of Event scale. Results indicated that childhood sexual abuse victims could be distinguished from nonvictims by a pattern of elevated anxiety, heightened interpersonal sensitivity, increased anger problems, more paranoid ideation, and increased obsessive-compulsive symptoms. The age at which the sexual assault took place was found to be related to current adult functioning, with women assaulted in adolescence displaying more elevations in hostility, interpersonal sensitivity, obsessive-compulsive symptoms, anxiety, and paranoid ideation than nonvictims. Women sexually abused in early childhood displayed only elevated a...

Alprazolam in the treatment of social phobia.

Abstract: Pharmacological treatment of social phobia has not been extensively studied. Recent reports suggest that social phobia may be treated with monoamine oxidase inhibitors, tricyclic antidepressants, beta-blockers, or clonidine. The authors describe four patients with social phobia who responded moderately to markedly well when treated with the triazolobenzodiazepine alprazolam. Patients with social phobia and patients with agoraphobia with panic attacks differ in the focus of anxiety, sensitivity to lactate infusion, and the pattern of symptoms during anxiety episodes. However, there is significant overlap in the clinical features of these two patient groups. The preliminary finding that several types of pharmacological agents that are effective in treating agoraphobia with panic attacks may also be effective in treating social phobia suggests that the two disorders may share some common pathophysiology.

Home-based behavioral-systems family therapy with disadvantaged juvenile delinquents.

Abstract: A replication of Alexander's behavioral-systems family therapy model was attempted for lower socioeconomic status juvenile offenders, most of whom had multiple offenses, including misdemeanors and felonies. Twenty-seven male and female delinquents who had either recently been placed out of the home or for whom placement was imminent were court referred to in-home time-unlimited family therapy (mean sessions=16). A comparison group of 27 lower risk delinquents received only probation. Outcome was measured by the number and severity of offenses during a 2½-year period following group assignment. The delinquents receiving the family therapy had a recidivism rate of 11% vs. 67% for the comparison group. Sex differences are presented, as well as differences between Alexander's studies and the present one which may account for the improved outcomes with more difficult families.

Postbiopsy pneumothorax: estimating the risk by chest radiography and pulmonary function tests

Abstract: Pulmonary function tests and chest radiographs of 160 patients who had had percutaneous needle biopsy of lung lesions were reviewed to determine the value of these examinations in estimating the risk of postbiopsy pneumothorax. Chest radiographs were evaluated subjectively for changes of obstructive and restrictive airway disease and for size and depth of lesion. Pulmonary function tests, consisting of simple spirometry (forced vital capacity, percentage of predicted forced vital capacity, forced expiratory volume in 1 sec, percentage of predicted forced expiratory volume in 1 sec, and [forced expiratory in 1 sec/forced vital capacity] X 100), and the pulmonologist's interpretation were evaluated. Pneumothorax developed in 46% (31/67) of patients who had obstructive airway disease according to the results of pulmonary function tests and in 42% (34/81) of those who had obstructive airway disease according to changes on chest radiographs, compared with 19% (10/53) and 25% (17/67) of those who had normal pul...

A suppressor T-lymphocyte cell line for autoimmune encephalomyelitis

Abstract: Experimental allergic encephalomyelitis (EAE) is a model for the in vitro and in vivo study of T-cell activation. It is an autoimmune disease mediated by T lymphocytes of the helper T-cell (Th) subset1,2. After sensitization to guinea-pig myelin basic protein in complete Freund's adjuvant, Lewis rats develop an autoimmune response to central nervous system (CNS) myelin basic protein, manifested clinically as paralysis and histologically by a perivas-cular mononuclear cell infiltrate of the CNS parenchyma. Suppressor cell regulation of EAE has long been suspected because Lewis rats, which spontaneously recover from active disease, are resistant to reinduction of active EAE, even though effector T-cell lines can be rescued from these recovered rats3. Using cyclosporin A, an immunosuppressive agent believed to inhibit Th cell function, suppressor T-cell (Ts) lines have now been generated from recovered Lewis rats. These Ts cells, when admixed with guinea pig myelin basic protein-specific Th cells, will prevent the adoptive transfer of EAE. The Ts cells appear to be CD4+, which explains previous observations that CD8+ lymphocytes are not important in the recovery of EAE in the rat. This is the first direct demonstration of Ts-cell regulation of EAE.

Penetrating intracranial wood wounds: clinical limitations of computerized tomography

Abstract: The case history of a patient with a periorbital penetrating wooden foreign body is presented. The computerized tomography (CT) densities of several different sources of wood were compared using an experimental model. The clinical usefulness and practical limitations of CT in the evaluation of intracranial foreign bodies is discussed, and the management of this type of injury is reviewed.

Role of dapsone hydroxylamine in dapsone-induced hemolytic anemia.

Abstract: The hemolytic anemia which frequently accompanies treatment of individuals with dapsone and other arylamine drugs is believed to be caused not by the parent drugs per se, but rather by metabolites which are formed during the clearance of the drugs in vivo. To determine whether the N-hydroxyarylamine metabolites of dapsone could be responsible for dapsone-induced hemolysis, dapsone, dapsone hydroxylamine (DDS-NOH) and monoacetyldapsone hydroxylamine were administered to rats which had previously received 51Cr-labeled red blood cells. All three compounds caused an increase in the rate of disappearance of radioactivity from the blood as compared with saline-treated controls. In parallel in vitro studies, incubation of 51Cr-labeled red blood cells with DDS-NOH, but not dapsone or monoacetyldapsone, induced a decrease in survival time of the radiolabeled cells when they were reintroduced into isologous rats. The disappearance of radioactivity from the blood was matched by its selective uptake into the spleen. The amount of damage (as measured by decreased red cell survival in vivo) was proportional to both concentration and time of exposure to DDS-NOH. The area under the blood concentration vs. time curve for total arylhydroxylamines (DDS-NOH + monacetyldapsone hydroxylamine) in rats given a hemotoxic dose of dapsone was similar to that of rats given an equitoxic dose of DDS-NOH. Collectively, these data indicate that the hydroxylamine metabolites of dapsone are direct acting hemolytic agents that are formed from dapsone in sufficient amounts to account for their being the sole mediators of dapsone-induced hemolytic anemia in the rat.