Showing papers by "Virginia Commonwealth University published in 1992"

Early enteral feeding, compared with parenteral, reduces postoperative septic complications. The results of a meta-analysis.

Abstract: This two-part meta-analysis combined data from eight prospective randomized trials designed to compare the nutritional efficacy of early enteral (TEN) and parenteral (TPN) nutrition in high-risk surgical patients. The combined data gave sufficient patient numbers (TEN, n = 118; TPN, n = 112) to adequately address whether route of substrate delivery affected septic complication incidence. Phase I (dropouts excluded) meta-analysis confirmed data homogeneity across study sites, that TEN and TPN groups were comparable, and that significantly fewer TEN patients experienced septic complications (TEN, 18%; TPN, 35%; p = 0.01). Phase II meta-analysis, an intent-to-treat analysis (dropouts included), confirmed that fewer TEN patients developed septic complications. Further breakdown by patient type showed that all trauma and blunt trauma subgroups had the most significant reduction in septic complications when fed enterally. In conclusion, this meta-analysis attests to the feasibility of early postoperative TEN in high-risk surgical patients and that these patients have reduced septic morbidity rates compared with those administered TPN.

Major depression and generalized anxiety disorder. Same genes, (partly) different environments?

Abstract: • Bivariate twin analysis can determine the extent to which two disorders share common genetic, familial environmental, or individual-specific environmental risk factors. We applied this method to lifetime diagnoses of major depression and generalized anxiety disorder as assessed at personal interview in a population-based sample of 1033 pairs of female same-sex twins. Three definitions of generalized anxiety disorder were used that varied in minimum duration (1 vs 6 months) and in the presence or absence of a diagnostic hierarchy. For all definitions of generalized anxiety disorder, the best-fitting twin model was the same. Familial environment played no role in the etiology of either condition. Genetic factors were important for both major depression and generalized anxiety disorder and were completely shared between the two disorders. A modest proportion of the nonfamilial environmental risk factors were shared between major depression and generalized anxiety disorder. Within the limits of our statistical power, our findings suggest that in women, the liability to major depression and generalized anxiety disorder is influenced by the same genetic factors, so that whether a vulnerable woman develops major depression or generalized anxiety disorder is a result of her environmental experiences.

Identification of rifampin-inducible P450IIIA4 (CYP3A4) in human small bowel enterocytes.

Abstract: Enzymes within the P450IIIA (CYP3A) subfamily appear to account for significant "first pass" metabolism of some drugs in the intestine. To identify which of the known P450IIIA genes are expressed in intestine, enterocyte RNA was hybridized on Northern blots with synthetic oligonucleotides complementary to hypervariable regions of hepatic P450IIIA4, P450IIIA5, and P450IIIA7 cDNAs. Hybridization was detected only with the P450IIIA4-specific oligonucleotide. The identity of the hybridizing mRNA was confirmed to be P450IIIA4 by direct sequencing of a DNA fragment amplified from enterocyte cDNA by the polymerase chain reaction. To determine if enterocyte P450IIIA4 is inducible, biopsies of small bowel mucosa were obtained from five volunteers before and after they received 7d of treatment with rifampin, a known inducer of P450IIIA4 in liver. Rifampin treatment resulted in a five- or eightfold mean increase (P < 0.05) in the biopsy concentration of P450IIIA4 mRNA when normalized for content of sucrase isomaltase or intestinal fatty acid binding protein mRNAs, respectively. Rifampin also induced P450IIIA immunoreactive protein in enterocytes in each of the subjects, as judged by immunohistochemistry, and resulted in a 10-fold increase in P450IIIA4-specific catalytic activity (erythromycin N-demethylation) in the one patient studied. Our identification of inducible P450IIIA4 in enterocytes may in part account for drug interactions characteristic of P450IIIA4 substrates and suggests a strategy for controlling entry into the body of a major class of xenobiotics.

Ultra-early evaluation of regional cerebral blood flow in severely head-injured patients using xenon-enhanced computerized tomography

Abstract: The role of cerebral ischemia in the pathophysiology of traumatic brain injury is unclear Cerebral blood flow (CBF) measurements with 133Xe have thus far revealed ischemia in a substantial number of patients only when performed between 4 and 12 hours postinjury But these studies cannot be performed sooner after injury, they cannot be done in patients with intracranial hematomas still in place, and they cannot detect focal ischemia Therefore, the authors performed CBF measurements in 35 comatose head-injured patients using stable xenon-enhanced computerized tomography (CT), simultaneously with the initial CT scan (at a mean (+/- standard error of the mean) interval of 31 +/- 21 hours after injury) Seven patients with diffuse cerebral swelling had significantly lower flows in all brain regions measured as compared to patients without swelling or with focal contusions; in four of the seven, cerebral ischemia (CBF less than or equal to 18 ml/100 gmmin-1) was present Acute intracranial hematomas were associated with decreased CBF and regional ischemia in the ipsilateral hemisphere, but did not disproportionately impair brain-stem blood flow Overall, global or regional ischemia was found in 11 patients (314%) There was no correlation between the presence of hypoxia or hypertension before resuscitation and the occurrence of ischemia, neither could ischemia be attributed to low pCO2 Ischemia was significantly associated with early mortality (p less than 002), whereas normal or high CBF values were not predictive of favorable short-term outcome These data support the hypothesis that ischemia is an important secondary injury mechanism after traumatic brain injury, and that trauma may share pathophysiological mechanisms with stroke in a large number of cases; this may have important implications for the use of hyperventilation and antihypertensive drugs in the acute management of severely head-injured patients, and may lead to testing of drugs that are effective or have shown promise in the treatment of ischemic stroke

Assembling crystals from clusters

Abstract: It is shown that the stability of a cluster can be substantially enhanced by changing its size and/or composition so as to take advantage of the electronic shell filling as well as close atomic packing. The interaction between two such clusters is found to be weak and can form the basis for synthesizing a new class of cluster-assembled crystals with uncommong properties.

Determinants of capital structure.

Abstract: This study analyzes the determinants of hospital capital structure in a new market setting that are created by the financial pressures of prospective payment and the intense price competition among hospitals Using California data, the study found hospital system affiliation, bed size, growth rate in revenues, operating risk, and asset structure affected both short- and long-term debt borrowings In addition, percentage of uncompensated care, profitability, and payer mix influenced short-term borrowings while market conditions and ownership affected long-term borrowings Most significant of all is the finding that smaller hospitals tend to borrow more, possibly because they cannot generate funds internally

A population-based twin study of alcoholism in women

Abstract: Objective. —To clarify the role of genetic factors in the etiology of alcoholism in women. Design and Setting. —Personal structured psychiatric interviews conducted by researchers "blinded" to the status of the co-twin in an epidemiologic sample of 1030 female-female twin pairs of known zygosity from the population-based Virginia Twin Registry. Measures. —Three definitions of lifetime prevalence of alcoholism based on Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised criteria: (1) alcoholism with tolerance or dependence; (2) alcoholism with or without tolerance-dependence; and (3) alcoholism with or without tolerance-dependence or problem drinking. Results. —Using narrow, intermediate, or broad definitions, the probandwise concordance for alcoholism was consistently higher in monozygotic than in dizygotic twin pairs. Multifactorial threshold models suggested that the heritability of liability to alcoholism in women is in the range of 50% to 60%. Conclusions. —The results support the hypothesis that genetic factors play a major role in the etiology of alcoholism in women. Women should be well represented in the efforts currently under way to elucidate the molecular basis of the genetic susceptibility to alcoholism. ( JAMA . 1992;268:1877-1882)

A population-based twin study of major depression in women. The impact of varying definitions of illness.

Abstract: Although depression aggregates in families, the degree to which this aggregation results from genetic vs environmental factors remains uncertain. We examined this question in 1033 female-female twin pairs from a population-based registry. Both members of each twin pair were "blindly" assessed by structured psychiatric interview. Nine commonly used definitions of major depression, which produced life-time prevalence rates ranging from 12% to 33%, were examined. For all definitions, the results of model fitting to twin correlations suggested that the liability to depression results from genetic factors and environmental experiences unique to the individual. For seven of the definitions, the estimated heritability of liability was similar, ranging from 33% to 45%. For the two definitions that included only primary cases of depression, the heritability was lower (21% to 24%). The results document that in women (1) genetic factors play a substantial, but not overwhelming, role in the cause of depression; (2) the tendency for depression to aggregate in families results largely from shared genetic and not from shared environmental factors; (3) except for definitions that exclude secondary cases, the magnitude of genetic influence is similar in broadly and narrowly defined forms of major depression; and (4) most environmental experiences of causative importance for depression are those not shared by members of an adult twin pair.

Hydrogen interactions with defects in crystalline solids

Abstract: Hydrogen interactions with imperfections in crystalline metals and semiconductors are reviewed. Emphasis is given to mechanistic experiments and theoretical advances contributing to predictive understanding. Important directions for future research are discussed.

Inhibition of calcium oxalate crystal growth in vitro by uropontin: another member of the aspartic acid-rich protein superfamily.

Abstract: The majority of human urinary stones are primarily composed of calcium salts. Although normal urine is frequently supersaturated with respect to calcium oxalate, most humans do not form stones. Inhibitors are among the multiple factors that may influence the complex process of urinary stone formation. We have isolated an inhibitor of calcium oxalate crystal growth from human urine by monoclonal antibody immunoaffinity chromatography. The N-terminal amino acid sequence and acidic amino acid content of this aspartic acid-rich protein, uropontin, are similar to those of other pontin proteins from bone, plasma, breast milk, and cells. The inhibitory effect of uropontin on calcium oxalate crystal growth in vitro supports the concept that pontins may have a regulatory role. This function would be analogous to that of other members of the aspartic acid-rich protein superfamily, which stereospecifically regulate the mineralization fronts of calcium-containing crystals.

A Comparison of Standard-Dose and High-Dose Epinephrine in Cardiac Arrest outside the Hospital

Abstract: Background. Experimental and uncontrolled clinical evidence suggests that intravenous epinephrine in doses higher than currently recommended may improve outcome after cardiac arrest. We conducted a prospective, multicenter study comparing standard-dose epinephrine with high-dose epinephrine in the management of cardiac arrest outside the hospital. Methods. Adult patients were enrolled in the study if they remained in ventricular fibrillation, or if they had asystole or electromechanical dissociation, at the time the first drug was to be administered to treat the cardiac arrest. Patients were randomly assigned to receive either 0.02 mg of epinephrine per kilogram of body weight (standard-dose group, 632 patients) or 0.2 mg per kilogram (high-dose group, 648 patients), both given intravenously. Results. In the standard-dose group 190 patients (30 percent) had a return of spontaneous circulation, as compared with 217 patients (33 percent) in the high-dose group; 136 patients (22 percent) in the stan...

Cognitive deficits following traumatic brain injury produced by controlled cortical impact.

Abstract: Traumatic brain injury produces significant cognitive deficits in humans. This experiment used a controlled cortical impact model of experimental brain injury to examine the effects of brain injury on spatial learning and memory using the Morris water maze task. Rats (n = 8) were injured at a moderate level of cortical impact injury (6 m/sec, 1.5-2.0 mm deformation). Eight additional rats served as a sham-injured control group. Morris water maze performance was assessed on days 11-15 and 30-34 following injury. Results revealed that brain-injured rats exhibited significant deficits (p less than 0.05) in maze performance at both testing intervals. Since the Morris water maze task is particularly sensitive to hippocampal dysfunction, the results of the present experiment support the hypothesis that the hippocampus is preferentially vulnerable to damage following traumatic brain injury. These results demonstrate that controlled cortical impact brain injury produces enduring cognitive deficits analogous to those observed after human brain injury.

Identifying Alterable Patterns in Employment Success for Highly Successful Adults with Learning Disabilities

Abstract: Adults with learning disabilities were studied to ascertain the patterns of successful functioning that promoted high levels of vocational success. This area of research has been neglected in the developing research base on adults with learning disabilities. In this study of 46 highly successful and 25 moderately successful adults with learning disabilities using ethnographic interviews, it was found that the overriding theme was control and that control was sought through the pursuit of two sets of themes--internal decisions and external manifestations. These themes transcended the entire sample, and the clear difference between the groups was the degree of attainment on the various elements the themes comprised. These elements and themes are discussed and a model of successful vocational functioning is developed and explained.

Blood pressure and intracranial pressure-volume dynamics in severe head injury: relationship with cerebral blood flow.

Abstract: Increased brain tissue stiffness following severe traumatic brain injury is an important factor in the development of raised intracranial pressure (ICP). However, the mechanisms involved in brain tissue stiffness are not well understood, particularly the effect of changes in systemic blood pressure. Thus, controversy exists as to the optimum management of blood pressure in severe head injury, and diverging treatment strategies have been proposed. In the present study, the effect of induced alterations in blood pressure on ICP and brain stiffness as indicated by the pressure-volume index (PVI) was studied during 58 tests of autoregulation of cerebral blood flow in 47 comatose head-injured patients. In patients with intact autoregulation mechanisms, lowering the blood pressure caused a steep increase in ICP (from 20 +/- 3 to 30 +/- 2 mm Hg, mean +/- standard error of the mean), while raising blood pressure did not change the ICP. When autoregulation was defective, ICP varied directly with blood pressure. Accordingly, with intact autoregulation, a weak positive correlation between PVI and cerebral perfusion pressure was found; however, with defective autoregulation, the PVI was inversely related to cerebral perfusion pressure. The various blood pressure manipulations did not significantly alter the cerebral metabolic rate of oxygen, irrespective of the status of autoregulation. It is concluded that the changes in ICP can be explained by changes in cerebral blood volume due to cerebral vasoconstriction or dilatation, while the changes in PVI can be largely attributed to alterations in transmural pressure, which may or may not be attenuated by cerebral arteriolar vasoconstriction, depending on the autoregulatory status. The data indicate that a decline in blood pressure should be avoided in head-injured patients, even when baseline blood pressure is high. On the other hand, induced hypertension did not consistently reduce ICP in patients with intact autoregulation and should only be attempted after thorough assessment of the cerebrovascular status and under careful monitoring of its effects.

Estimating the probability of failure when testing reveals no failures

Abstract: Formulas for estimating the probability of failure when testing reveals no errors are introduced. These formulas incorporate random testing results, information about the input distribution; and prior assumptions about the probability of failure of the software. The formulas are not restricted to equally likely input distributions, and the probability of failure estimate can be adjusted when assumptions about the input distribution change. The formulas are based on a discrete sample space statistical model of software and include Bayesian prior assumptions. Reusable software and software in life-critical applications are particularly appropriate candidates for this type of analysis. >

Ham-2 corrects the class I antigen-processing defect in RMA-S cells.

Abstract: The murine major histocompatibility complex (MHC) contains two genes (Ham-1 and Ham-2) that encode members of a super-family of ATP-dependent transport proteins. These genes are believed to mediate the transport of peptide antigen from the cytoplasm into the lumen of the endoplasmic reticulum for binding by MHC class I molecules. Evidence for such a function has come from the rescue of class I surface expression by a cloned copy of the human homologue of Ham-1, PSF-1, in a human cell line that is defective in antigen processing. A mutant murine cell line, RMA-S, has an identical antigen-processing-defective phenotype. Here we show that expression of a cloned copy of the Ham-2 gene in RMA-S cells results in recovery of the ability to process and present class I-restricted antigens to cytotoxic T lymphocytes, and in partial recovery of class I surface expression. Processing defects for classical (H-2 K and D) and non-classical (Qa1 and HMT) class I molecules are corrected by Ham-2. These data indicate that both MHC-linked transporter genes are probably required for class I antigen processing, and that the functional transporter in this pathway may consist of a Ham-1/Ham-2 heterodimer.

Environmental Factors Influencing Accounting Disclosure Requirements of Global Stock Exchanges

Abstract: The globalization of capital markets has resulted in a great deal of attention being focused on problems created by accounting diversity in different countries. A number of studies have documented variations in accounting disclosure and reporting practices and standards in different countries. Diverse environmental factors have been cited in the literature to explain differences in disclosure levels between countries. This paper examines the relationship between environmental factors and the accounting disclosure requirements of stock exchanges in different countries. A cross-national disclosure model is developed to investigate the relationship of selected environmental factors and stock exchange disclosure requirements of 35 stock exchanges in different countries. Five environmental factors are used to explain the variation observed in disclosure requirements of the different stock exchanges. The five factors examined are: degree of economic development, type of economy, size of the equity market, activity on the equity market, and dispersion of stock ownership in the equity market. The overall results obtained from the cross-sectional regression indicate that the level of disclosure requirements of stock exchanges is related to the selected environmental factors in different countries. Of die five factors examined, however, only size of the equity market is found to be a significant explanatory variable.

Relationship between drug use and other problem behaviors in urban adolescents.

Abstract: This study tested the generality of Jessor and Jessor's (1977) problem behavior theory, which states that a variety of problem behaviors constitute a behavioral syndrome in normal adolescents. Relationships among 5 adolescent problem behaviors (cigarette use, alcohol use, marijuana use, delinquency, and sexual intercourse) were examined in 7th-grade boys (n = 556) and girls (n = 715), and 9th-grade boys (n = 481) and girls (n = 485) in an urban school system in which the majority of students were African American and from low-income families. Measures of problem behavior frequency were positively correlated with each other and negatively correlated with several measures of conventional behavior. Confirmatory factor analyses replicated findings of previous studies that a single common factor underlies adolescent problem behaviors.

Identification of a functionally relevant cannabinoid receptor on mouse spleen cells that is involved in cannabinoid-mediated immune modulation.

Abstract: Extensive behavioral and biochemical characterization of cannabinoid-mediated effects on the central nervous system has revealed at least three lines of evidence supporting the role of a putative guanine nucleotide-binding protein-coupled cannabinoid receptor for cannabimimetic effects, (i) stereoselectivity, (ii) inhibition of the adenylate cyclase/cAMP second messenger system, and (iii) radioligand-binding studies with the synthetic cannabinoid [3H]CP-55,940 indicating a high degree of specific binding to brain tissue preparations. Based on recent findings from our laboratory demonstrating that delta 9-tetrahydrocannabinol markedly inhibited forskolin-stimulated cAMP accumulation in mouse spleen cells, the presence of a guanine nucleotide-binding protein-coupled cannabinoid receptor associated with mouse spleen cells and its functional role in immune modulation were investigated. In the present studies, stereoselective immune modulation was observed with the synthetic bicyclic cannabinoid (-)-CP-55,940 versus (+) CP-56,667 and with 11-OH-delta 8-tetrahydrocannabinol-dimethylheptyl, (-)-HU-210 versus (+)-HU-211. In both cases, the (-)-enantiomer demonstrated greater immunoinhibitory potency than the (+)-isomer, as measured by the in vitro sheep red blood cell antibody-forming cell response. Radioligand binding studies produced a saturation isotherm exhibiting approximately 45-65% specific binding to mouse spleen cells. Scatchard analysis demonstrated a single binding site on spleen cells, possessing a Kd of 910 pM and a Bmax of approximately 1000 receptors/spleen cell. RNA polymerase chain reaction of isolated splenic RNA using specific primers for the cannabinoid receptor resulted in the amplification of a 854-kilobase predicted product that hybridized with cannabinoid receptor cDNA, demonstrating the presence of cannabinoid receptor mRNA in mouse spleen. Together, these findings strongly support the role of a cannabinoid receptor in immune modulation by cannabimimetic agents.

Binding of hydrogen molecules by a transition-metal ion.

Abstract: Using self-consistent field molecular-orbital theory, we show that the interaction of hydrogen molecules with a ${\mathrm{Ni}}^{+}$ ion is characteristically different from that with a neutral Ni atom. While hydrogen chemisorbs dissociatively on the neutral metal atom, it is bound to the cation in its molecular form. The atomic bonding is a consequence of the Pauli exclusion principle whereas the bonding of the molecular hydrogen results from an electrostatic interaction. We predict that a ${\mathrm{Ni}}^{+}$ ion can bind at least six hydrogen molecules.

Practitioners’ Personal and Professional Attitudes and Behaviors Toward Religion and Spirituality

Abstract: This article presents findings from a study that examined the attitudes and behaviors toward religion and spirituality held by 328 randomly selected Virginia licensed clinical social workers, psychologists, and professional counselors. Significant differences were found among the three groups, with social workers generally holding a middle position in comparison with psychologists and professional counselors. As a whole, respondents were found to value the religious or spiritual dimension in their own lives, to respect the function it serves for people in general, and to address, to some extent, religious and spiritual issues in practice. Limited professional training in this area was reported, however, with 79% (n = 259) of the respondents stating that religious or spiritual issues were rarely or never addressed during the course of their graduate education and training. Implications for social work education and practice are discussed.

Human disc phospholipase A2 is inflammatory.

Abstract: Human discs have been demonstrated to contain high levels of phospholipase A2. As the enzyme responsible for the liberation of arachidonic acid from membranes, this enzyme has a theoretical inflammatory potential. Herniated lumbar discs have a higher level of phospholipase A2 than do normal discs. The purpose of this study was to evaluate the inflammatory capability of purified human disc phospholipase A2. Phospholipase A2 extracted and purified from human disc was found to be inflammatory. Its inflammatory capability was directly related to its ability to function enzymatically. When the enzyme was treated with parabromophenacyl bromide (p-BPB) to specifically alkylate the active site histidine and block catalytic activity, the ability of the modified protein to produce edema was markedly reduced. Careful regulation of the activity of this enzyme is important in vivo because its inflammatory potential could result in disc degeneration and nerve injury.

Opportunities for integration of pharmacokinetics, pharmacodynamics, and toxicokinetics in rational drug development.

Abstract: Clinical Pharmacology and Therapeutics (1992) 51, 465–473; doi:10.1038/clpt.1992.47

Screening for drinking disorders in the elderly using the CAGE questionnaire.

Abstract: Objective To assess the performance of the CAGE questionnaire in identifying elderly medicine outpatients with drinking problems. Design Cross-sectional design, with the alcohol module of the Diagnostic Interview Schedule as the criterion standard. Setting The outpatient medical practice of an urban university teaching hospital. Patients Consecutive patients 18 years or older who signed a consent form approved by the university's institutional review board. For this study, 323 patients ≥60 years old. Main Outcome Measures Sensitivity, specificity, receiver operating characteristics (ROC) curve and positive predictive value for CAGE scores of 0–4 for patients 60 years or older. Results Thirty-three percent of the sample group met study criteria for a history of drinking problems, including 63% of the male patients and 22% of the female patients. The sensitivity and specificity for a cut-off score of one for all patients was 86% and 78%, respectively, and 70% and 91% for a cut-off of two. The calculation of the area under the ROC curve was .86, and the positive predictive value of CAGE scores of 0–4 were 33%, 66%, 79%, 82%, and 94%, respectively. The predictive value for any score was higher in males than females, reflecting the higher prevalence of problems in the male population. Conclusions The CAGE can effectively discriminate elderly patients with a history of drinking problems from those without such a history. The chosen cut-off score should consider the prevalence of drinking problems in the population being tested.

Efficacy and cost-effectiveness of autologous bone marrow transplantation in metastatic breast cancer. Estimates using decision analysis while awaiting clinical trial results.

Abstract: Objective. —To assess the efficacy and cost-effectiveness of standard chemotherapy and high-dose chemotherapy with autologous bone marrow transplantation (ABMT) in metastatic breast cancer. Design. —Decision analysis model using a Markov process. Setting. —Response and recurrence rates from the published literature for standard therapy and from case series of ABMT. Costs were based on local charges and on adjusted Medicare data. Patients. —Hypothetical cohorts of women with metastatic breast cancer who had no bone marrow involvement and no comorbid illness. Intervention. —The standard chemotherapy cohort received cyclophosphamide, doxorubicin, and fluorouracil. The ABMT cohort was treated with intense induction chemotherapy, then additional high-dose chemotherapy following a remission, with ABMT support. Main Outcome Measures. —Anticipated survival, incremental cost per year of life, and incremental cost per quality-adjusted year of life gained using a 5-year time horizon. Rigorous sensitivity analyses were done, including assessing a benefit "tail" of normal life expectancy for those free of disease after 5 years. Results. —ABMT was the preferred approach under almost all assumptions, but the size of the benefit varied greatly. ABMT had a survival benefit of 6.0 months at 5 years at an incremental cost of $115 800 per year of life saved. If patients who were free of disease after 5 years had normal survival, the benefit was 18.1 months at an incremental cost of $28 600 per year. The benefit of ABMT was primarily dependent on whether the recurrence risk was constant or decreases after a finite period of time. Conclusion. —Using reasonable assumptions, ABMT provided a substantial benefit but at a cost that may be untenable. Decision analysis highlights the limitations in the currently available data and the assumptions made for the emotional question of using ABMT in metastatic breast cancer. The model supports the need for randomized clinical trials. (JAMA. 1992;267:2055-2061)